Ploidy stability in grapevines following long term storage in vitro

A modified method to prepare root tip squashes was used for the routine examination of chromosomes of grapevines developed from in vitro shoot cultures. The results established that adventitious buds obtained by culture of fragmented shoot apices were diploid, and that storage at 9.5 °C of multiple shoot cultures of eight Vitis genotypes for periods up to 12 months did not affect the ploidy level of plants regenerated from them

A robust, discrete-gradient descent procedure for optimisation with time-dependent PDE and norm constraints

Many physical questions in fluid dynamics can be recast in terms of norm constrained optimisation problems; which in-turn, can be further recast as unconstrained problems on spherical manifolds. Due to the nonlinearities of the governing PDEs, and the computational cost of performing optimal control on such systems, improving the numerical convergence of the optimisation procedure is crucial. Borrowing tools from the optimisation on manifolds community we outline a numerically consistent, discrete formulation of the direct-adjoint looping method accompanied by gradient descent and line-search algorithms with global convergence guarantees. We numerically demonstrate the robustness of this formulation on three example problems of relevance in fluid dynamics and provide an accompanying library SphereManOpt

Genetic influences on social attention in free-ranging rhesus macaques

An ethological approach to attention predicts that organisms orient preferentially to valuable sources of information in the environment. For many gregarious species, orienting to other individuals provides valuable social information but competes with food acquisition, water consumption and predator avoidance. Individual variation in vigilance behaviour in humans spans a continuum from inattentive to pathological levels of interest in others. To assess the comparative biology of this behavioural variation, we probed vigilance rates in free-ranging macaques during water drinking, a behaviour incompatible with the gaze and postural demands of vigilance. Males were significantly more vigilant than females. Moreover, vigilance showed a clear genetic component, with an estimated heritability of 12%. Monkeys carrying a relatively infrequent ‘long’ allele of TPH2, a regulatory gene that influences serotonin production in the brain, were significantly less vigilant compared to monkeys that did not carry the allele. These findings resonate with the hypothesis that the serotonin pathway regulates vigilance in primates and by extension provoke the idea that individual variation in vigilance and its underlying biology may be adaptive rather than pathological

A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis

BACKGROUND Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown. METHODS We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. RESULTS A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P=0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group. CONCLUSIONS In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24. opens in new tab; ISRCT number, N14174793. opens in new tab.

An integrated analysis and comparison of serum, saliva and sebum for COVID-19 metabolomics.

The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions

Rhythmic Diurnal Gene Expression in Human Adipose Tissue From Individuals Who Are Lean, Overweight, and Type 2 Diabetic

OBJECTIVE Previous animal studies suggest a functional relationship between metabolism, type 2 diabetes, and the amplitude of daily rhythms in white adipose tissue (WAT). However, data interpretation is confounded by differences in genetic background and diet or limited sampling points. We have taken the novel approach of analyzing serial human WAT biopsies across a 24-h cycle in controlled laboratory conditions.RESEARCH DESIGN AND METHODS Lean (n = 8), overweight/obese (n = 11), or overweight/obese type 2 diabetic (n = 8) volunteers followed a strict sleep-wake and dietary regimen for 1 week prior to the laboratory study. They were then maintained in controlled light-dark conditions in a semirecumbent posture and fed hourly during wake periods. Subcutaneous WAT biopsies were collected every 6 h over 24 h, and gene expression was measured by quantitative PCR.RESULTS Lean individuals exhibited significant (P 0.05) of increased body weight or type 2 diabetes on rhythmic gene expression.CONCLUSIONS The robust nature of these rhythms and their relative phasing indicate that WAT now can be considered as a peripheral tissue suitable for the study of in vivo human rhythms. Comparison of data between subject groups clearly indicates that obesity and type 2 diabetes are not related to the amplitude of rhythmic WAT gene expression in humans maintained under controlled conditions. Diabetes 60:1577-1581, 201

Structural Basis for the Autoinhibition and STI-571 Inhibition of c-Kit Tyrosine Kinase

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Estimating trace deposition time with circadian biomarkers: a prospective and versatile tool for crime scene reconstruction

Linking biological samples found at a crime scene with the actual crime event represents the most important aspect of forensic investigation, together with the identification of the sample donor. While DNA profiling is well established for donor identification, no reliable methods exist for timing forensic samples. Here, we provide for the first time a biochemical approach for determining deposition time of human traces. Using commercial enzyme-linked immunosorbent assays we showed that the characteristic 24-h profiles of two circadian hormones, melatonin (concentration peak at late night) and cortisol (peak in the morning) can be reproduced from small samples of whole blood and saliva. We further demonstrated by analyzing small stains dried and stored up to 4 weeks the in vitro stability of melatonin, whereas for cortisol a statistically significant decay with storage time was observed, although the hormone was still reliably detectable in 4-week-old samples. Finally, we showed that the total protein concentration, also assessed using a commercial assay, can be used for normalization of hormone signals in blood, but less so in saliva. Our data thus demonstrate that estimating normalized concentrations of melatonin and cortisol represents a prospective approach for determining deposition time of biological trace samples, at least from blood, with promising expectations for forensic applications. In the broader context, our study opens up a new field of circadian biomarkers for deposition timing of forensic traces; future studies using other circadian biomarkers may reveal if the time range offered by the two hormones studied here can be specified more exactly