bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep problems in active duty military personnel seeking treatment for posttraumatic stress disorder: presence, change, and impact on outcomes
Authors: Taylor Daniel J , Pruiksma Kristi E , Hale Willie , McLean Carmen P , Zandberg Laurie J , Brown Lily , Mintz Jim , Young-McCaughan Stacey , Peterson Alan L , Yarvis Jeffrey S , Dondanville Katherine A , Litz Brett T , Roache John , Foa Edna B
Published: April 2020

Study Objectives

To examine sleep disorder symptom reports at baseline and posttreatment in a sample of active duty U.S. Army Soldiers receiving treatment for posttraumatic stress disorder (PTSD). Explore sleep-related predictors of outcomes.

Methods

Sleep was evaluated in 128 participants in a parent randomized clinical trial comparing Spaced formats of Prolonged Exposure (PE) or Present Centered Therapy and a Massed format of PE. In the current study, Spaced formats were combined and evaluated separately from Massed.

Results

At baseline, the average sleep duration was < 5 h per night on weekdays/workdays and < 6 h per night on weekends/off days. The majority of participants reported clinically significant insomnia, clinically significant nightmares, and probable sleep apnea and approximately half reported excessive daytime sleepiness at baseline. Insomnia and nightmares improved significantly from baseline to posttreatment in all groups, but many patients reported clinically significant insomnia (>70%) and nightmares (>38%) posttreatment. Excessive daytime sleepiness significantly improved only in the Massed group, but 40% continued to report clinically significant levels at posttreatment. Short sleep (Spaced only), clinically significant insomnia and nightmares, excessive daytime sleepiness, and probable sleep apnea (Massed only) at baseline predicted higher PTSD symptoms across treatment course. Short weekends/off days sleep predicted lower PTSD symptom improvement in the Spaced treatments.

Conclusions

Various sleep disorder symptoms were high at baseline, were largely unchanged with PTSD treatment, and were related to worse PTSD treatment outcomes. Studies are needed with objective sleep assessments and targeted sleep disorders treatments in PTSD patients.

Clinical Trial Registration

NCT01049516.
Aggressiveness and Deoxynivalenol Production of Nebraska Isolates of Fusarium boothii and F. graminearum
Authors: Valverde-Bogantes Esteban , Bolanos-Carriel Carlos , Hallen-Adams Heather E. , McMaster Niki , Schmale David G. , Wegulo Stephen N.
Published: April 2020

Significant losses in wheat result from Fusarium head blight (FHB) and its associated mycotoxin deoxynivalenol (DON). The predominant FHB pathogen in North America is Fusarium graminearum. F. boothii was recently confirmed for the first time in the United States as a causal agent of FHB in Nebraska wheat fields. This greenhouse study compared the aggressiveness and DON production in wheat among 13 F. graminearum and three F. boothii isolates from Nebraska. Spikes of the susceptible spring wheat cultivar Wheaton at anthesis were spray-inoculated with spores of the isolates. Severity data were used to calculate the area under the disease progress curve (AUDPC). DON concentration in the grain was quantified by gas chromatography/mass spectrometry. F. graminearum isolates were more aggressive and produced more DON than F. boothii isolates. Mean AUDPC values were 1,171 and 885 percent days for F. graminearum and F. boothii, respectively. Mean DON values were 41.0 and 13.6 µg/g for F. graminearum and F. boothii, respectively. Although only three available F. boothii isolates were used, the results are in agreement with previous studies that found F. graminearum be more aggressive and toxigenic in wheat than F. boothii.
Sensitivity of Fusarium graminearum to Metconazole and Tebuconazole Fungicides Before and After Widespread Use in Wheat in the United States
Authors: Anderson Nolan R. , Freije Anna N. , Bergstrom Gary C. , Bradley Carl A. , Cowger Christina , Faske Travis , Hollier Clayton , Kleczewski Nathan , Padgett Guy B. , Paul Pierce , Price Trey , Wise Kiersten A.
Published: April 2020

