Cognitive effects of a 30-min aerobic exercise bout on adults with overweight/obesity and type 2 diabetes.

BACKGROUND: Several studies document reliable brain health benefits of acute exercise bouts. However, no prior studies have explored such effects among those living with co-morbid overweight/obesity and type 2 diabetes (T2DM), both of which are conditions associated with cognitive performance decrements. PURPOSE: To examine the impact of a 30-min bout of moderate-intensity aerobic exercise on executive function among adults with overweight/obesity and T2DM, employing a widely used experimental paradigm. METHODS: Thirty adults with overweight/obesity and T2DM were randomly assigned to moderate (30% maximal heart rate reserve) and minimal (r.p.m. 30-50; work load 5) intensity aerobic exercise. Pre-exercise to post-exercise changes in Stroop interference and Go/No-Go scores were compared across conditions. RESULTS: Primary analyses revealed no overall effect of exercise condition on changes in Stroop or Go/No-Go performance. Post-hoc moderation analyses indicated that Stroop interference scores were reduced, following moderate exercise among female participants and among those who were more physically active. CONCLUSION: The current study revealed no reliable benefit of acute aerobic exercise for overweight and obese individuals living with T2DM overall. There may be limited benefits for women and more and active subgroups, but the precise nature of such benefits remains unclear.

A capabilities approach to population health and public policy-making.

BACKGROUND: The objective of this study is to outline a capabilities approach to the social determinants of population health and to compare its explanatory power and implications for public policy-making with psychosocial approaches. METHODS: A model linking the structures of economic and social relations to health outcomes is developed and logistic methods used to confirm its base validity for a representative sample of 16,488 citizens in 19 developed democracies drawn from the World Values Surveys of 1990 and 2005. Self-reported health is the dependent variable. Age, gender, education, employment status, self-mastery, income, autonomy at work, ties to family and friends, subjective social status, associational memberships and sense of national belonging are considered. RESULTS: At baseline, risk ratios reflecting movement from the 25th to 75th percentile in the distribution of the variable indicate that increases in income reduce the likelihood of poor health (0.78; 0.73-0.82) as does higher autonomy at work (0.90; 0.85-0.94) but so does access to social resources reflected in ties to family and friends (0.89; 0.86-0.92), associational memberships (0.93; 0.89-0.98), subjective social status (0.77; 0.54-0.90) while the absence of feelings of national belonging increases the likelihood of poor health (1.14; 1.06-1.23). CONCLUSION: The results suggest that population health is dependent on the distribution of social as well as economic resources along the dimensions predicted by a capabilities model. Governments should be attentive to the impact of policy on the distribution of social, as well as economic, resources.

Food safety objective approach for controlling Clostridium botulinum growth and toxin production in commercially sterile foods.

As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (ΣR), and preventing an increase in levels (ΣI) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods.

Molecular and cellular themes in inflammation and immunology.

This issue of the Journal of Pathology contains a series of cutting-edge review articles that deal with the broad issue of inflammatory and immunological disease mechanisms. Of necessity, these reviews deal with selected topics but the mixture of articles on specific signalling pathways and mediators with articles addressing individual organ systems provides a broad overview of the field. These contributions provide insight into current areas of debate in inflammation and immunology. In particular, they highlight current interest in the interface between innate and adaptive immunity and present intriguing prospects for future therapeutic developments in a variety of disease areas.

Do septins have a role in cancer?

Septins are an evolutionarily conserved family of genes that encode a P loop-based GTP-binding domain flanked by a polybasic domain and (usually) a coiled-coil region. They have roles in cytokinesis, vesicle trafficking, polarity determination, and can form membrane diffusion barriers, as well as in microtubule and actin dynamics. Septins can form hetero-oligomeric complexes and possibly function as dynamic protein scaffolds. Recently, it has been shown that there are at least 13 human septin genes that exhibit extensive alternate splicing. There are complex patterns of human septin gene expression and recently it has been found that alterations in septin expression are seen in human diseases including neoplasia. This review summarises the essential properties of septins and outlines the accumulating evidence for their involvement in human neoplasia. Septins may belong to the class of cancer critical genes where alteration in expression profile (including alterations in the spectrum of transcripts expressed) may underpin their role in neoplasia as opposed to specific mutational events.

The yeast two-hybrid system for identifying protein-protein interactions.

The yeast two-hybrid assay is a system for identifying and analysing protein-protein interactions. Since the original description in 1989, the technique has provided insight into many biological pathways. A variety of adaptations to the technique have been developed that allow analysis of protein-DNA, protein-RNA, or small molecule-protein interactions. Recent developments now allow the use of these technologies to perform global analyses of all such interactions that occur in cells. The information gained from these approaches is uncovering many aspects of the complex networks that underlie normal cellular processes and how they are perturbed in disease states.

Modeling the growth of Listeria monocytogenes in cured ready-to-eat processed meat products by manipulation of sodium chloride, sodium diacetate, potassium lactate, and product moisture content.

