bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic bioenergetic adaptations compensate for reduced mitochondrial content in HER2-driven mammary tumors
Authors: Frangos Sara M , Brunetta Henver S , Wang Dongdong , Jabile Maria Joy Therese , Ma David W L , Muller William J , Khursigara Cezar M , Fisher-Wellman Kelsey H , Steinberg Gregory R , Holloway Graham P 
Published: November 2024

ABSTRACTIt is now recognized that mitochondria play a crucial role in tumorigenesis, however, it has become clear that tumor metabolism varies significantly between cancer types. The failure of recent clinical trials attempting to directly target tumor respiration with inhibitors of oxidative phosphorylation has highlighted the critical need for additional studies comprehensively assessing mitochondrial bioenergetics. Therefore, we systematically assessed the bulk tumor and mitochondrial metabolic phenotype between murine HER2-driven mammary cancer tumors and paired benign mammary tissue. Transcriptomic and proteomic profiling revealed that HER2-driven mammary tumors are characterized by a downregulation of mitochondrial genes/proteins compared to benign mammary tissue, including a general downregulation of OXPHOS subunits comprising Complexes I-IV. Despite this observation, mitochondrial respiration supported by both carbohydrate-derived substrates (pyruvate) and lipids (palmitoyl-carnitine) was several-fold higher in HER2-driven tumors which persisted regardless of normalization method (i.e. wet weight, total protein content and when corrected for mitochondrial content). This upregulated respiratory capacity could not be explained by OXPHOS uncoupling; however, several subunits/regulators of Complex V function were not downregulated in the tumors, suggesting possible compensatory effects may contribute to high respiratory rates. Furthermore, tumor mitochondria displayed a smaller and more punctate morphology, aligning with a general reduction in mitochondrial fusion and increase in mitochondrial fission markers, which could contribute to improved OXPHOS efficiency. Together, this data highlights that the typical correlation of mitochondrial content and respiratory capacity may not apply to all tumor types and implicates the activation of mitochondrial respiration supporting tumorigenesis in this model.
Emergence of a Novel Reassortant Clade 2.3.2.1c Avian Influenza A/H5N1 Virus Associated with Human Cases in Cambodia
Authors: Siegers Jurre Y. , Xie Ruopeng , Byrne Alexander M.P. , Edwards Kimberly M. , Hu Shu , Yann Sokhoun , Sin Sarath , Tok Songha , Chea Kimlay , Horm Sreyviseth , Rith Chenthearath , Keo Seangmai , Pum Leakhena , Duong Veasna , Auerswald Heidi , Phou Yisuong , Kol Sonita , Spiegel Andre , Harvey Ruth , Tum Sothyra , Sorn San , Seng Bunnary , Sengdoeurn Yi , Darapheak Chau , Savuth Chin , Hak Makara , Ieng Vanra , Patel Sarika , Thielen Peter , Claes Filip F. , Lewis Nicola S. , Sovann Ly , Dhanasekaran Vijaykrishna , Karlsson Erik A. 
Published: November 2024

I.AbstractAfter nearly a decade without reported human A/H5N1 infections, Cambodia faced a sudden resurgence with 16 cases between February 2023 and August 2024, all caused by A/H5 clade 2.3.2.1c viruses. Fourteen cases involved a novel reassortant A/H5N1 virus with gene segments from both clade 2.3.2.1c and clade 2.3.4.4b viruses. The emergence of this novel genotype underscores the persistent and ongoing threat of avian influenza in Southeast Asia. This study details the timeline and genomic epidemiology of these infections and related poultry outbreaks in Cambodia.
Decoding Liver Cancer Prognosis: From Multi-omics Subtypes, Prognostic Models to Single Cell Validation
Authors: Wang Yanbin , Wu Yuqi , Zhang Hong , Liu Xinyue , Ling Jing , Zhou Xiao , Song Anping , Sun Li , Qiu Hong , Yuan Xianglin , Xiong Hua , Zou Yanmei 
Published: November 2024

