bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for Caenorhabditis elegans neuron classes
Authors: Lorenzo Ramiro , Onizuka Michiho , Defrance Matthieu , Laurent Patrick 
Published: May 2020

AbstractSingle-cell RNA-sequencing (scRNA-seq) of the Caenorhabditis elegans nervous system offers the unique opportunity to obtain a partial expression profile for each neuron within a known connectome. Building on recent scRNA-seq data and on a molecular atlas describing the expression pattern of ∼800 genes at the single cell resolution, we designed an iterative clustering analysis aiming to match each cell-cluster to the ∼100 anatomically defined neuron classes of C. elegans. This heuristic approach successfully assigned 97 of the 118 neuron classes to a cluster. Sixty two clusters were assigned to a single neuron class and 15 clusters grouped neuron classes sharing close molecular signatures. Pseudotime analysis revealed a maturation process occurring in some neurons (e.g. PDA) during the L2 stage. Based on the molecular profiles of all identified neurons, we predicted cell fate regulators and experimentally validated unc-86 for the normal differentiation of RMG neurons. Furthermore, we observed that different classes of genes functionally diversify sensory neurons, interneurons and motorneurons. Finally, we designed 15 new neuron class-specific promoters validated in vivo. Amongst them, 10 represent the only specific promoter reported to this day, expanding the list of neurons amenable to genetic manipulations.
Substrate specificities of Escherichia coli ItaT that acetylates aminoacyl-tRNAs
Authors: Zhang Chuqiao , Yashiro Yuka , Sakaguchi Yuriko , Suzuki Tsutomu , Tomita Kozo 
Published: May 2020

Abstract
Escherichia coli ItaT toxin reportedly acetylates the α-amino group of the aminoacyl-moiety of Ile-tRNAIle specifically, using acetyl-CoA as an acetyl donor, thereby inhibiting protein synthesis. The mechanism of the substrate specificity of ItaT had remained elusive. Here, we present functional and structural analyses of E. coli ItaT, which revealed the mechanism of ItaT recognition of specific aminoacyl-tRNAs for acetylation. In addition to Ile-tRNAIle, aminoacyl-tRNAs charged with hydrophobic residues, such as Val-tRNAVal and Met-tRNAMet, were acetylated by ItaT in vivo. Ile-tRNAIle, Val-tRNAVal and Met-tRNAMet were acetylated by ItaT in vitro, while aminoacyl-tRNAs charged with other hydrophobic residues, such as Ala-tRNAAla, Leu-tRNALeu and Phe-tRNAPhe, were less efficiently acetylated. A comparison of the structures of E. coli ItaT and the protein N-terminal acetyltransferase identified the hydrophobic residues in ItaT that possibly interact with the aminoacyl moiety of aminoacyl-tRNAs. Mutations of the hydrophobic residues of ItaT reduced the acetylation activity of ItaT toward Ile-tRNAIlein vitro, as well as the ItaT toxicity in vivo. Altogether, the size and shape of the hydrophobic pocket of ItaT are suitable for the accommodation of the specific aminoacyl-moieties of aminoacyl-tRNAs, and ItaT has broader specificity toward aminoacyl-tRNAs charged with certain hydrophobic amino acids.
Two children with extra-nodalMycobacterium aviumcomplex infection
Authors: Markland Ali , Tan Ben , Adamko Darryl , Diener Tania , Levett Paul N , Wiebe Sheldon , Wang Hui , Podberezin Mark , Saczek Krysztof , Milbrandt Kris , Essalah Abdulhafid , Quan William , Deneer Harry 
Published: May 2020

AbstractMycobacterium avium complex (MAC) is usually considered an opportunistic organism, which infects immunocompromised children or those with structural airway abnormalities. We present two cases of MAC infection affecting immune competent children, likely from hot tubs with primary involvement of pulmonary and urinary systems. These cases highlight the importance of asking about hot tub use in immune competent children with suspected or confirmed MAC infections.
Theory of generalized Josephson effects
Authors: Beekman Aron J 
Published: May 2020

