bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent evolution between PALI1 and JARID2 for the allosteric activation of PRC2
Authors: Zhang Qi , Agius Samuel C. , Flanigan Sarena F. , Levina Vitalina , Owen Brady M. , Davidovich Chen 
Published: May 2020

ABSTRACTThe polycomb repressive complex 2 (PRC2) is a histone methyltransferase that maintains cell identities. JARID2 is the only accessory subunit of PRC2 that known to trigger an allosteric activation of methyltransferase. Yet, this mechanism cannot be generalised to all PRC2 variants as, in vertebrates, JARID2 is mutually exclusive with most of the accessory subunits of PRC2. Here we provide functional and structural evidence that the vertebrate-specific PRC2 accessory subunit PALI1 emerged through a convergent evolution to mimic JARID2 at the molecular level. Mechanistically, PRC2 methylates PALI1 K1241, which then binds to the PRC2-regulatory subunit EED to allosterically activate PRC2. PALI1 K1241 is methylated in mouse and human cell lines and is essential for PALI1-induced allosteric activation of PRC2. High-resolution crystal structures revealed that PALI1 mimics the regulatory interactions formed between JARID2 and EED. Independently, PALI1 also facilitates DNA and nucleosome binding by PRC2. In acute myelogenous leukemia cells, overexpression of PALI1 leads to cell differentiation, with the phenotype abrogated by a separation-of-function PALI1 mutation, defective in allosteric activation and active in DNA binding. Collectively, we show that PALI1 facilitates catalysis and substrate binding by PRC2 and provide evidence that subunit-induced allosteric activation is a general property of holo-PRC2 complexes.
Callose deposition is essential for the completion of cytokinesis in the unicellular alga,Penium margaritaceum
Authors: Davis Destiny J. , Wang Minmin , Sørensen Iben , Rose Jocelyn K.C. , Domozych David S. , Drakakaki Georgia 
Published: May 2020

AbstractCytokinesis in land plants involves the formation of a cell plate that develops into the new cell wall. Callose is a β-1,3 glucan that transiently accumulates at later stages of cell plate development and is thought to stabilize the delicate membrane network of the cell plate as it expands. Cytokinetic callose deposition is currently considered specific to multicellular plant species as it has not been detected in unicellular algae. Here we present callose at the cytokinesis junction of the unicellular charophyte,Penium margaritaceum. Notably, callose deposition at the division plane ofP. margaritaceumshowed distinct, spatiotemporal patterns that could represent distinct roles of this polymer in cytokinesis and cell wall assembly. Pharmacological inhibition of cytokinetic callose deposition by Endosidin 7 treatment resulted in cytokinesis defects, consistent with the essential role for this polymer inP. margaritaceumcell division. Cell wall deposition and assembly at the isthmus zone was also affected by the absence of callose, demonstrating the dynamic nature of new wall assembly inP. margaritaceum. The identification of candidate callose synthase genes provides molecular evidence for callose biosynthesis inP. margaritaceum. The evolutionary implications of cytokinetic callose in this unicellular Zygnematopycean alga is discussed in the context of the conquest of land by plants.Summary StatementEvolutionarily conserved callose inPenium margaritaceumis essential for the completion of cytokinesis.
Rapid and Inexpensive Whole-Genome Sequencing of SARS-CoV-2 using 1200 bp Tiled Amplicons and Oxford Nanopore Rapid Barcoding
Authors: Freed Nikki E. , Vlková Markéta , Faisal Muhammad B. , Silander Olin K. 
Published: May 2020

AbstractRapid and cost-efficient whole-genome sequencing of SARS-CoV-2, the virus that causes COVID-19, is critical for understanding viral transmission dynamics. Here we show that using a new multiplexed set of primers in conjunction with the Oxford Nanopore Rapid Barcode library kit allows for faster, simpler, and less expensive SARS-CoV-2 genome sequencing. This primer set results in amplicons that exhibit lower levels of variation in coverage compared to other commonly used primer sets. Using five SARS-CoV-2 patient samples with Cqvalues between 20 and 31, we show that high-quality genomes can be generated with as few as 10,000 reads (approximately 5 Mbp of sequence data). We also show that mis-classification of barcodes, which may be more likely when using the Oxford Nanopore Rapid Barcode library prep, is unlikely to cause problems in variant calling. This method reduces the time from RNA to genome sequence by more than half compared to the more standard ligation-based Oxford Nanopore library preparation method at considerably lower costs.
Optimized pseudotyping conditions for the SARS-COV2 Spike glycoprotein
Authors: Johnson Marc C. , Lyddon Terri D. , Suarez Reinier , Salcedo Braxton , LePique Mary , Graham Maddie , Ricana Clifton , Robinson Carolyn , Ritter Detlef G. 
Published: May 2020

