Periapical cytokine expression in sickle cell disease.

PubMed

Ferreira, Shirlene Barbosa Pimentel; de Brito, Luciana Carla Neves; Oliveira, Michelle Pimenta; Maciel, Kamilla Faria; Martelli Júnior, Hercílio; Vieira, Leda Quercia; Sobrinho, Antônio Paulino Ribeiro

2015-03-01

Sickle cell anemia (SCA) is the most prevalent genetic disease worldwide. Patients with SCA exhibit increased levels of proinflammatory mediators as part of a permanently activated immunoinflammatory status. The aim of this study was to evaluate the mRNA expression levels of the cytokines interferon (IFN-γ), tumor necrosis factor, interleukin (IL-1β, IL-17A, IL-10), receptor activator for nuclear factor kappa B ligand, and the chemokines CCL2/MCP-1 and CCL5 in the periapical interstitial fluid from SCA individuals compared with healthy individuals. Samples were collected from 12 teeth of SCA patients and 12 non-SCA patients with apical periodontitis. In addition, 12 teeth were sampled from the periapical region of healthy patients with vital pulp (control). The expression of cytokine mRNA was detected by using real-time polymerase chain reaction. The expression of mRNA for the Th1-associated cytokines IFN-γ, tumor necrosis factor-α, and IL-1β were significantly higher in SCA individuals than in the control individuals (P < .05). Among Th1-associated cytokines, only IFN-γ was significantly increased in non-SCA compared with control patients (vital pulp). The expression of IL-17A mRNA was significant higher in SCA cases than in control samples (P < .05), whereas the IL-10 mRNA expression was significantly increased in SCA and non-SCA individuals when compared with the control group. Similar levels of receptor activator for nuclear factor kappa B ligand, CCL2, and CCL5 mRNA expression were observed in all samples. However, no significant differences were observed in the expression of cytokine or chemokine mRNA between SCA and non-SCA individuals (P > .05). The results were able to demonstrate that SCA patients presented prone proinflammatory ability, despite the fact that any differences in periapical immune responses between SCA and non-SCA individuals were not observed. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Brisk deep-tendon reflexes as a distinctive phenotype in an Argentinean spinocerebellar ataxia type 2 pedigree.

PubMed

Rosa, Alberto L; Molina, Irma; Kowaljow, Valeria; Conde, Cecilia B

2006-01-01

Slow saccades, postural/intention tremor, peripheral neuropathy, and decreased deep-tendon reflexes are valuable neurological signs for clinical suspicion of spinocerebellar ataxia type 2 (SCA2). We report the presence of abnormally brisk deep-tendon reflexes in nonsymptomatic carriers and mildly and severely affected subjects of a large Argentinean SCA2 pedigree. The identification of this distinctive SCA2 phenotype in an entire pedigree reinforces the current concept that clinical algorithms are of limited value as indicators for genetic testing in SCA. Combined with published pedigrees of SCA2 manifesting as levodopa-responsive parkinsonism, this finding suggests that modifier genes could influence the clinical phenotype of SCA2. Copyright (c) 2005 Movement Disorder Society.

Evaluation of popcorn germplasm for resistance to Sesamia nonagrioides attack.

PubMed

Butrón, A; Sandoya, G; Revilla, P; Ordás, A; Malvar, R A

2005-10-01

Popcorn adapted to Spanish conditions could be an interesting and profitable alternative to field corn. However, little is known about breeding popcorn germplasm for adaptation to Spain. Sesamia nonagrioides Lefèvbre is the main insect pest affecting popcorn quality and yield under Spanish growing conditions. The objectives of the study were the search for sources of resistance to S. nonagrioides among popcorn germplasm and to study the genetics of the resistance to S. nonagrioides attack. Eight breeding populations along with a five-inbred line diallel and two popcorn commercial checks were evaluated under S. nonagrioides infestation in 2 yr. Significant differences were found among general combining ability (GCA) effects for days to silking, S. nonagrioides tunnel length, general appearance of the ear, kernel moisture, and yield. Specific combining ability (SCA) effects were found to be significant for yield and ear damage. Therefore, heterotic patterns among popcorn materials should be taken into account to generate new popcorn hybrids that are not only more productive but also have higher kernel quality. Breeding popcorn populations BSP4APC0 and PSPW1C1 could be base germplasms in a breeding program for obtaining parental inbreds of healthy kernel popcorn hybrids. New inbred lines could be generated from the cross BP1 x BP2 that would have improved GCA and SCA effects for S. nonagrioides resistance when crossed to South American inbreds.

Cardiac side population cells and Sca-1-positive cells.

PubMed

Nagai, Toshio; Matsuura, Katsuhisa; Komuro, Issei

2013-01-01

Since the resident cardiac stem/progenitor cells were discovered, their ability to maintain the architecture and functional integrity of adult heart has been broadly explored. The methods for isolation and purification of the cardiac stem cells are crucial for the precise analysis of their developmental origin and intrinsic potential as tissue stem cells. Stem cell antigen-1 (Sca-1) is one of the useful cell surface markers to purify the cardiac progenitor cells. Another purification strategy is based on the high efflux ability of the dye, which is a common feature of tissue stem cells. These dye-extruding cells have been called side population cells because they locate in the side of dye-retaining cells after fluorescent cell sorting. In this chapter, we describe the methodology for the isolation of cardiac SP cells and Sca-1 positive cells.

Determinants of academic performance in children with sickle cell anaemia

PubMed Central

2013-01-01

Background Some factors are known to influence the academic performance of children with Sickle Cell Anaemia (SCA). Information on their effects in these children is limited in Nigeria. The factors which influence academic performance of children with SCA in Enugu, Nigeria are determined in this study. Methods Consecutive children with SCA aged 5–11 years were recruited at the weekly sickle cell clinic of the University of Nigeria Teaching Hospital (UNTH) Enugu, Nigeria. Their age- and sex- matched normal classmates were recruited as controls. The total number of days of school absence for 2009/2010 academic session was obtained for each pair of pupils from the class attendance register. Academic performance was assessed using the average of the overall scores in the three term examinations of same session. Intelligence ability was determined with Draw-A-Person Quotient (DAPQ) using the Draw-A-Person Test while socio-economic status was determined using the occupational status and educational attainment of each parent. Results Academic performance of children with SCA showed statistically significant association with their socio-economic status (χ2 = 9.626, p = 0.047), and significant correlation with DAPQ (r = 0.394, p = 0.000) and age (r = -0.412, p = 0.000). However, no significant relationship existed between academic performance and school absence in children with SCA (r = -0.080, p = 0.453). Conclusions Academic performance of children with SCA is influenced by their intelligence ability, age and socio-economic status but not negatively affected by their increased school absenteeism. PMID:24246094

Determinants of academic performance in children with sickle cell anaemia.

PubMed

Ezenwosu, Osita U; Emodi, Ifeoma J; Ikefuna, Anthony N; Chukwu, Barth F; Osuorah, Chidiebere D

2013-11-19

Some factors are known to influence the academic performance of children with Sickle Cell Anaemia (SCA). Information on their effects in these children is limited in Nigeria. The factors which influence academic performance of children with SCA in Enugu, Nigeria are determined in this study. Consecutive children with SCA aged 5-11 years were recruited at the weekly sickle cell clinic of the University of Nigeria Teaching Hospital (UNTH) Enugu, Nigeria. Their age- and sex- matched normal classmates were recruited as controls. The total number of days of school absence for 2009/2010 academic session was obtained for each pair of pupils from the class attendance register. Academic performance was assessed using the average of the overall scores in the three term examinations of same session. Intelligence ability was determined with Draw-A-Person Quotient (DAPQ) using the Draw-A-Person Test while socio-economic status was determined using the occupational status and educational attainment of each parent. Academic performance of children with SCA showed statistically significant association with their socio-economic status (χ2 = 9.626, p = 0.047), and significant correlation with DAPQ (r = 0.394, p = 0.000) and age (r = -0.412, p = 0.000). However, no significant relationship existed between academic performance and school absence in children with SCA (r = -0.080, p = 0.453). Academic performance of children with SCA is influenced by their intelligence ability, age and socio-economic status but not negatively affected by their increased school absenteeism.

Neurochemical abnormalities in premanifest and early spinocerebellar ataxias.

PubMed

Joers, James M; Deelchand, Dinesh K; Lyu, Tianmeng; Emir, Uzay E; Hutter, Diane; Gomez, Christopher M; Bushara, Khalaf O; Eberly, Lynn E; Öz, Gülin

2018-04-01

To investigate whether early neurochemical abnormalities are detectable by high-field magnetic resonance spectroscopy (MRS) in individuals with spinocerebellar ataxias (SCAs) 1, 2, 3, and 6, including patients without manifestation of ataxia. A cohort of 100 subjects (N = 18-21 in each SCA group, including premanifest mutation carriers; mean score on the Scale for the Assessment and Rating of Ataxia [SARA] <10 for all genotypes, and 22 matched controls) was scanned at 7 Tesla to obtain neurochemical profiles of the cerebellum and brainstem. A novel multivariate approach (distance-weighted discrimination) was used to combine regional profiles into an "MRS score." MRS scores robustly distinguished individuals with SCA from controls, with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6). Premanifest mutation carriers with estimated disease onset within 10 years had MRS scores in the range of early-manifest SCA subjects. Levels of neuronal and glial markers significantly correlated with SARA and an Activities of Daily Living score in subjects with SCA. Regional neurochemical alterations were different between SCAs at comparable disease severity, with SCA2 displaying the most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6. Neurochemical abnormalities are detectable in individuals before manifest disease, which may allow premanifest enrollment in future SCA trials. Correlations with ataxia and quality-of-life scores show that neurochemical levels can serve as clinically meaningful endpoints in trials. Ranking of SCA types by degree of neurochemical abnormalities indicates that the neurochemistry may reflect synaptic function or density. Ann Neurol 2018;83:816-829. © 2018 American Neurological Association.

Spinocerebellar ataxia: a critical review of cognitive and socio-cognitive deficits.

PubMed

Giocondo, Flora; Curcio, Giuseppe

2018-02-01

The primary aim of this contribution is to provide a critical discussion on cognitive and sociocognitive implications of spinocerebellar ataxias (SCAs) subtypes. The term SCA refers to a group of neurodegenerative disorders that have been increasingly investigated in the last years, sharing the characteristic of progressive ataxia resulting from degeneration of cerebellum and its connections. In past decades only involvement of cerebellum in behaviour and timing has been investigated, bringing to the belief about its central role in timing of movement and sensation, particularly for short intervals of time. Only very recently the cerebellum has been considered as a potentially important centre for cognitive processing and related spheres of social cognition, so that several studies with SCA patients have been carried out on these topics: as a consequence a section of this review will be dedicated to this important aspect. After a brief discussion on most commonly used methods to assess cognitive and socio-cognitive abilities in SCAs, cognitive and socio-cognitive profiles of principal SCA subtypes have been thoroughly reviewed and critically discussed. Due to the very poor literature in this field the most common SCA variants have been fully included (i.e. SCA1, SCA2, SCA3, SCA6 and SCA7). A comparative summary of the main characteristics of cognitive and social cognition deficit in SCA subtypes has been proposed together with a research agenda for future investigation in this field principally aimed at using measures of cognition and/or social cognition as potential predictors of the extent and progression of disease.

A Third Locus for Autosomal Dominant Cerebellar Ataxia Type 1 Maps to Chromosome 14q24.3-qter: Evidence for the Existence of a Fourth Locus

PubMed Central

Stevanin, Giovanni; Le Guern, Eric; Ravisé, Nicole; Chneiweiss, Hervé; Dürr, Alexandra; Cancel, Géraldine; Vignal, Alain; Boch, Anne-Laure; Ruberg, Merle; Penet, Christiane; Pothin, Yolaine; Lagroua, Isabelle; Haguenau, Michel; Rancurel, Gérald; Weissenbach, Jean; Agid, Yves; Brice, Alexis

1994-01-01

The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage analysis in a non-SCA1/non-SCA2 family and have confirmed its existence in a second such family. We suggest designating this new locus “SCA3.” Combined analysis of the two families restricted the SCA3 locus to a 15-cM interval between markers D14S67 and D14S81. The gene for Machado-Joseph disease (MJD), a clinically different form of ADCA type I, has been recently assigned to chromosome 14q24.3-q32. Although the SCA3 locus is within the MJD region, linkage analyses cannot yet demonstrate whether they result from mutations of the same gene. Linkage to all three loci (SCA1, SCA2, and SCA3) was excluded in another family, which indicates the existence of a fourth ADCA type I locus. PMID:8279460

Cognitive findings in spinocerebellar ataxia type 2: relationship to genetic and clinical variables.

PubMed

Le Pira, Francesco; Zappalà, Giuseppe; Saponara, Riccardo; Domina, Elisabetta; Restivo, Domenico; Reggio, Ester; Nicoletti, Alessandra; Giuffrida, Salvatore

2002-09-15

Several authors have recently reported a broad cognitive impairment in autosomal dominant cerebellar ataxias (ADCAs) patients. However, only a few studies on neuropsychological features in spinocerebellar ataxia type 2 (SCA2) patients are present in the current literature. The aim of this study is to evaluate the cognitive impairment in a wide sample of SCA2 patients and to verify the role of different disease-related factors (age of onset, disease duration, and clinical severity) on intellectual abilities. We administered a battery of neuropsychological tests assessing handedness, attention, short- and long-term verbal and visuo-spatial memory, executive functions, constructive abilities, general intellectual abilities and depression to 18 SCA2 patients belonging to eight families who came to our observation. Evidence of impaired verbal memory, executive functions and attention was found. The cognitive status was partially related to clinical severity rather than to disease duration or age at onset of symptoms. We partially confirmed data on cognitive defects already reported by others but we also found defective attention skills as well as significant lower performances in a nonverbal intelligence task.

The Error Structure of the SMAP Single and Dual Channel Soil Moisture Retrievals

NASA Astrophysics Data System (ADS)

Dong, Jianzhi; Crow, Wade T.; Bindlish, Rajat

2018-01-01

Knowledge of the temporal error structure for remotely sensed surface soil moisture retrievals can improve our ability to exploit them for hydrologic and climate studies. This study employs a triple collocation analysis to investigate both the total variance and temporal autocorrelation of errors in Soil Moisture Active and Passive (SMAP) products generated from two separate soil moisture retrieval algorithms, the vertically polarized brightness temperature-based single-channel algorithm (SCA-V, the current baseline SMAP algorithm) and the dual-channel algorithm (DCA). A key assumption made in SCA-V is that real-time vegetation opacity can be accurately captured using only a climatology for vegetation opacity. Results demonstrate that while SCA-V generally outperforms DCA, SCA-V can produce larger total errors when this assumption is significantly violated by interannual variability in vegetation health and biomass. Furthermore, larger autocorrelated errors in SCA-V retrievals are found in areas with relatively large vegetation opacity deviations from climatological expectations. This implies that a significant portion of the autocorrelated error in SCA-V is attributable to the violation of its vegetation opacity climatology assumption and suggests that utilizing a real (as opposed to climatological) vegetation opacity time series in the SCA-V algorithm would reduce the magnitude of autocorrelated soil moisture retrieval errors.

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6

PubMed Central

Tezenas du Montcel, Sophie; Durr, Alexandra; Rakowicz, Maria; Nanetti, Lorenzo; Charles, Perrine; Sulek, Anna; Mariotti, Caterina; Rola, Rafal; Schols, Ludger; Bauer, Peter; Dufaure-Garé, Isabelle; Jacobi, Heike; Forlani, Sylvie; Schmitz-Hübsch, Tanja; Filla, Alessandro; Timmann, Dagmar; van de Warrenburg, Bart P; Marelli, Cecila; Kang, Jun-Suk; Giunti, Paola; Cook, Arron; Baliko, Laszlo; Bela, Melegh; Boesch, Sylvia; Szymanski, Sandra; Berciano, José; Infante, Jon; Buerk, Katrin; Masciullo, Marcella; Di Fabio, Roberto; Depondt, Chantal; Ratka, Susanne; Stevanin, Giovanni; Klockgether, Thomas; Brice, Alexis; Golmard, Jean-Louis

2014-01-01

Background The most common spinocerebellar ataxias (SCA)—SCA1, SCA2, SCA3, and SCA6—are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. Methods We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. Results For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (−0.105±0.005 and −0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: −0.049±0.002 and −0.090±0.009, respectively; normal: +0.013±0.005 and −0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. Conclusions These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. ClinicalTrials.gov, number NCT01037777 and NCT00136630 for the French patients. PMID:24780882

Cardiac Stem Cell Secretome Protects Cardiomyocytes from Hypoxic Injury Partly via Monocyte Chemotactic Protein-1-Dependent Mechanism

PubMed Central

Park, Chi-Yeon; Choi, Seung-Cheol; Kim, Jong-Ho; Choi, Ji-Hyun; Joo, Hyung Joon; Hong, Soon Jun; Lim, Do-Sun

2016-01-01

Cardiac stem cells (CSCs) were known to secrete diverse paracrine factors leading to functional improvement and beneficial left ventricular remodeling via activation of the endogenous pro-survival signaling pathway. However, little is known about the paracrine factors secreted by CSCs and their roles in cardiomyocyte survival during hypoxic condition mimicking the post-myocardial infarction environment. We established Sca-1+/CD31− human telomerase reverse transcriptase-immortalized CSCs (Sca-1+/CD31− CSCshTERT), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31− CSCshTERT sustained proliferation ability even after long-term culture exceeding 100 population doublings, and represented multi-differentiation potential into cardiomyogenic, endothelial, adipogenic, and osteogenic lineages. Dominant factors secreted from Sca-1+/CD31− CSCshTERT were EGF, TGF-β1, IGF-1, IGF-2, MCP-1, HGF R, and IL-6. Among these, MCP-1 was the most predominant factor in Sca-1+/CD31− CSCshTERT conditioned medium (CM). Sca-1+/CD31− CSCshTERT CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31− CSCshTERT CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31− CSCshTERT exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31− CSCshTERT CM protected cardiomyocytes from hypoxic injury partly via MCP-1-dependent mechanism. Thus, they are valuable sources for in vitro and in vivo studies in the cardiovascular field. PMID:27231894

The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2.

PubMed Central

Stevanin, G; Cancel, G; Dürr, A; Chneiweiss, H; Dubourg, O; Weissenbach, J; Cann, H M; Agid, Y; Brice, A

1995-01-01

SCA3, the gene for spinal cerebellar ataxia 3, was recently mapped to a 15-cM interval between D14S67 and D14S81 on chromosome 14q, by linkage analysis in two families of French ancestry. The SCA3 candidate region has now been refined by linkage analysis with four new microsatellite markers (D14S256, D14S291, D14S280, and AFM343vf1) in the same two families, in which 19 additional individuals were genotyped, and in a third French family. Combined two-point linkage analyses show that the new markers, D14S280 and AFM343vf1, are tightly linked to the SCA3 locus, with maximal lod scores, at recombination fraction, (theta) = .00, of 7.05 and 13.70, respectively. Combined multipoint and recombinant haplotype analyses localize the SCA3 locus to a 3-cM interval flanked by D14S291 and D14S81. The same allele for D14S280 segregates with the disease locus in the three kindreds. This allele is frequent in the French population, however, and linkage disequilibrium is not clearly established. The SCA3 locus remains within the 29-cM region on 14q24.3-q32.2 containing the gene for the Machado-Joseph disease, which is clinically related to the phenotype determined by SCA3, but it cannot yet be concluded that both diseases result from alterations of the same gene. PMID:7825578

Suppression Analysis Reveals a Functional Difference between the Serines in Positions Two and Five in the Consensus Sequence of the C-Terminal Domain of Yeast RNA Polymerase II

PubMed Central

Yuryev, A.; Corden, J. L.

1996-01-01

The largest subunit of RNA polymerase II contains a repetitive C-terminal domain (CTD) consisting of tandem repeats of the consensus sequence Tyr(1)Ser(2)Pro(3)Thr(4) Ser(5)Pro(6) Ser(7). Substitution of nonphosphorylatable amino acids at positions two or five of the Saccharomyces cerevisiae CTD is lethal. We developed a selection ssytem for isolating suppressors of this lethal phenotype and cloned a gene, SCA1 (suppressor of CTD alanine), which complements recessive suppressors of lethal multiple-substitution mutations. A partial deletion of SCA1 (sca1Δ::hisG) suppresses alanine or glutamate substitutions at position two of the consensus CTD sequence, and a lethal CTD truncation mutation, but SCA1 deletion does not suppress alanine or glutamate substitutions at position five. SCA1 is identical to SRB9, a suppressor of a cold-sensitive CTD truncation mutation. Strains carrying dominant SRB mutations have the same suppression properties as a sca1Δ::hisG strain. These results reveal a functional difference between positions two and five of the consensus CTD heptapeptide repeat. The ability of SCA1 and SRB mutant alleles to suppress CTD truncation mutations suggest that substitutions at position two, but not at position five, cause a defect in RNA polymerase II function similar to that introduced by CTD truncation. PMID:8725217

Breeding maize for resistance to ear rot caused by Fusarium moniliforme.

PubMed

Hefny, M; Attaa, S; Bayoumi, T; Ammar, S; El-Bramawy, M

2012-01-15

Maize ear rots are among the most important impediments to increased maize production in Egypt. The present research was conducted to estimate combining abilities, heterosis and correlation coefficients for resistance to ear rot disease in seven corn inbred lines and their 21 crosses under field conditions. Results demonstrated that both additive and non-additive gene actions were responsible for the genetic expression of all characters with the preponderance of non-additive actions for days to 50% silking. The parental line L51 was the best combiner for earliness, low infection severity %, high phenols content, short plants and reasonable grain yield, while L101 was good combiner for low ear rot infection only. The cross: L122 x L84, L122 x L101, L51 x L101, L76 x L36, L76 x L84, L36 x L84, L36 x L81 and L36 x L101 which involved one or both parents with good General Combining Ability (GCA) effects expressed useful significant heterosis and Specific Combining Ability (SCA) effects for low infection severity %, high phenol contents, early silking, tall plants and high grain yield. Phenotypic and genotypic correlation coefficients suggest that selection for resistance to ear rot should identify lines with high yielding ability, early silking, tall plants, high phenols content and chitinase activity.

Comparison of ScaRaB, GOES 8, Aircraft, and Surface Observations of the Absorption of Solar Radiation by Clouds

NASA Technical Reports Server (NTRS)

Pope, Shelly K.; Valero, Francisco P. J.; Collins, William D.; Minnis, Patrick

2002-01-01

Data obtained by the Scanner for Radiation Budget (ScaRaB) instrument on the Meteor 3 satellite have been analyzed and compared to satellite (GOES 8), aircraft (Radiation Measurement System, RAMS), and surface (Baseline Solar Radiation Network (BSRN), Solar and Infrared Observations System (SIROS), and RAMS) measurements of irradiance obtained during the Atmospheric Radiation Measurements Enhanced Shortwave Experiment (ARESE). It is found that the ScaRaB data covering the period from March 1994 to February 1995 (the instrument's operational lifetime) indicate excess absorption of solar radiation by the cloudy atmosphere in agreement with previous aircraft, surface, and GOES 8 results. The full ScaRaB data set combined with BSRN and SIROS surface observations gives an average all-sky absorptance of 0.28. The GOES 8 data set combined with RAMS surface observations gives an average all-sky absorptance of 0.26. The aircraft data set (RAMS) gives a mean all-sky absorptance of 0.24 (for the column between 0.5 and 13 km).

Loss of Intrinsic Organization of Cerebellar Networks in Spinocerebellar Ataxia Type 1: Correlates with Disease Severity and Duration

PubMed Central

Peri, Eitan; Chen, E. Elinor; Ben-Jacob, Eshel; Gomez, Christopher M.

2011-01-01

The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of cerebellar degenerative disorders, characterized by progressive gait unsteadiness, hand incoordination, and dysarthria. The mutational mechanism in SCA1, a dominantly inherited form of SCA, consists of an expanded trinucleotide CAG repeat. In SCA1, there is loss of Purkinje cells, neuronal loss in dentate nucleus, olives, and pontine nuclei. In the present study, we sought to apply intrinsic functional connectivity analysis combined with diffusion tensor imaging to define the state of cerebellar connectivity in SCA1. Our results on the intrinsic functional connectivity in lateral cerebellum and thalamus showed progressive organizational changes in SCA1 noted as a progressive increase in the absolute value of the correlation coefficients. In the lateral cerebellum, the anatomical organization of functional clusters seen as parasagittal bands in controls is lost, changing to a patchy appearance in SCA1. Lastly, only fractional anisotropy in the superior peduncle and changes in functional organization in thalamus showed a linear dependence to duration and severity of disease. The present pilot work represents an initial effort describing connectivity biomarkers of disease progression in SCA1. The functional changes detected with intrinsic functional analysis and diffusion tensor imaging suggest that disease progression can be analyzed as a disconnection syndrome. PMID:20886327

Bilateral subclavian origin of the bronchial arteries combined with absence of other origins.

PubMed

Jie, Bing; Sun, Xi-Wen; Yu, Dong; Jiang, Sen

2014-08-01

There are numerous anatomical variations of the sites of origin of the bronchial arteries (BAs). A subclavian origin of a BA involves an aberrant artery that originates from the subclavian artery (SCA) or its branches. However, the aberrant artery usually originates directly from the SCA, and an SCA-origin BA arising from the branches of the SCA is rare. We herein present an extremely rare case of a right BA arising from the ipsilateral costocervical trunk, and a left BA arising from the ipsilateral thyrocervical trunk, in the absence of other origins of the BA. This anatomical variation was detected during pretherapeutic evaluation by multidetector-row computed tomography and confirmed by selective angiography. Recognition of these anatomic variations is important to surgical, diagnostic, and interventional radiologic procedures in the thorax.

Diallel analysis of corn for special use as corn grits: determining the main genetic effects for corn gritting ability.

PubMed

Conrado, T V; Scapim, C A; Bignotto, L S; Pinto, R J B; Freitas, I L J; Amaral, A T; Pinheiro, A C

2014-08-26

Corn grits are used for various purposes such as flakes, snacks, livestock feed, hominy, extruded products, beer, etc. The grit size proportion varies according to the hybrid, and thus, once the use of the grits is linked to the particle size, determining the genetic effects is essential to develop hybrids for any specific use. For this purpose a complete diallel series of crosses, involving eight parents, was performed near Maringá, PR, Brazil. The objective of this study was to evaluate the general (GCA) and specific (SCA) combining abilities of 28 progeny for selection of hybrids for breeding programs and extraction of inbred lines for hybrid development. The response variables, such as plant height, ear insertion height, crop stand, grain yield, and grits, small grits and bran production, were gauged and appraised for each of the 28 progeny. The trait effects and GCA were significant for all response variables, while for SCA, only grain yield and crop stand showed significance (P < 0.05), according to Griffing (1955) analysis. A significant weak negative partial correlation was found between grain yield and grits conversion. In relation to the hybrid selection for breeding programs, the parent IAC Nelore was highly recommended for recurrent selection and the hybrids IPR 119 x HT 392 and IAC Nelore x HD 332 for the extraction of pure lines for hybrid development.

Engaging Key Stakeholders in Climate Change: A Community-Based Project for Youth-Led Participatory Climate Action

NASA Astrophysics Data System (ADS)

Trott, Carlie D.

Few studies have examined how youth think about, and take action on climate change and far fewer have sought to facilitate their engagement using participatory methods. This dissertation evaluated the impacts of Science, Camera, Action! (SCA), a novel after-school program that combined climate change education with participatory action through photovoice. The specific aims of this study were to: (1) Evaluate the impacts of SCA on youth participants' climate change knowledge, attitudes, and behaviors; (2) Examine how SCA participation served to empower youth agency; and (3) Explore SCA's influence on youths' science engagement. Participants were 55 youths (ages 10 to 12) across three Boys and Girls Club sites in Northern Colorado. SCA's Science component used interactive activities to demonstrate the interrelationships between Earth's changing climate, ecosystems, and sustainable actions within communities. Photovoice, SCA's Camera component, was used to explore youths' climate change perspectives and to identify opportunities for their active engagement. Finally, SCA's Action component aimed to cultivate youth potential as agents of change in their families and communities through the development and implementation of youth-led action projects. Action projects included local policy advocacy, a tree-planting campaign, a photo gallery opening, development of a website, and the establishment of a Boys and Girls Club community garden. To evaluate SCA impacts, a combination of survey and focus group methods were used. Following the program, youth demonstrated increased knowledge of the scientific and social dimensions of the causes and consequences of climate change, as well as its solutions through human action. Though participants expressed a mix of positive (e.g., hope) and negative (e.g., sadness) emotions about climate change, they left the program with an increased sense of respect for nature, an enhanced sense of environmental responsibility, and a greater sense of urgency towards the need for climate change action. Further, participants reported increased engagement in personal pro-environmental behaviors, an enhanced sense of agency in the context of climate change, and provided strong evidence of their role as agents of change in family and community contexts. Through SCA, participants gained a deeper appreciation for science (e.g., in school, careers, and society) and reported increased interest, participation, confidence, and performance in school science. Findings contribute to the vast and growing psychology literature on climate change perceptions and action, and from the understudied perspective of youth. Through a combination of innovative methods and interactive projects, the youth in this study gained a number of psychosocial and educational benefits, while tangibly contributing to the sustainable transformation of their families and communities. Findings of this dissertation have implications for educational programs, youth organizing, and interventions aimed to strengthen youths' active engagement with critical social and scientific issues that impact their lives.

Partial Body Weight-Supported Treadmill Training in Spinocerebellar Ataxia.

PubMed

de Oliveira, Laura Alice Santos; Martins, Camilla Polonini; Horsczaruk, Carlos Henrique Ramos; da Silva, Débora Cristina Lima; Vasconcellos, Luiz Felipe; Lopes, Agnaldo José; Meira Mainenti, Míriam Raquel; Rodrigues, Erika de Carvalho

2018-01-01

The motor impairments related to gait and balance have a huge impact on the life of individuals with spinocerebellar ataxia (SCA). Here, the aim was to assess the possibility of retraining gait, improving cardiopulmonary capacity, and challenging balance during gait in SCA using a partial body weight support (BWS) and a treadmill. Also, the effects of this training over functionality and quality of life were investigated. Eight SCA patients were engaged in the first stage of the study that focused on gait training and cardiovascular conditioning. From those, five took part in a second stage of the study centered on dynamic balance training during gait. The first and second stages lasted 8 and 10 weeks, respectively, both comprising sessions of 50 min (2 times per week). The results showed that gait training using partial BWS significantly increased gait performance, treadmill inclination, duration of exercise, and cardiopulmonary capacity in individuals with SCA. After the second stage, balance improvements were also found. Combining gait training and challenging tasks to the postural control system in SCA individuals is viable, well tolerated by patients with SCA, and resulted in changes in capacity for walking and balance.

Partial Body Weight-Supported Treadmill Training in Spinocerebellar Ataxia

PubMed Central

Martins, Camilla Polonini; Horsczaruk, Carlos Henrique Ramos; da Silva, Débora Cristina Lima; Meira Mainenti, Míriam Raquel; Rodrigues, Erika de Carvalho

2018-01-01

Background and Purpose The motor impairments related to gait and balance have a huge impact on the life of individuals with spinocerebellar ataxia (SCA). Here, the aim was to assess the possibility of retraining gait, improving cardiopulmonary capacity, and challenging balance during gait in SCA using a partial body weight support (BWS) and a treadmill. Also, the effects of this training over functionality and quality of life were investigated. Methods Eight SCA patients were engaged in the first stage of the study that focused on gait training and cardiovascular conditioning. From those, five took part in a second stage of the study centered on dynamic balance training during gait. The first and second stages lasted 8 and 10 weeks, respectively, both comprising sessions of 50 min (2 times per week). Results The results showed that gait training using partial BWS significantly increased gait performance, treadmill inclination, duration of exercise, and cardiopulmonary capacity in individuals with SCA. After the second stage, balance improvements were also found. Conclusion Combining gait training and challenging tasks to the postural control system in SCA individuals is viable, well tolerated by patients with SCA, and resulted in changes in capacity for walking and balance. PMID:29535874

Applications systems verification and transfer project. Volume 3: Operational applications of satellite snow cover observations in California

NASA Technical Reports Server (NTRS)

Brown, A. J.; Hannaford, J. F.

1981-01-01

Five southern Sierra snowmelt basins and two northern Sierra-Southern Cascade snowmelt basins were used to evaluate the effect on operational water supply forecasting from satellite imagery. Manual photointerpretation techniques were used to obtain SCA and equivalent snow line for the years 1973 to 1979 for the seven test basins using LANDSAT imagery and GOES imagery. The use of SCA was tested operationally in 1977-79. Results indicate the addition of SCA improve the water supply forecasts during the snowmelt phase for these basins where there may be an unusual distribution of snowpack throughout the basin, or where there is a limited amount of real time data available. A high correlation to runoff was obtained when SCA was combined with snow water content data obtained from reporting snow sensors.

Heterotic patterns in rapeseed (Brassica napus L.): I. Crosses between spring and Chinese semi-winter lines.

PubMed

Qian, W; Sass, O; Meng, J; Li, M; Frauen, M; Jung, C

2007-06-01

Chinese semi-winter rapeseed is genetically diverse from Canadian and European spring rapeseed. This study was conducted to evaluate the potential of semi-winter rapeseed for spring rapeseed hybrid breeding, to assess the genetic effects involved, and to estimate the correlation of parental genetic distance (GD) with hybrid performance, heterosis, general combining ability (GCA) and specific combining ability (SCA) in crosses between spring and semi-winter rapeseed lines. Four spring male sterile lines from Germany and Canada as testers were crossed with 13 Chinese semi-winter rapeseed lines to develop 52 hybrids, which were evaluated together with their parents and commercial hybrids for seed yield and oil content in three sets of field trials with 8 environments in Canada and Europe. The Chinese parental lines were not adapted to local environmental conditions as demonstrated by poor seed yields per se. However, the hybrids between the Chinese parents and the adapted spring rapeseed lines exhibited high heterosis for seed yield. The average mid-parent heterosis was 15% and ca. 50% of the hybrids were superior to the respective hybrid control across three sets of field trials. Additive gene effects mainly contributed to hybrid performance since the mean squares of GCA were higher as compared to SCA. The correlation between parental GD and hybrid performance and heterosis was found to be low whereas the correlation between GCA((f + m)) and hybrid performance was high and significant in each set of field trials, with an average of r = 0.87 for seed yield and r = 0.89 for oil content, indicating that hybrid performance can be predicted by GCA((f + m)). These results demonstrate that Chinese semi-winter rapeseed germplasm has a great potential to increase seed yield in spring rapeseed hybrid breeding programs in Canada and Europe.

Mutant Ataxin-1 Inhibits Neural Progenitor Cell Proliferation in SCA1

PubMed Central

Cvetanovic, Marija; Hu, Yuan-Shih; Opal, Puneet

2017-01-01

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by the expansion of a polyglutamine (Q) repeat tract in the protein ataxin-1 (ATXN1). Beginning as a cerebellar ataxic disorder, SCA1 progresses to involve the cerebral cortex, hippocampus, and brainstem. Using SCA1 knock-in mice that mirror the complexity of the human disease, we report a significant decrease in the capacity of adult neuronal progenitor cells (NPCs) to proliferate. Remarkably, a decrease in NPCs proliferation can be observed in vitro, outside the degenerative milieu of surrounding neurons or glia, demonstrating that mutant ATXN1 acting cell autonomously within progenitor cells interferes with their ability to proliferate. Our findings suggest that compromised adult neurogenesis contributes to the progressive pathology of the disease particularly in areas such as the hippocampus and cerebral cortex where stem cells provide neurotropic factors and participate in adult neurogenesis. These findings not only shed light on the biology of the disease but also have therapeutic implications in any future stem cell- based clinical trials. PMID:27306906

Mutant Ataxin-1 Inhibits Neural Progenitor Cell Proliferation in SCA1.

PubMed

Cvetanovic, Marija; Hu, Yuan-Shih; Opal, Puneet

2017-04-01

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by the expansion of a polyglutamine (Q) repeat tract in the protein ataxin-1 (ATXN1). Beginning as a cerebellar ataxic disorder, SCA1 progresses to involve the cerebral cortex, hippocampus, and brainstem. Using SCA1 knock-in mice that mirror the complexity of the human disease, we report a significant decrease in the capacity of adult neuronal progenitor cells (NPCs) to proliferate. Remarkably, a decrease in NPCs proliferation can be observed in vitro, outside the degenerative milieu of surrounding neurons or glia, demonstrating that mutant ATXN1 acting cell autonomously within progenitor cells interferes with their ability to proliferate. Our findings suggest that compromised adult neurogenesis contributes to the progressive pathology of the disease particularly in areas such as the hippocampus and cerebral cortex where stem cells provide neurotropic factors and participate in adult neurogenesis. These findings not only shed light on the biology of the disease but also have therapeutic implications in any future stem cell-based clinical trials.

Genetic effects and genotype × environment interactions govern seed oil content in Brassica napus L.

PubMed

Guo, Yanli; Si, Ping; Wang, Nan; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Zou, Jitao; Fu, Tingdong; Shen, Jinxiong

2017-01-05

As seed oil content (OC) is a key measure of rapeseed quality, better understanding the genetic basis of OC would greatly facilitate the breeding of high-oil cultivars. Here, we investigated the components of genetic effects and genotype × environment interactions (GE) that govern OC using a full diallel set of nine parents, which represented a wide range of the Chinese rapeseed cultivars and pure lines with various OCs. Our results from an embryo-cytoplasm-maternal (GoCGm) model for diploid seeds showed that OC was primarily determined by genetic effects (V G ) and GE (V GE ), which together accounted for 86.19% of the phenotypic variance (V P ). GE (V GE ) alone accounted for 51.68% of the total genetic variance, indicating the importance of GE interaction for OC. Furthermore, maternal variance explained 75.03% of the total genetic variance, embryo and cytoplasmic effects accounted for 21.02% and 3.95%, respectively. We also found that the OC of F 1 seeds was mainly determined by maternal effect and slightly affected by xenia. Thus, the OC of rapeseed was simultaneously affected by various genetic components, including maternal, embryo, cytoplasm, xenia and GE effects. In addition, general combining ability (GCA), specific combining ability (SCA), and maternal variance had significant influence on OC. The lines H2 and H1 were good general combiners, suggesting that they would be the best parental candidates for OC improvement. Crosses H3 × M2 and H1 × M3 exhibited significant SCA, suggesting their potentials in hybrid development. Our study thoroughly investigated and reliably quantified various genetic factors associated with OC of rapeseed by using a full diallel and backcross and reciprocal backcross. This findings lay a foundation for future genetic studies of OC and provide guidance for breeding of high-oil rapeseed cultivars.

Assessing the Accuracy of Passive Microwave Estimates of Snow Water Equivalent in Data-Scarce Regions for Use in Water Resource Applications: A Case Study in the Upper Helmand Watershed, Afghanistan

DTIC Science & Technology

2011-03-01

to remotely sensed SCA and SWE. The first analysis, a comparison to SCA imagery, tests the models ability to correctly estimate the snow extent...remotely sensed data (Con- galton and Green 2009). The producer’s accuracies consistently show the model underestimating the snow extent at the end...and K. Green. 2009. Assessing the accuracy of remotely sensed data: principals and practices, Second edition. CRC Press, Taylor & Francis Group

Two in one: report of a patient with spinocerebellar ataxia types 2 and 10.

PubMed

Kapur, Sachin S; Goldman, Jennifer G

2012-09-01

To report a rare case of the coexistence of 2 spinocerebellar ataxia (SCA) mutations in a single patient. Case report. University hospital, Movement Disorders Center. A 54-year-old man of Mexican, American Indian, and French descent with an 11-year history of gait and limb ataxia. Findings of clinical examination, magnetic resonance imaging, and video electroencephalographic monitoring. Neurologic history revealed a gradually progressive gait and limb ataxia along with muscle cramps and sensory symptoms in his distal extremities; examination revealed executive dysfunction, dysarthria, ataxia, and sensory neuronopathy. Episodes of loss of awareness were reported, but electroencephalograms were negative. Brain imaging demonstrated severe cerebellar and brainstem atrophy. Genetic evaluation of the case revealed mutations in both the SCA2 and SCA10 genes. Our patient has a unique combination of genetic mutations for 2 different SCAs, types 2 and 10, which to our knowledge, has not been previously reported. His clinical phenotype is largely consistent with SCA2, but his possible seizures and Mexican heritage suggest influences of SCA10.

Protein Sectors: Statistical Coupling Analysis versus Conservation

PubMed Central

Teşileanu, Tiberiu; Colwell, Lucy J.; Leibler, Stanislas

2015-01-01

Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed “sectors”. The method applies spectral analysis to a matrix obtained by combining correlation information with sequence conservation. It has been asserted that the protein sectors identified by SCA are functionally significant, with different sectors controlling different biochemical properties of the protein. Here we reconsider the available experimental data and note that it involves almost exclusively proteins with a single sector. We show that in this case sequence conservation is the dominating factor in SCA, and can alone be used to make statistically equivalent functional predictions. Therefore, we suggest shifting the experimental focus to proteins for which SCA identifies several sectors. Correlations in protein alignments, which have been shown to be informative in a number of independent studies, would then be less dominated by sequence conservation. PMID:25723535

Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study

PubMed Central

2010-01-01

Background Diagnostic options for pulmonary tuberculosis in resource-poor settings are commonly limited to smear microscopy. We investigated whether bleach concentration by sedimentation and sputum cytology analysis (SCA) increased the positivity rate of smear microscopy for smear-positive tuberculosis. Methods We did a prospective diagnostic study in a Médecins Sans Frontières-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test. Results Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear (≥1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p = 0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p = 0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p = 0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p = 0.016), respectively. Conclusions The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context. PMID:20858253

The histone deacetylase HDAC3 is essential for Purkinje cell function, potentially complicating the use of HDAC inhibitors in SCA1

PubMed Central

Venkatraman, Anand; Hu, Yuan-Shih; Didonna, Alessandro; Cvetanovic, Marija; Krbanjevic, Aleksandar; Bilesimo, Patrice; Opal, Puneet

2014-01-01

Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease caused by a pathogenic glutamine repeat expansion in the protein ataxin-1 (ATXN1). One likely mechanism mediating pathogenesis is excessive transcriptional repression induced by the expanded ATXN-1. Because ATXN1 binds HDAC3, a Class I histone deacetylase (HDAC) that we have found to be required for ATXN1-induced transcriptional repression, we tested whether genetically depleting HDAC3 improves the phenotype of the SCA1 knock-in mouse (SCA1154Q/2Q), the most physiologically relevant model of SCA1. Given that HDAC3 null mice are embryonic lethal, we used for our analyses a combination of HDAC3 haploinsufficient and Purkinje cell (PC)-specific HDAC3 null mice. Although deleting a single allele of HDAC3 in the context of SCA1 was insufficient to improve cerebellar and cognitive deficits of the disease, a complete loss of PC HDAC3 was highly deleterious both behaviorally, with mice showing early onset ataxia, and pathologically, with progressive histologic evidence of degeneration. Inhibition of HDAC3 may yet have a role in SCA1 therapy, but our study provides cautionary evidence that this approach could produce untoward effects. Indeed, the neurotoxic consequences of HDAC3 depletion could prove relevant, wherever pharmacologic inhibition of HDAC3 is being contemplated, in disorders ranging from cancer to neurodegeneration. PMID:24594842

A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder

PubMed Central

Chue, Pierre; Chue, James

2016-01-01

Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55–3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI formulation, there is the advantage of improved adherence and simplified treatment in the long-term management of SCA. PMID:26869795

A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder.

PubMed

Chue, Pierre; Chue, James

2016-01-01

Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55-3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI formulation, there is the advantage of improved adherence and simplified treatment in the long-term management of SCA.

Recent Successes and Future Plans for NASA's Space Communications and Navigation Testbed on the International Space Station

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Sankovic, John M.; Johnson, Sandra K.; Lux, James P.; Chelmins, David T.

2014-01-01

Flexible and extensible space communications architectures and technology are essential to enable future space exploration and science activities. NASA has championed the development of the Space Telecommunications Radio System (STRS) software defined radio (SDR) standard and the application of SDR technology to reduce the costs and risks of using SDRs for space missions, and has developed an on-orbit testbed to validate these capabilities. The Space Communications and Navigation (SCaN) Testbed (previously known as the Communications, Navigation, and Networking reConfigurable Testbed (CoNNeCT)) is advancing SDR, on-board networking, and navigation technologies by conducting space experiments aboard the International Space Station. During its first year(s) on-orbit, the SCaN Testbed has achieved considerable accomplishments to better understand SDRs and their applications. The SDR platforms and software waveforms on each SDR have over 1500 hours of operation and are performing as designed. The Ka-band SDR on the SCaN Testbed is NASAs first space Ka-band transceiver and is NASA's first Ka-band mission using the Space Network. This has provided exciting opportunities to operate at Ka-band and assist with on-orbit tests of NASA newest Tracking and Data Relay Satellites (TDRS). During its first year, SCaN Testbed completed its first on-orbit SDR reconfigurations. SDR reconfigurations occur when implementing new waveforms on an SDR. SDR reconfigurations allow a radio to change minor parameters, such as data rate, or complete functionality. New waveforms which provide new capability and are reusable across different missions provide long term value for reconfigurable platforms such as SDRs. The STRS Standard provides guidelines for new waveform development by third parties. Waveform development by organizations other than the platform provider offers NASA the ability to develop waveforms itself and reduce its dependence and costs on the platform developer. Each of these new waveforms requires a waveform build environment for the particular SDR, helps assess the usefulness of the platform provider documentation, and exercises the objectives of STRS Standard and the SCaN Testbed. There is considerable interest in conducting experiments using the SCaN Testbed from NASA, academia, commercial companies, and other space agencies. There are approximately 25 experiments or activities supported by the project underway or in development, with more proposals ready, as time and funding allow, and new experiment solicitations available. NASA continues development of new waveforms and applications in communications, networking, and navigation, the first university experimenters are beginning waveform development, which will support the next generation of communications engineers, and international interest is beginning with space agency partners from European Space Agency (ESA) and the Centre National d'Etudes Spatiales (CNES). This paper will provide an overview of the SCaN Testbed and discuss its recent accomplishments and experiment activities.Its recent successes in Ka-band operations, reception of the newest GPS signals, SDR reconfigurations, and STRS demonstration in space when combined with the future experiment portfolio have positioned the SCaN Testbed to enable future space communications and navigation capabilities for exploration and science.

Derivation of an induced pluripotent stem cell line (MUSIi004-A) from dermal fibroblasts of a 48-year-old spinocerebellar ataxia type 3 patient.

PubMed

Ritthaphai, Alisa; Wattanapanitch, Methichit; Pithukpakorn, Manop; Heepchantree, Worapa; Soi-Ampornkul, Rungtip; Mahaisavariya, Panchalee; Triwongwaranat, Daranporn; Pattanapanyasat, Kovit; Vatanashevanopakorn, Chinnavuth

2018-05-21

Dermal fibroblasts were obtained from a 48-year-old female patient with spinocerebellar ataxia type 3 (SCA3). Fibroblasts were reprogrammed by nucleofection with episomal plasmids, carrying L-MYC, LIN28, OCT4, SOX2, KLF4, EBNA-1 and shRNA against p53. The SCA3 patient-specific iPSC line, MUSIi004-A, was characterized by immunofluorescence staining to verify the expression of pluripotent markers. The iPSC line exhibited an ability to differentiate into three germ layers by embryoid body (EB) formation. Karyotypic analysis of the MUSIi004-A line was normal. The mutant allele was still present in the iPSC line. This iPSC line represents a useful tool for studying neurodegeneration in SCA3. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Assimilation of snow covered area information into hydrologic and land-surface models

USGS Publications Warehouse

Clark, M.P.; Slater, A.G.; Barrett, A.P.; Hay, L.E.; McCabe, G.J.; Rajagopalan, B.; Leavesley, G.H.

2006-01-01

This paper describes a data assimilation method that uses observations of snow covered area (SCA) to update hydrologic model states in a mountainous catchment in Colorado. The assimilation method uses SCA information as part of an ensemble Kalman filter to alter the sub-basin distribution of snow as well as the basin water balance. This method permits an optimal combination of model simulations and observations, as well as propagation of information across model states. Sensitivity experiments are conducted with a fairly simple snowpack/water-balance model to evaluate effects of the data assimilation scheme on simulations of streamflow. The assimilation of SCA information results in minor improvements in the accuracy of streamflow simulations near the end of the snowmelt season. The small effect from SCA assimilation is initially surprising. It can be explained both because a substantial portion of snowmelts before any bare ground is exposed, and because the transition from 100% to 0% snow coverage occurs fairly quickly. Both of these factors are basin-dependent. Satellite SCA information is expected to be most useful in basins where snow cover is ephemeral. The data assimilation strategy presented in this study improved the accuracy of the streamflow simulation, indicating that SCA is a useful source of independent information that can be used as part of an integrated data assimilation strategy. ?? 2005 Elsevier Ltd. All rights reserved.

Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells.

PubMed

Wu, Qiong; Zhan, Jinxi; Pu, Shiming; Qin, Liu; Li, Yun; Zhou, Zuping

2017-01-03

Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31- subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31- subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending.

Inheritance of downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) resistance in grapevines.

PubMed

Poolsawat, O; Mahanil, S; Laosuwan, P; Wongkaew, S; Tharapreuksapong, A; Reisch, B I; Tantasawat, P A

2013-12-13

Downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) are two of the major diseases of most grapevine (Vitis vinifera L.) cultivars grown in Thailand. Therefore, breeding grapevines for improved downy mildew and anthracnose resistance is crucial. Factorial crosses were made between three downy mildew and/or anthracnose resistant lines ('NY88.0517.01', 'NY65.0550.04', and 'NY65.0551.05'; male parents) and two or three susceptible cultivars of V. vinifera ('Black Queen', 'Carolina Black Rose', and/or 'Italia'; female parents). F1 hybrid seedlings were evaluated for downy mildew and anthracnose resistance using a detached/excised leaf assay. For both diseases, the general combining ability (GCA) variance among male parents was significant, while the variance of GCA among females and the specific combining ability (SCA) variance were not significant, indicating the prevalence of additive over non-additive gene actions. The estimated narrow sense heritabilities of downy mildew and anthracnose resistance were 55.6 and 79.2%, respectively, suggesting that downy mildew/anthracnose resistance gene(s) were highly heritable. The 'Carolina Black Rose x NY65.0550.04' cross combination is recommended for future use.

Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

PubMed

Duarte, João Valente; Faustino, Ricardo; Lobo, Mercês; Cunha, Gil; Nunes, César; Ferreira, Carlos; Januário, Cristina; Castelo-Branco, Miguel

2016-10-01

Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Markers of nonselective and specific NK cell activation.

PubMed

Fogel, Leslie A; Sun, Michel M; Geurs, Theresa L; Carayannopoulos, Leonidas N; French, Anthony R

2013-06-15

NK cell activation is controlled by the integration of signals from cytokine receptors and germline-encoded activation and inhibitory receptors. NK cells undergo two distinct phases of activation during murine CMV (MCMV) infection: a nonselective phase mediated by proinflammatory cytokines and a specific phase driven by signaling through Ly49H, an NK cell activation receptor that recognizes infected cells. We sought to delineate cell surface markers that could distinguish NK cells that had been activated nonselectively from those that had been specifically activated through NK cell receptors. We demonstrated that stem cell Ag 1 (Sca-1) is highly upregulated during viral infections (to an even greater extent than CD69) and serves as a novel marker of early, nonselective NK cell activation. Indeed, a greater proportion of Sca-1(+) NK cells produced IFN-γ compared with Sca-1(-) NK cells during MCMV infection. In contrast to the universal upregulation of Sca-1 (as well as KLRG1) on NK cells early during MCMV infection, differential expression of Sca-1, as well as CD27 and KLRG1, was observed on Ly49H(+) and Ly49H(-) NK cells late during MCMV infection. Persistently elevated levels of KLRG1 in the context of downregulation of Sca-1 and CD27 were observed on NK cells that expressed Ly49H. Furthermore, the differential expression patterns of these cell surface markers were dependent on Ly49H recognition of its ligand and did not occur solely as a result of cellular proliferation. These findings demonstrate that a combination of Sca-1, CD27, and KLRG1 can distinguish NK cells nonselectively activated by cytokines from those specifically stimulated through activation receptors.

Slowly progressive cerebellar ataxia and cervical dystonia: clinical presentation of a new form of spinocerebellar ataxia?