Abstract
The DC Josephson effect is the flow of supercurrent across a weak link between two superconductors with different values of their order parameters, the phase. We formulate this notion for any kind of spontaneous continuous symmetry breaking. The quantity that flows between the two systems is the zero-wavenumber Noether current associated with the broken symmetry. The AC Josephson effect is the oscillation of current due to the energy difference between the two systems caused by an imposed asymmetric chemical potential of Noether charge. As an example of novel physics, a Josephson effect is predicted between two crystalline solids, potentially measurable as a force periodic in the separation distance.
ChurchInAction: the role of religious interventions in times of COVID-19
Authors: del Castillo Fides A , Biana Hazel T , Joaquin Jeremiah Joven B 
Published: May 2020

Abstract
In a recently published letter to the editor of this journal, the authors have called for the need to establish psychological support structures that cater to people’s mental health in this time of the coronavirus disease 2019 pandemic. To be more holistic, we extend this call to include people’s spiritual well-being as well. We highlight the initiatives of the Philippines’ religious sector. In particular, we report some of the interventions made by the Roman Catholic Church that have led to the social media hashtag, #ChurchInAction. These religious and spiritual interventions showcase the efforts of the Philippine Church and play an important role in providing assistance in time of public health crisis.
Promoter Activity-Based Case-Control Association Study onSLC6A4Highlighting Hypermethylation and Altered Amygdala Volume in Male Patients With Schizophrenia
Authors: Ikegame Tempei , Bundo Miki , Okada Naohiro , Murata Yui , Koike Shinsuke , Sugawara Hiroko , Saito Takeo , Ikeda Masashi , Owada Keiho , Fukunaga Masaki , Yamashita Fumio , Koshiyama Daisuke , Natsubori Tatsunobu , Iwashiro Norichika , Asai Tatsuro , Yoshikawa Akane , Nishimura Fumichika , Kawamura Yoshiya , Ishigooka Jun , Kakiuchi Chihiro , Sasaki Tsukasa , Abe Osamu , Hashimoto Ryota , Iwata Nakao , Yamasue Hidenori , Kato Tadafumi , Kasai Kiyoto , Iwamoto Kazuya 
Published: May 2020

AbstractAssociations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding gene SLC6A4 and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations of SLC6A4 in schizophrenia (SZ). We examined CpG sites of SLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using 3 independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site in SLC6A4 in male patients with SZ in all 3 cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and that in vitro DNA methylation at this CpG site diminished the promoter activity of SLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site in SLC6A4 is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.
0020 Differentially Expressed Genes Using Saliva Samples from Nurses Rotating Shifts
Authors: Imes C C , Monica M A , Chasens E R , Conley Y P 
Published: May 2020

Abstract

Introduction
Globally, millions of people work night or rotating shifts (i.e., shift work), including nurses and other healthcare providers. Shift work can cause insufficient and mistimed sleep which disrupts the normal circadian rhythm. Shift work is associated with an increased risk for cardio-metabolic disorders and certain cancers. This descriptive, single group, within-subject, repeated-measures study explored the effect of shift work on gene expression levels in a sample of female nurses engaged in rotating shifts.

Methods
Saliva samples were collected from ten nurses without sleep or alertness medication use or a sleep disorder. The samples were collected using DNA Genotek RNA stabilizing saliva kits after participants worked at least 3 consecutive day shifts (~ 7:30 pm) and 3 consecutive night shifts (~7:30 am). Takara Smarter Stranded Total RNA Seq Kit was used following manufacturer’s instructions on an Illumina NextSeq500. CLC Genomic Workbench 12 (Qiagen) was used for quality control, aligning the sequence reads, normalization, and differential expression analyses. Genes with log2 fold changes of ± 2.0 were included in gene set enrichment and pathway analyses using Ingenuity Pathway Analysis (IPA; Qiagen).