Fusarium head blight (FHB) caused primarily by Fusarium graminearum, is a major disease of wheat in the United States. FHB is managed in part by applications of demethylation inhibitor (DMI) triazole fungicides during anthesis. The objective of this study was to examine the sensitivity of U.S. populations of F. graminearum to the DMI triazole fungicides metconazole and tebuconazole. Isolates of F. graminearum collected from wheat between 1981 and 2014 were tested for fungicide sensitivity using mycelial growth assays to determine the effective concentration at which 50% of fungal growth was inhibited (EC50). A total of 45 isolates were tested for metconazole sensitivity and 47 for sensitivity to tebuconazole. Isolates were analyzed in groups based on collection date. Groupings consisted of isolates collected prior to widespread fungicide use in wheat (designated as year 2000) or after fungicides became available for use in wheat. The mean EC50 for isolates collected prior to 2000 was 0.0240 µg/ml for metconazole and 0.1610 µg/ml for tebuconazole. For both fungicides, isolates collected between 2000 and 2014 had significantly higher (P = 0.05) mean EC50 values (mean EC50 = 0.0405 and 0.3311 µg/ml for metconazole and tebuconazole, respectively) compared with isolates collected prior to 2000. Isolate, year, and state of collection all affected the mean EC50 values of isolates collected between 2000 and 2014. A single isolate collected from Illinois in 2012 exhibited EC50 values of 0.1734 µg/ml for metconazole and 1.7339 µg/ml for tebuconazole, indicating reduced sensitivity compared with the mean EC50 of other isolates collected between 2000 and 2014. This study is the first step toward developing a fungicide sensitivity monitoring program for F. graminearum in the United States.
Discrete action control for prosthetic digits
Authors: Krasoulis Agamemnon , Nazarpour Kianoush
Published: April 2020

Objective

We aim to develop a paradigm for simultaneous and independent control of multiple degrees of freedom (DOFs) for upper-limb prostheses.

Approach

We introduceaction control, a novel method to operate prosthetic digits with surface electromyography (EMG) based on multi-label, multi-class classification. At each time step, the decoder classifies movement intent for each controllable DOF into one of three categories: open, close, or stall (i.e., no movement). We implemented a real-time myoelectric control system using this method and evaluated it by running experiments with one unilateral and two bilateral amputees. Participants controlled a six-DOF bar interface on a computer display, with each DOF corresponding to a motor function available in multi-articulated prostheses.

Main results

We show that action control can significantly and systematically outperform the state-of-the-art method of position control via multi-output regression in both task- and non-task-related measures. Improvements in median task performance ranged from 20.14% to 62.32% for individual participants. Analysis of a post-experimental survey revealed that all participants rated action higher than position control in a series of qualitative questions and expressed an overall preference for the former.

Significance

Action control has the potential to improve the dexterity of upper-limb prostheses. In comparison with regression-based systems, it only requires discrete instead of real-valued ground truth labels, typically collected with motion tracking systems. This feature makes the system both practical in a clinical setting and also suitable for bilateral amputation. This work is the first demonstration of myoelectric digit control in bilateral upper-limb amputees. Further investigation and pre-clinical evaluation are required to assess the translational potential of the method.
Revised (β-phenyl) stereochemistry of ultrapotent μ opioid BU72
Authors: Munro Thomas A.
Published: April 2020

In its crystal structure in complex with the μ opioid receptor (μOR), the opioid BU72 exhibits extreme deviations from the expected geometry.1Three of these involve the phenyl group. There is also unexplained electron density next to the benzylic carbon. Here I show that inverting the benzylic configuration fills this unexplained density and eliminates the phenyl group outliers, along with all but one of the others. I propose that this is the correct structure of BU72.
Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China
Authors: Lu Jing , Plessis Louis du , Liu Zhe , Hill Verity , Kang Min , Lin Huifang , Sun Jiufeng , François Sarah , Kraemer Moritz U G , Faria Nuno R , McCrone John T , Peng Jingju , Xiong Qianlin , Yuan Runyu , Zeng Lilian , Zhou Pingping , Liang Chuming , Yi Lina , Liu Jun , Xiao Jianpeng , Hu Jianxiong , Liu Tao , Ma Wenjun , Li Wei , Su Juan , Zheng Huanying , Peng Bo , Fang Shisong , Su Wenzhe , Li Kuibiao , Sun Ruilin , bai Ru , Tang Xi , Liang Minfeng , Quick Josh , Song Tie , Rambaut Andrew , Loman Nick , Raghwani Jayna , Pybus Oliver G , Ke Changwen
Published: April 2020

COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China’s most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the province’s large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing.

Highlights

1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020

Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples.

Genomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation.

Large-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong
Detecting SARS-CoV-2 at point of care: Preliminary data comparing Loop-mediated isothermal amplification (LAMP) to PCR
Authors: Österdahl Marc F , Lee Karla A , Lochlainn Mary Ni , Wilson Stuart , Douthwaite Sam , Horsfall Rachel , Sheedy Alyce , Goldenberg Simon D , Stanley Christopher J , Spector Tim D , Steves Claire J
Published: April 2020

Background

The need for a fast and reliable test for COVID-19 is paramount in managing the current pandemic. A cost effective and efficient diagnostic tool as near to the point of care (PoC) as possible would be a game changer in current testing. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 minutes, alongside standard methods in a real-life clinical setting.

Methods

This service improvement project piloted a research RT-LAMP method on nasal and pharyngeal swabs on 21 residents in a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We calculated the sensitivity, specificity, positive and negative predictive values of a single RT-LAMP swab compared to RT-PCR, as per STARD guidelines. We also recorded vital signs of patients to correlate clinical and laboratory information.

