bluuebunny/crossref_metadata_2025 huggingface dataset:
Light sets the brain’s daily clock by regional quickening and slowing of the molecular clockworks at dawn and dusk
Authors: Kim Suil , McMahon Douglas G.
Published: June 2020

How daily clocks in the brain are set by light to local environmental time and encode the seasons is not fully understood. The suprachiasmatic nucleus (SCN) is a central circadian clock that orchestrates physiology and behavior in tune with daily and seasonal light cycles. Here we have found that optogenetically simulated light input to explanted SCN changes the waveform of the molecular clockworks from sinusoidal in free-running conditions to highly asymmetrical shapes with accelerated synthetic (rising) phases and extended degradative (falling) phases marking clock advances and delays at simulated dawn and dusk. Daily waveform changes are sufficient to entrain to simulated winter and summer photoperiods, and to non-24h periods. SCN imaging further reveals that acute waveform shifts are greatest in the ventrolateral SCN, while period effects are greatest in the dorsomedial SCN. Thus, circadian entrainment is encoded by SCN clock gene waveform changes that arise from spatiotemporally distinct intrinsic responses within the SCN neural network.
Functional synchronization between hippocampal sEEG, parietal ECoG and scalp EEG during a verbal working memory task
Authors: Dimakopoulos Vasileios , Boran Ece , Hilfiker Peter , Stieglitz Lennart , Grunwald Thomas , Mégevand Pierre , Sarnthein Johannes
Published: June 2020

Background

The maintenance of items in working memory (WM) relies on a widespread network of brain areas where synchronization between electrophysiological recordings may reflect functional coupling. While the coupling from hippocampus to scalp EEG is well established, we provide here direct cortical recordings for a fine-grained analysis.

Methods

A patient performed a WM task where a string of letters was presented all at once, thus separating the encoding period from the maintenance period. We recorded sEEG from the hippocampus, temporo-parietal ECoG from a 64-contact grid electrode, and scalp EEG.

Results

Power spectral density (PSD) showed a clear task dependence: PSD in the posterior parietal lobe (10 Hz) and in the hippocampus (20 Hz) peaked towards the end of the maintenance period.

Inter-area synchronization was characterized by the phase locking value (PLV). WM maintenance enhanced PLV between hippocampal sEEG and scalp EEG specifically in the theta range [6 7] Hz.

PLV from hippocampus to parietal cortex increased during maintenance in the [9 10] Hz alpha and the 20 Hz range.

When analyzing the information flow to and from auditory cortex by Granger causality, the flow was from auditory cortex to hippocampus with a peak in the [8 18] Hz range while letters were presented, and this flow was subsequently reversed during maintenance, while letters were maintained in memory.

Conclusions

The increased functional interaction between hippocampus and cortex through synchronized oscillatory activity and the directed information flow provide physiological basis for reverberation of memory items during maintenance. This points to a network for working memory that is bound by coherent oscillations involving cortical areas and hippocampus.

SIGNIFICANCE STATEMENT

Hippocampal activity is known for its role in cognitive tasks involving episodic memory or spatial navigation, but its role in working memory and its sensitivity to workload is still under debate. Here, we investigated hippocampal and cortical activity while a subject maintained sets of letters in verbal working memory for a few seconds to guide action.

After confirming the coupling between hippocampal oscillations and oscillations on the scalp, we found during maintenance that hippocampal oscillations increased coupling differentially to several areas of cortex by recording directly from the cortex.. During encoding of the letters, information flow was from auditory cortex to hippocampus and subsequently reversed during maintenance, thus providing a physiological basis for memory encoding and maintenance.

This demonstrates a network for working memory that is bound by coherent oscillations that underlie the functional connectivity between cortical areas and hippocampus.
Coral cover surveys corroborate predictions on reef adaptive potential to thermal stress
Authors: Selmoni Oliver , Lecellier Gaël , Vigliola Laurent , Berteaux-Lecellier Véronique , Joost Stéphane
Published: June 2020

As anomalous heat waves are causing the widespread decline of coral reefs worldwide, there is an urgent need to identify coral populations tolerant to thermal stress. Heat stress adaptive potential is the degree of tolerance expected from evolutionary processes and, for a given reef, depends on the arrival of propagules from reefs exposed to recurrent thermal stress. For this reason, assessing spatial patterns of thermal adaptation and reef connectivity is of paramount importance to inform conservation strategies.

