Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth

Objective: Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from obese dams during the suckling period. However, it is unclear whether this is because of alterations in leptin and hypothalamic appetite regulators at birth. Design: Female Sprague-Dawley rats were fed palatable high-fat diet (HFD) or chow for 5 weeks to induce obesity before mating. The same diet continued during gestation. At day 1, after birth, plasma and hypothalamus were collected from male and female pups. Measurements: Body weight and organ mass were recorded. Leptin and insulin levels were measured in the plasma by radioimmunoassay. Hypothalamic mRNA expression of neuropeptide-Y (NPY), pro-opiomelanocortin, leptin receptor and its downstream signal, STAT3 (signal transducer and activator of transcription 3), were measured using real-time PCR. Results: Body and organ weights of pups from obese dams were similar to those from lean dams, across both genders. However, plasma leptin levels were significantly lower in offspring from obese dams (male: 0.53±0.13 vs 1.05±0.21 ng ml-1; female: 0.33±0.09 vs 2.12±0.57 ng ml-1, respectively; both P<0.05). Hypothalamic mRNA expression of NPY, pro-opiomelanocortin, leptin receptor and STAT3 were also significantly lower in pups from obese dams. Conclusion: Long-term maternal obesity, together with lower leptin levels in pups from obese dams may contribute to the lower expression of key appetite regulators on day 1 of life, suggesting altered intrauterine neuron development in response to intrauterine overnutrition, which may contribute to eating disorders later in life. © 2009 Macmillan Publishers Limited All rights reserved

Maternal overnutrition impacts offspring adiposity and brain appetite markers-modulation by postweaning diet

Maternal obesity has long-term consequences for the development of hypothalamic neurones involved in energy homeostasis and the metabolic profile in offspring. In the present study, we compared the effects of maternal obesity induced by longstanding high-fat diet (HFD) with milder postnatal overfeeding during suckling induced by litter size reduction. Female Sprague-Dawley rats consumed chow (C) or HFD. On postnatal day 1, litters from chow dams were adjusted to three per dam (small litter, CS) versus 12 control (normal litter, CN). Litters from HFD dams were adjusted to 12 per dam and fed HFD after weaning to induce obesity (HN). Thus, two degrees of maternal overnutrition were produced (CS and HN). To test whether postweaning diet can amplify the effects of maternal obesity, male offspring weaned onto chow or HFD were followed to 21 weeks. Maternal postnatal overnutrition (CS) and HFD-induced maternal obesity (HN) increased body weight and fat mass in offspring compared to those from control dams (CN). Significant glucose intolerance was induced by both degrees of maternal overnutrition, but only in offspring consuming HFD. HFD-induced maternal obesity (HN) was linked to increased offspring leptin, insulin, lipids, insulin resistance and hyperphagia, and was exaggerated by postweaning HFD. No effect of maternal postnatal overnutrition (CS) was seen on these parameters. Hypothalamic signal transducer and activator of transcription-3 and suppressor of cytokine signalling-3 mRNA were significantly elevated by maternal HFD (HN) in the HFD-fed offspring. The data obtained suggest that even mild maternal overnutrition (CS) led to increased adiposity, glucose intolerance and altered brain appetite regulators in offspring. A greater impact of HFD-induced maternal obesity was evident. Marked additive effects were observed when animals consumed a HFD postweaning. © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd

Oscillatory behavior of two nonlinear microbial models of soil carbon decomposition

A number of nonlinear models have recently been proposed for simulating soil carbon decomposition. Their predictions of soil carbon responses to fresh litter input and warming differ significantly from conventional linear models. Using both stability analysis and numerical simulations, we showed that two of those nonlinear models (a two-pool model and a three-pool model) exhibit damped oscillatory responses to small perturbations. Stability analysis showed the frequency of oscillation is proportional to √(ε⁻¹-1) Ks/Vs in the two-pool model, and to √(ε⁻¹-1) Kl/Vl in the three-pool model, where ε is microbial growth efficiency, Ks and Kl are the half saturation constants of soil and litter carbon, respectively, and /Vs and /Vl are the maximal rates of carbon decomposition per unit of microbial biomass for soil and litter carbon, respectively. For both models, the oscillation has a period of between 5 and 15 years depending on other parameter values, and has smaller amplitude at soil temperatures between 0 and 15°C. In addition, the equilibrium pool sizes of litter or soil carbon are insensitive to carbon inputs in the nonlinear model, but are proportional to carbon input in the conventional linear model. Under warming, the microbial biomass and litter carbon pools simulated by the nonlinear models can increase or decrease, depending whether ε varies with temperature. In contrast, the conventional linear models always simulate a decrease in both microbial and litter carbon pools with warming. Based on the evidence available, we concluded that the oscillatory behavior and insensitivity of soil carbon to carbon input are notable features in these nonlinear models that are somewhat unrealistic. We recommend that a better model for capturing the soil carbon dynamics over decadal to centennial timescales would combine the sensitivity of the conventional models to carbon influx with the flexible response to warming of the nonlinear model.15 page(s

The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways

Prostate cancer is the second leading cause of cancer related deaths in men from the western world. Treatment of prostate cancer has relied on androgen deprivation therapy for the past 50 years. Response rates are initially high (70-80%), however almost all patients develop androgen escape and subsequently die within 1-2 years. Unlike breast cancer, alternative approaches (chemotherapy and radiotherapy) do not increase survival time. The high rate of prostate cancer mortality is therefore strongly linked to both development of androgen escape and the lack of alternate therapies. AR mutations and amplifications can not explain all cases of androgen escape and post-translational modification of the AR has become an alternative theory. However recently it has been suggested that AR co-activators e.g. SRC-1 or pathways the bypass the AR (Ras/MAP kinase or PI3K/Akt) may stimulated prostate cancer progression independent of the AR. This review will focus on how AR coactivators may act to increase AR transactivation during sub-optimal DHT concentrations and also how signal transduction pathways may promote androgen escape via activation of transcription factors, e.g. AP-1, c-Myc and Myb, that induce cell proliferation or inhibit apoptosis