Findings

The novel method accurately detected 8/10 PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of the novel test were 80% and 73% respectively. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 83%. We also observed hypothermia to be a significant early clinical sign in a number of COVID-19 patients in this setting.

Interpretation

RT-LAMP testing for SARS-CoV-2 was found to be promising, fast, easy to use and to work equivalently to RT-PCR methods. Definitive studies to evaluate this method in larger cohorts are underway. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the point of care. This method could be deployed in mobile testing units in the community, care homes and hospitals to detect disease early and prevent spread.
The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migrationin vivo
Authors: Cedric Bressan , Alessandra Pecora , Dave Gagnon , Marina Snapyan , Simon Labrecque , Paul De Koninck , Martin Parent , Armen Saghatelyan
Published: April 2020

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and a considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice revealed that decrease in ATP levels force cells into the stationary phase and induce autophagy. Genetic impairment of autophagy in neuroblasts using either inducible conditional mice or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases in order to sustain neuronal migration.

Highlights

ADP levels dynamically change during cell migration

A decrease in ATP levels leads to cell pausing and autophagy induction via AMPK

Autophagy is required to sustain neuronal migration by recycling focal adhesions

Autophagy level is dynamically modulated by migration-promoting and inhibiting cues
A bacterial tragedy of the commons that masks the actual frequency of mutants
Authors: Neves Henrique Iglesias , Machado Gabriella Trombini , dos Santos Ramos Taíssa Cristina , Yang Hyun Mo , Yagil Ezra , Spira Beny
Published: April 2020

The frequency of mutants in a population is central to the understanding of evolution. Mutant frequency is usually assessed by plating a bacterial culture on selective medium in which only specific rare mutants can grow, assuming that all mutant cells present on the plate are able to form colonies. Here we show an exception to this rule. Wild-typeEscherichia colicells are unable to grow with glycerol-2-phosphate (G2P) as a carbon source. In contrast, PHO-constitutive mutants can hydrolyse G2P to glycerol and form colonies on plates having G2P as their sole carbon source. However, the frequency of PHO-constitutive colonies on the selective plate is exceptionally low. Here we show that such mutations occur at a relatively high rate, but the growth of the existing mutants is inhibited due to a competition with the surrounding wild-type cells for the limited amounts of glycerol produced by the mutants. This scenario in which neither the wild-type nor the majority of the mutants are able to grow constitutes an unavoidable case of the ‘tragedy of the commons’. Evidence shows that the few mutants that do form colonies derive from micro-clusters of mutants on the selective plate. In addition, a mathematical model describes the fate of the wild-type and mutant populations on the selective plate.
Lactobacillus pentosus KCA1 Decreases Vaginal and Gut Microbiota Associated with Bacterial Vaginosis (BV), Down-regulates IL-1 beta in Women of Child-Bearing Age and Modulates Bacterial Genes Related to Metabolic Functions
Authors: Anukam Kingsley C , Ejike Chinwe E , Agbakoba Nneka R , Oguejiofor Charlotte B
Published: April 2020

Introduction

Bacterial vaginosis which affects 14-50% of reproductive-aged women in Nigeria is misdiagnosed and under-reported. Treatment option is antibiotics, which leads to recurrent infections. The objectives of this study are three folds, first to determine effects of oral feeding of Lactobacillus pentosus KCA1 on the vaginal and gut microbiota of women diagnosed with BV; to measure the level of two proinflammatory cytokines IL-1 beta, before and after KCA1 consumption and to determine the relative abundance of bacterial metabolic genes.

Methods

Seven women diagnosed with BV by Nugent score (7-10) were recruited to provide vaginal and gut sample before and after 14 days oral intake of 3 grams of Lactobacillus pentosus KCA1. The DNA from the swabs were processed for 16S rRNA metagenomics using Illumina MiSeq platform. The paired-end sequence FASTQ reads were imported into Illumina Basespace pipeline for quality check (QC). In addition, EzBioCloud pipeline was use for alpha and beta diversity estimation using PKSSU4.0 version and open reference UCLUST_MC2 for OTUs picking at 97% cut-off. Blood samples were analyzed using ELISA technique. PICRUSt was used to predict the metabolic functions from the 16S rRNA gene dataset.

Results

On average, there was no significant difference at p=0.05 in the alpha indices typified by Shannon index. The beta diversity showed different clustering positions with PCoA. However, at individual taxonomic categories, there was a significant decrease in the relative abundance of some genera associated with bacterial vaginosis after KCA1 feeding with a corresponding increase of Lactobacillus genera. Bacterial genes related to defence systems were up-regulated in the vagina. There was a 2-fold down-regulation of IL-1 beta after consumption of KCA1.