AbstractPurposeHepatocellular carcinoma (HCC) is a highly aggressive tumor characterized by significant heterogeneity and invasiveness, leading to a lack of precise individualized treatment strategies and poor patient outcomes. This necessitates the urgent development of accurate patient stratification methods and targeted therapies based on distinct tumor characteristics.Experimental DesignBy integrating gene expression data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO), we identified subtypes through a multi-omics consensus clustering approach amalgamated from 10 clustering techniques. Subsequently, we developed a prognostic model, employing machine learning algorithms, based on subtype classification features. Finally, by analyzing single cell sequencing data, we investigated the mechanisms driving prognostic variations among distinct subtypes.ResultsFirst, we developed a novel consensus clustering method that categorizes liver cancer patients into two subtypes, CS1 and CS2. Second, we constructed a prognostic prediction model, which demonstrated superior predictive accuracy compared to several models published in the past five years. Finally, we observed differences between CS1 and CS2 in various metabolic pathways, biological processes, and signaling pathways, such as fatty acid metabolism, hypoxia levels, PI3K-AKT and MIF signaling pathway.
UCF-MultiOrgan-Path:A Benchmark Dataset of Histopathologic Images for Deep Learning-Based Organ Classification
Authors: Hossain Md Sanzid Bin , Piazza Yelena , Braun Jacob , Bilic Anthony , Hsieh Michael , Fouissi Samir , Borowsky Alexander , Kaseb Hatem , Renduchintala Chaithanya , Fraser Amoy , Wray Britney-Ann , Chen Chen , Wang Liqiang , Husain Mujtaba , Hadley Dexter 
Published: November 2024

ABSTRACTA pathologist typically diagnoses tissue samples by examining glass slides under a light microscope. The entire tissue specimen can be stored digitally as a Whole Slide Image (WSI) for further analysis. However, managing and diagnosing large numbers of images manually is time-consuming and requires specialized expertise. Consequently, computer-aided diagnosis of these pathology images is an active research area, with deep learning showing promise in disease classification and cancer cell segmentation. Robust deep learning models need many annotated images, but public datasets are limited, often constrained to specific organs, cancer types, or binary classifications, which limits generalizability. To address this, we introduce the UCF multi-organ histopathologic (UCF-MultiOrgan-Path) dataset, containing 977 WSIs from cadaver tissues across 15 organ classes, including lung, kidney, liver, and pancreas. This dataset includes ∼2.38 million patches of 512×512 pixels. For technical validation, we provide patch-based and slide-based approaches for patch- and slide-level classification. Our dataset, containing millions of patches, can serve as a benchmark for training and validating deep learning models in multi-organ classification.
Analysis of Glomerular Transcriptomes from Nephrotic Patients SuggestAPOL1Risk Variants Impact Parietal Epithelial Cells
Authors: Gonzalez-Vicente Agustin , Crawford Dana C. , Bush William S. , Wu Zhenzhen , Bruggeman Leslie A. , Nair Viji , Eichinger Felix , Wessely Oliver , Kretzler Matthias , O’Toole John F. , Sedor John R. ,   Kidney Precision Medicine Project,   Nephrotic Syndrome Study Network
Published: November 2024

ABSTRACTThe disproportionate risk for idiopathic proteinuric podocytopathies in Black people is explained, in part, by the presence of two risk alleles (G1 or G2) in theAPOL1gene. The pathogenic mechanisms responsible for this genetic association remain incompletely understood. We analyzed glomerular RNASeq transcriptomes from patients with idiopathic nephrotic syndrome of which 72 had inferred African ancestry (AA) and 152 did not (noAA). Using gene coexpression networks we found a significant association betweenAPOL1risk allele number and the coexpression metamodule 2 (MM2), even after adjustment for eGFR and proteinuria at biopsy. Unadjusted Kaplan-Meier curves showed that unlike noAA, AA with the highest tertile of MM2 gene activation scores were less likely to achieve complete remission (p≤0.014). Characteristic direction (ChDir) identified a signature of 1481 genes, which separated patients withAPOL1risk alleles from those homozygous for referenceAPOL1. Only in AA, the tertile with the highest activation scores of these 1481 genes was less likely to achieve complete remission (p≤0.022) and showed a trend to faster progression to the composite event of kidney failure or loss of 40% eGFR (p≤0.099). The MM2 and ChDir genes significantly overlapped and were both enriched for Epithelial Mesenchymal Transition and inflammation terms. Finally, MM2 significantly overlapped with a parietal epithelial cell (PEC)-identity gene signature but not with a podocyte identity signature. Podocytes expressing variant APOL1s may generate inflammatory signals that activate PECs by paracrine mechanisms contributing toAPOL1nephropathy.
A spatial single-cell atlas of the claustro-insular region uncovers key regulators of neuronal identity and excitability
Authors: Fodoulian Leon , Boillat Madlaina , Moulinier Marie , Carleton Alan , Rodriguez Ivan 
Published: November 2024

