bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAF6 signaling in T cells is crucial for the pathogenicity of experimental autoimmune encephalomyelitis
Authors: Kamiyama Naganori , Saechue Benjawan , Sachi Nozomi , Dewayani Astri , Chalalai Thanyakorn , Ozaka Sotaro , Ariki Shimpei , Soga Yasuhiro , Kagoshima Yomei , Ekronarongchai Supanuch , Hidano Shinya , Kobayashi Takashi 
Published: December 2023

Abstract
Multiple sclerosis (MS) is an incurable chronic autoimmune disease affecting the central nervous system (CNS). Although IL-17-producing helper T (Th17) cells are thought to be one of the exacerbating factors in MS, the underlying pathogenic mechanism is incompletely understood. TNF receptor-associated factor 6 (TRAF6) deficient T cells exhibited enhanced Th17 cell differentiation, however, the physiological relevance of TRAF6 in T cells remains unknown. Here, we induced experimental autoimmune encephalomyelitis (EAE) in T cell-specific TRAF6 deficient (TRAF6ΔT) mice to investigate the role of TRAF6 in T cells during the course of MS using an EAE model. Although Th17 cell differentiation was enhanced in TRAF6ΔT mice, mutant mice were resistant to EAE. In contrast, TRAF6 loss did not affect regulatory T-cell differentiation. Consistent with the severity of EAE, a small number of infiltrating T cells and a small area of demyelination were observed in the CNS of TRAF6ΔT mice. Moreover, myelin oligodendrocyte glycoprotein-induced IL-17 production in TRAF6-deficient T cells was significantly suppressed. We further confirmed lower levels of CD69 and granulocyte-macrophage colony-stimulating factor in Th17 cells of TRAF6ΔT mice than in wild-type mice. In contrast, the expression of IL-10 and cytotoxic T-lymphocyte-associated protein 4 in T cells was significantly elevated in the absence of TRAF6 because of enhanced T-cell receptor signaling. Collectively, TRAF6 signaling in T cells contributes to the pathogenesis of EAE by regulating the pathogenicity and autoantigen reactivity of Th17 cells.
GRB 201015A: from seconds to months of optical monitoring and supernova discovery
Authors: Belkin S , Pozanenko A S , Minaev P Y , Pankov N S , Volnova A A , Rossi A , Stratta G , Benetti S , Palazzi E , Moskvitin A S , Burhonov O , Rumyantsev V V , Klunko E V , Inasaridze R Ya , Reva I V , Kim V , Jelinek M , Kann D A , Volvach A E , Volvach L N , Xu D , Zhu Z , Fu S , Mkrtchyan A A 
Published: December 2023

ABSTRACT
We present full photometric coverage and spectroscopic data for soft gamma-ray burst GRB 201015A with a redshift z = 0.426. Our data span a time range of 85 d following the detection of GRB. These observations revealed an underlying supernova SN 201015A with a maximum at 8.54 ± 1.48 d (rest frame) and an optical peak absolute magnitude $-19.45_{-0.47}^{+0.85}$ mag. The SN stands out clearly, since the contribution of the afterglow at this time is not dominant, which made it possible to determine SN’s parameters. A comparison of these parameters reveals that the SN 201015A is the earliest (the minimum Tmax) known SN associated with GRBs. Spectroscopic observations during the SN decay stage showed broad lines, indicating a large photospheric velocity, and identified this SN as a Type Ic-BL. Thus, the SN 201015A associated with the GRB 201015A becomes the 27th SN/GRB confirmed by both photometric and spectroscopic observations. Using the results of spectral analysis based on the available data of Fermi-GBM experiment, the parameters Ep,i = 20.0 ± 8.5 keV and Eiso = (1.1 ± 0.2) × 1050 erg were obtained. According to the position of the burst on the Ep,i–Eiso correlation, GRB 201015A was classified as a type II (long) GRB, which was also confirmed by the T90,i–EH diagram.
Long-term and Landmark Analysis of Transcatheter versus Surgical Aortic-Valve Replacement in Severe Aortic Stenosis
Authors: Zhang Xiaowen , Kang Lina , Wang Lian , Wang Kun , Xu Wei , Xu Biao , Zhang Xinlin 
Published: December 2023