Conclusion

Our findings suggest that Lactobacillus pentosus KCA1 taken orally, lowers pro-inflammatory cytokine, IL-1 beta and decreases the relative abundance of BV-associated bacteria.
Role of transmembrane helix 6 in substrate recognition of the amino acid transporter MhsT
Authors: Focht Dorota , Neumann Caroline , Lyons Joseph , Bilbao Ander Eguskiza , Blunck Rikard , Malinauskaite Lina , Schwarz Ilona O. , Javitch Jonathan A , Quick Matthias , Nissen Poul
Published: April 2020

MhsT ofBacillus haloduransis a transporter of hydrophobic amino acids and a homologue of the eukaryotic SLC6 family of Na+-dependent symporters for amino acids, neurotransmitters, osmolytes, or creatine. The broad range of transported amino acids by MhsT prompted the investigation of the substrate recognition mechanism. Here, we report six new substrate-bound structures of MhsT, which, in conjunction with functional studies, reveal how the flexibility of a Gly-Met-Gly (GMG) motif in the unwound region of transmembrane segment 6 (TM6) is central for the recognition of substrates of different size by tailoring the binding site shape and volume. MhsT mutants, harboring substitutions within the unwound GMG loop and substrate binding pocket that mimick the binding sites of eukaryotic SLC6A18/B0AT3 and SLC6A19/B0AT1 transporters of neutral amino acids, exhibited impaired transport of aromatic amino acids that require a large binding site volume. Conservation of a general (G/A/C)ΦG motif among eukaryotic members of SLC6 family suggests a role for this loop in a common mechanism for substrate recognition and translocation by SLC6 transporters of broad substrate specificity.
Transcriptional Regulators of theGolli/Myelin Basic ProteinLocus Integrate Additive and Stealth Activities
Authors: Bagheri Hooman , Friedman Hana , Siminovitch Kathy , Peterson Alan
Published: April 2020

Myelin is composed of plasma membrane spirally wrapped around axons and compacted into dense sheaths by myelin associated proteins. In the central nervous system (CNS), myelin is elaborated by neuroepithelial derived oligodendrocytes and in the peripheral nervous system (PNS) by neural crest derived Schwann cells. While some myelin proteins are unique to only one lineage,myelin basic protein(Mbp) is expressed in both. Overlapping theMbpgene isGolli, a transcriptional unit that is expressed widely both within and beyond the nervous system. A super-enhancer domain within theGolli/Mbplocus contains multiple enhancers shown previously to drive reporter construct expression specifically in oligodendrocytes or Schwann cells. In order to determine the contribution of each enhancer to theGolli/Mbpexpression program and examine if interactions among these enhancers occur, we derived mouse lines in which enhancers were deleted, either singly or in different combinations, and relative mRNA accumulation was measured at key stages of development. Although super-enhancers have been shown to facilitate interaction among their component enhancers, the enhancers investigated here demonstrated functions that were largely additive. However, enhancers demonstrating autonomous activity strictly in one cell lineage, when missing, were found to significantly reduce output in the other thus revealing cryptic “stealth” activity. Further,Golliaccumulation in all cell types investigated was markedly and uniformly attenuated by the absence of a key oligodendrocyte enhancer. Our observations expose a novel level of enhancer interaction and are consistent with a model in which enhancer-mediated DNA looping underlies higher-orderGolli/Mbpregulatory organization.

AUTHOR SUMMARY

The control of transcription is mediated through regulatory sequences that engage in a lineage and developmentally contextual manner. TheGolli/Mbplocus gives rise to several mRNAs and whileMbpmRNAs accumulate exclusively in the two glial cell types that elaborate myelin,GollimRNAs accumulate in diverse cell types both within and beyond the nervous system. To determine how the differentGolli/Mbpenhancers distribute their activities and to reveal if they operate as autonomous agents or have functionally significant interactions with each other we derived multiple enhancer knock-out lines. Comparing the developmental accumulation ofMbpandGollimRNAs revealed that the autonomous targeting capacity of multiple enhancers accurately predicted their in-situ contributions. Also, they acted in a largely additive manner indicating significant individual autonomy that can be accounted for by a simple chromatin looping model. Unexpectedly, we also uncovered cryptic “stealth” activity emanating from these same enhancers in lineages where they show no autonomous targeting capacity thus providing new insight into the control of lineage specific gene expression.
PhANNs, a fast and accurate tool and web server to classify phage structural proteins
Authors: Cantu Vito Adrian , Salamon Peter , Seguritan Victor , Redfield Jackson , Salamon David , Edwards Robert A. , Segall Anca M.
Published: April 2020

For any given bacteriophage genome or phage sequences in metagenomic data sets, we are unable to assign a function to 50-90% of genes. Structural protein-encoding genes constitute a large fraction of the average phage genome and are among the most divergent and difficult-to-identify genes using homology-based methods. To understand the functions encoded by phages, their contributions to their environments, and to help gauge their utility as potential phage therapy agents, we have developed a new approach to classify phage ORFs into ten major classes of structural proteins or into an “other” category. The resulting tool is named PhANNs (Phage Artificial Neural Networks). We built a database of 538,213 manually curated phage protein sequences that we split into eleven subsets (10 for cross-validation, one for testing) using a novel clustering method that ensures there are no homologous proteins between sets yet maintains the maximum sequence diversity for training. An Artificial Neural Network ensemble trained on features extracted from those sets reached a test F1-score of 0.875 and test accuracy of 86.2%. PhANNs can rapidly classify proteins into one of the ten classes, and non-phage proteins are classified as “other”, providing a new approach for functional annotation of phage proteins. PhANNs is open source and can be run from our web server or installed locally.

