Increasing Higher Alcohols and Acetates in Low-Alcohol Beer by Proteases.

The market of non-alcoholic and low-alcohol beer has grown continuously thanks to the advocacy for healthy and responsible drinking. Non-alcoholic and low-alcohol products usually possess less higher alcohols and acetates and more aldehyde off-flavors due to the manufacturing processes. The employment of non-conventional yeasts partially mitigates this problem. In this study, we used proteases to optimize the wort amino acid profile for better aroma production during yeast fermentation. The design of experiments was applied to increase the leucine molar fraction, aiming to boost 3-methylbutan-1-ol and 3-methylbutyl acetate (banana-like aromas). This led to an increase from 7% to 11% leucine in wort after protease treatment. The aroma output in the subsequent fermentation, however, was yeast-dependent. An 87% increase of 3-methylbutan-1-ol and a 64% increase of 3-methylbutyl acetate were observed when Saccharomycodes ludwigii was used. When Pichia kluyveri was employed, higher alcohols and esters from valine and isoleucine were increased: 58% more of 2-methylpropyl acetate, 67% more of 2-methylbutan-1-ol, and 24% more of 2-methylbutyl acetate were observed. Conversely, 3-methylbutan-1-ol decreased by 58% and 3-methylbutyl acetate largely remained the same. Apart from these, the amounts of aldehyde intermediates were increased to a varying extent. The impact of such increases in aromas and off-flavors on the perception of low-alcohol beer remains to be evaluated by sensory analysis in future studies.

Packing a punch: understanding how flavours are produced in lager fermentations.

Beer is one of the most popular beverages in the world and it has an irreplaceable place in culture. Although invented later than ale, lager beers dominate the current market. Many factors relating to the appearance (colour, clarity and foam stability) and sensory characters (flavour, taste and aroma) of beer, and other psychological determinants affect consumers' perception of the product and defines its drinkability. This review takes a wholistic approach to scrutinise flavour generation in the brewing process, focusing particularly on the contribution of the raw ingredients and the yeasts to the final flavour profiles of lager beers. In addition, we examine current developments to improve lager beer flavour profiles for the modern consumers.

Personality, environmental stressors, and diarrhea in Rhesus macaques: An interactionist perspective.

Previous research has repeatedly shown both personality and psychological stress to predict gastrointestinal disorders and chronic diarrhea in humans. The goal of the present research was to evaluate the role of personality, as well as psychological stressors (i.e., housing relocations and rearing environment), in predicting chronic diarrhea in captive Rhesus macaques, with particular attention to how personality regulated the impact of such stressors. Subjects were 1,930 R. macaques at the California National Primate Research Center reared in a variety of environments. All subjects took part in an extensive personality evaluation at approximately 90-120 days of age. Data were analyzed using generalized linear models to determine how personality, rearing condition, housing relocations, and personality by environment interactions, predicted both diarrhea risk (an animal's risk for having diarrhea at least once) and chronic diarrhea (how many repeated bouts of diarrhea an animal had after their initial bout). Much like the human literature, we found that certain personality types (i.e., nervous, gentle, vigilant, and not confident) were more likely to have chronic diarrhea, and that certain stressful environments (i.e., repeated housing relocations) increased diarrhea risk. We further found multiple interactions between personality and environment, supporting the "interactionist" perspective on personality and health. We conclude that while certain stressful environments increase risk for chronic diarrhea, the relative impact of these stressors is highly dependent on an animal's personality.

The expression of miRNA encoded by C19MC and miR-371-3 strongly varies among individual placentas but does not differ between spontaneous and induced abortions.

miRNAs of the largest human miRNA gene cluster at all, i.e., C19MC, are almost exclusively expressed in the placenta. Nevertheless, only little is known about the interindividual variation of their expression and even about possible influence of gestational age, conflicting data is reported as well as for miRNAs of the much smaller miR-371-3 cluster. Our present study aims at the analyses of the expression of miRNAs from both clusters at different times of pregnancy, possible differences between placenta samples obtained from spontaneous or induced abortions in the first trimester, and the possible variation of miRNA expression at different sites within same placentas. miR-371a-3p, miR-372-3p, miR-373-3p, miR-517a-3p, and miR-520c-3p were quantified in 85 samples and miR-371a-3p was quantified in maternal serum samples taken immediately before delivery. While for miRNA-517a-3p and miR-520c-3p the expression increased with increasing gestational age, the present study revealed strong interindividual differences in the expression of miR-371-3 in full-term placental tissue as well as for miRNAs of the C19MC cluster, where the levels differed to a much lesser extent than for the former microRNAs. Also, strong interindividual differences were noted between the serum samples but differences related to the site of the placenta where the sample has been taken from were excluded. For neither of the data from placental tissue, the study revealed differences between the spontaneous and induced abortion group. Thus, the differences do not in general seem to be related to first trimester abortion. It remains to be elucidated whether or not they affect other prenatal processes.

