Milk whey protein concentration and mRNA associated with β-lactoglobulin phenotype

Two common genetic variants of β-lactoglobulin (β-lg), A and B, exist as co- dominant alleles in dairy cattle (Aschaffenburg, 1968). Numerous studies have shown that cows homozygous for β-lg A have more β-lg and less α-lactalbumin (α-la) and casein in their milk than cows expressing only the B variant of β-lg (Ng-Kwai-Hang et al. 1987; Graml et al. 1989; Hill, 1993; Hill et al. 1995, 1997). These differences have a significant impact on the processing characteristics of the milk. For instance, the moisture-adjusted yield of Cheddar cheese is up to 10% higher using milk from cows of the β-lg BB phenotype compared with milk from cows expressing only the A variant (Hill et al. 1997). All these studies, however, describe compositional differences associated with β-lg phenotype in established lactation only. No information is available on the first few weeks of lactation, when there are marked changes in the concentrations of β-lg and α-la (Pérez et al. 1990)

Experimental validation of variance estimation in the statistical energy analysis of a structural-acoustic system

The Statistical Energy Analysis (SEA) approach has largely been used in vibro-acoustic modelling to predict the averaged energy in coupled vibrating structures and acoustic cavities. The average is performed over an ensemble of nominally identical built-up systems where random responses are observed at high frequencies after excitation. Over the years, this approach has been extended to predict the energy variance employing the statistics of the Gaussian Orthogonal Ensemble, and numerical and experimental evidence has supported the predictions of the mean and variance of energy of coupled vibrating structures. However, little experimental evidence is found to validate the prediction of the variance of energy in coupled structural-acoustic systems. In this work, the mean and variance of energies predicted from a statistical energy analysis model have been validated with experimental measurements on a structural-acoustic system, comprised by a flat thin plate coupled to an enclosed acoustic volume. The structural system has been randomised by adding small masses on arbitrary positions on the plate, whereas the randomisation of the acoustic cavity is achieved by allocating rigid baffles in random positions within the acoustic volume. In general, good agreement is found between the predictions of the model and the experimental results. Bose Cor

Epigenetics in the nervous system

It is becoming increasingly clear that epigenetic modifications are critical factors in the regulation of gene expression. With regard to the nervous system, epigenetic alterations play a role in a diverse set of processes and have been implicated in a variety of disorders. Gaining a more complete understanding of the essential components and underlying mechanisms involved in epigenetic regulation could lead to novel treatments for a number of neurological and psychiatric conditions

Lessons from Toxicology: Developing a 21st‑Century Paradigm for Medical Research

Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved

Discriminative Value of Inflammatory Biomarkers for Suspected Sepsis

Circulating biomarkers can facilitate sepsis diagnosis enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

SIRT1 Regulates HIV Transcription via Tat Deacetylation

The human immunodeficiency virus (HIV) Tat protein is acetylated by the transcriptional coactivator p300, a necessary step in Tat-mediated transactivation. We report here that Tat is deacetylated by human sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent class III protein deacetylase in vitro and in vivo. Tat and SIRT1 coimmunoprecipitate and synergistically activate the HIV promoter. Conversely, knockdown of SIRT1 via small interfering RNAs or treatment with a novel small molecule inhibitor of the SIRT1 deacetylase activity inhibit Tat-mediated transactivation of the HIV long terminal repeat. Tat transactivation is defective in SIRT1-null mouse embryonic fibroblasts and can be rescued by expression of SIRT1. These results support a model in which cycles of Tat acetylation and deacetylation regulate HIV transcription. SIRT1 recycles Tat to its unacetylated form and acts as a transcriptional coactivator during Tat transactivation

The impact of language barriers on trust formation in multinational teams

This study systematically investigates how language barriers influence trust formation in multinational teams (MNTs). Based on 90 interviews with team members, team leaders, and senior managers in 15 MNTs in three German automotive corporations, we show how MNT members’ cognitive and emotional reactions to language barriers influence their perceived trustworthiness and intention to trust, which in turn affect trust formation. We contribute to diversity research by distinguishing the exclusively negative language effects from the more ambivalent effects of other diversity dimensions. Our findings also illustrate how surface-level language diversity may create perceptions of deep-level diversity. Furthermore, our study advances MNT research by revealing the specific influences of language barriers on team trust, an important mediator between team inputs and performance outcomes. It thereby encourages the examination of other team processes through a language lens. Finally, our study suggests that multilingual settings necessitate a reexamination and modification of the seminal trust theories by Mayer, Davis and Schoorman (1995) and McAllister (1995). In terms of practical implications, we outline how MNT leaders can manage their subordinates’ problematic reactions to language barriers and how MNT members can enhance their perceived trustworthiness in multilingual settings