Author Summary

Bacteriophages (phages, viruses that infect bacteria) are the most abundant biological entity on Earth. They outnumber bacteria by a factor of ten. As phages are very different within them and from bacteria, and we have comparatively few phage genes in our database, we are unable to assign function to 50%-90% of phage genes. In this work, we developed PhANNs, a machine learning tool that can classify a phage gene as one of ten structural roles, or “other”. This approach does not require a similar gene to be known.
Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue
Authors: Bayram Jan , Malcova Ivana , Sinkovec Larisa , Holubova Jana , Streparola Gaia , Jurnecka David , Kucera Jan , Sedlacek Radislav , Sebo Peter , Kamanova Jana
Published: April 2020

Bordetella bronchisepticaandBordetella pertussisare closely related respiratory pathogens that evolved from a common bacterial ancestor. WhileB. bronchisepticahas an environmental reservoir and mostly establishes chronic infections in a broad range of mammals,B. pertussisis a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity ofB. bronchiseptica, the cytotoxicity induced byB. pertussisBteA (BpBteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression inB. pertussis. We show that presence of an alanine residue inserted at position 503 (A503) ofBpBteA accounts for its strongly attenuated cytotoxic potency. Deletion of A503 fromBpBteA greatly enhanced the cytotoxic activity ofB. pertussisB1917 on mammalian HeLa cells and expression ofBpBteAΔA503 was highly toxic toSaccharomyces cerevisiaecells.Vice versa, insertion of A503 intoB. bronchisepticaBteA (BbBteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, production ofBpBteAΔA503 increased virulence ofB. pertussisB1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effectorBpBteA may represent an evolutionary adaptation that fine-tunesB. pertussisvirulence and host immune response.

Author summary

Pertussis remains the least-controlled vaccine-preventable infectious disease and the mechanisms by whichBordetella pertussissubverts defense mechanisms of human airway mucosa remain poorly understood. We found thatB. pertussishad the cytotoxic activity of its type III secretion system-delivered effector BteA strongly attenuated by insertion of an alanine residue at position 503 as compared to the BteA homologue of the animal pathogenB. bronchiseptica. This functional adaptation reduced the capacity ofB. pertussisto suppress host inflammatory response and may contribute to an acute course of the pulmonary form of human infant pertussis.
LCM-seq identifies robust markers of vulnerable and resistant human midbrain dopamine neurons
Authors: Aguila Julio , Cheng Shangli , Kee Nigel , Cao Ming , Deng Qiaolin , Hedlund Eva
Published: April 2020

Defining transcriptional profiles of substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopamine neurons in human is critical to understanding their differential vulnerability in Parkinson Disease. However, reported marker profiles for these neuron populations are derived predominantly from rodents, utilize small sample sizes and display extensive variability between studies. Here, we map selective expression profiles of dopamine neurons in an extensive collection of human SNc and VTA using laser capture microdissection coupled with Smart-seq2 RNA sequencing (LCM-seq). By applying a bootstrapping strategy as sample input to DESeq2, we identify 33 differentially expressed SNc- or VTA-specific markers and we also compute the minimal cohort size required to identify differentially expressed genes (DEGs) that are concordant regardless of cohort size. Among the identified DEGs,ZCCHC12, CDH13andSERPINE2, are minimally required to distinguish SNc or VTA dopamine neurons in both human and mouse. In summary, our study identifies novel markers, besides previously identified ones, which will be instrumentsal for future studies aiming to modulate dopamine neuron resilience as well as validate cell identity of stem cell-derived dopamine neurons.
Proteins and Ions Compete for Membrane Interaction: the case of Lactadherin
Authors: De Lio A. M. , Paul D. , Jain R. , Morrissey J. H. , Pogorelov T. V.
Published: April 2020

Charged molecular species, such as ions, play a vital role in the life of the cell. In particular, divalent calcium ions (Ca2+) are critical for activating cellular membranes. Interactions between Ca2+and anionic phosphatidylserine (PS) lipids result in structural changes of the plasma membrane and are vital for many signaling pathways, such as the tightly regulated blood coagulation cascade. Upon cell damage, PS lipids are externalized to the outer leaflet, where they are not only exposed to Ca2+, but also to proteins. Lactadherin is a glycoprotein, important for cell-adhesion, that can act as an anticoagulant. While a number of experimental studies have been performed on lactadherin’s C2 domain’s (LactC2) binding affinity for PS molecules, an atomistic description of LactC2 interactions with PS lipids in the plasma membrane is lacking. We performed extensive all-atom molecular dynamics simulations of mixed lipid bilayers and experimental characterization of LactC2-membrane interactions in the presence and absence of Ca2+and characterized PS-Ca2+and PS-LactC2 interactions to guide our understanding of how these interactions initiate and impede blood coagulation, respectively. The captured spontaneously formed long-lived PS-Ca2+and PS-LactC2 complexes revealed that the protein side chains involved in PS-LactC2 interactions appear to be affected by the presence of Ca2+. The degree of LactC2 insertion into the lipid bilayer also appears to be dependent on the presence of Ca2+. Characterizing the interactions between Ca2+and LactC2 with PS lipids can lead to a greater understanding of the activation and regulation of the blood coagulation cascade and of the basis of charged species interactions with the lipid membrane.

STATEMENT OF SIGNIFICANCE

Lactadherin plays an important role in cellular signaling including blood coagulation. Many of these processes involve lactadherin interacting with the lipids of the cell plasma membrane. Lactadherin acts as an anticoagulant and contributes to a number of health issues. Understanding the interactions that drive lactadherin’s anticoagulant properties can lead to potential new drug targets.
Understanding cloud ERP continuance intention and individual performance: a TTF-driven perspective
Authors: Cheng Yung-Ming
Published: April 2020

Purpose

This study's purpose is to propose a hybrid model based on expectation-confirmation model (ECM) and technology acceptance model (TAM) to examine whether organizational users' perceived task-technology fit (TTF) in cloud enterprise resource planning (ERP) as an antecedent to user beliefs can directly and indirectly affect their continuance intention of cloud ERP and individual performance.

Design/methodology/approach

Sample data for this study were collected from end users of cloud ERP working in companies in Taiwan. A total of 500 questionnaires were distributed in the 50 sample companies, and 355 (71.0%) usable questionnaires were analyzed using structural equation modeling in this study.

Findings

This study showed that organizational users' perceived TTF contributed positively to their perceived usefulness, confirmation and perceived ease of use of cloud ERP, which in turn directly and indirectly led to their satisfaction with cloud ERP, continuance intention of cloud ERP and individual performance; that is, this study's findings strongly supported the research model integrating ECM, TAM and TTF model with all hypothesized links being significant.

Originality/value

This study contributes to an understanding of the TTF model in explaining organizational users' cloud ERP continuance intention that is difficult to explain with only their utilitarian perceptions of cloud ERP. Further, it is especially worth mentioning that this study places considerably more emphasis upon organizational users' individual performance greatly driven by their perceived TTF in cloud ERP and continuance intention of cloud ERP. Thus, this study's empirical evidence on incorporating ECM, TAM and TTF model can significantly enhance better understanding of the outcomes for cloud ERP continuance intention and shed light on the possible formulation of a richer post-adoption model.
Towards successful strategies to overcome BPR implementation issues: case of Sri Lanka
Authors: Fasna M.F.F. , Gunatilake Sachie
Published: April 2020

Purpose

Currently, most of the organisations that undertake business process reengineering (BPR) projects with the intention of enhancing their business performance are encountering several issues throughout their endeavours. As these BPR implementation issues are perceived as one of the key contributory factors leading to BPR project failures, it is crucial to adopt timely strategies to overcome these issues. Hence, this study is focused on identifying the strategies to be adopted to overcome BPR implementation issues.

Design/methodology/approach

Four case studies were conducted in organisations that have successfully implemented BPR projects within last five years. In total, 14 semi-structured interviews were conducted among the different stakeholders who got involved in the selected BPR projects for identifying the issues faced and the strategies that they have adopted during their project implementation.

Findings

Study derived twenty-seven issues faced by the Sri Lankan organisations during different phases of BPR projects, and forty-five unique strategies to deal with these derived BPR implementation issues.

Originality/value

This study contributes to the field by exploring the issues in implementing BPR projects that should be given enough consideration to ensure the success of BPR projects in the Sri Lankan context along with the strategies to overcome the issues encountered throughout them. It is expected that the findings of this study would be useful in ensuring the success of future BPR projects.
Internationalisation business processes in an under-supported policy contexts: evidence from Italian SMEs
Authors: Jafari-Sadeghi Vahid , Dutta Dev K. , Ferraris Alberto , Del Giudice Manlio
Published: April 2020

Purpose

The main objective of this research was to identify the key critical determinants of internationalisation business processes that entrepreneurs adopted in under-supported policy contexts.

