ATP increases [Ca2+]i and activates a Ca2+-dependent Cl− current in rat ventricular fibroblasts

Key Points

• Fibroblasts isolated from adult rat ventricles consistently respond to (5–100 μM) ATP.
• ATP, ADP, and UTP all elicit similar dose-dependent increases in [Ca²⁺]_i.
• ATP also activates an outwardly rectifying Cl⁻ current; in contrast, ADP and UTP have much smaller electrophysiological effects.
• This ATP-dependent Cl⁻ current is markedly reduced when: i) [Ca²⁺]_i is buffered with BAPTA, or ii) the intrinsic phospholipase C activity in these fibroblasts is inhibited.
• PCR analysis suggests that the ATP-induced current is generated by the Ca²⁺-activated Cl⁻ current transcript TMEM 16F, also denoted ANO6.
• These findings reveal new physiological and pharmacological principles that regulate ventricular fibroblast function.

 

New Findings

• What is the central question of this study?

  Although electrophysiological and biophysical characteristics of heart fibroblasts have been studied in detail, their responses to prominent paracrine agents in the myocardium have not been adequately addressed. Our experiments characterize changes in cellular electrophysiology and intracellular calcium in response to ATP.

• What is the main finding and its importance?

  In rat ventricular fibroblasts maintained in cell culture we find that ATP activates a specific subset of Ca²⁺-activated Cl⁻ channels as a consequence of binding to P2Y purinoceptors and then activating phospholipase C. This response is not dependent on [Ca²⁺]_o but requires an increase in [Ca²⁺]_i and is modulated by the type of nucleotide that is the purinergic agonist.

Abstract

Effects of adenosine 5′-triphosphate (ATP) on enzymatically isolated rat ventricular fibroblasts maintained in short-term (36–72 hrs) cell culture were examined. Immunocytochemical staining of these cells revealed that a fibroblast, as opposed to a myofibroblast, phenotype was predominant. ATP, ADP or UTP all produced large increases in intracellular Ca²⁺ [Ca²⁺]_i. Voltage-clamp studies (amphotericin-perforated patch) showed that ATP (1–100 μM) activated an outwardly rectifying current, having a reversal potential very close to the Nernst potential for Cl⁻. In contrast, ADP was much less effective and UTP produced no detectable current. The nonselective Cl⁻ channel blockers niflumic acid, DIDS and NPPB (each at 100 μM), blocked the responses to 100 μM ATP. 2-MTATP, an agonist for P2Y purinoceptors activated a very similar outwardly rectifying C1⁻ current. The P2Y receptor antagonists, suramin and PPADS (100 μM each), significantly inhibited the Cl⁻ current produced by 100 μM ATP. ATP was able to activate this Cl⁻ current when [Ca²⁺]_o was removed, but not when [Ca²⁺]_i was buffered with BAPTA-AM. In the presence of the phospholipase C (PLC) inhibitor U73122, this Cl⁻ current could not be activated. PCR analysis revealed strong signals for a number of P2Y purinoceptors; and also for the Ca²⁺-activated Cl⁻ channel, TMEM 16F (also denoted ANO-6). In summary, these results demonstrate that activation of P2Y receptors by ATP causes a PLC-dependent increase in [Ca²⁺]_i, followed by activation of a Ca²⁺-dependent Cl⁻ current in rat ventricular fibroblasts.

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Whole-Genome Analysis of an Extensively Drug-Resistant Acinetobacter baumannii Strain XDR-BJ83: Insights into the Mechanisms of Resistance of an ST368 Strain from a Tertiary Care Hospital in China

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


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Is There an Association Between Use of Amoxicillin-Clavulanate and Resistance to Third-Generation Cephalosporins in Klebsiella pneumoniae and Escherichia coli at the Hospital Level?

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


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First Description in Greece of mphC-Positive Staphylococci Causing Subclinical Mastitis in Ewes

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


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Issue Information

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Editorial Board

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Autonomic rhythms in health and disease

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A Nonsense Variant in the ACADVL Gene in German Hunting Terrier Dogs with Exercise Induced Metabolic Myopathy

Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1) peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD). Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C>A or p.(Tyr576*). The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, which we propose to name exercise induced metabolic myopathy (EIMM), and the identification of the first canine pathogenic ACADVL variant. Our findings provide a large animal model for a known human disease and will enable genetic testing to avoid the unintentional breeding of affected offspring.

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African-American women’s Upward Economic Mobility and Small for Gestational Age Births: A Population-Based Study

Abstract

Background The relationship between African-American women's upward economic mobility and small for gestational age (weight for gestational < 10th percentile, SGA) rates is incompletely understood. Objective To ascertain the extent to which African-American women's upward economic mobility from early-life impoverishment is coupled with reduced SGA rates. Methods Stratified and multilevel logistic regression analyses were completed on the Illinois transgenerational dataset of African-American infants (1989–1991) and their Chicago-born mothers (1956–1976) with linked U.S. census income information. Results Impoverished-born (defined as lowest quartile of neighborhood income distribution) African-American women (n = 4891) who remained impoverished by the time of delivery had a SGA rate of 19.7%. Individuals who achieved low (n = 5827), modest (n = 2254), or high (n = 732) upward economic mobility by adulthood had lower SGA rates of 17.2, 14.8, and 13.7%, respectively; RR = 0.9 (0.8–0.9), 0.8 (0.7–0.8), and 0.7 (0.6–0.8), respectively. In adjusted (controlling for traditional individual-level risk factors) multilevel regression models, there was a decreasing linear trend in SGA rates with increasing levels of upward economic mobility; the adjusted RR of SGA birth for impoverished-born African-American women who experienced low, modest, of high (compared to no) upward mobility equaled 0.95 (0.91, 0.99), 0.90 (0.83, 0.98), and 0.86 (0.75, 0.98), respectively, p < 0.05. Conclusions African-American women's upward economic mobility from early-life residence in poor urban communities is associated with lower SGA rates independent of adulthood risk status.

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Maternal Obesity and Risk of Preterm Birth and Low Birthweight in Hawaii PRAMS, 2000–2011

Abstract

Objective Maternal obesity is a risk factor for preterm birth, a leading cause of infant morbidity and mortality. Native Hawaiian and other Pacific Islanders (NHOPI) have high rates of poor birth outcomes. Despite the high rates of obesity in NHOPI in Hawaii, the association with preterm birth has not been examined in this population. Methods We performed a retrospective cohort study of 20,061 women using data collected by Hawaii's Pregnancy Risk Assessment Monitoring System (PRAMS) from 2000 to 2011. We investigated the contribution of maternal age, pre-pregnancy BMI, gestational diabetes, hypertension, race, socioeconomic status, and smoking to our primary outcomes of preterm birth and low birthweight using multivariable logistic regression, stratified by NHOPI versus non-NHOPI race. Results Pre-pregnancy obesity was more common in NHOPI than non-NHOPI women (23.9 and 10.5%, respectively; p < 0.01). Overall, the risk for preterm birth increased with maternal obesity (BMI ≥ 30.0; aOR = 1.24, 95% CI 1.06–1.45, p < 0.01), compared with normal weight women. Among NHOPI women, the prevalence of preterm birth was elevated compared with non-NHOPI women although the prevalence of low birth weight was lower. After adjusting for confounders, risk for preterm birth and low birth weight were elevated in NHOPI women compared with White women. Maternal obesity did not significantly affect the risk of prematurity within the NHOPI group. Conclusions for Practice Our study demonstrates an association between maternal pre-pregnancy obesity and preterm deliveries in Hawaii. NHOPI have high rates of pre-pregnancy obesity as well as increased risk of both preterm delivery and low birthweight when compared to White women. Further data are needed to assess interactions between race, maternal health, and neonatal morbidity, and to identify ways to improve birth outcomes for minority populations in the state of Hawaii.