PubMed

Kuoppamäki, Mikko; Giunti, Paula; Quinn, Niall; Wood, Nicholas W; Bhatia, Kailash P

2003-02-01

We describe 5 cases with a rare combination of young-onset, slowly progressive cerebellar ataxia and cervical dystonia. Two were sporadic, whereas the other 3 were familial, including 2 from one family. The age of onset of these cases was between 16 and 37 years. The presenting symptom was cervical dystonia and/or dystonic head tremor in 3 patients and hand or lower limb tremor in 2. In 2 cases, cervical dystonia and/or dystonic head tremor developed approximately 6 to 10 years before cerebellar dysfunction, and in three they developed at the same time. Apart from cervical dystonia, there was mild dystonic limb involvement in 2 cases, but generalized dystonia was not seen. Cerebellar ataxia was slowly progressive. A literature search showed 10 cases of cervical dystonia associated with genetically undetermined (n = 5) or genetically proven (n = 5) spinocerebellar ataxia (SCA). When the genotype was known, these patients had either SCA3, 6, 7, or 12. However, our 5 cases (or their first-degree relatives) tested negative for SCA1, 2, 3, 6, and 7, and in the 4 cases (or their first-degree relatives) tested for SCA12, the result was negative. We propose that this rare phenotype manifesting as a combination of cerebellar ataxia and cervical dystonia may represent one or more new, as yet uncharacterized, genotypes of inherited young-onset spinocerebellar ataxia. Copyright Movement Disorder Society

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ito, Akihiko; Inatomi, Motoko; Huntzinger, Deborah N.

The seasonal-cycle amplitude (SCA) of the atmosphere–ecosystem carbon dioxide (CO 2) exchange rate is a useful metric of the responsiveness of the terrestrial biosphere to environmental variations. It is unclear, however, what underlying mechanisms are responsible for the observed increasing trend of SCA in atmospheric CO 2 concentration. Using output data from the Multi-scale Terrestrial Model Intercomparison Project (MsTMIP), we investigated how well the SCA of atmosphere–ecosystem CO 2 exchange was simulated with 15 contemporary terrestrial ecosystem models during the period 1901–2010. Also, we made attempt to evaluate the contributions of potential mechanisms such as atmospheric CO 2, climate, land-use,more » and nitrogen deposition, through factorial experiments using different combinations of forcing data. Under contemporary conditions, the simulated global-scale SCA of the cumulative net ecosystem carbon flux of most models was comparable in magnitude with the SCA of atmospheric CO 2 concentrations. Results from factorial simulation experiments showed that elevated atmospheric CO 2 exerted a strong influence on the seasonality amplification. When the model considered not only climate change but also land-use and atmospheric CO 2 changes, the majority of the models showed amplification trends of the SCAs of photosynthesis, respiration, and net ecosystem production (+0.19 % to +0.50 % yr -1). In the case of land-use change, it was difficult to separate the contribution of agricultural management to SCA because of inadequacies in both the data and models. The simulated amplification of SCA was approximately consistent with the observational evidence of the SCA in atmospheric CO 2 concentrations. Large inter-model differences remained, however, in the simulated global tendencies and spatial patterns of CO 2 exchanges. Further studies are required to identify a consistent explanation for the simulated and observed amplification trends, including their underlying mechanisms. Nevertheless, this study implied that monitoring of ecosystem seasonality would provide useful insights concerning ecosystem dynamics.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ito, Akihiko; Inatomi, Motoko; Huntzinger, Deborah N.

The seasonal-cycle amplitude (SCA) of the atmosphere–ecosystem carbon dioxide (CO 2) exchange rate is a useful metric of the responsiveness of the terrestrial biosphere to environmental variations. It is unclear, however, what underlying mechanisms are responsible for the observed increasing trend of SCA in atmospheric CO 2 concentration. Using output data from the Multi-scale Terrestrial Model Intercomparison Project (MsTMIP), we investigated how well the SCA of atmosphere–ecosystem CO 2 exchange was simulated with 15 contemporary terrestrial ecosystem models during the period 1901–2010. Also, we made attempt to evaluate the contributions of potential mechanisms such as atmospheric CO 2, climate, land-use,more » and nitrogen deposition, through factorial experiments using different combinations of forcing data. Under contemporary conditions, the simulated global-scale SCA of the cumulative net ecosystem carbon flux of most models was comparable in magnitude with the SCA of atmospheric CO 2 concentrations. Results from factorial simulation experiments showed that elevated atmospheric CO 2 exerted a strong influence on the seasonality amplification. When the model considered not only climate change but also land-use and atmospheric CO 2 changes, the majority of the models showed amplification trends of the SCAs of photosynthesis, respiration, and net ecosystem production (+0.19 % to +0.50 % yr –1). In the case of land-use change, it was difficult to separate the contribution of agricultural management to SCA because of inadequacies in both the data and models. The simulated amplification of SCA was approximately consistent with the observational evidence of the SCA in atmospheric CO 2 concentrations. Large inter-model differences remained, however, in the simulated global tendencies and spatial patterns of CO 2 exchanges. Further studies are required to identify a consistent explanation for the simulated and observed amplification trends, including their underlying mechanisms. Furthermore, this study implied that monitoring of ecosystem seasonality would provide useful insights concerning ecosystem dynamics.« less

Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model.

PubMed

Toonen, Lodewijk J A; Overzier, Maurice; Evers, Melvin M; Leon, Leticia G; van der Zeeuw, Sander A J; Mei, Hailiang; Kielbasa, Szymon M; Goeman, Jelle J; Hettne, Kristina M; Magnusson, Olafur Th; Poirel, Marion; Seyer, Alexandre; 't Hoen, Peter A C; van Roon-Mom, Willeke M C

2018-06-22

Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in transcriptional dysregulation, which can contribute to the cellular toxicity and neurodegeneration. Since the exact causative mechanisms underlying this process have not been fully elucidated, gene expression analyses in brains of transgenic SCA3 mouse models may provide useful insights. Here we characterised the MJD84.2 SCA3 mouse model expressing the mutant human ataxin-3 gene using a multi-omics approach on brain and blood. Gene expression changes in brainstem, cerebellum, striatum and cortex were used to study pathological changes in brain, while blood gene expression and metabolites/lipids levels were examined as potential biomarkers for disease. Despite normal motor performance at 17.5 months of age, transcriptional changes in brain tissue of the SCA3 mice were observed. Most transcriptional changes occurred in brainstem and striatum, whilst cerebellum and cortex were only modestly affected. The most significantly altered genes in SCA3 mouse brain were Tmc3, Zfp488, Car2, and Chdh. Based on the transcriptional changes, α-adrenergic and CREB pathways were most consistently altered for combined analysis of the four brain regions. When examining individual brain regions, axon guidance and synaptic transmission pathways were most strongly altered in striatum, whilst brainstem presented with strongest alterations in the pi-3 k cascade and cholesterol biosynthesis pathways. Similar to other neurodegenerative diseases, reduced levels of tryptophan and increased levels of ceramides, di- and triglycerides were observed in SCA3 mouse blood. The observed transcriptional changes in SCA3 mouse brain reveal parallels with previous reported neuropathology in patients, but also shows brain region specific effects as well as involvement of adrenergic signalling and CREB pathway changes in SCA3. Importantly, the transcriptional changes occur prior to onset of motor- and coordination deficits.

Decadal trends in the seasonal-cycle amplitude of terrestrial CO 2 exchange resulting from the ensemble of terrestrial biosphere models

DOE PAGES

Ito, Akihiko; Inatomi, Motoko; Huntzinger, Deborah N.; ...

2016-05-12

The seasonal-cycle amplitude (SCA) of the atmosphere–ecosystem carbon dioxide (CO 2) exchange rate is a useful metric of the responsiveness of the terrestrial biosphere to environmental variations. It is unclear, however, what underlying mechanisms are responsible for the observed increasing trend of SCA in atmospheric CO 2 concentration. Using output data from the Multi-scale Terrestrial Model Intercomparison Project (MsTMIP), we investigated how well the SCA of atmosphere–ecosystem CO 2 exchange was simulated with 15 contemporary terrestrial ecosystem models during the period 1901–2010. Also, we made attempt to evaluate the contributions of potential mechanisms such as atmospheric CO 2, climate, land-use,more » and nitrogen deposition, through factorial experiments using different combinations of forcing data. Under contemporary conditions, the simulated global-scale SCA of the cumulative net ecosystem carbon flux of most models was comparable in magnitude with the SCA of atmospheric CO 2 concentrations. Results from factorial simulation experiments showed that elevated atmospheric CO 2 exerted a strong influence on the seasonality amplification. When the model considered not only climate change but also land-use and atmospheric CO 2 changes, the majority of the models showed amplification trends of the SCAs of photosynthesis, respiration, and net ecosystem production (+0.19 % to +0.50 % yr –1). In the case of land-use change, it was difficult to separate the contribution of agricultural management to SCA because of inadequacies in both the data and models. The simulated amplification of SCA was approximately consistent with the observational evidence of the SCA in atmospheric CO 2 concentrations. Large inter-model differences remained, however, in the simulated global tendencies and spatial patterns of CO 2 exchanges. Further studies are required to identify a consistent explanation for the simulated and observed amplification trends, including their underlying mechanisms. Furthermore, this study implied that monitoring of ecosystem seasonality would provide useful insights concerning ecosystem dynamics.« less

Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050: Modelling Based on Demographics, Excess Mortality, and Interventions

PubMed Central

Piel, Frédéric B.; Hay, Simon I.; Gupta, Sunetra; Weatherall, David J.; Williams, Thomas N.

2013-01-01

Background The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions. Methods and Findings First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400–398,800) in 2010 to 404,200 (CI: 242,500–657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900–106,100]; 2050: 140,800 [CI: 95,500–200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600–48,800]; 2050: 44,700 [CI: 27,100–70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700–59,100]; 2050: 33,900 [CI: 15,900–64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800–6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800–14,232,700) newborns with SCA globally, 85% (CI: 81%–88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions. Conclusions Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India. Please see later in the article for the Editors' Summary PMID:23874164

Combining ability analysis for within-boll yield components in upland cotton (Gossypium hirsutum L.).

PubMed

Imran, M; Shakeel, A; Azhar, F M; Farooq, J; Saleem, M F; Saeed, A; Nazeer, W; Riaz, M; Naeem, M; Javaid, A

2012-08-24

Cotton is an important cash crop worldwide, accounting for a large percentage of world agricultural exports; however, yield per acre is still poor in many countries, including Pakistan. Diallel mating system was used to identify parents for improving within-boll yield and fiber quality parameters. Combining ability analysis was employed to obtain suitable parents for this purpose. The parental genotypes CP-15/2, NIAB Krishma, CIM-482, MS-39, and S-12 were crossed in complete diallel mating under green house conditions during 2009. The F₀ seed of 20 hybrids and five parents were planted in the field in randomized complete block design with three replications during 2010. There were highly significant differences among all F₁ hybrids and their parents. Specific combining ability (SCA) variance was greater than general combining ability (GCA) variance for bolls per plant (9.987), seeds per boll (0.635), seed density (5.672), lint per seed (4.174), boll size (3.69), seed cotton yield (0.315), and lint percentage (0.470), showing predominance of non-additive genes; while seed volume (3.84) was controlled by additive gene action based on maximum GCA variance. Cultivar MS-39 was found to be the best general combiner for seed volume (0.102), seeds per boll (0.448), and lint per seed (0.038) and its utilization produced valuable hybrids, including MS-39 x NIAB Krishma and MS-39 x S-12. The parental line CIM-482 had high GCA effects for boll size (0.33) and seeds per boll (0.90). It also showed good SCA with S-12 and NIAB Krishma for bolls per plant, with CP- 15/2 for boll size, and with MS-39 for seeds per boll. The hybrids, namely, CP-15/2 x NIAB Krishma, NIAB Krishma x S-12, NIAB Krishma x CIM-482, MS-39 x NIAB Krishma, MS-39 x CP-15/2, and S-12 x MS-39 showed promising results. Correlation analysis revealed that seed cotton yield showed significant positive correlation with bolls per plant, boll size and seeds per boll while it showed negative correlation with lint percentage and lint per seed. Seed volume showed significant negative correlation with seed density. Seeds per boll were positively correlated with boll size and negatively correlated with bolls per plant lint percentage and lint per seed. Similarly, lint per seed exhibited positive correlation with lint percentage and boll size showed significantly negative correlation with bolls per plant. Presence of non-additive genetic effects in traits like bolls per plant, seeds per boll, lint per seed, seed cotton yield, and lint percentage is indicative of later generation selection or heterosis breeding may be adopted. For boll size, seed volume and seed density early generation selection may be followed because of the presence of additive gene action. The parental material used in this study and cross combinations obtained from these parents may be exploited in future breeding endeavors.

Trajectories of Change in Students' Self-Concepts of Ability and Values in Math and College Major Choice

ERIC Educational Resources Information Center

Musu-Gillette, Lauren E.; Wigfield, Allan; Harring, Jeffrey R.; Eccles, Jacquelynne S.

2015-01-01

This study extends previous research on the long-term connections between motivation constructs in expectancy-value theory and achievement outcomes. Using growth mixture modelling, we examined trajectories of change for 421 students from 4th grade through college in their self-concept of ability (SCA) in math, interest in math, and perceived…

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

PubMed Central

Wang, Lisa; Aasly, Jan O.; Annesi, Grazia; Bardien, Soraya; Bozi, Maria; Brice, Alexis; Carr, Jonathan; Chung, Sun J.; Clarke, Carl; Crosiers, David; Deutschländer, Angela; Eckstein, Gertrud; Farrer, Matthew J.; Goldwurm, Stefano; Garraux, Gaetan; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Klein, Christine; Jeon, Beom; Kim, Yun J.; Lesage, Suzanne; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pihlstrøm, Lasse; Pramstaller, Peter P.; Park, Sung S.; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Silburn, Peter A.; Theuns, Jessie; Tan, Eng K.; Tomiyama, Hiroyuki; Toft, Mathias; Van Broeckhoven, Christine; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius M.; Krüger, Rejko

2015-01-01

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. PMID:26354989

MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases.

PubMed

Politi, Letterio Salvatore; Bianchi Marzoli, Stefania; Godi, Claudia; Panzeri, Marta; Ciasca, Paola; Brugnara, Gianluca; Castaldo, Anna; Di Bella, Daniela; Taroni, Franco; Nanetti, Lorenzo; Mariotti, Caterina

2016-05-01

Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT.

PubMed

Sciammarella, Maria; Shrestha, Uttam M; Seo, Youngho; Gullberg, Grant T; Botvinick, Elias H

2017-08-03

SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99m Tc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P < 0.001). The visually assessed image findings in static and dynamic SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion based on SCA. The CFR measured with dynamic SPECT is fully objective, with better sensitivity and specificity, available only with the data generated from the dynamic SPECT method.

Degeneration of ingestion-related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7.

PubMed

Rüb, U; Brunt, E R; Petrasch-Parwez, E; Schöls, L; Theegarten, D; Auburger, G; Seidel, K; Schultz, C; Gierga, K; Paulson, H; van Broeckhoven, C; Deller, T; de Vos, R A I

2006-12-01

Dysphagia, which can lead to nutritional deficiencies, weight loss and dehydration, represents a risk factor for aspiration pneumonia. Although clinical studies have reported the occurrence of dysphagia in patients with spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3), type 6 (SCA6) and type 7 (SCA7), there are neither detailed clinical records concerning the kind of ingestive malfunctions which contribute to dysphagia nor systematic pathoanatomical studies of brainstem regions involved in the ingestive process. In the present study we performed a systematic post mortem study on thick serial tissue sections through the ingestion-related brainstem nuclei of 12 dysphagic patients who suffered from clinically diagnosed and genetically confirmed spinocerebellar ataxias assigned to the CAG-repeat or polyglutamine diseases (two SCA2, seven SCA3, one SCA6 and two SCA7 patients) and evaluated their medical records. Upon pathoanatomical examination in all of the SCA2, SCA3, SCA6 and SCA7 patients, a widespread neurodegeneration of the brainstem nuclei involved in the ingestive process was found. The clinical records revealed that all of the SCA patients were diagnosed with progressive dysphagia and showed dysfunctions detrimental to the preparatory phase of the ingestive process, as well as the lingual, pharyngeal and oesophageal phases of swallowing. The vast majority of the SCA patients suffered from aspiration pneumonia, which was the most frequent cause of death in our sample. The findings of the present study suggest (i) that dysphagia in SCA2, SCA3, SCA6 and SCA7 patients may be associated with widespread neurodegeneration of ingestion-related brainstem nuclei; (ii) that dysphagic SCA2, SCA3, SCA6 and SCA7 patients may suffer from dysfunctions detrimental to all phases of the ingestive process; and (iii) that rehabilitative swallow therapy which takes specific functional consequences of the underlying brainstem lesions into account might be helpful in preventing aspiration pneumonia, weight loss and dehydration in SCA2, SCA3, SCA6 and SCA7 patients.

Rare frequency of downbeat positioning nystagmus in spinocerebellar ataxia type 31.

PubMed

Yabe, Ichiro; Matsushima, Masaaki; Yoshida, Kunihiro; Ishikawa, Kinya; Shirai, Shinichi; Takahashi, Ikuko; Sasaki, Hidenao

2015-03-15

Spinocerebellar ataxia type 31 (SCA31) and spinocerebellar ataxia type 6 (SCA6) are the most frequent types of spinocerebellar degeneration in Japan. Previous reports described that it was difficult to distinguish SCA6 and SCA31 in clinical situations. There is not much difference except that the onset age of SCA31 is slightly higher than that of SCA6. Therefore we surveyed our medical records retrospectively, and then compared clinical symptoms of SCA6 and SCA31. As previously stated, the onset age of SCA31 is higher than that of SCA6. Gaze-evoked nystagmus is more frequent in SCA6 than in SCA31. The percentage in downbeat positioning nystagmus (DPN) is as high as 63% in SCA6. In contrast, DPN in SCA31 is rare and subtle. Our study suggests that the presence of DPN is an important sign that can differentiate SCA6 from SCA31 clinically. Copyright © 2015 Elsevier B.V. All rights reserved.

Bounds on the number of hidden neurons in three-layer binary neural networks.

PubMed

Zhang, Zhaozhi; Ma, Xiaomin; Yang, Yixian

2003-09-01

This paper investigates an important problem concerning the complexity of three-layer binary neural networks (BNNs) with one hidden layer. The neuron in the studied BNNs employs a hard limiter activation function with only integer weights and an integer threshold. The studies are focused on implementations of arbitrary Boolean functions which map from [0, 1]n into [0, 1]. A deterministic algorithm called set covering algorithm (SCA) is proposed for the construction of a three-layer BNN to implement an arbitrary Boolean function. The SCA is based on a unit sphere covering (USC) of the Hamming space (HS) which is chosen in advance. It is proved that for the implementation of an arbitrary Boolean function of n-variables (n > or = 3) by using SCA, [3L/2] hidden neurons are necessary and sufficient, where L is the number of unit spheres contained in the chosen USC of the n-dimensional HS. It is shown that by using SCA, the number of hidden neurons required is much less than that by using a two-parallel hyperplane method. In order to indicate the potential ability of three-layer BNNs, a lower bound on the required number of hidden neurons which is derived by using the method of estimating the Vapnik-Chervonenkis (VC) dimension is also given.

Central auditory processing in patients with spinocerebellar ataxia.

PubMed

Zeigelboim, Bianca Simone; de Carvalho, Hugo Amilton Santos; Teive, Hélio Afonso Ghizoni; Liberalesso, Paulo Breno Noronha; Jurkiewicz, Ari Leon; da Silva Abdulmassih, Edna Márcia; Marques, Jair Mendes; Cordeiro, Mara Lúcia

2015-09-01

Autosomal dominant spinocerebellar ataxias (SCAs) are a group of rare and heterogeneous neurodegenerative diseases characterized by the presence of progressive cerebellar ataxia. Although the symptomatology of SCAs is well known, information regarding central auditory functioning in these patients is lacking. Therefore, we assessed the central auditory processing disorders (CAPD) in patients with different subtypes of SCA. In a retrospective cross-sectional study, we subjected 43 patients with SCAs to otorhinolaryngological, audiological, Brainstem Auditory Evoked Potential (BAEP) and acoustic immittance evaluations as well as CAPD tests, namely the Standard Spondaic Word (SSW) and the Random Gap Detection Test (RGDT). Most patients (83.7%) reported an imbalance when walking; many reported difficulty speaking (48.8%), dizziness (41.8%), and dysphagia (39.5%). In the audiometric test, 14/43 patients (32.5%) presented alterations, including 4/12 patients with SCA3 (33.3%), 1/8 patients with SCA2 (12.5%), 1/1 patient with SCA4 (100%), 1/1 patient with SCA6 (100%), 1/1 patient with SCA7 (100%), 3/6 patients with SCA10 (50%), and 3/14 patients with an undetermined type of SCA (21.4%). In the BAEP test, 20/43 patients (46.5%) presented alterations (11.6% na orelha esquerda e 34.9% bilateralmente), including 7/12 patients with SCA3 (58.3%), 5/8 patients with SCA2 (62.5%), 1/1 patient with SCA4 (100%), 1/1 patient with SCA6 (100%), 1/1 patient with SCA7 (100%), 4/6 patients with SCA10 (66.7%), and 2/14 patients with an undetermined type of SCA (14.2%). In the SSW, 22/40 patients (55%) presented alterations (2.5% in the right ear, 15% in the left ear, and 37.5% bilaterally), including 6/10 patients (60%) with SCA3, 3/8 (37.5%) with SCA2, 1/1 (100%) with SCA4, 1/1 (100%) with SCA6, 1/1 (100%) with SCA7, 4/5 (80%) with SCA10, and 8/14 (57.1%) with an undetermined type SCA. For the RGDT, 30/40 patients (75%) presented alterations, including 8/10 (80%) with SCA3, 6/8 (75%) with SCA2, 1/1 (100%) with SCA4, 1/1 (100%) with SCA6, 1/1 (100%) with SCA7, 4/5 (80%) with SCA10, and 9/14 (64.3%) with an undetermined type of SCA. In immittance testing, 19/43 patients (44.1%) presented alterations, including 6/12 (50%) with SCA3, 4/8 (50%) with SCA2, 1/1 (100%) with SCA4, 1/1 (100%) with SCA6, 1/1 (100%) with SCA7, 2/6 (33.3%) with SCA10, and 4/14 (28.6%) with an undetermined type of SCA. A majority of patients exhibited SSW test deficits, with a predominance of bilateralism, and three-fourths had impaired RGDT performance, pointing to difficulties with binaural integration and temporal resolution. Assessment of CAPD is important for therapeutic follow ups in patients with SCA. Copyright © 2015 Elsevier B.V. All rights reserved.

scaRNAs regulate splicing and vertebrate heart development.

PubMed

Patil, Prakash; Kibiryeva, Nataliya; Uechi, Tamayo; Marshall, Jennifer; O'Brien, James E; Artman, Michael; Kenmochi, Naoya; Bittel, Douglas C

2015-08-01

Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and splice isoforms of several genes that regulate heart development (e.g., GATA4, NOTCH2, DAAM1, DICER1, MBNL1 and MBNL2). In addition, we used antisense morpholinos to knock down the expression of two scaRNAs (scarna1 and snord94) in zebrafish and saw a corresponding disruption of heart development with an accompanying alteration in splice isoforms of cardiac regulatory genes. Based on these combined results, we hypothesize that scaRNA modification of spliceosomal RNAs assists in fine tuning the spliceosome for dynamic selection of mRNA splice isoforms. Our results are consistent with disruption of splicing patterns during early embryonic development leading to insufficient communication between the first and second heart fields, resulting in conotruncal misalignment and TOF. Our findings represent a new paradigm for determining the mechanisms underlying congenital cardiac malformations. Copyright © 2015. Published by Elsevier B.V.

Parkinsonism in Spinocerebellar Ataxia

PubMed Central

Park, Hyeyoung; Kim, Han-Joon; Jeon, Beom S.

2015-01-01

Spinocerebellar ataxia (SCA) presents heterogeneous clinical phenotypes, and parkinsonism is reported in diverse SCA subtypes. Both levodopa responsive Parkinson disease (PD) like phenotype and atypical parkinsonism have been described especially in SCA2, SCA3, and SCA17 with geographic differences in prevalence. SCA2 is the most frequently reported subtype of SCA related to parkinsonism worldwide. Parkinsonism in SCA2 has unique genetic characteristics, such as low number of expansions and interrupted structures, which may explain the sporadic cases with low penetrance. Parkinsonism in SCA17 is more remarkable in Asian populations especially in Korea. In addition, an unclear cutoff of the pathologic range is the key issue in SCA17 related parkinsonism. SCA3 is more common in western cohorts. SCA6 and SCA8 have also been reported with a PD-like phenotype. Herein, we reviewed the epidemiologic, clinical, genetic, and pathologic features of parkinsonism in SCAs. PMID:25866756

Quantitative assessment of brain stem and cerebellar atrophy in spinocerebellar ataxia types 3 and 6: impact on clinical status.

PubMed

Eichler, L; Bellenberg, B; Hahn, H K; Köster, O; Schöls, L; Lukas, C

2011-05-01

Cerebellar and brain stem atrophy are important features in SCA3, whereas SCA6 has been regarded as a "pure" cerebellar disease. However, recent neuropathologic studies have described additional brain stem involvement in SCA6. We, therefore, aimed to investigate the occurrence and impact of regional infratentorial brain volume differences in patients with SCA3 and SCA6. Thirty-four patients with genetically proved SCA (SCA3, n = 17; SCA6, n = 17) and age-matched healthy control subjects (n = 51) were included. In all subjects, high-resolution T1-weighted images were acquired with a 1.5T MR imaging scanner. Individual brain stem and cerebellar volumes were calculated by using semiautomated volumetry approaches. For all patients with SCA, clinical dysfunction was scored according to the ICARS. Multiple regression analysis was used to identify the contribution of regional volumes to explain the variance in clinical dysfunction in each SCA genotype. Cerebellar volumes were lower in patients with SCA6 compared with controls and with those with SCA3. In contrast to controls, brain stem volume loss was observed in patients with SCA3 (P < .001) and, to a lesser extent, in those with SCA6 (P = .027). Significant linear dependencies were found between ICARS and cerebellum volume (SCA3: R(2) = 0.29, P = .02; SCA6: R(2) = 0.29, P = .03) and between ICARS and brain stem volume (SCA3: R(2) = 0.49, P = .002; SCA6: R(2) = 0.39, P < .01) in both subtypes. Both cerebellar and brain stem atrophy contributed independently to the variance in clinical dysfunction in SCA6, while in SCA3, only brain stem atrophy was of relevance. Our current findings in accordance with recent neuroradiologic and pathoanatomic studies suggest brain stem and cerebellar volume loss as attractive surrogate markers of disease severity in SCA3 and SCA6.

Diallel crosses for resistance to Macrophomina phaseolina and Thanatephorus cucumeris on cowpea.

PubMed

Lima, L R L; Damasceno-Silva, K J; Noronha, M A; Schurt, D A; Rocha, M M

2017-09-27

This study aimed at identifying and selecting through partial diallel analysis, segregating populations of cowpea resistant to Macrophomina phaseolina and Thanatephorus cucumeris, based on the evaluation of general (GCA) and specific combining ability (SCA), involved in the genetic control of resistance. For this reason, 19 grouped cowpea genotypes, considering the resistance to these pathogens, were crossed in partial diallel scheme 14 x 5, during 2013 and 2014. The 70 F 2 populations and the 19 parents were evaluated in a greenhouse as the reaction to pathogens, separately. The diallel analysis was performed according to the model of partial diallel proposed by Geraldi and Miranda Filho (1988). The additive effects predominated in the genetic control of the traits severity of charcoal rot (SEV) and area under the disease progress curve (AUDPC) to web blight, enabling the achievement of genetic gain with selection of resistant strains. Analyzing the effects of GCA, the parents BR 14-Mulato, BRS Tumucumaque and BRS Guariba, have a higher concentration of favorable alleles, highlighting, according to the values of SCA, the combinations BR 14-Mulato x MNC02-675F-4-10, BRS Tumucumaque x IT98K-1092-1, BRS Tumucumaque x MNC02-675F-4-10, BRS Tumucumaque x MNC02-675F-9-2, BRS Guariba x IT98K-1092-1, BRS Guariba x MNC02-675F-4-9, and BRS Guariba x MNC02-675F-4-10, as the most promising and indicated to obtain lines resistant to M. phaseolina and T. cucumeris in cowpea, simultaneously.

[Copy number variation of trinucleotide repeat in dynamic mutation sites of autosomal dominant cerebellar ataxias related genes].

PubMed

Chen, Pu; Ma, Mingyi; Shang, Huifang; Su, Dan; Zhang, Sizhong; Yang, Yuan

2009-12-01

To standardize the experimental procedure of the gene test for autosomal dominant cerebellar ataxias (ADCA), and provide the basis for quantitative criteria of the dynamic mutation of spinocerebellar ataxia (SCA) genes in Chinese population. Genotyping of the dynamic mutation loci of the SCA1, SCA2, SCA3, SCA6 and SCA7 genes was performed, using florescence PCR-capillary electrophoresis followed by DNA sequencing, to investigate the variation range of copy number of CAG tandem repeat of the genes in 263 probands of ADCA pedigrees and 261 non-related normal controls. Based on the sequencing result, the bias of the CAG copy number estimation using capillary electrophoresis with different DNA controls was compared to analyze the technical detailes of the electrophresis method in testing the dynamic mutation sites. PCR products containing dynamic mutation loci of the SCA genes showed significantly higher mobility than that of molecular weigh marker with relatively balanced GC content. This was particularly obvious in the SCA2, SCA 6 and SCA7 genes whereas the deviation of copy number could be corrected to +/-1 when known CAG copy number fragments were used as controls. The mobility of PCR products was primarily related to the copy number of CAG repeat when the fragments contained normal CAG repeat. In the 263 ADCA pedigrees, 6 (2.28%) carried SCA1 gene mutation, 8 (3.04%) had SCA2 mutation and 81 (30.80%) harbored SCA3 mutation. The gene mutation of SCA6 and SCA7 was not found. The normal variation range of the CAG repeat was 17-36 copies in SCA1 gene, 13-30 copies in SCA2, 14-39 copies in SCA3, 6-16 copies in SCA6 and 6-13 copies in SCA7. The heterozygosity was 76.1%, 17.7%, 74.4%, 72.1% and 41.3%, respectively. The mutation range of the CAG repeat was 49-56 copies in SCA1 gene, 36-41 copies in SCA2, 59-81 copies in SCA3. Neither homozygous mutation of an SCA gene nor double heterozygous mutation of the SCA genes was observed in the study. The copy number of the CAG repeat in SCA genes could be calculated accurately based on the result of florescence PCR-capillary electrophoresis when limited amount of known repeat copy number controls were used. Our result supported that the notion that SCA3 gene mutation was the most common cause for ADCA, and the obtained data would be helpful for establishing quantitative criteria of the dynamic mutation of the SCA genes in Chinese.

Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

PubMed

Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H L; Zhang, Jianyi

2014-01-01

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01). IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent.

PubMed

Paradisi, Irene; Ikonomu, Vassiliki; Arias, Sergio

2016-03-01

Dominantly inherited ataxias (spinocerebellar ataxias, SCAs) are a genetically heterogeneous group of neurologic diseases characterized by progressive cerebellar and spinal tract degeneration with ataxia and other signs, common to all known subtypes. Several types are relatively frequent worldwide, but in several countries, one specific SCA may show a higher prevalence owing to founder phenomena. In Venezuela, genetic epidemiological features of SCAs have been assessed during the last 30 years; mutations in ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), CACNA1A (SCA6), ATXN7 (SCA7), ATXN8 (SCA8), ATXN10 (SCA10), TBP (SCA17) and ATN1 (dentatorubral pallidoluysian atrophy, DRPLA) loci were searched among 115 independent families. SCA7 was the most frequent subtype (26.6%), followed by SCA3 (25.0%), SCA2 (21.9%), SCA1 (17.2%), SCA10 (4.7%) and DRPLA (3.1%); in 43% of the families, the subtype remained unidentified. SCA7 mutations displayed strong geographic aggregation in two independent founder foci, and SCA1 showed a very remote founder effect for a subset of families. SCA10 families were scattered across the country, but all had an identical in-phase haplotype carried also by Mexican, Brazilian and Sioux patients, supporting a very old common Amerindian origin. Prevalence for dominant SCAs in Venezuela was estimated as 1:25 000 nuclear families, provenances of which are either Caucasoid, African or Amerindian.

Health-related quality of life in patients with spinocerebellar ataxia.

PubMed

Sánchez-López, C R; Perestelo-Pérez, L; Escobar, A; López-Bastida, J; Serrano-Aguilar, P

2017-04-01

The progressive deterioration of patients with spinocerebellar ataxia (SCA) has a major impact on their health-related quality of life (HRQOL). This study evaluates HRQOL in a sample of patients diagnosed with SCA and aims to estimate the predictive ability of a set of sociodemographic variables for the different dimensions of the General Health Questionnaire. A total of 80 patients diagnosed with SCA were assessed using a sociodemographic questionnaire and the SF-36 General Health Questionnaire. The sociodemographic variables studied were sex, age, presence of a carer, employment status, and time elapsed from diagnosis of the disease. The 8 subscales of the SF-36 show positive and significant correlations to one another. Mean scores obtained on each SF-36 subscale differ between women and men, although this difference is significant only on the general health subscale, with men scoring higher than women. We found significant age differences on the vitality and social function subscales, with higher scores among younger patients (< 34 years). The variable 'presence of a carer' accounts for most of the total variance of the questionnaire. The SF-36 is a valid and useful instrument for evaluating HRQOL in patients diagnosed with SCA. Presence of a carer seems to be a determinant of self-perceived quality of life in these patients. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

SCA8 Repeat Expansion: Large CTA/CTG Repeat Alleles Are More Common in Ataxic Patients, Including Those with SCA6

PubMed Central

Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

2003-01-01

We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85–399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as α1A-voltage–dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients. PMID:12545428

SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6.

PubMed

Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

2003-03-01

We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85-399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as alpha(1A)-voltage-dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients.

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

PubMed

Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger

2016-04-01

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

Delay and Disruption Tolerant Networking MACHETE Model

NASA Technical Reports Server (NTRS)

Segui, John S.; Jennings, Esther H.; Gao, Jay L.

2011-01-01

To verify satisfaction of communication requirements imposed by unique missions, as early as 2000, the Communications Networking Group at the Jet Propulsion Laboratory (JPL) saw the need for an environment to support interplanetary communication protocol design, validation, and characterization. JPL's Multi-mission Advanced Communications Hybrid Environment for Test and Evaluation (MACHETE), described in Simulator of Space Communication Networks (NPO-41373) NASA Tech Briefs, Vol. 29, No. 8 (August 2005), p. 44, combines various commercial, non-commercial, and in-house custom tools for simulation and performance analysis of space networks. The MACHETE environment supports orbital analysis, link budget analysis, communications network simulations, and hardware-in-the-loop testing. As NASA is expanding its Space Communications and Navigation (SCaN) capabilities to support planned and future missions, building infrastructure to maintain services and developing enabling technologies, an important and broader role is seen for MACHETE in design-phase evaluation of future SCaN architectures. To support evaluation of the developing Delay Tolerant Networking (DTN) field and its applicability for space networks, JPL developed MACHETE models for DTN Bundle Protocol (BP) and Licklider/Long-haul Transmission Protocol (LTP). DTN is an Internet Research Task Force (IRTF) architecture providing communication in and/or through highly stressed networking environments such as space exploration and battlefield networks. Stressed networking environments include those with intermittent (predictable and unknown) connectivity, large and/or variable delays, and high bit error rates. To provide its services over existing domain specific protocols, the DTN protocols reside at the application layer of the TCP/IP stack, forming a store-and-forward overlay network. The key capabilities of the Bundle Protocol include custody-based reliability, the ability to cope with intermittent connectivity, the ability to take advantage of scheduled and opportunistic connectivity, and late binding of names to addresses.

Differences between Spinocerebellar Ataxias and Multiple System Atrophy-Cerebellar Type on Proton Magnetic Resonance Spectroscopy

PubMed Central

Chen, Hung-Chieh; Soong, Bing-Wen; Guo, Wan Yuo; Wu, Hsiu-Mei; Chang, Cheng-Yen

2012-01-01

Purpose A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C). Material and Methods This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA) types 1, 2, 3, 6 and 17 (N = 94) and MSA-C (N = 62), and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. Results When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p<0.002). The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005). The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p<0.018). The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p<0.04). The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p<0.0005). In the early stages of diseases (SARA score<10), significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p<0.017). The Cho/Cr was lower in MSA-C or SCA2 (p<0.0005). Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p<0.016). Conclusion By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study. PMID:23118909

Local incentive spirometry improves peak expiratory flow rate in teenage sickle cell anaemia patients: a randomized pilot trial.

PubMed

Adeniyi, A F; Saminu, K S

2011-09-01

Efforts to promote better health of sickle cell anaemia (SCA) patients in low-income countries through the use of cheap and available alternatives are desirable. We investigated whether a locally designed incentive spirometry will improve peak expiratory flow rate (PEFR) of teenage SCA patients. Forty-nine SCA teenagers were randomized into either the SCA spirometry or the SCA control groups, which had 24 and 25 patients respectively. They were initially compared with 25 matched non-SCA teenagers. The SCA spirometry group went through a six-week, thrice-daily local incentive spirometry while the control did not go through the exercise. The PEFR of the SCA spirometry group improved significantly (p = 0.001) between the third and sixth week (211.04 ± 55.67 to 292.08 ± 40.86 litres/min) unlike that of the SCA control group (p = 0.605). At six weeks, PEFR of the SCA spirometry group improved significantly (t=0.624, p=0.003) over that of the SCA control group. However, the improved PEFR of the SCA spirometry group did not match that of their non-SCA counterparts. Locally designed incentive spirometry improved PEFR of the SCA teenagers significantly in six weeks of spirometry exercise. Routine improvement in PEFR of SCA patients with the aid of incentive spirometry should be encouraged to improve lung function.

Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study

PubMed Central

2013-01-01

Background All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. PMID:24225362

SCaLeM: A Framework for Characterizing and Analyzing Execution Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chavarría-Miranda, Daniel; Manzano Franco, Joseph B.; Krishnamoorthy, Sriram

2014-10-13

As scalable parallel systems evolve towards more complex nodes with many-core architectures and larger trans-petascale & upcoming exascale deployments, there is a need to understand, characterize and quantify the underlying execution models being used on such systems. Execution models are a conceptual layer between applications & algorithms and the underlying parallel hardware and systems software on which those applications run. This paper presents the SCaLeM (Synchronization, Concurrency, Locality, Memory) framework for characterizing and execution models. SCaLeM consists of three basic elements: attributes, compositions and mapping of these compositions to abstract parallel systems. The fundamental Synchronization, Concurrency, Locality and Memory attributesmore » are used to characterize each execution model, while the combinations of those attributes in the form of compositions are used to describe the primitive operations of the execution model. The mapping of the execution model’s primitive operations described by compositions, to an underlying abstract parallel system can be evaluated quantitatively to determine its effectiveness. Finally, SCaLeM also enables the representation and analysis of applications in terms of execution models, for the purpose of evaluating the effectiveness of such mapping.« less

The natural history of spinocerebellar ataxia type 1, 2, 3, and 6

PubMed Central

Jacobi, H.; Bauer, P.; Giunti, P.; Labrum, R.; Sweeney, M.G.; Charles, P.; Dürr, A.; Marelli, C.; Globas, C.; Linnemann, C.; Schöls, L.; Rakowicz, M.; Rola, R.; Zdzienicka, E.; Schmitz-Hübsch, T.; Fancellu, R.; Mariotti, C.; Tomasello, C.; Baliko, L.; Melegh, B.; Filla, A.; Rinaldi, C.; van de Warrenburg, B.P.; Verstappen, C.C.P.; Szymanski, S.; Berciano, J.; Infante, J.; Timmann, D.; Boesch, S.; Hering, S.; Depondt, C.; Pandolfo, M.; Kang, J.-S.; Ratzka, S.; Schulz, J.; Tezenas du Montcel, S.

2011-01-01

Objective: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. Methods: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0–40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0–16) count. Results: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. Conclusions: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression. PMID:21832228

Postural Tremor and Ataxia Progression in Spinocerebellar Ataxias

PubMed Central

Gan, Shi-Rui; Wang, Jie; Figueroa, Karla P.; Pulst, Stefan M.; Tomishon, Darya; Lee, Danielle; Perlman, Susan; Wilmot, George; Gomez, Christopher M.; Schmahmann, Jeremy; Paulson, Henry; Shakkottai, Vikram G.; Ying, Sarah H.; Zesiewicz, Theresa; Bushara, Khalaf; Geschwind, Michael D.; Xia, Guangbin; Subramony, S. H.; Ashizawa, Tetsuo; Kuo, Sheng-Han

2017-01-01

Background Postural tremor can sometimes occur in spinocerebellar ataxias (SCAs). However, the prevalence and clinical characteristics of postural tremor in SCAs are poorly understood, and whether SCA patients with postural tremor have different ataxia progression is not known. Methods We studied postural tremor in 315 patients with SCA1, 2, 3, and 6 recruited from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), which consists of 12 participating centers in the United States, and we evaluated ataxia progression in these patients from January 2010 to August 2012. Results Among 315 SCA patients, postural tremor was most common in SCA2 patients (SCA1, 5.8%; SCA2, 27.5%; SCA3, 12.4%; SCA6, 16.9%; p = 0.007). SCA3 patients with postural tremor had longer CAG repeat expansions than SCA3 patients without postural tremor (73.67 ± 3.12 vs. 70.42 ± 3.96, p = 0.003). Interestingly, SCA1 and SCA6 patients with postural tremor had a slower rate of ataxia progression (SCA1, β = –0.91, p < 0.001; SCA6, β = –1.28, p = 0.025), while SCA2 patients with postural tremor had a faster rate of ataxia progression (β = 1.54, p = 0.034). We also found that the presence of postural tremor in SCA2 patients could be influenced by repeat expansions of ATXN1 (β = –1.53, p = 0.037) and ATXN3 (β = 0.57, p = 0.018), whereas postural tremor in SCA3 was associated with repeat lengths in TBP (β = 0.63, p = 0.041) and PPP2R2B (β = –0.40, p = 0.032). Discussion Postural tremor could be a clinical feature of SCAs, and the presence of postural tremor could be associated with different rates of ataxia progression. Genetic interactions between ataxia genes might influence the brain circuitry and thus affect the clinical presentation of postural tremor. PMID:29057148

Postural Tremor and Ataxia Progression in Spinocerebellar Ataxias.

PubMed

Gan, Shi-Rui; Wang, Jie; Figueroa, Karla P; Pulst, Stefan M; Tomishon, Darya; Lee, Danielle; Perlman, Susan; Wilmot, George; Gomez, Christopher M; Schmahmann, Jeremy; Paulson, Henry; Shakkottai, Vikram G; Ying, Sarah H; Zesiewicz, Theresa; Bushara, Khalaf; Geschwind, Michael D; Xia, Guangbin; Subramony, S H; Ashizawa, Tetsuo; Kuo, Sheng-Han

2017-01-01

Postural tremor can sometimes occur in spinocerebellar ataxias (SCAs). However, the prevalence and clinical characteristics of postural tremor in SCAs are poorly understood, and whether SCA patients with postural tremor have different ataxia progression is not known. We studied postural tremor in 315 patients with SCA1, 2, 3, and 6 recruited from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA), which consists of 12 participating centers in the United States, and we evaluated ataxia progression in these patients from January 2010 to August 2012. Among 315 SCA patients, postural tremor was most common in SCA2 patients (SCA1, 5.8%; SCA2, 27.5%; SCA3, 12.4%; SCA6, 16.9%; p = 0.007). SCA3 patients with postural tremor had longer CAG repeat expansions than SCA3 patients without postural tremor (73.67 ± 3.12 vs. 70.42 ± 3.96, p = 0.003). Interestingly, SCA1 and SCA6 patients with postural tremor had a slower rate of ataxia progression (SCA1, β = -0.91, p < 0.001; SCA6, β = -1.28, p = 0.025), while SCA2 patients with postural tremor had a faster rate of ataxia progression (β = 1.54, p = 0.034). We also found that the presence of postural tremor in SCA2 patients could be influenced by repeat expansions of ATXN1 (β = -1.53, p = 0.037) and ATXN3 (β = 0.57, p = 0.018), whereas postural tremor in SCA3 was associated with repeat lengths in TBP (β = 0.63, p = 0.041) and PPP2R2B (β = -0.40, p = 0.032). Postural tremor could be a clinical feature of SCAs, and the presence of postural tremor could be associated with different rates of ataxia progression. Genetic interactions between ataxia genes might influence the brain circuitry and thus affect the clinical presentation of postural tremor.

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

PubMed Central

Bakeer, Nihal; James, Jeanne; Roy, Swarnava; Wansapura, Janaka; Shanmukhappa, Shiva Kumar; Lorenz, John N.; Osinska, Hanna; Backer, Kurt; Huby, Anne-Cecile; Shrestha, Archana; Niss, Omar; Fleck, Robert; Quinn, Charles T.; Taylor, Michael D.; Purevjav, Enkhsaikhan; Aronow, Bruce J.; Towbin, Jeffrey A.; Malik, Punam

2016-01-01

Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA. PMID:27503873

[A case of 77-year-old male with spinocerebellar ataxia type 31 with left dominant dystonia].

PubMed

Saito, Rie; Kikuno, Shota; Maeda, Meiko; Uesaka, Yoshikazu; Ida, Masahiro

2014-01-01

We report on the case of a 77-year-old male with genetically proven spinocerebellar ataxia type 31 (SCA31) who had dystonia. He was referred to our hospital for evaluation following a 6-year history of slowly progressive unsteadiness of his left leg during walking and dysarthria at the age of 62 years old. On the basis of his symptoms, we diagnosed him as spinocerebellar degeneration (SCD), and prescribed taltirelin hydrate. However, his symptoms continued to worsen. He required a cane for walking at the age of 63 years, and a wheelchair at the age of 66 years. He was admitted to our hospital following acute cerebral infarction at the age of 77 years. On examination at admission, right hemiparesis and cerebellar ataxia were detected. And left hallux moved involuntarily toward the top surface of the foot at rest, that is dystonia. The dystonia was not associated with cerebral infarction, because it had been several years with dystonia that he got cerebral infarction. Genetic analysis revealed that this patient harbored a heterozygous SCA31 mutation. Previously there have been no reports of SCA31 associated with dystonia. Our case report support clinical heterogeneity of SCA31, and highlight the importance of considering this type in patients with dystonia and ataxia. Patients with the combination of dystonia and ataxia and a family history of a neurodegenerative disorder should be tested for SCA31.

Dynamical cluster approximation plus semiclassical approximation study for a Mott insulator and d-wave pairing

NASA Astrophysics Data System (ADS)

Kim, SungKun; Lee, Hunpyo

2017-06-01

Via a dynamical cluster approximation with N c = 4 in combination with a semiclassical approximation (DCA+SCA), we study the doped two-dimensional Hubbard model. We obtain a plaquette antiferromagnetic (AF) Mott insulator, a plaquette AF ordered metal, a pseudogap (or d-wave superconductor) and a paramagnetic metal by tuning the doping concentration. These features are similar to the behaviors observed in copper-oxide superconductors and are in qualitative agreement with the results calculated by the cluster dynamical mean field theory with the continuous-time quantum Monte Carlo (CDMFT+CTQMC) approach. The results of our DCA+SCA differ from those of the CDMFT+CTQMC approach in that the d-wave superconducting order parameters are shown even in the high doped region, unlike the results of the CDMFT+CTQMC approach. We think that the strong plaquette AF orderings in the dynamical cluster approximation (DCA) with N c = 4 suppress superconducting states with increasing doping up to strongly doped region, because frozen dynamical fluctuations in a semiclassical approximation (SCA) approach are unable to destroy those orderings. Our calculation with short-range spatial fluctuations is initial research, because the SCA can manage long-range spatial fluctuations in feasible computational times beyond the CDMFT+CTQMC tool. We believe that our future DCA+SCA calculations should supply information on the fully momentum-resolved physical properties, which could be compared with the results measured by angle-resolved photoemission spectroscopy experiments.

77 FR 75766 - Federal Acquisition Regulation; Nondisplacement of Qualified Workers Under Service Contracts

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... offeror's ingenuity in proposing a technical approach or solution based on limitations of the existing... solution. Another respondent expressed concern that the rule would limit offerors' ability to craft innovative solutions to Government requirements. Response: Under the SCA, the successor contractor must pay...

Excessive daytime somnolence in spinocerebellar ataxia type 1.

PubMed

Dang, Dien; Cunnington, David

2010-03-15

Autosomal dominant spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders which result in dysfunction of the neuronal systems of the spinal cord, brainstem, and cerebellum. The manifestations of daytime somnolence and abnormal sleep behavior have been described in SCA type 3 (SCA3) and SCA type 6 (SCA6), but as yet have not been described in SCA type 1 (SCA1). We report two cases of sleep disturbance, fatigue and excessive daytime somnolence in individuals with SCA1 and their progress through several therapies. These case studies are unique as they describe excessive daytime somnolence and sleep abnormalities in SCA1.

Positive Psychological Factors are Linked to Successful Cognitive Aging Among Older Persons Living with HIV/AIDS.

PubMed

Moore, David J; Fazeli, Pariya L; Moore, Raeanne C; Woods, Steven P; Letendre, Scott L; Jeste, Dilip V; Grant, Igor

2018-05-01

We aimed to characterize successful cognitive aging (SCA) among older HIV-infected (HIV+) and HIV-uninfected (HIV-) adults, and to determine associations with positive psychological factors and health-related quality of life (HRQoL). Ninety-nine HIV+ and 46 HIV- older adults (≥ 50 years) completed measures of neurocognition, positive psychological factors, and HRQoL. Using study-defined SCA criteria (i.e., no cognitive or everyday impairment or major depressive disorder), we compared positive psychological factors and HRQoL across four groups: HIV+/SCA+, HIV+/SCA-, HIV-/SCA+, HIV-/SCA-. SCA was identified in 29% of the HIV+ sample compared to 61% of the HIV- sample (p < 0.01). HIV+/SCA+ participants had higher scores on 8 of 10 measures of positive psychological factors as well as better HRQoL (ps < 0.05) as compared to the HIV+/SCA- group. Furthermore, the HIV+/SCA+ participants had comparable scores on these factors as HIV- adults. Fewer HIV+ than HIV- participants met SCA criteria; however, the level of positive psychological factors among the HIV+/SCA+ group was comparable to the HIV- sample. Our findings present opportunities for interventions to optimize positive psychological factors and potentially improve SCA among older HIV+ adults.

Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics.

PubMed

Fujioka, Shinsuke; Sundal, Christina; Wszolek, Zbigniew K

2013-01-18

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.

Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

PubMed Central

2013-01-01

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments. PMID:23331413

Challenges in sleep stage R scoring in patients with autosomal dominant spinocerebellar ataxias (SCA1, SCA2 and SCA3) and oculomotor abnormalities: a whole night polysomnographic evaluation.

PubMed

Seshagiri, Doniparthi Venkata; Sasidharan, Arun; Kumar, Gulshan; Pal, Pramod Kumar; Jain, Sanjeev; Kutty, Bindu M; Yadav, Ravi

2018-02-01

Spinocerebellar ataxias are progressive neurodegenerative disorders characterized by progressive cerebellar features with additional neuro-axis involvement. Oculomotor abnormality is one of the most frequent manifestations. This study was done to assess the polysomnographic abnormalities in patients with Spinocerebellar ataxia (SCA1, SCA2 and SCA3) and also to evaluate whether oculomotor abnormalities interfere with sleep stage R scoring. The study was carried out using 36 genetically positive SCA patients. All patients underwent neurological examination with special focus on oculomotor function (optokinetic nystagmus-OKN and extraocular movement restriction-EOM). The sleep quality was measured with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Disease severity was assessed with International Cooperative Ataxia Rating Scale (ICARS). All the patients underwent over-night video-polysomnography (VPSG). Out of 36 patients studied, the data of 34 patients [SCA1 (n = 12), SCA2 (n = 13), SCA3 (n = 9)] were used for final analysis. Patients from SCA1, SCA2, and SCA3 category did not show significant differences in age and diseases severity (ICARS). All patients had vertical OKN impairment. Oculomotor impairment was higher in SCA2 patients. Sleep macro-architecture analysis showed absent stage R sleep, predominantly in SCA2 (69%) followed by SCA3 (44%) and SCA1 (8%). Patients showed a strong negative correlation of stage R sleep percentage with disease severity and oculomotor dysfunction. Voluntary saccadic eye movement velocity and rapid eye movements (REMs) in sleep are strongly correlated. The more severe the saccadic velocity impairment, the less likely was it to generate REMs (rapid eye movements) during stage R. Accordingly 69% of SCA2 patients with severe occulomotor impairments showed absent stage R as per the AASM sleep scoring. We presume that the impaired REMs generation in sleep could be due to oculomotor abnormality and has resulted in spuriously low or absent stage R sleep percentage in SCA patients with conventional VPSG scoring rules. The present study recommends the modification of AASM scoring rules for stage R in patients with oculomotor abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

Knockdown of acid-sensing ion channel 1a (ASIC1a) suppresses disease phenotype in SCA1 mouse model.

