Novel Role of Y1 Receptors in the Coordinated Regulation of Bone and Energy Homeostasis

The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y recep- tors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1/ mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1/ mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, con- ditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Further- more, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by non- hypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors

HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells

In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC–T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection

Comparison of contact patterns relevant for transmission of respiratory pathogens in Thailand and the Netherlands using respondent-driven sampling

Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand

Adherence to yoga and exercise interventions in a 6-month clinical trial

<p>Abstract</p> <p>Background</p> <p>To determine factors that predict adherence to a mind-body intervention in a randomized trial.</p> <p>Design</p> <p>We analyzed adherence data from a 3-arm trial involving 135 generally healthy seniors 65–85 years of age randomized to a 6-month intervention consisting of: an Iyengar yoga class with home practice, an exercise class with home practice, or a wait-list control group. Outcome measures included cognitive function, mood, fatigue, anxiety, health-related quality of life, and physical measures. Adherence to the intervention was obtained by class attendance and biweekly home practice logs.</p> <p>Results</p> <p>The drop-out rate was 13%. Among the completers of the two active interventions, average yoga class attendance was 77% and home practice occurred 64% of all days. Average exercise class attendance was 69% and home exercise occurred 54% of all days. There were no clear effects of adherence on the significant study outcomes (quality of life and physical measures). Class attendance was significantly correlated with baseline measures of depression, fatigue, and physical components of health-related quality of life. Significant differences in baseline measures were also found between study completers and drop-outs in the active interventions. Adherence was not related to age, gender, or education level.</p> <p>Conclusion</p> <p>Healthy seniors have good attendance at classes with a physically active intervention. Home practice takes place over half of the time. Decreased adherence to a potentially beneficial intervention has the potential to decrease the effect of the intervention in a clinical trial because subjects who might sustain the greatest benefit will receive a lower dose of the intervention and subjects with higher adherence rates may be functioning closer to maximum ability before the intervention. Strategies to maximize adherence among subjects at greater risk for low adherence will be important for future trials, especially complementary treatments requiring greater effort than simple pill-taking.</p

Parental phonological memory contributes to prediction of outcome of late talkers from 20 months to 4 years: a longitudinal study of precursors of specific language impairment

Background Many children who are late talkers go on to develop normal language, but others go on to have longer-term language difficulties. In this study, we considered which factors were predictive of persistent problems in late talkers. Methods Parental report of expressive vocabulary at 18 months of age was used to select 26 late talkers and 70 average talkers, who were assessed for language and cognitive ability at 20 months of age. Follow-up at 4 years of age was carried out for 24 late and 58 average talkers. A psychometric test battery was used to categorize children in terms of language status (unimpaired or impaired) and nonverbal ability (normal range or more than 1 SD below average). The vocabulary and non-word repetition skills of the accompanying parent were also assessed. Results Among the late talkers, seven (29%) met our criteria for specific language impairment (SLI) at 4 years of age, and a further two (8%) had low nonverbal ability. In the group of average talkers, eight (14%) met the criteria for SLI at 4 years, and five other children (8%) had low nonverbal ability. Family history of language problems was slightly better than late-talker status as a predictor of SLI.. The best predictors of SLI at 20 months of age were score on the receptive language scale of the Mullen Scales of Early Learning and the parent's performance on a non-word repetition task. Maternal education was not a significant predictor of outcome. Conclusions In this study, around three-quarters of late talkers did not have any language difficulties at 4 years of age, provided there was no family history of language impairment. A family history of language-literacy problems was found to be a significant predictor for persisting problems. Nevertheless, there are children with SLI for whom prediction is difficult because they did not have early language delay

Inter-annual decrease in pulse rate and peak frequency of Southeast Pacific blue whale song types

The decrease in the frequency of two southeast Pacific blue whale song types was examined over decades, usingacoustic data from several different sources ranging between the Equator and Chilean Patagonia. The pulse rate ofthe song units as well as their peak frequency were measured using two different methods (summed auto-correlationand Fourier transform). The sources of error associated with each measurement were assessed. There was a lineardecline in both parameters for the more common song type (southeast Pacific song type n ◦ 2). An abbreviated analysisalso showed a frequency decline in the scarcer southeast Pacific song type n ◦ 1 between 1970 to 2014, revealing thatboth song types are declining at similar rates. We discussed the use of measuring both pulse rate and peak frequencyto examine the frequency decline. Finally, a comparison of the rates of frequency decline with other song typesreported in the literature is presented.La décroissance en fréquence des deux chants de baleine bleue de l'océan pacifique sud est est examiné sur plusieurs décennies en utilisant comme source des données acoustiques de l'Equateur à la Patagonie chilienne. La fréquence de pulsation et la fréquence pic des signaux sont mesurés en utilisant deux méthodes distinctes (auto-corrélation sommée et transformée de Fourier rapide). Les sources d'erreur associées à chaque mesure sont estimées. Il y a un déclin linéaire de ces deux fréquences pour le chant le plus commun de cette zone (chant du Pacifique Sud Est n°2, SEP2). Un analyse plus rapide montre aussi une baisse linéaire, entre 1970 et 2014, de la fréquence du chant SEP1, plus rarement enregistré dans cette zone. Ces deux baisses ont des amplitudes similaires. L'intérêt de mesurer la fréquence de pulsation et la fréquence pic de façon concomitante est estimé. Enfin, une comparaison globale des déclins en fréquence de tous les types de chants de baleines bleues est fournie

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research