Differential inhibition of postnatal brain, spinal cord and body growth by a growth hormone antagonist

BACKGROUND: Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH. RESULTS: Before 50 days of postnatal age, GHA reduces spinal cord weight more than brain weight, but less than body weight. Thereafter, GHA ceases to inhibit the increase in body weight, which approaches control levels by day 150. In contrast, GHA continues to act on the CNS after day 50, reducing spinal cord growth to a greater extent and for a longer duration than brain growth. CONCLUSIONS: Judging from its inhibition by GHA, GH differentially affects the magnitude, velocity and duration of postnatal growth of the brain, spinal cord and body. GH promotes body enlargement more than CNS growth early in postnatal life. Later, its CNS effects are most obvious in the spinal cord, which continues to exhibit GH dependence well into adulthood. As normal CNS growth slows, so does its inhibition by GHA, suggesting that reduced trophic effects of GH contribute to the postnatal slowing of CNS growth. GHA is a highly useful tool for studying the role of endogenous GH on organ-specific growth during aging

Comparing Diet and Exercise Monitoring Using Smartphone App and Paper Diary: A Two-Phase Intervention Study

Background: There is increasing recognition that personalized approaches may be more effective in helping people establish healthier eating patterns and exercise more, and that this approach may be particularly effective in adolescents. Objective: The objective of this study was to investigate the use of a smartphone app (FoodWiz2) in supporting healthy lifestyle choices in adolescence. Methods: Participants (N=34: 11 male, 23 female) aged 16-19 years in full- or part-time education were recruited from sixth form colleges, schools, and other further education establishments in Norfolk and Suffolk, United Kingdom, between February and May 2015. Participants recorded food intake and exercise using a paper diary for 4-5 weeks and then used the app for the same duration. Initial nutrition education and general support were provided during the paper diary use, but the app included personalized messages sent in response to app activity. At the end of each study phase, participants completed an online questionnaire to describe their experience of using the paper diary and app. Results: Record completion declined throughout the study, possibly affected by examination pressure. Food intake data showed increased fruit consumption and significantly reduced consumption of chocolate snacks (P=.01) and fizzy drinks (P=.002) among participants using the app. Questionnaire responses indicated that the app was generally preferred to the paper diary, in particular, the app was seen as less boring to use (P=.03) and more acceptable in social settings (P<.001). Conclusions: This app-based approach has shown the potential for a more effective approach to improving adolescent diet and exercise levels

Alleviating the non-ultralocality of coset sigma models through a generalized Faddeev-Reshetikhin procedure

The Faddeev-Reshetikhin procedure corresponds to a removal of the non-ultralocality of the classical SU(2) principal chiral model. It is realized by defining another field theory, which has the same Lax pair and equations of motion but a different Poisson structure and Hamiltonian. Following earlier work of M. Semenov-Tian-Shansky and A. Sevostyanov, we show how it is possible to alleviate in a similar way the non-ultralocality of symmetric space sigma models. The equivalence of the equations of motion holds only at the level of the Pohlmeyer reduction of these models, which corresponds to symmetric space sine-Gordon models. This work therefore shows indirectly that symmetric space sine-Gordon models, defined by a gauged Wess-Zumino-Witten action with an integrable potential, have a mild non-ultralocality. The first step needed to construct an integrable discretization of these models is performed by determining the discrete analogue of the Poisson algebra of their Lax matrices.Comment: 31 pages; v2: minor change

Genetic prediction of complex traits: integrating infinitesimal and marked genetic effects

Genetic prediction for complex traits is usually based on models including individual (infinitesimal) or marker effects. Here, we concentrate on models including both the individual and the marker effects. In particular, we develop a ''Mendelian segregation'' model combining infinitesimal effects for base individuals and realized Mendelian sampling in descendants described by the available DNA data. The model is illustrated with an example and the analyses of a public simulated data file. Further, the potential contribution of such models is assessed by simulation. Accuracy, measured as the correlation between true (simulated) and predicted genetic values, was similar for all models compared under different genetic backgrounds. As expected, the segregation model is worthwhile when markers capture a low fraction of total genetic variance. (Résumé d'auteur

Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al

Escherichia coli induces apoptosis and proliferation of mammary cells

Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Incidence trend and risk factors for campylobacter infections in humans in Norway

BACKGROUND: The objectives of the study were to evaluate whether the increase in incidence of campylobacteriosis observed in humans in Norway from 1995 to 2001 was statistically significant and whether different biologically plausible risk factors were associated with the incidence of campylobacteriosis in the different counties in Norway. METHODS: To model the incidence of domestically acquired campylobacteriosis from 1995 to 2001, a population average random effect poisson model was applied (the trend model). To case data and assumed risk-factor/protective data such as sale of chicken, receiving treated drinking water, density of dogs and grazing animals, occupation of people in the municipalities and climatic factors from 2000 and 2001, an equivalent model accounting for geographical clustering was applied (the ecological model). RESULTS: The increase in incidence of campylobacteriosis in humans in Norway from 1995 to 2001 was statistically significant from 1998. Treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. The two-level modelling technique showed no evidence of clustering of campylobacteriosis in any particular county. Aggregation of data on municipality level makes interpretation of the results at the individual level difficult. CONCLUSION: The increase in incidence of Campylobacter infections in humans from 1995 to 2001 was statistically significant from 1998. Treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. Campylobacter infections did not appear to be clustered in any particular county in Norway