bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the critical role of androgen receptor signaling in avian sexual development
Authors: Lengyel Kamila , Rudra Mekhla , Berghof Tom V. L. , Leitão Albertine , Frankl-Vilches Carolina , Dittrich Falk , Duda Denise , Klinger Romina , Schleibinger Sabrina , Sid Hicham , Trost Lisa , Vikkula Hanna , Schusser Benjamin , Gahr Manfred 
Published: October 2024

AbstractGonadal hormone activities mediated by androgen and estrogen receptors, along with cell-autonomous mechanisms arising from the absence of sex-chromosome dosage compensation, are key factors in avian sexual development. In this study, we generate androgen receptor (AR) knockout chickens (AR−/−) to explore the role of androgen signaling in avian sexual development. Despite developing sex-typical gonads and gonadal hormone production, AR−/− males and females are infertile. While few somatic sex-specific traits persist (body size, spurs, and tail feathers), crucial sexual attributes such as comb, wattles and sexual behaviors remain underdeveloped in both sexes. Testosterone treatment of young AR−/− males fails to induce crow behavior, comb development, or regression of the bursa of Fabricius, which are testosterone-dependent phenotypes. These findings highlight the significance of androgen receptor mechanisms in fertility and sex-specific traits in chickens, challenging the concept of a default sex in birds and emphasizing the dominance of androgen signaling in avian sexual development.
Long-lived topological time-crystalline order on a quantum processor
Authors: Xiang Liang , Jiang Wenjie , Bao Zehang , Song Zixuan , Xu Shibo , Wang Ke , Chen Jiachen , Jin Feitong , Zhu Xuhao , Zhu Zitian , Shen Fanhao , Wang Ning , Zhang Chuanyu , Wu Yaozu , Zou Yiren , Zhong Jiarun , Cui Zhengyi , Zhang Aosai , Tan Ziqi , Li Tingting , Gao Yu , Deng Jinfeng , Zhang Xu , Dong Hang , Zhang Pengfei , Jiang Si , Li Weikang , Lu Zhide , Sun Zheng-Zhi , Li Hekang , Wang Zhen , Song Chao , Guo Qiujiang , Liu Fangli , Gong Zhe-Xuan , Gorshkov Alexey V. , Yao Norman Y. , Iadecola Thomas , Machado Francisco , Wang H. , Deng Dong-Ling 
Published: October 2024

AbstractTopologically ordered phases of matter elude Landau’s symmetry-breaking theory, featuring a variety of intriguing properties such as long-range entanglement and intrinsic robustness against local perturbations. Their extension to periodically driven systems gives rise to exotic new phenomena that are forbidden in thermal equilibrium. Here, we report the observation of signatures of such a phenomenon—a prethermal topologically ordered time crystal—with programmable superconducting qubits arranged on a square lattice. By periodically driving the superconducting qubits with a surface code Hamiltonian, we observe discrete time-translation symmetry breaking dynamics that is only manifested in the subharmonic temporal response of nonlocal logical operators. We further connect the observed dynamics to the underlying topological order by measuring a nonzero topological entanglement entropy and studying its subsequent dynamics. Our results demonstrate the potential to explore exotic topologically ordered nonequilibrium phases of matter with noisy intermediate-scale quantum processors.
Double-strand breaks in facultative heterochromatin require specific movements and chromatin changes for efficient repair
Authors: Wensveen Marieke R. , Dixit Aditya A. , van Schendel Robin , Kendek Apfrida , Lambooij Jan-Paul , Tijsterman Marcel , Colmenares Serafin U. , Janssen Aniek 
Published: October 2024

AbstractDNA double-strand breaks (DSBs) must be properly repaired within diverse chromatin domains to maintain genome stability. Whereas euchromatin has an open structure and is associated with transcription, facultative heterochromatin is essential to silence developmental genes and forms compact nuclear condensates, called polycomb bodies. Whether the specific chromatin properties of facultative heterochromatin require distinct DSB repair mechanisms remains unknown. Here, we integrate single DSB systems in euchromatin and facultative heterochromatin in Drosophila melanogaster and find that heterochromatic DSBs rapidly move outside polycomb bodies. These DSB movements coincide with a break-proximal reduction in the canonical heterochromatin mark histone H3 Lysine 27 trimethylation (H3K27me3). We demonstrate that DSB movement and loss of H3K27me3 at heterochromatic DSBs depend on the histone demethylase dUtx. Moreover, loss of dUtx specifically disrupts completion of homologous recombination at heterochromatic DSBs. We conclude that DSBs in facultative heterochromatin require dUtx-mediated loss of H3K27me3 to promote DSB movement and repair.
Gustatory interface for operative assessment and taste decoding in patients with tongue cancer
Authors: Wang Xiner , Bai Guo , Liang Jizhi , Xie Qianyang , Chen Zhaohan , Zhou Erda , Li Meng , Wei Xiaoling , Sun Liuyang , Zhang Zhiyuan , Yang Chi , Tao Tiger H. , Zhou Zhitao 
Published: October 2024

AbstractTaste, a pivotal sense modality, plays a fundamental role in discerning flavors and evaluating the potential harm of food, thereby contributing to human survival, physical and mental health. Patients with tongue cancer may experience a loss of taste following extensive surgical resection with flap reconstruction. Here, we designed a gustatory interface that enables the non-invasive detection of tongue electrical activities for a comprehensive operative assessment. Moreover, it decodes gustatory information from the reconstructed tongue without taste buds. Our gustatory interface facilitates the recording and analysis of electrical activities on the tongue, yielding an electrical mapping across the entire tongue surface, which delineates the safe margin for surgical management and assesses flap viability for postoperative structure monitoring and prompt intervention. Furthermore, the gustatory interface helps patients discern tastes with an accuracy of 97.8%. Our invention offers a promising approach to clinical assessment and management and holds potential for improving the quality of life for individuals with tongue cancer.
The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission
Authors: Majzoub Marwan E. , Paramsothy Sudarshan , Haifer Craig , Parthasarathy Rohit , Borody Thomas J. , Leong Rupert W. , Kamm Michael A. , Kaakoush Nadeem O. 
Published: October 2024

AbstractBacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.
Systemically injected oxygen within rapidly dissolving microbubbles improves the outcomes of severe hypoxaemia in swine
Authors: Mancebo Julia Garcia , Sack Kristen , Hartford Jay , Dominguez Saffron , Balcarcel-Monzon Michelle , Chartier Elizabeth , Nguyen Tien , Cole Alexis R. , Sperotto Francesca , Harrild David M. , Polizzotti Brian D. , Everett Allen D. , Packard Alan B. , Dearling Jason , Nedder Arthur G. , Warfield Simon , Yang Edward , Lidov Hart G. W. , Kheir John N. , Peng Yifeng 
Published: October 2024

AbstractAcute respiratory failure can cause profound hypoxaemia that leads to organ injury or death within minutes. When conventional interventions are ineffective, the intravenous administration of oxygen can rescue patients from severe hypoxaemia, but at the risk of microvascular obstruction and of toxicity of the carrier material. Here we describe polymeric microbubbles as carriers of high volumes of oxygen (350–500 ml of oxygen per litre of foam) that are stable in storage yet quickly dissolve following intravenous injection, reverting to their soluble and excretable molecular constituents. In swine with profound hypoxaemia owing to acute and temporary (12 min) upper-airway obstruction, the microbubble-mediated delivery of oxygen led to: the maintenance of critical oxygenation, lowered burdens of cardiac arrest, improved survival, and substantially improved neurologic and kidney function in surviving animals. Our findings underscore the importance of maintaining a critical threshold of oxygenation and the promise of injectable oxygen as a viable therapy in acute and temporary hypoxaemic crises.
Image processing tools for petabyte-scale light sheet microscopy data
Authors: Ruan Xiongtao , Mueller Matthew , Liu Gaoxiang , Görlitz Frederik , Fu Tian-Ming , Milkie Daniel E. , Lillvis Joshua L. , Kuhn Alexander , Gan Chong Johnny , Hong Jason Li , Herr Chu Yi Aaron , Hercule Wilmene , Nienhaus Marc , Killilea Alison N. , Betzig Eric , Upadhyayula Srigokul 
Published: October 2024

