bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Point-of-care Blood Gas Testing in the Intensive Care Unit through Diagnostic Stewardship: A Value Improvement Project
Authors: Tchou Michael J. , May Sally , Holcomb John , Tanner-Edwards Ethan , Good Kathy , Frazier Matthew , Stalets Erika L. , Dewan Maya
Published: June 2020

Introduction:

Overutilization of point-of-care (POC) testing may reduce the overall value of care due to high-cost cartridges, need for staff training, and quality assurance requirements.

Methods:

The Diagnostic Stewardship group at Cincinnati Children’s Hospital Medical Center assembled a multidisciplinary team to reduce the use of POC blood gas testing by 20% in the pediatric intensive care unit (PICU). Key drivers of test overutilization included poor knowledge of cost, concern with testing turnaround time, and a lack of a standard definition of when a POC test was appropriate. We calculated weekly the outcome measure of POC blood gas tests per PICU patient-day and a balancing measure of blood gas result turnaround time using data extracted from the electronic medical record. Interventions focused on staff education, the establishment of a standard practice guideline for the use of POC testing, and improving turnaround time for laboratory blood gas testing.

Results:

Over the baseline period starting July 2016, a median of 0.94 POC blood gas tests per PICU patient-day was ordered. After initial staff training, the rate was reduced to 0.60 tests per PICU patient-day and further reduced to 0.41 tests per PICU patient-day after a formal policy change was adopted. We have sustained this rate for 15 months through June 2018. Institutional direct cost savings were estimated to be $19,000 per year.

Conclusions:

Our improvement initiative was associated with a significant and rapid reduction in the use of POC testing in the PICU. Interventions focused on cost awareness, and a formal guideline helped establish a consensus around appropriate utilization.
Gluconobacter aidae sp. nov., an acetic acid bacteria isolated from tropical fruits in Thailand
Authors: Yukphan Pattaraporn , Charoenyingcharoen Piyanat , Malimas Sukunphat , Muramatsu Yuki , Nakagawa Yasuyoshi , Tanasupawat Somboon , Yamada Yuzo
Published: June 2020

Two bacterial strains, isolates AC10Tand AC20, which were reported in a previous study on the diversity of acetic acid bacteria in Thailand, were subjected to a taxonomic study. The phylogenetic analysis based on the 16S rRNA gene sequences showed that the two isolates were located closely to the type strains ofGluconobacter oxydansandGluconobacter roseus. However, the two isolates formed a separate cluster from the type strains of the two species. The genomic DNA of isolate AC10Twas sequenced. The assembled genomes of the isolate were analysed for average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH). The results showed that the highest ANI and dDDH values between isolate AC10TandG. oxydansDSM 3503Twere 91.15 and 68.2 %, which are lower than the suggested values for species delineation. The genome-based tree was reconstructed and the phylogenetic lineage based on genome sequences showed that the lineage of isolate AC10Twas distinct fromG. oxydansDSM 3503Tand its related species. The two isolates were distinguished fromG. oxydansand their relatives by their phenotypic characteristics and MALDI-TOF profiles. Therefore, the two isolates, AC10T(=BCC 15749T=TBRC 11329T=NBRC 103576T) and AC20 (=BCC 15759=TBRC 11330=NBRC 103579), can be assigned to an independent species within the genusGluconobacter, and the nameGluconobacter aidaesp. nov. is proposed for the two isolates.
Genetic diversity increases food-web persistence in the face of climate warming
Authors: Barbour Matthew A. , Kliebenstein Daniel J. , Bascompte Jordi
Published: June 2020

Genetic diversity provides the raw material for species to adapt and persist in the face of climate change. Yet, the extent to which these genetic effects scale at the level of ecological communities remains unclear. Here we experimentally test the effect of plant genetic diversity on the persistence of an insect food web under a current and future warming scenario. We found that plant genetic diversity increased food-web persistence by increasing the intrinsic growth rates of species across multiple trophic levels. This positive effect was robust to a 3°C warming scenario and resulted from allelic variation at two genes that control the biosynthesis of chemical defenses. Our results suggest that the ongoing loss of genetic diversity may undermine the persistence and functioning of ecosystems in a changing world.

One Sentence Summary

The loss of genetic diversity accelerates the extinction of inter-connected species from an experimental food web.
Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons
Authors: Tsang Anthony H. , Nuzacci Danae , Darwish Tamana , Samudrala Havish , Blouet Clémence
Published: June 2020

The nucleus of the solitary tract (NTS) is emerging as a major site of action for the appetite-suppressive effects of leading pharmacotherapies currently investigated for the treatment of obesity. However, our understanding of how NTS neurons regulate appetite remains incomplete. Here we used NTS nutrient sensing as an entry point to characterize stimulus-defined neuronal ensembles engaged by the NTS to produce physiological satiety. Using activity-dependent expression of genetically-encoded circuit analysis tools, we found that NTS detection of leucine engages NTS prolactin-releasing peptide (PrRP) neurons to inhibit AgRP neurons via a population of leptin-receptor-expressing neurons in the dorsomedial hypothalamus. This circuit is necessary for the anorectic response to NTS leucine, the appetite-suppressive effect of high protein diets, and the long-term control of energy balance. These results extends the integrative capability of AgRP neurons to include brainstem nutrient sensing inputs.
Visualizing dendritic characteristics of corticotropin-releasing hormone neurons at single-cell resolution in the whole mouse brain
Authors: Wang Yu , Hu Pu , Shan Qinghong , Huang Chuan , Huang Zhaohuan , Chen Peng , Li Anan , Gong Hui , Zhou Jiang-Ning
Published: June 2020