In this work, we applied a seascape genomics framework to characterize the spatial patterns of thermal adaptation and connectivity for coral reefs of New Caledonia (Southern Pacific). In this approach, remote sensing of seascape conditions was combined with genomic data from three coral species. For every reef of the region, we computed a probability of heat stress adaptation, and two indices forecasting inbound and outbound connectivity. We then compared our indicators to field survey data, and observed that decrease of coral cover after heat stress was lower at reefs predicted with high probability of adaptation and inbound connectivity. Last, we discussed how these indicators can be used to inform local conservation strategies and preserve the adaptive potential of New Caledonian reefs.
Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation
Authors: Gann Mareike A. , King Bradley R. , Dolfen Nina , Veldman Menno P. , Chan Kimberly L. , Puts Nicolaas A. J. , Edden Richard A. E. , Davare Marco , Swinnen Stephan P. , Mantini Dante , Robertson Edwin M. , Albouy Geneviève
Published: June 2020

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof- of-concept study employed a comprehensive multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and striatum during motor learning. Our results indicate that stimulation influenced task-relatedconnectivitypatterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in bothactivityandconnectivityin fronto-striato-hippocampal networks. This study provides the first experimental evidence that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.
Atrophy associated with tau pathology precedes overt cell death in a mouse model of progressive tauopathy
Authors: Fung Christine W. , Guo Jia , Figueroa Helen Y. , Konofagou Elisa E. , Duff Karen E.
Published: June 2020

In the early stages of Alzheimer’s disease (AD), tau pathology first develops in the entorhinal cortex (EC), then spreads to the hippocampus and at later stages, to the neocortex. Pathology in the neocortex correlates with impaired cognitive performance. Overall, tau pathology correlates well with neurodegeneration but the spatial and temporal association between tau pathology and overt volume loss is unclear. Usingin vivomagnetic resonance imaging (MRI) with tensor-based morphometry (TBM) we mapped the spatio-temporal pattern of structural changes in a mouse model of AD-like progressive tauopathy. A novel, co-registeredin vivoMRI atlas identified particular regions in the medial temporal lobe (MTL) that had significant volume reduction. The medial entorhinal cortex (MEC) and pre-/para-subiculum (PPS) had the most significant atrophy at the early stage, but atrophy then spread into the hippocampus, most notably, the CA1, dentate gyrus (DG) and subiculum (Sub). TBM-related atrophy in the DG and Sub preceded overt cell loss that has been reported inex vivostudies in the same mouse model. By unifying anex vivo3D reconstruction of tau pathology with the TBM-MRI results we mapped the progression of atrophy in the MTL with the corresponding spread of tau pathology. Our study shows that there is an association between the spread of tau pathology and TBM-related atrophy from the EC to the hippocampus, but atrophy in the DG and Sub preceded overt cell loss.

One Sentence Summary

Spread of tau pathology in a mouse model of Alzheimer’s disease assessed by MRI was associated with reduced brain tissue volume but not neuronal loss.
Assessing Attention Orienting in Mice: A Novel Touchscreen Adaptation of the Posner-Style Cueing Task
Authors: Li S. , May C. , Hannan AJ. , Johnson KA. , Burrows EL.
Published: June 2020

Atypical attention orienting has been found to be impaired in many neuropsychological disorders, but the underlying neural mechanism remains unclear. Attention can be oriented exogenously (i.e., driven by salient stimuli) or endogenously (i.e., driven by one’s goals or intentions). Genetic mouse models are useful tools to investigate the neurobiology of cognition, but a well-established assessment of attention orienting in mice is missing. This study aimed to adapt the Posner task, a widely used attention orienting task in humans, for use in mice using touchscreen technology and to test the effects of two attention-modulating drugs, methylphenidate (MPH) and atomoxetine (ATX), on the performance of mice during this task. In accordance with human performance, mice responded more quickly and more accurately to validly cued targets compared to invalidly cued targets, thus supporting mice as a valid animal model to study the neural mechanisms of attention orienting. This is the first evidence that mice can be trained to voluntarily maintain their nose-poke on a touchscreen and to complete attention orienting tasks using exogenous peripheral cues and endogenous symbolic cues. The results also showed no significant effects of MPH and ATX on attention orienting, although MPH improved overall response times in mice during the exogenous orienting task. In summary, the current study provides a critical translational task for assessing attention orienting in mice and to investigate the effects of attention-modulating drugs on attention orienting.
The Synthesis Success Calculator: Predicting the Rapid Synthesis of DNA Fragments with Machine Learning
Authors: Halper Sean M. , Hossain Ayaan , Salis Howard M.
Published: June 2020

The synthesis and assembly of long DNA fragments has greatly accelerated synthetic biology and biotechnology research. However, long turnaround times or synthesis failures create unpredictable bottlenecks in the design-build-test-learn cycle. We developed a machine learning model, called the Synthesis Success Calculator, to predict whether a long DNA fragment can be readily synthesized with a short turnaround time. The model also identifies the sequence determinants associated with the synthesis outcome. We trained a random forest classifier using biophysical features and a compiled dataset of 1076 DNA fragment sequences to achieve high predictive performance (F1score of 0.928 on 251 unseen sequences). Feature importance analysis revealed that repetitive DNA sequences were the most important contributor to synthesis failures. We then applied the Synthesis Success Calculator across large sequence datasets and found that 84.9% of theEscherichia coliMG1655 genome, but only 34.4% of sampled plasmids in NCBI, could be readily synthesized. Overall, the Synthesis Success Calculator can be applied on its own to prevent synthesis failures or embedded within optimization algorithms to design large genetic systems that can be rapidly synthesized and assembled.
TraceQC: An R package for quality control of CRISPR lineage tracing data
Authors: Hu Jingyuan , Al-Ouran Rami , Zhang Xiang , Liu Zhandong , Jeong Hyun-Hwan
Published: June 2020

