Structural Principles in Robo Activation and Auto-Inhibition

This is the author accepted manuscript. The final version is available from Elsevier (Cell Press) via the DOI in this record.Proper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos’ switch from “off” to “on” states remains unclear. Here, we report a 3.6 Å crystal structure of the intact human Robo2 ectodomain (domains D1–8). We demonstrate that Robo cis dimerization via D4 is conserved through hRobo1, 2, and 3 and the C. elegans homolog SAX-3 and is essential for SAX-3 function in vivo. The structure reveals two levels of auto-inhibition that prevent premature activation: (1) cis blocking of the D4 dimerization interface and (2) trans interactions between opposing Robo receptors that fasten the D4-blocked conformation. Complementary experiments in mouse primary neurons and C. elegans support the auto-inhibition model. These results suggest that Slit stimulation primarily drives the release of Robo auto-inhibition required for dimerization and activation.ICRFIS

The Relationship between the Level of Fatness and Fitness during Adolescence and the Risk Factors of Metabolic Disorders in Adulthood

BACKGROUND: The purpose of the current study was to investigate the association between the level of obesity and physical fitness (PF) during adolescence and the risk factors of metabolic disorders during adulthood. METHODS: In the current analysis, 3,993 Korean adults (mean age, 38.70 +/- 1.69 years) were recruited. The level of body index (BI) and PF were examined during adolescence through high school record, and their health examination data, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), total cholesterol (TC), and current body mass index (BMI) were obtained from National Health Insurance Corporation Data. Gender-specific analyses were administered to compare health exam data across the level of BI, the level of PF, and a mixed level of BI and PF. RESULTS: Most obese males during high school had statistically higher SBP, DBP, FG, and BMI in adulthood, and most obese females had higher BMI, as compared to most lean males or females. Least fit males during high school had statistically higher BMI in adulthood, and least fit females had statistically higher SBP, DBP, FG, TC, and BMI, as compared to most fit males or females. There was a significant relationship between the mixed level of BI and PF and SBP, DBP, TC and current BMI in both genders. CONCLUSION: Maintaining a healthy level of body weight and PF during adolescence is recommended to prevent the development of metabolic diseases in adulthood.ope

Management of locally recurrent nasopharyngeal carcinoma

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.Peer reviewe

ACR appropriateness criteria® nasal cavity and paranasal sinus cancers

The American College of Radiology (ACR) Appropriateness Criteria are evidence‐based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer‐reviewed journals and the application of well‐established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407–418, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136245/1/hed24639.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136245/2/hed24639_am.pd

Smart Moves: Effects of Relative Brain Size on Establishment Success of Invasive Amphibians and Reptiles

Brain size relative to body size varies considerably among animals, but the ecological consequences of that variation remain poorly understood. Plausibly, larger brains confer increased behavioural flexibility, and an ability to respond to novel challenges. In keeping with that hypothesis, successful invasive species of birds and mammals that flourish after translocation to a new area tend to have larger brains than do unsuccessful invaders. We found the same pattern in ectothermic terrestrial vertebrates. Brain size relative to body size was larger in species of amphibians and reptiles reported to be successful invaders, compared to species that failed to thrive after translocation to new sites. This pattern was found in six of seven global biogeographic realms; the exception (where relatively larger brains did not facilitate invasion success) was Australasia. Establishment success was also higher in amphibian and reptile families with larger relative brain sizes. Future work could usefully explore whether invasion success is differentially associated with enlargement of specific parts of the brain (as predicted by the functional role of the forebrain in promoting behavioural flexibility), or with a general size increase (suggesting that invasion success is facilitated by enhanced perceptual and motor skills, as well as cognitive ability)

Food preferences of golden jackals and sympatric red foxes in European temperate climate agricultural area (Hungary)

Differences in food preferences between two sympatric canids, the golden jackal (Canis aureus), which is currently spreading from south-east Europe and is a little-known species in Europe, and the red fox (Vulpes vulpes) were investigated. Data on diet composition and food availability were collected over a 13-season period, in a temperate climate agricultural area of Hungary. We found that jackals and foxes preferred small mammals (Ivlev’s electivity index, Eis0.38 and 0.39, respectively), and avoided towards wild boar (Eis -0.43 and -0.56, respectively) and cervids (Eis-0.92 and -0.94, respectively). Jackals preferred pheasant less than foxes (Eis0.06 and 0.51, respectively). Within small mammals, both predators preferred the open field living species, with the forest living species being less favoured. The relationship between the available biomass of small mammals, as the primarily important food resource for both canids, and the proportion of consumed biomass of small mammals was not close. This was probably as a result of abundant food resources and high trophic flexibility of the golden jackal and red fox allowing these two closely related carnivores to coexist sympatrically in Central European areas without resource partitioning

Global warming and Bergmann’s rule: do central European passerines adjust their body size to rising temperatures?

Recent climate change has caused diverse ecological responses in plants and animals. However, relatively little is known about homeothermic animals’ ability to adapt to changing temperature regimes through changes in body size, in accordance with Bergmann’s rule. We used fluctuations in mean annual temperatures in south-west Germany since 1972 in order to look for direct links between temperature and two aspects of body size: body mass and flight feather length. Data from regionally born juveniles of 12 passerine bird species were analysed. Body mass and feather length varied significantly among years in eight and nine species, respectively. Typically the inter-annual changes in morphology were complexly non-linear, as was inter-annual variation in temperature. For six (body mass) and seven species (feather length), these inter-annual fluctuations were significantly correlated with temperature fluctuations. However, negative correlations consistent with Bergmann’s rule were only found for five species, either for body mass or feather length. In several of the species for which body mass and feather length was significantly associated with temperature, morphological responses were better predicted by temperature data that were smoothed across multiple years than by the actual mean breeding season temperatures of the year of birth. This was found in five species for body mass and three species for feather length. These results suggest that changes in body size may not merely be the result of phenotypic plasticity but may hint at genetically based microevolutionary adaptations

Analyzing the Decision to get Flu Shot: An Empirical Study

Influenza vaccination has been shown to be cost effective in reducing morbidity and mortality and in decreasing work absenteeism and use of health-care resources. The purpose of this study was to identify predictors and beliefs regarding people's vaccination decision against the influenza. It was hypothesized that Health Belief Model (HBM) categories, such as severity of illness, vaccine effectiveness and side effects of the vaccine, affect the decision to get flu shot. In addition, we examined psychological effects, such as time preference, subjective probability of flu, and attitude toward risk. A questionnaire surveys was conducted in the USA, in 2004. The questions included HBM categories and the psychological effects. The results indicate that the main predictors of past immunization against influenza are: the estimated effectiveness of the vaccination, periodic blood test, perceived severity of flu illness, side effects of vaccine (negative effect), having health anxieties, and subjective probability of being infected. Based upon these results, it is recommended to enlarging people's knowledge regarding the influenza illness, its potential risks, and the potential benefits of the vaccine