Loss of Endometrial Plasticity in Recurrent Pregnancy Loss

© 2015 AlphaMed Press.Menstruation drives cyclic activation of endometrial progenitor cells, tissue regeneration, and maturation of stromal cells, which differentiate into specialized decidual cells prior to and during pregnancy. Aberrant responsiveness of human endometrial stromal cells (HESCs) to deciduogenic cues is strongly associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular maturation. MeDIP-seq analysis of HESCs did not reveal gross perturbations in CpG methylation in RPL cultures, although quantitative differences were observed in or near genes that are frequently deregulated in vivo. However, RPL was associated with a marked reduction in methylation of defined CA-rich motifs located throughout the genome but enriched near telomeres. Non-CpG methylation is a hallmark of cellular multipotency. Congruently, we demonstrate that RPL is associated with a deficiency in endometrial clonogenic cell populations. Loss of epigenetic stemness features also correlated with intragenic CpG hypomethylation and reduced expression of HMGB2, coding high mobility group protein 2. We show that knockdown of this sequence-independent chromatin protein in HESCs promotes senescence and impairs decidualization, exemplified by blunted time-dependent secretome changes. Our findings indicate that stem cell deficiency and accelerated stromal senescence limit the differentiation capacity of the endometrium and predispose for pregnancy failure. Stem Cells 2016;34:346-356 Recurrent pregnancy loss is caused by endometrial stem cell deficiency, triggering heightened tissue senescence and impaired decidualization

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine

The evolution of health policy guidelines for assisted reproduction in the Republic of Ireland, 2004-2009

This analysis reports on Irish regulatory policies for in vitro fertilisation (IVF) from 2004-2009, in the context of membership changes within the Medical Council of Ireland. To achieve this, the current (2009) edition of the Guide to Professional Conduct & Ethics was compared with the immediately preceding version (2004). The statutory composition of the Medical Council from 2004-2009 was also studied. Content analysis of the two editions identified the following differences: 1) The 2004 guide states that IVF "should only be used after thorough investigation has failed to reveal a treatable cause of the infertility", while the 2009 guide indicates IVF "should only be used after thorough investigation has shown that no other treatment is likely to be effective"; 2) The 2004 stipulation stating that fertilized ovum (embryo) "must be used for normal implantation and must not be deliberately destroyed" is absent from the 2009 guidelines; 3) The option to donate "unused fertilised ova" (embryos) is omitted from the 2009 guidelines; 4) The 2009 guidelines state that ART should be offered only by "suitably qualified professionals, in appropriate facilities, and according to the international best practice"; 5) The 2009 guidelines introduce criteria that donations as part of a donor programme should be "altruistic and non-commercial". These last two points represent original regulatory efforts not appearing in the 2004 edition. The Medical Practitioners Act 2007 reduced the number of physicians on the Medical Council to 6 (of 25) members. The ethical guidelines from 2004 preceded this change, while the reconstituted Medical Council published the 2009 version. Between 2004 and 2009, substantial modifications in reproductive health policy were incorporated into the Medical Council's ethical guidelines. The absence of controlling Irish legislation means that patients and IVF providers in Ireland must rely upon these guidelines by default. Our critique traces the evolution of public policy on IVF during a time when the membership of the Medical Council changed radically; reduced physician contribution to decision-making was associated with diminished protection for IVF-derived embryos in Ireland. Considerable uncertainty on IVF practice in Ireland remains

Alcohol use behaviors and risk of metabolic syndrome in South Korean middle-aged men

