Δευτέρα, 6 Νοεμβρίου 2017

Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of Perilipin 5?

Abstract

Intramyocellular lipids (IMCL) hamper insulin sensitivity albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes patients (T2DM), Trained subjects have high levels of Perilipin 5 (PLIN5). Here, we tested if the fraction of PLIN5 coated LDs is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from 8 Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5- LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in GIR. Trained and T2DM subjects stored IMCL differently; Trained had a higher number of LDs compared to T2DM (0.037 ± 0.004 μm−2vs. 0.023 ± 0.003 μm−2, P = 0.024), that were non-significantly smaller (0.27 ± 0.01 μm2vs. 0.32 ± 0.02 μm2, P = 0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM (1.65 ± 0.21 AU vs. 0.89 ± 0.09 AU, P = 0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake, adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relation between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox.

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Local Oscillatory Properties of the Dendritic Membrane of Hippocampal Pyramidal Neurons: a Simulation Study

Foci of epileptic activity, generated as a result of synchronization of periodic burst discharges in neuronal networks, are often localized in the hippocampus. Using a model approach, we investigated the possibility of and biophysical conditions for the appearance of local oscillatory processes in dendrites possessing voltage-dependent channels (which is typical of pyramidal neurons of the hippocampus). The study was performed on a computer model of the membrane with active conductivities inherent in dendrites of pyramidal neurons of the CA3 area. It was found that such a membrane compartment subjected to tonic synaptic excitatory influences can function as a local generator of stable depolarization of a low or a high level or as a generator producing membrane potential oscillations (local oscillator). Each of these modes corresponds to a certain range of the synaptic excitation intensity; with increasing temperature, the range within which the oscillator properties are manifested is narrowed, while the range within which high-level stable depolarization is generated is expanded.



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EEG Activities and the Sustained Attention Performance

We investigated the relations between EEG activity and sustained attention in humans. A visual version of the conjunctive continuous performance task (CCPT-V) was used as a measure of sustained attention. Twenty university students voluntarily participated in the study; they were divided into two groups, good and weak, according to their results in the CCPT-V. The spectral power of EEG recorded from Fz, Cz, and Pz was analyzed under three conditions (eyes open, eyes closed, and CCPT-V) in four frequency ranges, theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–60 Hz) in three channels. Results of repeatedmeasures MANOVA showed the significance of the effects of conditions and channels with respect to the alpha and theta but not to the beta and gamma powers. There was no significant effect of the group, but, when comparing the alpha power under three conditions, the good group showed lower spectral powers. It has been concluded that cerebral neuronal systems producing alpha and theta oscillations play a role in sustained attention, and this can be shown by EEG recording and in the respective test.



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Cortical Visual Evoked Potentials in Subjects with Auditory Deprivation (Congenital Deafness)

In 30 healthy men (age 19–25 years) with normal hearing and 30 men of the same age suffering from complete congenital deafness, we examined peculiarities of the cortical visual evoked potentials, VEPs (photostimulation of the right and left eye by LED flashes, recording from loci O1 and O2). It was found that subjects with auditory deprivation demonstrated significantly shorter (P < 0.05–0.001) peak latencies of the early VEP components (P1, N2, and P2), while peak latencies of the late waves (N2 and P3) were greater (P < 0.05) than the corresponding indices in the control group. Peak-to-peak amplitudes of all VEP components in deaf subjects were about two to three times lower than those in subjects with normal hearing (P < 0.05–0.001). The mean total duration of the VEPs in deaf persons was significantly greater than in the control group (P < 0.05). Therefore, loss of the auditory function in deaf subjects results, due to cross-modal transformations, in substantial modifications of the potentials reflecting perception of the visual signals.



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Inhibitors of Poly(ADP-Ribose)Polymerase-1 as Agents Providing Correction of Brain Dysfunctions Induced by Experimental Diabetes

The effects of 1,5-isoquinolinediol (IQD) and nicotinamide (NAm), inhibitors of poly-(ADP-ribose) polymerase-1 (PARP-1), on inflammatory processes and activation of PARP-1 under conditions of the development of experimental diabetic neuropathy, DN (a complication of streptozotocin-induced type-1 diabetes) in rats were studied. The content of IL-4 in blood serum in the case of DN was 50% higher, while that of monocyte-chemotactic protein-1 was 90% higher than those in the control. The content of gamma-interferon also increased, while the content of the granulocyte-macrophage colony-stimulating factor did not change. Against the background of activation of PARP-1 and a decrease in the content of the substrate of this enzyme nicotinamide adenine dinucleotide (NAD) in the brain, fragmentation of PARP-1 was intensified; an increase in the ratio of the contents of a 89 kDa fragment/intact enzyme molecules proved this fact. The mentioned two structurally dissimilar PARP-1 inhibitors partly or entirely normalized the above parameters under DN conditions. These results demonstrate that PARP-1 is one of the main functional targets in realization of the effects of IQD and NAm. At the same time, the spectrum of action of these inhibitors is wider. In particular, they affect the level of proinflammatory cytokines. The ability of the investigated PARP-1 inhibitors to prevent cell death in the brain by suppressing activation and fragmentation of the above-mentioned enzyme shows that other types of action of these agents at the molecular level are possible; these may be the maintenance of the genome integrity in the brain structures under DN conditions and preventing the development of inflammatory processes. Thus, the examined inhibitors can be used in the future in the treatment of brain dysfunctions that are complications of type-1 diabetes mellitus.



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Cerebral Activities in Rats within Different Periods after Experimental Unilateral Cerebral Ischemia

A model of cerebral ischemia in the left hemisphere was established in rats by occlusion of the left middle cerebral artery (MCAO). Twenty-five Sprague-Dawley rats were divided into five groups, the control (C) group and animals 4, 24, 48h, and one week (4h, 24h, 48h, and 1w, respectively) after MCAO. The footprint pattern test (FPT) was used to compare the gait in the MCAO groups with that in the C group. Ongoing EEGs were recorded and analyzed (spectral power densities of different rhythms were calculated). Somatosensory evoked potentials (SSEPs) were induced by stimulation of the right median nerve and averaged. Rats of group 4h displayed significantly worse gait parameters compared to those in the C group (P < 0.01). The 24h, 48h, and 1w groups demonstrated no significant differences from this aspect, as compared with the C group (P > 0.05). Compared with the latter group, mean EEG mean powers of the EEG rhythms in the MCAO groups were significantly lower (P < 0.01), latencies of the SSEP components were longer, and peak amplitudes were reduced significantly (P < 0.01). All EEG and SSEP parameters demonstrated trends toward normal values with increase in the time interval after MCAO but were not restored completely. Therefore, functional behavioral tests, EEG, and SSEP monitoring at different phases after experimental cerebral ischemia can provide detailed valuable information on the states of neural activities, which are well correlated with the motor function recovery.



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Ethical Responsibilities of The Authors



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Cancer genomics: The driving force of cancer evolution



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Navigating complexity to breed disease-resistant crops



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Gene expression: Principles of gene regulation across tissues



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Navigating complexity to breed disease-resistant crops

Navigating complexity to breed disease-resistant crops

Navigating complexity to breed disease-resistant crops, Published online: 07 November 2017; doi:10.1038/nrg.2017.82

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Disease-resistant crops have the potential to reduce crop losses. This Review discusses how advances in genetic and genomic technologies are contributing to efforts by plant breeders to generate durable, broad-spectrum disease resistance in crop plants.

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Gene expression: Principles of gene regulation across tissues

Gene expression: Principles of gene regulation across tissues

Gene expression: Principles of gene regulation across tissues, Published online: 07 November 2017; doi:10.1038/nrg.2017.94



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Cancer genomics: The driving force of cancer evolution

Cancer genomics: The driving force of cancer evolution

Cancer genomics: The driving force of cancer evolution, Published online: 07 November 2017; doi:10.1038/nrg.2017.95

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Two novel comprehensive analyses in Cell provide important insights into the dynamics of tumour evolution and the mutational burden of a wide range of cancer types.

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Public health approach to minimize the prevalence and associated sequels of leishmaniasis in the affected regions

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Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1371-1372



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Necessity to strengthen prevention activities and expand treatment services to accomplish global elimination of Hepatitis C

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1101-1102



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The effect of space face games on the amount of children attention with attention deficit hyperactivity disorders

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Zahra Shahmoradi, Jahangir Maghsoudi, Mostafa Najafi, Saeed Pahlavanzadeh

Annals of Tropical Medicine and Public Health 2017 10(5):1341-1344

Introduction: As ever play therapy using a special toy which is produced with therapeutic target in children with attention deficit hyperactivity disorders (ADHDs) has not been conducted, this study was carried out with the aim to determine the effect of space face games on the attention of children with ADHDs. Materials and Methods: In this research, 72 children with ADHDs referred to Isfahan's Noor psychiatric clinic were randomly placed in two test and control groups. Attention level of both groups was evaluated using continuous performance test before and after the intervention. The space face games in the test group were used for 16 sessions. Statistical analysis of data was conducted using descriptive and analytical statistics in SPSS Software Version 18. Findings: The average score of attention had no significant difference between the two groups before the intervention, but the number of correct answer in the test group was significantly more than the control group and the number of provided errors and the number of removed errors were significantly lower than the control group immediately after the intervention. Conclusion: Space face games are effective in the promotion of attention in children with ADHDs.