Corticotropin-releasing hormone (CRH) is an important neuromodulator with wide distribution in the brain. Here, we screened the CRH-IRES-Cre;Ai32 mouse line to reveal the morphologies of individual CRH neurons throughout the mouse brain by using fluorescence micro-optical sectioning tomography (fMOST) system. Diverse dendritic morphologies and projection fibers were found in various brain regions. Reconstructions showed hypothalamic CRH neurons had the smallest somatic volumes and simplest dendritic branches, and CRH neurons in several regions shared a bipolar morphology. Further investigations in the medial prefrontal cortex unveiled somatic depth-dependent morphologies that exhibited three types of connections and CRH neurons in the anterior parvicellular area of hypothalamus had fewer and smaller Herring bodies whereas in the periventricular area had more and larger Herring bodies that were present within fibers projecting to the third ventricle. Our findings provide the most comprehensive intact morphologies of CRH neurons throughout the mouse brain that is currently available.
Presence of endogenous viral elements negatively correlates with FeLV susceptibility in puma and domestic cat cells
Authors: Chiu Elliott S. , VandeWoude Sue
Published: June 2020

While feline leukemia virus (FeLV) has been shown to infect felid species other than the endemic domestic cat host, differences in FeLV susceptibility among species has not been evaluated. Previous reports have noted a negative correlation between enFeLV copy number and exogenous FeLV infection outcomes in domestic cats. Since felids outside the genusFelisdo not harbor enFeLV genomes, we hypothesized absence of enFeLV results in more severe disease consequences in felid species lacking these genomic elements. We infected primary fibroblasts isolated from domestic cats (Felis catus) and pumas (Puma concolor) with FeLV and quantitated proviral and viral antigen loads. Domestic cat enFeLVenvand LTR copy numbers were determined for each individual and compared to FeLV viral outcomes. FeLV proviral and antigen levels were also measured in 6 naturally infected domestic cats and 11 naturally infected Florida panthers (P. concolor coryi). We demonstrated that puma fibroblasts are more permissive to FeLV than domestic cat cells, and domestic cat FeLV restriction was highly related to enFeLV LTR copy number. Terminal tissues from FeLV-infected Florida panthers and domestic cats had similar exFeLV proviral copy numbers, but Florida panther tissues have higher FeLV antigen loads. Our work indicates enFeLV LTR elements negatively regulate exogenous FeLV replication. Further,Puma concolorlacking enFeLV are more permissive to FeLV infection than domestic cats, suggesting endogenization can play a beneficial role in mitigating exogenous retroviral infections. Conversely, presence of endogenous retroelements may relate to new host susceptibility during viral spillover events.

Importance

Feline leukemia virus (FeLV) can infect a variety of felid species. Only the primary domestic cat host and related small cat species harbor a related endogenous virus in their genomes. Previous studies noted a negative association between the endogenous virus copy number and exogenous virus infection in domestic cats. This report shows that puma cells, which lack endogenous FeLV, produce more virus more rapidly than domestic cat fibroblasts following cell culture challenge. We document a strong association between domestic cat cell susceptibility and FeLV long terminal repeat (LTR) copy number, similar to observations in natural FeLV infections. Viral replication does not, however, correlate with FeLVenvcopy number, suggesting this effect is specific to FeLV LTR elements. This discovery indicates a protective capacity of the endogenous virus against the exogenous form, either via direct interference or indirectly via gene regulation, and may suggest evolutionary outcomes of retroviral endogenization.
Structural determinants within the adenovirus early region 1A protein spacer region necessary for tumourigenesis
Authors: Molloy David P , Grand Roger J
Published: June 2020

It has long been established that group-A adenoviruses (HAdV-A12, -A18 and -A31) can cause tumours in new-born rodents with tumourigenicity related to the presence of a unique spacer region located between conserved regions 2 and 3 within the Ad12E1A protein. Group B adenoviruses are weakly oncogenic whereas most of the remaining human adenoviruses are non-oncogenic. In order to understand better the relationship between the structure of the AdE1A spacer region and oncogenicity of HAdVs the structure of synthetic peptides identical or very similar to the adenovirus12 E1A spacer region have been determined to be α-helical using NMR spectroscopy. This contrasts significantly with some previous suggestions that this region is unstructured. Using available predictive algorithms, the structures of spacer regions from other E1As were also examined and the extent of predicted α-helix was found to correlate reasonably well with the tumorigenicity of the respective viruses.

