bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shrinking in the dark: Parallel endosymbiont genome erosions are associated with repeated host transitions to an underground life
Authors: Beasley-Hall Perry G. , Kinjo Yukihiro , Rose Harley A. , Walker James , Foster Charles S. P. , Kovacs Toby G. L. , Bourguignon Thomas , Ho Simon Y. W. , Lo Nathan 
Published: September 2023

ABSTRACTMicrobial symbioses have had profound impacts on the evolution of animals. Conversely, changes in host biology may impact the evolutionary trajectory of symbionts themselves.Blattabacterium cuenotiis present in almost all cockroach species and enables hosts to subsist on a nutrient-poor diet. To investigate if host biology has impactedBlattabacteriumat the genomic level, we sequenced and analysed 25 genomes from Australian soil-burrowing cockroaches (Blaberidae: Panesthiinae) which have undergone at least seven independent subterranean transitions from above-ground, wood-feeding ancestors. We find at least three independent instances of genome erosion have occurred inBlattabacteriumstrains exclusive to Australian soil-burrowing cockroaches. Such shrinkages have involved the repeated inactivation of genes involved in amino acid biosynthesis and nitrogen recycling, the core role of Blattabacterium in the host-symbiont relationship. The most drastic of these erosions have occurred in hosts thought to have transitioned underground the earliest relative to other lineages. AsBlattabacteriumis unable to fulfil its core function in such host groups, our findings suggest soil-burrowing cockroaches must acquire these nutrients from novel sources. Our study represents one of the first cases, to our knowledge, of parallel host adaptations leading to concomitant parallelism in their mutualistic symbionts, further underscoring the intimate relationship between these two partners.
PlexinD1 deficiency in CD11c+ dendritic cells exacerbates airway hyperresponsiveness and enhances IgE and mucus production in allergic asthma
Authors: Shan Lianyu , Matloubi Mojdeh , Okwor Ifeoma , Kung Sam , Almiski Mohamed Sadek , Basu Sujata , Halayko Andrew , Koussih Latifa , Gounni Abdelilah S. 
Published: September 2023

AbstractDendritic cells (DC) play a crucial role in regulating allergic asthma. We have demonstrated that the absence of semaphorin3E (Sema3E) exacerbates asthma features in acute and chronic asthma models. However, the role of plexinD1 in these events, especially in DC is unknown. Therefore, we investigated the role of plexinD1 in CD11c+ DC in the HDM model of asthma. CD11c+ DC-specific plexinD1 knockout mice and wild-type mice were subjected to HDM acute allergen protocol. Airway hyperresponsiveness (AHR) parameters were measured using the FlexiVent ventilator. Lung tissue and bronchoalveolar lavage fluid (BALF) were processed by flow cytometry. Cytokines and antibodies were measured using mesoscale and ELISA. Collagen deposition and mucus production were visualized by histological staining, and associated genes were investigated using Real-time PCR. We showed that DC-specific plexinD1 knockout mice exhibited exacerbated airway hyperresponsiveness, including increased airway resistance and tissue elastance. These mice displayed enhanced levels of mucus production and collagen gene expression compared to wild-type mice. These events were accompanied by enhanced recruitment of conventional DCs, specifically CD11b+ cDC2, into the lungs and higher levels of total and HDM-specific serum IgE inCD11cPLXND1KOcompared to wild-type counterparts. Mechanistically, a significantly higher level of IgE in the co-culture of B-DCs isolated fromCD11cPLXND1KOmice compared to DCs isolated from wild-type mice. Overall, our data reveals that the Sema3E-plexinD1 signalling pathway in CD11c+ DC is critical in modulating asthma features.Graphical Abstract
Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology
Authors: Philip Drake T. , Goins Nigel M. , Catanzaro Nicholas J. , Misumi Ichiro , Whitmire Jason K. , Atkins Hannah M. , Lazear Helen M. 
Published: September 2023

