Apatite from NWA 10153 and NWA 10645 : the key to deciphering magmatic and fluid evolution history in Nakhlites

Apatites from Martian nakhlites NWA 10153 and NWA 10645 were used to obtain insight into their crystallization environment and the subsequent postcrystallization evolution path. The research results acquired using multi-tool analyses show distinctive transformation processes that were not fully completed. The crystallization history of three apatite generations (OH-bearing, Cl-rich fluorapatite as well as OH-poor, F-rich chlorapatite and fluorapatite) were reconstructed using transmission electron microscopy and geochemical analyses. Magmatic OH-bearing, Cl-rich fluorapatite changed its primary composition and evolved toward OH-poor, F-rich chlorapatite because of its interaction with fluids. Degassing of restitic magma causes fluorapatite crystallization, which shows a strong structural affinity for the last episode of system evolution. In addition to the three apatite generations, a fourth amorphous phase of calcium phosphate has been identified with Raman spectroscopy. This amorphous phase may be considered a transition phase between magmatic and hydrothermal phases. It may give insight into the dissolution process of magmatic phosphates, help in processing reconstruction, and allow to decipher mineral interactions with hydrothermal fluids

mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons

Neurogenesis is the process of neuron generation, which occurs not only during embryonic development but also in restricted niches postnatally. One such region is called the subventricular zone (SVZ), which gives rise to new neurons in the olfactory bulb (OB). Neurons that are born postnatally migrate through more complex territories and integrate into fully functional circuits. Therefore, differences in the differentiation of embryonic and postnatally born neurons may exist. Dendritogenesis is an important process for the proper formation of future neuronal circuits. Dendritogenesis in embryonic neurons cultured in vitro was shown to depend on the mammalian target of rapamycin (mTOR). Still unknown, however, is whether mTOR could regulate the dendritic arbor morphology of SVZ‐derived postnatal OB neurons under physiological conditions in vivo. The present study used in vitro cultured and differentiated SVZ‐derived neural progenitors and found that both mTOR complex 1 and mTOR complex 2 were required for the dendritogenesis of SVZ‐derived neurons. Furthermore, using a combination of in vivo electroporation of neural stem cells in the SVZ and genetic and pharmacological inhibition of mTOR, it was found that mTOR was crucial for the growth of basal and apical dendrites in postnatally born OB neurons under physiological conditions and contributed to the stabilization of their basal dendrites. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1308–1327, 201

Proteomic analysis of carp seminal plasma provides insights into the immune response to bacterial infection of the male reproductive system

Aeromonas salmonicida is recognized as a significant bacterial pathogen in ulcerative disease of cyprinid fish. However, the mechanism of immunity to these bacteria in common carp is still not well understood, especially the immune regulation in the gonad to bacterial infection. The aims of our study were to analyze changes in the seminal plasma proteome following A. salmonicida infection in carp males. The observed pathological changes in the tissue (liver, spleen, kidney and testis) morphology and upregulation of immune-related genes (tnfa2, il6a) confirmed the successful infection challenge. Using mass spectrometry-based label-free quantitative proteomics, we identified 1402 seminal plasma proteins, and 44 proteins (20 up- and 24 downregulated) were found to be differentially abundant between infected and control males. Most differentially abundant proteins were involved in the immune response mechanisms, such as acute phase response, complement activation and coagulation, inflammation, lipid metabolism, cell-cell and cell-matrix adhesion, creatine-phosphate biosynthesis and germ cell-Sertoli cell junction signaling. Bacterial infection also caused profound changes in expression of selected genes in the testis and hematopoietic organs, which contributed to changes in seminal proteins. The altered seminal proteins and bacterial proteins in seminal plasma may serve as valuable markers of infection in the testis

Astrocytic β-catenin signaling via TCF7L2 regulates synapse development and social behavior

The Wnt/β-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/β-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/β-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior

Tuberous sclerosis complex neuropathology requires glutamate-cysteine ligase

Introduction: Tuberous sclerosis complex (TSC) is a genetic disease resulting from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical tubers and subependymal giant cell astrocytomas (SEGAs). However, the current treatment with mTOR inhibitors has critical limitations. We aimed to identify new targets for TSC pharmacotherapy. Results: The results of our shRNA screen point to glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme in glutathione synthesis, as a contributor to TSC-related phenotype. GCLC inhibition increased cellular stress and reduced mTOR hyperactivity in TSC2-depleted neurons and SEGA-derived cells. Moreover, patients’ brain tubers showed elevated GCLC and stress markers expression. Finally, GCLC inhibition led to growth arrest and death of SEGA-derived cells. Conclusions: We describe GCLC as a part of redox adaptation in TSC, needed for overgrowth and survival of mutant cells, and provide a potential novel target for SEGA treatment. Electronic supplementary material The online version of this article (doi:10.1186/s40478-015-0225-z) contains supplementary material, which is available to authorized users

Igf1r Signaling Is Indispensable for Preimplantation Development and Is Activated via a Novel Function of E-cadherin

Insulin-like growth factor I receptor (Igf1r) signaling controls proliferation, differentiation, growth, and cell survival in many tissues; and its deregulated activity is involved in tumorigenesis. Although important during fetal growth and postnatal life, a function for the Igf pathway during preimplantation development has not been described. We show that abrogating Igf1r signaling with specific inhibitors blocks trophectoderm formation and compromises embryo survival during murine blastocyst formation. In normal embryos total Igf1r is present throughout the membrane, whereas the activated form is found exclusively at cell contact sites, colocalizing with E-cadherin. Using genetic domain switching, we show a requirement for E-cadherin to maintain proper activation of Igf1r. Embryos expressing exclusively a cadherin chimera with N-cadherin extracellular and E-cadherin intracellular domains (NcEc) fail to form a trophectoderm and cells die by apoptosis. In contrast, homozygous mutant embryos expressing a reverse-structured chimera (EcNc) show trophectoderm survival and blastocoel cavitation, indicating a crucial and non-substitutable role of the E-cadherin ectodomain for these processes. Strikingly, blastocyst formation can be rescued in homozygous NcEc embryos by restoring Igf1r signaling, which enhances cell survival. Hence, perturbation of E-cadherin extracellular integrity, independent of its cell-adhesion function, blocked Igf1r signaling and induced cell death in the trophectoderm. Our results reveal an important and yet undiscovered function of Igf1r during preimplantation development mediated by a unique physical interaction between Igf1r and E-cadherin indispensable for proper receptor activation and anti-apoptotic signaling. We provide novel insights into how ligand-dependent Igf1r activity is additionally gated to sense developmental potential in utero and into a bifunctional role of adhesion molecules in contact formation and signaling

Médiateurs lipidiques bioactifs au cours du développement et de l'implantation de l'embryon de brebis

In mammals, a reciprocal interaction between the implantation-competent blastocyst and the receptive uterus is required for successful implantation. Although various molecular pathways are known to participate in this cross talk, a comprehensive understanding of the implantation process is still missing. Gene expression studies and genetically engineered mouse models have provided evidences that bioactive lipids, also called lipid mediators, serve as important signalling molecules in coordinating the series of events during early pregnancy including preimplantation embryo formation and development, implantation and postimplantation growth. In the present studies we intended to understand the role of lipid mediators as lysophosphatidic acid (LPA) and prostaglandins (PGs) in early embryonic development and implantation in sheepChez les mammifères, des interactions réciproques entre le blastocyste prêt à s implanter et l utérus en état de le recevoir est nécessaire pour permettre la réussite de l implantation et l établissement de la gestation. Bien que de nombreuses voies métaboliques soient connues pour participer à ces échanges, une compréhension intégrée du processus de l implantation fait encore défaut. Les études d expression de gènes et l élaboration de modèles génétiques chez la souris ont apportées des preuves que les lipides bioactifs ou médiateurs lipidiques, sont d importantes molécules de signalisation et qui coordonnent des séries d événements au début de la gestation dont la formation et le développement de l embryon pré-implantatoire, l implantation et la croissance post-implantatoire. Dans ces travaux nous avons tenté de comprendre le rôle des médiateurs lipidiques tel l acide lysophosphatidique (LPA) et les prostaglandines (PGs) au début du développement de l embryon et au cours de l implantation chez le mouton.VERSAILLES-BU Sciences et IUT (786462101) / SudocSudocFranceF

