NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.

BACKGROUND: Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer's, Parkinson's, and Huntington's disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose long-projecting axons are often vulnerable in neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring axonal ATP levels for axonal transport, critical for axonal function. METHODS: We generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting a NAD hydrolase, sterile alpha and TIR motif-containing protein 1 (SARM1), prevented axonal deficits caused by NMNAT2 loss. This study used a combination of techniques, including genetics, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos. RESULTS: We provide in vivo evidence that NMNAT2 in glutamatergic neurons is required for axonal survival. Using in vivo and in vitro studies, we demonstrate that NMNAT2 maintains the NAD-redox potential to provide "on-board" ATP via glycolysis to vesicular cargos in distal axons. Exogenous NAD+ supplementation to NMNAT2 KO neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate both in vitro and in vivo that reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons. CONCLUSION: NMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.

Caenorhabditis elegans foraging patterns follow a simple rule of thumb.

Rules of thumb are behavioral algorithms that approximate optimal behavior while lowering cognitive and sensory costs. One way to reduce these costs is by simplifying the representation of the environment: While the theoretically optimal behavior may depend on many environmental variables, a rule of thumb may use a smaller set of variables that performs reasonably well. Experimental proof of this simplification requires an exhaustive mapping of all relevant combinations of several environmental parameters, which we performed for Caenorhabditis elegans foraging by covering systematically combinations of food density (across 4 orders of magnitude) and food type (across 12 bacterial strains). We found that worms' response is dominated by a single environmental variable: food density measured as number of bacteria per unit surface. They disregard other factors such as biomass content or bacterial strain. We also measured experimentally the impact on fitness of each type of food, determining that the rule is near-optimal and therefore constitutes a rule of thumb that leverages the most informative environmental variable. These results set the stage for further investigations into the underlying genetic and neural mechanisms governing this simplification process, and into its role in the evolution of decision-making strategies.

NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.

Background: Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer's, Parkinson's, and Huntington's disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose long-projecting axons are often vulnerable in neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring axonal ATP levels for axonal transport, critical for axonal function. Methods: We generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting a NAD hydrolase, sterile alpha and TIR motif-containing protein 1 (SARM1), prevented axonal deficits caused by NMNAT2 loss. This study used a combination of genetics, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos. Results: We provide in vivo evidence that NMNAT2 in glutamatergic neurons is required for axonal survival. Using in vivo and in vitro studies, we demonstrate that NMNAT2 maintains the NAD-redox potential to provide "on-board" ATP via glycolysis to vesicular cargos in distal axons. Exogenous NAD+ supplementation to NMNAT2 KO neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate both in vitro and in vivo that reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons. Conclusion: NMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.

Variation in carbon and nitrogen concentrations among peatland categories at the global scale.

Peatlands account for 15 to 30% of the world's soil carbon (C) stock and are important controls over global nitrogen (N) cycles. However, C and N concentrations are known to vary among peatlands contributing to the uncertainty of global C inventories, but there are few global studies that relate peatland classification to peat chemistry. We analyzed 436 peat cores sampled in 24 countries across six continents and measured C, N, and organic matter (OM) content at three depths down to 70 cm. Sites were distinguished between northern (387) and tropical (49) peatlands and assigned to one of six distinct broadly recognized peatland categories that vary primarily along a pH gradient. Peat C and N concentrations, OM content, and C:N ratios differed significantly among peatland categories, but few differences in chemistry with depth were found within each category. Across all peatlands C and N concentrations in the 10-20 cm layer, were 440 ± 85.1 g kg-1 and 13.9 ± 7.4 g kg-1, with an average C:N ratio of 30.1 ± 20.8. Among peatland categories, median C concentrations were highest in bogs, poor fens and tropical swamps (446-532 g kg-1) and lowest in intermediate and extremely rich fens (375-414 g kg-1). The C:OM ratio in peat was similar across most peatland categories, except in deeper samples from ombrotrophic tropical peat swamps that were higher than other peatlands categories. Peat N concentrations and C:N ratios varied approximately two-fold among peatland categories and N concentrations tended to be higher (and C:N lower) in intermediate fens compared with other peatland types. This study reports on a unique data set and demonstrates that differences in peat C and OM concentrations among broadly classified peatland categories are predictable, which can aid future studies that use land cover assessments to refine global peatland C and N stocks.