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Assessment of health-related quality of life in spine treatment: conversion from SF-36 to VR-12

Health-related quality-of-life outcomes have been collected with the Medical Outcomes Study (MOS) Short Form 36 (SF-36) survey. Boston University School of Public Health has developed algorithms for the conversion of SF-36 to VR-12 physical component summary (PCS) and mental component summary (MCS).

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A novel preoperative trajectory evaluation method for l5-s1 transforaminal percutaneous endoscopic lumbar discectomy

L5-S1 transforaminal PELD is a demanding procedure due to structures like iliac crest, L5 transverse process, hypertrophic L5-S1 facet joint, and sacral ala. There has been no definite preoperative evaluation method to evaluate the surgical validity of L5-S1 transforaminal PELD.

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Rod fracture in adult spinal deformity surgery fused to the sacrum: prevalence, risk factors and impact on health related quality of life in 526 patients

Risk factors associated with rod fracture (RF) following adult spinal deformity (ASD) surgery fused to the sacrum remain debatable and the impact of RF on patient-reported outcomes (PROs) after ASD surgery has not been investigated.

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De novo transcriptomics reveal distinct phototransduction signaling components in the retina and skin of a color-changing vertebrate, the hogfish ( Lachnolaimus maximus )

Abstract

Across diverse taxa, an increasing number of photoreceptive systems are being discovered in tissues outside of the eye, such as in the skin. Dermal photoreception is believed to serve a variety of functions, including rapid color change via specialized cells called chromatophores. In vitro studies of this system among color-changing fish have suggested the use of a phototransduction signaling cascade that fundamentally differs from that of the retina. Thus, the goal of this study was to identify phototransduction genes and compare their expression in the retina and skin of a color-changing fish, the hogfish Lachnolaimus maximus. De novo transcriptomics revealed the expression of genes that may underlie distinct, yet complete phototransduction cascades in L. maximus retina and skin. In contrast to the five visual opsin genes and cGMP-dependent phototransduction components expressed in the retina of L. maximus, only a single short-wavelength sensitive opsin (SWS1) and putative cAMP-dependent phototransduction components were expressed in the skin. These data suggest a separate evolutionary history of phototransduction in the retina and skin of certain vertebrates and, for the first time, indicate an expression repertoire of genes that underlie a non-retinal phototransduction pathway in the skin of a color-changing fish.

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Modulation of the frontal-parietal network by low intensity anti-phase 20 Hz transcranial electrical stimulation boosts performance in the attentional blink task

Publication date: Available online 27 February 2018
Source:International Journal of Psychophysiology
Author(s): Zachary Yaple, Roman Vakhrushev
Performance in the attentional blink task has been demonstrated to be directly influenced by alpha and beta neural oscillatory activity. In two experiments we stimulated the right parietal cortex and left frontal cortex with transcranial alternating current stimulation. For the first experiment we targeted only the right parietal cortex and found a non-significant increase in performance from 20 Hz stimulation. In the second experiment we applied two stimulators to the right parietal and left frontal cortex and found a significant increase in performance from 20 Hz tACS with a phase difference of 180°. Since low intensity stimulation has been shown to inhibit cortical excitability, and anti-phasic stimulation has been hypothesized to decrease presynaptic activation in one region and drive postsynaptic spikes in the other, we suggest that low intensity anti-phasic 20 Hz stimulation inhibited the parietal cortex, thereby disinhibiting the frontal cortex. This visual attention mechanism supposedly reduces processing of distractor stimuli and enhances processing of target stimuli. This study reveals that the frontal-parietal visual attention network may be modulated with low intensity 20 Hz anti-phase tACS.



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Group III/IV muscle afferents plays an independent role for the arterial baroreflex resetting during exercise in humans: is it the end of the road?

Abstract

The cardiovascular response to exercise is governed by both central and peripheral mechanisms that promote alterations in parasympathetic and sympathetic neural activities to the heart and blood vessels to meet the metabolic demands of working skeletal muscle in an intensity-dependent manner.

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QTL for tuber morphology traits in diploid potato

Abstract

A diploid, potato mapping population consisting of 149 individuals was assessed in three consecutive years for important agronomic and quality traits: tuber shape, regularity of tuber shape, eye depth, mean tuber weight, and tuber flesh color. Analysis of variance showed that the genotype had the largest influence on the phenotypic scores but effect of the genotype × year interactions was also strong. Using this data and an existing genetic map, a quantitative trait loci (QTL) analysis was conducted. From four to seven QTL were detected for each trait except tuber flesh color, which was determined by a major QTL on chromosome III explaining 76.8% of the trait variance. Additionally, a minor QTL for flesh color was localized on chromosome II. For the other traits, significant QTL were detected: for tuber shape on chromosome X, for regularity of tuber shape on chromosome III, for eye depth on chromosome IV, and for tuber weight on chromosome I. Some detected QTL confirmed previous studies, but new ones were also identified.

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2p24.2 (rs7552) is a susceptibility locus for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

The population of Brazil is highly admixed, with each individual showing variable levels of Amerindian, European and African ancestry, which may interfere in the genetic susceptibility of known risk loci to nonsyndromic cleft lip with or without cleft palate (NSCL±P). Here we investigated 5 reported genome-wide loci for NSCL±P in an ancestry-structured case-control study containing 1,697 Brazilian participants (831 NSCL±P and 866 healthy controls). SNPs rs7552 in 2q24.2, rs8049367 in 16p13.3, rs1880646, rs7406226, rs9891446 in 17p13, rs1588366 in 17q23.2 and rs73039426 in 19q13.11 were genotyped using TaqMan allelic discrimination assays and genomic ancestry was estimated using a panel of 40 biallelic short insertion/deletion polymorphic markers informative of the Brazilian population. Logistic regression analysis of the single-markers revealed rs7552 in 2p24.2 as a susceptibility risk marker for NSCL±P, yielding an OR of 1.71 (95% CI: 1.31-2.24, p=9x10^-6) in the homozygous state. Several SNP-SNP interactions containing rs7552 reached significance after adjustment for multiple tests (both Bonferroni assumption and 1000 permutation test), with the most significant interaction involving the 3-loci among rs7552, rs9891446 and rs73039426 (p=6.1x10^-9 and p_{1000 permutation}=0.001). Our study is the first to support the association of rs7552 in 2p24.2 with NSCL±P in the highly admixed Brazilian population.

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Regulatory network analysis of LINC00472, a long noncoding RNA downregulated by DNA hypermethylation in colorectal cancer

Colorectal cancer (CRC), one of the common malignant cancers in the world, is caused by accumulated alterations of genetic and epigenetic factors over a long period of time. Along with that protein-coding genes being identified as oncogenes or tumor suppressors in CRC, a number of lncRNAs have also been found to be associated with CRC. Considering the important regulatory role of lncRNAs, the first goal of this study was to identify CRC-associated lncRNAs from a public database. One such lncRNA, LINC00472, was verified to be downregulated in CRC cell lines and cancer tissues compared with adjacent tissues. In addition, the silencing of LINC00472 seemed to be caused by DNA hypermethylation at its promoter region. Furthermore, the expression of LINC00472 and DNA methylation of promoter were significantly correlated with clinicopathological features. And DNA hypermethylation of LINC00472 may serve as a better diagnostic biomarker than its expression for CRC. Finally, we predicted the functions of LINC00472 and constructed a regulatory network to found LINC00472 may be involved in cell cycle and cell proliferation processes. Our results may provide a clue to further research into the function and regulatory machinism of LINC00472 in CRC.

