Characteristics of Convective Sources of Gravity Waves and Sprites Present in Satellite IR Images During the SpreadFEx 2005 Campaign

We developed a technique to identify and estimate the size, intensity, and Tropopause overshoot of thunderstorm convective cores expected to be significant sources of gravity waves. The work was based on GOES IR images of South America on the night of 30 September to 1 October and 25–26 October 2005, as part of the Spread F Experiment (SpreadFEx) in Brazil in 2005. We also characterized, for the first time, the convective activity of three small TLE producing thunderstorms that yielded 11 TLEs on 25–26 October 2005. The campaign occurred during the dry to wet season transition in central Brazil, marked by the presence of extra-tropical cyclogenesis over the Atlantic Ocean, and cold fronts penetrating inland. The Tropopause temperature was typically −76°C with a corresponding altitude of ~15 200 m. Vigorous convective cores capable of generating strong gravity waves were located in convective regions having areas with cloud top temperatures ≤−76°C. They had typical cloud-top temperature deficits of ΔT−2.0°C to −8.0°C from the average surroundings, implying overshoot heights of 200 to 3100 m, which are within the typical range. Fast vertical development and high horizontal growth rates were associated with a large number of simultaneously active vigorous convective cores, indicating that their dynamics may have determined the spatial-temporal development of the thunderstorms analyzed. Moderate convective cores were also present in areas with cloud top −76°C≤T≤−70°C. They had ΔT of −1.9°C to −5.3°C producing overshoots between 80–300 m. All convective cores had typical diameters of 5–20 km and their size tended to increase with ΔT, there was a 57% correlation between the two parameters. Analysis of the relationship of cloud top T with positive and negative cloud-to-ground lightning (+/−CG) occurrence rate and with peak current showed that lighting activity may provide an independent way to identify convective cores and measure their intensity, since they were characterized by a high incidence of low peak current −CGs that forms the bulk of the −CG population

Density-dependence of functional development in spiking cortical networks grown in vitro

During development, the mammalian brain differentiates into specialized regions with distinct functional abilities. While many factors contribute to functional specialization, we explore the effect of neuronal density on the development of neuronal interactions in vitro. Two types of cortical networks, dense and sparse, with 50,000 and 12,000 total cells respectively, are studied. Activation graphs that represent pairwise neuronal interactions are constructed using a competitive first response model. These graphs reveal that, during development in vitro, dense networks form activation connections earlier than sparse networks. Link entropy analysis of dense net- work activation graphs suggests that the majority of connections between electrodes are reciprocal in nature. Information theoretic measures reveal that early functional information interactions (among 3 cells) are synergetic in both dense and sparse networks. However, during later stages of development, previously synergetic relationships become primarily redundant in dense, but not in sparse networks. Large link entropy values in the activation graph are related to the domination of redundant ensembles in late stages of development in dense networks. Results demonstrate differences between dense and sparse networks in terms of informational groups, pairwise relationships, and activation graphs. These differences suggest that variations in cell density may result in different functional specialization of nervous system tissue in vivo.Comment: 10 pages, 7 figure

Structural basis of phosphatidylinositol 3-kinase C2α function

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine

Structural basis of phosphatidylinositol 3-kinase C2α function

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine

Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1

Combination antiretroviral therapy (cART) can effectively suppress HIV-1 replication, but the latent viral reservoir in resting memory CD4+ T cells is impervious to cART and represents a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 represents a possible strategy for elimination of this reservoir. In this study we describe the discovery of 1,2,9,10-tetramethoxy-7H-dibenzo[de,g]quinolin-7-one (57704) which reactivates latent HIV-1 in several cell-line models of latency (J89GFP, U1 and ACH-2). 57704 also increased HIV-1 expression in 3 of 4 CD8+-depleted blood mononuclear cell preparations isolated from HIV-1-infected individuals on suppressive cART. In contrast, vorinostat increased HIV-1 expression in only 1 of the 4 donors tested. Importantly, 57704 does not induce global T cell activation. Mechanistic studies revealed that 57704 reactivates latent HIV-1 via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. 57704 was found to be an agonist of PI3K with specificity to the p110a isoform, but not the p110β, δ or γ isoforms. Taken together, our work suggests that 57704 could serve as a scaffold for the development of more potent activators of latent HIV-1. Furthermore, it highlights the involvement of the PI3K/Akt pathway in the maintenance of HIV-1 latency. © 2014 Doyon et al

Factors affecting the determination of threshold doses for allergenic foods: How much is too much?

Background: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. Objective: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. Methods: In September 1999,12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. Results: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows\u27 milk, and egg; limited data were available for other foods, such as fish and mustard. Conclusions: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

Somatic PIK3R1 Variation as a Cause of Vascular Malformations and Overgrowth

PurposeSomatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.MethodsAffected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.ResultsThe phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone.ConclusionSomatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway

Temporal variation of condition and prey-predator status for a schilbid catfish Eutropiichthys vacha (Hamilton, 1822) in the Ganges River, northwestern Bangladesh through multi-model inferences

1229-1237The current study provide the baseline information on the temporal (monthly) variations of condition through multiple functions (allometric, KA; Fulton’s, KF; relative, KR) and prey-predator status through relative weight (WR) for Eutropiichthys vacha (Hamilton, 1822) from the Ganges River, northwestern Bangladesh over one year. The smallest individuals were 6.5 and 6.2 cm in TL, whereas the largest were 19.9 and 20.6 cm in TL for males and females, respectively. No significant differences were observed in the length frequency distribution, LFDs (p = 0.8152) for both sexes. KF was significantly correlated with TL for both sexes (p KF was treated as the best condition factor therefore, well-being of E. vachaa. There was no significant correlation among TL vs KA, TL vs KR and TL vs WR for males and females, respectively. But BW showed highly significant correlations with all condition factors, i.e., BW vs KA; BW vs KF; BW vs KR, and BW vs WR (p WR revealed no significant dissimilarities from 100 for males (p = 0.432) unlike females (p = 0.023), based on Wilcoxon signed-rank tests, suggesting that habitat was more suitable for males than females for food availability relative to predator presence. Moreover, this study assessed for the first time the effect of temperature and rainfall on monthly KF for E. vacha in the Ganges River. The Pearson correlation test found no significant relation between temperature and KF (r = 0.2226, p = 0.4868 for males; r = 0.2172, p = 0.4977 for females), but significant correlations were found between rainfall and KF (r = 0.6357, p = 0.0263 for males and r = 0.6983, p = 0.0115 for females)