bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abiotic conditions shape spatial and temporal morphological variation in North American birds
Authors: Youngflesh Casey , Saracco James F. , Siegel Rodney B. , Tingley Morgan W. 
Published: February 2022

AbstractAbiotic environmental conditions play a key role in driving the size and shape of organisms. Quantifying environment-morphology relationships is important not only for understanding the fundamental processes driving phenotypic diversity within and among species (1), but also for predicting how species will respond to ongoing global change (2). Despite a clear set of expectations motivated by ecological theory (3), broad evidence in support of generalizable effects of abiotic conditions, such as temperature (4), on spatial and temporal intraspecific morphological variation has been limited. Using standardized data from over 250,000 captures of 105 landbird species, we assessed intraspecific shifts in bird morphology since 1989 while simultaneously measuring spatial morphological gradients across the North American continent. Across bird species, we found strong spatial and temporal trends in body size, with warmer temperatures associated with smaller body sizes both at more equatorial latitudes and in more recent years. The magnitude of these thermal effects varied both across and within species, with results suggesting it is the warmest, rather than the coldest, temperatures driving both spatial and temporal trends. Across elevation, we found that body size declines as relative wing length increases, likely due to the benefits that longer wings confer for flight in thin air environments. Our results provide support for both existing and new large-scale ecomorphological gradients and highlight how the response of functional tradeoffs to abiotic variation drives morphological change.Significance StatementCharacterizing how the size and shape of organisms varies over space and time is key to understanding the processes that create ecological communities and for predicting how species will respond to climate change. Across more than 100 species of North American birds, we show that within species the size and shape of individuals varies substantially across space and time. Warmer temperatures are associated with smaller body sizes, likely due to the importance of body size for thermoregulation. As the climate continues to warm, these species will likely continue to shrink. We also provide the first large-scale evidence of an increase in wing length with elevation, a pattern that could be attributed to thinner air in high elevation environments.
Yclon: Ultrafast clustering of B cell clones from high-throughput immunoglobulin repertoire sequencing data
Authors: Gervásio João , Ferreira Alice , Felicori Liza F. 
Published: February 2022

AbstractMotivationThe next-generation sequencing technologies have transformed our understanding of immunoglobulin (Ig) profiles in various immune states. Clonotyping, which groups Ig sequences into B cell clones, is crucial in investigating the diversity of repertoires and changes in antigen exposure. Despite its importance, there is no widely accepted method for clonotyping, and existing methods are computationally intensive for large sequencing datasets.ResultsTo address this challenge, we introduce YClon, a fast and efficient approach for clonotyping Ig repertoire data. YClon uses a hierarchical clustering approach, similar to other methods, to group Ig sequences into B cell clones in a highly sensitive and specific manner. Notably, our approach outperforms other methods by being more than 30 to 5000 times faster in processing the repertoires analyzed. Astonishingly, YClon can effortlessly handle up to 2 million Ig sequences on a standard laptop computer. This enables in-depth analysis of large and numerous antibody repertoires.Availability and implementationYClon was implemented in Python3 and is freely available on GitHub(https://github.com/jao321/YClon.git)Contact:joaodgervasio@gmail.com,liza@icb.ufmg.br
Integrating Fossil Flowers into the Angiosperm Phylogeny using a Total Evidence Approach
Authors: López-Martínez Andrea M. , Schönenberger Jürg , von Balthazar Maria , González-Martínez César A. , Ramírez-Barahona Santiago , Sauquet Hervé , Magallón Susana 
Published: February 2022

ABSTRACTFossil flowers are essential to infer past angiosperm evolutionary processes. The assignment of fossil flowers to extant clades has traditionally relied on morphological similarity and on apomorphies shared with extant taxa. The use of explicit phylogenetic analyses to establish their affinity has so far remained limited. In this study, we built a comprehensive framework to investigate the phylogenetic placement of 24 exceptionally preserved fossil flowers. For this, we assembled a new species-level dataset of 30 floral traits for 1201 extant species that were sampled to represent the stem and crown nodes of all angiosperm families. We explored multiple analytical approaches to integrate the fossils into the phylogeny, including different phylogenetic estimation methods, topological-constrained analyses, and a total evidence approach combining molecular and morphological data of extant and fossil species. Our results were widely consistent across approaches, with minor differences in the support of fossils at different phylogenetic positions. The placement of some fossils is in agreement with previously suggested relationships, but for others, a new placement is indicated. We also identified fossils that are well constrained within particular extant families, whereas others showed high phylogenetic uncertainty. Finally, we present recommendations for future total evidence analyses, regarding the selection of fossils and appropriate methodologies, and provide some perspectives on how to integrate fossils into the investigation of divergence times and the temporal evolution of morphological traits.
Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge
Authors: Malhi Harman , Homad Leah J. , Wan Yu-Hsin , Poudel Bibhav , Fiala Brooke , Borst Andrew J. , Wang Jing Yang , Walkey Carl , Price Jason , Wall Abigail , Singh Suruchi , Moodie Zoe , Handa Simran , Correnti Colin , Stoddard Barry L. , Veesler David , Pancera Marie , Olson James , King Neil P. , McGuire Andrew T. 
Published: February 2022

Summary/AbstractEpstein-Barr virus (EBV) is a cancer-associated pathogen responsible for 140,000 deaths per year. EBV is also the etiological agent of infectious mononucleosis and is associated with multiple sclerosis and rheumatoid arthritis. Thus, an EBV vaccine could alleviate significant morbidity and mortality. EBV is orally transmitted and has tropism for both epithelial cells and B cells which are present in the oral cavity. Therefore, a prophylactic vaccine would need to prevent infection of both cell types. Passive transfer neutralizing monoclonal antibodies targeting the viral gH/gL glycoprotein complex prevent experimental EBV infection in humanized mice and rhesus macaques, suggesting that gH/gL is an attractive vaccine candidate. Here, we produced and evaluated the immunogenicity of several nanoparticle immunogens displaying gH/gL with distinct valencies and geometries. After one or two immunizations, all nanoparticles elicited superior binding and neutralizing titers relative to monomeric gH/gL. Antibodies elicited by a computationally designed self-assembling nanoparticle that displays 60 copies of the gH/gL protein conferred protection against a lethal dose of EBV in a humanized mouse challenge model, whereas antibodies elicited by monomeric gH/gL did not. Taken together, these data motivate further development of gH/gL nanoparticle vaccine candidates for EBV.
Asymmetric requirement for α-tubulin over β-tubulin
Authors: Wethekam Linnea C. , Moore Jeffrey K. 
Published: February 2022

AbstractHow cells regulate the supply of α- and β-tubulin monomers to meet the demand for αβ- heterodimers while avoiding consequences of monomer imbalance is not understood. We investigate the role of gene copy number in tubulin regulation and how shifting the expression of α- or β-tubulin genes impacts tubulin proteostasis and microtubule function. We find that α- tubulin gene copy number is important for maintaining an excess α-tubulin protein compared to β-tubulin protein and preventing accumulation of super-stoichiometric β-tubulin. Super- stoichiometric β-tubulin is toxic to cells, leading to loss of microtubules, formation of non- microtubule assemblies of tubulin, and disrupted cell proliferation. In contrast, decreased β- tubulin or increased α-tubulin has minor effects. We provide evidence that cells rapidly equilibrate the concentration of α-tubulin protein during shifts in α-tubulin isotype expression to maintain a ratio in excess of β-tubulin. We propose an asymmetric relationship between α- and β-tubulins, where α-tubulins are maintained in excess to supply αβ-heterodimers and limit the accumulation of β-tubulin monomers.
Density-dependent environments can select for extremes of body size
Authors: Coulson Tim , Felmy Anja , Passoni Gioele , Montgomery Robert A , Gaillard Jean-Michel , udson Peter HJ , Travis Joseph , Bassar Ronald D , Tuljapurkar Shripad , Marshall Dustin J , Clegg Sonya 
Published: February 2022

AbstractBody size variation is an enigma. We do not understand why species achieve the sizes they do, and this means we also do not understand the circumstances under which gigantism or dwarfism is selected. We develop size-structured integral projection models to explore evolution of body size and life history speed. We make few assumptions and keep models simple: all functions remain constant across models except for the one that describes development of body size with age. We set sexual maturity to occur when size attains 80% of the asymptotic size, which is typical of a large mammal, and allow negative density dependence to only affect either reproduction or juvenile survival. Fitness – the quantity that is maximized by adaptive evolution – is carrying capacity in our models, and we are consequently interested in how it changes with size at sexual maturity, and how this association varies with development rate. The simple models generate complex dynamics while providing insight into the circumstances when extremes of body size evolve. The direction of selection leading to either gigantism or dwarfism crucially depends on the proportion of the population that is sexually mature, which in turn depends on how the development function determines the survivorship schedule. The developmental trajectories consequently interact with size-specific survival or reproductive rates to determine the best life history and the optimal body size emerges from that interaction. These dynamics result in trade-offs between different components of the life history, with the form of the trade-off that emerges depending upon where in the life history density dependence operates most strongly. Empirical application of the approach we develop has potential to help explain the enigma of body size variation across the tree of life.
Relative positioning of B and T cell epitopes drives immunodominance
Authors: Biavasco Riccardo , De Giovanni Marco 
Published: February 2022

AbstractHumoral immunity is crucial for protection against invading pathogens. Broadly neutralizing antibodies (bnAbs) provide sterilizing immunity by targeting conserved regions of viral variants and represent the goal of most vaccination approaches. While antibodies can be selected to bind virtually any region of a given antigen, consistent induction of bnAbs in the context of influenza and HIV has been representing a major roadblock. Many possible explanations have been considered, however, none of the arguments proposed so far seems to fully recapitulate the observed counter-selection for broadly protective antibodies.Antibodies can influence antigen presentation by enhancing the processing of CD4 epitopes adjacent to the binding region while suppressing the overlapping ones. We analyzed the relative positioning of dominant B and T cell epitopes in published antigens that elicit strong and poor humoral responses. In strong immunogenic antigens, regions bound by immunodominant antibodies are frequently adjacent to CD4 epitopes, potentially boosting their presentation. Conversely, poorly immunogenic regions targeted by bnAbs in HIV and influenza overlap with clusters of dominant CD4 epitopes, potentially conferring an intrinsic disadvantage for bnAb-bearing B cells in germinal centers.Here we propose the theory of immunodominance relativity, according to which relative positioning of immunodominant B and CD4 epitopes within a given antigen drives immunodominance. Thus, we suggest that relative positioning of B-T epitopes may be one additional mechanism that cooperates with other previously described processes to influence immunodominance. If demonstrated, this theory can improve the current understanding of immunodominance, provide a novel explanation on HIV and influenza escape from humoral responses, and pave the way for new rational design of universal vaccines.
First comprehensive identification of proteins with increased O-GlcNAc levels during pressure overload hypertrophy
Authors: Zhu Wei Zhong , Palazzo Teresa , Zhou Mowei , Ledee Dolena , Olson Heather M , Paša-Tolić Ljiljana , Olson Aaron K. 
Published: February 2022

ABSTRACTProtein posttranslational modifications (PTMs) by O-GlcNAc globally rise during pressure-overload hypertrophy (POH). However, only a few specific proteins with altered O-GlcNAc levels during POH are known primarily because this PTM is easily lost during standard mass spectrometry (MS) conditions used for protein identification. Methodologies have recently emerged to stabilize the O-GlcNAc moiety for MS analysis. Accordingly, our goal was to determine the proteins undergoing changes in O-GlcNAc levels during POH. We used C57/Bl6 mice subjected to Sham or transverse aortic constriction (TAC) to create POH. From the hearts, we stabilized and labelled the O-GlcNAc moiety with tetramethylrhodamine azide (TAMRA) before enriching by TAMRA immunoprecipitation (IP). We used LC-MS to identify the captured O-GlcNAcylated proteins. We identified a total of 707 O-GlcNAcylated proteins in Sham and POH. Two hundred thirty-three of these proteins were significantly increased in POH over Sham whereas no proteins were significantly decreased in POH. We examined two MS identified proteins, CPT1B and PDH, to validate the MS data by immunoprecipitation. We corroborated increased O-GlcNAc levels during POH for the metabolic enzymes CPT1B and PDH. Enzyme activity assays showed higher O-GlcNAcylation increased CPT1 activity and decreased PDH activity. In summary, we generated the first comprehensive list of proteins with changes in O-GlcNAc levels during POH and, to our knowledge, the largest list for any cardiac pathology. Our results demonstrate the large number of proteins and cellular processes affected by O-GlcNAc during POH and serve as a guide for testing specific O-GlcNAc-regulated mechanisms.
Genome-wide analyses of histone modifications and chromatin accessibility reveal the distinct genomic compartments in the Irish potato famine pathogen Phytophthora infestans
Authors: Chen Han , Shu Haidong , Fang Yufeng , Song Wenrui , Li Zhi , Fang Yujie , Wang Yuanchao , Dong Suomeng 
Published: February 2022

AbstractPhytophthora infestans, the causal agent of potato late blight, is a devastating plant disease that leads to Irish potato famine and threatens world-wide food security. Despite the genome of P. infestans has provided fundamental resource for studying the aggressiveness of this pandemic pathogen, the epigenomes remain poorly understood. Here, utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS), we demonstrate post-translational modifications (PTM) at P. infestans core histone H3. The PTMs not only include these prevalent modifications in eukaryotes, and also some novel marks, such as H3K53me2 and H3K122me3. We focused on the trimethylations of H3K4, H3K9 and H3K27 and H3K36, and profiled P. infestans epigenomes employing Native Chromatin Immunoprecipitation followed by sequencing (N-ChIP-seq). In parallel, we mapped P. infestans chromomatin accessibility by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We found that adaptive genomic compartments display significantly higher levels of H3K9me3 and H3K27me3, and are generally in condense chromatin. Interestingly, we observed that genes encoding virulence factors, such as effectors, are enriched in open chromatin regions that barely have the four histone modifications. With a combination of genomic, epigenomic, transcriptomic strategies, our study illustrates the epigenetic states in P. infestans, which will help to study genomic functions and regulations in this pathogen.Author summaryEpigenetics play an important role in various biological processes of eukaryotes, including pathogenicity of plant pathogens. However, the epigenetic landscapes are marginally known in oomycetes that are fungal-like organisms and comprise lots of destructive plant pathogens. In this study, using the Irish potato famine pathogen Phytophthora infestans as a model, we conducted genome-wide studies of histone post modifications and chromatin accessibility, and demonstrate the relationship of gene expression and evolution with the epigenetic marks. We found that one of the most important classes of virulence proteins, effectors, are enriched in open chromatin regions that barely have eu- and hetero-chromatic marks. This study provides an overview of the oomycete epigenetic atlas, and advances our understanding of the regulation of virulence factors in plant pathogens.
Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection
Authors: Bohrer Andrea C. , Castro Ehydel , Tocheny Claire E. , Assmann Maike , Schwarz Benjamin , Bohrnsen Eric , Makiya Michelle A. , Legrand Fanny , Hilligan Kerry L. , Baker Paul J. , Torres-Juarez Flor , Hu Zhidong , Ma Hui , Wang Lin , Niu Liangfei , Zilu Wen , Lee Sang H. , Kamenyeva Olena ,   Tuberculosis Imaging Program, Kauffman Keith D. , Donato Michele , Sher Alan , Barber Daniel L. , Via Laura E. , Scriba Thomas J. , Khatri Purvesh , Song Yanzheng , Wong Ka-Wing , Bosio Catharine M. , Klion Amy D. , Mayer-Barber Katrin D. 
Published: February 2022

SUMMARYInflux of eosinophils into the lungs is typically associated with type-II responses during allergy, fungal and parasitic infections. However, we previously reported that eosinophils accumulate in lung lesions during type-I inflammatory responses to Mycobacterium tuberculosis (Mtb) in humans, macaques, and mice where they contribute to host resistance. Here we show eosinophils migrate into the lungs of macaques and mice as early as one week after Mtb-exposure. In mice this influx was CCR3 independent and instead required cell-intrinsic expression of the oxysterol-receptor GPR183, which is highly expressed on human and macaque eosinophils. Murine eosinophils interacted directly with bacilli-laden alveolar macrophages, which upregulated the oxysterol-synthesizing enzyme Ch25h, and eosinophil recruitment was impaired in Ch25h deficient mice. Our findings show that eosinophils are among the first cells from circulation to sense and respond to Mtb infection of alveolar macrophages and reveal a novel role for GPR183 in the migration of eosinophils into lung tissue.
HIGHLIGHTSIn mice and macaques eosinophils accumulate early in Mtb-infected lungs preceding neutrophils Eosinophils interact with Mtb-infected cells in the alveoli in miceEarly pulmonary eosinophil migration occurs independently of CCR3 in miceEarly lung migration in mice requires Ch25h and eosinophil-intrinsic GPR183 expression
Lifespan can be extended during a specific time window early in life
Authors: Aiello G. , Sabino C. , Pernici D. , Audano M. , Antonica F. , Gianesello M. , Quattrone A. , Mitro N. , Romanel A. , Soldano A. , Tiberi L. 
Published: February 2022

AbstractLifespan is determined by complex and tangled mechanisms that are largely unknown. The early postnatal stage has been proposed to play a role in lifespan, but its contribution is still controversial. Here, we found that a short rapamycin treatment during early life can prolong lifespan in Mus musculus and Drosophila melanogaster. Notably, the same treatment at later time points has no evident effect on lifespan, suggesting that we found a crucial time-window involved in lifespan modulation. We discovered that sulfotransferases are upregulated during early rapamycin treatment both in newborn mice and Drosophila larvae. Furthermore, overexpression of the sulfotransferase dST1 triggers an increment in the lifespan of Drosophila melanogaster. Our findings unveil a novel link between early-life treatments and long-term effects on lifespan.One Sentence SummaryEarly life events increase lifespan.
Mosaic receptor-binding domain nanoparticles induce protective immunity against SARS-CoV-2 challenges
Authors: Lee Dan Bi , Kim Hyojin , Jeong Ju Hwan , soon Jang Ui , Chang You Yeon , Roh Seokbeom , Jeon Hyunbum , Kim Eun Jeong , Han Su Yeon , Maeng Jin Young , Magez Stefan , Radwanska Magdalena , Mun Ji Young , Jun Hyun Sik , Lee Gyudo , Song Min-Suk , Lee Hye-Ra , Chung Mi Sook , Baek Yun Hee , Kim Kyung Hyun 
Published: February 2022

AbstractRecurrent spillovers of α- and β-coronaviruses (CoV) such as acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-2, and possibly human CoV (NL63, 229E, OC43, and HKU1) have caused serious morbidity and mortality worldwide. Six receptor binding domains (RBDs) derived from α- and β-CoV that are considered to have originated from animals and cross-infected humans were linked to proliferating cell nuclear antigen (PCNA) heterotrimeric subunits, PCNA1, PCNA2, and PCNA3. These were used to form a scaffold-based mosaic multivalent antigen, 6RBD-np. Electron microscopic and atomic force microscopic images show a ring-shaped disk with six protruding RBDs, like jewels in a crown, with a size of 40 nm. Prime-boost immunizations with 6RBD-np in BALB/c mice elicited strong, dose-dependent antibody responses. In human angiotensin converting enzyme 2-transgenic mice, the same immunization induced full-protection against SARS-CoV-2 wild type and Delta challenges, resulting in a 100% survival rate. The mosaic 6RBD-np provides a potential platform for developing a pan-CoV vaccine against newly emerging SARS-CoV-2 variants and future CoV spillovers.SignificanceDespite the arsenal of COVID-19 vaccines, hospitalization and mortality associated with SARS-CoV-2 (acute respiratory syndrome coronavirus 2) variants remain high. There is an urgent need to develop next-generation COVID vaccines that provide broad protection against diseases by current and newly emerging SARS-CoV-2 variants. In this study, six receptor binding domains (RBDs) derived from α- and β-CoV were linked to proliferating cell nuclear antigen (PCNA) heterotrimeric scaffolds. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens. The prime-boost immunization in BALB/c and human angiotensin converting enzyme 2-transgenic mice with the 6RBD-np elicited strong, dose-dependent antibody responses and induced full-protection against both the SARS-CoV-2 wild type (WT) and Delta challenges. This study provides proof-of-concept that the mosaic 6RBD-np induces 100% protection against SARS-CoV-2 WT and Delta. It provides the potential of co-displaying heterologous antigens for novel vaccine designs, which can be deployed countering future pandemics.