843 research outputs found
Expression of MHC II genes
Innate and adaptive immunity are connected via antigen processing and
presentation (APP), which results in the presentation of antigenic peptides to
T cells in the complex with the major histocompatibility (MHC) determinants.
MHC class II (MHC II) determinants present antigens to CD4+ T cells, which are
the main regulators of the immune response. Their genes are transcribed from
compact promoters that form first the MHC II enhanceosome, which contains
DNA-bound activators and then the MHC II transcriptosome with the addition of
the class II transactivator (CIITA). CIITA is the master regulator of MHC II
transcription. It is expressed constitutively in dendritic cells (DC) and
mature B cells and is inducible in most other cell types. Three isoforms of
CIITA exist, depending on cell type and inducing signals. CIITA is regulated at
the levels of transcription and post-translational modifications, which are
still not very clear. Inappropriate immune responses are found in several
diseases, including cancer and autoimmunity. Since CIITA regulates the
expression of MHC II genes, it is involved directly in the regulation of the
immune response. The knowledge of CIITA will facilitate the manipulation of the
immune response and might contribute to the treatment of these diseases
Non-linear rheology of active particle suspensions: Insights from an analytical approach
We consider active suspensions in the isotropic phase subjected to a shear
flow. Using a set of extended hydrodynamic equations we derive a variety of
{\em analytical} expressions for rheological quantities such as shear viscosity
and normal stress differences. In agreement to full-blown numerical
calculations and experiments we find a shear thickening or -thinning behaviour
depending on whether the particles are contractile or extensile. Moreover, our
analytical approach predicts that the normal stress differences can change
their sign in contrast to passive suspensions.Comment: 11 pages, 10 figures, appear in PR
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Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report
Background
We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD).
Case presentation
A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects.
Conclusions
This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway
Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb
Transcriptional elongation of most eukaryotic genes by RNA polymerase II requires the kinase activity of the positive transcription elongation factor b (P-TEFb). The catalytically active P-TEFb complex becomes inactive when sequestered into the large complex by the cooperative actions of 7SK snRNA and HEXIM1. In this study, we report that HEXIM1 forms oligomers in cells. This oligomerization is mediated by its predicted coiled-coil region in the C-terminal domain and 7SK snRNA that binds a basic region within the central part of HEXIM1. Alanine-mutagenesis of evolutionary conserved leucines in the coiled-coil region and the digestion of 7SK snRNA by RNase A treatment prevent this oligomerization. Importantly, mutations of the N-terminal part of the coiled-coil region abrogate the ability of HEXIM1 to bind and inhibit P-TEFb. Finally, the formation of HEXIM1 oligomers via the C-terminal part of the coiled-coil or basic regions is critical for the inhibition of transcription. Our results suggest that two independent regions in HEXIM1 form oligomers to incorporate P-TEFb into the large complex and determine the inhibition of transcriptional elongation
The prolate-to-oblate shape transition of phospholipid vesicles in response to frequency variation of an AC electric field can be explained by the dielectric anisotropy of a phospholipid bilayer
The external electric field deforms flaccid phospholipid vesicles into
spheroidal bodies, with the rotational axis aligned with its direction.
Deformation is frequency dependent: in the low frequency range (~ 1 kHz), the
deformation is typically prolate, while increasing the frequency to the 10 kHz
range changes the deformation to oblate. We attempt to explain this behaviour
with a theoretical model, based on the minimization of the total free energy of
the vesicle. The energy terms taken into account include the membrane bending
energy and the energy of the electric field. The latter is calculated from the
electric field via the Maxwell stress tensor, where the membrane is modelled as
anisotropic lossy dielectric. Vesicle deformation in response to varying
frequency is calculated numerically. Using a series expansion, we also derive a
simplified expression for the deformation, which retains the frequency
dependence of the exact expression and may provide a better substitute for the
series expansion used by Winterhalter and Helfrich, which was found to be valid
only in the limit of low frequencies. The model with the anisotropic membrane
permittivity imposes two constraints on the values of material constants:
tangential component of dielectric permittivity tensor of the phospholipid
membrane must exceed its radial component by approximately a factor of 3; and
the membrane conductivity has to be relatively high, approximately one tenth of
the conductivity of the external aqueous medium.Comment: 17 pages, 6 figures; accepted for publication in J. Phys.: Condens.