<p>Abstract</p> <p>Background</p> <p>It is thought that small volumes of alcohol may have positive effects on health. However, excessive drinking results in serious health problems. An accurate method to determine individual alcohol use behaviors are needed to assess objectively the extent to which drinking affects health. This study investigated the association between risk of metabolic syndrome (MetS) and alcohol use behaviors in middle-aged South Korean men using the Alcohol Use Disorders Identification Test.</p> <p>Methods</p> <p>This study used data from the South Korea National Health and Nutrition Examination (KNHANES) IV (2008), which extracted the standard survey household by using the proportional systematic sampling method. Data of 714 participants from KNHANES IV, 2008 were analyzed using Surveyfreq and Surveylogistic regression to investigate the association between MetS and alcohol use behaviors in middle-aged South Korean men.</p> <p>Results</p> <p>After adjustment for education, smoking, and physical activity, alcohol use behaviors were significantly associated with an increased risk of hypertension [odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.5-4.06 in the hazardous group; OR = 2.99, 95% CI = 1.84-4.92 in the problem group]; impaired fasting glucose (OR = 2.15, 95% CI = 1.16-3.99 in the hazardous group; OR = 2.48, 95% CI = 1.42-4.33 in the problem group); dyslipidemia (OR = 2.19, 95% CI = 1.38-3.47 in the problem group); abdominal obesity (OR = 1.93, 95% CI = 1.17-3.19 in the hazardous group; OR = 1.85, 95% CI = 1.17-2.92 in the problem group); and MetS (OR = 2.16, 95% CI = 1.24-3.77 in the hazardous group; OR = 2.54, 95% CI = 1.41-4.58 in problem group).</p> <p>Conclusions</p> <p>This study found that excessive alcohol use behaviors increased the risk of hypertension, diabetes, dyslipidemia, abdominal obesity, and MetS. Considering the rising rate of alcohol consumption and heavy drinking at single sittings, a culture of less risky alcohol consumption must be established to promote health among middle-aged men.</p

Impact of Human Management on the Genetic Variation of Wild Pepper, Capsicum annuum var. glabriusculum

Management of wild peppers in Mexico has occurred for a long time without clear phenotypic signs of domestication. However, pre-domestication management could have implications for the population's genetic richness. To test this hypothesis we analysed 27 wild (W), let standing (LS) and cultivated (C) populations, plus 7 samples from local markets (LM), with nine polymorphic microsatellite markers. Two hundred and fifty two alleles were identified, averaging 28 per locus. Allele number was higher in W, and 15 and 40% less in LS and C populations, respectively. Genetic variation had a significant population structure. In W populations, structure was associated with ecological and geographic areas according to isolation by distance. When LM and C populations where included in the analysis, differentiation was no longer apparent. Most LM were related to distant populations from Sierra Madre Oriental, which represents their probable origin. Historical demography shows a recent decline in all W populations. Thus, pre-domestication human management is associated with a significant reduction of genetic diversity and with a loss of differentiation suggesting movement among regions by man. Measures to conserve wild and managed populations should be implemented to maintain the source and the architecture of genetic variation in this important crop relative

In Vivo Functional Genomic Studies of Sterol Carrier Protein-2 Gene in the Yellow Fever Mosquito

A simple and efficient DNA delivery method to introduce extrachromosomal DNA into mosquito embryos would significantly aid functional genomic studies. The conventional method for delivery of DNA into insects is to inject the DNA directly into the embryos. Taking advantage of the unique aspects of mosquito reproductive physiology during vitellogenesis and an in vivo transfection reagent that mediates DNA uptake in cells via endocytosis, we have developed a new method to introduce DNA into mosquito embryos vertically via microinjection of DNA vectors in vitellogenic females without directly manipulating the embryos. Our method was able to introduce inducible gene expression vectors transiently into F0 mosquitoes to perform functional studies in vivo without transgenic lines. The high efficiency of expression knockdown was reproducible with more than 70% of the F0 individuals showed sufficient gene expression suppression (<30% of the controls' levels). At the cohort level, AeSCP-2 expression knockdown in early instar larvae resulted in detectable phenotypes of the expression deficiency such as high mortality, lowered fertility, and distorted sex ratio after induction of AeSCP-2 siRNA expression in vivo. The results further confirmed the important role of AeSCP-2 in the development and reproduction of A. aegypti. In this study, we proved that extrachromosaomal transient expression of an inducible gene from a DNA vector vertically delivered via vitellogenic females can be used to manipulate gene expression in F0 generation. This new method will be a simple and efficient tool for in vivo functional genomic studies in mosquitoes