AbstractThe claustro-insular region is an evolutionarily conserved and extensively interconnected brain area, critical for functions such as attention, cognitive flexibility, interoception, and affective processing. Despite its importance, its cellular composition and organization remain poorly characterized, hindering a comprehensive understanding of the mechanisms underlying its diverse functions. By combining single-cell RNA sequencing and spatial transcriptomics, we created a high-resolution atlas of this region in mice, uncovering distinct neuronal subtypes and unexpected complexity. Leveraging this atlas, we investigated the role of NR4A2, a neuropsychiatric risk factor expressed in several claustro-insular neuronal subtypes. In anNr4a2haploinsufficiency model, we found that only claustrum neurons exhibited shifts in molecular identity. This identity shift, which involved the activation of a transcription factor cascade, was associated with alterations in neuronal firing activity. Our findings provide new insights into the cellular architecture of the claustro-insular region and highlightsNr4a2as a master regulator of its component’s identities.
A novel CCDC112-dependent process of sperm midpiece formation and epididymal maturation
Authors: Graffeo Maddison L. , Nguyen Joseph , Parast Farin Yazdan , Merriner D. Jo , Dunleavy Jessica E.M. , Korneev Denis , Okuda Hidenobu , O’Connor Anne E. , Conrad Donald F. , Nosrati Reza , Houston Brendan , O’Bryan Moira K. 
Published: November 2024

AbstractThe sperm mitochondrial sheath has proposed functions in structural support and energy production for motility. Here we define coiled coil domain containing protein 112, CCDC112, as crucial for male fertility, specifically in the assembly and function of the mitochondrial sheath. We unveiled a previously unrecognised process of epididymal mitochondrial sheath maturation. Sperm mitochondrial sheaths are structurally immature upon exiting the testis and continue to mature as they transit from the caput to the cauda epididymis. Data reveal the critical role of CCDC112 in mitochondrial morphogenesis during sheath formation. A lack of CCDC112 lead to significantly reduced mitochondrial respiration capacity, irregular flagellar waveforms, diminished progressive motility and a failure of sperm to traverse the female reproductive tract to the site of fertilisation and penetrate the zonae pellucidae of oocytes. Finally, we identify CCDC112 as a component of the distal appendages of the mother centriole and identify a facilitative role in core tail assembly. Collectively, CCDC112 is a key regulator of sperm mitochondrial sheath assembly while further expanding the understanding of spermatogenesis, energy generation and flagella kinematics.
Distribution of haploid chromosomes into separate nuclei in two pathogenic fungi
Authors: Xu Yan , Tian Lei , Tan Jinyi , Li Josh , O’Neil Nigel , Hirst Martin , Hieter Phil , Zhang Yuelin , Li Xin 
Published: November 2024

AbstractThe presence of nuclei defines eukaryotes, enabling compartmentalization of macromolecules and cellular regulation. Inside the nucleus, chromosome numbers vary greatly across organisms, both in terms of ploidy status and haploid chromosome number. For cells harboring multiple nuclei as in many fungal mycelia and animal muscle cells, each healthy nucleus is traditionally believed to carry at least one haploid set of chromosomes. Abnormal chromosome numbers in nuclei are often associated with aging, diseases such as cancer, developmental disorders or lethality. Here we report a surprising discovery that chromosomes in haploid cells of the fungal speciesSclerotinia sclerotiorumandBotrytis cinereaare segregated into separate nuclei, with each nucleus containing only a fraction of the chromosomes. This is the first report of eukaryotic cells that partition chromosome subsets into distinct nuclei, bringing new questions and opening fresh avenues for chromosome biology.
Climate and predation drive variation of diel activity patterns in chacma baboons (Papio ursinus) across southern Africa
Authors: Dzingwena L. , Thel L. , Choisy M. , Garbett R. , Wilkinson Anita , Venter J. , Fritz H. , Huchard E. , Prugnolle F. , Rougeron V. 
Published: November 2024

AbstractAnimals need to adjust their diel activity patterns to fulfil their energy and social requirements whilst avoiding predation risk and environmental constraints. The chacma baboon (Papio ursinus) is a highly adjustable primate occupying a variety of habitats in southern Africa, yet little is known about its diel activity patterns in different environments. We used camera trap data collected from 2016 to 2022 in 29 sites in South Africa and Zimbabwe to characterise the diel activity pattern variations of chacma baboons in different biomes (savanna, nama-karoo, fynbos, forest, thicket and grassland). We quantified activity using non-parametric kernel density functions and extracted activity level estimates, times of wake up, sleep and activity peaks. Chacma baboons’ activity levels significantly decrease by approximately 2.84% with a unit increase in latitude. We did not find any significant effect of latitude on “wake up” and “go to sleep” time of chacma baboons. Within a day, chacma baboons are more active in the morning and the afternoon and their diel activity levels decreased with temperature, and precipitation throughout the day, but increased with predator activity at night and morning. The results show that chacma baboons can flexibly adjust to local conditions in rapidly changing southern African environments.
Presaccadic attentional shifts are not modulated by saccade amplitude
Authors: Zimmermann Bortoluzzi Luan , Carlos-Lima Estêvão , Mueller de Melo Gabriela , Hongjin Song Zhu Melissa , Rohenkohl Gustavo 
Published: November 2024

ABSTRACTHumans constantly explore the visual environment through saccades, bringing relevant visual stimuli to the center of the gaze. Before the eyes begin to move, visual attention is directed to the intended saccade target. As a consequence of this presaccadic shift of attention (PSA), visual perception is enhanced at the future gaze position. PSA has been investigated in a variety of saccade amplitudes, from microsaccades to locations that exceed the oculomotor range. Interestingly, recent studies have shown that PSA effects on visual perception are not equally distributed around the visual field. However, it remains unknown whether the magnitude of presaccadic perceptual enhancement varies with the amplitude of the saccades. Here, we measured contrast sensitivity thresholds during saccade planning in a two-alternative forced-choice (2AFC) discrimination task in human observers. Filtered pink noise (1/f) patches, presented at four eccentricities scaled in size according to the cortical magnification factor were used as visual targets. This method was adopted to mitigate well-known eccentricity effects on perception, thereby enabling us to explore the effects associated to saccade amplitudes. First, our results show that saccade preparation enhanced contrast sensitivity in all tested locations. Importantly, we found that this presaccadic perceptual enhancement was not modulated by the amplitude of the saccades. These findings suggest that presaccadic attention operates consistently across different saccade amplitudes, enhancing visual processing at intended gaze positions regardless of saccade size.
Contactin-1 is a critical neuronal cell surface receptor for perineuronal net structure
Authors: Sinha Ashis , Nickerson Gabrielle , Bouyain Samuel , Matthews Russell T. 
Published: November 2024

ABSTRACTPerineuronal nets (PNNs), are neuron-specific substructures within the neural extracellular matrix (ECM). These reticular structures form on a very small subset of neurons in the central nervous system (CNS) and yet have a profound impact in regulating neuronal development and physiology. PNNs are well-established as key regulators of plasticity in the CNS. Their appearance coincides with the developmental transition of the brain more to less plastic state. And, importantly, numerous studies have demonstrated that indeed PNNs play a primary role in regulating this transition. There is, however, a growing literature implicating PNNs in numerous roles in neural physiology beyond their role in regulating developmental plasticity. Accordingly, numerous studies have shown PNNs are altered in a variety of neurological and neuropsychiatric diseases, linking them to these conditions. Despite the growing interest in PNNs, the mechanisms by which they modulate neural functions are poorly understood. We believe the limited mechanistic understanding of PNNs is derived from the fact that there are limited models, tools or techniques that specifically target PNNs in a cell-autonomous manner and without also disrupting the surrounding neural ECM. These limitations are primarily due to our incomplete understanding of PNN composition and structure. In particular, there is little understanding of the neuronal cell surface receptors that nucleate these structures on subset of neurons on which they form in the CNS. Therefore, the main focus our work is to identify the neuronal cell surface proteins critical for PNN formation and structure. In our previous studies we demonstrated PNN components are immobilized on the neuronal surface by two distinct mechanisms, one dependent on the hyaluronan backbone of PNNs and the other mediated by a complex formed by receptor protein tyrosine phosphatase zeta (RPTPζ) and tenascin-R (Tnr). Here we first demonstrate that the Tnr-RPTPζ complex in PNNs is bound to the cell surface by a glycosylphosphatidylinositol (GPI)-linked receptor protein. Using a biochemical and structural approach we demonstrate the GPI-linked protein critical for binding the Tnr-RPTPζ complex in PNNs is contactin-1 (Cntn1). We further show the binding of this complex in PNNs by Cntn1 is critical for PNN structure. We believe identification of CNTN1 as a key cell-surface protein for PNN structure is a very significant step forward in our understanding of PNN formation and structure and will offer new strategies and targets to manipulate PNNs and better understand their function.
Chronic mycobacteria infection triggers macrophage senescence
Authors: Scarpa E. , Oliveri D. , Moschetti G. , Griego A. , Vianello A. , Rondelli D. , Antinori B. , Marchello G. , Santarelli P. , Albanese M. , Franzè S. , Cidonio G. , Manganaro L. , Lorè Nicola I. , Rizzello L. 
Published: November 2024

ABSTRACTChronic infections with intracellular pathogens such asMycobacterium abscessus(Mab) pose significant health challenges due to their capacity to persist within host cells and evade immune responses. This study investigates the cellular responses to chronic Mab infection in macrophages, particularly focusing on cellular senescence. Using an in vitro model of chronic infection in murine alveolar-like macrophages, we found that Mab induces a senescent phenotype characterised by decreased proliferation, altered morphology, DNA damage signalling activation, and upregulation of senescence markers such as p21 and SA-β-galactosidase. Intriguingly, senescent macrophages secreted pro-inflammatory cytokines, consistent with a senescence-associated secretory phenotype (SASP), which promoted secondary senescence in neighbouring uninfected cells. This paracrine transmission of senescence underscores a potentially deleterious effect ofMab-induced SASP on tissue microenvironments, fostering a pro-inflammatory niche that may contribute to pathogen persistence. These findings highlightMab-induced senescence as a key factor in chronic infection pathology, suggesting that targeting senescent cells and SASP-related pathways could enhance treatment outcomes in chronic bacterial infections.
Single-molecule imaging reveals the role of membrane-binding motif and C-terminal domain of RNase E in its localization and diffusion inEscherichia coli
Authors: Troyer Laura , Wang Yu-Huan , Shobhna  , Kim Seunghyeon , Woo Jeechul , Tajkhorshid Emad , Kim Sangjin 
Published: November 2024

ABSTRACTInEscherichia coli, RNase E is the key enzyme for RNA processing and mRNA degradation. Despite the conserved function across bacteria, the domain composition of RNase E varies significantly among species, possibly affecting the enzyme’s subcellular localization, mobility, and function. In this work, we used super-resolution microscopy to find that 93% of RNase E is localized to the membrane inE. coliand exhibits slow diffusion comparable to polysomes diffusing in the cytoplasm. By replacing the native amphipathic membrane targeting sequence (MTS) with a transmembrane motif, we discovered that the MTS results in slower diffusion and stronger membrane binding than a transmembrane motif. Additionally, the evolutionarily divergent C-terminal domain (CTD) was shown to grant slow diffusion of RNase E but to weaken its membrane binding. By analyzing how membrane localization and diffusion of RNase E affect mRNA degradation ratesin vivo, we provide new insights into RNase E’s role in the spatiotemporal organization of RNA processes in bacterial cells.