Results
Participants were all female, white, and mostly healthy with a mean ± SD age of 27.2 ± 4.5 years. Compared to the post-day shift samples, a total of 287 genes were differentially expressed at a log2 fold change of ± 2.0 in the post-night shift samples. The genes with the greatest increase in expression levels were: PRDX5, SLC7A5, FCGR1A, DNAJC7, PSMD4, and PER1. The genes with the greatest decrease in expression levels were: PPIP5K2, SCART1, CASP10, SLC24A4, and OSBP. Based on the IPA analyses, the differentially expressed genes play a role in gene expression, cell signaling, cell death and survival, and RNA damage and repair.

Conclusion
Significant differential gene expression in pathways associated with poor health were observed among female nurses engaged in rotating shifts. Potential molecular and cellular functions were identified that may be the mechanisms resulting in the increased health risks associated with shift work.

Support
University of Pittsburgh School of Nursing Center for Research and Evaluation Pilot/Feasibility Study Program
0021 RNA Sequencing Reveals Transcriptomic Changes in Individuals with Insomnia
Authors: Mithani S , Yun S , Pattinson C , Kim H , Guedes V , Fink A , Weljie A , Gehrman P , Gill J 
Published: May 2020

Abstract

Introduction
Insomnia affects 10–20% of the US population and is associated with negative health and psychosocial sequelae. Despite the public health impact of insomnia little is known about its underlying molecular mechanisms. The purpose of this study is to examine differentially expressed genes in 15 patients with chronic insomnia and age- and sex-matched good sleepers (n=15).

Methods
We performed total RNA-seq on 30 whole blood samples collected at 09:00 at 150 bp paired-ends on the Illumina NovaSeq-6000 platform. Alignment was performed using the STAR version 2.7.2a software on the human reference genome (GRCh38). Differential gene expression analysis was performed using DESeq2 version 1.24.0. Pathway analysis was performed using IPA, release 2019-08-30.

Results
An average of 86.7 million paired end reads per sample were sequenced. We found that 289 genes were differentially expressed in insomnia patients with a log fold change (LFC) ±0.50 and had a FDR p-value &lt; 0.05. Top dysregulated genes include CSMD1 (L2FC=-2.78; p=1.35E-06), DUX4L9 (L2FC=3.40; p=2.81E-06) and GRM4 (L2FC=2.45; p=4.50E-05). Among the functionally relevant genes, CSMD encodes a complement control protein that is known to participate in the complement activation and inflammation in the developing central nervous system. UTS2 (L2FC=1.778; p=8.94E-06) is involved in regulation of orexin A and B activity and rapid eye movement during sleep. Ingenuity Pathway Analysis revealed 3 associated networks: Hematological, Hereditary Disorder, Organismal Injury and Abnormalities (score: 46), Developmental, Hereditary Disorder, Metabolic Disease (score: 43), and Cell Cycle, Cell mediated Immune Response, Cellular Development (score: 43).

Conclusion
Overall, our study revealed dysregulated genes in individuals who suffer from insomnia. Notably, dysregulation of these functionally relevant genes could impair functional brain connectivity and synaptic function. Further investigation of these biological pathways will be useful to elucidate the pathogenesis of insomnia and identify novel biomarkers or drug targets for developing improved diagnostics and therapeutics.

Support
National Institutes of Nursing Research, Graduate Partnership Program
0034 When Should You Sleep to Maximize Alertness?
Authors: Vital-Lopez F , Doty T J , Balkin T J , Reifman J 
Published: May 2020

Abstract

Introduction
Working under sleep-restricted conditions may curtail safety and productivity. We could potentially minimize the negative effects of sleep restriction by optimizing the timing of sleep. However, to date, there are no algorithms that can determine the optimal sleep time to maximize alertness when most needed.

Methods
Our previously validated unified model of performance predicts the recuperative effects of sleep on alertness. Here, we extended this model to predict the likelihood of an individual falling and remaining asleep at any given moment, as a function of recent sleep history and time of day. Then, we combined the model with an optimization algorithm to provide optimal sleep recommendations for a given work/rest schedule. Specifically, using the model to predict the effectiveness of different sleep schedules, the algorithm determines when to sleep and for how long, so as to maximize alertness at desired times. The algorithm takes as inputs the 1) user-provided sleep history, 2) periods when the user has an opportunity to sleep, and 3) desired periods for maximum alertness, and provides as outputs sleep recommendations that are physiologically feasible and optimize alertness for the desired period. We assessed the algorithm by computing and comparing sleep recommendations for five previously published experimental studies of sleep restriction, including diurnal and nocturnal sleep.

Results
Compared to the original sleep schedules in the studies, our algorithm identified sleep recommendations that increased the predicted alertness by up to 33% and by 18% on average. These results suggest that the algorithm can tailor the timing of sleep to each specific sleep-restriction condition so as to maximize its benefits.

Conclusion
Our algorithm provides automated, customized guidance to enhance the recuperative benefits of limited sleep opportunities to maximize alertness at the most needed times. As such, it is the first quantitative sleep optimization tool for fatigue-management systems.

Support
This work was sponsored by the Military Operational Medicine Research Area Directorate of the U.S. Army Medical Research and Development Command, Ft. Detrick, MD.
0066 Glycinergic Postsynaptic Inhibition is Responsible for the Suppression of Hypoglossal Motoneuron Activity During Naturally-Occurring REM Sleep
Authors: Tobin C , Fung S J , Xi M , Chase M H 
Published: May 2020

Abstract

Introduction
The present study was undertaken to explore the role of glycinergic postsynaptic inhibition and monoaminergic disfacilitation (a withdrawal of excitatory noradrenergic and serotonergic inputs) in the control of hypoglossal motoneuron activity during REM sleep. Accordingly, glycinergic, noradrenergic and serotonergic antagonists were microinjected into the hypoglossal nucleus, and their effects on the hypoglossal nerve activity during REM sleep were examined in chronically-instrumented, unanesthetized cats.

Methods
Adults cats were prepared for monitoring behavioral states of sleep and wakefulness, and for extracellular recordings from hypoglossal nerve. Strychnine (a glycinergic antagonist) and a mixture of prazosin (a noradrenergic antagonist) and methysergide (a serotonergic antagonist) were microinjected, separately, into the hypoglossal nucleus during naturally-occurring states of sleep and wakefulness.

Results
During REM sleep, compared to non-REM sleep, the hypoglossal nerve activity decreased by 17.4±1.5% (n=17) in the control recordings (prior to the injection of strychnine). Following the microinjection of strychnine, there was only a mean decrease of 7.2±1.2% (n=12) in the nerve activity during REM sleep versus NREM sleep. The strychnine effect was statistically significant compared to control (p&lt;0.001; unpaired t-test), which indicates that strychnine blocks REM sleep-related suppression of hypoglossal nerve activity. In contrast, the microinjection of prazosin and methysergide did not significantly reduce the hypoglossal nerve activity during REM sleep (control: 15.9±2.3, n=9 vs. prazosin+methysergide: 12.6±1.4%, n=10, p=0.229, unpaired t-test).

Conclusion
The present results demonstrate that the microapplication of strychnine, but not prazosin and methysergide, into the hypoglossal nucleus significantly reduces the suppression of the hypoglossal nerve activity during naturally-occurring REM sleep. We therefore suggest that glycinergic postsynaptic inhibition is primarily responsible for the suppression of hypoglossal motoneuron activity during REM sleep.

