Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Osteoporosis-related fracture case definitions for population-based administrative data

<p>Abstract</p> <p>Background</p> <p>Population-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions.</p> <p>Methods</p> <p>Thirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates.</p> <p>Results</p> <p>For hip fracture, sex-specific differences were observed in the magnitude of under- and over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions.</p> <p>Conclusions</p> <p>The validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.</p

Thar She Blows! A Novel Method for DNA Collection from Cetacean Blow

Background: Molecular tools are now widely used to address crucial management and conservation questions. To date, dart biopsying has been the most commonly used method for collecting genetic data from cetaceans; however, this method has some drawbacks. Dart biopsying is considered inappropriate for young animals and has recently come under scrutiny from ethical boards, conservationists, and the general public. Thus, identifying alternative genetic collection techniques for cetaceans remains a priority, especially for internationally protected species. Methodology/Principal Findings: In this study, we investigated whether blow-sampling, which involves collecting exhalations from the blowholes of cetaceans, could be developed as a new less invasive method for DNA collection. Our current methodology was developed using six bottlenose dolphins, Tursiops truncatus, housed at the National Aquarium, Baltimore (USA), from which we were able to collect both blow and blood samples. For all six individuals, we found that their mitochondrial and microsatellite DNA profile taken from blow, matched their corresponding mitochondrial and microsatellite DNA profile collected from blood. This indicates that blow-sampling is a viable alternative method for DNA collection. Conclusion/Significance: In this study, we show that blow-sampling provides a viable and less invasive method for collection of genetic data, even for small cetaceans. In contrast to dart biopsying, the advantage of this method is that it capitalizes on the natural breathing behaviour of dolphins and can be applied to even very young dolphins. Both biopsy and blow-sampling require close proximity of the boat, but blow-sampling can be achieved when dolphins voluntarily bowride and involves no harmful contact

Comparative study of imaging at 3.0 T versus 1.5 T of the knee

The objectives of the study were to compare MR imaging at 1.5 and 3.0 T in the same patients concerning image quality and visualization of cartilage pathology and to assess diagnostic performance using arthroscopy as a standard of reference. Twenty-six patients were identified retrospectively as having comparative 1.5 and 3.0 T MR studies of the knee within an average of 102 days. Standard protocols included T1-weighted and fat-saturated intermediate-weighted fast spin-echo sequences in three planes; sequence parameters had been adjusted to account for differences in relaxation at 3.0 T. Arthroscopy was performed in 19 patients. Four radiologists reviewed each study independently, scored image quality, and analyzed pathological findings. Sensitivities, specificities, and accuracies in diagnosing cartilage lesions were calculated in the 19 patients with arthroscopy, and differences between 1.5 and 3.0 T exams were compared using paired Student’s t tests with a significance threshold of p &lt; 0.05. Each radiologist scored the 3.0 T studies higher than those obtained at 1.5 T in visualizing anatomical structures and abnormalities (p &lt; 0.05). Using arthroscopy as a standard of reference, diagnosis of cartilage abnormalities was improved at 3.0 T with higher sensitivity (75.7% versus 70.6%), accuracy (88.2% versus 86.4%), and correct grading of cartilage lesions (51.3% versus 42.9%). Diagnostic confidence scores were higher at 3.0 than 1.5 T (p &lt; 0.05) and signal-to-noise ratio at 3.0 T was approximately twofold higher than at 1.5 T. MRI at 3.0 T improved visualization of anatomical structures and improved diagnostic confidence compared to 1.5 T. This resulted in significantly better sensitivity and grading of cartilage lesions at the knee

Fitness Cost of Resistance to Bt Cotton Linked with Increased Gossypol Content in Pink Bollworm Larvae

