bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable tug-of-war between kinesin-1 and cytoplasmic dynein upon different ATP and roadblock concentrations
Authors: Monzon Gina A. , Scharrel Lara , DSouza Ashwin , Santen Ludger , Diez Stefan 
Published: June 2020

ABSTRACTThe maintenance of intracellular processes like organelle transport and cell division depend on bidirectional movement along microtubules. These processes typically require kinesin and dynein motor proteins which move with opposite directionality. Because both types of motors are often simultaneously bound to the cargo, regulatory mechanisms are required to ensure controlled directional transport. Recently, it has been shown that parameters like mechanical motor activation, ATP concentration and roadblocks on the microtubule surface differentially influence the activity of kinesin and dynein motors in distinct manners. However, how these parameters affect bidirectional transport systems has not been studied. Here, we investigate the regulatory influence of these three parameter using in vitro gliding motility assays and stochastic simulations. We find that the number of active kinesin and dynein motors determines the transport direction and velocity, but that variations in ATP concentration and roadblock density have no significant effect. Thus, factors influencing the force balance between opposite motors appear to be important, whereas the detailed stepping kinetics and bypassing capabilities of the motors have only little effect.
Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses
Authors: Schmidt Fabian , Weisblum Yiska , Muecksch Frauke , Hoffmann Hans-Heinrich , Michailidis Eleftherios , Lorenzi Julio C. C. , Mendoza Pilar , Rutkowska Magdalena , Bednarski Eva , Gaebler Christian , Agudelo Marianna , Cho Alice , Wang Zijun , Gazumyan Anna , Cipolla Melissa , Caskey Marina , Robbiani Davide F. , Nussenzweig Michel C. , Rice Charles M. , Hatziioannou Theodora , Bieniasz Paul D. 
Published: June 2020

AbstractThe emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARS-CoV-2-specific antibodies. Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay. The assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.
The Identification of A ROS Responsive Motif that is regulated by snoRNP inArabidopsis
Authors: Cheng Han , Sun Mingan , Guo Dianjing 
Published: June 2020

AbstractA GGGCC motif (site II like motif) was identified from the upstream sequences of reactive oxygen species (ROS) and light induced genes in Arabidopsis. This motif is highly enriched within the −50 to −250 bp region of the induced genes, and it is also specifically distributed in the same region in mouse and human genome. EMSA experiments revealed that several nuclear factors (NFs) bind to this motif, and the binding activities altered under H2O2treatment. Two C/D family snoRNP proteins, namely fibrillarin 2 and NOP56, were identified from the site II like motif binding NFs. Several C/D family snoRNA, including R63, U24a and Z15, were also cloned from the motif binding NFs. These data suggest new regulatory roles of snoRNP in Arabidopsis.
SARS-CoV-2 virus and antibodies in front-line Health Care Workers in an acute hospital in London: preliminary results from a longitudinal study
Authors: Houlihan Catherine F , Vora Nina , Byrne Thomas , Lewer Dan , Heaney Judith , Moore David A. , Matthews Rebecca , Adam Sajida , Enfield Louise , Severn Abigail , McBride Angela , Spyer Moira , Beale Rupert , Cherepanov Peter , Gaertner Kathleen , Edwards Sarah , Shahmanesh Maryam , Ng Kevin , Faulkner Nikhil , Cornish Georgina , Walker Naomi , Michie Susan , Manley Ed , Lorencatto Fabiana , Gilson Richard , Gandhi Sonia , Gamblin Steve , Kassiotis George , McCoy Laura E , Swanton Charles , Hayward Andrew , Nastouli Eleni 
Published: June 2020

AbstractBackgroundAlthough SARS-CoV-2 infection in Healthcare Workers (HCWs) is a public health concern, there is little description of their longitudinal antibody response in the presence or absence of SARS-CoV-2 and symptoms. We followed HCWs in an acute London hospital to measure seroconversion and RNA detection at the peak of the pandemic.MethodsWe enrolled 200 patient-facing HCWs between 26 March and 8 April 2020 and collected twice-weekly self-administered nose and throat swabs, symptom data and monthly blood samples. Swabs were tested for SARS-CoV-2 by PCR, and serum for antibodies to spike protein by ELISA and flow cytometry.FindingsDuring the first month, 42/200 (21%) HCWs were PCR positive in at least one nose and throat swab. Only 8/42 HCW (19%) who were PCR positive during the study period had symptoms that met current case definition. Of 181 HCWs who provided enrollment and follow-up blood samples, 82/181 (45.3%) were seropositive. In 33 HCWs who had positive serology at baseline but were PCR negative, 32 remained PCR negative. One HCW had a PCR positive swab six days after enrollment, likely representing waning infection.ConclusionThe high seropositivity and RNA detection in these front-line HCWs brings policies to protect staff and patients into acute focus. Our findings have implications for planning for the ‘second wave’ and for vaccination campaigns in similar settings. The evidence of asymptomatic SARS-CoV-2 infection indicates that asymptomatic HCW surveillance is essential, while our study sets the foundations to answer pertinent questions around the duration of protective immune response and the risk of re-infection.
Long identical sequences found in multiple bacterial genomes reveal frequent and widespread exchange of genetic material between distant species
Authors: Sheinman Michael , Arkhipova Ksenia , Arndt Peter F. , Dutilh Bas E. , Hermsen Rutger , Massip Florian 
Published: June 2020

AbstractHorizontal transfer of genomic elements is an essential force that shapes microbial genome evolution. Horizontal Gene Transfer (HGT) occurs via various mechanisms and has been studied in detail for a variety of systems. However, a coarse-grained, global picture of HGT in the microbial world is still missing. One reason is the difficulty to process large amounts of genomic microbial data to find and characterise HGT events, especially for highly distant organisms. Here, we exploit the fact that HGT between distant species creates long identical DNA sequences in genomes of distant species, which can be found efficiently using alignment-free methods. We analysed over 90 000 bacterial genomes and thus identified over 100 000 events of HGT. We further developed a mathematical model to analyse the statistical properties of those long exact matches and thus estimate the transfer rate between any pair of taxa. Our results demonstrate that long-distance gene exchange (across phyla) is very frequent, as more than 8% of the bacterial genomes analysed have been involved in at least one such event. Finally, we confirm that the function of the transferred sequences strongly impact the transfer rate, as we observe a 3.5 order of magnitude variation between the most and the least transferred categories. Overall, we provide a unique view of horizontal transfer across the bacterial tree of life, illuminating a fundamental process driving bacterial evolution.
Biophysical characterization of the inactivation ofE. colitransketolase by aqueous co-solvents
Authors: Morris Phattaraporn , García-Arrazola Ribia , Rios-Solis Leonardo , Dalby Paul A. 
Published: June 2020

AbstractTransketolase (TK) has been previously engineered, using semi-rational directed evolution and substrate walking, to accept increasingly aliphatic, cyclic and then aromatic substrates. This has ultimately led to the poor water solubility of new substrates, as a potential bottleneck to further exploitation of this enzyme in biocatalysis. Here we used a range of biophysical studies to characterise the response of bothE. coliapo- and holo-TK activity and structure to a range of commonly used polar organic co-solvents: acetonitrile (MeCN),n- butanol (nBuOH), ethyl acetate (EToAc), isopropanol (iPrOH), and tetrahydrofuran (THF). The mechanism of enzyme deactivation was found to be predominantly via solvent-induced local unfolding. Holo-TK is thermodynamically more stable than apo-TK and yet for four of the five co-solvents it retained less activity than apo-TK after exposure to organic solvents, indicating that solvent tolerance was not correlated to global conformational stability. The co-solvent concentrations required for complete enzyme inactivation was inversely proportional to co-solvent log(P), while the unfolding rate was directly proportional, indicating that the solvents interact with and partially unfold the enzyme through hydrophobic contacts. Aggregation was not found to be the driving mechanism of enzyme inactivation, but was in some cases an additional impact of solvent-induced local or global unfolding.TK was found to be tolerant to 15% (v/v) iPrOH, 10% (v/v) MeCN, or 6% (v/v) nBuOH over 3 hours. This work indicates that future attempts to engineer the enzyme to better tolerate co-solvents should focus on increasing the stability of the protein to local unfolding, particularly in and around the cofactor-binding loops.
The Profiling of Bisecting N-acetylglucosamine (GlcNAc) Modification in Human Amniotic Membrane by Glycomic and Glycoproteomic Analyses
Authors: Chen Qiushi , Zhang Yuanliang , Zhang Keren , Liu Jie , Pan Huozhen , Wang Xinran , Li Siqi , Hu Dandan , Lin Zhilong , Zhao Yun , Hou Guixue , Guan Feng , Li Hong , Liu Siqi , Ren Yan 
Published: June 2020

AbstractIt is acknowledged that the bisecting N-acetylglucosamine (GlcNAc) structure, a GlcNAc linked to the core β-mannose residue via a β1,4 linkage, represents a special type of N-glycosylated modification and has been reported to be involved in various biological processes, such as cell adhesion and fetal development. Clark et al. has found that the majority of N-glycans in human trophoblasts bearing a bisecting GlcNAc. This type of glycan has been reported to help trophoblasts get resistant to natural killer (NK) cell-mediated cytotoxicity, and this would provide a possible explanation for the question how could the mother nourish a fetus within herself without rejection. Herein, we hypothesized that human amniotic membrane which is the last barrier for the fetus may also express bisecting type glycans to protect the fetus. To test this hypothesis, glycomic analysis of human amniotic membrane was performed, and the bisecting N-glycans with high abundance were detected. In addition, we re-analyzed our proteomic data with high fractionation and amino acid sequence coverage from human amniotic membrane, which had been released for the exploration of human missing proteins. The presence of bisecting GlcNAc peptides was revealed and confirmed. A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc, 25 of which are for the first time to be reported to have this type of modification. These results provide the profiling of bisecting GlcNAc modification in human amniotic membrane and benefit to the function studies of glycoproteins with bisecting GlcNAc modification and the function studies in immune suppression of human placenta. The mass spectrometry placenta data are available via ProteomeXchange (PXD010630).
Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation
Authors: Yoon Hye-Jin , Jeong Hyunah , Lee Hyung Ho , Jang Soonmin 
Published: June 2020

AbstractThe lysosomal membrane protein NPC1 (Niemann-Pick type C1) and NPC2 (Niemann-Pick type C2) are main players of cholesterol control in lysosome and it is known that mutation on these proteins leads to cholesterol trafficking related disease, called Niemann-Pick disease type C (NPC) disease. The mutation R518W or R518Q on NPC1 is one of such disease-related mutations, causing reduced cholesterol transport by half, resulting in accumulation of cholesterol and lipids in late endosomal/lysosomal region of the cell. Even though there has been significant progress in understanding cholesterol transport by NPC1 in combination with NPC2, especially after the structural determination of full length NPC1 in 2016, many details such as interaction of full length NPC1 with NPC2, molecular motions responsible for cholesterol transport during and after this interaction, and structure and function relations of many mutations are still not well understood.We report the extensive molecular dynamics simulations to gain insight into the structure and motions of NPC1 lumenal domain for cholesterol transport and disease behind the mutation (R518W). It is found that the mutation induces structural shift of NTD (N-terminal domain), toward the loop region in MLD (middle lumenal domain), which is believed to play central role in interaction with NPC2 protein, such that the interaction with NPC2 protein might be less favorable compare to wild NPC1. Also, the simulation indicates the possible re-orientation of the NTD, aligning to form an internal tunnel, after receiving the cholesterol from NPC2 with wild NPC1 unlike the mutated one, a possible pose for further action in cholesterol trafficking. We believe the current study can provide better understanding on the cholesterol transport by NPC1, especially the role of NTD of NPC1, in combination with NPC2 interaction.Synopsismodeling study of cholesterol binding protein NPC1
Conflict detection in a sequential decision task is associated with increased cortico-subthalamic coherence and prolonged subthalamic oscillatory response in the beta band
Authors: Patai Zita Eva , Foltynie Tom , Limousin Patricia , Akram Harith , Zrinzo Ludvic , Bogacz Rafal , Litvak Vladimir 
Published: June 2020

AbstractMaking accurate decisions often involves the integration of current and past evidence. Here we examine the neural correlates of conflict and evidence integration during sequential decision making. Patients implanted with deep-brain stimulation (DBS) electrodes and age-matched healthy controls performed an expanded judgement task, in which they were free to choose how many cues to sample. Behaviourally, we found that while patients sampled numerically more cues, they were less able to integrate evidence and showed suboptimal performance. Using recordings of Magnetoencephalography (MEG) and local field potentials (LFP, in patients) in the subthalamic nucleus (STN), we found that beta oscillations signalled conflict between cues within a sequence. Following cues that differed from previous cues, beta power in the STN and cortex first decreased and then increased. Importantly, the conflict signal in the STN outlasted the cortical one, carrying over to the next cue in the sequence. Furthermore, after a conflict, there was an increase in coherence between the dorsal premotor cortex and subthalamic nucleus in the beta band. These results extend our understanding of cortico-subcortical dynamics of conflict processing, and do so in a context where evidence must be accumulated in discrete steps, much like in real life. Thus, the present work leads to a more nuanced picture of conflict monitoring systems in the brain and potential changes due to disease.
Small scale variability in soil moisture drives infection of vulnerable juniper populations by invasive forest pathogen
Authors: Donald Flora , Green Sarah , Searle Kate , Cunniffe Nik J. , Purse Bethan V. 
Published: June 2020

