bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retention of ES cell-derived 129S genome drives NLRP1 hypersensitivity and transcriptional deregulation inNlrp3−/−mice
Authors: Weiss Felix D. , Alvarez Yubell , Sahu Anshupa , Shakeri Farhad , Lee Hye Eun , Gellner Anne-Kathrin , Buness Andreas , Latz Eicke , Meissner Felix 
Published: January 2024

AbstractImmune response genes are highly polymorphic in humans and mice, with heterogeneity amongst loci driving strain-specific host defense responses. The inadvertent retention of polymorphic loci can introduce confounding phenotypes, leading to erroneous conclusions, and impeding scientific advancement. In this study, we employ a combination of RNAseq and variant calling analyses and identify a substantial region of 129S genome, including the highly polymorphicNlrp1locus proximal toNlrp3, in one of the most commonly used mouse models of NLRP3 deficiency. We show that increased expression of 129S NLRP1b sensitizesNlrp3−/−macrophages to NLRP1 inflammasome activation. Furthermore, the presence of 129S genome leads to altered gene and protein regulation across multiple cell-types, including of the key tissue-resident macrophage marker, TIM4. To address the challenge of resolving NLRP3-dependent phenotypes, we introduce and validate a conditionalNlrp3allele, enabling precise temporal and cell-type-specific control overNlrp3deletion. Our study establishes a generic framework to identify functionally relevant SNPs and assess genomic contamination in transgenic mice. This allows for unambiguous attribution of phenotypes to the target gene and advances the precision and reliability of research in the field of host defense responses.
Synergistic Modulation of Macrophages by Methotrexate and RELA siRNA Folate-Liposome: A Precision Therapy to Prevent Joint Degradation in Collagen-Induced Arthritic Rats
Authors: Nasra Simran , Bhatia Dhiraj , Kumar Ashutosh 
Published: January 2024

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and joint destruction. Current treatments, such as Methotrexate (MTX), while effective, often have therapeutic limitations like high plasma Cmaxand lack of sustained release. This study explores a synergistic approach to RA therapy using folate-liposomal co-delivery of MTX and RELA siRNA, aimed at RAW264.7 macrophage repolarization through inhibition of the NF-κB pathway. Extensive invitro characterizations demonstrate the stability and biocompatibility of this combinatorial therapy in folate-liposomes. In collagen-induced arthritis (CIA) rat model, we observed a reduction in synovial inflammation and improved mobility following treatment. The combined MTX and RELA siRNA approach indirectly inhibits inflammatory cytokines and other biochemical parameters such as Rheumatoid factor (RF) and C-reactive protein (CRP). The targeted macrophage delivery yields a marked therapeutic effect in RAW264.7 murine macrophages, potentially modulating the M1 to M2 macrophage polarization. Overall, this research presents a promising avenue for innovative therapies in RA management by inhibiting the inflammatory cascade and preventing joint damage.
Sequence-based modelling of bacterial genomes enables accurate antibiotic resistance prediction
Authors: Wiatrak Maciej , Weimann Aaron , Dinan Adam , Brbić Maria , Floto R. Andres 
Published: January 2024

AbstractRapid detection of antibiotic-resistant bacteria and understanding the mecha- nisms underlying antimicrobial resistance (AMR) are major unsolved problems that pose significant threats to global public health. However, existing methods for predicting antibiotic resistance from genomic sequence data have had lim- ited success due to their inability to model epistatic effects and generalize to novel variants. Here, we present GeneBac, a deep learning method for predicting antibiotic resistance from DNA sequence through the integration of interactions between genes. We apply GeneBac to two distinct bacterial species and show that it can successfully predict the minimum inhibitory concentration (MIC) of multiple antibiotics. We use the WHO Mycobacterium tuberculosis mutation cat- alogue to demonstrate that GeneBac accurately predicts the effects of different variants, including novel variants that have not been observed during training. GeneBac is a modular framework which can be applied to a number of tasks including gene expression prediction, resistant gene identification and strain clus- tering. We leverage this modularity to transfer learn from the transcriptomic data to improve performance on the MIC prediction task.
Thermal energetics of bats of the family Vespertilionidae: an evolutionary approach
Authors: Ayala-Berdon Jorge , Medina-Bello Kevin I. , Carballo-Morales Jorge D. , Saldaña-Vázquez Romeo A. , Villalobos Federico 
Published: January 2024