Importance

This research analysed small peptides equivalent to a region within the human adenovirus early region 1A protein that confers, in part, tumour inducing properties to varying degrees on several viral strains in rats and mice. The oncogenic spacer region is alpha-helical, which contrasts with previous suggestions that this region is unstructured. The helix is characterised by a stretch of amino acids rich in alanine residues that are organised into a hydrophobic or ‘water-hating’ surface that is considered to form a major site of interaction with cellular protein targets that mediate tumour formation. The extent of alpha-helix in E1A from other adenovirus species can be correlated to a limited degree to the tumourigenicity of that virus. Some serotypes show significant differences in predicted structural propensity suggesting the amino acid type and physicochemical properties are also of importance.
Development of a whole cell biosensor for detection of 2, 4-diacetylphloroglucinol-producing bacteria from grassland soil
Authors: Hansen Morten Lindqvist , He Zhiming , Wibowo Mario , Jelsbak Lars
Published: June 2020

FluorescentPseudomonasspp. producing the antibiotic 2,4-diacetylphloroglucinol (DAPG) are ecologically important in the rhizosphere as they can control phytopathogens and contribute to disease suppressiveness. While studies of DAPG-producingPseudomonashave predominantly focused on rhizosphere niches, the ecological role of DAPG as well as the distribution and dynamics of DAPG-producing bacteria remains less well understood for other environments such as bulk soil and grassland, where the level of DAPG producers are predicted to be low. Here, we construct a whole cell biosensor for detection of DAPG and DAPG-producing bacteria from environmental samples.

We show that the sensor is highly specific towards DAPG, with a sensitivity in the low nanomolar range (<20 nm). This sensitivity is comparable to the DAPG levels identified in rhizosphere samples by chemical analysis. The biosensor enables guided isolation of DAPG-producingPseudomonas. Using the biosensor, we probed the same grassland soil sampling site to isolate genetically related DAPG-producingPseudomonas kilonensisstrains over a period of 12 months. Next, we used the biosensor to determine the frequency of DAPG-producing Pseudomonads within three different grassland soil sites and show that DAPG producers can constitute part of thePseudomonaspopulation in the range of 0.35-17% at these sites. Finally, we show that the biosensor enables detection of DAPG produced by non-Pseudomonasspecies.

Our studies show that a whole-cell biosensor for DAPG detection can facilitate isolation of bacteria that produce this important secondary metabolite and provide insight into the population dynamics of DAPG producers in natural grassland soil.

IMPORTANCE

The interest has grown for bacterial biocontrol agents as biosustainable alternatives to pesticides to increase crop yields. Currently, we have a broad knowledge of antimicrobial compounds, such as DAPG, produced by bacteria growing in the rhizosphere surrounding plant roots. However, compared to the rhizosphere niches, the ecological role of DAPG as well as the distribution and dynamics of DAPG-producing bacteria remains less well understood for other environments such as bulk and grassland soil. Currently, we are restricted to chemical methods with detection limits and time-consuming PCR-based and probe-hybridization approaches to detect DAPG and its respective producer. In this study, we have developed a whole-cell biosensor, which can circumvent the labor-intensive screening process, as well as increase the sensitivity at which DAPG is detected. This enables quantification of relative amounts of DAPG-producers, which in turn increases our understanding of the dynamics and ecology of these producers in natural soil environments.
A rod conformation of thePyrococcus furiosusRad50 coiled coil
Authors: Soh Young-Min , Basquin Jerome , Gruber Stephan
Published: June 2020

The Rad50-Mre11 nuclease complex plays a vital role in DNA repair in all domains of life. It recognizes and processes DNA double-strand breaks. Rad50 proteins fold into an extended structure with a ~20-60 nm long coiled coil connecting a globular ABC ATPase domain with a zinc hook dimerization domain. A published structure of an archaeal Rad50 zinc hook shows coiled coils pointing away from each other. Here we present the crystal structure of an alternate conformation displaying co-aligned coiled coils. Archaeal Rad50 may thus switch between rod-shaped and ring-like conformations as recently proposed for a bacterial homolog.
Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA
Authors: Ratcliff Jeremy , Nguyen Dung , Andersson Monique , Simmonds Peter
Published: June 2020

Accurate identification of individuals infected with SARS-CoV-2 is crucial for efforts to control the ongoing COVID-19 pandemic. Polymerase chain reaction (PCR)-based assays are the gold standard for detecting viral RNA in patient samples and are used extensively in clinical settings. Most currently used quantitative PCR (RT-qPCRs) rely upon real-time detection of PCR product using specialized laboratory equipment. To enable the application of PCR in resource-poor or non-specialist laboratories, we have developed and evaluated a nested PCR method for SARS-CoV-2 RNA using simple agarose gel electrophoresis for product detection. Using clinical samples tested by conventional qPCR methods and RNA transcripts of defined RNA copy number, the nested PCR based on the RdRP gene demonstrated high sensitivity and specificity for SARS-CoV-2 RNA detection in clinical samples, but showed variable and transcript length-dependent sensitivity for RNA transcripts. Samples and transcripts were further evaluated in an additional N protein real-time quantitative PCR assay. As determined by 50% endpoint detection, the sensitivities of three RT-qPCRs and nested PCR methods varied substantially depending on the transcript target with no method approaching single copy detection. Overall, these findings highlight the need for assay validation and optimization and demonstrate the inability to precisely compare viral quantification from different PCR methodologies without calibration.
Enhanced anti-amyloid effect of combined leptin and pioglitazone in APP/PS1 transgenic mice
Authors: Liu Yao , Hanson Kelsey A. , McCormack Graeme , Dittmann Justin , Vickers James C. , Fernandez-Martos Carmen M. , King Anna E.
Published: June 2020

Background

Alzheimer’s disease (AD) has challenged single-target therapeutic strategies, raising the possibility that combined therapies may offer a more effective treatment strategy.

Objective

There is substantial evidence for the efficacy of leptin (L) (neuroprotective hormone) and pioglitazone (P) (anti-inflammatory agent) as monotherapies in AD. We have previouly shown that combination treatment of L+P in APP/PS1 mice at the onset of pathology significantly improved memory and reduced brain Aβ levels relative to control mice. In this new study, we sought to replicate our previous findings in a new cohort of APP/PS1 mouse to further confirm whether the combined treatment of L+P is superior to each treatment individually.

Methods

We have re-evaluated the effects of L+P co-treatment in APP/PS1 mice using thioflavin-S staining, MOAβ immunolabeling and enzyme-linked immunosorbent assay (ELISA) to examine effects on Aβ levels and pathology, relative to animals that received L or P individually. To explore mechanism of regulation, we used Western blotting to examine the expression of the peroxisome-proliferator activated receptor γ (PPARγ), due to its potential role in the regulation of the inflammatory response.

Results

We demonstrated that combining L and P significantly enhances the anti-Aβ effect of L or P in the hippocampus of APP/PS1 mice. Western blot analysis indicated that Aβ reduction was accompanied by up-regulation of the PPARγ levels.

Conclusion

Our findings suggest that combining L and P significantly enhances the anti-Aβ effect of L or P in the hippocampus of APP/PS1 mice, and may be a potential new effective strategy for AD therapy.
Mutalyzer 2: Next Generation HGVS Nomenclature Checker
Authors: Lefter Mihai , Vis Jonathan K. , Vermaat Martijn , den Dunnen Johan T. , Taschner Peter E.M. , Laros Jeroen F.J.
Published: June 2020

Unambiguous variant descriptions are of utmost importance in clinical genetic diagnostics, scientific literature, and genetic databases. The Human Genome Variation Society (HGVS) publishes a comprehensive set of guidelines on how variants should be correctly and unambiguously described. We present the implementation of the Mutalyzer 2 tool suite, designed to automatically apply the HGVS guidelines so users do not have to deal with the HGVS intricacies explicitly to check and correct their variant descriptions. Mutalyzer is profusely used by the community, having processed over 133 million descriptions since its launch. Over a five year period, Mutalyzer reported a correct input in approximately 50% of cases. In 41% of the cases either a syntactic or semantic error was identified and for approximately 7% of cases, Mutalyzer was able to automatically correct the description.
Male-male interactions select for conspicuous male colouration in damselflies
Authors: Khan Md Kawsar , Herberstein Marie E.
Published: June 2020

Male ornamentation, such as conspicuous male colouration, can evolve through female mate choice. Alternatively, in species without overt female mate preference, conspicuous male colouration can evolve via intrasexual selection to resolve male-male competition or to prevent costly male-male mating attempts. Here, we investigated the drivers of conspicuous male colouration in an ontogenetic colour changing damselfly,Xanthagrion erythroneurum, where the juvenile males are yellow and change colour to red upon sexual maturity. We first showed that red males were chromatically and achromatically more conspicuous than the yellow males. We then quantified the condition of the males and showed that red males were larger and in better condition than yellow males. We tested female preference in a choice experiment where we artificially manipulated male colour, and found that females did not choose mates based on male colouration. We further tested whether the male colouration affected male-male interactions. We presented red and yellow males in the breeding arena, and found that red males received less intra- and interspecific aggression than yellow males. Our study experimentally showed, for the first time, that male conspicuousness is not a target of female mate choice in damselflies. Intra- and interspecific male-male interactions therefore appear to be the driver of conspicuous male colouration in damselflies.
Modelling donor screening strategies to reduce the risk of SARS-CoV-2 via fecal microbiota transplantation
Authors: Olesen Scott W. , Zaman Amanda , Osman Majdi , Ramakrishna Bharat
Published: June 2020

The potential for transmission of SARS-CoV-2 shed in stool via fecal microbiota transplantation is not yet known, and the effectiveness of various testing strategies to prevent FMT-based transmission has also not yet been quantified. Here we use a mathematical model to simulate the utility of different testing strategies.
Analysis of pluripotency transcription factor interactions reveals preferential binding of NANOG to SOX2 rather than NANOG or OCT4
Authors: Mistri Tapan Kumar , Kelly David , Mak John , Colby Douglas , Mullin Nicholas , Chambers Ian
Published: June 2020