AbstractThe SARS-COV2 Spike glycoprotein is solely responsible for binding to the host cell receptor and facilitating fusion between the viral and host membranes. The ability to generate viral particles pseudotyped with SARS-COV2 Spike is useful for many types of studies, such as characterization of neutralizing antibodies or development of fusion-inhibiting small molecules. Here we characterized the use of a codon-optimized SARS-COV2 Spike glycoprotein for the generation of pseudotyped HIV-1, MLV, and VSV particles. The full-length Spike protein functioned inefficiently with all three systems but was enhanced over 10-fold by deleting the last 19 amino acids of the cytoplasmic tail of Spike. Infection of 293FT target cells was only possible if the cells were engineered to stably express the human ACE-2 receptor, but stably introducing an additional copy of this receptor did not further enhance susceptibility. Stable introduction of the Spike activating protease TMPRSS2 further enhanced susceptibility to infection by 5-10 fold. Substitution of the signal peptide of the Spike protein with an optimal signal peptide did not enhance or reduce infectious particle production. However, modification of a single amino acid in the furin cleavage site of Spike (R682Q) enhanced infectious particle production another 10-fold. With all enhancing elements combined, the titer of pseudotyped particles reached almost 106infectious particles/ml. Finally, HIV-1 particles pseudotyped with SARS-COV2 Spike was successfully used to detect neutralizing antibodies in plasma from COVID-19 patients, but not plasma from uninfected individuals.ImportanceWhen working with pathogenic viruses, it is useful to have rapid quantitative tests for viral infectivity that can be performed without strict biocontainment restrictions. A common way of accomplishing this is to generate viral pseudoparticles that contain the surface glycoprotein from the pathogenic virus incorporated into a replication-defective viral particle that contains a sensitive reporter system. These pseudoparticles enter cells using the glycoprotein from the pathogenic virus leading to a readout for infection. Conditions that block entry of the pathogenic virus, such as neutralizing antibodies, will also block entry of the viral pseudoparticles. However, viral glycoproteins often are not readily suited for generating pseudoparticles. Here we describe a series of modifications that result in the production of relatively high titer SARS-COV2 pseudoparticles that are suitable for detection of neutralizing antibodies from COVID-19 patients.
Phenotypic and molecular characterization of extended spectrum β-lactamase producingEscherichia coliandKlebsiella pneumoniaeisolates from various samples of animal origin from Assam, India
Authors: Das Leena , Borah Probodh , Sharma R.K. , Malakar Dipika , Saikia G.K. , Sharma K. , Tamuly S. , Dutta Rupam 
Published: May 2020

AbstractExtended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae has become a major threat globally. Here we have characterized ESBL producingE. coliandK. pneumoniaefrom various sources, studied antibiogram and resistance gene profiles. Out of 385 samples, 31 (8.05%) were positive for ESBL producingE. coli. Such isolates could be recovered from 10.05, 8.33, 15.63, 6.67 and 4.35 per cent of cattle milk, curd, chicken, pork and cattle faeces samples, respectively. A total of 59 (15.32%) samples were positive for ESBL producingK. pneumoniae, which were isolated from 14.35, 6.25, 21.43 and 34.78 per cent cattle milk, chicken, beef and cattle faeces, respectively. All the 90 isolates were confirmed as ESBL producers by CDT and ESBL-E strip tests. Antibiogram revealed that 74.19% and 69.49% of the ESBL producingE. coliandK. pneumoniaeisolates, respectively showed resistance to ceftizoxime, 25.81% and 23.73% to both co-trimoxazole and tetracycline, 19.35% and 25.42% to ciprofloxacin, 9.68% and 16.95% to chloramphenicol, 3.23% and 5.08% to pipercillin-tazobactam, and 3.23% and 3.39% to gentamicin. Resistance gene profiling showedblaCTX-M gene as most predominant (100%). TheblaTEM gene was found in 54.84% and 55.93%,blaSHV gene in 90.32% and 77.97%,Sul1 gene in 90.32% and 86.44% of ESBL producingE. coliandK. pneumoniaeisolates, respectively. TheInt1 gene was detected in 70.97% and 62.71% isolates, whileqnrB gene was found in 3.23% and 10.17% ofE. coliand K. pneumoniaeisolates, respectively.
Predicting the end-stage of the COVID-19 epidemic in Brazil
Authors: Fitzgibbon W.E. , Morgan J.J. , Webb G.F. , Wu Y. 
Published: May 2020