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Delivering comprehensive sexuality education among youths to eventually achieve human immunodeficiency virus-free generation

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1103-1104



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Mobilizing youth population to spread peace in the conflict-affected regions of Central Africa

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1394-1395



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Young people acting as ambassadors for the accomplishment of women-related sustainable development goals

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1105-1106



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Preventing the outbreaks of food-borne botulism and minimizing the risk of fatality

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Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1360-1361



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Universal health coverage: Necessity, monitoring, and the vision ahead

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1107-1108



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Prevention and control of Hepatitis A in developing nations: Public health perspective

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1382-1384



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Building an effective mechanism to respond to the repeated outbreaks of cholera in the african region

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1109-1110



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Comparison of two educational methods, lecturing and simulation, in adherence to ventilator set guidelines among emergency medicine residents

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Hossein Saidi, Mahdi Rezai, Mani Mofidi, Reza Mosaddegh, Azra Riahi, Mohamad Tahmasbi Sisakht

Annals of Tropical Medicine and Public Health 2017 10(5):1318-1321

Background: Due to developments in science, there is the need to develop approaches in the field of medical education. The utilization of educational technologies such as computers and instructional videos has been introduced rapidly into the education curriculum. This study compared video training tutorial method in ventilator settings with video traditional methods (lectures). Materials and Methods: In this statistical research, 33 assistant training groups lecture and video tutorial (video tutorial) were divided into two groups. The assistants in ventilator settings by observing the experimenter, the ventilators were assessed using the checklist. Research Findings: Adjusting the ventilator before and after training assistant was 13 (40%) and 18 (5.54%), respectively. However, in both groups after training, there was significant increase accuracy in the ventilator settings, but there was no significant difference between the two methods. Conclusion: The use of video tutorials and without training could be effective as attending lectures.

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Combating infectious diseases on the global scale in the era of the sustainable development goals

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1111-1112



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Thrombocytopenia and bleeding: Existed but little mentioned in Zika virus infection

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Somsri Wiwanitkit, Viroj Wiwanitkit

Annals of Tropical Medicine and Public Health 2017 10(5):1355-1356



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Developing a mechanism to reduce after effects and track health workers affected by terrorism

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1113-1114



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Fast-tracking efforts to accomplish the global elimination of trachoma by 2020

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Saurabh RamBihariLal Shrivastava, Prateek Saurabh Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1366-1367



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Meeting the sexual and reproductive health needs of young people in developing nations

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1115-1116



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How can we respond to the challenge of insufficient physical activity?

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1377-1378



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Implementing maternal death surveillance and response through the Millennium Villages Project: World Health Organization

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1117-1118



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Public health measures to minimize exposure to arsenic and associated morbidities

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1388-1389



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International agencies working together to empower adolescent girls in Mozambique: A community-based intervention

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Saurabh R Shrivastava, Prateek S Shrivastava, Jegadeesh Ramasamy

Annals of Tropical Medicine and Public Health 2017 10(5):1119-1120



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Comment on: “Gálvez et al.: Interactive pediatric emergency checklists to the palm of your hand - How the pedi crisis app traveled around the world”



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Infant spinal anesthesia: Do girls need a larger dose of local anesthetic?



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Xenon-augmented pediatric anesthesia: A small step closer?



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Ultra-modified Rapid Sequence Induction



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Reply to Adam Adler and Arvind Chandrakantan regarding their comment “Nursing initiated tracheal extubation in PACU, the risk of delegating critical anesthesiology tasks in the interest of speed”



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In this issue: December 2017



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Caution with the Posey® Cufflator™ cuff pressure manometers



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Judging causal associations in observational research on caudal anesthesia and hypospadias repair



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Reviewers List



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Issue Information



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Improving Genomic Prediction in Cassava Field Experiments Using Spatial Analysis

Cassava (Manihot esculenta Crantz) is an important staple food in sub-Saharan Africa. Breeding experiments were conducted at the International Institute of Tropical Agriculture in cassava to select elite parents. Taking into account the heterogeneity in the field while evaluating these trials can increase the accuracy in estimation of breeding values. We used an exploratory approach using the parametric spatial kernels Power, Spherical, and Gaussian to determine the best kernel for a given scenario. The spatial kernel was fit simultaneously with a genomic kernel in a genomic selection model. Predictability of these models was tested through a 10-fold cross-validation method repeated five times. The best model was chosen as the one with the lowest prediction root mean squared error compared to that of the base model having no spatial kernel. Results from our real and simulated data studies indicated that predictability can be increased by accounting for spatial variation irrespective of the heritability of the trait. In real data scenarios we observed that the accuracy can be increased by a median value of 3.4%. Through simulations we showed that a 21% increase in accuracy can be achieved. We also found that Range (row) directional spatial kernels, mostly Gaussian, explained the spatial variance in 71% of the scenarios when spatial correlation was significant.



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Studies of cortical connectivity using optical circuit mapping methods

Abstract

An important consideration when probing the function of any neuron is to uncover the source of synaptic input onto the cell, its intrinsic physiology and efferent targets. Over the years, electrophysiological approaches have generated considerable insight into these properties in a variety of cortical neuronal subtypes and circuits. However, as researchers explore neuronal function in greater detail, they are increasingly turning to optical techniques to bridge the gap between local network interactions and behaviour. The application of optical methods has increased dramatically over the last decade, spurred on by the optogenetic revolution. In this review, we provide an account of recent innovations, providing researchers with a primer detailing circuit mapping strategies in the cerebral cortex. We will focus on technical aspects of performing neurotransmitter uncaging and channelrhodopsin-assisted circuit mapping, with the aim of identifying common pitfalls that can negatively influence the collection of reliable data.

This article is protected by copyright. All rights reserved



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Journal Clubs in Sports Medicine Fellowship Programs: Results From a National Survey and Recommendations for Quality Improvement

imageBackground: Journal club is a pervasive component of graduate medical education, yet there is no gold standard as to format and logistics. Methods: Survey of primary care sports medicine fellowship directors in the United States. Results: Sixty-nine program directors completed the online questionnaire (40% response rate). There were some common aspects to journal club exhibited by a majority of programs, including the general format, required attendance by fellows and expected or required attendance by faculty, the expectation that participants had at least read the article before the meeting, and that meetings occurred during the workday in the work setting without provision of food. There was considerable variation on other aspects, including the objectives of journal club, who had primary responsibility for organizing the session, the criteria for selection of articles, who was invited to attend, and the perceived problems with journal club. Conclusions: This is the first survey investigating the current state of journal club in primary care sports medicine fellowship programs. Several opportunities for educational enhancements exist within journal clubs in primary care sports medicine, including the use of structured tools to guide discussion, providing mechanisms to evaluate the journal club experience as a whole, inviting multidisciplinary team members (eg, statisticians) to discussions, and ensuring that objectives are explicitly stated to participants.

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Treatment of Primary Acute Patellar Dislocation: Systematic Review and Quantitative Synthesis of the Literature

imagePurpose: The aim of this study was to evaluate clinical outcomes, rate of redislocation, and complications after conservative or surgical procedures used to treat primary acute patellar dislocation. Methods: A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases using various combinations of the keywords "patella," "dislocation," "treatment," "acute," "primary" was performed. The following data were extracted: demographics, chondral defects and soft tissue lesions, outcome measurements, type of management, recurrence of instability, and complications. Results: A total of 2134 knees in 2086 patients were included, with an average age at dislocation of 20.3 years. The average Kujula score was 75.6 for patients treated conservatively and 88.7 for patients undergoing surgical treatment in the short–medium follow-up (less than 5 years); the average Kujula score was 87.5 for patients treated conservatively and 86.6 for patients undergoing surgical treatment in the long-term follow-up (more than 5 years). The rate of recurrence was significantly lower in the surgical group (25%) than in the conservative group (36.4%). The overall complication rate was 6.5% (29 of 441 knees) in the surgical management group. No complications were reported for patients treated conservatively. Conclusions: Surgical treatment of primary acute patellar dislocation leads to significantly lower rate of redislocation and provides better short–medium clinical outcomes, whereas in the long-term follow-up, results of patients treated conservatively were as good as those of surgical patients. Further randomized controlled trials, describing anatomical abnormalities and soft-tissue integrity that may influence the choice of treatment, are needed. Level of Evidence: Systematic review, level IV.

