Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice

Cerebrovascular disease in childhood - Neuropsychological investigation of 14 cases

There are few studies about the development of a child after a cerebrovascular accident (CVA), and they usually describe problems such as diminishing in intellectual capacities, difficulties in linguistic and visual-motor skills, as well as in spatial organization and integration. In this study, there were 28 children participating, being 14 placed in the experimental group (EG) after clinical diagnosis and ischemic CVA imaging, and other 14 children without past history of CVA, who formed the control group (CG). The neuropsychological research protocol included an intelligence test, a visual-motor coordination test, human figure drawing, a cortical functions battery and the medical records of the children from the EG. The analysis of the results of this study revealed that the best performances after the CVA are related to the shortest time of functional recovery; CG presented better performances than EG in all the instruments used, in cognitive, perceptual and motor skills. It has been noticed that CVA may lead to intellectual reduction in case of a recurrence of the vascular insult.651414

Decentralized Estimation over Orthogonal Multiple-access Fading Channels in Wireless Sensor Networks - Optimal and Suboptimal Estimators

Optimal and suboptimal decentralized estimators in wireless sensor networks (WSNs) over orthogonal multiple-access fading channels are studied in this paper. Considering multiple-bit quantization before digital transmission, we develop maximum likelihood estimators (MLEs) with both known and unknown channel state information (CSI). When training symbols are available, we derive a MLE that is a special case of the MLE with unknown CSI. It implicitly uses the training symbols to estimate the channel coefficients and exploits the estimated CSI in an optimal way. To reduce the computational complexity, we propose suboptimal estimators. These estimators exploit both signal and data level redundant information to improve the estimation performance. The proposed MLEs reduce to traditional fusion based or diversity based estimators when communications or observations are perfect. By introducing a general message function, the proposed estimators can be applied when various analog or digital transmission schemes are used. The simulations show that the estimators using digital communications with multiple-bit quantization outperform the estimator using analog-and-forwarding transmission in fading channels. When considering the total bandwidth and energy constraints, the MLE using multiple-bit quantization is superior to that using binary quantization at medium and high observation signal-to-noise ratio levels

Stroke in patients with sickle cell disease - Clinical and neurological aspects

The aim of this study was to characterize a group of patients (n=8) with sickle cell disease (SCD) and ischemic stroke concerning the clinical, neurological, imaging and progressive aspects. Data were collected from records and completed with an interview of patients and their parents. In this study there were 8 patients with ages ranging from 10 to 23 years old; SCD diagnosis was given between one and two years of age with clinical features of fatigue and anemia. The stroke was ischemic in all individuals and the first cerebrovascular event occurred before 6 years of age; 3 patients had recurrence of stroke despite prophylactic blood transfusion therapy and both cerebral hemispheres were affected in 4 patients. Clinical and neurological current features observed were: acute pain crises, sialorrhea, mouth breathing, motor, and neuropsychological impairments resulting from cortical-subcortical structure lesions.661303

Cerebrovascular disease: language acquisition in preschool children

We describe ten children, aging 5 years and 1 month until 5 years and 11 months, when the phonoaudiological assessment was conducted. They are divided according to cerebrovascular disease, in CVD group (CVD-G) and control group (cG). Children were seen and CVD was confirmed in the acute phase at UNICAMP hospital. Audiologic assessment, protocol for Infant language assessment, and Peabody picture vocabulary test were used in the evaluations. The qualitative analysis of the subjects from a phonoaudiological and neurological point of view has shown the recovery of acquired language desorder (ALD) with no influence whatsoever in the development of 2 subjects and subtle language and/or learning process alterations for 3 subjects. The cases study has revealed that all aspects of language development in preschool children should be analyzed in an individual, quantitative, and qualitative basis to lead to conclusive findings.633B80781

Mitochondrial-dependent apoptosis in Huntington's disease human cybrids

We investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) vs. control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. Furthermore, apoptotic nuclei morphology and a moderate increase in caspase-3 activation, as well as increased levels of superoxide ions and hydroperoxides were observed in HD cybrids upon 3-NP or STS treatment. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death, linked to the loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their moderate susceptibility to mitochondrial-dependent apoptosi

In vitro binding and survival assays of Leishmania parasites to peripherical blood monocytes and monocyte-derived macrophages isolated from dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

<p>Abstract</p> <p>Background</p> <p>There are a few works considering the characterization of canine monocyte-derived macrophages as well as a standardized procedure for isolation, culture, and infection of these cells with <it>Leishmania</it>. We have performed several modifications in order to improve the canine monocyte-derived macrophage cultures. In addition, we have done a comparative study between monocytes and monocyte-derived macrophages from dogs naturally and experimentally infected with <it>L. chagasi</it>.</p> <p>Results</p> <p>In the presence of exogenous serum, opsonized <it>Leishmania </it>promastigotes binds better to monocytes/macrophages than without serum. Otherwise, this binding occurs due to the strict correlation between the opsonized biologic particles with the third receptor of the complement (CR3-CD11b/CD18). In fact, our assays with CD11b confirmed the importance of this receptor for canine cells and the <it>L. chagasi </it>experimental system. Moreover, monocytes obtained from naturally infected dogs have shown a higher number of monocytes bounded to promastigotes. The experimental results regarding survival have shown that promastigote forms of opsonized <it>L. chagasi </it>were more infective, because we found higher numbers of promastigotes bound to the different cells. As a consequence, after forty-eight hours of binding, higher numbers of amastigotes appeared inside monocyte-macrophages.</p> <p>Conclusion</p> <p>These studies have given support to continue comparative studies involving canine monocytes, monocyte-derived macrophages and peritoneal macrophages. Since we have standardized the canine cell culture, we are looking forward to determining the phenotypic properties of these cells before and after <it>L. chagasi </it>infection using flow cytometry.</p

CENP-V is required for centromere organization, chromosome alignment and cytokinesis

The mechanism of mitotic chromosome condensation is poorly understood, but even less is known about the mechanism of formation of the primary constriction, or centromere. A proteomic analysis of mitotic chromosome scaffolds led to the identification of CENP-V, a novel kinetochore protein related to a bacterial enzyme that detoxifies formaldehyde, a by-product of histone demethylation in eukaryotic cells. Overexpression of CENP-V leads to hypercondensation of pericentromeric heterochromatin, a phenotype that is abolished by mutations in the putative catalytic site. CENP-V depletion in HeLa cells leads to abnormal expansion of the primary constriction of mitotic chromosomes, mislocalization and destabilization of the chromosomal passenger complex (CPC) and alterations in the distribution of H3K9me3 in interphase nucleoplasm. CENP-V-depleted cells suffer defects in chromosome alignment in metaphase, lagging chromosomes in anaphase, failure of cytokinesis and rapid cell death. CENP-V provides a novel link between centromeric chromatin, the primary constriction and the CPC