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Stretch-induced Ca2+-independent ATP release in hippocampal astrocytes

Abstract

Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether/how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. In contrast, two recent papers report vesicular ATP release using more direct assays. In the present work, by using patch-clamped "ATP-sniffer-cells", we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes. Following an "on-cell-like" mechanical stimulus of a single astrocyte, a Ca²⁺-independent single large non-quantal ATP release occurred, in contrast to the Ca²⁺-dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation-induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knock-down of P2 × 7 receptor channels. Functional P2 × 7 channel were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non-quantal ATP release depends on P2 × 7 channels in astrocytes.

This article is protected by copyright. All rights reserved

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Neural predictors of gait stability when walking freely in the real-world

Gait impairments during real-world locomotion are common in neurological diseases. However, very little is currently known about the neural correlates of walking in the real world and on which regions of the b...

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A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy

Abstract

Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.

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Review of reduction factors by buildings for gamma radiation from radiocaesium deposited on the ground due to fallout

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Hiroko Yoshida-Ohuchi, Norihiro Matsuda, Kimiaki Saito
In order to estimate residents' external dose due to radionuclide exposure resulting from fallout deposit on the ground, the shielding and dose reduction effects provided by structures such as houses and workplaces are taken into account as most individuals spend a large portion of their time indoors. Many works on both calculation and measurement for European and American settlements have been reported and factors such as, shielding factors, protection factors, reduction factors, and location factors have been determined. However, measurement data for Japanese settlements are lacking. Thus, the Japanese government used reduction factors given in the International Atomic Energy Agency documents from American and European settlements when Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident occurred. The United Nations Scientific Committee on the Effects of Atomic Radiation used location factors from European settlements for the same reason. Soon after the FDNPP accident, several measurements and calculations were performed to obtain specific reduction factors for Japanese settlements due to this lack of data. This research reviews previous studies that determined factors such as, shielding factors, protection factors, reduction factors, and location factors and summarizes specific results for Japan. We discuss the issues in determining these factors and in applying them to estimate indoor dose. The contribution of surface contamination to the indoor ambient dose equivalent rate is also discussed.



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7Be concentration in the near-surface layer of the air in Bialystok (north-eastern Poland) in the years 1992–2010

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Jacek Kapała, Maria Karpińska, Stanisław Mnich, Anna Gromotowicz-Popławska, Grzegorz Kulesza
Weekly measurements of air ⁷Be concentrations (n = 769) were performed in the years 1992–2010 in Bialystok (north-eastern Poland) using gamma spectrometry. The arithmetic mean (AM) concentration of ⁷Be was 2.51 mBq m⁻³, and the median (M) was 2.24 mBq m⁻³ (range 0.47–7.81 mBq m⁻³). The observed ⁷Be concentrations were within the range of levels recorded in Europe. Typical seasonal variability was observed. Concentrations of ⁷Be in the warm season (May, June, July) were almost twice as high as those in the cold season (November, December, January).A correlation was found between weekly ⁷Be concentrations and mean weekly values of relative humidity, temperature, and wind speed throughout the observation period. Pearson's correlation coefficients were −0.63, p < 0.001; 0.477, p < 0.001; −0.288, p < 0.001, respectively.The correlation coefficient between sunspot number and mean annual ⁷Be concentrations in the air in the years 1992–2010 was −0.609.



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Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27





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Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27





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Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27





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Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27





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Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27





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Whole Sequences and Characteristics of mcr-1-Harboring Plasmids of Escherichia coli Strains Isolated from Livestock in South Korea

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


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Circulation of Highly Drug-Resistant Clostridium difficile Ribotypes 027 and 001 in Two Tertiary-Care Hospitals in Mexico

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


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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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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 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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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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Genetic Interactions Between BOB1 and Multiple 26S Proteasome Subunits Suggest a Role for Proteostasis in Regulating Arabidopsis Development

Protein folding and degradation are both required for protein quality control, an essential cellular activity that underlies normal growth and development. We investigated how BOB1, an Arabidopsis thaliana small heat shock protein, maintains normal plant development. bob1 mutants exhibit organ polarity defects and have expanded domains of KNOX gene expression. Some of these phenotypes are ecotype specific suggesting that other genes function to modify them. Using a reverse genetic approach we identified an interaction between BOB1 and FIL, a gene required for abaxial organ identity. We also performed an EMS enhancer screen using the bob1-3 allele to identify pathways that are sensitized by a loss of BOB1 function. This screen identified genetic, but not physical, interactions between BOB1 and the proteasome subunit RPT2a. Two other proteasome subunits, RPN1a and RPN8a, also interact genetically with BOB1. Both BOB1 and the BOB1-interacting proteasome subunits had previously been shown to interact genetically with the transcriptional enhancers AS1 and AS2, genes known to regulate both organ polarity and KNOX gene expression. Our results suggest a model in which BOB1 mediated protein folding and proteasome mediated protein degradation form a functional proteostasis module required for ensuring normal plant development.

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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-MeC₂₈ 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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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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Landiolol hydrochloride to successfully treat refractory ventricular arrhythmia during weaning from cardiopulmonary bypass

We effectively treated refractory ventricular arrhythmia (RVA) at the time of weaning from the cardiopulmonary bypass (CPB) during aortic valve replacement with landiolol for three patients who failed to respond to electrical defibrillation. Demographic data, comorbid factors, and preoperative finding were noted [Table 1].

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K911 - Preparing for Medicare's New MBI Format

Sponsored by ZOLL Data Management. In this Knowledge911 video on the RescueNet Billing system, we'll be walking you through the steps necessary to prepare your system for the new Medicare MBI numbers. Medicare expects to roll out this new format in April of 2018 and you'll need to prepare your system beforehand to accommodate these new identification numbers.

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Cost-utility analysis of cervical deformity surgeries using one-year outcome

Cost-utility analysis, a special case of cost-effectiveness analysis, estimates the ratio between the cost of an intervention to the benefit it produces in number of quality-adjusted life years. Cervical deformity correction has not been evaluated in terms of cost-utility and in the context of value-based health care. Our objective, therefore, was to determine the cost-utility ratio of cervical deformity correction.

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CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles [Genetics]

Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of...

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The ZBED6-IGF2 axis has a maȷor effect on growth of skeletal muscle and internal organs in placental mammals [Genetics]

A single nucleotide substitution in the third intron of insulin-like growth factor 2 (IGF2) is associated with increased muscle mass and reduced subcutaneous fat in domestic pigs. This mutation disrupts the binding of the ZBED6 transcription factor and leads to a threefold up-regulation of IGF2 expression in pig skeletal muscle....

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Pivotal roles of PCNA loading and unloading in heterochromatin function [Genetics]

In Saccharomyces cerevisiae, heterochromatin structures required for transcriptional silencing of the HML and HMR loci are duplicated in coordination with passing DNA replication forks. Despite major reorganization of chromatin structure, the heterochromatic, transcriptionally silent states of HML and HMR are successfully maintained throughout S-phase. Mutations of specific components of the...

