Homogeneous percolation versus arrested phase separation in attractively-driven nanoemulsion colloidal gels

We elucidate mechanisms for colloidal gelation of attractive nanoemulsions depending on the volume fraction (ϕ) of the colloid. Combining detailed neutron scattering, cryo-transmission electron microscopy and rheological measurements, we demonstrate that gelation proceeds by either of two distinct pathways. For ϕ sufficiently lower than 0.23, gels exhibit homogeneous fractal microstructure, with a broad gel transition resulting from the formation and subsequent percolation of droplet–droplet clusters. In these cases, the gel point measured by rheology corresponds precisely to arrest of the fractal microstructure, and the nonlinear rheology of the gel is characterized by a single yielding process. By contrast, gelation for ϕ sufficiently higher than 0.23 is characterized by an abrupt transition from dispersed droplets to dense clusters with significant long-range correlations well-described by a model for phase separation. The latter phenomenon manifests itself as micron-scale “pores” within the droplet network, and the nonlinear rheology is characterized by a broad yielding transition. Our studies reinforce the similarity of nanoemulsions to solid particulates, and identify important qualitative differences between the microstructure and viscoelastic properties of colloidal gels formed by homogeneous percolation and those formed by phase separation.United States. Army Research Office (Institute for Collaborative Biotechnologies. Grant W911NF- 09-0001)National Science Foundation (U.S.) (Grants CMMI-1120724 and DMR-1006147

Practice transformations to optimize the delivery of HIV primary care in community healthcare settings in the United States: A program implementation study.

BackgroundThe United States HIV care workforce is shrinking, which could complicate service delivery to people living with HIV (PLWH). In this study, we examined the impact of practice transformations, defined as efficiencies in structures and delivery of care, on demonstration project sites within the Workforce Capacity Building Initiative, a Health Resources and Services Administration (HRSA) Ryan White HIV/AIDS Program Special Projects of National Significance (SPNS).Methods and findingsData were collected at 14 demonstration project sites in 7 states and the District of Columbia. Organizational assessments were completed at sites once before and 4 times after implementation. They captured 3 transformation approaches: maximizing the HIV care workforce (efforts to increase the number of existing healthcare workforce members involved in the care of PLWH), share-the-care (team-based care giving more responsibility to midlevel providers and staff), and enhancing client engagement in primary HIV care to reduce emergency and inpatient care (e.g., care coordination). We also obtained Ryan White HIV/AIDS Program Services Reports (RSRs) from sites for calendar years (CYs) 2014-2016, corresponding to before, during, and after transformation. The RSR include data on client retention in HIV care, prescription of antiretroviral therapy (ART), and viral suppression. We used generalized estimating equation (GEE) models to analyze changes among sites implementing each practice transformation approach. The demonstration projects had a mean of 18.5 prescribing providers (SD = 23.5). They reported data on more than 13,500 clients per year (mean = 969/site, SD = 1,351). Demographic characteristics remained similar over time. In 2014, a majority of clients were male (71% versus 28% female and 0.2% transgender), with a mean age of 47 (interquartile range [IQR] 37-54). Racial/ethnic characteristics (48% African American, 31% Hispanic/Latino, 14% white) and HIV risk varied (31% men who have sex with men; 31% heterosexual men and women; 7% injection drug use). A substantial minority was on Medicaid (41%). Across sites, there was significant uptake in practices consistent with maximizing the HIV care workforce (18% increase, p < 0.001), share-the-care (25% increase, p < 0.001), and facilitating patient engagement in HIV primary care (13% increase, p < 0.001). There were also significant improvements over time in retention in HIV care (adjusted odds ratio [aOR] = 1.03; 95% confidence interval [CI] 1.02-1.04; p < 0.001), ART prescription levels (aOR = 1.01; 95% CI 1.00-1.01; p < 0.001), and viral suppression (aOR = 1.03; 95% CI 1.02-1.04; p < 0.001). All outcomes improved at sites that implemented transformations to maximize the HIV care workforce or improve client engagement. At sites that implemented share-the-care practices, only retention in care and viral suppression outcomes improved. Study limitations included use of demonstration project sites funded by the Ryan White HIV/AIDS Program (RWHAP), which tend to have better HIV outcomes than other US clinics; varying practice transformation designs; lack of a true control condition; and a potential Hawthorne effect because site teams were aware of the evaluation.ConclusionsIn this study, we found that practice transformations are a potential strategy for addressing anticipated workforce challenges among those providing care to PLWH. They hold the promise of optimizing the use of personnel and ensuring the delivery of care to all in need while potentially enhancing HIV care continuum outcomes

Graph-based analysis of the metabolic exchanges between two co-resident intracellular symbionts, baumannia cicadellinicola and sulcia muelleri with their insect host, homalodisca coagulata

International audienceEndosymbiotic bacteria from different species can live inside cells of the same eukaryotic organism. Metabolic exchanges occur between host and bacteria but also between different endocytobionts. Since a complete genome annotation is available for both, we built the metabolic network of two endosymbiotic bacteria, Sulcia muelleri and Baumannia cicadellinicola, that live inside specific cells of the sharpshooter Homalodisca coagulata and studied the metabolic exchanges involving transfers of carbon atoms between the three. We automatically determined the set of metabolites potentially exogenously acquired (seeds) for both metabolic networks. We show that the number of seeds needed by both bacteria in the carbon metabolism is extremely reduced. Moreover, only three seeds are common to both metabolic networks, indicating that the complementarity of the two metabolisms is not only manifested in the metabolic capabilities of each bacterium, but also by their different use of the same environment. Furthermore, our results show that the carbon metabolism of S. muelleri may be completely independent of the metabolic network of B. cicadellinicola. On the contrary, the carbon metabolism of the latter appears dependent on the metabolism of S. muelleri, at least for two essential amino acids, threonine and lysine. Next, in order to define which subsets of seeds (precursor sets) are sufficient to produce the metabolites involved in a symbiotic function, we used a graph-based method, PITUFO, that we recently developed. Our results highly refine our knowledge about the complementarity between the metabolisms of the two bacteria and their host. We thus indicate seeds that appear obligatory in the synthesis of metabolites are involved in the symbiotic function. Our results suggest both B. cicadellinicola and S. muelleri may be completely independent of the metabolites provided by the co-resident endocytobiont to produce the carbon backbone of the metabolites provided to the symbiotic system (., thr and lys are only exploited by B. cicadellinicola to produce its proteins)

Gene expression meta-analysis of Parkinson’s disease and its relationship with Alzheimer’s disease

Abstract Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common neurodegenerative diseases and have been suggested to share common pathological and physiological links. Understanding the cross-talk between them could reveal potentials for the development of new strategies for early diagnosis and therapeutic intervention thus improving the quality of life of those affected. Here we have conducted a novel meta-analysis to identify differentially expressed genes (DEGs) in PD microarray datasets comprising 69 PD and 57 control brain samples which is the biggest cohort for such studies to date. Using identified DEGs, we performed pathway, upstream and protein-protein interaction analysis. We identified 1046 DEGs, of which a majority (739/1046) were downregulated in PD. YWHAZ and other genes coding 14–3-3 proteins are identified as important DEGs in signaling pathways and in protein-protein interaction networks (PPIN). Perturbed pathways also include mitochondrial dysfunction and oxidative stress. There was a significant overlap in DEGs between PD and AD, and over 99% of these were differentially expressed in the same up or down direction across the diseases. REST was identified as an upstream regulator in both diseases. Our study demonstrates that PD and AD share significant common DEGs and pathways, and identifies novel genes, pathways and upstream regulators which may be important targets for therapy in both diseases

Exploring links between greenspace and sudden unexpected death: A spatial analysis

Greenspace has been increasingly recognized as having numerous health benefits. However, its effects are unknown concerning sudden unexpected death (SUD), commonly referred to as sudden cardiac death, which constitutes a large proportion of mortality in the United States. Because greenspace can promote physical activity, reduce stress and buffer air pollutants, it may have beneficial effects for people at risk of SUD, such as those with heart disease, hypertension, and diabetes mellitus. Using several spatial techniques, this study explored the relationship between SUD and greenspace. We adjudicated 396 SUD cases that occurred from March 2013 to February 2015 among reports from emergency medical services (EMS) that attended out-of-hospital deaths in Wake County (central North Carolina, USA). We measured multiple greenspace metrics in each census tract, including the percentages of forest, grassland, average tree canopy, tree canopy diversity, near-road tree canopy and greenway density. The associations between SUD incidence and these greenspace metrics were examined using Poisson regression (non-spatial) and Bayesian spatial models. The results from both models indicated that SUD incidence was inversely associated with both greenway density (adjusted risk ratio [RR] = 0.82, 95% credible/ confidence interval [CI]: 0.69–0.97) and the percentage of forest (adjusted RR = 0.90, 95% CI: 0.81–0.99). These results suggest that increases in greenway density by 1 km/km2 and in forest by 10% were associated with a decrease in SUD risk of 18% and 10%, respectively. The inverse relationship was not observed between SUD incidence and other metrics, including grassland, average tree canopy, near-road tree canopy and tree canopy diversity. This study implies that greenspace, specifically greenways and forest, may have beneficial effects for people at risk of SUD. Further studies are needed to investigate potential causal relationships between greenspace and SUD, and potential mechanisms such as promoting physical activity and reducing stress

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed “fragment recruitment,” addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed “extreme assembly,” made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin