bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional survey of ovarian bacteriomes in the cereal weevil,Sitophilus oryzae, shows down-regulation of immune effectors at the onset of sexual maturity
Authors: Ferrarini Mariana Galvão , Vallier Agnès , Dell’Aglio Elisa , Balmand Séverine , Vincent-Monégat Carole , Debbache Mériem , Maire Justin , Parisot Nicolas , Zaidman-Rémy Anna , Heddi Abdelaziz , Rebollo Rita 
Published: February 2023

AbstractInsects often establish long-term relationships with intracellular symbiotic bacteria,i.e. endosymbionts, that provide them with essential nutrients such as amino acids and vitamins. Endosymbionts are typically confined within specialized host cells called bacteriocytes that may form an organ, the bacteriome. Compartmentalization within host cells is paramount for protecting the endosymbionts and also avoiding chronic activation of the host immune system. In the cereal weevilSitophilus oryzae, bacteriomes are present as a single organ at the larval foregut-midgut junction, and in adults, at the apex of midgut mesenteric caeca and at the apex of the four ovarioles. While the adult midgut endosymbionts experience a drastic proliferation during early adulthood followed by complete elimination through apoptosis and autophagy, ovarian endosymbionts are maintained throughout the weevil lifetime by unknown mechanisms. Bacteria present in ovarian bacteriomes are thought to be involved in the maternal transmission of endosymbionts through infection of the female germline, but the exact mode of transmission is not fully understood. Here, we show that endosymbionts are able to colonize the germarium in one-week-old females, pinpointing a potential infection route of oocytes. To identify potential immune regulators of ovarian endosymbionts, we have analyzed the transcriptomes of the ovarian bacteriomes through young adult development, from one-day-old adults to sexually mature ones. In contrast with midgut bacteriomes, immune effectors are downregulated in ovarian bacteriomes at the onset of sexual maturation. We hypothesize that relaxation of endosymbiont control by antimicrobial peptides might allow bacterial migration and potential oocyte infection, ensuring endosymbiont transmission.
Identification and characterization of a proliferative cell population in estrogen receptor-positive metastatic breast cancer through spatial and single-cell transcriptomics
Authors: Yoshitake Ryohei , Mori Hitomi , Ha Desiree , Wu Xiwei , Wang Jinhui , Wang Xiaoqiang , Saeki Kohei , Chang Gregory , Shim Hyun Jeong , Chan Yin , Chen Shiuan 
Published: February 2023

AbstractBackgroundIntratumor heterogeneity is a hallmark of most solid tumors, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing technologies to profile spatially resolved cell populations within estrogen receptor-positive (ER+) metastatic breast cancers and elucidate their importance in estrogen-dependent tumor growth.MethodsSpatial transcriptomics and single-cell RNA-sequencing were performed on two patient-derived xenografts (PDXs) of “ER-high” metastatic breast cancers with opposite estrogen-mediated growth responses: estrogen-suppressed GS3 (80–100% ER) and estrogen-stimulated SC31 (30–75% ER) models. The analyses included samples treated with and without 17β-estradiol. The findings were validated via scRNA-seq analyses on “ER-low” estrogen-accelerating PDX, GS1 (5% ER). The results from our spatial and single-cell analyses were further supported by the analysis of a publicly available single cell dataset and a protein-based dual immunohistochemical (IHC) evaluation using three important clinical markers [i.e., ER, progesterone receptor (PR), and Ki67]. The translational implication of these results was assessed by clinical outcome analyses on public breast cancer cohorts.ResultsOur novel space-gene-function study revealed a “proliferative” cell population in addition to three major spatially distinct compartments within ER+metastatic breast cancers. These compartments showed functional diversity (i.e., estrogen-responsive, proliferative, hypoxia-induced, and inflammation-related). The “proliferative (MKI67+)” population, not “estrogen-responsive” compartment, was crucial for estrogen-dependent tumor growth, leading to the acquisition of luminal B features. The cells with induction of typical estrogen-responsive genes such asPGRwere not directly linked to estrogen-dependent proliferation. Additionally, the dual IHC analyses demonstrated the distinct contribution of the Ki67+proliferative cells toward estrogen-mediated growth and their response to palbociclib, a CDK4/6 inhibitor. The gene signatures developed from the proliferative, hypoxia-induced, and inflammation-related compartments were significantly correlated with worse clinical outcomes, while patients with the high estrogen-responsive scores showed better prognosis, confirming that the estrogen-responsive compartment would not be directly associated with estrogen-dependent tumor progression.ConclusionsFor the first time, our study elucidated a “proliferative” cell population distinctly distributed in ER+metastatic breast cancers. They contribute differently toward progression of these cancers, and the gene signature in the “proliferative” compartment is an important determinant of luminal cancer subtypes.
Sterile triggers drive joint inflammation in TNF and IL-1β dependent mouse arthritis models
Authors: Thiran Alexandra , Petta Ioanna , Blancke Gillian , Thorp Marie , Plankaert Guillaume , Jans Maude , Andries Vanessa , Barbry Korneel , Hochepied Tino , Vanhove Christian , Gracey Eric , Dumas Emilie , Manuelo Teddy , Josipovic Ivan , van Loo Geert , Elewaut Dirk , Vereecke Lars 
Published: February 2023

AbstractArthritis is the most common extra-intestinal complication in inflammatory bowel disease (IBD). Conversely, arthritis patients are at risk for developing IBD and often display subclinical gut inflammation. These observations suggest a shared disease etiology, commonly termed ‘the gut-joint-axis’. The clinical association between gut and joint inflammation is further supported by the success of common therapeutic strategies and microbiota dysbiosis in both conditions. Most data however support a correlative relationship between gut & joint inflammation, while causative evidence is lacking. Using two independent transgenic mouse arthritis models, either TNF or IL1β dependent, we demonstrate that arthritis develops independently of the microbiota and intestinal inflammation, since both lines develop full-blown articular inflammation under germ-free conditions. In contrast, TNF-driven gut inflammation is fully rescued in germ-free conditions indicating that the microbiota is driving TNF-induced gut inflammation. Together, our study demonstrates that, although common inflammatory pathways may drive both gut and joint inflammation, the molecular triggers initiating such pathways are distinct in these tissues.
Epigenetic Regulation Explains The Functionality Behind Colon Cancer Specific Biomarker Septin9
Authors: Vizkeleti Laura , Kiss Csaba , Tisza Viktoria , Szigeti Aniko , Gellert Akos , Csabai Istvan , Pongor Lorinc S. , Spisak Sandor 
Published: February 2023

