3,059 research outputs found
Gitelman syndrome
Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia, is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion. The prevalence is estimated at approximately 1:40,000 and accordingly, the prevalence of heterozygotes is approximately 1% in Caucasian populations, making it one of the most frequent inherited renal tubular disorders. In the majority of cases, symptoms do not appear before the age of six years and the disease is usually diagnosed during adolescence or adulthood. Transient periods of muscle weakness and tetany, sometimes accompanied by abdominal pain, vomiting and fever are often seen in GS patients. Paresthesias, especially in the face, frequently occur. Remarkably, some patients are completely asymptomatic except for the appearance at adult age of chondrocalcinosis that causes swelling, local heat, and tenderness over the affected joints. Blood pressure is lower than that in the general population. Sudden cardiac arrest has been reported occasionally. In general, growth is normal but can be delayed in those GS patients with severe hypokalemia and hypomagnesemia
Partial change in EphA4 knockout mouse phenotype: Loss of diminished GFAP upregulation following spinal cord injury
In a previous study we found that the EphA4 receptor inhibits regeneration following spinal cord injury by blocking regrowth of axons and regulation of astrocyte reactivity. In our original studies using EphA4 null mice [Goldshmit et al., J. Neurosci., 2004] we found attenuated astrocyte reactivity following spinal cord injury. Several other studies have now supported the role of EphA4 in regulating neural regeneration but a recent study [Herrmann et al., Exp. Neurol., 2010] did not find an effect of EphA4 on astrocyte reactivity. Re-examination of astrocytic gliosis following injury in our current cohort of EphA4 null mice revealed that they no longer showed attenuation of astrocyte reactivity, however other EphA4 null mouse phenotypes, such as decreased size of the dorsal funiculus were unaltered. We hypothesised that long-term breeding on the C57Bl/6 background may influence the EphA4-mediated astrocyte phenotype and compared astrocytic gliosis at 4 days following spinal cord injury in wildtype and EphA4 null mice on the C57Bl/6 background and backcrossed C57Bl/6Ă129Sv(F2) mice, as well as wildtype 129Sv mice. 129Sv mice had increased GFAP expression and increased numbers of reactive GFAP astrocytes compared to C57Bl/6 mice. There was no significant effect of EphA4 deletion on GFAP expression in C57Bl/6 mice or the F2 crosses other than a moderately decreased number of EphA4 null astrocytes in C57Bl/6 mice using one of two antibodies. Therefore, there has been an apparent change in EphA4-mediated astroglial phenotype associated with long term breeding of the EphA4 colony but it does not appear to be influenced by background mouse strain
ĂCAROS TROMBICULĂDEOS: REVISĂO DE UMA PARASITOSE NEGLIGENCIADA EM ANIMAIS DE COMPANHIA
A trombiculose ĂŠ uma parasitose causada por ĂĄcaros trombiculĂdeos (Acari: Trombiculidae) que afeta vertebrados, incluindo cĂŁes, gatos e o ser humano. Ă a fase larvar dos ĂĄcaros trombiculĂdeos que se caracteriza por ser parasita obrigatĂłrio e responsĂĄvel pelo aparecimento de sinais clĂnicos. Estes incluem prurido, vĂĄrias lesĂľes cutâneas, podendo, em alguns casos, surgir distĂşrbios gastrointestinais, neurolĂłgicos ou mesmo a morte do animal quando as infestaçþes sĂŁo massivas. Apesar da sua distribuição mundial, incluindo em Portugal, esta ĂŠ uma parasitose negligenciada, sobretudo no contexto da medicina veterinĂĄria de animais de companhia. Os estudos existentes sĂŁo escassos, contribuindo para o seu desconhecimento, e a sua verdadeira prevalĂŞncia nestes animais ĂŠ pouco conhecida a nĂvel mundial. Apesar do seu papel enquanto vetores de agentes patogĂŠnicos nĂŁo ser claro, alguns estudos jĂĄ demonstraram a presença de ADN de Anaplasma spp., Bartonella spp., Borrelia spp. e Rickettsia spp., em trombiculĂdeos.
O facto de os ĂĄcaros trombiculĂdeos afetarem vĂĄrias espĂŠcies animais, incluindo os animais de companhia e o ser humano, bem como o seu potencial papel no ciclo de manutenção de vĂĄrios agentes infeciosos, revela a importância de um maior conhecimento acerca desta parasitose, tanto ao nĂvel da comunidade cientĂfica como da comunidade mĂŠdico veterinĂĄria. Assim, esta revisĂŁo pretende reunir os dados disponĂveis Ă data quanto Ă epidemiologia, caracterĂsticas clĂnicas e tratamento desta parasitose, com especial enfoque em Portugal
A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection
There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP
Relating the CMSSM and SUGRA models with GUT scale and Super-GUT scale Supersymmetry Breaking
While the constrained minimal supersymmetric standard model (CMSSM) with
universal gaugino masses, m_{1/2}, scalar masses, m_0, and A-terms, A_0,
defined at some high energy scale (usually taken to be the GUT scale) is
motivated by general features of supergravity models, it does not carry all of
the constraints imposed by minimal supergravity (mSUGRA). In particular, the
CMSSM does not impose a relation between the trilinear and bilinear soft
supersymmetry breaking terms, B_0 = A_0 - m_0, nor does it impose the relation
between the soft scalar masses and the gravitino mass, m_0 = m_{3/2}. As a
consequence, tan(\beta) is computed given values of the other CMSSM input
parameters. By considering a Giudice-Masiero (GM) extension to mSUGRA, one can
introduce new parameters to the K\"ahler potential which are associated with
the Higgs sector and recover many of the standard CMSSM predictions. However,
depending on the value of A_0, one may have a gravitino or a neutralino dark
matter candidate. We also consider the consequences of imposing the
universality conditions above the GUT scale. This GM extension provides a
natural UV completion for the CMSSM.Comment: 16 pages, 11 figures; added erratum correcting several equations and
results in Sec.2, Sec.3 and 4 remain unaffected and conclusions unchange
Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome
Background: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). Objective: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. Methods: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. Results: We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad TH1/TH2/TH17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by TH1 effector T cells. Conclusions: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV
A search for new physics is presented based on an event signature of at least
three jets accompanied by large missing transverse momentum, using a data
sample corresponding to an integrated luminosity of 36 inverse picobarns
collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector
at the LHC. No excess of events is observed above the expected standard model
backgrounds, which are all estimated from the data. Exclusion limits are
presented for the constrained minimal supersymmetric extension of the standard
model. Cross section limits are also presented using simplified models with new
particles decaying to an undetected particle and one or two jets
Combined search for the quarks of a sequential fourth generation
Results are presented from a search for a fourth generation of quarks
produced singly or in pairs in a data set corresponding to an integrated
luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in
2011. A novel strategy has been developed for a combined search for quarks of
the up and down type in decay channels with at least one isolated muon or
electron. Limits on the mass of the fourth-generation quarks and the relevant
Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a
simple extension of the standard model with a sequential fourth generation of
fermions. The existence of mass-degenerate fourth-generation quarks with masses
below 685 GeV is excluded at 95% confidence level for minimal off-diagonal
mixing between the third- and the fourth-generation quarks. With a mass
difference of 25 GeV between the quark masses, the obtained limit on the masses
of the fourth-generation quarks shifts by about +/- 20 GeV. These results
significantly reduce the allowed parameter space for a fourth generation of
fermions.Comment: Replaced with published version. Added journal reference and DO
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