A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance

YesLong-term and reversible changes in body weight are typical of seasonal animals. Thyroid hormone (TH) and retinoic acid (RA) within the tanycytes and ependymal cells of the hypothalamus have been implicated in the photoperiodic response. We investigated signalling downstream of RA and how this links to the control of body weight and food intake in photoperiodic F344 rats. Chemerin, an inflammatory chemokine, with a known role in energy metabolism, was identified as a target of RA. Gene expression of chemerin (Rarres2) and its receptors were localised within the tanycytes and ependymal cells, with higher expression under long (LD) versus short (SD) photoperiod, pointing to a physiological role. The SD to LD transition (increased food intake) was mimicked by 2 weeks of ICV infusion of chemerin into rats. Chemerin also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response. By contrast, acute ICV bolus injection of chemerin on a 12h:12h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24hr. We describe the hypothalamic ventricular zone as a key site of neuroendocrine regulation, where the inflammatory signal, chemerin, links TH and RA signaling to hypothalamic remodeling.BBSRC (grant number BB/K001043/1) and the Scottish Government

Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics

Background: The use of tumour xenografts is a well-established research tool in cancer genomics but has not yet been comprehensively evaluated for cancer epigenomics. Methods: In this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K Beadchips and MeDIP-seq. Results: Controlled for confounding host (mouse) sequences, comparison of primary PDXs and matching patient tumours in a rare (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the assayed CpG sites undergo major (Δβ ≥ 0.51) methylation changes in a cancer-specific manner as a result of the xenografting procedure. No significant subsequent methylation changes were observed after a second round of xenografting between primary and secondary PDXs. Based on computational simulation using publically available methylation data, we additionally show that future studies comparing two groups of PDXs should use 15 or more samples in each group to minimise the impact of xenografting-associated changes in methylation on comparison results. Conclusions: Our results from rare and common cancers indicate that PDXs are a suitable discovery tool for cancer epigenomics and we provide guidance on how to overcome the observed limitations

Multisystem afflictions in former National Football League players

Background: The long-term health consequences of participation in American style football (ASF) are not well understood. Methods: We conducted a retrospective cohort study of men who had played in the NFL after 1960. Participants were studied using a standardized self-administered questionnaire designed to determine both the exposure history to ASF and the prevalence of chronic pain, sleep apnea, cardiometabolic disease, and neurocognitive impairment. Logistic regression and negative binomial regression models were used to assess associations between age, ethnicity, body-mass index during professional football career, field position, and football career duration with individual and multiple afflictions. Results: In this cohort of former NFL players (n = 3745), approximately one quarter of the eligible former players (27%) reported two or more medical afflictions (chronic pain, cardiometabolic disease, sleep apnea, or neurocognitive impairment). Career duration was significantly associated with an increase in the number of comorbidities. Age, race, and body-mass index were associated with all affliction categories, other than neurocognitive impairment, which was similarly prevalent in middle-aged players and older players. Earlier age when first playing the sport was protective against cardiometabolic affliction. Conclusions: Former NFL players report significant combinations of cross-system afflictions. Future work will be required to determine mechanistic underpinnings. However, attention to the whole player, rather than specific organ systems seems critical to improve long-term health outcomes in former ASF professional athletes

Scherk-Schwarz Supersymmetry Breaking for Quasi-localized Matter Fields and Supersymmetry Flavor Violation

We examine the soft supersymmetry breaking parameters induced by the Scherk-Schwarz (SS) boundary condition in 5-dimensional orbifold field theory in which the quark and lepton zero modes are quasi-localized at the orbifold fixed points to generate the hierarchical Yukawa couplings. In such theories, the radion corresponds to a flavon to generate the flavor hierarchy and at the same time plays the role of the messenger of supersymmetry breaking. As a consequence, the resulting soft scalar masses and trilinear $A$-parameters of matter zero modes at the compactification scale are highly flavor-dependent, thereby can lead to dangerous flavor violations at low energy scales. We analyze in detail the low energy flavor violations in SS-dominated supersymmetry breaking scenario under the assumption that the compactification scale is close to the grand unification scale and the 4-dimensional effective theory below the compactification scale is given by the minimal supersymmetric standard model. Our analysis can be applied to any supersymmetry breaking mechanism giving a sizable $F$-component of the radion superfield, e.g. the hidden gaugino condensation model.Comment: revtex4, 22 pages, some numerical errors are corrected in phenomenological analysis, main conclusion does not chang

Reexamining nonstandard interaction effects on supernova neutrino flavor oscillations

Several extensions of the standard electroweak model allow new four-fermion interactions (nu_a nu_b * ff) with strength eps_ab*G_F, where (a,b) are flavor indices. We revisit their effects on flavor oscillations of massive (anti)neutrinos in supernovae, in order to achieve, in the region above the protoneutron star, an analytical treatment valid for generic values of the neutrino mixing angles (omega,phi,psi)=(theta_12,theta_13,theta_23). Assuming that eps_ab<<1, we find that the leading effects on the flavor transitions occurring at high (H) and low (L) density along the supernova matter profile can be simply embedded through the replacements phi-->phi+eps_H and omega-->omega+eps_L, respectively, where eps_H and eps_L are specific linear combinations of the eps_ab's. Similar replacements hold for eventual oscillations in the Earth matter. From a phenomenological point of view, the most relevant consequence is a possible uncontrolled bias (phi-->phi+eps_H) in the value of the mixing angle phi inferred by inversion of supernova neutrino data. Such a drawback, however, does not preclude the discrimination of the neutrino mass spectrum hierarchy (direct or inverse) through supernova neutrino oscillations.Comment: Text clarified, one figure added. To appear in PR

Race and sex differences in dropout from the STRRIDE trials

Purpose: To determine if race and sex differences exist in determinants and timing of dropout among individuals enrolled in an exercise and/or caloric restriction intervention. Methods: A total of 947 adults with dyslipidemia (STRRIDE I, STRRIDE AT/RT) or prediabetes (STRRIDE-PD) were randomized to either inactive control or to 1 of 10 exercise interventions, ranging from doses of 8–23 kcal/kg/week, intensities of 50%–75% (Formula presented.) peak, and durations of 6–8 months. Two groups included resistance training, and one included a dietary intervention (7% weight loss goal). Dropout was defined as an individual withdrawn from the study, with the reasons for dropout aggregated into determinant categories. Timing of dropout was defined as the last session attended and aggregated into phases (i.e., “ramp” period to allow gradual adaptation to exercise prescription). Utilizing descriptive statistics, percentages were generated according to categories of determinants and timing of dropout to describe the proportion of individuals who fell within each category. Results: Black men and women were more likely to be lost to follow-up (Black men: 31.3% and Black women: 19.6%), or dropout due to work responsibilities (15.6% and 12.5%), “change of mind” (12.5% and 8.9%), transportation issues (6.3% and 3.6%), or reported lack of motivation (6.3% and 3.6%). Women in general noted lack of time more often than men as a reason for dropout (White women: 22.4% and Black women: 22.1%). Regardless of race and sex, most participants dropped out during the ramp period of the exercise intervention; with Black women (50%) and White men (37.1%) having the highest dropout rate during this period. Conclusion: These findings emphasize the importance of targeted retention strategies when aiming to address race and sex differences that exist in determinants and timing of dropout among individuals enrolled in an exercise and/or caloric restriction intervention

Tobacco quit intentions and behaviors among cigar smokers in the united states in response to covid-19

Combustible tobacco users appear to be at greater risk for serious complications from COVID-19. This study examined cigar smokers’ perceived risk of COVID-19, quit intentions, and behaviors during the current pandemic. We conducted an online study between 23 April 2020 to 7 May 2020, as part of an ongoing study examining perceptions of different health effects of cigars. All participants used cigars in the past 30 days (n = 777). Three-quarters of the sample (76.0%) perceived they had a higher risk of complications from COVID-19 compared to non-smokers. The majority of participants (70.8%) intended to quit in the next six months due to COVID-19, and almost half of the sample (46.5%) reported making a quit attempt since the start of the COVID-19 pandemic. Far more participants reported increasing their tobacco use since COVID-19 started (40.9%) vs. decreasing their tobacco use (17.8%). Black or African American participants, participants who reported using a quitline, and participants with higher COVID-19 risk perceptions had higher intentions to quit using tobacco due to COVID-19, and higher odds of making a quit attempt since COVID-19 started. More research is needed to understand how tobacco users are perceiving COVID-19 risks and changing their tobacco use behaviors

Tunneling of quantum rotobreathers

We analyze the quantum properties of a system consisting of two nonlinearly coupled pendula. This non-integrable system exhibits two different symmetries: a permutational symmetry (permutation of the pendula) and another one related to the reversal of the total momentum of the system. Each of these symmetries is responsible for the existence of two kinds of quasi-degenerated states. At sufficiently high energy, pairs of symmetry-related states glue together to form quadruplets. We show that, starting from the anti-continuous limit, particular quadruplets allow us to construct quantum states whose properties are very similar to those of classical rotobreathers. By diagonalizing numerically the quantum Hamiltonian, we investigate their properties and show that such states are able to store the main part of the total energy on one of the pendula. Contrary to the classical situation, the coupling between pendula necessarily introduces a periodic exchange of energy between them with a frequency which is proportional to the energy splitting between quasi-degenerated states related to the permutation symmetry. This splitting may remain very small as the coupling strength increases and is a decreasing function of the pair energy. The energy may be therefore stored in one pendulum during a time period very long as compared to the inverse of the internal rotobreather frequency.Comment: 20 pages, 11 figures, REVTeX4 styl

Tourism Destination Management: A Collaborative Approach

Collaboration is a key factor of sustainable growth across territories and industrial sectors. Tourism, one of the largest industries in the world, has been subject to strongest innovation in the last years. Main reasons of this reside both in the availability of new ICTs - Information and Communication Technologies - and organizational models, which directly connect tourists among them and with service providers, and in the always more personalized supply of tourism experience. Tourism destinations can benefit of such innovations if they are able to reorganize the territorial tourism offer around different pattern of collaboration in order to give 2.0 tourists opportunities to live an augmented tourism experience. This paper deals with the possible forms of collaborative networks that can rise within a destination with a focus on relationships between services delivered by the Tourism Destination and the requests of services at the different phases of the tourist 2.0 lifecycle

Confusing non-standard neutrino interactions with oscillations at a neutrino factory

Most neutrino mass theories contain non-standard interactions (NSI) of neutrinos which can be either non-universal (NU) or flavor-changing (FC). We study the impact of such interactions on the determination of neutrino mixing parameters at a neutrino factory using the so-called ``golden channels'' \pnu{e}\to\pnu{\mu} for the measurement of \theta_{13}. We show that a certain combination of FC interactions in neutrino source and earth matter can give exactly the same signal as oscillations arising due to \theta_{13}. This implies that information about \theta_{13} can only be obtained if bounds on NSI are available. Taking into account the existing bounds on FC interactions, this leads to a drastic loss in sensitivity in \theta_{13}, at least two orders of magnitude. A near detector at a neutrino factory offers the possibility to obtain stringent bounds on some NSI parameters. Such near site detector constitutes an essential ingredient of a neutrino factory and a necessary step towards the determination of \theta_{13} and subsequent study of leptonic CP violation.Comment: 23 pages, 5 figures, improved version, accepted for publication in Phs. Rev. D, references adde