FASEB bioAdvances最新文献_第5页

Gene expression analysis identifies hub genes and pathways distinguishing fatal from survivor outcomes of Ebola virus disease 基因表达分析确定了区分埃博拉病毒病致死与存活结果的枢纽基因和通路

IF 2.5

FASEB bioAdvances Pub Date : 2024-07-29 DOI: 10.1096/fba.2024-00055

Melvin Mensah-Bonsu, Christopher Doss, Clay Gloster, Perpetua Muganda

{"title":"Gene expression analysis identifies hub genes and pathways distinguishing fatal from survivor outcomes of Ebola virus disease","authors":"Melvin Mensah-Bonsu, Christopher Doss, Clay Gloster, Perpetua Muganda","doi":"10.1096/fba.2024-00055","DOIUrl":"https://doi.org/10.1096/fba.2024-00055","url":null,"abstract":"The Ebola virus poses a severe public health threat, yet understanding factors influencing disease outcomes remains incomplete. Our study aimed to identify critical pathways and hub genes associated with fatal and survivor Ebola disease outcomes. We analyzed differentially expressed hub genes (DEGs) between groups with fatal and survival outcomes, as well as a healthy control group. We conducted additional analysis to determine the functions and pathways associated with these DEGs. We found 13,198 DEGs in the fatal and 12,039 DEGs in the survival group compared to healthy controls, and 1873 DEGs in the acute fatal and survivor groups comparison. Upregulated DEGs in the comparison between the acute fatal and survivor groups were linked to ECM receptor interaction, complement and coagulation cascades, and PI3K-Akt signaling. Upregulated hub genes identified from the acute fatal and survivor comparison (FGB, C1QA, SERPINF2, PLAT, C9, SERPINE1, F3, VWF) were enriched in complement and coagulation cascades; the downregulated hub genes (IL1B, 1L17RE, XCL1, CXCL6, CCL4, CD8A, CD8B, CD3D) were associated with immune cell processes. Hub genes CCL2 and F2 were unique to fatal outcomes, while CXCL1, HIST1H4F, and IL1A were upregulated hub genes unique to survival outcomes compared to healthy controls. Our results demonstrate for the first time the association of EVD outcomes to specific hub genes and their associated pathways and biological processes. The identified hub genes and pathways could help better elucidate Ebola disease pathogenesis and contribute to the development of targeted interventions and personalized treatment for distinct EVD outcomes.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"298-310"},"PeriodicalIF":2.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mouse developmental defects, but not paraganglioma tumorigenesis, upon conditional Complex II loss in early Sox10+ cells 早期 Sox10+ 细胞中条件性复合体 II 缺失会导致小鼠发育缺陷，但不会导致副神经节瘤肿瘤发生

IF 2.5

FASEB bioAdvances Pub Date : 2024-07-24 DOI: 10.1096/fba.2024-00056

Elizabeth P. Lewis, Fatimah Al Khazal, Brandon Wilbanks, Naomi M. Gades, Patricia Ortega-Sáenz, José López-Barneo, Igor Adameyko, L. James Maher III

