AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Elevated AMP/ATP ratio activates AMPK, which inhibits energy-consuming processes and activates ...energy-producing processes to restore the energy homeostasis inside the cell. AMPK activators, metformin and thiazolidinediones, are used for the treatment of type II diabetes. Recently, reports have indicated that AMPK may also be a beneficial target for cancer treatment. Cancer cells have characteristic metabolic changes different from normal cells and, being a key metabolic regulator, AMPK may regulate the switch. AMPK may act to inhibit tumorigenesis through regulation of cell growth, cell proliferation, autophagy, stress responses and cell polarity.
Understanding host-microbial interactions in the rumen and its influence on desirable production traits may lead to potential microbiota manipulation or genetic selection for improved cattle feed ...efficiency. This study investigated the host transcriptome and its correlation with the rumen archaea and bacteria differential abundance of two pure beef cattle breeds (Angus and Charolais) and one composite beef hybrid (Kinsella) divergent for residual feed intake (RFI; low-RFI vs. high-RFI). Using RNA-Sequencing of rumen tissue and 16S rRNA gene amplicon sequencing, differentially expressed genes (FDR ≤ 0.05, |log2(Fold-change) >|2) and differentially abundant (p-value < 0.05) archaea and bacteria amplicon sequence variants (ASV) were determined. Significant correlations between gene expression and ASVs (p-value < 0.05) were determine using Spearman correlation. Interesting associations with muscle contraction and the modulation of the immune system were observed for the genes correlated with bacterial ASVs. Potential functional candidate genes for feed efficiency status were identified for Angus (CCL17, CCR3, and CXCL10), Charolais (KCNK9, GGT1 and IL6), and Kinsella breed (ESR2). The results obtained here provide more insights regarding the applicability of target host and rumen microbial traits for the selection and breeding of more feed efficient beef cattle.
The TET (ten-eleven translocation) family of α-ketoglutarate (α-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), ...5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of α-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development.
Animal’s feed efficiency in growing cattle (i.e. the animal ability to reach a market or adult BW with the least amount of feed intake), is a key factor in the beef cattle industry. Feeding systems ...have made huge progress to understand dietary factors influencing the average animal feed efficiency. However, there exists a considerable amount of animal-to-animal variation around the average feed efficiency observed in beef cattle reared in similar conditions, which is still far from being understood. This review aims to identify biological determinants and molecular pathways involved in the between-animal variation in feed efficiency with particular reference to growing beef cattle phenotyped for residual feed intake (RFI). Moreover, the review attempts to distinguish true potential determinants from those revealed through simple associations or indirectly linked to RFI through their association with feed intake. Most representative and studied biological processes which seem to be connected to feed efficiency were reviewed, such as feeding behaviour, digestion and methane production, rumen microbiome structure and functioning, energy metabolism at the whole body and cellular levels, protein turnover, hormone regulation and body composition. In addition, an overall molecular network analysis was conducted for unravelling networks and their linked functions involved in between-animal variation in feed efficiency. The results from this review suggest that feeding and digestive-related mechanisms could be associated with RFI mainly because they co-vary with feed intake. Although much more research is warranted, especially with high-forage diets, the role of feeding and digestive related mechanisms as true determinants of animal variability in feed efficiency could be minor. Concerning the metabolic-related mechanisms, despite the scarcity of studies using reference methods it seems that feed efficient animals have a significantly lower energy metabolic rate independent of the associated intake reduction. This lower heat production in feed efficient animals may result from a decreased protein turnover and a higher efficiency of ATP production in mitochondria, both mechanisms also identified in the molecular network analysis. In contrast, hormones and body composition could not be conclusively related to animal-to-animal variation in feed efficiency. The analysis of potential biological networks underlying RFI variations highlighted other significant pathways such as lipid metabolism and immunity and stress response. Finally, emerging knowledge suggests that metabolic functions underlying genetic variation in feed efficiency could be associated with other important traits in animal production. This emphasizes the relevance of understanding the biological basis of relevant animal traits to better define future balanced breeding programmes.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that controls many aspects of cellular physiology, including transcription, translation, cell size, cytoskeletal organization and ...autophagy. Recent advances in the mTOR signaling field have found that mTOR exists in two heteromeric complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the integration of many signals, including growth factors, insulin, nutrients, energy availability and cellular stressors such as hypoxia, osmotic stress, reactive oxygen species and viral infection. In this review we highlight recent advances in the mTOR signaling field that relate to how the two mTOR complexes are regulated, and we discuss stress conditions linked to the mTOR signaling network that have not been extensively covered in other reviews. Given the diversity of signals that have been shown to impinge on mTOR, we also speculate on other signal-transduction pathways that may be linked to mTOR in the future.