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Neuromuscular Training Availability and Efficacy in Preventing Anterior Cruciate Ligament Injury in High School Sports: A Retrospective Cohort Study

imageObjective: To document neuromuscular training (NMT) availability and its relationship to anterior cruciate ligament (ACL) injuries in 4 major high school sports by gender, sport, and rural/urban geography, with the hypothesis that increased exposure to NMT would be associated with fewer ACL injuries. Design: A retrospective cohort study. Setting: All Minnesota high schools identified in the Minnesota State High School League (MSHSL) database for fall 2014 boys' football and soccer, and girls' volleyball and soccer. Participants: All high school athletic directors were surveyed to report their school's fall 2014 experience; 53.5% returned the survey reporting experience with one or more of the sports. Intervention: Athletic directors documented each sport's preseason and in-season exposure to NMT (plyometric exercises, proximal/core muscle strengthening, education and feedback regarding proper body mechanics, and aerobics) and licensed athletic trainers. Main Outcomes: Reported ACL injuries by sport, gender and rural/urban. Results: More than two-thirds of teams incorporated facets of NMT into their sport. Among male athletes, soccer players exposed to licensed athletic trainers experienced significantly fewer ACL injuries (P

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Neuroendocrine Dysfunction in a Young Athlete With Concussion: A Case Report

imageAbstract: An 18-year-old female ringette and basketball player presented to our sport concussion clinic 27 months after concussion with fatigue, headache, exercise intolerance, polyuria, nocturia, and difficulties concentrating. Her history was remarkable for 4 previous concussions. Her neurologic examination was normal. Neuroendocrine screen including thyroid function, morning cortisol, glucose, and insulin-like growth factor-1 (screening test for growth hormone deficiency) were normal. Further testing for growth hormone deficiency with an insulin hypoglycemia test revealed severe growth hormone deficiency. Urine and serum electrolytes were borderline normal, suggesting partial diabetes insipidus. Treatments with growth hormone replacement lead to complete recovery. This case highlights the importance of maintaining a high index of suspicion for neuroendocrine abnormalities in athletes with persistent symptoms after sport concussion. Symptoms can be nonspecific and go undiagnosed for years, but appropriate recognition and treatment can restore function.

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Depression, Anxiety, and Alcohol Use in Elite Rugby League Players Over a Competitive Season

imageObjective: To assess the prevalence of symptoms of depression, anxiety, and rates of alcohol misuse in elite rugby league players in Australasia. Design: A cross-sectional, epidemiological study with repeated measures. Setting: Surveys were conducted during the 2015 preseason and in-season. Participants: Four hundred four elite rugby league players participated preseason and 278 players in-season. Main Outcome Measures: Symptoms of depression were measured using the Patient Health Questionnaire-9 scale, symptoms of generalized anxiety disorder (GAD) with the GAD-7 scale, and the Alcohol Use Disorders Identification Test Consumption scale was used to assess hazardous alcohol use. Results: The overall prevalence of depression was 12.6% preseason and 10.1% in-season. Generalized anxiety disorder had a prevalence of 14.6% and 10.1% for these 2 periods. Overall, 68.6% of players had hazardous levels of alcohol use preseason, and 62.8% in-season. There was no significant difference for any of the main outcomes between the periods. Players with a history of mental illnesses had 5.62 greater odds (95% confidence interval [CI], 2.62-12.04) of depression than those without during preseason, and 22.08 greater odds (95% CI, 7.77-62.71) in-season. Players reporting ≥3 previous concussions had 2.02 greater odds (95% CI, 1.07-3.82) of depression than those reporting ≤2 in the preseason sample. Conclusions: Rugby league players have a lower prevalence of depression compared with studies of the general population and other athletes, but a higher prevalence of GAD, and high rates of alcohol misuse. Clubs may consider implementing regular screening for these conditions. Further prospective research to determine causality of independent factors is required.

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Rankings of High School Sports Injury Rates Differ Based on Time Loss Assessments

imageObjective: To examine how injury definition inclusiveness affects the rank order of injury rates in 27 high school (HS) sports. Design: The National Athletic Treatment, Injury and Outcomes Network (NATION) used certified athletic trainers (ATs) to collect injury and athlete-exposure (AE) data in practices and competitions for 27 HS sports during the 2011/2012 to 2013/2014 academic years. Time loss (TL) injuries resulted in ≥24 hours of participation restriction. Nontime loss (NTL) injuries resulted in

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Carbon Monoxide Exposure in Youth Ice Hockey

imageObjective: To examine the effect of ice resurfacer type on carboxyhemoglobin levels in youth hockey players. We hypothesized that players in arenas with electric resurfacers would have normal, stable carboxyhemoglobin levels during games, whereas those in arenas with internal combustion engine (IC) resurfacers would have an increase in carboxyhemoglobin levels. Design: Prospective cohort study. Setting: Enclosed ice arenas in the northeastern United States. Participants: Convenience sample of players aged 8 to 18 years old in 16 games at different arenas. Eight arenas (37 players) used an IC ice resurfacer and 8 arenas (36 players) an electric resurfacer. Interventions: Carboxyhemoglobin levels (SpCO) were measured using a pulse CO-oximeter before and after the game. Arena air was tested for carbon monoxide (CO) using a metered gas detector. Players completed symptom questionnaires. Main Outcome Measures: The change in SpCO from pregame to postgame was compared between players at arenas with electric versus IC resurfacers. Results: Carbon monoxide was present at 6 of 8 arenas using IC resurfacers, levels ranged from 4 to 42 parts per million. Carbon monoxide was not found at arenas with electric resurfacers. Players at arenas with IC resurfacers had higher median pregame SpCO levels compared with those at electric arenas (4.3% vs 1%, P

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Anterior Knee Impingement in a High-Level Football Punter: A Case Report and Description of the Active–Passive Knee Extension Test

imageAbstract: A 22-year-old football punter complained of anterior knee pain deep to his patellar tendon that occurred every time the knee of his kicking leg reached full extension during a punt. Arthroscopy confirmed anterior impingement between a fibrous tissue eminence directly anterior to his anterior cruciate ligament (ACL) and the intercondylar roof in full extension. With the eminence removed, full extension no longer caused impingement as demonstrated arthroscopically. He resumed punting at maximal effort 6 weeks postoperatively without pain. We report the active–passive knee extension test, a physical examination maneuver designed to identify patients with anterior knee impingement between tissue anterior to the ACL and the intercondylar roof. This test is a helpful part of the clinical examination in detecting these lesions.

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Disparities in Athletic Trainer Staffing in Secondary School Sport: Implications for Concussion Identification

imageObjective: First, to assess whether teams at schools with an athletic trainer (AT) on staff had a higher number of diagnosed concussions than teams without medical personnel present. Second, to assess whether the variability in employment of a certified AT by Washington state high schools is patterned by socioeconomic and demographic characteristics. Design: Cross-sectional survey. Setting: Washington state public high schools. Participants: Stratified random sample of football and soccer coaches (n = 270 teams, 144 schools). Independent Variables: Presence of an AT and school characteristics (percentage of students qualifying for free or reduced price lunch, rural location, enrollment). Results: Football and boys' soccer teams at schools with an AT had a significantly greater number of athletes with diagnosed concussions compared to teams at schools without an AT (P

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In Response to: Keep the Physical in Physical Education

No abstract available

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Predictors of quality of life improvement after surgery for metastatic tumors of the spine: prospective cohort study

Surgical decompression and stabilization followed by radiosurgery represents an effective method for local tumor control and neurologic preservation for patients with metastatic epidural spinal cord compression. We have previously demonstrated improvement in HrQOL after this combined modality treatment ("hybrid therapy").

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How a diverse research ecosystem has generated new rehabilitation technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. ...

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Wireless intraoral tongue control of an assistive robotic arm for individuals with tetraplegia

For an individual with tetraplegia assistive robotic arms provide a potentially invaluable opportunity for rehabilitation. However, there is a lack of available control methods to allow these individuals to fu...

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Authors’ answers on comment of Abellona et al on Metabolomic analysis for noninvasive diagnosis of hepatic fibrosis degree in patients with chronic hepatitis C

We are pleased to recognize the interest of Abellona ER et al to our study, despite its negative results. Indeed, negative studies are often neglected by the scientific community, but nevertheless may be especially useful to discuss the methodology and how to move further. More specifically one of the criticism of Abellona ER et al was regarding the originality of the study and the small sample size investigated. Indeed, we are well aware of the studies cited by colleagues with similar sample sizes [1,2].

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Authors’ answers on comment of Abellona et al on Metabolomic analysis for noninvasive diagnosis of hepatic fibrosis degree in patients with chronic hepatitis C

We are pleased to recognize the interest of Abellona ER et al to our study, despite its negative results. Indeed, negative studies are often neglected by the scientific community, but nevertheless may be especially useful to discuss the methodology and how to move further. More specifically one of the criticism of Abellona ER et al was regarding the originality of the study and the small sample size investigated. Indeed, we are well aware of the studies cited by colleagues with similar sample sizes [1,2].

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Abnormal Cortical Neural Synchrony During Working Memory in Schizophrenia

Working memory (WM) encompasses the encoding, maintenance, and retrieval of mental representations that guide behavior (Baddeley, 2012; Miyake and Shah, 1999). Recent experimental studies have demonstrated that people with schizophrenia (PSZ) have WM storage capacity deficits which is not simply explained by instability in WM mental representation (Gold et al., 2010) or attentional deficits (Erickson et al., 2015), suggesting that problems in multiple neural processes might contribute to limited WM capacity in PSZ.

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RLS patients show better nocturnal performance in the Simon task due to diminished visuo-motor priming

The restless legs syndrome (RLS) is a sensory-motor disorder characterized by uncomfortable sensations, especially in the legs, combined with an urge to move. The symptoms are most pronounced at rest in the evening and at night (Allen et al., 2014b; Allen, 2015). In spite of the circadian variation of those sensory and motor symptoms, diurnal changes of potentially associated cognitive functions as well as the underlying neurophysiological and neuroanatomical processes have not yet been investigated.

