Τετάρτη 28 Μαρτίου 2018

High-intensity intermittent “5–10–15” running reduces body fat, and increases lean body mass, bone mineral density, and performance in untrained subjects

Abstract

The present study examined the effect of intense intermittent running with 5 s sprints on body composition, fitness level, and performance in untrained subjects aged 36–53 years. For 7 weeks, the subjects carried out 3 days a week 5–10–15 training consisting of 3–9 blocks of 4 repetitions of 15, 10, and 5 s low-, moderate-, and high-speed running, respectively. Body fat mass was 4.3% lower (P < 0.01), and lean body mass and bone mineral density was 1.1 and 0.9% higher (P < 0.01), respectively, after compared to before the intervention period (INT). The plasma bone turnover markers osteocalcin increased (P < 0.01) by 147%, and procollagen-type I N propeptide and carboxy-terminal collagen crosslinks increased (P < 0.05) by 84 and 76%, respectively. Furthermore, the training improved performance in 1500 m (P < 0.001), 3 km (P < 0.001), Yo–Yo intermittent endurance test (P < 0.01), and incremental treadmill running (P < 0.001) by 8.1, 9.9, 17.2, and 23.9%, respectively. Furthermore, blood lactate after running at 85% of maximal aerobic speed was lower (P < 0.01) after compared to before the INT. Thus, 7 weeks of 5–10–15 training resulted in significant health beneficial changes and better performance in untrained subject.



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Incidence of Multidrug-Resistant Organism Among Children Admitted to Pediatric Intensive Care Unit in a Developing Country

Microbial Drug Resistance, Ahead of Print.


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Vps74 Connects the Golgi Apparatus and Telomeres in Saccharomyces cerevisiae

In mammalian cell culture, the Golgi apparatus fragment upon DNA damage. GOLPH3, a Golgi component, is a phosphorylation target of DNA-PK after DNA damage and contributes to Golgi fragmentation. The function of the yeast (Saccharomyces cerevisiae) ortholog of GOLPH3, Vps74, in the DNA damage response has been little studied, although genome-wide screens suggested a role at telomeres. In this study we investigated the role of Vps74 at telomeres and in the DNA damage response. We show that Vps74 decreases the fitness of telomere defective cdc13-1 cells and contributes to the fitness of yku70 cells. Importantly, loss of Vps74 in yku70 cells exacerbates the temperature dependent growth defects of these cells in a Chk1 and Mec1-dependent manner. Furthermore, Exo1 reduces the fitness of vps74 yku70 cells suggesting that ssDNA contributes to the fitness defects of vps74 yku70 cells. Systematic genetic interaction analysis of vps74, yku70 and yku70 vps74 cells suggests that vps74 causes a milder but similar defect to that seen in yku70 cells. vps74 cells have slightly shorter telomeres and loss of VPS74 in yku70 or mre11 cells further shortens the telomeres of these cells. Interestingly, loss of Vps74 leads to increased levels of Stn1, a partner of Cdc13 in the CST telomere capping complex. Overexpression of Stn1 was previously shown to cause telomere shortening, suppression of cdc13-1 and enhancement of yku70 growth defects, suggesting that increased levels of Stn1 may be the route by which Vps74 affects telomere function. These results establish Vps74 as a novel regulator of telomere biology.



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A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2

The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1 end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1 end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ~14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen's design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10–4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations.



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Third time's a charm: Oral midazolam vs intranasal dexmedetomidine for preoperative anxiolysis in an autistic pediatric patient

Pediatric Anesthesia, Volume 28, Issue 4, Page 370-371, April 2018.


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The impact of Narcotrend™ EEG‐guided propofol administration on the speed of recovery from pediatric procedural sedation—A randomized controlled trial

Pediatric Anesthesia, EarlyView.


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Issue Information

Pediatric Anesthesia, Volume 28, Issue 4, Page i-iii,311, April 2018.


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Fat embolism syndrome in a child triggered by surgical tourniquet release: A case report

Pediatric Anesthesia, Volume 28, Issue 4, Page 371-372, April 2018.


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In this issue: April 2018

Pediatric Anesthesia, Volume 28, Issue 4, Page 313-313, April 2018.


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Parent and anesthetist attitudes toward rectal analgesic suppositories in pediatric daycase surgery: A multi‐center cross‐sectional survey

Pediatric Anesthesia, Volume 28, Issue 4, Page 372-373, April 2018.


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Pediatric perioperative outcomes group: Defining core outcomes for pediatric anesthesia and perioperative medicine

Pediatric Anesthesia, Volume 28, Issue 4, Page 314-315, April 2018.


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Hepatocellular carcinoma after direct-acting antiviral agents: can liver stiffness kinetics help identify patients at lower risk?



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Hepatocellular carcinoma after direct-acting antiviral agents: can liver stiffness kinetics help identify patients at lower risk?



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Detecting violation in abstract pitch patterns with mismatch negativity

Psychophysiology, EarlyView.


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Guidance of spatial attention during associative learning: Contributions of predictability and intention to learn

Psychophysiology, EarlyView.


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DNA Methylation Possible Adjunct to Screening for Neurodevelopmental Syndromes: DNA methylation signatures were identified for several neurodevelopmental Mendelian disorders, and hold promise as a supplement to standard procedures for screening and detection of these diseases

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 755-756, April 2018.


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Isosorbide dinitrate in nephronophthisis treatment

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1023-1026, April 2018.


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The psychosocial impact of 22q11 deletion syndrome on patients and families: A systematic review

American Journal of Medical Genetics Part A, EarlyView.


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Associations between laterality of orofacial clefts and medical and academic outcomes

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1037-1037, April 2018.


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Biallelic loss‐of‐function WNT5A mutations in an infant with severe and atypical manifestations of Robinow syndrome

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1030-1036, April 2018.


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Autosomal dominant Robinow syndrome associated with a novel DVL3 splice mutation

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 992-996, April 2018.


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A homozygous TTN gene variant associated with lethal congenital contracture syndrome

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1001-1005, April 2018.


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Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys)

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 997-1000, April 2018.


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A recurrent mutation causing Melnick‐Needles syndrome in females confers a severe, lethal phenotype in males

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 980-984, April 2018.


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Low serum fatty acid levels in pregnancies with fetal gastroschisis: A prospective study

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 915-924, April 2018.


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Patients Express Satisfaction, Understanding of Whole‐Genome Sequencing: In primary care and cardiology, patients were generally satisfied with their physicians' communication of WGS results, but expectations about its clinical benefits were not met

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 754-755, April 2018.