Matte
HMBA Releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and Activates HIV Transcription
Hexamethylene bisacetamide (HMBA) is a potent inducer of cell differentiation and HIV production in chronically infected cells. However, its mechanism of action remains poorly defined. In this study, we demonstrate that HMBA activates transiently the PI3K/Akt pathway, which leads to the phosphorylation of HEXIM1 and the subsequent release of active positive transcription elongation factor b (P-TEFb) from its transcriptionally inactive complex with HEXIM1 and 7SK small nuclear RNA (snRNA). As a result, P-TEFb is recruited to the HIV promoter to stimulate transcription elongation and viral production. Despite the continuous presence of HMBA, the released P-TEFb reassembles rapidly with 7SK snRNA and HEXIM1. In contrast, a mutant HEXIM1 protein that cannot be phosphorylated and released from P-TEFb and 7SK snRNA via the PI3K/Akt pathway antagonizes this HMBA-mediated induction of viral production. Thus, our studies reveal how HIV transcription is induced by HMBA and suggest how modifications in the equilibrium between active and inactive P-TEFb could contribute to cell differentiation
Dystrophy in Istria: Molecular Genetic Approach. Part II: Analysis of Genetic Polymorphisms
One of the world highest prevalence estimates of myotonic dystrophy (DM) has been reported in the Croatian region Istria. To analyse the population genetic characteristics of DM locus in Istria, two intragenic and three extragenic polymorphic markers were tested. The Southern blot technique was used for D19S63 locus analysis, whereas PCR analysis was performed for CKMM, Alu polymorphism, DMPK (G/T) intron 9/HinfI polymorphism, and D19S207 genetic markers. The compound haplotypes segregating with DM were established. A complete association between the DM mutation and D19S63, D19S207, intron 9/HinfI polymorphism and Alu polymorphism markers were found. In all DM chromosomes: D19S63 and Alu markers had the allele 1 in common; D19S207 had the allele 3 in common, DMPK (G/T) intron 9/HinfI marker had the allele 2 in common. The analysis of CKMM polymorphism revealed genotype heterogeneity; in DM chromosomes either allele 2 or allele 4 were found.
The haplotype analysis in the population of Croatian Istria supports the linkage disequilibrium between the DM mutation and Alu polymorphism, intron 9/HinfI polymorphism, D19S63 and D19S207 markers as reported worldwide. The results of the haplotype analysis suggest a common origin of the mutation in Istrian population
Treatment of Cluster Headache in Pregnancy and Lactation
Cluster headache (CH) is a neurovascular headache syndrome characterized by headache attacks that occur with a circadian and circannual periodicity. The calculated prevalence of CH in reproductive-aged women is 7.5 of 100,000 women. Although data suggest that CH during pregnancy is a relatively rare condition, when it does occur, attacks remain unchanged in character and severity in the majority of patients. Thus, treatment of CH in pregnant and lactating women may remain a significant therapeutic challenge. This manuscript briefly reviews the epidemiology of CH in women, and then focuses on treatment options for both acute and preventative management of CH in pregnant and lactating women
Nef binds p6* in gagpol during replication of human immunodeficiency virus type 1
The atypical Nef protein (NefF12) from human immunodeficiency virus type 1 strain F12 (HIV-1F12) interferes with virion production and infectivity via a mysterious mechanism. The correlation of these effects with the unusual perinuclear subcellular localization of NefF12 suggested that the wild-type Nef protein could bind to assembly intermediates in late stages of viral replication. To test this hypothesis, Nef from HIV-1NL4-3 was fused to an endoplasmic reticulum (ER) retention signal (NefKKXX). This mutant NefKKXX protein recapitulated fully the effects of NefF12 on Gag processing and virion production, either alone or as a CD8 fusion protein. Importantly, the mutant NefKKXX protein also localized to the intermediate compartment, between the ER and the trans-Golgi network. Furthermore, Nef bound the GagPol polyprotein in vitro and in vivo. This binding mapped to the C-terminal flexible loop in Nef and the transframe p6* protein in GagPol. The significance of this interaction was demonstrated by a genetic assay in which the release of a mutant HIV-1 provirus lacking the PTAP motif in the late domain that no longer binds Tsg101 was rescued by a Nef.Tsg101 chimera. Importantly, this rescue as well as incorporation of Nef into HIV-1 virions correlated with the ability of Nef to interact with GagPol. Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1.<br /
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EHMTI-0184. Ictal adiponectin levels are modulated by pain severity and treatment response in episodic migraineurs
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