A levels of endogenous gonadal hormones and their relationship with selected coronary artery disease risk factors among young women post myocardial infarction

In recent decades a significant raise in the incidence of myocardial infarction among young women has been recorded. It is presumed that, apart from the classical risk factors, other reasons exist for premature atherosclerosis in young women, related to the homeostasis of gonadal hormones. The aim of the study was to analyze the levels of gonadal hormones (estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, testosterone and dehydroepiandrosterone) measured in the luteal phase, in 65 normally menstruating women post myocardial infarction (MI) and to investigate a possible relationship between the hormone profile and selected coronary artery disease (CAD) risk factors. The levels of gonadal hormones: estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, testosterone and dehydroepiandrosterone were measured in the luteal phase. All examined women had normal mean levels of gonadal hormones. In the post MI patients leading a sedentary life style, a significantly lower mean progesterone concentration was observed (16.29 ± 9.11 versus 29.43 ± 21.14 nmol/l, p < 0.05) and significantly higher mean testosterone concentration (2.34 ± 0.98 versus 1.76 ± 1.09 nmol/l, p < 0.05) when compared to patients from the same group, but leading a more active life. In obese post MI women (BMI ≥ 30 kg/m2) a lower mean concentration of progesterone was detected (18.02 ± 8.12 versus 26.16 ± 14.72 nmol/l, p < 0.05), than in slimmer patients from the same group. In post MI women with a positive family history for CAD, a significantly higher mean concentration of testosterone was detected (2.31 ± 1.22 versus 1.67 ± 0.74 nmol/l, p < 0.05) than in patients with no family history. The results suggest a correlation between levels of gonadal hormones and classical CAD risk factors

Lysophosphatidic acid signaling during embryo development in sheep: Involvement in prostaglandin synthesis

We investigated the lysophosphatidic acid (LPA) pathway during early pregnancy in sheep. LPA was detected in the uteri of early-stage pregnant ewes. Using quantitative RT-PCR, the expression of autotaxin, the LPA-generating enzyme, was found in the endometrium and conceptus. In the latter autotaxin, transcript levels were low on d 12-14 and increased on d 15-16, in parallel with the level of LPA. Autotaxin was localized in the luminal epithelium and superficial glands of the endometrium and in trophectoderm cells of the conceptus. The expression of G protein-coupled receptors for LPA was also examined in the ovine conceptus. LPA receptor LPAR1 and LPAR3 transcripts were expressed during early pregnancy and displayed a peak on d 14, whereas the highest level of protein for both receptors was observed at d 17. LPAR1 was localized in cellular membranes and nuclear compartments of the trophectoderm cells, whereas LPAR3 was revealed only in membranes. LPA activated phosphorylation of the MAPK ERK1/2 in ovine trophectoderm-derived cells. Moreover, the bioactive lipid increased the proliferation of trophectoderm cells in culture, as shown by thymidine and bromodeoxyuridine incorporation. Furthermore, LPA induced changes to the organization of beta-actin and alpha-tubulin, suggesting a role for it in rearrangement of trophectoderm cells cytoskeleton. Because a link had previously been established between prostaglandin and LPA pathways, we analyzed the effect of LPA on prostaglandin synthesis. LPA induced an increase in the release of prostaglandin F2alpha and prostaglandin E2, with no significant modifications to cytosolic phospholipase A2alpha and prostaglandin synthase-2 expression. Taken together, our results suggest a new role for LPA-mediated signaling in the ovine conceptus at the time of implantation