Effect of moderate to very low fat defined formula diets on serum lipids in healthy subjects

Serum total cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride levels were studied in healthy male and female subjects consuming for one-week periods a diet of conventional food (CF) providing 42% of energy as fat, principally butter fat, and then in random order nutritionally complete, defined formula diets of moderate (32%) to very low (1%) fat content. Compared to CF, the formula with 32% of energy as corn oil lowered serum cholesterol by 25% and the ratio of total to HDL-cholesterol by 13%. Low (9%) and very low (1–3%) fat formulas reduced HDL-cholesterol by as much as 40%, raised the total: HDL-cholesterol ratio by about 20% and raised serum triglyceride levels by as much as 100%. When low and very low fat formulas were ingested for three weeks, these effects persisted although maximal responses occurred during the first week. These results demonstrated that a moderate fat formula diet with a high P/S ratio had a more favorable effect on serum lipid levels than various low fat formulas. Low fat conventional food diets should be studied in long-term controlled metabolic experiments before such diets are recommended to the general population for coronary heart disease or cancer prevention.     

Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection

Type 2 diabetes (T2D) is one of the prominent causes of morbidity and mortality in the United States and beyond, reaching global pandemic proportions. One hallmark of T2D is dysfunctional glucose-stimulated insulin secretion from the pancreatic β-cell. Insulin is secreted via the recruitment of insulin secretory granules to the plasma membrane, where the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and SNARE regulators work together to dock the secretory granules and release insulin into the circulation. SNARE proteins and their regulators include the Syntaxins, SNAPs, Sec1/Munc18, VAMPs, and double C2-domain proteins. Recent studies using genomics, proteomics, and biochemical approaches have linked deficiencies of exocytosis proteins with the onset and progression of T2D. Promising results are also emerging wherein restoration or enhancement of certain exocytosis proteins to β-cells improves whole-body glucose homeostasis, enhances β-cell function, and surprisingly, protection of β-cell mass. Intriguingly, overexpression and knockout studies have revealed novel functions of certain exocytosis proteins, like Syntaxin 4, suggesting that exocytosis proteins can impact a variety of pathways, including inflammatory signaling and aging. In this review, we present the conventional and unconventional functions of β-cell exocytosis proteins in normal physiology and T2D and describe how these insights might improve clinical care for T2D.     

Exploring the impact of software requirements on system-wide goals: a method using satisfaction arguments and i* goal modelling

This paper describes the application of requirements engineering concepts to support the analysis of the impact of new software systems on system-wide goals. Requirements on a new or revised software component of a socio-technical system not only have implications on the goals of the subsystem itself, but they also impact upon the goals of the existing integrated system. In industries such as air traffic management and healthcare, impacts need to be identified and demonstrated in order to assess concerns such as risk, safety, and accuracy. A method called PiLGRIM was developed which integrates means-end relationships within goal modelling with knowledge associated with the application domain. The relationship between domain knowledge and requirements, as described in a satisfaction argument, adds traceability rationale to help determine the impacts of new requirements across a network of heterogeneous actors. We report procedures that human analysts follow to use the concepts of satisfaction arguments in a software tool for i* goal modelling. Results were demonstrated using models and arguments developed in two case studies, each featuring a distinct socio-technical system??a new controlled airspace infringement detection tool for NATS (the UK??s air navigation service provider), and a new version of the UK??s HIV/AIDS patient reporting system. Results provided evidence towards our claims that the conceptual integration of i* and satisfaction arguments is usable and useful to human analysts, and that the PiLGRIM impact analysis procedures and tool support are effective and scalable to model and analyse large and complex socio-technical systems.     

Organizing Sexuality: Silencing and the Push–Pull Process of Co-sexuality in the Workplace

How human beings think about, talk about, and organize around sexuality is changing. Growing social legitimization for sexual minority relationships and a more fluid social understanding of sexual identities has shifted how we bound “normal” sexuality. In the workplace, these shifting norms affect employees of all sexual identities who must make sense of new policies and complex daily practices. This paper introduces the concept of co-sexuality, the push-and-pull process of communicatively organizing around sexuality. Using this concept, we take a grounded theory approach to exploring how employees of various sexualities and in different occupations understand “normal” sexuality and subsequently organize around it. Ultimately, participants described being silenced or silencing another to maintain sexual “norms” at work.     

Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg^2.39, His^2.43 and Glu^3.46, which makes a polar lock with T^6.37. These alignments and models provide useful tools for understanding class B GPCR function.