Development of ketosis in high-producing dairy cows contributes to several animal health issues and highlights the need for a better understanding of the genetic basis of metabolic diseases. To ...evaluate the pattern of differential gene expression in the liver of cows under negative energy balance (NEB), and under subclinical and clinical ketosis, a meta-analysis of gene expression and genome-wide association studies results was performed. An initial systematic review identified 118 articles based on the key words “cow,” “liver,” “negative energy balance,” “ketosis,” “expression,” “qPCR,” “microarray,” “proteomic,” “RNA-Seq,” and “GWAS.” After further screening for only peer-reviewed and pertinent articles for gene expression during NEB and clinical and subclinical ketosis (considering plasma levels of β-hydroxybutyrate), 20 articles were included in the analysis. From the systematic review, 430 significant SNPs identified by genome-wide association studies (GWAS) were assigned to genes reported in gene expression studies by considering chromosome and base pair positions in the ARS-UCD 1.2 bovine assembly. Venn diagrams were created to integrate the data obtained in the systematic review, and Gene Ontology enrichment analysis was carried out using official gene names. A QTL enrichment analysis was also performed to identify potential positional candidate loci. Twenty-four significant SNPs were located within the coordinates of differentially expressed genes located on chromosomes 2, 3, 6, 9, 11, 14, 27, and 29. Three significant metabolic pathways were associated with NEB and subclinical and clinical ketosis. In addition, 2 important genes, PPARA (peroxisome proliferator activated receptor alpha) and ACACA (acetyl-coenzyme A carboxylase α), were identified, which were differentially expressed in the 3 metabolic conditions. The PPARA gene is involved in the regulation of lipid metabolism and fatty liver disease and the ACACA gene encodes an enzyme that catalyzes the carboxylation of acetyl-coenzyme A to malonyl-coenzyme A, which is a rate-limiting step in fatty acid synthesis. Gene network analysis revealed co-expression interactions among 34 genes associated with functions involving fatty acid transport and fatty acid metabolism. For the annotated QTL, 9 QTL were identified for ketosis. The genes FN1 (fibronectin 1) and PTK2 (protein tyrosine kinase 2), which are mainly involved in cell adhesion and formation of extracellular matrix constituents, were enriched for QTL previously associated with the trait “ketosis” on chromosome 2 and for the trait “milk iron content” on chromosome 14, respectively. This integration of gene expression and GWAS data provides an additional understanding of the genetic background of NEB and subclinical and clinical ketosis in dairy cattle. Thus, it is a useful approach to identify biological mechanisms underlying these metabolic conditions in dairy cattle.
In this paper the authors derive a higher-order shear deformation theory for modeling functionally graded plates accounting for extensibility in the thickness direction.
The explicit governing ...equations and boundary conditions are obtained using the principle of virtual displacements under Carrera’s Unified Formulation. The static and eigenproblems are solved by collocation with radial basis functions.
The efficiency of the present approach is assessed with numerical results including deflection, stresses, free vibration, and buckling of functionally graded isotropic plates and functionally graded sandwich plates.
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development
. The central melanocortin system ...acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure
. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
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GO toxicity during zebrafish larvae development: non-dose-dependent effects (DA: dopamine; dat: dopamine transporter).
•GO exposure changed cardiac, locomotor and morphological ...parameters in vivo.•GO toxicity showed non-dose-dependent effect.•Dopamine-related alterations may be associated with autophagosome formation.
Although graphene oxide (GO), a nanomaterial with hexagonal planar layer, has been widely studied due to its applications in neurobiology that include drug delivery and tissue engineering, additional studies to assess its potential toxic effects are still needed. Thus, this study evaluated the effects of GO exposure (at 5, 10, 50 or 100mg/L) during six consecutive days on mortality, hatching, spontaneous movement, heart rate, morphology, locomotion behavior, acetylcholinesterase (AChE) activity, dopamine levels and relative gene expression of developmental neurology-related genes using zebrafish larvae. In the 5mg/L dose, synapsin IIa expression up-regulation was seen concomitantly with down-regulation of dat expression, showing a potential compensatory mechanism. Moreover, the 10mg/L exposure caused an increase in heart rate, in absolute turn angle, brain cell damage and a decrease in dopamine levels. These alterations may be associated with autophagosome formation found in GO-exposed larval brain. No changes were observed on higher doses of GO exposure, probably due to nanomaterial agglomeration. Taken together, these results show that toxic effects of GO exposure are not dose-dependent, and are preeminent in lower concentrations. Additional studies are needed to deepen the specific mechanisms of GO neurotoxicity and are required to elucidate its potential biomedical use.