Mixed methods evaluation of simulation-based training for postpartum hemorrhage management in Guatemala.

BACKGROUND: To assess if simulation-based training (SBT) of B-Lynch suture and uterine balloon tamponade (UBT) for the management of postpartum hemorrhage (PPH) impacted provider attitudes, practice patterns, and patient management in Guatemala, using a mixed-methods approach. METHODS: We conducted an in-country SBT course on the management of PPH in a governmental teaching hospital in Guatemala City, Guatemala. Participants were OB/GYN providers (n = 39) who had or had not received SBT before. Surveys and qualitative interviews evaluated provider knowledge and experiences with B-Lynch and UBT to treat PPH. RESULTS: Multiple-choice surveys indicated that providers who received SBT were more comfortable performing and teaching B-Lynch compared to those who did not (p = 0.003 and 0.005). Qualitative interviews revealed increased provider comfort with B-Lynch compared to UBT and identified multiple barriers to uterine balloon tamponade implementation. CONCLUSIONS: Simulation-based training had a stronger impact on provider comfort with B-Lynch compared to uterine balloon tamponade. Qualitative interviews provided insight into the challenges that hinder uptake of uterine balloon tamponade, namely resource limitations and decision-making hierarchies. Capturing data through a mixed-methods approach allowed for more comprehensive program evaluation.

Caracterización epidemiológica del cáncer de mama / Epidemiological characterization of cancer breast

Con el objetivo de realizar la caracterización epidemiológica del cáncer de mama de las pacientes que asisten a la consulta externa de ginecología oncológica en el Instituto Guatemalteco de Seguridad Social (IGSS) de enero a marzo de 2,018, se realizó un estudio descriptivo transversal en 155 pacientes que acudieron a la clínica de mama del Hospital de Gineco Obstetricia del IGSS, con una media de edad de 62 años, el adenocarcinoma ductal infiltrante es el tipo histológico más frecuente en nuestra población tanto en edad reproductiva como en menopausia. Como factor protector el 69% dio lactancia materna. La etapa clínica más comúnmente diagnosticada es IIA. El Luminal A, el más frecuentemente diagnosticado por inmunohistoquímica, seguido del Luminal B y HER2neu. Se diagnostican pacientes mayormente en etapas clínicas tempranas (I y II).

In order to carry out the epidemiological characterization of breast cancer in patients attending the outpatient gynecology oncology consultation at the Guatemalan Social Security Institute (IGSS) from January to March 2018, a descriptive cross-sectional study was carried out in 155 patients who attended the breast clinic of the IGSS Obstetrics Gynecology Hospital, with a mean age of 62 years, infiltrating ductal adenocarcinoma is the most frequent histological type in our population both in reproductive age and in menopause. As a protective factor, 69% breastfed. The most diagnosed clinical stage is IIA. Luminal A, the most frequently diagnosed by immunohistochemistry, followed by Luminal B and HER2neu. Patients are diagnosed mostly in early clinical stages (I and II).

Nitrate Levels in Rural Drinking Water in Belize.

