Optimizing the Extraction of Procyanidins Oligomers through Decamer

The extraction of procyanidins from a food is influenced by food matrix, extraction solvent, sample particle size, sample to solvent ratio, as well as other factors. Many of these parameters can easily be controlled in a laboratory to improve or target the extraction of low or high molecular weight oligomers. As various oligomers have differing biological and functional qualities, preferred extraction of one group of oligomers may be a desired target. In the following study, we describe the influence of solvent polarity and composition, solvent-solute ratio and particle size on the extraction of procyanidin oligomers monomer through decamer. The solvents evaluated included dimethyl sulfoxide (DMSO), acetone and methanol

WALKING WITH AND WITHOUT HIGH HEELS ON A DECLINED SURFACE

The purpose of this pilot study was to investigate body segment ROMs while walking with and without high heels on flat and declined surfaces. Eight healthy, active, female college students (BH: 1.67 ± .08 m, BW: 57.8 ± 7.03 kg) were recruited in the study. The participants randomly performed three trials of walking on level ground and a declined surface in both high heels and tennis shoes using 2D motion analysis. Results indicated that the ROMs were significantly decreased on a declined slope, regardless of the type of shoes. Considering shoe types, the body segments’ ROMs were reduced during the high heels conditions except for the trunk segment for both surfaces. This enhanced control of locomotion during decline and/or high-heeled walking

Processing-induced changes in total phenolics and procyanidins in clingstone peaches

Abstract: Clingstone peaches contain a wide array of complex secondary plant metabolites and polyphenolics, and increasing evidence indicates that many of these components are important in human health. Oligomeric flavan-3-ol metabolites (procyanidins) are particularly interesting owing to their potent antioxidant activity and protective cardiovascular effects. To date, little information is available on how postharvest and processing conditions impact levels of phenolics and procyanidins in fruit. This research addresses the impact of lye peeling, freezing, storage temperature (4 and 30°C) and three different time-temperature sterilisation combinations on levels of total phenolics (TPs) in Ross clingstone peaches. Additionally, we describe the profile of procyanidin oligomers (monomers through heptamers) in clingstone and freestone peaches and demonstrate a dramatic decrease in procyanidins in thermally processed peaches. TP levels ranged between 316 and 397 mg kg À1 in peeled peaches and between 376 and 609 mg kg À1 in unpeeled peaches. Cold storage at 4°C for 14 days or freezing and storing at À12°C for 3 months produced no loss in TPs. Peaches stored at 30°C for 24 h resulted in a 1.7-fold increase in TPs. Studies of TPs in peaches processed at temperatures of 213°F for 40 min, 220°F for 10 min and 230°F for 2.4 min indicate that processing above 213°F decreases levels of both TPs (up to 21%) and procyanidins (up to 100%). Processing at 213°F for 40 min produced no significant loss in TPs. Furthermore, studies reveal that a 30-43% loss in phenolic levels occurs during the first 3 months in storage after canning. It is clear that both storage and thermal processing conditions profoundly impact the levels of polyphenolics in peaches. More interestingly, these studies indicate that peaches are a rich source of procyanidins, having profiles similar to those found in cocoa, apples, wine and tea

Association between arterial stiffness and variations in estrogen-related genes

available in PMC 2010 April 1.Increased arterial stiffness and wave reflection have been identified as cardiovascular disease risk factors. In light of significant sex differences and the moderate heritability of vascular function measures, we hypothesized that variation in the genes coding for oestrogen receptors α (ESR1) and β (ESR2) and aromatase (CYP19A1) is associated with aortic stiffness and pressure wave reflection as measured by non-invasive arterial tonometry. In all, 1261 unrelated Framingham Offspring Study participants who attended the seventh examination cycle (mean age 62±10 years, 52% women) and had arterial tonometry and genotyping data were included in the study. Analysis of covariance was used to assess the association of polymorphisms with forward wave amplitude, augmented pressure, augmentation index (AI), carotid–femoral pulse wave velocity and mean arterial pressure with adjustment for potential confounders. In the sex-pooled analysis, those homozygous for the minor allele at any of four ESR1 variants that were in strong linkage disequilibrium ((TA)n, rs2077647, rs2234693 and rs9340799) had on an average 18% higher augmented pressure and 16% greater AI compared with carriers of one or two major alleles (P=0.0002–0.01). A similar magnitude of association was detected in those homozygous for the common allele at two ESR2 single-nucleotide polymorphisms (P=0.007–0.02). Our results are consistent with the hypothesis that variation in ESR1 and ESR2, but not CYP19A1, is associated with an increased wave reflection that may contribute to associations between these variants and adverse clinical events demonstrated earlier. Our findings will need to be replicated in additional cohorts

Evaluating the Impact of Intravitreal Aflibercept on Diabetic Retinopathy Progression in the VIVID-DME and VISTA-DME Studies

Purpose To evaluate the impact of intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Tarrytown, NY) versus laser on progression of diabetic retinopathy (DR) severity in Intravitreal Aflibercept Injection in Vision Impairment due to DME (VIVID-DME) and Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA-DME). Design Secondary and exploratory analyses of 2 phase 3, randomized, controlled studies. Participants All patients with a baseline Diabetic Retinopathy Severity Scale (DRSS) score based on fundus photograph (full analysis), patients who progressed to proliferative DR (PDR) (safety analysis) in VIVID-DME (n = 403) and VISTA-DME (n = 459), or both. Methods We randomized patients with diabetic macular edema (DME) to intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation at baseline and sham injections at every visit. Main Outcome Measures Proportions of patients with 2-step or more and 3-step or more improvements from baseline in DRSS score, who progressed to PDR, and who underwent panretinal photocoagulation (PRP). Results Among patients with an assessable baseline DRSS score, most showed moderately severe or severe nonproliferative DR. The proportions of patients treated with 2q4, 2q8, and laser with a 2-step or more improvement in DRSS score at week 100 were 29.3%, 32.6%, and 8.2%, respectively, in VIVID-DME and 37.0%, 37.1%, and 15.6%, respectively, in VISTA-DME; the proportions with a 3-step or more improvement in DRSS score were 7.3%, 2.3%, and 0%, respectively, and 22.7%, 19.9%, and 5.2%, respectively. Fewer patients in the 2q4 and 2q8 groups versus the laser group progressed to PDR at week 100 in VISTA-DME (1.5% and 2.2% vs. 5.3%) and VIVID-DME (3.2% and 2.0% vs. 12.3%). The proportions of patients who underwent PRP were 2.9%, 0.7%, and 4.5%, respectively, in VIVID-DME and 1.9%, 0.7%, and 5.2%, respectively, in VISTA-DME. The most frequent serious ocular adverse event at week 100 was cataract (pooled intravitreal aflibercept, 1.7% of patients; laser, 3.5% of patients). Conclusions These analyses demonstrate the benefit of intravitreal aflibercept over laser with respect to DR progression, suggesting a benefit on DME, and on underlying DR

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Background: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. Design: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population

BurstCube: A CubeSat for gravitational wave counterparts

BurstCube aims to expand sky coverage in order to detect, localize, and rapidly disseminate information about gamma-ray bursts (GRBs). BurstCube is a\u276U\u27 CubeSat with an instrument comprised of 4 Cesium Iodide (CsI) scintillators coupled to arrays of Silicon photo-multipliers (SiPMs) and will be sensitive to gamma-rays between 50 keV and 1 MeV. BurstCube will assist current observatories, such as Swift and Fermi, in the detection of GRBs as well as provide astronomical context to gravitational wave (GW) events detected by LIGO, Virgo, and KAGRA. BurstCube is currently in its development phase with a launch readiness date in early 2022

The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer

Large-scale human genetic data(1-3) have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)(4-6). VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2 alpha (HIF2A) stabilization(6,7). We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 (CCND1) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele Cat rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1 expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYC expression from the ccRCC metastasis-associated amplicons at 8q21.3-q24.3 (ref. (8)). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants.Peer reviewe

piRNAs Can Trigger a Multigenerational Epigenetic Memory in the Germline of C. elegans

SummaryTransgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C.elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs.Graphical AbstractHighlights► Multigenerational inheritance and piRNAs converge on same nuclear silencing pathway ► HRDE1/WAGO-9 and chromatin factors required for inheritance of piRNA silencing ► piRNAs can induce multigenerational silencing for more than 20 generations. ► Long-term memory independent of piRNA triggers but remains dependent on nuclear pathwayMultigenerational inheritance and piRNAs converge on same silencing pathway, in which both nuclear WAGOs and chromatin factors are required. The piRNA trigger can be lost, but the nuclear silencing pathway maintains the silencing for more than 20 generations