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Challenges associated with parenting youth with neurofibromatosis: A qualitative investigation

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 959-968, April 2018.


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Table of Contents, Volume 176A, Number 4, April 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 749-752, April 2018.


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In this issue

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 757-757, April 2018.


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Cover Image, Volume 176A, Number 4, April 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 4, April 2018.


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Publication schedule for 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 753-753, April 2018.


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First‐year growth in children with Noonan syndrome: Associated with feeding problems?

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 951-958, April 2018.


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Newly described recessive MYH11 disorder with clinical overlap of Multisystemic smooth muscle dysfunction and Megacystis microcolon hypoperistalsis syndromes

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1011-1014, April 2018.


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Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 936-944, April 2018.


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Three novel GJB2 (connexin 26) variants associated with autosomal dominant syndromic and nonsyndromic hearing loss

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 945-950, April 2018.


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Epigastric hernia contiguous with the laparoscopic port site after endoscopic robotic total prostatectomy

Asian Journal of Endoscopic Surgery, EarlyView.


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Safety and feasibility of laparoscopic gastrectomy accompanied by D1+ lymph node dissection for early gastric cancer in elderly patients

Asian Journal of Endoscopic Surgery, EarlyView.


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Is postponed laparoscopic cholecystectomy justified for acute cholecystitis appearing early after onset?

Asian Journal of Endoscopic Surgery, EarlyView.


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Preoperative weight loss program involving a 20‐day very low‐calorie diet for obesity before laparoscopic gastrectomy for gastric cancer

Asian Journal of Endoscopic Surgery, EarlyView.


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Patients’ preoperative background causes gastric stasis after laparoscopy‐assisted pylorus‐preserving gastrectomy

Asian Journal of Endoscopic Surgery, EarlyView.


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Is fascial defect closure with intraperitoneal onlay mesh superior to standard intraperitoneal onlay mesh for laparoscopic repair of large incisional hernia?

Asian Journal of Endoscopic Surgery, EarlyView.


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Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future

Abstract

Purpose of Review

Universal stool banks (USBs) have emerged as a potential model for scaling access to fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI). In this review, we outline the historical barriers constraining access to FMT, the evidence on methods and outcomes of USBs, and potential future directions for expanding access.

Recent Findings

Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities.

Summary

USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need



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The IBD and PSC Phenotypes of PSC-IBD

Abstract

Purpose of review

To review the characteristics of IBD and PSC that occur in association, as well as their reciprocal influences on disease evolution, in adult and pediatric populations.

Recent findings

IBD co-existing with PSC is genetically and clinically distinct from IBD alone. It is frequently characterized by pancolitis, rectal sparing, and possibly backwash ileitis, as well as a threefold increased risk of colorectal dysplasia. Adults and children with colitis and PSC appear to be at increased risk of active endoscopic and histologic disease in the absence of symptoms compared to individuals without PSC. PSC occurring with Crohn's disease has been observed to be less severe than PSC co-existing with ulcerative colitis, independent of its association with small duct disease. Recent studies suggest that colectomy is associated with a decreased risk of recurrent PSC after liver transplantation, challenging the traditional teaching that PSC and IBD evolve independently.

Summary

While much about the gut-liver axis in PSC-IBD remains poorly understood, the IBD associated with PSC has a unique phenotype, of which subclinical inflammation is an important component. Additional research is needed to characterize further the potentially protective role of colectomy against recurrent PSC post-liver transplantation and to investigate the influence of IBD control and/or colectomy on PSC progression.



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CMV Infection in Pediatric IBD

Abstract

Purpose of Review

Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD.

Recent Findings

Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up.

Summary

In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.



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New policies needed for civilian air medevac transportation

Lawmakers should evaluate billing issues and insurance company procedure to guide healthcare policy and protect patients

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AT&T announces nationwide launch of FirstNet

"The launch of the network core comes a year into the FirstNet public-private partnership" FirstNet Senior Vice President Chris Sambar said

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Gait Variability and Energy Cost of Over-Ground Walking in Persons with Multiple Sclerosis: A Cross-sectional study

Objective This study examined the associations between gait variability based on common spatiotemporal parameters and energetic cost of walking (Cw) in persons with multiple sclerosis (pwMS). Design Eighty-six pwMS underwent the 6-minute walk (6MW) while wearing a portable metabolic unit. The Cw was generated by dividing the net steady-state VO2 (mL/kg/min) by walking speed during the 6MW. Participants further completed two trials of walking on the GAITRite mat at a self-selected pace for measuring spatiotemporal parameters. Variability of step length, step time, stride length, swing time, stance time, stride velocity, and single and double support time was indexed by the coefficient of variation. Results Variability in the spatiotemporal variables and Expanded Disability Status Scale (EDSS) scores were significantly correlated with Cw (i.e., (|rho|=.25 - .36). Multivariate analysis revealed that disability (EDSS; β = .186), stance time variability (β = 1.446) and step length variability (β = -1.216) explained significant variance (R2 = .38; p<.001 in cw. conclusion we provide evidence of the positive association between gait variability and cw during over-ground walking pwms. findings highlight need for interventions aiming to reduce thereby reducing energetic demands this population. corresponding author emerson sebasti department kinesiology physical education anderson hall dekalb il usa. tel.: fax: email: esebastiao funding: no funding was received work disclosure: authors declare conflict interest related work. copyright wolters kluwer health inc. all rights reserved.>

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Discharge Patterns for Ischemic and Hemorrhagic Stroke Patients Going from Acute Care Hospitals to Inpatient and Skilled Nursing Rehabilitation