{"title":"Mouse developmental defects, but not paraganglioma tumorigenesis, upon conditional Complex II loss in early Sox10+ cells","authors":"Elizabeth P. Lewis, Fatimah Al Khazal, Brandon Wilbanks, Naomi M. Gades, Patricia Ortega-Sáenz, José López-Barneo, Igor Adameyko, L. James Maher III","doi":"10.1096/fba.2024-00056","DOIUrl":"10.1096/fba.2024-00056","url":null,"abstract":"In humans, loss of heterozygosity for defective alleles of any of the four subunits of mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH, also Complex II of the electron transport chain) can lead to paraganglioma tumors in neuroendocrine cells. With the goal of developing mouse models of this rare disorder, we have developed various SDH conditional loss strategies. Based on recent lineage tracing studies, we hypothesized that conditional SDHC loss in early embryogenesis during migration of primordial neural crest cells that form the susceptible chromaffin cells of the adrenal medulla might induce paraganglioma. We triggered low levels of detectable SDHC loss in Sox10+ cells at E11.5 of mouse development. We report that, rather than developing adrenal medulla paraganglioma (pheochromocytoma), offspring survived with evidence of neural crest cell dysfunction. Phenotypes included mild lower extremity gait anomalies suggestive of neural tube closure defects and patches of unpigmented fur consistent with neural crest-derived melanocyte dysfunction. These defects were not observed in mice lacking Sdhc knockout. Our results add to existing data suggesting that, unlike humans, even early embryonic (Sox10-driven) SDHx loss is inadequate to trigger paraganglioma in mice of the genetic backgrounds that have been investigated. Instead, low levels of tricarboxylic acid cycle-deficient neural crest cells cause mild developmental defects in hind limb and melanocyte function. This new model may be of interest for studies of metabolism during early neural crest cell development.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"327-336"},"PeriodicalIF":2.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141808605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reduction of pathological retinal neovascularization, vessel obliteration, and artery tortuosity by PEDF protein in an oxygen-induced ischemic retinopathy rat model 在氧气诱导的缺血性视网膜病变大鼠模型中，PEDF 蛋白可减少病理性视网膜新生血管、血管阻塞和动脉迂曲

IF 2.5

FASEB bioAdvances Pub Date : 2024-07-19 DOI: 10.1096/fba.2024-00059

Shiying Zhao, Alexander V. Tschulakow, Subha S. Karthikeyan, Kun Wang, Stefan Kochanek, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer

{"title":"Reduction of pathological retinal neovascularization, vessel obliteration, and artery tortuosity by PEDF protein in an oxygen-induced ischemic retinopathy rat model","authors":"Shiying Zhao, Alexander V. Tschulakow, Subha S. Karthikeyan, Kun Wang, Stefan Kochanek, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer","doi":"10.1096/fba.2024-00059","DOIUrl":"10.1096/fba.2024-00059","url":null,"abstract":"Retinopathy of prematurity (ROP) is a severe retinal disease in premature infants characterized by pathological neovascularization, obliteration of retinal vessels and increased vessel tortuosity. Currently, there are no completely satisfactory treatments for ROP. Pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, appears late in gestation and its deficiency may be linked to development of ROP. This study investigates the preclinical efficacy of PEDF protein alone or in combination with VEGF antagonists for treating ROP. The safety of PEDF protein in the rat eye was assessed using functional in vivo measurements and histology. The efficacy of intravitreal injections (IVI) of various treatments was evaluated in a rat oxygen-induced retinopathy (OIR) model using in vivo imaging and flatmount analyses. No functional or histological side-effects were found in rat eyes after intravitreal PEDF protein injection. PEDF protein alone or combined with anti-VEGF drugs significantly reduced pathological neovascularization and vessel obliteration, comparable to the effects of anti-VEGF drugs alone. Regarding arterial tortuosity, treatment with a combination of PEDF, and VEGF antagonist was more effective than treatment with anti-VEGF alone. IVI of PEDF protein is safe. PEDF protein alone or combined with VEGF antagonists shows similar efficacy in reducing pathological neovascularization and vessel obliteration as anti-VEGF agents. Furthermore, only treatments involving PEDF protein, alone or with VEGF antagonists, significantly improved the quality of retinal vasculature. Thus, PEDF protein alone or combined with anti-VEGF agents presents a promising alternative to current anti-VEGF treatments for ROP.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"311-326"},"PeriodicalIF":2.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxidative stress mediates nucleocytoplasmic shuttling of KPNA2 via AKT1-CDK1 axis-regulated S62 phosphorylation 氧化应激通过AKT1-CDK1轴调控的S62磷酸化介导KPNA2的核细胞质穿梭运动

IF 2.5

FASEB bioAdvances Pub Date : 2024-07-05 DOI: 10.1096/fba.2024-00078

Jie-Xin Huang, Chun-I Wang, Chia-Yu Kuo, Ting-Wei Chang, Yu-Chin Liu, Ting-Feng Hsiao, Chih-Liang Wang, Chia-Jung Yu

{"title":"Oxidative stress mediates nucleocytoplasmic shuttling of KPNA2 via AKT1-CDK1 axis-regulated S62 phosphorylation","authors":"Jie-Xin Huang, Chun-I Wang, Chia-Yu Kuo, Ting-Wei Chang, Yu-Chin Liu, Ting-Feng Hsiao, Chih-Liang Wang, Chia-Jung Yu","doi":"10.1096/fba.2024-00078","DOIUrl":"10.1096/fba.2024-00078","url":null,"abstract":"Karyopherin α 2 (KPNA2, importin α1), a transport factor shuttling between the nuclear and cytoplasmic compartments, is involved in the nuclear import of proteins and participates in cellular processes such as cell cycle regulation, apoptosis, and transcriptional regulation. However, it is still unclear which signaling regulates the nucleocytoplasmic distribution of KPNA2 in response to cellular stress. In this study, we report that oxidative stress increases nuclear retention of KPNA2 through alpha serine/threonine-protein kinase (AKT1)-mediated reduction of serine 62 (S62) phosphorylation. We first found that AKT1 activation was required for H2O2-induced nuclear accumulation of KPNA2. Immunoprecipitation and quantitative proteomic analysis revealed that the phosphorylation of KPNA2 at S62 was decreased under H2O2-induced oxidative stress. We showed that cyclin-dependent kinase 1 (CDK1), a kinase responsible for KPNA2 S62 phosphorylation, contributes to the localization of KPNA2 in the cytoplasm. AKT1 knockdown increased KPNA2 S62 phosphorylation and inhibited CDK1 activation. Furthermore, H2O2-induced AKT1 activation promoted nuclear KPNA2 interaction with nucleophosmin 1 (NPM1), resulting in attenuation of NPM1-mediated cyclin D1 gene transcription. Thus, we infer that the AKT1-CDK1 axis regulates the nucleocytoplasmic shuttling and function of KPNA2 through spatiotemporal regulation of KPNA2 S62 phosphorylation under oxidative stress conditions.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 8","pages":"276-288"},"PeriodicalIF":2.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141673676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Social defeat stress impairs systemic iron metabolism by activating the hepcidin–ferroportin axis 社会失败压力通过激活血红素-铁蛋白轴损害全身铁代谢

IF 2.5

FASEB bioAdvances Pub Date : 2024-07-02 DOI: 10.1096/fba.2024-00071

Emiko Kasahara, Ayumi Nakamura, Kenki Morimoto, Shiho Ito, Mika Hori, Atsuo Sekiyama

{"title":"Social defeat stress impairs systemic iron metabolism by activating the hepcidin–ferroportin axis","authors":"Emiko Kasahara, Ayumi Nakamura, Kenki Morimoto, Shiho Ito, Mika Hori, Atsuo Sekiyama","doi":"10.1096/fba.2024-00071","DOIUrl":"10.1096/fba.2024-00071","url":null,"abstract":"Chronic psychological stress has been reported to decrease circulating iron concentrations and impair hematopoiesis. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of psychological stress on biological iron metabolism by using the social defeat stress (SDS) model, a widely used model of depression. Compared with control mice, mice subjected to SDS (SDS mice) had lower social interaction (SI) behavior. The SDS mice also showed impaired hematopoiesis, as evidenced by reduced circulating red blood cell counts, elevated reticulocyte counts, and decreased plasma iron levels. In the SDS mice, the iron contents in the bone marrow decreased, whereas those in the spleen increased, suggesting dysregulation in systemic iron metabolism. The concentrations of plasma hepcidin, an important regulator of systemic iron homeostasis, increased in the SDS mice. Meanwhile, the concentrations of ferroportin, an iron transport protein negatively regulated by hepcidin, were lower in the spleen and duodenum of the SDS mice than in those of the control mice. Treatment with dalteparin, a hepcidin inhibitor, prevented the decrease in plasma iron levels in the SDS mice. The gene expression and enzyme activity of furin, which converts the precursor hepcidin to active hepcidin, were high and positively correlated with plasma hepcidin concentration. Thus, furin activation might be responsible for the increased plasma hepcidin concentration. This study is the first to show that psychological stress disrupts systemic iron homeostasis by activating the hepcidin–ferroportin axis. Consideration of psychological stressors might be beneficial in the treatment of diseases with iron-refractory anemia.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 8","pages":"263-275"},"PeriodicalIF":2.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141687049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages Tristetraprolin介导巨噬细胞对分枝杆菌感染的免疫逃避。

