bluuebunny/crossref_metadata_2025 huggingface dataset:
A2G2: A Python wrapper to perform very large alignments in semi-conserved regions
Authors: Hleap Jose Sergio , Cristescu Melania E. , Steinke Dirk
Published: May 2020

Amplicons to Global Gene (A2G2) is a Python wrapper that uses MAFFT and an “Amplicon to Gene” strategy to align very large numbers of sequences while improving alignment accuracy. It is specially developed to deal with conserved genes, where traditional aligners introduce a significant amount of gaps.A2G2leverages theadd sequencesoption of MAFFT to align the sequences to a global reference gene and a local reference region. Both of these references can be consensus sequences of trusted sources. Efficient parallelization of these tasks allowsA2G2to align a very large number of sequences (> 500K) in a reasonable amount of time.A2G2can be imported in Python for easier integration with other software, or can be run via command line.

Availability

A2G2is implemented in Python 3 (3.6) and depends on MAFFT availability. Other package requirements can be found in the requirements.txt file athttps://github.com/jshleap/A2G.A2G2is also available via PyPi (https://pypi.org/project/A2G). It is licensed under the LGPLv3.

Supplementary information

Supplementary material is available at github as jupyter notebook.
smORFer: a modular algorithm to detect small ORFs in prokaryotes
Authors: Bartholomäus Alexander , Kolte Baban , Mustafayeva Ayten , Goebel Ingrid , Fuchs Stephan , Engelmann Susanne , Ignatova Zoya
Published: May 2020

Emerging evidence places small proteins (≤ 50 amino acids) more centrally in physiological processes. Yet, the identification of functional small proteins and the systematic genome annotation of their cognate small open reading frames (smORFs) remains challenging both experimentally and computationally. Ribosome profiling or Ribo-Seq (that is a deep sequencing of ribosome-protected fragments) enables detecting of actively translated open-reading frames (ORFs) and empirical annotation of coding sequences (CDSs) using the in-register translation pattern that is characteristic for genuinely translating ribosomes. Multiple identifiers of ORFs that use 3-nt periodicity in Ribo-Seq data sets have been successful in eukaryotic smORF annotation. Yet, they have difficulties evaluating prokaryotic genomes due to the unique architecture of prokaryotic genomes (e.g. polycistronic messages, overlapping ORFs, leaderless translation, non-canonical initiation etc.). Here, we present our new algorithm, smORFer, which performs with high accuracy in prokaryotic organisms in detecting smORFs. The unique feature of smORFer is that it uses integrated approach and considers structural features of the genetic sequence along with in-register translation and uses Fourier transform to convert these parameters into a measurable score to faithfully select smORFs. The algorithm is executed in a modular way and dependent on the data available for a particular organism allows using different modules for smORF search.
KOMB: Graph-Based Characterization of Genome Dynamics in Microbial Communities
Authors: Balaji Advait , Sapoval Nicolae , Seto Charlie , Elworth R.A. Leo , Nute Michael G. , Savidge Tor , Segarra Santiago , Treangen Todd J.
Published: May 2020

Characterizing metagenomic samples via kmer-based, database-dependent taxonomic classification methods has provided crucial insight into underlying host-associated microbiome dynamics. However, novel approaches are needed that are able to track microbial community dynamics within metagenomes to elucidate genome flux in response to perturbations and disease states. Here we describe KOMB, a novel approach for tracking homologous regions within microbiomes. KOMB utilizes K-core graph decomposition on metagenome assembly graphs to identify repetitive and homologous regions to varying degrees of resolution. K-core performs a hierarchical decomposition which partitions the graph into shells containing nodes having degree at least K, called K-shells, yieldingO(V + E) complexity compared to exact betweenness centrality complexity ofO(V E) found in prior related approaches. We show through rigorous validation on simulated, synthetic, and real metagenomic datasets that KOMB accurately recovers and profiles repetitive and homologous genomic regions across organisms in the sample. KOMB can also identify functionally-rich regions in Human Microbiome Project (HMP) datasets, and can be used to analyze longitudinal data and identify pivotal taxa in fecal microbiota transplantation (FMT) samples. In summary, KOMB represents a novel approach to microbiome characterization that can efficiently identify sequences of interest in metagenomes.
Extracting the Dynamics of Behavior in Decision-Making Experiments
Authors: Roy Nicholas A. , Bak Ji Hyun ,   The International Brain Laboratory, Akrami Athena , Brody Carlos D. , Pillow Jonathan W.
Published: May 2020

Understanding how animals update their decision-making behavior over time is an important problem in neuroscience. Decision-making strategies evolve over the course of learning, and continue to vary even in well-trained animals. However, the standard suite of behavioral analysis tools is ill-equipped to capture the dynamics of these strategies. Here, we present a flexible method for characterizing time-varying behavior during decision-making experiments. We show that it successfully captures trial-to-trial changes in an animal’s sensitivity to not only task-relevant stimuli, but also task-irrelevant covariates such as choice, reward, and stimulus history. We use this method to derive insights from training data collected in mice, rats, and human subjects performing auditory discrimination and visual detection tasks. With this approach, we uncover the detailed evolution of an animal’s strategy during learning, including adaptation to time-varying task statistics, suppression of sub-optimal strategies, and shared behavioral dynamics between subjects within an experimental population.
The dorsal and ventral default mode networks are dissociably modulated by the valence and vividness of imagined events
Authors: Lee Sangil , Parthasarathi Trishala , Kable Joseph W.
Published: May 2020

