bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drab and distant birds are studied less than their fancy-feathered friends
Authors: Fischer Silas E. , Otten Joshua G. , Lindsay Andrea M. , Miles Donald B. , Streby Henry M. 
Published: October 2023

AbstractHuman decisions are influenced by implicit biases, and scientists do not exist in an objectivity vacuum. Subconscious biases in scientists’ choices about which species to study may beget distorted knowledge bases and stagnant paradigms. Disparities in biological knowledge can result from bias in study species selection within a cycle of policymaking, funding, and publication, all subject to implicit biases. Here, we show that ornithological research in the USA and Canada is biased toward birds with greater aesthetic salience and those with larger breeding ranges and ranges that encompass more universities. We quantified components of aesthetic salience (e.g., color, pattern/contrast, body size) of 293 passerines and near-passerines based on empirically documented human visual preferences and investigated whether these components were associated with research effort. We also quantified each species’ breeding range size and the number of universities within that range. Accounting for phylogenetic relatedness, we found that these metrics of aesthetics, familiarity, and accessibility combined to explain 45% of the variation in the number of published papers about each species from 1965–2020. On average, birds in the top 10% of aesthetic salience were studied 3.0X more than birds in the bottom 10%, and publication numbers were predicted most strongly by color and pattern components of aesthetic salience. Birds in the top 10% of breeding range size and university abundance were studied 3.8X and 3.5X more often than species in the bottom 10% of those categories, respectively. Species listed as Endangered and those featured on journal covers have greater aesthetic salience scores than other species. We discuss how these biases may influence perceived relative value of species with respect to culture and conservation. The disparities in empirical knowledge we describe here perpetuate a positive feedback loop, thus widening the gap between the avian “haves” and “have-nots”, with some questions answered repeatedly while potentially critical discoveries are left undiscovered.“All animals are equal, but some animals are more equal than others.” —George Orwell,Animal Farm(1945)
Single nuclei sequencing reveals C4photosynthesis is based on rewiring of ancestral cell identity networks
Authors: Swift Joseph , Luginbuehl Leonie H. , Schreier Tina B. , Donald Ruth M. , Lee Travis A. , Nery Joseph R. , Ecker Joseph R. , Hibberd Julian M. 
Published: October 2023

SummaryIn multicellular systems changes to the patterning of gene expression drive modifications in cell function and trait evolution. One striking example is found in more than sixty plant lineages where compartmentation of photosynthesis between cell types allowed the evolution of the efficient C4pathway from the ancestral C3state. The molecular events enabling this transition are unclear. We used single nuclei sequencing to generate atlases for C3rice and C4sorghum during photomorphogenesis. Our analysis revealed that initiation of photosynthesis gene expression is conditioned by cell identity. In both species a conserved cistrome defines each cell type, and photosynthesis genes switching expression from mesophyll in rice to bundle sheath in sorghum acquire hallmarks of bundle sheath identity. The sorghum bundle sheath has also acquired gene networks associated with C3guard cells. We conclude C4photosynthesis is based on rewiring incisthat exapts cell identity networks of C3plants.
The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth
Authors: Franklin Aaron , Layton Abigail J. , Mize Todd , Salgueiro Vivian C. , Sullivan Rudi , Benedict Samuel T. , Gurcha Sudagar S. , Anso Itxaso , Besra Gurdyal S. , Banzhaf Manuel , Lovering Andrew L. , Williams Spencer J. , Guerin Marcelo E. , Scott Nichollas E. , Prados-Rosales Rafael , Lowe Elisabeth C. , Moynihan Patrick J. 
Published: October 2023

AbstractMycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important amongst these are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are both trafficked out of the bacterium to the host via unknown mechanisms. An important class of exported LM/LAM is the capsular derivative of these molecules which is devoid of its lipid anchor. Here, we describe the identification of a glycoside hydrolase family 76 enzyme that we term LamH which specifically cleaves α-1,6-mannoside linkages within LM and LAM, driving its export to the capsule releasing its phosphatidyl-myo-inositol mannoside lipid anchor. Unexpectedly, we found that the catalytic activity of this enzyme is important for efficient exit from stationary phase cultures where arabinomannan acts as a signal for growth phase transition. Finally, we demonstrate that LamH is important forMycobacterium tuberculosissurvival in macrophages. These data provide a new framework for understanding the biological role of LAM in mycobacteria.
Bayesian Fluorescence Framework for integrative modeling of biomolecules
Authors: Peulen Thomas-Otavio , Sali Andrej 
Published: October 2023

AbstractFluorescence spectroscopic and imaging techniques, such as fluorescence-correlation spectroscopy, image correlation spectroscopy, time-resolved fluorescence spectroscopy, and intensity-based spectroscopy, can provide sparse time-dependent positional and inter-fluorophore distance information for macromolecules and their complexesin vitroand in living cells. Here, we formulated a Bayesian framework for processing and using the fluorescence data for interpreting by static and dynamic models of biomolecules. We introduceBayesian Fluorescence Framework(BFF) as part of the open-sourceIntegrative Modeling Platform(IMP) software environment, facilitating the development of modeling protocols based in part on fluorescence data. BFF improves the accuracy, precision, and completeness of the resulting models by formulating the modeling problem as a sampling problem dependent on general and flexible libraries of (i) atomic and coarse-grained molecular representations of single-state models, multi-state models, and dynamic processes, (ii) Bayesian data likelihoods and priors, as well as (iii) sampling schemes. To illustrate the framework, we apply it to a sample synthetic single-molecule FRET dataset of the human transglutaminase 2. We show how to integrate time-resolved fluorescence intensities, fluorescence correlation spectroscopy curves, and fluorescence anisotropies to simultaneously resolve dynamic structures, state populations, and molecular kinetics. As BFF is part of IMP, fluorescence data can be easily integrated with other data types to solve challenging modeling problems.Statement of SignificanceBayesian Framework for Fluorescence(BFF) is software that implements a probabilistic framework for processing experimental fluorescence data to provide input information for Bayesian integrative structure modeling. BFF facilitates constructing integrative modeling protocols based in part on fluorescence data by reducing the required fluorescence spectroscopy and microscopy domain knowledge. In addition, it improves the precision and accuracy of the resulting models.
Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts
Authors: Cañizo Carmen G. , Guerrero-Ramos Félix , Escavy Mercedes Perez , Lodewijk Iris , Suárez-Cabrera Cristian , Morales Lucía , Nunes Sandra P , Munera-Maravilla Ester , Rubio Carolina , Sánchez Rebeca , Rodriguez-Izquierdo Marta , Martínez de Villarreal Jaime , Real Francisco X. , Castellano Daniel , Martín-Arriscado Cristina , Pablos David Lora , Antolín Alfredo Rodríguez , Dueñas Marta , Paramio Jesús M. , Martínez Victor G. 
Published: October 2023

ABSTRACTBACKGROUNDNon-muscle-invasive bladder cancer (NMIBC) poses clinical challenges due to its high recurrence and progression rates. While Bacillus Calmette-Guérin (BCG) remains as the gold standard treatment for high-risk NMIBC, recent irruption of anti-PD-1/PD-L1 drugs claims for a comprehensive understanding of the tumour microenvironment (TME) of these tumors.METHODSThe present prospective study consisted on the analysis 98 fresh NMIBC samples, tumor and non-pathological tissue, via flow cytometry. Final analysis included distribution of 11 cell types and the expression of PD-L1 in 66 tumor and 62 non-pathological tissue biopsies from 73 NMIBC patients (84.4% paired samples). The results were validated using publicly available transcriptomic data, and histology.RESULTSIn comparison to non-pathological tissue, the TME of NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution. Heterogeneous PD-L1 expression was observed across subsets, with cancer cells as primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are enriched in high grade NMIBC tumors, but only myoCAF were associated with higher rates of progression and recurrence, as we confirmed in three independent transcriptomic cohorts (888 total patients). We further validated the prognostic value of myoCAFs by tissue micro-array.CONCLUSIONThis comprehensive analysis provides a roadmap to establish the full landscape of the NMIBĆs TME, highlighting myoCAFs as potential prognostic markers.FUNDINGThis study was funded by FC AECC (INVES222946GARC), Consejería de Educación, Ciencia y Universidades de la CAM (2018-T2/BMD-10342), Hoffmann-La Roche, Ministerio de Ciencia e Innovación (INMUNOEPIBLA) and ISCIII/FEDER (CIBERONC CB16/12/00489)
Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria
Authors: Monteagudo-Cascales Elizabet , Gumerov Vadim M. , Fernández Matilde , Matilla Miguel A. , Gavira José A. , Zhulin Igor B. , Krell Tino 
Published: October 2023

AbstractPurines and their derivatives are key molecules for controlling intracellular energy homeostasis and nucleotide synthesis. In eukaryotes, including humans, purines also act as signaling molecules that mediate extracellular communication and control key cellular processes, such as proliferation, migration, differentiation, and apoptosis. However, the signaling role of purines in bacteria is largely unknown. Here, by combining structural and sequence information, we define a purine-binding motif, which is present in sensor domains of thousands of bacterial receptors that modulate motility, gene expression, metabolism and second messenger turnover. The screening of compound libraries and microcalorimetric titrations of selected sensor domains validated their ability to specifically bind purine derivatives. The physiological relevance of purine sensing was demonstrated in a second messenger signaling system that modulates c-di-GMP levels.
Regulation of NRF2 by Phosphoinositides and Small Heat Shock Proteins
Authors: Chen Changliang , Chen Mo , Wen Tianmu , Awasthi Poorwa , Carrillo Noah D. , Anderson Richard A. , Cryns Vincent L. 
Published: October 2023

AbstractReactive oxygen species (ROS) are generated by aerobic metabolism, and their deleterious effects are buffered by the cellular antioxidant response, which prevents oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of the antioxidant response. Basal levels of NRF2 are kept low by ubiquitin-dependent degradation of NRF2 by E3 ligases, including the Kelch-like ECH-associated protein 1 (KEAP1). Here, we show that the stability and function of NRF2 is regulated by the type I phosphatidylinositol phosphate kinase γ (PIPKIγ), which binds NRF2 and transfers its product phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to NRF2. PtdIns(4,5)P2binding recruits the small heat shock protein HSP27 to the complex. Silencing PIPKIγ or HSP27 destabilizes NRF2, reduces expression of its target gene HO-1, and sensitizes cells to oxidative stress. These data demonstrate an unexpected role of phosphoinositides and HSP27 in regulating NRF2 and point to PIPKIγ and HSP27 as drug targets to destabilize NRF2 in cancer.In briefPhosphoinositides are coupled to NRF2 by PIPKIγ, and HSP27 is recruited and stabilizes NRF2, promoting stress-resistance.
Senescence of endplate osteoclasts induces sensory innervation and spinal pain
Authors: Pan Dayu , Benkato Kheiria Gamal , Han Xuequan , Zheng Jinjian , Kumar Vijay , Wan Mei , Zheng Junying , Cao Xu 
Published: October 2023

AbstractSpinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
Analytical method for reconstructing the stress on a spherical particle from its surface deformation
Authors: Krüger Lea Johanna , te Vrugt Michael , Bröker Stephan , Wallmeyer Bernhard , Betz Timo , Wittkowski Raphael 
Published: October 2023