IF 2.5

FASEB bioAdvances Pub Date : 2024-06-29 DOI: 10.1096/fba.2024-00022

Jiawei Wei, Huan Ning, Octavio Ramos-Espinosa, Christopher S. Eickhoff, Rong Hou, Qinghong Wang, Mingui Fu, Ethan Y. Liu, Daping Fan, Daniel F. Hoft, Jianguo Liu

{"title":"Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages","authors":"Jiawei Wei, Huan Ning, Octavio Ramos-Espinosa, Christopher S. Eickhoff, Rong Hou, Qinghong Wang, Mingui Fu, Ethan Y. Liu, Daping Fan, Daniel F. Hoft, Jianguo Liu","doi":"10.1096/fba.2024-00022","DOIUrl":"10.1096/fba.2024-00022","url":null,"abstract":"Immune evasion of Mycobacterium tuberculosis (Mtb) facilitates intracellular bacterial growth. The mechanisms of immune evasion, however, are still not fully understood. In this study, we reveal that tristetraprolin (TTP), one of the best characterized RNA-binding proteins controlling the stability of targeted mRNAs, mediates innate immune evasion of mycobacteria. We found that TTP knockout mice displayed reduced bacterial burden in the early stage after Mtb aerosol challenge. Macrophages deficient in TTP also showed an inhibition in intracellular mycobacterial growth. Live mycobacteria induced TTP protein expression in macrophages, which was blocked by the mTOR inhibitor rapamycin. Rapamycin and AZD8055 specifically blocked 4EBP1 phosphorylation in infected macrophages and suppressed intracellular BCG growth. Rapamycin promoted TTP protein degradation through the ubiquitination pathway, whereas the proteasome inhibitor MG-132 blocked rapamycin function and thus stabilized TTP protein. TTP induction suppressed the expression of iNOS/TNF-α/IL-12/IL-23, and weakened protective immune responses in macrophages, whereas rapamycin enhanced the bactericidal effects through TTP inhibition. Moreover, blocking TTP binding increased the expression of TNF-α and iNOS and suppressed intracellular mycobacterial growth. Overall, our study reveals a novel role for RNA-binding protein TTP in Mtb immune evasion mechanisms and provides a potential target for host-directed therapy against tuberculosis (TB).","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 8","pages":"249-262"},"PeriodicalIF":2.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bactericidal human monoclonal antibody 1B1 shows specificity for meningococcal factor H binding protein variant 2 and displaces human factor H 杀菌人类单克隆抗体 1B1 对脑膜炎球菌因子 H 结合蛋白变体 2 具有特异性，并能取代人类因子 H。

IF 2.5

FASEB bioAdvances Pub Date : 2024-06-27 DOI: 10.1096/fba.2023-00077

Daniele Veggi, Chelsy C. Chesterman, Laura Santini, Ying Huang, Nicola Pacchiani, Jeannette Sierra, Lynn Chen, Jason Laliberte, Federica Bianchi, Roberta Cozzi, Elisabetta Frigimelica, Domenico Maione, Oretta Finco, Matthew J. Bottomley

