677 research outputs found
Association among SNAP-25 gene DdeI and MnlI polymorphisms and hemodynamic changes during methylphenidate use: A functional near-infrared spectroscopy study
Objective: To investigate the interaction of treatment-related hemodynamic changes with genotype status for Synaptosomal associated protein 25 (SNAP-25) gene in participants with attention deficit hyperactivity disorder (ADHD) on and off single dose short-acting methylphenidate treatment with functional near-infrared spectroscopy (fNIRS). Method: A total of 15 right-handed adults and 16 right-handed children with DSM-IV diagnosis of ADHD were evaluated. Ten milligrams of short-acting methylphenidate was administered in a crossover design. Results: Participants with SNAP-25 DdeI T/T genotype had decreased right deoxyhemoglobin ([HHb]) with treatment. SNAP-25 MnlI genotype was also associated with right deoxyhemoglobin ([HbO2]) and [HHb] changes as well as left [HHb] change. When the combinations of these genotypes were taken into account, the participants with [DdeI C/C or T/C and MnlI G/G or T/G] genotype had increased right [HHb] with MPH use whereas the participants with [DdeI T/T and MnlI T/T] or [DdeI T/T and MnlI G/G or T/G] genotypes had decreased right prefrontal [HHb]. Conclusions: These results suggested that SNAP-25 polymorphism might be associated with methylphenidate induced brain hemodynamic changes in ADHD participants. © 2011 SAGE Publications
Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance
The mitotic kinesin KIF11 (also called Eg5) plays critical roles in spindle functions. Although a number of small-molecule inhibitors of KIF11 are currently in clinical development, drug-resistance could be developed through compensation by another kinesin called KIF15. Using a newly developed infrared-based cell system, we discovered that the effectiveness of one of the latest generations of KIF11 inhibitor (SB743921) could be enhanced with several inhibitors of Aurora A kinase. Evidence including live-cell imaging and isobologram analysis indicated that targeting KIF11 and Aurora A together promoted monoastral spindle formation and mitotic catastrophe synergistically, supporting a model of parallel pathways of centrosome regulation by Aurora A and KIF11. We also developed a KIF15-dependent SB743921-resistance cell model. Significantly, the drug-resistance could also be overcome with Aurora A inhibitors. These results provide a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved
Spinal cord compression secondary to extramedullary hematopoiesis in thalassemia intermedia
Extramedullary hematopoiesis associated with thalassemia causing spinal cord compression is an extremely rare event in the course of the disease. Documentation with an imaging technique, such as MRI, is mandatory. A patient with thalassemia intermedia, who developed paraparesis in spite of transfusion, underwent surgical decompression. Rapid neurological improvement was observed postoperatively and this neurological condition was protected with adequate hemoglobin level. Management of these patients remains controversial. Various modes of therapy such as surgical decompression, radiotherapy, and transfusion are discussed and the related literature is reviewed
Creutzfeldt-Jacob Disease: a case report
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
Genetic Dominant Variants in STUB1, Segregating in Families with SCA48, Display In Vitro Functional Impairments Indistinctive from Recessive Variants Associated with SCAR16.
Variants in STUB1 cause both autosomal recessive (SCAR16) and dominant (SCA48) spinocerebellar ataxia. Reports from 18 STUB1 variants causing SCA48 show that the clinical picture includes later-onset ataxia with a cerebellar cognitive affective syndrome and varying clinical overlap with SCAR16. However, little is known about the molecular properties of dominant STUB1 variants. Here, we describe three SCA48 families with novel, dominantly inherited STUB1 variants (p.Arg51_Ile53delinsProAla, p.Lys143_Trp147del, and p.Gly249Val). All the patients developed symptoms from 30 years of age or later, all had cerebellar atrophy, and 4 had cognitive/psychiatric phenotypes. Investigation of the structural and functional consequences of the recombinant C-terminus of HSC70-interacting protein (CHIP) variants was performed in vitro using ubiquitin ligase activity assay, circular dichroism assay and native polyacrylamide gel electrophoresis. These studies revealed that dominantly and recessively inherited STUB1 variants showed similar biochemical defects, including impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP. Our findings expand the molecular understanding of SCA48 but also mean that assumptions concerning unaffected carriers of recessive STUB1 variants in SCAR16 families must be re-evaluated. More investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases
Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences
Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood
No relation between EFHC2 gene polymorphism and Idiopathic generalized epilepsy.
Background: Idiopathic generalized epilepsy (IGE) is an epilepsy form
without an underlying brain lesion or neurological indication or
symptom. Recent investigations on the genetic origins of IGE and its
subtypes report that certain mutations of various ion and non-ion
channels genes in the central nervous system may be associated with
IGE. Purpose: In this study we evaluated the relation between IGE and
S430Y polymorphism in EFHC2 gene in a Turkish population.
Material/Methods: The study enrolled 96 healthy volunteers (47 male, 49
female), served as controls, and 96 IGE patients (41 male, 55 female),
IGE diagnosis was confirmed in the neurology department. DNA
extractions were performed. The presence of S430Y polymorphism in the
exon 9 of EFHC2 gene were analyzed by Real-Time PCR. The findings
obtained from the control and patient groups were compared. Results: In
the patient group there was one heterozygous male with 685 T>C
mutation. In the control group, there were two objects with 685 T>C
mutation; one heterozygous male, one heterozygous female. 662 G>A
mutation was determined in neither controls nor patients. Conclusion:
In our series of 96 IGE patients and 96 healthy controls, there was no
relation between S430Y polymorphism in EFHC2 gene and IGE presence
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE
In this small note we are concerned with the solution of Forward-Backward
Stochastic Differential Equations (FBSDE) with drivers that grow quadratically
in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem
is a comparison result that allows comparing componentwise the signs of the
control processes of two different qgFBSDE. As a byproduct one obtains
conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
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