Recent work has shown that the brain’s default mode network (DMN) is active when people imagine the future. Here we test whether future imagination can be decomposed into two dissociable psychological processes linked to different subcomponents of the DMN. While measuring brain activity with fMRI as subjects imagine future events, we manipulate the vividness of these events to modulate the demands for scene construction, and we manipulate the valence of these events to modulate the demands for evaluation. We found that one subcomponent of the DMN, the ventral DMN or medial temporal lobe subsystem, responds to the vividness but not the valence of imagined events. In contrast, another subcomponent, the dorsal or core DMN, responds to the valence but not the vividness of imagined events. This separate modifiability of different subcomponents of the DMN by vividness and valence provides strong evidence for a neurocognitive dissociation between (1) the construction of novel, imagined scenes from individual components from memory and (2) the evaluation of these constructed events as desirable or undesirable.

Significance Statement

Previous work has suggested that imagination may depend on separate neural networks involved in the construction and evaluation of imagined future events. This study provides strong neural evidence for this dissociation by demonstrating that two components of the brain’s default mode network (DMN) uniquely and specifically respond to different aspects of imagination. The vividness of imagined events modulates the ventral DMN, but not the dorsal DMN, while the valence of imagined events modulates the dorsal DMN, but not the ventral DMN. This supports the dissociable engagement of these sub-networks in constructing and evaluating imagined future events.
Machine learning analysis of the bleomycin-mouse model reveals the compartmental and temporal inflammatory pulmonary fingerprint
Authors: Bordag Natalie , Biasin Valentina , Schnoegl Diana , Valzano Francesco , Jandl Katharina , Nagy Bence M. , Sharma Neha , Wygrecka Malgorzata , Kwapiszewska Grazyna , Marsh Leigh M.
Published: May 2020

The bleomycin mouse-model is the extensively used model to study pulmonary fibrosis, however, the inflammatory cell kinetics and their compartmentalisation is still incompletely understood. Here we assembled historical flow cytometry data, totalling 303 samples and 16 inflammatory-cell populations, and applied advanced data modelling and machine learning methods to conclusively detail these kinetics.

Three days post-bleomycin, the inflammatory profile was typified by acute innate inflammation, pronounced neutrophilia, especially of SiglecF+neutrophils, and alveolar macrophage loss. Between 14 and 21 days, rapid-responders were increasingly replaced by T and B cells, and monocyte-derived alveolar macrophages. Multi-colour imaging revealed the spatial-temporal cell distribution and the close association of T cells with deposited collagen.

Unbiased immunophenotyping and data modelling exposed the dynamic shifts in immune-cell composition over the course of bleomycin-triggered lung injury. These results and workflow provides a reference point for future investigations, and can easily be applied in the analysis of other datasets.
High burden ofMycoplasma genitaliumand other reproductive tract infections among pregnant women in Papua New Guinea
Authors: Scoullar Michelle J. L. , Boeuf Philippe , Peach Elizabeth , Fidelis Ruth , Tokmun Kerryanne , Melepia Pele , Elijah Arthur , Bradshaw Catriona S. , Fehler Glenda , Siba Peter M. , Erskine Simon , Mokany Elisa , Kennedy Elissa , Umbers Alexandra J. , Luchters Stanley , Robinson Leanne J. , Wong Nicholas C. , Vallely Andrew , Badman Steven G. , Vallely Lisa M. ,   HMHB Study Team, Fowkes Freya J. I. , Morgan Christopher , Pomat William , Crabb Brendan S. , Beeson James G.
Published: May 2020

There is a pressing need for detailed knowledge of the range of pathogens, extent of co-infection and clinical impact of reproductive tract infections (RTIs) among pregnant women. Here, we report on RTIs (Mycoplasma genitalium, Chlamydia trachomatis,Neisseria gonorrhoeae,Trichomonas vaginalis,Treponema pallidum subspecies pallidum,bacterial vaginosis and vulvovaginal candidiasis) and other sexual and reproductive health indicators among 699 pregnant women in Papua New Guinea (PNG). We found widespreadM. genitaliuminfection (12.5% of women), the first time this pathogen has been reported in PNG, with no evidence of macrolide resistance. Most pregnant women (76.2%) had at least one RTI, most of which are treatable. Excluding syphilis, sexually-transmitted infections were detected in 37.8% women. Syndromic management of infections is greatly inadequate and there was remarkably little use of contraception; 98.4% report never having used barrier contraception. This work has implications for improving maternal and child health in PNG.

