Oral hydratation with a low osmolality solution in dehydrated children with diarrheic diseases: controlled clinical trial

A clinical trial was conducted to compare the efficacy of a low-osmolarity solution (245 mOsm/L), and a standard oral rehydration solution (ORS) recommended by WHO for children dehydrated by diarrhea. Group 1 (69 children) received WHO/ORS (311 mOsml/L) and group 2 (71 children) received a low-osmolarity solution (245 mOsm/L). Rehydration was successful in 88.4% in group 1 and 92.9% in group 2 (p = 0.35). Rehydration was completed in 5.2 h (SD +/- 1.8) in group 1 and 5.5 (SD +/- 1.7) in group 2 (p = 0.31). Stool output was 6.3 g/kg/h (SD +/- 5.0) in group 1 and 5.6 g/kg/h (SD +/- 5.1) in group 2 (p = 0.94). Sodium at rehydration-completion was 139.3 mEq/L (SD +/- 7.1) in group 1 and 136.7 mEq/L (SD +/- 4.3) in group 2 (p = 0.014). Group 1 was under observation for 21 hours (SD +/- 5.7) and group 2, for 22 hours (SD +/- 5.6). Stool output in group 1 was 5.2 g/kg/h (SD 4.1) and 4.2 gr./kg/h (SD +/- 4.1) in group 2 (p = 0.16). In group 1, 23.1% required intravenous solutions and 9.8% in group 2 (p = 0.03). In treating dehydrated children, the low-osmolarity solution diminished the need for intravenous solutions, corrected most plasmatic sodium disorders, and produced no-risk of developing hyponatremia.     

avrPto enhances growth and necrosis caused by Pseudomonas syringae pv.tomato in tomato lines lacking either Pto or Prf

AvrPto was introduced into three tomato genotypes with two biotic agents to study its role in compatible interactions. avrPto enhanced the capacity of the Pseudomonas syringae pv. tomato strain T1 to induce necrotic symptoms on tomato plants that lacked either Pto or Prf genes. The enhanced necrosis correlated with a small increase in bacterial growth. In planta expression of avrPto in isolation did not elicit necrosis in the absence of a functional Prf gene.     

Fetal surfactant as a source of arachidonate in human amniotic fluid

The factors responsible for the onset of labor in women are not well understood but it is clear that parturition is associated with increased production of prostanoids and release of arachidonic acid by intrauterine tissues. Pulmonary surfactant is secreted from the fetal lung into the amniotic fluid where its concentration increases toward term. In this paper we have shown that the ability of fetal surfactant to stimulate prostaglandin production by amnion cells is greatly enhanced by pre-incubating surfactant with amniotic fluid. This is due to the release of fatty acids, including arachidonate, from the lipids of fetal surfactant by the sequential action of phospholipase C and diglyceride lipase. Thus, in addition to providing the amnion with a source of arachidonate derived from the intracellular transfer of arachidonate from surfactant phosphatidylcholine to phosphatidylethanolamine and phosphatidylinositol in amnion cells, fetal surfactant also contributes to the pool of free arachidonate in amniotic fluid.     

The Pleckstrin Homology and Phosphotyrosine Binding Domains of Insulin Receptor Substrate 1 Mediate Inhibition of Apoptosis by Insulin

Insulin and insulin-like growth factor 1 (IGF-1) evoke diverse biological effects through receptor-mediated tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. We investigated the elements of IRS-1 signaling that inhibit apoptosis of interleukin 3 (IL-3)-deprived 32D myeloid progenitor cells. 32D cells have few insulin receptors and no IRS proteins; therefore, insulin failed to inhibit apoptosis during IL-3 withdrawal. Insulin stimulated mitogen-activated protein kinase in 32D cells expressing insulin receptors (32D^IR) but failed to activate the phosphatidylinositol 3 (PI 3)-kinase cascade or to inhibit apoptosis. By contrast, insulin stimulated the PI 3-kinase cascade, inhibited apoptosis, and promoted replication of 32D^IR cells expressing IRS-1. As expected, insulin did not stimulate PI 3-kinase in 32D^IR cells, which expressed a truncated IRS-1 protein lacking the tail of tyrosine phosphorylation sites. However, this truncated IRS-1 protein, which retained the NH₂-terminal pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains, mediated phosphorylation of PKB/akt, inhibition of apoptosis, and replication of 32D^IR cells during insulin stimulation. These results suggest that a phosphotyrosine-independent mechanism mediated by the PH and PTB domains promoted antiapoptotic and growth actions of insulin. Although PI 3-kinase was not activated, its phospholipid products were required, since LY294002 inhibited these responses. Without IRS-1, a chimeric insulin receptor containing a tail of tyrosine phosphorylation sites derived from IRS-1 activated the PI 3-kinase cascade but failed to inhibit apoptosis. Thus, phosphotyrosine-independent IRS-1-linked pathways may be critical for survival and growth of IL-3-deprived 32D cells during insulin stimulation.     

LSD1 Overexpression Is Associated with Poor Prognosis in Basal-Like Breast Cancer,and Sensitivity to PARP Inhibition

LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.     

Genome-Wide Association Mapping for Yield and Other Agronomic Traits in an Elite Breeding Population of Tropical Rice (Oryza sativa)

Genome-wide association mapping studies (GWAS) are frequently used to detect QTL in diverse collections of crop germplasm, based on historic recombination events and linkage disequilibrium across the genome. Generally, diversity panels genotyped with high density SNP panels are utilized in order to assay a wide range of alleles and haplotypes and to monitor recombination breakpoints across the genome. By contrast, GWAS have not generally been performed in breeding populations. In this study we performed association mapping for 19 agronomic traits including yield and yield components in a breeding population of elite irrigated tropical rice breeding lines so that the results would be more directly applicable to breeding than those from a diversity panel. The population was genotyped with 71,710 SNPs using genotyping-by-sequencing (GBS), and GWAS performed with the explicit goal of expediting selection in the breeding program. Using this breeding panel we identified 52 QTL for 11 agronomic traits, including large effect QTLs for flowering time and grain length/grain width/grain-length-breadth ratio. We also identified haplotypes that can be used to select plants in our population for short stature (plant height), early flowering time, and high yield, and thus demonstrate the utility of association mapping in breeding populations for informing breeding decisions. We conclude by exploring how the newly identified significant SNPs and insights into the genetic architecture of these quantitative traits can be leveraged to build genomic-assisted selection models.     

Frugivorous Bats Maintain Functional Habitat Connectivity in Agricultural Landscapes but Rely Strongly on Natural Forest Fragments

Anthropogenic changes in land use threaten biodiversity and ecosystem functioning by the conversion of natural habitat into agricultural mosaic landscapes, often with drastic consequences for the associated fauna. The first step in the development of efficient conservation plans is to understand movement of animals through complex habitat mosaics. Therefore, we studied ranging behavior and habitat use in Dermanura watsoni (Phyllostomidae), a frugivorous bat species that is a valuable seed disperser in degraded ecosystems. Radio-tracking of sixteen bats showed that the animals strongly rely on natural forest. Day roosts were exclusively located within mature forest fragments. Selection ratios showed that the bats foraged selectively within the available habitat and positively selected natural forest. However, larger daily ranges were associated with higher use of degraded habitats. Home range geometry and composition of focal foraging areas indicated that wider ranging bats performed directional foraging bouts from natural to degraded forest sites traversing the matrix over distances of up to three hundred meters. This behavior demonstrates the potential of frugivorous bats to functionally connect fragmented areas by providing ecosystem services between natural and degraded sites, and highlights the need for conservation of natural habitat patches within agricultural landscapes that meet the roosting requirements of bats.     

Mass Media and the Contagion of Fear: The Case of Ebola in America

Background

In the weeks following the first imported case of Ebola in the U. S. on September 29, 2014, coverage of the very limited outbreak dominated the news media, in a manner quite disproportionate to the actual threat to national public health; by the end of October, 2014, there were only four laboratory confirmed cases of Ebola in the entire nation. Public interest in these events was high, as reflected in the millions of Ebola-related Internet searches and tweets performed in the month following the first confirmed case. Use of trending Internet searches and tweets has been proposed in the past for real-time prediction of outbreaks (a field referred to as “digital epidemiology”), but accounting for the biases of public panic has been problematic. In the case of the limited U. S. Ebola outbreak, we know that the Ebola-related searches and tweets originating the U. S. during the outbreak were due only to public interest or panic, providing an unprecedented means to determine how these dynamics affect such data, and how news media may be driving these trends.

Methodology

We examine daily Ebola-related Internet search and Twitter data in the U. S. during the six week period ending Oct 31, 2014. TV news coverage data were obtained from the daily number of Ebola-related news videos appearing on two major news networks. We fit the parameters of a mathematical contagion model to the data to determine if the news coverage was a significant factor in the temporal patterns in Ebola-related Internet and Twitter data.

Conclusions

We find significant evidence of contagion, with each Ebola-related news video inspiring tens of thousands of Ebola-related tweets and Internet searches. Between 65% to 76% of the variance in all samples is described by the news media contagion model.     

Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease

A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5–10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48h and 96h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.