bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding access to SARS-CoV-2 IgG and IgM serologic testing using fingerstick whole blood, plasma, and rapid lateral flow assays
Authors: Anderson Mark , Holzmayer Vera , Vallari Ana , Taylor Russell , Moy James , Cloherty Gavin 
Published: April 2021

AbstractSerologic testing for SARS-CoV-2 antibodies can be used to confirm diagnosis, estimate seroprevalence, screen convalescent plasma donors, and assess vaccine efficacy. Several logistical and infrastructure challenges limit access to SARS-CoV-2 serologic testing. Dried blood spot (DBS) samples have been used for serology testing of various diseases in resource-limited settings. We examined the use of DBS samples and capillary blood (fingerstick) plasma collected in Microtainer tubes for SARS-CoV-2 testing with the automated Abbott ARCHITECT™ SARS-CoV-2 IgG (List 6R86) and IgM assays and use of venous whole blood with a prototype PANBIO™ rapid point-of-care lateral flow SARS-CoV-2 IgG assay. The ARCHITECT™ SARS-CoV-2 IgG assay was initially optimized for use with DBS, venous and capillary plasma, and venous whole blood collected from patients with symptoms and PCR-confirmed COVID-19 and negative asymptomatic controls. Assay linearity and reproducibility was confirmed with 3 contrived DBS samples, with sample stability and signal recovery after 14 days at room temperature. ARCHITECT™ SARS-CoV-2 IgG and IgM assay results showed high concordance between fingerstick DBS and venous DBS samples, and between fingerstick DBS and venous whole blood samples (n=61). Discordant results were seen in 3 participants (2 IgG, 1 IgM) who were in the process of seroreversion at the time of sample collection and had results near the assay cutoff. Use of fingerstick plasma collected in Microtainer tubes (n=109) showed 100% concordant results (R2=0.997) with matched patient venous plasma on the ARCHITECT™ SARS-CoV-2 IgG assay. High concordance of assay results (92.9% positive, 100% negative) was also observed for the PANBIO™ SARS-CoV-2 IgG assay compared to the ARCHITECT™ SARS-CoV-2 IgG assay run with matched venous plasma (n=61). Fingerstick DBS and plasma samples are easy and inexpensive to collect and, along with the use of rapid point-of-care testing platforms, will expand access to SARS-CoV-2 serology testing, particularly in resource-limited areas.
Cross-Species Analysis Defines the Conservation of Anatomically-Segregated VMH Neuron Populations
Authors: Affinati Alison H. , Sabatini Paul V. , True Cadence , Tomlinson Abigail J. , Kirigiti Melissa , Lindsley Sarah R. , Li Chien , Olson David P. , Kievit Paul , Myers Martin G. , Rupp Alan C. 
Published: April 2021

ABSTRACTThe ventromedial hypothalamic nucleus (VMH) controls diverse behaviors and physiologic functions, suggesting the existence of multiple VMH neural subtypes with distinct functions. Combing Translating Ribosome Affinity Purification with RNA sequencing (TRAP-seq) data with snRNA-seq data, we identified 24 mouse VMH neuron clusters. Further analysis, including snRNA-seq data from macaque tissue, defined a more tractable VMH parceling scheme consisting of 6 major genetically- and anatomically-differentiated VMH neuron classes with good cross-species conservation. In addition to two major ventrolateral classes, we identified three distinct classes of dorsomedial VMH neurons. Consistent with previously-suggested unique roles for leptin receptor (Lepr)-expressing VMH neurons,Leprexpression marked a single dorsomedial class. We also identified a class of glutamatergic VMH neurons that resides in the tuberal region, anterolateral to the neuroanatomical core of the VMH. This atlas of conserved VMH neuron populations provides an unbiased starting point for the analysis of VMH circuitry and function.
Coupled exoskeleton assistance simplifies control and maintains metabolic benefits: a simulation study
Authors: Bianco Nicholas A. , Franks Patrick W. , Hicks Jennifer L. , Delp Scott L. 
Published: April 2021