Objective To explore variation in acute care use of inpatient (IRF) and skilled nursing (SNF) rehabilitation following ischemic and hemorrhagic stroke. Design A secondary analysis of Medicare claims data linked to IRF and SNF assessment files (2013-2014). Results The sample included 122,084 stroke patients discharged to IRF or SNF from 3,677 acute hospitals. Of the acute hospitals, 3,649 discharged patients with an ischemic stroke (range 1-402 patients/hospital, median=15) compared to 1,832 acute hospitals that discharged patients with hemorrhagic events (range 1-73 patients/hospital, median=4). The intraclass correlation (ICC) examined variation in discharge settings attributed to acute hospitals (Ischemic ICC=0.318, Hemorrhagic ICC=0.176). Patients >85 years and those with greater numbers of comorbid conditions were more likely to discharge to SNF. Comparison of self-care and mobility across stroke type suggests that patients with ischemic stroke have higher functional abilities at admission. Conclusion This study suggests demographic and clinical differences among stroke patients admitted for post-acute rehabilitation at IRF and SNF settings. Furthermore, examination of variation in ischemic and hemorrhagic stroke discharges suggests acute facility level differences and indicates a need for careful consideration of patient and facility factors when comparing the effectiveness of IRF and SNF rehabilitation. Author Disclosures: Conflict of Interest: None declared. Funding: This study was supported with funding from the Agency for Healthcare Quality and Research (R01-HS024711, R24-HS022134), National Institutes of Health (R01-AG033134; R24-HD065702; R01-HD069443; and K01- HD086290), National Institute on Aging OAIC (5P30-AG024832), Institute for Translational Sciences (UL1TR000071). Financial benefits to the authors: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. Correspondence: Timothy A. Reistetter, University of Texas Medical Branch, Department of Occupational Therapy, 301 University Blvd, Galveston, Texas 77555-1142. Email: tareiste@utmb.edu. Phone (409)772-944. Fax (409)747-1615 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The efficiency of a Multi-Component Training for Prospective Memory Among Healthy Older Adults: A Single-Blind, Randomized Controlled Within-Participants Crossover Trial

OBJECTIVE The main objective of the present trial was to evaluate the efficiency of a preventative multi-component prospective memory (PM) training among healthy older adults. DESIGN This study was a two-arm within-participants trial with 4 and 12-week follow-ups. Allocation ratio was 1:1 and pre- and post-training measurements were included. A total number of 25 healthy older adults were enrolled (M = 63.32, SD = 4.44). Participants were randomly allocated into two conditions: (i) PM training: participants underwent a multi-component PM training, and (ii) control: participants were not contacted during the training phase. After the training phase was finished, participants crossed over to undergo the condition they did not experience before. The differences between pre- and post-training measures of PM, activities of daily living, negative mood (depression) and anxiety were assessed. All changes in the measurements were analyzed using general linear method (GLM). This trial is registered at isrctn.com (#ISRCTN57600070). RESULTS Multi-component PM training program was significantly effective on both subjective and objective PM performances among healthy older adults. Moreover, the training had significant positive effects on activities of daily living (Independence) among participants. Also, negative mood and anxiety levels were reduced after the training was finished. CONCLUSIONS This multi-component PM training improved PM performance and activities of daily living and reduce negative mood (depression) and anxiety levels among healthy older adults. Rahimah Ibrahim, Research Associate, Malaysian Research Institute on Aging, Universiti Putra Malaysia (UPM), Serdang, Selangor, 43400, Malaysia. Associate Professor, Department of Human Development and Family Studies, Faculty of Human Ecology, Universiti Putra Malaysia (UPM), Serdang, Selangor, 43400 Malaysia. Tel-Fax: +603-8946 7149 Email: imahibrahim@upm.edu.my No funding was received. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Reversible Visual Field Defect after Isolated Intraventricular Hemorrhage

No abstract available

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…why remifentanil?



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Emergency Reporting releases ‘Ten Useful Apps for First Responders’ e-book

New e-book highlights ten mobile apps for firefighters and EMS personnel. BELLINGHAM, Wash. — Emergency Reporting (ER), a leader in cloud-based Fire and EMS records management, has released a free e-book titled "Ten Useful Apps for First Responders." The e-book, available for download on the ER website, features an app on each page, including a summary, screenshots, a list of useful ...

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Mapping and Predicting Non-Linear Brassica rapa Growth Phenotypes Based on Bayesian and Frequentist Complex Trait Estimation

Predicting phenotypes based on genotypes and understanding the effects of complex multi-locus traits on plant performance requires a description of the underlying developmental processes, growth trajectories, and their genomic architecture. Using data from Brassica rapa genotypes grown in multiple density settings and seasons, we applied a hierarchical Bayesian Function-Valued Trait (FVT) approach to fit logistic growth curves to leaf phenotypic data (length and width) and characterize leaf development. We found evidence of genetic variation in phenotypic plasticity of rate and duration of leaf growth to growing season. In contrast, the magnitude of the plastic response for maximum leaf size was relatively small, suggesting that growth dynamics vs. final leaf sizes have distinct patterns of environmental sensitivity. Consistent with patterns of phenotypic plasticity, several QTL-by-year interactions were significant for parameters describing leaf growth rates and durations but not leaf size. In comparison to frequentist approaches for estimating leaf FVT, Bayesian trait estimation resulted in more mapped QTL that tended to have greater average LOD scores and to explain a greater proportion of trait variance. We then constructed QTL-based predictive models for leaf growth rate and final size using data from one treatment (uncrowded plants in one growing season). Models successfully predicted non-linear developmental phenotypes for genotypes not used in model construction and, due to a lack of QTL-by-treatment interactions, predicted phenotypes across sites differing in plant density.



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A Genomic Reference Panel for Drosophila serrata

Here we describe a collection of re-sequenced inbred lines of Drosophila serrata, sampled from a natural population situated deep within the species endemic distribution in Brisbane, Australia. D. serrata is a member of the speciose montium group whose members inhabit much of south east Asia and has been well studied for aspects of climatic adaptation, sexual selection, sexual dimorphism, and mate recognition. We sequenced 110 lines that were inbred via 17-20 generations of full-sib mating at an average coverage of 23.5x with paired-end Illumina reads. 15,228,692 biallelic SNPs passed quality control after being called using the Joint Genotyper for Inbred Lines (JGIL). Inbreeding was highly effective and the average levels of residual heterozygosity (0.86%) were well below theoretical expectations. As expected, linkage disequilibrium decayed rapidly, with r2 dropping below 0.1 within 100 base pairs. With the exception of four closely related pairs of lines which may have been due to technical errors, there was no statistical support for population substructure. Consistent with other endemic populations of other Drosophila species, preliminary population genetic analyses revealed high nucleotide diversity and, on average, negative Tajima's D values. A preliminary GWAS was performed on a cuticular hydrocarbon trait, 2-Me-C28 revealing 4 SNPs passing Bonferroni significance residing in or near genes. One gene Cht9 may be involved in the transport of CHCs from the site of production (oenocytes) to the cuticle. Our panel will facilitate broader population genomic and quantitative genetic studies of this species and serve as an important complement to existing D. melanogaster panels that can be used to test for the conservation of genetic architectures across the Drosophila genus.