AbstractDespite advancements in early cancer detection and prevention methods, colorectal cancer (CRC) remains a significant global health problem. It is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Additionally, there has been a marked increase of incidence in young adults, and the reasons for this tendency are not fully understood. Therefore, the need for more effective diagnostic methods of assessing disease risk at early stage is crucial.One of the newly developed blood-based circulating biomarkers with promising potential is the short hypermethylated region located at the Septin9 intronic region. Several clinical studies have proven its performance and applicability. However, the molecular mechanism behind this consistent and recurrent feature present in most of the CRC and related precancerous stages and why it is specific and advantageous for CRC development are poorly understood.Here, we used comprehensive epigenetic and gene expression profile analyses from different sources of human clinical samples and cell line data to link specific hypermethylation events at the Septin9 intronic loci, which initiate alternative transcription of the Septin9 gene.Through our investigation of TCGA-COAD RNA-seq samples (n=287), we found that there was no significant difference in global Septin9 levels between normal and tumor samples. However, we did observe a significant alteration in the transcript variant ratio between v1 and v2, suggesting the use of an alternative promoter. Our findings were further supported by our analysis of ATAC-seq data, which revealed that the v2 promoter conferred higher chromatin accessibility, which correlated with the expression of the v2 isoform. However, this was not supported by promoter or enhancer activity as measured by H3K27ac signals. Hypermethylation at the v2 promoter was confirmed in tumor samples, providing a possible explanation for the switch in variants.Protein sequence analysis confirmed small differences between Septin9 variant ‘A’(v1) and ‘B’(v2). However, AlphaFold2 indicates a substantial difference at the N terminus, which could impact protein phosphorylation. We hypothesize, that variant ‘A’ (v1) and variant ‘B’ (v2) are required for normal cell functions but shifting the balance towards v1 is more favourable for the tumor.Although very little is known about Septin9 and its function in CRC biology, we are confident that our study will help to emphasize the importance of understanding regulatory mechanisms behind tumor-specific biomarkers and helps to improve the application.
Analysis of AlphaFold and molecular dynamics structure predictions of mutations in serpins
Authors: Garrido-Rodríguez Pedro , Carmena-Bargueño Miguel , de la Morena-Barrio María Eugenia , Bravo-Pérez Carlos , de la Morena-Barrio Belén , Cifuentes-Riquelme Rosa , Lozano María Luisa , Pérez-Sánchez Horacio , Corral Javier 
Published: February 2023

AbstractSerine protease inhibitors (serpins) include thousands of structurally conserved proteins playing key roles in many organisms. Mutations affecting serpins may disturb their conformation, leading to inactive forms. Unfortunately, conformational consequences of mutations affecting serpins are difficult to predict. In this study we integrate experimental data of patients with mutations affecting one serpin with the predictions obtained by AlphaFold and molecular dynamics. FiveSERPINC1mutations causing antithrombin deficiency, the strongest congenital thrombophilia, (p.Arg79Cys; p.Pro112Ser, p.Met283Val; p.Pro352insValPheLeuPro, and p.Glu241_Leu242delinsValLeuValLeuValAsnThrArgThr-Ser) were selected from a cohort of 350 unrelated patients based on functional, biochemical, and crystallographic evidence supporting a folding defect. AlphaFold gave an accurate prediction for the wild-type antithrombin structure. However, it only produced native structures for all variants, regardless of its complexity andin-vivoconformational consequences. Similarly, molecular dynamics of up to 1000 ns at temperatures that caused conformational transitions did not show significant changes in the native structure of wild-type or variants. In conclusion, one predictive tool of protein folding, AlphaFold, and a simulation method for analyzing the physical movements of atoms and molecules, molecular dynamics, force predictions into the native stressed conformation at conditions with experimental evidence supporting a conformational change to relaxed structures. It is necessary to improve predictive strategies for serpins that consider the conformational sensitivity of these molecules.
Cell-free multi-omics analysis reveals tumor status-informative signatures in gastrointestinal cancer patients’ plasma
Authors: Tao Yuhuan , Xing Shaozhen , Zuo Shuai , Bao Pengfei , Jin Yunfan , Li Yu , Wu Yingchao , Chen Shanwen , Wang Xiaojuan , Zhu Yumin , Feng Ying , Zhang Xiaohua , Wang Xianbo , Xi Qiaoran , Lu Qian , Wang Pengyuan , Lu Zhi John 
Published: February 2023