DeltaPhish: Detecting Phishing Webpages in Compromised Websites

The large-scale deployment of modern phishing attacks relies on the automatic exploitation of vulnerable websites in the wild, to maximize profit while hindering attack traceability, detection and blacklisting. To the best of our knowledge, this is the first work that specifically leverages this adversarial behavior for detection purposes. We show that phishing webpages can be accurately detected by highlighting HTML code and visual differences with respect to other (legitimate) pages hosted within a compromised website. Our system, named DeltaPhish, can be installed as part of a web application firewall, to detect the presence of anomalous content on a website after compromise, and eventually prevent access to it. DeltaPhish is also robust against adversarial attempts in which the HTML code of the phishing page is carefully manipulated to evade detection. We empirically evaluate it on more than 5,500 webpages collected in the wild from compromised websites, showing that it is capable of detecting more than 99% of phishing webpages, while only misclassifying less than 1% of legitimate pages. We further show that the detection rate remains higher than 70% even under very sophisticated attacks carefully designed to evade our system.Comment: Preprint version of the work accepted at ESORICS 201

Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake

The appetite suppressing effect of tobacco is a major driver of smoking behaviour; however few studies have addressed the effects of chronic cigarette smoke exposure (SE) on appetite, body weight and metabolic markers. We compared the effects of SE to equivalent food restriction (pair-fed, PF), against sham-exposure, on body weight, adiposity, cytokines, and levels of uncoupling proteins (UCP) and brain neuropeptide Y (NPY) in male Balb/C mice. SE rapidly induced anorexia, and after 12 weeks, SE and PF groups were lighter than control animals (23.9 ± 0.2, 25.5 ± 0.5, 26.8 ± 0.4 g respectively, P < 0.05). White fat (WAT) masses were reduced by both SE and PF. Plasma leptin and insulin were reduced in SE mice; insulin was further reduced by PF. Brown fat UCP1 and 3 mRNA were increased in SE animals relative to PF animals, possibly promoting thermogenesis. WAT mRNA expression of the inflammatory cytokine, TNFα was doubled by SE, while IL-6 was reduced by both PF and SE. Hypothalamic NPY content was increased by SE (89.3 ± 2.8 vs. 75.9 ± 2.4 ng control, P < 0.05), and more by PF (100.7 ± 3.4 ng, P < 0.05 compared to both groups), suggesting disinhibition due to reduced adipose derived leptin. In contrast to equivalent food restriction, cigarette smoke exposure reduced body weight and total hypothalamic NPY, and increased thermogenesis and markers of inflammation. The suppressed hypothalamic NPY and increased UCPs may contribute to the spontaneous hypophagia and extra weight loss in SE animals. These findings contribute to our understanding of weight loss in smoking-related lung disease, suggesting a greater impact than that due to anorexia alone. Crown Copyright © 2008

Rejecting another pains the self: The impact of perceived future rejection

The current investigation examined whether people would experience a higher level of pain after rejecting another person, especially for those high in evaluative concern, through increased perceptions of future rejection. Three experiments provide converging support to these predictions. After reliving a past rejecting experience (Experiments 1 and 2) and concurrently rejecting another person (Experiment 3), the source of rejection experienced a higher level of pain than participants in the control conditions. We also found that evaluative concern, either primed (Experiment 2) or measured (Experiment 3) moderated the above effect, such that this effect was only observed among participants high in evaluative concern, but not among those low in evaluative concern. Moreover, perceived future rejection mediated the moderating effect of evaluative concern and rejecting another person on the levels of pain that people experience (Experiment 3). These findings contribute to the literature by showing a mechanism explaining why rejecting another person pains the self and who are more susceptible to this influence.postprin

Defect filtering for thermal expansion induced dislocations in III-V lasers on silicon

Epitaxially integrated III-V semiconductor lasers for silicon photonics have the potential to dramatically transform information networks, but currently, dislocations limit performance and reliability even in defect tolerant InAs quantum dot (QD) based lasers. Despite being below critical thickness, QD layers in these devices contain previously unexplained misfit dislocations, which facilitate non-radiative recombination. We demonstrate here that these misfit dislocations form during post-growth cooldown due to the combined effects of (1) thermal-expansion mismatch between the III-V layers and silicon and (2) precipitate and alloy hardening in the active region. By incorporating an additional sub-critical thickness, indium-alloyed misfit dislocation trapping layer, we leverage these mechanical hardening effects to our advantage, successfully displacing 95% of misfit dislocations from the QD layer in model structures. Unlike conventional dislocation mitigation strategies, the trapping layer reduces neither the number of threading dislocations nor the number of misfit dislocations. It simply shifts the position of misfit dislocations away from the QD layer, reducing the defects' impact on luminescence. In full lasers, adding a misfit dislocation trapping layer both above and below the QD active region displaces misfit dislocations and substantially improves performance: we measure a twofold reduction in lasing threshold currents and a greater than threefold increase in output power. Our results suggest that devices employing both traditional threading dislocation reduction techniques and optimized misfit dislocation trapping layers may finally lead to fully integrated, commercially viable silicon-based photonic integrated circuits.Comment: 9 pages, 6 figure