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Transcriptome Analysis of Litsea cubeba Floral Buds Reveals the Role of Hormones and Transcription Factors in the Differentiation Process

Background:

Litsea cubeba (Lour.) Pers. is an important economic plant that is rich in valuable essential oil. The essential oil is often used as a raw material for perfumes, food additives, insecticides and bacteriostats. Most of the essential oil is contained in the fruit, and the quantity and quality of fruit are dependent on the flowers. To explore the molecular mechanism of floral bud differentiation, high-throughput RNA sequencing was used to detect differences in the gene expression of L. cubeba female and male floral buds at three differentiation stages.

Results:

This study obtained 160.88 Gbp of clean data that were assembled into 100,072 unigenes, and a total of 38,658 unigenes were annotated. A total of 27,521 simple sequence repeats (SSRs) were identified after scanning the assembled transcriptome, and the mono-nucleotide repeats were predominant, followed by di-nucleotide and tri-nucleotide repeats. A total of 12,559 differentially expressed genes (DEGs) were detected from the female (F) and male (M) floral bud comparisons. The gene ontology (GO) databases revealed that these DEGs were primarily contained in "metabolic processes", "cellular processes", and "single-organism processes". The Kyoto Encyclopedia of Genes and Genomes (KEGG) databases suggested that the DEGs belonged to "plant hormone signal transduction" and accounted for a relatively large portion in all of these comparisons. We analyzed the expression level of plant hormone-related genes and detected the contents of several relevant plant hormones in different stages. The results revealed that the dynamic changes in each hormone content were almost consistent with the expression levels of relevant genes. The transcription factors selected from the DEGs were analyzed. Most DEGs of MADS-box were upregulated and most DEGs of bZIP were downregulated. The expression trends of the DEGs were nearly identical in female and male floral buds, and qRT-PCR analysis revealed consistency with the transcriptome data.

Conclusions:

We sequenced and assembled a high-quality L. cubeba floral bud transcriptome, and the data appeared to be well replicated (n = 3) over three developmental time points during flower development. Our study explored the changes in the contents of several plant hormones during floral bud differentiation using biochemical and molecular biology techniques, and the changes in expression levels of several flower development related transcription factors. These results revealed the role of these factors (i.e., hormones and transcription factors) and may advance our understanding of their functions in flower development in L. cubeba.



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Photosensitive Alternative Splicing of the Circadian Clock Gene timeless Is Population Specific in a Cold-Adapted Fly, Drosophila montana

To function properly, organisms must adjust their physiology, behavior and metabolism in response to a suite of varying environmental conditions. One of the central regulators of these changes is organisms' internal circadian clock, and recent evidence has suggested that the clock genes are also important in the regulation of seasonal adjustments. In particular, thermosensitive splicing of the core clock gene timeless in a cosmopolitan fly, Drosophila melanogaster, has implicated this gene to be involved in thermal adaptation. To further investigate this link we examined the splicing of timeless in a northern malt fly species, Drosophila montana, which can withstand much colder climatic conditions than its southern relative. We studied northern and southern populations from two different continents (North America and Europe) to find out whether and how the splicing of this gene varies in response to different temperatures and day lengths. Interestingly, we found that the expression of timeless splice variants was sensitive to differences in light conditions, and while the flies of all study populations showed a change in the usage of splice variants in constant light compared to LD 22:2, the direction of the shift varied between populations. Overall, our findings suggest that the splicing of timeless in northern Drosophila montana flies is photosensitive, rather than thermosensitive and highlights the value of studying multiple species and populations in order to gain perspective on the generality of gene function changes in different kinds of environmental conditions.



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Identification of Two Distinct Classes of the Human INO80 Complex Genome-Wide

Chromatin remodeling and histone modifying enzymes play a critical role in shaping the regulatory output of a cell. Although much is known about these classes of proteins, identifying the mechanisms by which they coordinate gene expression programs remains an exciting topic of investigation. One factor that may contribute to the targeting and activity of chromatin regulators is local chromatin landscape. We leveraged genomic approaches and publically-available datasets to characterize the chromatin landscape at targets of the human INO80 chromatin remodeling complex (INO80-C). Our data revealed two classes of INO80-C targets with distinct chromatin signatures. The predominant INO80-C class was enriched for open chromatin, H3K27ac, and representative subunits from each of the three INO80-C modules (RUVBL1, RUVBL2, MCRS1, YY1). We named this class Canonical INO80. Notably, we identified an unexpected class of INO80-C targets that contained only the INO80 ATPase and harbored a repressive chromatin signature characterized by inaccessible chromatin, H3K27me3, and the methyltransferase EZH2. We named this class Non-Canonical INO80 (NC-INO80). Biochemical approaches indicated that INO80-C and the H3K27 acetyltransferase P300 physically interact, suggesting INO80-C and P300 may jointly coordinate chromatin accessibility at Canonical INO80 sites. No interaction was detected between INO80-C and EZH2, indicating INO80-C and EZH2 may engage in a separate form of regulatory crosstalk at NC-INO80 targets. Our data indicate that INO80-C is more compositionally heterogenous at its genomic targets than anticipated. Moreover, our data suggest there is an important link between INO80-C and histone modifying enzymes that may have consequences in developmental and pathological contexts.



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Genomic Context Analysis of de Novo STXBP1 Mutations Identifies Evidence of Splice Site DNA-Motif Associated Hotspots

Mutations within STXBP1 have been associated with a range of neurodevelopmental disorders implicating the pleotropic impact of this gene. Although the frequency of de novo mutations within STXBP1 for selective cohorts with early onset epileptic encephalopathy is more than 1%, there is no evidence for a hotspot within the gene. In this study, we analyzed the genomic context of de novo STXBP1 mutations to examine whether certain motifs indicated a greater risk of mutation. Through a comprehensive context analysis of 136 de novo/rare mutation (SNV/Indels) sites in this gene, strikingly 26.92% of all SNV mutations occurred within 5bp upstream or downstream of a 'GTA' motif (P < 0.0005). This implies a genomic context modulated mutagenesis. Moreover, 51.85% (14 out of 27) of the 'GTA' mutations are splicing compared to 14.70% (20 out of 136) of all reported mutations within STXBP1. We also noted that 11 of these 14 'GTA' associated mutations are de novo in origin. Our analysis provides strong evidence of DNA motif modulated mutagenesis for STXBP1 de novo splicing mutations.



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A Metagenome-Wide Association Study and Arrayed Mutant Library Confirm Acetobacter Lipopolysaccharide Genes Are Necessary for Association with Drosophila melanogaster

A metagenome wide association (MGWA) study of bacterial host association determinants in Drosophila predicted that LPS biosynthesis genes are significantly associated with host colonization. We were unable to create site-directed mutants for each of the predicted genes in Acetobacter, so we created an arrayed transposon insertion library using Acetobacter fabarum DsW_054 isolated from Drosophila. Creation of the A. fabarum DsW_054 gene knock-out library was performed by combinatorial mapping and Illumina sequencing of random transposon insertion mutants. Transposon insertion locations for 6,418 mutants were successfully mapped, including hits within 63% of annotated genes in the A. fabarum DsW_054 genome. For 45/45 members of the library, insertion sites were verified by arbitrary PCR and Sanger sequencing. Mutants with insertions in four different LPS biosynthesis genes were selected from the library to validate the MGWA predictions. Insertion mutations in two genes biosynthetically upstream of Lipid-A formation, lpxC and lpxB, show significant differences in host association, whereas mutations in two genes encoding LPS biosynthesis functions downstream of Lipid-A biosynthesis had no effect. These results suggest an impact of bacterial cell surface molecules on the bacterial capacity for host association. Also, the transposon insertion mutant library will be a useful resource for ongoing research on the genetic basis for Acetobacter traits.



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A Genome-Wide Association Study for Host Resistance to Ostreid Herpesvirus in Pacific Oysters (Crassostrea gigas)

Ostreid herpesvirus (OsHV) can cause mass mortality events in Pacific oyster aquaculture. While various factors impact on the severity of outbreaks, it is clear that genetic resistance of the host is an important determinant of mortality levels. This raises the possibility of selective breeding strategies to improve the genetic resistance of farmed oyster stocks, thereby contributing to disease control. Traditional selective breeding can be augmented by use of genetic markers, either via marker-assisted or genomic selection. The aim of the current study was to investigate the genetic architecture of resistance to OsHV in Pacific oyster, to identify genomic regions containing putative resistance genes, and to inform the use of genomics to enhance efforts to breed for resistance. To achieve this, a population of ~1,000 juvenile oysters were experimentally challenged with a virulent form of OsHV, with samples taken from mortalities and survivors for genotyping and qPCR measurement of viral load. The samples were genotyped using a recently-developed SNP array, and the genotype data were used to reconstruct the pedigree. Using these pedigree and genotype data, the first high density linkage map was constructed for Pacific oyster, containing 20,353 SNPs mapped to the ten pairs of chromosomes. Genetic parameters for resistance to OsHV were estimated, indicating a significant but low heritability for the binary trait of survival and also for viral load measures (h2 0.12 – 0.25). A genome-wide association study highlighted a region of linkage group 6 containing a significant QTL affecting host resistance. These results are an important step toward identification of genes underlying resistance to OsHV in oyster, and a step toward applying genomic data to enhance selective breeding for disease resistance in oyster aquaculture.



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A Survey of Virus Recombination Uncovers Canonical Features of Artificial Chimeras Generated During Deep Sequencing Library Preparation

Chimeric reads can be generated by in vitro recombination during the preparation of high-throughput sequencing libraries. Our attempt to detect biological recombination between the genomes of dengue virus (DENV; +ssRNA genome) and its mosquito host using the Illumina Nextera sequencing library preparation kit revealed that most, if not all, detected host–virus chimeras were artificial. Indeed, these chimeras were not more frequent than with control RNA from another species (a pillbug), which was never in contact with DENV RNA prior to the library preparation. The proportion of chimera types merely reflected those of the three species among sequencing reads. Chimeras were frequently characterized by the presence of 1-20 bp microhomology between recombining fragments. Within-species chimeras mostly involved fragments in opposite orientations and located less than 100 bp from each other in the parental genome. We found similar features in published datasets using two other viruses: Ebola virus (EBOV; -ssRNA genome) and a herpesvirus (dsDNA genome), both produced with the Illumina Nextera protocol. These canonical features suggest that artificial chimeras are generated by intra-molecular template switching of the DNA polymerase during the PCR step of the Nextera protocol. Finally, a published Illumina dataset using the Flock House virus (FHV; +ssRNA genome) generated with a protocol preventing artificial recombination revealed the presence of 1-10 bp microhomology motifs in FHV–FHV chimeras, but very few recombining fragments were in opposite orientations. Our analysis uncovered sequence features characterizing recombination breakpoints in short-read sequencing datasets, which can be helpful to evaluate the presence and extent of artificial recombination.



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Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology

Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that significantly deviated from neutrality either experienced soft sweeps or population-specific hard sweeps. Interestingly, while most hard sweeps occurred on genes involved in sialic acid recognition, most soft sweeps involved genes associated with recycling, degradation and activation, transport, and transfer functions. We propose that the lack of signatures of recent positive selection for the majority of the sialic acid biology genes is consistent with the view that these genes regulate immune responses against ancient rather than contemporary cosmopolitan or geographically restricted pathogens.



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Maize Transposable Elements Ac/Ds as Insertion Mutagenesis Tools in Candida albicans

In nonmodel systems, genetic research is often limited by the lack of techniques for the generation and identification of gene mutations. One approach to overcome this bottleneck is the application of transposons for gene tagging. We have established a two-element transposon tagging system, based on the transposable elements Activator (Ac)/Dissociation (Ds) from maize, for in vivo insertion mutagenesis in the fungal human pathogen Candida albicans. A nonautonomous Ds transposon carrying a selectable marker was constructed into the ADE2 promoter on chromosome 3 and a codon usage-adapted Ac transposase gene was inserted into the neutral NEUT5L locus on chromosome 5. In C. albicans cells expressing the transposase, the Ds element efficiently excised and reintegrated elsewhere in the genome, which makes the Ac/Ds transposons promising tools for saturating insertion mutagenesis in clinical strains of C. albicans.