AbstractDuring cancer development, host’s tumorigenesis and immune signals are released to and informed by circulating molecules, like cell-free DNA (cfDNA) and RNA (cfRNA) in blood. However, these two kinds of molecules are still not systematically compared in gastrointestinal cancer. Here, we profiled 4 types of cell-free omics data from colorectal and stomach cancer patients, and assayed 15 types of genomic, epi-genomic, and transcriptomic variations. First, we demonstrated that the multi-omics data were more capable of detecting cancer genes than the single-omics data, where cfRNAs were more sensitive and informative than cfDNAs in terms of detection ratio, variation type, altered number, and enriched functional pathway. Moreover, we revealed several peripheral immune signatures that were suppressed in cancer patients and originated from specific circulating and tumor-microenvironment cells. Particularly, we defined a γδ-T-cell score and a cancer-associated-fibroblast (CAF) score using the cfRNA-seq data of 143 cancer patients. They were informative of clinical status like cancer stage, tumor size, and survival. In summary, our work reveals the cell-free multi-molecular landscape of colorectal and stomach cancer, and provides a potential monitoring utility in blood for the personalized cancer treatment.
Hmrbase2: A comprehensive database of hormones and their receptors
Authors: Kaur Dashleen , Arora Akanksha , Patiyal Sumeet , Raghava Gajendra Pal Singh 
Published: February 2023

AbstractBackground and objectiveHormones are essential for cell communication and hence regulate various physiological processes. The discrepancies in the hormones or their receptors can break this communication and cause major endocrinological disorders. It is, therefore, indispensable for the therapeutics and diagnostics of hormonal diseases.MethodsWe collected widespread information on peptide and non-peptide hormones and hormone receptors. The information was collected from HMDB, UniProt, HORDB, ENDONET, PubChem and literature.ResultsHmrbase2 is an updated version of Hmrbase. The current version contains a total of 12056 entries which is more than twice the entries in the previous version. These include 7406, 753, and 3897 entries for peptide hormones, non-peptide hormones and hormone receptors, respectively, from 803 organisms compared to the 562 organisms in the previous version. The database also hosts 5662 hormone receptor pairs. The source organism, function, and subcellular location are provided for peptide hormones and receptors and properties like melting point; water solubility is provided for non-peptide hormones. Besides browsing and keyword search, an advanced search option has also been provided. Additionally, a similarity search module has been incorporated, enabling users to run similarity searches against peptide hormone sequences using BLAST and Smith-Waterman.ConclusionsTo make the database accessible to various users, we designed a user-friendly, responsive website that can be easily used on smartphones, tablets, and desktop computers. The updated database version, Hmrbase2, offers improved data content compared to the previous version. Homebase 2.0 is freely available athttps://webs.iiitd.edu.in/raghava/hmrbase2.
A cortical mechanism linking saliency detection and motor reactivity in rhesus monkeys
Authors: Novembre Giacomo , Lacal Irene , Benusiglio Diego , Quarta Eros , Schito Andrea , Grasso Stefano , Caratelli Ludovica , Caminiti Roberto , Mayer Alexandra Battaglia , Iannetti Gian Domenico 
Published: February 2023

AbstractSudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFP) recorded from the dorso-lateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force: a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was maximal at the scalp vertex, in all respects similar to the human ‘vertex potential’. Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the EEG electrodes contralateral to the limb exerting force, and in the LFP recorded from deep rather than superficial cortical layers, suggesting a direct effect of the vertex potential on the motor output determining the behavior. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to salient sensory events.
scDecouple: Decoupling cellular response from infected proportion bias in scCRISPR-seq
Authors: Meng Qiuchen , Wei Lei , Ma Kun , Shi Ming , Lin Xinyi , Ho Joshua W. K. , Li Yinqing , Zhang Xuegong 
Published: February 2023

AbstractMotivationscCRISPR-seq is an emerging high-throughput CRISPR screening technology that combines CRISPR screening with single-cell sequencing technologies. It provides rich information on the mechanism of gene regulation. However, when scCRISPR-seq is applied in a population of heterogeneous cells, the true cellular response to perturbation is coupled with infected proportion bias of guide RNAs (gRNAs) across different cell clusters. The mixing of these effects introduces noise into scCRISPR-seq data analysis and thus obstacles to relevant studies.ResultsWe developed scDecouple to decouple true cellular response of perturbation from the influence of infected proportion bias. scDecouple first models the distribution of gene expression profiles in perturbed cells and then iteratively finds the maximum likelihood of cell cluster proportions as well as the cellular response for each gRNA. We demonstrated its performance in a series of simulation experiments. By applying scDecouple to real scCRISPR-seq data, we found that scDecouple enhances the identification of biologically perturbation-related genes. scDecouple can benefit scCRISPR-seq data analysis, especially in the case of heterogeneous samples or complex gRNA libraries.AvailabilityscDecouple is freely available athttps://github.com/MengQiuchen/scDecouple.Contactweilei92@tsinghua.edu.cn,yinqingl@tsinghua.edu.cn
Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health
Authors: Chen Keying , Cambi Franca , Kozai Takashi D.Y. 
Published: February 2023