AbstractLight sheet microscopy is a powerful technique for high-speed three-dimensional imaging of subcellular dynamics and large biological specimens. However, it often generates datasets ranging from hundreds of gigabytes to petabytes in size for a single experiment. Conventional computational tools process such images far slower than the time to acquire them and often fail outright due to memory limitations. To address these challenges, we present PetaKit5D, a scalable software solution for efficient petabyte-scale light sheet image processing. This software incorporates a suite of commonly used processing tools that are optimized for memory and performance. Notable advancements include rapid image readers and writers, fast and memory-efficient geometric transformations, high-performance Richardson–Lucy deconvolution and scalable Zarr-based stitching. These features outperform state-of-the-art methods by over one order of magnitude, enabling the processing of petabyte-scale image data at the full teravoxel rates of modern imaging cameras. The software opens new avenues for biological discoveries through large-scale imaging experiments.
Diverse rhizosphere-associated Pseudomonas genomes from along a Wadden Island salt marsh transition zone
Authors: Mei Siyu , Wang Miao , Salles Joana Falcão , Hackl Thomas 
Published: October 2024

AbstractSoil microbes are key drivers of ecosystem processes promoting nutrient cycling, system productivity, and resilience. While much is known about the roles of microbes in established systems, their impact on soil development and the successional transformation over time remains poorly understood. Here, we provide 67 diverse, rhizosphere-associated Pseudomonas draft genomes from an undisturbed salt march primary succession spanning >100 years of soil development. Pseudomonas are cosmopolitan bacteria with a significant role in plant establishment and growth. We obtained isolates associated with Limonium vulgare and Artemisia maritima, two typical salt marsh perennial plants with roles in soil stabilization, salinity regulation, and biodiversity support. We anticipate that our data, in combination with the provided physiochemical measurements, will help identify genomic signatures associated with the different selective regimes along the successional stages, such as varying soil complexity, texture, and nutrient availability. Such findings would advance our understanding of Pseudomonas’ role in natural soil ecosystems and provide the basis for a better understanding of the roles of microbes throughout ecosystem transformations.
Unraveling the relative abundance of psychobiotic bacteria in children with Autism Spectrum Disorder
Authors: Darwesh Mennat-Allah K. , Bakr Wafaa , Omar Tarek E. I. , El-Kholy Mohammed A. , Azzam Nashwa Fawzy 
Published: October 2024

AbstractAutism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits. Accumulated evidence has shown a link between alterations in the composition of gut microbiota and both neurobehavioural and gastrointestinal symptoms in children with ASD which are related to the genera Lactobacillus and Bifidobacterium. These genera have been recently categorized as “psychobiotics”. Moreover, this study aimed to compare the relative abundance of psychobiotics (L. plantarum, L. reuteri, and B. longum) to the total gut microbiome in typically developing (TD) children and those with ASD in order to correlate the distribution of psychobiotic with the severity and sensory impairments in autism. The ASD children were assessed using the Childhood Autism Rating Scale (CARS), while sensory impairments were evaluated using the Short Sensory Profile (SSP). Furthermore, the gut microbiome was analyzed using the quantitative real-time PCR. The study revealed a statistically significant increase in the relative abundance of L. reuteri and L. plantarum in the TD group in comparison to ASD children. Regarding the SSP total score of ASD children, a statistically significant negative correlation was found between both Lactobacillus and L. plantarum with the under-responsive subscale. For the Autism Treatment Evaluation Checklist (ATEC) score, B. longum and Lactobacillus showed a significant positive correlation with Health/Physical/Behaviour.
Exploring the properties of antituberculosis drugs through QSPR graph models and domination-based topological descriptors
Authors: S Thilsath Parveen , Bommahalli Jayaraman Balamurugan , Siddiqui Muhammad Kamran 
Published: October 2024

AbstractTuberculosis (TB) is a global health concern caused by the bacterium Mycobacterium tuberculosis. This infectious disease primarily affects the lungs but can also impact other organs. Effective TB control involves early diagnosis, appropriate treatment with a combination of antibiotics, and public health measures to prevent transmission. However, ongoing challenges include drug-resistant strains and socioeconomic factors influencing its prevalence. Drugs such as isoniazid, pyrazinamide, ethambutol, ethionamide, linezolid, and levofloxacin are approved for the treatment of drug-susceptible tuberculosis. The properties and other activities of the drug, can be analyzed by modelling its chemical structure in terms of a molecular graph $$G=\left(V,E\right)$$, by considering the atoms as the vertex set $$V\left(G\right)$$ and the bonds between the two atoms as the edge set $$E\left(G\right)$$. A molecular descriptor or topological index of $$G$$ represents the corresponding chemical molecule as a numerical value. Domination is one of the key concepts in the molecular structure used to analyze the properties of atoms. In this article, the domination distance-based topological indices of the drugs isoniazid, pyrazinamide, ethambutol, ethionamide, linezolid, and levofloxacin are computed to conduct QSPR (Quantitative Structure–Property Relationship) analysis, exploring their physicochemical and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. Quadratic regression is then used in the QSPR analysis to examine the physicochemical and ADMET properties of these drugs. The results of this analysis indicate that the domination Schultz index and domination SM index are the indices most strongly correlated with the majority of the physicochemical and ADMET properties. The QSPR analysis can also be extended to analogs of these drugs and to other treatment drugs, such as rifampin and rifapentine, to further explore their properties.
Identification of shared gene expression programs activated in multiple modes of torpor across vertebrate clades
Authors: Weir Kurt , Vega Natasha , Busa Veronica F. , Sajdak Ben , Kallestad Les , Merriman Dana , Palczewski Krzysztof , Carroll Joseph , Blackshaw Seth 
Published: October 2024

AbstractTorpor encompasses diverse adaptations to extreme environmental stressors such as hibernation, aestivation, brumation, and daily torpor. Here we introduce StrokeofGenus, an analytic pipeline that identifies distinct transcriptomic states and shared gene expression patterns across studies, tissues, and species. We use StrokeofGenus to study multiple and diverse forms of torpor from publicly-available RNA-seq datasets that span eight species and two classes. We identify three transcriptionally distinct states during the cycle of heterothermia: euthermia, torpor, and interbout arousal. We also identify torpor-specific gene expression patterns that are shared both across tissues and between species with over three hundred million years of evolutionary divergence. We further demonstrate the general sharing of gene expression patterns in multiple forms of torpor, implying a common evolutionary origin for this process. Although here we apply StrokeofGenus to analysis of torpor, it can be used to interrogate any other complex physiological processes defined by transient transcriptomic states.
Evolution of mechanical properties of organic-rich shale during thermal maturation
Authors: Wang Jianfeng , Liu Dayong , Shi Jianfei , Yang Chao , Liu Yuke , Wang Guozhi , Guo Huijuan , Liu Peng , Xiong Yongqiang , Peng Ping’an 
Published: October 2024

AbstractAccurate assessment of the mechanical properties of organic matter, clay matrix, and bulk shale during maturation remains a challenge. Here, we aim to assess the mechanical properties of organic-rich shale during maturation using a combination of nanoindentation methods and various geochemical analyses, i.e., mineral composition, mass loss rate, chemical structure of organic matter, and Rock-Eval analyses. Results show that the evolution of mechanical properties of organic matter in shale during maturation can be divided into: the main oil-generation stage, and the condensate oil and gas generation stage. The stiffening of organic matter in the shale is mainly due to increased aromaticity and condensation of aromatic groups. The clay matrix experiences a slight decrease in hardness and Young’s modulus at low maturity levels due to the generation of liquid hydrocarbons. However, overall, the clay matrix becomes stiffer as the shale matures due to shale dehydration, expulsion or cracking of liquid hydrocarbons, transformation of clay minerals, and hardening of organic matter. The Young’s modulus and hardness of bulk shale generally increase with increasing maturity. This is closely related to the hardening of organic matter and clay matrix, as well as the development of the more compact and dense microstructure in the shale.
A systematic review and meta-analysis of GFAP gene variants in Alexander disease
Authors: Grossi Alice , Rosamilia Francesca , Carestiato Silvia , Salsano Ettore , Ceccherini Isabella , Bachetti Tiziana 
Published: October 2024

