Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland

We have developed a mouse model of diet-induced obesity that shows numerous abnormalities relating to mammary gland function. Animals ate 40% more calories when offered a high-fat diet and gained weight at three times the rate of controls. They exhibited reduced conception rates, increased peripartum pup mortality, and impaired lactogenesis. The impairment of lactogenesis involved lipid accumulation in the secretory epithelial cells indicative of an absence of copius milk secretion. Expression of mRNAs for -casein, whey acid protein, and -lactalbumin were all decreased immediately postpartum but recovered as lactation was established over 2–3 days. Expression of acetyl-CoA carboxylase (ACC)- mRNA was also decreased at parturition as was the total enzyme activity, although there was a compensatory increase in the proportion in the active state. By day 10 of lactation, the proportion of ACC in the active state was also decreased in obese animals, indicative of suppression of de novo fatty acid synthesis resulting from the supply of preformed fatty acids in the diet. Although obese animals consumed more calories in the nonpregnant and early pregnant states, they showed a marked depression in fat intake around day 9 of pregnancy before food intake recovered in later pregnancy. Food intake increased dramatically in both lean and obese animals during lactation although total calories consumed were identical in both groups. Thus, despite access to high-energy diets, the obese animals mobilized even more adipose tissue during lactation than their lean counterparts. Obese animals also exhibited marked abnormalities in alveolar development of the mammary gland, which may partially explain the delay in differentiation evident during lactogenesis

Evaluation of children's centres in England (ECCE) : strand 1: first survey of children's centre leaders in the most deprived areas

This report is the first output from the Evaluation of Children's Centres in England (ECCE), a six year study commissioned by the Department for Education and undertaken by NatCen Social Research, the University of Oxford and Frontier Economics. The aim of ECCE is to provide an in-depth understanding of children's centre services, including their effectiveness in relation to different management and delivery approaches and the cost of delivering different types of services. The aim of Strand 1 is to profile children’s centres in the most disadvantaged areas, providing estimates on different aspects of provision with which to select centres for subsequent stages of the evaluation and to explore different models of provision. The findings below relate to 500 children's centres that are representative of all phase 1 and 2 centres (i.e. those in the 30percent most deprived areas).</p

Diverse CD81 proteins support hepatitis C virus infection.

Hepatitis C virus (HCV) entry is dependent on CD81. To investigate whether the CD81 sequence is a determinant of HCV host range, we expressed a panel of diverse CD81 proteins and tested their ability to interact with HCV. CD81 large extracellular loop (LEL) sequences were expressed as recombinant proteins; the human and, to a low level, the African green monkey sequences bound soluble HCV E2 (sE2) and inhibited infection by retrovirus pseudotype particles bearing HCV glycoproteins (HCVpp). In contrast, mouse or rat CD81 proteins failed to bind sE2 or to inhibit HCVpp infection. However, CD81 proteins from all species, when expressed in HepG2 cells, conferred susceptibility to infection by HCVpp and cell culture-grown HCV to various levels, with the rat sequence being the least efficient. Recombinant human CD81 LEL inhibited HCVpp infectivity only if present during the virus-cell incubation, consistent with a role for CD81 after virus attachment. Amino acid changes that abrogate sE2 binding (I182F, N184Y, and F186S, alone or in combination) were introduced into human CD81. All three amino acid changes in human CD81 resulted in a molecule that still supported HCVpp infection, albeit with reduced efficiency. In summary, there is a remarkable plasticity in the range of CD81 sequences that can support HCV entry, suggesting that CD81 polymorphism may contribute to, but alone does not define, the HCV susceptibility of a species. In addition, the capacity to support viral entry is only partially reflected by assays measuring sE2 interaction with recombinant or full-length CD81 proteins

Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.

AIM: To investigate the mechanism of action for body weight loss with semaglutide. MATERIALS AND METHODS: This randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed. RESULTS: After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P < 0.0001), and during the subsequent evening meal (P = 0.0401) and snacks (P = 0.0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P < 0.0001). Fasting overall appetite suppression scores were improved with semaglutide versus placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass. CONCLUSION: After 12 weeks' treatment, ad libitum energy intake was substantially lower with semaglutide versus placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods

Analysis of magnetization and a spin state crossover in the multiferroic Ca3_3Co2−x_{2-x}Mnx_xO6_6

Ca_3Co_{2-x}Mn_xO_6 (x ~ 0.96) is a multiferroic with spin-chains of alternating Co(2+) and Mn(4+) ions. The spin state of Co(2+) remains unresolved, due to a discrepancy between high temperature X-ray absorption (S=3/2) and low temperature neutron (S=1/2) measurements. Using a combination of magnetic modeling and crystal-field analysis, we show that the existing low temperature data cannot be reconciled within a high spin scenario by invoking spin-orbit or Jahn-Teller distortions. To unify the experimental results, we propose a spin-state crossover with specific experimental predictions.Comment: 4 pages, 3 figure

Quantum mechanics and geodesic deviation in the brane world

We investigate the induced geodesic deviation equations in the brane world models, in which all the matter forces except gravity are confined on the 3-brane. Also, the Newtonian limit of induced geodesic deviation equation is studied. We show that in the first Randall-Sundrum model the Bohr-Sommerfeld quantization rule is as a result of consistency between the geodesic and geodesic deviation equations. This indicates that the path of test particle is made up of integral multiples of a fundamental Compton-type unit of length $h/mc$.Comment: 5 pages, no figure

Evaluation of children’s centres in England (ECCE). Strand 1: First survey of children’s centre leaders in the most deprived areas

This is the final version of the report. Available from the Department for Education via the link in this record.The evaluation of children’s centres in England (ECCE) is a 6-year study commissioned by the Department for Education (DfE) and undertaken by NatCen Social Research, the University of Oxford and Frontier Economics. The aim of this report is to profile children’s centres in the most disadvantaged areas, providing estimates on different aspects of provision and to explore different models of provision. The profile covers all main aspects of provision including management, staff, services, users and finance and involves nearly 500 children’s centres, representative of all phase 1 and 2 centres in the most disadvantaged area