A central composite second-order response surface design was employed to determine the influences of added sodium chloride (0.8 to 3.6%), sodium diacetate (0 to 0.2%), potassium lactate syrup (0.25 to 9.25%), and finished-product moisture (45.5 to 83.5%) on the predicted growth rate of Listeria monocytogenes in cured ready-to-eat (RTE) meat products. Increased amounts of both sodium diacetate (P < 0.11) and potassium lactate (P < 0.001) resulted in significant reductions in the growth rate constants of L monocytogenes. Increased finished-product moisture (P < 0.11) significantly increased growth rate constants. The nfluence of sodium chloride was not statistically significant. The second-order statistical factor for lactate was significant (P < 0.01), but all two-way interactions were not. In general, predicted growth rates exceeded actual growth rates obtained from inoculation studies of four cured RTE meat products (wieners, smoked-cooked ham, light bologna, and cotto salami). The final model will be useful to food technologists in determining formulations that will result in finished cured RTE meat products in which L. monocytogenes is not likely to grow.

Expression of the p53 homologue p63alpha and DeltaNp63alpha in the neoplastic sequence of Barrett's oesophagus: correlation with morphology and p53 protein.

BACKGROUND: While loss of p53 function is a key oncogenic step in human tumorigenesis, mutations of p53 are generally viewed as late events in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's oesophagus. Recent reports of a series of genes (p63, p73, and others) exhibiting close homology to p53 raise the possibility that abnormalities of these p53 family members may exert their influence earlier in the sequence. AIM: Following recent characterisation of expression of p63 and a major isoform DeltaNp63 by generation of an antiserum that recognises p63 isoforms, but not p53, our aim was a comparative study of expression of p63 protein and p53 protein in a morphologically well defined biopsy series representative of all stages of the metaplasia-dysplasia-carcinoma sequence in Barrett's oesophagus. METHODS: A series of 60 biopsy cases representing normal oesophagus through to invasive adenocarcinoma were stained, using immunohistochemistry, with antibodies to p63 and p53. All biopsies derived from patients with endoscopic and histopathological substantiation of a diagnosis of traditional/classical Barrett's oesophagus. RESULTS: There was exact concordance in p53 and p63 expression in more advanced forms of neoplasia, high grade dysplasia, and invasive adenocarcinoma, while p63, but not p53, was detected in the proliferative compartment of some non-neoplastic oesophageal tissue, in both squamous mucosa and in the non-neoplastic metaplastic glandular epithelium. CONCLUSIONS: In neoplastic Barrett's oesophagus there is upregulation of both p63 and p53 while p63 isoforms may well have an important role in epithelial biology in both non-metaplastic and metaplastic mucosa of the oesophagus. While abnormalities of p53 function represent an indisputable and critical element of neoplastic transformation, other closely linked genes and their proteins have a role in both the physiology and pathophysiology of the oesophageal mucosa.

The Trp53 pathway is induced in vivo by low doses of gamma radiation.

The induction of the Trp53 response after very low doses (0.01-1 Gy) of ionizing radiation was studied in the adult mouse using immunochemical and immunohistochemical methods. We found a detectable response at 0.01 Gy and an increased induction of Trp53 with increasing dose in both radiation-resistant and radiation-sensitive tissues. These results suggest that there is no lower threshold for induction. This response was heterogeneous, since cells that received the same dose had different staining intensities, suggesting that the induction of Trp53 is not based simply on dose-dependent responses to DNA damage. These data also demonstrate the exquisite sensitivity of the Trp53 pathway and show that this response is controlled by cell- and tissue-specific factors that have yet to be defined.

Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence.

The two prohibitin proteins, Phb1p and Phb2p(BAP37), have been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging.

Measuring a cell's response to stress: the p53 pathway.

The characterization of complex cellular responses to diverse stimuli can be studied by the use of emerging chip-based technologies.

Gadd45 mutations are uncommon in human tumour cell lines.

GADD45 is an evolutionarily conserved gene that encodes a small acidic, nuclear protein and is an example of a p53 responsive gene. Gadd45 protein has been shown to interact with PCNA and also p21waf1. It has been implicated in growth arrest, DNA repair, chromatin structure and signal transduction. The confusing biochemical data has been clarified by the demonstration that Gadd45 null mice have a phenotype strikingly similar to that of p53 null mice, being tumour prone and showing marked genomic instability. We have tested the hypothesis that mutations in the GADD45 coding region might substitute for p53 abnormalities in tumour cell lines where p53 is wild type. After generating cDNA from mRNA in a panel of 24 cell lines we sequenced the GADD45 cDNA and have demonstrated that no mutations can be observed, even in the p53 wild type cell lines. Such data suggest that Gadd45 mutations are uncommon in human cancer. From this we postulate that, despite the phenotype of the GADD45 null mouse, GADD45 is unlikely to be the key mechanistic determinant of the tumour suppressor activity of the p53 pathway.

The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck.

Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent studies have focused on the TP53 tumour suppressor gene, analysing its gene status and protein status. When looking at p53 protein expression, using immunohistochemistry, no correlation to patient outcome has been seen for the whole group of SCCHN. However, a significant association between p53 expression and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning the prognostic significance of mutations in the TP53 gene, results differ. But when restricting analysis to tumours with mutations causing an obvious change in protein, TP53 mutation was found to be a strong and independent variable for prognosticating survival. This review article gives an up-to-date overview of the p53 molecule and evaluates its possible prognostic role in SCCHN. Today it is clear that the p53 pathway is very important in SCCHN biology and potentially in its treatment. The function and importance of a few other cell cycle proteins connected to p53 are also discussed.