Motivation

The CRISPR-based lineage tracing system is emerging as a powerful new sequencing tool to track cell lineages by marking cells with irreversible genetic mutations. Accurate reconstruction of cell lineages from CRISPR-based data is sensitive to noise. Quality control is critical for filtering out low-quality data points. Yet, existing quality control tools for RNA-seq and DNA-seq do not measure features specific for the CRISPR-linear tracing system.

Results

We introduce TraceQC, a quality control package to overcome challenges with measuring the quality of CRISPR-based lineage tracing data and help in interpreting and constructing lineage trees.

Availability

The R package is available athttps://github.com/LiuzLab/TraceQC.

Contact

zhandong.liu@bcm.eduorhyun-hwan.jeong@bcm.edu
Wnt ligands are not required for planar cell polarity in theDrosophilawing or notum
Authors: Ewen-Campen Ben , Comyn Typhaine , Vogt Eric , Perrimon Norbert
Published: June 2020

Thefrizzled(fz) anddisheveled(dsh) genes are highly conserved members of the core planar cell polarity (PCP) pathway and of the Wnt signaling pathway. Given these dual functions, a number of studies have examined whether Wnt ligands may provide a global, tissue-scale orientation cue for PCP establishment during development, and these studies have reached differing conclusions. In this study, we re-examine this issue in theDrosophila melanogasterwing and notum using split-Gal4 co-expression analysis, systematic pairwise and triple somatic CRISPR-based knock-outs and double RNAi experiments. Pairwise loss-of-function experiments targetingwgtogether with other Wnt genes does not produce PCP defects, neither via somatic CRISPR nor RNAi. In addition, somatic knock-out ofevi(akawntless), which is required for the secretion of all Wnt ligands expressed in these tissues, did not produce detectable PCP phenotypes. Altogether, we were unable to find support for the hypothesis that Wnt ligands contribute to PCP signaling in theDrosophilawing or notum.
Intracranial self-stimulation and concomitant behaviors following systemic methamphetamine administration inHnrnph1mutant mice
Authors: Borrelli Kristyn N. , Langan Carly R. , Dubinsky Kyra R. , Szumlinski Karen K. , Carlezon William A. , Chartoff Elena H. , Bryant Camron D.
Published: June 2020

Rationale

Addiction to methamphetamine (MA) is a major public health issue in the United States. While psychostimulant use disorders are heritable, their genetic basis remains poorly understood. We previously identified heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1;H1) as a quantitative trait gene underlying sensitivity to MA-induced locomotor activity. Mice heterozygous for a frameshift deletion in the first coding exon of H1 (H1+/-) showed reduced MA phenotypes including oral self-administration, locomotor activity, dopamine release, and dose-dependent differences in MA conditioned place preference. However, the effects of H1+/-on innate and MA-modulated reward sensitivity are not known.

Objectives

We examined innate reward sensitivity and modulation by MA in H1+/-mice via intracranial self-stimulation (ICSS).

Methods

We used intracranial self-stimulation (ICSS) of the medial forebrain bundle to assess shifts in reward sensitivity following acute, ascending doses of MA (0.5-4.0 mg/kg, i.p.) using a within-subjects design. We also assessed video-recorded behaviors during ICSS testing sessions.

Results

H1+/-mice displayed reduced normalized maximum response rates, H1+/-females showed lower normalized M50 values compared to wild-type females following MA, and H1+/-influenced ICSS responding relative to maximum baseline rates. There was a dose-dependent reduction in distance to the response wheel following MA administration, providing an additional measure of reward-related behavior.

Conclusions

H1+/-mice displayed reduced reward facilitation following MA in a sex- and dose-dependent manner. This result expands upon the set of MA-induced phenotypes observed in H1+/-mice.
DUSP7 Regulates the Activity of ERK2 to Promote Proper Chromosome Alignment During Cell Division
Authors: Guo Xiao , Garcia Yenni A. , Ramirez Ivan , Velasquez Erick F. , Gao Lucy W. , Gholkar Ankur A. , Whitelegge Julian P. , Tofig Bobby , Damoiseaux Robert , Torres Jorge Z.
Published: June 2020

