FSH prevents depletion of the resting follicle pool by promoting follicular number and morphology in fresh and cryopreserved primate ovarian tissues following xenografting

Background: Cryopreservation and transplantation of ovarian tissue is one option for re-establishing ovarian function, but optimal conditions for graft sustainment and follicular survival are still considered experimental. The present study aims to analyze the effect of FSH treatment on the resting follicle pool in fresh and cryopreserved primate ovarian tissues following xenografting. Methods: Ovarian tissues from adult marmosets were grafted freshly or following cryopreservation to ovarectomized nude mice treated with FSH 25 IU twice daily post transplantation or left untreated as controls. Grafts were retrieved 2 or 4 weeks after transplantation to evaluate the number and morphological appearance of follicles. Results: Early start of FSH treatment within 1 week following transplantation partly prevents primordial follicle loss in fresh and frozen-thawed tissues, whereas after a 3 weeks time interval this effect is present only in fresh tissues. A similar positive effect of early, but not later FSH treatment on primary follicles is seen in fresh tissues compared to only marginal effects in frozen-thawed tissues. The percentage of morphologically normal follicles is generally increased in FSH treated tissues, whereas the percentage of primary follicles over all primordial and primary follicles is increased by FSH only in freshly-grafted tissues. Conclusions: FSH treatment alleviates depletion of the resting follicle pool and promotes normal follicular morphology both in freshly and frozen-thawed grafted tissues. In previously cryopreserved tissues, applying to most of the tissues intended for clinical use in fertility preservation attempts, its positive effect on primordial follicle numbers and potential graft sustainment is dependent on an early start of treatment within one week of transplantation

Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

rs1004819 Is the Main Disease-Associated IL23R Variant in German Crohn's Disease Patients: Combined Analysis of IL23R, CARD15, and OCTN1/2 Variants

The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC

Coitus-Free Sexual Transmission of Zika Virus in a Mouse Model

Zika virus (ZIKV) is an arboviral infection that may be sexually transmitted. The present study aims to determine if accessory sex glands are a potential source of infectious virus and important in sexual transmission. Male interferon type I receptor knockout (Ifnar−/−) mice were challenged subcutaneously with a Puerto Rican ZIKV isolate. Reproductive tissues were harvested seven days after viral challenge and artificial insemination fluid derived from epididymis or homogenized accessory sex glands (seminal plasma) was obtained. Naïve interferon type I and II receptor knockout (AG129) females were pretreated with progesterone, and inoculated intravaginally with either epididymal flush or seminal plasma from ZIKV-infected males. ZIKV RNA was demonstrated in the artificial insemination fluid and ZIKV antigen was detected in epididymal epithelial cells but not within seminiferous tubules at the time of artificial insemination fluid collection. Peripheral viremia, demonstrated by ZIKV RNA in whole blood samples of females from each challenge group was observed. Infectious virus was present in both epididymal fluid and seminal plasma. These studies provide evidence of passage of virus from epididymal flush and seminal plasma to naïve females via artificial insemination and provides a model for the study of sexual transmission of ZIKV

Resolving structure and function of metaorganisms through a holistic framework combining reductionist and integrative approaches

Current research highlights the importance of associated microbes in contributing to the functioning, health, and even adaptation of their animal, plant, and fungal hosts. As such, we are witnessing a shift in research that moves away from focusing on the eukaryotic host sensu stricto to research into the complex conglomerate of the host and its associated microorganisms (i.e., microbial eukaryotes, archaea, bacteria, and viruses), the so-called metaorganism, as the biological entity. While recent research supports and encourages the adoption of such an integrative view, it must be understood that microorganisms are not involved in all host processes and not all associated microorganisms are functionally important. As such, our intention here is to provide a critical review and evaluation of perspectives and limitations relevant to studying organisms in a metaorganism framework and the functional toolbox available to do so. We note that marker gene-guided approaches that primarily characterize microbial diversity are a first step in delineating associated microbes but are not sufficient to establish proof of their functional relevance. More sophisticated tools and experiments are necessary to reveal the specific functions of associated microbes. This can be accomplished through the study of metaorganisms in less complex environments, the targeted manipulation of microbial associates, or work at the mechanistic level with the toolbox available in model systems. We conclude that the metaorganism framework is a powerful new concept to help provide answers to longstanding biological questions such as the evolution and ecology of organismal complexity and the importance of organismal symbioses to ecosystem functioning. The intricacy of the metaorganism requires a holistic framework combining reductionist and integrative approaches to resolve metaorganism identities and to disclose the various roles that microorganisms play in the biology of their hosts

Long-term salinity tolerance is accompanied by major restructuring of the coral bacterial microbiome.

Scleractinian corals are assumed to be stenohaline osmoconformers, although they are frequently subjected to variations in seawater salinity due to precipitation, freshwater run-off and other processes. Observed responses to altered salinity levels include differences in photosynthetic performance, respiration and increased bleaching and mortality of the coral host and its algal symbiont, but a study looking at bacterial community changes is lacking. Here, we exposed the coral Fungia granulosa to strongly increased salinity levels in short- and long-term experiments to disentangle temporal and compartment effects of the coral holobiont (i.e. coral host, symbiotic algae and associated bacteria). Our results show a significant reduction in calcification and photosynthesis, but a stable microbiome after short-term exposure to high-salinity levels. By comparison, long-term exposure yielded unchanged photosynthesis levels and visually healthy coral colonies indicating long-term acclimation to high-salinity levels that were accompanied by a major coral microbiome restructuring. Importantly, a bacterium in the family Rhodobacteraceae was succeeded by Pseudomonas veronii as the numerically most abundant taxon. Further, taxonomy-based functional profiling indicates a shift in the bacterial community towards increased osmolyte production, sulphur oxidation and nitrogen fixation. Our study highlights that bacterial community composition in corals can change within days to weeks under altered environmental conditions, where shifts in the microbiome may enable adjustment of the coral to a more advantageous holobiont composition.This work was supported by King Abdullah Univer-sity of Science and Technology (KAUST), Center CompetitiveFunding (CCF) Program URF/1/1973-02

Testosterone: action, deficiency, substitution.

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High levels of floridoside at high salinity link osmoadaptation with bleaching susceptibility in the cnidarian-algal endosymbiosis

Coral reefs are in global decline mainly due to increasing sea surface temperatures triggering coral bleaching. Recently, high salinity has been linked to increased thermotolerance and decreased bleaching in the sea anemone coral model Aiptasia. However, the underlying processes remain elusive. Using two Aiptasia host­–endosymbiont pairings, we induced bleaching at different salinities and show reduced reactive oxygen species (ROS) release at high salinities, suggesting a role of osmoadaptation in increased thermotolerance. A subsequent screening of osmolytes revealed that this effect was only observed in algal endosymbionts that produce 2-O-glycerol-α-D-galactopyranoside (floridoside), an osmolyte capable of scavenging ROS. This result argues for a mechanistic link between osmoadaptation and thermotolerance, mediated by ROS-scavenging osmolytes (e.g., floridoside). This sheds new light on the putative mechanisms underlying the remarkable thermotolerance of corals from water bodies with high salinity such as the Red Sea or Persian/Arabian Gulf and holds implications for coral thermotolerance under climate change.publishe