bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 in Tunisia (North Africa): IgG and IgG subclass antibody responses to SARS-CoV-2 according to disease severity
Authors: Benabdessalem Chaouki , Marzouki Soumaya , Hamouda Wafa Ben , Trabelsi Khaled , Boumaiza Mohamed , Hamouda Sonia Ben , Ouni Rym , Bchiri Soumaya , Chaaban Amani , Gdoura Meriem , Gorgi Yousr , Sfar Imen , Yalaoui Sadok , Khelil Jalila Ben , Hamzaoui Agnes , Abdallah Meya , Cherif Yosra , Petres Stéphane , Pun Mok Chris Ka , Escriou Nicolas , Quesney Sébastien , Dellagi Koussay , Bettaieb Jihene , Rourou Samia , Barbouche Mohamed Ridha , Ahmed Melika Ben 
Published: March 2022

SummaryCoronavirus disease 2019 (COVID-19) expresses a wide spectrum of disease severity. We investigated the profile of IgG and IgG subclass antibody responses to SARS– CoV-2 in Tunisian patients with COVID-19 according to disease severity (86 patients with severe disease and 63 with mild to moderate disease). Two in house developed ELISA with excellent performance were used to test for antibodies to the nucleocapsid (N) protein and the receptor-binding domain of the spike antigen (S-RBD) of SARS-CoV-2. IgG, IgG1 and IgG3 antibodies were significantly higher in patients with severe disease compared to non-severe disease. Antibodies to S-RBD or the N protein were dominated by IgG1 and IgG3 or IgG1/IgG3 and IgG2 subclasses respectively. In patients with severe disease, IgG antibodies ‘ appearance to S-RBD was delayed compared to the N protein. IgG subclass imbalance may reflect the pathophysiology of COVID-19 and may herald disease aggravation. This study brings information on the immune responses to SARS-CoV-2 in North African patients and completes the picture drawn on COVID-19 in different African populations and worldwide.
First detection of Powassan Virus lineage I in field-collected Dermacentor variabilis from New York, USA
Authors: Hart Charles , Hassett Erin , Vogels Chantal B.F. , Shapley Daniel , Grubaugh Nathan D. , Thangamani Saravanan 
Published: March 2022

ABSTRACTPowassan virus (POWV) is a tick-borne flavivirus that can cause lethal or debilitating neurological illness. It is canonically transmitted by Ixodes genus ticks but may interact with sympatric Dermacentor species. Here, we report the first detection of POWV lineage I from a pool of field-collected D. variabilis in New York state.
HIF1A modulate glycolysis function to governs mouse ovarian microenvironment metabolic plasticity in aging single cell resolution
Authors: Zhang Xiaoyu , Gunewardena Sumedha , Liu Yan , Wang Ning 
Published: March 2022

AbstractThe molecular machinery of ovarian aging and female age-related pathway remain unclear. Here, we utilized single-cell RNA-seq to profile over 9815 cells from both young and old female mouse and identified age-related alterations in the female somatic microenvironment. Interestingly, by aging-related signature calculation, we examined HIF1A in mouse ovarian cell aging regulated roles which effect pathways included glycolysis, TCA, OXPHOS and fatty acid metabolism. Additionally, inactivated HIF1A, decreased glycolysis was observed. Comparison analysis reveals the aging related regulon; metabolic and nutrient absorption changes provides a comprehensive understanding of the cell-type-specific mechanisms underlying mouse ovarian aging at single-cell resolution. This study, revealing new potential candidate biomarkers for the diagnosis of aging-associated ovary pathology.
PhD and postdoc training outcomes at EMBL: changing career paths for life scientists in Europe
Authors: Lu Junyan , Velten Britta , Klaus Bernd , Ramm Mauricio , Huber Wolfgang , Coulthard-Graf Rachel 
Published: March 2022