AbstractBackgroundPrevious reports of long-term outcomes of TAVR focus on higher risk patients and suggest potential temporal changes. The indications of TAVR have expanded to low-risk patients. We aimed to evaluate the long-term and temporal performances of transcatheter aortic valve replacement (TAVR) compared to surgical aortic valve replacement (SAVR).MethodsRandomized controlled trials reporting outcomes with at least 1-year follow-up were included. The primary outcome was the composite of all-cause death or disabling stroke.ResultsWe included 8 trials with 8,749 patients. TAVR was associated with a higher risk of long-term (5-year) primary outcome compared to SAVR among higher-risk (odds ratio [OR], 1.25; 95% CI, 1.07–1.47) but not lower-risk participants (1.0 [0.77–1.29]). However, a significant temporal interaction was detected in both risk profiles. TAVR with balloon-expandable valves was associated with a higher risk of long-term primary outcome compared to SAVR (1.38 [1.2–1.6]), whereas no statistical difference was found with self-expanding valves (1.03 [0.89–1.19]). There was a significant interaction between the two valve systems, and a temporal interaction was detected in both systems. Overall landmark analysis revealed a lower risk in TAVR within the initial 30 days (0.76 [0.6, 0.96]), comparable between 30 days to 2 years (1.04 [0.85, 1.28]), and higher beyond 2 years (1.36 [1.15– 1.61]). Analysis for all-cause death generated largely similar results.ConclusionsTAVR was associated with a higher long-term risk of primary outcome compared to SAVR in higher-risk patients and with balloon-expandable valves. However, a characteristic temporal interaction was documented in all subgroups. Future studies are warranted to test these findings.
Learning the fitness dynamics of pathogens from phylogenies
Authors: Lefrancq Noémie , Duret Loréna , Bouchez Valérie , Brisse Sylvain , Parkhill Julian , Salje Henrik 
Published: December 2023

AbstractThe dynamics of pathogen genetic diversity, including the emergence of lineages with increased fitness, is a foundational concept of disease ecology with key public health implications. However, the identification of distinct lineages and estimation of associated fitness remain challenging, and are rarely done outside densely sampled systems. Here, we present a scalable framework that summarizes changes in population composition in phylogenies, allowing for the automatic detection of lineages based on shared fitness and evolutionary relationships. We apply our approach to a broad set of viruses and bacteria (SARS-CoV-2, H3N2 influenza,Bordetella pertussisandMycobacterium tuberculosis)and identify previously undiscovered lineages, as well as specific amino acid changes linked to fitness changes, the findings of which are robust to uneven and limited observation. This widely-applicable framework provides an avenue to monitor evolution in real-time to support public health action and explore fundamental drivers of pathogen fitness.One sentence summaryUsing an agnostic framework we shed light on changes in population composition in phylogenetic trees, allowing for the automatic detection of circulating lineages and estimation of fitness dynamics.
Dengue Virus Serotype 2 Cosmopolitan C Genotype Reemerges with a New Subclade in Southwest Region of Bangladesh
Authors: Setu Md. Ali Ahasan , Das Prosanto Kumar , Ahammed Toukir , Saha Shuvo , Hasan Adib , Kumar P K Shishir , Das Samiran , Ahamed Tanvir , Hossain KM Amran , Al-Emran Hassan M. , Hossain M. Anwar , Jahid Iqbal Kabir 
Published: December 2023

AbstractIn 2023, the Dengue virus (DENV) outbreak infected over 0.3 million cases and 1500 deaths in Bangladesh. Although the the serotype and genotype data were unavailable. Our study conducted serotyping and genomic surveillance in four districts of Southwest Bangladesh between September and October 2023. The surveillance data from 2019 to 2023 extracted from the Directorate General of Health Services in Bangladesh indicated a significant increase of Dengue infections in 2023, particularly during September-November. The two-layered hypothesis examination confirmed that, despite endemic months, 2023 dengue outbreak had a higher morbidity rate compared to previous years (2019-2022) in Southwest of Bangladesh. Serotyping and E gene sequence analysis of 25 randomly selected positive samples reveals that DENV-2 was the sole serotype circulating in this region during the study period. Genomic analysis exposed a new subclade of DENV-2, classified under Cosmopolitan genotype within C clade, distinct from previous years Bangladeshi variants until 2022. This subclade, possibly migrating from India, might be emerged during COVID-19 pandemic years and exhibited higher morbidity rates, thus challenging our existing mitigation strategies. This investigation provides valuable insights for public health interventions and underscores the importance of continuous genomic surveillance in managing Dengue outbreaks.
Single-cell transcriptomics reveals cellular hierarchies and aberrant CTS contraction-mediated premature hair regression in androgenetic alopecia
Authors: Li Guo , Yang Li , Duan Shixin , Chen Mengting , Zhang Yujin , Liu Fangfen , Tang Yan , Wang Yunying , Li Jiayun , Xu San , Wu Zheng , Wang Ben , Zhao Zhixiang , Shi Wei , Xie Hongfu , Deng Zhili , Li Ji 
Published: December 2023