AbstractAssistive exoskeletons can reduce the metabolic cost of walking, and recent advances in exoskeleton device design and control have resulted in large metabolic savings. Most exoskeleton devices provide assistance at either the ankle or hip. Exoskeletons that assist multiple joints have the potential to provide greater metabolic savings, but can require many actuators and complicated controllers, making it difficult to design effective assistance. Coupled assistance, when two or more joints are assisted using one actuator or control signal, could reduce control dimensionality while retaining metabolic benefits. However, it is unknown which combinations of assisted joints are most promising and if there are negative consequences associated with coupled assistance. Since designing assistance with human experiments is expensive and time-consuming, we used musculoskeletal simulation to evaluate metabolic savings from multi-joint assistance and identify promising joint combinations. We generated 2D muscle-driven simulations of walking while simultaneously optimizing control strategies for simulated lower-limb exoskeleton assistive devices to minimize metabolic cost. Each device provided assistance either at a single joint or at multiple joints using massless, ideal actuators. To assess if control could be simplified for multi-joint exoskeletons, we simulated different control strategies in which the torque provided at each joint was either controlled independently or coupled between joints. We compared the predicted optimal torque profiles and changes in muscle and whole-body metabolic power consumption across the single joint and multi-joint assistance strategies. We found multi-joint devices–whether independent or coupled–provided 50% greater metabolic savings than single joint devices. The coupled multi-joint devices were able to achieve most of the metabolic savings produced by independently-controlled multi-joint devices. Our results indicate that device designers could simplify multi-joint exoskeleton designs by reducing the number of torque control parameters through coupling, while still maintaining large reductions in metabolic cost.
The view of microbes as energy converters illustrates the trade-off between growth rate and yield
Authors: Wilken St. Elmo , Frazão Victor Vera , Saadat Nima P. , Ebenhöh Oliver 
Published: April 2021

AbstractThe application of thermodynamics to microbial growth has a long tradition that originated in the middle of the 20thcentury. This approach reflects the view that self-replication is a thermodynamic process that is not fundamentally different from mechanical thermodynamics. The key distinction is that a free energy gradient is not converted into mechanical (or any other form of) energy, but rather into new biomass. As such, microbes can be viewed as energy converters that convert a part of the energy contained in environmental nutrients into chemical energy that drives self-replication. Before the advent of high-throughput sequencing technologies, only the most central metabolic pathways were known. However, precise measurement techniques allowed for the quantification of exchanged extracellular nutrients and heat of growing microbes with their environment. These data, together with the absence of knowledge of metabolic details, drove the development of so-called black box models, which only consider the observable interactions of a cell with its environment and neglect all details of how exactly inputs are converted into outputs. Now, genome sequencing and genome-scale metabolic models provide us with unprecedented detail about metabolic processes inside the cell. However, the derived modelling approaches make surprisingly little use of thermodynamic concepts. Here, we review classical black box models and modern approaches that integrate thermodynamics into genome-scale metabolic models. We also illustrate how the description of microbial growth as an energy converter can help to understand and quantify the trade-off between microbial growth rate and yield.PerspectiveMicrobial growth is the foundation of many biotechnological applications. The key to optimizing microbial growth lies in thermodynamics, similar to how classical thermodynamics helped optimize steam engines in the 19thcentury.Genome-scale metabolic models have become widely available, and are used to predict microbial growth. These predictions often fail because these models do not distinguish between growth rate and yield.Classical black box models present a sound thermodynamic theory, by viewing microbes as energy converters. Incorporating such concepts into genome-scale metabolic models has the promise to advance our fundamental understanding of microbial growth, and thus to improve the predictive power of these models.
Polygenic adaptation from standing genetic variation allows rapid ecotype formation
Authors: Fuhrmann Nico , Prakash Celine , Kaiser Tobias S. 
Published: April 2021