AbstractThe life sciences are training growing numbers of PhDs and postdocs, who increasingly engage in collaborative research. The impact of these changes on the careers of researchers is, however, unclear. Here, we report an analysis of the training outcomes for 2284 researchers who completed a PhD or postdoc at the European Molecular Biology Laboratory (EMBL) between 1997 and 2020. This is the first such study published from a European institute and first time-resolved analysis globally. The most common career outcomes were in academic research, service and teaching (1263 alumni, 55%), including 636 principal investigators (PIs). A broad spectrum of other career paths was also represented, including in industry research (332, 15%) and science-related professions (349, 15%). Our analysis indicates that, although there is increased competition for PI roles, life scientists continue to enter and excel in careers that drive research and innovation.
Integrating temporal single-cell gene expression modalities for trajectory inference and disease prediction
Authors: Ranek Jolene S. , Stanley Natalie , Purvis Jeremy E. 
Published: March 2022

AbstractCurrent methods for analyzing single-cell datasets have relied primarily on static gene expression measurements to characterize the molecular state of individual cells. However, capturing temporal changes in cell state is crucial for the interpretation of dynamic phenotypes such as the cell cycle, development, or disease progression. RNA velocity infers the direction and speed of transcriptional changes in individual cells, yet it is unclear how these temporal gene expression modalities may be leveraged for predictive modeling of cellular dynamics. Here, we present the first task-oriented benchmarking study that investigates integration of temporal sequencing modalities for dynamic cell state prediction. We benchmark eight integration approaches on eight datasets spanning different biological contexts, sequencing technologies, and species. We find that integrated data more accurately infers biological trajectories and achieves increased performance on classifying cells according to perturbation and disease states. Furthermore, we show that simple concatenation of spliced and unspliced molecules performs consistently well on classification tasks and can be used over more memory intensive and computationally expensive methods. This work provides users with practical recommendations for task-specific integration of single-cell gene expression modalities.
A Morphogenetic Wave that Generates Mesenchymal-to-Epithelial Transition in the Lateral Plate Mesoderm
Authors: Asleh Manar Abboud , Zaher Mira , Jadon Julian , Shaulov Lihi , Yelin Ronit , Schultheiss Thomas M. 
Published: March 2022

AbstractMost mesodermal cells undergo multiple cycles of transition between an epithelial and mesenchymal state during embryonic development. While many studies have addressed the process of epithelial-to-mesenchymal transition (EMT), comparatively less is known regarding the complementary process, mesenchymal-to-epithelial transition (MET), which is essential for organogenesis and has also been proposed to be important for cancer metastasis. The current study investigated MET using the lateral plate mesoderm (LPM) of the chick embryo as a model system. We find that MET in the LPM proceeds as a wave, which divides the LPM into distinct mesenchymal, transition, and epithelial zones. In the multilayered mesenchymal zone, many apical epithelial markers, including N-Cadherin (N-Cad), Par-3 and Zo-1, but not atypical protein kinase C (aPKC), are detected as dispersed, partially co-localizing aggregates associated with cell-cell contacts. The transition zone is characterized by the appearance of aPKC and the formation of rosette-like structures characterized by wedge-shaped cells that are apical-basal polarized, with strong co-localization of apical polarity markers, but not yet arranged into distinct epithelial sheets. The transition zone is also enriched in mitotic cells. Subsequently, the rosettes resolve into two well-defined epithelial sheets that constitute the coelomic epithelium, the lining of the internal body cavity.Prior to any overt signs of apical-basal polarity, fibronectin (FN) begins to accumulate at the future basal side of the incipient epithelium. Interference with Extracellular Matrix (ECM)-integrin signaling through disruption of focal adhesion kinase (FAK) or Talin function hindered the normal progression of the epithelialization process. Cells with disrupted FAK or Talin function retained mesenchymal-like characteristics with respect to cellular morphology and apical-basal marker distribution.We propose a two-stage process for MET in the LPM. Initially, in the polarization phase, ECM-integrin-dependent signaling imparts apical-basal polarity, culminating in the activation of aPKC, to drive cell intercalation and rosette formation. Subsequently in the resolution phase, polarized rosette cells, perhaps facilitated by the weakening of cell-cell interactions that occurs during mitosis, expand their apical surface, and spread out to form new connections laterally to their fully epithelial neighbors. This sequence of events is propagated as a wave through the LPM, thus generating an integrated coelomic epithelium.
Rule-based habitat suitability modelling for the reintroduction of the grey wolf (Canis lupus) in Scotland
Authors: Gwynn Vashti , Symeonakis Elias 
Published: March 2022

AbstractThough native to Scotland, the grey wolf (Canis lupus) was extirpated c.250 years ago as part of a global eradication drive. The global population has recently expanded, now occupying 67% of its former range. Evidence is growing that apex predators provide a range of ecological benefits, most stemming from the reduction of overgrazing by deer – something from which Scotland suffers. In this study, we build a rule-based habitat suitability model for wolves on the Scottish mainland. From existing literature, we identify the most important variables as land cover, prey density, road density and human density, and establish thresholds of suitability for each. Fuzzy membership functions are used to assign suitability values to each variable, followed by fuzzy overlay to combine all four: a novel approach to habitat suitability modelling for terrestrial mammals. Model sensitivity is tested for land cover and prey density, as these variables constitute a knowledge gap and an incomplete dataset, respectively. The Highlands and Grampian mountains emerge strongly and consistently as the most suitable areas, largely due to high negative covariance between prey density and road/human density. Sensitivity testing reveals the models are fairly robust to changes in prey density, but less robust to changes in the scoring of land cover, with the latter altering the distribution of land mainly through the 70 – 100% suitability range. However, in statistical significance tests, only the least and most generous versions of the model emerge as giving significantly different results. Depending on the version of the model, a contiguous area of between 10,139km2 and 18,857km2 is shown to be 80 to 100% suitable. This could be sufficient to support between 50 and 94 packs of four wolves, if the average pack range size is taken to be 200km2. We conclude that in terms of habitat availability, reintroduction should be feasible.
Individually unique, fixed stripe configurations ofOctopus chierchiaeallow for photoidentification in long-term studies
Authors: Liu Benjamin , Song Leo , Kelkar Saumitra , Ramji Anna , Caldwell Roy 
Published: March 2022

AbstractThe Lesser Pacific Striped Octopus,Octopus chierchiae, is a small iteroparous octopus known to inhabit intertidal regions of the Pacific coast of Central America. Many details about its life history and ecology remain unknown. For apparently rare and delicate animals such asO. chierchiae, non-extractive sampling methods are necessary to study individuals and populations over time. After photographically documenting the physical development of 25 octopuses from hatching, we have concluded thatO. chierchiaehas individually unique stripe configurations that remain constant throughout their post-hatchling lifetimes. Furthermore, using photographs taken of animals in captivity on different dates over many months, we show that untrained volunteers can accurately identify whether or not a pair of images depicts the same individual octopus. These results demonstrate that laboratory-reared individuals could be identified via photographs taken at different points in their lifetimes, which suggests wild individuals can also be recognized and observed for longitudinal field studies. In addition, our results imply potential for photoidentification and community science to be used as non-extractive, non-intrusive sampling methods for future studies of wildO. chierchiae.
Metagenomic profiling and transfer dynamics of antibiotic resistance determinants in a full-scale granular sludge wastewater treatment plant
Authors: Calderón-Franco David , Sarelse Roel , Christou Stella , Pronk Mario , van Loosdrecht Mark C.M. , Abeel Thomas , Weissbrodt David G. 
Published: March 2022

