Evidence for epistasis between <Emphasis Type="Italic">SLC6A4</Emphasis> and <Emphasis Type="Italic">ITGB3</Emphasis> in autism etiology and in the determination of platelet serotonin levels

Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Early and specific gene expression triggered by rice resistance gene Pi33 in response to infection by ACE1 avirulent blast fungus

* Our view of genes involved in rice disease resistance is far from complete. Here we used a gene-for-gene relationship corresponding to the interaction between atypical avirulence gene ACE1 from Magnaporthe grisea and rice resistance gene Pi33 to better characterize early rice defence responses induced during such interaction. * Rice genes differentially expressed during early stages of Pi33/ACE1 interaction were identified using DNA chip-based differential hybridization and QRT-PCR survey of the expression of known and putative regulators of disease resistance. * One hundred genes were identified as induced or repressed during rice defence response, 80% of which are novel, including resistance gene analogues. Pi33/ACE1 interaction also triggered the up-regulation of classical PR defence genes and a massive down-regulation of chlorophyll a/b binding genes. Most of these differentially expressed genes were induced or repressed earlier in Pi33/ACE1 interaction than in the gene-for-gene interaction involving Nipponbare resistant cultivar. * Besides demonstrating that an ACE1/Pi33 interaction induced classical and specific expression patterns, this work provides a list of new genes likely to be involved in rice disease resistance.     

Effects of the occurrence of a cyclone and the dominance of a bamboo species on the dynamics of subtropical forest fragments

With the intensification of global warming, the occurrence of large‐scale natural events is becoming even more common in tropical regions, which can impact the structure of plant communities. In this study, we evaluated the isolated and combined effects of an extratropical cyclone and the dominance of a native bamboo species (Merostachys skvortzovii) on floristic composition, diversity, demographic rates and the increment of trees in Atlantic Forest fragments in Southern Brazil. In 2014 (T1) and 2016 (T2), we sampled 56 plots of 200 m² for the effects of an extratropical cyclone in 2009 (T0). We also evaluated another 60 plots of the same size not in the direct path of this cyclone. Half of the plots in each group were covered by dense groupings of bamboos, as a result of past human activities, which could potentially limit natural regeneration. We observed an increase in richness and diversity indices (H′ and 1/D) from the first (T0) to the following assessments (T1 an T2) on the sites affected by the cyclone, when compared to non‐affected sites. After the cyclone, both density and basal area they decreased, but there was an increase in recruitment, mortality, turnover rates and basal area, as well as basal increment. The diameter increment on surviving individuals was higher in cyclone‐affected sites than in non‐affected sites. Bamboo cover did not affect richness or demographic rates (except mortality between T0 and T1). Natural impacts of this nature can lead to significant alterations of demographic rates, allowing the input of new species and influencing the pace of demographic processes.     

Application of a multiphase microreactor chemostat for the determination of reaction kinetics of Staphylococcus carnosus

Bioprocess and Biosystems Engineering - Bioreactors at the microliter scale offer a promising approach to accelerate bioprocess development. Advantages of such microbioreactors include a reduction...     

Mechanisms Involved in the Anti-Inflammatory Action of a Polysulfated Fraction from Gracilaria cornea in Rats

The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI) were investigated using a paw edema model induced in rats by different inflammatory agents (carrageenan, dextran, serotonin, bradykinin, compound 48/80 or L-arginine). Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously - s.c., significantly inhibited rat paw edema induced by carrageenan and dextran, as confirmed by myeloperoxidase and Evans’ blue assessments, respectively. Gc-FI (9 mg/kg, s.c.) inhibited rat paw edema induced by histamine, compound 48/80 and L-arginine. Additionally, Gc-FI (9 mg/kg, s.c.) inhibited Cg-induced edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2 mRNA and protein levels compared with those of the carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with ZnPP IX, a specific heme oxygenase-1 (HO-1) inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena.     

The Availability and Consistency of Dengue Surveillance Data Provided Online by the World Health Organization

Background

The use of high quality disease surveillance data has become increasingly important for public health action against new threats. In response, countries have developed a wide range of disease surveillance systems enabled by technological advancements. The heterogeneity and complexity of country data systems have caused a growing need for international organizations such as the World Health Organization (WHO) to coordinate the standardization, integration, and dissemination of country disease data at the global level for research and policy. The availability and consistency of currently available disease surveillance data at the global level are unclear. We investigated this for dengue surveillance data provided online by the WHO.

Methods and Findings

We extracted all dengue surveillance data provided online by WHO Headquarters and Regional Offices (RO’s). We assessed the availability and consistency of these data by comparing indicators within and between sources. We also assessed the consistency of dengue data provided online by two example countries (Brazil and Indonesia). Data were available from WHO for 100 countries since 1955 representing a total of 23 million dengue cases and 82 thousand deaths ever reported to WHO. The availability of data on DengueNet and some RO’s declined dramatically after 2005. Consistency was lacking between sources (84% across all indicators representing a discrepancy of almost half a million cases). Within sources, data at high spatial resolution were often incomplete.

Conclusions

The decline of publicly available, integrated dengue surveillance data at the global level will limit opportunities for research, policy, and advocacy. A new financial and operational framework will be necessary for innovation and for the continued availability of integrated country disease data at the global level.     

Insights into the Skeletonization,Lifestyle, and Affinity of the Unusual Ediacaran Fossil Corumbella

The Ediacaran fossil Corumbella is important because it is hypothesized to be a scyphozoan cnidarian, and thus might be one of the rare examples of bona fide Neoproterozoic animals. Unfortunately, its mode of life, style of skeletonization, and taxonomic affinity have been very controversial. Here, we use X-ray micro-CT, SEM, and taphonomic analysis to compare preservational modes of Corumbella, in order to better understand the symmetry, mode of construction, preservational style, and taxonomy of this group. Results suggest that articulated and disarticulated specimens of Corumbella from the Ediacaran of Brazil, Paraguay, and the United States, although sometimes preserved very differently, represent the same taxon—Corumbella werneri. Corumbellids had a thick but flexible theca and probably lived with their basalmost part anchored in the sediment, much like Conotubus. When considered together, these results suggest that Corumbella was one of the first animals to build a skeleton, employing a lamellar microfabric similar to conulariids.     

Daily rhythms related to distinct social tasks inside an eusocial bee colony

A bee colony is often compared to a multicellular organism, mainly because of its spatial organization. We propose that a temporal organization of equal importance is also present. To support this view, we studied the reproductive processes of two closely related species of stingless bees. Stingless bees enable observations of daily rhythms that are performed by distinct social classes. The emergent process, POP, is cyclic and consists of the building and provisioning of brood cells by the worker bees and egg-laying by the queen. Colonies were kept in the laboratory under constant conditions with the exit tube opening to the environment; thus, foragers had direct access to environmental cycles. At a later stage of the experiment, the exit tube was closed by a sieve; in this case, bees had their own stock of food, but the environmental LD cycle could still be detected when they were inside the exit tube. Daily POP rhythms were present and showed distinct temporal patterns in each species. A third condition was imposed on one of the species only: the exit tube was closed by a sieve and maintained inside a box that was provided with constant illumination. In this colony, the POP rhythm was perturbed by the destruction of the brood cells. Restoration of POP consisted of a rapid reconstruction of cells followed by a late oviposition in the same day. As different rhythmic patterns were detected, but showed regular timings with respect to one another, an interpretation based upon the concept of an internal temporal order is suggested.