Human cell division is a highly regulated process that relies on the accurate capture and movement of chromosomes to the metaphase plate. Errors in the fidelity of chromosome congression and alignment can lead to improper chromosome segregation, which is correlated with aneuploidy and tumorigenesis. Here we show that the dual specificity phosphatase DUSP7 is important for regulating chromosome alignment. DUSP7 bound to ERK2 and regulated the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of DUSP7, but not catalytic dead mutants, led to a marked decrease in phopho-ERK2 and mitotic chromosome misalignment, while knockdown of DUSP7 also led to defective chromosome congression that resulted in a prolonged mitosis. Consistently, chemical inhibition of the MEK kinase that phosphorylates ERK2 or ERK2 itself led to chromosome alignment defects. Our results support a model where MEK phosphorylation and DUSP7 dephosphorylation regulate the levels of active phospho-ERK2 to promote proper cell division.
ScRNA-seq discover cell cluster change under OAB——ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway
Authors: Xiang Boyu , Hu Xiangyu , Li Haoxuan , Ma Li , Zhou Hao , Wei Ling , Fan Jue , Zheng Ji
Published: June 2020

Objective

Previous study indicated that bladder cells which express ACE2 were a potential infection route of 2019-nCov. This study observed some differences of bladder cell cluster and their ACE2 expression between OAB mice and healthy mice, indicating the change of infectious possibility and pathway under overactive bladder (OAB) circumstance.

Material and method

Pubic dataset acquisition was used to get ACE2 expression in normal human bladder and mice bladder (GSE129845). We built up over OAB model and studied the impact on cell typing and ACE2 expression. By way of using single-cell RNA sequencing (scRNA-seq) technique, bladder cell clustering and ACE2 expression in various cell types were measured respectively.

Result

In pubic database (healthy human and mice bladder), ACE2 expression in humans and mice is concentrated in bladder epithelial cells. The disappearance of umbrella cells, a component of bladder epithelial, was found in our OAB model. In the two mouse bladder samples, ACE2 expression of epithelial cells is 34.1%, also the highest of all cell types.

Conclusion

The disappearance of umbrella cell may alternate the infection pathway of 2019-nCov and relate to the onset and progression of OAB.
Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways
Authors: Hudert Christian A. , Alisi Anna , Anstee Quentin M. , Crudele Annalisa , Draijer Laura G. ,   EU-PNAFLD investigators, Furse Samuel , Hengstler Jan G. , Jenkins Benjamin , Karnebeek Kylie , Kelly Deirdre A. , Koot Bart G. , Koulman Albert , Meierhofer David , Snowden Stuart G. , van Mourik Indra , Vreugdenhil Anita , Wiegand Susanna , Mann Jake P.
Published: June 2020

Background & aims

Genome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics.

Methods

960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1.

Results

rs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (P<0.001) whilst rs2642438G>A in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1.

Conclusions

There are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD.
Impact of Governmental interventions on epidemic progression and workplace activity during the COVID-19 outbreak
Authors: Ram Sumit Kumar , Sornette Didier
Published: June 2020

In the first quarter of 2020, the COVID-19 pandemic brought the world to a state of paralysis. During this period, humanity has seen by far the largest organized travel restrictions and unprecedented efforts and global coordination to contain the spread of the SARS-CoV-2 virus. Using large scale human mobility and fine grained epidemic incidence data, we develop a framework to understand and quantify the effectiveness of the interventions implemented by various countries to control epidemic growth. Our analysis reveals the importance of timing and implementation of strategic policy in controlling the epidemic. Through our analysis, we also unearth significant spatial diffusion of the epidemic before and during the lock-down measures in several countries, casting doubt on the effectiveness or on the implementation quality of the proposed Governmental policies.
Building comprehension to enhance vaccination intentions: Evidence from the United States and Italy
Authors: Porumbescu Greg , Cucciniello Maria , Pin Paolo , Melegaro Alessia
Published: June 2020

Building on Cognitive Load Theory and the Elaboration Likelihood Model of Persuasion this study attempts to deepen our understanding of how health information campaigns related to vaccination work. We predict that including statistical information in health information campaigns will serve as a distraction that suppresses comprehension that renders the campaign less effective at persuading the public to vaccinate. Results from a survey experiment conducted on samples of US (n = 605) and Italian parents (n = 505) show support for the hypothesized relationship depends upon the form of comprehension (comprehension of how vaccines work versus comprehension of potential adverse effects of vaccinating). Specifically, both US and Italian parents show including statistical information reduces comprehension of how vaccines work, in turn reducing parents’ intentions to vaccinate themselves and their children. We find no support for the hypothesized mechanism when comprehension of potential adverse effects of vaccinating acts as the process variable.
Losing ground at the wrong time: Trends in self-reported influenza vaccination uptake in Switzerland, Health Survey 2007–2017
Authors: Zürcher Kathrin , Zwahlen Marcel , Berlin Claudia , Egger Matthias , Fenner Lukas
Published: June 2020

Objectives

We studied time trends in seasonal influenza vaccination and associations with socioeconomic and health-related determinants in Switzerland, overall and in people aged ≥ 65 years.

Design

Three cross-sectional surveys.

Participants

Individuals who participated in the Swiss Health Surveys 2007, 2012, and 2017. We calculated the proportion reporting influenza vaccination in the last 12 months, and performed multivariable logistic regression analyses.

Results

The proportion of reporting a history of influenza vaccination overall was 31.9% (95% confidence intervals [95% CI] 31.4–32.4); and dropped from 34.5% in 2007 to 28.8% in 2017. The uptake of vaccination within the past 12 months was 16% in 2007 and similar in 2012 and 2017 (around 14%). In people with chronic disease, uptake dropped from 43.8% in 2007 to 37.1% in 2012 and to 31.6% in 2017 (p<0.001). In people aged ≥ 65 years, uptake dropped from 47.8% in 2007 to 38.5% in 2012 to 36.2% in 2017 (p<0.001). Similarly, a decrease in vaccine uptake was seen in people with poor self-reported health status (39.4%, 33.1%, and 27.0%). In logistic regression, self-reported vaccination coverage decreased in the 65 to 75 years old (adjusted odds ratio (aOR) aOR 0.56, 95% Cl 0.48–0.66 between 2007 and 2012; aOR 0.89, 95% CI 0.77–1.03). Uptake was positively associated with the ≥ 65 age group, living in French-speaking and urban areas, history of smoking, bad self-reported health status, private/semiprivate health insurance, having a medical profession, and having any underlying chronic disease. Use of any alternative medicine therapy was negatively associated with influenza vaccination (aOR 0.72, 95% CI 0.67–0.80).

Conclusion

Influenza vaccination coverage was low in older and chronically ill persons. Significant efforts are required in preparing for the flu season 2020/21 to reduce the double burden of COVID-19 and seasonal influenza. These efforts should include campaigns but also novel approaches using social media.

Strengths and limitations of this study

Data analysis of the Swiss Health Survey 2007, 2012, and 2017 focussing on influenza vaccine uptake overall and in the age group ≥65 years in Switzerland.

The Swiss Health Survey is a nationwide, representative survey that is repeated every five years using the same methodology.

Analyses were weighted and adjusted for a wide range of important cofactors.

We calculated percent of people reporting having been vaccinated and associations between vaccination status and socio-demographic and health-related factors.

Influenza vaccination status is self-reported in the Swiss Health Survey and the reliability of the data not ascertained.
THE ERA OF CORONAVIRUS; KNOWLEDGE, ATTITUDE, PRACTICES, AND BARRIERS TO HAND HYGIENE AMONG MAKERERE UNIVERSITY STUDENTS AND KATANGA COMMUNITY RESIDENTS
Authors: Nuwagaba Julius , Ashok Dave Darshit , Balizzakiwa Thomas , Kisengula Ibrahim , Nagaddya Edna Joyce , Rutayisire Meddy
Published: June 2020

Background

China reported the Novel Coronavirus at the end of the year 2019 which was, later on, declared a Pandemic by the WHO. Proper hand hygiene was identified as one of the simplest most cost-effective Covid-19 control and prevention measures. It is therefore very important to understand the compliance of the community to hand hygiene.

Method

A descriptive cross-sectional study was conducted among the undergraduate students of Makerere University and residents of Katanga slum from 17th to 22nd of March, 2020. An interviewer guided questionnaire with questions on knowledge, attitude, practice, and barriers to hand hygiene was used in data collection. The collected data was analyzed using Microsoft office excel 2016 and STATA 15 software. A 95% confidence interval was used and statistical significance was P<0.05.

Results

Only 8.4% of the participants had good knowledge of hand hygiene. 11.7% of the university students had good knowledge compared to 0.9% of the Katanga residents. 29.0% of the participants had a good attitude while 50.1% had a moderate attitude to hand hygiene. University students were 6.3 times (OR: 6.3, 95%C1: (2.1 – 18.5), P=0.001) more likely to have good knowledge while Katanga residents were 3.6 times (OR: 3.6, 95%C1: (1.5 – 8.4), P=0.003) more likely to have good attitude to hand hygiene. Only 19.6% accomplished all the seven steps of handwashing. 38.4% of the participants still greeted by handshaking and 60.1% noted lack of soap as a barrier to hand hygiene and 62.9% reported having more than three barriers to hand hygiene. Participants that had been taught handwashing were more likely to have better hand hygiene knowledge and practice.

Conclusion

Despite a fair attitude, deficiency of knowledge coupled with many barriers such as Lack of soap hindered the Practice of proper hand hygiene. Public health involvement to promote hand hygiene must be promoted.
Pollen Explains Flu-Like and COVID-19 Seasonality
Authors: Hoogeveen Martijn J. , van Gorp Eric C.M. , Hoogeveen Ellen K.
Published: June 2020

Current models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone, including associated behavior, do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be antiviral, anti-influenza and allergenic, plays a role in immuno-activation, and seems to create a bio-aerosol lowering the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics including COVID-19.

We tested the Pollen-Flu Seasonality Theory for 2016–2020 flu-like seasons, including COVID-19, in The Netherlands with its 17 million inhabitants. We combined changes in flu-like incidence per 100K/Dutch citizens (code: ILI) with weekly pollen counts and meteorological data. Finally, a discrete, predictive model is tested using pollen and meteorological threshold values displaying inhibitory effects on flu-like incidence.