Case-control study of male germ cell tumors nested in a cohort of car-manufacturing workers: Findings from the occupational history.

BACKGROUND: To examine whether the previously observed excess risk of male germ cell cancer in a cohort of car-manufacturing workers can be attributed to occupational activities inside and/or outside the car industry. METHODS: A nested case-control study among workers in six plants included 205 cases of germ cell cancer and 1,105 controls, individually matched by year of birth (±2 years). Job periods of the individual occupational histories were coded based on the International Standard Classification of Occupations (ISCO) and the industrial classification of economic activities (NACE). Odds ratios (ORs) and corresponding 95%-confidence intervals (CI) for ever-never and cumulative employment were calculated by conditional multivariate logistic regression adjusted for cryptorchidism. RESULTS: Significantly increased risks were observed for machinery fitters and assemblers (A) (OR = 1.8, 95% CI 1.25-2.53) and "workers not elsewhere classified" (OR = 2.10, 95% CI 1.27-3.54), but no trend was observed for employment duration in either occupational group. Stratification of job group A by metal-cutting and non-cutting jobs yielded ORs of 1.87 (95% CI 1.31-2.67) and of 1.24 (95% CI 0.68-2.28), respectively. Among "plumbers, welders, sheet & structural metal workers" (adjusted OR 1.4, 95% CI 0.99-1.95) only "structural metal preparers and erectors" showed a substantially increased risk (OR = 2.30; 95% CI 1.27-4.27). CONCLUSIONS: Our results do not fully explain the increased incidence of germ cell cancer in the cohort, but support previous findings showing increased risks among metal workers. These risks were most strongly pronounced in metal-cutting activities.

Logistic regression models to predict solvent accessible residues using sequence- and homology-based qualitative and quantitative descriptors applied to a domain-complete X-ray structure learning set.

A working example of relative solvent accessibility (RSA) prediction for proteins is presented. Novel logistic regression models with various qualitative descriptors that include amino acid type and quantitative descriptors that include 20- and six-term sequence entropy have been built and validated. A domain-complete learning set of over 1300 proteins is used to fit initial models with various sequence homology descriptors as well as query residue qualitative descriptors. Homology descriptors are derived from BLASTp sequence alignments, whereas the RSA values are determined directly from the crystal structure. The logistic regression models are fitted using dichotomous responses indicating buried or accessible solvent, with binary classifications obtained from the RSA values. The fitted models determine binary predictions of residue solvent accessibility with accuracies comparable to other less computationally intensive methods using the standard RSA threshold criteria 20 and 25% as solvent accessible. When an additional non-homology descriptor describing Lobanov-Galzitskaya residue disorder propensity is included, incremental improvements in accuracy are achieved with 25% threshold accuracies of 76.12 and 74.79% for the Manesh-215 and CASP(8+9) test sets, respectively. Moreover, the described software and the accompanying learning and validation sets allow students and researchers to explore the utility of RSA prediction with simple, physically intuitive models in any number of related applications.

HMGA2 expression distinguishes between different types of postpubertal testicular germ cell tumour.