AbstractThe oomycete plant pathogen,Phytophthora austrocedri, is an aggressive killer of cypress trees causing severe mortality of Chilean cedar (Austrocedrus chilensis) in Argentina since the 1940s and now common juniper (Juniperus communiss.l.) in the UK. Rapid mortality of key UK juniper populations was first observed in the early 2000s; the causal agent of mortality was confirmed asP. austrocedriin 2012 and the pathogen has now been widely detected - but is not ubiquitous - in juniper populations across Scotland and England. Although juniper has a broad distribution across the northern hemisphere, the UK incidence ofP. austrocedriremains the only confirmed infection of juniper populations globally. Juniper is an important species for biodiversity, so it is imperative to understand the abiotic and biotic drivers of emergentP. austrocedriinfection to inform detection, containment and conservation strategies to manage juniper populations across the full extent of its range.As management of UK juniper populations is primarily conducted at a local level, we investigated field scale drivers of disease – in three, geographically separate populations with different infection histories. Variation in the proportion of juniper showing symptoms - discoloured or dead foliage – was measured using stratified sampling across along key environmental gradients within each 100-hectare population, including juniper density identified from aerial imagery. Potential predictors of infection included altitude, slope, distance to nearest watercourse, soil moisture (mean percentage volumetric water content), area of red deer browsing damage and area of commonly associated vascular plant species. We assessed support in the data for alternative models explaining the spatial distribution ofP. austrocedrisymptoms using full subset covariate selection and Deviance Information Criteria (DIC). Despite differences in environmental gradients and infection histories between populations, area of juniper symptomatic forP. austrocedriincreased with waterlogging, increasing with soil moisture in sites where soils had higher peat or clay contents, and decreasing with proximity to watercourses where sites had shallower, sandier soils. These results are consistent with key drivers identified at both local and landscape scale in Chilean cedar. Our approach enables identification of site-specific disease management strategies including prioritisation of inspections in microsites with high soil moisture and promoting conservation measures such as creation of sites for natural regeneration in drier microsites to minimise pathogen spread and maximise the resilience of existing juniper populations.
Martial arts training is related to implicit intermanual transfer of visuomotor adaptation
Authors: Werner Susen , Hasegawa Koki , Kanosue Kazuyuki , Strüder Heiko K. , Göb Tobias , Vogt Tobias 
Published: June 2020

AbstractRecent work identified an explicit and implicit transfer of motor learning with one limb to the other untrained limb. Here we pursue the idea that different individual factors differently contribute to the amount of explicit and implicit intermanual transfer of sensorimotor adaptation. In particular we tested a group of judo athletes who show enhanced right-hemispheric involvement in motor control and a group of equally trained athletes as control participants. After adaptation to a 60° visual rotation, we estimated awareness of the perturbation and transfer to the untrained, non-dominant left hand in two experiments. We measured the total amount of intermanual transfer (explicit plus implicit) by telling the participants to repeat what was learned during adaptation and the amount of implicit transfer by instructing the participants to refrain from using what was learned but to perform movements as during baseline. We found no difference between the total intermanual transfer of judokas and running experts, with mean absolute transfer values of 42.4° and 47.0°. Implicit intermanual transfer was very limited but larger in judo than in general sports athletes, with mean values of 5.2° and 1.6°. A multiple linear regression analysis further revealed that total intermanual transfer, which largely represents the explicit transfer, is related to awareness of the perturbation while implicit intermanual transfer can be predicted by judo training, amount of total training, speed of adaptation and handedness scores. The findings are discussed in relation to neuronal mechanisms such as hemispheric interactions and functional specialization underlying intermanual transfer of motor learning.
The mRNA translation landscape in the synaptic neuropil
Authors: Glock Caspar , Biever Anne , Tushev Georgi , Bartnik Ina , Nassim-Assir Belquis , Dieck Susanne tom , Schuman Erin M. 
Published: June 2020

AbstractTo form and modify synaptic connections and store information, neurons continuously remodel their proteomes. The impressive length of dendrites and axons imposes unique logistical challenges to maintain synaptic proteins at locations remote from the transcription source (the nucleus). The discovery of thousands of mRNAs near synapses suggested that neurons overcome distance and gain autonomy by producing proteins locally1. It is not known, however if, how and when localized mRNAs are translated into protein. To investigate the translational landscape in neuronal subregions, we performed simultaneous RNA-seq and Ribo-seq from microdissected rodent brain slices to identify and quantify the transcriptome and translatome in cell bodies as well as dendrites and axons (neuropil). More than 4800 transcripts were translated in synaptic regions. Thousands of transcripts were differentially translated between somatic and synaptic regions, with scaffold and signaling molecules mostly arising from local sources. Furthermore, specific mRNA features were identified that regulate the efficiency of mRNA translation. The findings overturn the view that local translation is a minor source of synaptic protein2and indicate that on-site translational control is an important mechanism to control synaptic strength.