ResearchPad - cellular-physiology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The left ventricle undergoes biomechanical and gene expression changes in response to increased right ventricular pressure overload]]> https://www.researchpad.co/article/N51034a10-0d22-497f-84f8-cbd530e51603 Right ventricular (RV) failure is a common endpoint in pulmonary hypertension. While most clinical and research efforts are focused on the RV, our research shows that the left ventricle undergoes bio‐mechanical and gene‐expression changes in response to RV pressure overload.

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<![CDATA[Changes in strength and power performance and serum hormone concentrations during 12 weeks of task‐specific or strength training in conscripts]]> https://www.researchpad.co/article/Na43b4246-7b22-450e-9ad9-3ec7b3f4d206 Successful strength and conditioning program for conscripts cannot be built without taking into account the fracture nature of training caused by military specific training requirements. It is important in the future that the leadership prioritizes quality‐controlled physical training and supports necessary changes. Strength and task‐specific training can lead to improvements in the battlefield, reduce the risk of overtraining, and prevent injuries caused by excessive running and loaded marching during the traditional military training.

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<![CDATA[Expression of genes for Kisspeptin (KISS1), Neurokinin B (TAC3), Prodynorphin (PDYN), and gonadotropin inhibitory hormone (RFRP) across natural puberty in ewes]]> https://www.researchpad.co/article/Na8ed0eef-e84e-490d-a407-6f2702b89b5f

Abstract

Expression of particular genes in hypothami of ewes was measured across the natural pubertal transition by in situ hybridization. The ewes were allocated to three groups (n = 4); prepubertal, postpubertal and postpubertally gonadectomized (GDX). Prepubertal sheep were euthanized at 20 weeks of age and postpubertal animals at 32 weeks. GDX sheep were also euthanized at 32 weeks, 1 week after surgery. Expression of KISS1, TAC3, PDYN in the arcuate nucleus (ARC), RFRP in the dorsomedial hypothalamus and GNRH1 in the preoptic area was quantified on a cellular basis. KISS1R expression by GNRH1 cells was quantified by double‐label in situ hybridization. Across puberty, detectable KISS1 cell number increased in the caudal ARC and whilst PDYN cell numbers were low, numbers increased in the rostral ARC. TAC3 expression did not change but RFRP expression/cell was reduced across puberty. There was no change across puberty in the number of GNRH1 cells that expressed the kisspeptin receptor (KISS1R). GDX shortly after puberty did not increase expression of any of the genes of interest. We conclude that KISS1 expression in the ARC increases during puberty in ewes and this may be a causative factor in the pubertal activation of the reproductive axis. A reduction in expression of RFRP may be a factor in the onset of puberty, removing negative tone on GNRH1 cells. The lack of changes in expression of genes following GDX suggest that the effects of gonadal hormones may differ in young and mature animals.

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<![CDATA[Fish oil reverses metabolic syndrome, adipocyte dysfunction, and altered adipokines secretion triggered by high‐fat diet‐induced obesity]]> https://www.researchpad.co/article/N7684225e-d2c5-454e-aac8-4a64b5e39e5c

Abstract

The effect of fish oil (FO) treatment on high‐fat (HF) diet‐induced obesity and metabolic syndrome was addressed by analyzing dysfunctions in cells of different adipose depots. For this purpose, mice were initially induced to obesity for 8 weeks following a treatment with FO containing high concentration of EPA compared to DHA (5:1), for additional 8 weeks (by gavage, 3 times per week). Despite the higher fat intake, the HF group showed lower food intake but higher body weight, glucose intolerance and insulin resistance, significant dyslipidemia and increased liver, subcutaneous (inguinal‐ING) and visceral (retroperitoneal‐RP) adipose depots mass, accompanied by adipocyte hypertrophy and decreased cellularity in both adipose tissue depots. FO treatment reversed all these effects, as well as it improved the metabolic activities of isolated adipocytes, such as glucose uptake and lipolysis in both depots, and de novo synthesis of fatty acids in ING adipocytes. HF diet also significantly increased both the pro and anti‐inflammatory cytokines expression by adipocytes, while HF + FO did not differ from control group. Collectively, these data show that the concomitant administration of FO with the HF diet is able to revert metabolic changes triggered by the diet‐induced obesity, as well as to promote beneficial alterations in adipose cell activities. The main mechanism underlying all systemic effects involves direct and differential effects on ING and RP adipocytes.