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Reply to "Lumbar Transforaminal Epidural Steroid Injection in Patients With Chronic Unilateral Radicular Pain"

No abstract available

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Retraction Re: Expression of Concern. Am J Phys Med Rehabil 2017;96:761

No abstract available

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Injury of the Hypothalamus in Patients With Hypoxic–Ischemic Brain Injury: A Diffusion Tensor Imaging Study

Objectives The survival rate for hypoxic–ischemic brain injury (HI-BI) is less than 20%. Several brain regions, including the caudate, hippocampus, and hypothalamus, are vulnerable to HI-BI. Hypothalamus is involved in regulation of temperature, sleep-wakefulness cycle, emotional behavior, and memory function. Using diffusion tensor imaging, we examined injury of the hypothalamus in patients with HI-BI. Methods Twelve patients with HI-BI and 27 healthy control subjects were recruited. The region of interest was defined for the hypothalamus and the fractional anisotropy and apparent diffusion coefficient were measured. Results The fractional anisotropy value was significantly lower in the patient group compared with the control group (P

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Three-Year Changes in Physical Activity and Subsequent Loss of Ability to Walk 400 m in Older Adults: The InCHIANTI Study

We examined the associations of maintaining or increasing physical activity (PA) for a 3-yr follow-up with subsequent incident inability to complete the 400-m walk test (i.e., mobility disability) for 6 yrs of follow-up in older adults. This study included 421 participants 65 yrs and older. The 400-m walk test was assessed at baseline and at 3-, 6-, and 9-yr follow-up. Physical activity was self-reported through a 6-point rating scale at baseline and 3-yr follow-up. Three-year cumulative PA (i.e., average at baseline and at 3-yr follow-up) and its changes (i.e., from baseline to 3-yr follow-up) were linked to subsequent incidence of mobility disability for 6 yrs of follow-up (i.e., from 3- to 9-yr follow-up), after adjustment for potential covariates. After the 3-yr period, incidence of mobility disability for the subsequent 6 yrs of follow-up occurred in 129 participants. The odds ratio (95% confidence interval) of incident mobility disability associated with 1-category increase in cumulative PA was 0.63 (0.41–0.97, P = 0.036). The odds ratio (95% confidence interval) of incident mobility disability associated with 1-category increase in changes in PA was 0.56 (0.38–0.84, P = 0.005). Hence, maintaining or increasing PA levels is associated with a reduced risk of mobility disability among older adults.

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Efficacy of Armeo® Robotic Therapy Versus Conventional Therapy on Upper Limb Function in Children With Hemiplegic Cerebral Palsy

Objective The aim of this study was to examine the efficacy of Armeo robotic therapy, compared with conventional therapy, on upper limb function in children with hemiplegic cerebral palsy. Design Thirty children with hemiplegic cerebral palsy, with ages ranging from 6 to 8 yrs, were selected for this randomized controlled study and randomly assigned to two groups. The study group (n = 15) received 12 wks of Armeo robotic therapy (45 min/session, 3 days/wk) and the control group (n = 15) received conventional therapy for the same period. The measured outcomes were the Modified Ashworth Scale and the Quality of Upper Extremity Skills Test, measured at baseline and after 12 wks of intervention. Results Children in the study group showed significant improvement in the mean values of all the measured variables, compared with those in the control group (P

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Ultrasound-Guided S1 Transforaminal Epidural Injection Using the In-Plane Approach and Color Doppler Imaging

Recently, several studies have investigated the effectiveness of the ultrasound-guided lumbosacral transforaminal epidural injection. However, the ultrasound-guided S1 transforaminal epidural injection using an out-of-plane approach, which was previously reported, may cause an intestinal injury or intravascular injection because the needle tip tends to be invisible in the out-of-plane approach. In this study, therefore, we report a new method of ultrasound-guided S1 transforaminal epidural injection using the in-plane approach and color Doppler. In addition, we also report the usefulness of color Doppler imaging for finding the S1 foramen and confirming the accuracy of the injection.

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Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model

Objectives Intervertebral disc (IVD) degenerates progressively with age and after injuries. In this study, we aimed to characterize early molecular events underlying disc degeneration using a mouse tail IVD injury model. Design We have established a transcutaneous minimally invasive approach to induce mouse tail IVD injury under fluoroscopic guidance. Morphological and molecular changes in the injured IVDs are compared with the baseline features of adjacent intact levels. Results After needle puncture, tail IVDs exhibited time-dependent histological changes. The aggrecan neoepitope VDIPEN was evident from 2 days to 4 wks after injury. A disintegrin and metalloproteinase domain-containing protein 8 (adam8) is a surface protease known to cleave fibronectin in the IVD. Gene expression of adam8 was elevated at all time points after injury, whereas the increase of C-X-C motif chemokine ligand (cxcl)-1 gene expression was statistically significant at 2 days and 2 wks after injury. Type 1 collagen gene expression decreased initially at day 2 but increased at 2 wks after injury, whereas no significant change in type 2 collagen gene expression was observed. The extracellular matrix gene expression pattern is consistent with fibrocartilage formation after injury. Conclusions Mouse tail IVDs degenerate after needle puncture, as demonstrated by histological changes and aggrecan degradation. The minimally invasive tail IVD injury model should prove useful to investigators studying mechanisms of IVD degeneration and repair.

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Trunk Exercises Improve Gait Symmetry in Parkinson Disease: A Blind Phase II Randomized Controlled Trial

Objective Deficits in step-to-step symmetry and trunk muscle activations have been linked to falls in Parkinson disease. Given such symptoms are poorly managed with anti-parkinsonian medications, alternate therapies are needed. This blind phase II randomized controlled trial sought to establish whether exercise can improve step-to-step symmetry in Parkinson disease. Design Twenty-four Parkinson disease patients with a falls history completed baseline assessments of symptom severity, balance confidence, mobility, and quality of life. Step-to-step symmetry was assessed by deriving harmonic ratios from three-dimensional accelerations collected for the head and trunk. Patients were randomly assigned to either 12 wks of exercise and falls prevention education or falls prevention education only. Both groups repeated the baseline tests 12 and 24 wks after the initial assessment. The Australian and New Zealand Clinical Trials Registry number is ACTRN12613001175763. Results At 12 wks, the exercise group had statistically significant and clinically relevant improvements in anterior-posterior step-to-step trunk symmetry. In contrast, the education group recorded statistically significant and clinically meaningful reductions in medial-lateral and vertical step-to-step trunk symmetry at 12 wks. Conclusions Given that step-to-step symmetry improved for the exercise group and declined for the education group after intervention, active interventions seem more suited to increasing independence and quality of life for people with Parkinson disease. To Claim CME Credits Complete the self-assessment activity and evaluation online at http://ift.tt/1l80W45 CME Objectives Upon completion of this article, the reader should be able to do the following: (1) Describe the effect deficits in trunk muscle function have on gait in individuals with Parkinson disease; (2) Identify the benefits of targeted trunk exercises on step-to-step symmetry; and (3) Discuss the benefits of improving step-to-step symmetry in individuals with Parkinson disease. Level Advanced Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

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Effectiveness of Shortwave Diathermy for Subacromial Impingement Syndrome and Value of Night Pain for Patient Selection: A Double-Blinded, Randomized, Placebo-Controlled Trial

Objective The aim of this study was to investigate the effectiveness of short wave diathermy (SWD) in patients with subacromial impingement syndrome. Design In this double-blinded, randomized, placebo-controlled trial, 57 patients (aged 35–65 yrs) were classified into night pain positive (NP[+]) (n = 28) and night pain negative (NP[−]) (n = 29) groups. Both groups were randomly assigned to SWD (NP[+], n = 14; NP[−], n = 14) and sham (NP[+], n = 15; NP[−], n = 14) subgroups. Visual analog scale, Constant-Murley Scale (CS), and Shoulder Disability Questionnaire (SDQ) scores were used for evaluation. Results There was only a significant difference in pain with activity at 1-mo (mean difference [MD], −1.65; 95% confidence interval, −3.01 to −0.28]) and 2-mo evaluations (MD, −2.1; 95% confidence interval, −3.51 to −0.69) between SWD versus sham groups. In the NP(+) SWD group, the CS pain score was significantly higher than in the NP(+) sham group at all evaluations after treatment. At 1 mo, the NP(−) SWD group showed significantly better pain, strength, total CS, and SDQ scores than the NP(−) sham group. At 2 mos, the pain, range of motion, strength, and total CS and SDQ scores were better in the NP(−) SWD group than in the NP(−) sham group (P

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Graduate Medical Education Funding and Curriculum in Physical Medicine and Rehabilitation: A Survey of Physical Medicine and Rehabilitation Department Chairs

This national survey highlights graduate medical education funding sources for physical medicine and rehabilitation (PM&R) residency programs as well as perceived funding stability, alignment of the current funding and educational model, the need of further education in postacute care settings, and the practice of contemporary PM&R graduates as perceived by PM&R department/division chairs. Approximately half of the reported PM&R residency positions seem to be funded by Centers of Medicare and Medicaid Services; more than 40% of PM&R chairs believe that their residency program is undersized and nearly a quarter feel at risk for losing positions. A total of 30% of respondents report PM&R resident experiences in home health, 15% in long-term acute care, and 52.5% in a skilled nursing facility/subacute rehabilitation facility. In programs that do not offer these experiences, most chairs feel that this training should be included. In addition, study results suggest that most PM&R graduates work in an outpatient setting. Based on the results that chairs strongly feel the need for resident education in postacute care settings and that most graduates go on to practice in outpatient settings, there is a potential discordance for our current Centers of Medicare and Medicaid Services graduate medical education funding model being linked to the acute care setting.