The pluripotency transcription factors (TFs) Nanog, Sox2, and Oct4 are at the centre of the gene regulatory network that controls cell identity in embryonic stem (ES) cells. However, the mechanisms by which these factors control cell fate, and their interactions with one another are not fully understood. Here we combine biophysical and novel biochemical assays to assess how these factors interact with each other quantitatively. A confocal microscopy method to detect binding of a target protein to a fluorescently labelled partner (coimmunoprecipitated bead imaging microscopy [CBIM]) is presented and used to demonstrate homotypic binding of Nanog and heterotypic binding between Nanog and Sox2 and between Nanog and Oct4. Using fluorescence correlation spectroscopy we show that in solution, Nanog but not Oct4 or Sox2 can form homomultimers. However, both Sox2 and Oct4 can form heterotypic multimers with Nanog in a manner that depends on the presence of tryptophan residues within the Nanog tryptophan repeat. Fluorescence Cross Correlation Spectroscopy shows the affinity of Nanog for dimer formation is in the order Sox2 > Nanog > Oct4. Importantly, live cell analysis demonstrates the existence of Nanog homomultimersin vivo. Together these findings extend understanding of the molecular interactions occurring between these central mediators of the pluripotency gene regulatory network at the single-molecule level.
The phosphatidylinositol 3-phosphate binding protein SNX4 controls ATG9A recycling and autophagy
Authors: Ravussin Anthony , Tooze Sharon A. , Stenmark Harald
Published: June 2020

Late endosomes and lysosomes (endolysosomes) receive proteins and cargo from the secretory, endocytic and autophagic pathways. Whereas these pathways and the degradative processes of endolysosomes are well characterized, less is understood about protein traffic from these organelles. In this study, we demonstrate the direct involvement of the phosphatidylinositol 3-phosphate (PI3P) binding SNX4 protein in membrane protein recycling from endolysosomes, and show that SNX4 is required for proper autophagic flux. We show that SNX4 mediates recycling of the transmembrane autophagy machinery protein ATG9A from endolysosomes to early endosomes, from where ATG9A is recycled to the trans-Golgi network in a retromer-dependent manner. Upon siRNA-mediated depletion of SNX4 or the retromer component VPS35, we observed accumulation of ATG9A on endolysosomes and early endosomes, respectively. Moreover, starvation-induced autophagosome biogenesis and autophagic flux were inhibited when SNX4 was downregulated. Altogether, we propose that proper ATG9A recycling by SNX4 sustains autophagy by preventing exhaustion of the available ATG9A pool.
JIP3 links lysosome transport to regulation of multiple components of the axonal cytoskeleton
Authors: Rafiq N.M. , Lyons L.L. , Gowrishankar S. , De Camilli P. , Ferguson S.M.
Published: June 2020

Lysosome axonal transport is important for the clearance of cargoes sequestered by the endocytic and autophagic pathways. Building on observations that mutations in the JIP3 (MAPK8IP3) gene result in lysosome-filled axonal swellings, we analyzed the impact of JIP3 depletion on the cytoskeleton of human neurons. Dynamic focal lysosome accumulations were accompanied by disruption of the axonal periodic scaffold (spectrin, F-actin and myosin II) throughout each affected axon. Additionally, axonal microtubule organization was locally disrupted at each lysosome-filled swelling. This local axonal microtubule disorganization was accompanied by accumulations of both F-actin and myosin II. These results indicate that transport of axonal lysosomes is functionally interconnected with mechanisms that control the organization and maintenance of the axonal cytoskeleton. They have potential relevance to human neurological disease arising from JIP3 mutations as well as for neurodegenerative diseases associated with the focal accumulations of lysosomes within axonal swellings such as Alzheimer’s disease.
Transporter genes in biosynthetic gene clusters predict metabolite characteristics and siderophore activity
Authors: Crits-Christoph Alexander , Bhattacharya Nicholas , Olm Matthew R. , Song Yun S. , Banfield Jillian F.
Published: June 2020

Biosynthetic gene clusters (BGCs) are operonic sets of microbial genes that synthesize specialized metabolites with diverse functions, including siderophores and antibiotics, which often require export to the extracellular environment. For this reason, genes for transport across cellular membranes are essential for the production of specialized metabolites, and are often genomically co-localized with BGCs. Here we conducted a comprehensive computational analysis of transporters associated with characterized BGCs. In addition to known exporters, in BGCs we found many importer-specific transmembrane domains that co-occur with substrate binding proteins possibly for uptake of siderophores or metabolic precursors. Machine learning models using transporter gene frequencies were predictive of known siderophore activity, molecular weights, and a measure of lipophilicity (logP) for corresponding BGC-synthesized metabolites. Transporter genes associated with BGCs were often equally or more predictive of metabolite features than biosynthetic genes. Given the importance of siderophores as pathogenicity factors, we used transporters specific for siderophore BGCs to identify both known and uncharacterized siderophore-like BGCs in genomes from metagenomes from the infant and adult gut microbiome. We find that 23% of microbial genomes from the infant gut have siderophore-like BGCs, but only 3% of those assembled from adult gut microbiomes do. While siderophore-like BGCs from the infant gut are predominantly associated withEnterobactericaeeandStaphylococcus, siderophore-like BGCs can be identified from taxa in the adult gut microbiome that have rarely been recognized for siderophore production. Taken together, these results show that consideration of BGC-associated transporter genes can inform predictions of specialized metabolite structure and function.
Genome-wide reduction in chromatin accessibility and unique transcription factor footprints in endothelial cells and fibroblasts in scleroderma skin
Authors: Tsou Pei-Suen , Palisoc Pamela J. , Ali Mustafa , Khanna Dinesh , Sawalha Amr H
Published: June 2020

Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by widespread fibrosis and vascular complications. We utilized an assay for genome-wide chromatin accessibility to examine the chromatin landscape and transcription factor footprints in both endothelial cells (ECs) and fibroblasts isolated from healthy controls and patients with diffuse cutaneous (dc) SSc. In both cell types, chromatin accessibility was significantly reduced in SSc patients compared to healthy controls. Genes annotated from differentially accessible chromatin regions were enriched in pathways and gene ontologies involved in the nervous system. In addition, our data revealed that chromatin binding of transcription factors SNAI2, ETV2, and ELF1 was significantly increased in dcSSc ECs, while recruitment of RUNX1 and RUNX2 was enriched in dcSSc fibroblasts. Significant elevation of SNAI2 and ETV2 levels in dcSSc ECs, and RUNX2 levels in dcSSc fibroblasts were confirmed. Further analysis of publicly available ETV2-target genes suggests that ETV2 may play a critical role in EC dysfunction in dcSSc. Our data, for the first time, uncovered the chromatin blueprint of dcSSc ECs and fibroblasts, and suggested that neural-related characteristics of SSc ECs and fibroblasts could be a culprit for dysregulated angiogenesis and enhanced fibrosis. Targeting these pathways and the key transcription factors identified might present novel therapeutic approaches for this disease.
Co-occurrence of SARS-CoV-2 and Respiratory Pathogens in the Frail Elderly
Authors: Wolfe Alan , Baunoch David , Wang Dakun , Gnewuch Ryan , Zhao Xinhua , Halverson Thomas , Cacdac Patrick , Huang Shuguang , Lauterbach Trisha , Luke Natalie
Published: June 2020

Background

Elderly SARS-CoV-2 patients are associated with higher hospitalization and mortality. Co-infection is critical in the severity of respiratory diseases. It is largely understudied for SARS-CoV-2.

Methods

Between March 24thand April 27th, 2020, nasopharyngeal and oropharyngeal swabs from 3,348 patients from nursing homes and assisted living facilities in 22 states in the US were tested by Capstone Healthcare for SARS-CoV-2, 24 other respiratory viruses, and 8 respiratory bacteria. Total nucleic acid was extracted with MagMAX™ Viral/Pathogen Ultra nucleic acid isolation kit. SARS-Co-V-2 was detected with the CDC 2019-novel coronavirus (2019-nCoV) diagnostic panel. Total nucleic acid was pre-amplified before analysis for other respiratory pathogens with Taqman OpenArray™ Respiratory Tract Microbiota Plate.

Results

Patients’ mean age was 76.9 years. SARS-CoV-2 was detected in 1,413 patients (42.2%). Among them, 1,082 (76.6%) and 737 (43.7%) patients were detected with at least one bacterium or another virus, respectively. SARS-CoV-2-positive patients were more likely to have bacterial co-occurrences (76.6%) than SARS-CoV-2-negative patients (70.0%) (p<0.0001). The most common co-occurring bacteria wereStaphylococcus aureusandKlebsiella pneumonia, detected in 55.8% and 40.1% SARS-CoV-2-positive patients, respectively.Staphylococcus aureuswas associated with SARS-CoV-2, with higher detection rates in SARS-CoV-2-positive patients (55.8%) than SARS-CoV-2-negative patients (46.2%) (p<0.0001). Human herpes virus 6 (HHV6) also was common and associated with SARS-CoV-2, with higher detection rates in SARS-CoV-2-positive patients (26.6%) than SARS-CoV-2-negative patients (19.1%) (p<0.0001).

Conclusions

SARS-CoV-2-positive patients are more likely to be positive for certain respiratory bacteria and viruses. This observation may help explain high hospitalization and mortality rates in older patients.
Modeling the Covid-19 Pandemic Response of the US States
Authors: Neofotistos Georgios , Kaxiras Efthimios
Published: June 2020

Background

The United States of America (USA) has been the country worst affected, in absolute terms, by the Covid-19 pandemic. The country comprises 50 states under a federal system. The impact of the pandemic has resulted in different responses at the state level, which are driven by differing intervention policies, demographics, connectedness and other factors. Understanding the dynamics of the Covid-19 pandemic at the state level is essential in predicting its future evolution.

Objective

Our objective is to identify and characterize multiple waves of the pandemic by analyzing the reported infected population curve in each of the 50 US states. Based on the intensity of the waves, characterized by declining, stationary, or increasing strengths, each state’s response can be inferred and quantified.

Methods

We apply a recently proposed multiple-wave model to fit the infected population data for each state in USA, and use the proposed Pandemic Response Index to quantify their response to the Covid-19 pandemic.

Results

We have analyzed reported infected cases from each one of the 50 USA states and the District of Columbia, based on the multiple-wave model, and present the relevant parameters. Multiple waves have been identified and this model is found to describe the data better. Each of the states can be classified into one of three distinct classes characterized by declining, increasing, or stationary strength of the waves following the initial one. The effectiveness of intervention measures can be inferred by the peak intensities of the waves, and states with similar population characteristics can be directly compared. We estimate how much lower the number of infections might have been, if early and strict intervention measures had been imposed to stop the disease spread at the first wave, as was the case for certain states. Based on our model’s results, we compute the value of the Pandemic Response Index, a recently introduced metric for quantifying in an objective manner the response to the pandemic.

Conclusions

Our results reveal a series of epidemic waves, characterizing USA’s pandemic response at the state level, and also infer to what extent the imposition of early intervention measures could have had on the spread and impact of the disease. As of June 11, 2020, only 19 states and the District of Columbia (40% of the total) clearly exhibit declining trends in the numbers of reported infected cases, while 13 states exhibit stationary and 18 states increasing trends in the numbers of reported cases.
Evaluation of two commercial and two non-commercial immunoassays for the detection of prior infection to SARS-CoV-2
Authors: Nilles Eric J. , Karlson Elizabeth W. , Norman Maia , Gilboa Tal , Fischinger Stephanie , Atyeo Caroline , Zhou Guohai , Bennett Christopher L. , Tolan Nicole V. , Oganezova Karina , Walt David R. , Alter Galit , Simmons Daimon P. , Schur Peter , Jarolim Petr , Baden Lindsey R.
Published: June 2020

Background

Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity.

Methods

We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result.

Results

The Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9-14 days (67-100%) and 15-21 days (69-100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH assays were less sensitive during early disease, particularly among immunosuppressed individuals.

Conclusions

The Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives.

SARS-CoV-2 immunoassays can be valuable tools for informing the global response, but many currently available assays have not been independently validated. We conducted a performance assessment of four assays including the Roche Diagnostics and Epitope Diagnostics immunoassays.
Cerebellar nuclei evolved by repeatedly duplicating a conserved cell type set
Authors: Kebschull Justus M , Ringach Noam , Richman Ethan B , Friedmann Drew , Kolluru Sai Saroja , Jones Robert C , Allen William E , Wang Ying , Zhou Huaijun , Cho Seung Woo , Chang Howard Y , Deisseroth Karl , Quake Stephen R , Luo Liqun
Published: June 2020

How have complex brains evolved from simple circuits? Here we investigated brain region evolution at cell type resolution in the cerebellar nuclei (CN), the output structures of the cerebellum. Using single-nucleus RNA sequencing in mice, chickens, and humans, as well as STARmap spatial transcriptomic analysis and whole-CNS projection tracing in mice, we identified a conserved cell type set containing two classes of region-specific excitatory neurons and three classes of region-invariant inhibitory neurons. This set constitutes an archetypal CN that was repeatedly duplicated to form new regions. Interestingly, the excitatory cell class that preferentially funnels information to lateral frontal cortices in mice becomes predominant in the massively expanded human Lateral CN. Our data provide the first characterization of CN transcriptomic cell types in three species and suggest a model of brain region evolution by duplication and divergence of entire cell type sets.
MeCP2 gates spatial learning-induced alternative splicing events in the mouse hippocampus
Authors: Brito David V.C. , Karaca Kubra Gulmez , Oliveira Ana M.M.
Published: June 2020

Long-term memory formation is supported by functional and structural changes of neuronal networks, which rely onde novogene transcription and protein synthesis. The modulation of the neuronal transcriptome in response to learning depends on transcriptional and post-transcriptional mechanisms. DNA methylation writers and readers regulate the activity-dependent genomic program required for memory consolidation. The most abundant DNA methylation reader, the Methyl CpG binding domain protein 2 (MeCP2), has been shown to regulate alternative splicing, but whether it establishes splicing events important for memory consolidation has not been investigated. In this study, we identified the alternative splicing profile of the mouse hippocampus in basal conditions and after a spatial learning experience, and investigated the requirement of MeCP2 for these processes. We observed that spatial learning triggers a wide-range of alternative splicing events in transcripts associated with structural remodeling and that virus-mediated knockdown of MeCP2 impairs learning-dependent post-transcriptional responses of mature hippocampal neurons. Furthermore, we found that MeCP2 preferentially affected the splicing modalities intron retention and exon skipping and guided the alternative splicing of distinct set of genes in baseline conditions and after learning. Lastly, comparative analysis of the MeCP2-regulated transcriptome with the alternatively spliced mRNA pool, revealed that MeCP2 disruption alters the relative abundance of alternatively spliced isoforms without affecting the overall mRNA levels. Overall our findings reveal that adult hippocampal MeCP2 is required to finetune alternative splicing events in basal conditions, as well as in response to spatial learning. This study provides new insight into how MeCP2 regulates brain function, particularly cognitive abilities, and sheds light onto the pathophysiological mechanisms of Rett syndrome, that is characterized by intellectual disability and caused by mutations in theMecp2gene.
Repositioning the customer support services: the next frontier of competitive advantage
Authors: Sheth Jagdish , Jain Varsha , Ambika Anupama
Published: June 2020

Purpose

This paper aims to analyze the present status of customer support services (CSS) and advocate the re-positioning of support services from an administrative cost center to a strategic profit center. Authors demonstrate how customer support or after sales services can be a source of competitive advantage and revenue generation for firms.

Design/methodology/approach

The study adopts a conceptual approach grounded in theoretical foundations of service dominant logic, customer loyalty and customer centricity along with practical illustrations from the industry.

Findings

Following the tenets of theory, review of existing research and analysis of the industry practices, the authors propose a new framework to enable the repositioning of customer service function. The key propositions include establishing customer support as separate business unit and insights center, introducing a new role of a C-level chief customer support officer to lead the customer support unit, adopting a customer-centric culture and process, enabling frontline IT support and investing in frontline employee skills development.

Research limitations/implications

Academics should examine the potential of customer support, where the strategic importance is low at present, leading to customer dissatisfaction. The new approach and positioning of customer support calls for a new direction for research in this area focusing on enablers, challenges and further implications. To succeed in this competitive era, firms should be conscious of the value of customer service and undertake concrete actions to generate value for all stakeholders.

Practical implications

Industry can use the new framework and re-position CSS of the organizations. The CSS unit can be different from other business units in the organizations. The CSS would evolve and emerge from the live customer insights. CSS unit can be managed by the C level chief CSS officer. Customer-centric culture would be developed and front line processes can be made customer-oriented by the officer. Thus, this paper and framework would provide new customer-centric directions to the organizations for effective functioning.

Originality/value

This is the original piece that has emerged from the experience and expertise of the authors.
Ability-based emotional intelligence and career adaptability: role in job-search success of university students
Authors: Mittal Shashank
Published: June 2020

Purpose

This study aims to investigate the specific role of the components of ability-based emotional intelligence (their relative importance) in building different aspects of career adaptabilities and job-search success of university students.

Design/methodology/approach

This study employed survey data from 729 full-time students enrolled in an Indian university. Hierarchical regression analyses were conducted to test the hypotheses, and the size of indirect effect was tested using SPSS PROCESS macro.

Findings

The ability-based emotional intelligence, along with the use and regulation of emotion in job-search success, plays a significant role in shaping career adaptabilities and job-search success. The ability to use and regulate emotions does have its impact on job-search success through a self-regulatory psychological resource of control and confidence over one's career. Self-emotional appraisal is necessary for an individual to be concerned for a career which forms the initiation of any job-search.

Research limitations/implications

Ability-based approach of enhancing emotional intelligence allows the university students to take a developmental approach in employment. This approach benefits the more “targeted approach to training interventions” provided by various stakeholders in the university, associated with career and employment.

Originality/value

Further, the study focuses on the psychological difficulties (over operational) faced by students in their employment endeavour. Both emotions and psychological resources are believed to play an important role in the career intervention. For instance, past researches have studied trait-based emotional intelligence as a personality construct. However, this study considers emotional intelligence as an ability-based aspect of intelligence, which “readily lends itself to interventions that can be enhanced through targeted training, coaching or counselling”.
Understanding retail quality of sporting goods stores: a text mining approach
Authors: Mao Luke Lunhua
Published: June 2020

Purpose

Sporting goods retailing is a significant sector within the sport industry with the total revenue of this sector reaching $52.2 billion in 2018. Beset with formidable competition, sporting goods stores are compelled to augment their merchandise with service and improve retail quality. The purpose of this study is to investigate retail quality of sporting goods stores (RQSGS).

Design/methodology/approach

Based on 27,793 online reviews of 1481 stores in the United States, this study used Leximancer 4.0, a text mining software, to identify critical retail quality dimensions associated with sporting goods stores, and further explored the most salient dimensions among different levels of ratings.

Findings

Customer service and store aspects are the two higher-order dimensions of RQSGS; holistic experience, manager and staff are three themes under customer service, and product, B&M store and online–offline integration are three themes under store aspects. Furthermore, extreme reviews focus more on customer service, whereas lukewarm reviews focus more on store aspects.

Practical implications

Knowledgeable staff, managers and online–offline integration are instrumental in creating superior retail quality. Sporting goods stores should enhance hedonic and social values for consumers in order to ward off online competitions.

Originality/value

This study explored retail quality dimensions that are pertinent to sporting goods retailing utilizing text mining methods. This study to certain extent cross-validated the existing retailing literature that is developed on alternative methods.