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Bilateral loss of cortical SEPs predict severe MRI lesions in neonatal hypoxic ischemic encephalopathy treated with hypothermia

Hypoxic-ischemic encephalopathy (HIE) in term neonates is a significant cause of infant mortality and morbidity. As a routine, early assessment of neonatal encephalopathy is based on clinical observation (graded by Sarnat and Sarnat, 1976), MRI and EEG recordings of brain electrical activity while the acquisition of somatosensory evoked potentials (SEPs) in the neonatal period is often hampered by logistic reasons. After moderate whole-body hypothermia (therapeutic hypothermia- TH) proved its efficacy and safety in reducing death and cerebral palsy and improving neurological outcome (Azzopardi et al, 2009), clinicians and researchers needed to test its influence on the most widely used prognostic tools.

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A six-gene expression toolbox for the glands, epithelium and chondrocytes in the mouse nasal cavity

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Publication date: Available online 6 November 2017
Source:Gene Expression Patterns
Author(s): Yong Wan, Matthew B. Rogers, Heather L. Szabo-Rogers
The nose is the central feature of the amniote face. In adults, the nose is a structurally and functionally complex organ that consists of bone, cartilage, glands and ducts. In an ongoing expression screen in our lab, we found several novel markers for specific tissues in the nasal region. Here, using in situ hybridization expression experiments, we report that Alx1, Ap-2β, Crispld1, Eya4, Moxd1, and Penk have tissue specific expression during murine nasal development. At E11.5, we observed that Alx1, Ap-2β, Crispld1, and Eya4 are expressed in the medial and lateral nasal prominences. We found that Moxd1 and Penk are expressed in the lateral nasal prominences. At E15.5, Alx1 is expressed in nasal septum. Ap-2β and Crispld1 are expressed in nasal glands and cartilages. Eya4 is expressed in olfactory epithelium. Intriguingly at E15.5 Moxd1 is expressed in all the nasal cartilage while the expression of Penk is restricted to chondrocytes contributing to the posterior nasal septum. The expression domains reported here suggest that these genes warrant functional studies to determine their role in nasal capsule morphogenesis.



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High-throughput method for extracting and visualizing the spatial gene expressions from in situ hybridization images: A case study of the early development of the sea anemone Nematostella vectensis

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Publication date: Available online 6 November 2017
Source:Gene Expression Patterns
Author(s): A.M. Abdol, Andrew Bedard, Imke Lansky, J.A. Kaandorp
Studying the spatial gene expression profiles from in situ hybridization images of the embryo is one of the first steps toward the comprehensive understanding of gene interactions in an organism. In the case of N. vectensis, extracting and collecting these data is a challenging task due to the difficulty of detecting the cell layer through the transparent body plan and changing morphology during the blastula and gastrula stages. Here, first, we introduce a method to algorithmically identify and track the cell layer in N. vectensis embryo from the late blastula to the late gastrula stage. With this, we will be able to extract spatial expression profiles of genes alongside the cell layer and consequently reconstructing the 1D representation of gene expression profiles. Furthermore, we use the morphological configurations of the embryo extracted from confocal images, to model the dynamics of embryos morphology during the gastrulation process in 2D. Ultimately, we provide a visualization tool for studying and comparing the extracted spatial gene expression profiles over the simulated embryo. We anticipate that our method of extraction and visualization to be a starting point for quantifying and collecting more in situ images from various sources, which can potentially accelerate our understanding of gene interactions in the early development of N. vectensis. The method allows researchers to visualize and compare the different gene expressions from different in situ images or different experiments. As an example, we were able to show the complementary expression of NvFoxA-NvSnailA and NvBra-NvErg in the central domain and central/external rings during the development which suggests the possible repression effects between each pair; as it has been discovered by functional analysis.



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Physical activity-based interventions using electronic feedback may be ineffective for reducing pain and disability in patients with chronic musculoskeletal pain: a systematic review with meta-analysis

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Publication date: Available online 6 November 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Crystian B. Oliveira, Márcia R. Franco, Chris G. Maher, Paulo H. Ferreira, Priscila K. Morelhão, Tatiana M. Damato, Cynthia Gobbi, Rafael Z. Pinto
ObjectiveTo investigate the effectiveness of physical activity-based interventions using electronic feedback to reduce pain and disability compared to minimal or no interventions in patients with chronic musculoskeletal pain.DesignSystematic review with meta-analysisData SourcesThe following electronic databases were searched: EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, SPORTDiscus, Web of Science, Physiotherapy Evidence Database (PEDro), and main clinical trial registers.Study SelectionRandomized controlled trials (RCTs) investigating the effect of physical activity interventions using electronic feedback (eg. physical activity monitors) on pain and disability compared to minimal or no intervention in adults with chronic musculoskeletal pain were considered eligible.Data ExtractionPooled effects were calculated using the standardized mean difference (SMD) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the overall quality of evidence.Data SynthesisFour published RCTs and four registered unpublished RCTs were included. For short-term follow-up, pooled estimations showed no significant differences between physical activity-based interventions compared to minimal intervention on pain intensity (two trials; n= 116; SMD=-0.50; 95% CI -1.91 to 0.91) and disability (two trials, n= 116; SMD=-0.81 95% CI -2.34 to 0.73). Similarly, non-significant results were found for the intermediate-term. According to GRADE, the overall quality of evidence was considered to be of low quality.ConclusionOur findings suggest that physical activity-based interventions using with electronic feedback may be ineffective for reducing pain and disability compared to minimal intervention for patients with chronic musculoskeletal pain. Clinicians should be cautious when implementing this intervention in patients with chronic musculoskeletal pain.



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Psychometric evaluation of the Brachial Assessment Tool Part 1: Reproducibility

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Publication date: Available online 6 November 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Bridget Hill Grad, Gavin Williams, John Olver, Scott Ferris, Andrea Bialocerkowski
ObjectiveTo evaluate reproducibility (reliability and agreement) of the Brachial Assessment Tool (BrAT) a new patient-reported outcome measure for adults with traumatic Brachial Plexus Injury (BPI)DesignProspective repeated measure designSettingOutpatient clinicsParticipantsAdults with confirmed traumatic BPIIntervention43 people (age range 19-82) with BPI completed the 31-item 4-response BrAT twice, 2 weeks apart. Results for the 3 subscales and summed score were compared at time 1 and time 2 to determine reliability including systematic differences using paired t tests; test retest using Intraclass Correlation Coefficient (ICC 1,1) and internal consistency using Cronbach alpha. Agreement parameters included standard error of measurement, minimal detectable change and limits of agreement.Main outcome measureThe BrATResultsTest retest reliability was excellent (ICC [1,1] = 0.90 – 0.97). Internal consistency was high (Cronbach alpha 0.90 - 0.98). Measurement error was relatively low (SEM range 3.1 - 8.8). A change of >4 for subscale 1, >6 for subscale 2, >4 for subscale 3 and >10 for the summed score is indicative of change over and above measurement error. Limits of agreement ranged from ± 4.4 (subscale 3) to 11.61 (summed score).ConclusionThese findings support the use of the BrAT as a reproducible patient reported outcome measure for adults with traumatic BPI with evidence of appropriate reliability and agreement for both individual and group comparisons. Further psychometric testing is required to establish the construct validity and responsiveness of the BrAT.



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Is there a limit on the civilian scope of practice?

The expectation of civilians to respond to emergencies has expanded from care of close friends and family to caring for bystanders and stopping attackers

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Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease

Abstract

The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.



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Association Between Small Intestinal Bacterial Overgrowth by Glucose Breath Test and Coronary Artery Disease

Abstract

Background

A possible role of gut bacteria and their metabolic by-products in the development of coronary artery disease (CAD) is suspected. There is a lack of studies evaluating the association of small intestinal bacterial overgrowth (SIBO) with the development of CAD.

Aim

To evaluate the frequency and risk factors for angiography-confirmed CAD in patients with or without SIBO.

Methods

A total of 1059 patients tested for SIBO using the glucose hydrogen/methane breath test from 2006 to 2014 were evaluated. In total, 160 had coronary artery angiography and were included in the study. SIBO-positive patients were compared to SIBO-negative patients. Demographic, clinical, and laboratory variables and the presence of CAD on coronary angiography were analyzed.

Results

Patients with SIBO had a higher frequency of CAD (78.9 vs. 38.6%, p < 0.001), diabetes mellitus (40.0 vs. 22.9%, p = 0.016), chronic kidney disease (26.7 vs. 12.9%, p = 0.025), use of angiotensin conversion enzyme inhibitor/blocker (45.5 vs. 32.9%, p = 0.008), and statins (75.6 vs. 61.4%, p = 0.004). Patients with SIBO had an increased number of coronary arteries affected compared to SIBO-negative patients (1-vessel disease 67.2 vs. 32.8%, p < 0.001; 2-vessel disease 85.7 vs. 14.3%, p < 0.001; and 3-vessel disease 82.4 vs. 17.6%, p < 0.001, respectively). In the stepwise multivariate logistic regression analysis, SIBO remained an independent risk factor for CAD (odds ratio 7.18, 95% confidence interval 3.09–16.67; p < 0.001).

Conclusion

SIBO was found to be associated with CAD and with the number of coronary arteries involved in this study from a single tertiary center. Further studies are necessary to confirm the association of SIBO with CAD. In the presence of risk factors, patients with SIBO may benefit from assessment for CAD.



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p63 and p73 repress CXCR5 chemokine receptor gene expression in p53-deficient MCF-7 breast cancer cells during genotoxic stress

Publication date: Available online 6 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Nikita A. Mitkin, Alisa M. Muratova, George V. Sharonov, Kirill V. Korneev, Ekaterina N. Sviriaeva, Dmitriy Mazurov, Anton M. Schwartz, Dmitry V. Kuprash
Many types of chemotherapeutic agents induce of DNA-damage that is accompanied by activation of p53 tumor suppressor, a key regulator of tumor development and progression. In our previous study we demonstrated that p53 could repress CXCR5 chemokine receptor gene in MCF-7 breast cancer cells via attenuation of NFkB activity. In this work we aimed to determine individual roles of p53 family members in the regulation of CXCR5 gene expression under genotoxic stress. DNA-alkylating agent methyl methanesulfonate caused a reduction in CXCR5 expression not only in parental MCF-7 cells but also in MCF-7-p53off cells with CRISPR/Cas9-mediated inactivation of the p53 gene. Since p53 knockout was associated with elevated expression of its p63 and p73 homologues, we knocked out p63 using CRISPR/Cas9 system and knocked down p73 using specific siRNA. The CXCR5 promoter activity, CXCR5 expression and CXCL13-directed migration in MCF-7 cells with inactivation of all three p53 family genes were completely insensitive to genotoxic stress, while pairwise p53+p63 or p53+p73 inactivation resulted in partial effects. Using deletion analysis and site-directed mutagenesis, we demonstrated that effects of NFkB on the CXCR5 promoter inversely correlated with p63 and p73 levels. Thus, all three p53 family members mediate the effects of genotoxic stress on the CXCR5 promoter using the same mechanism associated with attenuation of NFkB activity. Understanding of this mechanism could facilitate prognosis of tumor responses to chemotherapy.



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Bilateral loss of cortical SEPs predict severe MRI lesions in neonatal hypoxic ischemic encephalopathy treated with hypothermia

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Publication date: Available online 6 November 2017
Source:Clinical Neurophysiology
Author(s): Agnese Suppiej, Ambra Cappellari, Giacomo Talenti, Elisa Cainelli, Matteo Di Capua, Augusta Janes, Daniela Longo, Rodica Mardari, Cristina Marinaccio, Stefano Pro, Paola Sciortino, Daniele Trevisanuto, Roberta Vittorini, Renzo Manara
ObjectiveThe introduction of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy calls for reevaluation of the prognostic role of somatosensory evoked potentials (SEPs).MethodsAmong 80 consecutive neonates undergoing hypothermia for hypoxic-ischemic encephalopathy, 58 performed SEPs and MRI at 4-14 days of life and were recruited in this multicenter study. SEPs were scored as: 0 (bilaterally/unilaterally recorded N20) or 1 (bilaterally absent N20). The severity of brain injury was scored using MRI.ResultsBilaterally absent N20 was observed in 10/58 neonates (17%); all had moderate/severe MRI abnormalities; 36/48 neonates (75%) with score 0 at SEPs had normal MRI. The positive predictive value of SEPs on MRI outcome was of 1.00, while the negative predictive value 0.72, sensitivity 0.48, specificity 1.00, with an accuracy of 0.78 (p<.001).ConclusionsBilateral absence of cortical SEPs predicts moderate/severe MRI pattern of injury.SignificanceTherapeutic hypothermia does not seem to significantly affect prognostic reliability of SEPs.



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RLS patients show better nocturnal performance in the Simon task due to diminished visuo-motor priming

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Publication date: Available online 6 November 2017
Source:Clinical Neurophysiology
Author(s): Rui Zhang, Wiebke Schrempf, Moritz D. Brandt, Moritz Mückschel, Christian Beste, Ann-Kathrin Stock
ObjectiveThe restless legs syndrome (RLS) is characterized by sensory-motor symptoms which usually occur predominantly at rest in the evening and at night. It is assumed that this circadian rhythm is caused by low dopamine levels in the evening. Yet, it has never been investigated whether RLS patients show diurnal variations in cognitive functions modulated by dopamine and what neurophysiological and functional neuroanatomical processes underlie such modulations.MethodsWe used a Simon task combined with EEG and source localization to investigate whether top-down response selection and/or automatic visuo-motor priming are subject to diurnal changes in RLS patients, as compared to matched healthy controls.ResultsWe found that RLS patients showed better task performance due to reduced visuo-motor priming in the evening, as reflected by smaller early lateralized readiness potential (e-LRP) amplitudes and decreased activation of the superior parietal cortex and premotor cortex. Top-down response selection and early attentional processing were unaffected by RLS.ConclusionsCounterintuitively, RLS patients show enhanced task performance in the evening, i.e. when experiencing dopaminergic deficiency. Yet, this may be explained by deficits in visuo-motor priming that lead to reduced false response tendencies.SignificanceThis study reveals a counterintuitive circadian variation of cognitive functions in RLS patients.



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Diarrheagenic Escherichia coli and Shigella with High Rate of Extended-Spectrum Beta-Lactamase Production: Two Predominant Etiological Agents of Acute Diarrhea in Shiraz, Iran

Microbial Drug Resistance , Vol. 0, No. 0.


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Staff Nurse – Vitalink - New Hanover Regional Medical Center

Staff Nurse – Vitalink Full-Time, Rotating Schedule New Hanover Regional Medical Center Wilmington, NC New Hanover Regional Medical Center's Emergency Transport Services (ETS) is a recognized leader at both state and national levels. Recent awards include: the 2016 American Heart Association Mission Lifeline Gold Award Recognition for EMS, AirLink, and VitaLink, the 2016 EMS National Association ...

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Critical Care Transport Paramedic – Vitalink - New Hanover Regional Medical Center

Critical Care Transport Paramedic – Vitalink Full-Time, Rotating Schedule New Hanover Regional Medical Center Wilmington, NC New Hanover Regional Medical Center's Emergency Transport Services (ETS) is a recognized leader at both state and national levels. Recent awards include: the 2016 American Heart Association Mission Lifeline Gold Award Recognition for EMS, AirLink, and VitaLink, the ...

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'Stop the Bleed' campaign continues outreach amid gun violence

In Chicago, more than 3,000 people have been shot this year, and the victim of a gunshot wound can bleed to death in only five minutes

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Fla. county residents can text 911 now

The feature came just before Senator Bill Nelson introduced legislation that calls for the expansion of federal grants to assist with next-generation 911 systems

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The Ubiquitin Ligase (E3) Psh1p Is Required for Proper Segregation of both Centromeric and Two-Micron Plasmids in Saccharomyces cerevisiae

Protein degradation by the ubiquitin-proteasome system is essential to many processes. We sought to assess its involvement in the turnover of mitochondrial proteins in Saccharomyces cerevisiae. We find that deletion of a specific ubiquitin ligase (E3), Psh1p, increases the abundance of a temperature-sensitive mitochondrial protein, mia40-4pHA, when it is expressed from a centromeric plasmid. Deletion of Psh1p unexpectedly elevates the levels of other proteins expressed from centromeric plasmids. Loss of Psh1p does not increase the rate of turnover of mia40-4pHA, affect total protein synthesis, or increase the protein levels of chromosomal genes. Instead, psh1 appears to increase the incidence of missegregation of centromeric plasmids relative to their normal 1:1 segregation. After generations of growth with selection for the plasmid, ongoing missegregation would lead to elevated plasmid DNA, mRNA, and protein, all of which we observe in psh1 cells. The only known substrate of Psh1p is the centromeric histone H3 variant Cse4p, which is targeted for proteasomal degradation after ubiquitination by Psh1p. However, Cse4p overexpression alone does not phenocopy psh1 in increasing plasmid DNA and protein levels. Instead, elevation of Cse4p leads to an apparent increase in 1:0 plasmid segregation events. Further, 2 μm high-copy yeast plasmids also missegregate in psh1, but not when Cse4p alone is overexpressed. These findings demonstrate that Psh1p is required for the faithful inheritance of both centromeric and 2 μm plasmids. Moreover, the effects that loss of Psh1p has on plasmid segregation cannot be accounted for by increased levels of Cse4p.



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Genomic Prediction Within and Across Biparental Families: Means and Variances of Prediction Accuracy and Usefulness of Deterministic Equations

A major application of genomic prediction (GP) in plant breeding is the identification of superior inbred lines within families derived from biparental crosses. When models for various traits were trained within related or unrelated biparental families (BPFs), experimental studies found substantial variation in prediction accuracy (PA), but little is known about the underlying factors. We used SNP marker genotypes of inbred lines from either elite germplasm or landraces of maize (Zea mays L.) as parents to generate in silico 300 BPFs of doubled-haploid lines. We analyzed PA within each BPF for 50 simulated polygenic traits, using genomic best linear unbiased prediction (GBLUP) models trained with individuals from either full-sib (FSF), half-sib (HSF), or unrelated families (URF) for various sizes ($${N}_{train}$$) of the training set and different heritabilities ($${h}^{2}).$$ In addition, we modified two deterministic equations for forecasting PA to account for inbreeding and genetic variance unexplained by the training set. Averaged across traits, PA was high within FSF (0.41–0.97) with large variation only for $${N}_{train} and $${h}^{2}$$$$ For HSF and URF, PA was on average ~40–60% lower and varied substantially among different combinations of BPFs used for model training and prediction as well as different traits. As exemplified by HSF results, PA of across-family GP can be very low if causal variants not segregating in the training set account for a sizeable proportion of the genetic variance among predicted individuals. Deterministic equations accurately forecast the PA expected over many traits, yet cannot capture trait-specific deviations. We conclude that model training within BPFs generally yields stable PA, whereas a high level of uncertainty is encountered in across-family GP. Our study shows the extent of variation in PA that must be at least reckoned with in practice and offers a starting point for the design of training sets composed of multiple BPFs.



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First Draft Genome Sequence of the Pathogenic Fungus Lomentospora prolificans (Formerly Scedosporium prolificans)

Here we describe the sequencing and assembly of the pathogenic fungus Lomentospora prolificans using a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. The resulting assembly is highly contiguous, containing a total of 37,627,092 bp with over 98% of the sequence in just 26 scaffolds. Annotation identified 8896 protein-coding genes. Pulsed-field gel analysis suggests that this organism contains at least 7 and possibly 11 chromosomes, the two longest of which have sizes corresponding closely to the sizes of the longest scaffolds, at 6.6 and 5.7 Mb.



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Mapping Loci That Control Tuber and Foliar Symptoms Caused by PVY in Autotetraploid Potato (Solanum tuberosum L.)

Potato tuber necrotic ringspot disease (PTNRD) is a tuber deformity associated with infection by the tuber necrotic strain of Potato virus Y (PVYNTN). PTNRD negatively impacts tuber quality and marketability, and poses a serious threat to seed and commercial potato production worldwide. PVYNTN symptoms differ in the cultivars Waneta and Pike: Waneta expresses severe PTNRD and foliar mosaic with vein and leaf necrosis, whereas Pike does not express PTNRD and mosaic is the only foliar symptom. To map loci that influence tuber and foliar symptoms, 236 F1 progeny of a cross between Waneta and Pike were inoculated with PVYNTN isolate NY090029 and genotyped using 12,808 potato SNPs. Foliar symptom type and severity were monitored for 10 wk, while tubers were evaluated for PTNRD expression at harvest and again after 60 d in storage. Pairwise correlation analyses indicate a strong association between PTNRD and vein necrosis ( = 0.4195). QTL analyses revealed major-effect QTL on chromosomes 4 and 5 for mosaic, 4 for PTNRD, and 5 for foliar necrosis symptoms. Locating QTL associated with PVY-related symptoms provides a foundation for breeders to develop markers that can be used to eliminate potato clones with undesirable phenotypes, e.g., those likely to develop PTNRD or to be symptomless carriers of PVY.



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Pervasive, Genome-Wide Transcription in the Organelle Genomes of Diverse Plastid-Bearing Protists

Organelle genomes are among the most sequenced kinds of chromosome. This is largely because they are small and widely used in molecular studies, but also because next-generation sequencing technologies made sequencing easier, faster, and cheaper. However, studies of organelle RNA have not kept pace with those of DNA, despite huge amounts of freely available eukaryotic RNA-sequencing (RNA-seq) data. Little is known about organelle transcription in nonmodel species, and most of the available eukaryotic RNA-seq data have not been mined for organelle transcripts. Here, we use publicly available RNA-seq experiments to investigate organelle transcription in 30 diverse plastid-bearing protists with varying organelle genomic architectures. Mapping RNA-seq data to organelle genomes revealed pervasive, genome-wide transcription, regardless of the taxonomic grouping, gene organization, or noncoding content. For every species analyzed, transcripts covered ≥85% of the mitochondrial and/or plastid genomes (all of which were ≤105 kb), indicating that most of the organelle DNA—coding and noncoding—is transcriptionally active. These results follow earlier studies of model species showing that organellar transcription is coupled and ubiquitous across the genome, requiring significant downstream processing of polycistronic transcripts. Our findings suggest that noncoding organelle DNA can be transcriptionally active, raising questions about the underlying function of these transcripts and underscoring the utility of publicly available RNA-seq data for recovering complete genome sequences. If pervasive transcription is also found in bigger organelle genomes (>105 kb) and across a broader range of eukaryotes, this could indicate that noncoding organelle RNAs are regulating fundamental processes within eukaryotic cells.



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The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid

Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displays a synergistic effect in vitro with the absence of glucose in medium of culture, which underlines the complex interactions that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs, and the role of MIG1, we performed RNA sequencing (RNA-seq) on four biological replicates exposed to combinations of these three parameters. We were able to characterize the (i) glucose response, (ii) response to acetic and butyric acid, (iii) MIG1 regulation of C. albicans, and (iv) genes responsible for WOA resistance. We identified a group of six genes linked to WOA sensitivity in a glucose-MIG1-dependent manner and inactivated one of these genes, the putative glucose transporter HGT16, in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOA resistance in the absence of glucose. This result points toward a mechanism of WOA sensitivity in C. albicans involving membrane transporters, which could be exploited to control yeast colonization in human body niches.



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Machine Learning Analysis Identifies Drosophila Grunge/Atrophin as an Important Learning and Memory Gene Required for Memory Retention and Social Learning

High-throughput experiments are becoming increasingly common, and scientists must balance hypothesis-driven experiments with genome-wide data acquisition. We sought to predict novel genes involved in Drosophila learning and long-term memory from existing public high-throughput data. We performed an analysis using PILGRM, which analyzes public gene expression compendia using machine learning. We evaluated the top prediction alongside genes involved in learning and memory in IMP, an interface for functional relationship networks. We identified Grunge/Atrophin (Gug/Atro), a transcriptional repressor, histone deacetylase, as our top candidate. We find, through multiple, distinct assays, that Gug has an active role as a modulator of memory retention in the fly and its function is required in the adult mushroom body. Depletion of Gug specifically in neurons of the adult mushroom body, after cell division and neuronal development is complete, suggests that Gug function is important for memory retention through regulation of neuronal activity, and not by altering neurodevelopment. Our study provides a previously uncharacterized role for Gug as a possible regulator of neuronal plasticity at the interface of memory retention and memory extinction.



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Comparison of Single Genome and Allele Frequency Data Reveals Discordant Demographic Histories

Inference of demographic history from genetic data is a primary goal of population genetics of model and nonmodel organisms. Whole genome-based approaches such as the pairwise/multiple sequentially Markovian coalescent methods use genomic data from one to four individuals to infer the demographic history of an entire population, while site frequency spectrum (SFS)-based methods use the distribution of allele frequencies in a sample to reconstruct the same historical events. Although both methods are extensively used in empirical studies and perform well on data simulated under simple models, there have been only limited comparisons of them in more complex and realistic settings. Here we use published demographic models based on data from three human populations (Yoruba, descendants of northwest-Europeans, and Han Chinese) as an empirical test case to study the behavior of both inference procedures. We find that several of the demographic histories inferred by the whole genome-based methods do not predict the genome-wide distribution of heterozygosity, nor do they predict the empirical SFS. However, using simulated data, we also find that the whole genome methods can reconstruct the complex demographic models inferred by SFS-based methods, suggesting that the discordant patterns of genetic variation are not attributable to a lack of statistical power, but may reflect unmodeled complexities in the underlying demography. More generally, our findings indicate that demographic inference from a small number of genomes, routine in genomic studies of nonmodel organisms, should be interpreted cautiously, as these models cannot recapitulate other summaries of the data.



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Localization of Cdc7 Protein Kinase During DNA Replication in Saccharomyces cerevisiae

DDK, a conserved serine-threonine protein kinase composed of a regulatory subunit, Dbf4, and a catalytic subunit, Cdc7, is essential for DNA replication initiation during S phase of the cell cycle through MCM2-7 helicase phosphorylation. The biological significance of DDK is well characterized, but the full mechanism of how DDK associates with substrates remains unclear. Cdc7 is bound to chromatin in the Saccharomyces cerevisiae genome throughout the cell cycle, but there is little empirical evidence as to specific Cdc7 binding locations. Using biochemical and genetic techniques, this study investigated the specific localization of Cdc7 on chromatin. The Calling Cards method, using Ty5 retrotransposons as a marker for DNA–protein binding, suggests Cdc7 kinase is preferentially bound to genomic DNA known to replicate early in S phase, including centromeres and origins of replication. We also discovered Cdc7 binding throughout the genome, which may be necessary to initiate other cellular processes, including meiotic recombination and translesion synthesis. A kinase dead Cdc7 point mutation increases the Ty5 retrotransposon integration efficiency and a 55-amino acid C-terminal truncation of Cdc7, unable to bind Dbf4, reduces Cdc7 binding suggesting a requirement for Dbf4 to stabilize Cdc7 on chromatin during S phase. Chromatin immunoprecipitation demonstrates that Cdc7 binding near specific origins changes during S phase. Our results suggest a model where Cdc7 is loosely bound to chromatin during G1. At the G1/S transition, Cdc7 binding to chromatin is increased and stabilized, preferentially at sites that may become origins, in order to carry out a variety of cellular processes.



