bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hot zone infection outbreaks on the dynamics of SARS-CoV-2 spread in the community at large
Authors: Wodarz Dominik , Komarova Natalia L. , Schang Luis M.
Published: November 2020

Transmission of SARS-CoV-2 appears especially effective in “hot zone” locations where individuals interact in close proximity. We present mathematical models describing two types of hot zones. First, we consider a metapopulation model of infection spread where transmission hot zones are explicitly described by independent demes in which the same people repeatedly interact (referred to as “static” hot zones, e.g. nursing homes, food processing plants, prisons, etc.). These are assumed to exists in addition to a “community at large” compartment in which virus transmission is less effective. This model yields a number of predictions that are relevant to interpreting epidemiological patterns in COVID19 data. Even if the rate of community virus spread is assumed to be relatively slow, outbreaks in hot zones can temporarily accelerate initial community virus growth, which can lead to an overestimation of the viral reproduction number in the general population. Further, the model suggests that hot zones are a reservoir enabling the prolonged persistence of the virus at “infection plateaus” following implementation of non-pharmaceutical interventions, which has been frequently observed in data. The second model considers “dynamic” hot zones, which can repeatedly form by drawing random individuals from the community, and subsequently dissolve (e.g. restaurants, bars, movie theaters). While dynamic hot zones can accelerate the average rate of community virus spread and can provide opportunities for targeted interventions, they do not predict the occurrence of infection plateaus or other atypical epidemiological dynamics. The models therefore identify two types of transmission hot zones with very different effects on the infection dynamics, which warrants further epidemiological investigations.
Risk of Polymyxin B-induced Acute Kidney Injury in Non-adjusted Dose Versus Adjusted Dose based on Renal Function: a retrospective cohort study
Authors: Zheng Guanhao , Zhou Shenghui , Du Ning , Cai Jiaqi , Bai Hao , He Juan , Bian Xiaolan
Published: November 2020

Background

This study aimed to observe the difference in risk of polymyxin B-induced acute kidney injury with or without dose adjustment by patients’ renal function.

Method

A retrospective cohort analysis was carried out for patients who were treated with polymyxin B in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from November 2018 to October 2019. Patients were divided into adjusted dosage group and non-adjusted dosage group depended on dosage adjustment with renal function or not. A comparison of acute kidney injury incidence between the two groups was the primary outcome of this research. The secondary outcome included hospital length of stay, microbiological cure, clinical cure, and 30-day mortality.

Result

A total of 115 patients met the requirements of this study and were included in the analysis. Thirty-five patients were included in the non-adjusted dosage group and 80 in the adjusted dosage group. Patients from both groups had similar characteristics. The total daily dose of polymyxin B in the Non-adjusted dosage group was significantly higher than the adjusted dosage group (1.98 mg/kg/d vs 1.59 mg/kg/d, P=0.001). For the primary outcome of this research, no significant difference in the incidence of acute kidney injury was observed in these two groups (47.5% vs 37.14%, P=0.304), as well as the secondary outcomes, including hospital length of stay, microbiological cure, clinical cure, 30-day mortality.

Conclusion

Dosing adjustment renally could not lower the risk of polymyxin B-induced acute kidney injury significantly. A non-adjusted dosing strategy of polymyxin B is recommended when patients suffered from various levels of renal impairment.
A Nasal Spray Solution of Grapefruit Seed Extract plus Xylitol Displays Virucidal Activity Against SARS-Cov-2In Vitro
Authors: Ferrer Gustavo , Betancourt Arian , Go Camille Celeste , Vazquez Hector , Westover Jonna B. , Cagno Valeria , Tapparel Caroline , Sanchez-Gonzalez Marcos A.
Published: November 2020

ABSTARCT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the ongoing pandemic coronavirus disease 2019 (COVID-19) has triggered worldwide concerted efforts in an attempt to identify effective therapies. In the present study, we have identified two candidate agents with potential activity against SARS-CoV-2 which can be administered intranasally, namely, xylitol and grape seed fruit extract (GSE). A commercially available nasal spray (Xlear) combining xylitol and GSE has been available for years, but the antiviral effects of this solution have not been documented. Thisin vitrostudy examined the virucidal effect of Xlear against SARS-CoV-2. To this end, two independent sets of experiments were carried out to test the hypothesis that Xlear is an effective (Experiment I) and replicable (Experiment II) means to deactivate SARS-CoV-2. When tested against SARS-CoV-2, the test compound GSE 0.2% was the only compound effective at reducing >3 log10 CCID50 infectious virus from, 3.67 log10 CCID50/0.1 mL to an undetectable amount of infectious virus. The present results validated by two independent sets of experiments, performed by different labs, on different viral strains, provide early evidence to encourage further pilot and clinical studies aimed at investigating the use of Xlear as a potential treatment for COVID-19
Visuomotor Activation of Inhibition-Processing in Pediatric Obsessive Compulsive Disorder: A Magnetoencephalography Study
Authors: Nishat Eman , Dockstader Colleen , Wheeler Anne L. , Tan Thomas , Anderson John A. E. , Mendlowitz Sandra , Mabbott Donald J. , Arnold Paul D. , Ameis Stephanie H.
Published: November 2020