Pregnancy toxemia (PT) is considered one of the most common metabolic diseases with high impact on the production of small ruminants. The objective of this study was investigate possible myocardial ...damage in goats affected with PT by the determination of serum myocardial biomarkers CK-MB and cTnI. A total of 44 goats affected with PT, and 10 apparently healthy goats (control group or CG) were used in the study. In goats with PT, the serum concentrations of cTnI (0.43 ng/mL) were significantly higher than that in CG goats (0.06 ng/mL). Although CK-MB showed no significant difference, it was approximately three times higher in animals with PT. The serum concentrations of insulin were significantly lower in PT goats (5.03 ppmol/L) compared to CG goats (10.66 pmol/L). The serum concentrations of cortisol in PT goats (155.41 nmol/L) were significantly higher than that in CG goats (36.58 nmol/L). Results of this study indicate that a clinically significant myocardial damage might occur in goats affected with PT leading to significant elevations in values of cTnI and CK-MB. Therefore, these parameters could be used as a potential prognostic indicator in goats affected with this important disease.
•The cTnI concentrations in the PT group (0.43 ng/mL) were higher than goats of control group (0.06 ng/mL) (p = .0238).•Higher concentrations of β-OHB, NEFA, glucose, cortisol, AST and GGT were observed in the goats of the PT group.•Elevations in the concentrations of cardiac biomarkers in PT group were sufficient to evidence cardiac injury.
In this paper we present a new application for Carrera’s unified Formulation (CUF) to analyse functionally graded plates.
In this paper the authors present explicit governing equations of a ...sinusoidal shear deformation theory for functionally graded plates. It addresses the bending and free vibration analysis and accounts for through-the-thickness deformations.
The equations of motion are interpolated by collocation with radial basis functions. Numerical examples demonstrate the efficiency of the present approach.
Abstract Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets ...enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na+ K+ -ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na+ K+ -ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na+ K+ -ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.
The onset of menopause and accompanying changes to ovarian hormones often precedes endothelial dysfunction in women. In particular, accelerated impairments in macrovascular and microvascular function ...coincide with the loss of estrogen, as does impaired endothelial responses to ischemia-reperfusion (IR) injury. In healthy, early postmenopausal women (
= 12; 3.9 ± 1.5 years since menopause) we tested the hypothesis that acute dietary nitrate (NO
) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison with placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO
-rich (BR
) and NO
-depleted (BR
) beetroot juice (BR) consumption, as well as following IR injury, and 15 min after IR to assess recovery. Analyses with repeated-measures general linear models revealed a condition × time interaction for brachial artery flow-mediated dilation (FMD;
= 0.04), and no interaction effect was found for the near-infrared spectroscopy-derived reperfusion slope (
= 0.86). Follow-up analysis showed a significant decline in FMD following IR injury with BR
in comparison with all other timepoints (all,
< 0.05), while this decline was not present with BR
(all,
> 0.05). Our findings demonstrate that a single dose of dietary NO
minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Trial registration number: NCT03644472.
In healthy, early postmenopausal women, a single dose of NO
-rich BR can protect against IR-induced endothelial dysfunction. This protection may be due to nitric oxide bioactivity during IR rather than improved endothelial function prior to the IR protocol per se.
Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy ...for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.
► Trans fat (TF) consumption can modify the neuronal plasticity causing motor diseases. ► TF-fed rats showed movement disorders, which was intensified by exercise. ► TF and lard decreased catalase ...activity, which was increased by exercise in TF group. ► Exercise increased striatal Na
+K
+-ATPase activity of lard and soybean-fed rats. ► TF inhibited benefits of exercise indicating its critical role in brain neurochemistry.
The influence of
trans fatty acids (FA) on development of orofacial dyskinesia (OD) and locomotor activity was evaluated. Rats were fed with diets enriched with 20% soybean oil (SO;
n
−
6 FA), lard (L; saturated FA) or hydrogenated vegetable fat (HVF;
trans FA) for 60 weeks. In the last 12 weeks each group was subdivided into sedentary and exercised (swimming). Brains of HVF and L-fed rats incorporated 0.33% and 0.20% of
trans FA, respectively, while SO-fed group showed no incorporation of
trans FA. HVF increased OD, while exercise exacerbated this in L and HVF-fed rats. HVF and L reduced locomotor activity, and exercise did not modify. Striatal catalase activity was reduced by L and HVF, but exercise increased its activity in the HVF-fed group. Na
+K
+-ATPase activity was not modified by dietary FA, however it was increased by exercise in striatum of SO and L-fed rats. We hypothesized that movement disorders elicited by HVF and less by L could be related to increased dopamine levels in striatum, which have been related to chronic
trans FA intake. Exercise increased OD possibly by increase of brain dopamine levels, which generates pro-oxidant metabolites. Thus, a long-term intake of
trans FA caused a small but significant brain incorporation of
trans FA, which favored development of movement disorders. Exercise worsened behavioral outcomes of HVF and L-fed rats and increased Na
+K
+-ATPase activity of L and SO-fed rats, indicating its benefits. HVF blunted beneficial effects of exercise, indicating a critical role of
trans FA in brain neurochemistry.
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