bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resource Allocation in Annual Plants
Authors: McMorris David , Ledder Glenn 
Published: April 2021

AbstractThe fitness of an annual plant can be thought of as how much fruit is produced by the end of its growing season. Under the assumption that annual plants grow to maximize fitness, we can use techniques from optimal control theory to understand this process. We introduce a model for resource allocation in annual plants which extends classical work by Iwasa and Roughgarden to a case where both carbohydrates and mineral nutrients are allocated to shoots, roots, and fruits in annual plants. We use optimal control theory to determine the optimal resource allocation strategy for the plant throughout its growing season as well as develop a numerical scheme to implement the model in MATLAB. Our results suggest that what is optimal for an individual plant is highly dependent on initial conditions, and optimal growth has the effect of driving a wide range of initial conditions toward common configurations of biomass by the end of a growing season.
Basal forebrain parvalbumin neurons modulate vigilant attention
Authors: Schiffino Felipe L. , McNally James M. , Brown Ritchie E. , Strecker Robert E. 
Published: April 2021

SummaryAttention is impaired in many neuropsychiatric disorders1and by sleep disruption, leading to decreased workplace productivity and increased risk of accidents2–4. Thus, understanding the underlying neural substrates is important for developing treatments. The basal forebrain (BF) is a brain region which degenerates in dementia5–7and is implicated in the negative effects of sleep disruption on vigilance and cognition8,9. Previous studies demonstrated that the BF controls cortical fast oscillations that underlie attention10–12and revealed the important role of cholinergic neurons13–15. However, the role of other neurochemically defined BF subtypes is unknown. Recent work has shown that one population of BF GABAergic neurons containing the calcium-binding protein parvalbumin (PV) control cortical fast oscillations and arousals from sleep16–19but their role in awake behavior is unclear. Thus, here we test the hypothesis that BF-PV neurons modulate vigilant attention in mice. A lever release version of the rodent psychomotor vigilance test (rPVT) was used to assess vigilant attention as measured by reaction time. Brief and continuous low power optogenetic excitation of BF-PV neurons (1s,473nm@5mW) that preceded the cue light signal by 0.5s improved vigilant attention as indicated by quicker reaction times. In contrast, both sleep deprivation (8h) and optogenetic inhibition of BF-PV neurons (1s,530nm@10mW) slowed reaction times. Importantly, BF-PV excitation rescued the reaction time deficits in sleep deprived mice. These findings reveal for the first time a role for BF-PV neurons in attention.HIGHLIGHTSOptogenetic methods tested the neural circuitry of vigilant attention in miceExcitation of basal forebrain parvalbumin neurons quickened reaction timesSleep deprivation or inhibition of parvalbumin neurons slowed reaction timesExcitation of parvalbumin neurons rescued deficits produced by sleep deprivation
The dynamics of subunit rotation in a eukaryotic ribosome
Authors: Freitas Frederico Campos , Fuchs Gabriele , de Oliveira Ronaldo Junio , Whitford Paul Charles 
Published: April 2021

AbstractProtein synthesis by the ribosome is coordinated by an intricate series of large-scale conformational rearrangements. Structural studies can provide information about long-lived states, however biological kinetics are controlled by the intervening free-energy barriers. While there has been progress describing the energy landscapes of bacterial ribosomes, very little is known about the energetics of large-scale rearrangements in eukaryotic systems. To address this topic, we constructed an all-atom model with simplified energetics and performed simulations of subunit rotation in the yeast ribosome. In these simulations, the small subunit (SSU; ~1MDa) undergoes spontaneous and reversible rotations (~ 8°). By enabling the simulation of this rearrangement under equilibrium conditions, these calculations provide initial insights into the molecular factors that control dynamics in eukaryotic ribosomes. Through this, we are able to identify specific inter-subunit interactions that have a pronounced influence on the rate-limiting free-energy barrier. We also show that, as a result of changes in molecular flexibility, the thermodynamic balance between the rotated and unrotated states is temperature-dependent. This effect may be interpreted in terms of differential molecular flexibility within the rotated and unrotated states. Together, these calculations provide a foundation, upon which the field may begin to dissect the energetics of these complex molecular machines.
Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis
Authors: Yamamoto Kei , Miura Haruko , Ishida Motohiko , Sawai Satoshi , Kondo Yohei , Aoki Kazuhiro 
Published: April 2021

AbstractActomyosin contractility generated cooperatively by nonmuscle myosin II and actin filaments plays essential roles in a wide range of biological processes, such as cell motility, cytokinesis, and tissue morphogenesis. However, it is still unknown how actomyosin contractility generates force and maintains cellular morphology. Here, we demonstrate an optogenetic method to induce relaxation of actomyosin contractility. The system, named OptoMYPT, combines a catalytic subunit of the type I phosphatase-binding domain of MYPT1 with an optogenetic dimerizer, so that it allows light-dependent recruitment of endogenous PP1c to the plasma membrane. Blue-light illumination was sufficient to induce dephosphorylation of myosin regulatory light chains and decrease in traction force at the subcellular level. The OptoMYPT system was further employed to understand the mechanics of actomyosin-based cortical tension and contractile ring tension during cytokinesis. We found that the relaxation of cortical tension at both poles by OptoMYPT accelerated the furrow ingression rate, revealing that the cortical tension substantially antagonizes constriction of the cleavage furrow. Based on these results, the OptoMYPT system will provide new opportunities to understand cellular and tissue mechanics.
A Multiscale Model of Traumatic Brain Injury Suggests Possible Mechanisms of Post-Traumatic Psychosis
Authors: Sakthivadivel Dalton A R 
Published: April 2021

AbstractTraumatic brain injury is a devastating injury to the brain that can have permanent or fatal effects, leading to life-long deficits or death. Among these effects is psychosis and schizophrenia, sometimes reported in the population of TBI sufferers. Here we evaluate a possible mechanism of post-traumatic psychosis, shedding light on the anomalous nature of psychosis as over-activity and brain injury as destruction. Using a multiscale model of the brain to relate molecular pathology to connectomic and macroscopic features of the brain, we identify cell lysis and membrane deformation as a possible mechanism for psychosis after injury. We also evaluate the reorganisation of functional networks and cortical activation post-injury, and find the features of a simulated brain under traumatic injury correlate with recorded results on the schizophrenic functional connectome. This provides a possible mechanism for post-traumatic psychosis, as well as a proof-of-principle of advanced multiscale modelling methods in computational psychiatry and neuromedicine. It also elaborates on the relationship between structure and function in the brain, information processing, and the delicate regulation of activity in healthy brains.
Genetic diversity, evolutionary dynamics and pathogenicity of ferret badger rabies virus variants in mainland China, 2008-2018
Authors: Miao Faming , Zhao Jinghui , Li Nan , Liu Ye , Chen Teng , Mi Lijuan , Yang Jinjin , Chen Qi , Zhang Fei , Feng Jie , Li Shunfei , Zhang Shoufeng , Hu Rongliang 
Published: April 2021

ABSTRACTIn contrast to dog associated human rabies cases decline year by year due to the rabies vaccination coverage rates increase in China, ferret badger (FB,Melogale moschata)–associated human rabies cases emerged in the 1990s, and are now an increasingly recognized problem in southeast China. To investigate epidemiology, temporal evolution dynamics, transmission characterization and pathogenicity of FB-associated rabies viruses (RABVs), from 2008 to 2018, we collected 3,622 FB brain samples in Jiangxi and Zhejiang Province, and detected 112 RABV isolates. Four FB-related lineages were identified by phylogenetic analysis (lineages A–D), the estimated Times to Most Recent Common Ancestor were 1941, 1990, 1937 and 1997 for lineages A–D respectively. Furthermore, although no FB-associated human rabies case has been reported there apart from Wuyuan area, FB-RABV isolates are mainly distributed in Jiangxi Province. Pathogenicity of FB-RABVs was assessed using peripheral inoculation in mice and in beagles with masseter muscles, mortality-rates ranging from 20% to 100% in mice and 0 to 20% in beagles in the groups infected with the various isolates. Screening of sera from humans with FB bites and no postexposure prophylaxis to rabies, revealed that 5 of 9 were positive for neutralizing antibodies of RABV. All the results above indicated that FB-RABV variants caused a lesser pathogenicity in mice, beagles and even humans. Vaccination in mice suggests that inactivated vaccine or recombinant subunit vaccine products can be used to control FB- associated rabies, however, oral vaccines for stray dogs and wildlife need to be developed and licensed in China urgently.IMPORTANCEIn recent years FB-associated rabies virus has been identified as a major life-threatening pathogen in some districts in China. To understand the risk to public health and the contemporary dynamics, the present study conducted extensive investigations on FB rabies, distribution, virus isolation, phylogeny analysis, pathogenicity determination of various FB rabies virus strains, besides, serologic epidemiology survey to those whom bit by FB was also collected. The results show that the majority of FBs dwell in southeast China, like Jiangxi and Zhejiang Province, Phylogenetic analysis indicates that all isolated FB RABVs evolved from dogs, and the FB RABV can separate into 4 distinct lineages distributed relatively independent in different areas. The isolate strains differ in pathogenicity, although they have relatively lower pathogenicity compared to dog rabies virus according to our study, the need for further study to licensed oral vaccines and FB RABV pathogenesis is emphasized in order to control rabies.
Prevalence of severe adverse events in health professionals after receiving the first dose of the COVID-19 vaccination in Togo, March 2021
Authors: Konu Yao Rodion , Gbeasor-Komlanvi Fifonsi Adjidossi , Yerima Mouhoudine , Sadio Arnold , Tchankoni Martin Kouame , Zida-Compaore Wendpouire Ida Carine , Nayo-Apetsianyi Josée , Afanvi Kossivi Agbélénbko , Agoro Sibabe , Salou Mounerou , Landoh Dadja Essoya , Nyansa Atany B. , Boko Essohanam , Mijiyawa Moustafa , Ekouevi Didier Koumavi 
Published: April 2021

AbstractIntroductionCovid-19 vaccines can cause adverse events (AE) that can lead to increased hesitation or fear of vaccination. This study aims at estimating the prevalence of severe adverse events (SAEs) and their associated factors among health professionals (HPs) vaccinated with COVISHIELD™ vaccine in Togo.MethodsA cross-sectional study was conducted from March 13th to 19th, 2021 in Togo among HPs who received the first dose of vaccine. An online self-administered questionnaire was used to collect data on sociodemographic characteristics and vaccination. SAEs were defined as one resulting in hospitalization, medical consultation, or inability to work the day following the administration of the vaccine. Regression analysis were performed to assess factors associated with SAEs.ResultsA total of 1,639 HP (70.2% male) with a median age [IQR] of 32 years [27-40] participated. At least one AE was reported among 71.6% (95%CI= [69.3-73.8]). The most commonly reported AEs were pain at the injection site (91.0%), asthenia (74.3%), headache (68.7%), soreness (55.0%), and fever (47.5%). An increased libido was also reported in 3.0% of HP. Among HP who experienced AEs, 18.2% were unable to go to work the day after vaccination, 10.5% consulted a medical doctor, and 1.0% were hospitalized. The SAE prevalence was 23.8% (95%CI= [21.8-25.9]). Being <30 years (aOR=5.54; p<0.001), or 30-49 years (aOR=3.62; p<0.001) and being female (aOR=1.97; p<0.001) were associated with SAEs.ConclusionDespite the occurrence of SAEs, current data collected in Togo about adverse events are reassuring with COVISHIELD™ vaccine and how they could be managed.Key pointsThe prevalence of severe adverse events (SAEs) after COVID-19 vaccination was high among health professionals in Togo, especially in the youths (under 30years).Despite the occurrence of SAEs, current data collected in Togo about adverse events are reassuring with COVISHIELD(TM) vaccine and provide information about how the could be managed.
mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection
Authors: Ivanova Ellie N. , Shwetar Jasmine , Devlin Joseph C. , Buus Terkild B. , Gray-Gaillard Sophie , Koide Akiko , Cornelius Amber , Samanovic Marie I. , Herrera Alberto , Mimitou Eleni P. , Zhang Chenzhen , Karmacharya Trishala , Desvignes Ludovic , Ødum Niels , Smibert Peter , Ulrich Robert J. , Mulligan Mark J. , Koide Shohei , Ruggles Kelly V. , Herati Ramin S. , Koralov Sergei B. 
Published: April 2021

AbstractSARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell dataset of peripheral blood of patients with acute COVID-19 and of healthy volunteers before and after receiving the SARS-CoV-2 mRNA vaccine and booster. We compared host immune responses to the virus and vaccine using transcriptional profiling, coupled with B/T cell receptor repertoire reconstruction. COVID-19 patients displayed an enhanced interferon signature and cytotoxic gene upregulation, absent in vaccine recipients. These findings were validated in an independent dataset. Analysis of B and T cell repertoires revealed that, while the majority of clonal lymphocytes in COVID-19 patients were effector cells, clonal expansion was more evident among circulating memory cells in vaccine recipients. Furthermore, while clonal αβ T cell responses were observed in both COVID-19 patients and vaccine recipients, dramatic expansion of clonal γδT cells was found only in infected individuals. Our dataset enables comparative analyses of immune responses to infection versus vaccination, including clonal B and T cell responses. Integrating our data with publicly available datasets allowed us to validate our findings in larger cohorts. To our knowledge, this is the first dataset to include comprehensive profiling of longitudinal samples from healthy volunteers pre/post SARS-CoV-2 vaccine and booster.
A novel strain of lumpy skin disease virus causes clinical disease in cattle in Hong Kong
Authors: Flannery John , Shih Barbara , Haga Ismar R. , Ashby Martin , Corla Amanda , King Simon , Freimanis Graham , Polo Noemi , Tse Anne Ching-Nga , Brackman Christopher J. , Chan Jason , Pun Patrick , Ferguson Andrew D. , Law Andy , Lycett Samantha , Batten Carrie , Beard Philippa M. 
Published: April 2021

SummaryLumpy skin disease virus (LSDV) is an emerging poxviral pathogen of cattle that is currently spreading throughout Asia. The disease situation is of high importance for farmers and policy makers in Asia. In October 2020, feral cattle in Hong Kong developed multifocal cutaneous nodules consistent with lumpy skin disease (LSD). Gross and histological pathology further supported the diagnosis and samples were sent to the OIE Reference Laboratory at The Pirbright Institute for confirmatory testing. LSDV was detected using quantitative polymerase chain reaction (qPCR) and additional molecular analyses. This is the first report of LSD in Hong Kong. Whole genome sequencing (WGS) of the strain LSDV/HongKong/2020 and phylogenetic analysis were carried out in order to identify connections to previous outbreaks of LSD, and better understand the drivers of LSDV emergence. Analysis of the 90 core poxvirus genes revealed LSDV/HongKong/2020 was a novel strain most closely related to the live-attenuated Neethling vaccine strains of LSDV and more distantly related to wildtype LSDV isolates from Africa, the Middle East and Europe. Analysis of the more variable regions located towards the termini of the poxvirus genome revealed genes in LSDV/HongKong/2020 with different patterns of grouping when compared to previously published wildtype and vaccine strains of LSDV. This work reveals that the LSD outbreak in Hong Kong in 2020 was caused by a different strain of LSDV than the LSD epidemic in the Middle East and Europe in 2015-2018. The use of WGS is highly recommended when investigating LSDV disease outbreaks.
Global profiling of human blood ILC subtypes reveals that NK cells produce homeostatic cytokine amphiregulin and sheds light on HIV-1 pathogenesis
Authors: Wang Yetao , Lifshitz Lawrence , Silverstein Noah J. , Mintzer Esther , Luk Kevin , St. Louis Pam , Brehm Michael A , Wolfe Scot A. , Deeks Steven G. , Luban Jeremy 
Published: April 2021

AbstractThe interrelatedness of human blood innate lymphoid cell (ILC) subsets, and how they are perturbed by HIV-1, remains unclear. Transcriptional and chromatin profiling separated blood ILCs into ILC2s, ILCPs, one cluster that included CD56dimand CD56−NK cells, and CD56hiNK cells that have features of both CD56dim/–NK cells and ILCs. In contrast to mice, human NK cells expressed tissue repair protein amphiregulin (AREG), with greater production by CD56hiNK cells than by ILCs. AREG was induced by TCF7/WNT signaling, IL-2, or IL-15, but not by inflammatory cytokines, and was inhibited by TGFB1, a cytokine elevated in people living with HIV-1. NK cell knockout of the TGFB1-stimulated WNT antagonist RUNX3 increased AREG production. In people living with HIV-1, AREG+NK cell percentage correlated with numbers of ILCs and CD4+T cells, and correlated inversely with inflammatory cytokine IL-6. RNA-Seq showed increased antiviral gene expression in all ILC subsets from people who were HIV-1 viremic, and increased expression of anti-inflammatory gene MYDGF in CD56hiNK cells from elite controllers. Functionally-defective CD56−NK cells were increased in people living with HIV-1 in inverse correlation with CD56dimNK cells, ILCs, and CD4+T cells. Experiments with human PBMCsex vivoand in humanized mice revealed that CD4+T cells and their production of IL-2 prevented CD56dimtransition to CD56−NK cells by activating mTOR, and, in people living with HIV-1, plasma IL-2 correlated with CD4+T cell number but not with CD8+T cells. These studies clarify how ILC subsets are interrelated and provide insight into how HIV-1 infection disrupts NK cells, including homeostatic functions of NK cells discovered here.Graphical Abstract
Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat
Authors: Kurnaeva Margarita A. , Zalevsky Arthur O. , Arifulin Eugene A. , Lisitsyna Olga M. , Tvorogova Anna V. , Shubina Maria Y. , Bourenkov Gleb P. , Tikhomirova Maria A. , Potashnikova Daria M. , Kachalova Anastasia I. , Musinova Yana R. , Golovin Andrey V. , Vassetzky Yegor S. , Sheval Eugene V. 
Published: April 2021

ABSTRACTDuring evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses.
Detection of precisely edited CRISPR/Cas9 alleles through co-introduced restriction-fragment length polymorphisms
Authors: Tsai-Morris Chon-Hwa , Hertafeld Sydney , Rosario Yvonne , Iben James , Chang Eric , Yi Ling , Coon Steven L. , Kaler Stephen G. , Dale Ryan , Feldman Benjamin 
Published: April 2021

ABSTRACTCRISPR/Cas9 is a powerful tool for producing genomicinsertions anddeletions (indels) to interrogate gene function. Modified CRISPR/Cas9 protocols can produce targeted genetic changes that are more precise than indels, but founder recovery is less efficient. Focusing on producing missense mutations in zebrafish usingsingle-strandedoligodeoxynucleotide (ssODN) donor templates, we pioneered a strategy of adding synonymous changes to create novelrestriction-enzyme (RE) sites, allowing detection of rare precise edits in a modified fluorescent-PCR fragment assay. We have named this process TIARS (test forincorporation ofaddedrecognitionsites). Aided by TIARS, we induced two distinct amino-acid substitutions (T979I and P1387S) in theatp7agene among somatic tissues of CRISPR-Cas9-treated F0zebrafish. One of these F0stransmitted the allele toatp7aT979I/+F1progeny, and trans-heterozygosity of this allele against a nullatp7aallele causes hypopigmentation, consistent with more severe pigment deficits in zebrafish or humans carrying only null mutations inatp7a/ATP7A. Design of ssODNs with novel RE recognition sites is labor-intensive, so we developed anin silicotool, TIARS Designer, and performed bioinformatic validation indicating that TIARS should be generalizable to other genes and experimental systems that employ donor template DNA.