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A Genetic Screen Identifies PRP18a, a Putative Second Step Splicing Factor Important for Alternative Splicing and a Normal Phenotype in Arabidopsis thaliana

Splicing of pre-mRNA involves two consecutive trans-esterification steps that take place in the spliceosome, a large dynamic ribonucleoprotein complex situated in the nucleus. In addition to core spliceosomal proteins, each catalytic step requires step-specific factors. Although the Arabidopsis thaliana genome encodes around 430 predicted splicing factors, functional information about these proteins is limited. In a forward genetic screen based on an alternatively-spliced GFP reporter gene in Arabidopsis thaliana, we identified a mutant impaired in putative step II factor PRP18a, which has not yet been investigated for its role in pre-mRNA splicing in plants. Step II entails cleavage at the 3' splice site accompanied by ligation of the 5' and 3' exons and intron removal. In the prp18 mutant, splicing of a U2-type intron with non-canonical AT-AC splice sites in GFP pre-mRNA is reduced while splicing of a canonical GT-AG intron is enhanced, resulting in decreased levels of translatable GFP mRNA and GFP protein. These findings suggest that wild-type PRP18a may in some cases promote splicing at weak, non-canonical splice sites. Analysis of genome-wide changes in alternative splicing in the prp18a mutant identified numerous cases of intron retention and a preponderance of altered 3' splice sites, suggesting an influence of PRP18a on 3' splice site selection. The prp18a mutant featured short roots on synthetic medium and small siliques, illustrating that wild-type PRP18a function is needed for a normal phenotype. Our study expands knowledge of plant splicing factors and provides foundational information and resources for further functional studies of PRP18 proteins in plants.



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Multivariate Analysis of the Cotton Seed Ionome Reveals a Shared Genetic Architecture

To mitigate the effects of heat and drought stress, a better understanding of the genetic control of physiological responses to these environmental conditions is needed. To this end, we evaluated an upland cotton (Gossypium hirsutum L.) mapping population under water-limited and well-watered conditions in a hot, arid environment. The elemental concentrations (ionome) of seed samples from the population were profiled in addition to those of soil samples taken from throughout the field site to better model environmental variation. The elements profiled in seeds exhibited moderate to high heritabilities, as well as strong phenotypic and genotypic correlations between elements that were not altered by the imposed irrigation regimes. Quantitative trait loci (QTL) mapping results from a Bayesian classification method identified multiple genomic regions where QTL for individual elements colocalized, suggesting that genetic control of the ionome is highly interrelated. To more fully explore this genetic architecture, multivariate QTL mapping was implemented among groups of biochemically related elements. This analysis revealed both additional and pleiotropic QTL responsible for coordinated control of phenotypic variation for elemental accumulation. Machine learning algorithms that utilized only ionomic data predicted the irrigation regime under which genotypes were evaluated with very high accuracy. Taken together, these results demonstrate the extent to which the seed ionome is genetically interrelated and predictive of plant physiological responses to adverse environmental conditions.



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Drought Sensitivity of Norway Spruce at the Species Warmest Fringe: Quantitative and Molecular Analysis Reveals High Genetic Variation Among and Within Provenances

Norway spruce (Picea abies) is by far the most important timber species in Europe, but its outstanding role in future forests is jeopardized by its high sensitivity to drought. We analyzed drought response of Norway spruce at the warmest fringe of its natural range. Based on a 35-year old provenance experiment we tested for genetic variation among and within seed provenances across consecutively occurring strong drought events using dendroclimatic time series. Moreover, we tested for associations between 1,700 variable SNPs and traits related to drought response, wood characteristics and climate-growth relationships. We found significant adaptive genetic variation among provenances originating from the species' Alpine, Central and Southeastern European range. Genetic variation between individuals varied significantly among provenances explaining up to 44% of the phenotypic variation in drought response. Varying phenotypic correlations between drought response and wood traits confirmed differences in selection intensity among seed provenances. Significant associations were found between 29 SNPs and traits related to drought, climate-growth relationships and wood properties which explained between 11 and 43% of trait variation, though 12 of them were due to single individuals having extreme phenotypes of the respective trait. The majority of these SNPs are located within exons of genes and the most important ones are preferentially expressed in cambium and xylem expansion layers. Phenotype-genotype associations were stronger if only provenances with significant quantitative genetic variation in drought response were considered. The present study confirms the high adaptive variation of Norway spruce in Central and Southeastern Europe and demonstrates how quantitative genetic, dendroclimatic and genomic data can be linked to understand the genetic basis of adaptation to climate extremes in trees.



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The Molecular and Genetic Characterization of Second Chromosome Balancers in Drosophila melanogaster

Balancer chromosomes are multiply inverted and rearranged chromosomes used in Drosophila melanogaster for many tasks, such as maintaining mutant alleles in stock and complex stock construction. Balancers were created before molecular characterization of their breakpoints was possible, so the precise locations of many of these breakpoints are unknown. Here, we report or confirm the positions of the 14 euchromatic breakpoints on the 2nd chromosome balancers SM1, SM5, CyO, and SM6a. This total includes three breakpoints involved in a complex rearrangement on SM5 that is associated with the duplication of two genomic regions. Unbiased sequencing of several balancers allowed us to identify stocks with incorrectly identified balancers as well as single and double crossover events that had occurred between 2nd chromosome balancers and their homologs. The confirmed crossover events that we recovered were at least 2 Mb from the closest inversion breakpoint, consistent with observations from other balancer chromosomes. Balancer chromosomes differ from one another both by large tracts of sequence diversity generated by recombination and by small differences, such as single nucleotide polymorphisms (SNPs). Therefore, we also report loss-of-function mutations carried by these chromosomes and unique SNP and InDel polymorphisms present on only single balancers. These findings provide valuable information about the structure of commonly used 2nd chromosome balancers and extend recent work examining the structure of X and 3rd chromosome balancers. Finally, these observations provide new insights into how the sequences of individual balancers have diverged over time.



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The End of a 60-year Riddle: Identification and Genomic Characterization of an Iridovirus, the Causative Agent of White Fat Cell Disease in Zooplankton

The planktonic freshwater crustacean of the genus Daphnia are a model system for biomedical research and, in particular, invertebrate-parasite interactions. Up until now, no virus has been characterized for this system. Here we report the discovery of an iridovirus as the causative agent of White Fat Cell Disease (WFCD) in Daphnia. WFCD is a highly virulent disease of Daphnia that can easily be cultured under laboratory conditions. Although it has been studied from sites across Eurasia for more than 60 years, its causative agent had not been described, nor had an iridovirus been connected to WFCD before now. Here we find that an iridovirus—the Daphnia iridescent virus 1 (DIV-1)—is the causative agent of WFCD. DIV-1 has a genome sequence of about 288 kbp, with 39% G+C content and encodes 367 predicted open reading frames. DIV-1 clusters together with other invertebrate iridoviruses but has by far the largest genome among all sequenced iridoviruses. Comparative genomics reveal that DIV-1 has apparently recently lost a substantial number of unique genes but has also gained genes by horizontal gene transfer from its crustacean host. DIV-1 represents the first invertebrate iridovirus that encodes proteins to purportedly cap RNA, and it contains unique genes for a DnaJ-like protein, a membrane glycoprotein and protein of the immunoglobulin superfamily, which may mediate host–pathogen interactions and pathogenicity. Our findings end a 60-year search for the causative agent of WFCD and add to our knowledge of iridovirus genomics and invertebrate–virus interactions.



