Abnormal infant islet morphology precedes insulin resistance in PCOS-like monkeys.

Polycystic ovary syndrome (PCOS) is prevalent in reproductive-aged women and confounded by metabolic morbidities, including insulin resistance and type 2 diabetes. Although the etiology of PCOS is undefined, contribution of prenatal androgen (PA) exposure has been proposed in a rhesus monkey model as premenopausal PA female adults have PCOS-like phenotypes in addition to insulin resistance and decreased glucose tolerance. PA female infants exhibit relative hyperinsulinemia, suggesting prenatal sequelae of androgen excess on glucose metabolism and an antecedent to future metabolic disease. We assessed consequences of PA exposure on pancreatic islet morphology to identify evidence of programming on islet development. Islet counts and size were quantified and correlated with data from intravenous glucose tolerance tests (ivGTT) obtained from dams and their offspring. Average islet size was decreased in PA female infants along with corresponding increases in islet number, while islet fractional area was preserved. Infants also demonstrated an increase in both the proliferation marker Ki67 within islets and the beta to alpha cell ratio suggestive of enhanced beta cell expansion. PA adult females have reduced proportion of small islets without changes in proliferative or apoptotic markers, or in beta to alpha cell ratios. Together, these data suggest in utero androgen excess combined with mild maternal glucose intolerance alter infant and adult islet morphology, implicating deviant islet development. Marked infant, but subtle adult, morphological differences provide evidence of islet post-natal plasticity in adapting to changing physiologic demands: from insulin sensitivity and relative hypersecretion to insulin resistance and diminished insulin response to glucose in the mature PCOS-like phenotype

Contributions of androgen and estrogen to fetal programming of ovarian dysfunction

In female mammals, including humans, deviations from normal androgenic or estrogenic exposure during fetal development are detrimental to subsequent adult ovarian function. Androgen deficiency, without accompanying estrogen deficit, has little apparent impact on ovarian development. Fetal estrogen deficiency, on the other hand, results in impaired oocyte and follicle development, immature and abnormal adult ovaries, and excessive ovarian stimulation from endogenous gonadotropins ultimately generating hemorrhagic follicles. Complete estrogen deficiency lasting into adulthood results in partial ovarian masculinization. Fetal androgen excess, on the other hand, mediated either by direct androgen action or following androgen aromatization to estrogen, reprograms ovarian development and reproductive neuroendocrinology to mimic that found in women with polycystic ovary syndrome: enlarged, polyfollicular, hyperandrogenic, anovulatory ovaries with accompanying LH hypersecretion. Oocyte developmental competence is also compromised. Insulin is implicated in the mechanism of both anovulation and deficient oocyte development. Fetal estrogen excess induces somewhat similar disruption of adult ovarian function to fetal androgen excess. Understanding the quality of the fetal female sex steroid hormone environment is thus becoming increasingly important in improving our knowledge of mechanisms underlying a variety of female reproductive pathologies

Increased Yield of ttbb at Hadron Colliders in Low-Energy Supersymmetry

Light bottom squarks and gluinos have been invoked to explain the b quark pair production excess at the Tevatron. We investigate the associated production of ttbb at hadron colliders in this scenario, and find that the rates for this process are enhanced over the Standard Model prediction. If light gluinos exist, it may be possible to detect them at the Tevatron, and they could easily be observed at the LHC.Comment: 5p, references added, version accepted to PR

The \u3cem\u3elet-7\u3c/em\u3e MicroRNA Family Members \u3cem\u3emir\u3c/em\u3e-48, \u3cem\u3emir\u3c/em\u3e-84, and mir-241 Function Together to Regulate Developmental Timing in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7 family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the hbl-1 3′ UTR and downregulating hbl-1 activity. Genetic analysis indicates that mir-48, mir-84, and mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes lin-28 and lin-46. These results indicate that let-7 family microRNAs function in combination to affect both early and late developmental timing decisions

Most \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e MicroRNAs are Individually Not Essential for Development or Viability

MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to post-transcriptionally inhibit gene expression. We report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C. elegans miRNAs. We find that the majority of miRNAs are not essential for the viability or development of C. elegans, and mutations in most miRNA genes do not result in grossly abnormal phenotypes. These observations are consistent with the hypothesis that there is significant functional redundancy among miRNAs or among gene pathways regulated by miRNAs. This study represents the first comprehensive genetic analysis of miRNA function in any organism and provides a unique, permanent resource for the systematic study of miRNAs

