scholarly journals Cell adhesion and immune response, two main functions altered in the transcriptome of seasonally regressed testes of two mammalian species

2022 ◽  
Author(s):  
Francisca M. Real ◽  
Miguel Lao-Perez ◽  
Miguel Burgos ◽  
Stefan Mundlos ◽  
Dario G. Lupianez ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Mammalian Species ◽  
Gene Expression Signature ◽  
Breeding Period ◽  
Seasonal Breeding ◽  
Analogous Data ◽  
Mediterranean Pine ◽  
Testis Regression

In species with seasonal breeding, male specimens undergo substantial testicular regression during the non-breeding period of the year. However, the molecular mechanisms that control this biological process are largely unknown. Here, we report a transcriptomic analysis on the Iberian mole, Talpa occidentalis, in which the desquamation of live, non-apoptotic germ cells is the major cellular event responsible for testis regression. By comparing testes at different reproductive states (active, regressing and inactive), we demonstrate that the molecular pathways controlling the cell adhesion function in the seminiferous epithelium, such as the MAPK, ERK and TGF-beta signalling, are altered during the regression process. In addition, inactive testes display a global upregulation of genes associated with immune response, indicating a selective loss of the immune privilege that normally operates in sexually active testes. Interspecies comparative analyses using analogous data from the Mediterranean pine vole, a rodent species where testis regression is controlled by halting meiosis entry, revealed a common gene expression signature in the regressed testes of these two evolutionary distant species. Our study advances in the knowledge of the molecular mechanisms associated to gonadal seasonal breeding, highlighting the existence of a conserved transcriptional program of testis involution across mammalian clades.

scholarly journals Mediterranean Pine Vole, Microtus duodecimcostatus: A Paradigm of an Opportunistic Breeder

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1639
Author(s):  
Miguel Lao-Pérez ◽  
Diaa Massoud ◽  
Francisca M. Real ◽  
Alicia Hurtado ◽  
Esperanza Ortega ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Geographic Area ◽  
Breeding Period ◽  
Functional Regression ◽  
The Earth ◽  
Poplar Plantations ◽  
Microtus Duodecimcostatus ◽  
Mediterranean Pine ◽  
Animal House ◽  
Testis Regression

Most mammalian species of the temperate zones of the Earth reproduce seasonally, existing a non-breeding period in which the gonads of both sexes undergo functional regression. It is widely accepted that photoperiod is the principal environmental cue controlling these seasonal changes, although several exceptions have been described in other mammalian species in which breeding depends on cues such as food or water availability. We studied the circannual reproductive cycle in males of the Mediterranean pine vole, Microtus duodecimcostatus, in the Southeastern Iberian Peninsula. Morphological, hormonal, functional, molecular and transcriptomic analyses were performed. As reported for populations of other species from the same geographic area, male voles captured in wastelands underwent seasonal testis regression in summer whereas, surprisingly, those living either in close poplar plantations or in our animal house reproduced throughout the year, showing that it is the microenvironment of a particular vole subpopulation what determines its reproductive status and that these animals are pure opportunistic, photoperiod-independent breeders. In addition, we show that several molecular pathways, including MAPK, are deregulated and that the testicular “immune privilege” is lost in the inactive testes, providing novel mechanisms linking seasonal testosterone reduction and testis regression.

Gene expression signature of exercise and change of diet on non-alcoholic fatty liver disease in mice

2021 ◽  
pp. 1-12
Author(s):  
L. Melo ◽  
A. Hagar ◽  
J.E. Klaunig
Keyword(s):  
Immune Response ◽  
Fatty Liver ◽  
Aerobic Exercise ◽  
Molecular Mechanisms ◽  
Exercise Intervention ◽  
Gene Expression Signature ◽  
Sequencing Analysis ◽  
Alcoholic Fatty Liver ◽  
Exercise Interventions ◽  
Expression Signature

Non-alcoholic fatty liver diseases (NAFLD) are particularly prevalent in the general Western adult population, with around one third of the population suffering from the disease. Evidence shows that NAFLD is associated with metabolic syndromes such as obesity, insulin resistance, and hypertension. Currently, the sole therapy for NAFLD involves exercise intervention. Studies showed that, with and without weight loss, exercise interventions produced a significant cutback in intrahepatic lipid content in humans, but better controlled studies that can investigate the cellular and molecular mechanisms are still lacking. In the current study we perform RNA sequencing analysis on liver samples from C57BL/6 mice submitted to aerobic exercise and diet interventions that are human-translatable and determine the genetic expression signature of exercise in the NAFLD onset. We show that aerobic exercise affects genes and pathways related to liver metabolism, muscle contraction and relaxation, immune response and inflammation, and development of liver cancer, counteracting non-alcoholic steatohepatitis and hepatocellular carcinoma development. While genes and pathways implicating immune response are activated by aerobic exercise in all interventions, the most effective intervention in terms of improvement of NASH is the combination of aerobic exercise with change of diet.

scholarly journals Divergent Seasonal Reproductive Patterns in Syntopic Populations of Two Murine Species in Southern Spain, Mus spretus and Apodemus sylvaticus

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 243
Author(s):  
Diaa Massoud ◽  
Miguel Lao-Pérez ◽  
Esperanza Ortega ◽  
Miguel Burgos ◽  
Rafael Jiménez ◽  
...  
Keyword(s):  
Serum Testosterone ◽  
Wood Mouse ◽  
Molecular Study ◽  
Apodemus Sylvaticus ◽  
Breeding Period ◽  
Seasonal Reproduction ◽  
Seasonal Breeding ◽  
Mus Spretus ◽  
Species Population ◽  
Testis Regression

In most mammals with seasonal reproduction, males undergo testis regression during the non-breeding period. We performed a morphological, hormonal, functional, and molecular study of the testes of sexually inactive males of two species of murine rodents, the wood mouse, Apodemus sylvaticus, and the Algerian mouse, Mus spretus, in syntopic populations of southern Iberian peninsula. Both species reproduce during most of the year, but wood mice stop breeding in the summer whereas Algerian mice do it in winter. Sexually inactive males of A. sylvaticus show complete testis regression with reduced levels of serum testosterone and abnormal distribution of cell-adhesion molecules. Contrarily, inactive males of M. spretus maintain almost normal spermotogenesis despite a significant reduction of androgenic function. The lack of an evident explanation for the divergent seasonal breeding patterns found in southern populations of A. sylvaticus and M. spretus, compared with northern ones, implies that very subtle species/population-specific features and/or non-conspicuous environmental cues probably operate to determine their seasonal breeding pattern. These results also support the notion that multiple models of circannual testis variation are possible for different populations of the same species, showing that the mechanisms controlling seasonal reproduction are in fact very plastic and fast evolving.

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

scholarly journals TAMI-07. THE IMMUNE MICROENVIRONMENT IN LOWER GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii214-ii214
Author(s):  
Anupam Kumar ◽  
Katharine Chen ◽  
Claudia Petritsch ◽  
Theodore Nicolaides ◽  
Mariarita Santi-Vicini ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Immune Cell ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Lower Grade ◽  
Functional Relationships

Abstract The determinants of the tumor-associated immune response in brain tumors are poorly understood. Using tumor samples from two molecularly distinct subtypes of lower grade glioma, MAPK-driven glioma with biallelic inactivation of CDKN2A (n=30) and IDH-mutant, 1p/19q-intact astrocytoma (n=29), we demonstrate qualitative and quantitative differences in the tumor-associated immune response and we investigate the molecular mechanisms involved. Histologically the MAPK-driven gliomas were comprised of pleomorphic xanthoastrocytoma (PXA) (n=11) and anaplastic PXA (n=19). Seven patients had paired samples from two sequential surgeries. Immune cell populations and their activity were determined by quantitative multiplex immunostaining and Digital Spatial Profiling and gene expression was analyzed by Nanostring. Functional studies were performed using established cell lines and two new patient-derived lines from MAPK-driven LGGs. MAPK-driven tumors exhibited an increased number of CD8+ T cells and tumor-associated microglial/macrophage (TAMs), including CD163+ TAMs, as compared to IDH-mutant astrocytoma. In contrast, IDH-mutant tumors had increased FOXP3+ immunosuppressive T regulatory cells. Transcriptional and protein level analyses in MAPK-driven tumors suggested an active cytotoxic T cell response with robust expression of granzyme B, present on 27% of CD8+ T cells, increased MHC class I expression, and altered cytokine profiles. Interestingly, MAPK-driven tumors also had increased expression of immunosuppressive molecules, including CXCR4, PD-L1, and VEGFA. Expression differences for cell surface and secreted proteins were confirmed in patient-derived tumor lines and functional relationships between altered chemokine expression and immune cell infiltration was investigated. Our data provide novel insights into the immune contexture of MAPK driven LGGs and suggest MAPK driven gliomas with biallelic inactivation of CDKN2A may be particularly vulnerable to immunotherapeutic modulation

scholarly journals SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marta Ferreira-Gomes ◽  
Andrey Kruglov ◽  
Pawel Durek ◽  
Frederik Heinrich ◽  
Caroline Tizian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune Reaction ◽  
Adaptive Immune Response ◽  
Gene Expression Signature ◽  
Spike Protein ◽  
Single Cell Level ◽  
Cell Level ◽  
Adaptive Immune

AbstractThe pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.

scholarly journals Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs

2021 ◽  
Vol 22 (12) ◽  
pp. 6644
Author(s):  
Xupeng Zang ◽  
Ting Gu ◽  
Wenjing Wang ◽  
Chen Zhou ◽  
Yue Ding ◽  
...  
Keyword(s):  
Immune Response ◽  
Spontaneous Abortion ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Gene Set ◽  
Cerna Network ◽  
Major Interest ◽  
End Stage ◽  
Insight Into

Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.

scholarly journals Transcriptome Analysis of the Cecal Tonsil of Jingxing Yellow Chickens Revealed the Mechanism of Differential Resistance to Salmonella

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 979 ◽  
Author(s):  
Fei Wang ◽  
Jin Zhang ◽  
Bo Zhu ◽  
Jie Wang ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Differential Resistance ◽  
Receptor Interaction ◽  
Salmonella Infection ◽  
Poultry Products ◽  
Food Borne ◽  
Cecal Tonsil ◽  
Iga Production

Salmonella is one of the most common food-borne pathogens. It can be transmitted between chickens, as well as to people by contaminated poultry products. In our study, we distinguished chickens with different resistances mainly based on bacterial loads. We compared the cecal tonsil transcriptomes between the susceptible and resistant chickens after Salmonella infection, aiming to identify the crucial genes participating in the antibacterial activity in the cecal tonsil. A total of 3214 differentially expressed genes (DEGs), including 2092 upregulated and 1122 downregulated genes, were identified between the two groups (fold change ≥ 2.0, padj < 0.05). Many DEGs were mainly involved in the regulation of two biological processes: crosstalk between the cecal tonsil epithelium and pathogenic bacteria, such as focal adhesion, extracellular-matrix–receptor interaction, and regulation of the actin cytoskeleton and host immune response including the cytokine–receptor interaction. In particular, the challenged resistant birds exhibited strong activation of the intestinal immune network for IgA production, which perhaps contributed to the resistance to Salmonella infection. These findings give insight into the mRNA profile of the cecal tonsil between the two groups after initial Salmonella stimulation, which may extend the known complexity of molecular mechanisms in chicken immune response to Salmonella.

Recent advances in the synthesis of fungal antigenic oligosaccharides

2017 ◽  
Vol 89 (7) ◽  
pp. 885-898 ◽  
Author(s):  
Vadim B. Krylov ◽  
Lucia Paulovičová ◽  
Ema Paulovičová ◽  
Yury E. Tsvetkov ◽  
Nikolay E. Nifantiev
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Cell Adhesion ◽  
Driving Force ◽  
Efficient Solutions ◽  
Carbohydrate Chemistry ◽  
Fungal Cell ◽  
Synthetic Methodologies ◽  
Novel Strategy ◽  
Constant Improvement

AbstractThe driving force for the constant improvement and development of new synthetic methodologies in carbohydrate chemistry is a growing demand for biologically important oligosaccharide ligands and neoglycoconjugates thereof for numerous biochemical investigations such as cell-to-pathogen interactions, immune response, cell adhesion, etc. Here we report our syntheses of the spacer-armed antigenic oligosaccharides related to three groups of the polysaccharides of the fungal cell-wall including α- and β-mannan, α- and β-glucan and galactomannan chains, which include new rationally designed synthetic blocks, efficient solutions for the stereoselective construction of glycoside bonds, and novel strategy for preparation of furanoside-containing oligosaccharides based on recently discovered pyranoside-into-furanoside (PIF) rearrangement.

Sign in / Sign up

Export Citation Format

Share Document