Developmental Acquisition of a Rapid Calcium-Regulated Vesicle Supply Allows Sustained High Rates of Exocytosis in Auditory Hair Cells

Auditory hair cells (HCs) have the remarkable property to indefinitely sustain high rates of synaptic vesicle release during ongoing sound stimulation. The mechanisms of vesicle supply that allow such indefatigable exocytosis at the ribbon active zone remain largely unknown. To address this issue, we characterized the kinetics of vesicle recruitment and release in developing chick auditory HCs. Experiments were done using the intact chick basilar papilla from E10 (embryonic day 10) to P2 (two days post-hatch) by monitoring changes in membrane capacitance and Ca2+ currents during various voltage stimulations. Compared to immature pre-hearing HCs (E10-E12), mature post-hearing HCs (E18-P2) can steadily mobilize a larger readily releasable pool (RRP) of vesicles with faster kinetics and higher Ca2+ efficiency. As assessed by varying the inter-pulse interval of a 100 ms paired-pulse depolarization protocol, the kinetics of RRP replenishment were found much faster in mature HCs. Unlike mature HCs, exocytosis in immature HCs showed large depression during repetitive stimulations. Remarkably, when the intracellular concentration of EGTA was raised from 0.5 to 2 mM, the paired-pulse depression level remained unchanged in immature HCs but was drastically increased in mature HCs, indicating that the Ca2+ sensitivity of the vesicle replenishment process increases during maturation. Concomitantly, the immunoreactivity of the calcium sensor otoferlin and the number of ribbons at the HC plasma membrane largely increased, reaching a maximum level at E18-P2. Our results suggest that the efficient Ca2+-dependent vesicle release and supply in mature HCs essentially rely on the concomitant engagement of synaptic ribbons and otoferlin at the plasma membrane

Does Habitual Physical Activity Increase the Sensitivity of the Appetite Control System? A Systematic Review.

BACKGROUND: It has been proposed that habitual physical activity improves appetite control; however, the evidence has never been systematically reviewed. OBJECTIVE: To examine whether appetite control (e.g. subjective appetite, appetite-related peptides, food intake) differs according to levels of physical activity. DATA SOURCES: Medline, Embase and SPORTDiscus were searched for articles published between 1996 and 2015, using keywords pertaining to physical activity, appetite, food intake and appetite-related peptides. STUDY SELECTION: Articles were included if they involved healthy non-smoking adults (aged 18-64 years) participating in cross-sectional studies examining appetite control in active and inactive individuals; or before and after exercise training in previously inactive individuals. STUDY APPRAISAL AND SYNTHESIS: Of 77 full-text articles assessed, 28 studies (14 cross-sectional; 14 exercise training) met the inclusion criteria. RESULTS: Appetite sensations and absolute energy intake did not differ consistently across studies. Active individuals had a greater ability to compensate for high-energy preloads through reductions in energy intake, in comparison with inactive controls. When physical activity level was graded across cross-sectional studies (low, medium, high, very high), a significant curvilinear effect on energy intake (z-scores) was observed. LIMITATIONS: Methodological issues existed concerning the small number of studies, lack of objective quantification of food intake, and various definitions used to define active and inactive individuals. CONCLUSION: Habitually active individuals showed improved compensation for the energy density of foods, but no consistent differences in appetite or absolute energy intake, in comparison with inactive individuals. This review supports a J-shaped relationship between physical activity level and energy intake. Further studies are required to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42015019696

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

A pesquisa de sangue oculto nas fezes associada a um questionário de sinais e sintomas na prevenção do câncer colo retal Faecal occult blood (FOB) test associated with a questionaire of signs and symptoms in screening for colorectal cancer

OBJETIVO: Determinar a eficácia de um programa de prevenção de Câncer Colo Retal (CCR) através do método da pesquisa de sangue oculto das fezes (PSO), e um questionário clínico (QSA). MATERIAL E MÉTODO: Foi realizada uma triagem através do PSO e do QSA em indivíduos acima de 50 anos, oriundos de uma campanha de prevenção de CCR em Joinville, SC. 387 indivíduos aderiram à campanha e 93 foram excluídos.. Foram definidos 3 grupos: 1- PSO +, com 20 sujeitos, QSA +, com 38 sujeitos e PSO e QSA negativos com 21 sujeitos. Foi definida como colonoscopia positiva aquela que detectou adenomas. RESULTADOS: O grupo 1 apresentou 22% de sensibilidade, 74% de especificidade, likelihood ratio positivo (LR) de 0, 9, acurácia de 56, 9, valor preditivo positivo (VPP) de 31,6 e negativo (VPN) de 64. O grupo 2 apresentou 71,4% de sensibilidade, 45,6 de especificidade, LR de 1,3, acurácia de 52,6, VPP de 32,6 e VPN de 81,3. O método apresentou 95,2% de sensibilidade, 63,2 de especificidade, LR de 2, 6, acurácia de 71, 8, VPP de 48.8 e VPN de 97.3. CONCLUSÃO: O método da PSO e QSA são complementares e efetivos como triagem em programas de prevenção de CCR.<br>The purpose of this study is to verify the efficacy of a strategy to screen colorectal cancer(CCR) and adenomas using the faecal occult blood test(PSO) and a questionnaire (QSA)based in signs and symptoms of CCR. METHODS: A program of prevention was done, and the patients answered the QSA and did the PSO type imunocromatograph. RESULTS: 387 people adhered do the program, 93 were excluded. Three groups were formed: 1: 20 persons, with PSO positive, 2:38 persons with QSA positive, and 3, with 21 persons with PSO and QSA negatives. Group 1 presented a sensibility of 22%, specificity of 74%, Likelihood ratio + of 0,9, accuracy of 56,9, Positive predictive value(VPP) of 31,6 and negative(VPN) of 64. Group 2 presented sensibility of 71,4%, 45,6% of specificity, Likelihood ratio + 1.3, accuracy of 52,6, VPP de 32,6 e VPN de 81,3. The QSA plus PSO method, presented a sensibility of 95,2%, 63,2 of specificity, accuracy of 71,8 ,Likelihood ratio of 2,6, VPP de 48,8 e VPN 81,3. In conclusion the method of PSO and QSA are complementary and seem effective in screening for CCR in preventive programs