Massive multiple-input multiple-output has been broadly accepted as one of the key candidate technologies for enabling next generation (5G) wireless network. To ensure system performance, an ...efficient frequency dependent precoding has to be in place to pre-compensate the frequency selective channel response in real time. This Letter presents a compact scalable frequency dependent precoding approach and its area-efficient field programmable gate arrays (FPGA) implementation. The proposed approach has been validated and well compared with other architectures both in the Matlab/Simulink and Xilinx FPGAs.
Past research has focused on the prevention and management of subacute rumen acidosis by manipulating the ration; however, the severity of acidosis varies even among animals fed a common high-grain ...diet. The objectives of this study were to compare the ruminal volatile fatty acid (VFA) profile and expression of genes involved in the metabolism of butyrate, the VFA most extensively metabolized by the ruminal epithelium, and intracellular pH regulation in ruminal epithelial cells between acidosis-resistant (AR) and acidosis-susceptible (AS) steers. Acidosis indexes (area per day under pH 5.8 divided by dry matter intake) were measured for 17 steers fed a common high-grain diet, and the 3 steers with the lowest (1.4±1.2 pH∙min/kg) and the 3 with the highest values (23.9±7.4 pH∙min/kg) were classified as AR and AS, respectively, and used in the subsequent study. The steers were force-fed a diet containing 85% grain at 60% of the expected daily intake (5.8±0.8 and 5.6±0.6kg for AR and AS, respectively) within 30min. Mean ruminal pH over the postprandial 6-h period was higher for AR compared with AS (6.02 vs. 5.55), and mean total VFA concentration was 74% for AR compared with AS (122 vs. 164mM). Molar proportion of butyrate in the ruminal fluid was 139% higher for AR compared with AS (17.5 vs. 7.33mol/100mol of VFA). Expression of monocarboxylate cotransporter isoform 1, sodium hydrogen exchanger isoforms 1 and 2, and anion exchangers (downregulated in adenoma and putative anion exchanger, isoform 1) did not differ between AR and AS steers. However, expression of sodium hydrogen exchanger isoform 3, which imports Na+ to the epithelial cell and exports H+ to the rumen, was 176% higher in AR steers than in AS steers. Higher ruminal pH for AR might be partly due to a faster rate of VFA absorption, lower VFA production, or both.
The transition from a high forage to a highly fermentable diet can induce digestive disorders in the rumen. To date, the host mechanisms that regulate the adaption to such dietary transition are ...largely unknown. To understand the molecular mechanisms involved in such phenomena, RNA-sequencing was performed to identify the changes in the transcriptome of ruminal epithelia during gradual transition from a diet containing 0% to 89% grain.
In total, the expression of 11,044, 11,322 and 11,282 genes were detected in ruminal epithelia of beef heifers (n = 15) fed 0%, 72% and 89% barley grain diet, respectively. The transcriptome profiles of rumen epithelia differed between low grain diet (LGD) (0% grain) and high grain diet (HGD) (72% and 89%), and HGD tended to reduce the expression of genes involved in epithelial catalytic and binding activities. When diet was changed from 72% to 89% grain, the mean ruminal pH change was significantly different among individual heifers with five of them decreased (down group (DG); from 6.30±0.09 to 5.87±0.15, P < 0.01) and five of them increased (up group (UG); from 5.84±0.42 to 6.35±0.37, P < 0.05). The functional analysis of differentially expressed (DE) genes revealed inhibited "Immune response of leukocytes", "Attraction of phagocytes", and "Cell movement of leukocytes" (P < 0.05) functions (Z-score = -2.2, -2.2 and -2.0, respectively) in DG, and inhibited "Concentration of lipid" and "Proliferation of epithelial cells" functions in UG (Z-score = -2.0, and -1.8, respectively). In addition, the expression of genes involved in ketogenesis (HMGCL) and lipid synthesis (SREBF2, FABP4) was increased in DG, while the expression of ketogenesis (ACAT2, HMGCS) and cholesterol synthesis related genes (HMGC and FDPS) were deceased in UG. Furthermore, the upstream regulators were found to be involved in the regulation of immune response and cell cycle progress, and SNP (g.46834311A > G) in FABP4 was identified between two groups of animals (P < 0.1).