{"title":"Bactericidal human monoclonal antibody 1B1 shows specificity for meningococcal factor H binding protein variant 2 and displaces human factor H","authors":"Daniele Veggi, Chelsy C. Chesterman, Laura Santini, Ying Huang, Nicola Pacchiani, Jeannette Sierra, Lynn Chen, Jason Laliberte, Federica Bianchi, Roberta Cozzi, Elisabetta Frigimelica, Domenico Maione, Oretta Finco, Matthew J. Bottomley","doi":"10.1096/fba.2023-00077","DOIUrl":"10.1096/fba.2023-00077","url":null,"abstract":"Thousands of disease cases and hundreds of deaths occur globally each year due to invasive meningococcal disease. Neisseria meningitidis serogroup B (MenB) is the leading cause of such disease in developed countries. Two vaccines, 4CMenB and MenB-fHbp, that protect against MenB are available and include one or two forms respectively of factor H binding protein (fHbp), a key protective antigen. Studies of circulating meningococci have identified over 1380 different fHbp amino acid sequences, which form three immunologically distinct clusters, termed variants 1, 2, and 3. Neither of the current vaccines contains a variant 2 antigen, which is less well characterized than fHbp variants 1 and 3. We characterized the interaction of fHbp variant 2 with humAb 1B1 using biochemical methods and live meningococcal assays. Further, we determined the crystal structure of the complex at 2.4 Å resolution, clearly revealing the epitope and providing the first detailed report of an antibody with distinct specificity for fHbp variant 2. Extensive mutagenesis and binding studies elucidated key hotspots in the interface. This combination of structural and functional studies provides a molecular explanation for the bactericidal potency and specificity of humAb 1B1 for fHbp variant 2. Our studies, focused on fHbp variant 2, expand the understanding of this previously under characterized group of the vast family of variants of fHbp, a virulence factor present on all meningococci. Moreover, the definition of a protective conformational epitope on fHbp variant 2 may support the design and development of novel variant 2-containing MenB vaccines affording greater breadth of protection.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 8","pages":"235-248"},"PeriodicalIF":2.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle PRLR基因编辑对牛耐热性、生长和雄性繁殖的影响

IF 2.5

FASEB bioAdvances Pub Date : 2024-06-18 DOI: 10.1096/fba.2024-00029

Camila J. Cuellar, Thiago F. Amaral, Paula Rodriguez-Villamil, F. Ongaratto, D. Onan Martinez, Rémi Labrecque, João D. de Agostini Losano, Eliab Estrada-Cortés, Jonathan R. Bostrom, Kyra Martins, D. Owen Rae, Jeremy Block, Quinn A. Hoorn, Bradford W. Daigneault, Jonathan Merriam, Michael Lohuis, Serdal Dikmen, João H. J. Bittar, Tatiane S. Maia, Daniel F. Carlson, Sabreena Larson, Tad S. Sonstegard, Peter J. Hansen

{"title":"Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle","authors":"Camila J. Cuellar, Thiago F. Amaral, Paula Rodriguez-Villamil, F. Ongaratto, D. Onan Martinez, Rémi Labrecque, João D. de Agostini Losano, Eliab Estrada-Cortés, Jonathan R. Bostrom, Kyra Martins, D. Owen Rae, Jeremy Block, Quinn A. Hoorn, Bradford W. Daigneault, Jonathan Merriam, Michael Lohuis, Serdal Dikmen, João H. J. Bittar, Tatiane S. Maia, Daniel F. Carlson, Sabreena Larson, Tad S. Sonstegard, Peter J. Hansen","doi":"10.1096/fba.2024-00029","DOIUrl":"10.1096/fba.2024-00029","url":null,"abstract":"Global warming is a major challenge to the sustainable and humane production of food because of the increased risk of livestock to heat stress. Here, the example of the prolactin receptor (PRLR) gene is used to demonstrate how gene editing can increase the resistance of cattle to heat stress by the introduction of mutations conferring thermotolerance. Several cattle populations in South and Central America possess natural mutations in PRLR that result in affected animals having short hair and being thermotolerant. CRISPR/Cas9 technology was used to introduce variants of PRLR in two thermosensitive breeds of cattle – Angus and Jersey. Gene-edited animals exhibited superior ability to regulate vaginal temperature (heifers) and rectal temperature (bulls) compared to animals that were not gene-edited. Moreover, gene-edited animals exhibited superior growth characteristics and had larger scrotal circumference. There was no evidence for deleterious effects of the mutation on carcass characteristics or male reproductive function. These results indicate the potential for reducing heat stress in relevant environments to enhance cattle productivity.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 8","pages":"223-234"},"PeriodicalIF":2.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerating the continuous community sharing of digital neuromorphology data 加速数字神经形态学数据的持续社区共享。

IF 2.5

FASEB bioAdvances Pub Date : 2024-06-17 DOI: 10.1096/fba.2024-00048

Carolina Tecuatl, Bengt Ljungquist, Giorgio A. Ascoli

{"title":"Accelerating the continuous community sharing of digital neuromorphology data","authors":"Carolina Tecuatl, Bengt Ljungquist, Giorgio A. Ascoli","doi":"10.1096/fba.2024-00048","DOIUrl":"10.1096/fba.2024-00048","url":null,"abstract":"The tree-like morphology of neurons and glia is a key cellular determinant of circuit connectivity and metabolic function in the nervous system of essentially all animals. To elucidate the contribution of specific cell types to both physiological and pathological brain states, it is important to access detailed neuroanatomy data for quantitative analysis and computational modeling. NeuroMorpho.Org is the largest online collection of freely available digital neural reconstructions and related metadata and is continuously updated with new uploads. Earlier in the project, we released multiple datasets together yearly, but this process caused an average delay of several months in making the data public. Moreover, in the past 5 years, >80% of invited authors agreed to share their data with the community via NeuroMorpho.Org, up from <20% in the first 5 years of the project. In the same period, the average number of reconstructions per publication increased 600%, creating the need for automatic processing to release more reconstructions in less time. The progressive automation of our pipeline enabled the transition to agile releases of individual datasets as soon as they are ready. The overall time from data identification to public sharing decreased by 63.7%; 78% of the datasets are now released in less than 3 months with an average workflow duration below 40 days. Furthermore, the mean processing time per reconstruction dropped from 3 h to 2 min. With these continuous improvements, NeuroMorpho.Org strives to forge a positive culture of open data. Most importantly, the new, original research enabled through reuse of datasets across the world has a multiplicative effect on science discovery, benefiting both authors and users.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 7","pages":"207-221"},"PeriodicalIF":2.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum 胆汁酸对小鼠回肠纵向平滑肌收缩力的不同调节作用

IF 2.5

FASEB bioAdvances Pub Date : 2024-06-17 DOI: 10.1096/fba.2024-00044

Peace N. Dike, Krishnakant G. Soni, Diana S. Chang, Geoffrey A. Preidis

{"title":"Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum","authors":"Peace N. Dike, Krishnakant G. Soni, Diana S. Chang, Geoffrey A. Preidis","doi":"10.1096/fba.2024-00044","DOIUrl":"10.1096/fba.2024-00044","url":null,"abstract":"Bile acids regulate gastrointestinal motility by mechanisms that are poorly understood. Standard isolated tissue bath assays might not recapitulate in vivo physiology if contractile responses to certain bile acids require direct application to the intestinal mucosa. We sought to determine the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids from intact segments of everted mouse ileum. Ileum from adult female C57BL/6J mice was isolated, gently everted over a notched metal rod, and mounted in tissue baths. Individual bile acids and agonists of bile acid receptors were added to the baths, and longitudinal smooth muscle contractile responses were quantified by isometric force transduction. Ursodeoxycholic acid robustly increased contractile responses in a dose-dependent manner. Deoxycholic acid stimulated contractility at low doses but inhibited contractility at high doses. Chenodeoxycholic acid, glycocholic acid, and lithocholic acid did not alter contractility. The dose-dependent increase in contractility resulting from the application of ursodeoxycholic acid was recapitulated by INT-777, an agonist of the Takeda G protein-coupled receptor 5 (TGR5), and by cevimeline, a muscarinic acetylcholine receptor agonist. Agonists to the nuclear receptors farnesoid X receptor, glucocorticoid receptor, pregnane X receptor, vitamin D receptor, and to the plasma membrane epidermal growth factor receptor did not modify baseline contractile patterns. These results demonstrate that gentle eversion of intact mouse ileum facilitates the quantification of longitudinal smooth muscle contractile responses to individual bile acids. Prokinetic effects of ursodeoxycholic acid and low-dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 7","pages":"200-206"},"PeriodicalIF":2.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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