An ancient testis-specific IQ motif-containing H gene regulates specific transcript isoform expression during spermatogenesis

Spermatogenic cells express more alternatively spliced RNAs than most whole tissues; however, the regulation of these events remains unclear. Here, we have characterized the function of a testis-specific IQ motif-containing H gene (Iqch) using a mutant mouse model. We found that Iqch is essential for the specific expression of RNA isoforms during spermatogenesis. Using immunohistochemistry of the testis, we noted that Iqch was expressed mainly in the nucleus of spermatocyte and spermatid, where IQCH appeared juxtaposed with SRRM2 and ERSP1 in the nuclear speckles, suggesting that interactions among these proteins regulate alternative splicing (AS). Using RNA-seq, we found that mutant Iqch produces alterations in gene expression, including the clear downregulation of testis-specific lncRNAs and protein-coding genes at the spermatid stage, and AS modifications – principally increased intron retention – resulting in complete male infertility. Interestingly, we identified previously unreported spliced transcripts in the wild-type testis, while mutant Iqch modified the expression and use of hundreds of RNA isoforms, favouring the expression of the canonical form. This suggests that Iqch is part of a splicing control mechanism, which is essential in germ cell biologyThis study was funded by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (PID2021-122507OB-I00 and PID2020-117491GB-I00) and the European Union NextGenerationEU/PRTR. P.N.-L. was supported by a pre-doctoral fellowship from the Ministerio de Ciencia e Innovación (PRE2019-088813) and M.L. was supported by a Juan de la Cierva postdoctoral contract (FJC2019-040385-I) from the Ministerio de Ciencia e Innovación. Open access funding provided by Consejo Superior de Investigaciones Cientıficas. Deposited in PMC for immediate releas

Zrsr2 and functional U12-dependent spliceosome are necessary for follicular development

SUMMARY ZRSR2 is a splicing factor involved in recognition of 30 -intron splice sites that is frequently mutated in myeloid malignancies and several tumors; however, the role of mutations of Zrsr2 in other tissues has not been analyzed. To explore the bio logical role of ZRSR2,we generated threeZrsr2 mutantmouse lines. AllZrsr2 mutant lines exhibited blood cell anomalies, and in two lines, oogenesis was blocked at the secondary follicle stage. RNA-seq of Zrsr2mu secondary follicles showed aberrations in gene expression and showed altered alternative splicing (AS) events involving enrichment of U12-type intron retention (IR), supporting the functional Zrsr2 action in minor spliceosomes. IR events were preferentially associated with centriole repli cation, protein phosphorylation, and DNA damage checkpoint. Notably, we found alterations in AS events of 50 meiotic genes. These results indicate that ZRSR2 mu tations alter splicing mainly in U12-type introns, which may affect peripheral blood cells, and impede oogenesis and female fertility

Las personas. Segundo ciclo, módulo 1

Existe una edición revisada del año 1994 con ISBN 84-369-2093-7Módulo de formación de adultos cuyo tema es el hombre y que está formado por cuatro unidades: El hombre se alimenta; El hombre se asoma al mundo y piensa; El hombre se reproduce ¿cuántos somos ya?; Y en España, ¿cuántos somos? ¿cómo estamos repartidos?. El tema se trata de forma interdisciplinar, abarcando conocimientos de Lengua, Matemáticas y Ciencias Naturales y Sociales. Este material funciona al mismo tiempo como libro de texto y como cuaderno de trabajo para el alumno.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Loss of the importin Kpna2 causes infertility in male mice by disrupting the translocation of testis-specific transcription factors

Summary: Karyopherins mediate the movement between the nucleus and cytoplasm of specific proteins in diverse cellular processes. Through a loss-of-function approach, we here examine the role of Karyopherin Subunit Alpha 2 (Kpna2) in spermatogenesis. Knockout male mice exhibited reduced body size and sperm motility, increased sperm abnormalities, and led to the dysregulation of testis gene expression and ultimately to infertility. Impaired mRNA expression mainly affected clusters of genes expressed in spermatids and spermatocytes. Downregulated genes included a set of genes that participate in cell adhesion and extracellular matrix (ECM) organization. We detected both the enrichment of some transcription factors that bind to regions around transcription start sites of downregulated genes and the impaired transport of specific factors to the nucleus of spermatid cells. We propose that Kpna2 is essential in the seminiferous tubules for promoting the translocation of testis-specific transcription factors that control the expression of genes related to ECM organization

El medio en que vivimos. Segundo ciclo, módulo 2

Existe otra edición revisada del año 1994 con ISBN 84-369-2094-5Libro de texto que corresponde al segundo módulo del segundo ciclo del programa de educación de adultos propuesto por el Centro Nacional de Educación Básica a Distancia (CENEBAD). Consta de cuatro unidades didácticas sobre el aire, el suelo y el paisaje, con ejercicios y actividades, tratadas de forma interdisciplinar, abarcando contenidos de las áreas de lengua, matemáticas, ciencias naturales y ciencias sociales. El alumno debe leer una obra literaria de entre varias recomendadas.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Medio y sociedad. Segundo ciclo, módulo 3

Libro de texto correspondiente al tercer módulo del segundo ciclo de educación a distancia de adultos propuesta por el Centro Nacional de Educación Básica a Distancia (CENEBAD). Consta de cuatro unidades didácticas sobre los beneficios que nos proporciona el medio físico en las que se trabajan de un modo interdisciplinar contenidos de las áreas de lengua, matemáticas, ciencias naturales y ciencias sociales. Se recomiendan varios libros de lectura como complemento, de los cuales el alumno debe leer uno y elaborar una ficha técnica.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Efficiency of Diagnostic Testing for Helicobacter pylori Infections: A Systematic Review

BACKGROUND: The most recommended treatment for a Helicobacter pylori infection is high doses of combined antibiotics. The objective of this article is to perform a systematic review of the economic evaluation studies applied to assess the efficiency of diagnostic testing for H. pylori infections, so that their main characteristics can be identified and to learn from the literature how the antimicrobial resistance (AMR) issue is incorporated into these economic evaluations. METHODS: We conducted a systematic review to compare the costs and clinical effectiveness of diagnostic strategies for H. pylori infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and extracted the items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: We found thirteen articles that were of good quality according to CHEERS: six studies focused on diagnostics of Helicobacter pylori infections associated with dyspepsia and four on duodenal ulcers. Testing was found to be the most cost-effective strategy in eight articles. Four studies considered AMR. CONCLUSIONS: Testing was more cost-effective than empirical treatment, except in cases of high prevalence (as with developing countries) or when patients could be stratified according to their comorbidities. The introduction of AMR into the model may change the efficiency of the testing strategy

Diagnostic testing for sepsis: A systematic review of economic evaluations

Introduction: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic evaluations to analyze the cost-effectiveness of diagnostic methods in sepsis and to draw lessons on the methods used to incorporate antimicrobial resistance (AMR) in these studies. Material and Methods: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the Consolidated Health Economic Evaluation Reporting standards (CHEERS) checklist was used to extract the information from the texts. Results: A total of 16 articles were found. A decision model was performed in 14. We found two ways to handle resistance while modelling: the test could identify infections caused by a resistant pathogen or resistance-related inputs, or outcomes were included (the incidence of AMR in sepsis patients, antibiotic use, and infection caused by resistant bacterial pathogens). Conclusion: Using a diagnostic technique to detect sepsis early on is more cost-effective than standard care. Setting a direct relationship between the implementation of a testing strategy and the reduction of AMR cases, we made several assumptions about the efficacy of antibiotics and the length-of-stay of patients

CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst

Fatty acid metabolism in the hypothalamus has an important role in food intake, but its specific role in AgRP neurons is poorly understood. Here, we examined whether carnitinea palmitoyltransferase 1A (CPT1A), a key enzyme in mitochondrial fatty acid oxidation, affects energy balance. To obtain Cpt1a KO mice and their control littermates, Cpt1a (flox/flox) mice were crossed with tamoxifen-inducible AgRP CreERT2 mice. Food intake and body weight were analyzed weekly in both males and females. At 12 weeks of age, metabolic flexibility was determined by ghrelin-induced food intake and fasting-refeeding satiety tests. Energy expenditure was analyzed by calorimetric system and thermogenic activity of brown adipose tissue. To study fluid balance the analysis of urine and water intake volumes; osmolality of urine and plasma; as well as serum levels of angiotensin and components of RAAS (renin-angiotensin-aldosterone system) were measured. At the central level, changes in AgRP neurons were determined by: (1) analyzing specific AgRP gene expression in RiboTag- Cpt1a KO mice obtained by crossing Cpt1a KO mice with RiboTag mice; (2) measuring presynaptic terminal formation in the AgRP neurons with the injection of the AAV1 -EF1a-DIO-synaptophysin-GFP in the arcuate nucleus of the hypothalamus; (3) analyzing AgRP neuronal viability and spine formations by the injection AAV9 -EF1a-DIO-mCherry in the arcuate nucleus of the hypothalamus; (4) analyzing in situ the specific AgRP mitochondria in the ZsGreen- Cpt1a KO obtained by breeding ZsGreen mice with Cpt1a KO mice. Two-way ANOVA analyses were performed to determine the contributions of the effect of lack of CPT1A in AgRP neurons in the sex. Changes in food intake were just seen in male Cpt1a KO mice while only female Cpt1a KO mice increased energy expenditure. The lack of Cpt1a in the AgRP neurons enhanced brown adipose tissue activity, mainly in females, and induced a substantial reduction in fat deposits and body weight. Strikingly, both male and female Cpt1a KO mice showed polydipsia and polyuria, with more reduced serum vasopressin levels in females and without osmolality alterations, indicating a direct involvement of Cpt1a in AgRP neurons in fluid balance. AgRP neurons from Cpt1a KO mice showed a sex-dependent gene expression pattern, reduced mitochondria and decreased presynaptic innervation to the paraventricular nucleus, without neuronal viability alterations. Our results highlight that fatty acid metabolism and CPT1A in AgRP neurons show marked sex differences and play a relevant role in the neuronal processes necessary for the maintenance of whole-body fluid and energy balance. The online version contains supplementary material available at 10.1186/s13293-023-00498-8. The online version contains supplementary material available at 10.1186/s13293-023-00498-8

CPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst

Highlights Fatty acid metabolism and CPT1A in AgRP neurons show marked sex-dependent differences in the control of feeding. Cpt1a gene deletion in AgRP neurons increases energy expenditure in females but not in males. CPT1A in AgRP neurons is involved in the control of thirst and fluid homeostasis. Cpt1a gene deletion in AgRP neurons induces morphological, mitochondrial, and gene expression alterations in a sex-dependent manner