The group of postpubertal testicular germ cell tumours encompasses lesions with highly diverse differentiation - seminomas, embryonal carcinomas, yolk sac tumours, teratomas and choriocarcinomas. Heterogeneous differentiation is often present within individual tumours and the correct identification of the components is of clinical relevance. HMGA2 re-expression has been reported in many tumours, including testicular germ cell tumours. This is the first study investigating HMGA2 expression in a representative group of testicular germ cell tumours with the highly sensitive method of quantitative real-time PCR as well as with immunohistochemistry. The expression of HMGA2 and HPRT was measured using quantitative real-time PCR in 59 postpubertal testicular germ cell tumours. Thirty specimens contained only one type of tumour and 29 were mixed neoplasms. With the exception of choriocarcinomas, at least two pure specimens from each subgroup of testicular germ cell tumour were included. In order to validate the quantitative real-time PCR data and gather information about the localisation of the protein, additional immunohistochemical analysis with an antibody specific for HMGA2 was performed in 23 cases. Expression of HMGA2 in testicular germ cell tumours depended on the histological differentiation. Seminomas and embryonal carcinomas showed no or very little expression, whereas yolk sac tumours strongly expressed HMGA2 at the transcriptome as well as the protein level. In teratomas, the expression varied and in choriocarcinomas the expression was moderate. In part, these results contradict data from previous studies but HMGA2 seems to represent a novel marker to assist pathological subtyping of testicular germ cell tumours. The results indicate a critical role in yolk sac tumours and some forms of teratoma.

Depression from childhood into late adolescence: Influence of gender, development, genetic susceptibility, and peer stress.

Depression is a debilitating mental illness with clear developmental patterns from childhood through late adolescence. Here, we present data from the Gene Environment Mood (GEM) study, which used an accelerated longitudinal cohort design with youth (N = 665) starting in 3rd, 6th, and 9th grades, and a caretaker, who were recruited from the general community, and were then assessed repeatedly through semistructured diagnostic interviews every 6 months over 3 years (7 waves of data) to establish and then predict trajectories of depression from age 8 to 18. First, we demonstrated that overall prevalence rates of depression over time, by age, gender, and pubertal status, in the GEM study closely match those trajectories previously obtained in past developmental epidemiological research. Second, we tested whether a genetic vulnerability-stress model involving 5-HTTLPR and chronic peer stress was moderated by developmental factors. Results showed that older aged adolescents with SS/SL genotype, who experienced higher peer chronic stress over 3 years, were the most likely to be diagnosed with a depressive episode over time. Girls experiencing greater peer chronic stress were the most likely to develop depression. This study used repeated assessments of diagnostic interviewing in a moderately large sample of youth over 3 years to show that depression rates increase in middle to late adolescence, or postpubertally, and that the gender difference in depression emerges earlier in adolescence (age 12.5), or postpubertally. Additionally, genetically susceptible older adolescents who experience chronic peer stress were the most likely to become depressed over time.

Robotic cholecystectomy and resident education: the UC Davis experience.

INTRODUCTION: The popularity of robotic surgery highlights the need for strategies to integrate this technique into surgical education. We present 5 year data for robotic cholecystectomy (RC) as a model for training residents. METHODS: Data were collected on all RC over 66 months. Duration for docking the robot (S2) and performing RC (S3), and surgical outcomes, were recorded. We used a linear mixed effects model to investigate learning curves. RESULTS: Thirty-eight trainees performed 160 RCs, with most performing more than four. One case was aborted due to haemodynamic instability, and two were converted to open surgery due to adhesions. There were no technical complications. The duration of S2 (mean = 6.2 ± 3.6 min) decreased considerably (p = 0.027). Trainees also demonstrated decrease in duration of S3 (mean = 38.4 ± 15.4 min), indicating improvement in technique (p = 0.008). CONCLUSIONS: RC is an effective model for teaching residents. Significant and reproducible improvement can be realized with low risk of adverse outcomes.

HMGA2 expression in white adipose tissue linking cellular senescence with diabetes.

There is a clear link between overweight, gain of white adipose tissue, and diabetes type 2 (T2D). The molecular mechanism of the gain of adipose tissue is linked with the expression of high mobility group protein AT-hook 2 (HMGA2), and recent studies revealed an association with a SNP near HMGA2. In this study, we investigated the gene expression of HMGA2, p14 (Arf) , CDKN1A, and BAX in human abdominal subcutaneous white adipose tissue from 157 patients. We found a significant higher HMGA2 expression in obese individuals than in non-obese patients. Furthermore, the HMGA2 expression in white adipose tissue in patient with type 2 diabetes was significantly higher than in nondiabetic patients. There is an association between the DNA-binding nonhistone protein HMGA2 and the risk of developing T2D that remains mechanistically unexplained so far. Likewise, p14(Arf), an inducer of cellular senescence, has been associated with the occurrence of T2D. The data of the present study provide evidence that both proteins act within the same network to drive proliferation of adipose tissue stem and precursor cells, senescence, and increased risk of T2D, respectively.

Insular organization of gene space in grass genomes.

Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands "gene insulae" to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes.