bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of two drug-like fragments that bind to the same cryptic binding pocket ofBurkholderia pseudomalleiDsbA
Authors: Petit Guillaume A. , Mohanty Biswarajan , McMahon Róisín M. , Nebl Stefan , Hilko David H. , Wilde Karyn L. , Scanlon Martin J. , Martin Jennifer L. , Halili Maria A. 
Published: March 2021

AbstractDiSulfideBond forming proteins (DSB) play a crucial role in the pathogenicity of many Gram-negative bacteria. Disulfide bond protein A (DsbA) catalyzes the formation of disulfide bonds necessary for the activity and stability of multiple substrate proteins, including many virulence factors. Hence, DsbA is an attractive target for the development of new drugs to combat bacterial infections. Here, we identified two fragments -1(bromophenoxy propanamide) and2(4-methoxy-N-phenylbenzenesulfonamide), that bind to the DsbA from the pathogenic bacteriumBurkholderia pseudomallei, the causative agent of melioidosis. Crystal structures of the oxidizedB. pseudomalleiDsbA (termed BpsDsbA) co-crystallized with1or2suggests that both fragments bind to a hydrophobic pocket that is formed by a change in the side chain orientation of tyrosine 110. This conformational change opens a “cryptic” pocket that is not evident in theapo-protein structure. This binding location was supported by 2D-NMR studies which identified a chemical shift perturbation of the tyrosine 110 backbone amide resonance of more than 0.05 ppm upon addition of 2 mM of fragment1and over 0.04 ppm upon addition of 1 mM of fragment2. Although binding was detected by both X-ray crystallography and NMR, the binding affinity (KD) for both fragments was low (above 2 mM), suggesting weak interactions with BpsDsbA. This conclusion is also supported by the modelled crystal structures which ascribe partial occupancy to the ligands in the cryptic binding pocket. Small fragments such as1and2are not expected to have high binding affinity due to their size and the relatively small surface area that can be involved in intermolecular interactions. However, their simplicity makes them ideal for functionalization and optimization. Identification of the binding sites of1and2to BpsDsbA could provide a starting point for the development of more potent novel antimicrobial compounds that target DsbA and bacterial virulence.SynopsisDescribes the binding properties of two drug-like fragments to a conformationally dynamic site in the disulfide-bond forming protein A fromBurkholderia pseudomallei.
Pseudohydrosme bognerisp. nov. (Araceae), a spectacular Critically Endangered (Possibly Extinct) species from Gabon, long confused withAnchomanes nigritianus
Authors: Moxon-Holt Lois , Cheek Martin 
Published: March 2021

SummaryA Gabonese taxon cultivated for decades in the botanic gardens of Europe asAnchomanes nigritianusis shown to be a new species to science, and on current evidence, is best placed as the fourth species of the Gabonese-centred, poorly known genusPseudohydrosme. Data on the morphological separation betweenAnchomanesandPseudohydrosmeare reviewed. Although phylogenomic studies may show in future that the two genera need to be merged, for the moment their separation is reinforced on morphological grounds.Anchomaneslacks the spathe tube, ovoid-globose, 2 – 4 locular pistil and thick, lobed stigma on a symmetric, stout style that we show to characterise the redelimitedPseudohydrosme. (Anchomaneshas oblong, polygonal, 1-locular pistils, stigmas asymmetric, sessile, thin and disc-like or on asymmetrical conical styles and are pointed or brush-like). In addition,Pseudohydrosme(where known) has stipitate (versus sessile) fruits and on current evidence lacks the lacticifers recorded fromAnchomanes. We test the hypothesis that the taxon is a new species to science, naming it asPseudohydrosme bogneri, and conclude that it is Critically Endangered (Possibly Extinct) using the IUCN 2012 standard.Pseudohydrosme bogneriappears to be the tenth documented probable global extinction of a plant species that has occurred among the narrowly endemic plant species of the Libreville area, Gabon.
Effects of stochasticity on the length and behaviour of ecological transients
Authors: Hastings Alan , Abbott Karen C. , Cuddington Kim , Francis Tessa , Lai Ying-Cheng , Morozov Andrew , Petrovskii Sergei , Zeeman Mary Lou 
Published: March 2021

AbstractThere is a growing recognition that ecological systems can spend extended periods of time far away from an asymptotic state, and that ecological understanding will therefore require a deeper appreciation for how long ecological transients arise. Recent work has defined classes of deterministic mechanisms that can lead to long transients. Given the ubiquity of stochasticity in ecological systems, a similar systematic treatment of transients that includes the influence of stochasticity is important. Stochasticity can of course promote the appearance of transient dynamics by preventing systems from settling permanently near their asymptotic state, but stochasticity also interacts with deterministic features to create qualitatively new dynamics. As such, stochasticity may shorten, extend, or fundamentally change a system’s transient dynamics. Here, we describe a general framework that is developing for understanding the range of possible outcomes when random processes impact the dynamics of ecological systems over realistic time scales. We emphasize that we can understand the ways in which stochasticity can either extend or reduce the lifetime of transients by studying the interactions between the stochastic and deterministic processes present, and we summarize both the current state of knowledge and avenues for future advances.
Exploring Integrated Environmental Viral Surveillance of Indoor Environments: A comparison of surface and bioaerosol environmental sampling in hospital rooms with COVID-19 patients
Authors: Dietz Leslie , Constant David A. , Fretz Mark , Horve Patrick F. , Olsen-Martinez Andreas , Stenson Jason , Wilkes Andrew , Martindale Robert G. , Messer William B. , Van Den Wymelenberg Kevin G. 
Published: March 2021

AbstractThe outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has dramatically transformed policies and practices surrounding public health. One such shift is the expanded emphasis on environmental surveillance for pathogens. Environmental surveillance methods have primarily relied upon wastewater and indoor surface testing, and despite substantial evidence that SARS-CoV-2 commonly travels through space in aerosols, there has been limited indoor air surveillance. This study investigated the effectiveness of integrated surveillance including an active air sampler, surface swabs and passive settling plates to detect SARS-CoV-2 in hospital rooms with COVID-19 patients and compared detection efficacy among sampling methods. The AerosolSense active air sampler was found to detect SARS-CoV-2 in 53.8% of all samples collected compared to 12.1% detection by passive air sampling and 14.8% detection by surface swabs. Approximately 69% of sampled rooms (22/32) returned a positive environmental sample of any type. Among positive rooms, ~32% had only active air samples that returned positive, while ~27% and ~9% had only one or more surface swabs or passive settling plates that returned a positive respectively, and ~32% had more than one sample type that returned a positive result. This study demonstrates the potential for the AerosolSense to detect SARS-CoV-2 RNA in real-world healthcare environments and suggests that integrated sampling that includes active air sampling is an important addition to environmental pathogen surveillance in support of public health.
What multiple Mendelian randomization approaches reveal about obesity and gout
Authors: Adams Charleen D. , Boutwell Brian B. 
Published: March 2021

AbstractBackground/ObjectivesGout is a painful arthritic disease. A robust canon of observational literature suggests strong relationships between obesity, high urate levels, and gout. But findings from observational studies can be fraught with confounding and reverse causation. They can conflict with findings from Mendelian randomization (MR), designed to tackle these biases. We aimed to determine whether the relationships between obesity, higher urate levels, and gout were causal using multiple MR approaches, including an investigation of how other closely related traits, LDL, HDL cholesterol, and triglyceride levels fit into the picture.Subjects/MethodsSummary results from genome-wide association studies of the five above-mentioned traits were extracted and used to perform two-sample (univariable, multivariable, and two-step) MR and MR mediation analysis.ResultsObesity increased urate (beta=0.127; 95% CI=0.098, 0.157; P-value=1.2E-17) and triglyceride levels (beta=0.082; 95% CI=0.065, 0.099; P-value=1.2E-21) and decreased HDL cholesterol levels (beta=-0.083; 95% CI=-0.101, −0.065; P-value=2.5E-19). Higher triglyceride levels increased urate levels (beta=0.198; 95% CI=0.146, 0.251; P-value=8.9E-14) and higher HDL levels decreased them (beta=-0.109; 95% CI=-0.148, −0.071; P-value=2.7E-08). Higher urate levels (OR=1.030; 95% CI=1.028, 1.032; P-value=1.1E-130) and obesity caused gout (OR=1.003; 95% CI=1.001, 1.004; P-value=1.3E-04). The mediation MR of obesity on gout with urate levels as a mediator revealed, however, that essentially all of the effect of obesity on gout is mediated through urate. The impact of obesity on LDL cholesterol was null (beta=-0.011; 95% CI=-0.030, 0.008; P-value=2.6E-01), thus it was not included in the multivariable MR. The multivariable MR of obesity, HDL cholesterol, and triglycerides on urate levels revealed that obesity has an effect on urate levels even when accounting for HDL cholesterol and triglyceride levels.ConclusionsObesity impacts gout indirectly by influencing urate levels and possibly other traits, such as triglycerides, that increase urate levels. Obesity’s impact on urate is exacerbated by its apparent ability to decrease HDL cholesterol.
Your pleasure is mine; when people share a musical emotional experience during a live music performance in a concert hall
Authors: Chabin Thibault , Gabriel Damien , Comte Alexandre , Haffen Emmanuel , Moulin Thierry , Pazart Lionel 
Published: March 2021

AbstractOver the years, several publications have proposed that musical sound could be an ancestral emotional way of communication, thus positing an ancestral biological function for music. Understanding how musical emotions, and the pleasure derived from music regardless of the musical valence, can be shared between individuals is a fascinating question, and investigating it can shed light on the function of musical reward. Is the pleasure felt at the individual level transmitted on a collective level? And if so, how? We investigated these questions in a natural setting during an international competition for orchestra conductors. Participants (n=15) used a dedicated smartphone app to report their subjective emotional experiences in real time during a concert. We recorded participant’s electrodermal activity (EDA) and cerebral activity with electroencephalography (EEG). The overall behavioral real time ratings suggest a possible social influence on the reported and felt pleasure. The physically closer the participants, the more similar their reported pleasure. We estimated the inter-individual cerebral coherence, which indicates the degree of mutual cerebral information between pairs of participants in the frequency domain. The results show that when people simultaneously reported either high or low pleasure, their cerebral activities were closer than for simultaneous neutral pleasure reports. Participants’ skin conductance levels were also more coupled when reporting higher emotional degrees simultaneously. More importantly, the participants who were physically closer had higher cerebral coherence, but only when they simultaneously reported intense pleasure. We propose that mechanisms of emotional contagion and/or emotional resonance could explain why a form of ‘emotional connecting force’ could arise between people.
Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets
Authors: Bye Alexander P , Hoepel Willianne , Mitchell Joanne L , Jégouic Sophie , Loureiro Silvia , Sage Tanya , de Taeye Steven , van Gils Marit , Kriek Neline , Cooper Nichola , Jones Ian , den Dunnen Jeroen , Gibbins Jonathan M 
Published: March 2021

AbstractA subset of patients with COVID-19 become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill COVID-19 patients are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesised that platelets might be susceptible to activation by anti-SARS-CoV-2 antibodies and contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike IgG enhanced platelet-mediated thrombosis on von Willebrand Factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on FcyRIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases syk and btk respectively or by the P2Y12 antagonist cangrelor.
Improved architectures for flexible DNA production using retrons across kingdoms of life
Authors: Lopez Santiago C. , Crawford Kate D. , Bhattarai-Kline Santi , Shipman Seth L. 
Published: March 2021

ABSTRACTExogenous DNA is a critical molecular tool for biology. This is particularly true for gene editing, where exogenous DNA can be used as a template to introduce precise changes to the sequence of a cell’s genome. This DNA is typically synthesized or assembledin vitroand then delivered to target cells. However, delivery can be inefficient, and low abundance of template DNA may be one reason that precise editing typically occurs at a low rate. It has recently been shown that producing DNA inside cells can using reverse transcriptases can increase the efficiency of genome editing. One tool to produce that DNA is a retron, a bacterial retroelement that has an endogenous role in phage defense. However, little effort has been directed at optimizing the retron for production of designed sequences when used as a component of biotechnology. Here, we identify modifications to the retron non-coding RNA that result in more abundant reverse transcribed DNA. We also test architectures of the retron operon that enable efficient reverse transcription across kingdoms of life from bacteria, to yeast, to cultured human cells. We find that gains in DNA production using modified retrons are portable from prokaryotic to eukaryotic cells. Finally, we demonstrate that increased production of RT-DNA results in more efficient genome editing in both prokaryotic and eukaryotic cells. These experiments provide a general framework for production of DNA using a retron for biotechnological applications.
Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts
Authors: Suda Kojiro , Moriyama Yohsuke , Masukagami Yumiko , Razali Nurhanani Binti , Chiu Yatzu , Nishimura Koutarou , Barbee Hunter , Takase Hiroshi , Sugiyama Shinju , Sato Yoshikatsu , Higashiyama Tetsuya , Johmura Yoshikazu , Nakanishi Makoto , Kono Keiko 
Published: March 2021

AbstractPlasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. Here, using budding yeast and normal human fibroblasts, we show that cellular senescence, irreversible cell cycle arrest contributing to organismal aging, is the long-term outcome of PMD. To identify the genes essential for PMD response, we developed a simple PMD-damaging assay using a detergent and performed a systematic yeast genome-wide screen. The screen identified 48 genes. The top hits in the screen are the endosomal sorting complexes required for transport (ESCRT) genes, encoding the well-described plasma membrane repair proteins in eukaryotes. Unexpectedly, the replicative lifespan regulator genes are enriched in our 48 hits. This finding suggests a close genetic association between the PMD response and the replicative lifespan regulations. Indeed, we show that PMD limits the replicative lifespan in budding yeast; the ESCRT activator AAA-ATPaseVPS4-overexpression extends it. These results suggest that PMD limits replicative lifespan in budding yeast. Moreover, in normal human fibroblasts, we find that PMD induces premature senescence via the Ca2+-p53 axis but not the major senescence pathway, ATM/ATR pathway. Consistent with the results in yeast, transient overexpression of ESCRT-III, CHMP4B, suppressed the PMD-dependent senescence in normal human fibroblasts. Our study proposes that PMD limits cellular lifespan in two different eukaryotic cell types and highlights an underappreciated but ubiquitous senescent cell subtype, namely PMD-dependent senescent cells.
Cross-linking/Mass Spectrometry Combined with Ion Mobility on a timsTOF Pro Instrument for Structural Proteomics
Authors: Ihling Christian H. , Piersimoni Lolita , Kipping Marc , Sinz Andrea 
Published: March 2021

AbstractThe combination of cross-linking/mass spectrometry (XL-MS) and ion mobility is still underexplored for conducting protein conformational and protein-protein interaction studies. We present a method for analyzing cross-linking mixtures on a timsTOF Pro mass spectrometer that allows separating ions based on their gas phase mobilities. Cross-linking was performed with three urea-based MS-cleavable cross-linkers that deliver distinct fragmentation patterns for cross-linked species upon collisional activation. The discrimination of cross-linked species from non-cross-linked peptides was readily performed based on their collisional cross sections. We demonstrate the general feasibility of our combined XL-MS/ion mobility approach for three protein systems of increasing complexity: (i) Bovine serum albumin, (ii)E. coliribosome, and (iii) HEK293T cell nuclear lysates. We identified a total of 508 unique cross-linking sites for BSA, 868 for theE. coliribosome, and 1,623 unique cross-links for nuclear lysates, corresponding to 1,088 intra- and 535 interprotein interactions and yielding 564 distinct protein-protein interactions. Our results underline the strength of combining XL-MS with ion mobility not only for deriving 3D-structures of single proteins, but also for performing system-wide protein interaction studies.TOC Graphic
The anthropometric and physical qualities of women’s rugby league Super League and international players; identifying differences in playing position and standard
Authors: Scantlebury Sean , McCormack Sam , Sawczuk Thomas , Emmonds Stacey , Collins Neil , Beech Jake , Ramirez Carlos , Owen Cameron , Jones Ben 
Published: March 2021