AbstractIntracortical microelectrodes have become a useful tool in neuroprosthetic applications in the clinic and to understand neurological disorders in basic neurosciences. Many of these brain-machine interface technology applications require successful long-term implantation with high stability and sensitivity. However, the intrinsic tissue reaction caused by implantation remains a major failure mechanism causing loss of recorded signal quality over time. Oligodendrocytes remain an underappreciated intervention target to improve chronic recording performance. These cells can accelerate action potential propagation and provides direct metabolic support for neuronal health and functionality. However, implantation injury causes oligodendrocyte degeneration and leads to progressive demyelination in surrounding brain tissue. Previous work highlighted that healthy oligodendrocytes are necessary for greater electrophysiological recording performance and the prevention of neuronal silencing around implanted microelectrodes over chronic implantation. Thus, we hypothesize that enhancing oligodendrocyte activity with a pharmaceutical drug, Clemastine, will prevent the chronic decline of microelectrode recording performance. Electrophysiological evaluation showed that the promyelination Clemastine treatment significantly elevated the signal detectability and quality, rescued the loss of multi-unit activity, and increased functional interlaminar connectivity over 16-weeks of implantation. Additionally, post-mortem immunohistochemistry showed that increased oligodendrocyte density and myelination coincided with increased survival of both excitatory and inhibitory neurons near the implant. Overall, we showed a positive relationship between enhanced oligodendrocyte activity and neuronal health and functionality near the chronically implanted microelectrode. This study shows that therapeutic strategy that enhance oligodendrocyte activity is effective for integrating the functional device interface with brain tissue over chronic implantation period.Abstract Figure
Serial Capture Affinity Purification and Integrated Structural Modeling of the H3K4me3 Binding and DNA Damage Related WDR76:SPIN1 Complex
Authors: Liu Xingyu , Zhang Ying , Wen Zhihui , Hao Yan , Banks Charles A.S. , Lange Jeffrey J. , Cesare Joseph , Bhattacharya Saikat , Slaughter Brian D. , Unruh Jay R. , Florens Laurence , Workman Jerry L. , Washburn Michael P. 
Published: February 2023

ABSTRACTWDR76 is a multifunctional protein involved in many cellular functions. With a diverse and complicated protein interaction network, dissecting the structure and function of specific WDR76 complexes is needed. We previously demonstrated the ability of the Serial Capture Affinity Purification (SCAP) method to isolate specific complexes by introducing two proteins of interest as baits at the same time. Here, we applied SCAP to dissect a subpopulation of WDR76 in complex with SPIN1, a histone marker reader that specifically recognizes trimethylated histone H3 lysine4 (H3K4me3). In contrast to the SCAP analysis of the SPIN1:SPINDOC complex, H3K4me3 was copurified with the WDR76:SPIN1 complex. In combination with crosslinking mass spectrometry, we built an integrated structural model of the complex which revealed that SPIN1 recognized the H3K4me3 epigenetic mark while interacting with WDR76. Lastly, interaction network analysis of copurifying proteins revealed the potential role of the WDR76:SPIN1 complex in the DNA damage response.TeaserIn contrast to the SPINDOC/SPIN1 complex, analyses reveal that the WDR76/SPIN1 complex interacts with core histones and is involved in DNA damage.