AbstractIn the One Health context, wastewater treatment plants (WWTPs) are central to safeguard water resources. Nonetheless, many questions remain about their effectiveness to prevent the dissemination of antimicrobial resistance (AMR). Most surveillance studies monitor the levels and removal of selected antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in intracellular DNA (iDNA) extracted from WWTP influents and effluents. The role of extracellular free DNA (exDNA) in wastewater is mostly overlooked. In this study, we analyzed the transfer of ARGs and MGEs in a full-scale Nereda® reactor removing nutrients with aerobic granular sludge. We tracked the composition and fate of the iDNA and exDNA pools of influent, sludge, and effluent samples. Metagenomics was used to profile the microbiome, resistome, and mobilome signatures of iDNA and exDNA extracts. Selected ARGs and MGEs were analyzed by qPCR. From 2,840 ARGs identified, the genesarr-3(2%), tetC(1.6%), sul1(1.5%), oqxB(1.2%), andaph(3”)-Ib(1.2%) were the most abundant among all sampling points and bioaggregates.Pseudomonas,Acinetobacter,Aeromonas,Acidovorax,Rhodoferax,andStreptomycespopulations were the main hosts of ARGs in the sludge. In the effluent, 478 resistance determinants were detected, of which 89% from exDNA potentially released by cell lysis during aeration in the reactor. MGEs and multiple ARGs were co-localized on the same extracellular genetic contigs. These can pose a risk for AMR dissemination by transformation into microorganisms of receiving water bodies. Total intracellular ARGs decreased 3-42% as a result of wastewater treatment. However, theermBandsul1genes increased by 2 and 1 log gene copies mL-1, respectively, in exDNA from influent to effluent. The exDNA fractions need to be considered in AMR surveillance, risk assessment, and mitigation.Graphical abstractHighlightsA DNA database from an AGS reactor was constructed to study the system resistome, mobilome, and microbiome.The generaPseudomonasandRhodoferaxwere the predominant ARG carriers in the system.MGEs and ARGs often co-localize on contigs recovered from the exDNA of the effluent.AGS plants are efficient at reducing ARB.The exDNA is an underestimated DNA fraction containing ARGs in the effluent.
The periplasmic chaperone Skp prevents misfolding of the secretory lipase A from Pseudomonas aeruginosa
Authors: Papadopoulos Athanasios , Busch Max , Reiners Jens , Hachani Eymen , Bäumers Miriam , Schmitt Lutz , Jaeger Karl-Erich , Kovacic Filip , Smits Sander H.J. , Kedrov Alexej 
Published: March 2022

AbstractPseudomonas aeruginosa is a wide-spread opportunistic human pathogen and a high-risk factor for immunodeficient people and patients with cystic fibrosis. The extracellular lipase A belongs to the virulence factors of P. aeruginosa. The lipase undergoes folding and activation in the periplasm prior the secretion. Here, we demonstrate that the ubiquitous periplasmic chaperone Skp of P. aeruginosa, but not SurA, FkpA, PpiD or YfgM, efficiently prevents misfolding of the aggregation-prone lipase A and facilitates its activation by a specific foldase LipH. Small-angle X-ray scattering visualizes the trimeric architecture of P. aeruginosa Skp and identifies two primary conformations of the chaperone, a compact and a widely open. We describe two binding modes of Skp to the lipase, with affinities of 20 nM and 2 μM, which correspond to 1:1 and 1:2 stoichiometry of the lipase:Skp complex. Two Skp trimers are required to stabilize the lipase via the apolar interactions, which are not affected by high salt concentrations typical for the sputum of cystic fibrosis patients. The chaperoning effect of Skp points to its potent role in maturation and secretion of the lipase in Pseudomonas species.
Molecular Basis for Variations in the Sensitivity of Pathogenic Rhodopsin Variants to 9-cis-Retinal
Authors: Roushar Francis J. , McKee Andrew G. , Kuntz Charles P. , Ortega Joseph T. , Penn Wesley D. , Woods Hope , Chamness Laura M. , Most Victoria , Meiler Jens , Jastrzebska Beata , Schlebach Jonathan P. 
Published: March 2022

AbstractOver 100 mutations in the rhodopsin gene have been linked to a spectrum of retinopathies that include retinitis pigmentosa and congenital stationary night blindness. Though most of these variants exhibit a loss of function, the molecular defects caused by these underlying mutations vary considerably. In this work, we utilize deep mutational scanning to quantitatively compare the plasma membrane expression of 123 known pathogenic rhodopsin variants in the presence and absence of the stabilizing cofactor 9-cis-retinal. We identify 69 retinopathy variants, including 20 previously uncharacterized variants, that exhibit diminished plasma membrane expression in HEK293T cells. 67 of these apparent class II variants exhibit a measurable increase in expression in the presence of 9-cis-retinal. However, the magnitude of the response to this molecule varies considerably across this spectrum of mutations. Evaluation of the observed shifts in relation to thermodynamic estimates for the coupling between binding and folding suggests underlying differences in stability constrains the magnitude of their response to retinal. Nevertheless, estimates from computational modeling suggest many of the least sensitive variants also directly compromise binding. Finally, we evaluate the functional properties of three previous uncharacterized, retinal-sensitive variants (ΔN73, S131P, and R135G) and show that two retain residual function in vitro. Together, our results provide a comprehensive experimental characterization of the proteostatic properties of retinopathy variants and their response to retinal.
ColorBayes: Improved color correction of high-throughput plant phenotyping images to account for local illumination differences
Authors: Lozano-Claros Diego , Custovic Eddie , Deng Guang , Whelan James , Lewsey Mathew G. 
Published: March 2022

AbstractBackgroundColor distortion is an inherent problem in image-based phenotyping systems that are illuminated by artificial light. This distortion is problematic when examining plants because it can cause data to be incorrectly interpreted. One of the leading causes of color distortion is the non-uniform spectral and spatial distribution of artificial light. However, color correction algorithms currently used in plant phenotyping assume that a single and uniform illuminant causes color distortion. These algorithms are consequently inadequate to correct the local color distortion caused by multiple illuminants common in plant phenotyping systems, such as fluorescent tubes and LED light arrays. We describe here a color constancy algorithm, ColorBayes, based on Bayesian inference that corrects local color distortions. The algorithm estimates the local illuminants using the Bayes’ rule, the maximum a posteriori, the observed image data, and prior illuminant information. The prior is obtained from light measurements and Macbeth ColorChecker charts located on the scene.ResultsThe ColorBayes algorithm improved the accuracy of plant color on images taken by an indoor plant phenotyping system. Compared with existing approaches, it gave the most accurate metric results when correcting images from a dataset of Arabidopsis thaliana images.The software is available at https://github.com/diloc/Color_correction.git.
Rapidly evolving genes underlie Aedes aegypti mosquito reproductive resilience during drought
Authors: Venkataraman Krithika , Shai Nadav , Lakhiani Priyanka , Zylka Sarah , Zhao Jieqing , Herre Margaret , Zeng Joshua , Neal Lauren A. , Molina Henrik , Zhao Li , Vosshall Leslie B. 
Published: March 2022

SUMMARYFemale Aedes aegypti mosquitoes impose a severe global public health burden as vectors of multiple viral pathogens. Under optimal environmental conditions, Aedes aegypti females have access to human hosts that provide blood proteins for egg development, conspecific males that provide sperm for fertilization, and freshwater that serves as an egg-laying substrate suitable for offspring survival. As global temperatures rise, Aedes aegypti females are faced with climate challenges like intense droughts and intermittent precipitation, which create unpredictable, suboptimal conditions for egg-laying. Here we show that under drought-like conditions simulated in the laboratory, females retain mature eggs in their ovaries for extended periods, while maintaining the viability of these eggs until they can be laid in freshwater. Using transcriptomic and proteomic profiling of Aedes aegypti ovaries, we identify two previously uncharacterized genes named tweedledee and tweedledum, each encoding a small, secreted protein that both show ovary-enriched, temporally-restricted expression during egg retention. These genes are mosquito-specific, linked within a syntenic locus, and rapidly evolving under positive selection, raising the possibility that they serve an adaptive function. CRISPR-Cas9 deletion of both tweedledee and tweedledum demonstrates that they are specifically required for extended retention of viable eggs. These results highlight an elegant example of taxon-restricted genes at the heart of an important adaptation that equips Aedes aegypti females with “insurance” to flexibly extend their reproductive schedule without losing reproductive capacity, thus allowing this species to exploit unpredictable habitats in a changing world.