AbstractAndrogenetic alopecia (AGA) is characterized by progressive miniaturization of hair, forming a distinctive patterned baldness in the scalp; yet, the mechanisms for hair miniaturization in this disease remain largely unknown. Here by single-cell transcriptome analysis, we describe a concise single-cell atlas, and identify the early changes in cell subpopulations, hair follicle (HF) stem cell fate determination and cell-cell communications in AGA anagen HF units. Thereinto, apoptotic loss of HF progenitor cells is significantly increased, correlated with HF miniaturization in AGA. Mechanistically, enhanced contraction of connective tissue sheath (CTS) activates the mechanosensitive channel PIEZO1, which triggers ectopic apoptosis of progenitor cells in human anagen HFs. Continuous CTS contraction during AGA causes long-term loss of progenitor cells via inducing persistent ectopic apoptosis through PIEZO1, eventually leading to premature hair regression. Most importantly, we show that targeting CTS contraction by ML-7, a selective myosin light chain kinase (MLCK) inhibitor, can obviously improve the growth of HFs from balding scalps of AGA patients. Our study reveals the cellular hierarchies and identifies CTS with increased muscle contraction activity as a driver of premature hair regression in AGA, highlighting CTS surrounding human HF as the therapeutic target for treating this disorder.
Identifying behavioral links to neural dynamics of multifiber photometry recordings in a mouse social behavior network
Authors: Chen Yibo , Chien Jonathan , Dai Bing , Lin Dayu , Chen Zhe Sage 
Published: December 2023

SUMMARYDistributed hypothalamic-midbrain neural circuits orchestrate complex behavioral responses during social interactions. How population-averaged neural activity measured by multi-fiber photometry (MFP) for calcium fluorescence signals correlates with social behaviors is a fundamental question. We propose a state-space analysis framework to characterize mouse MFP data based on dynamic latent variable models, which include continuous-state linear dynamical system (LDS) and discrete-state hidden semi-Markov model (HSMM). We validate these models on extensive MFP recordings during aggressive and mating behaviors in male-male and male-female interactions, respectively. Our results show that these models are capable of capturing both temporal behavioral structure and associated neural states. Overall, these analysis approaches provide an unbiased strategy to examine neural dynamics underlying social behaviors and reveals mechanistic insights into the relevant networks.
High spatiotemporal resolution radial encoding single vessel fMRI
Authors: Jiang Yuanyuan , Pais-Roldán Patricia , Pohmann Rolf , Yu Xin 
Published: December 2023

AbstractHigh-field preclinical functional MRI (fMRI) has enabled the high spatial resolution mapping of vessel-specific hemodynamic responses, i.e. single-vessel fMRI. In contrast to investigating neuronal sources of the fMRI signal, single vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI has hindered hemodynamic mapping of intracortical microvessels. Here, we implemented the radial encoding MRI scheme to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel-specific functional mapping with 50×50 µm in-plane resolution at 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro-venules, the radial encoding-based single-vessel fMRI enables the differentiation of the intravascular and extravascular effects from the draining venules.
Vision rescue via chemically engineered endogenous retinal ganglion cells
Authors: Shoaib Rana Muhammad , Sandrosyan Aregnazan , Mahato Biraj 
Published: December 2023

AbstractLoss of retinal ganglion cells (RGCs) is the final common end point for many optic neuropathies, ultimately leading to irreversible vision loss. Endogenous RGC regeneration from Müller cells presents a promising approach to treat these diseases, but mammalian retinas lack regenerative capacity. Here, we report a small molecule cocktail that causes endogenous Müller cell proliferation, migration, and specification to newly generated chemically induced RGCs (CiRGCs) in NMDA injured mice retina. Notably, regenerated CiRGCs extend axons towards optic nerve, and rescue vision post-NMDA treatment. Moreover, we successfully reprogrammed human primary Müller glia and fibroblasts into CiRGCs using this chemical-only approach, as evidenced by RGC-specific gene expression and chromatin signature. Additionally, we show that interaction between SOX4 and NF-kB determine CiRGC fate from Müller cells. We anticipate endogenous CiRGCs would have therapeutic potential in rescuing vision for optic nerve diseases.
TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43
Authors: Godoy-Corchuelo Juan M. , Ali Zeinab , Brito Armas Jose M. , Martins-Bach Aurea B. , García-Toledo Irene , Fernández-Beltrán Luis C. , López-Carbonero Juan I. , Bascuñana Pablo , Spring Shoshana , Jimenez-Coca Irene , Muñoz de Bustillo Alfaro Ramón A. , Sánchez-Barrena Maria J. , Nair Remya R. , Nieman Brian J. , Lerch Jason P. , Miller Karla L. , Ozdinler Hande P , Fisher Elizabeth M.C. , Cunningham Thomas J. , Acevedo-Arozena Abraham , Corrochano Silvia 
Published: December 2023

AbstractTDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as “TDP-43 proteinopathies”. Aggregates of TDP-43 are present in the brains and spinal cords of >97% of amyotrophic lateral sclerosis (ALS), and in brains of ∼50% of frontotemporal dementia (FTD) patients. While mutations in the TDP-43 gene (TARDBP) are usually associated with ALS, many clinical reports have linked these mutations to cognitive impairments and/or FTD, but also to other neurodegenerative disorders including Parkinsonism (PD) or progressive supranuclear palsy (PSP). TDP-43 is a ubiquitously expressed, highly conserved RNA-binding protein that is involved in many cellular processes, mainly RNA metabolism. To investigate systemic pathological mechanisms in TDP-43 proteinopathies, aiming to capture the pleiotropic effects of TDP-43 mutations, we have further characterised a mouse model carrying a point mutation (M323K) within the endogenousTardbpgene. Homozygous mutant mice developed cognitive and behavioural deficits as early as 3 months of age. This was coupled with significant brain structural abnormalities, mainly in the cortex, hippocampus, and white matter fibres, together with progressive cortical interneuron degeneration and neuroinflammation. At the motor level, progressive phenotypes appeared around 6 months of age. Thus, cognitive phenotypes appeared to be of a developmental origin with a mild associated progressive neurodegeneration, while the motor and neuromuscular phenotypes seemed neurodegenerative, underlined by a progressive loss of upper and lower motor neurons as well as distal denervation. This is accompanied by progressive elevated TDP-43 protein and mRNA levels in cortex and spinal cord of homozygous mutant mice from 3 months of age, together with increased cytoplasmic TDP-43 mislocalisation in cortex, hippocampus, hypothalamus, and spinal cord at 12 months of age. In conclusion, we find thatTardbpM323K homozygous mutant mice model many aspects of human TDP-43 proteinopathies, evidencing a dual role for TDP-43 in brain morphogenesis as well as in the maintenance of the motor system, making them an idealin vivomodel system to study the complex biology of TDP-43.
The Primary Cilium and its Hedgehog Signaling in Nociceptors Contribute to Inflammatory and Neuropathic Pain
Authors: Fitzsimons Lindsey A. , Staurengo-Ferrari Larissa , Bogen Oliver , Araldi Dioneia , Bonet Ivan J. M. , Jordan Ethan E. , Levine Jon D. , Tucker Kerry L. 
Published: December 2023

AbstractThe primary cilium, a 1-3 μm long hair-like structure protruding from the surface of almost all cells in the vertebrate body, is critical for neuronal development and also functions in the adult. As the migratory neural crest settles into dorsal root ganglia (DRG) sensory neurons elaborate a single primary cilium at their soma that is maintained into adult stages. While it is not known if primary cilia are expressed in nociceptors, or their potential function in the mature DRG neuron, recent studies have shown a role for Hedgehog, whose signaling demonstrates a dependence on primary cilia, in nociceptor sensitization. Here we report the expression of primary cilia in rat and mouse nociceptors, where they modulate mechanical nociceptive threshold, and contribute to inflammatory and neuropathic pain. When siRNA targetingIft88, a primary cilium-specific intra-flagellar transport (IFT) protein required for ciliary integrity, was administered by intrathecal injection, in the rat, it resulted in loss ofIft88mRNA in DRG, and primary cilia in neuronal cell bodies, which was associated with an increase in mechanical nociceptive threshold, and abrogation of hyperalgesia induced by the pronociceptive inflammatory mediator, prostaglandin E2, and painful peripheral neuropathy induced by a neurotoxic chemotherapy drug, paclitaxel. To provide further support for the role of the primary cilium in nociceptor function we also administered siRNA for another IFT protein,Ift52.Ift52 siRNA results in loss ofIft52 in DRG and abrogates paclitaxel-induced painful peripheral neuropathy. Attenuation of Hedgehog-induced hyperalgesia byIft88knockdown supports a role for the primary cilium in the hyperalgesia induced by Hedgehog, and attenuation of paclitaxel chemotherapy-induced neuropathy (CIPN) by cyclopamine, which attenuates Hedgehog signaling, suggests a role of Hedgehog in CIPN. Our findings support a role of nociceptor primary cilia in the control of mechanical nociceptive threshold and in inflammatory and neuropathic pain, the latter, at least in part, Hedgehog dependent.
Genetically encoded tool for manipulation of ΔΨm identifies the latter as the driver of integrative stress response induced by ATP Synthase dysfunction
Authors: Choe Mangyu , Titov Denis V. 
Published: December 2023

AbstractMitochondrial membrane potential (ΔΨm) is one of the key parameters controlling cellular bioenergetics. Investigation of the role of ΔΨm in live cells is complicated by a lack of tools for its direct manipulation without off-target effects. Here, we adopted the uncoupling protein UCP1 from brown adipocytes as a genetically encoded tool for direct manipulation of ΔΨm. We validated the ability of exogenously expressed UCP1 to induce uncoupled respiration and lower ΔΨm in mammalian cells. UCP1 expression lowered ΔΨm to the same extent as chemical uncouplers but did not inhibit cell proliferation, suggesting that it manipulates ΔΨm without the off-target effects of chemical uncouplers. Using UCP1, we revealed that elevated ΔΨm is the driver of the Integrated Stress Response induced by ATP synthase inhibition in mammalian cells.
Is there a neural common factor for visual illusions?
Authors: Jastrzębowska Maya A. , Ozkirli Ayberk , Cretenoud Aline F. , Draganski Bogdan , Herzog Michael H. 
Published: December 2023

AbstractIt is tempting to map interindividual variability in human perception to variability in brain structure or neural activity. Indeed, it has been shown that susceptibility to size illusions correlates with the size of primary visual cortex V1. Yet contrary to common belief, illusions correlate only weakly at the perceptual level, raising the question of how they can correlate with a localized neural measure. In addition, mounting evidence suggests that there is substantial interindividual variability not only in neural function and anatomy but also in the mapping between the two, which further challenges the findings of a neural common factor for illusions. To better understand these questions, here, we re-evaluated previous studies by correlating illusion strengths in a battery of 13 illusions with the size of visual areas and population receptive field sizes. We did not find significant correlations either at the perceptual level or between illusion susceptibility and visual functional neuroanatomy.
Numerical Simulation of Transdermal Delivery of Drug Nanocarriers Using Solid Microneedles
Authors: Newell Ben , Zhan Wenbo 
Published: December 2023

AbstractSolid microneedles can successfully puncture the stratum corneum and thus enable the drugs to migrate from the adhesive patch to the viable skin tissues for therapy. The treatment in different skin layers can vary greatly. However, how to improve its effectiveness remains less understood. In this study, numerical simulation is employed to predict the transport and disposition of drugs in each skin layer and blood using a skin model rebuilt from the real skin anatomical structure. The therapeutic effect is assessed by exposure to drugs over time. Results reveal the dominance of diffusion in determining the transport of nanosized drug carriers and free drugs in viable skin tissues. Delivery outcomes are highly sensitive to drug delivery system properties. Increasing the nanocarrier partition coefficient or diffusion coefficient in the skin can successfully enhance the treatment in entire skin tissue and blood. The enhancement can also be obtained by reducing the microneedle spacing or patch thickness. However, several properties should be optimised individually with respect to the target site’s location, including the microneedle length, diffusion coefficient of nanocarriers in the skin, drug release rate and nanocarrier vascular permeability. Drug concentrations in the blood can be effectively increased when administered to skin areas rich in capillaries; whereas, the treatment in the skin tissues slightly would reduce simultaneously. Furthermore, delivery results are insensitive to changes in lymphatic function and the properties of free drugs introduced by the medicated patch. These findings can be used to improve transdermal drug delivery for better treatment.