Palmitic Acid-Induced NAD+ Depletion is Associated with the Reduced Function of SIRT1 and Increased Expression of BACE1 in Hippocampal Neurons

Increased levels of circulating fatty acids, such as palmitic acid (PA), are associated with the development of obesity, insulin resistance, type-2 diabetes and metabolic syndrome. Furthermore, these diseases are linked to an increased risk of cancer, cardiovascular diseases, mild cognitive impairment and even Alzheimer’s disease (AD). However, the precise actions of elevated PA levels on neurons and their association with neuronal metabolic disruption that leads to the expression of pathological markers of AD, such as the overproduction and accumulation of the amyloid-β peptide, represent an area of intense investigation. A possible molecular mechanism involved in the effects of PA may be through dysfunction of the NAD⁺ sensor enzyme, SIRT1. Therefore, the aim of the present study was to analyze the relationship between the effects of PA metabolism on the function of SIRT1 and the upregulation of BACE1 in cultured hippocampal neurons. PA reduced the total amount of NAD⁺ in neurons that caused an increase in p65 K310 acetylation due to inhibition of SIRT1 activity and low protein content. Furthermore, BACE1 protein and its activity were increased, and BACE1 was relocated in neurites after PA exposure.

     

Tuberculosis y hacinamiento carcelario desde la perspectiva de las inequidades sociales en salud en Colombia, 2018

Introduction:

Prison population is affected by tuberculosis (TB) due to prison overcrowding. This situation reflects an inequity in health, understood as an unfair and avoidable difference between individuals and populations.

Objective:

To estimate the conditions of prison overcrowding as health inequity in prison population suffering from TB in Colombia during 2018.

Materials and methods:

This is an ecological study to estimate inequities at the national level in prison population through the use of the World Health Organization methodology for the measurement of inequalities. Based on data from the public health surveillance system, the incidence of TB was taken as an indicator and the percentage of overcrowding as an equity stratifier. Simple and complex measures of inequality were calculated.

Results:

The relative inequality between the lowest and highest quintiles of crowding showed that TB incidence among prison population with the highest crowding was 1.92 times that of the group with the lowest crowding. The inequality index identified an excess of 724 TB cases per 100,000 among those with the highest concentration of overcrowding. The health concentration index was -0.121, which shows that the incidence was concentrated in the group with the most overpopulation.

Conclusion:

In Colombia, prison population in overcrowded conditions and suffering from TB has to face unfair and avoidable inequalities as compared with those not living in these conditions. Policies are required to reduce overcrowding and improve living conditions in prisons.     

Elastin-like Peptide amphiphiles form nanofibers with tunable length

Peptide amphiphiles (PAs) self-assemble nanostructures with potential applications in drug delivery and tissue engineering. Some PAs share environmentally responsive behavior with their peptide components. Here we report a new type of PAs biologically inspired from human tropoelastin. Above a lower critical solution temperature (LCST), elastin-like polypeptides (ELPs) undergo a reversible inverse phase transition. Similar to other PAs, elastin-like PAs (ELPAs) assemble micelles with fiber-like nanostructures. Similar to ELPs, ELPAs have inverse phase transition behavior. Here we demonstrate control over the ELPAs fiber length and cellular uptake. In addition, we observed that both peptide assembly and nanofiber phase separation are accompanied by a distinctive secondary structure attributed primarily to a type-1 β turn. We also demonstrate increased solubility of hydrophobic paclitaxel (PAX) in the presence of ELPAs. Due to their biodegradability, biocompatibility, and environmental responsiveness, elastin-inspired biopolymers are an emerging platform for drug and cell delivery; furthermore, the discovery of ELPAs may provide a new and useful approach to engineer these materials into stimuli-responsive gels and drug carriers.     

Collection protocol for human pancreas

This dissection and sampling procedure was developed for the Network for Pancreatic Organ Donors with Diabetes (nPOD) program to standardize preparation of pancreas recovered from cadaveric organ donors. The pancreas is divided into 3 main regions (head, body, tail) followed by serial transverse sections throughout the medial to lateral axis. Alternating sections are used for fixed paraffin and fresh frozen blocks and remnant samples are minced for snap frozen sample preparations, either with or without RNAse inhibitors, for DNA, RNA, or protein isolation. The overall goal of the pancreas dissection procedure is to sample the entire pancreas while maintaining anatomical orientation. Endocrine cell heterogeneity in terms of islet composition, size, and numbers is reported for human islets compared to rodent islets. The majority of human islets from the pancreas head, body and tail regions are composed of insulin-containing β-cells followed by lower proportions of glucagon-containing α-cells and somatostatin-containing δ-cells. Pancreatic polypeptide-containing PP cells and ghrelin-containing epsilon cells are also present but in small numbers. In contrast, the uncinate region contains islets that are primarily composed of pancreatic polypeptide-containing PP cells. These regional islet variations arise from developmental differences. The pancreas develops from the ventral and dorsal pancreatic buds in the foregut and after rotation of the stomach and duodenum, the ventral lobe moves and fuses with the dorsal. The ventral lobe forms the posterior portion of the head including the uncinate process while the dorsal lobe gives rise to the rest of the organ. Regional pancreatic variation is also reported with the tail region having higher islet density compared to other regions and the dorsal lobe-derived components undergoing selective atrophy in type 1 diabetes. Additional organs and tissues are often recovered from the organ donors and include pancreatic lymph nodes, spleen and non-pancreatic lymph nodes. These samples are recovered with similar formats as for the pancreas with the addition of isolation of cryopreserved cells. When the proximal duodenum is included with the pancreas, duodenal mucosa may be collected for paraffin and frozen blocks and minced snap frozen preparations.     

