Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines

Oertelt-Prigione S, Parol R, Krohn S, Preißner R, Regitz-Zagrosek V. Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines. BMC Medicine. 2010;8(1): 70.© 2010 Oertelt-Prigione et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Gatekeeper of pluripotency: a common Oct4 transcriptional network operates in mouse eggs and embryonic stem cells

BACKGROUND: Oct4 is a key factor of an expanded transcriptional network (Oct4-TN) that governs pluripotency and self-renewal in embryonic stem cells (ESCs) and in the inner cell mass from which ESCs are derived. A pending question is whether the establishment of the Oct4-TN initiates during oogenesis or after fertilisation. To this regard, recent evidence has shown that Oct4 controls a poorly known Oct4-TN central to the acquisition of the mouse egg developmental competence. The aim of this study was to investigate the identity and extension of this maternal Oct4-TN, as much as whether its presence is circumscribed to the egg or maintained beyond fertilisation. RESULTS: By comparing the genome-wide transcriptional profile of developmentally competent eggs that express the OCT4 protein to that of developmentally incompetent eggs in which OCT4 is down-regulated, we unveiled a maternal Oct4-TN of 182 genes. Eighty of these transcripts escape post-fertilisation degradation and represent the maternal Oct4-TN inheritance that is passed on to the 2-cell embryo. Most of these 80 genes are expressed in cancer cells and 37 are notable companions of the Oct4 transcriptome in ESCs. CONCLUSIONS: These results provide, for the first time, a developmental link between eggs, early preimplantation embryos and ESCs, indicating that the molecular signature that characterises the ESCs identity is rooted in oogenesis. Also, they contribute a useful resource to further study the mechanisms of Oct4 function and regulation during the maternal-to-embryo transition and to explore the link between the regulation of pluripotency and the acquisition of de-differentiation in cancer cells

The relevance of mitochondrial DNA variants fluctuation during reprogramming and neuronal differentiation of human iPSCs

The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production of pluripotent patient-specific cell lines used for disease modeling, drug screening, and cell therapy. Integrity of nuclear DNA (nDNA) is mandatory to allow iPSCs utilization, while quality control of mitochondrial DNA (mtDNA) is rarely included in the iPSCs validation process. In this study, we performed mtDNA deep sequencing during the transition from parental fibroblasts to reprogrammed iPSC and to differentiated neuronal precursor cells (NPCs) obtained from controls and patients affected by mitochondrial disorders. At each step, mtDNA variants, including those potentially pathogenic, fluctuate between emerging and disappearing, and some having functional implications. We strongly recommend including mtDNA analysis as an unavoidable assay to obtain fully certified usable iPSCs and NPCs

PDGFA-associated protein 1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification

The establishment of protective humoral immunity is dependent on the ability of mature B cells to undergo antibody gene diversification while adjusting to the physiological stressors induced by activation with the antigen. Mature B cells diversify their antibody genes by class switch recombination (CSR) and somatic hypermutation (SHM), which are both dependent on efficient induction of activation-induced cytidine deaminase (AID). Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation and ensures efficient antibody diversification by promoting their survival and optimal function

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women