AbstractAlexander disease (ALXDRD) is a rare neurodegenerative disorder of astrocytes resulting from pathogenic variants in the GFAP gene. The genotype-phenotype correlation remains elusive due to the variable expressivity of clinical manifestations. In an attempt to clarify the effects of GFAP variants in ALXDRD, numerous studies were collected and analyzed. In particular, we systematically searched for GFAP variants associated with ALXDRD and collected information on the location within the gene and protein, prediction of deleteriousness/pathogenicity, occurrence, sex and country of origin of patients, DNA source, genetic testing, and clinical signs. To identify possible associations, statistical analyses and meta-analyses were applied, thus revealing a higher than expected percentage of adult patients with ALXDRD. Furthermore, substitution of Arginine, the most frequently altered residue among the 550 predominantly missense causative GFAP variants collected, were mostly de novo and more prevalent in early-onset forms of ALXDRD. The effect of defective splicing in modifying the impact of GFAP variants on the age of onset of ALXDRD was also postulated after evaluating the distribution of the corresponding deleterious predictive values. In conclusion, not only previously unrecognized genotype-phenotype correlations were revealed in ALXDRD, but also subtle mechanisms could explain the variable manifestations of the ALXDRD clinical phenotype.
A randomized clinical trial testing digital mindset intervention for knee osteoarthritis pain and activity improvement
Authors: Boswell Melissa A. , Evans Kris M. , Ghandwani Disha , Hastie Trevor , Zion Sean R. , Moya Paula L. , Giori Nicholas J. , Hicks Jennifer L. , Crum Alia J. , Delp Scott L. 
Published: October 2024

AbstractThis randomized clinical trial evaluated the effectiveness of short, digital interventions in improving physical activity and pain for individuals with knee osteoarthritis. We compared a digital mindset intervention, focusing on adaptive mindsets (e.g., osteoarthritis is manageable), to a digital education intervention and a no-intervention group. 408 participants with knee osteoarthritis completed the study online in the US. The mindset intervention significantly improved mindsets compared to both other groups (P < 0.001) and increased physical activity levels more than the no-intervention group (mean = 28.6 points, P = 0.001), but pain reduction was not significant. The mindset group also showed significantly greater improvements in the perceived need for surgery, self-imposed physical limitations, fear of movement, and self-efficacy than the no-intervention and education groups. This trial demonstrates the effectiveness of brief digital interventions in educating about osteoarthritis and further highlights the additional benefits of improving mindsets to transform patients’ approach to disease management. The study was prospectively registered (ClinicalTrials.gov: NCT05698368, 2023-01-26).
Insights into the cotranscriptional and translational control mechanisms of the Escherichia coli tbpA thiamin pyrophosphate riboswitch
Authors: Grondin Jonathan P. , Geffroy Mélanie , Simoneau-Roy Maxime , Chauvier Adrien , Turcotte Pierre , St-Pierre Patrick , Dubé Audrey , Moreau Julie , Massé Eric , Penedo J. Carlos , Lafontaine Daniel A. 
Published: October 2024

AbstractRiboswitches regulate gene expression by modulating their structure upon metabolite binding. These RNA orchestrate several layers of regulation to achieve genetic control. Although Escherichia coli riboswitches modulate translation initiation, several cases have been reported where riboswitches also modulate mRNA levels. Here, we characterize the regulation mechanisms of the thiamin pyrophosphate (TPP) tbpA riboswitch in E. coli. Our results indicate that the tbpA riboswitch modulates both levels of translation and transcription and that TPP sensing is achieved more efficiently cotranscriptionally than post-transcriptionally. The preference for cotranscriptional binding is also observed when monitoring the TPP-dependent inhibition of translation initiation. Using single-molecule approaches, we observe that the aptamer domain freely fluctuates between two main structures involved in TPP recognition. Our results suggest that translation initiation is controlled through the ligand-dependent stabilization of the riboswitch structure. This study demonstrates that riboswitch cotranscriptional sensing is the primary determinant in controlling translation and mRNA levels.