AbstractWe develop a dynamic model of a COVID-19 epidemic as a system of differential equations. The model incorporates an asymptomatic infectious stage and a symptomatic infectious stage. We apply the model to the current COVID-19 epidemic in Brazil. We compare the model output to current epidemic data, and project forward in time possible end-stages of the epidemic in Brazil. The model emphasizes the importance of reducing asymptomatic infections in controlling the epidemic.
Worsening of pre-existing psychiatric conditions during the COVID-19 pandemic
Authors: Gobbi Susanna , Płomecka Martyna Beata , Ashraf Zainab , Radziński Piotr , Neckels Rachael , Lazzeri Samuel , Dedić Alisa , Bakalović Asja , Hrustić Lejla , Skórko Beata , Es haghi Sarvin , Almazidou Kristina , Rodríguez-Pino Luis , Beyza Alp A. , Jabeen Hafsa , Waller Verena , Shibli Dana , A Behnam Mehdi , Arshad Ahmed Hussain , Barańczuk-Turska Zofia , Haq Zeeshan , Qureshi Salah U , Jawaid Ali 
Published: May 2020

AbstractThis study anonymously examined 2,734 psychiatric patients worldwide for worsening of their pre-existing psychiatric condition during the COVID-19 pandemic. Valid responses mainly from 12 featured countries indicated self-reported worsening of psychiatric conditions in 2/3rd of the patients assessed that was validated through their significantly higher scores on scales for general psychological disturbance, post-traumatic stress disorder, and depression. Female gender, feeling no control of the situation and reporting dissatisfaction with the response of the state during the COVID-19 pandemic, and reduced interaction with family and friends increased the worsening of pre-existing psychiatric conditions, whereas optimism, ability to share concerns with family and friends and using social media like usual were associated with less worsening. An independent clinical investigation from the USA confirmed worsening of psychiatric conditions during the COVID-19 pandemic based on identification of new symptoms that necessiated clinical interventions such as dose adjustment or starting new medications in more than half of the patients.
Early Impact of COVID-19 on Individuals with Eating Disorders: A survey of ~1000 Individuals in the United States and the Netherlands
Authors: Termorshuizen Jet D. , Watson Hunna J. , Thornton Laura M. , Borg Stina , Flatt Rachael E. , MacDermod Casey M. , Harper Lauren E. , van Furth Eric F. , Peat Christine M. , Bulik Cynthia M. 
Published: May 2020

ABSTRACTWe received rapid ethical permission to evaluate the early impact of COVID-19 on people with eating disorders. Participants in the United States (US, N=511) and the Netherlands (NL, N=510), recruited through ongoing studies and social media, completed an online baseline survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with diagnoses. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover.
Changes in intake of dairy product subgroups and risk of type 2 diabetes: modelling specified food substitutions in the Danish Diet, Cancer and Health cohort
Authors: Ibsen Daniel B. , Overvad Kim , Laursen Anne Sofie D. , Halkjær Jytte , Tjønneland Anne , Kilpeläinen Tuomas O. , Parner Erik T. , Jakobsen Marianne U. 
Published: May 2020

AbstractWe investigated the association between an increased intake of one dairy product subgroup at the expense of another within a 5-year period and the subsequent 10-year risk of developing type 2 diabetes. Effect modification by the initial level of the dairy product intake was also examined. The cohort included 39,438 men and women with two measurements of diet assessed using food frequency questionnaires (FFQ) administered in 1993-1997 and 1999-2003. Dairy products were skimmed milk, semi-skimmed milk, whole-fat milk, buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Type 2 diabetes cases were ascertained from the Danish National Diabetes Register. The pseudo-observation method was used to calculate risk differences (RD) with 95% confidence intervals (CI). Among participants aged 56-59 years at hand-in of the follow-up FFQ, increased intake of whole-fat yogurt in place of skimmed, semi-skimmed or whole-fat milk was associated with a reduced risk (RD% [95% CI]: −0.8% [−1.3, −0.2]; −0.6% [−1,1, −0.1]; −0.7 [−1.2, −0.1]; per 50g/d, respectively). Among participants aged 60-64 and 65-72, substitution of skimmed milk for semi-skimmed milk was associated with an increased risk of type 2 diabetes (0.5% [0.2, 0.7]; 0.4% [0.1, 0.7]; per 50g/d, respectively). No effect modification by the initial intake of milk products was observed. Our results suggest that substitution of whole-fat yogurt for milk among those aged 56-59 decreases the risk of type 2 diabetes and substitution of skimmed milk for semi-skimmed milk was associated with an increased risk of type 2 diabetes among those aged 60-64 and 65-72, regardless of the initial intake level.
A searchable image resource ofDrosophilaGAL4-driver expression patterns with single neuron resolution
Authors: Meissner Geoffrey W. , Nern Aljoscha , Dorman Zachary , DePasquale Gina M. , Forster Kaitlyn , Gibney Theresa , Hausenfluck Joanna H. , He Yisheng , Iyer Nirmala , Jeter Jennifer , Johnson Lauren , Johnston Rebecca M. , Lee Kelley , Melton Brian , Yarbrough Brianna , Zugates Christopher T. , Clements Jody , Goina Cristian , Otsuna Hideo , Rokicki Konrad , Svirskas Robert R. , Aso Yoshinori , Card Gwyneth M. , Dickson Barry J. , Ehrhardt Erica , Goldammer Jens , Ito Masayoshi , Kainmueller Dagmar , Korff Wyatt , Mais Lisa , Minegishi Ryo , Namiki Shigehiro , Rubin Gerald M. , Sterne Gabriella R. , Wolff Tanya , Malkesman Oz ,   FlyLight Project Team
Published: May 2020

AbstractPrecise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage ofDrosophilaneuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale. We are releasing aligned images of 74,000 such adult central nervous systems. An anticipated use of this resource is to bridge the gap between neurons identified by electron or light microscopy. Identifying individual neurons that make up each GAL4 expression pattern improves the prediction of split-GAL4 combinations targeting particular neurons. To this end we have made the images searchable on the NeuronBridge website. We demonstrate the potential of NeuronBridge to rapidly and effectively identify neuron matches based on morphology across imaging modalities and datasets.
Design and Performance Evaluation of a Wearable Passive Cable-driven Shoulder Exoskeleton
Authors: Asgari Morteza , Phillips Elizabeth A. , Dalton Britt M. , Rudl Jennifer L. , Crouch Dustin L. 
Published: May 2020

AbstractThe mechanical assistance provided by exoskeletons could potentially replace, assist, or rehabilitate upper extremity function in patients with mild to moderate shoulder disability to perform activities of daily living. While many exoskeletons are “active” (e.g. motorized), mechanically passive exoskeletons may be a more practical and affordable solution to meet a growing clinical need for continuous, home-based movement assistance. In the current study, we designed, fabricated, and evaluated the performance of a wearable, passive, cable-driven shoulder exoskeleton (WPCSE) prototype. An innovative feature of the WPCSE is a modular spring-cam-wheel system that can be custom designed to compensate for any proportion of the shoulder elevation moment due to gravity over a large range of shoulder motion. The force produced by the spring-cam-wheel system is transmitted over the superior aspect of the shoulder to an arm cuff through a Bowden cable. The results from mechanical evaluation revealed that the modular spring-cam-wheel system could successfully produce an assistive positive shoulder elevation moment that matched the desired, theoretical moment. However, when measured from the physical WPCSE prototype, the moment was lower (up to 30%) during positive shoulder elevation and higher (up to 120%) during negative shoulder elevation due primarily to friction. Even so, our biomechanical evaluation showed that the WPCSE prototype reduced the root mean square (up to 35%) and peak (up to 33%) muscular activity, as measured by electromyography, of several muscles crossing the shoulder during shoulder elevation and horizontal adduction/abduction movements. These preliminary results suggest that our WPCSE may be suitable for providing movement assistance to people with shoulder disability.
Shared PKS modules in biosynthesis of synergistic laxaphycins
Authors: Heinilä LMP , Fewer DP , Jokela J , Wahlsten M , Jortikka A , Sivonen K 
Published: May 2020

AbstractCyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced byScytonema hofmanniiPCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. To our knowledge, laxaphycins are the first clearly distinct polyketide synthase and non-ribosomal peptide synthetase hybrid natural products with shared branched biosynthesis. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.
Gene Expression Changes Occurring at Bolting Time are Associated with Leaf Senescence in Arabidopsis
Authors: Hinckley Will E , Brusslan Judy A. 
Published: May 2020

AbstractIn plants, the vegetative to reproductive phase transition (termed bolting in Arabidopsis) generally precedes age-dependent leaf senescence (LS). Many studies describe a temporal link between bolting time and LS, as plants that bolt early, senesce early, and plants that bolt late, senesce late. However, the molecular mechanisms underlying this relationship are unknown and are potentially agriculturally important, as they may allow for the development of crops that can overcome early LS caused by stress-related early phase transition. We hypothesized that gene expression changes associated with bolting time were regulating LS. We used a mutant that displays both early bolting and early LS as a model to test this hypothesis. An RNA-seq time series experiment was completed to compare the early bolting mutant to vegetative WT plants of the same age. This allowed us to identify bolting time-associated genes (BAGs) expressed in an older rosette leaf at the time of inflorescence emergence. The BAG list contains many well characterized LS regulators (ORE1, WRKY45, NAP, WRKY28), and GO analysis revealed enrichment for LS and LS-related processes. These bolting associated LS regulators likely contribute to the temporal coupling of bolting time to LS.