Background

The ability to inhibit a response is a component of executive control that is impaired in many individuals with obsessive compulsive disorder (OCD) and may contribute to clinical symptoms. This study explored whether neural processing during response inhibition, measured using magnetoencephalography (MEG), differed in a sample of medication-naïve youth with OCD, compared to typically developing controls (TDC).

Methods

Data was acquired from 20 medication-naïve children and youth with OCD (11.9 ± 2.1 SD years) and 14 TDC (12.3 ± 2.1 SD years). MEG was used to localize and characterize neural activity during a Go/No-Go task. Regional differences in amplitude of activity during a Go and No-Go condition between OCD versus TDC were examined.

Results

In response to the visual cue presented during the Go condition, participants with OCD showed significantly increased amplitude of activity in the primary motor (MI) cortex compared to TDC. A trend towards decreased amplitude of activity in the orbitofrontal cortex in OCD versus TDC was also found during stop errors in the No-Go condition.

Conclusion

Our preliminary study in a small medication-naïve sample suggests that neural response within motor and orbitofrontal regions may be altered during Go/No-Go Task performance, and that MEG as an imaging tool may be sensitive to detecting such differences.
Airway tissue stem cells reutilize the embryonic proliferation regulator, Tgfß-Id2 axis, for tissue regeneration
Authors: Kiyokawa Hirofumi , Yamaoka Akira , Matsuoka Chisa , Tokuhara Tomoko , Abe Takaya , Morimoto Mitsuru
Published: November 2020

During development, quiescent basal stem cells are derived from proliferative primordial progenitors through the cell cycle slowdown. In contrast, quiescent basal cells contribute to tissue repair during adult tissue regeneration by shifting from slow-cycling to proliferating and subsequently back to slow-cycling. Although sustained basal cell proliferation results in tumorigenesis, the molecular mechanisms regulating these transitions remain unknown. Using temporal single-cell transcriptomics of developing murine airway progenitors andin vivogenetic validation experiments, we found that Tgfß signaling slowed down cell cycle by inhibitingId2expression in airway progenitors and contributed to the specification of slow-cycling basal cell population during development. In adult tissue regeneration, reduced Tgfß signaling restoredId2expression and initiated epithelial regeneration.Id2overexpression andTgfbr2knockout enhanced epithelial proliferation; however, persistentId2expression in basal cells drove hyperplasia at a rate that resembled a precancerous state. Together, the Tgfß-Id2 axis commonly regulates the proliferation transitions in airway basal cells during development and regeneration, and its fine-tuning is critical for normal regeneration while avoiding basal cell hyperplasia.
Hybrid Living Capsules Autonomously Produced by Engineered Bacteria
Authors: Birnbaum Daniel P. , Manjula-Basavanna Avinash , Kan Anton , Joshi Neel S.
Published: November 2020

Bacterial cellulose (BC) has excellent material properties and can be produced cheaply and sustainably through simple bacterial culture, but BC-producing bacteria lack the extensive genetic toolkits of model organisms such asEscherichia coli. Here, we describe a simple approach for producing highly programmable BC materials through incorporation of engineeredE. coli. The acetic acid bacteriumGluconacetobacter hanseniiwas co-cultured with engineeredE. coliin droplets of glucose-rich media to produce robust cellulose capsules, which were then colonized by theE. coliupon transfer to selective lysogeny broth media. We show that the encapsulatedE. colican produce engineered protein nanofibers within the cellulose matrix, yielding hybrid capsules capable of sequestering specific biomolecules from the environment and enzymatic catalysis. Furthermore, we produced capsules capable of altering their own bulk physical properties through enzyme-induced biomineralization. This novel system, based on autonomous biological fabrication, significantly expands the functionality of BC-based living materials.
BEEM-Static: Accurate inference of ecological interactions from cross-sectional metagenomic data
Authors: Li Chenhao , Av-Shalom Tamar V. , Gerald Tan Jun Wei , Samantha Kwah Junmei , Chng Kern Rei , Nagarajan Niranjan
Published: November 2020

Motivation

The structure and function of diverse microbial communities is underpinned by ecological interactions that remain uncharacterized. With rapid adoption of metagenomic sequencing for studying microbiomes, data-driven inference of microbial interactions based on abundance correlations is widely used, but with the drawback that ecological interpretations may not be possible. Leveraging cross-sectional metagenomic datasets for unravelling ecological structure in a scalable manner thus remains an open problem.