ABSTRACTThermal energetics define the way animals spend energy for thermoregulation. In this regard, numerous studies have determined that body mass (Mb) is the most influential morphological trait affecting the thermal traits in different species of birds and mammals. However, most of the studies have been focused on the basal metabolic rate (BMR), while other thermal traits have been less studied.We addressed this gap by examining thermal variables on bats of the family Vespertilionidae. Using open-flow respirometry, we measuredBMR, absolute thermal conductance (C’), lower and upper critical temperatures (TLCandTUC), and the breadth of the thermoneutral zone (TNZb) of 15 bat species varying inMbfrom ∼ 4.0 to 21.0 g from central Mexico. We: 1) combined our empirical data with information gathered from the bibliography and conducted phylogenetic analyses to investigate the relationship betweenMband thermal traits, and 2) mapped the thermal energetic values along the phylogeny to explore how they may have evolved.We found a positive relationship betweenMbandBMRand absoluteC’, and a negative relationship betweenMbandTLCandTUC. However, we did not find a relationship betweenMbandTNZbin bats. The phylogenetic approach suggested that over the evolutionary history of bats,BMRandC’ have decreased whileTLCandTUChave increased.Our results suggest that adaptive changes inMband thermal traits may have influenced the geographical distribution and the use of energy-saving strategies of the different species of bats of the family Vespertilionidae.
Microbiome-induced Increases and Decreases in Bone Tissue Strength can be Initiated After Skeletal Maturity
Authors: Liu C , Cyphert E.L. , Stephen S.J. , Wang B. , Morales A.L. , Nixon J.C. , Natsoulas N.R. , Garcia M. , Blazquez Carmona P. , Vill A.C. , Donnelly E.L. , Brito I.L. , Vashishth D. , Hernandez C.J. 
Published: January 2024

AbstractRecent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.
Progressive heterogeneity of enlarged and irregularly shaped apicoplasts inP. falciparumpersister blood stages after drug treatment
Authors: Micchelli Chiara E. , Percopo Caroline , Traver Maria , Brzostowski Joseph , Amin Shuchi N. , Prigge Sean T. , Sá Juliana M. , Wellems Thomas E. 
Published: January 2024

AbstractMorphological modifications and shifts in organelle relationships are hallmarks of dormancy in eukaryotic cells. Communications between altered mitochondria and nuclei are associated with metabolic quiescence of cancer cells that can survive chemotherapy. In plants, changes in the pathways between nuclei, mitochondria, and chloroplasts are associated with cold stress and bud dormancy.Plasmodium falciparumparasites, the deadliest agent of malaria in humans, contain a chloroplast-like organelle (apicoplast) derived from an ancient photosynthetic symbiont. Antimalarial treatments can fail because a small fraction of the blood stage parasites enter dormancy and recrudesce after drug exposure. Altered mitochondrial-nuclear interactions in these persisters have been described forP. falciparum, but interactions of the apicoplast remained to be characterized. In the present study, we examined the apicoplasts of persisters obtained after exposure to dihydroartemisinin (a first-line antimalarial drug) followed by sorbitol treatment, or after exposure to sorbitol treatment alone. As previously observed, the mitochondrion of persisters was consistently enlarged and in close association with the nucleus. In contrast, the apicoplast varied from compact and oblate, like those of active ring stage parasites, to enlarged and irregularly shaped. Enlarged apicoplasts became more prevalent later in dormancy, but regular size apicoplasts subsequently predominated in actively replicating recrudescent parasites. All three organelles, nucleus, mitochondrion, and apicoplast, became closer during dormancy. Understanding their relationships in erythrocytic-stage persisters may lead to new strategies to prevent recrudescences and protect the future of malaria chemotherapy.Significance StatementDormancy of blood-stage malaria parasites (as persister forms) frequently undermines treatment and may facilitate the evolution of drug resistance. Here, we examine changes that occur in dormancy with twoP. falciparumorganelles relative to the nucleus: the mitochondrion and the plastid-like apicoplast. As previously reported, the mitochondrion of persisters is consistently enlarged, irregularly shaped, and shifted into close apposition with the nucleus. However, apicoplasts exhibit a greater variety of shapes, volumes, and relative positioning during dormancy: some persisters maintain a regular appearing apicoplast, while others show dramatically altered apicoplasts, reminiscent of the chloroplast swelling and degradation that occurs with death from reactive oxygen species in various plant cells. Improved understanding of these processes will support new approaches in antimalarial chemotherapy.
Accuracy of phylogenetic reconstructions from continuous characters analyzed under parsimony and its parametric correlates
Authors: Tagliacollo Victor A , de Pinna Mario , Chuctaya Junior , Datovo Alessio 
Published: January 2024

