856 research outputs found
Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome, West syndrome, and X-linked infantile spasms sharing the common features of generally intractable early seizures and mental retardation. Disease-causing mutations are distributed in both the catalytic domain and in the large COOH terminus. In this report, we examine the functional consequences of some Rett mutations of CDKL5 together with some synthetically designed derivatives useful to underline the functional domains of the protein. The mutated CDKL5 derivatives have been subjected to in vitro kinase assays and analyzed for phosphorylation of the TEY (Thr-Glu-Tyr) motif within the activation loop, their subcellular localization, and the capacity of CDKL5 to interact with itself. Whereas wild-type CDKL5 autophosphorylates and mediates the phosphorylation of the methyl-CpG-binding protein 2 (MeCP2) in vitro, Rett-mutated proteins show both impaired and increased catalytic activity suggesting that a tight regulation of CDKL5 is required for correct brain functions. Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif. Eventually, we show that the COOH terminus regulates CDKL5 properties; in particular, it negatively influences the catalytic activity and is required for its proper sub-nuclear localization. We propose a model in which CDKL5 phosphorylation is required for its entrance into the nucleus whereas a portion of the COOH-terminal domain is responsible for a stable residency in this cellular compartment probably through protein-protein interactions
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All-sky search for short gravitational-wave bursts in the second Advanced LIGO and Advanced Virgo run
We present the results of a search for short-duration gravitational-wave transients in the data from the second observing run of Advanced LIGO and Advanced Virgo. We search for gravitational-wave transients with a duration of milliseconds to approximately one second in the 32-4096 Hz frequency band with minimal assumptions about the signal properties, thus targeting a wide variety of sources. We also perform a matched-filter search for gravitational-wave transients from cosmic string cusps for which the waveform is well modeled. The unmodeled search detected gravitational waves from several binary black hole mergers which have been identified by previous analyses. No other significant events have been found by either the unmodeled search or the cosmic string search. We thus present the search sensitivities for a variety of signal waveforms and report upper limits on the source rate density as a function of the characteristic frequency of the signal. These upper limits are a factor of 3 lower than the first observing run, with a 50% detection probability for gravitational-wave emissions with energies of ∼10-9 Mc2 at 153 Hz. For the search dedicated to cosmic string cusps we consider several loop distribution models, and present updated constraints from the same search done in the first observing run
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Search for intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network
Gravitational-wave astronomy has been firmly established with the detection of gravitational waves from the merger of ten stellar-mass binary black holes and a neutron star binary. This paper reports on the all-sky search for gravitational waves from intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network. The search uses three independent algorithms: two based on matched filtering of the data with waveform templates of gravitational-wave signals from compact binaries, and a third, model-independent algorithm that employs no signal model for the incoming signal. No intermediate mass black hole binary event is detected in this search. Consequently, we place upper limits on the merger rate density for a family of intermediate mass black hole binaries. In particular, we choose sources with total masses M=m1+m2ϵ[120,800] M and mass ratios q=m2/m1ϵ[0.1,1.0]. For the first time, this calculation is done using numerical relativity waveforms (which include higher modes) as models of the real emitted signal. We place a most stringent upper limit of 0.20 Gpc-3 yr-1 (in comoving units at the 90% confidence level) for equal-mass binaries with individual masses m1,2=100 M and dimensionless spins χ1,2=0.8 aligned with the orbital angular momentum of the binary. This improves by a factor of ∼5 that reported after Advanced LIGO's first observing run
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Search for Eccentric Binary Black Hole Mergers with Advanced LIGO and Advanced Virgo during Their First and Second Observing Runs
When formed through dynamical interactions, stellar-mass binary black holes (BBHs) may retain eccentric orbits (e > 0.1 at 10 Hz) detectable by ground-based gravitational-wave detectors. Eccentricity can therefore be used to differentiate dynamically formed binaries from isolated BBH mergers. Current template-based gravitational-wave searches do not use waveform models associated with eccentric orbits, rendering the search less efficient for eccentric binary systems. Here we present the results of a search for BBH mergers that inspiral in eccentric orbits using data from the first and second observing runs (O1 and O2) of Advanced LIGO and Advanced Virgo. We carried out the search with the coherent WaveBurst algorithm, which uses minimal assumptions on the signal morphology and does not rely on binary waveform templates. We show that it is sensitive to binary mergers with a detection range that is weakly dependent on eccentricity for all bound systems. Our search did not identify any new binary merger candidates. We interpret these results in light of eccentric binary formation models. We rule out formation channels with rates ⪆100 Gpc-3 yr-1 for e > 0.1, assuming a black hole mass spectrum with a power-law index ≲2
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Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model
We present results from a semicoherent search for continuous gravitational
waves from the low-mass X-ray binary Scorpius X-1, using a hidden Markov model
(HMM) to track spin wandering. This search improves on previous HMM-based
searches of LIGO data by using an improved frequency domain matched filter, the
-statistic, and by analysing data from Advanced LIGO's second
observing run. In the frequency range searched, from to
, we find no evidence of gravitational radiation. At
, the most sensitive search frequency, we report an upper
limit on gravitational wave strain (at 95\% confidence) of when marginalising over source inclination angle. This is the
most sensitive search for Scorpius X-1, to date, that is specifically designed
to be robust in the presence of spin wandering
Severe diarrhea outbreak in beef calves (Bos indicus) caused by G6P[11], an emergent genotype of bovine rotavirus group A
The episodes of diarrhea caused by neonatal bovine rotavirus group A (BoRVA) constitute one of the major health problems in the calf rearing worldwide. The main G (VP7) and P (VP4) genotypes of BoRVA strains involved in the etiology of diarrhea in calves are G6P[1], G10P[11], G6P[5], and G8P[1]. However, less frequently, other G and P genotypes have been described in BoRVA strains identified in diarrheic fecal samples of calves. This study describes the identification and molecular characterization of an emerging genotype (G6P[11]) in BoRVA strains involved in the etiology of a diarrhea outbreak in beef calves in a cattle herd of high production in extensive management system. The diarrhea outbreak, which showed high morbidity (60%) and lethality (7%) rates, occurred in calves (n= 384) Nelore (Bos indicus) up to 30-day-old from the State of Mato Grosso do Sul, Brazil. BoRVA was identified in 80% (16/20) of the fecal samples analyzed by polyacrylamide gel electrophoresis (PAGE) technique. In all PAGE-positive fecal samples were amplified products with 1,062-bp and 876-bp in the RT-PCR assays for VP7 (G type) and VP4 (VP8*) (P type) of BoRVA, respectively. The nucleotide sequence analysis of VP7 and VP4 genes of four wild-type BoRVA strains showed G6-III P[11]-III genotype/lineage. The G6P[11] genotype has been described in RVA strains of human and animal hosts, however, in calves this genotype was only identified in some cross-sectional studies and not as a single cause of diarrhea outbreaks in calves with high morbidity and lethality rates as described in this study. The monitoring of the G and P genotypes of BoRVA strains involved in diarrhea outbreaks in calves is important for both animal and public health by allowing the identification of the most frequent genotypes, the characterization of novel genotypes and to identify reassortments with genotypes described in animal and human hosts. The results of this study show the importance of the monitoring of the genotypes of BoRVA strains involved in episodes of bovine neonatal diarrhea as for characterization of frequency of occurrence and pathogenic potential of uncommon genotypes as for monitoring of the emergency of different BoRVA genotypes not included in commercial vaccines
Escherichia coli O157:H7 Productor de toxina Shiga aisladas de muestras de agua relacionadas a Establecimientos pecuarios de engorde a corral
Recientemente han ocurrido brotes debido vegetales contaminados por Escherichia coli productor de toxina Shiga (stec). Estos productos frescos se contaminan a través del contacto directo de heces bovinas (abono), o indirectamente a través de irrigación con agua contaminada. Este estudio tuvo como objetivo establecer la prevalencia de stec O157:H7 en muestras de agua relacionadas a establecimientos pecuarios de engorde a corral (epec) de la provincia de Entre Ríos, Argentina, y su eventual relación con cepas vinculadas a enfermedad transmitida por alimentos. Usando como indicadores microbiológicos, coliformes, Escherichia coli, y anaerobios sufito-reductores, se estudió la eficiencia en el saneamiento de los efluentes de un epec que contaba con un sistema de lagunas sanitarias. Entre abril/2009 y julio/2011 se estudiaron 320 muestras de agua vinculadas a efluentes de 11 epec. Las cepas fueron caracterizadas feno-genotípicamente y subtipificadas por macrorrestricción y electroforesis de campo pulsado. Algunos de los perfiles identificados están incluidos en la base de datos nacional, correspondiendo a cepas obtenidas de casos de Síndrome Urémico Hemolítico, diarrea, muestras alimenticias y de origen animal. Los epec deben implementar estrategias de control con objeto de limitar el ingreso de stec en el medioambiente acuático. En el sistema de lagunas sanitarias estudiado se constató una franca disminución de los indicares utilizados pero insuficiente para eliminar su aporte al ambiente. La optimización de su funcionamiento es función de su mantenimiento, en especial la frecuente remoción de barros de las primeras piletas
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