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<![CDATA[Unexpected effects of the MIP‐CreER transgene and tamoxifen on β‐cell growth in C57Bl6/J male mice]]> https://www.researchpad.co/article/5bd0510e40307c64fb333bbe

Abstract

Transgenic mouse models have been fundamental in the discovery of factors that regulate β‐cell development, mass, and function. Several groups have recently shown that some of these models display previously uncharacterized phenotypes due to the transgenic system itself. These include impaired islet function and increased β‐cell mass due to the presence of a human growth hormone (hGH) minigene as well as impaired β‐cell proliferation in response to tamoxifen (TM) administration. We aimed to determine how these systems impact β‐cell mass and proliferation during high fat diet (HFD). To this end, we utilized C57Bl6/J male MIP‐CreER mice, which are known to express hGH, or wild‐type (WT) mice treated with vehicle corn oil or TM. In the absence of TM, MIP‐CreER mice fed a chow diet have increased β‐cell mass due to hypertrophy, whereas replication is unchanged. Similarly, after 1 week on HFD, MIP‐CreER mice have increased β‐cell mass compared to WT, and this is due to hypertrophy rather than increased proliferation. To assess the impact of TM on β‐cell proliferation and mass, WT mice were treated with vehicle corn oil or TM and then fed a chow diet or HFD for 3 days. We observed that TM‐treated mice have improved glucose homeostasis on chow diet but impaired β‐cell proliferation in response to 3 days HFD feeding. These results unveil additional complications associated with commonly used pancreas‐specific mouse models.

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<![CDATA[Deep‐targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans]]> https://www.researchpad.co/article/5b04c2d5463d7e27b5abe310

Abstract

We found variants from the Angiotensinogen‐Converting Enzyme (ACE), Angiotensin Type 1 Receptor (AGTR1), Aldosterone Synthase (CYP11B2), and Adducin (ADD1) genes exhibited intensity‐dependent associations with the ambulatory blood pressure (BP) response following acute exercise, or postexercise hypotension (PEH). In a validation cohort, we sequenced exons from these genes for their associations with PEH. Obese (30.9 ± 3.6 kg m−2) adults (n = 23; 61% African Americans [AF], 39% Caucasian) 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) completed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects wore an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing using the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for further statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing corrected p‐values under time adjusted linear models for 19 hourly BP measurements per subject. After vigorous intensity over 19 h among ACE,AGTR1,CYP11B2, and ADD1 variants passing multiple testing thresholds, as the #MA increased, systolic (SBP) and/or diastolic BP decreased 12 mmHg (P = 4.5E‐05) to 30 mmHg (P = 6.4E‐04) among AF only. In contrast, after moderate intensity over 19 h among ACE and CYP11B2 variants passing multiple testing thresholds, as the #MA increased, SBP increased 21 mmHg (P = 8.0E‐04) to 22 mmHg (P = 8.2E‐04) among AF only. In this replication study, ACE,AGTR1,CYP11B2, and ADD1 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. Renal variants should be explored further with a multi‐level “omics” approach for associations with PEH among a large, ethnically diverse sample of adults with hypertension.

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<![CDATA[Carbonic anhydrase 2‐like in the giant clam, Tridacna squamosa: characterization, localization, response to light, and possible role in the transport of inorganic carbon from the host to its symbionts]]> https://www.researchpad.co/article/5b467fed463d7e5f40bc6df3

