An automated high-content screening image analysis pipeline for the identification of selective autophagic inducers in human cancer cell lines.

Automated image processing is a critical and often rate-limiting step in high-content screening (HCS) workflows. The authors describe an open-source imaging-statistical framework with emphasis on segmentation to identify novel selective pharmacological inducers of autophagy. They screened a human alveolar cancer cell line and evaluated images by both local adaptive and global segmentation. At an individual cell level, region-growing segmentation was compared with histogram-derived segmentation. The histogram approach allowed segmentation of a sporadic-pattern foreground and hence the attainment of pixel-level precision. Single-cell phenotypic features were measured and reduced after assessing assay quality control. Hit compounds selected by machine learning corresponded well to the subjective threshold-based hits determined by expert analysis. Histogram-derived segmentation displayed robustness against image noise, a factor adversely affecting region growing segmentation

Human Social Behavior and Demography Drive Patterns of Fine-Scale Dengue Transmission in Endemic Areas of Colombia

Dengue is known to transmit between humans and A. aegypti mosquitoes living in neighboring houses. Although transmission is thought to be highly heterogeneous in both space and time, little is known about the patterns and drivers of transmission in groups of houses in endemic settings. We carried out surveys of PCR positivity in children residing in 2-block patches of highly endemic cities of Colombia. We found high levels of heterogeneity in PCR positivity, varying from less than 30% in 8 of the 10 patches to 56 and 96%, with the latter patch containing 22 children simultaneously PCR positive (PCR22) for DEN2. We then used an agent-based model to assess the likely eco-epidemiological context of this observation. Our model, simulating daily dengue dynamics over a 20 year period in a single two block patch, suggests that the observed heterogeneity most likely derived from variation in the density of susceptible people. Two aspects of human adaptive behavior were critical to determining this density: external social relationships favoring viral introduction (by susceptible residents or infectious visitors) and immigration of households from non-endemic areas. External social relationships generating frequent viral introduction constituted a particularly strong constraint on susceptible densities, thereby limiting the potential for explosive outbreaks and dampening the impact of heightened vectorial capacity. Dengue transmission can be highly explosive locally, even in neighborhoods with significant immunity in the human population. Variation among neighborhoods in the density of local social networks and rural-to-urban migration is likely to produce significant fine-scale heterogeneity in dengue dynamics, constraining or amplifying the impacts of changes in mosquito populations and cross immunity between serotypes

On the characterisation of a Bragg spectrometer with X-rays from an ECR source

Narrow X-ray lines from helium-like argon emitted from a dedicated ECR source have been used to determine the response function of a Bragg crystal spectrometer equipped with large area spherically bent silicon (111) or quartz (10$\bar{1}$) crystals. The measured spectra are compared with simulated ones created by a ray-tracing code based on the expected theoretical crystal's rocking curve and the geometry of the experimental set-up.Comment: Version acceptee (NIM

Highly charged ion X-rays from Electron-Cyclotron Resonance Ion Sources

Radiation from the highly-charged ions contained in the plasma of Electron-Cyclotron Resonance Ion Sources constitutes a very bright source of X-rays. Because the ions have a relatively low kinetic energy ($\approx 1$ eV) transitions can be very narrow, containing only small Doppler broadening. We describe preliminary accurate measurements of two and three-electron ions with Z=16--18. We show how these measurement can test sensitively many-body relativistic calculations or can be used as X-ray standards for precise measurements of X-ray transitions in exotic atoms

The Extrachromosomal EAST Protein of Drosophila Can Associate with Polytene Chromosomes and Regulate Gene Expression

The EAST protein of Drosophila is a component of an expandable extrachromosomal domain of the nucleus. To better understand its function, we studied the dynamics and localization of GFP-tagged EAST. In live larval salivary glands, EAST-GFP is highly mobile and localizes to the extrachromosomal nucleoplasm. When these cells are permeabilized, EAST-GFP rapidly associated with polytene chromosomes. The affinity to chromatin increases and mobility decreases with decreasing salt concentration. Deleting the C-terminal residues 1535 to 2301 of EAST strongly reduces the affinity to polytene chromosomes. The bulk of EAST-GFP co-localizes with heterochromatin and is absent from transcriptionally active chromosomal regions. The predominantly chromosomal localization of EAST-GFP can be detected in non-detergent treated salivary glands of pupae as they undergo apoptosis, however not in earlier stages of development. Consistent with this chromosomal pattern of localization, genetic evidence indicates a role for EAST in the repression of gene expression, since a lethal east mutation is allelic to the viable mutation suppressor of white-spotted. We propose that EAST acts as an ion sensor that modulates gene expression in response to changing intracellular ion concentrations

Consumption of key food groups during the postpartum period in low-income, non-Hispanic black mothers

The postpartum period can impact diet quality and subsequently place women at greater risk for overweight or obesity. This study examined consumption of key food groups during the first 2 years postpartum among low income, non-Hispanic black, first-time mothers. Data were from the Infant Care, Feeding and Risk of Obesity Study, a cohort of 217 mother–infant dyads, followed from 3 to 18 months postpartum, collected from 2003 to 2007. At each study visit (3, 6, 9, 12, and 18 months) 24-h dietary recalls were collected. Consumption levels were compared to those recommended from the 2010 Dietary Guidelines for Americans (DGAs) for each of the following food groups: fruits, vegetables, grains, whole grains, protein foods and dairy, as well as an estimated upper limit for sugar-sweetened beverage (SSB) consumption. At each time point, mothers met recommended intake levels for grains and protein foods only. In random-intercept logistic regression models, no demographic or household characteristics were associated with a likelihood of consuming recommended levels for any of the food groups according to the DGAs. Given the low intake of fruits, vegetables, whole grains and lean protein foods and high intake of SSBs and refined grains, interventions targeting women's diet during the postpartum period are warranted

Consumption of obesogenic foods in non-Hispanic black mother–infant dyads

Obesity continues to be a problem in the United States. Of particular concern is the epidemic of early childhood obesity. A significant predictor of child diet is maternal diet, but little is known about this relationship during infancy. This study examined the association between maternal and infant consumption of key food groups from 6 to 18 months using data from the Infant Care, Feeding, and Risk of Obesity Study, a prospective cohort of 217 non-Hispanic black, low-income, first-time mothers. Using data from 24-hr dietary recalls collected during in-home visits at 6, 9, 12, and 18 months, we assessed longitudinal associations between mother and child intake of both energy-dense, nutrient-poor (obesogenic) food groups and fibre-, nutrient-rich food groups using random intercept logistic regression. Both mothers and their infants had high intake of sugar-sweetened beverages, desserts, and sweets and low intake of vegetables and whole grains. Infant consumption of key food groups was strongly associated with maternal consumption, suggesting the need for focused interventions to target maternal diet as a pathway to decreasing risk for the establishment of poor dietary patterns early in life