Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion.

The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001

Perception and awareness of diabetes risk and reported risk-reducing behaviors in adolescents

IMPORTANCE: Lifestyle change is central to diabetes risk reduction in youth with overweight or obesity. Feeling susceptible to a health threat can be motivational in adults. OBJECTIVE: To evaluate associations between diabetes risk perception and/or awareness and health behaviors in youth. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2011 to 2018. Participants included youths aged 12 to 17 years with body mass index (BMI) in the 85th percentile or higher without known diabetes. Analyses were conducted from February 2022 to February 2023. MAIN OUTCOMES AND MEASURES: Outcomes included physical activity, screen time, and attempted weight loss. Confounders included age, sex, race and ethnicity, and objective diabetes risk (BMI, hemoglobin A1c [HbA1c]). EXPOSURES: Independent variables included diabetes risk perception (feeling at risk) and awareness (told by clinician), as well as potential barriers (eg, food insecurity, household size, insurance). RESULTS: The sample included 1341 individuals representing 8 716 794 US youths aged 12 to 17 years with BMI in the 85th percentile or higher for age and sex. The mean age was 15.0 years (95% CI, 14.9-15.2 years) and mean BMI z score was 1.76 (95% CI 1.73-1.79). Elevated HbA1c was present in 8.6% (HbA1c 5.7%-6.4%: 8.3% [95% CI, 6.5%-10.5%]; HbA1c ≥6.5%: 0.3% [95% CI, 0.1%-0.7%]). Nearly one-third of youth with elevated HbA1c reported risk perception (30.1% [95% CI, 23.1%-38.1%), while one-quarter (26.5% [95% CI, 20.0%-34.2%]) had risk awareness. Risk perception was associated with increased TV watching (β = 0.3 hours per day [95% CI, 0.2-0.5 hours per day]) and approximately 1 less day per week with at least 60 minutes of physical activity (β = -1.2 [95% CI, -2.0 to -0.4) but not with nutrition or weight loss attempts. Awareness was not associated with health behaviors. Potential barriers had mixed associations: larger households (≥5 members vs 1-2) reported lower consumption of non-home-prepared meals (OR 0.4 [95% CI, 0.2-0.7]) and lower screen time (β = -1.1 hours per day [95% CI, -2.0 to -0.3 hours per day), while public insurance (vs private) was associated with approximately 20 fewer minutes per day of physical activity (β = -20.7 minutes per day [95% CI, 35.5 to -5.8 minutes per day]). CONCLUSIONS AND RELEVANCE: In this cross-sectional study including a US-representative sample of adolescents with overweight or obesity, diabetes risk perception and awareness were not associated with greater engagement in risk-reducing behaviors in youth. These findings suggest the need to address barriers to engagement in lifestyle change, including economic disadvantage

Relación entre el sentido de vida e ideación suicida en varones que consumen sustancias psicoactivas

