2,219 research outputs found
CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons
The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Cav channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Cav channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cav channels, and failed to modulate LVA Cav channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Cav channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as INa(v) or IK(v) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Cav channels. © 2007 Elsevier Ltd. All rights reserved
The flavor puzzle in multi-Higgs models
We reconsider the flavor problem in the models with two Higgs doublets. By
studying two generation toy models, we look for flavor basis independent
constraints on Yukawa couplings that will give us the mass hierarchy while
keeping all Yukawa couplings of the same order. We then generalize our findings
to the full three generation Standard Model. We find that we need two
constraints on the Yukawa couplings to generate the observed mass hierarchy,
and a slight tuning of Yukawa couplings of order 10%, much less than the
Standard Model. We briefly study how these constraints can be realized, and
show how flavor changing currents are under control for mixing in
the near-decoupling limit.Comment: 26 pages, typos are corrected, references are added, the final
versio
An introduction to Graph Data Management
A graph database is a database where the data structures for the schema
and/or instances are modeled as a (labeled)(directed) graph or generalizations
of it, and where querying is expressed by graph-oriented operations and type
constructors. In this article we present the basic notions of graph databases,
give an historical overview of its main development, and study the main current
systems that implement them
The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation.
Mast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate
Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.
Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present
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Genetic analysis of a major international collection of cultivated apple varieties reveals previously unknown historic heteroploid and inbred relationships
Domesticated apple (Malus x domestica Borkh.) is a major global crop and the genetic diversity held within the pool of cultivated varieties is important for the development of future cultivars. The aim of this study was to investigate the diversity held within the domesticated form, through the analysis of a major international germplasm collection of cultivated varieties, the UK National Fruit Collection, consisting of over 2,000 selections of named cultivars and seedling varieties. We utilised Diversity Array Technology (DArT) markers to assess the genetic diversity within the collection. Clustering attempts, using the software STRUCTURE revealed that the accessions formed a complex and historically admixed group for which clear clustering was challenging. Comparison of accessions using the Jaccard similarity coefficient allowed us to identify clonal and duplicate material as well as revealing pairs and groups that appeared more closely related than a standard parent-offspring or full-sibling relations. From further investigation, we were able to propose a number of new pedigrees, which revealed that some historically important cultivars were more closely related than previously documented and that some of them were partially inbred. We were also able to elucidate a number of parent-offspring relationships that had resulted in a number of important polyploid cultivars. This included reuniting polyploid cultivars that in some cases dated as far back as the 18th century, with diploid parents that potentially date back as far as the 13th century
Brazilian montane rainforest expansion induced by Heinrich Stadial 1 event
The origin of modern disjunct plant distributions in the Brazilian Highlands with strong floristic affinities
to distant montane rainforests of isolated mountaintops in the northeast and northern Amazonia and
the Guyana Shield remains unknown. We tested the hypothesis that these unexplained biogeographical
patterns reflect former ecosystem rearrangements sustained by widespread plant migrations possibly
due to climatic patterns that are very dissimilar from present-day conditions. To address this issue, we
mapped the presence of the montane arboreal taxa Araucaria, Podocarpus, Drimys, Hedyosmum, Ilex,
Myrsine, Symplocos, and Weinmannia, and cool-adapted plants in the families Myrtaceae, Ericaceae, and
Arecaceae (palms) in 29 palynological records during Heinrich Stadial 1 Event, encompassing a latitudinal
range of 30°S to 0°S. In addition, Principal Component Analysis and Species Distribution Modelling were
used to represent past and modern habitat suitability for Podocarpus and Araucaria. The data reveals
two long-distance patterns of plant migration connecting south/southeast to northeastern Brazil and
Amazonia with a third short route extending from one of them. Their paleofloristic compositions suggest
a climatic scenario of abundant rainfall and relative lower continental surface temperatures, possibly
intensified by the effects of polar air incursions forming cold fronts into the Brazilian Highlands. Although
these taxa are sensitive to changes in temperature, the combined pollen and speleothems proxy data
indicate that this montane rainforest expansion during Heinrich Stadial 1 Event was triggered mainly by
a less seasonal rainfall regime from the subtropics to the equatorial region.This work was funded by FAPESP research grant 2015/50683-2 to P.E. De Oliveira, VULPES Project, Belmount
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Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model
The alignment in flavour space of the Yukawa matrices of a general
two-Higgs-doublet model results in the absence of tree-level flavour-changing
neutral currents. In addition to the usual fermion masses and mixings, the
aligned Yukawa structure only contains three complex parameters, which are
potential new sources of CP violation. For particular values of these three
parameters all known specific implementations of the model based on discrete
Z_2 symmetries are recovered. One of the most distinctive features of the
two-Higgs-doublet model is the presence of a charged scalar. In this work, we
discuss its main phenomenological consequences in flavour-changing processes at
low energies and derive the corresponding constraints on the parameters of the
aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP.
References added. Discussion slightly extended. Conclusions unchange
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