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Selection on Expected Maximum Haploid Breeding Values Can Increase Genetic Gain in Recurrent Genomic Selection

Genomic selection (GS) offers the possibility to estimate the effects of genome-wide molecular markers, which can be used to calculate genomic estimated breeding values (GEBVs) for individuals without phenotypes. GEBVs can serve as a selection criterion in recurrent GS, maximizing single-cycle but not necessarily long-term genetic gain. As simple genome-wide sums, GEBVs do not take into account other genomic information, such as the map positions of loci and linkage phases of alleles. Therefore, we herein propose a novel selection criterion called expected maximum haploid breeding value (EMBV). EMBV predicts the expected performance of the best among a limited number of gametes that a candidate contributes to the next generation, if selected. We used simulations to examine the performance of EMBV in comparison with GEBV as well as the recently proposed criterion optimal haploid value (OHV) and weighted GS. We considered different population sizes, numbers of selected candidates, chromosome numbers and levels of dominant gene action. Criterion EMBV outperformed GEBV after about 5 selection cycles, achieved higher long-term genetic gain and maintained higher diversity in the population. The other selection criteria showed the potential to surpass both GEBV and EMBV in advanced cycles of the breeding program, but yielded substantially lower genetic gain in early to intermediate cycles, which makes them unattractive for practical breeding. Moreover, they were largely inferior in scenarios with dominant gene action. Overall, EMBV shows high potential to be a promising alternative selection criterion to GEBV for recurrent genomic selection.



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Synopsis of the SOFL Plant-Specific Gene Family

SUPPRESSOR OF PHYB-4#5DOMINANT (sob5-D) was previously identified as a suppressor of the phyB-4 long-hypocotyl phenotype in Arabidopsis thaliana. Overexpression of SOB5 conferred dwarf phenotypes similar to those observed in plants containing elevated levels of cytokinin (CK) nucleotides and nucleosides. Two SOB-FIVE- LIKE (SOFL) proteins, AtSOFL1 and AtSOFL2, which are more similar at the protein level to each other than they are to SOB5, conferred similar phenotypes to the sob5-D mutant when overexpressed. We used protein sequences of founding SOFL gene family members to perform database searches and identified a total of 289 SOFL homologs in genomes of 89 angiosperm species. Phylogenetic analysis results implied that the SOFL gene family emerged during the expansion of angiosperms and later evolved into four distinct clades. Among the newly identified gene family members are four previously unreported Arabidopsis SOFLs. Multiple sequence alignment of the 289 SOFL protein sequences revealed two highly conserved domains; SOFL-A and SOFL-B. We used overexpression and site-directed mutagenesis studies to demonstrate that SOFL domains are necessary for SOB5 and AtSOFL1's overexpression phenotypes. Examination of the subcellular localization patterns of founding Arabidopsis thaliana SOFLs suggested they may be localized in the cytoplasm and/or the nucleus. Overall, we report that SOFLs are a plant-specific gene family characterized by two conserved domains that are important for function.



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Genomic Predictions and Genome-Wide Association Study of Resistance Against Piscirickettsia salmonis in Coho Salmon (Oncorhynchus kisutch) Using ddRAD Sequencing

Piscirickettsia salmonis is one of the main infectious diseases affecting coho salmon (Oncorhynchus kisutch) farming, and current treatments have been ineffective for the control of this disease. Genetic improvement for P. salmonis resistance has been proposed as a feasible alternative for the control of this infectious disease in farmed fish. Genotyping by sequencing (GBS) strategies allow genotyping of hundreds of individuals with thousands of single nucleotide polymorphisms (SNPs), which can be used to perform genome wide association studies (GWAS) and predict genetic values using genome-wide information. We used double-digest restriction-site associated DNA (ddRAD) sequencing to dissect the genetic architecture of resistance against P. salmonis in a farmed coho salmon population and to identify molecular markers associated with the trait. We also evaluated genomic selection (GS) models in order to determine the potential to accelerate the genetic improvement of this trait by means of using genome-wide molecular information. A total of 764 individuals from 33 full-sib families (17 highly resistant and 16 highly susceptible) were experimentally challenged against P. salmonis and their genotypes were assayed using ddRAD sequencing. A total of 9,389 SNPs markers were identified in the population. These markers were used to test genomic selection models and compare different GWAS methodologies for resistance measured as day of death (DD) and binary survival (BIN). Genomic selection models showed higher accuracies than the traditional pedigree-based best linear unbiased prediction (PBLUP) method, for both DD and BIN. The models showed an improvement of up to 95% and 155% respectively over PBLUP. One SNP related with B-cell development was identified as a potential functional candidate associated with resistance to P. salmonis defined as DD.



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Systematic Complex Haploinsufficiency-Based Genetic Analysis of Candida albicans Transcription Factors: Tools and Applications to Virulence-Associated Phenotypes

Genetic interaction analysis is a powerful approach to the study of complex biological processes that are dependent on multiple genes. Because of the largely diploid nature of the human fungal pathogen Candida albicans, genetic interaction analysis has been limited to a small number of large-scale screens and a handful for gene-by-gene studies. Complex haploinsufficiency, which occurs when a strain containing two heterozygous mutations at distinct loci shows a phenotype that is distinct from either of the corresponding single heterozygous mutants, is an expedient approach to genetic interactions analysis in diploid organisms. Here, we describe the construction of a barcoded-library of 133 heterozygous TF deletion mutants and deletion cassettes for designed to facilitate complex haploinsufficiency-based genetic interaction studies of the TF networks in C. albicans. We have characterized the phenotypes of these heterozygous mutants under a broad range of in vitro conditions using both agar-plate and pooled signature tag-based assays. Consistent with previous studies, haploinsufficiency is relative uncommon. In contrast, a set of 12 TFs enriched in mutants with a role in adhesion were found to have altered competitive fitness at early time points in a murine model of disseminated candidiasis. Finally, we characterized the genetic interactions of a set of biofilm related TFs in the first two steps of biofilm formation, adherence and filamentation of adherent cells. The genetic interaction networks at each stage of biofilm formation are significantly different indicating that the network is not static but dynamic.