AbstractAdaptive ecotype formation is the first step to speciation, but the genetic underpinnings of this process are poorly understood. Marine midges of the genusClunio(Diptera) have recolonized Northern European shore areas after the last glaciation. In response to local tide conditions they have formed different ecotypes with respect to timing of adult emergence, oviposition behavior and larval habitat. Genomic analysis confirms the recent establishment of these ecotypes, reflected in massive haplotype sharing between ecotypes, irrespective of whether there is ongoing gene flow or geographic isolation. QTL mapping and genome screens reveal patterns of polygenic adaptation from standing genetic variation. Ecotype-associated loci prominently include circadian clock genes, as well as genes affecting sensory perception and nervous system development, hinting to a central role of these processes in ecotype formation. Our data show that adaptive ecotype formation can occur rapidly, with ongoing gene flow and largely based on a re-assortment of existing alleles.
Behavioural stress feedback loops in benthic invertebrates caused by pH drop-induced metabolites
Authors: Feugere Lauric , Angell Lauren , Fagents James , Nightingale Rebecca , Rowland Kirsty , Skinner Saffiyah , Hardege Jorg , Bartels-Hardege Helga , Valero Katharina C. Wollenberg 
Published: April 2021

AbstractStudies on pH stress in marine animals typically focus on direct or species-specific aspects. We here test the hypothesis that a drop to pH = 7.6 indirectly affects the intra- and interspecific interactions of benthic invertebrates by means of chemical communication. We recorded fitness-relevant behaviours of small hermit crabsDiogenes pugilator, green shore crabsCarcinus maenas, and harbour ragwormsHediste diversicolorin response to short-term pH drop, and to putative stress metabolites released by conspecifics or gilt-head sea breamSparus aurataduring 30 minutes of acute pH drop. Not only did acute pH drop itself impair time to find a food cue in small hermit crabs and burrowing in harbour ragworms, but similar effects were observed under exposure to pH drop-induced stress metabolites. Stress metabolites fromS. aurata,but not its regular control metabolites, also induced avoidance responses in all recipient species. Here, we confirm that a short-term abrupt pH drop, an abiotic stressor, has the capacity to trigger the release of metabolites which induce behavioural responses in conspecific and heterospecific individuals, which can be interpreted as a behavioural cost. Our findings that stress responses can be indirectly propagated through means of chemical communication warrant further research to confirm the effect size of the behavioural impairments caused by stress metabolites and to characterise their chemical nature.
Genomic Analysis of Hypoxia Inducible Factor Alpha Evolution in Ray-finned Fishes (Actinopterygii)
Authors: Townley Ian K. , Rees Bernard B. 
Published: April 2021

AbstractTwo rounds of genome duplication (GD) in the ancestor of vertebrates, followed by additional GD during the evolution of ray-finned fishes (Actinopterygii), expanded certain gene families, including those encoding the hypoxia inducible transcription factor (HIF). The present study analyzed Actinopterygian genomes for duplicates of HIFα, the subunit that confers oxygen-dependent gene regulation. In contrast to tetrapod vertebrates that retain three HIFα genes from the ancestral vertebrate GD, four HIFα forms were found in the genomes of primitive Actinopterygians (spotted gar and Asian arowana). All four forms have been retained in zebrafish and related species (Otocephala) and salmonids and their sister taxa (northern pike) but one of them (HIF4α) was lost during the evolution of more derived fishes (Neoteleostei). In addition, the current analyses confirm that Otocephala retain duplicates of HIF1α and HIF2α from the teleost-specific GD, provide new evidence of salmonid-specific duplicates of HIF1α, HIF2α, and HIF3α, and reveal a broad distribution of a truncated form of HIF2α in salmonids and Neoteleostei. This study delivers a comprehensive view of HIFα evolution in the ray-finned fishes, highlights the need for a consistent nomenclature, and suggests avenues for future research on this critical transcription factor.
Stripenn detects architectural stripes from chromatin conformation data using computer vision
Authors: Yoon Sora , Vahedi Golnaz 
Published: April 2021

AbstractArchitectural stripes tend to form at genomic regions harboring genes with salient roles in cell identity and function. Therefore, the accurate identification and quantification of these features is essential for the understanding of lineage-specific gene regulation. Here, we present Stripenn, an algorithm rooted in computer vision to systematically detect and quantitate architectural stripes from chromatin conformation measurements of various technologies. We demonstrate that Stripenn outperforms existing methods, highlight its biological applications in the context of B and T lymphocytes, and examine the role of sequence variation on architectural stripes by studying the conservation of these features in inbred strains of mice. In summary, Stripenn is a computational method which borrows concepts from widely used image processing techniques for demarcation and quantification of architectural stripes.
Emergent vulnerability to intensive coastal anthropogenic disturbances in mangrove forests
Authors: Li Yangfan , Zhang Zhen , Yang Yi , Li Yi 
Published: April 2021

AbstractMangrove forests, as one of the most productive coastal ecosystems in tropical and subtropical areas, provide multiple valuable ecosystem services for human well-being. Mangrove coverage has been declining dramatically across much of developing regions due to extensive coastal anthropogenic disturbances such as reclamation, aquaculture, and seawall construction. As coastal human activities increase, there is urgent need to understand not only the direct loss, but also the vulnerability of mangroves to anthropogenic disturbances. In this study, we evaluated spatial pattern of mangrove vulnerability based on the conceptual framework of “Exposure-Sensitivity-Resilience” using geospatial datasets in mainland China. We find that within all 25,829 ha mangroves in five coastal provinces of mainland China in 2015, nearly 76% of mangroves was exposed or threatened by anthropogenic disturbances. Coastal reclamation and aquaculture were the key threats causing mangrove vulnerability. The overall distribution of high, medium and low vulnerability was following similar trend of aquaculture distribution, which suggests aquaculture was the greatest anthropogenic disturbance agent to mangroves. Hotspot regions for mangrove vulnerability are located at the developing provinces such as Guangxi and Hainan. This study provides the first spatially explicit evidence of the vulnerability of mangrove forests to intensive coastal anthropogenic disturbances at national scale, cloud serve as a benchmark for navigating coastal ecological redline management and coastal ecosystem restoration.
SARS-CoV-2 receptor binding domain fusion protein efficiently neutralizes virus infection
Authors: Chaouat Abigael , Achdout Hagit , Kol Inbal , Berhani Orit , Roi Gil , Vitner Einat B. , Melamed Sharon , Politi Boaz , Zahavy Eran , Brizic Ilija , Rovis Tihana Lenac , Alfi Or , Wolf Dana , Jonjic Stipan , Israely Tomer , Mandelboim Ofer 
Published: April 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic, causing health and economic problems. Currently, as dangerous mutations emerge there is an increased demand for specific treatments for SARS-CoV-2 infected patients. The spike glycoprotein on the virus membrane binds to the angiotensin converting enzyme 2 (ACE2) receptor on host cells through its receptor binding domain (RBD) to mediate virus entry. Thus, blocking this interaction may inhibit viral entry and consequently stop infection. Here, we generated fusion proteins composed of the extracellular portions of ACE2 and RBD fused to the Fc portion of human IgG1 (ACE2-Ig and RBD-Ig, respectively). We demonstrate that ACE2-Ig is enzymatically active and that it can be recognized by the SARS-CoV-2 RBD, independently of its enzymatic activity. We further show that RBD-Ig efficiently inhibits in vitro and in vivo SARS-CoV-2 infection, better than ACE2-Ig. Mechanistically we show that anti-spike antibodies generation, ACE2 enzymatic activity and ACE2 surface expression were not affected by RBD-Ig. Finally, we show that RBD-Ig is more efficient than ACE2-Ig at neutralizing high virus concentration infection. We thus propose that RBD-Ig physically blocks virus infection by binding to ACE2 and that RBD-Ig should be used for the treatment of SARS-CoV-2-infected patients.Author SummarySARS-CoV-2 infection caused serious socio-economic and health problems around the globe. As dangerous mutations emerge, there is an increased demand for specific treatments for SARS-CoV-2 infected patients. SARS-CoV-2 infection starts via binding of SARS-CoV-2 spike protein receptor binding domain (RBD) to its receptor, ACE2, on host cells. To intercept this binding, we generated Ig-fusion proteins. ACE2-Ig was generated to possibly block RBD by binding to it and RBD-Ig to block ACE2. We indeed showed that the fusion proteins bind to their respective target. We found that it is more efficient to inhibit SARS-CoV-2 infection by blocking ACE2 receptor with RBD-Ig. We also showed that RBD-Ig does not interfere with ACE2 activity or surface expression. Importantly, as our treatment does not target the virus directly, it may be efficient against any emerging variant. We propose here that RBD-Ig physically blocks virus infection by binding to ACE2 and thus it may be used for the treatment of SARS-CoV-2-infected patients.
The entorhinal cortex modulates trace fear memory formation and neuroplasticity in the lateral amygdala via cholecystokinin
Authors: Feng Hemin , Su Junfeng , Fang Wei , Chen Xi , He Jufang 
Published: April 2021

AbstractAlthough the neural circuitry underlying fear memory formation is important in fear-related mental disorders, it is incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. Moreover, we used the loss of function and rescue experiments to demonstrate that release of the neuropeptide cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons extend from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of sensory signals to the LA and formation of trace fear memory. Altogether, we suggest a model where sensory stimuli trigger the release of CCK from EC neurons, which potentiates sensory signals to the LA, ultimately influencing neural plasticity and trace fear memory formation.
Low dose inocula of SARS-CoV-2 B.1.1.7 variant initiate more robust infections in the upper respiratory tract of hamsters than earlier D614G variants
Authors: Mok Bobo Wing-Yee , Liu Honglian , Lau Siu-Ying , Deng Shaofeng , Liu Siwen , Tam Rachel Chun-Yee , Ng Timothy Ting-Leung , Leung Jake Siu-Lun , Wang Pui , To Kelvin Kai-Wang , Chan Jasper Fuk-Woo , Chan Kwok-Hung , Yuen Kwok-Yung , Siu Gilman Kit-Hang , Chen Honglin 
Published: April 2021

AbstractThere is a lack of experimental evidence to explain how the B.1.1.7 variant spreads more quickly than pre-existing variants in humans. We found that B.1.1.7 displays increased competitive fitness over earlier D614G lineages in anin-vitrosystem. Furthermore,, we demonstrated that B.1.1.7 variant is able to replicate and shed more efficiently in the nasal cavity than other variants with lower dose and shorter duration of exposure.
Range‐wide population viability analyses reveal high sensitivity to wildflower harvesting in extreme environments
Authors: Treurnicht Martina , Schurr Frank M. , Slingsby Jasper A. , Esler Karen J. , Pagel Jörn 
Published: April 2021

Abstract

The ecological effects of harvesting from wild populations are often uncertain, especially since the sensitivity of populations to harvesting can vary across species’ geographical ranges. In the Cape Floristic Region (CFR, South Africa) biodiversity hotspot, wildflower harvesting is widespread and economically important, providing an income to many rural communities. However, with very few species studied to date, and without considering range‐wide sensitivity to harvesting, there is limited information available to ensure the sustainability of wildflower harvesting.

We studied geographical variation in sensitivity to wildflower harvesting for 26 Proteaceae shrubs with fire‐driven life cycles using population viability analyses. We developed stochastic, density‐dependent population models that were parameterised from individual demographic rates (adult fecundity, seedling recruitment and adult fire survival) and local environmental conditions across the geographical ranges of the study species. We then simulated the effects of harvesting on populations in different environments across species ranges. Our model simulations predicted extinction risk per population, and we derived extinction probabilities over 100 years in response to different harvesting regimes. We used these population‐level extinction probabilities to quantify inter‐ and intraspecific variation in sensitivity to wildflower harvesting, and to explore how geographical variation in sensitivity depends on environmental conditions (climate, soil fertility and fire disturbance).

We detected considerable inter‐ and intraspecific variation in sensitivity to wildflower harvesting for the 26 study species. This held for both ‘nonsprouters’ and ‘resprouters’ (species with low and high fire persistence ability, respectively). Intraspecific variation in sensitivity to harvesting showed varying geographical patterns and associated with environmental variation. Notably, sensitivity was high towards range edges and at the climatic extremes of species ranges respectively.

Synthesis and applications. We show the importance of combining spatial demographic data, density‐dependent population dynamics and environmental variation when assessing sensitivity to harvesting across species' geographical ranges. Our findings caution against the application of general harvesting guidelines irrespective of species, geographical location or local environmental conditions. Our range‐wide population viability analyses provide insights for developing species‐specific, spatially nuanced guidelines for conservation management. Our approach also identifies species and areas to prioritise for monitoring to prevent the overexploitation of harvested species.