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Effect of Stretching on Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model

Objective Stretching of fascia is an important component of manual and movement therapies. We previously showed that in pigs, a unilateral thoracolumbar fascia injury combined with movement restriction (hobble) produced contralateral loss of fascia mobility (shear strain during passive trunk flexion measured with ultrasound) similar to findings in human subjects with chronic low back pain. We now tested whether such abnormalities could be reversed by removing the hobble with or without daily stretching for 1 mo. Design Thirty pigs were randomized to control, injury, or injury + hobble for 8 wks. The hobble restricted hip extension ipsilateral to the injury. At week 8, the injury + hobble group was subdivided into continued hobble, removed hobble, and removed hobble + stretching (passively extending the hip for 10 min daily). Results Removing hobbles restored normal gait speed but did not restore fascia mobility. Daily passive stretching was not superior to removing hobbles, as there was no significant improvement in fascia mobility with either treatment group (removed hobble or stretching). Conclusions Reduced fascia mobility in response to injury and movement restriction worsens over time and persists even when movement is restored. Reversing fascia abnormalities may require either longer than 1 mo or a different treatment "dose" or modality.

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The Emergence of the Rehabilitative Strategy: The Driving Forces in the United States

The aim of this essay was to show the impact that driving forces have had on the emergence of rehabilitation as a health strategy in the United States. Specifically, this essay (1) identifies the driving forces that have addressed the development of rehabilitation, (2) examines how the rehabilitative strategy has been driven by the driving forces through turning points and facilitators, and (3) identifies the barriers of each force against the development of rehabilitation. Critical and scoping review of the literature was conducted from the late 1910s until the end of the century. War, economy, the power of the state, and science were identified as the driving forces that led rehabilitation to become a health strategy complementing prevention, promotion, cure, and palliation. World War I and II played as a stimulus for rehabilitation, federal funding facilitated its development, acts, amendments, and governmental programs enabled its implementation, and the acknowledgment of physical medicine and rehabilitation as medical field contributed to its international recognition as health strategy. World Health Organization's International Classification of Functioning, Disability and Health is also identified as an emerging facilitator of rehabilitation. Based on the example of United States, this article closes with recommendations toward the implementation of rehabilitation as a health strategy in countries where so far this has not occurred.

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Effect of Full-Length Carbon Fiber Insoles on Lower Limb Kinetics in Patients With Midfoot Osteoarthritis: A Pilot Study

Objectives We investigated the effects of full-length carbon fiber (FCF) insoles on gait, muscle activity, kinetics, and pain in patients with midfoot osteoarthritis (OA). Design We enrolled 13 patients with unilateral midfoot OA (mild: Visual Analog Scale [VAS] range, 1–3; moderate, VAS range, 4–7) and healthy controls. All participants were asked to walk under two conditions: with and without FCF insole. The outcome measures were ground reaction force, quantitative gait parameters, electromyography activities and pain severity (VAS). Results In the patients with moderate midfoot OA, significantly longer gait cycle and higher muscle activity of lower limb during loading-response phase were observed while walking without FCF insoles. In the mild midfoot OA group, there was no significant difference in VAS score (without, 2.0 ± 1.0 vs. with, 2.0 ± 0.5) with FCF insole use. However, significantly reduced VAS score (without, 5.5 ± 1.4 vs. with, 2.0 ± 0.5) and muscle activity of the tibialis anterior and increased muscle activity of gastrocnemius were observed in the moderate midfoot OA group by using an FCF insole (P

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Lumbar Transforaminal Epidural Steroid Injection in Patients With Chronic Unilateral Radicular Pain

No abstract available

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Association Between Sensorimotor Impairments and Functional Brain Changes in Patients With Low Back Pain: A Critical Review

Low back pain (LBP) coincides with sensorimotor impairments, for example, reduced lumbosacral tactile and proprioceptive acuity and postural control deficits. Recent functional magnetic resonance imaging studies suggest that sensorimotor impairments in LBP may be associated with brain changes. However, no consensus exists regarding the relationship between functional brain changes and sensorimotor behavior in LBP. Therefore, this review critically discusses the available functional magnetic resonance imaging studies on brain activation related to nonnociceptive somatosensory stimulation and motor performance in individuals with LBP. Four electronic databases were searched, yielding nine relevant studies. Patients with LBP showed reduced sensorimotor-related brain activation and a reorganized lumbar spine representation in higher-order (multi)sensory processing and motor regions, including primary and secondary somatosensory cortices, supplementary motor area, and superior temporal gyrus. These results may support behavioral findings of sensorimotor impairments in LBP. In addition, patients with LBP displayed widespread increased sensorimotor-evoked brain activation in regions often associated with abnormal pain processing. Overactivation in these regions could indicate an overresponsiveness to sensory inputs that signal potential harm to the spine, thereby inducing overgeneralized protective responses. Hence, functional brain changes could contribute to the development and recurrence of LBP. However, future studies investigating the causality between sensorimotor-related brain function and LBP are imperative.

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Battlefield Acupuncture: An Emerging Method for Easing Pain

No abstract available

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Tyraminergic modulation of agonistic outcomes in crayfish

Abstract

Octopamine, a biogenic amine, modulates various behaviors, ranging from locomotion and aggression to learning and memory in invertebrates. Several studies recently demonstrated that tyramine, the biological precursor of octopamine, also affects behaviors independent of octopamine. Here we investigated the involvement of tyramine in agonistic interaction of the male crayfish Procambarus clarkii. When male crayfish fight, larger animals (3–7% difference in body length) are more likely to win. By contrast, direct injection of tyramine or octopamine counteracted the physical advantage of larger animals. Tyramine or octopamine-injected naive large animals were mostly beaten by untreated smaller naive animals. This pharmacological effect was similar to the loser effect in which subordinate larger animals are frequently beaten by smaller animals. Furthermore, loser effects were partly eliminated by either injection of epinastine, an octopamine blocker, or yohimbine, a tyramine blocker, and significantly diminished by injection of a mixture of both blockers. We also observed that tyramine levels in the subesophageal ganglion were remarkably increased in subordinate crayfish after losing a fight. These results suggest that tyramine modulates aggressive levels of crayfish and contributes to the loser effect in parallel with octopamine.

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Transient and sustained ERP activity related to feedback processing in the probabilistic selection task

Publication date: Available online 27 February 2018
Source:International Journal of Psychophysiology
Author(s): Robert West, Kira Bailey, Stephen Anderson
Feedback processing represents a fundamental component of adaptive decision-making. Extensive research using event-related brain potentials (ERPs) has explored the medial frontal feedback negativity (FN), P3a, and P3b components in the context of feedback processing. Additionally, recent studies examining the neural correlates of feedback processing in a gambling task revealed transient and sustained ERP activity over the lateral frontal and posterior regions of the scalp. Consistent with the neuroimaging literature, source analysis has localized this ERP activity to the lateral and medial frontal cortex, as well as the temporal-occipital and medial occipital cortices. The current experiments examine whether the pattern of transient medial frontal and sustained lateral frontal and posterior ERP activity extend to a reinforcement learning task, and may thereby represent a general property of feedback processing. Consistent with a large literature, the ERP data revealed the FN-P3a and P3b. In addition, these data revealed sustained ERP activity over the lateral frontal and posterior regions. These findings contribute to our understanding of the temporal dynamics of feedback processing across broadly distributed cortical and subcortical networks that are sensitive to the valence and probability of positive and negative outcomes.



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Valid but Invalid: Suboptimal ImPACT© Baseline Performance in University Athletes

ABSTRACTPurposeTo investigate the frequency of valid yet suboptimal Immediate Postconcussion Assessment and Cognitive Test© (ImPACT) performance in university athletes and to explore the benefit of subsequent ImPACT administrations.MethodsThis descriptive laboratory study involved baseline administration of ImPACT to 769 university athletes per the institution's concussion management protocol. Testing was proctored in groups of ≤ 2 participants. Participants who scored below the 16th percentile according to ImPACT normative data were re-administered ImPACT up to two additional times as these scores were thought to be potentially indicative of suboptimal effort or poor understanding of instructions. Descriptive analyses were used to examine validity indicators and individual Verbal and Visual Memory, Visual Motor Speed and Reaction Time ImPACT composite scores in initial and subsequent administrations.ResultsBased on ImPACT's validity criteria, 1% (9/769) of administrations were invalid and 14.6% (112/769) had one or more composite score 16th percentile. Clinicians must be aware of suboptimal ImPACT performance as it limits the clinical utility of the baseline assessment. Further research is needed to address factors leading to "valid" but invalid baseline performance. Purpose To investigate the frequency of valid yet suboptimal Immediate Postconcussion Assessment and Cognitive Test© (ImPACT) performance in university athletes and to explore the benefit of subsequent ImPACT administrations. Methods This descriptive laboratory study involved baseline administration of ImPACT to 769 university athletes per the institution's concussion management protocol. Testing was proctored in groups of ≤ 2 participants. Participants who scored below the 16th percentile according to ImPACT normative data were re-administered ImPACT up to two additional times as these scores were thought to be potentially indicative of suboptimal effort or poor understanding of instructions. Descriptive analyses were used to examine validity indicators and individual Verbal and Visual Memory, Visual Motor Speed and Reaction Time ImPACT composite scores in initial and subsequent administrations. Results Based on ImPACT's validity criteria, 1% (9/769) of administrations were invalid and 14.6% (112/769) had one or more composite score 16th percentile. Clinicians must be aware of suboptimal ImPACT performance as it limits the clinical utility of the baseline assessment. Further research is needed to address factors leading to "valid" but invalid baseline performance. Corresponding Author: Samuel R. Walton, 210 Emmet St. S, Department of Kinesiology, University of Virginia, Charlottesville, VA, United States, 22904. Telephone: 1-207-991-0659, Fax: 1-434-982-1389, srw2rf@virginia.edu No authors received funding for this study. The authors have no conflicts of interest to report. The results of the current study do not constitute endorsement by ACSM. The authors declare that the results of this study are clear and honest, were not fabricated or falsified and that the data were not manipulated in any way to intentionally portray anything but those outcomes which were empirically observed. Accepted for Publication: 20 February 2018 © 2018 American College of Sports Medicine

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In reply

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Ultrasound versus fiberscope-guided tracheal intubation

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Issue Information - Editorial Board

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Grass leaves as potential hominin dietary resources

Publication date: April 2018
Source:Journal of Human Evolution, Volume 117
Author(s): Oliver C.C. Paine, Abigale Koppa, Amanda G. Henry, Jennifer N. Leichliter, Daryl Codron, Jacqueline Codron, Joanna E. Lambert, Matt Sponheimer
Discussions about early hominin diets have generally excluded grass leaves as a staple food resource, despite their ubiquity in most early hominin habitats. In particular, stable carbon isotope studies have shown a prevalent C4 component in the diets of most taxa, and grass leaves are the single most abundant C4 resource in African savannas. Grass leaves are typically portrayed as having little nutritional value (e.g., low in protein and high in fiber) for hominins lacking specialized digestive systems. It has also been argued that they present mechanical challenges (i.e., high toughness) for hominins with bunodont dentition. Here, we compare the nutritional and mechanical properties of grass leaves with the plants growing alongside them in African savanna habitats. We also compare grass leaves to the leaves consumed by other hominoids and demonstrate that many, though by no means all, compare favorably with the nutritional and mechanical properties of known primate foods. Our data reveal that grass leaves exhibit tremendous variation and suggest that future reconstructions of hominin dietary ecology take a more nuanced approach when considering grass leaves as a potential hominin dietary resource.



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The costal skeleton of the Regourdou 1 Neandertal

Publication date: Available online 26 February 2018
Source:Journal of Human Evolution
Author(s): Asier Gómez-Olivencia, Trenton Holliday, Stéphane Madelaine, Christine Couture-Veschambre, Bruno Maureille
The morphology and size of the Neandertal thorax is a subject of growing interest due to its link to general aspects of body size and shape, including physiological aspects related to bioenergetics and activity budgets. However, the number of well-preserved adult Neandertal costal remains is still low. The recent finding of new additional costal remains from the Regourdou 1 (R1) skeleton has rendered this skeleton as one of the most complete Neandertal costal skeletons with a minimum of 18 ribs represented, five of which are complete or virtually complete. Here we describe for the first time all the rib remains from R1 and compare them to a large modern Euroamerican male sample as well as to other published Neandertal individuals. The costal skeleton of this individual shows significant metric and morphological differences from our modern human male comparative sample. The perceived differences include: dorsoventrally large 1st and 2nd ribs, 3rd ribs with a very closed dorsal curvature and large maximum diameters at the posterior angle, a large tubercle-iliocostal line distance in the 4th rib, thick shafts at the dorsal end of its 6th ribs, thick mid-shafts of the 8th ribs, large articular tubercles at the 9th ribs, and thick shafts of the 11th and 12th ribs. Here we also describe a new mesosternal fragment: the left lateral half of sternebral segments 4 and 5. This portion reveals that the mesosternum of R1 had a sternal foramen in its inferiormost preserved sternal segment and supports previous estimation of the total length of this mesosternum.The new costal remains from R1 support the view that Neandertals, when compared with modern humans, show a significantly different thorax, consistent with differences found in other anatomical regions such as the vertebral column and pelvis.



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Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats

New Findings

• What is the central question of this study?

  Does fetal hypothyroidism in rats alter uterine contractions and structure in the adult offspring?

• What is the main finding and its importance?

  Our study indicated that maternal hypothyroidism during pregnancy increased gestational length and decreased litter size as well as delayed puberty onset; in addition, maternal hypothyroidism caused irregular uterine contractions and histological changes in the uterus in the female offspring. This model may contribute to a better understanding of the cellular and molecular mechanisms involved in uterine contractions in fetal hypothyroidism, studies which are not possible in humans, and may help for establishing therapeutic methods for these disorders observed in uterine contractions.

Abstract

Thyroid hormones play an essential role in fetal growth. Hypothyroidism impairs reproductive function in both humans and animals. This study aims to assess the effects of fetal hypothyroidism on uterine smooth muscle contraction and structure in the adult offspring. The control group consumed tap water, while the hypothyroid group received water containing 0.025% of 6-propyl-2-thiouracial throughout gestation from mating until delivery. Isometric contractility and histological changes in uterine tissue were evaluated in female Wistar rats. We tested the effects of carbachol (10⁻¹⁰–10⁻³ M) and oxytocin (10⁻¹³–10⁻⁸ M) on uterine smooth muscle contraction in the fetal hypothyroid (FH) and control groups. Compared to controls, carbachol induced contractions with lower amplitude in the FH group (area under the curve: 1820.0 ± 250.0 vs. 1370.0 ± 125.0 arbitrary units, p < 0.001, in the control and FH groups, respectively) and frequency (86.4 ± 7.3 vs. 37.0 ± 6.1 arbitrary units, p < 0.001). Similarly after exposure to oxytocin, the amplitude (6614.0 ± 492.2 vs. 4793.0 ± 735.2 arbitrary units, p < 0.001) and frequency (367.4 ± 32.0 vs. 167.0 ± 39.0 arbitrary units, p < 0.001) of uterine contractions in the FH group were significantly lower than in the controls. In addition, the thickness of the endometrium and smooth muscle layer, and the cross-sectional area of the uterus were also significantly lower in the FH groups. Gestational length was longer and litter size was smaller in FH rats compared to controls; FH offspring also had delayed puberty. In conclusion, thyroid hormone deficiency during pregnancy increased gestational length and decreased litter size; delayed puberty onset, reduced uterine rhythmic contractions and resulted in uterine structural changes in the offspring.

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Does local factors alter discharge times after surgery?

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Positive end-expiratory pressure-induced increase in external jugular venous pressure does not predict fluid responsiveness in laparoscopic prostatectomy

Abstract

Background

Dynamic change in central venous pressure (CVP) was associated with fluid responsiveness. External jugular venous pressure (EJVP) may reliably estimate CVP and have the advantages of being less invasive. We investigated whether increase in EJVP induced by positive end-expiratory pressure (PEEP) could be a reliable predictor of fluid responsiveness in patients undergoing robot-assisted laparoscopic prostatectomy (RALP).

Methods

Fifty patients who underwent RALP with steep Trendelenburg position were enrolled. PEEP of 10 cmH₂O was applied for 5 min and then 300 ml of colloid was administered. EJVP, stroke volume variation (SVV), and cardiac index calculated by pulse contour method were measured before and after the PEEP challenge and colloid administration. Increase in cardiac index > 10% was used to define the fluid responsiveness.

Results

Twenty-six patients were fluid responders. Neither the increase in EJVP after the initial PEEP nor SVV was significantly different between responders and non-responders. They were not significantly correlated with an increase in cardiac index. The areas under the receiver operating characteristic curve (AUC) of these two variables were not significantly greater than 0.5. However, a post hoc analysis revealed that AUC of a decrease in EJVP after removal of PEEP was significantly greater than 0.50.

Conclusion

Our study results suggested that SVV and increase in EJVP after applying PEEP were not accurate predictors of fluid responsiveness during RALP. Further studies are required to find an adequate preload index in robot-assisted urologic surgery with steep Trendelenburg position.

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Candidate genes for cooperation and aggression in the social wasp Polistes dominula

Abstract

Cooperation and aggression are ubiquitous in social groups, and the genetic mechanisms underlying these behaviours are of great interest for understanding how social group formation is regulated and how it evolves. In this study, we used a candidate gene approach to investigate the patterns of expression of key genes for cooperation and aggression in the brain of a primitively eusocial wasp, Polistes dominula, during colony founding, when multiple foundresses can join the same nest and establish subtle hierarchies of dominance. We used a comparative approach to select candidate genes for cooperation and aggression looking at two previously published studies on global gene expression in wasps and ants. We tested the expression of these genes in P. dominula wasps that were either displaying aggressive behaviour (dominant and single foundresses) or cooperation (subordinate foundresses and workers) towards nestmates. One gene in particular, the egg yolk protein vitellogenin, known for its reproductive role in insects, displayed patterns of expression that strongly matched wasp social rank. We characterize the genomic context of vitellogenin by building a head co-expression gene network for P. dominula, and we discuss a potential role for vitellogenin as a mediator of social interactions in wasps.

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Spirituality for Mental Health and Well-Being of Adult Refugees in Europe

Abstract

This article reports on a pre- and post-test experimental study with 4504 refugees in 38 camps across nine destination countries. The aim was to examine the role of spirituality and a specially designed spiritual education programme in promoting mental health of refugees. A pre- and post-test experimental design has been used with three scales to examine the outcome measures: (1) the trauma screening questionnaire (2) life orientation test-revised and (3) mental health inventory-38. Results showed that compared with pre-test scores, the average post-test scores of the refugees on the trauma questionnaire were lower, and higher on optimism measure, and mental health inventory. Voluntary participation, full attendance and self-practice willingness were favourable predictors of refugee mental health. Hierarchical regression model showed that self-practice willingness was the most important predictor of positive mental health of refugees. Findings make a case for interventions for refugees grounded in cultural competency and spirituality.

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Examining Difference in Immigration Stress, Acculturation Stress and Mental Health Outcomes in Six Hispanic/Latino Nativity and Regional Groups

Abstract

Little is known about the specific behavioral health impact of acculturation stressors that affect Hispanic/Latino immigrant sub-groups. These immigration-related stressors and traumatic events may have differential impact on depression depending on country/region of origin. Using a measure of immigration and acculturation stress, the current study sought to determine differences in the impact of stress on six sub-groups of Hispanic immigrants. Data on stress and depression were examined using a large, representative adult immigrant sample (N = 641). Controlling for age, gender and years in the US, factorial analysis of covariance revealed significant differences on total Hispanic Stress Inventory 2 (HSI2) stress appraisal scores based on country/region of origin. Pair wise comparisons between country/region of origin groups revealed that Mexicans had higher levels of stress compared to Cuban or Dominican immigrants. Several patterns of differential stress were also found within sub-domains of the HSI2. Using regression models, HSI2 stress appraisals and their interaction with country of origin proved to not be significant predictors of depression (PHQ9), while gender and age were significant. Differences in HSI2 stress that are based on nativity may be moderated by cultural resilience that ultimately serves a protective role to prevent the onset of depression.

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Comparing spiking and slow wave activity from invasive electroencephalography in patients with and without seizures

Publication date: Available online 27 February 2018
Source:Clinical Neurophysiology
Author(s): Brian Nils Lundstrom, Christian Meisel, Jamie Van Gompel, Matt Stead, Greg Worrell
ObjectivesTo develop quantitative measures for estimating seizure probability, we examine intracranial EEG data from patient groups with three qualitative seizure probabilities: patients with drug resistant focal epilepsy (high), these patients during cortical stimulation (intermediate), and patients who have no history of seizures (low).MethodsPatients with focal epilepsy were implanted with subdural electrodes during presurgical evaluation. Patients without seizures were implanted during treatment with motor cortex stimulation for atypical facial pain.ResultsThe rate and amplitude of spikes correlate with qualitative seizure probability across patient groups and with proximity to the seizure onset zone in focal epilepsy patients. Spikes occur earlier during the negative oscillation of underlying slow activity (0.5-2 Hz) when seizure probability is increased. Similarly, coupling between slow and fast activity is increased.ConclusionsThere is likely a continuum of sharply contoured activity between non-epileptiform and epileptiform. Characteristics of spiking and how spikes relate to slow activity can be combined to predict seizure onset zones.SignificanceIntracranial EEG data from patients without seizures represent a unique comparison group and highlight changes seen in spiking and slow wave activity with increased seizure probability. Slow wave activity and related physiology are an important potential biomarker for estimating seizure probability.



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Intra-operative characterisation of subthalamic oscillations in Parkinson’s disease

Publication date: Available online 27 February 2018
Source:Clinical Neurophysiology
Author(s): Xinyi Geng, Xin Xu, Andreas Horn, Ningfei Li, Zhipei Ling, Peter Brown, Shouyan Wang
ObjectiveThis study aims to use the activities recorded directly from the deep brain stimulation (DBS) electrode to address the focality and distinct nature of the local field potential (LFP) activities of different frequency.MethodsPre-operative and intra-operative magnetic resonance imaging (MRI) were acquired from patients with Parkinson's disease (PD) who underwent DBS in the subthalamic nucleus and intra-operative LFP recording at rest and during cued movements. Images were reconstructed and 3-D visualized using Lead-DBS® toolbox to determine the coordinates of contact. The resting spectral power and movement-related power modulation of LFP oscillations were estimated.ResultsBoth subthalamic LFP activity recorded at rest and its modulation by movement had focal maxima in the alpha, beta and gamma bands. The spatial distribution of alpha band activity and its modulation was significantly different to that in the beta band. Moreover, there were significant differences in the scale and timing of movement related modulation across the frequency bands.ConclusionSubthalamic LFP activities within specific frequency bands can be distinguished by spatial topography and pattern of movement related modulation.SignificanceAssessment of the frequency, focality and pattern of movement related modulation of subthalamic LFPs reveals a heterogeneity of neural population activity in this region. This could potentially be leveraged to finesse intra-operative targeting and post-operative contact selection.



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Does Acute Radio-Frequency Electromagnetic Field Exposure Affect Visual Event-Related Potentials in Healthy Adults?

Publication date: Available online 27 February 2018
Source:Clinical Neurophysiology
Author(s): Anna Dalecki, Sarah P. Loughran, Adam Verrender, Catriona A. Burdon, Nigel A.S. Taylor, Rodney J. Croft
ObjectiveTo use improved methods to address the question of whether acute exposure to radio-frequency (RF) electromagnetic fields (RF-EMF) affects early (80-200 ms) sensory and later (180-600 ms) cognitive processes as indexed by event-related potentials (ERPs).MethodsThirty-six healthy subjects completed a visual discrimination task during concurrent exposure to a Global System for Mobile Communications (GSM)-like, 920 MHz signal with peak-spatial specific absorption rate for 10 g of tissue of 0 W/kg of body mass (Sham), 1 W/kg (Low RF) and 2 W/kg (High RF). A fully randomised, counterbalanced, double-blind design was used.ResultsP1 amplitude was reduced (p = .02) and anterior N1 latency was increased (p = .04) during Exposure compared to Sham. There were no effects on any other ERP latencies or amplitudes.ConclusionsRF-EMF exposure may affect early perceptual (P1) and preparatory motor (anterior N1) processes. However, only two ERP indices, out of 56 comparisons, were observed to differ between RF-EMF exposure and Sham, suggesting that these observations may be due to chance.SignificanceTheseobservationsare consistent with previous findings that RF-EMF exposure has no reliable impact on cognition (e.g., accuracy and response speed).



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Interictal regional paroxysmal fast activity on scalp EEG is common in patients with underlying gliosis

Publication date: Available online 27 February 2018
Source:Clinical Neurophysiology
Author(s): Gopal Krishna Dash, Chaturbhuj Rathore, Malcolm K Jeyaraj, Pandurang Wattamwar, Sankara P Sarma, Kurupath Radhakrishnan
ObjectiveInterictal regional paroxysmal fast activity (RPFA) on scalp EEG is common in patients with focal cortical dysplasia (FCD). Little data exists regarding the presence of RPFA in other etiologies.MethodsWe studied the association between RPFA and etiology on MRI in patients with drug resistant focal epilepsy undergoing presurgical evaluation in 2011. RPFA was defined as ≥3 consecutive spikes with a frequency of ≥10Hz lasting ≥300 ms but <4 seconds.Results626 patients fulfilled the inclusion criteria. Of these, 138 (22%) patients had RPFA while rest had other interictal epileptiform discharges (IEDs). RPFA was located at posterior head region in 52.2% patients, frontal regions in 24.6% patients and over temporal regions in 17.4% patients. Focal gliosis (61, 44%) and FCD (27, 19%) were common etiologies in patients with RPFA. Compared to patients with other IEDs, patients with RPFA were more likely to have focal gliosis (61/138 vs. 39/488; p<0.0001) or FCD (27/138 vs 37/488; p<0.001) as the etiology of epilepsy.ConclusionIn developing countries, focal gliosis is more common than FCD as the underlying etiology in patients with RPFA on scalp EEG.SignificanceFocal gliosis should be considered as one of the common substrate for RPFA on scalp EEG.



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The dual-gate model for pentameric ligand-gated ion channels activation and desensitization

Abstract

Pentameric ligand-gated ion channels (pLGICs) mediate fast neurotransmission in the nervous system. Their dysfunction is associated with psychiatric, neurological and neurodegenerative disorders such as schizophrenia, epilepsy and Alzheimer's disease. Understanding their biophysical and pharmacological properties, both at the functional and structural levels, thus holds many therapeutic promises. In addition to their agonist-elicited activation, most pLGICs display another key allosteric property, namely desensitization, in which they enter a shut state refractory to activation upon sustained agonist binding. While the activation mechanisms of several pLGICs have been revealed at near-atomic resolution, the structural foundation of desensitization has long remained elusive. Recent structural and functional data now suggest that the activation and desensitization gates are distinct, and are located at both sides of the ion channel. Such a "dual gate mechanism" accounts for the marked allosteric effects of channel blockers, a feature illustrated herein by theoretical kinetics simulations. Comparison with other classes of ligand- and voltage-gated ion channels show that this dual gate mechanism emerges as a common theme for the desensitization and inactivation properties of structurally unrelated ion channels.

This article is protected by copyright. All rights reserved

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Response to letter to the editor by Finn et al. (2018)

Abstract

In their letter to the editor regarding our recent paper, Finn and colleagues, propose that the heightened motoneurone responsiveness in chronic hypoxia (CH) compared to acute hypoxia (AH) may relate primarily to greater peripheral fatigue in AH than CH, rather than motoneuronal adaptations to hypoxia.

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Airborne gamma-ray spectra processing: Extracting photopeaks

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Eugene Druker
The acquisition of information from the airborne gamma-ray spectra is based on the ability to evaluate photopeak areas in regular spectra from natural and other sources. In airborne gamma-ray spectrometry, extraction of photopeaks of radionuclides from regular one-second spectra is a complex problem. In the region of higher energies, difficulties are associated with low signal level, i.e. low count rates, whereas at lower energies difficulties are associated with high noises due to a high signal level. In this article, a new procedure is proposed for processing the measured spectra up to and including the extraction of evident photopeaks. The procedure consists of reducing the noise in the energy channels along the flight lines, transforming the spectra into the spectra of equal resolution, removing the background from each spectrum, sharpening the details, and transforming the spectra back to the original energy scale. The resulting spectra are better suited for examining and using the photopeaks. No assumptions are required regarding the number, locations, and magnitudes of photopeaks. The procedure does not generate negative photopeaks. The resolution of the spectrometer is used for the purpose. The proposed methodology, apparently, will contribute also to study environmental problems, soil characterization, and other near-surface geophysical methods.



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Anesthesia of thoracic surgery in children

Summary

Providing anesthesia in children with thoracic disease is a challenging task. The effects of the underlying disease, the surgical interventions, and preexisting condition of the patient need to be considered when planning perioperative care. The perioperative care for children undergoing thoracic surgery requires specific techniques adapted to the pediatric physiology and anatomy. This review is focused on anesthetic strategies for thoracic surgery with an emphasis on perioperative analgesia including neuraxial techniques.

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Intentional tracheoesophageal fistula cannulation for gastric decompression in type C esophageal atresia

Summary

We describe a nonsurgical technique for managing gastric distention in infants with type C esophageal atresia, involving intubating the trachea with an umbilical catheter and entering the stomach through the fistula as soon as a flexible bronchoscope found its wide-open orifice. This technique might have a special role when gastric distention precedes other commonly used preventive measures.

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