β-arrestin regulates estradiol membrane-initiated signaling in hypothalamic neurons.

Estradiol (E2) action in the nervous system is the result of both direct nuclear and membrane-initiated signaling (EMS). E2 regulates membrane estrogen receptor-α (ERα) levels through opposing mechanisms of EMS-mediated trafficking and internalization. While ß-arrestin-mediated mERα internalization has been described in the cortex, a role of ß-arrestin in EMS, which underlies multiple physiological processes, remains undefined. In the arcuate nucleus of the hypothalamus (ARH), membrane-initiated E2 signaling modulates lordosis behavior, a measure of female sexually receptivity. To better understand EMS and regulation of ERα membrane levels, we examined the role of ß-arrestin, a molecule associated with internalization following agonist stimulation. In the present study, we used an immortalized neuronal cell line derived from embryonic hypothalamic neurons, the N-38 line, to examine whether ß-arrestins mediate internalization of mERα. β-arrestin-1 (Arrb1) was found in the ARH and in N-38 neurons. In vitro, E2 increased trafficking and internalization of full-length ERα and ERαΔ4, an alternatively spliced isoform of ERα, which predominates in the membrane. Treatment with E2 also increased phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2) in N-38 neurons. Arrb1 siRNA knockdown prevented E2-induced ERαΔ4 internalization and ERK1/2 phosphorylation. In vivo, microinfusions of Arrb1 antisense oligodeoxynucleotides (ODN) into female rat ARH knocked down Arrb1 and prevented estradiol benzoate-induced lordosis behavior compared with nonsense scrambled ODN (lordosis quotient: 3 ± 2.1 vs. 85.0 ± 6.0; p < 0.0001). These results indicate a role for Arrb1 in both EMS and internalization of mERα, which are required for the E2-induction of female sexual receptivity

A Minority of Patients with Type 1 Diabetes Routinely Downloads and Retrospectively Reviews Device Data.

BackgroundIn type 1 diabetes (T1D), periodic review of blood glucose and insulin dosing should be performed, but it is not known how often patients review these data on their own. We describe the proportion of patients with T1D who routinely downloaded and reviewed their data at home.Materials and methodsA cross-sectional survey of 155 adults and 185 caregivers of children with T1D at a single academic institution was performed. "Routine Downloaders" (downloaded four or more times in the past year) were also considered "Routine Reviewers" if they reviewed their data most of the time they downloaded from devices. Logistic regression was used to identify factors associated with being a Routine Reviewer.ResultsOnly 31% of adults and 56% of caregivers reported ever downloading data from one or more devices, whereas 20% and 40%, respectively, were considered Routine Downloaders. Only 12% of adults and 27% of caregivers were Routine Reviewers. Mean hemoglobin A1c was lower in Routine Reviewers compared with non-Routine Reviewers (7.2±1.0% vs. 8.1±1.6% [P=0.03] in adults and 7.8±1.4% vs. 8.6±1.7% [P=0.001] in children). In adjusted analysis of adults, the odds ratio of being a Routine Reviewer of one or more devices for every 10-year increase in age was 1.5 (95% confidence interval, 1.1, 2.1 [P=0.02]). For every 10 years since diabetes diagnosis, the odds ratio of being a Routine Reviewer was 1.7 (95% confidence interval, 1.2, 2.4 [P=0.01]). For caregivers, there were no statistically significant factors associated with being a Routine Reviewer.ConclusionsA minority of T1D patients routinely downloads and reviews data from their devices on their own. Further research is needed to understand obstacles, provide better education and tools for self-review, and determine if patient self-review is associated with improved glycemic control

A Digital Inclusive Society Study - Understanding the Social Impacts of Information Communication Technology (ICT) Usage in China

This paper discusses the role of self-efficacy to computer novices through a longitudinal study. The researchers conducted this study by collaborating with three non-government organizations (NGOs) for which funding was received from one government unit and a large local charitable organization. A new model was developed to examine the influence of Internet self-efficacy and outcome expectations on usage intention and perceived user competence. Behavioral modeling training courses were offered to matured adults aged 50 and above in two separate studies over a year. Questionnaires and cognitive knowledge assessments were distributed. In general, the findings in the two studies validated the impacts and antecedents of Internet self-efficacy and outcome expectations on usage intention. Limitations and implications of this study are provided following the sections on research model and hypotheses, design and discussion on findings

Repeatability and reliability of exploratory behavior in proactive and reactive zebrafsh, Danio rerio

Behavioral responses to novel situations often vary and can belong to a suite of correlated behaviors. Characteristic behaviors of different personality types (e.g. stress coping styles) are generally consistent across contexts and time. Here, we compare the repeatability and reliability of exploratory behaviors between zebrafsh strains selectively bred to display contrasting behavioral responses to stressors that represent the proactive-reactive axis. Specifically, we measure exploratory behavior of individual fish in an open field test over five weeks. We quantified the stationary time, average swimming speed and time spent by a fish in the center area. We found a number of strain differences for each behavioral measure. Stationary time was the most repeatable and reliable measure for assessing proactive-reactive behavioral differences. Reactive zebrafish generally showed the highest reliability and repeatability of exploratory behavior compared to proactive zebrafish and a separate wild caught strain. Given the increased interest in the evolutionary consequences and proximate mechanisms of consistent individual differences, it will be important to continue to investigate how different selective pressures may influence expression of stress coping styles and their effects on the consistency of an animal’s behavior

Capecitabine as Salvage Treatment for Lymphoepithelioma-Like Carcinoma of Lung

AbstractLymphoepithelioma-like carcinoma (LELC) of lung has previously demonstrated good clinical response to 5-fluorouracil containing chemotherapy regimen, similar to the observation in undifferentiated nasopharyngeal carcinoma. Capecitabine, which is converted into active 5-fluorouracil within tumor cells, has been found effective in colorectal, breast, and recently nasopharyngeal carcinomas. We report our experience in five patients with advanced or metastatic LELC of lung who were treated with single agent capecitabine as salvage chemotherapy. The finding of disease control in three of five patients, especially with exceptionally durable stable disease (14.8 months) in one patient, suggests the potential clinical activity of capecitabine in LELC of lung. Future studies on capecitabine-containing chemotherapy regimens in LELC of lung are warranted

A Contextual Examination of Gender Role Conflict Among College Football Players

This mixed methods study examined the contextual nature of gender role conflict (GRC). Using a quasi-experimental design, 153 male college football players were randomly assigned to two groups wherein they were instructed to report levels of GRC based on the assigned life domain (within the football environment vs. life outside of football). Results indicated that participants did not differ significantly in levels of GRC across life domains, but did reveal that life domain (within the football environment) moderated the significant relationship between Restrictive Affectionate Behavior Between Men (RABBM) and life satisfaction. Qualitative findings provided support for quantitative results, and described ways that football players express emotions and affection toward other men within this unique context. Results can help psychologists design interventions that normalize and encourage affective and emotional expression within the domain of football, with the intent of teaching players to transfer these behaviors to life domains outside of football

Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

Metropolitan quantum key distribution with silicon photonics

Photonic integrated circuits (PICs) provide a compact and stable platform for quantum photonics. Here we demonstrate a silicon photonics quantum key distribution (QKD) transmitter in the first high-speed polarization-based QKD field tests. The systems reach composable secret key rates of 950 kbps in a local test (on a 103.6-m fiber with a total emulated loss of 9.2 dB) and 106 kbps in an intercity metropolitan test (on a 43-km fiber with 16.4 dB loss). Our results represent the highest secret key generation rate for polarization-based QKD experiments at a standard telecom wavelength and demonstrate PICs as a promising, scalable resource for future formation of metropolitan quantum-secure communications networks

H0LiCOW XII. Lens mass model of WFI2033-4723 and blind measurement of its time-delay distance and H0H_0

We present the lens mass model of the quadruply-imaged gravitationally lensed quasar WFI2033-4723, and perform a blind cosmographical analysis based on this system. Our analysis combines (1) time-delay measurements from 14 years of data obtained by the COSmological MOnitoring of GRAvItational Lenses (COSMOGRAIL) collaboration, (2) high-resolution $\textit{Hubble Space Telescope}$ imaging, (3) a measurement of the velocity dispersion of the lens galaxy based on ESO-MUSE data, and (4) multi-band, wide-field imaging and spectroscopy characterizing the lens environment. We account for all known sources of systematics, including the influence of nearby perturbers and complex line-of-sight structure, as well as the parametrization of the light and mass profiles of the lensing galaxy. After unblinding, we determine the effective time-delay distance to be $4784_{-248}^{+399}~\mathrm{Mpc}$, an average precision of $6.6\%$. This translates to a Hubble constant $H_{0} = 71.6_{-4.9}^{+3.8}~\mathrm{km~s^{-1}~Mpc^{-1}}$, assuming a flat $\Lambda$CDM cosmology with a uniform prior on $\Omega_\mathrm{m}$ in the range [0.05, 0.5]. This work is part of the $H_0$ Lenses in COSMOGRAIL's Wellspring (H0LiCOW) collaboration, and the full time-delay cosmography results from a total of six strongly lensed systems are presented in a companion paper (H0LiCOW XIII).Comment: Version accepted by MNRAS. 29 pages including appendix, 17 figures, 6 tables. arXiv admin note: text overlap with arXiv:1607.0140

Mechanisms for Temperature Modulation of Feeding in Goldfish and Implications on Seasonal Changes in Feeding Behavior and Food Intake

In fish models, seasonal change in feeding is under the influence of water temperature. However, the effects of temperature on appetite control can vary among fish species and the mechanisms involved have not been fully characterized. Using goldfish (Carassius auratus) as a model, seasonal changes in feeding behavior and food intake were examined in cyprinid species. In our study, foraging activity and food consumption in goldfish were found to be reduced with positive correlation to the gradual drop in water temperature occurring during the transition from summer (28.4 ± 2.2°C) to winter (15.1 ± 2.6°C). In goldfish with a 4-week acclimation at 28°C, their foraging activity and food consumption were notably higher than their counterparts with similar acclimation at 15°C. When compared to the group at 28°C during summer, the attenuation in feeding responses at 15°C during the winter also occurred with parallel rises of leptin I and II mRNA levels in the liver. Meanwhile, a drop in orexin mRNA along with concurrent elevations of CCK, MCH, POMC, CART, and leptin receptor (LepR) transcript expression could be noted in brain areas involved in feeding control. In short-term study, goldfish acclimated at 28°C were exposed to 15°C for 24 h and the treatment was effective in reducing foraging activity and food intake. The opposite was true in reciprocal experiment with a rise in water temperature to 28°C for goldfish acclimated at 15°C. In parallel time-course study with lowering of water temperature from 28 to 15°C, short-term exposure (6–12 h) of goldfish to 15°C could also increase leptin I and II mRNA levels in the liver. Similar to our seasonality study, transcript level of orexin was reduced along with up-regulation of CCK, MCH, POMC, CART, and LepR gene expression in different brain areas. Our results, as a whole, suggest that temperature-driven regulation of leptin output from the liver in conjunction with parallel modulations of orexigenic/anorexigenic signals and leptin responsiveness in the brain may contribute to the seasonal changes of feeding behavior and food intake observed in goldfish