El suicidio se muestra como una problemática en aumento a nivel mundial. Por ello, diversas prácticas en psicología intentan intervenir en esta problemática a través del descubrimiento de un sentido de vida. El objetivo de esta investigación consistió en identificar qué relación existe entre el sentido de vida y la ideación suicida en adultos varones que consumen sustancias psicoactivas. La muestra estuvo compuesta por 151 adultos varones entre los 18 y 62 años (M=23, DE=9.7) que consumen sustancias psicoactivas y pertenecen a dos centros de rehabilitación de Lima-Perú. Asimismo, se aplicaron dos instrumentos: el Test de sentido de vida (PIL) de Crumbaugh y Maholick y la Escala de ideación suicida (SSI) de Beck, de los cuales se adaptaron y describieron las propiedades psicométricas para dicha muestra. Los resultados evidencian que entre el sentido de vida y la ideación suicida existe una correlación negativa estadísticamente significativa (rho=-.425) con un tamaño del efecto medio (Ferguson, 2009). Además, los resultados del análisis factorial exploratorio indican una estructura interna unidimensional para ambas pruebas con una varianza única explicada de 40.7% para el SSI y 41.01% para el PIL; se hallaron coeficientes de consistencia interna significativos para el PIL (¿=.87) y el SSI (¿ = .84) y; en base a la información recolectada, se realizaron baremos generales para el análisis y la interpretación de las puntuaciones derivadas de muestras similares.Suicide appears to be a growing problem worldwide. For this reason, various practices in psychology try to intervene in this problem through the discovery of a meaning of life. The objective of this research was to identify the relationship between the meaning of life and suicidal ideation in male adults who use psychoactive substances. The sample consisted of 151 male adults between 18 and 62 years old (M = 23, SD = 9.7) who consume psychoactive substances and belong to two rehabilitation centers in Lima-Peru. Likewise, two instruments were applied: the Crumbaugh and Maholick Meaning of Life Test (PIL) and the Beck Scale of Suicidal Ideation (SSI), of which the psychometric properties were adapted and described for said sample. The results show that between the sense of life and suicidal ideation there is a statistically significant negative correlation (rho = -. 425) with a medium effect size (Ferguson, 2009). Furthermore, the results of the exploratory factor analysis indicate a one-dimensional internal structure for both tests with a single explained variance of 40.7% for the SSI and 41.01% for the PIL; significant internal consistency coefficients were found for the PIL (¿ = .87) and the SSI (¿ = .84) and; based on the information collected, general scales were made for the analysis and interpretation of the scores derived from similar samples

Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear. DESIGN: To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth. RESULTS: We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants. CONCLUSION: We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC

Dynamical Aspects of Initial/Boundary Value Problems for Ordinary Differential Equations

Abstract is not available in full text.Published versio

Induction of temperate cyanophage AS-1 by heavy metal – copper

BACKGROUND: It has been reported that some marine cyanophage are temperate and can be induced from a lysogenic phase to a lytic phase by different agents such as heavy metals. However, to date no significant reports have focused on the temperate nature of freshwater cyanophage/cyanobacteria. Previous experiments with cyanophage AS-1 and cyanobacteria Anacystis nidulans have provided some evidence that AS-1 may have a lysogenic life cycle in addition to the characterized lytic cycle. RESULTS: In this study, the possible temperate A. nidulans was treated with different concentrations of heavy metal-copper. CuSO(4 )with concentrations of 3.1 × 10(-3 )M, 3.1 × 10(-4 )M, 3.1 × 10(-5 )M and 3.1 × 10(-6 )M were used to detect the induction of AS-1 from A. nidulans. The population of the host, unicellular cyanobacteria Anacystis nidulans, was monitored by direct count and turbidity while the amount of virus produced was derived from plaque forming units (PFU) by a direct plating method. The ratio of AS-1 release from A. nidulans was also determined. From these results it appears that AS-1 lysogenic phage can be induced by copper at concentrations from 3.1 × 10(-6 )M to 3.1 × 10(-4 )M. Maximal phage induction occurred at 6 hours after addition of copper, with an optimal concentration of 3.1 × 10(-6 )M. CONCLUSION: Cu(2+ )is a significant inducer for lysogenic cyanobacterial cells and consequently would be a potential control agent in the cyanobacteria population in fresh water ecosystems

Composition, nanostructure, and optical properties of silver and silver-copper lusters

Lusters are composite thin layers of coinage metal nanoparticles in glass displaying peculiar optical properties and obtained by a process involving ionic exchange, diffusion, and crystallization. In particular, the origin of the high reflectance (golden-shine) shown by those layers has been subject of some discussion. It has been attributed to either the presence of larger particles, thinner multiple layers or higher volume fraction of nanoparticles. The object of this paper is to clarify this for which a set of laboratory designed lusters are analysed by Rutherford backscattering spectroscopy, transmission electron microscopy, x-ray diffraction, and ultraviolet-visible spectroscopy. Model calculations and numerical simulations using the finite difference time domain method were also performed to evaluate the optical properties. Finally, the correlation between synthesis conditions, nanostructure, and optical properties is obtained for these materials