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Prevent controlled substance diversion with a digital record of entry

Careful monitoring, witnessed documentation and a record of any actions will protect controlled substances in the ambulance from theft

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Comment on: “Effect of High-Intensity Interval Training on Total, Abdominal and Visceral Fat Mass: A Meta-Analysis”



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Change of Direction Speed: Toward a Strength Training Approach with Accentuated Eccentric Muscle Actions

Abstract

There is growing evidence that eccentric strength training appears to have benefits over traditional strength training (i.e., strength training with combined concentric and eccentric muscle actions) from muscular, neuromuscular, tendinous, and metabolic perspectives. Eccentric muscle strength is particularly needed to decelerate and stabilize the body during the braking phase of a jump exercise or during rapid changes of direction (CoD) tasks. However, surprisingly little research has been conducted to elucidate the effects of eccentric strength training or strength training with accentuated eccentric muscle actions on CoD speed performance. In this current opinion article, we present findings from cross-sectional studies on the relationship between measures of eccentric muscle strength and CoD speed performance. In addition, we summarize the few available studies on the effects of strength training with accentuated eccentric muscle actions on CoD speed performance in athletic populations. Finally, we propose strength training with accentuated eccentric muscle actions as a promising element in strength and conditioning programs of sports with high CoD speed demands. Our findings from five cross-sectional studies revealed statistically significant moderate- to large-sized correlations (r = 0.45–0.89) between measures of eccentric muscle strength and CoD speed performance in athletic populations. The identified three intervention studies were of limited methodological quality and reported small- to large-sized effects (d = 0.46–1.31) of strength training with accentuated eccentric muscle actions on CoD speed performance in athletes. With reference to the available but preliminary literature and from a performance-related point of view, we recommend strength and conditioning coaches to include strength training with accentuated eccentric muscle actions in training routines of sports with high CoD speed demands (e.g., soccer, handball, basketball, hockey) to enhance sport-specific performance. Future comparative studies are needed to deepen our knowledge of the effects of strength training with accentuated eccentric muscle actions on CoD speed performance in athletes.



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Author’s Reply to Andreato et al.: Comment on: “Effect of High-Intensity Interval Training on Total, Abdominal and Visceral Fat Mass: A Meta-Analysis”



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Laughter as a social rejection cue: Influence of prior explicit experience of social rejection on cardiac signs of “freezing”

Publication date: Available online 28 March 2018
Source:International Journal of Psychophysiology
Author(s): Helmut K. Lackner, Katharina Reiter-Scheidl, Nilüfer Aydin, Corinna M. Perchtold, Elisabeth M. Weiss, Ilona Papousek
The study aimed at investigating the immediate cardiac effect of the sudden perception of other people's laughter after experimentally manipulating healthy participants' proneness to experience laughter as a cue of social threat. We expected that participants would show cardiac signs of freezing (i.e., sustained heart rate deceleration immediately after perception of the laughter) after prior social rejection but not or less so after prior acceptance, due to an increased bias to perceive the ambiguous social signal as a cue of social threat and rejection after rejection had been primed. Contrary to expectations, the perception of other people's laughter elicited a decelerative (freezing) response regardless of whether it was preceded by the experience of social rejection or acceptance. The response was prolonged in participants who had been accepted beforehand compared to those who had been rejected. The findings indicate that, given a relevant social context, other people's laughter can be a powerful cue of social threat and rejection also in healthy individuals. Prolonged heart rate deceleration after an ambiguous social signal may facilitate the processing of significant social information in the socially threatening situation. The study adds to the literature rendering the course of the immediate transient heart rate response a useful tool in social rejection research. Additionally, the findings suggested that in some cases the further progress of transient heart rate changes in more extended time-windows (about 30 s) may provide additional relevant information about the processing of social cues.



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Exploring the maximum duration of the contingent negative variation

Publication date: Available online 28 March 2018
Source:International Journal of Psychophysiology
Author(s): Jonas Röhricht, Han-Gue Jo, Marc Wittmann, Stefan Schmidt
While the contingent negative variation (CNV) has been the subject of extensive research over the last fifty years, the maximum duration during which such cortical negativity can be maintained has, to the best of our knowledge, never been systematically explored. Participants were presented with the classic S1–S2 paradigm task, where a warning stimulus (S1) acts as a cue for the appearance of an imperative stimulus (S2). A fast motor response was required upon S2 arrival. Inter-stimulus intervals (ISIs) of 2.5, 5, 7.5 and 10 s duration were presented in blocked fashion. Data was analysed using both cortical voltage referenced to linked mastoids and the current source density (CSD) technique, which maximizes the cortical origin of the measured voltage. Mean late CNV (lCNV) amplitude was found to be significantly higher for fast reaction time (RT) trials when CSD data was split according to the median into 'fast' and 'slow' RT halves. Post-hoc comparisons showed that this RT effect was particularly strong for the 10 s condition. This may be explained by the lack of an lCNV component and thus of cortical negativity prior to S2 in the 10 s condition. Our results suggest that intervals of a duration between 7.5 and 10 s represent the upper boundary during which the lCNV component can be elicited.



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Evaluation of particulate 137Cs discharge from a mountainous forested catchment using reservoir sediments and sinking particles

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Publication date: September 2018
Source:Journal of Environmental Radioactivity, Volume 189
Author(s): Hironori Funaki, Kazuya Yoshimura, Kazuyuki Sakuma, Shatei Iri, Yoshihiro Oda
The time and size dependencies of particulate 137Cs concentrations in a reservoir were investigated to evaluate the dynamics of 137Cs pollution from a mountainous forested catchment. Sediment and sinking particle samples were collected using a vibracorer and a sediment trap at the Ogaki Dam Reservoir in Fukushima, which is located in the heavily contaminated area that formed as a result of the Fukushima Dai-ichi Nuclear Power Plant accident of 2011. The inventory of 137Cs discharged into the reservoir during the post-accident period (965 days) was estimated to be approximately 3.0 × 1012–3.9 × 1012 Bq, which is equivalent to 1.1%–1.4% of the initial estimated catchment inventory. The particulate 137Cs concentration showed a decline with time, but the exponent value between the specific surface area and the 137Cs concentration for the fine-sized (<63 μm) particle fraction remained almost constant from the immediate aftermath of the accident. These quantitative findings obtained by reconstructing the contamination history of particulate 137Cs in reservoir sediments and sinking particles have important implications for the evaluation of 137Cs dynamics in mountainous forested catchments.



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