The Root Extract of the Medicinal Plant Pelargonium sidoides Is a Potent HIV-1 Attachment Inhibitor

Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs.     

Exploration of the Canyon-Incised Continental Margin of the Northeastern United States Reveals Dynamic Habitats and Diverse Communities

The continental margin off the northeastern United States (NEUS) contains numerous, topographically complex features that increase habitat heterogeneity across the region. However, the majority of these rugged features have never been surveyed, particularly using direct observations. During summer 2013, 31 Remotely-Operated Vehicle (ROV) dives were conducted from 494 to 3271 m depth across a variety of seafloor features to document communities and to infer geological processes that produced such features. The ROV surveyed six broad-scale habitat features, consisting of shelf-breaching canyons, slope-sourced canyons, inter-canyon areas, open-slope/landslide-scar areas, hydrocarbon seeps, and Mytilus Seamount. Four previously unknown chemosynthetic communities dominated by Bathymodiolus mussels were documented. Seafloor methane hydrate was observed at two seep sites. Multivariate analyses indicated that depth and broad-scale habitat significantly influenced megafaunal coral (58 taxa), demersal fish (69 taxa), and decapod crustacean (34 taxa) assemblages. Species richness of fishes and crustaceans significantly declined with depth, while there was no relationship between coral richness and depth. Turnover in assemblage structure occurred on the middle to lower slope at the approximate boundaries of water masses found previously in the region. Coral species richness was also an important variable explaining variation in fish and crustacean assemblages. Coral diversity may serve as an indicator of habitat suitability and variation in available niche diversity for these taxonomic groups. Our surveys added 24 putative coral species and three fishes to the known regional fauna, including the black coral Telopathes magna, the octocoral Metallogorgia melanotrichos and the fishes Gaidropsarus argentatus, Guttigadus latifrons, and Lepidion guentheri. Marine litter was observed on 81% of the dives, with at least 12 coral colonies entangled in debris. While initial exploration revealed the NEUS region to be both geologically dynamic and biologically diverse, further research into the abiotic conditions and the biotic interactions that influence species abundance and distribution is needed.     

Peptidomic analyses of mouse astrocytic cell lines and rat primary cultured astrocytes

Astrocytes play an active role in the modulation of synaptic transmission by releasing cell-cell signaling molecules in response to various stimuli that evoke a Ca(2+) increase. We expand on recent studies of astrocyte intracellular and secreted proteins by examining the astrocyte peptidome in mouse astrocytic cell lines and rat primary cultured astrocytes, as well as those peptides secreted from mouse astrocytic cell lines in response to Ca(2+)-dependent stimulations. We identified 57 peptides derived from 24 proteins with LC-MS/MS and CE-MS/MS in the astrocytes. Among the secreted peptides, four peptides derived from elongation factor 1, macrophage migration inhibitory factor, peroxiredoxin-5, and galectin-1 were putatively identified by mass-matching to peptides confirmed to be found in astrocytes. Other peptides in the secretion study were mass-matched to those found in prior peptidomics analyses on mouse brain tissue. Complex peptide profiles were observed after stimulation, suggesting that astrocytes are actively involved in peptide secretion. Twenty-six peptides were observed in multiple stimulation experiments but not in controls and thus appear to be released in a Ca(2+)-dependent manner. These results can be used in future investigations to better understand stimulus-dependent mechanisms of astrocyte peptide secretion.     

Recent divergences and size decreases of eastern gorilla populations

Compared with other African apes, eastern gorillas (Gorilla beringei) have been little studied genetically. We used analysis of autosomal DNA genotypes obtained from non-invasively collected faecal samples to estimate the evolutionary histories of the two extant mountain gorilla populations and the closely related eastern lowland gorillas. Our results suggest that eastern lowland gorillas and mountain gorillas split beginning some 10 000 years ago, followed 5000 years ago by the split of the two mountain gorilla populations of Bwindi Impenetrable National Park and the Virungas Massif. All three populations have decreased in effective population size, with particularly substantial 10-fold decreases for the mountain gorillas. These dynamics probably reflect responses to habitat changes resulting from climate fluctuations over the past 20 000 years as well as increasing human influence in this densely populated region in the last several thousand years.