Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Individualization as driving force of clustering phenomena in humans

One of the most intriguing dynamics in biological systems is the emergence of clustering, the self-organization into separated agglomerations of individuals. Several theories have been developed to explain clustering in, for instance, multi-cellular organisms, ant colonies, bee hives, flocks of birds, schools of fish, and animal herds. A persistent puzzle, however, is clustering of opinions in human populations. The puzzle is particularly pressing if opinions vary continuously, such as the degree to which citizens are in favor of or against a vaccination program. Existing opinion formation models suggest that "monoculture" is unavoidable in the long run, unless subsets of the population are perfectly separated from each other. Yet, social diversity is a robust empirical phenomenon, although perfect separation is hardly possible in an increasingly connected world. Considering randomness did not overcome the theoretical shortcomings so far. Small perturbations of individual opinions trigger social influence cascades that inevitably lead to monoculture, while larger noise disrupts opinion clusters and results in rampant individualism without any social structure. Our solution of the puzzle builds on recent empirical research, combining the integrative tendencies of social influence with the disintegrative effects of individualization. A key element of the new computational model is an adaptive kind of noise. We conduct simulation experiments to demonstrate that with this kind of noise, a third phase besides individualism and monoculture becomes possible, characterized by the formation of metastable clusters with diversity between and consensus within clusters. When clusters are small, individualization tendencies are too weak to prohibit a fusion of clusters. When clusters grow too large, however, individualization increases in strength, which promotes their splitting.Comment: 12 pages, 4 figure

Men's values-based factors on prostate cancer risk genetic testing: A telephone survey

BACKGROUND: While a definitive genetic test for Hereditary Prostate Cancer (HPC) is not yet available, future HPC risk testing may become available. Past survey data have shown high interest in HPC testing, but without an in-depth analysis of its underlying rationale to those considering it. METHODS: Telephone computer-assisted interviews of 400 men were conducted in a large metropolitan East-coast city, with subsequent development of psychometric scales and their correlation with intention to receive testing. RESULTS: Approximately 82% of men interviewed expressed that they "probably" or "definitely" would get genetic testing for prostate cancer risk if offered now. Factor analysis revealed four distinct, meaningful factors for intention to receive genetic testing for prostate cancer risk. These factors reflected attitudes toward testing and were labeled "motivation to get testing," "consequences and actions after knowing the test result," "psychological distress," and "beliefs of favorable outcomes if tested" (α = 0.89, 0.73, 0.73, and 0.60, respectively). These factors accounted for 70% of the total variability. The domains of motivation (directly), consequences (inversely), distress (inversely), and positive expectations (directly) all correlated with intention to receive genetic testing (p < 0.001). CONCLUSIONS: Men have strong attitudes favoring genetic testing for prostate cancer risk. The factors most associated with testing intention include those noted in past cancer genetics studies, and also highlights the relevance in considering one's motivation and perception of positive outcomes in genetic decision-making

AKT1 Loss Correlates with Episomal HPV16 in Vulval Intraepithelial Neoplasia

Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy

Hacking into bacterial biofilms: a new therapeutic challenge

Microbiologists have extensively worked during the past decade on a particular phase of the bacterial cell cycle known as biofilm, in which single-celled individuals gather together to form a sedentary but dynamic community within a complex structure, displaying spatial and functional heterogeneity. In response to the perception of environmental signals by sensing systems, appropriate responses are triggered, leading to biofilm formation. This process involves various molecular systems that enable bacteria to identify appropriate surfaces on which to anchor themselves, to stick to those surfaces and to each other, to construct multicellular communities several hundreds of micrometers thick, and to detach from the community. The biofilm microbial community is a unique, highly competitive, and crowded environment facilitating microevolutionary processes and horizontal gene transfer between distantly related microorganisms. It is governed by social rules, based on the production and use of "public" goods, with actors and recipients. Biofilms constitute a unique shield against external aggressions, including drug treatment and immune reactions. Biofilm-associated infections in humans have therefore generated major problems for the diagnosis and treatment of diseases. Improvements in our understanding of biofilms have led to innovative research designed to interfere with this process