bluuebunny/crossref_metadata_2025_split huggingface dataset:
Students as Community Vaccinators: Implementation of a Service-Learning COVID-19 Vaccination Program
Authors: Griswold Andrew R. , Klein Julia , Dusaj Neville , Zhu Jeff , Keeler Allegra , Abramson Erika L. , Gurvitch Dana 
Published: January 2022

ABSTRACTBackgroundService-learning is an integral component of medical education. While the COVID-19 pandemic has caused massive educational disruptions, it has also catalyzed innovation in service-learning as real-time responses to pandemic-related problems. For example, the limited number of qualified providers was a potential barrier to local and national SARS-CoV-2 vaccination efforts. Foreseeing this hurdle, New York State temporarily allowed healthcare professional trainees to vaccinate, enabling medical students to support an overwhelmed healthcare system and contribute to the community. Yet, it was the responsibility of medical schools to interpret these rules and implement the vaccination programs. Here the authors describe a service-learning vaccination program directed towards underserved communities.MethodsWeill Cornell Medicine (WCM) rapidly developed a faculty-led curriculum to prepare students to communicate with patients about the COVID-19 vaccines and to administer intramuscular injections. Qualified students were deployed to public vaccination clinics located in underserved neighborhoods across New York City in collaboration with an established community partner. The educational value of the program was evaluated with retrospective survey.ResultsThroughout the program, which lasted from February to June 2021, 128 WCM students worked at 103 local events, helping to administer 26,889 vaccine doses. Analysis of student evaluations revealed this program taught fundamental clinical skills, increasing comfort giving intramuscular injection from 2% to 100% and increasing comfort talking to patients about the COVID-19 vaccine from 30% to 100%. Qualitatively participants described the program as a transformative service-learning experience.ConclusionAs new virus variants emerge, nations battle recurrent waves of infection, and vaccine eligibility expands to include children and boosters, the need for effective vaccination plans continues to grow. The program described here offers a novel framework that academic medical centers could adapt to increase vaccine access in their local community and provide students with a uniquely meaningful educational experience.
The C-terminal domain of SEC-10 is fundamental for exocyst function, Spitzenkörper organization and cell morphogenesis in Neurospora crassa
Authors: Figueroa-Meléndez Alfredo , Martínez-Núñez Leonora , Rico-Ramírez Adriana M. , Martínez-Andrade Juan M. , Munson Mary , Riquelme Meritxell 
Published: January 2022

AbstractThe exocyst is a conserved multimeric complex that participates in the final steps of the secretion of vesicles. In the filamentous fungus Neurospora crassa, the exocyst is crucial for polar growth, morphology, and the organization of the Spitzenkörper (Spk), the apical body where secretory vesicles accumulate before being delivered to the plasma membrane. In the highly polarized cells of N. crassa, the exocyst subunits SEC-3, SEC-5, SEC-6, SEC-8, and SEC-15 were previously found localized at the plasma membrane of the cells’ apices, while EXO-70 and EXO-84 occupied the frontal outer layer of the Spk, occupied by vesicles. The localization of SEC-10 had remained so far elusive. In this work, SEC-10 was tagged with the green fluorescent protein (GFP) either at its N- or C-terminus and found localized at the plasma membrane of growing hyphal tips, similar to what was previously observed for some exocyst subunits. While expression of an N-terminally tagged version of SEC-10 at its native locus was fully viable, expression of a C-terminally tagged version at its native locus resulted in severe hyphal growth and polarity defects. Additionally, a sec-10 knockout mutant in a heterokaryotic state (with genetically different nuclei) was viable but showed a strongly aberrant phenotype, confirming that this subunit is essential to maintain hyphal morphogenesis. Transmission electron microscopy analysis revealed the lack of a Spk in the SEC-10-GFP strain, suggesting a critical role of the exocyst in the vesicular organization at the Spk. Mass spectrometry analysis revealed fewer peptides of exocyst subunits interacting with SEC-10-GFP than with GFP-SEC-10, suggesting an essential role of the C-terminus of SEC-10 in exocyst assembly and/or stability. Altogether, our data suggest that an unobstructed C-terminus of SEC-10 is indispensable for the exocyst complex function and that a GFP tag could be blocking important subunit-subunit interactions.
Red harvester ant (Order: Hymenoptera) preference for cover crop seeds in South Texas
Authors: Elliott Lilly , Rivera Daniella , Noval Adrian , Choudhury Robin A. , Penn Hannah J. 
Published: January 2022

AbstractHarvester ants are known to selectively forage seeds, potentially impacting nearby plant community composition. In agricultural areas, harvester ants may be viewed as pests by foraging on crop seeds or as beneficials by preferentially removing weed seeds. However, little work has been done on harvester ant preferences for cover crop seeds. Local observations suggest that ants may take cover crop seeds, but no studies have evaluated ant agricultural impacts or seed preferences in the Lower Rio Grande Valley (LRGV). We examined red harvester ant (Pogonomyrmex barbatus Smith) preferences for commonly used cover crop seeds in the LRGV (vetch, oat, fescue, sunn hemp, and radish with wheatgrass as a control) and a commonly used bacterial seed inoculation treatment meant to increase root nodulation. We tested seed sets using choice tests housed in seed depots located within the foraging range of ant colonies with no prior exposure to the selected seeds. Of the evaluated cover crop seeds, wheatgrass and oat were the first to be removed entirely from the depot, with vetch remaining after 24 h. When we inoculated the two most preferred seeds to determine if there was a preference for non-inoculated seeds, we found no difference between inoculated and non-inoculated seeds. There were also significant changes in activity over time for both trials. These data indicate that harvester ant foraging preferences and activity can inform grower management recommendations regarding the risks of using certain cover crops and months sowing should be conducted in fields with known harvester ant presence.
Metabolic basis for the evolution of a common pathogenic Pseudomonas aeruginosa variant
Authors: Mould Dallas L. , Stevanovic Mirjana , Ashare Alix , Schultz Daniel , Hogan Deborah A 
Published: January 2022

AbstractMicrobes frequently evolve in reproducible ways. Here, we show that differences in specific metabolic regulation explain the frequent presence of lasR loss-of-function mutations in the bacterial pathogen Pseudomonas aeruginosa. While LasR contributes to virulence, lasR mutants have been associated with more severe disease. A model based on the intrinsic growth kinetics for a wild type strain and its LasR- derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. The evolution of LasR- lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. LasR- lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR- cells in a CbrB-controlled manner. We propose that in vivo metabolomes are a major driver of pathogen evolution, which may influence the progression of disease and its treatment.
Limb Specific Failure of Proliferation and Translation in the Mesenchyme Leads to Skeletal Defects in Diamond Blackfan Anemia
Authors: Hom Jimmy , Karnavas Theodoros , Hartman Emily , Papoin Julien , Tang Yuefeng , Dulmovits Brian M. , Khan Mushran , Patel Hiren , Bondy Jedediah , Edelman Morris , Touraine Renaud , Chanoz-Poulard Geneviève , Ottenberg Gregory , Maynard Robert , Adams Douglas J. , Robledo Raymond F. , Grande Daniel A , Marambaud Philippe , Barnes Betsy J , Durand Sébastien , Narla Anupama , Ellis Steven , Zon Leonard I. , Peters Luanne L. , Da Costa Lydie , Lipton Jeffrey M. , Ackert-Bicknell Cheryl L. , Blanc Lionel 
Published: January 2022

AbstractRibosomopathies are a class of disorders caused by defects in the structure or function of the ribosome and characterized by tissue-specific abnormalities. Diamond Blackfan anemia (DBA) arises from different mutations, predominantly in genes encoding ribosomal proteins (RPs). Apart from the anemia, skeletal defects are among the most common anomalies observed in patients with DBA, but they are virtually restricted to radial ray and other upper limb defects. What leads to these site-specific skeletal defects in DBA remains a mystery. Using a novel mouse model for RP haploinsufficiency, we observed specific, differential defects of the limbs. Using complementary in vitro and in vivo approaches, we demonstrate that reduced WNT signaling and subsequent increased β-catenin degradation in concert with increased expression of p53 contribute to mesenchymal lineage failure. We observed differential defects in the proliferation and differentiation of mesenchymal stem cells (MSCs) from the forelimb versus the hind limbs of the RP haploinsufficient mice that persisted after birth and were partially rescued by allelic reduction of Trp53. These defects are associated with a global decrease in protein translation in RP haploinsufficient MSCs, with the effect more pronounced in cells isolated from the forelimbs. Together these results demonstrate translational differences inherent to the MSC, explaining the site-specific skeletal defects observed in DBA.
Structure of theLysinibacillus sphaericusTpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX
Authors: Williamson Lainey J. , Galchenkova Marina , Best Hannah L. , Bean Richard J. , Munke Anna , Awel Salah , Pena Gisel , Knoska Juraj , Schubert Robin , Doerner Katerina , Park Hyun-Woo , Bideshi Dennis K. , Henkel Alessandra , Kremling Viviane , Klopprogge Bjarne , Lloyd-Evans Emyr , Young Mark , Valerio Joana , Kloos Marco , Sikorski Marcin , Mills Grant , Bielecki Johan , Kirkwood Henry , Kim Chan , de Wijn Raphael , Lorenzen Kristina , Xavier P. Lourdu , Rahmani Aida , Gelisio Luca , Yefanov Oleksandr , Mancuso Adrian P. , Federici Brian , Chapman Henry N. , Crickmore Neil , Rizkallah Pierre J. , Berry Colin , Oberthür Dominik 
Published: January 2022

AbstractTpp49Aa1 fromLysinibacillus sphaericusis a Toxin_10 family protein that – in combination with Cry48Aa1, a 3-domain crystal protein - has potent mosquitocidal activity, specifically againstCulex quinquefasciatusmosquitoes. MHz serial femtosecond crystallography at a nano-focused X-ray free electron laser, allowed rapid and high-quality data collection to determine the Tpp49Aa1 structure at 1.62 Å resolution from native nanocrystals. This revealed the packing of Tpp49Aa1 within these nanocrystals, isolated from sporulated bacteria, as a homodimer with a large intermolecular interface, shedding light on natural crystallization. Complementary experiments conducted at varied pH also enabled investigations of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals. Using modelling, we propose a potential interaction between Tpp49Aa1 and Cry48Aa1 that may play a role in their codependency and broaden our understanding of this two-component system. We expand the known target range, demonstrating Tpp49Aa1/Cry48Aa1 susceptibility of larvae fromAnopheles stephensi, Aedes albopictusandCulex tarsalis– substantially increasing the potential use of this toxin pair in mosquito control. Further functional insights are gained usingCulexcell lines to characterise cellular models for future investigations into Cry48Aa1/Tpp49Aa1 mechanism of action and to demonstrate transient detrimental effects of individual toxin components.Significance StatementThe Tpp49Aa1/Cry48Aa1 protein pair kills mosquito larvae. Innovative use of nano-focused X-ray free electron laser to match the size of natural Tpp49Aa1 nanocrystals and the highest beam intensity available in any XFEL for high-throughput data collection, allowed structural resolution to 1.62 Å.Tpp proteins show a range of interactions with different partners to elicit toxicity. To gain insight into Tpp49Aa1, its interaction with Cry48Aa1 was modelled. We also establish cell-based assays of Tpp49Aa1/Cry48Aa1 activity.We expand the known target range to include three more mosquito species:Anopheles stephensi, Aedes albopictusandCulex tarsalis. This study will underpin future Tpp mode of action investigations and aid insecticide optimization against mosquito vectors of emerging diseases such as West Nile Virus and malaria.
Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation
Authors: Stieger Kevin C. , Eles James R. , Ludwig Kip A. , Kozai Takashi D.Y. 
Published: January 2022

AbstractBackgroundNeural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz).ObjectiveWe hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent.MethodsWe quantified how asymmetric stimulation waveforms delivered at 10 Hz or 100 Hz for 30s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the leading phase to the return phase of charge-balanced cathodal- and anodal-first waveforms.ResultsNeurons within 40-60μm of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and the preferential activation of 20-90 % of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity increased over time for some waveforms at 10 Hz, but decreased more at 100 Hz than other waveforms.ConclusionThese data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation.
FRaeppli, a multispectral imaging toolbox for cell tracing and dense tissue analysis in zebrafish
Authors: Caviglia Sara , Unterweger Iris A. , Gasiūnaitė Akvilė , Vanoosthuyse Alexandre E. , Cutrale Francesco , Trinh Le A. , Fraser Scott E. , Neuhauss Stephan C. F. , Ober Elke A. 
Published: January 2022

AbstractVisualizing cell shapes, interactions and lineages of differentiating cells is instrumental for understanding organ development and repair. Across species, strategies for stochastic multicolour labelling have greatly facilitated tracking cells in in vivo and mapping neuronal connectivity. Nevertheless, integrating multi-fluorophore information into the context of developing tissues in zebrafish is challenging given their cytoplasmic localization and spectral incompatibility with commonly used fluorescent markers. Here, we developed FRaeppli (Fish-Raeppli) expressing bright membrane-or nuclear-targeted fluorescent proteins for efficient cell shape analysis and tracking. High spatiotemporal activation flexibility is provided by the Gal4/UAS system together with Cre/lox and/or PhiC31integrase. The distinct spectra of the FRaeppli fluorescent proteins allow simultaneous imaging with GFP and infrared subcellular reporters or tissue landmarks. By tailoring hyperspectral protocols for time-efficient acquisition, we demonstrate FRaeppli’s suitability for live imaging of complex internal organs, like the liver. Combining FRaeppli with polarity markers revealed previously unknown canalicular topologies between differentiating hepatocytes, reminiscent of the mammalian liver, suggesting shared developmental mechanisms. The multispectral FRaeppli toolbox thus enables the comprehensive analysis of intricate cellular morphologies, topologies and tissue lineages at single-cell resolution in zebrafish.
SLiMAn: an integrative web server for exploring short linear motif-mediated interactions in interactomes
Authors: Reys Victor , Labesse Gilles 
Published: January 2022

AbstractCells express thousands of macromolecules, and their functioning relies on multiple networks of intermolecular interactions. These interactions can be experimentally determine at different spatial and temporal resolutions. But, physical interfaces are not often delineated directly especially in high-throughput experiments. However, numerous three-dimensional structures of complexes have been already solved and sequence conservation allows comparative modeling of additional complexes. A large fraction of protein-protein interactions involves domain and so-called SLiMs (for Short Linear Motifs). Often, SLiMs lie in disordered regions or loops. Their small size and loosely folded nature prevent straightforward detection. SLiMAn (Short Linear Motif Analysis), a new web server is provided to help thorough analysis of interactomics data. Starting from a list of putative interactants such as the output of an interactomics study, SLiMs (from ELM) and SLiM-recognition domains (from Pfam) are extracted and potential pairing are displayed. Additionally, filters are available to dig into the predicted results such as the motif E-value, IUpred2 scoring functions for disorder or BioGRID interaction matches. When structural templates are available, a given SLiM and its recognition domain can be modeled using SCWRL. We illustrate, here, the use of SLiMAn on three distinct examples including one real-case study. We oversee wide-range applications for SLiMAn in the context of massive analysis of protein-protein interactions at proteome-wide scale. This new web server is made freely available at http://sliman.cbs.cnrs.fr.
Mechanisms of A-type lamin targeting to nuclear ruptures are disrupted in LMNA- and BANF1-associated progerias
Authors: Sears Rhiannon M. , Roux Kyle J. 
Published: January 2022

AbstractMutations in the genes LMNA and BANF1 can lead to accelerated aging syndromes called progeria. The protein products of these genes, A-type lamins and BAF, respectively, are nuclear envelope (NE) proteins that interact and participate in various cellular processes, including nuclear envelope rupture and repair. BAF localizes to sites of nuclear rupture and recruits NE-repair machinery, including the LEM-domain proteins, ESCRT-III complex, A-type lamins, and membranes. Here, we show that it is a mobile, nucleoplasmic population of A-type lamins that is rapidly recruited to ruptures in a BAF-dependent manner via BAF’s association with the Ig-like β fold domain of A-type lamins. These initially mobile lamins become progressively stabilized at the site of rupture. Farnesylated prelamin A and lamin B1 fail to localize to nuclear ruptures, unless that farnesylation is inhibited. Progeria-associated LMNA mutations inhibit the recruitment affected A-type lamin to nuclear ruptures, due to either permanent farnesylation or inhibition of BAF binding. A progeria-associated BAF mutant targets to nuclear ruptures but is unable to recruit A-type lamins. Together, these data reveal the mechanisms that determine how lamins respond to nuclear ruptures and how progeric mutations of LMNA and BANF1 impair recruitment of A-type lamins to nuclear ruptures.
Assessing the global impact of targeted conservation actions on species abundance
Authors: Jellesmark Sean , Blackburn Tim M. , Dove Shawn , Geldmann Jonas , Visconti Piero , Gregory Richard D. , McRae Louise , Hoffmann Mike 
Published: January 2022

SummaryIn recent years, vertebrate population abundance has declined at unprecedented rates (WWF 2020). In response, targeted conservation measures – such as breeding programs or species-specific habitat management – have been applied to halt population declines, aid population recovery, and reduce and reverse the loss of biodiversity (Salafsky et al. 2008; Bolam et al. 2020). Until now, assessments of conservation actions have focused on the extent to which they reduce extinction risk, impact populations within protected areas, or increase the global area of land under protection (Hoffmann et al. 2010, 2015; Barnes et al. 2016; Maxwell et al. 2020; Bolam et al. 2020; Grace et al. 2021a). Here, we record and analyze conservation actions for 26,904 vertebrate populations from 4,629 species, to measure the impact of targeted conservation on vertebrate abundance. Using a counterfactual approach to represent population trends in the absence of conservation, we demonstrate that targeted actions have delivered substantial positive effects on the abundance of recipient vertebrate populations worldwide. We show that, in the absence of conservation, a global indicator of vertebrate abundance would have declined even more. Positive population trends were associated with vertebrate populations subject to species or habitat management. We demonstrate that targeted conservation actions can help to reverse global biodiversity loss and show the value of counterfactual analysis for impact evaluation – an important step towards reversing biodiversity declines.
Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP- 2ε in vomeronasal sensory neurons
Authors: Lin Jennifer M. , Mitchell Tyler A. , Rothstein Megan , Pehl Alison , Taroc Ed Zandro M. , Katreddi Raghu Ram , Parra Katherine E. , Zuloaga Damian G. , Simoes-Costa Marcos , Forni Paolo E. 
Published: January 2022

SUMMARYNeuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remains a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here we demonstrated that the identity of postmitotic/maturing vomeronasal sensory neurons (VSNs), and vomeronasal dependent behaviors can be reprogrammed through the rescue of tfap2e/AP-2ε expression in the AP-2ε mice, and partially reprogrammed by inducing ectopic AP-2ε expression in mature apical VSNs. We suggest that the transcription factor AP-2ε can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes.GRAPHICAL ABSTRACT