We found a highly significant inverse association of r(224) = –.38 between pollen and changes in flu-like incidence corrected for incubation period, confirming our expectations for the 2019/2020 COVID-19 season. The associations become stronger when taking into account incubation time, which satisfies the temporality criteria. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = –.48 (p < .001) when thresholds of 610 total pollen grains/m3 per week, 120 allergenic pollen grains/m3 per week, and a solar radiation of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a supportive factor, temperature makes no difference, and relative humidity associates even with flu-like incidence increases.

We conclude that pollen is a predictor for the inverse seasonality of flu-like epidemics including COVID-19, and solar radiation is a co-inhibitor. The observed seasonality of COVID-19 during Spring, suggests that COVID-19 may revive in The Netherlands after week 33, the start being preceded by the relative absence of pollen, and follows standard pollen-flu seasonality patterns.
Cumulative Active and Recovery Rates Based Criterion for Gradual Lockdown Exit: A Global Observation of SARS Cov-2 Management
Authors: Raje Dhananjay V , Bajaj Abhay , Chakraborty Moumita , Purohit Hemant J
Published: June 2020

On March 11, 2020 the World Health Organization (WHO) had declared SARS-CoV-2 pandemic; and at present there are over 6 million cases across the globe. Based on the interim guidelines of WHO, most of the countries opted for social distancing with lockdown as the only way to control the pandemic. This led to ‘Manufacturing’ shut down, which acted as a spanner in the wheel for international supply chain leading to pressure on governments to review the protocols of the lockdown. We studied epidemiological parameters for 18 countries and obtained crossover time point referring to cumulative case active and case recovery rates and the time point for the peak positive confirmation rate in a time window of 92 days; and linked with the respective governmental decisions. For countries awaiting crossover, time series non-linear models could be used for predicting the crossover point. A sample study was carried out for India. The median time for reaching crossover for 12 countries was 37 days, while peak positive confirmation rate was 30 days after their first intervention. These countries enforced strict lockdown regulations and have shown constant improvement in their recovery rate even after crossover time point. A phase wise relaxation of lockdown is evident after crossover point in most of these countries. The crossover time point with the subsequent increasing recovery rate can be a strategy for lockdown relaxation as evident from the experiences of few countries. Also, we propose a criterion based on 28 cumulative recovery and fatality rate for micro-management of lockdown.
Circulating fibrocytes can identify people with a poor prognosis in idiopathic pulmonary fibrosis
Authors: Stewart Iain D. , Nanji Henry , Figueredo Grazziela , Fahy William A. , Maher Toby M. , Ask Antje J. , Maharaj Shyam , Ask Kjetil , Kolb Martin , Jenkins Gisli R.
Published: June 2020

Objective

Circulating fibrocytes are elevated in idiopathic pulmonary fibrosis, but the relationship between fibrocyte level with lung function decline and outcomes is lacking replication in prospective clinical study. We aim to validate the utility of circulating fibrocyte levels as a prognostic biomarker in idiopathic pulmonary fibrosis.

Methods

We tested associations between circulating fibrocyte levels, mortality, disease progression and longitudinal lung function in a well-defined prospective observational study of pulmonary fibrosis (PROFILE; NCT01134822). A subset of recruited participants had blood samples processed for fibrocyte measurement, with flow cytometry based on CD45 and collagen-I gating. Associations were tested using univariable and multivariable generalised linear models. Mortality data were subsequently combined with an independent cohort in a mixed-effect multilevel analysis.

Results

In 102 participants with idiopathic pulmonary fibrosis, an empirically defined cutpoint of 2.22% was associated with a greater risk of overall mortality in adjusted analysis (Hazard Ratio 2.24 95% CI 1.06-4.72). A 2.5 fold greater risk of mortality was supported in a pooled analysis with a historic cohort for a larger sample of 162 participants of idiopathic pulmonary fibrosis, specifically (Hazard Ratio 2.49 95% CI 2.41-2.56). A previously defined mortality risk threshold of 5% circulating fibrocytes was not reproducible in this cohort, circulating fibrocytes were not significantly elevated above non-specific interstitial pneumonia or healthy controls.. We found no association of fibrocytes with lung function or disease progression.

Conclusions

In a prospective clinical cohort of idiopathic pulmonary fibrosis, circulating fibrocytes of 2.22% or above are associated with greater mortality, but do not associate with disease related decline in lung function.

What is the key question?

Can circulating fibrocytes provide reproducible prognostic biomarker value in fibrotic lung disease?

What is the bottom line?

Greater proportions of fibrocytes isolated from circulating leukocyte populations are associated with an increase risk of mortality in idiopathic pulmonary fibrosis, but no association was observed with disease related decline in lung function.

Why read on?