Relationship between nondestructive firmness measurements and commercially important ripening fruit stages for peaches, nectarines and plums

Fruit firmness measurement is a good way to monitor fruit softening and to predict bruising damage during harvest and postharvest handling. Ripening protocols traditionally utilize a destructive penetrometer-type fruit firmness measure to monitor ripening. Until recently, methods of assessing fruit texture properties nondestructively were not commercially available. The nondestructive Sinclair iQ™ firmness tester was investigated to monitor ripening and predict bruising susceptibility in stone fruit. This work was carried out on four peach, three plum, and five nectarine cultivars over two seasons. The correlations between destructive and nondestructive firmness measurements were significant (p-value = 0.0001), although too low for commercial applications as they varied from r2 = 0.60–0.71 according to fruit type. Using a different approach, the relationship between destructive and nondestructive firmness measures was characterized in terms of segregating these fruit according to their stages of ripening. This was done by using discriminant analysis (66–90% agreement in ripeness stage classification was observed in validation tests). Discriminant analysis consistently segregated nondestructive firmness measured fruit into commercially important classes (“ready to eat”, “ready to buy”, “mature and immature”). These represented key ripening stages with different bruising potentials and consumer acceptance. This work points out the importance to relate nondestructive measurements directly to important commercial physiological stages rather than to correlate them with the current standard penetrometer values. Thus, destructive and nondestructive firmness measurements can be directly used to identify the stage of ripeness and potential susceptibility to bruising during postharvest changes. Further work is recommended to evaluate the performance of this nondestructive sensor in segregating fruit according to their stage of ripeness under packinghouse or processing plant conditions

Epigenetic Mechanism Underlying the Development of Polycystic Ovary Syndrome (PCOS)-Like Phenotypes in Prenatally Androgenized Rhesus Monkeys

The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05). Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β) signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans

Signatures of HyperCharge Axions in Colliders

If in addition to the standard model fields, a new pseudoscalar field that couples to hypercharge topological number density, the hypercharge axion, exists, it can be produced in colliders in association with photons or Z bosons, and detected by looking for its decay into photons or Z's. For a range of masses below a TeV and coupling above a fraction of 1/TeV, existing data from LEP II and the Tevatron can already put interesting constraints, and in future colliders accessible detection range is increased significantly. The hypercharge axion can help in explaining the matter-antimatter asymmetry in the universe.Comment: 11 pages, 8 figures, uses axodraw.st

Evaluation of a community-based participatory physical activity promotion project: effect on cardiovascular disease risk profiles of school employees

<p>Abstract</p> <p>Background</p> <p>The efficacy of physical activity in improving cardiovascular disease (CVD) risk profiles has been well established. However, the effectiveness of health promotion programs implemented at the community level remains controversial. This study evaluated a school-based work-site physical activity program.</p> <p>Methods</p> <p>Using a community-based participatory research model, a work-site wellness intervention was implemented in a rural public school system in Southwestern Oklahoma. During the 2005-2006 school year, 187 participants (mean age 45 years) completed a pre intervention screening for CVD risk factors followed by a physical activity promotion program. Post intervention screening was conducted after a 6 month period. During both screening sessions, body composition, blood pressure, lipids, glucose and self-reported physical activity levels were assessed. The focus of the intervention was on promoting physical activity. Opportunities for in school physical activity were created by marking hallways, adding a treadmill in each school, and allowing teachers to use planning periods for physical activity.</p> <p>Results</p> <p>During the post intervention screening, compared to pre intervention levels, participants had lower total, low, and high density lipoprotein-cholesterol (t = 5.9, p < 0.0001, t = 2.6, p = 0.01, and t = 13.2, p < 0.0001 respectively), lower systolic blood pressure (t = 2.9, p = 0.004), and higher self-reported physical activity levels (Sign t = -1.901, p = 0.06).</p> <p>Conclusions</p> <p>A successful participatory program was associated with improvements in several CVD risk factors among school employees. Limitations of this study such as seasonal variation in the outcome variables and lack of a control group limit our ability to draw solid conclusions about the effectiveness of the intervention.</p

Profile Characteristics of Cut Tooth Surfaces Developed by Rotating Instruments

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68018/2/10.1177_00220345570360062301.pd