AbstractParticipation in women’s rugby league has been growing since the foundation of the English women’s rugby league Super League in 2017. However, the evidence base to inform women’s rugby league remains sparse. This study provides the largest quantification of anthropometric and physical qualities of women’s rugby league players to date, identifying differences between positions (forwards & backs) and playing standard (Women’s Super League [WSL] vs. International). The height, weight, body composition, lower body strength, jump height, speed and aerobic capacity of 207 players were quantified during the pre-season period. Linear mixed models and effects sizes were used to determine differences between positions and standards. Forwards were significantly (p < 0.05) heavier (forwards: 82.5 ± 14.8kg; backs: 67.7 ± 9.2kg) and have a greater body fat % (forwards: 37.7 ± 6.9%; backs: 30.4 ± 6.3%) than backs. Backs had significantly greater lower body power measured via jump height (forwards: 23.5 ± 4.4cm; backs: 27.6 ± 4.9cm), speed over 10m (forwards: 2.12 ± 0.14s; backs: 1.98 ± 0.11s), 20m (forwards: 3.71 ± 0.27s; backs: 3.46 ± 0.20s), 30m (forwards: 5.29 ± 0.41s; backs: 4.90 ± 0.33s), 40m (forwards: 6.91 ± 0.61s; backs: 6.33 ± 0.46s) and aerobic capacity (forwards: 453.4 ± 258.8m; backs: 665.0 ± 298.2m) than forwards. Additionally, international players were found to have greater anthropometric and physical qualities in comparison to their WSL counterparts. This study adds to the limited evidence base surrounding the anthropometric and physical qualities of elite women’s rugby league players. Comparative values for anthropometric and physical qualities are provided which practitioners may use to evaluate the strengths and weaknesses of players, informing training programs to prepare players for the demands of women’s rugby league.
STRESS, an automated geometrical characterization of deformable particles forin vivomeasurements of cell and tissue mechanical stresses
Authors: Gross Ben , Shelton Elijah , Gomez Carlos , Campàs Otger 
Published: March 2021

AbstractFrom cellular mechanotransduction to the formation of embryonic tissues and organs, mechanics has been shown to play an important role in the control of cell behavior and embryonic development. Most of our existing knowledge of how mechanics affects cell behavior comes fromin vitrostudies, mainly because measuring cell and tissue mechanics in 3D multicellular systems, and especiallyin vivo, remains challenging. Oil microdroplet sensors, and more recently gel microbeads, use surface deformations to directly quantify mechanical stresses within developing tissues,in vivoandin situ, as well as in 3Din vitrosystems like organoids or multicellular spheroids. However, an automated analysis software able to quantify the spatiotemporal evolution of stresses and their characteristics from particle deformations is lacking. Here we develop STRESS (Surface Topography Reconstruction for Evaluation of Spatiotemporal Stresses), an analysis software to quantify the geometry of deformable particles of spherical topology, such as microdroplets or gel microbeads, that enables the automatic quantification of the temporal evolution of stresses in the system and the spatiotemporal features of stress inhomogeneities in the tissue. As a test case, we apply these new code to measure the temporal evolution of mechanical stresses using oil microdroplets in developing zebrafish tissues. Starting from a 3D timelapse of a droplet, the software automatically calculates the statistics of local anisotropic stresses, decouples the deformation modes associated with tissue- and cell-scale stresses, obtains their spatial features on the droplet surface and analyzes their spatiotemporal variations using spatial and temporal stress autocorrelations. The automated nature of the analysis will help users obtain quantitative information about mechanical stresses in a wide range of 3D multicellular systems, from developing embryos or tissue explants to organoids.Author summaryThe measurement of mechanical stresses in 3D multicellular systems, such as living tissues, has been very challenging because of a lack in technologies for this purpose. Novel microdroplet techniques enable direct, quantitativein situmeasurements of mechanical stresses in these systems. However, computational tools to obtain mechanical stresses from 3D images of microdroplets in an automated and accurate manner are lacking. Here we develop STRESS, an automated analysis software to analyze the spatiotemporal characteristics of mechanical stresses from microdroplet deformations in a wide range of systems, from living embryonic tissues and tissue explants to organoids and multicellular spheroids.