Fitness costs of resistance to Bacillus thuringiensis (Bt) crops occur in the absence of Bt toxins, when individuals with resistance alleles are less fit than individuals without resistance alleles. As costs of Bt resistance are common, refuges of non-Bt host plants can delay resistance not only by providing susceptible individuals to mate with resistant individuals, but also by selecting against resistance. Because costs typically vary across host plants, refuges with host plants that magnify costs or make them less recessive could enhance resistance management. Limited understanding of the physiological mechanisms causing fitness costs, however, hampers attempts to increase costs. In several major cotton pests including pink bollworm (Pectinophora gossypiella), resistance to Cry1Ac cotton is associated with mutations altering cadherin proteins that bind this toxin in susceptible larvae. Here we report that the concentration of gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol to the larval diet decreased larval weight and survival, and increased the fitness cost affecting larval growth, but not survival. Across cadherin genotypes, the cost affecting larval growth increased as the gossypol concentration of larvae increased. These results suggest that increased accumulation of plant defensive chemicals may contribute to fitness costs associated with resistance to Bt toxins

Evaluation of the psychometric properties of the London Measure of Unplanned Pregnancy in Brazilian Portuguese

Background: Estimates of unplanned pregnancy worldwide are of concern, especially in low and middle-income countries, including Brazil. Although the contraceptive prevalence rate is high in Brazil, almost half of all pregnancies are reported as unintended. The only source of nationally representative data about pregnancy intention is the Demographic and Health Survey, as with many other countries. In more recent years, however, it has been realized that concept of unintended pregnancy is potentially more complex and requires more sophisticated measurement strategies, such as the London Measure of Unplanned Pregnancy (LMUP). The LMUP has been translated and validated in other languages, but not Portuguese yet. In this study, we evaluate the psychometric properties of the LMUP in the Portuguese language, Brazilian version. Methods: A Brazilian Portuguese version of the LMUP was produced via translation and back-translation. After piloting, the mode of administration was changed from self-completion to interviewer-administration. The measure was field tested with pregnant, postpartum, and postabortion women recruited at maternity and primary health care services in Sao Paulo city. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Construct validity was assessed using principal components analysis and hypothesis testing. Scaling was assessed with Mokken analysis. Results: 759 women aged 15–44 completed the Brazilian Portuguese LMUP. There were no missing data. The measure was acceptable and well targeted. Reliability testing demonstrated good internal consistency (alpha = 0.81, all item-rest correlations >0.2). Validity testing confirmed that the measure was unidimensional and that all hypotheses were met: there were lower LMUP median scores among women in the extreme age groups (p<0.001), among non-married women (p<0.001) and those with lower educational attainment (p<0.001). The Loevinger H coefficient was 0.60, indicating a strong scale. Conclusion: The Brazilian Portuguese LMUP is a valid and reliable measure of pregnancy planning/intention that is now available for use in Brazil. It represents a useful addition to the public health research and surveillance toolkit in Brazil

Similar Genetic Basis of Resistance to Bt Toxin Cry1Ac in Boll-Selected and Diet-Selected Strains of Pink Bollworm

Genetically engineered cotton and corn plants producing insecticidal Bacillus thuringiensis (Bt) toxins kill some key insect pests. Yet, evolution of resistance by pests threatens long-term insect control by these transgenic Bt crops. We compared the genetic basis of resistance to Bt toxin Cry1Ac in two independently derived, laboratory-selected strains of a major cotton pest, the pink bollworm (Pectinophora gossypiella [Saunders]). The Arizona pooled resistant strain (AZP-R) was started with pink bollworm from 10 field populations and selected with Cry1Ac in diet. The Bt4R resistant strain was started with a long-term susceptible laboratory strain and selected first with Bt cotton bolls and later with Cry1Ac in diet. Previous work showed that AZP-R had three recessive mutations (r1, r2, and r3) in the pink bollworm cadherin gene (PgCad1) linked with resistance to Cry1Ac and Bt cotton producing Cry1Ac. Here we report that inheritance of resistance to a diagnostic concentration of Cry1Ac was recessive in Bt4R. In interstrain complementation tests for allelism, F1 progeny from crosses between AZP-R and Bt4R were resistant to Cry1Ac, indicating a shared resistance locus in the two strains. Molecular analysis of the Bt4R cadherin gene identified a novel 15-bp deletion (r4) predicted to cause the loss of five amino acids upstream of the Cry1Ac-binding region of the cadherin protein. Four recessive mutations in PgCad1 are now implicated in resistance in five different strains, showing that mutations in cadherin are the primary mechanism of resistance to Cry1Ac in laboratory-selected strains of pink bollworm from Arizona