Support
5R01NS094062
0070 The Effects of Acute Blue Wavelength Light Exposure on Functional Brain Connectivity and Mood
Authors: Alkozei A , Dailey N S , Bajaj S , Vanuk J R , Raikes A C , Grandner M A , Killgore W D 
Published: May 2020

Abstract

Introduction
Blue wavelength light is an effective treatment for delayed sleep phase syndrome, seasonal affective disorder and bipolar depression. The role of blue light in regulating melatonin production has been extensively studied, but other potential neurophysiological effects remain poorly understood. Some studies have suggested that daily blue light exposure may modulate functional brain responses within the amygdala and prefrontal cortex (PFC), potentially explaining blue light’s antidepressant effect. In this study we investigated the effects of a single 30-minute session of blue light exposure on functional resting state connectivity between the amygdala and PFC.

Methods
Twenty-nine healthy 18–32 year olds were randomly assigned to either receive 30 minutes of blue (n=17) or non-blue (amber) light (n=12) exposure followed by a 7-minute resting state scan. Pre- and post light exposure, participants completed the Positive and Negative Affect Scale, as a measure of state affect.

Results
Individuals who received blue versus amber light showed greater positive connectivity between the right amygdala and the left dorsolateral prefrontal cortex (DLPFC) (x=-24, y=46, z=18, k=90, volume p-FDR corrected, p&lt;0.001). Increased amygdala-DLFC connectivity correlated with greater decreases in negative mood for the blue (ρ=-.55, p=0.03), but not the amber group. Using Granger Causality, we found that the directionality of information flow between these two areas was bidirectional (p&lt;0.0025).

Conclusion
Blue light exposure appears to facilitate greater information flow between the amygdala and the DLPFC at rest, potentially enhancing cognitive processes that regulate arousal and mood. As blue light exposure has been shown to enhance attention and learning, using blue light exposure during practice of emotional regulation strategies, such as reappraisal, may further increase the beneficial effects of blue light on mood. In order to use blue light exposure in a more targeted manner for sleep and mood disorders, further research into the underlying neurophysiological mechanisms is needed.

Support
This research was supported by a USAMRAA grant to WDSK (W81XWH-14-1-0571) as well as by an Arizona Health Education Centers (AHEC) Research Grant to AA.
0079 Blue Light Exposure Enhances Neural Efficiency of the Task Positive Network During a Cognitive Interference Task
Authors: Killgore W D , Dailey N S , Raikes A C , Vanuk J R , Taylor E , Grandner M A , Alkozei A 
Published: May 2020

Abstract

Introduction
Light exposure has powerful effects on the circadian timing of sleep and wake, primarily through the regulation of the secretion of melatonin. However, it is becoming clear that light has additional alerting effects beyond its primary effect on the circadian system. Exposure to light, particularly blue-wavelength light, has been shown to acutely increase brain activation, alertness, and some elementary aspects of cognitive performance such as working memory and emotional anticipation during the day. Whether blue light exposure can have longer-lasting effects on brain activation and performance during more complex cognitive control tasks up to 30-minutes after light cessation is unknown.

Methods
In a sample of 30 healthy adults, we examined the effects of a single 30-minute exposure to either blue (n=14) or amber placebo (n=16) light on subsequent brain activation and performance during the Multi-Source Interference Task (MSIT) measured a half-hour after light cessation using functional magnetic resonance imaging. Mean activation in all regions showing increased task-related activation (i.e., Task Positive Network; TPN) and regions showing decreased activation (i.e., Default Mode Network; DMN) at p&lt;.001 (FWE corrected) was extracted separately for each network in SPM12 and compared between light conditions.

Results
Performance metrics for the MSIT, including accuracy, response time, and cognitive throughput, did not differ between the blue and amber conditions, suggesting that performance was sustained equally between light conditions. However, brain activation within the TPN to the interference condition of the MSIT was significantly lower (p=.024) in the blue relative to the amber condition, with no group differences observed for suppression of the DMN.

Conclusion
Compared to amber, a single exposure to blue light was associated with enhanced neural efficiency a half-hour later as demonstrated by reduced TPN activation to achieve the same level of cognitive performance. Blue light may be an effective method for optimizing neurocognitive performance under some conditions.

Support
US Army Medical Research and Materiel Command: W81XWH-14-1-0571