The mechanical forces that cells experience from the tissue surrounding them are crucial for their behavior and development. Experimental studies of such mechanical forces require a method for measuring them. A widely used approach in this context is bead deformation analysis, where spherical particles are embedded into the tissue. The deformation of the particles then allows to reconstruct the mechanical stress acting on them. Existing approaches for this reconstruction are either very time-consuming or not sufficiently general. In this article, we present an analytical approach to this problem based on an expansion in solid spherical harmonics that allows us to find the complete stress tensor describing the stress acting on the tissue. Our approach is based on the linear theory of elasticity and uses an ansatz derived by Love. We clarify the conditions under which this ansatz can be used, making our results useful also for other contexts in which this ansatz is employed. Our method can be applied to arbitrary radial particle deformations and requires a very low computational effort. The usefulness of the method is demonstrated by an application to experimental data.STATEMENT OF SIGNIFICANCEMeasurements of mechanical forces acting on cells in a tissue are important for understanding the physical behavior of biological systems, but they are also quite challenging. A common strategy is to place a spherical bead inside the tissue and to then reconstruct the mechanical stress from the bead deformation that this stress causes. Here, we introduce a novel analytical method using which this reconstruction can be achieved. This method is significantly faster than numerical approaches and significantly more general than existing analytical techniques, such that it can be expected to find a broad range of applications in mechanobiology.
Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant
Authors: VanOudenhove Jennifer , Liu Yuxin , Nelakanti Raman , Kim Dongjoo , Busarello Emma , Ovalle Natalia Tijaro , Qi Zhihong , Mamillapalli Padmavathi , Siddon Alexa , Bai Zhiliang , Axtmayer Alfredo , Corso Cheryl , Kothari Shalin , Foss Francine , Isufi Iris , Tebaldi Toma , Gowda Lohith , Fan Rong , Seropian Stuart , Halene Stephanie 
Published: October 2023

AbstractDuring the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The SARS-CoV-2 mRNA vaccines are important tools in preventing severe disease, yet their efficacy in the post-transplant setting remains unclear, especially in patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated the humoral and adaptive immune responses to the SARS-CoV-2 mRNA vaccination series in 42 HSCT recipients and 5 healthy controls. Peripheral blood mononuclear nuclear cells and serum were prospectively collected before and after each dose of the SARS-CoV-2 vaccine. Post-vaccination responses were assessed by measuring anti-spike IgG and nucleocapsid titers, and antigen specific T cell activity, before and after vaccination. In order to examine mechanisms behind a lack of response, pre-and post-vaccine samples were selected based on humoral and cellular responses for single-cell RNA sequencing with TCR and BCR sequencing. Our observations revealed that while all participants eventually mounted a humoral response, transplant recipients had defects in memory T cell populations that were associated with an absence of T cell response, some of which could be detected pre-vaccination.
How Much Does TRPV1 Deviate from An Ideal MWC-Type Protein
Authors: Li Shisheng , Zheng Jie 
Published: October 2023

AbstractMany ion channels are known to behave as an allosteric protein, coupling environmental stimuli captured by specialized sensing domains to the opening of a central pore. The classic Monod-Wyman-Changeux (MWC) model, originally proposed to describe binding of gas molecules to hemoglobin, has been widely used for analyzing ion channel gating. Here we address the issue of how accurate the MWC model predicts activation of the capsaicin receptor TRPV1 by vanilloids. Taking advantage of a concatemeric design that makes it possible to lock TRPV1 in states with zero-to-four bound vanilloid molecules, we showed quantitatively that the overall gating behavior is satisfactorily predicted by the MWC model. There is however a small yet detectable subunit position effect: ligand binding to two kitty-corner subunits is 0.4-to-0.6 kcal/mol more effective in inducing opening than binding to two neighbor subunits. This difference, less than 10% of the overall energetic contribution from ligand binding, is not expected in hemoglobin, in which each subunit is related equivalently to all the other subunits.SignificanceThe MWC model, proposed more than 50 years ago, is elegantly simple yet powerful in predicting the behavior of allosteric proteins like hemoglobin. Its prediction power for ion channel gating has been beautifully demonstrated in the studies of BK channels. Our present work aims to determine how accurate the MWC model predicts TRPV1 activation induced by vanilloids. Our findings support the notion that the evolutionary drive upon allosteric proteins applies generally to multi-subunit proteins.
Health impact and cost-effectiveness of expanding routine immunization coverage in India through Intensified Mission Indradhanush: a quasi-experimental study and economic evaluation
Authors: Clarke-Deelder Emma , Suharlim Christian , Chatterjee Susmita , Portnoy Allison , Brenzel Logan , Ray Arindam , Cohen Jessica , Menzies Nicolas A , Resch Stephen C 
Published: October 2023

AbstractBackgroundMany children do not receive a full schedule of childhood vaccines, yet there is limited evidence on the cost-effectiveness of strategies for improving vaccination coverage. We evaluated the cost-effectiveness of periodic intensification of routine immunization (PIRI), a widely applied strategy for increasing vaccination coverage.MethodsIntensified Mission Indradhanush (IMI) was a large-scale PIRI intervention implemented in India in 2017–2018. In 40 sampled districts, we measured the incremental economic cost of IMI using primary data, and used a quasi-experimental impact evaluation to estimate incremental vaccination doses delivered. We estimated deaths and disability-adjusted life years (DALYs) averted using the Lives Saved Tool and reported cost-effectiveness from government provider and societal perspectives.FindingsIn sampled districts, IMI had an estimated incremental cost of 2021US$15.7 (95% uncertainty interval: 11.9 to 20.1) million from a provider perspective and increased vaccine delivery by an estimated 2.2 (−0.5 to 4.8) million doses, averting an estimated 1,413 (−350 to 3,129) deaths. The incremental cost was $7.14 per dose ($3.20 to dominated), $95.24 per zero-dose child reached ($45.48 to dominated), $375.98 ($168.54 to dominated) per DALY averted, $413.96 ($185.56 to dominated) per life-year saved, and $11,133 ($4,990 to dominated) per under-five death averted. At a cost-effectiveness threshold of 1x per-capita GDP per DALY averted, IMI was estimated to be cost-effective with 89% probability.InterpretationThis evidence suggests IMI was both impactful and cost-effective for improving vaccination coverage. As vaccination programs expand coverage, unit costs may increase due to the higher costs of reaching currently unvaccinated children.FundingBill & Melinda Gates Foundation
Movement-related drivers of exposure to West Nile virus by American robins (Turdus migratorius)
Authors: Jahn Alex E. , Koller Kyle , Martin Lynn B. , Smiley Tara M. , Verrett Taylor B. , Ketterson Ellen D. , Williams Emily J. , Becker Daniel J. 
Published: October 2023

AbstractThe ecological processes that determine how individual animals become hosts to zoonotic pathogens is a topic of rapidly growing interest. However, how such exposure is mediated by context (e.g., season, location), host behavior (e.g., migration distance) and host demographics is generally poorly understood. We evaluated seasonal exposure to West Nile Virus of American robins sampled in Indiana and compared our results to those of previous studies. Because robins that breed in Indiana are partial migrants (i.e., only a portion of the population migrates), we evaluated their probability of exposure to WNV as a function of whether they migrated or not and of their movement distance. We also tagged a subset of breeding robins with tracking devices to evaluate their potential to disperse the virus between Indiana and other regions of the continent. We found that robins that breed in Indiana are exposed to WNV at a higher rate than that detected in previous studies, but found no correlation between robin exposure and whether a robin migrated or not, nor with migration distance, season, sex, and breeding latitude (for robins overwintering in Indiana). Our tracking data indicate that robins that breed in Indiana migrate several hundred miles to overwinter in the southeastern US. The mean duration of their return to Indiana in spring is 10.3 days, which is less than the maximum infectious period found for robins in previous studies, suggesting that they have the capacity to move WNV long distances in spring. However, we still know little about the physiological capacity of robins to migrate while being infectious, which could inhibit the dispersal of the virus through robin migration. Future research on the physiological, ecological and behavioral factors mediating the exposure of birds to WNV will lend insight into the role that robins and other birds play in the transmission ecology of the virus.