Methods

We present an expectation-maximization algorithm (BEEM-Static) that can be applied to cross-sectional datasets to infer interaction networks based on an ecological model (generalized Lotka-Volterra). The method exhibits robustness to violations in model assumptions by using statistical filters to identify and remove corresponding samples.

Results

Benchmarking against 10 state-of-the-art correlation based methods showed that BEEM-Static can infer presence and directionality of ecological interactions even with relative abundance data (AUC-ROC>0.85), a task that other methods struggle with (AUC-ROC<0.63). In addition, BEEM-Static can tolerate a high fraction of samples (up to 40%) being not at steady state or coming from an alternate model. Applying BEEM-Static to a large public dataset of human gut microbiomes (n=4,617) identified multiple stable equilibria that better reflect ecological enterotypes with distinct carrying capacities and interactions for key species.

Conclusion

BEEM-Static provides new opportunities for mining ecologically interpretable interactions and systems insights from the growing corpus of metagenomic data.
The SC-SNc pathway boosts appetitive locomotion in predatory hunting
Authors: Huang Meizhu , Li Dapeng , Pei Qing , Xie Zhiyong , Gu Huating , Liu Aixue , Chen Zijun , Wang Yi , Sun Fangmiao , Li Yulong , Zhang Jiayi , He Miao , Xie Yuan , Zhang Fan , Qi Xiangbing , Shang Congping , Cao Peng
Published: November 2020

Appetitive locomotion is essential for organisms to approach rewards, such as food and prey. How the brain controls appetitive locomotion is poorly understood. In a naturalistic goal-directed behavior—predatory hunting, we demonstrate an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to boost appetitive locomotion. The SC-SNc pathway transmitted locomotion-speed signals to dopamine neurons and triggered dopamine release in the dorsal striatum. Activation of this pathway increased the speed and frequency of approach during predatory hunting, an effect that depended on the activities of SNc dopamine neurons. Conversely, synaptic inactivation of this pathway impaired appetitive locomotion but not defensive or exploratory locomotion. Together, these data revealed the SC as an important source to provide locomotion-related signals to SNc dopamine neurons to boost appetitive locomotion.
Differences in functional connectivity distribution after transcranial direct-current stimulation: a connectivity density point of view
Authors: Tang Bohao , Zhao Yi , Venkataraman Archana , Tsapkini Kyrana , Lindquist Martin A , Pekar James , Caffo Brian
Published: November 2020

In this manuscript we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting state functional magnetic resonance imaging association with an intervention. Specifically, we consider 47 primary progressive aphasia (PPA) patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, tDCS (transcranial direct-current stimulation and language therapy) vs sham (language therapy only), in a clinical trial. We propose a novel approach to analyze the effect of direct stimulation on functional connectivity. We estimate the density of correlations among the regions of interest (ROIs) and study the difference in the density post-intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. This approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared to edge-wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.
A comparison of machine learning models versus clinical evaluation for mortality prediction in patients with sepsis
Authors: van Doorn William P.T.M. , Stassen Patricia M. , Borggreve Hella F. , Schalkwijk Maaike J. , Stoffers Judith , Bekers Otto , Meex Steven J.R.
Published: November 2020

Introduction

Patients with sepsis who present to an emergency department (ED) have highly variable underlying disease severity, and can be categorized from low to high risk. Development of a risk stratification tool for these patients is important for appropriate triage and early treatment. The aim of this study was to develop machine learning models predicting 31-day mortality in patients presenting to the ED with sepsis and to compare these to internal medicine physicians and clinical risk scores.

Methods

A single-center, retrospective cohort study was conducted amongst 1,344 emergency department patients fulfilling sepsis criteria. Laboratory and clinical data that was available in the first two hours of presentation from these patients were randomly partitioned into a development (n=1,244) and validation dataset (n=100). Machine learning models were trained and evaluated on the development dataset and compared to internal medicine physicians and risk scores in the independent validation dataset. The primary outcome was 31-day mortality.

Results

A number of 1,344 patients were included of whom 174 (13.0%) died. Machine learning models trained with laboratory or a combination of laboratory + clinical data achieved an area-under-the ROC curve of 0.82 (95% CI: 0.80-0.84) and 0.84 (95% CI: 0.81-0.87) for predicting 31-day mortality, respectively. In the validation set, models outperformed internal medicine physicians and clinical risk scores in sensitivity (92% vs. 72% vs. 78%;p<0.001,all comparisons) while retaining comparable specificity (78% vs. 74% vs. 72%;p>0.02). The model had higher diagnostic accuracy with an area-under-the-ROC curve of 0.85 (95%CI: 0.78-0.92) compared to abbMEDS (0.63,0.54-0.73), mREMS (0.63,0.54-0.72) and internal medicine physicians (0.74,0.65-0.82).

Conclusion

Machine learning models outperformed internal medicine physicians and clinical risk scores in predicting 31-day mortality. These models are a promising tool to aid in risk stratification of patients presenting to the ED with sepsis.
COVI-Prim survey: Challenges for Austrian and German general practitioners during initial phase of COVID-19
Authors: Siebenhofer Andrea , Huter Sebastian , Avian Alexander , Mergenthal Karola , Schaffler-Schaden Dagmar , Spary-Kainz Ulrike , Bachler Herbert , Flamm Maria
Published: November 2020

Background

Coronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.

Methods

2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).

Results

The completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.

Conclusion

Primary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.

Registration

Trial registration at the German Clinical Trials Register: DRKS00021231

Primary Funding Source

The study was financed by the cooperating University Institutes without any external financial support.
Lithium inhibits tryptophan catabolism via the inflammation-induced kynurenine pathway in human microglia
Authors: Göttert Ria , Fidzinski Pawel , Kraus Larissa , Schneider Ulf Christoph , Holtkamp Martin , Endres Matthias , Gertz Karen , Kronenberg Golo
Published: November 2020

Activation of the kynurenine pathway may lead to depletion of the serotonin precursor tryptophan, which has been implicated in the neurobiology of depression. This study describes a mechanism whereby lithium inhibits inflammatory tryptophan breakdown. Upon activation, immortalized human microglia showed a robust increase in indoleamine-2,3-dioxygenase (IDO1) mRNA transcription, IDO1 protein expression, and activity. Further, chromatin immunoprecipitation verified enriched binding of both STAT1 and STAT3 to theIDO1promoter. Lithium counteracted these effects, increasing inhibitory GSK3βS9phosphorylation and reducing STAT1S727and STAT3Y705phosphorylation levels in activated cells. Experiments in primary human microglia and human induced pluripotent stem cell (hiPSC)-derived microglia corroborated lithium’s effects. Moreover, IDO activity was reduced by GSK3 inhibitor SB-216763 and STAT inhibitor nifuroxazide via downregulation of P-STAT1S727and P-STAT3Y705. Our study demonstrates that lithium inhibits the inflammatory kynurenine pathway in the microglia compartment of the human brain.
Emerging Concern of Scientific Fraud: Deep Learning and Image Manipulation
Authors: Qi Chang , Zhang Jian , Luo Peng
Published: November 2020

Scientific fraud by image duplications and manipulations within western blot images is a rising problem. Currently, problematic western blot images are mainly detected by checking repeated bands or through visual observation. However, the completeness of the above methods in detecting problematic images has not been demonstrated. Here we show that Generative Adversarial Nets (GANs) can generate realistic western blot images that indistinguishable from real western blots. The overall accuracy of researchers for identifying synthetic western blot images is 0.52, which almost equal to blind guess (0.5). We found that GANs can generate western blot images with bands of the expected lengths, widths, and angles in desired positions that can fool researchers. For the case study, we find that the accuracy of detecting the synthetic western blot images is related to years of researchers performed studies relevant to western blots, but there was no apparent difference in accuracy among researchers with different academic degrees. Our results demonstrate that GANs can generate fake western blot images to fool existing problematic image detection methods. Therefore, more information is needed to ensure that the western blots appearing in scientific articles are real. We argue to require every western blot image to be uploaded along with a unique identifier generated by the laboratory machine and to peer review these images along with the corresponding submitted articles, which may reduce the incidence of scientific fraud.
CloneSeq: A Highly Sensitive Single-cell Analysis Platform for Comprehensive Characterization of Cells from 3D Culture
Authors: Bavli Danny , Sun Xue , Kozulin Chen , Ennis Dena , Motzik Alex , Biran Alva , Brielle Shlomi , Alajem Adi , Meshorer Eran , Buxboim Amnon , Ram Oren
Published: November 2020

Single-cell assays have revealed the scope and importance of heterogeneity in many biological systems. However, in many cases, single cell limited sensitivity is a major hurdle for uncovering the full range of cellular variation. To overcome this limitation, we developed a complementary single cell technology, CloneSeq that combines clonal expansion under controlled culture conditions inside three-dimensional (3D) hydrogel spheres and droplet-based RNA sequencing (RNA-seq). We show that unlike single cell transcriptomes, clonal cells maintain cell states and share similar transcriptional profiles. CloneSeq analysis of Non-small-cell lung carcinoma (NSCLC) cells revealed the presence of novel cancer-specific subpopulations, including cancer stem-like cells (CSLCs). Standard single cell RNA-seq assays as well as cell-to-clone tracing by genetic barcoding failed to identify these rare CSLCs. In addition to CSLCs, clonal expansion within 3D soft microenvironments supported cellular stemness of embryonic stem cells (ESCs) that retained their pluripotent state in the absence of pluripotent media and improved epigenetic reprogramming efficiency of mouse embryonic fibroblasts. Our results demonstrate the capacity of CloneSeq, which can be effectively adapted to different biological systems, to discover rare and previously hidden subpopulations of cells, including CSLCs, by leveraging the broader expression space within clones.
Mechanism of autonomous synchronization of the circadian KaiABC rhythm
Authors: Sasai Masaki
Published: November 2020

The cyanobacterial circadian clock can be reconstituted by mixing three proteins, KaiA, KaiB, and KaiC, in vitro. In this protein mixture, oscillations of the phosphorylation level of KaiC molecules are synchronized to show the coherent oscillations of the ensemble of many molecules. However, the mechanism of this synchronization remains elusive. In this paper, we explain a theoretical model that considers the multifold feedback relations among the structure and reactions of KaiC. The simulated KaiC hexamers show stochastic switch-like transitions at the level of single molecules, which are synchronized in the ensemble through the sequestration of KaiA into the KaiC-KaiB-KaiA complexes. The proposed mechanism quantitatively reproduces the synchronization that was observed by mixing two oscillating solutions in different phases. The model results suggest that biochemical assays with varying concentrations of KaiA or KaiB can be used to test this hypothesis.
Heterotrimeric kinesin-2 motor subunit, KLP68D, localisesDrosophilaodour receptor coreceptor in the distal domain of the olfactory cilia
Authors: Jana Swadhin C. , Jain Akanksha , Dutta Priya , Singh Anjusha , Adusumilli Lavanya , Girotra Mukul , Shirolikar Seema , Ray Krishanu
Published: November 2020

Ciliary localisation of the odour receptor coreceptor (Orco) is essential for insect olfaction. Here, we show that in theDrosophilaantenna Orco enters the bipartite cilia expressed on the olfactory sensory neurons in two discrete, one-hour intervals after the adult eclosion. Genetic analyses suggest that the heterotrimeric kinesin-2 is essential for Orco transfer from the base into the cilium. Using in vitro pulldown assay, we show that Orco binds to the C-terminal tail domain of KLP68D, the β-subunit of kinesin-2. Reduced Orco enrichment decreases electrophysiological response to odours and loss of olfactory behaviour. Finally, we show that kinesin-2 function is necessary to compact Orco to an approximately four-micron stretch at the distal portion of the ciliary outer-segment bearing singlet microtubule filaments. Altogether, these results highlight an independent, tissue-specific regulation of Orco entry at specific developmental stages and its localisation to a ciliary subdomain by kinesin-2.

Graphical Abstract

Author Summary

Jana, Jain, Dutta et al., show that the odour receptor coreceptor only enters the cilia expressed on olfactory sensory neurons at specified developmental stages requiring heterotrimeric kinesin-2. The motor also helps to localise the coreceptor in a compact, environment-exposed domain at the ciliary outer-segment.

Highlights:

Odorant receptor coreceptor (Orco) selectively enters the olfactory cilia.

Orco localises in a specific domain at the distal segment of the olfactory cilium.

Orco/ORx binds to the C-terminal tail domain of the kinesin-2β motor subunit.

Orco entry across the transition zone and its positioning require Kinesin-2.
Debates about vaccines and climate change on social media networks: a study in contrasts
Authors: Schonfeld Justin , Qian Edward , Sinn Jason , Cheng Jeffery , Anand Madhur , Bauch Chris T.
Published: November 2020

Vaccines and climate change have much in common. In both cases, a scientific consensus contrasts with a divided public opinion. They also exemplify coupled human-environment systems involving common pool resources. Here we used machine learning algorithms to analyze the sentiment of 87 million tweets on climate change and vaccines in order to characterize Twitter user sentiment and the structure of user and community networks. We found that the vaccine conversation was characterized by much less interaction between individuals with differing sentiment toward vaccines. Community-level interactions followed this pattern, showing less interaction between communities of opposite sentiment toward vaccines. Additionally, vaccine community networks were more fragmented and exhibited numerous isolated communities of neutral sentiment. Finally, pro-vaccine individuals overwhelmingly believed in anthropogenic climate change, but the converse was not true. We propose mechanisms that might explain these results, pertaining to how the spatial scale of an environment system can structure human populations.
Entropy-driven translocation of disordered proteins through the Gram-positive bacterial cell wall
Authors: Halladin David K. , Ortega Fabian E. , Ng Katharine M. , Footer Matthew J. , Mitić Nenad S. , Malkov Saša N. , Gopinathan Ajay , Huang Kerwyn Casey , Theriot Julie A.
Published: November 2020