Abstract

The fluted giant clam, Tridacna squamosa, lives in symbiosis with zooxanthellae which reside extracellularly inside a tubular system. Zooxanthellae fix inorganic carbon (Ci) during insolation and donate photosynthate to the host. Carbonic anhydrases catalyze the interconversion of CO 2 and HCO3, of which carbonic anhydrase 2 (CA2) is the most ubiquitous and involved in many biological processes. This study aimed to clone a CA2 homolog (CA2‐like) from the fleshy and colorful outer mantle as well as the thin and whitish inner mantle of T. squamosa, to determine its cellular and subcellular localization, and to examine the effects of light exposure on its gene and protein expression levels. The cDNA coding sequence of CA2‐like from T. squamosa comprised 789 bp, encoding 263 amino acids with an estimated molecular mass of 29.6 kDa. A phenogramic analysis of the deduced CA2‐like sequence denoted an animal origin. CA2‐like was not detectable in the shell‐facing epithelium of the inner mantle adjacent to the extrapallial fluid. Hence, CA2‐like is unlikely to participate directly in light‐enhanced calcification. By contrast, the outer mantle, which contains the highest density of tertiary tubules and zooxanthellae, displayed high level of CA2‐like expression, and CA2‐like was localized to the tubule epithelial cells. More importantly, exposure to light induced significant increases in the protein abundance of CA2‐like in the outer mantle. Hence, CA2‐like could probably take part in the increased supply of inorganic carbon (Ci) from the host clam to the symbiotic zooxanthellae when the latter conduct photosynthesis to fix Ci during light exposure.

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<![CDATA[Variation in the repulsive guidance molecule family in human populations]]> https://www.researchpad.co/article/5c82b4d6d5eed0c484e5d648

Abstract

Repulsive guidance molecules, RGMA, RGMB, and RGMC, are related proteins discovered independently through different experimental paradigms. They are encoded by single copy genes in mammalian and other vertebrate genomes, and are ~50% identical in amino acid sequence. The importance of RGM actions in human physiology has not been realized, as most research has focused on non‐human models, although mutations in RGMC are the cause of the severe iron storage disorder, juvenile hemochromatosis. Here I show that repositories of human genomic and population genetic data can be used as starting points for discovery and for developing new testable hypotheses about each of these paralogs in human biology and disease susceptibility. Information was extracted, aggregated, and analyzed from the Ensembl and UCSC Genome Browsers, the Exome Aggregation Consortium, the Genotype‐Tissue Expression project portal, the cBio portal for Cancer Genomics, and the National Cancer Institute Genomic Data Commons data site. Results identify extensive variation in gene expression patterns, substantial alternative RNA splicing, and possible missense alterations and other modifications in the coding regions of each of the three genes, with many putative mutations being detected in individuals with different types of cancers. Moreover, selected amino acid substitutions are highly prevalent in the world population, with minor allele frequencies of up to 37% for RGMA and up to 8% for RGMB. These results indicate that protein sequence variation is common in the human RGM family, and raises the possibility that individual variants will have a significant population impact on human physiology and/or disease predisposition.

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<![CDATA[Intestine‐specific expression of human chimeric intestinal alkaline phosphatase attenuates Western diet‐induced barrier dysfunction and glucose intolerance]]> https://www.researchpad.co/article/5c09e692d5eed0c484348ee6

Abstract

Intestinal epithelial cell derived alkaline phosphatase (IAP) dephosphorylates/detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen. We have earlier demonstrated that consumption of high‐fat high‐cholesterol containing western type‐diet (WD) significantly reduces IAP activity, increases intestinal permeability leading to increased plasma levels of LPS and glucose intolerance. Furthermore, oral supplementation with curcumin that increased IAP activity improved intestinal barrier function as well as glucose tolerance. To directly test the hypothesis that targeted increase in IAP would protect against WD‐induced metabolic consequences, we developed intestine‐specific IAP transgenic mice where expression of human chimeric IAP is under the control of intestine‐specific villin promoter. This chimeric human IAP contains domains from human IAP and human placental alkaline phosphatase, has a higher turnover number, narrower substrate specificity, and selectivity for bacterial LPS. Chimeric IAP was specifically and uniformly overexpressed in these IAP transgenic (IAPTg) mice along the entire length of the intestine. While IAP activity reduced from proximal P1 segment to distal P9 segment in wild‐type (WT) mice, this activity was maintained in the IAPTg mice. Dietary challenge with WD impaired glucose tolerance in WT mice and this intolerance was attenuated in IAPTg mice. Significant decrease in fecal zonulin, a marker for intestinal barrier dysfunction, in WD fed IAPTg mice and a corresponding decrease in translocation of orally administered nonabsorbable 4 kDa FITC dextran to plasma suggests that IAP overexpression improves intestinal barrier function. Thus, targeted increase in IAP activity represents a novel strategy to improve WD‐induced intestinal barrier dysfunction and glucose intolerance.

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