Design/methodology/approach

This research utilised a case-study design, incorporating multiple case examples, applying non-probability purposive selection criteria. A total of five in-depth, structured 90-min to two-hour case interviews were conducted with Italian entrepreneurs, in which four out of the five cases selected are goods-oriented, and one is services oriented.

Findings

Regarding internal entrepreneurial motives, four crucial determinants were recognised: (1) Making more profit, (2) Expanding market, (3) Personal tendency to export and (4) Obtaining social respect. Regarding external networking capabilities, two key factors were identified: (1) Developing relationships with an international partner or representative and (2) Maintaining relationships with industry-relevant authorities.

Research limitations/implications

The data gathered for this paper depends on self-announcing, expanding the likelihood of being one-sided for social desirability answers. The sample of research is also limited to small and medium businesses and has covered a limited number of companies.

Originality/value

An under-supported policy context forces international entrepreneurs to make their own arrangements and tailor their business process through personal initiative and interactions with network partners. Taking advantage of field-based data, this paper is probably one of the earliest research studies to identify several internal and external factors impacting on firm internationalisation business processes in the low policy support context for entrepreneurship.
Numerical simulation of Fisher's type equation via a collocation technique based on re-defined quintic B-splines
Authors: Dhiman Neeraj , Chauhan Amit , Tamsir Mohammad , Chauhan Anand
Published: April 2020

Purpose

A collocation technique based on re-defined quintic B-splines over Crank-Nicolson is presented to solve the Fisher's type equation. We take three cases of aforesaid equation. The stability analysis and rate of convergence are also done.

Design/methodology/approach

The quintic B-splines are re-defined which are used for space integration. Taylor series expansion is applied for linearization of the nonlinear terms. The discretization of the problem gives up linear system of equations. A Gaussian elimination method is used to solve these systems.

Findings

Three examples are taken for analysis. The analysis gives guarantee that the present method provides much better results than previously presented methods in literature. The stability analysis and rate of convergence show that the method is unconditionally stable and quadratic convergent for Fisher's type equation. Moreover, the present method is simple and easy to implement, so it may be considered as an alternative method to solve PDEs.

Originality/value

This work is the original work of authors which is neither published nor submitted anywhere else for publication.
Proteomic analysis of CHIKV‐infected human fibroblast‐like synoviocytes: Identification of host factors potentially associated with CHIKV replication and cellular pathogenesis
Authors: Sukkaew Apamas , Suksatu Ampa , Roytrakul Sittiruk , Smith Duncan R. , Ubol Sukathida
Published: April 2020

Chikungunya virus (CHIKV) is a mosquito‐borne virus that causes arthralgic fever. Fibroblast‐like synoviocytes play a key role in joint damage in inflammatory arthritides and can additionally serve as target cells for CHIKV infection. To gain a better understanding of CHIKV‐induced arthralgia, the interaction between CHIKV and synoviocytes was investigated at the protein level. A gel‐enhanced liquid chromatography‐mass spectrometry (GeLC‐MS/MS) approach was used to examine protein expression from primary human fibroblast‐like synoviocytes (HFLS) infected with clinical isolates of CHIKV at 12 and 24 hr post infection. Our analysis identified 259 and 241 proteins of known function that were differentially expressed (>1.5 or <−1.5 fold change) following CHIKV infection at 12 and 24 hpi, respectively. These proteins are involved in cellular homeostasis, including cellular trafficking, cytoskeletal organization, immune response, metabolic process, and protein modification. Some of these proteins have previously been reported to participate in arthralgia/arthritis and the death of infected cells. Our results provide information on the CHIKV‐induced modulation of cellular proteins of HFLS at an early stage of infection, as well as highlighting biological processes associated with CHIKV infection in the main target cells of the joint.
Responses and resilience of tallgrass prairie streams to patch‐burn grazing
Authors: Fulgoni Jessica N. , Whiles Matt R. , Dodds Walter K. , Larson Danelle M. , Jackson Karen E. , Grudzinski Bartosz P.
Published: April 2020

Patch‐burn grazing (PBG) can promote terrestrial heterogeneity and biodiversity, but can temporarily increase stream nutrients and ecosystem metabolism, and alter macroinvertebrate assemblages. The impacts of grazing on stream channel morphology and post‐PBG recovery patterns are unclear.

We assessed the influence of grazing in PBG managed grassland streams in Missouri, USA, and subsequent recovery when grazing ceased for 2 years. We hypothesized that grazing would degrade water quality, stream biotic integrity and channel morphology, but that riparian fencing would mitigate these effects. We predicted that biological and chemical variables in unfenced streams would return to pre‐PBG levels within 2 years after grazing ceased, but channel morphology would not.

Six small headwater streams (two in ungrazed control watersheds, two in PBG watersheds with 10 m fenced riparian zones and two in PBG unfenced) were sampled over 7 years; 2 years before PBG, 3 years during PBG and 2 years post‐PBG. We sampled macroinvertebrates and water chemistry monthly when water was present and surveyed channel morphology at least once each study period.

During grazing, unfenced watersheds showed the greatest changes in channel width, depth and area. During the post‐PBG period, one of the two unfenced watersheds showed partial recovery of channel morphology. Although grazing increased concentrations of nutrients and chlorophyll‐a, concentrations returned to pre‐PBG conditions after grazing ceased, indicating recovery. Very fine organic sediments increased in the unfenced watersheds compared to the control during grazing but recovered afterwards. Contributions of Chironomidae to total invertebrate abundance increased in the unfenced watersheds during grazing, and then decreased during the post‐PBG period.

Riparian fencing mostly mitigated effects of grazing on the streams. Unfenced streams were resilient to effects of grazing in a PBG managed grassland, with most metrics recovering within 2 years after grazing ceased, except for channel morphology.

Synthesis and applications. Grazing in a patch‐burn grazed managed grassland coupled with riparian fencing could be an effective conservation tool for land managers of prairies, with relatively modest influences on stream water quality and biotic integrity. Persistent changes in stream channel morphology and effects of longer periods of grazing deserve further research.
Sex‐biased ceRNA networks reveal that OSCAR can promote proliferation and migration of lung adenocarcinoma in women
Authors: Wang Dong , Yang Na , Xie Shengzhi
Published: April 2020

Lung adenocarcinoma (LUAD) is one of several malignant tumours with the highest incidence rates. Currently, there is an urgent need for effective diagnostic and therapeutic targets for LUAD in clinical practice. Numerous studies have shown that there may be differences in the development pattern of LUAD between male and female patients, leading to the need for differential treatment. At the same time, previous studies have shown that competitive endogenous (ce)RNA plays an important role in the development of LUAD, but there is no relevant research on whether there is a gender difference in the ceRNA network of LUAD. In this study, we constructed gender‐independent, male‐specific, and female‐specific ceRNA networks using RNA sequencing results from TCGA database. Subsequently, through analysis of the core genes of the ceRNA network, we determined that the male and female ceRNA networks indeed display different features. In addition, we also found that the osteoclast‐associated receptor (OSCAR) gene was a potential diagnostic target for detecting LUAD in females, and that increased expression of this gene promoted the proliferation and migration of A549 and H1975 LUAD cell lines; more specifically, A549 and H1975 are male and female LUAD cell lines, respectively. This suggests that the OSCAR gene has the potential to serve as target molecule for the diagnosis and treatment of female‐specific LUADs.
Current situation of clinical islet transplantation from allogeneic toward xenogeneic
Authors: Matsumoto Shinichi , Shimoda Masayuki
Published: April 2020

Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but islet transplantation could make a type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non‐heart‐beating and living donors were used; in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donors are the only source.

To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, although there is the risk of developing serious or novel infection. Therefore, the World Health Organization has been interested in xenotransplantation, and the International Xenotransplantation Association (IXA) has published consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently an efficient method to overcome xenorejection is an important research target. In addition to traditional immunosuppressive drugs and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once the xenorejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients.
A Systematic Review of the Effects of Perinatal Alcohol Exposure and Perinatal Marijuana Exposure on Adult Neurogenesis in the Dentate Gyrus
Authors: Reid Hannah M.O. , Lysenko‐Martin Melanie R. , Snowden Taylor M. , Thomas Jennifer D. , Christie Brian R.
Published: April 2020

Background

Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both drugs have the capacity to affect working memory, one function of the hippocampal formation; however, there is a paucity of data on how perinatal exposure to alcohol or cannabis impacts the process of adult neurogenesis.

Methods

This systematic review examines immunohistochemical data from adult rat and mouse models that assess perinatal alcohol or perinatal marijuana exposure. A comprehensive list of search terms was designed and used to search 3 separate databases. All results were imported to Mendeley and screened by 2 authors. Consensus was reached on a set of final papers that met the inclusion criteria, and their results were summarized.

Results

Twelve papers were identified as relevant, 10 of which pertained to the effects of perinatal alcohol on the adult hippocampus, and 2 pertained to the effects of perinatal marijuana on the adult hippocampus. Cellular proliferation in the dentate gyrus was not affected in adult rats and mice exposed to alcohol perinatally. In general, perinatal alcohol exposure did not have a significant and reliable effect on the maturation and survival of adult born granule neurons in the dentate gyrus. In contrast, interneuron numbers appear to be reduced in the dentate gyrus of adult rats and mice exposed perinatally to alcohol. Perinatal marijuana exposure was also found to reduce inhibitory interneuron numbers in the dentate gyrus.

Conclusions

Perinatal alcohol exposure and perinatal marijuana exposure both act on inhibitory interneurons in the hippocampal formation of adult rats. These findings suggest simultaneous perinatal alcohol and marijuana exposure (SAM) may have a dramatic impact on inhibitory processes in the dentate gyrus.