The identified genes, upstream regulators, and SNP could be potential genetic markers that may account for the varied individual ruminal pH responses to the dietary transition stress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective of this study was to investigate the effect of time of first colostrum feeding on the passive transfer of IgG and on bacterial colonization in the intestine of neonatal dairy calves. ...Twenty-seven male Holstein calves were randomly assigned to 1 of 3 treatments at birth: calves were fed colostrum at 45 min (0 h, n = 9), 6 h (n = 9), or 12 h after birth (n = 9). Calves were fed pooled, heat-treated colostrum (62 g of IgG/L) at their respective feeding times at 7.5% of birth body weight and fed milk replacer at 2.5% of birth body weight per meal every 6 h thereafter. Blood samples were taken every 3 h using a jugular catheter and were analyzed for determination of serum IgG by radial immunodiffusion. At 51 h after birth, calves were euthanized for collection of tissue and digesta of the distal jejunum, ileum, and colon. Quantitative real-time PCR was used to estimate the prevalence of Bifidobacterium spp., Lactobacillus spp., Fecalibacterium prausnitzii, Clostridium cluster XIVa, and total Escherichia coli. Delaying colostrum feeding by 6 h (35.6 ± 1.88%) and 12 h (35.1 ± 3.15%) decreased the maximum apparent efficiency of absorption of IgG compared with feeding colostrum immediately after birth (51.8 ± 4.18%) and delayed the time to maximum serum IgG concentration (24 h vs. 15 h, respectively). Moreover, 12-h calves tended to have a lower prevalence of Bifidobacterium spp. (0.12 ± 0.017%) and Lactobacillus spp. (0.07 ± 0.019%) associated with the colon mucosa compared with 0-h calves (1.24 ± 0.648% and 0.26 ± 0.075%, respectively). In addition, 6-h (0.26 ± 0.124%) and 12-h (0.49 ± 0.233%) calves had a lower prevalence of total E. coli associated with ileum mucosa compared with 0-h calves (1.20 ± 0.458%). These findings suggest that delaying colostrum feeding within 12 h of life decreases the passive transfer of IgG and may delay the colonization of bacteria in the intestine, possibly leaving the calf vulnerable to infections during the preweaning period.
The present study was conducted to assess rumen bacteria in lactating cows with different milk protein yield, aiming to understand the role of rumen bacteria in this trait. Cows with high milk ...protein yield (high milk yield and high milk protein content, HH; n = 20) and low milk protein yield (low milk yield and low milk protein content, LL; n = 20) were selected from 374 mid-lactation Holstein dairy cows fed a high-grain diet. Measurement of the rumen fermentation products showed that the concentrations of ruminal total volatile fatty acids, propionate, butyrate, and valerate and the proportion of isobutyrate were higher in the HH cows than in the LL cows. Amplicon sequencing analysis of the rumen bacterial community revealed that the richness (Chao 1 index) of rumen microbiota was higher in the LL cows than in the HH cows. Among the 10 predominant bacterial phyla (relative abundance being >0.10%, present in >60% of animals within each group), the relative abundance of Proteobacteria was 1.36-fold higher in the HH cows than in the LL cows. At the genus level, the relative abundance of Succinivibrio was significantly higher and that of Clostridium tended to be higher in the LL cows than in the HH cows. Sharpea was 2.28-fold enriched in the HH cows compared with the LL cows. Different relationships between the relative abundances of rumen microbial taxa and volatile fatty acid concentrations were observed in the HH and the LL animals, respectively. Succinivibrio and Prevotella were positively correlated with acetate, propionate, and valerate in the LL cows, whereas Sharpea was positively correlated with propionate and valerate concentrations in the HH cows. Collectively, our results revealed that rumen bacterial richness and the relative abundances of several bacterial taxa significantly differed between dairy cows with high and low milk protein yields, suggesting the potential roles of rumen microbiota contributing to milk protein yield in dairy cows.
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