ABSTRACTType III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (Ifnlr1-/-), both the IFN-λ and the IFN-αβ receptor (Ifnar1-/-Ifnlr1-/-), or IFN-λ cytokines (Ifnl2/3-/-) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions, independent of a direct effect on viral load. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity, and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils or blocking CXCL9 protected against severe HSV-1 skin lesions inIfnlr1-/-mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection, and suggest potential applications for IFN-λ in treating viral skin infections.Graphical Abstract
Cell2Sentence: Teaching Large Language Models the Language of Biology
Authors: Levine Daniel , Rizvi Syed Asad , Lévy Sacha , Pallikkavaliyaveetil Nazreen , Zhang David , Chen Xingyu , Ghadermarzi Sina , Wu Ruiming , Zheng Zihe , Vrkic Ivan , Zhong Anna , Raskin Daphne , Han Insu , de Oliveira Fonseca Antonio Henrique , Caro Josue Ortega , Karbasi Amin , Dhodapkar Rahul M. , van Dijk David 
Published: September 2023

AbstractWe introduce Cell2Sentence (C2S), a novel method to directly adapt large language models to a biological context, specifically single-cell transcriptomics. By transforming gene expression data into “cell sentences,” C2S bridges the gap between natural language processing and biology. We demonstrate cell sentences enable the fine-tuning of language models for diverse tasks in biology, including cell generation, complex cell-type annotation, and direct data-driven text generation. Our experiments reveal that GPT-2, when fine-tuned with C2S, can generate biologically valid cells based on cell type inputs, and accurately predict cell types from cell sentences. This illustrates that language models, through C2S fine-tuning, can acquire a significant understanding of single-cell biology while maintaining robust text generation capabilities. C2S offers a flexible, accessible framework to integrate natural language processing with transcriptomics, utilizing existing models and libraries for a wide range of biological applications.
An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies
Authors: Wang Yiquan , Lv Huibin , Lei Ruipeng , Yeung Yuen-Hei , Shen Ivana R. , Choi Danbi , Teo Qi Wen , Tan Timothy J.C. , Gopal Akshita B. , Chen Xin , Graham Claire S. , Wu Nicholas C. 
Published: September 2023

ABSTRACTDespite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and inaccessibility of datasets for model training. In this study, we curated a dataset of >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains. We then leveraged this dataset to develop a lightweight memory B cell language model (mBLM) for sequence-based antibody specificity prediction. Model explainability analysis showed that mBLM captured key sequence motifs of HA stem antibodies. Additionally, by applying mBLM to HA antibodies with unknown epitopes, we discovered and experimentally validated many HA stem antibodies. Overall, this study not only advances our molecular understanding of antibody response to influenza virus, but also provides an invaluable resource for applying deep learning to antibody research.
Sperm length evolution in relation to body mass is shaped by multiple trade-offs in tetrapods
Authors: Koçillari L. , Cattelan S. , Rasotto M.B. , Seno F. , Maritan A. , Pilastro A. 
Published: September 2023

AbstractSperm size is highly variable across species and is influenced by various factors including fertilization mode, female reproductive traits and sperm competition. Despite considerable efforts, many questions about sperm size variation remain open. Variation in body size may affect sperm size evolution through its influence on these factors, but the extent to which sperm size variation is linked to body mass remains elusive. In this study, we use the general theory of Pareto Optimality to investigate the relationship between sperm size and body mass across tetrapods. We find that tetrapods fall within a triangular-shaped Pareto front in the trait space of body mass and sperm length suggesting that the evolution of sperm size in relation to body size is shaped by trade-offs. We then explore the three main factors predicted to influence sperm size evolution, namely sperm competition, clutch size and genome size. Our results demonstrate that body mass optimally shapes sperm size evolution in tetrapods mainly through its association with sperm competition and clutch size. Finally, we show that the triangular-shaped Pareto front is maintained when tested separately within mammals, birds, endothermic species and internal fertilizers, suggesting that similar evolutionary trade-offs characterize the evolution of sperm size in relation to body size within taxonomic/phylogenetic and functional subgroups of tetrapods. This study provides insights into the evolutionary mechanisms driving interspecific sperm size variation and highlights the importance of considering multiple trade-offs in optimizing reproductive traits.
ORM-mediated regulation of sphingolipid biosynthesis is essential for nodule formation inAeschynomene evenia
Authors: Nouwen Nico , Pervent Marjorie , El M’Chirgui Franck , Tellier Frédérique , Rios Maëlle , Araújo Natasha Horta , Klopp Christophe , Gressent Frédéric , Arrighi Jean-François 
Published: September 2023

AbstractLegumes are able to establish symbiotic interactions with nitrogen-fixing rhizobia that are accomodated in root-derived organs, the nodules. Rhizobia recognition triggers a plant symbiotic signalling pathway activating two coordinated processes: infection and nodule organogenesis. How these are orchestrated in legumes species utilizing intercellular infection and lateral root-base nodulation remain elusive. Here, we show thatAeschynomene eveniaOROSOMUCOID PROTEIN 1 (AeORM1), a key regulator of sphingolipid biosynthesis, is required for nodule formation in this legume species. UsingA. evenia orm1mutants, we demonstrate that alterations in AeORM1 function result in numerous early aborted nodules, exhibiting defense-like reactions, and shortened lateral roots. Consistantly,AeORM1was expressed during lateral root initiation and elongation, including at lateral root bases where nodule primordia form in the presence of symbiotic bradyrhizobia. Sphingolipidomics revealed that mutations inAeORM1leaded to sphingolipid overaccumulation in roots, in particular the very-long-chain-fatty-acid (VLCFA)-containing ceramids relative to the wild-type plants. Taken together, our findings reveal that AeORM1-regulated sphingolipid homeostasis is essential for rhizobial infection and nodule organogenesis, and indicate a shared requirement for nodule formation and lateral root development inA. evenia.
Prioritizing ecological connectivity among protected areas in Colombia using a functional approach for birds
Authors: Linero Triana Daniela , Correa-Ayram Camilo Andrés , Velásquez-Tibatá Jorge 
Published: September 2023

AbstractEcological connectivity among protected areas (PAs) is essential to improve biodiversity conservation and management effectiveness in the long term under global change. Developing strategic plans and identifying spatial priorities are practical actions for establishing and strengthening interconnected networks of PAs. In Colombia, this planning is fundamental to conserve its extraordinary bird diversity in the face of multiple threats, including climate change and deforestation. We develop a connectivity model focused on multiple bird species to identify critical sites to preserve the ecological connections among PAs in Colombia. Based on land cover data and expert knowledge, we created movement resistance surfaces and modeled Least-Cost Corridors among terrestrial PAs for 26 forest-dependent species. We also used circuit and least-cost models to locate conservation priorities and restoration opportunities, estimating the potential gain in connectivity with the Equivalent Connected Area (ECA) index. We found 581,531 km2belonging to corridors among PAs for all focal species. Priority sites for movement within corridors covered 212,551 km2and were predominantly located across Andean and Amazonian forests. Restoration opportunities covered 79,203 km2and were concentrated in agricultural lands of the Andes and Caribbean regions. Restoring these areas could increase the national forest cover by 7% and connectivity by 14%. Our results provide a national-level assessment of functional connectivity priorities to maintain and improve the interconnections among PAs. This assessment could guide efforts related to conservation, restoration, and implementation of management tools that facilitate the movement of native species across transformed lands. These actions are crucial to meet the targets outlined in the post-2020 global biodiversity framework to achieve well-connected systems of PAs during this decade and until 2050.
Development and implementation of an integrated preclinical atherosclerosis database
Authors: Xiang Rachel , Wang Yihua , Shuey Megan M. , Carvajal Brigett , Wells Quinn S. , Beckman Joshua A. , Jaffe Iris Z. 
Published: September 2023

AbstractBackgroundBasic scientists have used preclinical animal models to explore mechanisms driving human diseases for decades, resulting in thousands of publications, each supporting causative inferences. Despite substantial advances in the mechanistic construct of disease, there has been limited translation from individual studies to advances in clinical care. An integrated approach to these individual studies has the potential to improve translational success.MethodsUsing atherosclerosis as a test case, we extracted data from the two most common mouse models of atherosclerosis (ApoE and LDLR knockout). We restricted analyses to manuscripts published in two well-established journals,Arteriosclerosis, Thrombosis, and Vascular BiologyandCirculation, as of query in 2021. Predefined variables including experimental conditions, intervention and outcomes were extracted from each publication to produce a preclinical atherosclerosis database.ResultsExtracted data include animal sex, diet, intervention type and distinct plaque pathologies (size, inflammation, lipid content). Procedures are provided to standardize data extraction, attribute interventions to specific genes and transform the database for use with available transcriptomics software. The database integrates hundreds of genes, each directly tested in vivo for causation in a murine atherosclerosis model. The database is provided to allow the research community to perform integrated analyses that reflect the global impact of decades of atherosclerosis investigation.ConclusionsFuture database uses include interrogation of sub-datasets associated with distinct plaque pathologies, cell-type or sex. We provide the methods and software needed to apply this approach to the extensive repository of peer-reviewed data utilizing preclinical models to interrogate mechanisms of diverse human diseases.
Triacylglycerol stability limits futile cycles and inhibition of carbon capture in oil-accumulating leaves
Authors: Johnson Brandon S. , Allen Doug K. , Bates Philip D. 
Published: September 2023

ABSTRACTEngineering plant vegetative tissue to accumulate triacylglycerols (TAG, e.g., oil) can increase the amount of oil harvested per acre to levels that exceed current oilseed crops. EngineeredNicotiana tabacum(tobacco) lines that accumulate 15% to 30% oil of leaf dry weight resulted in starkly different metabolic phenotypes. In-depth analysis of the leaf lipid accumulation and14CO2metabolic tracing mechanistically described metabolic adaptations to the leaf oil engineering. An oil-for-membrane lipid tradeoff in the 15% oil line (referred to as HO) was surprisingly not further exacerbated when lipid production was enhanced to 30% (LEC2 line). The HO line exhibited a futile cycle that limited TAG yield through exchange with starch, altered carbon flux into various metabolite pools and end products, and suggested overlapping pathways of the glyoxylate cycle and photorespiration that limited CO2assimilation by 50%. In contrast, inclusion of the LEC2 transcription factor in tobacco improved TAG stability, alleviated the TAG-to-starch futile cycle, and recovered CO2assimilation and plant growth comparable to wild type but with much higher lipid levels in the leaves. Thus, the unstable production of storage reserves and futile cycling limit vegetative oil engineering approaches. The capacity to overcome futile cycles and maintain enhanced stable TAG levels in LEC2 demonstrated the importance of considering unanticipated metabolic adaptations while engineering vegetative oil crops.
ERF and WRKY transcription factors regulateIDAand abscission timing in Arabidopsis
Authors: Galindo-Trigo Sergio , Bågman Anne-Maarit , Ishida Takashi , Sawa Shinichiro , Brady Siobhán M. , Butenko Melinka A. 
Published: September 2023

AbstractPlants shed organs like leaves, petals or fruits through the process of abscission. Monitoring cues like age, resource availability, biotic and abiotic stresses allows plants to abscise organs in a timely manner. How these signals are integrated in the molecular pathways that drive abscission is largely unknown. TheINFLORESCENCE DEFICIENT IN ABSCISSION(IDA) gene is one of the main drivers of floral organ abscission in Arabidopsis and is known to transcriptionally respond to most abscission-regulating cues. Interrogating theIDApromoterin silicoandin vitrowe identified transcription factors that can potentially modulateIDAexpression. We functionally characterized the importance of ERF and WRKY binding sites forIDAexpression during floral organ abscission, with WRKYs being of special relevance to mediateIDAupregulation in response to biotic stress in tissues destined for separation. We further characterized WRKY57 as a positive regulator ofIDAandIDA-likegene expression in abscission zones. Our findings highlight the promise of promoter element-targeted approaches to modulate the responsiveness of the IDA signaling pathway to harness controlled abscission timing for improved crop productivity.HighlightERF and WRKY transcription factors distinctly contribute to the regulation ofIDAexpression and thereby abscission timing. WRKY57 modulates abscission via redundant IDA/IDA-like peptides.
Preferences of people living with HIV for features of tuberculosis preventive treatment regimens – a discrete choice experiment
Authors: Aschmann Hélène E. , Musinguzi Allan , Kadota Jillian L. , Namale Catherine , Kakeeto Juliet , Nakimuli Jane , Akello Lydia , Welishe Fred , Nakitende Anne , Berger Christopher , Dowdy David W. , Cattamanchi Adithya , Semitala Fred C. , Kerkhoff Andrew D. 
Published: September 2023

AbstractBackgroundTuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens.MethodsWe conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. In nine random choice tasks, participants chose between two hypothetical TPT regimens with different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects). We analyzed preferences using hierarchical Bayesian estimation, latent class analysis, and willingness-to-trade simulations.ResultsOf 400 PLHIV, 392 (median age 44, 72% female, 91% TPT-experienced) had high quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6 – 33.2), followed by frequency (20.5% [95% CI 19.7 – 21.3]), duration (19.5% [95% CI 18.6 – 20.5]), and need for ART dosage adjustment (18.2% [95% CI 17.2 – 19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N=222; 57%); another was averse to ART dosage adjustment (N=107; 27%); and the last prioritized short and tolerable regimens (N=63; 16%). All groups highly valued fewer pills per dose. Participants were willing to accept a regimen of 2.8 months’ additional duration [95% CI: 2.4 – 3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4 – 4.8] months for weekly rather than daily dosing, and 2.2 [95% CI 1.3 – 3.0] months to avoid ART dosage adjustment.ConclusionsTo align with preferences of PLHIV, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing, and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.
Assessing the impact of the Gamma variant on COVID-19 Patient admissions in a Southern Brazilian tertiary hospital - A comparison of dual pandemic phases
Authors: Domino Natalia R , Lapinscki Bruna A , Zhen Felipe , Yamaguto Guilherme , Costa Emanueli C S , Moriya Vitor L , Pereira Luciane A , Petterle Ricardo , Nogueira Meri B , Raboni Sonia M 
Published: September 2023

AbstractSince the first case of COVID-19, Brazil has undergone infection waves with distinct characteristics. The description of new variants has alerted the emergence of more contagious or virulent viruses. The variant of concern Gamma emerged in Brazil and caused an epidemic wave, but its spread outside the country was limited. We report the clinical-epidemiological profile of hospitalized patients with COVID-19 by comparing two periods. A retrospective cohort study was performed. The primary outcome was to assess individuals with COVID-19 admitted in wards and intensive care units at CHC-UFPR between March 2020 and July 2021, correlating demographic, clinical-epidemiologic, and survival data with the most prevalent viral variant found in each period. We used Kaplan-Meier analysis to estimate the probability of survival and receiver operating characteristic curves to evaluate laboratory tests to find a cutoff point for poor outcomes. Data from 2,887 individuals were analyzed, 1,495 and 1,392 from the first and second periods, respectively. Hospitalization predominated among males in both periods, and the median age was significantly lower in the second one. The frequency of comorbidities was similar. Various demographic factors, clinical assessments, and laboratory tests were examined in relation to greater severity. When comparing the two studied periods, we observed predominance of the Wild virus during the first wave and the Gamma variant during the second, with no significant difference in outcomes. The findings suggest that despite the association of many factors with increased severity, the temporal variation between the two periods did not result in a notable divergence in the measured outcomes. The COVID-19 pandemic has lasted for a long time, with periods marked by peaks of cases, often caused by the emergence of viral variants, resulting in higher infection rates and rapid dissemination but, for variant Gamma, no apparent greater virulence.