Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32 °C instead of 37 °C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process

Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-α

The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsuli-naemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonely) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone

Antioksidativna aktivnost etanolnih ekstrakata Solanum Retroflexum

In this paper the antioxidant activity of ethanolic extracts from Solanum retroflexum Dun fruits were investigated. The extracts were obtained by classical technique and by Soxhlet extraction. In order to investigate the possibilities of future utilization of Solanum retroflexum fruits, the antioxidant activity, by FRAP and DPPH method was determined. Results showed the extract obtained by 75% ethanol and classic extraction during 45 minutes at 60°C, had the highest antioxidant activity, both for DPPH and FRAP method (EC50 was 60,67 μg/mL and 1,55 μmol Fe2+/mg, respectively). There was good correlation of results for antioxidant activity obtained by both methods and for all analyzed extracts.Rad se bavi ispitivanjem antioksidativne aktivnosti etanolnih ekstrakata ploda biljke Solanum retroflexum Dun. Ekstrakti su dobijeni tehnikama klasične i Soxhlet extrakcije. Potencijalna antioksidativna aktivnost je ispitana FRAP i DPPH metodama. Rezultati su pokazali da ekstrakt dobijen klasičnom ekstrakcijom sa 75% rastvorom etanola na 60°C i za vreme 45 minuta, ima najveću antioksidativnu aktivnost (EC50 = 60,67 μg/ml, 1,55 μmol Fe2+/mg), kao i da postoji dobra korelacija rezultata dobijenih obema metodama u slučaju svih analiziranih ekstrakata

A convergence on Boolean algebras generalizing the convergence on the Aleksandrov cube

We compare the forcing related properties of a complete Boolean algebra B with the properties of the convergences $\lambda_s$ (the algebraic convergence) and $\lambda_{ls}$ on B generalizing the convergence on the Cantor and Aleksandrov cube respectively. In particular we show that $\lambda_{ls}$ is a topological convergence iff forcing by B does not produce new reals and that $\lambda_{ls}$ is weakly topological if B satisfies condition $(\hbar)$ (implied by the ${\mathfrak t}$-cc). On the other hand, if $\lambda_{ls}$ is a weakly topological convergence, then B is a $2^{\mathfrak h}$-cc algebra or in some generic extension the distributivity number of the ground model is greater than or equal to the tower number of the extension. So, the statement "The convergence $\lambda_{ls}$ on the collapsing algebra B=\ro ((\omega_2)^{<\omega}) is weakly topological" is independent of ZFC

Caffeine exposure induces browning features in adipose tissue in vitro and in vivo

Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo. Stem cell-derived adipocytes exposed to caffeine (1 mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans

KIR gene content diversity in four Iranian populations

Killer cell immunoglobulin-like receptors (KIR) regulate natural killer cell response against infection and malignancy. KIR genes are variable in the number and type, thereby discriminating individuals and populations. Herein, we analyzed the KIR gene content diversity in four native populations of Iran. The KIR genomic diversity was comparable between Bakhtiari and Persian and displayed a balance of A and B KIR haplotypes, a trend reported in Caucasian and African populations. The KIR gene content profiles of Arab and Azeri were comparable and displayed a preponderance of B haplotypes, a scenario reported in the natives of America, India, and Australia. A majority of the B haplotype carriers of Azeri and Arab had a centromeric gene-cluster (KIR2DS2-2DL2-2DS3-2DL5). Remarkably, this cluster was totally absent from the American natives but occurred at highest frequencies in the natives of India and Australia in combination with another gene cluster at the telomeric region (KIR3DS1-2DL5-2DS5-2DS1). Therefore, despite having similar frequencies of B haplotypes, the occurrence of B haplotype-specific KIR genes, such as 2DL2, 2DL5, 3DS1, 2DS1, 2DS2, 2DS3, and 2DS5 in Azeri and Arab were substantially different from the natives of America, India, and Australia. In conclusion, each Iranian population exhibits distinct KIR gene content diversity, and the Indo-European KIR genetic signatures of the Iranians concur with geographic proximity, linguistic affinity, and human migrations

Monitoring of species' genetic diversity in Europe varies greatly and overlooks potential climate change impacts.

Genetic monitoring of populations currently attracts interest in the context of the Convention on Biological Diversity but needs long-term planning and investments. However, genetic diversity has been largely neglected in biodiversity monitoring, and when addressed, it is treated separately, detached from other conservation issues, such as habitat alteration due to climate change. We report an accounting of efforts to monitor population genetic diversity in Europe (genetic monitoring effort, GME), the evaluation of which can help guide future capacity building and collaboration towards areas most in need of expanded monitoring. Overlaying GME with areas where the ranges of selected species of conservation interest approach current and future climate niche limits helps identify whether GME coincides with anticipated climate change effects on biodiversity. Our analysis suggests that country area, financial resources and conservation policy influence GME, high values of which only partially match species' joint patterns of limits to suitable climatic conditions. Populations at trailing climatic niche margins probably hold genetic diversity that is important for adaptation to changing climate. Our results illuminate the need in Europe for expanded investment in genetic monitoring across climate gradients occupied by focal species, a need arguably greatest in southeastern European countries. This need could be met in part by expanding the European Union's Birds and Habitats Directives to fully address the conservation and monitoring of genetic diversity

NGS Nominated CELA1, HSPG2, and KCNK5 as Candidate Genes for Predisposition to Balkan Endemic Nephropathy

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants-CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN

MUC2 polymorphisms are associated with endometriosis development and infertility: a case-control study

<p>Abstract</p> <p>Background</p> <p>Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (<it>MUC2</it>) with the risk of endometriosis and endometriosis-related infertility.</p> <p>Methods</p> <p>This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within <it>MUC2 </it>gene were performed by using <it>Taqman </it>genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by <it>χ</it>²test.</p> <p>Results</p> <p>Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (<it>P </it>= 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (<it>P </it>= 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in <it>MUC2 </it>also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility.</p> <p>Conclusions</p> <p><it>MUC2 </it>polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.</p