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Genome-Wide Analysis of DNA Methylation During Ovule Development of Female-Sterile Rice fsv1

The regulation of female fertility is an important field of rice sexual reproduction research. DNA methylation is an essential epigenetic modification that dynamically regulates gene expression during development processes. However, few reports have described the methylation profiles of female-sterile rice during ovule development. In this study, ovules were continuously acquired from the beginning of megaspore mother cell meiosis until the mature female gametophyte formation period, and global DNA methylation patterns were compared in the ovules of a high-frequency female-sterile line (fsv1) and a wild-type rice line (Gui99) using whole-genome bisulfite sequencing (WGBS). Profiling of the global DNA methylation revealed hypo-methylation, and 3471 significantly differentially methylated regions (DMRs) were observed in fsv1 ovules compared with Gui99. Based on functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of differentially methylated genes (DMGs), we observed more DMGs enriched in cellular component, reproduction regulation, metabolic pathway, and other pathways. In particular, many ovule development genes and plant hormone-related genes showed significantly different methylation patterns in the two rice lines, and these differences may provide important clues for revealing the mechanism of female gametophyte abortion.



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Architecture and Distribution of Introns in Core Genes of Four Fusarium Species

Removal of introns from transcribed RNA represents a crucial step during the production of mRNA in eukaryotes. Available whole-genome sequences and expressed sequence tags (ESTs) have increased our knowledge of this process and revealed various commonalities among eukaryotes. However, certain aspects of intron structure and diversity are taxon-specific, which can complicate the accuracy of in silico gene prediction methods. Using core genes, we evaluated the distribution and architecture of Fusarium circinatum spliceosomal introns, and linked these characteristics to the accuracy of the predicted gene models of the genome of this fungus. We also evaluated intron distribution and architecture in F. verticillioides, F. oxysporum, and F. graminearum, and made comparisons with F. circinatum. Results indicated that F. circinatum and the three other Fusarium species have canonical 5' and 3' splice sites, but with subtle differences that are apparently not shared with those of other fungal genera. The polypyrimidine tract of Fusarium introns was also found to be highly divergent among species and genes. Furthermore, the conserved adenosine nucleoside required during the first step of splicing is contained within unique branch site motifs in certain Fusarium introns. Data generated here show that introns of F. circinatum, as well as F. verticillioides, F. oxysporum, and F. graminearum, are characterized by a number of unique features such as the CTHAH and ACCAT motifs of the branch site. Incorporation of such information into genome annotation software will undoubtedly improve the accuracy of gene prediction methods used for Fusarium species and related fungi.



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A New Diagnostic Resource for Ceratitis capitata Strain Identification Based on QTL Mapping

The Mediterranean fruit fly Ceratitis capitata (Wiedemann) is a destructive agricultural pest and the subject of exclusion efforts in many countries. Suppression and eradication of invasive populations to prevent its establishment is facilitated by the release of sterile males using the sterile insect technique (SIT). In SIT release areas, it is critical to accurately discriminate between released sterile males and wild individuals to detect extremely rare invasive individuals in areas inundated with millions of sterile male flies. Current methods for discrimination exist but are not always definitive, and a more reliable method is necessary. To address this, we developed a genotyping assay that can be used to discriminate between sterile males from the SIT strain and wild individuals. This was achieved by identifying single nucleotide polymorphisms (SNPs) linked to the maintained traits that facilitate male-only releases, white pupae (wp) and temperature-sensitive lethal (tsl), via QTL mapping. This resulted in the identification of one SNP that was in near-perfect linkage disequilibrium between genotype at this locus and the pupal color phenotype. Medfly from many SIT colonies and wild individuals from across its geographic range were genotyped for this locus, and results show its consistency in identifying SIT flies. In addition, linkage and QTL mapping of wp and tsl have larger impacts as they can serve as foundational tools to identify the genetic basis of traits that facilitate the separation of males from female flies, which can be used to develop SIT programs in related species.



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Genetic Screening for EMS-Induced Maize Embryo-Specific Mutants Altered in Embryo Morphogenesis

We have previously identified embryo-specific (emb) mutations that resulted in maize kernels containing abnormal embryos with normal-appearing endosperm among the progeny of active Robertson's Mutator stocks. Our rationale for the mutant screen described here is that it should be possible to produce ethyl methane sulfonate (EMS)-induced emb mutations at a frequency higher than that obtained by transposon mutagenesis and with greater ease. This proved to be the case when we screened for mutations that are embryo-specific among progeny of materials generated with EMS-treated pollen. The EMS-induced emb mutation frequency reported here is nearly three times the 4.5% we obtained with the transposable element stocks. The 45 mutants reported here were all tested for germination capacity and nearly all were lethal. The embryo phenotypes of 34 mutations were examined by dissection of the mature embryos. All were found to be retarded in development and morphologically abnormal. Half of the mutants in this group were blocked in the proembryo and transition stages. They likely include mutations in nuclear genes coding for plastid proteins. The other 17 are mainly blocked in the coleoptilar stage, or in later stages with a low frequency. This group likely includes mutations in genes regulating the completion of shoot apical meristem (SAM) development and accompanying morphogenetic events. Most of the complementation tests using 19 of the mutations in 35 unique combinations complimented each other, except for two pairs of mutations with similar phenotypes. Our results provide additional evidence for the presence of many emb loci in the maize genome.



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Linkage Analysis and Association Mapping QTL Detection Models for Hybrids Between Multiparental Populations from Two Heterotic Groups: Application to Biomass Production in Maize (Zea mays L.)

Identification of quantitative trait loci (QTL) involved in the variation of hybrid value is of key importance for cross-pollinated species such as maize (Zea mays L.). In a companion paper, we illustrated a new QTL mapping population design involving a factorial mating between two multiparental segregating populations. Six biparental line populations were developed from four founder lines in the Dent and Flint heterotic groups. They were crossed to produce 951 hybrids and evaluated for silage performances. Previously, a linkage analysis (LA) model that assumes each founder line carries a different allele was used to detect QTL involved in General and Specific Combining Abilities (GCA and SCA, respectively) of hybrid value. This previously introduced model requires the estimation of numerous effects per locus, potentially affecting QTL detection power. Using the same design, we compared this "Founder alleles" model to two more parsimonious models, which assume that (i) identity in state at SNP alleles from the same heterotic group implies identity by descent (IBD) at linked QTL ("SNP within-group" model) or (ii) identity in state implies IBD, regardless of population origin of the alleles ("Hybrid genotype" model). This last model assumes biallelic QTL with equal effects in each group. It detected more QTL on average than the two other models but explained lower percentages of variance. The "SNP within-group" model appeared to be a good compromise between the two other models. These results confirm the divergence between the Dent and Flint groups. They also illustrate the need to adapt the QTL detection model to the complexity of the allelic variation, which depends on the trait, the QTL, and the divergence between the heterotic groups.



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Mechanisms of Transmission Ratio Distortion at Hybrid Sterility Loci Within and Between Mimulus Species

Hybrid incompatibilities are a common correlate of genomic divergence and a potentially important contributor to reproductive isolation. However, we do not yet have a detailed understanding of how hybrid incompatibility loci function and evolve within their native species, or why they are dysfunctional in hybrids. Here, we explore these issues for a well-studied, two-locus hybrid incompatibility between hybrid male sterility 1 (hms1) and hybrid male sterility 2 (hms2) in the closely related yellow monkeyflower species Mimulus guttatus and M. nasutus. By performing reciprocal backcrosses with introgression lines (ILs), we find evidence for gametic expression of the hms1-hms2 incompatibility. Surprisingly, however, hybrid transmission ratios at hms1 do not reflect this incompatibility, suggesting that additional mechanisms counteract the effects of gametic sterility. Indeed, our backcross experiment shows hybrid transmission bias toward M. guttatus through both pollen and ovules, an effect that is particularly strong when hms2 is homozygous for M. nasutus alleles. In contrast, we find little evidence for hms1 transmission bias in crosses within M. guttatus, providing no indication of selfish evolution at this locus. Although we do not yet have sufficient genetic resolution to determine if hybrid sterility and transmission ratio distortion (TRD) map to the same loci, our preliminary fine-mapping uncovers a genetically independent hybrid lethality system involving at least two loci linked to hms1. This fine-scale dissection of TRD at hms1 and hms2 provides insight into genomic differentiation between closely related Mimulus species and reveals multiple mechanisms of hybrid dysfunction.



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The Effect of Common Inversion Polymorphisms In(2L)t and In(3R)Mo on Patterns of Transcriptional Variation in Drosophila melanogaster

Chromosomal inversions are a ubiquitous feature of genetic variation. Theoretical models describe several mechanisms by which inversions can drive adaptation and be maintained as polymorphisms. While inversions have been shown previously to be under selection, or contain genetic variation under selection, the specific phenotypic consequences of inversions leading to their maintenance remain unclear. Here we use genomic sequence and expression data from the Drosophila Genetic Reference Panel (DGRP) to explore the effects of two cosmopolitan inversions, In(2L)t and In(3R)Mo, on patterns of transcriptional variation. We demonstrate that each inversion has a significant effect on transcript abundance for hundreds of genes across the genome. Inversion-affected loci (IAL) appear both within inversions as well as on unlinked chromosomes. Importantly, IAL do not appear to be influenced by the previously reported genome-wide expression correlation structure. We found that five genes involved with sterol uptake, four of which are Niemann-Pick Type 2 orthologs, are upregulated in flies with In(3R)Mo but do not have SNPs in linkage disequilibrium (LD) with the inversion. We speculate that this upregulation is driven by genetic variation in mod(mdg4) that is in LD with In(3R)Mo. We find that there is little evidence for a regional or position effect of inversions on gene expression at the chromosomal level, but do find evidence for the distal breakpoint of In(3R)Mo interrupting one gene and possibly disassociating the two flanking genes from regulatory elements.



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Serotonin Drives Predatory Feeding Behavior via Synchronous Feeding Rhythms in the Nematode Pristionchus pacificus

Feeding behaviors in a wide range of animals are regulated by the neurotransmitter serotonin, although the exact neural circuits and associated mechanism are often unknown. The nematode Pristionchus pacificus can kill other nematodes by opening prey cuticles with movable teeth. Previous studies showed that exogenous serotonin treatment induces a predatory-like tooth movement and slower pharyngeal pumping in the absence of prey; however, physiological functions of serotonin during predation and other behaviors in P. pacificus remained completely unknown. Here, we investigate the roles of serotonin by generating mutations in Ppa-tph-1 and Ppa-bas-1, two key serotonin biosynthesis enzymes, and by genetic ablation of pharynx-associated serotonergic neurons. Mutations in Ppa-tph-1 reduced the pharyngeal pumping rate during bacterial feeding compared with wild-type. Moreover, the loss of serotonin or a subset of serotonergic neurons decreased the success of predation, but did not abolish the predatory feeding behavior completely. Detailed analysis using a high-speed camera revealed that the elimination of serotonin or the serotonergic neurons disrupted the timing and coordination of predatory tooth movement and pharyngeal pumping. This loss of synchrony significantly reduced the efficiency of successful predation events. These results suggest that serotonin has a conserved role in bacterial feeding and in addition drives the feeding rhythm of predatory behavior in Pristionchus.



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Genome Dynamics of Hybrid Saccharomyces cerevisiae During Vegetative and Meiotic Divisions

Mutation and recombination are the major sources of genetic diversity in all organisms. In the baker's yeast, all mutation rate estimates are in homozygous background. We determined the extent of genetic change through mutation and loss of heterozygosity (LOH) in a heterozygous Saccharomyces cerevisiae genome during successive vegetative and meiotic divisions. We measured genome-wide LOH and base mutation rates during vegetative and meiotic divisions in a hybrid (S288c/YJM789) S. cerevisiae strain. The S288c/YJM789 hybrid showed nearly complete reduction in heterozygosity within 31 generations of meioses and improved spore viability. LOH in the meiotic lines was driven primarily by the mating of spores within the tetrad. The S288c/YJM789 hybrid lines propagated vegetatively for the same duration as the meiotic lines, showed variable LOH (from 2 to 3% and up to 35%). Two of the vegetative lines with extensive LOH showed frequent and large internal LOH tracts that suggest a high frequency of recombination repair. These results suggest significant LOH can occur in the S288c/YJM789 hybrid during vegetative propagation presumably due to return to growth events. The average base substitution rates for the vegetative lines (1.82 x 10–10 per base per division) and the meiotic lines (1.22 x 10–10 per base per division) are the first genome-wide mutation rate estimates for a hybrid yeast. This study therefore provides a novel context for the analysis of mutation rates (especially in the context of detecting LOH during vegetative divisions), compared to previous mutation accumulation studies in yeast that used homozygous backgrounds.



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Whole Genome Sequence Analysis of Mutations Accumulated in rad27{Delta} Yeast Strains with Defects in the Processing of Okazaki Fragments Indicates Template-Switching Events

Okazaki fragments that are formed during lagging strand DNA synthesis include an initiating primer consisting of both RNA and DNA. The RNA fragment must be removed before the fragments are joined. In Saccharomyces cerevisiae, a key player in this process is the structure-specific flap endonuclease, Rad27p (human homolog FEN1). To obtain a genomic view of the mutational consequence of loss of RAD27, a S. cerevisiae rad27 strain was subcultured for 25 generations and sequenced using Illumina paired-end sequencing. Out of the 455 changes observed in 10 colonies isolated the two most common types of events were insertions or deletions (INDELs) in simple sequence repeats (SSRs) and INDELs mediated by short direct repeats. Surprisingly, we also detected a previously neglected class of 21 template-switching events. These events were presumably generated by quasi-palindrome to palindrome correction, as well as palindrome elongation. The formation of these events is best explained by folding back of the stalled nascent strand and resumption of DNA synthesis using the same nascent strand as a template. Evidence of quasi-palindrome to palindrome correction that could be generated by template switching appears also in yeast genome evolution. Out of the 455 events, 55 events appeared in multiple isolates; further analysis indicates that these loci are mutational hotspots. Since Rad27 acts on the lagging strand when the leading strand should not contain any gaps, we propose a mechanism favoring intramolecular strand switching over an intermolecular mechanism. We note that our results open new ways of understanding template switching that occurs during genome instability and evolution.



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Differential Expression of miRNAs in the Respiratory Tree of the Sea Cucumber Apostichopus japonicus Under Hypoxia Stress

The sea cucumber, an important economic species, has encountered high mortality since 2013 in northern China because of seasonal environmental stress such as hypoxia, high temperature, and low salinity. MicroRNAs (miRNAs) are important in regulating gene expression in marine organisms in response to environmental change. In this study, high-throughput sequencing was used to investigate alterations in miRNA expression in the sea cucumber under different levels of dissolved oxygen (DO). Nine small RNA libraries were constructed from the sea cucumber respiratory trees. A total of 26 differentially expressed miRNAs, including 12 upregulated and 14 downregulated miRNAs, were observed in severe hypoxia (DO 2 mg/L) compared with mild hypoxia (DO 4 mg/L) and normoxic conditions (DO 8 mg/L). Twelve differentially expressed miRNAs were clustered in severe hypoxia. In addition, real-time PCR revealed that 14 randomly selected differentially expressed miRNAs showed significantly increased expressions in severe hypoxia and the expressions of nine miRNAs, including key miRNAs such as Aja-miR-1, Aja-miR-2008, and Aja-miR-184, were consistent with the sequencing results. Moreover, gene ontology and pathway analyses of putative target genes suggest that these miRNAs are important in redox, transport, transcription, and hydrolysis under hypoxia stress. Notably, novel-miR-1, novel-miR-2, and novel-miR-3 were specifically clustered and upregulated in severe hypoxia, which may provide new insights into novel "hypoxamiR" identification. These results will provide a basis for future studies of miRNA regulation and molecular adaptive mechanisms in sea cucumbers under hypoxia stress.



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Effects of {beta}-hydroxy-{beta}-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults

Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during BR and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60–76 yr) completed 10 days BR followed by 8-wk RT rehabilitation. Subjects were randomized to either HMB (3 g/day HMB; n = 11) or control (CON; n = 8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission (MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy [poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR (P < 0.05, main effect for time), and muscle triglyceride content tended to increase following BR in the HMB group (P = 0.055). RT rehabilitation increased OXPHOS complex II protein (P < 0.05), and total OXPHOS content tended (P = 0.0504) to be higher in HMB group. In addition, higher levels of DRP1 and MFN2 were maintained in the HMB group after RT (P < 0.05). BNIP3 and poly-ub proteins were significantly reduced following rehabilitation in both groups (P < 0.05). Collectively, these data suggest that HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation.

NEW & NOTEWORTHY Mitochondrial content and dynamics remained unchanged over 10 days of BR in older adults. HMB stimulated intramuscular lipid storage as triacylglycerol following 10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and dynamics during the 8-wk resistance exercise rehabilitation program.



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Lower body negative pressure reduces optic nerve sheath diameter during head-down tilt

The microgravity ocular syndrome (MOS) results in significant structural and functional ophthalmic changes during 6-mo spaceflight missions consistent with an increase in cerebrospinal fluid (CSF) pressure compared with the preflight upright position. A ground-based study was performed to assess two of the major hypothesized contributors to MOS, headward fluid shifting and increased ambient CO2, on intracranial and periorbital CSF. In addition, lower body negative pressure (LBNP) was assessed as a countermeasure to headward fluid shifting. Nine healthy male subjects participated in a crossover design study with five head-down tilt (HDT) conditions: –6, –12, and –18° HDT, –12° HDT with –20 mmHg LBNP, and –12° HDT with a 1% CO2 environment, each for 5 h total. A three-dimensional volumetric scan of the cranium and transverse slices of the orbita were collected with MRI, and intracranial CSF volume and optic nerve sheath diameter (ONSD) were measured after 4.5 h HDT. ONSD increased during –6° (P < 0.001), –12° (P < 0.001), and –18° HDT (P < 0.001) and intracranial CSF increased during –12° HDT (P = 0.01) compared with supine baseline. Notably, LBNP was able to reduce the increases in ONSD and intracranial CSF during HDT. The addition of 1% CO2 during HDT, however, had no further effect on ONSD, but rather ONSD increased from baseline in a similar magnitude to –12° HDT with ambient air (P = 0.001). These findings demonstrate the ability of LBNP, a technique that targets fluid distribution in the lower limbs, to directly influence CSF and may be a promising countermeasure to help reduce increases in CSF.

NEW & NOTEWORTHY This is the first study to demonstrate the ability of lower body negative pressure to directly influence cerebrospinal fluid surrounding the optic nerve, indicating potential use as a countermeasure for increased cerebrospinal fluid on Earth or in space.



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