BACKGROUND: Health issues have been associated with the consumption of high levels of nitrates in drinking water. Rural agricultural communities in Belize play a large role in the economic growth of the country. These communities obtain drinking water directly from the ground and may be susceptible to nitrate consumption and at risk of developing diseases associated with nitrates. OBJECTIVES: The present study examined nitrate levels in Belize's rural water supply with the aim of assessing its suitability for human and livestock consumption. The study also provides baseline data for monitoring the concentration of nitrates to prevent public health hazards in Belize. METHODS: Forty-three (43) water samples from reservoirs, wells, vats, and standpipes were collected from 40 villages in Belize and analyzed for nitrates using the cadmium reduction method. Nitrates were detected with an Orion® AquaMate® 8000 UV-Vis spectrophotometer at 520 nm. The Belize Coastal Zone Management Authority and Institute laboratory analyzed all water samples for nitrates. RESULTS: Except for four water samples from four different sites, all analyzed water samples were found to contain nitrate levels below 10 mg/L. Nitrate levels above 10 mg/L were seen in a few samples in the northern part of the country, probably due to agricultural activities in these areas. CONCLUSIONS: Belize's rural drinking water contains low levels of nitrates, except for a few villages where the levels exceeded the acceptable limit of 10 mg/L. Higher levels of nitrates detected in a few villages need regular evaluation and monitoring to avoid public health issues as well as prevent harm to livestock. COMPETING INTERESTS: The authors declare no competing financial interests.

Adolescentes mujeres y jóvenes adultas frente a los temas de embarazo y aborto: ¿Percepciones diferentes según la edad? Estudio realizado en Quito, Ecuador (2017) / Adolescent women and young adults facing the issues of pregnancy and abortion: Different perceptions according to age? Study conducted in Quito, Ecuador (2017) / Adolescentes e mulheres jovens que enfrentam as questões da gravidez e do aborto: Percepções diferentes de acordo com a idade? Estudo realizado em Quito, Equador (2017)

Resumen: El objetivo del estudio fue analizar las percepciones acerca del embarazo y aborto en dos grupos de mujeres. Se encuestó a 100 adolescentes y a 100 jóvenes adultas de la ciudad de Quito; además, con una entrevista semiestructurada, se indagó sobre sus vivencias. Se encontraron diferencias entre los grupos sobre las percepciones de embarazo, entre ellas: requisitos para ser madres, responsabilidades propias y de los abuelos, emociones, apoyo social y mejor opción frente al embarazo. En relación al aborto, existen diferencias en cuanto a su percepción general y de apoyo social. Se presentan resultados sobre sentimientos en el momento del aborto y de su estado actual, sobre la decisión, reacción de la pareja, entre otras. Los resultados indican la importancia de reenfocar la educación sexual, tomando en cuenta las etapas de desarrollo, basados en información pertinente.

Abstract: The objective of the study was to analyze the perceptions about pregnancy and abortion in two groups of women. One hundred adolescents and 100 young adults from Quito were surveyed; in addition, using a semi-structured interview, information about their experiences was collected. Differences on the perceptions of pregnancy were found between the two groups, subjects such as the requirements to be mothers, their own and grandparents' responsibilities, emotions, social support, and choices in relation to pregnancy. Regarding abortion, there were differences concerning its general perception and social support. Results about feelings at the time of the abortion and in its current state, about the decision, the couple's reaction, among others, are presented. The results highlight the importance of refocusing sexual education, considering the stages of development of women, and relevant scientific information.

Resumo: O objetivo do estudo foi analisar as percepções sobre gravidez e aborto em dois grupos de mulheres. Foram pesquisadas ​​100 adolescentes e 100 adultas jovens da cidade de Quito; também, com uma entrevista semiestruturada, eles foram questionados sobre suas experiências. Houve diferenças entre os grupos quanto às percepções da gravidez, dentre elas: requisitos para ser mãe, responsabilidades próprias e dos avós, emoções, apoio social e melhor opção contra a gravidez. Em relação ao aborto, existem diferenças em termos de percepção geral e apoio social. São apresentados resultados sobre sentimentos no momento do aborto e seu estado atual, sobre a decisão, a reação do casal, entre outros. Os resultados indicam a importância de reorientar a educação sexual, levando em conta os estágios de desenvolvimento, baseados em informações pertinente.