Cells across all kingdoms of life actively partition molecules between discrete cellular compartments. In Gram-positive bacteria, a thick and highly cross-linked peptidoglycan cell wall separates the bacterial membrane from the extracellular space, imposing a barrier that must be crossed by proteins whose functions require that they be exposed on the bacterial cell surface1,2. Some surface-exposed proteins, such as theListeria monocytogenesactin nucleation-promoting factor ActA3, remain associated with the bacterial membrane yet somehow thread through tens of nanometers of dense, cross-linked cell wall to expose their N-terminus on the outer surface4,5. Here, we show that entropy can drive the translocation of disordered transmembrane proteins through the Gram-positive cell wall. We develop a physical model predicting that the entropic constraint imposed by a thin periplasm is sufficient to drive translocation of an intrinsically disordered protein like ActA across a porous barrier similar to the cell wall. Consistent with this scenario, we demonstrate experimentally that translocation depends on both the dimensions of the cell envelope and the length of the disordered protein, and that translocation is reversible. We also show that disordered regions from eukaryotic nuclear pore complex proteins are capable of entropy-driven translocation through Gram-positive cell walls. These observations suggest that entropic forces alone, rather than chaperones or chemical energy, are sufficient to drive translocation of certain Gram-positive surface proteins for exposure on the outer surface of the cell wall.
Npas4aexpression in the teleost forebrain is associated with stress coping style differences in fear learning
Authors: Baker Matthew R , Wong Ryan Y
Published: November 2020

Learning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive-reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4aandgabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly highernpas4aexpression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the magnitude of expression of activity-dependent genes likenpas4amay be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.
DNA Methylation Patterns Expose Variations in Enhancer-Chromatin Modifications during Embryonic Stem Cell Differentiation
Authors: Alajem Adi , Roth Hava , Ratgauzer Sofia , Bavli Danny , Motzik Alex , Lahav Shlomtzion , Peled Itay , Ram Oren
Published: November 2020

In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1-versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.

Author summary

Cellular dynamics are underlined by numerous regulatory layers. The regulatory mechanism of interest in this work are enhancers. Enhancers are regulatory regions responsible, mainly, for increasing the possibility of transcription of a certain gene. Enhancers are marked by two distinct chemical groups-H3K4me1 and H3K27ac on the tail of histones. Histones are the proteins responsible for DNA packaging into condensed chromatin structure. In contrast, DNA methylation is a chemical modification often found on enhancers, and is traditionally associated with repression. A long debated question revolves around the functional relevance of DNA methylation in the context of enhancers. Here, we combined the two regulatory layers, histone marks and DNA methylation, to a single measurement that can highlight DNA methylation separately on each histone mark but at the same genomic region. When isolated with H3K4me1, enhancers showed higher levels of methylation compared to H3K27ac. As we measured the same genomic locations, we show that differences of DNA methylation between these marks can only be explained by cellular heterogeneity. We also demonstrated that these enhancers tend to play roles in stem cell differentiation and expression levels of the genes they control correlate with cell-to-cell variation.
Human capital, income diversification and bank performance–an empirical study of East African banks
Authors: Githaiga Peter Nderitu
Published: November 2020

Purpose

The purpose of this paper is to examine whether income diversification moderates the relationship between human capital and bank performance.

Design/methodology/approach

The study uses a sample of 53 banks and panel data for the years 2010–2018. The hypotheses are tested through hierarchical multiple regression and the choice between fixed effect and random effect estimation is based on the results of the Hausman test.

Findings

The study finds that human capital and income diversification significantly influence bank performance; however, the direction of the causality varies. While human capital has a positive effect, income diversification has a negative effect. Additionally, the interaction term has a negative and significant effect on bank performance, inferring that income diversification has an antagonistic effect on the human capital and bank performance relationship. For the control variable, liquidity and asset quality negatively affects bank performance while capitalization has a positive effect.

Research limitations/implications

Human capital was measured as human capital efficiency (HCE), which is a quantitative measure of human capital, hence future studies can use qualitative measures. Also, the study focused on commercial banks in East Africa, future researcher may possibly consider other regions and industries, which would shed more insights.