We present associations and limitations of circulating fibrocytes in the largest sample of individuals with pulmonary fibrosis, recruited into a prospective observational study, and replicate prognositic insights from a historic cohort.
Combined oropharyngeal/nasal swab is equivalent to nasopharyngeal sampling for SARS-CoV-2 diagnostic PCR
Authors: Desmet Tania , De Paepe Peter , Boelens Jerina , Coorevits Liselotte , Padalko Elizaveta , Vandendriessche Stien , Leroux-Roels Isabel , Aerssens Annelies , Callens Steven , Van Braeckel Eva , Malfait Thomas , Vermassen Frank , Verhasselt Bruno
Published: June 2020

Background

Early 2020, a COVID-19 epidemic became a public health emergency of international concern. To address this pandemic broad testing with an easy, comfortable and reliable testing method is of utmost concern. The nasopharyngeal (NP) swab sampling is the reference method though hampered by international supply shortages. A new oropharyngeal/nasal (OP/N) sampling method was investigated using the more readily available throat swab.

Methods

In this prospective observational study 36 COVID-19 patients were tested with both a NP and combined OP/N swab for SARS-CoV-2 RNA by PCR. In hospitalized suspect patients, who tested negative on both swabs, extensive retesting was performed. The sensitivity of NP versus combined OP/N swab sampling on admission and the correlation between viral RNA loads recovered was investigated.

Results

35 patients were diagnosed with SARS-CoV-2 by means of either NP or OP/N sampling. The paired swabs were both positive in 31 patients. The one patient who tested negative on both NP and OP/N swab on admission, was ultimately diagnosed on bronchoalveolar lavage fluid. A strong correlation was found between the viral RNA loads of the paired swabs (r = 0.76; P < 0.05). The sensitivity of NP and OP/N analysis in hospitalized patients (n = 28) was 89.3% and 92.7% respectively.

Conclusions

This study demonstrates equivalence of NP and OP/N sampling for detection of SARS-CoV-2 by means of rRT-PCR. Sensitivity of both NP and OP/N sampling is very high in hospitalized patients.
Exosomes isolated from two different cell lines using three different isolation techniques show variation in physical and molecular characteristics
Authors: Dash Manish , Palaniyandi Kanagaraj , Ramalingam Satish , Sahabudeen S. , Raja N S
Published: June 2020

Exosomes are the nanoscopic lipid bi-layered extracellular vesicles with the potential to be utilized as targeted therapeutics. In our investigation, we compared three major exosome isolation techniques that were Total Exosome Isolation reagent (TEI), Protein organic solvent precipitation (PROSPR) and differential ultracentrifugation (UC) based on the biophysical and physicochemical characteristics of exosomes isolated from COLO 205 and MCF-7 cancer cell’s conditioned media with an aim to select a suitable method for translational studies. 3D image analysis and particle size distribution of exosomes from their HRTEM images depicted the morphological differences. Molecular and analytical characterization of exosomes using western blotting, Raman and ATR-FTIR spectroscopy and the multivariate analysis on the spectral data obtained, assessed for better molecular specifications and purity of particle. TEI method isolated exosomes with higher exosomal yield, purity, and recovery directly translatable into drug delivery and targeted therapeutics whereas ultracentrifuge had good recovery of particle morphology but showed particle aggregation and yielded exosomes with smaller mean size. PROSPR technique isolated a mixture of EVs, showed lower protein recovery in PAGE and western blotting but higher spectroscopic protein to lipid ratio and distinguishable EV population in multivariate analysis compared to exosomes isolated by TEI and UC. This comparative study should help in choosing a specific exosome isolation technique required for the objective of downstream applications.
Fitness landscape of a dynamic RNA structure
Authors: Soo Valerie WC , Swadling Jacob B , Faure Andre J , Warnecke Tobias
Published: June 2020

RNA structures are dynamic. As a consequence, mutational effects can be hard to rationalize with reference to a single static native structure. We reasoned that deep mutational scanning experiments, which couple molecular function to fitness, should capture mutational effects across multiple conformational states simultaneously. Here, we provide a proof-of-principle that this is indeed the case, using the self-splicing group I intron from Tetrahymena thermophila as a model system. We comprehensively mutagenized two 4-bp segments of the intron that come together to form the P1 extension (P1ex) helix at the 5’ splice site and, following cleavage at the 5’ splice site, dissociate to allow formation of an alternative helix (P10) at the 3’ splice site. Using an in vivo reporter system that couples splicing activity to fitness in E. coli, we demonstrate that fitness is driven jointly by constraints on P1ex and P10 formation and that patterns of epistasis can be used to infer the presence of intramolecular pleiotropy. Importantly, using a machine learning approach that allows quantification of mutational effects in a genotype-specific manner, we show that the fitness landscape can be deconvoluted to implicate P1ex or P10 as the effective genetic background in which molecular fitness is compromised or enhanced. Our results highlight deep mutational scanning as a tool to study transient but important conformational states, with the capacity to provide critical insights into the evolution and evolvability of RNAs as dynamic ensembles. Our findings also suggest that, in the future, deep mutational scanning approaches might help us to reverse-engineer dynamic interactions and critical non-native states from a single fitness landscape.
Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue
Authors: Cui Xin , Jing Jia , Wu Rui , Cao Qiang , Li Fenfen , Li Ke , Wang Shirong , Yu Liqing , Schwartz Gary , Shi Huidong , Shi Hang , Xue Bingzhong
Published: June 2020

Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a novel fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NTF3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NTF3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NTF3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NTF3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC+/-). Increasing NTF3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC+/- mice or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NTF3 is an important fat-derived neurotrophic factor regulating SNS innervation, energy metabolism and obesity.
Unlocking Elementary Conversion Modes: ecmtool unveils all capabilities of metabolic networks
Authors: Clement Tom J. , Baalhuis Erik B. , Teusink Bas , Bruggeman Frank J. , Planqué Robert , de Groot Daan H.
Published: June 2020

The metabolic capabilities of cells determine their biotechnological potential, fitness in ecosystems, pathogenic threat levels, and function in multicellular organisms. Their comprehensive experimental characterisation is generally not feasible, particularly for unculturable organisms. In principle, the full range of metabolic capabilities can be computed from an organism’s annotated genome using metabolic network reconstruction. However, current computational methods cannot deal with genome-scale metabolic networks. Part of the problem is that these methods aim to enumerate all metabolic pathways, while computation of all (elementally balanced) conversions between nutrients and products would suffice. Indeed, the elementary conversion modes (ECMs, defined by Urbanczik and Wagner) capture the full metabolic capabilities of a network, but the use of ECMs has not been accessible, until now. We extend and explain the theory of ECMs, implement their enumeration inecmtool, and illustrate their applicability. This work contributes to the elucidation of the full metabolic footprint of any cell.
RNA interference dynamics in juvenileFasciola hepaticaare altered duringin vitrogrowth and development
Authors: McCusker Paul , Hussain Wasim , McVeigh Paul , McCammick Erin , Clarke Nathan G. , Robb Emily , McKay Fiona M. , Brophy Peter M. , Timson David J. , Mousley Angela , Marks Nikki J. , Maule Aaron G.
Published: June 2020

For over a decade RNA interference (RNAi) has been an important molecular tool for functional genomics studies in parasitic flatworms. Despite this, our understanding of RNAi dynamics in many flatworm parasites, such as the temperate liver fluke (Fasciola hepatica), remains rudimentary. The ability to maintain developing juvenile flukein vitroprovides the opportunity to perform functional studies during development of the key pathogenic life stage. Here, we investigate the RNAi competence of developing juvenile liver fluke. Firstly, all life stages examined possess, and express, core candidate RNAi effectors encouraging the hypothesis that all life stages ofF. hepaticaare RNAi competent. RNAi effector analyses supported growing evidence that parasitic flatworms have evolved a separate clade of RNAi effectors with unknown function. Secondly, we assessed the impact of growth / development duringin vitroculture on RNAi inF. hepaticajuveniles and found that during the first week post-excystment liver fluke juveniles exhibit quantitatively lower RNAi mediated transcript knockdown when maintained in growth inducing media. This did not appear to occur in olderin vitrojuveniles, suggesting that rapidly shifting transcript dynamics over the first week following excystment alters RNAi efficacy after a single 24 hour exposure to double stranded (ds)RNA. Finally, RNAi efficiency was found to be improved through use of a repeated dsRNA exposure methodology that has facilitated silencing of genes in a range of tissues, thereby increasing the utility of RNAi as a functional genomics tool inF. hepatica.
MlaFEDB displays flippase activity to promote phospholipid transport towards the outer membrane of Gram-negative bacteria
Authors: Hughes Gareth W. , Sridhar Pooja , Nestorow Stephanie A. , Wotherspoon Peter J. , Cooper Benjamin F. , Knowles Timothy J.
Published: June 2020

MlaFEDB is a Gram-negative inner membrane protein complex involved in the inter membrane trafficking of phospholipids. Originally proposed to transport phospholipids in a retrograde direction, recent evidence suggests MlaFEDB may actually export phospholipids from the inner membrane to the periplasmic carrier protein, MlaC, potentially suggesting a role in either anterograde trafficking of phospholipids to the outer membrane or bidirectional phospholipid movement. MlaFEDB is part of the ABC transporter superfamily of proteins and has been shown to hydrolyse ATP through the cytoplasmic facing MlaF component. However, the movement of PLs from FEDB to MlaC has been shown to occur in an ATP independent fashion hence the role of ATP hydrolysis within this complex remains unclear. In this study we sought to elucidate the role of ATP and provide evidence to suggest MlaFEDB has flippase activity, utilising ATP hydrolysis to translocate phospholipids from the outer to the inner leaflet of the IM. We also show that in the absence of ATP MlaFEDB mediates the loading of MlaC with phospholipids directly from the inner leaflet only. Our data provides a novel role for MlaFEDB and presents a link between Mla driven phospholipid transport and ATP hydrolysis.