Invasions and Extinctions Reshape Coastal Marine Food Webs

The biodiversity of ecosystems worldwide is changing because of species loss due to human-caused extinctions and species gain through intentional and accidental introductions. Here we show that the combined effect of these two processes is altering the trophic structure of food webs in coastal marine systems. This is because most extinctions (∼70%) occur at high trophic levels (top predators and other carnivores), while most invasions are by species from lower trophic levels (70% macroplanktivores, deposit feeders, and detritivores). These opposing changes thus alter the shape of marine food webs from a trophic pyramid capped by a diverse array of predators and consumers to a shorter, squatter configuration dominated by filter feeders and scavengers. The consequences of the simultaneous loss of diversity at top trophic levels and gain at lower trophic levels is largely unknown. However, current research suggests that a better understanding of how such simultaneous changes in diversity can impact ecosystem function will be required to manage coastal ecosystems and forecast future changes

RAPD and Internal Transcribed Spacer Sequence Analyses Reveal Zea nicaraguensis as a Section Luxuriantes Species Close to Zea luxurians

Genetic relationship of a newly discovered teosinte from Nicaragua, Zea nicaraguensis with waterlogging tolerance, was determined based on randomly amplified polymorphic DNA (RAPD) markers and the internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA using 14 accessions from Zea species. RAPD analysis showed that a total of 5,303 fragments were produced by 136 random decamer primers, of which 84.86% bands were polymorphic. RAPD-based UPGMA analysis demonstrated that the genus Zea can be divided into section Luxuriantes including Zea diploperennis, Zea luxurians, Zea perennis and Zea nicaraguensis, and section Zea including Zea mays ssp. mexicana, Zea mays ssp. parviglumis, Zea mays ssp. huehuetenangensis and Zea mays ssp. mays. ITS sequence analysis showed the lengths of the entire ITS region of the 14 taxa in Zea varied from 597 to 605 bp. The average GC content was 67.8%. In addition to the insertion/deletions, 78 variable sites were recorded in the total ITS region with 47 in ITS1, 5 in 5.8S, and 26 in ITS2. Sequences of these taxa were analyzed with neighbor-joining (NJ) and maximum parsimony (MP) methods to construct the phylogenetic trees, selecting Tripsacum dactyloides L. as the outgroup. The phylogenetic relationships of Zea species inferred from the ITS sequences are highly concordant with the RAPD evidence that resolved two major subgenus clades. Both RAPD and ITS sequence analyses indicate that Zea nicaraguensis is more closely related to Zea luxurians than the other teosintes and cultivated maize, which should be regarded as a section Luxuriantes species

Structured film-viewing preferences and practices : a quantitative analysis of hierarchies in screen and content selection amongst young people in Flanders

Aleit Veenstra, Philippe Meers and Daniel Biltereyst address a specific segment of a typical small-market audience—Flemish youth film viewers. Their study “Structured Film Viewing Preferences and Practices: A Quantitative Analysis of Hierarchies in Screen and Content Selection among Young People in Flanders” deals with one of the symptomatic problems of the era of convergent audiences, the multiplication of screens used for domestic consumption of audiovisual content. Building an intriguing empirical design, Veenstra and her colleagues aim to identify patterns of screen selection and their relation to the perceived value of Hollywood, European and domestic Flemish films. Their conclusion is that there are well-articulated hierarchies applied by the audience members in the selection of both film titles and reception screens and that, to put it simply, in the case of screens, size matters

The Necrotic Signal Induced by Mycophenolic Acid Overcomes Apoptosis-Resistance in Tumor Cells

The amount of inosine monophosphate dehydrogenase (IMPDH), a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP), is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA) are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42.Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA–mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL–overexpressing cells). All tested cells remained sensitive to MPA–mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers.These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells