bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the antiviral mechanism of different MARCH factors
Authors: Umthong Supawadee , Lynch Brian , Timilsina Uddhav , Waxman Brandon , Ivey Emily B. , Stavrou Spyridon 
Published: December 2020

ABSTRACTThe Membrane Associated RING-CH (MARCH) proteins belong to a family of E3 ubiquitin ligases, whose main function is to remove transmembrane proteins from the plasma membrane. Recent work has shown that the human MARCH1, 2 and 8 are antiretroviral factors that target the Human Immunodeficiency virus-1 (HIV-1) envelope glycoproteins by reducing their incorporation in the budding virions. Nevertheless, the dearth of information regarding the antiviral mechanism of this family of proteins necessitates further examination. In this study, using both the human MARCH proteins and their mouse homologues, we provide a comprehensive analysis of the antiretroviral mechanism of this family of proteins. Moreover, we show that human MARCH proteins restrict to varying degrees the envelope glycoproteins of a diverse number of viruses. This report sheds light on the important antiviral function of MARCH proteins and their significance in cell intrinsic immunity.
Long-read assemblies reveal structural diversity in genomes of organelles - an example withAcacia pycnantha
Authors: Syme Anna E. , McLay Todd G.B. , Udovicic Frank , Cantrill David J. , Murphy Daniel J. 
Published: December 2020

AbstractAlthough organelle genomes are typically represented as single, static, circular molecules, there is evidence that the chloroplast genome exists in two structural haplotypes and that the mitochondrial genome can display multiple circular, linear or branching forms. We sequenced and assembled chloroplast and mitochondrial genomes of the Golden Wattle,Acacia pycnantha,using long reads, iterative baiting to extract organelle-only reads, and several assembly algorithms to explore genomic structure. Using ade novoassembly approach agnostic to previous hypotheses about structure, we found different assemblies revealed contrasting arrangements of genomic segments; a hypothesis supported by mapped reads spanning alternate paths.
RoDiCE: Robust differential protein co-expression analysis for cancer complexome
Authors: Matsui Yusuke , Abe Yuichi , Uno Kohei , Miyano Satoru 
Published: December 2020

AbstractMotivationThe full spectrum of abnormalities in cancer-associated protein complexes remains largely unknown. Comparing the co-expression structure of each protein complex between tumor and healthy cells may provide insights regarding cancer-specific protein dysfunction. However, the technical limitations of mass spectrometry-based proteomics, including contamination with biological protein variants, causes noise that leads to non-negligible over- (or under-) estimating co-expression.ResultsWe propose a robust algorithm for identifying protein complex aberrations in cancer based on differential protein co-expression testing. Our method based on a copula is sufficient for improving identification accuracy with noisy data compared to conventional linear correlation-based approaches. As an application, we use large-scale proteomic data from renal cancer to show that important protein complexes, regulatory signaling pathways, and drug targets can be identified. The proposed approach surpasses traditional linear correlations to provide insights into higher order differential co-expression structures.Availability and Implementationhttps://github.com/ymatts/RoDiCE.
Fam72acontrols the balance between error-prone and error-free DNA repair during antibody diversification
Authors: Rogier Mélanie , Moritz Jacques , Robert Isabelle , Lescale Chloé , Heyer Vincent , Thomas-Claudepierre Anne-Sophie , Abello Arthur , Deriano Ludovic , Reina-San-Martin Bernardo 
Published: December 2020

AbstractEfficient humoral responses rely on DNA damage, mutagenesis and error-prone DNA repair. B cell receptor diversification through somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by cytidine deamination in DNA mediated by activation induced cytidine deaminase (AID)1and by the subsequent excision of the resulting uracils by Uracil DNA glycosylase (UNG) and by mismatch repair (MMR) proteins2–4. Although uracils arising in DNA are faithfully repaired2–7, it is not known how these pathways are co-opted to generate mutations and double stranded DNA breaks (DSBs) in the context of SHM and CSR2,4,8. Here we have performed a genome-wide CRISPR/Cas9 knockout screen for genes involved in CSR. The screen identified FAM72A, a protein that interacts with the nuclear isoform of UNG (UNG2)9and that is overexpressed in several cancers9. We show that the FAM72A-UNG2 interaction controls the protein levels of UNG2 and that CSR is defective inFam72a−/−B cells due to the specific upregulation of UNG2. Moreover, we show that inFam72a−/−B cells SHM is reduced by 5-fold and that upregulation of UNG2 results in a skewed mutation pattern. Our results are consistent with a model in which FAM72A interacts with UNG2 to control its physiological level by triggering its degradation. Consequently, deficiency inFam72aleads to supraphysiological levels of UNG2 and enhanced uracil excision, shifting the balance from error-prone to error-free DNA repair. Our findings have potential implications for tumorigenesis, asFam72aoverexpression would lead to reduced UNG2 levels, shifting the balance toward mutagenic DNA repair and rendering cells more prone to acquire mutations.
Distinct VIP interneurons in the cingulate cortex encode anxiogenic and social stimuli
Authors: Johnson Connor , Kretsge Lisa N. , Yen William W. , Sriram Balaji , Jimenez Jessica C. , Jinadasa Tushare J. , O’Connor Alexandra , Sky Liu Ruichen , Nguyen Thanh P. H. , Cho Eun Seon , Fuchs Erelle , Spevack Eli D. , Velasco Berta Escude , Hausmann Frances S. , Cruz-Martín Alberto 
Published: December 2020

ABSTRACTA hallmark of higher-order cortical regions is their functional heterogeneity, but it is not well understood how these areas encode such diverse information. The anterior cingulate cortex (ACC), for example, is important in both emotional regulation and social cognition. Previous work shows activation of the ACC to anxiety-related and social stimuli, but it is unknown how subpopulations or microcircuits within the ACC simultaneously encode these distinct stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to alter the activity of many cells in local cortical microcircuits, but it is unknown whether the activity of VIP cells in the ACC (VIPACC) encodes anxiety-related or social information. Using in vivo calcium imaging and miniscopes in freely behaving mice to monitor VIPACCactivity, we identified distinct, non-overlapping subpopulations of VIPACCthat preferentially activated to either anxiogenic, anxiolytic, social, or non-social stimuli. We determined that stimulus-selective cells encode the animal’s behavioral states and VIP interneuron clusters may co-activate, improving this encoding. Finally, we used trans-synaptic tracing to show that VIPACCreceive widespread inputs from regions implicated in emotional regulation and social cognition. These findings demonstrate not only that the ACC is not homogeneous in its function, but also that there is marked functional heterogeneity even within disinhibitory interneuron populations. This work contributes to our understanding of how the cortex encodes information across diverse contexts and provides insight into the complexity of neural processes involved in anxiety and social behavior.
Population genetics of recent colonization suggests the importance of recurrent immigration on remote islands
Authors: Aoki Daisuke , Matsui Shin , Esashi Mari , Nishiumi Isao , Nagata Junco , Takagi Masaoki 
Published: December 2020

AbstractAimFounder effects and recurrent immigration are two major factors that potentially contribute to genetic differentiation and population persistence in the early-stage of remote island colonization. However, their relative importance remains controversial. By conducting population genetics analyses of multiple remote island populations of the bull-headed shrike established naturally within several decades, we examined the relative contributions of founder effects and recurrent immigration on these island populations.LocationJapanTaxonLanius bucephalusMethodsWe used 15 microsatellite loci to analyze the population genetics of four newly established island populations and five Japanese mainland populations. Allelic richness, heterozygosity, genetic differentiation, and the strength of the genetic bottleneck were compared among the islands. Two analyses, STRUCTURE and the DAPC, were conducted to assess the relative influence of founder effects and recurrent immigration on genetic differentiation. Temporal samples collected over eight years on Minami-Daito Island were used to detect any change in genetic structure due to recurrent immigration.ResultsThe founder effect strongly influenced genetic differentiation on the most remote oceanic island, Chichi-jima Island. However, this population became extinct 20 years after colonization, possibly owing to a lack of recurrent immigration. The founder effect moderately influenced a land-bridge island, Kikai-jima Island, indicating the presence of a relatively large founder population without recurrent immigration. Surprisingly, another distant oceanic island, Minami-Daito Island, was likely subject to multiple recurrent immigration events from the mainland, which obscured any genetic differentiation previously established by the founder effect.Main conclusionUnderlying the island-specific population dynamics of colonization, founder effects contributed to the genetic differentiation among the three studied island populations. Importantly, however, recurrent immigration strongly affected the population persistence and subsequent evolutionary processes of remote island populations, potentially overwhelming the founder effect. We argue the importance of recurrent immigration in highly remote island colonization, which has been previously overlooked.
Risk factors for community transmission of SARS-CoV-2. A cross-sectional study in 116,678 people
Authors: Kjetland Eyrun F. , Kalleberg Karl Trygve , Søraas Camilla Lund , Hammarström Bato , Myklebust Tor Åge , Jenum Synne , Axelsen Eyvind , Lind Andreas , Bævre-Jensen Roar , Jørgensen Silje Bakken , Pettersen Frank Olav , Solberg Lene B. , Hadley Cathrine Lund , Istre Mette S. , Liestøl Knut , Dahl John Arne , Ursin Giske , Søraas Arne 
Published: December 2020

AbstractBackgroundThe risk factors for SARS-CoV-2 transmission are not well characterised in Western populations. We sought to identify potential risk factors for transmission and actionable information to prevent for SARS-CoV-2.MethodsIndividuals tested for SARS-CoV-2 at four major laboratories were invited. In addition, participants were sampled by convenience after a media campaign. Self-reported test results were compared with laboratory results, demographic data and behavioural facts were collected using a digital platform. In a cross-sectional design positive cases were compared with negative and untested control groups.FindingsApproximately 14 days after a countrywide lockdown in Norway, 116,678 participants were included. Median age was 46 years, 44% had children in preschool or in school; 18% were practicing health professionals. International flights, contact with infected, and gatherings of more than 50 people, were associated with high risk. Health professionals who used public transport were at higher risk of testing positive than those who did not. Having undergone light infections, the last six months was strongly associated with lower odds ratio of SARS-CoV-2 positivity. Contact with children, use of hand sanitiser and use of protective gloves in private were also associated with lower odds ratio of testing positive for SARS-CoV-2.InterpretationFurther research is needed to explore if being a parent or looking after children is associated with lower risk of SARS-CoV-2 positivity in the next phases of the pandemic. Immunological research should be done to determine the effects of prior trivial infections on SARS-CoV-2 infection. We confirm that large gatherings during the pandemic should be avoided and those who are infected, or under suspicion thereof, posed very high risks to others this population.
Risk Assessment and Mitigation of Airborne Disease Transmission in Orchestral Wind Instrument Performance
Authors: Abraham Aliza , He Ruichen , Shao Siyao , Kumar S. Santosh , Wang Changchang , Guo Buyu , Trifonov Maximilian , Placucci Rafael Grazzini , Willis Mele , Hong Jiarong 
Published: December 2020

AbstractThere has been growing concern about high risk of airborne infection during wind instrument performance as the COVID-19 pandemic evolves. In collaboration with 16 musicians from the Minnesota Orchestra, we employ multiple experimental and numerical techniques to quantify the airflow and aerosol concentration emitted from ten wind instruments under realistic performance conditions. For all instruments, the extent of the flow and aerosol influence zones are limited to 30 cm. Further away, the thermal plume generated by the human body is the dominant source of flow. Flow and aerosol concentration vary in response to changes in music amplitude, pitch, and note duration, depending on playing technique and instrument geometry. Covering the trumpet bell with speaker cloth and placing filters above the instrument outlet can substantially reduce the aerosol concentration. Our findings indicate that with appropriate risk mitigation strategies, musical instrument performance can be conducted with low risk of airborne disease transmission.
Spotlight on the dark figure: Exhibiting dynamics in the case detection ratio of COVID-19 infections in Germany
Authors: Schneble Marc , De Nicola Giacomo , Kauermann Göran , Berger Ursula 
Published: December 2020

AbstractThe case detection ratio of COVID-19 infections varies over time due to changing testing capacities, modified testing strategies and also, apparently, due to the dynamics in the number of infected itself. In this paper we investigate these dynamics by jointly looking at the reported number of detected COVID-19 infections with non-fatal and fatal outcomes in different age groups in Germany. We propose a statistical approach that allows us to spotlight the case detection ratio and quantify its changes over time. With this we can adjust the case counts reported at different time points so that they become comparable. Moreover we can explore the temporal development of the real number of infections, shedding light on the dark number. The results show that the case detection ratio has increased and, depending on the age group, is four to six times higher at the beginning of the second wave compared to what it was at the peak of the first wave. The true number of infection in Germany in October was considerably lower as during the peak of the first wave, where only a small fraction of COVID-19 infections were detected. Our modelling approach also allows quantifying the effects of different testing strategies on the case detection ratio. The analysis of the dynamics in the case detection rate and in the true infection figures enables a clearer picture of the course of the COVID-19 pandemic.
Improving the heterologous production of fungal peroxygenases through an episomalPichia pastorispromoter and signal peptide shuffling system
Authors: Püllmann Pascal , Weissenborn Martin J. 
Published: December 2020

ABSTRACTFungal Peroxygenases (UPOs) have emerged as oxyfunctionalization catalysts of tremendous interest in recent years. However, their widespread use in the field of biocatalysis is still hampered by their challenging heterologous production, substantially limiting the panel of accessible enzymes for investigation and enzyme engineering. Building upon previous work on UPO production in yeast, we have developed a combined promoter and -signal peptide shuffling system for episomal high throughput UPO production in the industrially relevant, methylotrophic yeastPichia pastoris. 11 endogenous and orthologous promoters were shuffled with a diverse set of 17 signal peptides. Three previously described UPOs were selected as first test set, leading to the identification of beneficial promoter/signal peptide combinations for protein production. We applied the system then successfully to produce two novel UPOs:MfeUPO fromMyceliophthora fergusiiandMhiUPO fromMyceliophthora hinnulea.To demonstrate the feasibility of the developed system to other enzyme classes, it was applied for the industrially relevant lipase CalB and the laccase Mrl2. In total, approximately 3200 transformants of eight diverse enzymes were screened and the best promoter/signal peptide combinations studied at various co-feeding, derepression and induction conditions. High volumetric production titers were achieved by subsequent creation of stable integration lines and harnessing orthologous promoters fromHansenula polymorpha. In most cases promising yields were also achieved without the addition of methanol under derepressed conditions. To foster the use of the episomal high throughput promoter/signal peptidePichia pastorissystem, we made all plasmids available through Addgene.
MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis
Authors: Carroll Patrick A. , Cheng Pei Feng , Freie Brian W , Kasinathan Sivakanthan , Gu Haiwei , Hedrich Theresa , Dowdle James A. , Venkataramani Vivek , Ramani Vijay , Raftery Daniel , Shendure Jay , Ayer Donald E. , Muller Charles H. , Eisenman Robert N. 
Published: December 2020

AbstractMale germ cell production is a metabolically-driven and apoptosis-prone process. Here we show that the glucose-sensing transcription factor MLX, and its binding partner MondoA, are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss ofMlxresults in altered metabolism as well as activation of multiple stress pathways and germ cell apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific germ cell transcripts and proteins, manifesting as oligoasthenoteratozoospermia (OAT). Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, apoptotic effectors and obligate components of male-specific germ cell development. Thesein vivoandin vitrostudies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors.Highlights-The MAX-like bHLHLZ protein MLX is required for male fertility, but not embryonic development.-MLX and its heterodimeric partner MondoA are each required for both male fertility and survival of male germ cell tumors.-Genomic analysis identifies direct MLX targets associated with metabolism, stress and male germ cell development.-Loss of MLX alters MYC network genome occupancy and transcriptional output.
Fucoidan but not 2’-Fucosyllactose could inhibit human norovirus replication in zebrafish larvae
Authors: Tan Malcolm Turk Hsern , Li Yan , Gorji Mohamad Eshaghi , Gong Zhiyuan , Li Dan 
Published: December 2020

AbstractHuman noroviruses (hNoVs) cause heavy disease burden worldwide and there is no clinically approved vaccination or antivirals hitherto. In this study, with the use of a zebrafish larvaein vivoplatform, we investigated the anti-hNoV potentials of fucoidan and 2’-Fucosyllactose (2’-FL). As a result, although both fucoidan and 2-’FL were able to block hNoV GII.4 virus-like particle (VLPs) from binding to type A saliva as expected, only fucoidan but not 2-’FL was able to inhibit the replication of hNoV GII.P16-GII.4 in zebrafish larvae, indicating the possible needs of higher molecular weights for fucosylated carbohydrates to exert anti-hNoV effect.
QKI 6 ameliorates CIRI through promoting synthesis of triglyceride in neuron and inhibiting neuronal apoptosis associated with SIRT1-PPARγ-PGC-1α axis
Authors: Liu Rui , Li Hongzeng , Deng Jingyuan , Wu Qunqiang , Liao Chunhua , Xiao Qun , Chang Qi 
Published: December 2020

AbstractThe stroke induced by ischemia of brain remains high incidence and death rate. The study wanted to confirm the effects of QKI 6 on the protection role in neurons of rat model of cerebral ischemia/reperfusion injury (CIRI). The rat model with CIRI induced by MCAO (middle cerebral artery occlusion) was well established and rat neurons were isolated to characterize the effects of QKI 6 mediated by SIRT1 on synthesis of triglyceride in neuron and neuronal apoptosis via activation of SIRT1-PPARγ-PGC-1α signaling pathway. The expression levels of SIRT1 or QKI 6, and acetylation level of QKI 6 was decreased in neurons of rat model with CIRI. QKI 6 deacetylated and mediated by SIRT1 that contributed to suppressing the progression of neuronal apoptosis in rat through promoting synthesis of triglyceridein vivoandin vitrovia SIRT1-PPARγ-PGC-1α signaling pathway, then inhibiting CIRI. In conclusion, our results demonstrated SIRT1 deacetylates QKI 6, the RNA-binding protein, that affects significantly the synthesis of triglyceride in neurons of CIRI rat model. Moreover, it activated transcription factor PGC-1α through post-transcriptional regulation of the expression of PPARγ, and further enhanced synthesis of triglyceride, thereby restrained the progression of neural apoptosis and CIRI.
Analysis of the intrinsic chromatin binding property of HIV-1 integrase and its regulation by LEDGF/p75 using human chromosomes spreads
Authors: Lapaillerie D. , Mauro E. , Lelandais B. , Ferran G. , Kuschner N. , Calmels C. , Métifiot M. , Rooryck C. , Ruff M. , Zimmer C. , Lesbats P. , Toutain J. , Parissi V. 
Published: December 2020

ABSTRACTRetroviral integration requires the stable insertion of the viral genome into the host chromosomes. During this process, the functional integration complex must associate with cellular chromatinviathe interaction between retroviral integrase and nucleosomes. The final association between the HIV-1 integration complex and the nucleosomal target DNA remains unclear and may involve the chromatin-binding properties of both the retroviral integrase and its cellular cofactor LEDGF/p75. To date, there is no experimental system allowing the direct monitoring of this protein association with chromatin to depict the molecular mechanism of this process fully. To investigate this and understand the LEDGF/p75-mediated chromatin tethering of HIV-1 integrase further, we used both biochemical approaches and an unedited chromosome-binding assays. Our study revealed that retroviral IN has an intrinsic ability to bind and recognize specific chromatin regions even in the absence of its cofactor. We also showed that this integrase chromatin-binding property was modulated by the interaction with its cofactor LEDGF/p75, which redirected the enzyme to alternative chromatin regions. Using these approaches, we also better determined the chronology of efficient LEDGF/p75-mediated targeting of HIV-1 integrase to chromatin. In addition to supporting a chromatin-binding function of the integrase protein acting in concert with LEDGF/p75 for the optimal association with the nucleosomal substrate, our work precisely elucidates the mechanism of action of LEDGF/p75 in this crucial integration step.