Practical implications

The results of this paper provide valuable insights. Bank managers can get a better understanding of the impact of human capital on bank performance, and the need to invest more in human capital development. Further, the study cautions bank managers that engaging in non-lending activities might destroy the economic value of human capital and ultimately lower performance. The study also recommends that policymakers should address the obstacles to banks' income diversification, for instance relaxing regulations restricting diversification; this might enable banks to leverage related financial service activities for optimal utilization of human capital and improve banks' profitability.

Originality/value

While a good number of previous studies investigated the direct effect of human capital and income diversification on the performance of banks, this study examines the moderating role of income diversification on the relationship between human capital and performance of banks in East Africa.
Uncovering the effects of prior founding experience of entrepreneurs on early board selection
Authors: Gasiorowski Laura , Lee Ahreum
Published: November 2020

Purpose

This study aims to show what type of directors founders (or entrepreneurs) first appoint to the board and how these appointments differ across experienced and novice entrepreneurs.

Design/methodology/approach

The sample consists of the human capital of board members in 443 new ventures in the computer software and information technology industries between 2000 and 2014. The hypotheses were tested using tobit regression.

Findings

The findings in this study reveal that compared to novice entrepreneurs, experienced entrepreneurs tend to appoint early boards with greater human capital (entrepreneurial, technical/scientific and industry-specific) and with greater functional diversity. In contrast, novice entrepreneurs tend to appoint early boards with greater finance and director experience.

Originality/value

The value of this research lies in filling the gap in the current literature by comparing the board appointment/selection behavior of novice and experienced entrepreneurs, which is relatively underexplored.
Innovation during crisis: exploring reaction of Swedish university libraries to COVID-19
Authors: Temiz Serdar , Salelkar Lakshmi Pradip
Published: November 2020

Purpose

While universities are using more digital tools such as learning management systems (canvas, blackboard, etc). or massive open online courses (MOOCS) such as MIT, OpenCourseWare, edX, Coursera, digitalization has also influenced university libraries. Digital services of academic libraries need exploration on how they provide digital services and how they respond to COVID-19. Therefore, the purpose of this paper is to explore and map digital services of academic libraries and their response to COVID-19 in Sweden.

Design/methodology/approach

Qualitative research approach is used in this study. Through a Web search, data was gathered from all 39 universities in Sweden through two means: visiting university and their respective library websites; examination of other documents provided by the university such as press releases, announcements. Evaluation of the content and digital services and libraries response to COVID-19 is conducted by thematic coding.

Findings

In response to the ongoing COVID-19 spread, a general trend seen among all is limited working hours, shutting down physical libraries for general public, unmanning operations. All 39 number of universities in Sweden have moved their offerings toward using online tools. The main themes that have been identified from our study are as follows: Availability of Information, Accessibility of resources, Collaboration with other actors, Increased use of existing services, motivation and support to practice social distancing.

Research limitations/implications

Owing to the limitations of COVID-19 conditions, time and other aspects, there was not any opportunity to visit the university libraries or book time to interview librarians or students, which led to limited level and imperfect research. There are many other activities that university libraries are offering to their employees and using their internal newsletters and email groups to reach their audience; as a result, some of digital services that are offered during COVID-19 might have not been noticed.

Practical implications

These findings can provide base to other universities on how to react to COVID-19 and bring more discussion.

Social implications

COVID-19 has big social impact on people. The findings present that libraries can go beyond their responsibilities and provide emotional and psychological support the community towards social distancing such as videos, social online meetings, live video workshops.

Originality/value

The findings from this study call for a review digital services of academic libraries and their response to COVID-19 in Sweden, so that best reactions and services could be understood.
The importance of public support in the implementation of green transportation in smart cities using smart vehicle bicycle communication transport
Authors: Li Ning , R. Parthasarathy , Padwal Harshila H.
Published: November 2020

Purpose

Smart mobility is a major guideline in the development of Smart Cities’ transport systems and management. The issue of transition into green, secure and sustainable transport modes, such as using bicycles, should be implemented in this case, along with the subjectivism of management.

Design/methodology/approach

The proposed technology reflects the Smart Bicycle vehicle model, which tracks cyclists and weather conditions and turns to electric motors in critical circumstances.

Findings

This reduces the physical load and battery consumption of cyclists which affects the Smart Cities’ ecology positively.

Originality/value

In Smart Vehicle Bicycle Communication Transport, the vehicle movement optimization technique is used for traffic scenarios to analyze traffic signaling systems that give better results in variable and dense traffic conditions.
How traditional gender roles hurt both women and men: negative processes and outcomes in mixed-gender negotiations
Authors: Rua Tuvana , Aytug Zeynep , Simarasl Nastaran , Lin Lianlian
Published: November 2020

Purpose

Based on the social role theory, role congruity theory and gender role conflict theory, this paper aims to investigate the mediating role of “relationship conflict” in the association between traditional gender role (TGR) endorsement and objective and subjective negotiation outcomes.

Design/methodology/approach

Two experimental negotiation studies (n1 = 138, n2 = 128) were conducted at a US university.

Findings

This paper presents three original and noteworthy findings: One, in mixed-gender negotiations, as a dyad’s TGR endorsement increases, final agreements become significantly more likely to favor men than women. Two, in mixed-gender negotiations, TGR endorsement is significantly associated with a decreased ability to establish a pleasant, mutually satisfactory and successful business relationship, resulting in a possible future economic cost due to lost opportunity. Three, the heightened relationship conflict during the negotiation mediates the negative association between TGR endorsement and women’s economic outcomes.

Research limitations/implications

Empirical findings support social role theory, role congruity theory and gender role conflict theory. The use of a distributive negotiation case and laboratory research methodology may limit the generalizability of findings.

Practical implications

Findings about the detrimental effects of TGR in mixed-gender negotiations magnify the importance of becoming aware of our TGR orientations and their potential negative consequences on our long-term collaborations. Also, it is necessary to provide negotiation trainings to both genders with regard to gender-driven conflicts and offer tools to prevent or tackle such conflicts.

Social implications

Negotiations are among the most consequential of social interactions as their results have a substantial impact on individuals’ careers and financial outcomes. Understanding the effect of TGRs is paramount to improve female representation, participation and effectiveness in management and leadership. Mixed-gender negotiations such as collective equality bargaining, workplace social interactions, work-life balance discourse are critical to establishing gender equality and fairness in organizations and societies.

Originality/value

Understanding how gender influences negotiation processes and outcomes and using the findings to improve both genders’ negotiation success are crucial to establishing fairness and equity in society and business. This research attempts to close a gap in the literature by focusing on the potential function of gender role orientation in explaining gender differences in negotiation.
Social impact bonds in the UK homeless sector: perspectives of front-line link workers
Authors: George Thomas , Rogers Jim , Roberts Amanda
Published: November 2020

Purpose

Social impact bonds (SIBs) have become a favoured way to fund public services, including housing, prison and homelessness projects, in an era of austerity. In a growing critical literature on SIBs, a largely absent voice is that of the link worker. This paper aims to focus on the views of link workers in a SIB funded project which works with long-term entrenched rough sleepers in the East of England.

Design/methodology/approach

Interviews with link workers were conducted with a thematic analysis echoing many of the views expressed in the critical literature not only about the problems but also some of the advantages that SIBs offer to this type of project.

Findings

Three key themes were discomfort with the funding mechanism; flexible and innovative interventions that SIBs make possible; and problems with the outcome measures that trigger payments. This study concludes that if SIBs are to achieve their promise of providing funding which leads to effective solutions to deeply ingrained social problems, there needs to be more careful evaluation of their true benefits in comparison to publicly funded projects, adoption of more appropriate and project-specific outcome measures and a much clearer explanation and justification of the way in which SIB funding works.

Originality/value

Few studies have specifically explored the perceptions of front-line link workers in the homelessness sector. This study highlights not only the concerns but also the benefits associated with the use of SIB as a funding mechanism within the homelessness sector.
Challenges and opportunities with H-2B visas: can luxury resorts survive without them?
Authors: Kubickova Marketa , Neal Rebecca
Published: November 2020

Purpose

This study aims to provide a deeper look into why luxury resorts engage in the H-2B visa program and the opportunities and challenges from the human resources employee perspective. Adequate staffing is a well-documented challenge for luxury resorts due to their location, seasonality and access to qualified labor. Many resorts turn to the H-2B non-immigrant visa to mitigate the issue.

Design/methodology/approach

This study consists of in-depth interviews with human resource employees. An additional survey centering on descriptive statistics, the level of engagement, cost and experience with H-2B visa programs was collected.

Findings

The findings of this study provide a deeper understanding why luxury resorts use H-2B employees in their operations. The results shed a deeper light on issues centering around the H-2B visa process, its uncertainty, cost and complexity.

Practical implications

Temporary H-2B workers are essential to the success of resort operation. Collaboration between the resort management and government agencies is essential as strategic solutions must be implemented. Resorts must explore diversified recruitment opportunities and the use of technology while keeping human labor in the center of its core operation.

Originality/value

The first exploratory study providing a deeper look into the many challenges’ luxury resorts face when using the H-2B visa program from the human resources employee perspective. A call for change is being made as the respondents established the need for H-2B workers, however, the system in place makes it difficult to obtain such employees and to continue resort operations.