ARTICLE SUMMARY LINE

This first report ofMycoplasma genitaliumin Papua New Guinea finds a high burden (12.5%) among 699 pregnant women. Additionally, more than one in two women were positive for a treatable reproductive tract infection associated with poor health outcomes.
Supramodal executive control of attention: evidence from unimodal and crossmodal dual conflict effects
Authors: Spagna Alfredo , Wu Tingting , Kim Kevin , Fan Jin
Published: May 2020

Although we have demonstrated that the executive control of attention acts supramodally as shown by significant correlation between conflict effects measures in visual and auditory tasks, no direct evidence of the equivalence in the computational mechanisms governing the allocation of executive control resources within and across modalities has been found. Here, in two independent groups of 40 participants, we examined the interaction effects of conflict processing in both unimodal (visual) and crossmodal (visual and auditory) dual-conflict paradigms (flanker conflict processing in Task 1 and then in the following Task 2) with a manipulation of the stimulus onset asynchrony (SOA). In both the unimodal and the crossmodal dual-conflict paradigms, the conflict processing of Task 1 interfered with the conflict processing of Task 2 when the SOA was short, reflecting an additive interference effect of Task 1 on Task 2 under the time constraints. These results suggest that there is a unified entity that oversees conflict processing acting supramodally by implementing comparable mechanisms in unimodal and crossmodal scenarios.
Severe murine schistosomiasis results from disruption of the modulation of anti-egg CD4 T cell response by immunodominance of a single egg epitope
Authors: Finger Eduardo , Coimbra Thaissa Melo Galante , Finardi de Souza Alessandra
Published: May 2020

This study exploits the consistent correlation between immunodominance of the major egg antigen Sm-p40234-246, a robust Th1/Th17 anti-egg CD4 response and severe liver immunopathology in experimental murine schistosomiasis as an experimental platform to analyze how different degrees of immunodominance affect CD4 modulation and disease outcome. The results show that strong immunodominance of a restricted egg epitope repertoire skews CD4 modulation towards a pathogenic Th1/Th17 pro-inflammatory response and that neutralizing this immunodominance generates an opposite and restorative effect. These results identify immunodominance as an important pathogenic component that influences CD4 modulation in experimental murine schistosomiasis and can be manipulated to treat this and maybe other CD4 mediated diseases.

Antigen informed CD4 modulation determines how efficiently the immune system neutralizes a threat; however, this process and its components are not fully comprehended. This study analyzes immunodominance as one component able to disrupt CD4 modulation and turn pathogenic an otherwise healthy immune response.
The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes
Authors: Wang Yihua , Burghardt Thomas P. , Worrell Gregory A. , Wang Hai-Long
Published: May 2020

Slow-wave sleep, defined by low frequency (<4 Hz) electrical brain activity, is a basic brain function affecting metabolite clearance and memory consolidation. Although the origin of low-frequency activity is related to cortical up and down states, the underlying cellular mechanism of how low-frequency activity becomes effective has remained elusive. We applied electrical stimulation to cultured glial astrocytes while monitored the trafficking of GFP-tagged intracellular vesicles using TIRFM. We found a frequency-dependent effect of electrical stimulation that electrical stimulation in low frequency elevates the mobility of astrocytic intracellular vesicles. We suggest a novel mechanism of brain modulation that electrical signals in the lower range frequencies embedded in brainwaves modulate the functionality of astrocytes for brain homeostasis and memory consolidation. This finding suggests a physiological mechanism whereby endogenous low-frequency brain oscillations enhance astrocytic function that may underlie some of the benefits of slow-wave sleep and highlights possible medical device approach for treating neurological diseases.
A Modular Microarray Imaging System for Highly Specific COVID-19 Antibody Testing
Authors: Hedde Per Niklas , Abram Timothy J. , Jain Aarti , Nakajima Rie , de Assis Rafael Ramiro , Pearce Trevor , Jasinskas Algis , Toosky Melody N. , Khan Saahir , Felgner Philip L. , Gratton Enrico , Zhao Weian
Published: May 2020

To detect the presence of antibodies in blood against SARS-CoV-2 in a highly sensitive and specific manner, here we describe a robust, inexpensive ($200), 3D-printable portable imaging platform (TinyArray imager) that can be deployed immediately in areas with minimal infrastructure to read coronavirus antigen microarrays (CoVAMs) that contain a panel of antigens from SARS-CoV-2, SARS-1, MERS, and other respiratory viruses. Application includes basic laboratories and makeshift field clinics where a few drops of blood from a finger prick could be rapidly tested in parallel for the presence of antibodies to SARS-CoV-2 with a test turnaround time of only 2-4 h. To evaluate our imaging device, we probed and imaged coronavirus microarrays with COVID-19-positive and negative sera and achieved a performance on par with a commercial microarray reader 100x more expensive than our imaging device. This work will enable large scale serosurveillance, which can play an important role in the months and years to come to implement efficient containment and mitigation measures, as well as help develop therapeutics and vaccines to treat and prevent the spread of COVID-19.
Dementias Platform UK Clinical Studies and Great Minds register: Protocol of a targeted brain health studies re-contact database
Authors: Koychev Ivan , Young Simon , Holve Heather , Yehuda Michael Ben , Gallacher John
Published: May 2020

Introduction

Efforts to de-risk neurodegenerative research have been hampered by the expense and time required to gather the rich longitudinal data needed for stratified experimental study recruitment. Dementias Platform UK (DPUK) is a public-private partnership that brings together data from over 40 cohorts in a standardised framework, which represents an until now unavailable opportunity to create such a resource through a streamlined brain health re-contact platform based on existing cohorts, as well as prospectively collected data.

Methods and analysis

The DPUK re-contact platform consists of an opt-in (Great Minds, GM) and an opt-out component (Clinical Studies register, CSR). GM requires invited DPUK cohort participants to consent to targeted re-contact at the GM website. Participants complete prospective browser- and smartphone-based cognitive tests and are given the option for remote genetic and actigraphy testing. The GM data is linked to the retrospective DPUK cohort dataset, including genotypic and longitudinal phenotypic data. The CSR is a solution for cohorts explicitly allowing targeted re-contact. Approved studies provide pre-screening criteria on the basis of the CSR/GM dataset, and individuals meeting these criteria are offered participation directly (GM) or through the parent DPUK cohort (CSR).

Ethics and dissemination

The database was approved by the South Central - Oxford C Research Ethics Committee, reference 18/SC/0268 on the 27th of June 2018 and amended on the 1st of November 2019. The availability of the Register to researchers will be disseminated through DPUK’s official communication channels as well as national and international scientific meetings.

Article Summary

Strengths and limitations of this study

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Solution for stratified recruitment into brain health studies on the basis of genetics and cross-cohort retrospective phenotypic data

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Prospective standardised data collection: medical history, cognition, actigraphy

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Explicit consent for re-contact on the basis of perceived dementia risk

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Recruitment on the basis of retrospective data limited by data variance between cohorts

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Limited scope for recruitment of symptomatic individuals due to need to register interest for research and respond to study offers through digital technology
Brain-behaviour relationships in the perceptual decision-making process through cognitive processing stages
Authors: Imani Elaheh , Harati Ahad , Pourreza Hamidreza , Moazami Goudarzi Morteza
Published: May 2020

Perceptual decision making, as a process of detecting and categorizing information, has been studied extensively over the last two decades. In this study, we investigated the neural characterization of the whole decision-making process by discovering the information processing stages. Such that, the timing and the neural signature of the processing stages were identified for individual trials. The association of stages duration with the stimulus coherency and spatial prioritization factors also revealed the importance of the evidence accumulation process on the speed of the whole decision-making process. We reported that the impact of the stimulus coherency and spatial prioritization on the neural representation of the decision-making process was consistent with the behavioral characterization as well. This study demonstrated that uncovering the cognitive processing stages provided more insights into the decision-making process.
Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord
Authors: Arulkandarajah Kalaimakan Hervé , Osterstock Guillaume , Lafont Agathe , Le Corronc Hervé , Escalas Nathalie , Corsini Silvia , Le Bras Barbara , Boeri Juliette , Czarnecki Antonny , Mouffle Christine , Bullier Erika , Hong Elim , Soula Cathy , Legendre Pascal , Mangin Jean-Marie
Published: May 2020

In the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate action potentials. Accordingly, the neuroepithelial progenitors (NEPs) giving rise to all neurons and glial cells during development have been reported to remain electrically passive. Here, we investigated the physiological properties of NEPs in the mouse spinal cord at the onset of spontaneous neural activity (SNA) initiating motor behavior in embryos. Using patch-clamp recordings, we discovered that spinal NEPs exhibit spontaneous membrane depolarizations during episodes of SNA. These recurrent depolarizations exhibited a ventral-to-dorsal gradient with the highest amplitude located in the floor-plate – the ventral-most part of the neuroepithelium. Paired-recordings revealed that NEPs are extensively coupled via gap-junctions and form a single electrical syncytium. Although other NEPs were electrically passive, we discovered that floor-plate NEPs have the unique ability to generate large Na+/Ca++action potentials. Unlike neurons, floor-plate action potentials relied primarily on the activation of voltage-gated T-type calcium channels (TTCCs).In situhybridization showed that all 3 known subtypes of TTCCs are highly and predominantly expressed in the floor-plate. During SNA, we found that acetylcholine released by motoneurons recurrently trigger floor-plate action potentials by acting through nicotinic acetylcholine receptors. Finally, by expressing the genetically encoded calcium indicator GCaMP6f in the floor plate, we demonstrated that neuroepithelial action potentials are associated with calcium waves and propagate along the entire length of the spinal cord. By unraveling a novel physiological mechanism generating electrical signals which can propagate independently from neurons across a neural structure, our work significantly changes our understanding of the development, origin and extent of electrical signaling in the central nervous system.

HIGHLIGHTS

Spinal neuroepithelial progenitors (NEP) are depolarized during spontaneous neural activity

NEPs form a single electrical syncytium connected by gap junctions

Floor-plate NEPs generate large Na+/Ca++action potentials in response to acetylcholine

Neuroepithelial action potentials propagate across the entire spinal cord
Culex pipiensL. andCulex restuansegg rafts harbor diverse bacterial communities compared to their midgut tissues
Authors: Juma Elijah O. , Kim Chang-Hyun , Dunlap Christopher , Allan Brian F. , Stone Chris M.
Published: May 2020

Background

The bacterial communities associated with mosquito eggs are an essential component of the mosquito microbiota, yet there are few studies characterizing and comparing the microbiota of mosquito eggs to other host tissues.

Methods

We sampled gravid femaleCulex pipiensandCulex restuansfrom the field, allowed them to oviposit in the laboratory, and characterized the microbiota associated with their egg rafts and midguts for comparison through MiSeq sequencing of the 16S rRNA gene.

Results

Bacterial richness was higher in egg rafts than in midguts for both species, and higher inCx pipiensL. thanCx. restuans. The midgut samples ofCx. pipiensandCx. restuanswere dominated byProvidencia. Culex pipiensL. andCx. restuansegg rafts samples were dominated byRalstoniaandNovosphingobium, respectively. NMDS ordination based on Bray-Curtis distance matrix revealed that egg raft samples, or midgut tissues harbored similar bacterial communities regardless of the mosquito species. Within each mosquito species, there were distinct clustering of bacterial communities between egg raft and midgut tissues.

Conclusion

These findings expand the list of described bacterial communities associated withCx. pipiensL. andCx. restuans and the additional characterization of the egg raft bacterial communities facilitates comparative analysis of mosquito host tissues, providing a basis for future studies seeking to understand any functional role of microbiota in mosquito biology.
Psychiatric Predictors of COVID-19 Outcomes in a Skilled Nursing Facility Cohort
Authors: Cercy Steven P.
Published: May 2020

The author has voluntarily withdrawn this manuscript because of questions raised about privacy issues in the conduct of this retrospective chart review. That issue is being contested by the author. Therefore, pending resolution of this matter, the author does not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Lifestyle acquired immunity, decentralized intelligent infrastructures and revised healthcare expenditures may limit pandemic catastrophe: a lesson from COVID-19
Authors: Ahmed Asif , Haque Tasnima , Rahman Mohammad Mahmudur
Published: May 2020

Human race has often faced pandemic with substantial number of fatalities. As COVID-19 pandemic reached and endured in every corner on earth, countries with moderate to strong healthcare support and expenditure seemed to struggle in containing disease transmission and casualties. COVID-19 affected countries have variability in demographic, socioeconomic and life style health indicators. At this context it is important to find out at what extent these parametric variations are actually modulating disease outcomes. To answer this, we have selected demographic, socioeconomic and health indicators e.g. population density, percentage of urban population, median age, health expenditure per capita, obesity, diabetes prevalence, alcohol intake, tobacco use, case fatality of non communicable diseases (NCDs) as independent variables. Countries were grouped according to these variables and influence on dependent variables e.g. COVID-19 test positive, case fatality and case recovery rates were statistically analyzed. The results suggest that countries with variable median age has significantly different outcome on test positive rate (P<0.01). Both median age (P=0.0397) and health expenditure per capita (P=0.0041) has positive relation with case recovery. Increasing number of test per 100K population showed positive and negative relation with number of positives per 100K population (P=0.0001) and percentage of test positives (P<0.0001) respectively. Alcohol intake per capita in liter (P=0.0046), diabetes prevalence (P=0.0389) and NCDs mortalities (P=0.0477) also showed statistical relation with case fatality rate. Further analysis revealed that countries with high healthcare expenditure along with high median age and increased urban population showed more case fatality but also had better recovery rate. Investment in health sector alone is insufficient in controlling pandemic severity. Intelligent and sustainable healthcare both in urban and rural settings and healthy lifestyle acquired immunity may reduce disease transmission and comorbidity induced fatalities respectively.
Estimating Household Transmission of SARS-CoV-2
Authors: Curmei Mihaela , Ilyas Andrew , Evans Owain , Steinhardt Jacob
Published: May 2020

Introduction and Goals

SARS-CoV-2 is transmitted both in the community and within households. Social distancing and lockdowns reduce community transmission but do not directly address household transmission. We provide quantitative measures of household transmission based on empirical data, and estimate the contribution of households to overall spread. We highlight policy implications from our analysis of household transmission, and more generally, of changes in contact patterns under social distancing.

Methods

We investigate the household secondary attack rate (SAR) for SARS-CoV-2, as well as Rh, which is the average number of within-household infections caused by a single index case. We identify previous works that estimated the SAR. We correct these estimates based on the false-negative rate of PCR testing and the failure to test asymptomatics. Results are pooled by a hierarchical Bayesian random-effects model to provide a meta-analysis estimate of the SAR. We estimate Rh using results from population testing in Vo’, Italy and contact tracing data that we curate from Singapore. The code and data behind our analysis are publicly available1.

Results

We identified nine studies of the household secondary attack rate. Our modeling suggests the SAR is heterogeneous across studies. The pooled central estimate of the SAR is 30% but with a posterior 95% credible interval of (0%, 67%) reflecting this heterogeneity. This corresponds to a posterior mean for the SAR of 30% (18%, 43%) and a standard deviation of 15% (9%, 27%). If results are not corrected for false negatives and asymptomatics, the pooled central estimate for the SAR is 20% (0%, 43%). From the same nine studies, we estimate Rh to be 0.47 (0.13, 0.77). Using contact tracing data from Singapore, we infer an Rh value of 0.32 (0.22, 0.42). Population testing data from Vo’ yields an Rh estimate of 0.37 (0.34, 0.40) after correcting for false negatives and asymptomatics.

Interpretation

Our estimates of Rh suggest that household transmission was a small fraction (5%-35%) of R before social distancing but a large fraction after (30%-55%). This suggests that household transmission may be an effective target for interventions. A remaining uncertainty is whether household infections actually contribute to further community transmission or are contained within households. This can be estimated given high-quality contact tracing data.

More broadly, our study points to emerging contact patterns (i.e., increased time at home relative to the community) playing a role in transmission of SARS-CoV-2. We briefly highlight another instance of this phenomenon (differences in contact between essential workers and the rest of the population), provide coarse estimates of its effect on transmission, and discuss how future data could enable a more reliable estimate.
COVIEdb: A database for potential immune epitopes of coronaviruses
Authors: Wu Jingcheng , Chen Wenfan , Zhou Jingjing , Zhao Wenyi , Chen Shuqing , Zhou Zhan
Published: May 2020

2019 novel coronavirus (2019-nCoV) has caused large-scale pandemic COVID-19 all over the world. It’s essential to find out which parts of the 2019-nCoV sequence are recognized by human immune system for vaccine development. And for the prevention of the potential outbreak of similar coronaviruses in the future, vaccines against immunogenic epitopes shared by different human coronaviruses are essential. Here we predict all the potential B/T-cell epitopes for SARS-CoV, MERS-CoV, 2019-nCoV and RaTG13-CoV based on the protein sequences. We found YFKYWDQTY in ORF1ab protein, VYDPLQPEL and TVYDPLQPEL in spike (S) protein might be pan-coronavirus targets for vaccine development. All the predicted results are stored in a database COVIEdb (http://biopharm.zju.edu.cn/coviedb/).
Decoding music-evoked emotions in the auditory and motor cortex
Authors: Putkinen Vesa , Nazari-Farsani Sanaz , Seppälä Kerttu , Karjalainen Tomi , Sun Lihua , Karlsson Henry K. , Hudson Matthew , Heikkilä Timo T. , Hirvonen Jussi , Nummenmaa Lauri
Published: May 2020

Music can induce strong subjective experience of emotions, but it is debated whether these responses engage the same neural circuits as emotions elicited by biologically significant events. We examined the functional neural basis of music-induced emotions in a large sample (n=102) of subjects who listened to emotionally engaging (happy, sad, fearful, and tender) pieces of instrumental music while their haemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). Ratings of the four categorical emotions and liking were used to predict haemodynamic responses in general linear model (GLM) analysis of the fMRI data. Multivariate pattern analysis (MVPA) was used to reveal discrete neural signatures of the four categories of music-induced emotions. To map neural circuits governing non-musical emotions, the subjects were scanned while viewing short emotionally evocative film clips. The GLM revealed that most emotions were associated with activity in the auditory, somatosensory and motor cortices, cingulate gyrus, insula, and precuneus. Fear and liking also engaged the amygdala. In contrast, the film clips strongly activated limbic and cortical regions implicated in emotional processing. MVPA revealed that activity in the auditory cortex in particular as well as in the primary motor cortices reliably discriminated the emotion categories. Our results indicate that different music-induced basic emotions have distinct representations in regions supporting auditory processing, motor control, somatosensation and interoception but do not strongly rely on limbic and medial prefrontal regions critical for emotions with survival value.
NK cells and CTLs are required to clear solid tumor in a novel model of patient-derived-xenograft
Authors: Le Duy Tri , Burt Bryan , Van Buren George , Abeynaike Shawn , Zalfa Cristina , Nikzad Rana , Kheradmand Farrah , Paust Silke
Published: May 2020

Existing patient-derived-xenograft (PDX) mouse models of solid tumors lack a fully tumor-donor matched “syngeneic” and functional immune system. We developed such a model by engrafting lymphopenic recipient mice with a fresh undisrupted piece of solid tumor, whereby tumor-infiltrating lymphocytes (TIL) expanded in the recipient mice for several weeks. Tumors engrafted in about seventy to eighty percent ofsyngeneic-immune-system-PDX (SIS-PDX) mice, which harbored tumor-exhausted immune-effector and functional immune-regulatory cells persisting for at least six-months post-engraftment. Interleukin-15 (IL-15)-stimulation in addition to immune checkpoint inhibition (ICI), prevented resistance, resulting in complete or partial response to combined treatment. Further, the depletion of Cytotoxic T lymphocytes (CTLs) and/or Natural Killer (NK) cells from combined immunotherapy in SIS-PDX mice revealed that both cell types are required for the maximal response to tumor. Our novel SIS-PDX model provides a valuable resource for powerful mechanistic and therapeutic studies designed to eradicate solid tumors.
CCM signaling complex (CSC) coupling both classic and non-classic progesterone receptor signaling
Authors: Abou-Fadel Johnathan , Jiang Xiaoting , Grajeda Brian , Padarti Akhil , Ellis Cameron C. , Zhang Jun
Published: May 2020

Excessive progesterone (PRG) may increase breast cancer risk under hormone therapy during postmenopause or hormonal contraception. As a sex steroid hormone, PRG exerts its cellular responses through signaling cascades involving classic (genomic), non-classic (non-genomic), or both combined responses by binding to either classic nuclear PRG receptors or non-classic membrane PRG receptors. Currently, the intricate balance and switch mechanisms between these two signaling cascades remain elusive. Three genes, KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3), have been demonstrated to form a CCM signaling complex (CSC). In this report, we discover that the CSC plays an essential role in coupling both classic and non-classic PRG signaling pathways by mediating crosstalk between them. The coupled signaling pathways were detailed through high throughput omics.

One Sentence Summary

We discover a novel signaling network among the CCM signaling complex (CSC), classic and non-classic progesterone receptors, and their ligands-progesterone/mifepristone, is dynamically modulated and fine-tuned with a series of feedback regulations; perturbation of this intricate balance, such as hormone therapy in the postmenopause or hormonal contraception regimen, or perturbed CSC signaling could result in increased risks in breast cancer or compromising tumor therapy.
Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein
Authors: Nikolaev EN , Indeykina MI , Brzhozovskiy AG , Bugrova AE , Kononikhin AS , Starodubtseva NL , Petrotchenko EV , Kovalev G , Borchers CH , Sukhikh GT
Published: May 2020

Detection of viral RNA by PCR is currently the main diagnostic tool for COVID-19 [1]. The PCR-based test, however, shows limited sensitivity, especially at early and late stages of the disease development [2,3], and is relatively time consuming. Fast and reliable complementary methods for detecting the viral infection would be of help in the current pandemia conditions. Mass-spectrometry is one of such possibilities. We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. Our approach shows confident identification of the N protein in patient samples even with the lowest viral loads and a much simpler preparation procedure. Our main protocol consists of virus inactivation by heating and adding of isopropanol, and tryptic digestion of the proteins sedimented from the swabs followed by MS analysis. A set of unique peptides, produced as a result of proteolysis of the nucleocapsid phosphoprotein of SARS-CoV-2, is detected. The obtained results can further be used to create fast parallel mass-spectrometric approaches for the detection of the virus in the nasopharyngeal mucosa, saliva, sputum and other physiological fluids.
Early Recovery Protocols Effect the Opioid Prescriptions at Discharge After Major Urologic Cancer Surgery
Authors: Carnes Kevin M. , Ata Ashar , Cangero Theodore , Mian Badar M.
Published: May 2020

Introduction

Early recovery after surgery (ERAS) protocols are designed limit the use of opioids during in-patient stay to facilitate recovery and early discharge. However, there are conflicting reports of opioids prescribed at discharge to these patients. We wished to evaluate the effect of early recovery efforts on the opioid prescriptions given at discharge after major urologic cancer surgery.

Methods

We reviewed opioid prescription data from patients discharged from our facility after major urologic cancer surgery from 2016 to 2018, including cystectomy, nephrectomy (total, partial) and prostatectomy. The opioid prescriptions were normalized to hydrocodone-5 mg tablet equivalents. Multivariable analysis was performed to evaluate the effect of various factors on opioid prescriptions at discharge.

Results

409 patients met the inclusion criteria, with 207 without ERAS and 202 on ERAS protocol. Potent opioid (oxycodone or hydrocodone) use was reduced from 92% to 43% and tramadol use increased from 8% to 57% (p < 0.001). Following ERAS, we noted reduction in opioid prescriptions for prostatectomy (30%, p < 0.001), cystectomy (27%, p = 0.02) and all nephrectomy procedures (32%, p < 0.001). On multivariable analysis for each procedure, ERAS protocol was a significant predictor of opioid prescriptions at discharge.

Conclusions

A significant decrease in the opioid prescriptions given at discharge was noted after major urologic cancer surgery with the use of ERAS protocols. There was a significant shift towards the use of less potent opioids. These findings provides a benchmark for further interventions and reduction in the outpatient opioid prescriptions after major urologic surgery.
Contributions of insula and superior temporal sulcus to interpersonal guilt and responsibility in social decisions
Authors: Gädeke Maria , Willems Tom , Ahmed Omar Salah , Weber Bernd , Hurlemann René , Schultz Johannes
Published: May 2020

This study investigated the neural mechanisms involved in feelings of interpersonal guilt and responsibility evoked by social decisions. In two studies (one during fMRI), participants repeatedly chose between safe and risky monetary outcomes in social contexts. Across conditions, each participant chose for both themselves and a partner (Socialcondition), or the partner chose for both themselves and the participant (Partnercondition), or the participant chose just for themselves (Solocondition, control). If the risky option was chosen in theSocialorPartnercondition, participant and partner could each receive either the high or the low outcome of a lottery with 50% probability, independently of each other. Participants were shown the outcomes for themselves and for their partner on each trial, and reported their momentary happiness every few trials. As expected, participant happiness decreased following both low lottery outcomes for themselves and for the partner. Crucially, happiness decreases following low outcomes for the partner were larger when the participant rather than their partner had made the choice, which fits an operational definition of guilt. This guilt effect was associated with BOLD signal increase in the left anterior insula. Connectivity between this region and the right inferior frontal gyrus varied depending on choice and experimental condition, suggesting that this part of prefrontal cortex is sensitive to guilt-related information during social choices. Variations in happiness were well explained by computational models based on participant’s and partner’s rewards and reward prediction errors. A model-based analysis revealed a left superior temporal sulcus cluster that tracked partner reward prediction errors that followed participant choices. Our findings identify neural mechanisms of guilt and social responsibility during social decisions under risk.
A developmental analysis of juxtavascular microglia dynamics and interactions with the vasculature
Authors: Mondo Erica , Becker Shannon C. , Kautzman Amanda G. , Schifferer Martina , Baer Christina E. , Chen Jiapei , Huang Eric J. , Simons Mikael , Schafer Dorothy P.
Published: May 2020

Microglia, the resident macrophages of the central nervous system (CNS), are dynamic cells, constantly extending and retracting their processes as they contact and functionally regulate neurons and other glial cells. There is far less known about microglia-vascular interactions, particularly under healthy steady-state conditions. Here, we use the male and female mouse cerebral cortex to show that a higher percentage of microglia associate with the vasculature during the first week of postnatal development compared to older ages and the timing of these associations are dependent on the fractalkine receptor (CX3CR1). Similar developmental microglia-vascular associations were detected in the prenatal human brain. Using live imaging in mice, we found that juxtavascular microglia migrated when microglia are actively colonizing the cortex and became stationary by adulthood to occupy the same vascular space for nearly 2 months. Further, juxtavascular microglia at all ages contact vascular areas void of astrocyte endfeet and the developmental shift in microglial migratory behavior along vessels corresponded to when astrocyte endfeet more fully ensheath vessels. Together, our data provide a comprehensive assessment of microglia-vascular interactions. They support a mechanism by which microglia use the vasculature to migrate within the developing brain parenchyma. This migration becomes restricted upon the arrival of astrocyte endfeet when juxtavascular microglia then establish a long-term, stable contact with the vasculature.

SIGNIFICANCE STATEMENT

We report the first extensive analysis of juxtavascular microglia in the healthy, developing and adult brain. Live imaging revealed that juxtavascular microglia within the cortex are highly motile and migrate along vessels as they are colonizing cortical regions. Using confocal, expansion, super-resolution, and electron microscopy, we determined that microglia associate with the vasculature at all ages in areas lacking full coverage astrocyte endfoot coverage and motility of juxtavascular microglia ceases as astrocyte endfeet more fully ensheath the vasculature. Our data lay the fundamental groundwork to investigate microglia-astrocyte crosstalk and juxtavascular microglial function in the healthy and diseased brain. They further provide a potential vascular-dependent mechanism by which microglia colonize the brain to later regulate neural circuit development.
Influence of the culture media on the aspect and growth of oilseed rape fungal pathogens
Authors: Ermel Magali , Jumel Stéphane , Bousset Lydia
Published: May 2020

While culturing fungal pathogens on artificial media, the phenotype, i.e. colony aspect, growth kinetics and in some case the pigment production can be used as discrimination criteria. Our aim was to enable the comparison between the growth kinetics of 8 fungal species, cultured simultaneously on 3 different media, and imaged under standardised conditions. Using a camera stand, taking pictures was quick and easy, producing homogeneous pictures, facilitating their comparison. The colony growth kinetics varied widely across the 8 species. The mycelium aspect and pigment production depended on the media and changed over time. Having standardised the imaging setup and grown species simultaneously allows proposing reference sets of pictures.
Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers
Authors: Wan W. , Clarke M. , Norris M. , Kolesnikova L. , Koehler A. , Bornholdt Z. , Becker S. , Saphire E.O. , Briggs J.A.G.
Published: May 2020

A key step in the life cycle of enveloped viruses is the budding of nascent virions from the host membrane. In filoviruses such as Ebola and Marburg virus, this process is achieved by the matrix protein VP40. When expressed alone, VP40 induces the budding of filamentous virus-like particles, suggesting that localization to the plasma membrane, oligomerization into a matrix layer, and the generation of membrane curvature are intrinsic properties of VP40. While a number of crystal structures of VP40 have been determined in various oligomerization states, there has been no direct information on the structure of assembled VP40 matrix layers within viruses or virus-like particles. Here, we present structures of Ebola and Marburg VP40 matrix layers in intact virus-like particles, as well as within intact Marburg viruses. We find that the matrix layers are formed from VP40 dimers which assemble into extended chains via C-terminal domain interactions. These chains stack into layers, forming a 2D lattice below the membrane surface. However, these 2D lattices are only locally ordered, forming a patchwork assembly across the membrane surfaces and suggesting that assembly may begin at multiple points. These observations define the structure and arrangement of the matrix protein layer that mediates the formation of filamentous filovirus particles.