ABSTRACTQuantitative traits are a source of evolutionary information often difficult to handle in cladistics. Tools exist to analyze this kind of data without subjective discretization, avoiding biases in the delimitation of categorical states. Nonetheless, the ability of continuous characters to accurately infer relationships is incompletely understood, particularly under parsimony analysis. This study evaluates the accuracy of phylogenetic reconstructions from simulated matrices of continuous characters evolving under alternative evolutionary processes and analyzed by parsimony. We generated 100 trees to simulate 9,000 matrices containing 26 terminals and 100 continuous characters evolving under: Brownian-Motion (BM), Ornstein-Uhlenbeck (OU) and Early-Burst (EB) processes assuming variable parametrizations. Our comparisons of cladograms revealed that matrices analyzed by parsimony carry phylogenetic signals to infer relationships, but the accuracy is higher for matrices simulated under BM, regardless of the parameterization schemes. Implementation of equal or implied weighting with multiple penalization strengths against homoplasies did not affect cladogram inferences. Accuracy of continuous characters in resolving relationships is skewed toward apical nodes of the trees. Our simulations provide controlled tests of the usefulness of quantitative traits in phylogenetics, specifically under neutral evolution, and demonstrate their effectiveness in estimating shallower nodes among recently diverged species, regardless of parameters and weighting schemes.
Streamlining the alignment of UAV and TLS forest point clouds: an approach based on ground and tree stems
Authors: Puletti Nicola , Innocenti Simone , Guasti Matteo 
Published: January 2024

AbstractAccurate co-registration of terrestrial and aerial point clouds may provide a high-resolution description of tree components for large forest areas. However, an automated approach for co-registering point clouds is still needed, given the challenges in geospatial data processing, particularly in complex topographical conditions. The main objective of this study is to present the application of a novel procedure for the co-registration of point clouds obtained from terrestrial and UAV surveys in Mediter-ranean forests.
Tractography-based automated identification of the retinogeniculate visual pathway with novel microstructure-informed supervised contrastive learning
Authors: Li Sipei , Zhang Wei , Yao Shun , He Jianzhong , Zhu Ce , Gao Jingjing , Xue Tengfei , Xie Guoqiang , Chen Yuqian , Torio Erickson F. , Feng Yuanjing , Bastos Dhiego CA , Rathi Yogesh , Makris Nikos , Kikinis Ron , Bi Wenya Linda , Golby Alexandra J , O’Donnell Lauren J , Zhang Fan 
Published: January 2024

ABSTRACTThe retinogeniculate visual pathway (RGVP) is responsible for carrying visual information from the retina to the lateral geniculate nucleus. Identification and visualization of the RGVP are important in studying the anatomy of the visual system and can inform the treatment of related brain diseases. Diffusion MRI (dMRI) tractography is an advanced imaging method that uniquely enablesin vivomapping of the 3D trajectory of the RGVP. Currently, identification of the RGVP from tractography data relies on expert (manual) selection of tractography streamlines, which is time-consuming, has high clinical and expert labor costs, and is affected by inter-observer variability. In this paper, we present a novel deep learning framework,DeepRGVP, to enable fast and accurate identification of the RGVP from dMRI tractography data. We design a novel microstructure-informed supervised contrastive learning method that leverages both streamline label and tissue microstructure information to determine positive and negative pairs. We propose a simple and successful streamline-level data augmentation method to address highly imbalanced training data, where the number of RGVP streamlines is much lower than that of non-RGVP streamlines. We perform comparisons with several state-of-the-art deep learning methods that were designed for tractography parcellation, and we show superior RGVP identification results using DeepRGVP. In addition, we demonstrate a good generalizability of DeepRGVP to dMRI tractography data from neurosurgical patients with pituitary tumors and we show DeepRGVP can successfully identify RGVPs despite the effect of lesions affecting the RGVPs. Overall, our study shows the high potential of using deep learning to automatically identify the RGVP.
Climate and urbanization drive changes in the habitat suitability ofSchistosoma mansonicompetent snails in Brazil
Authors: Glidden Caroline K. , Singleton Alyson L. , Chamberlin Andrew , Tuan Roseli , Palasio Raquel G.S. , Caldeira Roberta Lima , Monteiro Antônio Miguel V. , Lwiza Kamazima M. M. , Liu Ping , Silva Vivian , Athni Tejas S. , Sokolow Susanne H. , Mordecai Erin A. , De Leo Giulio A. 
Published: January 2024

ABSTRACTSchistosomiasis is a neglected tropical disease caused bySchistosomaparasites.Schistosomaare obligate parasites of freshwaterBiomphalariasnails, so controlling snail populations is critical to reducing transmission risk. As snails are sensitive to environmental conditions, we expect their distribution is significantly impacted by global change. Here, we leveraged machine learning, remote sensing, and 30 years of snail occurrence records to map the historical and current distribution of competentBiomphalariathroughout Brazil. We identified key features influencing the distribution of suitable habitat and determined howBiomphalariahabitat has changed with climate and urbanization over the last three decades. Our models show that climate change has driven broad shifts in snail host range, whereas expansion of urban and peri-urban areas has driven localized increases in habitat suitability. Elucidating change inBiomphalariadistribution – while accounting for non-linearities that are difficult to detect from local case studies – can help inform schistosomiasis control strategies.
Fascin structural plasticity mediates flexible actin bundle construction
Authors: Gong Rui , Reynolds Matthew J. , Carney Keith R. , Hamilton Keith , Bidone Tamara C. , Alushin Gregory M. 
Published: January 2024

SummaryFascin crosslinks actin filaments (F-actin) into bundles that support tubular membrane protrusions including filopodia and stereocilia. Fascin dysregulation drives aberrant cell migration during metastasis, and fascin inhibitors are under development as cancer therapeutics. Here, we use cryo-electron microscopy, cryo-electron tomography coupled with custom denoising, and computational modeling to probe fascin’s F-actin crosslinking mechanisms across spatial scales. Our fascin crossbridge structure reveals an asymmetric F-actin binding conformation that is allosterically blocked by the inhibitor G2. Reconstructions of seven-filament hexagonal bundle elements, variability analysis, and simulations show how structural plasticity enables fascin to bridge varied inter-filament orientations, accommodating mismatches between F-actin’s helical symmetry and bundle hexagonal packing. Tomography of many-filament bundles and modeling uncovers geometric rules underlying emergent fascin binding patterns, as well as the accumulation of unfavorable crosslinks that limit bundle size. Collectively, this work shows how fascin harnesses fine-tuned nanoscale structural dynamics to build and regulate micron-scale F-actin bundles.
Improving the application of Important Plant Areas to conserve threatened habitats: a case study of Uganda
Authors: Richards Sophie L. , Kalema James , Ojelel Samuel , Williams Jenny , Darbyshire Iain 
Published: January 2024

AbstractImportant Plant Areas (IPAs) are a successful method of identifying priority areas for plant conservation. Assessment of IPAs, however, often relies on criteria related to species, while incorporation of habitats has been less consistent. Using Uganda as a case study, we test the application of the threatened habitat criterion – criterion C. We identified nationally threatened habitats using Red List of Ecosystems criteria and assess, for the first time, how differing application of thresholds under criterion C can influence IPA network outcomes. Eleven threatened habitats were identified, with declines switching from predominantly forest to savanna after the mid-20thcentury. Significantly, we found current IPA guidance on use of Criterion C needlessly limits the number of sites that qualify as IPAs. The “five best sites” threshold is reserved for countries where quantitative data is unavailable, however, the application of the relevant thresholds to quantitative data largely generated fewer than five IPAs, comparably limiting conservation opportunities identified. We recommend, therefore, that the “five best” threshold is available for application on both qualitative and quantitative data. This will bolster the value of IPAs in conserving and restoring threatened and ecologically important habitats under the Kunming-Montreal Global Biodiversity Framework.
Vascular damage and excessive proliferation compromise liver function after extended hepatectomy in mice
Authors: Rudder Maxime De , Manco Rita , Coubeau Laurent , Fontaine Alix , Bertrand Claude , Leclercq Isabelle A. , Dili Alexandra 
Published: January 2024

AbstractSurgical resection remains the gold standard for liver tumor treatment, yet the emergence of post-operative liver failure, known as the small for size syndrome (SFSS), poses a substantial challenge. The activation of hypoxia sensors in a SFSS liver remnant initiated early angiogenesis, improving vascular architecture, safeguarding against liver failure and reducing mortality. The study aimed to elucidate vascular remodeling mechanisms in SFSS, its impact on hepatocyte function and subsequent liver failure. Mice underwent extended partial hepatectomy to induce SFSS, a subset were exposed to hypoxia immediately after surgery. Hypoxia bolstered post- hepatectomy survival rates. Early proliferation of liver sinusoidal cells coupled with augmented recruitment of endothelial progenitor cells (EPC) via the VEGF/SDF-1α pathway resulted in heightened vascular density, improved lobular perfusion, and limited hemorrhagic events in the regenerating liver under hypoxia. The administration of G-CSF mimicked the effects of hypoxia on vascular remodeling and EPC recruitment, though it failed to rescue survival. Compared to normoxia, hypoxia restrained hepatocyte proliferation yet improved the function of the regenerating remnant, favoring functional preservation in the liver remnant. Injection of AAV8- TBG-HNF4α virus for hepatocyte-specific overexpression of HNF4α, the master regulator of hepatocyte function, enforced functionality in proliferating hepatocytes. The combination, only, of HNF4α overexpression and G-CSF treatment rescued survival post-SFSS-setting hepatectomy. In summary, SFSS arises due to imbalance and desynchronized interplay between functional regeneration and vascular restructuring. To enhance survival following SFSS-hepatectomy, a two- pronged strategy is essential, addressing the preservation of function in the proliferating parenchymal cells alongside the simultaneous mitigation of vascular harm.One Sentence SummaryCombined treatment with G-CSF and HNF4α overexpression rescues vascular damage and function to improve survival after extended hepatectomy in mice.