To examine the genetic and environmental influences on variances in weight, height, and BMI, from birth through 19 years of age, in boys and girls from three continents.
Cross-sectional twin study. ...Data obtained from a total of 23 twin birth-cohorts from four countries: Canada, Sweden, Denmark, and Australia. Participants were Monozygotic (MZ) and dizygotic (DZ) (same- and opposite-sex) twin pairs with data available for both height and weight at a given age, from birth through 19 years of age. Approximately 24,036 children were included in the analyses.
Heritability for body weight, height, and BMI was low at birth (between 6.4 and 8.7% for boys, and between 4.8 and 7.9% for girls) but increased over time, accounting for close to half or more of the variance in body weight and BMI after 5 months of age in both sexes. Common environmental influences on all body measures were high at birth (between 74.1-85.9% in all measures for boys, and between 74.2 and 87.3% in all measures for girls) and markedly reduced over time. For body height, the effect of the common environment remained significant for a longer period during early childhood (up through 12 years of age). Sex-limitation of genetic and shared environmental effects was observed.
Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in pre-adolescent years and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. As gene-environment correlation and interaction is likely, it is also necessary to identify the genetic variants that may predispose individuals to obesity.
In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing ...survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H
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and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.
An observational study of 790 to over 3,000 herds was conducted to estimate the within-herd prevalence and cow-level risk factors for ketosis in dairy cattle in herds that participate in a Dairy Herd ...Improvement Association (DHIA) program. Ketosis or hyperketolactia (KET) was diagnosed as milk β-hydroxybutyrate ≥0.15 mmol/L at first DHIA test when tested within the first 30 d in milk. Seven hundred ninety-five herds providing at least 61 first milk tests from June 2014 to December 2015 were used to estimate the provincial within-herd prevalence of KET. All herds on DHIA in Ontario (n = 3,042) were used to construct cow-level multilevel logistic regression models to investigate the association of DHIA collected variables with the odds of KET at first DHIA milk test. Primiparous and multiparous animals were modeled independently. The cow-level KET prevalence in Ontario was 21%, with an average within-herd prevalence of 21% (standard deviation = 10.6) for dairy herds enrolled in a DHIA program. The prevalence of KET had a distinct seasonality with the lowest prevalence occurring from July to November. Automatic milking systems (AMS) were associated with increased within-herd prevalence, as well as increased odds of KET in multiparous animals at first test (odds ratio: 1.45; 95% confidence interval: 1.30 to 1.63). Jersey cattle had over 1.46 times higher odds of KET than Holstein cattle. Milk fat yield ≥1.12 kg/d at the last test of the previous lactation was associated with decreased odds of KET in the current lactation (odds ratio: 0.56; 95% confidence interval: 0.53 to 0.59). Increased days dry and longer calving intervals, for multiparous animals, and older age at first calving for primiparous animals increased the odds of KET at first test. This study confirms previous findings that increased days dry, longer calving intervals, and increased age at first calving are associated with increased odds of KET and is the first report of increased KET in herds with AMS and in relation to milk fat yield at the final test of the previous lactation. Feeding management on AMS herds likely contributes to the increased prevalence of KET and further work is required to investigate modifications to current management to minimize risk. Milk fat yield during the previous lactation may be representative of energy partitioning.
The Lamina Cribrosa is a part of the optic nerve head acting as a scaffold for collecting the retinal ganglion cell axons. It can be modeled as a poroelastic material where the saturated porosity ...stands for the capillary network running inside the collagen beams. Our aim is to study the interaction between tissue porosity, deformation and hemodynamics. To this end we first focus on the derivation of a poroelastic model in a rather general case, using as a prototype a model of species diffusion in an elastic material. Then we outline the clinical significance of the mechanical behavior of the Lamina Cribrosa and show, through numerical simulations, how an increased intraocular pressure results in a deformation affecting porosity and blood perfusion. We emphasize how the model behavior relies on the free energy expression.
We study model self-propelled crawlers which derive their propulsive capabilities from the tangential resistance to motion offered by the environment. Two types of relationships between tangential ...forces and slip velocities are considered: a linear, Newtonian one and a non-linear one of Bingham-type. Different behaviors result from the two different rheologies. These differences and their implications in terms of motility performance are discussed. Our aim is to develop new tools and insight for future studies of cell motility by crawling.
► We analyze model, self-propelled crawlers on viscous substrates. ► Both linear (Newtonian) and non-linear (Bingham-type) substrates are considered. ► We show that exploiting non-linearities is the key to achieve motion by shape change. ► Large strains allow for net advancement even in the case of a linear rheology. ► The direction of motion can be inverted by changing the substrate's rheology.
Treatment of hyperketonemia with oral propylene glycol has proven efficacy but the cure rate remains moderate. Dexamethasone has long been suggested as a treatment for hyperketonemia, even though ...evidence of its efficacy is contradictory. The objective of this randomized controlled trial was to evaluate the effect of adding a single intramuscular injection of 20mg of dexamethasone to oral propylene glycol therapy for hyperketonemia blood β-hydroxybutyrate (BHB) ≥1.2mmol/L. All cows between 3 and 16d in milk on 4 dairy farms in New York State were tested once weekly for hyperketonemia using a handheld ketone meter. All enrolled animals received 312g (300mL) of propylene glycol orally once daily for 4d and either a single injection of dexamethasone or an equivalent volume of sterile saline. A total of 509 animals were enrolled, with 254 and 255 in the placebo and dexamethasone groups, respectively. Treatment with dexamethasone decreased the odds of being hyperketonemic in the second week posttreatment; however, the odds of hyperketonemia in the first week posttreatment only decreased in those animals that were treated at a BHB blood concentration between 1.2 and 1.5mmol/L. For the 8% of cows with blood BHB >3.2mmol/L at enrollment, receiving dexamethasone increased the odds of being hyperketonemic the following week. We detected no difference between treatment groups in the odds of postpartum disease or in milk production. For cows with initial BHB of 1.2 to 1.5mmol/L, treatment with dexamethasone tended to reduce the odds of pregnancy at first insemination. Based on the small and conditional benefits of dexamethasone and a lack of difference in milk yield or disease incidence, we do not recommend the use of dexamethasone to treat hyperketonemia.
Abstract
Study question
Does reproductive aging alter the expression of genes involved in NAD+ metabolism in the mammalian oocyte?
Summary answer
We found that aging alters the expression of thirty ...genes encoding for NAD+-producing and NAD+-consuming enzymes pathway in mouse MII oocytes.
What is known already
NAD, a multifunctional metabolite in living cells, is known to convert between its oxidized NAD+ and reduced NADH forms during nutrients breakdown; the intracellular NAD+/NADH redox state reflects cell ability in generating ATP energy. NAD+ is utilized by proteins that control gene expression, DNA repair, apoptosis, mitochondrial biogenesis (i.e. sirtuins). Raising NAD+ by inducing its biosynthesis leads to sirtuins activation, so directly linking the cellular redox state with signalling events. The NAD+ pool is set by a critical balance between NAD+ biosynthetic and NAD+ consuming pathways. NAD(P)H levels declined in aged oocytes and NAD+ precursors seem to counteract ovarian aging.
Study design, size, duration
Pools of 25 oocytes at MII stage were obtained from young (4–8 weeks) and reproductively aged (48–52 weeks) CD–1 mice and processed for the analysis of 41 genes participating in NAD+ biosynthetic and NAD+ consuming pathways NAD+ pathways. Each experiment was performed three times and data were subjected to bioinformatic analysis to unravel potential age-related effects on NAD metabolism.
Participants/materials, setting, methods
Mice were superovulated by intraperitoneal injection of PMSG followed by hCG 48h apart. MII oocytes were isolated by 0.3 mg/ml hyaluronidase. RNA was obtained from each sample by Arcturus PicoPure Kit, and reverse transcribed. Each cDNA was analysed in triplicate by employing a NAD Metabolism H41 Predesigned panel for use with SYBR® Green, containing 41 genes of the NAD pathway, 2 housekeeping genes and 6 control probes. Raw data were analysed by DataAssist software.
Main results and the role of chance
The comparison between aged and young oocytes were focused on genes showing an absolute fold change (FC) <0.7 or > 1.4, a present call in at least the 50% of experiments and a p-Value <0.05 (ANOVA). Excluding transcripts showing a concordant value < 80%, n.30 differentially expressed genes (DEGs) were found: n.26 transcripts down-expressed and n.4 genes up-regulated. Data obtained by Ingenuity Pathways Analysis (IPA) software (Ingenuity Systems) provide evidence that NAD+ biosynthesis in aged oocytes is severely compromised.
Limitations, reasons for caution
Our results on animal model must be taken with caution. Validation of NAD+ precursor or activators of NAD+ biosynthesis in vivo administration is required.
Wider implications of the findings: Present results demonstrate that aging affect oocyte genes involved in the regulation of NAD+ availability and supports the hypothesis that modulation of NAD+ metabolism may be an “anti-aging” strategy. Overall, these data laid the foundation for a central role of NAD+ metabolism in the maintenance of oocyte competenc
Trial registration number
Not applicable
Several rapid tests for use on farm have been validated for the detection of hyperketonemia (HK) in dairy cattle, however the reported sensitivity and specificity of each method varies and no single ...study has compared them all. Meta-analysis of diagnostic test accuracy is becoming more common in human medical literature but there are few veterinary examples. The objective of this work was to perform a systematic review and meta-analysis to determine the point-of-care testing method with the highest combined sensitivity and specificity, the optimal threshold for each method, and to identify gaps in the literature.
A comprehensive literature search resulted in 5196 references. After removing duplicates and performing relevance screening, 23 studies were included for the qualitative synthesis and 18 for the meta-analysis. The three index tests evaluated in the meta-analysis were: the Precision Xtra® handheld device measuring beta-hydroxybutyrate (BHB) concentration in whole blood, and Ketostix® and KetoTest® semi-quantitative strips measuring the concentration of acetoacetate in urine and BHB in milk, respectively.
The diagnostic accuracy of the 3 index tests relative to the reference standard measurement of BHB in serum or whole blood between 1.0–1.4mmol/L was compared using the hierarchical summary receiver operator characteristic (HSROC) method. Subgroup analysis was conducted for each index test to examine the accuracy at different thresholds. The impact of the reference standard threshold, the reference standard method, the prevalence of HK in the population, the primary study source and risk of bias of the primary study was explored using meta-regression.
The Precision Xtra® device had the highest summary sensitivity in whole blood BHB at 1.2mmol/L, 94.8% (CI95%: 92.6–97.0), and specificity, 97.5% (CI95%: 96.9–98.1). The threshold employed (1.2–1.4mmol/L) did not impact the diagnostic accuracy of the test. The Ketostix® and KetoTest® strips had the highest summary sensitivity and specificity when the trace and weak positive thresholds were used, respectively.
Controlling for the source of publication, HK prevalence and reference standard employed did not impact the estimated sensitivity and specificity of the tests. Including only peer-reviewed studies reduced the number of primary studies evaluating the Precision Xtra® by 43% and Ketostix® by 33%. Diagnosing HK with blood, urine or milk are valid options, however, the diagnostic inaccuracy of urine and milk should be considered when making economic and treatment decisions.
To elucidate molecular mechanisms underlying oocyte senescence, we investigated whether oocytes from female mice of advanced
reproductive age exhibit a precocious postovulatory aging that, in turn, ...may be responsible for the precocious activation
of an apoptotic program. During a 9-h in vitro culture, the frequency of oocytes showing MII aberrations, spontaneous activation,
and cellular fragmentation increased in old oocytes ( P < 0.05), whereas it did not change in the young group. In old oocytes, the activities of MPF (a complex of the cyclin-dependent
kinase cdc2 and cyclin B1) and MAPK (mitogen-activated protein kinase) decreased precociously, showing a first drop as early
as 3 h after the beginning of in vitro culture ( P < 0.05). Immunoblotting and immunocytochemical analysis revealed that, in oocytes of the old group, reduction of BCL2 expression
at protein level occurred earlier than in the young group ( P < 0.05) and was not associated to the loss of BCL2 transcripts detected by RT-PCR. These changes are followed by an abrupt
increase of the rate of TUNEL-positive oocytes after 24 h of culture to a value of 67% ± 6%. Exposure of young oocytes to
20 μM roscovitine or 20 μM U0126, specific inhibitors of MPF and MAPK, resulted in the decreased percentage of oocytes showing
positive immunostaining for BCL2 and in an increased rate of DNA fragmentation. Present results suggest that the developmental
competence of oocytes ovulated by aging mice may be negatively influenced by a downregulation of MPF and MAPK activities that
in turn induces the activation of a proapoptotic signaling pathway.
Abstract
Oocytes from old mice cultured after ovulation exhibit a failure in the mechanism that control metaphase II state inducing
the activation of a pro-apoptotic pathway through the precocious degradation of BCL2 protein.
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