PubMed

Vig, Parminder J S; Hearst, Scoty M; Shao, Qingmei; Lopez, Maripar E

2014-08-01

The mutated ataxin-1 protein in spinocerebellar ataxia 1 (SCA1) targets Purkinje cells (PCs) of the cerebellum and causes progressive ataxia due to loss of PCs and neurons of the brainstem. The exact mechanism of this cellular loss is still not clear. Currently, there are no treatments for SCA1; however, understanding of the mechanisms that regulate SCA1 pathology is essential for devising new therapies for SCA1 patients. We previously established a connection between the loss of intracellular calcium-buffering and calcium-signalling proteins with initiation of neurodegeneration in SCA1 transgenic (Tg) mice. Recently, acid-sensing ion channel 1a (ASIC1a) have been implicated in calcium-mediated toxicity in many brain disorders. Here, we report generating SCA1 Tg mice in the ASIC1a knockout (KO) background and demonstrate that the deletion of ASIC1a gene expression causes suppression of the SCA1 disease phenotype. Loss of the ASIC1a channel in SCA1/ASIC1a KO mice resulted in the improvement of motor deficit and decreased PC degeneration. Interestingly, the expression of the ASIC1 variant, ASIC1b, was upregulated in the cerebellum of both SCA1/ASIC1a KO and ASIC1a KO animals as compared to the wild-type (WT) and SCA1 Tg mice. Further, these SCA1/ASIC1a KO mice exhibited translocation of PC calcium-binding protein calbindin-D28k from the nucleus to the cytosol in young animals, which otherwise have both cytosolic and nuclear localization. Furthermore, in addition to higher expression of calcium-buffering protein parvalbumin, PCs of the older SCA1/ASIC1a KO mice showed a decrease in morphologic abnormalities as compared to the age-matched SCA1 animals. Our data suggest that ASIC1a may be a mediator of SCA1 pathogenesis and targeting ASIC1a could be a novel approach to treat SCA1.

Issues Related to Assessing Listening Ability.

ERIC Educational Resources Information Center

Mead, Nancy A.

The National Assessment of Educational Progress (NAEP) and the Speech Communication Association (SCA) initiated a pilot study to test the feasibility of assessing speaking and listening skills. A pool of 56 items was developed and then field tested at four sites which represented a variety of national regions, of size and type of cities, and of…

Association between Proton Magnetic Resonance Spectroscopy Measurements and CAG Repeat Number in Patients with Spinocerebellar Ataxias 2, 3, or 6

PubMed Central

Wang, Po-Shan; Chen, Hung-Chieh; Wu, Hsiu-Mei; Lirng, Jiing-Feng; Wu, Yu-Te; Soong, Bing-Wen

2012-01-01

The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA. PMID:23094053

Single coronary artery originating from the right sinus Valsalva and ability to work.

PubMed

De Rosa, Roberto; Ratti, Gennaro; Gerardi, Donato; Tedeschi, Carlo; Lamberti, Monica

2015-01-01

We present a case of a 56-year-old male electrician who was admitted to the hospital with atrial fibrillation, atypical chest pain and dyspnea. He gave a history that on the morning he had working for almost 4 hours carrying out various activities with considerable physical effort. After cardioversion, conventional coronary angiography revealed a suspect of single coronary vessel (SCA) arising from the right sinus of Valsalva. The patient underwent multislice computed tomography that showed a SCA arising from the right sinus Valsalva and dividing in Right Coronary Artery (RCA) and Left Main coronary artery (LM). The finding of posterior course of the LM without atherosclerotic has proved crucial for the expression of an opinion of working capacity even with limitation.

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins

PubMed Central

Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

2013-01-01

Purpose To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features. Materials and Methods Tissue excised from a genetically engineered mouse model of sarcoma was imaged using a subcellular resolution microendoscope after topical application of a fluorescent anatomical contrast agent: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma. Results Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach. Conclusion The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue. PMID:23824589

Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis.

PubMed

van der Waaij, Laurens A; van Dullemen, Hendrik M; Porte, Robert J

2005-09-01

Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the value of cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs. premalignant or malignant (MCA, MCAC) lesions. A search in PubMed was performed with the search terms cyst, pancrea, and fluid. Articles about cyst fluid analysis of pancreatic lesions that contained the individual data of at least 7 patients were included in the study. Data of all individual patients were combined and were plotted in scatter grams. Cutoff levels were determined. Twelve studies were included, which comprised data of 450 patients. Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity 44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%). A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity 98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggested PC or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed malignant cells in 48% of MCAC (n = 111). Most pancreatic cystic tumors should be resected without the need for cyst fluid analysis. However, in asymptomatic patients, in patients with an increased surgical risk, and, in patients in whom there is a diagnostic uncertainty about the presence of a PC, cyst fluid analysis helps to determine the optimal therapeutic strategy.

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins.

PubMed

Mueller, Jenna L; Harmany, Zachary T; Mito, Jeffrey K; Kennedy, Stephanie A; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G; Willett, Rebecca M; Brown, J Quincy; Ramanujam, Nimmi

2013-01-01

To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features. TISSUE EXCISED FROM A GENETICALLY ENGINEERED MOUSE MODEL OF SARCOMA WAS IMAGED USING A SUBCELLULAR RESOLUTION MICROENDOSCOPE AFTER TOPICAL APPLICATION OF A FLUORESCENT ANATOMICAL CONTRAST AGENT: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma. Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach. The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue.

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

PubMed

Lim, S W; Zhao, Y; Chua, E; Law, H Y; Yuen, Y; Pavanni, R; Wong, M C; Ng, I S; Yoon, C S; Puong, K Y; Lim, S H; Tan, E K

2006-07-31

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study.

PubMed

Diallo, Alhassane; Jacobi, Heike; Cook, Arron; Labrum, Robyn; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Marelli, Cecilia; Mariotti, Caterina; Nanetti, Lorenzo; Panzeri, Marta; Rakowicz, Maria; Sobanska, Anna; Sulek, Anna; Schmitz-Hübsch, Tanja; Schöls, Ludger; Hengel, Holger; Melegh, Bela; Filla, Alessandro; Antenora, Antonella; Infante, Jon; Berciano, José; van de Warrenburg, Bart P; Timmann, Dagmar; Boesch, Sylvia; Pandolfo, Massimo; Schulz, Jörg B; Bauer, Peter; Giunti, Paola; Kang, Jun-Suk; Klockgether, Thomas; Tezenas du Montcel, Sophie

2018-04-01

Spinocerebellar ataxias are dominantly inherited progressive ataxia disorders that can lead to premature death. We aimed to study the overall survival of patients with the most common spinocerebellar ataxias (SCA1, SCA2, SCA3, and SCA6) and to identify the strongest contributing predictors that affect survival. In this longitudinal cohort study (EUROSCA), we enrolled men and women, aged 18 years or older, from 17 ataxia referral centres in ten European countries; participants had positive genetic test results for SCA1, SCA2, SCA3, or SCA6 and progressive, otherwise unexplained, ataxias. Survival was defined as the time from enrolment to death for any reason. We used the Cox regression model adjusted for age at baseline to analyse survival. We used prognostic factors with a p value less than 0·05 from a multivariate model to build nomograms and assessed their performance based on discrimination and calibration. The EUROSCA study is registered with ClinicalTrials.gov, number NCT02440763. Between July 1, 2005, and Aug 31, 2006, 525 patients with SCA1 (n=117), SCA2 (n=162), SCA3 (n=139), or SCA6 (n=107) were enrolled and followed up. The 10-year survival rate was 57% (95% CI 47-69) for SCA1, 74% (67-81) for SCA2, 73% (65-82) for SCA3, and 87% (80-94) for SCA6. Factors associated with shorter survival were: dysphagia (hazard ratio 4·52, 95% CI 1·83-11·15) and a higher value for the Scale for the Assessment and Rating of Ataxia (SARA) score (1·26, 1·19-1·33) for patients with SCA1; older age at inclusion (1·04, 1·01-1·08), longer CAG repeat length (1·16, 1·03-1·31), and higher SARA score (1·15, 1·10-1·20) for patients with SCA2; older age at inclusion (1·44, 1·20-1·74), dystonia (2·65, 1·21-5·53), higher SARA score (1·26, 1·17-1·35), and negative interaction between CAG and age at inclusion (0·994, 0·991-0·997) for patients with SCA3; and higher SARA score (1·17, 1·08-1·27) for patients with SCA6. The nomogram-predicted probability of 10-year survival showed good discrimination (c index 0·905 [SD 0·027] for SCA1, 0·822 [0·032] for SCA2, 0·891 [0·021] for SCA3, and 0·825 [0·054] for SCA6). Our study provides quantitative data on the survival of patients with the most common spinocerebellar ataxias, based on a long follow-up period. These results have implications for the design of future interventional studies of spinocerebellar ataxias; for example, the prognostic survival nomogram could be useful for selection and stratification of patients. Our findings need validation in an external population before they can be used to counsel patients and their families. European Union 6th Framework programme, German Ministry of Education and Research, Polish Ministry of Scientific Research and Information Technology, European Union 7th Framework programme, and Fondation pour la Recherche Médicale. Copyright © 2018 Elsevier Ltd. All rights reserved.

SmallSat Database

NASA Technical Reports Server (NTRS)

Petropulos, Dolores; Bittner, David; Murawski, Robert; Golden, Bert

2015-01-01

The SmallSat has an unrealized potential in both the private industry and in the federal government. Currently over 70 companies, 50 universities and 17 governmental agencies are involved in SmallSat research and development. In 1994, the U.S. Army Missile and Defense mapped the moon using smallSat imagery. Since then Smart Phones have introduced this imagery to the people of the world as diverse industries watched this trend. The deployment cost of smallSats is also greatly reduced compared to traditional satellites due to the fact that multiple units can be deployed in a single mission. Imaging payloads have become more sophisticated, smaller and lighter. In addition, the growth of small technology obtained from private industries has led to the more widespread use of smallSats. This includes greater revisit rates in imagery, significantly lower costs, the ability to update technology more frequently and the ability to decrease vulnerability of enemy attacks. The popularity of smallSats show a changing mentality in this fast paced world of tomorrow. What impact has this created on the NASA communication networks now and in future years? In this project, we are developing the SmallSat Relational Database which can support a simulation of smallSats within the NASA SCaN Compatability Environment for Networks and Integrated Communications (SCENIC) Modeling and Simulation Lab. The NASA Space Communications and Networks (SCaN) Program can use this modeling to project required network support needs in the next 10 to 15 years. The SmallSat Rational Database could model smallSats just as the other SCaN databases model the more traditional larger satellites, with a few exceptions. One being that the smallSat Database is designed to be built-to-order. The SmallSat database holds various hardware configurations that can be used to model a smallSat. It will require significant effort to develop as the research material can only be populated by hand to obtain the unique data required. When completed it will interface with the SCENIC environment to allow modeling of smallSats. The SmallSat Relational Database can also be integrated with the SCENIC Simulation modeling system that is currently in development. The SmallSat Relational Database simulation will be of great significance in assisting the NASA SCaN group to understand the impact the smallSats have made which have populated the lower orbit around our mother earth. What I have created and worked on this summer session 2015, is the basis for a tool that will be of value to the NASA SCaN SCENIC Simulation Environment for years to come.

Isolation and expression of scabrous, a gene regulating neurogenesis in Drosophila.

PubMed

Mlodzik, M; Baker, N E; Rubin, G M

1990-11-01

Mutations in the Drosophila scabrous (sca) gene affect eye and bristle development, leading to irregular spacing of ommatidia and bristle duplications in the adult fly. We have cloned the sca gene by P-element tagging. The sca transcription unit is 12 kb and consists of four exons that are joined in a 3.2-kb mRNA. In an enhancer trap screen we have isolated several P[lacZ] insertions close to the sca transcription start site. We have examined the expression pattern of sca by in situ hybridization to sca transcripts, by beta-galactosidase localization in the P[lacZ] lines, and by immunocytochemistry with an anti-sca antiserum. During embryogenesis, sca is expressed in a dynamic pattern associated with neural development. During imaginal development, sca is mainly expressed in the R8 photoreceptor precursor cells in the eye imaginal disc and in sensory organ precursor cells in other discs. In the wing disc, sca expression is coextensive with the anlagen for bristles and is controlled by genes of the achaete-scute complex. Based on its loss-of-function phenotype, expression pattern, and the predicted structure of its product, a secreted peptide with homology to the fibrinogen gene family, we propose that sca encodes a signal involved in lateral inhibition within individual domains of the developing nervous system.

Possible reduced penetrance of expansion of 44 to 47 CAG/CAA repeats in the TATA-binding protein gene in spinocerebellar ataxia type 17.

PubMed

Oda, Masaya; Maruyama, Hirofumi; Komure, Osamu; Morino, Hiroyuki; Terasawa, Hideo; Izumi, Yuishin; Imamura, Tohru; Yasuda, Minoru; Ichikawa, Keiji; Ogawa, Masafumi; Matsumoto, Masayasu; Kawakami, Hideshi

2004-02-01

Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by expansion of CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. Because the number of triplets in patients with SCA17 in previous studies ranged from 43 to 63, the normal number of trinucleotide units has been considered to be 42 or less. However, some healthy subjects in SCA17 pedigrees carry alleles with the same number of expanded repeats as patients with SCA17. To investigate the minimum number of CAG/CAA repeats in the TBP gene that causes SCA17. We amplified the region of the TBP gene containing the CAG/CAA repeat by means of polymerase chain reaction and performed fragment and sequence analyses. The subjects included 734 patients with SCA (480 patients with sporadic SCA and 254 patients with familial SCA) without CAG repeat expansions at the SCA1, SCA2, Machado-Joseph disease, SCA6, SCA7, or dentatorubral-pallidolluysian atrophy loci, with 162 healthy subjects, 216 patients with Parkinson disease, and 195 with Alzheimer disease as control subjects. Eight patients with SCA possessed an allele with more than 43 CAG/CAA repeats. Among the non-SCA groups, alleles with 43 to 45 repeats were seen in 3 healthy subjects and 2 with Parkinson disease. In 1 SCA pedigree, a patient with possible SCA17 and her healthy sister had alleles with 45 repeats. A 34-year-old man carrying alleles with 47 and 44 repeats (47/44) had developed progressive cerebellar ataxia and myoclonus at 25 years of age, and he exhibited dementia and pyramidal signs. He was the only affected person in his pedigree, although his father and mother carried alleles with mildly expanded repeats (44/36 and 47/36, respectively). In another pedigree, 1 patient carried a 43-repeat allele, whereas another patient had 2 normal alleles, indicating that the 43-repeat allele may not be pathologic in this family. We estimate that 44 CAG/CAA repeats is the minimum number required to cause SCA17. However, the existence of unaffected subjects with mildly expanded triplets suggests that the TBP gene mutation may not penetrate fully. Homozygosity of alleles with mildly expanded triplet repeats in the TBP gene might contribute to the pathologic phenotype.

Impacts of the EA and SCA patterns on the 20th century NAO-winter precipitation relationship in Europe

NASA Astrophysics Data System (ADS)

Comas-Bru, Laia; McDermott, Frank

2013-04-01

Much of the 20th century multi-decadal variability in the NAO-winter precipitation relationship over the N. Atlantic / European sector can be ascribed to the combined effects of the North Atlantic Oscillation (NAO) and either the East Atlantic pattern (EA) or the Scandinavian pattern (SCA). The NAO, EA and SCA indices employed here are defined as the three leading vectors of the cross-correlation matrix calculated from monthly sea-level pressure anomalies for 138 complete winters from the 20CRv2 dataset (Compo et al., 2011). Winter precipitation data over Europe for the entire 20th century is derived from the high resolution CRU-TS3.1 climate dataset (Mitchell and Jones, 2005). Here we document for the first time, that different NAO/EA and NAO/SCA combinations systematically influence winter precipitation conditions in Europe as a consequence of NAO dipole migrations. We find that the zero-correlated line of the NAO-winter precipitation relationship migrates southwards when the EA is in the opposite phase to the NAO. This can be related to a south-westwards migration of the NAO dipole under these conditions, as shown by teleconnectivity maps. Similarly, a clockwise movement of the NAO-winter climate correlated areas occurs when the phase of the SCA is opposite to that of the NAO, reflecting a clockwise movement of the NAO dipole under these conditions. An important implication of these migrations is that they influence the spatial and temporal stationarity of climate-NAO relationships. As a result, the link between winter precipitation patterns and the NAO is not straightforward in some regions such as the southern UK, Ireland and France. For instance, much of the inter-annual variability in the N-S winter precipitation gradient in the UK, originally attributed to inter-annual and inter-decadal variability of the NAO, reflects the migration of the NAO dipole, linked to linear combinations of the NAO and the EA. Our results indicate that when the N-S winter precipitation gradient is accentuated by the occurrence of a positive EA during positive NAO winters, drier conditions than normal are found in the southern UK. This is consistent, for example, with the severe winter drought of 1976, when computed NAO and EA indices were both positive (0.97 and 1.87, respectively), illustrating the modulating effect of NAO/EA combinations on winter precipitation patterns in the southern UK. References: Compo GP et al. 2011. The Twentieth Century Reanalysis Project. Quarterly Journal of the Royal Meteorological Society, 137 (654), 1-28. Mitchell TD, Jones PD. 2005. An improved method for constructing a database of monthly climate observations and associated high-resolution grids. International Journal of Climatology, 25, 693-712.

Cell biology of spinocerebellar ataxia.

PubMed

Orr, Harry T

2012-04-16

Ataxia is a neurological disorder characterized by loss of control of body movements. Spinocerebellar ataxia (SCA), previously known as autosomal dominant cerebellar ataxia, is a biologically robust group of close to 30 progressive neurodegenerative diseases. Six SCAs, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are caused by expansion of a CAG repeat that encodes a polyglutamine tract in the affected protein. How the mutated proteins in these polyglutamine SCAs cause disease is highly debated. Recent work suggests that the mutated protein contributes to pathogenesis within the context of its "normal" cellular function. Thus, understanding the cellular function of these proteins could aid in the development of therapeutics.

Breeding Potential of Introgression Lines Developed from Interspecific Crossing between Upland Cotton (Gossypium hirsutum) and Gossypium barbadense: Heterosis, Combining Ability and Genetic Effects

PubMed Central

Li, Xingli; Pei, Wenfeng

2016-01-01

Upland cotton (Gossypium hirstum L.), which produces more than 95% of the world natural cotton fibers, has a narrow genetic base which hinders progress in cotton breeding. Introducing germplasm from exotic sources especially from another cultivated tetraploid G. barbadense L. can broaden the genetic base of Upland cotton. However, the breeding potential of introgression lines (ILs) in Upland cotton with G. barbadense germplasm integration has not been well addressed. This study involved six ILs developed from an interspecific crossing and backcrossing between Upland cotton and G. barbadense and represented one of the first studies to investigate breeding potentials of a set of ILs using a full diallel analysis. High mid-parent heterosis was detected in several hybrids between ILs and a commercial cultivar, which also out-yielded the high-yielding cultivar parent in F1, F2 and F3 generations. A further analysis indicated that general ability (GCA) variance was predominant for all the traits, while specific combining ability (SCA) variance was either non-existent or much lower than GCA. The estimated GCA effects and predicted additive effects for parents in each trait were positively correlated (at P<0.01). Furthermore, GCA and additive effects for each trait were also positively correlated among generations (at P<0.05), suggesting that F2 and F3 generations can be used as a proxy to F1 in analyzing combining abilities and estimating genetic parameters. In addition, differences between reciprocal crosses in F1 and F2 were not significant for yield, yield components and fiber quality traits. But maternal effects appeared to be present for seed oil and protein contents in F3. This study identified introgression lines as good general combiners for yield and fiber quality improvement and hybrids with high heterotic vigor in yield, and therefore provided useful information for further utilization of introgression lines in cotton breeding. PMID:26730964

Breeding Potential of Introgression Lines Developed from Interspecific Crossing between Upland Cotton (Gossypium hirsutum) and Gossypium barbadense: Heterosis, Combining Ability and Genetic Effects.

PubMed

Zhang, Jinfa; Wu, Man; Yu, Jiwen; Li, Xingli; Pei, Wenfeng

2016-01-01

Upland cotton (Gossypium hirstum L.), which produces more than 95% of the world natural cotton fibers, has a narrow genetic base which hinders progress in cotton breeding. Introducing germplasm from exotic sources especially from another cultivated tetraploid G. barbadense L. can broaden the genetic base of Upland cotton. However, the breeding potential of introgression lines (ILs) in Upland cotton with G. barbadense germplasm integration has not been well addressed. This study involved six ILs developed from an interspecific crossing and backcrossing between Upland cotton and G. barbadense and represented one of the first studies to investigate breeding potentials of a set of ILs using a full diallel analysis. High mid-parent heterosis was detected in several hybrids between ILs and a commercial cultivar, which also out-yielded the high-yielding cultivar parent in F1, F2 and F3 generations. A further analysis indicated that general ability (GCA) variance was predominant for all the traits, while specific combining ability (SCA) variance was either non-existent or much lower than GCA. The estimated GCA effects and predicted additive effects for parents in each trait were positively correlated (at P<0.01). Furthermore, GCA and additive effects for each trait were also positively correlated among generations (at P<0.05), suggesting that F2 and F3 generations can be used as a proxy to F1 in analyzing combining abilities and estimating genetic parameters. In addition, differences between reciprocal crosses in F1 and F2 were not significant for yield, yield components and fiber quality traits. But maternal effects appeared to be present for seed oil and protein contents in F3. This study identified introgression lines as good general combiners for yield and fiber quality improvement and hybrids with high heterotic vigor in yield, and therefore provided useful information for further utilization of introgression lines in cotton breeding.

Suppression of calbindin-D28k expression exacerbates SCA1 phenotype in a disease mouse model.

PubMed

Vig, Parminder J S; Wei, Jinrong; Shao, Qingmei; Lopez, Maripar E; Halperin, Rebecca; Gerber, Jill

2012-09-01

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a polyglutamine tract in the mutant protein ataxin-1. The cerebellar Purkinje cells (PCs) are the major targets of mutant ataxin-1. The mechanism of PC death in SCA1 is not known; however, previous work indicates that downregulation of specific proteins involved in calcium homeostasis and signaling by mutant ataxin-1 is the probable cause of PC degeneration in SCA1. In this study, we explored if targeted deprivation of PC specific calcium-binding protein calbindin-D28k (CaB) exacerbates ataxin-1 mediated toxicity in SCA1 transgenic (Tg) mice. Using behavioral tests, we found that though both SCA1/+ and SCA1/+: CaB null (-/+) double mutants exhibited progressive impaired performance on the rotating rod, a simultaneous enhancement of exploratory activity, and absence of deficits in coordination, the double mutants were more severely impaired than SCA1/+ mice. With increasing age, SCA1/+ mice showed a progressive loss in the expression and localization of CaB and other PC specific calcium-binding and signaling proteins. In double mutants, these changes were more pronounced and had an earlier onset. Gene expression profiling of young mice exhibiting no behavior or biochemical deficits revealed a differential expression of many genes common to SCA1/+ and CaB-/+ lines, and unique to SCA1/+: CaB-/+ phenotype. Our study provides further evidence for a critical role of CaB in SCA1 pathogenesis, which may help identify new therapeutic targets to treat SCA1 or other cerebellar ataxias.

Sudden Cardiac Arrest (SCA) Risk Assessment

MedlinePlus

... HRS Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... people of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...

Inheritance of Resistance to Sorghum Shoot Fly, Atherigona soccata in Sorghum, Sorghum bicolor (L.) Moench

PubMed Central

Mohammed, Riyazaddin; Are, Ashok Kumar; Munghate, Rajendra Sudhakar; Bhavanasi, Ramaiah; Polavarapu, Kavi Kishor B.; Sharma, Hari Chand

2016-01-01

Sorghum production is affected by a wide array of biotic constraints, of which sorghum shoot fly, Atherigona soccata is the most important pest, which severely damages the sorghum crop during the seedling stage. Host plant resistance is one of the major components to control sorghum shoot fly, A. soccata. To understand the nature of gene action for inheritance of shoot fly resistance, we evaluated 10 parents, 45 F1's and their reciprocals in replicated trials during the rainy and postrainy seasons. The genotypes ICSV 700, Phule Anuradha, ICSV 25019, PS 35805, IS 2123, IS 2146, and IS 18551 exhibited resistance to shoot fly damage across seasons. Crosses between susceptible parents were preferred for egg laying by the shoot fly females, resulting in a susceptible reaction. ICSV 700, ICSV 25019, PS 35805, IS 2123, IS 2146, and IS 18551 exhibited significant and negative general combining ability (gca) effects for oviposition, deadheart incidence, and overall resistance score. The plant morphological traits associated with expression of resistance/susceptibility to shoot fly damage such as leaf glossiness, plant vigor, and leafsheath pigmentation also showed significant gca effects by these genotypes, suggesting the potential for use as a selection criterion to breed for resistance to shoot fly, A. soccata. ICSV 700, Phule Anuradha, IS 2146 and IS 18551 with significant positive gca effects for trichome density can also be utilized in improving sorghums for shoot fly resistance. The parents involved in hybrids with negative specific combining ability (sca) effects for shoot fly resistance traits can be used in developing sorghum hybrids with adaptation to postrainy season. The significant reciprocal effects of combining abilities for oviposition, leaf glossy score and trichome density suggested the influence of cytoplasmic factors in inheritance of shoot fly resistance. Higher values of variance due to specific combining ability (σ2s), dominance variance (σ2d), and lower predictability ratios than the variance due to general combining ability (σ2g) and additive variance (σ2a) for shoot fly resistance traits indicated the predominance of dominance type of gene action, whereas trichome density, leaf glossy score, and plant vigor score with high σ2g, additive variance, predictability ratio, and the ratio of general combining ability to the specific combining ability showed predominance of additive type of gene action indicating importance of heterosis breeding followed by simple selection in breeding shoot fly-resistant sorghums. Most of the traits exhibited high broadsense heritability, indicating high inheritance of shoot fly resistance traits. PMID:27200020

Brain pathology of spinocerebellar ataxias.

PubMed

Seidel, Kay; Siswanto, Sonny; Brunt, Ewout R P; den Dunnen, Wilfred; Korf, Horst-Werner; Rüb, Udo

2012-07-01

The autosomal dominant cerebellar ataxias (ADCAs) represent a heterogeneous group of neurodegenerative diseases with progressive ataxia and cerebellar degeneration. The current classification of this disease group is based on the underlying genetic defects and their typical disease courses. According to this categorization, ADCAs are divided into the spinocerebellar ataxias (SCAs) with a progressive disease course, and the episodic ataxias (EA) with episodic occurrences of ataxia. The prominent disease symptoms of the currently known and genetically defined 31 SCA types result from damage to the cerebellum and interconnected brain grays and are often accompanied by more specific extra-cerebellar symptoms. In the present review, we report the genetic and clinical background of the known SCAs and present the state of neuropathological investigations of brain tissue from SCA patients in the final disease stages. Recent findings show that the brain is commonly seriously affected in the polyglutamine SCAs (i.e. SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) and that the patterns of brain damage in these diseases overlap considerably in patients suffering from advanced disease stages. In the more rarely occurring non-polyglutamine SCAs, post-mortem neuropathological data currently are scanty and investigations have been primarily performed in vivo by means of MRI brain imaging. Only a minority of SCAs exhibit symptoms and degenerative patterns allowing for a clear and unambiguous diagnosis of the disease, e.g. retinal degeneration in SCA7, tau aggregation in SCA11, dentate calcification in SCA20, protein depositions in the Purkinje cell layer in SCA31, azoospermia in SCA32, and neurocutaneous phenotype in SCA34. The disease proteins of polyglutamine ataxias and some non-polyglutamine ataxias aggregate as cytoplasmic or intranuclear inclusions and serve as morphological markers. Although inclusions may impair axonal transport, bind transcription factors, and block protein quality control, detailed molecular and pathogenetic consequences remain to be determined.

High relative frequency of SCA1 in Poland reflecting a potential founder effect.

PubMed

Krysa, Wioletta; Sulek, Anna; Rakowicz, Maria; Szirkowiec, Walentyna; Zaremba, Jacek

2016-08-01

Spinocerebellar ataxias (SCAs) have irregular distributions worldwide. SCA1 is the most frequent in Poland, and no cases of SCA3 of Polish origin has yet been identified. In view of such patterns of SCAs occurrence, the relative frequency, geographical distribution and a possible founder effect of SCA1 were investigated. DNA samples of 134 probands with SCA1 and 228 controls were analysed. The genotyping of four markers, D6S89, D6S109, D6S274, D6S288, around the ATXN1 gene (SCA1) and sequencing of the selected variant of D6S89 were performed. The relative frequency of SCA1 was 68 %. The studied SCA1 pedigrees were irregularly distributed, with the highest concentration in Central Poland. Haplotyping revealed the association of ATXN1 gene mutation with a 197-bp variant of D6S89 marker (63 % of probands) and with a 184-bp variant of DS6274 (50.7 % of probands). Out of 61 SCA1 probands from Mazowieckie, 41 carried the same 197-bp variant. SCA1 relative frequency in Poland shows the highest value compared with the data from other countries worldwide. Due to the association with the mutation obtained for the investigated markers and the SCA1 pedigrees concentration in Central Poland, we hypothesise that it represents a potential founder effect.

Higher prevalence of wheezing and lower FEV1 and FVC percent predicted in adults with sickle cell anaemia: A cross-sectional study.

PubMed

Musa, Baba M; Galadanci, Najibah A; Rodeghier, Mark; Debaun, Michael R

2017-02-01

Respiratory symptoms including wheezing are common in adults with sickle cell anaemia (SCA), even in the absence of asthma. However, the prevalence of spirometry changes and respiratory symptoms in adults with SCA is unknown. Using a cross-sectional study design, we tested the hypothesis that adults with SCA (cases) would have higher rates of lower airway obstruction and wheezing than those without SCA (controls) using the American Thoracic Society Division of Lung Diseases' questionnaire. Patients were adults with SCA aged between 18 and 65 years. Controls were consecutive unselected individuals without SCA who presented to an outpatient general medicine clinic. We enrolled 150 adults with SCA and 287 consecutive controls without SCA. The median age was 23.0 and 27.0 years for adults with and without SCA, respectively. Cases were more likely to report cough without a cold (35.0% vs 18.6%, P < 0.001), lower forced expiratory volume in 1 s (FEV 1 ) % predicted (70.1% vs 82.1%, P = 0.001) and lower forced vital capacity (FVC) % predicted (67.4% vs 74.9%, P = 0.001) than controls. In the multivariable model, wheezing was significantly associated with SCA status (OR = 1.69, 95% CI = 1.08-2.65, P = 0.024). Similarly, FEV 1 % predicted was significantly associated with SCA status and wheezing (P = 0.001 for both). Adults with SCA experience a higher rate of wheezing and impaired respiratory functions compared with controls from the same region. © 2016 Asian Pacific Society of Respirology.

Difference in the effects of tandospirone on ataxia in various types of spinocerebellar degeneration: an open-label study.

PubMed

Takei, Asako; Hamada, Shinsuke; Homma, Sanae; Hamada, Keiko; Tashiro, Kunio; Hamada, Takeshi

2010-12-01

The aim of this study was to investigate the effects of tandospirone on ataxia in various types of spinocerebellar degeneration (SCD). Fifteen milligram per day of tandospirone was administered to 39 patients with SCD (spinocerebellar atrophy (SCA) 1, five patients; SCA2, six patients; Machado-Joseph disease (MJD), 14 patient; SCA6, five patients; multiple system atrophy-cerebellar type (MSA-C), seven patients; and multiple system atrophy-Parkinson type (MSA-P), two patients). All patients were assessed before and 4 weeks after administration of the drug using the international cooperative ataxia rating scale total score (ARS), total length traveled (TLT) of body stabilometry, and a self-rating depression scale. Statistically, ARS showed a significant difference in MJD (p = 0.005) and SCA6 (p = 0.043). TLT also showed a significant difference in MJD (p = 0.002) and SCA6 (p = 0.043). Eight of 39 patients (SCA1, 1/5; SCA2, 0/6; MJD, 4/14; SCA6, 3/5; MSA-C, 0/7; and MSA-P, 0/2) showed more than a five point reduction in ARS, and 13 of 39 patients (SCA1, 0/5; SCA2, 1/6; MJD, 8/14; SCA6, 4/5; MSA-C, 0/7; and MSA-P, 0/2) showed a reduction of TLT. Our data indicate that the effects of tandospirone on ataxia are different between types of SCD. Therefore, tandospirone is useful for cerebellar ataxia in patients with MJD and SCA6.

Seroprevalence of parvovirus B19 antibodies and evidence of viremia among Nigerian patients with sickle cell anemia.

PubMed

Iwalokun, Bamidele Abiodun; Iwalokun, Senapon Olusola; Hodonu, Semande Olufunmilayo

2013-07-01

Clinical, biochemical and molecular evidence for the sickle cell anemia (SCA) crisis in Nigerian patients arising from parvovirus b19 infection remains inadequate. This study determined the prevalence and correlates of anti-parvovirus b19 antibodies in a population of SCA patients and non-SCA healthy controls in Lagos, Nigeria. In this prospective cross-sectional study, we enrolled 73 confirmed SCA patients from 5 district hospitals in Lagos and 81 sex and age-matched non-SCA healthy controls. Serum sample from each study participant was screened for anti-parvovirus b19 by ELISA and PCR techniques. Standard biomedical assays were also done. Anti-parvovirus b19 IgM and IgG antibodies were detected in 22 (14.3%) and 97 (62.9%) of the 154 sera screened, 13 (17.8%) and 45 (61.6%) in SCA patients; 9 (11.1%) and 52 (64.2%) in non-SCA controls. The overall seronegativity rate was 19.5%. Parvovirus B19 DNA was found in 2 (11.1%) of the 18 IgM seropositive SCA serum samples screened. On the whole, parvovirus b19 infection was more commonly asymptomatic in non-SCA controls but caused significant elevation in liver enzymes in infected SCA patients (P < 0.05). The risk of acute parvovirus b19 infection increased 65 times during unsteady state among the SCA patients. Although no deaths of infected patients were recorded during the study, age below 12 years, hospitalization and overcrowded environment were risk factors for infection. We conclude that parvovirus b19 is common in SCA patients, incurring greater susceptibility to infections.

Cell biology of spinocerebellar ataxia

PubMed Central

2012-01-01

Ataxia is a neurological disorder characterized by loss of control of body movements. Spinocerebellar ataxia (SCA), previously known as autosomal dominant cerebellar ataxia, is a biologically robust group of close to 30 progressive neurodegenerative diseases. Six SCAs, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are caused by expansion of a CAG repeat that encodes a polyglutamine tract in the affected protein. How the mutated proteins in these polyglutamine SCAs cause disease is highly debated. Recent work suggests that the mutated protein contributes to pathogenesis within the context of its “normal” cellular function. Thus, understanding the cellular function of these proteins could aid in the development of therapeutics. PMID:22508507

Expansion of the Spinocerebellar Ataxia Type 10 (SCA10) Repeat in a Patient with Sioux Native American Ancestry

PubMed Central

Liu, Jilin; McFarland, Karen N.; Landrian, Ivette; Hutter, Diane; Teive, Hélio A. G.; Rasmussen, Astrid; Mulligan, Connie J.; Ashizawa, Tetsuo

2013-01-01

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described “SCA10 haplotype”. This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas. PMID:24278426

A novel population of local pericyte precursor cells in tumor stroma that require Notch signaling for differentiation.

PubMed

Patenaude, Alexandre; Woerher, Stefan; Umlandt, Patricia; Wong, Fred; Ibrahim, Rawa; Kyle, Alastair; Unger, Sandy; Fuller, Megan; Parker, Jeremy; Minchinton, Andrew; Eaves, Connie J; Karsan, Aly

2015-09-01

Pericytes are perivascular support cells, the origin of which in tumor tissue is not clear. Recently, we identified a Tie1(+) precursor cell that differentiates into vascular smooth muscle, in a Notch-dependent manner. To understand the involvement of Notch in the ontogeny of tumor pericytes we used a novel flow immunophenotyping strategy to define CD146(+)/CD45(-)/CD31(-/lo) pericytes in the tumor stroma. This strategy combined with ex vivo co-culture experiments identified a novel pericyte progenitor cell population defined as Sca1(hi)/CD146(-)/CD45(-)/CD31(-). The differentiation of these progenitor cells was stimulated by co-culture with endothelial cells. Overexpression of the Notch ligand Jagged1 in endothelial cells further stimulated the differentiation of Sca1(hi)/CD146(-)/CD45(-)/CD31(-) cells into pericytes, while inhibition of Notch signaling with a γ-secretase inhibitor reduced this differentiation. However, Notch inhibition specifically in Tie1-expressing cells did not change the abundance of pericytes in tumors, suggesting that the pericyte precursor is distinct from the vascular smooth muscle cell precursor. Transplant experiments showed that the bone marrow contributes minimally to tumor pericytes. Immunophenotyping revealed that Sca1(hi)/CD146(-)/CD45(-)/CD31(-) cells have greater potential to differentiate into pericytes and have increased expression of classic mesenchymal stem cell markers (CD13, CD44, Nt5e and Thy-1) compared to Sca1(-/lo)/CD146(-)/CD45(-)/CD31(-) cells. Our results suggest that a local Sca1(hi)/CD146(-)/CD45(-)/CD31(-) pericyte progenitor resides in the tumor microenvironment and requires Notch signaling for differentiation into mature pericytes. Copyright © 2015 Elsevier Inc. All rights reserved.

Image analysis driven single-cell analytics for systems microbiology.

PubMed

Balomenos, Athanasios D; Tsakanikas, Panagiotis; Aspridou, Zafiro; Tampakaki, Anastasia P; Koutsoumanis, Konstantinos P; Manolakos, Elias S

2017-04-04

Time-lapse microscopy is an essential tool for capturing and correlating bacterial morphology and gene expression dynamics at single-cell resolution. However state-of-the-art computational methods are limited in terms of the complexity of cell movies that they can analyze and lack of automation. The proposed Bacterial image analysis driven Single Cell Analytics (BaSCA) computational pipeline addresses these limitations thus enabling high throughput systems microbiology. BaSCA can segment and track multiple bacterial colonies and single-cells, as they grow and divide over time (cell segmentation and lineage tree construction) to give rise to dense communities with thousands of interacting cells in the field of view. It combines advanced image processing and machine learning methods to deliver very accurate bacterial cell segmentation and tracking (F-measure over 95%) even when processing images of imperfect quality with several overcrowded colonies in the field of view. In addition, BaSCA extracts on the fly a plethora of single-cell properties, which get organized into a database summarizing the analysis of the cell movie. We present alternative ways to analyze and visually explore the spatiotemporal evolution of single-cell properties in order to understand trends and epigenetic effects across cell generations. The robustness of BaSCA is demonstrated across different imaging modalities and microscopy types. BaSCA can be used to analyze accurately and efficiently cell movies both at a high resolution (single-cell level) and at a large scale (communities with many dense colonies) as needed to shed light on e.g. how bacterial community effects and epigenetic information transfer play a role on important phenomena for human health, such as biofilm formation, persisters' emergence etc. Moreover, it enables studying the role of single-cell stochasticity without losing sight of community effects that may drive it.

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients.

PubMed

Pallis, Flavia Rubia; Conran, Nicola; Fertrin, Kleber Yotsumoto; Olalla Saad, Sara Terezinha; Costa, Fernando Ferreira; Franco-Penteado, Carla Fernanda

2014-01-01

Inflammation, leucocyte and red cell adhesion to the endothelium contribute to the pathogenesis of sickle cell anaemia. Neutrophils appear to be important for vaso-occlusion, however, eosinophils may also participate in this phenomenon. The role of eosinophils in the pathophysiology of sickle cell anaemia (SCA) and the effect of hydroxycarbamide (HC) therapy on the functional properties of these cells are not understood. Patients with SCA and those on HC therapy (SCAHC) were included in the study. SCAHC individuals presented significantly lower absolute numbers of eosinophils than SCA. Furthermore, SCAHC eosinophils demonstrated significantly lower adhesive properties, compared to SCA eosinophils. SCA and SCAHC eosinophils presented greater spontaneous migration when compared with control eosinophils. Baseline eosinophil peroxidase and reactive oxygen species release was higher for SCA individuals than for control individuals, as were plasma levels of eosinophil derived neurotoxin. SCAHC eosinophil degranulation was lower than that of SCA eosinophil degranulation. Eotaxin-1 and RANTES levels were higher in the plasma of SCA and SCAHC individuals, when compared with controls. These data suggest that eosinophils exist in an activated state in SCA and indicate that these cells play a role in the vaso-occlusive process. The exact mechanism by which HC may alter SCA eosinophil properties is not clear. © 2013 John Wiley & Sons Ltd.

Seroprevalence of parvovirus B19 antibodies and evidence of viremia among Nigerian patients with sickle cell anemia

PubMed Central

Iwalokun, Bamidele Abiodun; Iwalokun, Senapon Olusola; Hodonu, Semande Olufunmilayo

2013-01-01

Clinical, biochemical and molecular evidence for the sickle cell anemia (SCA) crisis in Nigerian patients arising from parvovirus b19 infection remains inadequate. This study determined the prevalence and correlates of anti-parvovirus b19 antibodies in a population of SCA patients and non-SCA healthy controls in Lagos, Nigeria. In this prospective cross-sectional study, we enrolled 73 confirmed SCA patients from 5 district hospitals in Lagos and 81 sex and age-matched non-SCA healthy controls. Serum sample from each study participant was screened for anti-parvovirus b19 by ELISA and PCR techniques. Standard biomedical assays were also done. Anti-parvovirus b19 IgM and IgG antibodies were detected in 22 (14.3%) and 97 (62.9%) of the 154 sera screened, 13 (17.8%) and 45 (61.6%) in SCA patients; 9 (11.1%) and 52 (64.2%) in non-SCA controls. The overall seronegativity rate was 19.5%. Parvovirus B19 DNA was found in 2 (11.1%) of the 18 IgM seropositive SCA serum samples screened. On the whole, parvovirus b19 infection was more commonly asymptomatic in non-SCA controls but caused significant elevation in liver enzymes in infected SCA patients (P < 0.05). The risk of acute parvovirus b19 infection increased 65 times during unsteady state among the SCA patients. Although no deaths of infected patients were recorded during the study, age below 12 years, hospitalization and overcrowded environment were risk factors for infection. We conclude that parvovirus b19 is common in SCA patients, incurring greater susceptibility to infections. PMID:23885266

Estimation of Handgrip Force from SEMG Based on Wavelet Scale Selection.

PubMed

Wang, Kai; Zhang, Xianmin; Ota, Jun; Huang, Yanjiang

2018-02-24

This paper proposes a nonlinear correlation-based wavelet scale selection technology to select the effective wavelet scales for the estimation of handgrip force from surface electromyograms (SEMG). The SEMG signal corresponding to gripping force was collected from extensor and flexor forearm muscles during the force-varying analysis task. We performed a computational sensitivity analysis on the initial nonlinear SEMG-handgrip force model. To explore the nonlinear correlation between ten wavelet scales and handgrip force, a large-scale iteration based on the Monte Carlo simulation was conducted. To choose a suitable combination of scales, we proposed a rule to combine wavelet scales based on the sensitivity of each scale and selected the appropriate combination of wavelet scales based on sequence combination analysis (SCA). The results of SCA indicated that the scale combination VI is suitable for estimating force from the extensors and the combination V is suitable for the flexors. The proposed method was compared to two former methods through prolonged static and force-varying contraction tasks. The experiment results showed that the root mean square errors derived by the proposed method for both static and force-varying contraction tasks were less than 20%. The accuracy and robustness of the handgrip force derived by the proposed method is better than that obtained by the former methods.

Serum levels of copeptin, C-reactive protein and cortisol in different severity groups of sickle cell anaemia.

PubMed

Akinlade, K S; Atere, A D; Rahamon, S K; Olaniyi, J A

2013-12-20

It is well known that individuals with SCA undergo constant physiological stress even, in steady state. However, there is little information on the relationship between the severity of sickle cell anaemia (SCA) and serum levels of biomarkers of stress. This study therefore determined the serum levels of copeptin, cortisol and CRP in adults with SCA in different severity groups. Sixty adults with sickle cell anaemia in steady state (27.1±6.3 years) and in vaso-occlusive crisis (24.9±4.9 years) were recruited into this cross-sectional study. Degree of severity (mild, moderate or severe) was determined using a scoring system incorporating annual number of blood transfusions, crisis and presence of anaemia, vaso-occlusive pain and organ complications. Standard methods were used for the determination of packed cell volume (PCV), total white blood cell count (WBC), blood pressure measurements and anthropometric indices. Serum levels of copeptin, cortisol and CRP were determined using ELISA with the ratios calculated accordingly. Data obtained were statistically analyzed using the Student's t-test, Mann Whitney U and Chi-square test as appropriate. P<0.05 was considered significant. The mean systolic blood pressure (SBP) and copeptin level were significantly higher in subjects with moderate SCA compared with those with mild SCA. Similarly SBP, pulse, WBC, copeptin and cortisol were significantly higher while body weight was significantly lower in subjects with severe SCA compared with subjects with mild SCA. However, WBC and cortisol-to-copeptin ratio were significantly higher in subjects with severe SCA compared with subjects with moderate SCA. There was progressive rise in serum levels of CRP from mild SCA through severe SCA but the differences were not statistically significant. Also, proportions of subjects with elevated SBP and WBC were higher than the proportion of subjects with lower SBP and WBC in the severe SCA group. Serum levels of cortisol, copeptin, and their ratio could differentiate severe SCA from mild or moderate SCA. Also, elevated systolic blood pressure and total white blood cell count are associated with severe sickle cell anaemia.

Assessment of biochemical liver function tests in relation to age among steady state sickle cell anemia patients.

PubMed

Akuyam, S A; Abubakar, A; Lawal, N; Yusuf, R; Aminu, S M; Hassan, A; Musa, A; Bello, A K; Yahaya, I A; Okafor, P A

2017-11-01

Multiorgan failure including liver dysfunction is a common finding in sickle cell anemia (SCA) patients, the cause of which is multifactorial with advancing age said to be a major determinant. There is a paucity of data on liver function among SCA patients in relation to age in northern Nigerian hospitals, including Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. This study was to assess the biochemical liver function tests (LFTs) as they relate to age among SCA patients in steady state, with a view to improving the overall monitoring of these patients. This study was carried out in ABUTH, Zaria, Northern Nigeria. LFTs were carried out in 100 SCA and 100 apparently healthy participants (controls). The SCA group was made up of fifty adults and fifty children diagnosed of SCA, whereas the control group was made up of fifty adults and fifty children who were apparently healthy and had hemoglobin AA. Paired two-tailed Student's t-test for matched samples and Pearson's linear correlation statistical methods were employed for the data analysis using Microsoft Office Excel 2007. A P ≤ 0.05 was considered as statistically significant. The serum concentrations of total bilirubin (TB), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and AST/ALT ratio were significantly higher in SCA patients compared to the controls (P = 0.001, P = 0.001, P = 0.05, P = 0.05 and P = 0.001, respectively). Serum total protein (TP) and ALB were significantly lower (P = 0.01 and P < 0.05, respectively) in SCA patients compared with the controls. The levels of TB, ALT, AST, ALP, and AST/ALT were significantly lower in SCA adults compared to SCA children, whereas TP and ALB were higher in SCA adults compared to the SCA children. There were significant negative correlations between age and each of TB, ALT, AST, ALP, and AST/ALT, and significant positive correlations between age and each of TP and ALB in SCA patients. There are mild LFTs derangements in SCA patients even in steady state with the extent of the abnormalities decreasing with advancing age of the patients.

[Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

PubMed

Ma, Yi-Ran; Ren, Si-Hua; He, Yu-Xin; Wang, Lin-Lin; Jin, Li; Hao, Yi-Wen

2012-10-01

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.

Vision related quality of life in spinocerebellar ataxia.

PubMed

Kedar, Sachin; Ghate, Deepta; Murray, Earnest L; Corbett, James J; Subramony, S H

2015-11-15

Spinocerebellar ataxia (SCA) leads to abnormal ocular motility and alignment. The objective of this study was to quantitatively assess vision, ocular motility and alignment and its impact on vision related quality of life (VRQOL) in SCA. Nineteen genetically diagnosed SCA subjects (11 SCA type 3, 3 SCA type 1 and 5 SCA type 6) participated at two university centers. All subjects completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ), 10-Item Neuro-Ophthalmic Supplement (NOS), scale for assessment and rating of ataxia (SARA) and ophthalmic examination. Twelve subjects seen at one of the 2 sites underwent quantitative ocular motility and alignment assessment. Composite scores for NEI-VFQ (mean 76.3±13) and NOS (mean 65.2±16.8) were significantly decreased in SCA subjects. NEI-VFQ subscale scores were decreased for general, near, distance and peripheral vision and driving. SCA patients had decreased low contrast sensitivity, stereoacuity and multiple ocular motility defects which included gaze limitation (9/12), nystagmus (5/12), distance esophoria (11/12), near exophoria (12/12) and receded near point of convergence. A significant negative correlation was noted between composite scores and distance convergence fusional amplitude. VRQOL is significantly decreased in SCA compared to normal population. All SCA patients should be screened for visual disability and referred for neuro-ophthalmic assessment promptly. Copyright © 2015 Elsevier B.V. All rights reserved.

Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6.

PubMed

Globas, Christoph; du Montcel, Sophie Tezenas; Baliko, Laslo; Boesch, Syliva; Depondt, Chantal; DiDonato, Stefano; Durr, Alexandra; Filla, Alessandro; Klockgether, Thomas; Mariotti, Caterina; Melegh, Bela; Rakowicz, Maryla; Ribai, Pascale; Rola, Rafal; Schmitz-Hubsch, Tanja; Szymanski, Sandra; Timmann, Dagmar; Van de Warrenburg, Bart P; Bauer, Peter; Schols, Ludger

2008-11-15

Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA.

mAb C19 targets a novel surface marker for the isolation of human cardiac progenitor cells from human heart tissue and differentiated hESCs.

PubMed

Leung, Hau Wan; Moerkamp, Asja T; Padmanabhan, Jayanthi; Ng, Sze-Wai; Goumans, Marie-José; Choo, Andre

2015-05-01

Cardiac progenitor cells (CPCs) have been isolated from adult and developing hearts using an anti-mouse Sca-1 antibody. However, the absence of a human Sca-1 homologue has hampered the clinical application of the CPCs. Therefore, we generated novel monoclonal antibodies (mAbs) specifically raised against surface markers expressed by resident human CPCs. Here, we explored the suitability of one of these mAbs, mAb C19, for the identification, isolation and characterization of CPCs from fetal heart tissue and differentiating cultures of human embryonic stem cells (hESCs). Using whole-cell immunization, mAbs were raised against Sca-1+ CPCs and screened for reactivity to various CPC lines by flow cytometry. mAb C19 was found to be specific for Sca-1+ CPCs, with high cell surface binding capabilities. mAb C19 stained small stem-like cells in cardiac tissue sections. Moreover, during differentiation of hESCs towards cardiomyocytes, a transient population of cells with mAb C19 reactivity was identified and isolated using magnetic-activated cell sorting. Their cell fate was tracked and found to improve cardiomyocyte purity from hESC-derived cultures. mAb C19+ CPCs, from both hESC differentiation and fetal heart tissues, were maintained and expanded in culture, while retaining their CPC-like characteristics and their ability to further differentiate into cardiomyocytes by stimulation with TGFβ1. Finally, gene expression profiling of these mAb C19+ CPCs suggested a highly angiogenic nature, which was further validated by cell-based angiogenesis assays. mAb C19 is a new surface marker for the isolation of multipotent CPCs from both human heart tissues and differentiating hESCs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Space-Based Reconfigurable Software Defined Radio Test Bed Aboard International Space Station

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Lux, James P.

2014-01-01

The National Aeronautical and Space Administration (NASA) recently launched a new software defined radio research test bed to the International Space Station. The test bed, sponsored by the Space Communications and Navigation (SCaN) Office within NASA is referred to as the SCaN Testbed. The SCaN Testbed is a highly capable communications system, composed of three software defined radios, integrated into a flight system, and mounted to the truss of the International Space Station. Software defined radios offer the future promise of in-flight reconfigurability, autonomy, and eventually cognitive operation. The adoption of software defined radios offers space missions a new way to develop and operate space transceivers for communications and navigation. Reconfigurable or software defined radios with communications and navigation functions implemented in software or VHDL (Very High Speed Hardware Description Language) provide the capability to change the functionality of the radio during development or after launch. The ability to change the operating characteristics of a radio through software once deployed to space offers the flexibility to adapt to new science opportunities, recover from anomalies within the science payload or communication system, and potentially reduce development cost and risk by adapting generic space platforms to meet specific mission requirements. The software defined radios on the SCaN Testbed are each compliant to NASA's Space Telecommunications Radio System (STRS) Architecture. The STRS Architecture is an open, non-proprietary architecture that defines interfaces for the connections between radio components. It provides an operating environment to abstract the communication waveform application from the underlying platform specific hardware such as digital-to-analog converters, analog-to-digital converters, oscillators, RF attenuators, automatic gain control circuits, FPGAs, general-purpose processors, etc. and the interconnections among different radio components.

[Study of oculomotor disorders in spinocerebellar ataxia genotype].

PubMed

Oda, Rie; Takemoto, Tsuyoshi; Kawai, Motoharu; Yamashita, Hiroshi

2006-01-01

Spinocerebellar degeneration (SCD) exhibits a variety of spinal and cerebullar symptoms and progress. The recent advent of molecular genetics has revealed triplet repeat mutation in the gene of SCD patients. Due to the underlying genetic defects, hereditary SCD is referred to as different spinocerebellar ataxia (SCA) genotypes. We conducted vestibular functional tests in 33 SCD patients, including 3 with SCA3 and 2 with SCA6. We compared the degree of lower extremity ataxia with the degree of oculomotor disorder by using eye tracking tests (ETT) and optokinetic pattern tests (OKP). Both SCA3 and SCA6 show high ETT score and low mean slowest phase velocity in OKP. This means that SCA3 and SCA6 tend to have oculomotor disorder precedes extremity ataxia. Oculomotor examination should thus prove to be a useful, senstive indicator in screening SCD patients from early disease onset, and in evaluating the disease progression and the effectiveness of treatment.

Erythroid Adhesion Molecules in Sickle Cell Anaemia Infants: Insights Into Early Pathophysiology.

PubMed

Brousse, Valentine; Colin, Yves; Pereira, Catia; Arnaud, Cecile; Odièvre, Marie Helene; Boutemy, Anne; Guitton, Corinne; de Montalembert, Mariane; Lapouméroulie, Claudine; Picot, Julien; Le Van Kim, Caroline; El Nemer, Wassim

2015-01-01

Sickle cell anaemia (SCA) results from a single mutation in the β globin gene. It is seldom symptomatic in the first semester of life. We analysed the expression pattern of 9 adhesion molecules on red blood cells, in a cohort of 54 SCA and 17 non-SCA very young infants of comparable age (median 144 days, 81-196). Haemoglobin F (HbF) level was unsurprisingly elevated in SCA infants (41.2% ± 11.2) and 2-4 fold higher than in non-SCA infants, yet SCA infants presented significantly decreased Hb level and increased reticulocytosis. Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density. No significant difference was found on mature red cells. Our findings demonstrate the very early onset of reticulocyte membrane modifications in SCA asymptomatic infants and allow an insight into the first pathological changes with the release of stress reticulocytes expressing a distinctive profile of adhesion molecules.

Bidirectional Connections between Depression and Ataxia Severity in Spinocerebellar Ataxia Type 3 Patients.

PubMed

Lin, Min-Ting; Yang, Jin-Shan; Chen, Ping-Ping; Qian, Mei-Zhen; Lin, Hui-Xia; Chen, Xiao-Ping; Shang, Xian-Jin; Wang, Dan-Ni; Chen, Yu-Chao; Jiang, Bin; Chen, Yi-Jun; Chen, Wan-Jin; Wang, Ning; Gan, Shi-Rui

2018-05-15

Spinocerebellar ataxia type 3 (SCA3), which is the most common subtype of SCA worldwide, exhibits common neuropsychological symptoms such as depression. However, the contribution of depression to the severity of SCA3 has not yet been thoroughly investigated. The present study investigated the prevalence of depression using Beck depression inventory in 104 molecularly confirmed SCA3 patients from China. The putative risk factors for depression and whether the depression could affect the severity of ataxia were established by multivariable linear regression models. The frequency of depression in the study subjects was 57.69% (60/104), which was higher than that in SCA3 patients from a subset of other populations. The gender (p = 0.03) and severity (p < 0.01) of ataxia were those risk factors that could affect depression. Conversely, depression (p < 0.01) together with the duration (p < 0.01) of SCA3 could also play a positive role in the severity of ataxia. The extremely common depression results from motor disability caused by ataxia; it also affects the disease severity of SCA3. These findings suggested that depression was a part of neurodegeneration in SCA3 and necessitated intensive focus and interventions while caring for SCA3 patients. © 2018 S. Karger AG, Basel.

A comparative study of perception of sickle cell anaemia by married Nigeria rural and urban women.

PubMed

Adeodu, O O; Alimi, T; Adekile, A D

2000-01-01

Environmental factors may influence perception of or attitude to chronic disorders. The perception of sickle cell anaemia (SCA by 165 married Nigerian rural and 507 urban women was studied to determine how living in an urban or rural environment may influence perception. None of the subjects had children with SCA. The instrument used for data collection was a structured questionnaire designed to enquire into their knowledge about the cause, precipitating factors for crises, clinical features of SCA and their opinions regarding traditional and modern treatment options for the disorder. As a group, urban women had better knowledge about SCA than rural women probably because their social environment afforded a wider scope for interaction with and information exchange among people. For most respondents, the educational institutions attended the health institutions in the locality and the electronic media were poor sources of information on SCA. The study showed a serious lack of information about important aspects of SCA among rural women. We think the training of primary health care providers as counsellors on SCA, the inclusion of instruction about SCA in the curriculum of schools and sustained outreach programmes on SCA on the electronic media would ensure early education of people in both rural and urban communities and help to improve perception of the disorder.

Friedreich's ataxia and other hereditary ataxias in Greece: an 18-year perspective.

PubMed

Koutsis, Georgios; Kladi, Athina; Karadima, Georgia; Houlden, Henry; Wood, Nicholas W; Christodoulou, Kyproula; Panas, Marios

2014-01-15

Limited data exist on the spectrum of heredoataxias in Greece, including the prevalence and phenotype of Friedreich's ataxia (FRDA) and the prevalence and subtypes of dominant spinocerebellar ataxias (SCAs). We analyzed clinically and investigated genetically for FRDA and triplet-repeat expansion SCAs a consecutive series of 186 patients with suspected heredoataxia referred to Athens over 18 years. For prevalence estimates we included patients with molecular diagnosis from Cyprus that were absent from the Athens cohort. The minimum prevalence of FRDA was ~0.9/100,000, with clusters of high prevalence in Aegean islands. FRDA was diagnosed in 73 probands. The genotypic and phenotypic spectrum of FRDA was similar to other populations, with one patient compound heterozygote for a known point mutation in FXN (Asn146Lys). Undiagnosed recessive ataxias included FRDA-like and spastic ataxias. The minimum prevalence of dominant SCAs was ~0.7/100,000. SCA1 (4), SCA7 (4), SCA2, SCA6, and SCA17 (1 each) probands were identified. A molecular diagnosis was reached in 31% of dominant cases. Undiagnosed dominant patients included a majority of type III autosomal dominant cerebellar ataxias. FRDA is the commonest heredoataxia in the Greek population with prevalence towards the lower end of other European populations. Dominant SCAs are almost as prevalent. SCA1, SCA2, SCA6, SCA7 and SCA17 patients complete the spectrum of cases with a specific molecular diagnosis. © 2013.

Depression comorbidity in spinocerebellar ataxia.

PubMed

Schmitz-Hübsch, Tanja; Coudert, Mathieu; Tezenas du Montcel, Sophie; Giunti, Paola; Labrum, Robyn; Dürr, Alexandra; Ribai, Pascale; Charles, Perrine; Linnemann, Christoph; Schöls, Ludger; Rakowicz, Maryla; Rola, Rafal; Zdzienicka, Elszbieta; Fancellu, Roberto; Mariotti, Caterina; Baliko, Lazlo; Melegh, Bela; Filla, Alessandro; Salvatore, Elena; van de Warrenburg, Bart P C; Szymanski, Sandra; Infante, Jon; Timmann, Dagmar; Boesch, Sylvia; Depondt, Chantal; Kang, Jun-Suk; Schulz, Jörg B; Klopstock, Thomas; Lossnitzer, Nicole; Löwe, Bernd; Frick, Caroline; Rottländer, Daniela; Schlaepfer, Thomas E; Klockgether, Thomas

2011-04-01

This is a description of the prevalence and profile of depressive symptoms in dominant spinocerebellar ataxia (SCA). Depressive symptoms were assessed in a convenience sample of 526 genetically confirmed and clinically affected patients (117 SCA1, 163 SCA2, 139 SCA3, and 107 SCA6) using the Patient Health Questionnaire (PHQ). In addition, depressive status according to the examiner and the use of antidepressants was recorded. Depression self-assessment was compared with an interview-based psychiatric assessment in a subset of 26 patients. Depression prevalence estimates were 17.1% according to the PHQ algorithm and 15.4% when assessed clinically. The sensitivity of clinical impression compared with PHQ classification was low (0.35), whereas diagnostic accuracy of PHQ compared with psychiatric interview in the subset was high. Antidepressants were used by 17.7% of patients and in >10% of patients without current clinically relevant depressive symptoms. Depression profile in SCA did not differ from a sample of patients with major depressive disorder except for the movement-related item. Neither depression prevalence nor use of antidepressants differed between genetic subtypes, with only sleep disturbance more common in SCA3. In a multivariate analysis, ataxia severity and female sex independently predicted depressive status in SCA. The PHQ algorithmic classification is appropriate for use in SCA but should stimulate further psychiatric evaluation if depression is indicated. Despite a higher risk for depression with more severe disease, the relation of depressive symptoms to SCA neurodegeneration remains to be shown. Copyright © 2011 Movement Disorder Society.

Principal Component Analysis of Cerebellar Shape on MRI Separates SCA Types 2 and 6 into Two Archetypal Modes of Degeneration

PubMed Central

Jung, Brian C.; Choi, Soo I.; Du, Annie X.; Cuzzocreo, Jennifer L.; Geng, Zhuo Z.; Ying, Howard S.; Perlman, Susan L.; Toga, Arthur W.; Prince, Jerry L.

2014-01-01

Although “cerebellar ataxia” is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes. PMID:22258915

Sudden Cardiac Arrest During Sports Activity in Middle Age

PubMed Central

Marijon, Eloi; Uy-Evanado, Audrey; Reinier, Kyndaron; Teodorescu, Carmen; Narayanan, Kumar; Jouven, Xavier; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S.

2015-01-01

Background Sports-associated sudden cardiac arrests (SCAs) occur mostly during middle age. We sought to determine burden, characteristics, and outcomes of SCA during sports among middle aged residents of a large US community. Methods and Results SCA cases aged 35–65 years were identified in a large, prospective, population-based study (2002–2013), with systematic and comprehensive assessment of their lifetime medical history. Of the 1,247 SCA cases, 63 (5%) occurred during sports activities at a mean age of 51.1±8.8 years, yielding an incidence of 21.7 (95%CI 8.1–35.4) per million per year. The incidence varied significantly based on sex, with a higher incidence among men (RR 18.68 95%CI 2.50–139.56) for sports SCA, as compared to all other SCA (RR 2.58, 95%CI 2.12–3.13). Sports SCA was also more likely to be a witnessed event (87 vs. 53%, P<0.001), with cardiopulmonary resuscitation (44 vs. 25%, P=0.001) and ventricular fibrillation (84 vs. 51%, P<0.0001). Survival to hospital discharge was higher for sports-associated SCA (23.2 vs. 13.6%, P=0.04). Sports SCA cases presented with known pre-existing cardiac disease in 16%, ≥1 cardiovascular risk factor in 56%, and overall, 36% of cases had typical cardiovascular symptoms during the week preceding SCA. Conclusions Sports-associated SCA in middle age represents a relatively small proportion of the overall SCA burden, reinforcing the idea of the high benefit-low risk nature of sports activity. Especially in light of current population aging trends, our findings emphasize that targeted education could maximize both safety and acceptance of sports activity in the older athlete. PMID:25847988

Genetic map of the spinocerebellar ataxia type 2 (SCA2) region on chromosome 12

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nechiporuk, A.; Frederick, T.; Pulst, S.M.

1994-09-01

The autosomal dominant ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive ataxia. At least four gene loci have been identified: SCA1 on chromosome (CHR) 6, SCA2 on CHR12, Machado-Joseph disease on CHR14, and SCA families that are not linked to any of the above loci. In addition, the gene causing dentato-rubro-pallido-luysian atrophy has been identified as an expanded CAG repeat on CHR 12p. As a necessary step in identifying the gene for SCA2, we now identified closer flanking markers. To do this we ordered microsatellite markers in the now identified closer flanking markers.more » To do this we ordered microsatellite markers in the region and then determined pairwise and multipoint lod scores between the markers and SCA2 in three large pedigrees with SCA. The following order was established with odds > 1,000:1 using six non-SCA pedigrees: D12S101-7.1cM-D12S58-0cM-IGF1-3.6cM-D12S78-1.4cM-D12S317-3.7cM-D12S84-0cM-D12S105-7.2cM-D12S79-7.0cM-PLA2. Using this ordered set of markers we examined linkage to SCA2 in three pedigrees of Italian, Austrian and French-Canadian descent. Pairwise linkage analysis resulted in significant positive lod scores for all markers. The highest pairwise lod score was obtained with D12S84/D12S105 (Z{sub max}=7.98, theta{sub max}=0.05). To further define the location of SCA2, we performed multipoint linkage analysis using the genetic map established above. The highest location score was obtained between D12S317 and D12S84/D12S105. A location of SCA2 between these loci was favored with odds > 100:1. These data likely narrow the SCA2 candidate region to approximately 3.7 cM. The relatively large large number of markers tightly linked to SCA2 will facilitate the assignment of additional SCA pedigrees to CHR12, and will help in the presymptomatic diagnosis of individuals in families with proven linkage to CHR12.« less

Abraham Lincoln did not have type 5 spinocerebellar ataxia.

PubMed

Sotos, John G

2009-10-20

An autosomal dominant genetic disorder, type 5 spinocerebellar ataxia (SCA5), occurs in multiple descendants of one paternal uncle and one paternal aunt of President Abraham Lincoln. It has been suggested that Lincoln himself had the disease and that his DNA should be tested for an SCA5-conferring gene. Herein, I review the pertinent phenotypes of Lincoln, his father, and his paternal grandmother, and conclude that 1) Lincoln's father did not have SCA5, and, therefore, that Lincoln was not at special risk of the disease; 2) Lincoln had neither subclinical nor visible manifestations of SCA5; 3) little evidence suggests SCA5 is a "Lincolnian" disorder; and 4) without additional evidence, Lincoln's DNA should not be tested for SCA5.

Diet of bottlenose dolphins (Tursiops truncatus) from the Gulf of Cadiz: Insights from stomach content and stable isotope analyses.

PubMed

Giménez, Joan; Marçalo, Ana; Ramírez, Francisco; Verborgh, Philippe; Gauffier, Pauline; Esteban, Ruth; Nicolau, Lídia; González-Ortegón, Enrique; Baldó, Francisco; Vilas, César; Vingada, José; G Forero, Manuela; de Stephanis, Renaud

2017-01-01

The ecological role of species can vary among populations depending on local and regional differences in diet. This is particularly true for top predators such as the bottlenose dolphin (Tursiops truncatus), which exhibits a highly varied diet throughout its distribution range. Local dietary assessments are therefore critical to fully understand the role of this species within marine ecosystems, as well as its interaction with important ecosystem services such as fisheries. Here, we combined stomach content analyses (SCA) and stable isotope analyses (SIA) to describe bottlenose dolphins diet in the Gulf of Cadiz (North Atlantic Ocean). Prey items identified using SCA included European conger (Conger conger) and European hake (Merluccius merluccius) as the most important ingested prey. However, mass-balance isotopic mixing model (MixSIAR), using δ13C and δ15N, indicated that the assimilated diet consisted mainly on Sparidae species (e.g. seabream, Diplodus annularis and D. bellottii, rubberlip grunt, Plectorhinchus mediterraneus, and common pandora, Pagellus erythrinus) and a mixture of other species including European hake, mackerels (Scomber colias, S. japonicus and S. scombrus), European conger, red bandfish (Cepola macrophthalma) and European pilchard (Sardina pilchardus). These contrasting results highlight differences in the temporal and taxonomic resolution of each approach, but also point to potential differences between ingested (SCA) and assimilated (SIA) diets. Both approaches provide different insights, e.g. determination of consumed fish biomass for the management of fish stocks (SCA) or identification of important assimilated prey species to the consumer (SIA).

Spinocerebellar ataxia type 7.

PubMed

Martin, Jean-Jacques

2012-01-01

Spinocerebellar ataxia type 7 (SCA7) is associated with progressive blindness, dominant transmission, and marked anticipation. SCA7 represents one of the polyglutamine expansion diseases with increase of CAG repeats. The gene maps to chromosome 3p12-p21.1. Normal values of CAG repeats range from 4 to 18. The SCA7 gene encodes a protein of largely unknown function, called ataxin-7. SCA7 is reported in many countries and ethnic groups. Its phenotypic expression depends on the number of expanded repeats. The infantile phenotype is very severe, with more than 100 repeats. The classic type has 50 to 55 repeats and is characterized by a combination of visual and ataxic disturbances lasting for 20-40 years.When the number of CAG repeats is between 36 and 43, the evolution is much slower, with few or no retinal abnormalities. A CAG repeat number from 18 to 35 is asymptomatic but predisposes to the development of the disorder when expanding to the pathological range through transmission. The diagnosis is made by molecular genetics. The neuropathology of the disorder includes atrophy of the spinocerebellar pathways, pyramidal tracts, and motor nuclei in the brainstem and spinal cord, a cone-rod sytrophy of the retina, and ataxin-7 immunoreactive neuronal intranuclear inclusions. The neuropathological features vary as a function of the number of CAG repeats. Present research deals mainly with the study of ataxin-7 in transfected neural cells and transgenic mouse models. 2012 Elsevier B.V. All rights reserved.

The Role of Clear Sky Identification in the Study of Cloud Radiative Effects: Combine Analysis from ISCCP and the Scanner of Radiation Budget (ScaRaB)

NASA Technical Reports Server (NTRS)

Rossow, W. B.; Stubenrauch, C. J.; Briand, V.; Hansen, James E. (Technical Monitor)

2001-01-01

Since the effect of clouds on the earth's radiation balance is often estimated as the difference of net radiative fluxes at the top of the atmosphere between all situations and monthly averaged clear sky situations of the same regions, a reliable identification of clear sky is important for the study of cloud radiative effects. The Scanner for Radiation Balance (ScaRaB) radiometer on board the Russian Meteor-3/7 satellite provided earth radiation budget observations from March 1994 to February 1995 with two ERBE-Re broad-band longwave and shortwave channels. Two narrow-band channels, in the infrared atmospheric window and in the visible band, have been added to the ScaRaB instrument to improve the cloud scene identification. The International Satellite Cloud Climatology Project (ISCCP) method for cloud detection and determination of cloud and surface properties uses the same narrow-band channels as ScaRaB, but is employed to a collection of measurements at a better spatial resolution of about 5 km. By applying the original ISCCP algorithms to the ScaRaB data, the clear sky frequency is about 5% lower than the one over quasi-simultaneous original ISCCP data, an indication that the ISCCP cloud detection is quite stable. However, one would expect an about 10 to 20% smaller clear sky occurrence over the larger ScaRaB pixels. Adapting the ISCCP algorithms to the reduced spatial resolution of 60 km and to the different time sampling of the ScaRaB data leads therefore to a reduction of a residual cloud contamination. A sensitivity study with time-space collocated ScaRaB and original ISCCP data at a spatial resolution of 1deg longitude x 1deg latitude shows that the effect of clear sky identification method plays a higher role on the clear sky frequency and therefore on the statistics than on the zonal mean values of the clear sky fluxes. Nevertheless, the zonal outgoing longwave fluxes corresponding to ERBE clear sky are in general about 2 to 10 W/sq m higher than those obtained from the ScaRaB adapted ISCCP clear sky identifications. The latter are close to (about 1 W/sq m higher) fluxes corresponding to clear sky regions from original ISCCP data, whereas ScaRaB clear sky LW fluxes obtained with the original ISCCP identification lie about 1 to 2 W/sq m below. Especially in the tropics where water vapor abundance is high, the ERBE clear sky LW fluxes seem to be systematically overestimated by about 4 W/sq m, and SW fluxes are lower by about 5 to 10 W/sq m. However, the uncertainty in the analysis of monthly mean zonal cloud radiative effects is also produced by the low frequency of clear sky occurrence, illustrated when averaging over pixels or even over regions of 4deg longitude x 5deg latitude, corresponding to the spatial resolution of General Circulation Models. The systematic bias in the clear sky fluxes is not reflected in the zonal cloud radiative effects, because the clear sky regions selected by the different algorithms can occur in different geographic regions with different cloud properties.

Regulating Anger under Stress via Cognitive Reappraisal and Sadness.

PubMed

Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

2017-01-01

Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., "sadness counteracts anger" (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants' subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one's ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was found to reduce the level of subjective anger more, but this difference only existed in non-stressful conditions. By contrast, irrespective of stress, the levels of aggressive behavior and related skin conductance after sadness induction were both significantly lower than those after CER induction or neutral emotion induction, thus suggesting the immunity of the regulatory effect of SCA strategy to the stress factor.

Regulating Anger under Stress via Cognitive Reappraisal and Sadness

PubMed Central

Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

2017-01-01

Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., “sadness counteracts anger” (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants’ subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one’s ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was found to reduce the level of subjective anger more, but this difference only existed in non-stressful conditions. By contrast, irrespective of stress, the levels of aggressive behavior and related skin conductance after sadness induction were both significantly lower than those after CER induction or neutral emotion induction, thus suggesting the immunity of the regulatory effect of SCA strategy to the stress factor. PMID:28855881

Evaluation of the performance of the Sydney Coordinated Adaptive Traffic System (SCATS) on Powell Boulevard in Portland, OR.

DOT National Transportation Integrated Search

2013-07-01

The Sydney Coordinated Adaptive Traffic System (SCATS) is used to mitigate traffic congestion along urban arterial corridors. Although there : has been research on SCATS performance, this report combines three different areas of research about SCA...

Pharmacometabolomic Signature of Ataxia SCA1 Mouse Model and Lithium Effects

PubMed Central

Wikoff, William R.; Gatchel, Jennifer R.; Wang, Lu; Barupal, Dinesh K.; Crespo-Barreto, Juan; Fiehn, Oliver

2013-01-01

We have shown that lithium treatment improves motor coordination in a spinocerebellar ataxia type 1 (SCA1) disease mouse model (Sca1154Q/+). To learn more about disease pathogenesis and molecular contributions to the neuroprotective effects of lithium, we investigated metabolomic profiles of cerebellar tissue and plasma from SCA1-model treated and untreated mice. Metabolomic analyses of wild-type and Sca1154Q/+ mice, with and without lithium treatment, were performed using gas chromatography time-of-flight mass spectrometry and BinBase mass spectral annotations. We detected 416 metabolites, of which 130 were identified. We observed specific metabolic perturbations in Sca1154Q/+ mice and major effects of lithium on metabolism, centrally and peripherally. Compared to wild-type, Sca1154Q/+ cerebella metabolic profile revealed changes in glucose, lipids, and metabolites of the tricarboxylic acid cycle and purines. Fewer metabolic differences were noted in Sca1154Q/+ mouse plasma versus wild-type. In both genotypes, the major lithium responses in cerebellum involved energy metabolism, purines, unsaturated free fatty acids, and aromatic and sulphur-containing amino acids. The largest metabolic difference with lithium was a 10-fold increase in ascorbate levels in wild-type cerebella (p<0.002), with lower threonate levels, a major ascorbate catabolite. In contrast, Sca1154Q/+ mice that received lithium showed no elevated cerebellar ascorbate levels. Our data emphasize that lithium regulates a variety of metabolic pathways, including purine, oxidative stress and energy production pathways. The purine metabolite level, reduced in the Sca1154Q/+ mice and restored upon lithium treatment, might relate to lithium neuroprotective properties. PMID:23936457

Falls in spinocerebellar ataxias: Results of the EuroSCA Fall Study.

PubMed

Fonteyn, Ella M R; Schmitz-Hübsch, Tanja; Verstappen, Carla C; Baliko, Laslo; Bloem, Bastiaan R; Boesch, Silvia; Bunn, Lisa; Charles, Perrine; Dürr, Alexandra; Filla, Allesandro; Giunti, Paola; Globas, Christoph; Klockgether, Thomas; Melegh, Bela; Pandolfo, Massimo; De Rosa, Anna; Schöls, Ludger; Timmann, Dagmar; Munneke, Marten; Kremer, Berry P H; van de Warrenburg, Bart P C

2010-06-01

To investigate the frequency, details, and consequences of falls in patients with autosomal dominant spinocerebellar ataxias (SCAs) and to derive specific disease-related risk factors that are associated with an increased fall frequency. Two hundred twenty-eight patients with SCA1, SCA2, SCA3, or SCA6, recruited from the EuroSCA natural history study, completed a fall questionnaire that assessed the frequency, consequences, and several details of falls in the previous 12 months. Relevant disease characteristics were retrieved from the EuroSCA registry. The database of the natural history study provided the ataxia severity scores as well as the number and nature of non-ataxia symptoms. Patients (73.6%) reported at least one fall in the preceding 12 months. There was a high rate of fall-related injuries (74%). Factors that were associated with a higher fall frequency included: disease duration, severity of ataxia, the presence of pyramidal symptoms, the total number of non-ataxia symptoms, and the genotype SCA3. Factors associated with a lower fall frequency were: the presence of extrapyramidal symptoms (more specifically dystonia of the lower limbs) and the genotype SCA2. The total number of non-ataxia symptoms and longer disease duration were independently associated with a higher fall frequency in a logistic regression analysis, while the presence of extrapyramidal symptoms was independently associated with a lower fall frequency. Our findings indicate that, in addition to more obvious factors that are associated with frequent falls, such as disease duration and ataxia severity, non-ataxia manifestations in SCA play a major role in the fall etiology of these patients.

Sudden cardiac arrests, automated external defibrillators, and medical emergency response plans in Tennessee high schools.

PubMed

Meredith, Mark L; Watson, Andrew M; Gregory, Andrew; Givens, Timothy G; Abramo, Thomas J; Kannankeril, Prince J

2013-03-01

Schools are important public locations of sudden cardiac arrest (SCA), and the American Heart Association (AHA) recommends medical emergency response plans (MERPs), which may include an automated external defibrillator (AED) in schools. The objective of this study was to determine the incidence of SCA and the prevalence of AEDs and MERPs in Tennessee high schools. Tennessee Secondary School Athletic Association member schools were surveyed regarding SCA on campus within 5 years, AED presence, and MERP characteristics. Of 378 schools, 257 (68%) completed the survey. There were 21 (5 student and 16 adult) SCAs on school grounds, yielding a 5-year incidence of 1 SCA per 12 high schools. An AED was present at 11 of 21 schools with SCA, and 6 SCA victims were treated with an AED shock. A linear increase in SCA frequency was noted with increasing school size (<500 students: 3.3% incidence, 500-1000: 6.5%, 1000-1500: 12.5%, ≥1500: 18.2%; P = 0.003). Of 257 schools, 71% had an MERP, 48% had an AED, and only 4% were fully compliant with AHA recommendations. Schools with a history of SCA were more likely to be compliant (19% vs. 3%, P = 0.011). The 5-year incidence of SCA in Tennessee high schools is 1 in 12, but increases to 1 in 7 for schools with more than 1000 students. Compliance with AHA guidelines for MERPs is poor, but improved in schools with recent SCA. Future recommendations should encourage the inclusion of AED placement in schools with more than 1000 students.

The insulin-like growth factor pathway is altered in Spinocerebellar ataxia type 1 and type 7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gatchel, Jennifer R.; Watase, Kei; Thaller, Christina

2008-01-29

Polyglutamine diseases are inherited neurodegenerative disorders caused by expansion of CAG trinucleotide repeats encoding a polyglutamine tract in the disease-causing proteins. There are nine of these disorders each having distinct features but also clinical and pathological similarities. In particular, spinocerebellar ataxia type 1 and 7 (SCA1 and SCA7) patients manifest cerebellar ataxia with corresponding degeneration of Purkinje cells. Given this common phenotype, we asked whether the two disorders share common molecular pathogenic events. To address this question we studied two genetically accurate mouse models of SCA1 and SCA7—Sca1154Q/2Q and Sca7266Q/5Q knock-in mice—that express the glutamine-expanded proteins from the respective endogenousmore » loci. We found common transcriptional changes in early symptomatic mice, with downregulation of Insulin-like growth factor binding protein 5 (Igfbp5) representing one of the most robust transcriptional changes that closely correlates with disease state. Interestingly, down-regulation of Igfbp5 occurred in granule neurons through a non-cell autonomous mechanism and was concomitant with activation of the Insulin-like growth factor I (Igf-I) pathway, and, in particular, the Igf-I receptor, expressed in part on Purkinje cells (PC). These data define a possible common pathogenic response in SCA1 and SCA7 and reveal the importance of neuron-neuron interactions in SCA1 and SCA7 pathogenesis. The sensitivity of Igfbp5 levels to disease state could render it and other components of its effector pathway useful as biomarkers in this class of diseases.« less

Combining ability, heritability and genotypic relations of different physiological traits in cacao hybrids

PubMed Central

de Almeida, Alex-Alan Furtado; Branco, Márcia Christina da Silva; Costa, Marcio Gilberto Cardoso; Ahnert, Dario

2017-01-01

Selecting parents and evaluating progenies is a very important step in breeding programs and involves approaches such as understanding the initial stages of growth and characterizing the variability among genotypes for different parameters, such as physiological, growth, biomass partitioning and nutrient translocation to the aerial part. In these cases, facilitating tools can be used to understand the involved gene dynamics, such as diallel crosses and genetic and phenotypic correlations. Our main hypothesis is that the contrasting phenotypes of these parental genotypes of cocoa used are due to genetic factors, and progenies derived from crosses of these parental genotypes are useful for breeding programs related to plant architecture, physiological parameters and translocation of mineral nutrients. We aimed to evaluate the combining abilities in progenies of cacao (Theobroma cacao L) originating from contrasting parents for canopy vigor. Emphasis was given to the evaluation of morphological and physiological parameters and the phenotypic and genotypic correlations to understand the dynamics of the action of the genes involved, as well as in expression profile from genes of gibberellins biosynthesis pathway in the parents. Fifteen F1 progenies were obtained from crosses of six clones (IMC 67, P4B, PUCALA, SCA 6, SCA 24 and SJ 02) that were evaluated in a randomized complete block design with four replicates of 12 plants per progeny, in a balanced half table diallel scheme. It is possible to identify and select plants and progenies of low, medium and high height, as there is expressive genetic variability for the evaluated parameters, some of these on higher additive effects, others on larger nonadditive effects and others under a balance of these effects. Most physiological parameters evaluated show that for selection of plants with the desired performance, no complex breeding methods would be necessary due to the high and medium heritability observed. Strong genetic components were observed from many of the correlations, which indicate the possibility to formulate selection indices for multi-traits, such as dwarfism or semidwarfism, tolerance to increase of leaf sodium concentrations and maintenance of the photosynthetic apparatus integrity under these conditions. Additionally, plants with higher carbon fixation, better water use, higher carboxylation efficiency and greater magnesium accumulation in leaves can be selected. PMID:28628670

Combining ability, heritability and genotypic relations of different physiological traits in cacao hybrids.

PubMed

Pereira, Allan Silva; de Almeida, Alex-Alan Furtado; Branco, Márcia Christina da Silva; Costa, Marcio Gilberto Cardoso; Ahnert, Dario

2017-01-01

Selecting parents and evaluating progenies is a very important step in breeding programs and involves approaches such as understanding the initial stages of growth and characterizing the variability among genotypes for different parameters, such as physiological, growth, biomass partitioning and nutrient translocation to the aerial part. In these cases, facilitating tools can be used to understand the involved gene dynamics, such as diallel crosses and genetic and phenotypic correlations. Our main hypothesis is that the contrasting phenotypes of these parental genotypes of cocoa used are due to genetic factors, and progenies derived from crosses of these parental genotypes are useful for breeding programs related to plant architecture, physiological parameters and translocation of mineral nutrients. We aimed to evaluate the combining abilities in progenies of cacao (Theobroma cacao L) originating from contrasting parents for canopy vigor. Emphasis was given to the evaluation of morphological and physiological parameters and the phenotypic and genotypic correlations to understand the dynamics of the action of the genes involved, as well as in expression profile from genes of gibberellins biosynthesis pathway in the parents. Fifteen F1 progenies were obtained from crosses of six clones (IMC 67, P4B, PUCALA, SCA 6, SCA 24 and SJ 02) that were evaluated in a randomized complete block design with four replicates of 12 plants per progeny, in a balanced half table diallel scheme. It is possible to identify and select plants and progenies of low, medium and high height, as there is expressive genetic variability for the evaluated parameters, some of these on higher additive effects, others on larger nonadditive effects and others under a balance of these effects. Most physiological parameters evaluated show that for selection of plants with the desired performance, no complex breeding methods would be necessary due to the high and medium heritability observed. Strong genetic components were observed from many of the correlations, which indicate the possibility to formulate selection indices for multi-traits, such as dwarfism or semidwarfism, tolerance to increase of leaf sodium concentrations and maintenance of the photosynthetic apparatus integrity under these conditions. Additionally, plants with higher carbon fixation, better water use, higher carboxylation efficiency and greater magnesium accumulation in leaves can be selected.

Stem cell antigen-1 in skeletal muscle function.

PubMed

Bernstein, Harold S; Samad, Tahmina; Cholsiripunlert, Sompob; Khalifian, Saami; Gong, Wenhui; Ritner, Carissa; Aurigui, Julian; Ling, Vivian; Wilschut, Karlijn J; Bennett, Stephen; Hoffman, Julien; Oishi, Peter

2013-08-15

Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age.

Long-term oral administration of the NMDA receptor antagonist memantine extends life span in spinocerebellar ataxia type 1 knock-in mice.

PubMed

Iizuka, Akira; Nakamura, Kazuhiro; Hirai, Hirokazu

2015-04-10

Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by extension of a CAG repeat in the Sca1gene. Although the mechanisms underlying the symptoms of SCA1 have not been determined, aberrant neuronal activation potentially contributes to the neuronal cell death characteristic of the disease. Here we examined the potential involvement of extrasynaptic N-methyl-d-aspartate receptor (NMDAR) activation in the pathogenesis of SCA1 by administering memantine, a low-affinity noncompetitive NMDAR antagonist, in SCA1 knock-in (KI) mice. In KI mice, the exon in the ataxin 1 gene is replaced with abnormally expanded 154CAG repeats. Memantine was administered orally to the SCA1 KI mice from 4 weeks of age until death. The treatment significantly attenuated body-weight loss and prolonged the life span of SCA1 KI mice. Furthermore, memantine significantly suppressed the loss of Purkinje cells in the cerebellum and motor neurons in the dorsal motor nucleus of the vagus, which are critical for motor function and parasympathetic function, respectively. These findings support the contribution of aberrant activation of extrasynaptic NMDARs to neuronal cell death in SCA1 KI mice and suggest that memantine may also have therapeutic benefits in human SCA1 patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hydroxyurea therapy for sickle cell anemia

PubMed Central

McGann, Patrick T; Ware, Russell E

2017-01-01

Introduction Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons. Areas covered In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxy-urea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA. Expert opinion In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest. PMID:26366626

Hydroxyurea therapy for sickle cell anemia.

PubMed

McGann, Patrick T; Ware, Russell E

2015-01-01

Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons. In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxyurea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA. In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest.

Improvement of Operational Streamflow Prediction with MODIS-derived Fractional Snow Covered Area Observations

NASA Astrophysics Data System (ADS)

Bender, S.; Burgess, A.; Goodale, C. E.; Mattmann, C. A.; Miller, W. P.; Painter, T. H.; Rittger, K. E.; Stokes, M.; Werner, K.

2013-12-01

Water managers in the western United States depend heavily on the timing and magnitude of snowmelt-driven runoff for municipal supply, irrigation, maintenance of environmental flows, and power generation. The Colorado Basin River Forecast Center (CBRFC) of the National Weather Service issues operational forecasts of snowmelt-driven streamflow for watersheds within the Colorado River Basin (CRB) and eastern Great Basin (EGB), across a wide variety of scales. Therefore, the CBRFC and its stakeholders consider snowpack observations to be highly valuable. Observations of fractional snow covered area (fSCA) from satellite-borne instrumentation can better inform both forecasters and water users with respect to subsequent snowmelt runoff, particularly when combined with observations from ground-based station networks and/or airborne platforms. As part of a multi-year collaborative effort, CBRFC has partnered with the Jet Propulsion Laboratory (JPL) under funding from NASA to incorporate observations of fSCA from NASA's Moderate Resolution Imaging Spectroradiometer (MODIS) into the operational CBRFC hydrologic forecasting and modeling process. In the first year of the collaboration, CBRFC and NASA/JPL integrated snow products into the forecasting and decision making processes of the CBRFC and showed preliminary improvement in operational streamflow forecasts. In late 2012, CBRFC and NASA/JPL began retrospective analysis of relationships between the MODIS Snow Covered Area and Grain size (MODSCAG) fSCA and streamflow patterns for several watersheds within the CRB and the EGB. During the 2013 snowmelt runoff season, CBRFC forecasters used MODIS-derived fSCA semi-quantitatively as a binary indicator of the presence or lack of snow. Indication of the presence or lack of snow by MODIS assisted CBRFC forecasters in determining the cause of divergence between modeled and recently observed streamflow. Several examples of improved forecasts from across the CRB and EGB, informed by MODIS-derived fSCA, are described. Our analysis shows the value of MODIS fSCA to CBRFC and to users of CBRFC's streamflow forecasts. The relationships between the MODIS fSCA and the melt season streamflow vary with the magnitude of runoff, which is important to resource managers. The analysis also emphasizes the importance of the invaluable collaboration between an operational forecasting agency (CBRFC) and a research-oriented agency (NASA/JPL) specializing in remote sensing science. The collaboration is expected to continue over the next several years as CBRFC and JPL work to further improve modeling of snowmelt and prediction of snowmelt-driven streamflow in the CRB and EGB.

Detection of Large Pathogenic Expansions in FRDA1, SCA10, and SCA12 Genes Using a Simple Fluorescent Repeat-Primed PCR Assay

PubMed Central

Cagnoli, Claudia; Michielotto, Chiara; Matsuura, Tohru; Ashizawa, Tetsuo; Margolis, Russell L.; Holmes, Susan E.; Gellera, Cinzia; Migone, Nicola; Brusco, Alfredo

2004-01-01

At least 18 human genetic diseases are caused by expansion of short tandem repeats. Here we describe a successful application of a fluorescent PCR method for the detection of expanded repeats in FRDA1, SCA10, and SCA12 genes. Although this test cannot give a precise estimate of the size of the expansion, it is robust, reliable, and inexpensive, and can be used to screen large series of patients. It proved useful for confirming the presence of large expansions in the Friedreich ataxia gene following an ambiguous result of long-range PCR, as well as rapid pre-screening for large repeat expansions associated with Friedreich ataxia and SCA10 and the shorter repeat expansions associated with SCA12. PMID:15096564

Nocturnal haemoglobin oxygen desaturation in urban and rural East African paediatric cohorts with and without sickle cell anaemia: a cross-sectional study.

PubMed

L'Esperance, V S; Ekong, T; Cox, S E; Makani, J; Newton, C R; Soka, D; Komba, A; Kirkham, F J; Hill, C M

2016-04-01

Low haemoglobin oxygen saturation (SpO2) predicts complications in children with sickle cell anaemia (SCA) in the North but there are few data from Africa, where the majority of the patients reside. We measured daytime and overnight SpO2 in children with SCA in routine follow-up clinic, and controls without symptoms of SCA, comparing rural (Kilifi, Kenya) and urban (Dar-es-Salaam, Tanzania) cohorts. Daytime SpO2 was lower in 65 Tanzanian children with SCA (TS; median 97 (IQR 94-100)%); p<0.0001) than in 113 Kenyan children with SCA (KS; 99 (98-100)%) and 20 Tanzanian controls (TC; 100 (98-100)%). Compared with 95 Kenyan children with SCA, in 54 Tanzanian children with SCA and 19 TC who returned for overnight oximetry, mean (KS 99.0 (96.7-99.8)%; TS 97.9 (95.4-99.3)%; TC 98.4 (97.5-99.1)%; p=0.01) and minimum nocturnal SpO2 (92 (86-95)%; 87 (78.5-91)%; 90 (83.5-93)% p=0.0001) were lower. The difference between children with SCA persisted after adjustment for haemoglobin (p=0.004). Urban Tanzanian children, with and without SCA, experience greater exposure to low daytime and night-time SpO2 compared with rural Kenyan children with SCA. Possible explanations include differences in the prevalence of obstructive sleep apnoea or asthma, alterations in the oxyhaemoglobin desaturation curve or cardiovascular compromise, for example, to shunting at atrial or pulmonary level secondary to increased pulmonary artery pressure. The fact that non-SCA siblings in the urban area are also affected suggests that environmental exposures, for example, air pollution, nutrition or physical exercise, may play a role. Further studies should determine aetiology and clinical relevance for the SCA phenotype in children resident in Africa. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A dominant spinocerebellar ataxia gene (SCA5) in a family descendent from the paternal grandparents of President Lincoln maps to chromosome 11

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ranum, L.P.W.; Lundgren, J.K.; Schut, L.J.

1994-09-01

Four different genes that cause spinocerebellar ataxia (SCA1, SCA2, Machado Joseph`s Disease (MJD)/SCA3 and SCA4) have been mapped to chromosomes 6p, 12q, 14q, and 16q, respectively. We have examined and collected 170 individuals (56 affected) from a previously unreported 10 generation kindred (the Lincoln Family) with a dominant ataxia that is clinically and genetically distinct from those previously mapped. The family has two major branches from Indiana and Kentucky. Of historical interest is that both branches descend from the paternal grandparents of President Abraham Lincoln. While the ataxia in this kindred is disabling, the most striking clinical distinction from SCA1,more » SCA2 and MJD/SCA3 is that it is generally not life threatening. This clinical difference is explained by the absence of bulbar paralysis and lower motor neuron degeneration that causes respiratory muscle weakness. We have mapped the gene, SCA5, using microsatellite markers spaced at 20-40 cM intervals throughout the genome. After 75 markers, the first to demonstrate a lod score greater than 3.0 was D11S871 (Zmax=5.05). Four additional markers from the centromeric region of chromosome 11 also gave lod scores greater than 3. The highest lod scores were 12.3 for both D11S905 ({theta}=0.056) and D11S913 ({theta}=0.030). Multipoint linkage and haplotype analyses indicate the most likely location for SCA5 is within the 7 cM interval between GATA2A01 and D11S913. A statistical analysis of the age of onset of parent-offspring pairs within the family supports (p<0.0002) the presence of anticipation. Several dramatic examples of anticipation have been observed in which grandmothers have onsets 10-20 years later in life than their daughters who have onsets 10-20 years later than their children. Interestingly, all four of the juvenile onset cases are maternally inherited, suggesting a maternal bias in anticipation for SCA5 rather than a paternal bias as seen with SCA1.« less

Tuberculosis in children with sickle cell anaemia: a retrospective study in French tertiary care centres.

PubMed

Droz, Nina; De Lauzanne, Agathe; Holvoet, Laurent; Missud, Florence; Benkerrou, Malika; Brousse, Valentine; Odièvre, Marie-Hélène; Faye, Albert; Koehl, Berengere

2017-06-01

Tuberculosis (TB) and sickle cell anaemia (SCA) may affect the same population of patients, particularly in Africa but also in high-TB incidence areas in developed countries. However, few data are available from children with SCA who develop TB. The aim of this study was to describe the clinical features and outcome of TB diagnosed in children with SCA. We conducted a retrospective, descriptive study in three referral centre of Sickle Cell Disease in Paris, France. We included 11 patients with SCA who develop TB. The median age at TB diagnosis was 11 years [7.5-14.5]. Two patients were asymptomatic and nine patients were symptomatic. Six patients had pulmonary TB (pulmonary, pleural and mediastinal lesions). Five patients had extrapulmonary TB (osteoarticular TB, hepatic TB, cervical and mediastinal TB). Mycobacterium tuberculosis was isolated in four of the 11 cases. All patients recovered after a median of 6 months of anti-TB treatment. The localisation of TB and outcome after treatment in our SCA patients were similar to the one observed in an age-and sex-matched control group of non-SCA patient with TB. despite the low number of patients included in our study, SCA does not seem to be a risk factor for severe TB. What is Known: • Tuberculosis (TB) remains a global health problem particularly in developing countries, and Sickle cell anaemia (SCA) is currently one of the most common genetic diseases in the world that mainly affects African populations. • Very few data are available on TB in SCA patients. What is New: • The features of TB in children with SCA seem to be comparable to those expected in general population, with favourable outcomes in response to standard treatment. • Monitoring the dosage of anti-TB treatments could be of interest because of the possible impact of SCA on drug metabolism.

An autopsy case of an aged patient with spinocerebellar ataxia type 2.

PubMed

Ishida, Chiho; Komai, Kiyonobu; Yonezawa, Kohei; Sakajiri, Ken-Ichi; Nitta, Eishun; Kawashima, Atsuhiro; Yamada, Masahito

2011-10-01

We report the case of a woman who developed limb clumsiness in her fifties and gait disturbance in her sixties. She was bedridden after bone fractures at age 75 and showed disorientation, slow eye movement, gaze palsy, ataxic speech, muscle atrophy and weakness, and areflexia with pathological reflex. She died of respiratory failure at age 85. This patient was diagnosed genetically as having spinocerebellar ataxia type 2 (SCA2), and the number of expanded CAG repeats was 41. At autopsy, the brain weighed 965 g, and the brainstem, cerebellum, frontal convexity and spinal cord were atrophic. Neuronal loss and gliosis were severe in the pontine nucleus, inferior olivary nucleus, cerebellar cortex, gracile and cuneate nuclei and moderate in the substantia nigra, cerebellar dentate nucleus, anterior horns of the spinal cord and dorsal root ganglia. Axonal loss was observed in the middle and inferior cerebellar peduncles, pyramidal tract and posterior column of the spinal cord. Senile plaques and neurofibrillary tangles (NFTs) were diffusely found in the cerebrum (plaque stage C; NFT stage IV). Expanded polyglutamine-immunoreactive inclusions in the neuronal cytoplasm were widely distributed in the CNS, and neuronal intranuclear inclusions were observed in the pontine nucleus and cerebral cortex. This patient in this autopsy case is a late-onset and aged patient with SCA2, and this is the first report of SCA2 combined with Alzheimer's disease (AD) pathology. Neuropathological findings in this patient, except for AD pathology, were consistent with those of reported SCA2 cases. However, the olivo-ponto-cerebellar system of this patient was relatively preserved and the cerebellar dentate nucleus was more involved as compared with previously reported cases. These results suggest that age at onset or the number of CAG repeat expansions could correlate with the distribution pattern of SCA2 neurodegeneration. © 2010 Japanese Society of Neuropathology.

Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia.

PubMed

Al-Naama, Lamia M; Hassan, Mea'ad K; Mehdi, Jawad K

2015-01-01

Sickle cell anemia (SCA) is an inherited blood disease with known complications as a result of certain pathophysiological dysfunctions. It has been suggested that an increase in oxidative stress contributes to the incidence of these changes. This study investigated the oxidant/antioxidant status of patients with SCA, and evaluated the effect of SCA on antioxidant enzymes and their cofactors. The study included 42 patients with SCA (in steady state), and a control group of 50 age-matched individuals without SCA. Serum malondialdehyde (MDA), copper, zinc, ferritin and iron levels, red blood cell (RBC) superoxide dismutase (SOD) and catalase levels were measured for the SCA and control groups. Significantly lower levels of antioxidant enzymes (RBC SOD and catalase) and higher serum MDA levels (biomarker of oxidative stress) were found in SCA patients compared to the control group (all p < 0.001). Increased levels of serum ferritin, iron and copper and decreased zinc concentrations were also found in the SCA patients compared to the control group (all p < 0.001). In the SCA group, there were significant negative correlations between MDA levels and RBC SOD, RBC catalase, and serum zinc levels (p < 0.01), while a significant positive correlation between MDA with serum copper and iron levels (p < 0.01) was observed. SCA is associated with alterations in markers of oxidative stress including an increased MDA level, decreased antioxidant enzyme levels, and altered levels of enzyme cofactors (zinc, copper, and iron). This suggests that these antioxidant enzymes could be used as effective therapeutic targets for the treatment of this disease and supplementation of patients with substances with antioxidant properties may reduce the complications of this disease.

Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia

PubMed Central

Piety, Nathaniel Z.; Yang, Xiaoxi; Kanter, Julie; Vignes, Seth M.; George, Alex; Shevkoplyas, Sergey S.

2016-01-01

Background The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age. Methods and Findings In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials. Conclusions Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings. PMID:26735691

MR Imaging in Spinocerebellar Ataxias: A Systematic Review.

PubMed

Klaes, A; Reckziegel, E; Franca, M C; Rezende, T J R; Vedolin, L M; Jardim, L B; Saute, J A

2016-08-01

Polyglutamine expansion spinocerebellar ataxias are autosomal dominant slowly progressive neurodegenerative diseases with no current treatment. MR imaging is the best-studied surrogate biomarker candidate for polyglutamine expansion spinocerebellar ataxias, though with conflicting results. We aimed to review quantitative central nervous system MR imaging technique findings in patients with polyglutamine expansion spinocerebellar ataxias and correlations with well-established clinical and molecular disease markers. We searched MEDLINE, LILACS, and Cochrane data bases of clinical trials between January 1995 and January 2016, for quantitative MR imaging volumetric approaches, MR spectroscopy, diffusion tensor imaging, or other quantitative techniques, comparing patients with polyglutamine expansion spinocerebellar ataxias (SCAs) with controls. Pertinent details for each study regarding participants, imaging methods, and results were extracted. After reviewing the 706 results, 18 studies were suitable for inclusion: 2 studies in SCA1, 1 in SCA2, 15 in SCA3, 1 in SCA7, 1 in SCA1 and SCA6 presymptomatic carriers, and none in SCA17 and dentatorubropallidoluysian atrophy. Cerebellar hemispheres and vermis, whole brain stem, midbrain, pons, medulla oblongata, cervical spine, striatum, and thalamus presented significant atrophy in SCA3. The caudate, putamen and whole brain stem presented similar sensitivity to change compared with ataxia scales after 2 years of follow-up in a single prospective study in SCA3. MR spectroscopy and DTI showed abnormalities only in cross-sectional studies in SCA3. Results from single studies in other polyglutamine expansion spinocerebellar ataxias should be replicated in different cohorts. Additional cross-sectional and prospective volumetric analysis, MR spectroscopy, and DTI studies are necessary in polyglutamine expansion spinocerebellar ataxias. The properties of preclinical disease biomarkers (presymptomatic) of MR imaging should be targeted in future studies. © 2016 by American Journal of Neuroradiology.

Associations between endothelial dysfunction and clinical and laboratory parameters in children and adolescents with sickle cell anemia

PubMed Central

Ferreira, Tatiane Anunciação; Machado, Vinícius Ramos; Perdiz, Marya Izadora; Lyra, Isa Menezes; Nascimento, Valma Lopes; Boa-Sorte, Ney; Andrade, Bruno B.; Ladeia, Ana Marice

2017-01-01

Background Hematological changes can drive damage of endothelial cells, which potentially lead to an early endothelial dysfunction in patients with sickle cell anemia (SCA). An association may exist between endothelial dysfunction and several clinical manifestations of SCA. The present study aims to evaluate the links between changes in endothelial function and clinical and laboratory parameters in children and adolescents with SCA. Methods This study included 40 children and adolescents with stable SCA as well as 25 healthy children; aged 6–18 years. All study subjects were evaluated for endothelial function using Doppler ultrasonography. In addition, a number of laboratory assays were performed, including reticulocyte and leukocyte counts as well as measurement of circulating levels of total bilirubin, C-reactive protein (CRP), glucose, lipoproteins and peripheral oxyhemoglobin saturation. These parameters were also compared between SCA patients who were undertaking hydroxyurea (HU) and those who were not. Results Flow-mediated vasodilation (FMD) values were found to be reduced in SCA patients compared with those detected in healthy controls. SCA individuals with lower FMD values exhibited higher number of hospital admissions due to vaso-occlusive events. Additional analyses revealed that patients who had decreased FMD values exhibited higher odds of acute chest syndrome (ACS) episodes. A preliminary analysis with limited number of individuals failed to demonstrate significant differences in FMD values between SCA individuals who were treated with HU and those who were not. Conclusions Children and adolescents with SCA exhibit impaired endothelial function. Reductions in FMD values are associated with ACS. These findings underline the potential use of FMD as screening strategy of SCA patients with severe prognosis at early stages. PMID:28863145

Stem Cell Antigen-1 Deficiency Enhances the Chemopreventive Effect of Peroxisome Proliferator-Activated Receptorγ Activation

PubMed Central

Yuan, Hongyan; Upadhyay, Geeta; Yin, Yuzhi; Kopelovich, Levy; Glazer, Robert I.

2011-01-01

Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPARγ and PTEN, and a reduction of pSer84PPARγ, pERK1/2 and PPARδ. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPARγ agonist GW7845 and insensitivity to PPARδ agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPARγ expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPARγ. PMID:21955520

[Spinocerebellar ataxia type 2 associated to pigmentary retinitis].

PubMed

Jiménez-Caballero, Pedro Enrique; Serviá, Mónica

2010-07-01

Ocular disorders are useful in the characterisation of the different types of spinocerebellar ataxias (SCA); pigmentary retinitis is an alteration that is specifically associated to SCA type 7 and is characterised by night blindness, sensitivity to glare and progressive narrowing of the visual field. A 34-year-old woman with clinical symptoms of progressive ataxia and visual impairment secondary to pigmentary retinitis. The patient had a personal history with an autosomal dominant pattern of a similar disorder in her father and paternal grandmother. In the genetic study she presented a triplet expansion in the SCA type 2 gene. CONCLUSIONS; Although pigmentary retinitis belongs to the SCA type 7 phenotype, our patient presented this retinal disorder, as in other cases of SCA type 2. A genetic study for SCA type 2 must therefore be conducted in patients with a degenerative ataxic clinical picture and who present evidence of pigmentary retinitis.

Diet of bottlenose dolphins (Tursiops truncatus) from the Gulf of Cadiz: Insights from stomach content and stable isotope analyses

PubMed Central

Marçalo, Ana; Ramírez, Francisco; Verborgh, Philippe; Gauffier, Pauline; Esteban, Ruth; Nicolau, Lídia; González-Ortegón, Enrique; Baldó, Francisco; Vilas, César; Vingada, José; G. Forero, Manuela; de Stephanis, Renaud

2017-01-01

The ecological role of species can vary among populations depending on local and regional differences in diet. This is particularly true for top predators such as the bottlenose dolphin (Tursiops truncatus), which exhibits a highly varied diet throughout its distribution range. Local dietary assessments are therefore critical to fully understand the role of this species within marine ecosystems, as well as its interaction with important ecosystem services such as fisheries. Here, we combined stomach content analyses (SCA) and stable isotope analyses (SIA) to describe bottlenose dolphins diet in the Gulf of Cadiz (North Atlantic Ocean). Prey items identified using SCA included European conger (Conger conger) and European hake (Merluccius merluccius) as the most important ingested prey. However, mass-balance isotopic mixing model (MixSIAR), using δ13C and δ15N, indicated that the assimilated diet consisted mainly on Sparidae species (e.g. seabream, Diplodus annularis and D. bellottii, rubberlip grunt, Plectorhinchus mediterraneus, and common pandora, Pagellus erythrinus) and a mixture of other species including European hake, mackerels (Scomber colias, S. japonicus and S. scombrus), European conger, red bandfish (Cepola macrophthalma) and European pilchard (Sardina pilchardus). These contrasting results highlight differences in the temporal and taxonomic resolution of each approach, but also point to potential differences between ingested (SCA) and assimilated (SIA) diets. Both approaches provide different insights, e.g. determination of consumed fish biomass for the management of fish stocks (SCA) or identification of important assimilated prey species to the consumer (SIA). PMID:28898268

Air to air view of Endeavour, OV-105, atop SCA approaches Ellington runway

NASA Technical Reports Server (NTRS)

1991-01-01

Air to air view of Endeavour, Orbiter Vehicle (OV) 105, atop a Shuttle Carrier Aircraft (SCA) NASA 911, a modified Boeing 747, approaches touchdown for a brief stopover at Ellington Field, near JSC. Visible below the spacecraft/aircraft combination are the NASA T-38 flight line, NASA aircraft hangars and facilities, and a runway. OV-105 rolled out at Rockwell's Palmdale facility on 04-25-91 to once more bring to four the total of NASA Shuttles available for flight assignment. The spacecraft and aircraft-tandem left Houston later on this day headed for another stop in Mississippi before landing in Florida on 05-07-91. This photograph was taken from a T-38 aircraft by Sheri J. Dunnette of JSC's Image Science Division (ISD).

Ensemble-based assimilation of fractional snow-covered area satellite retrievals to estimate the snow distribution at Arctic sites

NASA Astrophysics Data System (ADS)

Aalstad, Kristoffer; Westermann, Sebastian; Vikhamar Schuler, Thomas; Boike, Julia; Bertino, Laurent

2018-01-01

With its high albedo, low thermal conductivity and large water storing capacity, snow strongly modulates the surface energy and water balance, which makes it a critical factor in mid- to high-latitude and mountain environments. However, estimating the snow water equivalent (SWE) is challenging in remote-sensing applications already at medium spatial resolutions of 1 km. We present an ensemble-based data assimilation framework that estimates the peak subgrid SWE distribution (SSD) at the 1 km scale by assimilating fractional snow-covered area (fSCA) satellite retrievals in a simple snow model forced by downscaled reanalysis data. The basic idea is to relate the timing of the snow cover depletion (accessible from satellite products) to the peak SSD. Peak subgrid SWE is assumed to be lognormally distributed, which can be translated to a modeled time series of fSCA through the snow model. Assimilation of satellite-derived fSCA facilitates the estimation of the peak SSD, while taking into account uncertainties in both the model and the assimilated data sets. As an extension to previous studies, our method makes use of the novel (to snow data assimilation) ensemble smoother with multiple data assimilation (ES-MDA) scheme combined with analytical Gaussian anamorphosis to assimilate time series of Moderate Resolution Imaging Spectroradiometer (MODIS) and Sentinel-2 fSCA retrievals. The scheme is applied to Arctic sites near Ny-Ålesund (79° N, Svalbard, Norway) where field measurements of fSCA and SWE distributions are available. The method is able to successfully recover accurate estimates of peak SSD on most of the occasions considered. Through the ES-MDA assimilation, the root-mean-square error (RMSE) for the fSCA, peak mean SWE and peak subgrid coefficient of variation is improved by around 75, 60 and 20 %, respectively, when compared to the prior, yielding RMSEs of 0.01, 0.09 m water equivalent (w.e.) and 0.13, respectively. The ES-MDA either outperforms or at least nearly matches the performance of other ensemble-based batch smoother schemes with regards to various evaluation metrics. Given the modularity of the method, it could prove valuable for a range of satellite-era hydrometeorological reanalyses.

Exploring the architectural trade space of NASAs Space Communication and Navigation Program

NASA Astrophysics Data System (ADS)

Sanchez, M.; Selva, D.; Cameron, B.; Crawley, E.; Seas, A.; Seery, B.

NASAs Space Communication and Navigation (SCaN) Program is responsible for providing communication and navigation services to space missions and other users in and beyond low Earth orbit. The current SCaN architecture consists of three independent networks: the Space Network (SN), which contains the TDRS relay satellites in GEO; the Near Earth Network (NEN), which consists of several NASA owned and commercially operated ground stations; and the Deep Space Network (DSN), with three ground stations in Goldstone, Madrid, and Canberra. The first task of this study is the stakeholder analysis. The goal of the stakeholder analysis is to identify the main stakeholders of the SCaN system and their needs. Twenty-one main groups of stakeholders have been identified and put on a stakeholder map. Their needs are currently being elicited by means of interviews and an extensive literature review. The data will then be analyzed by applying Cameron and Crawley's stakeholder analysis theory, with a view to highlighting dominant needs and conflicting needs. The second task of this study is the architectural tradespace exploration of the next generation TDRSS. The space of possible architectures for SCaN is represented by a set of architectural decisions, each of which has a discrete set of options. A computational tool is used to automatically synthesize a very large number of possible architectures by enumerating different combinations of decisions and options. The same tool contains models to evaluate the architectures in terms of performance and cost. The performance model uses the stakeholder needs and requirements identified in the previous steps as inputs, and it is based in the VASSAR methodology presented in a companion paper. This paper summarizes the current status of the MIT SCaN architecture study. It starts by motivating the need to perform tradespace exploration studies in the context of relay data systems through a description of the history NASA's space communicati- n networks. It then presents the generalities of possible architectures for future space communication and navigation networks. Finally, it describes the tools and methods being developed, clearly indicating the architectural decisions that have been taken into account as well as the systematic approach followed to model them. The purpose of this study is to explore the SCaN architectural tradespace by means of a computational tool. This paper describes the tool, while the tradespace exploration is underway.

Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.

PubMed Central

Takano, H; Cancel, G; Ikeuchi, T; Lorenzetti, D; Mawad, R; Stevanin, G; Didierjean, O; Dürr, A; Oyake, M; Shimohata, T; Sasaki, R; Koide, R; Igarashi, S; Hayashi, S; Takiyama, Y; Nishizawa, M; Tanaka, H; Zoghbi, H; Brice, A; Tsuji, S

1998-01-01

To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs. PMID:9758625

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance.

PubMed

Bevilacqua, Elisa; Ordóñez, Elena; Hurtado, Ivan; Rueda, Laura; Mazzone, Eléonora; Cirigliano, Vincenzo; Jani, Jacques C

2017-08-23

To study patient choice regarding testing for sex chromosome aneuploidy (SCA) and the performance of cell-free DNA (cfDNA) screening for SCA. Patient choice regarding screening for SCA and factors influencing this choice were evaluated in a single center. In a subsequent two-center study, cases that screened positive for SCA were analyzed to determine the positive predictive value (PPV) for each SCA. In all, 1,957 (61.9%) of the 3,162 patients undergoing cfDNA testing opted for SCA screening. Regression analysis demonstrated that independent predictors of a patient's decision for SCA were earlier gestational age, spontaneous conception, and cfDNA chosen as a primary method of screening. A total of 161 cases screened positive for SCA and follow-up data were available for 118 (73.3%). Forty-six of the 61 cases of 45,X were false-positive results and 15 were concordant with the fetal karyotype (PPV = 24.6%). Seventeen of the 22 cases of 47,XXX were false positive and 5 concordant (PPV = 22.7%). Eleven of the 30 cases of 47,XXY were false positive and 19 concordant (PPV = 63.3%). All 5 cases of 47,XYY were correctly identified, thus yielding a PPV of 100%. More than half of the patients undergoing cfDNA aneuploidy screening also opted for SCA testing, but they were less likely to do so in the presence of an increased risk of trisomy. SCAs involving the X chromosome had a lower PPV than those involving the Y chromosome. © 2017 S. Karger AG, Basel.

Inter-association task force recommendations on emergency preparedness and management of sudden cardiac arrest in high school and college athletic programs: a consensus statement.

PubMed

Drezner, Jonathan A; Courson, Ron W; Roberts, William O; Mosesso, Vincent N; Link, Mark S; Maron, Barry J

2007-03-01

To assist high school and college athletic programs prepare for and respond to sudden cardiac arrest (SCA). This consensus statement summarizes our current understanding of SCA in young athletes, defines the necessary elements for emergency preparedness, and establishes uniform treatment protocols for the management of SCA. SCA is the leading cause of death in young athletes. The increasing presence of and timely access to automated external defibrillators (AEDs) at sporting events provides a means of early defibrillation and the potential for effective secondary prevention of sudden cardiac death. An Inter-Association Task Force was sponsored by the National Athletic Trainers' Association to develop consensus recommendations on emergency preparedness and management of SCA in athletes. Comprehensive emergency planning is needed for high school and college athletic programs to ensure an efficient and structured response to SCA. Essential elements of an emergency action plan include establishing an effective communication system, training of anticipated responders in cardiopulmonary resuscitation and AED use, access to an AED for early defibrillation, acquisition of necessary emergency equipment, coordination and integration of onsite responder and AED programs with the local emergency medical services system, and practice and review of the response plan. Prompt recognition of SCA, early activation of the emergency medical services system, the presence of a trained rescuer to initiate cardiopulmonary resuscitation, and access to early defibrillation are critical in the management of SCA. In any collapsed and unresponsive athlete, SCA should be suspected and an AED applied as soon as possible for rhythm analysis and defibrillation if indicated.

Progression of Dysphagia in Spinocerebellar Ataxia Type 6.

PubMed

Isono, Chiharu; Hirano, Makito; Sakamoto, Hikaru; Ueno, Shuichi; Kusunoki, Susumu; Nakamura, Yusaku

2017-06-01

Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant triplet repeat disease, predominantly affects the cerebellum with a late onset and generally good prognosis. Dysphagia is commonly associated with the outcomes of neurodegenerative diseases such as SCA6. Although the characteristics of dysphagia have been rarely reported in SCA6, our previous study indicated that dysphagia is generally milder in SCA6 than in SCA3, another inherited ataxia with multisystem involvement. However, abnormalities in the pharyngeal phase in SCA6 were indistinguishable from those in SCA3, with no explainable reason. To determine the reason, we repeatedly performed videofluoroscopic examinations (VF) in 14 patients with SCA6. The results showed that the gross progression of dysphagia was apparently slow, but four patients had progressive dysphagia at an early disease stage; dysphagia began within 10 years from the onset of ataxia and rapidly progressed. A common clinical feature of the four patients was a significantly older age at the onset of ataxia (74.0 vs. 60.3 years), associated with significantly shorter triplet repeats. This finding surprisingly indicated that patients who had shorter repeats and thereby later onset and potentially better prognoses were at risk for dysphagia-associated problems. Ischemic changes, homozygous mutation, and diabetes mellitus as well as aging might have contributed to the observed progressive dysphagia. We found that conventionally monitored somatosensory evoked potentials at least partly reflected progressive dysphagia. Despite the small study group, our findings suggest that clinicians should carefully monitor dysphagia in patients with SCA6 who are older at disease onset (>60 years).

Rapid Onset of Motor Deficits in a Mouse Model of Spinocerebellar Ataxia Type 6 Precedes Late Cerebellar Degeneration1,2,3

PubMed Central

Ljungberg, Lovisa; Cormier, Alexander; Quilez, Sabrina

2015-01-01

Abstract Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant cerebellar ataxia that has been associated with loss of cerebellar Purkinje cells. Disease onset is typically at midlife, although it can vary widely from late teens to old age in SCA6 patients. Our study focused on an SCA6 knock-in mouse model with a hyper-expanded (84X) CAG repeat expansion that displays midlife-onset motor deficits at ∼7 months old, reminiscent of midlife-onset symptoms in SCA6 patients, although a detailed phenotypic analysis of these mice has not yet been reported. Here, we characterize the onset of motor deficits in SCA684Q mice using a battery of behavioral assays to test for impairments in motor coordination, balance, and gait. We found that these mice performed normally on these assays up to and including at 6 months, but motor impairment was detected at 7 months with all motor coordination assays used, suggesting that motor deficits emerge rapidly during a narrow age window in SCA684Q mice. In contrast to what is seen in SCA6 patients, the decrease in motor coordination was observed without alterations in gait. No loss of cerebellar Purkinje cells or striatal neurons were observed at 7 months, the age at which motor deficits were first detected, but significant Purkinje cell loss was observed in 2-year-old SCA684Q mice, arguing that Purkinje cell death does not significantly contribute to the early stages of SCA6. PMID:26730403

The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

PubMed Central

Matsuda, Shunichi; Matsumoto, Hideyuki; Furubayashi, Toshiaki; Hanajima, Ritsuko; Tsuji, Shoji; Ugawa, Yoshikazu; Terao, Yasuo

2015-01-01

The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients. PMID:25706752

Cognitive functioning in children from Nigeria with sickle cell anemia.

PubMed

Oluwole, Olubusola B; Noll, Robert B; Winger, Daniel G; Akinyanju, Olu; Novelli, Enrico M

2016-11-01

Cognitive impairment is a major neurological complication of sickle cell anemia (SCA) in the United States, but there are limited studies of cognitive impairment in Nigeria, the country with the highest SCA burden. We hypothesized that children from Nigeria with SCA have worse cognitive functioning than comparison children and explored the association between lower cognitive functioning and key laboratory demographic and socioeconomic variables among children with SCA. We conducted a cross-sectional survey, supplemented by anthropomorphic and laboratory data, among a convenience sample of children from Nigeria with and without SCA. We administered the Wechsler Intelligence Scale for Children, Version IV. Our primary outcome measures included (1) estimated IQ (Est. IQ), (2) working memory (WM), and (3) processing speed (PS). The sample included 56 children with SCA (mean age 9.20 [SD 2.75], 46.43% girls) and 44 comparison children (mean age 9.41 [SD 2.49], 40.91% girls). Children with SCA performed worse on Est. IQ (84.58 vs. 96.10, P = 0.006) and PS (86.69 vs 96.91, P = 0.009) than comparison children. There was no significant difference in WM between both groups. Factors associated with lower Est. IQ and PS among children with SCA included age, maternal education, weight-for-age Z scores, and height-for age Z scores. In this small sample of children from Nigeria, we found worse cognitive functioning in children with SCA than in comparison children, and that sociodemographic and anthropomorphic factors were correlated with cognitive functioning. © 2016 Wiley Periodicals, Inc.

The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling.

PubMed

Wang, Xiaohong; Hu, Qingsong; Nakamura, Yasuhiro; Lee, Joseph; Zhang, Ge; From, Arthur H L; Zhang, Jianyi

2006-07-01

Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.

Alteration of Lymphocyte Phenotype and Function in Sickle Cell Anemia: Implications for Vaccine Responses

PubMed Central

Balandya, Emmanuel; Reynolds, Teri; Obaro, Stephen; Makani, Julie

2016-01-01

Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper : CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27+IgMhighIgDlow memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research. PMID:27237467

Glial S100B Positive Vacuoles In Purkinje Cells: Earliest Morphological Abnormality In SCA1 Transgenic Mice

PubMed Central

VIG, Parminder J.S.; LOPEZ, Maripar E.; WEI, Jinrong; D’SOUZA, David R.; SUBRAMONY, SH; HENEGAR, Jeffrey; FRATKIN, Jonathan D.

2007-01-01

Spinocerebellar ataxia-1 (SCA1) is caused by the expansion of a polyglutamine repeat within the disease protein, ataxin-1. The overexpression of mutant ataxin-1 in SCA1 transgenic mice results in the formation of cytoplasmic vacuoles in Purkinje neurons (PKN) of the cerebellum. PKN are closely associated with neighboring Bergmann glia. To elucidate the role of Bergmann glia in SCA1 pathogenesis, cerebellar tissue from 7 days to 6 wks old SCA1 transgenic and wildtype mice were used. We observed that Bergmann glial S100B protein is localized to the cytoplasmic vacuoles in SCA1 PKN. These S100B positive cytoplasmic vacuoles began appearing much before the onset of behavioral abnormalities, and were negative for other glial and PKN marker proteins. Electron micrographs revealed that vacuoles have a double membrane. In the vacuoles, S100B colocalized with receptors of advanced glycation end-products (RAGE), and S100B co-immunoprecipated with cerebellar RAGE. In SCA1 PKN cultures, exogenous S100B protein interacted with the PKN membranes and was internalized. These data suggest that glial S100B though extrinsic to PKN is sequestered into cytoplasmic vacuoles in SCA1 mice at early postnatal ages. Further, S100B may be binding to RAGE on Purkinje cell membranes before these membranes are internalized. PMID:18176630

ScaRaB: first results of absolute and cross calibration

NASA Astrophysics Data System (ADS)

Trémas, Thierry L.; Aznay, Ouahid; Chomette, Olivier

2015-10-01

ScaRaB (SCAnner for RAdiation Budget) is the name of three radiometers whose two first flight models have been launched in 1994 and 1997. The instruments were mounted on-board Russian satellites, METEOR and RESURS. On October 12th 2011, a last model has been launched from the Indian site of Sriharikota. ScaRaB is a passenger of MEGHA-TROPIQUES, an Indo-French joint Satellite Mission for studying the water cycle and energy exchanges in the tropics. ScaRaB is composed of four parallel and independent channels. Channel-2 and channel-3 are considered as the main ones. Channel-1 is dedicated to measure solar radiance (0.5 to 0.7 μm) while channel-4 (10 to 13 μm) is an infrared window. The absolute calibration of ScaRab is assured by internal calibration sources (black bodies and a lamp for channel-1). However, during the commissioning phase, the lamp used for the absolute calibration of channel-1 revealed to be inaccurate. We propose here an alternative calibration method based on terrestrial targets. Due to the spectral range of channel-1, only calibration over desert sites (temporal monitoring) and clouds (cross band) is suitable. Desert sites have been widely used for sensor calibration since they have a stable spectral response over time. Because of their high reflectances, the atmospheric effect on the upward radiance is relatively minimal. In addition, they are spatially uniform. Their temporal instability without atmospheric correction has been determined to be less than 1-2% over a year. Very-high-altitude (10 km) bright clouds are good validation targets in the visible and near-infrared spectra because of their high spectrally consistent reflectance. If the clouds are very high, there is no need to correct aerosol scattering and water vapor absorption as both aerosol and water vapor are distributed near the surface. Only Rayleigh scattering and ozone absorption need to be considered. This method has been found to give a 4% uncertainty. Radiometric cross calibration of Earth observation sensors is a crucial need to guarantee or quantify the consistency of measurements from different sensors. ScaRaB is compatible with CERES mission. Two main spectral bands are measured by the radiometer: A short-wave channel (0.2 to 4 μm) dedicated to solar fluxes and a Total channel (0.2 to 200 μm) for fluxes combining the infrared earth radiance and the albedo. The earth long-wave radiance is isolated by subtracting the short-wave channel to the Total channel. Both Earth Radiation Budget missions (CERES and ScaRaB) have the same specification: to provide an accuracy of ~1% in the measurement of short-wave and long-wave radiances and an estimation of the short-wave and long-wave fluxes less than 10 W/m2. We use the CERES PAPS and Cross-Track SSF datasets for direct radiances and fluxes comparisons during two validation phases. The first one occurred during April 17th to June 8th (51 days) in 2012 and the second one occurred between March 22th and May 31st 2015. The first validation campaign has been held with the CERES team using the Terra FM2 data. The CERES PAPS mode was used to align the swath scan, in order to increase the collocated pixels between the two instruments. This campaign allowed us to validate the ScaRaB radiances and to refine the error budget. The second validation campaign aims to provide a temporal monitoring of ScaRab calibration.

Aortic Sca-1+ Progenitor Cells Arise from the Somitic Mesoderm Lineage in Mice.

PubMed

Steinbach, Sarah K; Wang, Tao; Carruthers, Martha H; Li, Angela; Besla, Rickvinder; Johnston, Adam P; Robbins, Clinton S; Husain, Mansoor

2018-05-31

Sca-1 + progenitor cells in the adult mouse aorta are known to generate vascular smooth muscle cells (VSMCs), but their embryological origins and temporal abundance are not known. Using tamoxifen-inducible Myf5-Cre ER mice, we demonstrate that Sca-1 + adult aortic cells arise from the somitic mesoderm beginning at E8.5 and continue throughout somitogenesis. Myf5 lineage-derived Sca-1 + cells greatly expand in situ, starting at 4 weeks of age, and become a major source of aortic Sca-1 + cells by 6 weeks of age. Myf5-derived adult aortic cells are capable of forming multicellular sphere-like structures in vitro and express the pluripotency marker Sox2. Exposure to transforming growth factor-β3 induces these spheres to differentiate into calponin-expressing VSMCs. Pulse-chase experiments using tamoxifen-inducible Sox2-Cre ERT2 mice at 8 weeks of age demonstrate that ∼35% of all adult aortic Sca-1 + cells are derived from Sox2 + cells. The present study demonstrates that aortic Sca-1 + progenitor cells are derived from the somitic mesoderm formed at the earliest stages of somitogenesis and from Sox2-expressing progenitors in adult mice.

Hematopoietic SCT for the Black African and non-Black African variants of sickle cell anemia.

PubMed

Lucarelli, G; Isgrò, A; Sodani, P; Marziali, M; Gaziev, J; Paciaroni, K; Gallucci, C; Cardarelli, L; Ribersani, M; Alfieri, C; De Angelis, G; Armiento, D; Andreani, M; Testi, M; Amato, A; Akinyanju, O O; Wakama, T T

2014-11-01

Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.

Left ventricular structural and functional changes evaluated by echocardiography and two-dimensional strain in patients with sickle cell disease.

PubMed

Bedirian, Ricardo; Soares, Andrea Ribeiro; Maioli, Maria Christina; de Medeiros, Jussara Fonseca Fernandes; Lopes, Agnaldo José; Castier, Marcia Bueno

2018-04-01

Patients with sickle cell disease have increased left ventricular size, which is not usually accompanied by changes in systolic function indexes. We assessed echocardiographic abnormalities present in patients with sickle cell anemia (SCA) and compared echocardiographic parameters to other sickle cell diseases (OSCD). A blind cross-sectional study with 60 patients with SCA and 16 patients with OSCD who underwent transthoracic echocardiography was performed. Echocardiographic findings were: left atrial volume index 47.7 ±11.5 ml/m² in SCA group and 31.7 ±8.42 ml/m² in OSCD group ( p < 0.001); left ventricular diastolic diameter index 3.47 ±0.37 cm/m² in SCA group and 2.97 ±0.41 cm/m² in OSCD group ( p < 0.001); left ventricular systolic diameter index 2.12 ±0.31 cm/m² in SCA group and 1.86 ±0.28 cm/m² in OSCD group ( p < 0.001). There were no differences in the left ventricular ejection fraction: 68.2 ±6.69% in SCA group and 67.1 ±6.21% in OSCD group ( p = 0.527). The ratio between mitral E wave and mean mitral annulus e' wave velocities was higher in the SCA group (7.72 ±1.54 vs. 6.70 ±1.65; p = 0.047). Mitral A wave correlated significantly with hemoglobin levels ( r = -0.340; p = 0.032). There was an increase of left ventricular and left atrial sizes in patients with SCA, compared to patients with OSCD, without changes in systolic or diastolic function in both groups. This could be due to the hyperkinetic state due to the more severe anemia in the SCA subjects.

Effectiveness of emergency response planning for sudden cardiac arrest in United States high schools with automated external defibrillators.

PubMed

Drezner, Jonathan A; Rao, Ashwin L; Heistand, Justin; Bloomingdale, Megan K; Harmon, Kimberly G

2009-08-11

US high schools are increasingly adopting automated external defibrillators (AEDs) for use in campus settings. We analyzed the effectiveness of emergency response planning for sudden cardiac arrest (SCA) in a large cohort of US high schools that had onsite AED programs. A cohort of US high schools with at least 1 onsite AED was identified from the National Registry for AED Use in Sports. A school representative completed a comprehensive survey on emergency planning and provided details of any SCA incident occurring within 6 months of survey completion. Surveys were completed between December 2006 and July 2007. In total, 1710 high schools with an onsite AED program were studied. Although 83% (1428 of 1710) of schools have an established emergency response plan for SCA, only 40% practice and review the plan at least annually with potential school responders. A case of SCA was reported by 36 of 1710 schools (2.1%). The 36 SCA victims included 14 high school student athletes (mean age, 16 years; range, 14 to 17 years) and 22 older nonstudents (mean age, 57 years; range, 42 to 71 years) such as employees and spectators. No cases were reported in student nonathletes. Of the 36 SCA cases, 35 (97%) were witnessed, 34 (94%) received bystander cardiopulmonary resuscitation, and 30 (83%) received an AED shock. Twenty-three SCA victims (64%) survived to hospital discharge, including 9 of the 14 student athletes and 14 of the 22 older nonstudents. School-based AED programs provide a high survival rate for both student athletes and older nonstudents who suffer SCA on school grounds. High schools are strongly encouraged to implement onsite AED programs as part of a comprehensive emergency response plan to SCA.

Passive Thermal Design Approach for the Space Communications and Navigation (SCaN) Testbed Experiment on the International Space Station (ISS)

NASA Technical Reports Server (NTRS)

Siamidis, John; Yuko, Jim

2014-01-01

The Space Communications and Navigation (SCaN) Program Office at NASA Headquarters oversees all of NASAs space communications activities. SCaN manages and directs the ground-based facilities and services provided by the Deep Space Network (DSN), Near Earth Network (NEN), and the Space Network (SN). Through the SCaN Program Office, NASA GRC developed a Software Defined Radio (SDR) testbed experiment (SCaN testbed experiment) for use on the International Space Station (ISS). It is comprised of three different SDR radios, the Jet Propulsion Laboratory (JPL) radio, Harris Corporation radio, and the General Dynamics Corporation radio. The SCaN testbed experiment provides an on-orbit, adaptable, SDR Space Telecommunications Radio System (STRS) - based facility to conduct a suite of experiments to advance the Software Defined Radio, Space Telecommunications Radio Systems (STRS) standards, reduce risk (Technology Readiness Level (TRL) advancement) for candidate Constellation future space flight hardware software, and demonstrate space communication links critical to future NASA exploration missions. The SCaN testbed project provides NASA, industry, other Government agencies, and academic partners the opportunity to develop and field communications, navigation, and networking technologies in the laboratory and space environment based on reconfigurable, software defined radio platforms and the STRS Architecture.The SCaN testbed is resident on the P3 Express Logistics Carrier (ELC) on the exterior truss of the International Space Station (ISS). The SCaN testbed payload launched on the Japanese Aerospace Exploration Agency (JAXA) H-II Transfer Vehicle (HTV) and was installed on the ISS P3 ELC located on the inboard RAM P3 site. The daily operations and testing are managed out of NASA GRC in the Telescience Support Center (TSC).

Flk-1+Sca-1- mesenchymal stem cells: functional characteristics in vitro and regenerative capacity in vivo

PubMed Central

Li, Yugang; Pan, Enshan; Wang, Yu; Zhu, Xiaoguang; Wei, Anyang

2015-01-01

Objectives: Mesenchymal stem cells (MSCs) represent a powerful tool in regenerative medicine because of their differentiation and migration capacities. We aimed to investigate the possibility of Flk-1+Sca-1- mesenchymal stem cells (Flk-1+Sca-1- MSCs) transplantation to repair erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). Methods: In this study, we isolated Flk-1+Sca-1- MSCs from bone marrow (bMSCs). Then, newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine for the purpose of tracking endogenous Flk-1+Sca-1- MSCs. Eight weeks later, 8 of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group) while another 8 rats were subject to Flk-1+Sca-1- MSCs treatment (DM+MSC group). All rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology. Results: Flk-1+Sca-1- MSCs could differentiate into skeletal muscle cells and endothelial cells in vivo and in vitro. Engrafted Flk-1+Sca-1- MSCs were shown to home to injured muscle, participate in myofibers repair and could partially reconstitute the sarcolemmal expression of myocardin and ameliorate the level of related specific pathological markers. Conclusion: Flk-1+Sca-1- MSCs could be used in the treatment erectile function in diabetes mellitus associated erectile dysfunction by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis. PMID:26617697

Accessory papillary muscles and papillary muscle hypertrophy are associated with sudden cardiac arrest of unknown cause.

PubMed

Uhm, Jae-Sun; Youn, Jong-Chan; Lee, Hye-Jeong; Park, Junbeom; Park, Jin-Kyu; Shim, Chi Young; Hong, Geu-Ru; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung

2015-10-15

The present study was performed for elucidating the associations between the morphology of the papillary muscles (PMs) and sudden cardiac arrest (SCA). We retrospectively reviewed history, laboratory data, electrocardiography, echocardiography, coronary angiography, and cardiac CT/MRI for 190 patients with SCA. The prevalence of accessory PMs and PM hypertrophy in patients with SCA of unknown cause was compared with that in patients with SCA of known causes and 98 age- and sex-matched patients without SCA. An accessory PM was defined as a PM with origins separated from the anterolateral and posteromedial PMs, or a PM that branched into two or three bellies at the base of the anterolateral or posteromedial PM. PM hypertrophy was defined as at least one of the two PMs having a diameter of ≥1.1cm. In 49 patients (age 49.9±15.9years; 38 men) the cause of SCA was unknown, whereas 141 (age 54.2±16.6years; 121 men) had a known cause. The prevalence of accessory PMs was significantly higher in the unknown-cause group than in the known-cause group (24.5% and 7.8%, respectively; p=0.002) or the no-SCA group (7.1%, p=0.003). The same was true for PM hypertrophy (unknown-cause 12.2%, known-cause 2.1%, p=0.010; no SCA group 1.0%, p=0.006). By logistic regression, accessory PM and PM hypertrophy were independently associated with sudden cardiac arrest of unknown cause. An accessory PM and PM hypertrophy are associated with SCA of unknown cause. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sudden cardiac arrest during sports activity in middle age.

PubMed

Marijon, Eloi; Uy-Evanado, Audrey; Reinier, Kyndaron; Teodorescu, Carmen; Narayanan, Kumar; Jouven, Xavier; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

2015-04-21

Sports-associated sudden cardiac arrests (SCAs) occur mostly during middle age. We sought to determine the burden, characteristics, and outcomes of SCA during sports among middle-aged residents of a large US community. Patients with SCA who were 35 to 65 years of age were identified in a large, prospective, population-based study (2002-2013), with systematic and comprehensive assessment of their lifetime medical history. Of the 1247 SCA cases, 63 (5%) occurred during sports activities at a mean age of 51.1±8.8 years, yielding an incidence of 21.7 (95% confidence interval, 8.1-35.4) per 1 million per year. The incidence varied significantly by sex, with a higher incidence among men (relative risk, 18.68; 95% confidence interval, 2.50-139.56) for sports SCAs compared with all other SCAs (relative risk 2.58; 95% confidence interval, 2.12-3.13). Sports SCA was also more likely to be a witnessed event (87% versus 53%; P<0.001) with cardiopulmonary resuscitation (44% versus 25%; P=0.001) and ventricular fibrillation (84% versus 51%; P<0.0001). Survival to hospital discharge was higher for sports-associated SCA (23.2% versus 13.6%; P=0.04). Sports SCA cases presented with known preexisting cardiac disease in 16% and ≥1 cardiovascular risk factors in 56%, and overall, 36% of cases had typical cardiovascular symptoms during the week preceding the SCA. Sports-associated SCA in middle age represents a relatively small proportion of the overall SCA burden, reinforcing the idea of the high-benefit, low-risk nature of sports activity. Especially in light of current population aging trends, our findings emphasize that targeted education could maximize both safety and acceptance of sports activity in the older athlete. © 2015 American Heart Association, Inc.

Association of leisure time physical activity and sports competition activities with high blood pressure levels: study carried out in a sample of Portuguese children and adolescents.

PubMed

Gaya, A R; Silva, P; Martins, C; Gaya, A; Ribeiro, J C; Mota, J

2011-05-01

A better understanding of the different domains and characteristics of children's and adolescent's physical activity (PA) could be a strategy to clarify the association of this behaviour with the early development of cardiovascular risk factors. To examine the relationship between leisure time physical activity (LTPA) and sports competition activities (SCA) with high blood pressure (HBP) levels in a sample of children and adolescents from Porto, Portugal. This is a cross-sectional study, which comprised 503 boys and 572 girls, aged 8-17 years old. LTPA and SCA were assed by self-reported. Students were assigned as active and non-active in SCA or LTPA according to their self-reported participation. Participants were classified as HBP when they are above of the last quartile for systolic and/or diastolic BP adjusted for gender and age. Do not be engaged in LTPA (OR: 1.47; 95% CI: 1.12; 1.93) and SCA (OR: 1.36; 95% CI: 1.02; 1.81) was significantly associated with the likelihood of being HBP. However, when cardiorespiratory fitness (CRF) (OR: 1.23; 95% CI: 0.91; 1.67) and body mass index (BMI) (OR: 1.31; 95% CI: 0.98; 1.75) were included on SCA model, the association between SCA with HBP did not showed significant results. Children and adolescents who are not engaged in SCA or LTPA are more likely to be classified as having HBP; however, the relationship between SCA and HBP was dependent of CRF and BMI. Further, PA strategies should take these differences on the relationship between HBP, SCA and LTPA. © 2011 Blackwell Publishing Ltd.

Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6).

PubMed

Sasaki, H; Kojima, H; Yabe, I; Tashiro, K; Hamada, T; Sawa, H; Hiraga, H; Nagashima, K

1998-02-01

SCA6 is an autosomal dominant spinocerebellar ataxia (SCA) caused by a small CAG repeat expansion of the gene encoding an alpha-1A-voltage-dependent Ca channel gene subunit on chromosome 19p13. A Japanese woman with SCA6, with a 7-year history of progressive pure cerebellar ataxia, died of malignant lymphoma. Systematic neuropathological examination showed that neuronal degeneration was confined to the cerebellar Purkinje cells and, to a lesser degree, the granular cells, without any involvement of other central nervous system structures. Such pathological selectivity correlates with the localized expression of the responsible gene, and coincides with the neurological manifestation. These findings might contribute to establishing the phenotype of the SCA6 via comparison with other dominant ataxias.

Development of NASA's Sample Cartridge Assembly: Design, Thermal Analysis, and Testing

NASA Technical Reports Server (NTRS)

O'Connor, Brian; Hernandez, Deborah; Duffy, James

2015-01-01

NASA's Sample Cartridge Assembly (SCA) project is responsible for designing and validating a payload that contains a materials research sample in a sealed environment. The SCA will be heated in the European Space Agency's (ESA) Low Gradient Furnace (LGF) that is housed inside the Material Science Research Rack (MSRR) located in the International Space Station (ISS). Sintered metals and crystal growth experiments in microgravity are examples of some of the types of materials research that may be performed with a SCA. The project's approach has been to use thermal models to guide the SCA through several design iterations. Various layouts of the SCA components were explored to meet the science and engineering requirements, and testing has been done to help prove the design. This paper will give an overview of the SCA design. It will show how thermal analysis is used to support the project. Also some testing that has been completed will also be discussed, including changes that were made to the thermal profile used during brazing.

The isolation and in vitro expansion of hepatic Sca-1 progenitor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clayton, Elizabeth, E-mail: Elizabeth.Clayton@ed.ac.uk; Forbes, Stuart J.

2009-04-17

The intra-hepatic population of liver progenitor cells expands during liver injury when hepatocyte proliferation is inhibited. These cells can be purified by density gradient centrifugation and cultured. Separated by size only this population contains small cells of hematopoietic, epithelial and endothelial lineages and is thought to contain liver stem cells. The identity of liver stem cells remains unknown although there is some evidence that tissue Sca1{sup +} CD45{sup -} cells display progenitor cell characteristics. We identified both intra-hepatic and gall bladder Sca1{sup +} cells following liver injury and expanded ex vivo Sca1 cells as part of heterogenous cell culture ormore » as a purified population. We found significant difference between the proliferation of Sca-1 cells when plated on laminin or collagen I while proliferation of heterogenous population was not affected by the extracellular matrix indicating the necessity for culture of Sca1{sup +} cells with laminin matrix or laminin producing cells in long term liver progenitor cell cultures.« less

SCA security verification on wireless sensor network node

NASA Astrophysics Data System (ADS)

He, Wei; Pizarro, Carlos; de la Torre, Eduardo; Portilla, Jorge; Riesgo, Teresa

2011-05-01

Side Channel Attack (SCA) differs from traditional mathematic attacks. It gets around of the exhaustive mathematic calculation and precisely pin to certain points in the cryptographic algorithm to reveal confidential information from the running crypto-devices. Since the introduction of SCA by Paul Kocher et al [1], it has been considered to be one of the most critical threats to the resource restricted but security demanding applications, such as wireless sensor networks. In this paper, we focus our work on the SCA-concerned security verification on WSN (wireless sensor network). A detailed setup of the platform and an analysis of the results of DPA (power attack) and EMA (electromagnetic attack) is presented. The setup follows the way of low-cost setup to make effective SCAs. Meanwhile, surveying the weaknesses of WSNs in resisting SCA attacks, especially for the EM attack. Finally, SCA-Prevention suggestions based on Differential Security Strategy for the FPGA hardware implementation in WSN will be given, helping to get an improved compromise between security and cost.

Sheltering the self from the storm: self-construal abstractness and the stability of self-esteem.

PubMed

Updegraff, John A; Emanuel, Amber S; Suh, Eunkook M; Gallagher, Kristel M

2010-01-01

Self-construal abstractness (SCA) refers to the degree to which people construe important bases of self-esteem in a broad, flexible, and abstract rather than a concrete and specific manner. This article hypothesized that SCA would be a unique predictor of self-esteem stability, capturing the degree to which people's most important bases of self-worth are resistant to disconfirmation. Two studies using a daily diary methodology examined relationships between SCA, daily self-esteem, and daily emotions and/or events. In Study 1, individual differences in SCA emerged as the most consistent and unique predictor of self-esteem stability. Furthermore, SCA contributed to self-esteem stability by buffering the influence of daily negative emotions on self-esteem. Study 2 manipulated SCA via a daily self-construal task and found an abstract versus concrete self-focus to buffer the influence of daily negative events on self-esteem. Implications of these findings for the study of the self and well-being are discussed.

Sleep Problems and Life Satisfaction as Predictors of Health in Men with Sex Chromosome Aneuploidies.

PubMed

Fjermestad, Krister W; Stokke, Simen

2018-01-01

More knowledge is needed about men with sex chromosome aneuploidies (SCA). We present self-reported data from 53 men with SCA (M age = 36.8 years, SD = 12.3, range 19-67). The Health Survey-Short Form (SF-36) measured eight health domains (physical functioning, role-physical, role-emotional, vitality, emotional health, social functioning, pain, general health). The Pittsburgh Sleep Quality Index measured sleep problems. The Personal Wellbeing Index measured satisfaction with eight life domains. Compared to norms, SCA reported poorer health (mean d = -0.80) and more sleep problems (mean d = -0.85). Differences between SCA and norms on personal well-being were small, except lower health satisfaction in SCA (d = -1.06). Seven of eight regression models predicting the SF-36 domains from life satisfaction and sleep problems were significant (explained variance 12.2% to 46.2%), except physical functioning (ns). Clinical assessment/intervention for a broad range of health and sleep problems is indicated for men with SCA.

Spinocerebellar ataxia type 6 in eastern India: Some new observations.

PubMed

Bhattacharyya, Kalyan B; Pulai, Debabrata; Guin, Deb Shankar; Ganguly, Goutam; Joardar, Anindita; Roy, Sarnava; Rai, Saurabh; Biswas, Atanu; Pandit, Alok; Roy, Arijit; Senapati, Asit Kumar

2016-01-01

Spinocerebellar ataxias (SCAs) are hereditary, autosomal dominant progressive neurodegenerative disorders showing clinical and genetic heterogeneity. They are usually manifested clinically in the third to fifth decade of life although there is a wide variability in the age of onset. More than 36 different types of SCAs have been reported so far and about half of them are caused by pathological expansion of the trinucleotide, Cytosine Alanine Guanine (CAG) repeat. The global prevalence of SCA is 0.3-2 per 100,000 population, SCA3 being the commonest variety worldwide, accounting for 20-50 per cent of all cases, though SCA 2 is generally considered as the commonest one in India. However, SCA6 has not been addressed adequately from India though it is common in the eastern Asian countries like, Japan, Korea and Thailand. The present study was undertaken to identify the prevalence of SCA6 in the city of Kolkata and the eastern part of India. 83 consecutive patients were recruited for the study of possible SCAs and their clinical features and genotype were investigated. 6 of the 83 subjects turned out positive for SCA6, constituting therefore, 13.33% of the patient pool. SCA6 is prevalent in the eastern part of India, though not as frequent as the other common varieties. Further community based studies are required in order to understand the magnitude of SCA6 in the eastern part, as well as in other regions of India.

Pulmonary hypertension among 5 to 18 year old children with sickle cell anaemia in Nigeria.

PubMed

Sokunbi, Ogochukwu J; Ekure, Ekanem N; Temiye, Edamisan O; Anyanwu, Roosevelt; Okoromah, Christy A N

2017-01-01

Pulmonary hypertension (PHT) is a significant cause of mortality in patients with sickle cell disease (SCD). Few studies on PHT in SCD have been carried out in children. This study aimed to estimate the prevalence of PHT in children with sickle cell anaemia (SCA) and determine its clinical and laboratory correlates. In this cross sectional study, evaluation involved obtaining bio-data, history and physical examination findings in 175 SCA subjects with haemoglobin genotype SS aged 5 to 18 years and 175 age and sex matched controls with haemoglobin genotype AA. PHT was determined using peak Tricuspid Regurgitant Velocity (TRV) obtained from echocardiography as a marker. Complete blood count (CBC), lactate dehydrogenase (LDH) assay, reticulocyte count, foetal haemoglobin (HbF) estimation as well as Human Immunodeficiency Virus (HIV) I and II, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) screening were done for patients with SCA. The mean peak TRV of subjects with SCA and controls was 2.2 ± 0.4 m/s and 1.9 ± 0.3 m/s respectively and prevalence of PHT among children with SCA and controls was 22.9% and 2.3% respectively. PHT in SCA correlated negatively with body mass index, haematocrit and haemoglobin. This study affirms that PHT prevalence is high in children with SCA in Nigeria. Cardiovascular examination for signs of PHT is recommended for children with SCA and if required, further echocardiographic assessment from as early as five years.

High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia.

PubMed

Grau, Marijke; Mozar, Anaïs; Charlot, Keyne; Lamarre, Yann; Weyel, Linda; Suhr, Frank; Collins, Bianca; Jumet, Stéphane; Hardy-Dessources, Marie-Dominique; Romana, Marc; Lemonne, Nathalie; Etienne-Julan, Maryse; Antoine-Jonville, Sophie; Bloch, Wilhelm; Connes, Philippe

2015-03-01

Human red blood cells (RBC) express an active and functional endothelial-like nitric oxide (NO) synthase (RBC-NOS). We report studies on RBC-NOS activity in sickle cell anaemia (SCA), a genetic disease characterized by decreased RBC deformability and vascular dysfunction. Total RBC-NOS content was not significantly different in SCA patients compared to healthy controls; however, using phosphorylated RBC-NOS-Ser(1177) as a marker, RBC-NOS activation was higher in SCA patients as a consequence of the greater activation of Akt (phosphorylated Akt-Ser(473) ). The higher RBC-NOS activation in SCA led to higher levels of S-nitrosylated α- and β-spectrins, and greater RBC nitrite and nitrotyrosine levels compared to healthy controls. Plasma nitrite content was not different between the two groups. Laser Doppler flowmetric experiments demonstrated blunted microcirculatory NO-dependent response under hyperthermia in SCA patients. RBC deformability, measured by ektacytometry, was reduced in SCA in contrast to healthy individuals, and pre-shearing RBC in vitro did not improve deformability despite an increase of RBC-NOS activation. RBC-NOS activation is high in freshly drawn blood from SCA patients, resulting in high amounts of NO produced by RBC. However, this does not result in improved RBC deformability and vascular function: higher RBC-NO is not sufficient to counterbalance the enhanced oxidative stress in SCA. © 2014 John Wiley & Sons Ltd.

Silent cerebral infarcts in very young children with sickle cell anaemia are associated with a higher risk of stroke.

PubMed

Cancio, Maria I; Helton, Kathleen J; Schreiber, Jane E; Smeltzer, Matthew P; Kang, Guolian; Wang, Winfred C

2015-10-01

Silent cerebral infarctions (SCI) are the most common neurological injury in children with sickle cell anaemia (SCA), but their incidence/prognosis in early childhood has not been well described. We report clinical, neuroradiological, psychometric and academic follow-up over an average period of 14 years in 37 children with SCA who had magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain between ages 7 and 48 months. Ten patients (27%) younger than age 5 years (Group I) had SCI, as did 12 (32%) older than 5 years (Group II). Fifteen (41%) had no lesions (Group III). Overt stroke or transient ischaemic attack occurred in 5/9 (56%) in Group I. Most Group I patients had progressive MRI abnormalities, concurrent stenosis, decreased cognitive ability, attention/executive function deficits and hindered academic attainment. The proportions of subjects in Group I with subsequent neurological events (P ≤ 0·006), progressive ischaemia (P ≤ 0·001) and vascular stenosis (P ≤ 0·006) were greater than in Groups II and III. Thus, SCI in young children with SCA may predict overt central nervous system events, progressive MRI abnormalities, stenosis, cognitive dysfunction and poor academic performance. Children younger than 5 years may benefit from MRI/MRA testing and should be considered for aggressive intervention when SCI are detected. © 2015 John Wiley & Sons Ltd.

SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity

PubMed Central

Yilmaz, Ömer H.; Kiel, Mark J.; Morrison, Sean J.

2006-01-01

Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1lowSca-1+Lineage-c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+CD48-, just as in normal young bone marrow. Thy-1lowSca-1+Lineage-c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+CD48-Sca-1+Lineage-c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated. PMID:16219798

SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity.

PubMed

Yilmaz, Omer H; Kiel, Mark J; Morrison, Sean J

2006-02-01

Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1 low Sca-1+ Lineage- c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+ CD48-, just as in normal young bone marrow. Thy-1 low Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+ CD48- Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated.

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function.

PubMed

Ferro, Austin; Carbone, Emily; Marzouk, Evan; Siegel, Asher; Nguyen, Donna; Polley, Kailen; Hartman, Jessilyn; Frederick, Kimberley; Ives, Stephen; Lagalwar, Sarita

2017-01-22

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ataxias and other movement disorders marked by progressive degeneration of the cerebellum. The goal of this protocol is to assess mitochondrial dysfunction in Spinocerebellar ataxia type 1 (SCA1) and assess the efficacy of pharmacological targeting of metabolic respiration via the water-soluble compound succinic acid to slow disease progression. This approach is applicable to other cerebellar diseases and can be adapted to a host of water-soluble therapies. Ex vivo analysis of mitochondrial respiration is used to detect and quantify disease-related changes in mitochondrial function. With genetic evidence (unpublished data) and proteomic evidence of mitochondrial dysfunction in the SCA1 mouse model, we evaluate the efficacy of treatment with the water-soluble metabolic booster succinic acid by dissolving this compound directly into the home cage drinking water. The ability of the drug to pass the blood brain barrier can be deduced using high performance liquid chromatography (HPLC). The efficacy of these compounds can then be tested using multiple behavioral paradigms including the accelerating rotarod, balance beam test and footprint analysis. Cytoarchitectural integrity of the cerebellum can be assessed using immunofluorescence assays that detect Purkinje cell nuclei and Purkinje cell dendrites and soma. These methods are robust techniques for determining mitochondrial dysfunction and the efficacy of treatment with water-soluble compounds in cerebellar neurodegenerative disease.

Air to air view of Endeavour, OV-105, atop SCA approaches Ellington runway

NASA Image and Video Library

1991-05-06

S91-36097 (6 May 1991) --- Air to air view of Endeavour, Orbiter Vehicle (OV) 105, atop a Shuttle Carrier Aircraft (SCA) NASA 911, a modified Boeing 747, approaches touchdown for a brief stopover at Ellington Field, near JSC. Visible below the spacecraft/aircraft combination are the NASA T-38 flight line, NASA aircraft hangars and facilities, and a runway. OV-105 rolled out at Rockwell's Palmdale facility on 04-25-91 to once more bring to four the total of NASA Shuttles available for flight assignment. The spacecraft and aircraft-tandem left Houston later on this day headed for another stop in Mississippi before landing in Florida on 05-07-91. This photograph was taken from a T-38 aircraft by Sheri J. Dunnette of JSC's Image Science Division (ISD).

KSC-2012-5026

NASA Image and Video Library

2012-09-12

CAPE CANAVERAL, Fla. - Jeff Moultrie, wearing a blue shirt, pilot on the Shuttle Carrier Aircraft, or SCA, speaks with news media inside the SCA at the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. The SCA will take space shuttle Endeavour from Florida to Los Angeles for public display. Photo credit: NASA/Kim Shiflett

Approach and Landing Tests Film Documentary

NASA Image and Video Library

2018-05-09

Documentary of shuttle Enterprise on the Shuttle Carrier Aircraft (SCA), separating from the SCA in flight, and in free-flight. Footage shows SCA pilots Fitzhugh “Fitz” Fulton and Tom McMurtry heading to the aircraft, and Gordon Fullerton and Fred Haise following a flight in the prototype shuttle. During the nearly one-year-long series of tests, Enterprise was taken aloft on the SCA to study the aerodynamics of the mated vehicles and, in a series of five free flights, tested the glide and landing characteristics of the orbiter prototype.

Alignment method for solar collector arrays

DOEpatents

Driver, Jr., Richard B

2012-10-23

The present invention is directed to an improved method for establishing camera fixture location for aligning mirrors on a solar collector array (SCA) comprising multiple mirror modules. The method aligns the mirrors on a module by comparing the location of the receiver image in photographs with the predicted theoretical receiver image location. To accurately align an entire SCA, a common reference is used for all of the individual module images within the SCA. The improved method can use relative pixel location information in digital photographs along with alignment fixture inclinometer data to calculate relative locations of the fixture between modules. The absolute locations are determined by minimizing alignment asymmetry for the SCA. The method inherently aligns all of the mirrors in an SCA to the receiver, even with receiver position and module-to-module alignment errors.

Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes.

PubMed

Khalyfa, Abdelnaby; Khalyfa, Ahamed A; Akbarpour, Mahzad; Connes, Phillippe; Romana, Marc; Lapping-Carr, Gabrielle; Zhang, Chunling; Andrade, Jorge; Gozal, David

2016-09-01

Sickle cell anaemia (SCA) is the most frequent genetic haemoglobinopathy, which exhibits a highly variable clinical course characterized by hyper-coagulable and pro-inflammatory states, as well as endothelial dysfunction. Extracellular microvesicles are released into biological fluids and play a role in modifying the functional phenotype of target cells. We hypothesized that potential differences in plasma-derived extracellular microvesicles (EV) function and cargo from SCA patients may underlie divergent clinical trajectories. Plasma EV from SCA patients with mild, intermediate and severe clinical disease course were isolated, and primary endothelial cell cultures were exposed. Endothelial cell activation, monocyte adhesion, barrier disruption and exosome cargo (microRNA microarrays) were assessed. EV disrupted the endothelial barrier and induced expression of adhesion molecules and monocyte adhesion in a SCA severity-dependent manner compared to healthy children. Microarray approaches identified a restricted signature of exosomal microRNAs that readily distinguished severe from mild SCA, as well as from healthy children. The microRNA candidates were further validated using quantitative real time polymerase chain reaction assays, and revealed putative gene targets. Circulating exosomal microRNAs may play important roles in predicting the clinical course of SCA, and in delineation of individually tailored, mechanistically-based clinical treatment approaches of SCA patients in the near future. © 2016 John Wiley & Sons Ltd.

Coilin association with Box C/D scaRNA suggests a direct role for the Cajal body marker protein in scaRNP biogenesis

PubMed Central

Enwerem, Isioma I.; Velma, Venkatramreddy; Broome, Hanna J.; Kuna, Marija; Begum, Rowshan A.; Hebert, Michael D.

2014-01-01

ABSTRACT Spliceosomal small nuclear ribonucleoproteins (snRNPs) are enriched in the Cajal body (CB). Guide RNAs, known as small Cajal body-specific RNAs (scaRNAs), direct modification of the small nuclear RNA (snRNA) component of the snRNP. The protein WRAP53 binds a sequence motif (the CAB box) found in many scaRNAs and the RNA component of telomerase (hTR) and targets these RNAs to the CB. We have previously reported that coilin, the CB marker protein, associates with certain non-coding RNAs. For a more comprehensive examination of the RNAs associated with coilin, we have sequenced the RNA isolated from coilin immunocomplexes. A striking preferential association of coilin with the box C/D scaRNAs 2 and 9, which lack a CAB box, was observed. This association varied by treatment condition and WRAP53 knockdown. In contrast, reduction of WRAP53 did not alter the level of coilin association with hTR. Additional studies showed that coilin degrades/processes scaRNA 2 and 9, associates with active telomerase and can influence telomerase activity. These findings suggest that coilin plays a novel role in the biogenesis of box C/D scaRNPs and telomerase. PMID:24659245

Long-term variability in Northern Hemisphere snow cover and associations with warmer winters

USGS Publications Warehouse

McCabe, Gregory J.; Wolock, David M.

2010-01-01

A monthly snow accumulation and melt model is used with gridded monthly temperature and precipitation data for the Northern Hemisphere to generate time series of March snow-covered area (SCA) for the period 1905 through 2002. The time series of estimated SCA for March is verified by comparison with previously published time series of SCA for the Northern Hemisphere. The time series of estimated Northern Hemisphere March SCA shows a substantial decrease since about 1970, and this decrease corresponds to an increase in mean winter Northern Hemisphere temperature. The increase in winter temperature has caused a decrease in the fraction of precipitation that occurs as snow and an increase in snowmelt for some parts of the Northern Hemisphere, particularly the mid-latitudes, thus reducing snow packs and March SCA. In addition, the increase in winter temperature and the decreases in SCA appear to be associated with a contraction of the circumpolar vortex and a poleward movement of storm tracks, resulting in decreased precipitation (and snow) in the low- to mid-latitudes and an increase in precipitation (and snow) in high latitudes. If Northern Hemisphere winter temperatures continue to warm as they have since the 1970s, then March SCA will likely continue to decrease.

Long-term variability in Northern Hemisphere snow cover and associations with warmer winters

USGS Publications Warehouse

McCabe, G.J.; Wolock, D.M.

2010-01-01

A monthly snow accumulation and melt model is used with gridded monthly temperature and precipitation data for the Northern Hemisphere to generate time series of March snow-covered area (SCA) for the period 1905 through 2002. The time series of estimated SCA for March is verified by comparison with previously published time series of SCA for the Northern Hemisphere. The time series of estimated Northern Hemisphere March SCA shows a substantial decrease since about 1970, and this decrease corresponds to an increase in mean winter Northern Hemisphere temperature. The increase in winter temperature has caused a decrease in the fraction of precipitation that occurs as snow and an increase in snowmelt for some parts of the Northern Hemisphere, particularly the mid-latitudes, thus reducing snow packs and March SCA. In addition, the increase in winter temperature and the decreases in SCA appear to be associated with a contraction of the circumpolar vortex and a poleward movement of storm tracks, resulting in decreased precipitation (and snow) in the low- to mid-latitudes and an increase in precipitation (and snow) in high latitudes. If Northern Hemisphere winter temperatures continue to warm as they have since the 1970s, then March SCA will likely continue to decrease. ?? 2009 Springer Science+Business Media B.V.

Morphological and Functional Attenuation of Degeneration of Peripheral Neurons by Mesenchymal Stem Cell-Conditioned Medium in Spinocerebellar Ataxia Type 1-Knock-in Mice.

PubMed

Suto, Nana; Mieda, Tokue; Iizuka, Akira; Nakamura, Kazuhiro; Hirai, Hirokazu

2016-08-01

Spinocerebellar ataxia type 1 (SCA1) is caused by the ataxin-1 protein (ATXN1) with an abnormally expanded polyglutamine tract and is characterized by progressive neurodegeneration. We previously showed that intrathecal injection of mesenchymal stem cells (MSCs) during the nonsymptomatic stage mitigates the degeneration of the peripheral nervous system (PNS) neurons in SCA1-knock-in (SCA1-KI) mice. We tested in this study whether the therapeutic effects of MSCs in SCA1-KI mice could be reproduced with MSC-releasing factor(s). To test the effects of MSC-releasing factor(s), we used MSC-conditioned medium (MSC-CM). MSC-CM was intrathecally and/or intravenously injected into young SCA1-KI mice, and the therapeutic effects were assessed in the PNS at later ages using immunostaining, electrophysiology, and behavioral tests. MSC-CM attenuated the degeneration of axons and myelin of spinal motor neurons. Consequently, the injected SCA1-KI mice exhibited smaller reductions in nerve conduction velocity in spinal motor neurons and reduced motor incoordination than the untreated mice. These results suggest that factors released from MSC mitigate the morphological and functional abnormalities in the PNS that are observed in SCA1-KI mice in a paracrine manner. © 2016 John Wiley & Sons Ltd.

Sickle cell anemia - Nitric oxide related genetic modifiers of hematological and biochemical parameters.

PubMed

Aguiar, Laura; Matos, Andreia; Gil, Ângela; Afonso, Conceição; Almeida, Salomé; Braga, Lígia; Lavinha, João; Kjollerstrom, Paula; Faustino, Paula; Bicho, Manuel; Inácio, Ângela

2016-01-01

Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms - rs2070744, rs1799983 and intron 4 VNTR. Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744_TT and the rs1799983_GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele at intron 4 VNTR. Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.

Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

PubMed

Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

2016-03-15

Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Improving Satellite Quantitative Precipitation Estimation Using GOES-Retrieved Cloud Optical Depth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenz, Ronald; Dong, Xiquan; Xi, Baike

To address significant gaps in ground-based radar coverage and rain gauge networks in the U.S., geostationary satellite quantitative precipitation estimates (QPEs) such as the Self-Calibrating Multivariate Precipitation Retrievals (SCaMPR) can be used to fill in both the spatial and temporal gaps of ground-based measurements. Additionally, with the launch of GOES-R, the temporal resolution of satellite QPEs may be comparable to that of Weather Service Radar-1988 Doppler (WSR-88D) volume scans as GOES images will be available every five minutes. However, while satellite QPEs have strengths in spatial coverage and temporal resolution, they face limitations particularly during convective events. Deep Convective Systemsmore » (DCSs) have large cloud shields with similar brightness temperatures (BTs) over nearly the entire system, but widely varying precipitation rates beneath these clouds. Geostationary satellite QPEs relying on the indirect relationship between BTs and precipitation rates often suffer from large errors because anvil regions (little/no precipitation) cannot be distinguished from rain-cores (heavy precipitation) using only BTs. However, a combination of BTs and optical depth (τ) has been found to reduce overestimates of precipitation in anvil regions (Stenz et al. 2014). A new rain mask algorithm incorporating both τ and BTs has been developed, and its application to the existing SCaMPR algorithm was evaluated. The performance of the modified SCaMPR was evaluated using traditional skill scores and a more detailed analysis of performance in individual DCS components by utilizing the Feng et al. (2012) classification algorithm. SCaMPR estimates with the new rain mask applied benefited from significantly reduced overestimates of precipitation in anvil regions and overall improvements in skill scores.« less

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.

PubMed

Lise, Stefano; Clarkson, Yvonne; Perkins, Emma; Kwasniewska, Alexandra; Sadighi Akha, Elham; Schnekenberg, Ricardo Parolin; Suminaite, Daumante; Hope, Jilly; Baker, Ian; Gregory, Lorna; Green, Angie; Allan, Chris; Lamble, Sarah; Jayawant, Sandeep; Quaghebeur, Gerardine; Cader, M Zameel; Hughes, Sarah; Armstrong, Richard J E; Kanapin, Alexander; Rimmer, Andrew; Lunter, Gerton; Mathieson, Iain; Cazier, Jean-Baptiste; Buck, David; Taylor, Jenny C; Bentley, David; McVean, Gilean; Donnelly, Peter; Knight, Samantha J L; Jackson, Mandy; Ragoussis, Jiannis; Németh, Andrea H

2012-01-01

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome.

Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

PubMed

Bateman, J B; Kojis, T L; Cantor, R M; Heinzmann, C; Ngo, J T; Spence, M A; Inana, G; Kivlin, J D; Curtis, D; Sparkes, R S

1993-01-01

Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns.

Glial S100B protein modulates mutant ataxin-1 aggregation and toxicity: TRTK12 peptide, a potential candidate for SCA1 therapy.

PubMed

Vig, Parminder J S; Hearst, Scoty; Shao, Qingmei; Lopez, Mariper E; Murphy, Henry A; Safaya, Eshan

2011-06-01

Non-cell autonomous involvement of glial cells in the pathogenesis of polyglutamine diseases is gaining recognition in the ataxia field. We previously demonstrated that Purkinje cells (PCs) in polyglutamine disease spinocerebellar ataxia-1 (SCA1) contain cytoplasmic vacuoles rich in Bergmann glial protein S100B. The vacuolar formation in SCA1 PCs is accompanied with an abnormal morphology of dendritic spines. In addition, S100B messenger RNA (mRNA) expression levels are significantly high in the cerebella of asymptomatic SCA1 transgenic (Tg) mice and increase further with age when compared with the age-matched wild-type animals. This higher S100B mRNA expression positively correlates with an increase in the number of vacuoles. To further characterize the function of S100B in SCA1 pathology, we explored the effects of S100B protein on GFP-ataxin-1 (ATXN1) with expanded polyglutamines [82Q] in HEK stable cell line. Externally added S100B protein to these cells induced S100B-positive vacuoles similar to those seen in SCA1 PCs in vivo. Further, we found that both externally added and internally expressed S100B significantly reduced GFP-ATXN1[82Q] inclusion body formation. In contrast, the addition of S100B inhibitory peptide TRTK12 reversed S100B-mediated effects. Interestingly, in SCA1 Tg mice, PCs containing S100B vacuoles also showed the lack of nuclear inclusions, whereas PCs without vacuoles contained nuclear inclusions. Additionally, TRTK12 treatment reduced abnormal dendritic growth and morphology of PCs in cerebellar slice cultures prepared from SCA1 Tg mice. Moreover, intranasal administration of TRTK12 to SCA1 Tg mice reduced cerebellar S100B levels in the particulate fractions, and these mice displayed a significant improvement in their performance deficit on the Rotarod test. Taken together, our results suggest that glial S100B may augment degenerative changes in SCA1 PCs by modulating mutant ataxin-1 toxicity/solubility through an unknown signaling pathway.

Glial S100B protein modulates mutant ataxin-1 aggregation and toxicity: TRTK12 peptide, a potential candidate for SCA1 therapy

PubMed Central

Vig, Parminder J.S.; Hearst, Scoty; Shao, Qingmei; Lopez, Maripar E; Murphy, Henry A; Safaya, Eshan

2011-01-01

Non-cell autonomous involvement of glial cells in the pathogenesis of polyglutamine diseases is gaining recognition in the ataxia field. We previously demonstrated that Purkinje cells (PCs) in polyglutamine disease spinocerebellar ataxia-1 (SCA1) contain cytoplasmic vacuoles rich in Bergmann glial (BG) protein S100B. The vacuolar formation in SCA1 PCs is accompanied with an abnormal morphology of dendritic spines. In addition, S100B mRNA expression levels are significantly high in the cerebella of asymptomatic SCA1 transgenic (Tg) mice and increase further with age when compared with the age-matched wildtype animals. This higher S100B mRNA expression positively correlates with an increase in the number of vacuoles. To further characterize the function of S100B in SCA1 pathology, we explored the effects of S100B protein on GFP-ataxin-1 (ATXN1) with expanded polyglutamines [82Q] in HEK stable cell line. Externally added S100B protein to these cells induced S100B positive vacuoles similar to those seen in SCA1 PCs in vivo. Further, we found that both externally added and internally expressed S100B significantly reduced GFP-ATXN1[82Q] inclusion body formation. In contrast, the addition of S100B inhibitory peptide TRTK12 reversed S100B mediated effects. Interestingly, in SCA1 Tg mice, PCs containing S100B vacuoles also showed the lack of nuclear inclusions, whereas, PCs without vacuoles contained nuclear inclusions. Additionally, TRTK12 treatment reduced abnormal dendritic growth and morphology of PCs in cerebellar slice cultures prepared from SCA1 Tg mice. Moreover, intranasal administration of TRTK12 to SCA1 Tg mice reduced cerebellar S100B levels in the particulate fractions and these mice displayed a significant improvement in their performance deficit on the Rotarod test. Taken together our results suggest that glial S100B may augment degenerative changes in SCA1 PCs by modulating mutant ataxin-1 toxicity/solubility through an unknown signaling pathway. PMID:21384195

Combined Targeting of BCL-2 and BCR-ABL Tyrosine Kinase Eradicates Chronic Myeloid Leukemia Stem Cells

PubMed Central

Mak, Po Yee; Mu, Hong; Zhou, Hongsheng; Mak, Duncan H.; Schober, Wendy; Leverson, Joel D.; Zhang, Bin; Bhatia, Ravi; Huang, Xuelin; Cortes, Jorge; Kantarjian, Hagop; Konopleva, Marina

2016-01-01

BCR-ABL tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML), but they rarely eliminate CML stem cells. Disease relapse is common upon therapy cessation, even in patients with complete molecular responses. Furthermore, once CML progresses to blast crisis (BC), treatment outcomes are dismal. We hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. We demonstrate increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin−Sca-1+cKit+ cells of inducible CML in mice as determined by CyTOF mass cytometry. Further, selective inhibition of BCL-2, aided by TKI-mediated MCL-1 and BCL-XL inhibition, markedly decreased leukemic Lin−Sca-1+cKit+ cell numbers and long-term stem cell frequency, and prolonged survival in a murine CML model. Additionally, this combination effectively eradicated CD34+CD38−, CD34+CD38+, and quiescent stem/progenitor CD34+ cells from BC CML patient samples. Our results suggest that BCL-2 is a key survival factor for CML stem/progenitor cells and that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve depth of response and cure rates of chronic phase and BC CML. PMID:27605552

Increased circulating fibrocytes are associated with higher reticulocyte percent in children with sickle cell anemia.

PubMed

Karafin, Matthew S; Dogra, Shibani; Rodeghier, Mark; Burdick, Marie; Mehrad, Borna; Rose, C Edward; Strieter, Robert M; DeBaun, Michael R; Strunk, Robert C; Field, Joshua J

2016-03-01

Interstitial lung disease is common in patients with sickle cell anemia (SCA). Fibrocytes are circulating cells implicated in the pathogenesis of pulmonary fibrosis and airway remodeling in asthma. In this study, we tested the hypotheses that fibrocyte levels are: (1) increased in children with SCA compared to healthy controls, and (2) associated with pulmonary disease. Cross-sectional cohort study of children with SCA who participated in the Sleep Asthma Cohort Study. Fibrocyte levels were obtained from 45 children with SCA and 24 controls. Mean age of SCA cases was 14 years and 53% were female. In children with SCA, levels of circulating fibrocytes were greater than controls (P < 0.01). The fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on the majority of cells and CCR2 and CCR7 expressed on a smaller subset. Almost half of fibrocytes demonstrated α-smooth muscle actin activation. Increased fibrocyte levels were associated with a higher reticulocyte count (P = 0.03) and older age (P = 0.048) in children with SCA. However, children with increased levels of fibrocytes were not more likely to have asthma or lower percent predicted forced expiratory volume in 1 sec/forced vital capacity (FEV1 /FVC) or FEV1 than those with lower fibrocyte levels. Higher levels of fibrocytes in children with SCA compared to controls may be due to hemolysis. Longitudinal studies may be able to better assess the relationship between fibrocyte level and pulmonary dysfunction. © 2015 Wiley Periodicals, Inc.

Design and Testing of Space Telemetry SCA Waveform

NASA Technical Reports Server (NTRS)

Mortensen, Dale J.; Handler, Louis M.; Quinn, Todd M.

2006-01-01

A Software Communications Architecture (SCA) Waveform for space telemetry is being developed at the NASA Glenn Research Center (GRC). The space telemetry waveform is implemented in a laboratory testbed consisting of general purpose processors, field programmable gate arrays (FPGAs), analog-to-digital converters (ADCs), and digital-to-analog converters (DACs). The radio hardware is integrated with an SCA Core Framework and other software development tools. The waveform design is described from both the bottom-up signal processing and top-down software component perspectives. Simulations and model-based design techniques used for signal processing subsystems are presented. Testing with legacy hardware-based modems verifies proper design implementation and dynamic waveform operations. The waveform development is part of an effort by NASA to define an open architecture for space based reconfigurable transceivers. Use of the SCA as a reference has increased understanding of software defined radio architectures. However, since space requirements put a premium on size, mass, and power, the SCA may be impractical for today s space ready technology. Specific requirements for an SCA waveform and other lessons learned from this development are discussed.

Shaft-Condylar Angle for surgical correction in neglected and displaced lateral humeral condyle fracture in children.

PubMed

Mulpruek, Pornchai; Angsanuntsukh, Chanika; Woratanarat, Patarawan; Sa-Ngasoongsong, Paphon; Tawonsawatruk, Tulyapruek; Chanplakorn, Pongsthorn

2015-09-01

To assess the outcome after using the Shaft-Condylar angle (SCA) as intraoperative reference for sagittal plane correction in displaced lateral humeral condyle fractures in children presented 3-weeks after injury. Ten children, with delayed presentation of a displaced lateral humeral condyle fracture and undergoing surgery during 1999-2011, were reviewed. The goal was to obtain a smooth articular surface with an intraoperative SCA of nearly 40° and nearest-anatomical carrying angle. They were allocated into two groups according to the postoperative SCA [Good-reduction group (SCA=30-50°), and Bad-reduction group (SCA<30°, >50°)] and the final outcomes were then compared. All fractures united without avascular necrosis. The Good-reduction group (n=7) showed a significant improvement in final range of motion and functional outcome compared to the Bad-reduction group (n=3) (p=0.02). However, there was no significant difference in pain, carrying angle and overall outcome between both groups. SCA is a possible intraoperative reference for sagittal alignment correction in late presented displaced lateral humeral condyle fractures.

Endothelial Activation by Platelets from Sickle Cell Anemia Patients

PubMed Central

Proença-Ferreira, Renata; Brugnerotto, Ana Flávia; Garrido, Vanessa Tonin; Dominical, Venina Marcela; Vital, Daiana Morelli; Ribeiro, Marilene de Fátima Reis; dos Santos, Melissa Ercolin; Traina, Fabíola; Olalla-Saad, Sara T.; Costa, Fernando Ferreira; Conran, Nicola

2014-01-01

Sickle cell anemia (SCA) is associated with a hypercoagulable state. Increased platelet activation is reported in SCA and SCA platelets may present augmented adhesion to the vascular endothelium, potentially contributing to the vaso-occlusive process. We sought to observe the effects of platelets (PLTs) from healthy control (CON) individuals and SCA individuals on endothelial activation, in vitro. Human umbilical vein endothelial cells (HUVEC) were cultured, in the presence, or not, of washed PLTs from CON or steady-state SCA individuals. Supernatants were reserved for cytokine quantification, and endothelial adhesion molecules (EAM) were analyzed by flow cytometry; gene expressions of ICAM1 and genes of the NF-κB pathway were analyzed by qPCR. SCA PLTs were found to be more inflammatory, displaying increased adhesive properties, an increased production of IL-1β and a tendency towards elevated expressions of P-selectin and activated αIIbβ3. Following culture in the presence of SCA PLTs, HUVEC presented significant augmentations in the expressions of the EAM, ICAM-1 and E-selectin, as well as increased IL-8 production and increased ICAM1 and NFKB1 (encodes p50 subunit of NF-κB) gene expressions. Interestingly, transwell inserts abolished the effects of SCA PLTs on EAM expression. Furthermore, an inhibitor of the NF-κB pathway, BAY 11-7082, also prevented the induction of EAM expression on the HUVEC surface by SCA PLTs. In conclusion, we find further evidence to indicate that platelets circulate in an activated state in sickle cell disease and are capable of stimulating endothelial cell activation. This effect appears to be mediated by direct contact, or even adhesion, between the platelets and endothelial cells and via NFκB-dependent signaling. As such, activated platelets in SCD may contribute to endothelial activation and, therefore, to the vaso-occlusive process. Results provide further evidence to support the use of anti-platelet approaches in association with other therapies for SCD. PMID:24551209

MODIS Snowcover in North America: A Comparison of Winter 2013/14 and 2014/15 to Median Condition

NASA Astrophysics Data System (ADS)

Trubilowicz, J. W.; Floyd, B. C.; D'Amore, D. V.; Bidlack, A.

2015-12-01

The winters from 2013-2015 had exceptionally low snow-packs in much of western North America. In particular, the winter of 2014/2015 had the lowest peak snow-water-equivalent (SWE) depths ever recorded in many areas of the Pacific Northwest. These low snow-packs have contributed to drought conditions from British Columbia to California. Along with the low SWE values, the snow covered area (SCA) of the previous two winters has been a significant departure from normal conditions. SCA is related to SWE, rain-on-snow events and the seasonal water supply, provides insulation for plant root systems from late season frost, and is an important factor in forest fire hazard, delaying the start of soil and fuel drying. Remote sensing can be a useful tool to monitor SCA over large regions, with the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments providing a suitable temporal (twice daily), and spatial resolution (500m) to create detailed maps, even with high frequencies of cloud covered days. While comparison of SWE at snow monitoring sites to historical values is a standard analysis, doing the same for SCA has been difficult due to the technical and logistical problems related to processing the large amounts of spatial data required to determine a 'normal' annual SCA cycle. Through the use of new cloud-based computation methods from Google Earth Engine, we have calculated the monthly median (from 2002-2015) MODIS SCA, at a 500 m resolution, for all of the major Pacific draining watersheds of North America. Determining the 'normal' SCA cycle of the past 13 years allowed us to compare the past two winters to the median SCA levels, showing which basins have seen the most significant departures from normal SCA levels. Results indicate more significant departures from normal in basins with significant maritime-influenced snow-packs.

Silent Corticotroph Adenomas After Stereotactic Radiosurgery: A Case–Control Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhiyuan; Ellis, Scott; Lee, Cheng-Chia

Purpose: To investigate the safety and effectiveness of stereotactic radiosurgery (SRS) in patients with a silent corticotroph adenoma (SCA) compared with patients with other subtypes of non–adrenocorticotropic hormone staining nonfunctioning pituitary adenoma (NFA). Methods and Materials: The clinical features and outcomes of 104 NFA patients treated with SRS in our center between September 1994 and August 2012 were evaluated. Among them, 34 consecutive patients with a confirmatory SCA were identified. A control group of 70 patients with other subtypes of NFA were selected for review based on comparable baseline features, including sex, age at the time of SRS, tumor size, marginmore » radiation dose to the tumor, and duration of follow-up. Results: The median follow-up after SRS was 56 months (range, 6-200 months). No patients with an SCA developed Cushing disease during the follow-up. Tumor control was achieved in 21 of 34 patients (62%) in the SCA group, compared with 65 of 70 patients (93%) in the NFA group. The median progression-free survival (PFS) was 58 months in the SCA group. The actuarial PFS was 73%, 46%, and 31% in the SCA group and was 94%, 87%, and 87% in the NFA group at 3, 5, and 8 years, respectively. Silent corticotroph adenomas treated with a dose of ≥17 Gy exhibited improved PFS. New-onset loss of pituitary function developed in 10 patients (29%) in the SCA group, whereas it occurred in 18 patients (26%) in the NFA group. Eight patients (24%) in the SCA group experienced worsening of a visual field deficit or visual acuity attributed to the tumor progression, as did 6 patients (9%) in the NFA group. Conclusion: Silent corticotroph adenomas exhibited a more aggressive course with a higher progression rate than other subtypes of NFAs. Stereotactic radiosurgery is an important adjuvant treatment for control of tumor growth. Increased radiation dose may lead to improved tumor control in SCA patients.« less

Leptin Induces Sca-1+ Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models

PubMed Central

Xie, Yao; Potter, Claire M.F.; Le Bras, Alexandra; Nowak, Witold N.; Gu, Wenduo; Bhaloo, Shirin Issa; Zhang, Zhongyi; Hu, Yanhua; Zhang, Li

2017-01-01

Objective— Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1+ vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1+ progenitor cells migration and neointimal formation and to understand the underlying mechanisms. Approach and Results— Sca-1+ progenitor cells from the vessel wall of Lepr+/+ and Lepr−/− mice were cultured and purified. The migration of Lepr+/+ Sca-1+ progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal–regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1+ progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP+ cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1+ cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr−/− mice 2 weeks post-surgery. However, transplantation of Lepr+/+ Sca-1+ progenitor cells into the adventitial side of injured artery in Lepr−/− mice significantly enhanced neointimal formation. Conclusions— Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1+ progenitor cells via leptin receptor–dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal–regulated kinase)-FAK pathways, which enhanced neointimal formation. PMID:28935755

Leptin Induces Sca-1+ Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models.

PubMed

Xie, Yao; Potter, Claire M F; Le Bras, Alexandra; Nowak, Witold N; Gu, Wenduo; Bhaloo, Shirin Issa; Zhang, Zhongyi; Hu, Yanhua; Zhang, Li; Xu, Qingbo

2017-11-01

Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1 + vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1 + progenitor cells migration and neointimal formation and to understand the underlying mechanisms. Sca-1 + progenitor cells from the vessel wall of Lepr +/+ and Lepr -/- mice were cultured and purified. The migration of Lepr +/+ Sca-1 + progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal-regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1 + progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP + cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1 + cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr -/- mice 2 weeks post-surgery. However, transplantation of Lepr +/+ Sca-1 + progenitor cells into the adventitial side of injured artery in Lepr -/- mice significantly enhanced neointimal formation. Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1 + progenitor cells via leptin receptor-dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal-regulated kinase)-FAK pathways, which enhanced neointimal formation. © 2017 The Authors.

DISCO-SCA and Properly Applied GSVD as Swinging Methods to Find Common and Distinctive Processes

PubMed Central

Van Deun, Katrijn; Van Mechelen, Iven; Thorrez, Lieven; Schouteden, Martijn; De Moor, Bart; van der Werf, Mariët J.; De Lathauwer, Lieven; Smilde, Age K.; Kiers, Henk A. L.

2012-01-01

Background In systems biology it is common to obtain for the same set of biological entities information from multiple sources. Examples include expression data for the same set of orthologous genes screened in different organisms and data on the same set of culture samples obtained with different high-throughput techniques. A major challenge is to find the important biological processes underlying the data and to disentangle therein processes common to all data sources and processes distinctive for a specific source. Recently, two promising simultaneous data integration methods have been proposed to attain this goal, namely generalized singular value decomposition (GSVD) and simultaneous component analysis with rotation to common and distinctive components (DISCO-SCA). Results Both theoretical analyses and applications to biologically relevant data show that: (1) straightforward applications of GSVD yield unsatisfactory results, (2) DISCO-SCA performs well, (3) provided proper pre-processing and algorithmic adaptations, GSVD reaches a performance level similar to that of DISCO-SCA, and (4) DISCO-SCA is directly generalizable to more than two data sources. The biological relevance of DISCO-SCA is illustrated with two applications. First, in a setting of comparative genomics, it is shown that DISCO-SCA recovers a common theme of cell cycle progression and a yeast-specific response to pheromones. The biological annotation was obtained by applying Gene Set Enrichment Analysis in an appropriate way. Second, in an application of DISCO-SCA to metabolomics data for Escherichia coli obtained with two different chemical analysis platforms, it is illustrated that the metabolites involved in some of the biological processes underlying the data are detected by one of the two platforms only; therefore, platforms for microbial metabolomics should be tailored to the biological question. Conclusions Both DISCO-SCA and properly applied GSVD are promising integrative methods for finding common and distinctive processes in multisource data. Open source code for both methods is provided. PMID:22693578

Semiotic-conceptual analysis: a proposal

NASA Astrophysics Data System (ADS)

Priss, Uta

2017-07-01

This paper provides the basic definitions of Semiotic-conceptual analysis (SCA), which is a mathematical modelling of signs as elements of a triadic relation. FCA concept lattices are constructed for each of the three sign components. It is demonstrated how core linguistic and semiotic notions (such as synonymy and icon) can be represented with SCA. While the usefulness of SCA has already been demonstrated in a number of applications and several propositions are proven in this paper, there are still many open questions as to what to do next with SCA. Therefore, this paper is meant as a proposal and encouragement for further development.

Biomechanics and biorheology of red blood cells in sickle cell anemia

PubMed Central

Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

2017-01-01

Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. PMID:27876368

Enuresis Is a Common and Persistent Problem Among Children and Young Adults with Sickle Cell Anemia

PubMed Central

Field, Joshua J.; Austin, Paul F.; An, Ping; Yan, Yan; DeBaun, Michael R.

2013-01-01

OBJECTIVES Enuresis and nocturia are common among children with sickle cell anemia (SCA). The objectives of this study were to describe the prevalence of enuresis and nocturia among children and young adults with SCA and determine the relationship, if any, between these symptoms and SCA-related morbidity. METHODS A prospective infant cohort of African-American children with SCA was previously established from the Cooperative Study for Sickle Cell Disease. Included in this cohort were children with SCA enrolled before 6 months of age for whom questions about enuresis and nocturia had been completed. RESULTS A total of 213 participants were included in this analysis. Sixty-nine individuals (33%) experienced enuresis over the course of the study. No children under 6 years of age were asked about enuresis. Thereafter, enuresis was most prevalent between the ages of 6 and 8 years (42%) and continued to be common in young adults ages 18 to 20 years (9%). Seventy-nine percent of individuals reported a history of nocturia. There was no association between enuresis or nocturia and an increased rate of pain or acute chest syndrome (ACS) episodes. CONCLUSIONS Enuresis and nocturia are common in children with SCA. Among adults with SCA, enuresis and nocturia are more persistent compared with adults in the general population. Enuresis and nocturia are not associated with an increased rate of pain or ACS. PMID:18384865

Evaluation of the SCA instrument for measuring patient satisfaction with cancer care administered via paper or via the Internet.

PubMed

Kamo, N; Dandapani, S V; Miksad, R A; Houlihan, M J; Kaplan, I; Regan, M; Greenfield, T K; Sanda, M G

2011-03-01

Patients' perspectives provide valuable information on quality of care. This study evaluates the feasibility and validity of Internet administration of Service Satisfaction Scale for Cancer Care (SCA) to assess patient satisfaction with outcome, practitioner manner/skill, information, and waiting/access. Primary data collected from November 2007 to April 2008. Patients receiving cancer care within 1 year were recruited from oncology, surgery, and radiation clinics at a tertiary care hospital. An Internet-based version of the 16-item SCA was developed. Participants were randomised to Internet SCA followed by paper SCA 2 weeks later or vice versa. Seven-point Likert scale responses were converted to a 0-100 scale (minimum-maximum satisfaction). Response distribution, Cronbach's alpha, and test-retest correlations were calculated. Among 122 consenting participants, 78 responded to initial SCA. Mean satisfaction scores for paper/Internet were 91/90 (outcome), 95/94 (practitioner manner/skill), 89/90 (information), and 86/86 (waiting/access). Response rate and item missingness were similar for Internet and paper. Except for practitioner manner/skill, test-retest correlations were robust r = 0.77 (outcome), 0.74 (information), and 0.75 (waiting/access) (all P < 0.001). Internet SCA administration is a feasible and a valid measurement of cancer care satisfaction for a wide range of cancer diagnoses, treatment modalities, and clinic settings.

Effect of curd washing on the properties of reduced-calcium and standard-calcium Cheddar cheese.

PubMed

Hou, Jia; McSweeney, Paul L H; Beresford, Thomas P; Guinee, Timothy P

2014-10-01

Washed (W) and nonwashed (NW) variants of standard (SCa) and reduced-calcium (RCa) Cheddar cheeses were made in triplicate, ripened for a 270-d period, and analyzed for composition and changes during maturation. Curd washing was applied to cheeses to give a target level of lactose plus lactic acid in cheese moisture of 3.9 g/100 g in the W cheese, compared with a value of 5.3 g/100 g of lactose plus lactic acid in cheese moisture in the control NW cheeses. The 4 cheese types were denoted standard calcium nonwashed (SCaNW), standard calcium washed (SCaW), reduced-calcium nonwashed (RCaNW), and reduced-calcium washed (RCaW). The mean calcium level was 760 mg/100 g in the SCaNW and SCaW and 660 mg/100 g in the RCaNW and RCaW cheeses. Otherwise the gross composition of all cheeses was similar, each with protein, fat, and moisture levels of ~26, 32, and 36 g/100 g, respectively. Curd washing significantly reduced the mean level of lactic acid in the SCaW cheese and residual lactose in both SCaW and RCaW cheeses. The mean pH of the standard-calcium cheese over the 270-d ripening period increased significantly with curd washing and ripening time, in contrast to the reduced-calcium cheese, which was not affected by the latter parameters. Otherwise curd washing had little effect on changes in populations of starter bacteria or nonstarter lactic acid bacteria, proteolysis, rheology, or color of the cheese during ripening. Descriptive sensory analysis at 270 d indicated that the SCaW cheese had a nuttier, sweeter, less fruity, and less rancid taste than the corresponding SCaNW cheese. In contrast, curd washing was not as effective in discriminating between the RCaW and RCaNW cheeses. The RCaW cheese had a more buttery, caramel odor and flavor, and a more bitter, less sweet, and nutty taste than the SCaW cheese, whereas the RCaNW had a more pungent and less fruity flavor, a less fruity odor, a saltier, more-bitter, and less acidic taste, and a more astringent mouthfeel than SCaNW. Washing of curd during manufacture provides a means of reducing the contents of lactic acid and residual lactose, increasing pH, and altering the sensory properties of Cheddar cheese, with the level of these effects being significantly less pronounced as the calcium content was reduced. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Maternal diabetes and high glucose in vitro trigger Sca1+ cardiac progenitor cell apoptosis through FoxO3a.

PubMed

Yang, Penghua; Yang, Wendy W; Chen, Xi; Kaushal, Sunjay; Dong, Daoyin; Shen, Wei-Bin

2017-01-22

Recent controversies surrounding the authenticity of c-kit + cardiac progenitor cells significantly push back the advance in regenerative therapies for cardiovascular diseases. There is an urgent need for research in characterizing alternative types of cardiac progenitor cells. Towards this goal, in the present study, we determined the effect of maternal diabetes on Sca1 + cardiac progenitor cells. Maternal diabetes induced caspase 3-dependent apoptosis in Sca1 + cardiac progenitor cells derived from embryonic day 17.5 (E17.5). Similarly, high glucose in vitro but not the glucose osmotic control mannitol triggered Sca1 + cardiac progenitor cell apoptosis in a dose- and time-dependent manner. Both maternal diabetes and high glucose in vitro activated the pro-apoptotic transcription factor, Forkhead O 3a (FoxO3a) via dephosphorylation at threonine 32 (Thr-32) residue. foxo3a gene deletion abolished maternal diabetes-induced Sca1 + cardiac progenitor cell apoptosis. The dominant negative FoxO3a mutant without the transactivation domain from the C terminus blocked high glucose-induced Sca1 + cardiac progenitor cell apoptosis, whereas the constitutively active FoxO3a mutant with the three phosphorylation sites, Thr-32, Ser-253, and Ser-315, being replaced by alanine residues mimicked the pro-apoptotic effect of high glucose. Thus, maternal diabetes and high glucose in vitro may limit the regenerative potential of Sca1 + cardiac progenitor cells by inducing apoptosis through FoxO3a activation. These findings will serve as the guide in optimizing the autologous therapy using Sca1 + cardiac progenitor cells in cardiac defect babies born exposed to maternal diabetes. Copyright © 2016. Published by Elsevier Inc.

Treatment Patterns and Antipsychotic Medication Adherence Among Commercially Insured Patients With Schizoaffective Disorder in the United States

PubMed Central

Joshi, Kruti; Lin, Jay; Lingohr-Smith, Melissa; Fu, Dong-Jing; Muser, Erik

2016-01-01

Abstract This study assessed real-world treatment patterns and antipsychotic (AP) medication adherence among commercially insured US patients with schizoaffective disorder (SCA). Continuously insured adults aged 18 years or older with a diagnosis of SCA from January 1, 2009, to December 31, 2012, were identified from the Clinformatics Data Mart database. Patients were categorized into 2 cohorts: incident or prevalent SCA. Demographics and clinical characteristics were evaluated during the baseline period. Use of psychiatric medications and adherence to AP medications were evaluated during a 12-month follow-up period after index diagnosis of SCA. Of the overall study population (N = 2713; mean age, 40.2 y; 52.7% female), 1961 patients (72.3%) (mean age, 38.7 y; 51.3% female) had incident SCA, and 752 patients (27.7%) (mean age, 43.9 y; 56.5% female) had prevalent SCA. Antipsychotics were used by 74.8% of patients in the overall study population during the follow-up period. The most commonly prescribed oral AP was risperidone (23.9%), followed by quetiapine (21.4%) and aripiprazole (20.4%). Use of any long-acting injectable APs in the overall study population during the follow-up period was less than 3%. A total of 49.0% and 38.0% of the overall study population had medication possession ratios and proportion of days covered for APs of 80% or greater, respectively. Overall use of long-acting injectable APs for the treatment of SCA is low, and adherence to AP medications, measured by both medication possession ratio and proportion of days covered, is suboptimal among patients with SCA in the real-world setting. PMID:27525965

The Romhilt-Estes electrocardiographic score predicts sudden cardiac arrest independent of left ventricular mass and ejection fraction.

PubMed

Darouian, Navid; Aro, Aapo L; Narayanan, Kumar; Uy-Evanado, Audrey; Rusinaru, Carmen; Reinier, Kyndaron; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

2017-07-01

The Romhilt-Estes point score system (RE) is an established ECG criterion for diagnosing left ventricular hypertrophy (LVH). In this study, we assessed for the first time, whether RE and its components are predictive of sudden cardiac arrest (SCA) independent of left ventricular (LV) mass. Sudden cardiac arrest (SCA) cases occurring between 2002 and 2014 in a Northwestern US metro region (catchment area approx. 1 million) were compared to geographic controls. ECGs and echocardiograms performed prior to the SCA and those of controls were acquired from the medical records and evaluated for the ECG criteria established in the RE score and for LV mass. Two hundred forty-seven SCA cases (age 68.3 ± 14.6, male 64.4%) and 330 controls (age 67.4 ± 11.5, male 63.6) were included in the analysis. RE scores were greater in cases than controls (2.5 ± 2.1 vs. 1.9 ± 1.7, p < .001), and SCA cases were more likely to meet definite LVH criteria (18.6% vs. 7.9%, p < .001). In a multivariable model including echocardiographic LVH and LV function, definite LVH remained independently predictive of SCA (OR 2.04, 95% CI 1.16-3.59, p = .013). The model was replicated with the individual ECG criteria, and only SV 1.2  ≥ 30 mm and delayed intrinsicoid deflection remained significant predictors of SCA. Left ventricular hypertrophy (LVH) as defined by the RE point score system is associated with SCA independent of echocardiographic LVH and reduced LV ejection fraction. These findings support an independent role for purely electrical LVH, in the genesis of lethal ventricular arrhythmias. © 2017 Wiley Periodicals, Inc.

Inter-association Task Force recommendations on emergency preparedness and management of sudden cardiac arrest in high school and college athletic programs: a consensus statement.

PubMed

Drezner, Jonathan A; Courson, Ron W; Roberts, William O; Mosesso, Vincent N; Link, Mark S; Maron, Barry J

2007-01-01

To assist high school and college athletic programs prepare for and respond to a sudden cardiac arrest (SCA). This consensus statement summarizes our current understanding of SCA in young athletes, defines the necessary elements for emergency preparedness, and establishes uniform treatment protocols for the management of SCA. Sudden cardiac arrest is the leading cause of death in young athletes. The increasing presence of and timely access to automated external defibrillators (AEDs) at sporting events provides a means of early defibrillation and the potential for effective secondary prevention of sudden cardiac death. An Inter-Association Task Force was sponsored by the National Athletic Trainers' Association to develop consensus recommendations on emergency preparedness and management of SCA in athletes. Comprehensive emergency planning is needed for high school and college athletic programs to ensure an efficient and structured response to SCA. Essential elements of an emergency action plan include establishment of an effective communication system, training of anticipated responders in cardiopulmonary resuscitation and AED use, access to an AED for early defibrillation, acquisition of necessary emergency equipment, coordination and integration of on-site responder and AED programs with the local emergency medical services system, and practice and review of the response plan. Prompt recognition of SCA, early activation of the emergency medical services system, the presence of a trained rescuer to initiate cardiopulmonary resuscitation, and access to early defibrillation are critical in the management of SCA. In any collapsed and unresponsive athlete, SCA should be suspected and an AED applied as soon as possible for rhythm analysis and defibrillation if indicated.

Inter Association Task Force recommendations on emergency preparedness and management of sudden cardiac arrest in high school and college athletic programs: a consensus statement.

PubMed

Drezner, Jonathan A; Courson, Ron W; Roberts, William O; Mosesso, Vincent N; Link, Mark S; Maron, Barry J

2007-01-01

To assist high school and college athletic programs prepare for and respond to a sudden cardiac arrest (SCA). This consensus statement summarizes our current understanding of SCA in young athletes, defines the necessary elements for emergency preparedness, and establishes uniform treatment protocols for the management of SCA. Sudden cardiac arrest is the leading cause of death in young athletes. The increasing presence of and timely access to automated external defibrillators (AEDs) at sporting events provides a means of early defibrillation and the potential for effective secondary prevention of sudden cardiac death. An Inter-Association Task Force was sponsored by the National Athletic Trainers' Association to develop consensus recommendations on emergency preparedness and management of SCA in athletes. Comprehensive emergency planning is needed for high school and college athletic programs to ensure an efficient and structured response to SCA. Essential elements of an emergency action plan include establishing an effective communication system, training of anticipated responders in cardiopulmonary resuscitation and AED use, access to an AED for early defibrillation, acquisition of necessary emergency equipment, coordination, and integration of on-site responder and AED programs with the local emergency medical services system, and practice and review of the response plan. Prompt recognition of SCA, early activation of the emergency medical services system, the presence of a trained rescuer to initiate cardiopulmonary resuscitation, and access to early defibrillation are critical in the management of SCA. In any collapsed and unresponsive athlete, SCA should be suspected and an AED applied as soon as possible for rhythm analysis and defibrillation if indicated.

Inter-association task force recommendations on emergency preparedness and management of sudden cardiac arrest in high school and college athletic programs: a consensus statement.

PubMed

Drezner, Jonathan A; Courson, Ron W; Roberts, William O; Mosesso, Vincent N; Link, Mark S; Maron, Barry J

2007-04-01

To assist high school and college athletic programs prepare for and respond to a sudden cardiac arrest (SCA). This consensus statement summarizes our current understanding of SCA in young athletes, defines the necessary elements for emergency preparedness, and establishes uniform treatment protocols for the management of SCA. Sudden cardiac arrest is the leading cause of death in young athletes. The increasing presence of and timely access to automated external defibrillators (AEDs) at sporting events provides a means of early defibrillation and the potential for effective secondary prevention of sudden cardiac death. An Inter-Association Task Force was sponsored by the National Athletic Trainers' Association to develop consensus recommendations on emergency preparedness and management of SCA in athletes. Comprehensive emergency planning is needed for high school and college athletic programs to ensure an efficient and structured response to SCA. Essential elements of an emergency action plan include establishing an effective communication system, training of anticipated responders in cardiopulmonary resuscitation and AED use, access to an AED for early defibrillation, acquisition of necessary emergency equipment, coordination and integration of onsite responder and AED programs with the local emergency medical services system, and practice and review of the response plan. Prompt recognition of SCA, early activation of the emergency medical services system, the presence of a trained rescuer to initiate cardiopulmonary resuscitation, and access to early defibrillation are critical in the management of SCA. In any collapsed and unresponsive athlete, SCA should be suspected and an AED applied as soon as possible for rhythm analysis and defibrillation if indicated.

Role of inositol 1,4,5-trisphosphate receptors in pathogenesis of Huntington's disease and spinocerebellar ataxias.

PubMed

Bezprozvanny, Ilya

2011-07-01

Huntington's disease (HD) and spinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative disorders. HD is caused by polyglutamine (polyQ) expansion in the amino-terminal region of a protein huntingtin (Htt) and primarily affects medium spiny striatal neurons (MSN). Many SCAs are caused by polyQ-expansion in ataxin proteins and primarily affect cerebellar Purkinje cells. The reasons for neuronal dysfunction and death in HD and SCAs remain poorly understood and no cure is available for the patients. Our laboratory discovered that mutant huntingtin, ataxin-2 and ataxin-3 proteins specifically bind to the carboxy-terminal region of the type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1), an intracellular Ca(2+) release channel. Moreover, we found that association of mutant huntingtin or ataxins with IP(3)R1 causes sensitization of IP(3)R1 to activation by IP(3) in planar lipid bilayers and in neuronal cells. These results suggested that deranged neuronal Ca(2+) signaling might play an important role in pathogenesis of HD, SCA2 and SCA3. In support of this idea, we demonstrated a connection between abnormal Ca(2+) signaling and neuronal cell death in experiments with HD, SCA2 and SCA3 transgenic mouse models. Additional data in the literature indicate that abnormal neuronal Ca(2+) signaling may also play an important role in pathogenesis of SCAl, SCA5, SCA6, SCA14 and SCA15/16. Based on these results I propose that IP(3)R and other Ca(2+) signaling proteins should be considered as potential therapeutic targets for treatment of HD and SCAs.

Bicistronic CACNA1A Gene Expression in Neurons Derived from Spinocerebellar Ataxia Type 6 Patient-Induced Pluripotent Stem Cells

PubMed Central

Bavassano, Carlo; Eigentler, Andreas; Stanika, Ruslan; Obermair, Gerald J.; Boesch, Sylvia; Dechant, Georg

2017-01-01

Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative disorder that is caused by a CAG trinucleotide repeat expansion in the CACNA1A gene. As one of the few bicistronic genes discovered in the human genome, CACNA1A encodes not only the α1A subunit of the P/Q type voltage-gated Ca2+ channel CaV2.1 but also the α1ACT protein, a 75 kDa transcription factor sharing the sequence of the cytoplasmic C-terminal tail of the α1A subunit. Isoforms of both proteins contain the polyglutamine (polyQ) domain that is expanded in SCA6 patients. Although certain SCA6 phenotypes appear to be specific for Purkinje neurons, other pathogenic effects of the SCA6 polyQ mutation can affect a broad spectrum of central nervous system (CNS) neuronal subtypes. We investigated the expression and function of CACNA1A gene products in human neurons derived from induced pluripotent stem cells from two SCA6 patients. Expression levels of CACNA1A encoding α1A subunit were similar between SCA6 and control neurons, and no differences were found in the subcellular distribution of CaV2.1 channel protein. The α1ACT immunoreactivity was detected in the majority of cell nuclei of SCA6 and control neurons. Although no SCA6 genotype-dependent differences in CaV2.1 channel function were observed, they were found in the expression levels of the α1ACT target gene Granulin (GRN) and in glutamate-induced cell vulnerability. PMID:28946818

DnaJ-1 and karyopherin α3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6

PubMed Central

Tsou, Wei-Ling; Hosking, Ryan R.; Burr, Aaron A.; Sutton, Joanna R.; Ouyang, Michelle; Du, Xiaofei; Gomez, Christopher M.; Todi, Sokol V.

2015-01-01

Spinocerebellar ataxia type 6 (SCA6) belongs to the family of CAG/polyglutamine (polyQ)-dependent neurodegenerative disorders. SCA6 is caused by abnormal expansion in a CAG trinucleotide repeat within exon 47 of CACNA1A, a bicistronic gene that encodes α1A, a P/Q-type calcium channel subunit and a C-terminal protein, termed α1ACT. Expansion of the CAG/polyQ region of CACNA1A occurs within α1ACT and leads to ataxia. There are few animal models of SCA6. Here, we describe the generation and characterization of the first Drosophila melanogaster models of SCA6, which express the entire human α1ACT protein with a normal or expanded polyQ. The polyQ-expanded version of α1ACT recapitulates the progressively degenerative nature of SCA6 when expressed in various fly tissues and the presence of densely staining aggregates. Additional studies identify the co-chaperone DnaJ-1 as a potential therapeutic target for SCA6. Expression of DnaJ-1 potently suppresses α1ACT-dependent degeneration and lethality, concomitant with decreased aggregation and reduced nuclear localization of the pathogenic protein. Mutating the nuclear importer karyopherin α3 also leads to reduced toxicity from pathogenic α1ACT. Little is known about the steps leading to degeneration in SCA6 and the means to protect neurons in this disease are lacking. Invertebrate animal models of SCA6 can expand our understanding of molecular sequelae related to degeneration in this disorder and lead to the rapid identification of cellular components that can be targeted to treat it. PMID:25954029

Effect of smoke-free legislation on the incidence of sudden circulatory arrest in the Netherlands.

PubMed

de Korte-de Boer, Dianne; Kotz, Daniel; Viechtbauer, Wolfgang; van Haren, Emiel; Grommen, Devina; de Munter, Michelle; Coenen, Harry; Gorgels, Anton P M; van Schayck, Onno C P

2012-07-01

To investigate whether smoke-free legislation in the Netherlands led to a decreased incidence of out-of-hospital sudden circulatory arrest (SCA). Smoke-free legislation was implemented in two phases: a workplace ban in 2004 and an extension of this ban to the hospitality sector on 1 July 2008. Weekly incidence data on SCA were obtained from the ambulance registry of South Limburg, the Netherlands. Three time periods were distinguished: the pre-ban period (1 January 2002-1 January 2004), the first post-ban period (1 January 2004-1 July 2008) and the second post-ban period (1 July 2008-1 May 2010). Trends in absolute SCA incidence were analysed using Poisson regression, adjusted for population size, ambient temperature, air pollution and influenza rates. A total of 2305 SCA cases were observed (mean weekly incidence 5.3±2.3 SD). The adjusted Poisson regression model showed a small but significant increase in SCA incidence during the pre-ban period (+0.20% cases per week, p=0.044). This trend changed significantly after implementation of the first ban (with -0.24% cases per week, p=0.043), translating into a 6.8% (22 cases) reduction in the number of SCA cases after 1 year of smoke-free legislation. No further decrease was seen after the second smoking ban. After introduction of a nationwide workplace smoking ban in 2004, a significant decrease in the incidence of out-of-hospital SCA was seen in South Limburg. Poor enforcement of the 2008 hospitality sector ban may account for the fact that no further decrease in the incidence of SCA was seen at this time.

Inter-Association Task Force Recommendations on Emergency Preparedness and Management of Sudden Cardiac Arrest in High School and College Athletic Programs: A Consensus Statement

PubMed Central

Drezner, Jonathan A; Courson, Ron W; Roberts, William O; Mosesso, Vincent N; Link, Mark S; Maron, Barry J

2007-01-01

Objective: To assist high school and college athletic programs prepare for and respond to a sudden cardiac arrest (SCA). This consensus statement summarizes our current understanding of SCA in young athletes, defines the necessary elements for emergency preparedness, and establishes uniform treatment protocols for the management of SCA. Background: Sudden cardiac arrest is the leading cause of death in young athletes. The increasing presence of and timely access to automated external defibrillators (AEDs) at sporting events provides a means of early defibrillation and the potential for effective secondary prevention of sudden cardiac death. An Inter-Association Task Force was sponsored by the National Athletic Trainers' Association to develop consensus recommendations on emergency preparedness and management of SCA in athletes. Recommendations: Comprehensive emergency planning is needed for high school and college athletic programs to ensure an efficient and structured response to SCA. Essential elements of an emergency action plan include establishment of an effective communication system, training of anticipated responders in cardiopulmonary resuscitation and AED use, access to an AED for early defibrillation, acquisition of necessary emergency equipment, coordination and integration of on-site responder and AED programs with the local emergency medical services system, and practice and review of the response plan. Prompt recognition of SCA, early activation of the emergency medical services system, the presence of a trained rescuer to initiate cardiopulmonary resuscitation, and access to early defibrillation are critical in the management of SCA. In any collapsed and unresponsive athlete, SCA should be suspected and an AED applied as soon as possible for rhythm analysis and defibrillation if indicated. PMID:17597956

Focused cerebellar laser light induced hyperthermia improves symptoms and pathology of polyglutamine disease SCA1 in a mouse model.

PubMed

Hearst, Scoty M; Shao, Qingmei; Lopez, Mariper; Raucher, Drazen; Vig, Parminder J S

2014-10-01

Spinocerebellar ataxia 1 (SCA1) results from pathologic glutamine expansion in the ataxin-1 protein (ATXN1). This misfolded ATXN1 causes severe Purkinje cell (PC) loss and cerebellar ataxia in both humans and mice with the SCA1 disease. The molecular chaperone heat-shock proteins (HSPs) are known to modulate polyglutamine protein aggregation and are neuroprotective. Since HSPs are induced under stress, we explored the effects of focused laser light induced hyperthermia (HT) on HSP-mediated protection against ATXN1 toxicity. We first tested the effects of HT in a cell culture model and found that HT induced Hsp70 and increased its localization to nuclear inclusions in HeLa cells expressing GFP-ATXN1[82Q]. HT treatment decreased ATXN1 aggregation by making GFP-ATXN1[82Q] inclusions smaller and more numerous compared to non-treated cells. Further, we tested our HT approach in vivo using a transgenic (Tg) mouse model of SCA1. We found that our laser method increased cerebellar temperature from 38 to 40 °C without causing any neuronal damage or inflammatory response. Interestingly, mild cerebellar HT stimulated the production of Hsp70 to a significant level. Furthermore, multiple exposure of focused cerebellar laser light induced HT to heterozygous SCA1 transgenic (Tg) mice significantly suppressed the SCA1 phenotype as compared to sham-treated control animals. Moreover, in treated SCA1 Tg mice, the levels of PC calcium signaling/buffering protein calbindin-D28k markedly increased followed by a reduction in PC neurodegenerative morphology. Taken together, our data suggest that laser light induced HT is a novel non-invasive approach to treat SCA1 and maybe other polyglutamine disorders.

Endogenous red blood cell membrane fatty acids and sudden cardiac arrest.

PubMed

Lemaitre, Rozenn N; King, Irena B; Sotoodehnia, Nona; Knopp, Robert H; Mozaffarian, Dariush; McKnight, Barbara; Rea, Thomas D; Rice, Kenneth; Friedlander, Yechiel; Lumley, Thomas S; Raghunathan, Trivellore E; Copass, Michael K; Siscovick, David S

2010-07-01

Little is known of the associations of endogenous fatty acids with sudden cardiac arrest (SCA). We investigated the associations of SCA with red blood cell membrane fatty acids that are end products of de novo fatty acid synthesis: myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1 n7), vaccenic acid (18:1 n7), stearic acid (18:0), oleic acid (18:1 n9), and a related fatty acid, cis-7 hexadecenoic acid (16:1 n9). We used data from a population-based case-control study where cases, aged 25 to 74 years, were out-of-hospital SCA patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to cases by age, sex, and calendar year, were randomly identified from the community (n = 415). All participants were free of prior clinically diagnosed heart disease. We observed associations of higher red blood cell membrane levels of 16:0, 16:1n-7, 18:1n-7, and 16:1n-9 with higher risk of SCA. In analyses adjusted for traditional SCA risk factors and trans- and n-3 fatty acids, a 1-SD-higher level of 16:0 was associated with 38% higher risk of SCA (odds ratio, 1.38; 95% confidence interval, 1.12-1.70) and a 1-SD-higher level of 16:1n-9 with 88% higher risk (odds ratio, 1.88; 95% confidence interval, 1.27-2.78). Several fatty acids that are end products of fatty acid synthesis are associated with SCA risk. Further work is needed to investigate if conditions that favor de novo fatty acid synthesis, such as high-carbohydrate/low-fat diets, might also increase the risk of SCA.

Air to air view of Endeavour, OV-105, atop SCA flies over JSC enroute to KSC

NASA Technical Reports Server (NTRS)

1991-01-01

Air to air view shows Endeavour, Orbiter Vehicle (OV) 105, atop a Shuttle Carrier Aircraft (SCA) NASA 911, a modified Boeing 747, flying over the Clear Lake / NASA JSC area prior to a brief stopover at Ellington Field, near JSC. JSC site appears behind and below the orbiter/aircraft combination with Clear Creek and Egret Bay Blvd in the foreground and Clear Lake and Galveston Bay in the background. OV-105 rolled out at Rockwell's Palmdale facility on 04-25-91 to once more bring to four the total of NASA Shuttles available for flight assignment. It left Houston later on this day headed for another stop in Mississippi before landing in Florida on 05-07-91. This photograph was taken from a T-38 aircraft by Sheri J. Dunnette of JSC's Image Sciences Division (ISD).

Biomechanics and biorheology of red blood cells in sickle cell anemia.

PubMed

Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

2017-01-04

Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical trial of acetazolamide in SCA6, with assessment using the Ataxia Rating Scale and body stabilometry.

PubMed

Yabe, I; Sasaki, H; Yamashita, I; Takei, A; Tashiro, K

2001-07-01

To investigate the effect of acetazolamide on spinocerebellar ataxia type 6 (SCA6). Acetazolamide (250-500 mg/day) was administered orally for 88 weeks to 6 patients with SCA6, and its effect was quantitatively monitored using the Ataxia Rating Scale (ARS) and body sway analysis by stabilometry. During administration of acetazolamide, the ARS score and the amplitude of body sway were significantly reduced compared with before administration. However, the response became weaker after 1 year of treatment. Although this was an open trial, the results suggested that acetazolamide can temporarily reduce the severity of symptoms during the progression of SCA6.

Biology and clinical relevance of noncoding sno/scaRNAs.

PubMed

Cao, Thuy; Rajasingh, Sheeja; Samanta, Saheli; Dawn, Buddhadeb; Bittel, Douglas C; Rajasingh, Johnson

2018-02-01

Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that perform various biological functions, including biochemical modifications of other RNAs, precursors of miRNA, splicing, and telomerase activity. The small Cajal body-associated RNAs (scaRNAs) are a subset of the snoRNA family and collect in the Cajal body where they perform their canonical function to biochemically modify spliceosomal RNAs prior to maturation. Failure of sno/scaRNAs have been implicated in pathology such as congenital heart anomalies, neuromuscular disorders, and various malignancies. Thus, understanding of sno/scaRNAs demonstrates the clinical value. Copyright © 2018 Elsevier Inc. All rights reserved.

Loss tolerant speech decoder for telecommunications

NASA Technical Reports Server (NTRS)

Prieto, Jr., Jaime L. (Inventor)

1999-01-01

A method and device for extrapolating past signal-history data for insertion into missing data segments in order to conceal digital speech frame errors. The extrapolation method uses past-signal history that is stored in a buffer. The method is implemented with a device that utilizes a finite-impulse response (FIR) multi-layer feed-forward artificial neural network that is trained by back-propagation for one-step extrapolation of speech compression algorithm (SCA) parameters. Once a speech connection has been established, the speech compression algorithm device begins sending encoded speech frames. As the speech frames are received, they are decoded and converted back into speech signal voltages. During the normal decoding process, pre-processing of the required SCA parameters will occur and the results stored in the past-history buffer. If a speech frame is detected to be lost or in error, then extrapolation modules are executed and replacement SCA parameters are generated and sent as the parameters required by the SCA. In this way, the information transfer to the SCA is transparent, and the SCA processing continues as usual. The listener will not normally notice that a speech frame has been lost because of the smooth transition between the last-received, lost, and next-received speech frames.

The Rickettsia Surface Cell Antigen 4 Applies Mimicry to Bind to and Activate Vinculin*

PubMed Central

Park, HaJeung; Lee, Jun Hyuck; Gouin, Edith; Cossart, Pascale; Izard, Tina

2011-01-01

Pathogenic Rickettsia species cause high morbidity and mortality, especially R. prowazekii, the causative agent of typhus. Like many intracellular pathogens, Rickettsia exploit the cytoskeleton to enter and spread within the host cell. Here we report that the cell surface antigen sca4 of Rickettsia co-localizes with vinculin in cells at sites of focal adhesions in sca4-transfected cells and that sca4 binds to and activates vinculin through two vinculin binding sites (VBSs) that are conserved across all Rickettsia. Remarkably, this occurs through molecular mimicry of the vinculin-talin interaction that is also seen with the IpaA invasin of the intracellular pathogen Shigella, where binding of these VBSs to the vinculin seven-helix bundle head domain (Vh1) displaces intramolecular interactions with the vinculin tail domain that normally clamp vinculin in an inactive state. Finally, the vinculin·sca4-VBS crystal structures reveal that vinculin adopts a new conformation when bound to the C-terminal VBS of sca4. Collectively, our data define the mechanism by which sca4 activates vinculin and interacts with the actin cytoskeleton, and they suggest important roles for vinculin in Rickettsia pathogenesis. PMID:21841197

Constructing Chimeric Antigen for Precise Screening of HTLV-I Infection.

PubMed

Heydari Zarnagh, Hafez; Hassanpour, Kazem; Rasaee, Mohammad Javad

2015-08-01

Individual preparation of two human T-cell lymphotropic virus type I (HTLV-I) diagnostic GST fused peptides (MTA-1 and GD21) is time-consuming and expensive. The aim of this study was to design a novel single chimeric antigen (SCA) to obviate separate expression of proteins and reduce the cost of reagent preparation. Structural protein fragments, including immunodominant B cell linear epitopes, were selected and different SCAs were designed. Tertiary structure, epitope exposure, solubility and stability were calculated for each SCA and compared with each other. The synthetic DNA encoding the interested SCA was sub-cloned into pET32a expression vector, expressed as a soluble form in Escherichia coli BL21 (DE3) cells and purified under native condition using affinity chromatography. The SDS-PAGE results indicated that thioredoxin-fused SCA was successfully expressed as a soluble form in E. coli BL21 (DE3) cells. The results of ELISA confirmed that SCA reacted with anti-HTLV-I antibodies in a concentration-dependent manner. Our results indicated that the designed SCA may be a good candidate for the screening of HTLV-I carriers with antigen-antibody-based tests.

Forward-looking Assimilation of MODIS-derived Snow Covered Area into a Land Surface Model

NASA Technical Reports Server (NTRS)

Zaitchik, Benjamin F.; Rodell, Matthew

2008-01-01

Snow cover over land has a significant impact on the surface radiation budget, turbulent energy fluxes to the atmosphere, and local hydrological fluxes. For this reason, inaccuracies in the representation of snow covered area (SCA) within a land surface model (LSM) can lead to substantial errors in both offline and coupled simulations. Data assimilation algorithms have the potential to address this problem. However, the assimilation of SCA observations is complicated by an information deficit in the observation SCA indicates only the presence or absence of snow, and not snow volume and by the fact that assimilated SCA observations can introduce inconsistencies with atmospheric forcing data, leading to non-physical artifacts in the local water balance. In this paper we present a novel assimilation algorithm that introduces MODIS SCA observations to the Noah LSM in global, uncoupled simulations. The algorithm utilizes observations from up to 72 hours ahead of the model simulation in order to correct against emerging errors in the simulation of snow cover while preserving the local hydrologic balance. This is accomplished by using future snow observations to adjust air temperature and, when necessary, precipitation within the LSM. In global, offline integrations, this new assimilation algorithm provided improved simulation of SCA and snow water equivalent relative to open loop integrations and integrations that used an earlier SCA assimilation algorithm. These improvements, in turn, influenced the simulation of surface water and energy fluxes both during the snow season and, in some regions, on into the following spring.

Increased adhesive and inflammatory properties in blood outgrowth endothelial cells from sickle cell anemia patients.

PubMed

Sakamoto, Tatiana Mary; Lanaro, Carolina; Ozelo, Margareth Castro; Garrido, Vanessa Tonin; Olalla-Saad, Sara Teresinha; Conran, Nicola; Costa, Fernando Ferreira

2013-11-01

The endothelium plays an important role in sickle cell anemia (SCA) pathophysiology, interacting with red cells, leukocytes and platelets during the vaso-occlusive process and undergoing activation and dysfunction as a result of intravascular hemolysis and chronic inflammation. Blood outgrowth endothelial cells (BOECs) can be isolated from adult peripheral blood and have been used in diverse studies, since they have a high proliferative capacity and a stable phenotype during in vitro culture. This study aimed to establish BOEC cultures for use as an in vitro study model for endothelial function in sickle cell anemia. Once established, BOECs from steady-state SCA individuals (SCA BOECs) were characterized for their adhesive and inflammatory properties, in comparison to BOECs from healthy control individuals (CON BOECs). Cell adhesion assays demonstrated that control individual red cells adhered significantly more to SCA BOEC than to CON BOEC. Despite these increased adhesive properties, SCA BOECs did not demonstrate significant differences in their expression of major endothelial adhesion molecules, compared to CON BOECs. SCA BOECs were also found to be pro-inflammatory, producing a significantly higher quantity of the cytokine, IL-8, than CON BOECs. From the results obtained, we suggest that BOEC may be a good model for the in vitro study of SCA. Data indicate that endothelial cells of sickle cell anemia patients may have abnormal inflammatory and adhesive properties even outside of the chronic inflammatory and vaso-occlusive environment of patients. © 2013.

Evidence suggesting possible SCA1 gene involvement in schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diehl, S.R.; Wange, S.; Sun, C.

Several findings suggest a possible role for the SCA1 gene on chromosome 6p in some cases of schizophrenia. First, linkage analyses in Irish pedigrees provided LOD scores up to 3.0 for one model tested using microsatellites closely linked to SCA1. Reanalysis of these data using affected sibpair methods yielded a significant result (p = 0.01) for one marker. An attempt to replicate this linkage finding was made using 44 NIMH families (206 individuals, 80 affected) and 12 Utah families (120 individuals, 49 affected). LOD scores were negative in these new families, even allowing for heterogeneity, as were results using affectedmore » sibpair methods. However, one Utah family provided a LOD score of 1.3. We also screened the SCA1 trinucleotide repeat to search for expansions characteristic of this disorder in these families and in 38 additional unrelated schizophrenics. We found 1 schizophrenic with 41 repeats, which is substantially larger than the maximum size of 36 repeats observed in previous studies of several hundred controls. We are now assessing whether the distribution of SCA1 repeats differs significantly in schizophrenia versus controls. Recent reports suggest possible anticipation in schizophrenia (also characteristic of SCA1) and a few cases of psychiatric symptoms suggesting schizophrenia have been observed in the highly related disorder DRPLA (SCA2), which is also based on trinucleotide repeat expansion. These findings suggest that further investigations of this gene and chromosome region may be a priority.« less

Involvement of specific calmodulin isoforms in salicylic acid-independent activation of plant disease resistance responses.

PubMed

Heo, W D; Lee, S H; Kim, M C; Kim, J C; Chung, W S; Chun, H J; Lee, K J; Park, C Y; Park, H C; Choi, J Y; Cho, M J

1999-01-19

The Ca2+ signal is essential for the activation of plant defense responses, but downstream components of the signaling pathway are still poorly defined. Here we demonstrate that specific calmodulin (CaM) isoforms are activated by infection or pathogen-derived elicitors and participate in Ca2+-mediated induction of plant disease resistance responses. Soybean CaM (SCaM)-4 and SCaM-5 genes, which encode for divergent CaM isoforms, were induced within 30 min by a fungal elicitor or pathogen, whereas other SCaM genes encoding highly conserved CaM isoforms did not show such response. This pathogen-triggered induction of these genes specifically depended on the increase of intracellular Ca2+ level. Constitutive expression of SCaM-4 and SCaM-5 in transgenic tobacco plants triggered spontaneous induction of lesions and induces an array of systemic acquired resistance (SAR)-associated genes. Surprisingly, these transgenic plants have normal levels of endogenous salicylic acid (SA). Furthermore, coexpression of nahG gene did not block the induction of SAR-associated genes in these transgenic plants, indicating that SA is not involved in the SAR gene induction mediated by SCaM-4 or SCaM-5. The transgenic plants exhibit enhanced resistance to a wide spectrum of virulent and avirulent pathogens, including bacteria, fungi, and virus. These results suggest that specific CaM isoforms are components of a SA-independent signal transduction chain leading to disease resistance.

Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

PubMed Central

Bateman, J B; Kojis, T L; Cantor, R M; Heinzmann, C; Ngo, J T; Spence, M A; Inana, G; Kivlin, J D; Curtis, D; Sparkes, R S

1993-01-01

Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns. PMID:7908152

Association of BCL11A genetic variant (rs11886868) with severity in β-thalassaemia major & sickle cell anaemia.

PubMed

Dadheech, Sneha; Madhulatha, D; Jainc, Suman; Joseph, James; Jyothy, A; Munshi, Anjana

2016-04-01

The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including β-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse β-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of β-thalassaemia major and SCA. a total of 620 samples (420 β-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with β-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. β-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of β-thalassaemia major as well as SCA was evaluated. There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in β-thalassaemia major as well as SCA. This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of β-thalassaemia as well as SCA.

Practical management of sudden cardiac arrest on the football field.

PubMed

Kramer, Efraim Benjamin; Botha, Martin; Drezner, Jonathan; Abdelrahman, Yasser; Dvorak, Jiri

2012-12-01

Sudden cardiac arrest (SCA) remains a tragic occurrence on the football field. The limits of preparticipation cardiovascular screening make it compulsory that prearranged emergency medical services be available at all football matches to immediately respond to any collapsed player. Management of SCA involves prompt recognition, immediate cardiopulmonary resuscitation (CPR) and early defibrillation. Any football player who collapses without contact with another player or obstacle should be regarded as being in SCA until proven otherwise. An automated external defibrillator (AED), or manual defibrillator if an AED is not available, should be immediately accessible on the field during competitions. This study presents guidelines for a practical and systematic approach to the management of SCA on the football field.

Linkage disequilibrium at the SCA2 locus

PubMed Central

Didierjean, O.; Cancel, G.; Stevanin, G.; Durr, A.; Burk, K.; Benomar, A.; Lezin, A.; Belal, S.; Abada-Bendid, M.; Klockgether, T.; Brice, A.

1999-01-01

Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.


Keywords: linkage disequilibrium; SCA2; trinucleotide repeat expansion; founder effect PMID:10353790

PRIMARY STROKE PREVENTION IN CHILDREN WITH SICKLE CELL ANEMIA LIVING IN AFRICA: THE FALSE CHOICE BETWEEN PATIENT-ORIENTED RESEARCH AND HUMANITARIAN SERVICE

PubMed Central

DEBAUN, MICHAEL R.; GALADANCI, NAJIBAH A.; KASSIM, ADETOLA A.; JORDAN, LORI C.; PHILLIPS, SHARON; ALIYU, MUKTAR H.

2016-01-01

In the United States, primary stroke prevention in children with sickle cell anemia (SCA) is now the standard of care and includes annual transcranial Doppler ultrasound evaluation to detect elevated intracranial velocities; and for those at risk, monthly blood transfusion therapy for at least a year followed by the option of hydroxyurea therapy. This strategy has decreased stroke prevalence in children with SCA from approximately 11% to 1%. In Africa, where 80% of all children with SCA are born, no systematic approach exists for primary stroke prevention. The two main challenges for primary stroke prevention in children with SCA in Africa include: 1) identifying an alternative to blood transfusion therapy, because safe monthly blood transfusion therapy is not feasible; and 2) assembling a health care team to implement and expand this effort. We will emphasize early triumphs and challenges to decreasing the incidence of strokes in African children with SCA. PMID:28066035

4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6

PubMed Central

Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E.; Watt, Alanna J.

2016-01-01

Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA684Q/+) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA684Q/84Q) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA684Q/84Q mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6. PMID:27381005

4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6.

PubMed

Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E; Watt, Alanna J

2016-07-06

Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA6(84Q/+)) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA6(84Q/84Q)) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA6(84Q/84Q) mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6.

SCA Waveform Development for Space Telemetry

NASA Technical Reports Server (NTRS)

Mortensen, Dale J.; Kifle, Multi; Hall, C. Steve; Quinn, Todd M.

2004-01-01

The NASA Glenn Research Center is investigating and developing suitable reconfigurable radio architectures for future NASA missions. This effort is examining software-based open-architectures for space based transceivers, as well as common hardware platform architectures. The Joint Tactical Radio System's (JTRS) Software Communications Architecture (SCA) is a candidate for the software approach, but may need modifications or adaptations for use in space. An in-house SCA compliant waveform development focuses on increasing understanding of software defined radio architectures and more specifically the JTRS SCA. Space requirements put a premium on size, mass, and power. This waveform development effort is key to evaluating tradeoffs with the SCA for space applications. Existing NASA telemetry links, as well as Space Exploration Initiative scenarios, are the basis for defining the waveform requirements. Modeling and simulations are being developed to determine signal processing requirements associated with a waveform and a mission-specific computational burden. Implementation of the waveform on a laboratory software defined radio platform is proceeding in an iterative fashion. Parallel top-down and bottom-up design approaches are employed.

Tissue transglutaminase crosslinks ataxin-1: Possible role in SCA1 pathogenesis

PubMed Central

D’Souza, D.R.; Wei, J.; Shao, Q.; Hebert, M.D.; Subramony, S.H.; Vig, P.J.S.

2007-01-01

Transglutaminase type 2 (TG2) has recently been implicated in crosslinking of mutant huntingtin protein into aggregates. Here we show that TG2 also crosslinks spinocerebellar ataxia-1 (SCA1) gene product ataxin-1. HeLa cell lysates expressing GFP tagged ataxin-1 with 2, 30 or 82 glutamines showed covalent crosslinking of ataxin-1 when incubated with exogenously added TG2. This crosslinking was inhibited by TG2 inhibitor cystamine. SCA1 transgenic mice which overexpress the mutant ataxin-1 in cerebellar Purkinje cells showed elevated nuclear TG2 in the absence of ataxin-1 nuclear aggregates. The addition of purified TG2 to the nuclear extracts or addition of SCA1 nuclear TG2 to GFP-Q82 HeLa cell lysates resulted in the formation of insoluble aggregates. These data indicate that ataxin-1 is a substrate of TG2. Further, in SCA1 TG2 may translocate to the nucleus in response to nuclear accumulation of mutant ataxin-1 at early stages of the disease. PMID:17045396

Sca-1(+) mesenchymal stromal cells inhibit splenic marginal zone B lymphocytes commitment through Caspase-3.

PubMed

Chen, Yaozhen; Yang, Jialei; Zhang, Hui-Jie; Fan, Hong; An, Ning; Xin, Jiajia; Li, Na; Xu, Jinmei; Yin, Wen; Wu, Zhongliang; Hu, Xingbin

2016-05-01

Mesenchymal stromal cells (MSCs) have been characterized as an important component of hematopoietic niche, which are capable of modulating the immune system through interaction with a wide range of immune cells. Marginal zone B cells, one main type of mature B lymphocytes, play a central role in eliciting antibody response against pathogens. However, how MSCs and its subpopulations regulate marginal zone B cells commitment is unknown yet. In this study, we assessed the contribution of Sca-1(+) MSCs on marginal zone B cells commitment. Our results showed that Sca-1(+) MSCs inhibit the commitment of marginal zone B lymphocytes. The inhibition was exerted through lowered Caspase-3 expression. Furthermore, we found marginal zone B lymphocytes in spleen of Caspase-3 knockout mice decreased and Caspase-3 knockout Sca-1(+) MSCs accounted for the MZB lymphocytes decrease. In conclusion, our investigation provided clues about Sca-1(+) MSCs regulation on the commitment of marginal zone B cells through Caspase-3 gene. © 2016 International Federation for Cell Biology.

Formulation Development of Spherical Crystal Agglomerates of Itraconazole for Preparation of Directly Compressible Tablets with Enhanced Bioavailability.

PubMed

Fadke, Janki; Desai, Jagruti; Thakkar, Hetal

2015-12-01

The objective of the present work was to formulate tablet dosage form of itraconazole with enhanced bioavailability. Spherical crystal agglomerates (SCA) of itraconazole prepared by quasi emulsification solvent diffusion method using Soluplus and polyethylene glycol 4000 (PEG 4000) showed increased solubility (540 μg/ml) in 0.1 N hydrochloric acid as compared to pure drug (12 μg/ml). A Fourier transform infrared (FTIR) study indicated compatibility of drug with the excipients. The developed SCA were spherical with smooth surface having an average size of 412 μm. The significantly improved micromeritic properties compared to the plain drug suggested its suitability for direct compression. The antifungal activity of itraconazole was retained in the SCA form as evidenced from the results of the disc diffusion method. The optimized SCA formulation could be easily compressed into tablet with desirable characteristics of hardness (5 kg/cm(2)) and disintegration time (6.3 min). The in vitro dissolution studies showed significant difference in the dissolution profiles of pure drug (21%) and SCA formulation (85%) which was even greater than that of marketed preparation (75%). In vivo pharmacokinetic showed significant enhancement in C max and AUC0-t with relative bioavailability of 225%. The SCA formulation seems to be promising for enhancement of oral bioavailability of itraconazole.

Prolonged cortical silent period but normal sensorimotor plasticity in spinocerebellar ataxia 6.

PubMed

Teo, James T H; Schneider, Susanne A; Cheeran, Binith J; Fernandez-del-Olmo, Miguel; Giunti, Paola; Rothwell, John C; Bhatia, Kailash P

2008-02-15

Spinocerebellar ataxia 6 (SCA6) is a hereditary disease characterized by a trinucleotide repeat expansion in the CACNA1A gene and late-onset bilateral cerebellar atrophy. It is unclear if there is significant pathology outside of the cerebellum. We used transcranial magnetic stimulation to assess sensorimotor cortical circuits and cortical plasticity in 8 SCA6 patients and 8 age-matched controls. Behavioral performance was assessed using a rhythmic tapping task. Neurophysiological measures of SCA6 patients showed a prolonged cortical silent period (CSP) but normal MEP recruitment curve, short-latency afferent inhibition, long-latency afferent inhibition and ipsilateral silent period. Paired-associative stimulation induction also increased motor-evoked potentials normally. SCA6 patients had greater variability with cued rhythmic tapping than normals and deteriorated when the cue was removed; in comparison, normal subjects had similar variability between cued and uncued rhythmic tapping. Analysis using a Wing-Kristofferson timing model indicated that both clock variance and motor delay variance were abnormal. Conclusion. In SCA6, the circuits for sensorimotor integration and the mechanisms for LTP-like plasticity in the sensorimotor cortex are unimpaired. A prolonged CSP in SCA6 just like in other cerebellar atrophies would suggest that this neurophysiological change typifies cerebellar dysfunction. 2007 Movement Disorder Society

Hydroxyurea for sickle cell anemia: What have we learned and what questions still remain?

PubMed Central

McGann, Patrick T.; Ware, Russell E.

2011-01-01

Purpose of review Sickle cell anemia (SCA) is a well-characterized severe hematological disorder with substantial morbidity and early mortality. Hydroxyurea is a potent inducer of fetal hemoglobin, and evidence over the past 25 years has documented its laboratory and clinical efficacy for both adults and children with SCA. Recent findings The Phase III study of hydroxyurea in infants (BABY HUG) has just been completed and preliminary results indicate equivocal benefits for organ protection during the two-year treatment period, but significant benefits for pain, acute chest syndrome, hospitalizations, and transfusions. Three new reports document the benefits of hydroxyurea on reducing mortality in SCA: two adult trials (LaSHS and MSH) and one pediatric study (Brazilian cohort). Recent results from the HUSTLE protocol suggest minimal genotoxicity or carcinogenicity with long-term hydroxyurea exposure. Summary The potential utility of hydroxyurea for all patients with SCA is clear and indisputable. With decades of accumulated evidence and documented efficacy with an acceptable long-term safety profile, it is time to consider hydroxyurea treatment the standard of care for all young patients with SCA. Exporting our knowledge and experience with hydroxyurea to developing nations with large medical burdens from SCA can help relieve global suffering from this condition. PMID:21372708

Microstructural, textural, and sensory characteristics of probiotic yogurts fortified with sodium calcium caseinate or whey protein concentrate.

PubMed

Akalın, A S; Unal, G; Dinkci, N; Hayaloglu, A A

2012-07-01

The influence of milk protein-based ingredients on the textural characteristics, sensory properties, and microstructure of probiotic yogurt during a refrigerated storage period of 28 d was studied. Milk was fortified with 2% (wt/vol) skim milk powder as control, 2% (wt/vol) sodium calcium caseinate (SCaCN), 2% (wt/vol) whey protein concentrate (WPC) or a blend of 1% (wt/vol) SCaCN and 1% (wt/vol) WPC. A commercial yogurt starter culture and Bifidobacterium lactis Bb12 as probiotic bacteria were used for the production. The fortification with SCaCN improved the firmness and adhesiveness. Higher values of viscosity were also obtained in probiotic yogurts with SCaCN during storage. However, WPC enhanced water-holding capacity more than the caseinate. Addition of SCaCN resulted in a coarse, smooth, and more compact protein network; however, WPC gave finer and bunched structures in the scanning electron microscopy micrographs. The use of SCaCN decreased texture scores in probiotic yogurt; probably due to the lower water-holding capacity and higher syneresis values in the caseinate-added yogurt sample. Therefore, the textural characteristics of probiotic yogurts improved depending on the ingredient variety. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Revascularization of the upper posterior circulation with the anterior temporal artery: an anatomical feasibility study.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T; Griswold, Dylan; Mokhtari, Pooneh; Payman, Andre; Tabani, Halima; Yousef, Sonia; Benet, Arnau

2017-09-22

OBJECTIVE In various disease processes, including unclippable aneurysms, a bypass to the upper posterior circulation (UPC) including the superior cerebellar artery (SCA) and posterior cerebral artery (PCA) may be needed. Various revascularization options exist, but the role of intracranial (IC) donors has not been scrutinized. The objective of this study was to evaluate the anatomical feasibility of utilizing the anterior temporal artery (ATA) for revascularization of the UPC. METHODS ATA-SCA and ATA-PCA bypasses were performed on 14 cadaver specimens. After performing an orbitozygomatic craniotomy and opening the basal cisterns, the ATA was divided at the M 3 -M 4 junction and mobilized to the crural cistern to complete an end-to-side bypass to the SCA and PCA. The length of the recipient artery between the anastomosis and origin was measured. RESULTS Seventeen ATAs were found. Successful anastomosis was performed in 14 (82%) of the ATAs. The anastomosis point on the PCA was 14.2 mm from its origin on the basilar artery. The SCA anastomosis point was 10.1 mm from its origin. Three ATAs did not reach the UPC region due to a common opercular origin with the middle temporal artery. The ATA-SCA bypass was also applied to the management of an incompletely coiled SCA aneurysm. CONCLUSIONS The ATA is a promising IC donor for UPC revascularization. The ATA is exposed en route to the proximal SCA and PCA through the pterional-orbitozygomatic approach. Also, the end-to-side anastomosis provides an efficient and straightforward bypass without the need to harvest a graft or perform multiple or difficult anastomoses.

Sudden Unexplained Cardiac Arrest in Apparently Healthy Children: A Single Center Experience

PubMed Central

Alapati, Srilatha; Strobel, Nathaniel; Hashmi, Sharukh; Bricker, John T.; Gupta-Malhotra, Monesha

2012-01-01

Objective To determine the causes of sudden cardiac arrest (SCA) in apparently healthy children in a single center in the era of primary prevention (screening questionnaire, SQ) and secondary prevention (automated external defibrillator, AED and automated implantable cardioverter defibrillator, AICD). Study Design Any child (0–18 year’s age) without prior known disease except for attention deficit disorder who underwent out-of-the hospital cardiopulmonary resuscitation was included in the study as SCA. Using retrospective chart review we evaluated the efficacy of the SQ, electrocardiogram (EKG), chest roentgenogram (CXR) and an echocardiogram. Results We found 44 out of 6,656 children admitted to intensive care with SCA; an AED was used in 39%, AICD placed in 18% and survival to hospital discharge was 50%. The etiology for SCA was identified in 57% of the cases, mostly in those above one year of age and among these the majority of had a cardiac etiology (50%) while 7% had rupture of an arteriovenous malformation. Stimulant medication use was seen in 11% of the SCA. In the best case scenario of hypothesized primary prevention, a prior SQ, CXR, EKG and echocardiogram may have detected 18%, 9%, 23% and 16% of at-risk cases respectively and 32% may have been detected with EKG and SQ together. Based on a historical control cohort, a positive EKG was significantly higher in children with SCA (p = 0.014). Conclusion An EKG along with a screening SQ may be more effective in identifying children who are potentially at-risk for SCA than a SQ alone. PMID:23052663

Outcomes from sudden cardiac arrest in US high schools: a 2-year prospective study from the National Registry for AED Use in Sports.

PubMed

Drezner, Jonathan A; Toresdahl, Brett G; Rao, Ashwin L; Huszti, Ella; Harmon, Kimberly G

2013-12-01

Sudden cardiac arrest (SCA) is the leading cause of death in athletes during exercise. The effectiveness of school-based automated external defibrillator (AED) programmes has not been established through a prospective study. A total of 2149 high schools participated in a prospective observational study beginning 1 August 2009, through 31 July 2011. Schools were contacted quarterly and reported all cases of SCA. Of these 95% of schools confirmed their participation for the entire 2-year study period. Cases of SCA were reviewed to confirm the details of the resuscitation. The primary outcome was survival to hospital discharge. School-based AED programmes were present in 87% of participating schools and in all but one of the schools reporting a case of SCA. Fifty nine cases of SCA were confirmed during the study period including 26 (44%) cases in students and 33 (56%) in adults; 39 (66%) cases occurred at an athletic facility during training or competition; 55 (93%) cases were witnessed and 54 (92%) received prompt cardiopulmonary resuscitation. A defibrillator was applied in 50 (85%) cases and a shock delivered onsite in 39 (66%). Overall, 42 of 59 (71%) SCA victims survived to hospital discharge, including 22 of 26 (85%) students and 20 of 33 (61%) adults. Of 18 student-athletes 16 (89%) and 8 of 9 (89%) adults who arrested during physical activity survived to hospital discharge. High school AED programmes demonstrate a high survival rate for students and adults who suffer SCA on school campus. School-based AED programmes are strongly encouraged.

IGF-1 in autosomal dominant cerebellar ataxia - open-label trial.

PubMed

Sanz-Gallego, Irene; Rodriguez-de-Rivera, Francisco J; Pulido, Irene; Torres-Aleman, Ignacio; Arpa, Javier

2014-01-01

The objective of this clinical open-label trial was to test the safety, tolerability and efficacy of IGF-1 therapy for autosomal dominant cerebellar ataxia (ADCA) patients. A total of 19 molecularly confirmed patients with SCA3, 1 patient with SCA6 and 6 patients with SCA7 completed our study. They were 8 females and 18 males, 28 to 74 years of age (average ± SD: 49.3 ± 14.1). Patients were treated with IGF-1 therapy with a dosage of 50 μg/kg twice a day for 12 months. The efficacy of this therapy was assessed by change from baseline on the scale for the assessment and rating of ataxia (SARA). Ten patients, consecutively selected, continued their assigned dosages in a second year open-label extension trial. A statistically significant improvement in SARA scores was observed for patients with SCA3, patients with SCA7 and all patients grouped together after the first year of IGF-1 therapy, while a stabilization of the disease was confirmed during the second year (extension study). The single patient with SCA6 showed 3 improvement points in SARA score after 3 four-month periods of IGF-1 therapy when compared with baseline measurements. Our data indicate that IGF-1 is safe and well tolerated in general. Our data, in comparison with results from previous cohorts, indicate a trend for IGF-1 treatment to stabilize the disease progression for patients with SCA, indicating that IGF-1 therapy is able to decrease the progressivity of ADCA.

Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type 10 (SCA10) expansions.

PubMed

Landrian, Ivette; McFarland, Karen N; Liu, Jilin; Mulligan, Connie J; Rasmussen, Astrid; Ashizawa, Tetsuo

2017-01-01

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta- and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 expansion alleles and to determine whether the instability originates outside of the interrupted region, we sequenced approximately 1 kb of the 5'-end of SCA10 expansions using the ATCCT-PCR product in individuals across multiple generations from four SCA10 families. We found that the greatest instability within this region occurred in paternal transmissions of the allele in stretches of pure ATTCT motifs while the intervening interrupted sequences were stable. Overall, the ATCCT interruption changes by only one to three repeat units and therefore cannot account for the instability across the length of the disease allele. We conclude that the AT-rich interruptions locally stabilize the SCA10 expansion at the 5'-end but do not completely abolish instability across the entire span of the expansion. In addition, analysis of the interruption alleles across these families support a parsimonious single origin of the mutation with a shared distant ancestor.

Subcallosal artery stroke: infarction of the fornix and the genu of the corpus callosum. The importance of the anterior communicating artery complex. Case series and review of the literature.

PubMed

Meila, Dan; Saliou, Guillaume; Krings, Timo

2015-01-01

Despite the variable anatomy of the anterior communicating artery (AcoA) complex, three main perforating branches can be typically identified the largest of which being the subcallosal artery (ScA). We present a case series of infarction in the vascular territory of the ScA to highlight the anatomy, the clinical symptomatology, and the presumed pathophysiology as it pertains to endovascular and surgical management of vascular pathology in this region. In this retrospective multicenter case series study of patients who were diagnosed with symptomatic ScA stroke, we analyzed all available clinical records, MRI, and angiographic details. Additionally, a review of the literature is provided. We identified five different cases of ScA stroke, leading to a subsequent infarction of the fornix and the genu of the corpus callosum. The presumed pathophysiology in non-iatrogenic cases is microangiopathy, rather than embolic events; iatrogenic SCA occlusion can present after both surgical and endovascular treatment of AcoA aneurysms that may occur with or without occlusion of the AcoA. Stroke in the vascular territory of the ScA leads to a characteristic imaging and clinical pattern. Ischemia involves the anterior columns of the fornix and the genu of the corpus callosum, and patients present with a Korsakoff's syndrome including disturbances of short-term memory and cognitive changes. We conclude that despite its small size, the ScA is an important artery to watch out for during surgical or endovascular treatment of AcoA aneurysms.

Haplotype Study in SCA10 Families Provides Further Evidence for a Common Ancestral Origin of the Mutation.

PubMed

Bampi, Giovana B; Bisso-Machado, Rafael; Hünemeier, Tábita; Gheno, Tailise C; Furtado, Gabriel V; Veliz-Otani, Diego; Cornejo-Olivas, Mario; Mazzeti, Pillar; Bortolini, Maria Cátira; Jardim, Laura B; Saraiva-Pereira, Maria Luiza

2017-12-01

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients from two Latin American countries were analysed, being 16 families from Brazil (29 patients) and 21 families from Peru (27 patients) as well as 49 healthy individuals from Indigenous Quechua population and 51 healthy Brazilian individuals. Four polymorphic markers spanning a region of 5.2 cM harbouring the ATTCT expansion were used to define the haplotypes, which were genotyped by different approaches. Our data have shown that 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both groups are not statistically different from Quechua controls (57%), but they are statistically different from Brazilian controls (12%) (p < 0.001). The most frequent expanded haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients with SCA10. These findings bring valuable evidence that ATTCT expansion may have arisen in a Native American chromosome.

Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ.

PubMed

Stucki, David M; Ruegsegger, Céline; Steiner, Silvio; Radecke, Julika; Murphy, Michael P; Zuber, Benoît; Saxena, Smita

2016-08-01

Spinocerebellar ataxia type 1 (SCA1), due to an unstable polyglutamine expansion within the ubiquitously expressed Ataxin-1 protein, leads to the premature degeneration of Purkinje cells (PCs), decreasing motor coordination and causing death within 10-15 years of diagnosis. Currently, there are no therapies available to slow down disease progression. As secondary cellular impairments contributing to SCA1 progression are poorly understood, here, we focused on identifying those processes by performing a PC specific proteome profiling of Sca1(154Q/2Q) mice at a symptomatic stage. Mass spectrometry analysis revealed prominent alterations in mitochondrial proteins. Immunohistochemical and serial block-face scanning electron microscopy analyses confirmed that PCs underwent age-dependent alterations in mitochondrial morphology. Moreover, colorimetric assays demonstrated impairment of the electron transport chain complexes (ETC) and decrease in ATPase activity. Subsequently, we examined whether the mitochondria-targeted antioxidant MitoQ could restore mitochondrial dysfunction and prevent SCA1-associated pathology in Sca1(154Q/2Q) mice. MitoQ treatment both presymptomatically and when symptoms were evident ameliorated mitochondrial morphology and restored the activities of the ETC complexes. Notably, MitoQ slowed down the appearance of SCA1-linked neuropathology such as lack of motor coordination as well as prevented oxidative stress-induced DNA damage and PC loss. Our work identifies a central role for mitochondria in PC degeneration in SCA1 and provides evidence for the supportive use of mitochondria-targeted therapeutics in slowing down disease progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Spinocerebellar ataxia type 1 and Machado-Joseph disease: Incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ranum, L.P.W.; Gomez, C.; Orr, H.T.

1995-09-01

The ataxias are a complex group of diseases with both environmental and genetic causes. Among the autosomal dominant forms of ataxia the genes for two, spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph disease (MJD), have been isolated. In both of these disorders the molecular basis of disease is the expansion of an unstable CAG trinucleotide repeat. To assess the frequency of the SCA1 and MJD trinucleotide repeat expansions among individuals diagnosed with ataxia, we have collected DNA from individuals representing 311 families with adult-onset ataxia of unknown etiology and screened these samples for trinucleotide repeat expansions within the SCA1 andmore » MJD genes. Within this group there are 149 families with dominantly inherited ataxia. Of these, 3% have SCA1 trinucleotide repeat expansions, whereas 21% were positive for the MJD trinucleotide expansion. Thus, together SCA1 and MJD represent 24% of the autosomal dominant ataxias in our group, and the frequency of MJD is substantially greater than that of SCA1. For the 57 patients with MJD trinucleotide repeat expansions, a strong inverse correlation between CAG repeat size and age at onset was observed (r = -.838). Among the MJD patients, the normal and affected ranges of CAG repeat size are 14-40 and 68-82 repeats, respectively. For SCA1 the normal and affected ranges are much closer, containing 19-38 and 40-81 CAG repeats, respectively. 30 refs., 1 fig., 3 tabs.« less

Genetic characterization of Spinocerebellar ataxia 1 in a South Indian cohort.

PubMed

Kumaran, Dhanya; Balagopal, Krishnan; Tharmaraj, Reginald George Alex; Aaron, Sanjith; George, Kuryan; Muliyil, Jayaprakash; Sivadasan, Ajith; Danda, Sumita; Alexander, Mathew; Hasan, Gaiti

2014-10-25

Spinocerebellar ataxia type 1 (SCA1) is a late onset autosomal dominant cerebellar ataxia, caused by CAG triplet repeat expansion in the ATXN1 gene. The frequency of SCA1 occurrence is more in Southern India than in other regions as observed from hospital-based studies. However there are no reports on variability of CAG repeat expansion, phenotype-genotype association and founder mutations in a homogenous population from India. Genomic DNA isolated from buccal mouthwash of the individuals in the cohort was used for PCR-based diagnosis of SCA1. Subsequently SNP's found within the ATXN1 loci were identified by Taqman allelic discrimination assays. Significance testing of the genotype-phenotype associations was calculated by Kruskal-Wallis ANOVA test with post-hoc Dunnett's test and Pearson's correlation coefficient. By genetic analysis of an affected population in Southern India we identified 21 pre-symptomatic individuals including four that were well past the average age of disease onset of 44 years, 16 symptomatic and 63 normal individuals. All pre-symptomatic cases harbor "pure" expansions of greater than 40 CAGs. Genotyping to test for the presence of two previously identified SNPs showed a founder effect of the same repeat carrying allele as in the general Indian population. We show that SCA1 disease onset is significantly delayed when transmission of the disease is maternal. Our finding of early disease onset in individuals with a paternally inherited allele could serve as valuable information for clinicians towards early detection of SCA1 in patients with affected fathers. Identification of older pre-symptomatic individuals (n = 4) in our cohort among individuals with a shared genetic and environmental background, suggests that second site genetic or epigenetic modifiers might significantly affect SCA1 disease progression. Moreover, such undetected SCA1 cases could underscore the true prevalence of SCA1 in India.

Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements.

PubMed

Tanguy Melac, Audrey; Mariotti, Caterina; Filipovic Pierucci, Antoine; Giunti, Paola; Arpa, Javier; Boesch, Sylvia; Klopstock, Thomas; Müller Vom Hagen, Jennifer; Klockgether, Thomas; Bürk, Katrin; Schulz, Jörg B; Reetz, Kathrin; Pandolfo, Massimo; Durr, Alexandra; Tezenas du Montcel, Sophie

2018-06-01

Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated. ClinicalTrials.gov: NCT02069509. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Synthesis and luminescence properties of polymer-rare earth complexes containing salicylaldehyde-type bidentate Schiff base ligand.

PubMed

Zhang, Dandan; Gao, Baojiao; Li, Yanbin

2017-08-01

Using molecular design and polymer reactions, two types of bidentate Schiff base ligands, salicylaldehyde-aniline (SAN) and salicylaldehyde-cyclohexylamine (SCA), were synchronously synthesized and bonded onto the side chain of polysulfone (PSF), giving two bidentate Schiff base ligand-functionalized PSFs, PSF-SAN and PSF-SCA, referred to as macromolecular ligands. Following coordination reactions between the macromolecular ligands and Eu(III) and Tb(III) ions (the reaction occurred between the bonded ligands SAN or SCA and the lanthanide ion), two series of luminescent polymer-rare earth complexes, PSF-SAN-Eu(III) and PSF-SCA-Tb(III), were obtained. The two macromolecular ligands were fully characterized by Fourier transform infrared (FTIR), 1 H NMR and UV absorption spectroscopy, and the prepared complexes were also characterized by FTIR, UV absorption spectroscopy and thermo-gravity analysis. On this basis, the photoluminescence properties of these complexes and the relationships between their structure and luminescence were investigated in depth. The results show that the bonded bidentate Schiff base ligands, SAN and SCA, can effectively sensitize the fluorescence emission of Eu(III) and Tb(III) ions, respectively. PSF-SAN-Eu(III) series complexes, namely the binary complex PSF-(SAN) 3 -Eu(III) and the ternary complex PSF-(SAN) 3 -Eu(III)-(Phen) 1 (Phen is the small-molecule ligand 1,10-phenanthroline), produce strong red luminescence, suggesting that the triplet state energy level of SAN is lower and well matched with the resonant energy level of the Eu(III) ion. By contrast, PSF-SAN-Eu(III) series complexes, namely the binary complex PSF-(SCA) 3 -Tb(III) and the ternary complex PSF-(SCA) 3 -Tb(III)-(Phen) 1 , display strong green luminescence, suggesting that the triplet state energy level of SCA is higher and is well matched with the resonant energy level of Tb(III). Copyright © 2017 John Wiley & Sons, Ltd.

Prevalence and Correlates of Metabolic Acidosis among Patients with Homozygous Sickle Cell Disease

PubMed Central

Maurel, Stéphane; Stankovic Stojanovic, Katia; Avellino, Virginie; Girshovich, Alexey; Letavernier, Emmanuel; Grateau, Gilles; Baud, Laurent; Girot, Robert; Lionnet, Francois

2014-01-01

Background and objectives Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms. Design, setting, participants, & measurements This study retrospectively analyzed 411 homozygous patients with SCA with a GFR≥60 ml/min per 1.73 m2, referred in a single center between 2007 and 2012. Acidosis and nonacidosis groups were compared for clinical and biologic data including SCA complications and hemolytic parameters. A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the setting of sickle cell–associated nephropathy, was further analyzed in order to better characterize metabolic acidosis. Results Metabolic acidosis was encountered in 42% of patients with SCA, with a higher prevalence in women (52% versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02 and P=0.03 in men and women, respectively), suggesting higher hemolytic activity in the former group. To note, fasting urine osmolality was low in the whole study population and was significantly lower in men with SCA in the acidosis group (392 versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis with a normal anion gap in 14 patients, characterized by a lower urinary pH (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and aldosterone were similar between the two groups and thus could not explain impaired urinary ammonium excretion. Conclusions These results suggest that the prevalence of metabolic acidosis in patients with SCA is underestimated and related to impaired ammonium availability possibly due to an altered corticopapillary gradient. Future studies should evaluate whether chronic metabolic acidosis correction may be beneficial in this population, especially in bone remodeling. PMID:24458070

Magnetomicrofluidics Circuits for Organizing Bioparticle Arrays

NASA Astrophysics Data System (ADS)

Abedini-Nassab, Roozbeh

Single-cell analysis (SCA) tools have important applications in the analysis of phenotypic heterogeneity, which is difficult or impossible to analyze in bulk cell culture or patient samples. SCA tools thus have a myriad of applications ranging from better credentialing of drug therapies to the analysis of rare latent cells harboring HIV infection or in Cancer. However, existing SCA systems usually lack the required combination of programmability, flexibility, and scalability necessary to enable the study of cell behaviors and cell-cell interactions at the scales sufficient to analyze extremely rare events. To advance the field, I have developed a novel, programmable, and massively-parallel SCA tool which is based on the principles of computer circuits. By integrating these magnetic circuits with microfluidics channels, I developed a platform that can organize a large number of single particles into an array in a controlled manner. My magnetophoretic circuits use passive elements constructed in patterned magnetic thin films to move cells along programmed tracks with an external rotating magnetic field. Cell motion along these tracks is analogous to the motion of charges in an electrical conductor, following a rule similar to Ohm's law. I have also developed asymmetric conductors, similar to electrical diodes, and storage sites for cells that behave similarly to electrical capacitors. I have also developed magnetophoretic circuits which use an overlaid pattern of microwires to switch single cells between different tracks. This switching mechanism, analogous to the operation of electronic transistors, is achieved by establishing a semiconducting gap in the magnetic pattern which can be changed from an insulating state to a conducting state by application of electrical current to an overlaid electrode. I performed an extensive study on the operation of transistors to optimize their geometry and minimize the required gate currents. By combining these elements into integrated circuits, I have built devices which are capable of organizing a precise number of cells into individually addressable array sites, similar to how a random access memory (RAM) stores electronic data. My programmable magnetic circuits allow for the organization of both cells and single-cell pairs into large arrays. Single cells can also potentially be retrieved for downstream high-throughput genomic analysis. In order to enhance the efficiency of the tool and to increase the delivery speed of the particles, I have also developed microfluidics systems that are combined with the magnetophoretic circuits. This hybrid system, called magnetomicrofluidics, is capable of rapidly organizing an array of particles and cells with the high precision and control. I have also shown that cells can be grown inside these chips for multiple days, enabling the long-term phenotypic analysis of rare cellular events. These types of studies can reveal important insights about the intercellular signaling networks and answer crucial questions in biology and immunology.

Comparing different snow products to assess spatio-temporal snow cover patterns in the Central Taurus Mountains, Turkey

NASA Astrophysics Data System (ADS)

Sturm, K.; Helmschrot, J.

2013-12-01

Snow and its spatial and temporal patterns are important for catchment hydrology in the semi-arid eastern Mediterranean. Since most of the annual rainfall is stored as snow during winter and released during drier conditions in spring and summer, downstream regions of the Taurus Mountains relying on snow water temporarily stored in reservoirs for agricultural use are heavily dependent on the timing of snowmelt discharge. Runoff is controlled by the amount of accumulated snow, its distribution, and the climatic conditions controlling spring snowmelt. Thus, knowledge about spatial and temporal snow cover dynamics is essential for sustainable water resources management. The lack of observations in high-altitude regions reinforces the application of different snow products for a better assessment of spatio-temporal snow cover patterns. To better assess the quality of such products, simulated daily snow cover and EO-based snow cover products were compared for the Egribuk subcatchment, in the Central Taurus Mountains, Turkey. Daily information on snow cover, depths, and snow water equivalent was derived from distributed hydrological modeling using the J2000 model. Furthermore, 8-day MODIS snow cover data from Terra (MOD10A2) and Aqua (MYD10A2) satellites at a spatial resolution of 500 m were synchronized to receive cloud-free images. From this effort, 253 images covering the period between 07/04/2002 and 12/27/2007 were used for further analyses. The products were analyzed individually to determine the number of snow-covered days in relation to freezing days, spring snowmelt onsets, and temporal patterns, reflecting the effect of altitude on the percentage snow-covered area (SCA) along a topographic gradient at various time-steps. Monthly and 8-day spatial patterns of a single snow season were also examined. When SCA peaks at all altitudes, in February and March, the results of both products show a good agreement regarding SCA extent. In contrast, the extent of SCA differs notably during snow accumulation and ablation periods, the highest deviations occurring in December, April, and May. The highest SCA inconsistencies are observed in the low and mid altitudes, whereas the higher elevations are snow-covered very early in the snow season as modeled by J2000. During these periods, J2000 simulates a significantly larger SCA than MODIS. The analysis of individual time steps suggests that the J2000 daily model does capture individual snow events, whereas the MODIS products fail to do so due to their temporal resolution. Furthermore, acquisition time and inner-daily melt and re-freezing effects may affect SCA estimates from MODIS data. In other cases, differences can clearly be associated to insufficient model input data, primarily due to limited spatial precipitation and temperature data. Our study indicates that individual products might provide inconsistent information on temporal and spatial snow cover. We recommend considering a combined analysis of different snow products in order to provide reliable information on snow cover dynamics, in particular in eastern Mediterranean high-altitude environments.

Side Channel Attacks on STTRAM and Low Overhead Countermeasures

DTIC Science & Technology

2017-03-20

introduce security vulnerabilities and expose the cache memory to side channel attacks. In this paper, we propose a side channel attack (SCA) model...where the adversary can monitor the supply current of the memory array to partially identify the sensi- tive cache data that is being read or written. We...propose solutions such as short retention STTRAM, obfuscation of SCA using 1-bit parity, multi-bit random write, and, neutral- izing the SCA using

EPICS SCA CLIENTS ON THE .NET X64 PLATFORM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timossi, Chris; Nishimura, Hiroshi

2006-10-19

We have developed a .NET assembly, which we call SCA.NET,which we have been using for building EPICS based control roomapplications at the Advanced Light Source (ALS). In this paper we reporton our experiences building a 64-bit version of SCA.NET and theunderlying channel access libraries for Windows XP x64 (using a dual coreAMD Athlon CPU). We also report on our progress in building newaccelerator control applications for this environment.

Mouse A6-positive hepatic oval cells derived from embryonic stem cells.

PubMed

Yin, Dong-zhi; Cai, Ji-ye; Zheng, Qi-chang; Chen, Zheng-wei; Zhao, Jing-xian; Yuan, You-neng

2014-02-01

Oval cells have a potential to differentiate into a variety of cell lineages including hepatocytes and biliary epithelia. Several models have been established to activate the oval cells by incorporating a variety of toxins and carcinogens, alone or combined with surgical treatment. Those models are obviously not suitable for the study on human hepatic oval cells. It is necessary to establish a new and efficient model to study the human hepatic oval cells. In this study, the hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were used to induce differentiation of mouse embryonic stem (ES) cells into hepatic oval cells. We first confirmed that hepatic oval cells derived from ES cells, which are bipotential, do exist during the course of mouse ES cells' differentiation into hepatic parenchymal cells. RT-PCR and transmission electron microscopy were applied in this study. The ratio of Sca-1+/CD34+ cells sorted by FACS in the induction group was increased from day 4 and reached the maximum on the day 8, whereas that in the control group remained at a low level. The differentiation ratio of Sca-1+/CD34+ cells in the induction group was significantly higher than that in the control group. About 92.48% of the sorted Sca-1+/CD34+ cells on the day 8 were A6 positive. Highly purified A6+/Sca-1+/CD34+ hepatic oval cells derived from ES cells could be obtained by FACS. The differentiation ratio of hepatic oval cells in the induction group (up to 4.46%) was significantly higher than that in the control group. The number of hepatic oval cells could be increased significantly by HGF and EGF. The study also examined the ultrastructures of ES-derived hepatic oval cells' membrane surface by atomic force microscopy. The ES-derived hepatic oval cells cultured and sorted by our protocols may be available for the future clinical application.

Identifying Patients at Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction: The e-MUST Study (Evaluation en Médecine d'Urgence des Stratégies Thérapeutiques des infarctus du myocarde).

PubMed

Karam, Nicole; Bataille, Sophie; Marijon, Eloi; Giovannetti, Olivier; Tafflet, Muriel; Savary, Dominique; Benamer, Hakim; Caussin, Christophe; Garot, Philippe; Juliard, Jean-Michel; Pires, Virginie; Boche, Thévy; Dupas, François; Le Bail, Gaelle; Lamhaut, Lionel; Laborne, François; Lefort, Hugues; Mapouata, Mireille; Lapostolle, Frederic; Spaulding, Christian; Empana, Jean-Philippe; Jouven, Xavier; Lambert, Yves

2016-12-20

In-hospital mortality of ST-segment-elevation myocardial infarction (STEMI) has decreased drastically. In contrast, prehospital mortality from sudden cardiac arrest (SCA) remains high and difficult to reduce. Identification of the patients with STEMI at higher risk for prehospital SCA could facilitate rapid triage and intervention in the field. Using a prospective, population-based study evaluating all patients with STEMI managed by emergency medical services in the greater Paris area (11.7 million inhabitants) between 2006 and 2010, we identified characteristics associated with an increased risk of prehospital SCA and used these variables to build an SCA prediction score, which we validated internally and externally. In the overall STEMI population (n=8112; median age, 60 years; 78% male), SCA occurred in 452 patients (5.6%). In multivariate analysis, younger age, absence of obesity, absence of diabetes mellitus, shortness of breath, and a short delay between pain onset and call to emergency medical services were the main predictors of SCA. A score built from these variables predicted SCA, with the risk increasing 2-fold in patients with a score between 10 and 19, 4-fold in those with a score between 20 and 29, and >18-fold in patients with a score ≥30 compared with those with scores <10. The SCA rate was 28.9% in patients with a score ≥30 compared with 1.6% in patients with a score ≤9 (P for trend <0.001). The area under the curve values were 0.7033 in the internal validation sample and 0.6031 in the external validation sample. Sensitivity and specificity varied between 96.9% and 10.5% for scores ≥10 and between 18.0% and 97.6% for scores ≥30, with scores between 20 and 29 achieving the best sensitivity and specificity (65.4% and 62.6%, respectively). At the early phase of STEMI, the risk of prehospital SCA can be determined through a simple score of 5 routinely assessed predictors. This score might help optimize the dispatching and management of patients with STEMI by emergency medical services. © 2016 American Heart Association, Inc.

Distinctive Clinical Profile of Blacks Versus Whites Presenting With Sudden Cardiac Arrest.

PubMed

Reinier, Kyndaron; Nichols, Gregory A; Huertas-Vazquez, Adriana; Uy-Evanado, Audrey; Teodorescu, Carmen; Stecker, Eric C; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S

2015-08-04

Sudden cardiac arrest (SCA) is a major contributor to mortality, but data are limited among nonwhites. Identification of differences in clinical profile based on race may provide opportunities for improved SCA prevention. In the ongoing Oregon Sudden Unexpected Death Study (SUDS), individuals experiencing SCA in the Portland, OR, metropolitan area were identified prospectively. Patient demographics, arrest circumstances, and pre-SCA clinical profile were compared by race among cases from 2002 to 2012 (for clinical history, n=126 blacks, n=1262 whites). Incidence rates were calculated for cases from the burden assessment phase (2002-2005; n=1077). Age-adjusted rates were 2-fold higher among black men and women (175 and 90 per 100 000, respectively) compared with white men and women (84 and 40 per 100 000, respectively). Compared with whites, blacks were >6 years younger at the time of SCA and had a higher prearrest prevalence of diabetes mellitus (52% versus 33%; P<0.0001), hypertension (77% versus 65%; P=0.006), and chronic renal insufficiency (34% versus 19%; P<0.0001). There were no racial differences in previously documented coronary artery disease or left ventricular dysfunction, but blacks had more prevalent congestive heart failure (43% versus 34%; P=0.04) and left ventricular hypertrophy (77% versus 58%; P=0.02) and a longer QTc interval (466±36 versus 453±41 milliseconds; P=0.03). In this US community, the burden of SCA was significantly higher in blacks compared with whites. Blacks with SCA had a higher prearrest prevalence of risk factors beyond established coronary artery disease, providing potential targets for race-specific prevention. © 2015 American Heart Association, Inc.

Relationship between the clinical global impression of severity for schizoaffective disorder scale and established mood scales for mania and depression.

PubMed

Turkoz, Ibrahim; Fu, Dong-Jing; Bossie, Cynthia A; Sheehan, John J; Alphs, Larry

2013-08-15

This analysis explored the relationship between ratings on HAM-D-17 or YMRS and those on the depressive or manic subscale of CGI-S for schizoaffective disorder (CGI-S-SCA). This post hoc analysis used the database (N=614) from two 6-week, randomized, placebo-controlled studies of paliperidone ER versus placebo in symptomatic subjects with schizoaffective disorder assessed using HAM-D-17, YMRS, and CGI-S-SCA scales. Parametric and nonparametric regression models explored the relationships between ratings on YMRS and HAM-D-17 and on depressive and manic domains of the CGI-S-SCA from baseline to the 6-week end point. A clinically meaningful improvement was defined as a change of 1 point in the CGI-S-SCA score. No adjustment was made for multiplicity. Multiple linear regression models suggested that a 1-point change in the depressive domain of CGI-S-SCA corresponded to an average 3.6-point (SE=0.2) change in HAM-D-17 score. Similarly, a 1-point change in the manic domain of CGI-S-SCA corresponded to an average 5.8-point (SE=0.2) change in YMRS score. Results were confirmed using local and cumulative logistic regression models in addition to equipercentile linking. Lack of subjects scoring over the complete range of possible scores may limit broad application of the analyses. Clinically meaningful score changes in depressive and manic domains of CGI-S-SCA corresponded to approximately 4- and 6-point score changes on HAM-D-17 and YMRS, respectively, in symptomatic subjects with schizoaffective disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

The influence of socioeconomic status on the hemoglobin level and anthropometry of sickle cell anemia patients in steady state at the Lagos University Teaching Hospital.

PubMed

Animasahun, B A; Temiye, E O; Ogunkunle, O O; Izuora, A N; Njokanma, O F

2011-01-01

Sickle cell anemia (SCA) has multisystemic manifestations and is associated with severe morbidity and high mortality. It commonly affects growth leading to wasting and stunting. This study aimed to determine the influence of socioeconomic status on the nutritional status using anthropometric measurements and steady-state hemoglobin, of children with homozygous SCA, aged 1 year to 10 years in steady state at the Lagos University Teaching Hospital. This is a cross-sectional study involving 100 children with SCA and 100 age-, sex-, and social class-matched controls that fulfilled the inclusion criteria. Social class was assessed using educational attainment and occupation of parents. Hemoglobin concentration was determined using the oxy-hemoglobin method. This study demonstrated a significantly lower mean weight and weight-for-height in the SCA patients than those of controls (P < 0.001). By contrast, this study did not demonstrate any statistical significant difference in the mean height and mean body mass index of SCA patients and controls (P = 0.06) and (P = 0.12), respectively. The mean weight, height, and body mass indices of the subjects and controls were consistently below those of the NCHS standards. The magnitude of the difference from the NCHS standard was also more pronounced in the subjects, increased with advancing age and affected male subjects more than females. Progressive declines in the anthropometric attainment and hemoglobin concentration were observed from social class 1 to 4; this was statistically significant in controls (P = 0.00) but not in subjects (P > 0.1). However, SCA patients had significantly lower values than controls in each of the social classes. Poor socioeconomic status has an adverse effect on the nutritional status and hemoglobin of SCA patients.

Increased protein kinase C gamma activity induces Purkinje cell pathology in a mouse model of spinocerebellar ataxia 14.

PubMed

Ji, Jingmin; Hassler, Melanie L; Shimobayashi, Etsuko; Paka, Nagendher; Streit, Raphael; Kapfhammer, Josef P

2014-10-01

Spinocerebellar ataxias (SCAs) are hereditary diseases leading to Purkinje cell degeneration and cerebellar dysfunction. Most forms of SCA are caused by expansion of CAG repeats similar to other polyglutamine disorders such as Huntington's disease. In contrast, in the autosomal dominant SCA-14 the disease is caused by mutations in the protein kinase C gamma (PKCγ) gene which is a well characterized signaling molecule in cerebellar Purkinje cells. The study of SCA-14, therefore, offers the unique opportunity to reveal the molecular and pathological mechanism eventually leading to Purkinje cell dysfunction and degeneration. We have created a mouse model of SCA-14 in which PKCγ protein with a mutation found in SCA-14 is specifically expressed in cerebellar Purkinje cells. We find that in mice expressing the mutated PKCγ protein the morphology of Purkinje cells in cerebellar slice cultures is drastically altered and mimics closely the morphology seen after pharmacological PKC activation. Similar morphological abnormalities were seen in localized areas of the cerebellum of juvenile transgenic mice in vivo. In adult transgenic mice there is evidence for some localized loss of Purkinje cells but there is no overall cerebellar atrophy. Transgenic mice show a mild cerebellar ataxia revealed by testing on the rotarod and on the walking beam. Our findings provide evidence for both an increased PKCγ activity in Purkinje cells in vivo and for pathological changes typical for cerebellar disease thus linking the increased and dysregulated activity of PKCγ tightly to the development of cerebellar disease in SCA-14 and possibly also in other forms of SCA. Copyright © 2014 Elsevier Inc. All rights reserved.

A prospective newborn screening and treatment program for sickle cell anemia in Luanda, Angola.

PubMed

McGann, Patrick T; Ferris, Margaret G; Ramamurthy, Uma; Santos, Brigida; de Oliveira, Vysolela; Bernardino, Luis; Ware, Russell E

2013-12-01

Over 300,000 infants are born annually with sickle cell anemia (SCA) in sub-Saharan Africa, and >50% die young from infection or anemia, usually without diagnosis of SCA. Early identification by newborn screening (NBS), followed by simple interventions dramatically reduced the mortality of SCA in the United States, but this strategy is not yet established in Africa. We designed and implemented a proof-of-principle NBS and treatment program for SCA in Angola, with focus on capacity building and local ownership. Dried bloodspots from newborns were collected from five birthing centers. Hemoglobin identification was performed using isoelectric focusing; samples with abnormal hemoglobin patterns were analyzed by capillary electrophoresis. Infants with abnormal FS or FSC patterns were enrolled in a newborn clinic to initiate penicillin prophylaxis and receive education, pneumococcal immunization, and insecticide-treated bed nets. A total of 36,453 infants were screened with 77.31% FA, 21.03% FAS, 1.51% FS, and 0.019% FSC. A majority (54.3%) of affected infants were successfully contacted and brought to clinical care. Compliance in the newborn clinic was excellent (96.6%). Calculated first-year mortality rate for babies with SCA compares favorably to the national infant mortality rate (6.8 vs. 9.8%). The SCA burden is extremely high in Angola, but NBS is feasible. Capacity building and training provide local healthcare workers with skills needed for a functional screening program and clinic. Contact and retrieval of all affected SCA infants remains a challenge, but families are compliant with clinic appointments and treatment. Early mortality data suggest screening and early preventive care saves lives. Copyright © 2013 Wiley Periodicals, Inc.

A study on the association between parvovirus B19 infection, serum tumour necrosis factor and C-reactive protein levels among Nigerian patients with sickle cell anaemia.

PubMed

Iwalokun, Bamidele Abiodun; Iwalokun, Senapon Olusola; Hodonu, Semande Olufunmilayo; Aina, Olugbenga Ayoola; Omilabu, Sunday

2012-11-01

Microbial burden involving parvovirus B19 infection has been recognised as a major cause of morbidity and mortality in sickle cell anaemia (SCA) patients. Given the recent reports of parvovirus B19 infection in Nigeria and the role of inflammation in sickle cell crisis, knowledge of the relationship between the two may be essential for deploying appropriate interventions in infected patients. This study determined the serum levels of tumour necrosis factor alpha (TNF-α) and C-reactive protein (CRP) as inflammatory markers in Nigerian SCA patients with and without parvovirus B19 infections. A total of 64 SCA patients aged 5-25 years and 41 age-matched apparently healthy volunteers with haemoglobin genotypes AA or AS were enrolled with consent into the study. Parvovirus B19 infection and serum levels of TNF-α and CRP were determined by the ELISA method. The overall prevalence rate of parvovirus B19 infection in the study subjects was 13.3%. This rate further showed gender variation and negative correlation with age. Significant (p < 0.05) increases in serum CRP and TNF-α levels, with further elevation in unsteady state SCA patients, were observed in comparison with the control. Unlike the control, 29.6% and 21.9% of the SCA patients elicited TNF-α and CRP above threshold levels, respectively. Parvovirus B19 infection was found to elicit greater increases in these inflammatory markers than in infected non-SCA controls. We conclude that parvovirus B19 infection is common in this environment, and that serum TNF-α and CRP are predictors of clinical inflammatory episodes in infected SCA patients.

Carriage of encapsulated bacteria in Gabonese children with sickle cell anaemia.

PubMed

Schaumburg, F; Biallas, B; Ngoune Feugap, E; Alabi, A S; Mordmüller, B; Kremsner, P G; Grobusch, M P; Lell, B; van der Linden, M; Peters, G; Adegnika, A A

2013-03-01

Sickle cell anaemia (SCA) is a haemoglobin disorder that alters the deformability of erythrocytes through abnormal polymerization of haemoglobin. Children with SCA have an increased risk of infections with encapsulated bacteria. To guide the antibiotic prophylaxis and vaccinations in children with SCA in Gabon, we characterized Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae from children with and without SCA. We performed a cross-sectional study and compared nasal and pharyngeal S. pneumoniae, Staph. aureus and H. influenzae isolates from SCA children (n = 73) with comparators matched for age, residence and sex (n = 143) in a matched-comparison analysis. The resistance pattern and capsular type were identified for each isolate. The total carriage rate for S. pneumoniae, Staph. aureus and H. influenzae was 13.8%, 46.7% and 12.5%, respectively, and did not differ between groups (p >0.05). The mean number of days under antibiotic treatment in the past year was higher in children with SCA than in controls (penicillin: 70.1 vs 0.1 days, p 0.00002). The total non-susceptibility rate was 30% for oral and parenteral (meningitis) penicillin in S. pneumoniae, resistance rates were 1.6% for oxacillin in Staph. aureus and 14.8% for ampicillin in H. influenzae. Susceptibility to antibiotic agents and distribution of capsular types did not differ significantly between both groups. In conclusion, carriage and resistance rates are similar in children with and without SCA. Our data provide the basis to guide empiric therapy of invasive diseases caused by S. pneumoniae, Staph. aureus and H. influenza in children in Gabon. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Endogenous red blood cell membrane fatty acids and sudden cardiac arrest

PubMed Central

Lemaitre, Rozenn N.; King, Irena B.; Sotoodehnia, Nona; Knopp, Robert H.; Mozaffarian, Dariush; McKnight, Barbara; Rea, Thomas D; Rice, Kenneth; Friedlander, Yechiel; Lumley, Thomas S.; Raghunathan, Trivellore E.; Copass, Michael K.; Siscovick, David S.

2010-01-01

Little is known of the associations of endogenous fatty acids with sudden cardiac arrest (SCA). We investigated the associations of SCA with red blood cell membrane fatty acids that are end products of de novo fatty acid synthesis: myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1 n7), vaccenic acid (18:1 n7), stearic acid (18:0), oleic acid (18:1 n9) and a related fatty acid cis-7 hexadecenoic acid (16:1 n9). We used data from a population-based case-control study, where cases, aged 25-74 years, were out-of-hospital sudden cardiac arrest patients, attended by paramedics in Seattle, Washington (n=265). Controls, matched to cases by age, sex and calendar year, were randomly identified from the community (n=415). All participants were free of prior clinically-diagnosed heart disease. We observed associations of higher red blood cell membrane levels of 16:0, 16:1n-7, 18:1n-7 and 16:1n-9 with higher risk of SCA. In analyses adjusted for traditional SCA risk factors and trans- and n-3 fatty acids, a one-standard-deviation-higher level of 16:0 was associated with 38% higher risk of SCA (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.12-1.70) and a one-standard deviation-higher level of 16:1n-9 with 88% higher risk (OR 1.88, 95% CI: 1.27-2.78). Several fatty acids that are end products of fatty acid synthesis are associated with SCA risk. Further work is needed to investigate if conditions that favor de novo fatty acid synthesis, such as high carbohydrate/low fat diets, might also increase the risk of SCA. PMID:20045147

Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

DTIC Science & Technology

2011-08-01

images. Flow Cytometry Assay of Stem Cell Markers SASCs (1 105) isolated from noninjured or injured muscle were collected and washed twice with...muscle. Results of flow cytometry further verified Sca-1 and CD34 expression in isolated SASCs, and a greater percentage of cells were positive for Sca-1...from both injured and control noninjured muscle were analyzed using flow cytometry for the immunofluorescent signal of Sca-1 and CD34. Results

Spinocerebellar ataxia type 6 with positional vertigo and acetazolamide responsive episodic ataxia.

PubMed

Jen, J C; Yue, Q; Karrim, J; Nelson, S F; Baloh, R W

1998-10-01

The SCA6 mutation, a small expansion of a CAG repeat in a calcium channel gene CACNA1A, was identified in three pedigrees. Point mutations in other parts of the gene CACNA1A were excluded and new clinical features of SCA6 reported--namely, central positional nystagmus and episodic ataxia responsive to acetazolamide. The three allelic disorders, episodic ataxia type 2, familial hemiplegic migraine, and SCA6, have overlapping clinical features.

Clinical and MRI findings in spinocerebellar ataxia type 5.

PubMed

Stevanin, G; Herman, A; Brice, A; Dürr, A

1999-10-12

Spinocerebellar ataxia type 5 (SCA5), one of the genetically heterogeneous autosomal dominant cerebellar ataxias, was assigned to chromosome 11 in a single family descending from the grandparents of President Abraham Lincoln. We report a second, apparently unrelated, SCA5 family of French origin. The overall clinical picture was a slowly progressive cerebellar syndrome beginning mostly in the third decade (27+/-10 years, range 14 to 40). MRI showed a marked global cerebellar atrophy similar to SCA6.

Which side of the balance determines the frequency of vaso-occlusive crises in children with sickle cell anemia: Blood viscosity or microvascular dysfunction?

PubMed

Charlot, Keyne; Romana, Marc; Moeckesch, Berenike; Jumet, Stéphane; Waltz, Xavier; Divialle-Doumdo, Lydia; Hardy-Dessources, Marie-Dominique; Petras, Marie; Tressières, Benoît; Tarer, Vanessa; Hue, Olivier; Etienne-Julan, Maryse; Antoine-Jonville, Sophie; Connes, Philippe

2016-01-01

Vascular resistance and tissue perfusion may be both affected by impaired vascular function and increased blood viscosity. Little is known about the effects of vascular function on the occurrence of painful vaso-occlusive crises (VOC) in children with sickle cell anemia (SCA). The aim of the present study was to determine which side of the balance (blood viscosity or vascular function) is the most deleterious in SCA and increases the risk for frequent hospitalized VOC. Microvascular function, microcirculatory oxygenation and blood viscosity were determined in a group of 22 SCA children/adolescents at steady state and a group of 13 healthy children/adolescents. Univariate analyses demonstrated blunted microvascular reactivity during local thermal heating test and decreased microcirculatory oxygenation in SCA children compared to controls. Multivariate analysis revealed that increased blood viscosity and decreased microcirculatory oxygenation were independent risk factors of frequent VOC in SCA. In contrast, the level of microvascular dysfunction does not predict VOC rate. In conclusion, increased blood viscosity is usually well supported in healthy individuals where vascular function is not impaired. However, in the context of SCA, microvascular function is impaired and any increase of blood viscosity or decrease in microcirculatory oxygenation would increase the risks for frequent VOC. Copyright © 2015 Elsevier Inc. All rights reserved.

Sca-1 Identifies a Distinct Androgen-Independent Murine Prostatic Luminal Cell Lineage with Bipotent Potential

PubMed Central

Kwon, Oh-Joon; Zhang, Li; Xin, Li

2016-01-01

Recent lineage tracing studies support the existence of prostate luminal progenitors that possess extensive regenerative capacity, but their identity remains unknown. We show that Sca-1 (Stem Cell Antigen-1) identifies a small population of murine prostate luminal cells that reside in the proximal prostatic ducts adjacent to the urethra. Sca-1+ luminal cells do not express Nkx3.1. They do not carry the secretory function, although they express the androgen receptor. These cells are enriched in the prostates of castrated mice. In the in vitro prostate organoid assay, a small fraction of the Sca-1+ luminal cells are capable of generating budding organoids that are morphologically distinct from those derived from other cell lineages. Histologically, this type of organoid is composed of multiple inner layers of luminal cells surrounded by multiple outer layers of basal cells. When passaged, these organoids retain their morphological and histological features. Finally, the Sca-1+ luminal cells are capable of forming small prostate glands containing both basal and luminal cells in an in vivo prostate regeneration assay. Collectively, our study establishes the androgen-independent and bipotent organoid-forming Sca-1+ luminal cells as a functionally distinct cellular entity. These cells may represent a putative luminal progenitor population and serve as a cellular origin for castration resistant prostate cancer. PMID:26418304

Primitive Sca-1 Positive Bone Marrow HSC in Mouse Model of Aplastic Anemia: A Comparative Study through Flowcytometric Analysis and Scanning Electron Microscopy

PubMed Central

Chatterjee, Sumanta; Basak, Pratima; Das, Prosun; Das, Madhurima; Pereira, Jacintha Archana; Dutta, Ranjan Kumar; Chaklader, Malay; Chaudhuri, Samaresh; Law, Sujata

2010-01-01

Self-renewing Hematopoietic Stem Cells (HSCs) are responsible for reconstitution of all blood cell lineages. Sca-1 is the “stem cell antigen” marker used to identify the primitive murine HSC population, the expression of which decreases upon differentiation to other mature cell types. Sca-1+ HSCs maintain the bone marrow stem cell pool throughout the life. Aplastic anemia is a disease considered to involve primary stem cell deficiency and is characterized by severe pancytopenia and a decline in healthy blood cell generation system. Studies conducted in our laboratory revealed that the primitive Sca-1+ BM-HSCs (bone marrow hematopoietic stem cell) are significantly affected in experimental Aplastic animals pretreated with chemotherapeutic drugs (Busulfan and Cyclophosphamide) and there is increased Caspase-3 activity with consecutive high Annexin-V positivity leading to premature apoptosis in the bone marrow hematopoietic stem cell population in Aplastic condition. The Sca-1bright, that is, “more primitive” BM-HSC population was more affected than the “less primitive” BM-HSC Sca-1dim  population. The decreased cell population and the receptor expression were directly associated with an empty and deranged marrow microenvironment, which is evident from scanning electron microscopy (SEM). The above experimental evidences hint toward the manipulation of receptor expression for the benefit of cytotherapy by primitive stem cell population in Aplastic anemia cases. PMID:21048851

SMC: SCENIC Model Control

NASA Technical Reports Server (NTRS)

Srivastava, Priyaka; Kraus, Jeff; Murawski, Robert; Golden, Bertsel, Jr.

2015-01-01

NASAs Space Communications and Navigation (SCaN) program manages three active networks: the Near Earth Network, the Space Network, and the Deep Space Network. These networks simultaneously support NASA missions and provide communications services to customers worldwide. To efficiently manage these resources and their capabilities, a team of student interns at the NASA Glenn Research Center is developing a distributed system to model the SCaN networks. Once complete, the system shall provide a platform that enables users to perform capacity modeling of current and prospective missions with finer-grained control of information between several simulation and modeling tools. This will enable the SCaN program to access a holistic view of its networks and simulate the effects of modifications in order to provide NASA with decisional information. The development of this capacity modeling system is managed by NASAs Strategic Center for Education, Networking, Integration, and Communication (SCENIC). Three primary third-party software tools offer their unique abilities in different stages of the simulation process. MagicDraw provides UMLSysML modeling, AGIs Systems Tool Kit simulates the physical transmission parameters and de-conflicts scheduled communication, and Riverbed Modeler (formerly OPNET) simulates communication protocols and packet-based networking. SCENIC developers are building custom software extensions to integrate these components in an end-to-end space communications modeling platform. A central control module acts as the hub for report-based messaging between client wrappers. Backend databases provide information related to mission parameters and ground station configurations, while the end user defines scenario-specific attributes for the model. The eight SCENIC interns are working under the direction of their mentors to complete an initial version of this capacity modeling system during the summer of 2015. The intern team is composed of four students in Computer Science, two in Computer Engineering, one in Electrical Engineering, and one studying Space Systems Engineering.

Stress hormones at rest and following exercise testing predict coronary artery disease severity and outcome.

PubMed

Popovic, Dejana; Damjanovic, Svetozar; Djordjevic, Tea; Martic, Dejana; Ignjatovic, Svetlana; Milinkovic, Neda; Banovic, Marko; Lasica, Ratko; Petrovic, Milan; Guazzi, Marco; Arena, Ross

2017-09-01

Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus. Forty Caucasian subjects with significant coronary artery lesions (≥50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3 min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 32 ± 10 months. Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p < .05), whereas ACTH and NT-pro-BNP were not significantly different (p > .05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE = 0.11, 0.10; p = .043, .04) for rest and recovery, respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE = 0.10, p = .049). Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events.

Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction

PubMed Central

Poerschke, Robyn L.; Moos, Philip J.

2010-01-01

Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to anticancer treatments, as well as certain selenocompounds. However, it is unknown if TR1 knockdown produces similar effect on the sensitivity of human lung cancer cells. To further elucidate the role of TR1 in the mechanism of selenocompounds in lung cancer, a lentiviral microRNA delivery system to knockdown TR1 expression in A549 human lung adenocarcinoma cells was utilized. Cell viability was assessed after 48 hr treatment with the selenocysteine prodrug selenazolidines 2-butylselenazolidine-4(R)-carboxylic acid (BSCA) and 2-cyclohexylselenazolidine-4-(R)-carboxylic acid (ChSCA), selenocystine (SECY), methylseleninic acid (MSA), 1,4-phenylenebis(methylene)selenocyanate (p-XSC), and selenomethionine (SEM). TR1 knockdown increased the cytotoxicity of BSCA, ChSCA, and SECY but did not sensitize cells to MSA, SEM, or p-XSC. GSH and TR1 depletion together decreased cell viability, while no change was observed with GSH depletion alone. Reactive oxygen species generation was induced only in TR1 knockdown cells treated with the selenazolidines or SECY. These three compounds also decreased total intracellular glutathione levels and oxidized thioredoxin, but in a TR1 independent manner. TR1 knockdown increased selenazolidine and SECY-induced mitochondrial membrane depolarization, as well as DNA strand breaks and AIF translocation from the mitochondria. These results indicate the ability of TR1 to modulate the cytotoxic effects of BSCA, ChSCA and SECY in human lung cancer cells through mitochondrial dysfunction. PMID:20920480

Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.

PubMed

Edamakanti, Chandrakanth Reddy; Do, Jeehaeh; Didonna, Alessandro; Martina, Marco; Opal, Puneet

2018-06-01

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the protein ATXN1, which is involved in transcriptional regulation. Although symptoms appear relatively late in life, primarily from cerebellar dysfunction, pathogenesis begins early, with transcriptional changes detectable as early as a week after birth in SCA1-knockin mice. Given the importance of this postnatal period for cerebellar development, we asked whether this region might be developmentally altered by mutant ATXN1. We found that expanded ATXN1 stimulates the proliferation of postnatal cerebellar stem cells in SCA1 mice. These hyperproliferating stem cells tended to differentiate into GABAergic inhibitory interneurons rather than astrocytes; this significantly increased the GABAergic inhibitory interneuron synaptic connections, disrupting cerebellar Purkinje cell function in a non-cell autonomous manner. We confirmed the increased basket cell-Purkinje cell connectivity in human SCA1 patients. Mutant ATXN1 thus alters the neural circuitry of the developing cerebellum, setting the stage for the later vulnerability of Purkinje cells to SCA1. We propose that other late-onset degenerative diseases may also be rooted in subtle developmental derailments.

Mutations In Rare Ataxia Genes Are Uncommon Causes of Sporadic Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Ji Yong; Lane, Jessica; Wahnich, Amanda; Chan, Sandy; Huang, Alden; Osborn, Greg E.; Klein, Eric; Mamah, Catherine; Perlman, Susan; Geschwind, Daniel H.; Coppola, Giovanni

2012-01-01

BACKGROUND Sporadic-onset ataxia is common in a tertiary care setting but a significant percentage remains unidentified despite extensive evaluation. Rare genetic ataxias, reported only in specific populations or families, may contribute to a percentage of sporadic ataxia. METHODS Patients with adult-onset sporadic ataxia, who tested negative for common genetic ataxias (SCA1, SCA2, SCA3, SCA6, SCA7, and/or Friedreich ataxia), were evaluated using a stratified screening approach for variants in seven rare ataxia genes. RESULTS We screened patients for published mutations in SYNE1 (n=80) and TGM6 (n=118), copy number variations in LMNB1 (n=40) and SETX (n=11), sequence variants in SACS (n=39) and PDYN (n=119), and the pentanucleotide insertion of spinocerebellar ataxia type 31 (n=101). Overall, we identified one patient with a LMNB1 duplication, one patient with a PDYN variant, and one compound SACS heterozygote, including a novel variant. CONCLUSIONS The rare genetic ataxias examined here do not significantly contribute to sporadic cerebellar ataxia in our tertiary care population. PMID:22287014

Trace elements in children suffering from sickle cell anemia: A case-control study.

PubMed

Sungu, Joseph K; Mukuku, Olivier; Mutombo, Augustin Mulangu; Mawaw, Paul; Aloni, Michel N; Luboya, Oscar N

2018-01-01

Information on serum albumin and trace elements among children suffering from Sickle Cell Anemia (SCA) was poorly documented in Africa. The aim of this study was to describe and to compare different values of trace elements with published reports from other parts of the world. We carried out a case-control study. Seventy-six steady state children suffering from SCA (Hb-SS). One hundred and fifty-two children were recruited with 76 (cases, Hb-SS) and 76 (control, Hb-AA) to compare the data. The mean age was 10.0 years (SD=5.4) in SCA children and 9.2 years (SD=4.7) in the control group. The mean level of zinc and magnesium were slightly lower in the Hb-SS group than in the Hb-AA group (P<.001). The first literature about trace elements in SCA is briefly reported in Central Africa. In our midst, zinc, magnesium, and selenium deficiencies underline the need for their systematic among all children with SCA to identify patients with these deficiencies and provide early management. © 2017 Wiley Periodicals, Inc.

Augmenting the SCaN Link Budget Tool with Validated Atmospheric Propagation

NASA Technical Reports Server (NTRS)

Steinkerchner, Leo; Welch, Bryan

2017-01-01

In any Earth-Space or Space-Earth communications link, atmospheric effects cause significant signal attenuation. In order to develop a communications system that is cost effective while meeting appropriate performance requirements, it is important to accurately predict these effects for the given link parameters. This project aimed to develop a Matlab(TradeMark) (The MathWorks, Inc.) program that could augment the existing Space Communications and Navigation (SCaN) Link Budget Tool with accurate predictions of atmospheric attenuation of both optical and radio-frequency signals according to the SCaN Optical Link Assessment Model Version 5 and the International Telecommunications Union, Radiocommunications Sector (ITU-R) atmospheric propagation loss model, respectively. When compared to data collected from the Advance Communications Technology Satellite (ACTS), the radio-frequency model predicted attenuation to within 1.3 dB of loss for 95 of measurements. Ultimately, this tool will be integrated into the SCaN Center for Engineering, Networks, Integration, and Communications (SCENIC) user interface in order to support analysis of existing SCaN systems and planning capabilities for future NASA missions.

Prevalence of spinocerebellar ataxia 36 in a US population.

PubMed

Valera, Juliana M; Diaz, Tatyana; Petty, Lauren E; Quintáns, Beatriz; Yáñez, Zuleima; Boerwinkle, Eric; Muzny, Donna; Akhmedov, Dmitry; Berdeaux, Rebecca; Sobrido, Maria J; Gibbs, Richard; Lupski, James R; Geschwind, Daniel H; Perlman, Susan; Below, Jennifer E; Fogel, Brent L

2017-08-01

To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States. A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the NOP56 gene. Fragment analysis of triplet repeat primed PCR products identified a GGCCTG hexanucleotide repeat expansion in intron 1 of NOP56 in 4 index cases. These 4 SCA36-positive families comprised 2 distinct ethnic groups: white (European) (2) and Asian (Japanese [1] and Vietnamese [1]). Individuals affected by SCA36 exhibited typical clinical features with gait ataxia and age at onset ranging between 35 and 50 years. Patients also suffered from ataxic or spastic limbs, altered reflexes, abnormal ocular movement, and cognitive impairment. In a US population, SCA36 was observed to be a rare disorder, accounting for 0.7% (4/577 index cases) of disease in a large undiagnosed ataxia cohort.

KSC-2012-2364

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, takes off from runway 15 at 7 a.m. EDT. The SCA will deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2360

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, waits on runway 15 for clearance from Kennedy’s air traffic control tower to begin takeoff at 7 a.m. EDT. The SCA will deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2363

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, takes off from runway 15 at 7 a.m. EDT. The SCA will deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2365

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, takes off from runway 15 at 7 a.m. EDT. The SCA will deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

Prolonged central motor conduction time of lower limb muscle in spinocerebellar ataxia 6.

PubMed

Chen, Jen-Tse; Lin, Yung-Yang; Lee, Yi-Chung; Soong, Bing-Wen; Wu, Zin-An; Liao, Kwong-Kum

2004-05-01

We investigated the function of corticospinal tract in spinocerebellar ataxia 6 (SCA6) by measuring the central motor conduction time (CMCT). Motor evoked potentials (MEP) of tibialis anterior (TA) muscle were elicited by magnetic stimulation to motor cortex and spinal cord in 9 SCA6 patients and 10 normal height- and age-matched subjects. CMCT in lower limb of SCA6 patients (18.1+/-1.9 ms) was significantly prolonged than that of the normal subjects (15.0+/-1.0 ms) ((p < 0.001). The prolonged CMCT was well correlated with the duration of disease (p = 0.005), but MEP amplitudes and stimulation intensities were not significantly different. These results indicate that the corticospinal tract function is also impaired and correlate with the disease duration in SCA6.

Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua*

PubMed Central

Fryer, John D.; Yu, Peng; Kang, Hyojin; Mandel-Brehm, Caleigh; Carter, Angela N.; Crespo-Barreto, Juan; Gao, Yan; Flora, Adriano; Shaw, Chad; Orr, Harry T.; Zoghbi, Huda Y.

2011-01-01

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by expansion of a translated CAG repeat in Ataxin-1 (ATXN1). To determine the long-term effects of exercise, we implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by upregulation of epidermal growth factor and consequential downregulation of Capicua, an ATXN1 interactor. Offspring of Capicua mutant mice bred to SCA1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reducing Capicua levels, either genetically or by exercise, mitigated the disease phenotypes. Thus, exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases. PMID:22053053

RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1

PubMed Central

Keiser, Megan S.; Geoghegan, James C.; Boudreau, Ryan L.; Lennox, Kim A.; Davidson, Beverly L.

2014-01-01

Spinocerebellar Ataxia Type 1 (SCA1) is an autosomal dominant late onset neurodegenerative disease caused by an expanded polyglutamine tract in ataxin-1. Here, we compared the protective effects of overexpressing ataxin-1-like using recombinant AAVs, or reducing expression of mutant ataxin-1 using virally delivered RNA interference (RNAi), in a transgenic mouse model of SCA1. For the latter, we used an artificial microRNA (miR) design that optimizes potency, efficacy and safety to suppress ataxin-1 expression (miS1). Delivery of either ataxin-1-like or miS1 viral vectors to SCA1 mice cerebella resulted in widespread cerebellar Purkinje cell transduction and improved behavioral and histological phenotypes. Our data indicate the utility of either approach as a possible therapy for SCA1 patients. PMID:23583610

Discovering governing equations from data by sparse identification of nonlinear dynamics

NASA Astrophysics Data System (ADS)

Brunton, Steven

The ability to discover physical laws and governing equations from data is one of humankind's greatest intellectual achievements. A quantitative understanding of dynamic constraints and balances in nature has facilitated rapid development of knowledge and enabled advanced technology, including aircraft, combustion engines, satellites, and electrical power. There are many more critical data-driven problems, such as understanding cognition from neural recordings, inferring patterns in climate, determining stability of financial markets, predicting and suppressing the spread of disease, and controlling turbulence for greener transportation and energy. With abundant data and elusive laws, data-driven discovery of dynamics will continue to play an increasingly important role in these efforts. This work develops a general framework to discover the governing equations underlying a dynamical system simply from data measurements, leveraging advances in sparsity-promoting techniques and machine learning. The resulting models are parsimonious, balancing model complexity with descriptive ability while avoiding overfitting. The only assumption about the structure of the model is that there are only a few important terms that govern the dynamics, so that the equations are sparse in the space of possible functions. This perspective, combining dynamical systems with machine learning and sparse sensing, is explored with the overarching goal of real-time closed-loop feedback control of complex systems. This is joint work with Joshua L. Proctor and J. Nathan Kutz. Video Abstract: https://www.youtube.com/watch?v=gSCa78TIldg

New 5 Kilowatt Free-Piston Stirling Space Converter Developments

NASA Astrophysics Data System (ADS)

Brandhorst, Henry W.

2007-01-01

NASA has recently funded development of a 5 kW (or greater) free-piston Stirling conversion system for reactor power systems. A nominal 5 kW converter allows two of these units to be dynamically balanced. A group of three dual-convertor combinations would yield the desired 30 kW. The status of this program will be presented. Goals include a specific power in excess of 140 W/kg at the converter level, lifetime in excess of five years and AC output. The initial step is the design and development of a nominal 5 kW per cylinder Stirling converter assembly (SCA) which will serve as a prototype of one or more SCAs that will make up the final 30 kW Stirling Converter Power System. Assumed requirements for this new converter for lunar fission power systems will be presented. The primary objective of this development effort will be to demonstrate a 5 kW SCA that can be tested to validate the viability of Stirling technology for space fission surface power systems.

New 5 Kilowatt Free-Piston Stirling Space Convertor Developments

NASA Technical Reports Server (NTRS)

Brandhorst, Henry W.

2007-01-01

NASA has recently funded development of a 5 kW (or greater) free-piston Stirling conversion system for reactor power systems. A nominal 5 kW convertor allows two of these units to be dynamically balanced. A group of three dual-convertor combinations would yield the desired 30 kW. The status of this program will be presented. Goals include a specific power in excess of 140 W/kg at the convertor level, lifetime in excess of five years and AC output. The initial step is the design and development of a nominal 5 kW per cylinder Stirling convertor assembly (SCA) which will serve as a prototype of one or more SCAs that will make up the final 30 kW Stirling Convertor Power System. Assumed requirements for this new convertor for lunar fission power systems will be presented. The primary objective of this development effort will be to demonstrate a 5 kW SCA that can be tested to validate the viability of Stirling technology for space fission surface power systems.

Machado Joseph disease maps to the same region of chromosome 14 as the spinocerebellar ataxia type 3 locus.

PubMed Central

Twist, E C; Casaubon, L K; Ruttledge, M H; Rao, V S; Macleod, P M; Radvany, J; Zhao, Z; Rosenberg, R N; Farrer, L A; Rouleau, G A

1995-01-01

Machado Joseph disease (MJD) is an autosomal dominantly inherited neuro-degenerative disorder primarily affecting the motor system. It can be divided into three phenotypes based on the variable combination of a range of clinical symptoms including pyramidal and extra-pyramidal features, cerebellar deficits, and distal muscle atrophy. MJD is thought to be caused by mutation of a single gene which has recently been mapped, using genetic linkage analysis, to a 29 cM region on chromosome 14q24.3-q32 in five Japanese families. A second disorder, spinocerebellar ataxia type 3 (SCA3), which has clinical symptoms similar to MJD, has also been linked to the same region of chromosome 14q in two French families. In order to narrow down the region of chromosome 14 which contains the MJD locus and to determine if this region overlaps with the predisposing locus for SCA3, we have performed genetic linkage analysis in seven MJD families, six of Portuguese/Azorean origin and one of Brazilian origin, using nine microsatellite markers mapped to 14q24.3-q32. Our results localise the MJD locus in these families to an 11 cM interval flanked by the markers D14S68 and AFM343vf1. In addition we show that this 11 cM interval maps within the 15 cM interval containing the SCA3 locus, suggesting that these diseases are allelic. PMID:7897622

VEGF ameliorates the ataxic phenotype in spinocerebellar ataxia type 1 (SCA1) mice

PubMed Central

Cvetanovic, Marija; Patel, Jay; Marti, Hugo H; Kini, Ameet R; Opal, Puneet

2012-01-01

SCA1 is an adult-onset, dominantly inherited neurodegenerative disease caused by expansion of a glutamine repeat tract in ATXN1. Although the precise function of ATXN1 remains elusive, it appears to play a role in transcriptional repression. We find that mutant ATXN1 suppresses transcription of the neurotrophic and angiogenic factor VEGF. We also show that genetic or pharmacologic replenishment of VEGF mitigates SCA1 pathogenesis, suggesting a novel therapeutic strategy for this incurable disease. PMID:22001907

Transfection of Murine and Human Hematopoietic Progenitors with Rearranged Immunoglobulin Genes

DTIC Science & Technology

1991-01-01

fluorouracil (SFU) to eliminate most cycling progenitors. Previous studies have shown that 5FU -treatment enriches for one early progenitor with high...Table I shows a time course of SCA-I positive cell expression various times post- 5FU treatment. Table 1 clearly shows that 5FU treatment can increase...the percentage of SCA-l-positive cells to 6-7% by day 7 post- 5FU treatment. The level of SCA-I expression falls to approximately 1% of total nucleated

Cognitive Networking With Regards to NASA's Space Communication and Navigation Program

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Paulsen, Phillip E.; Vaden, Karl R.; Ponchak, Denise S.

2013-01-01

This report describes cognitive networking (CN) and its application to NASA's Space Communication and Networking (SCaN) Program. This report clarifies the terminology and framework of CN and provides some examples of cognitive systems. It then provides a methodology for developing and deploying CN techniques and technologies. Finally, the report attempts to answer specific questions regarding how CN could benefit SCaN. It also describes SCaN's current and target networks and proposes places where cognition could be deployed.

KSC-2009-3433

NASA Image and Video Library

2009-06-02

CAPE CANAVERAL, Fla. – Against a setting sun, space shuttle Atlantis, atop a Shuttle Carrier Aircraft, or SCA, is towed from the runway at NASA's Kennedy Space Center in Florida. The SCA is a modified Boeing 747 jetliner. Atlantis returned from California atop the SCA after its May 24 landing at Edwards Air Force Base, concluding mission STS-125. The ferry flight from Edwards Air Force Base began June 1. Atlantis' next assignment is the STS-129 mission, targeted to launch in November 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-3431

NASA Image and Video Library

2009-06-02

CAPE CANAVERAL, Fla. – After a two-day trip from California, space shuttle Atlantis, atop a Shuttle Carrier Aircraft, or SCA, is towed from the runway at NASA's Kennedy Space Center in Florida. The SCA is a modified Boeing 747 jetliner. Atlantis returned from California atop the SCA after its May 24 landing at Edwards Air Force Base, concluding mission STS-125. The ferry flight from Edwards Air Force Base began June 1. Atlantis' next assignment is the STS-129 mission, targeted to launch in November 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-3432

NASA Image and Video Library

2009-06-02

CAPE CANAVERAL, Fla. – After a two-day trip from California, space shuttle Atlantis, atop a Shuttle Carrier Aircraft, or SCA, is towed from the runway at NASA's Kennedy Space Center in Florida. The SCA is a modified Boeing 747 jetliner. Atlantis returned from California atop the SCA after its May 24 landing at Edwards Air Force Base, concluding mission STS-125. The ferry flight from Edwards Air Force Base began June 1. Atlantis' next assignment is the STS-129 mission, targeted to launch in November 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-3464

NASA Image and Video Library

2009-06-01

CAPE CANAVERAL, Fla. – At Biggs Army Air Field in El Paso, Texas, the Shuttle Carrier Aircraft, or SCA, a modified Boeing 747, is ready to take off after an overnight stop at Biggs Army Air Field in El Paso, Texas. The shuttle and SCA left Edwards Air Force Base in California for its return to Florida.Atlantis is being returned to Florida on a ferry flight on the SCA. Atlantis' next assignment is the STS-129 mission, targeted to launch in November 2009. Photo credit: NASA/Ben Smegelsky

Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.

PubMed

Yao, H; Jiang, F; Hu, H; Gao, Y; Zhu, Z; Zhang, H; Wang, Y; Guo, Y; Liu, L; Yuan, Y; Zhou, L; Wang, J; Du, B; Qu, N; Zhang, R; Dong, Y; Xu, H; Chen, F; Jiang, H; Liu, Y; Zhang, L; Tian, Z; Liu, Q; Zhang, C; Pan, X; Yang, S; Zhao, L; Wang, W; Liang, Z

2014-07-01

To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Estimation de la superficie du couvert nival a partir d'une combinaison des donnees de teledetection MODIS et AMSR-E dans un contexte de prevision des crues printanieres au Quebec

NASA Astrophysics Data System (ADS)

Bergeron, Jean

Snow cover estimation is a principal source of error for spring streamflow simulations in Québec, Canada. Optical and near infrared remote sensing can improve snow cover area (SCA) estimation due to high spatial resolution but is limited by cloud cover and incoming solar radiation. Passive microwave remote sensing is complementary by its near-transparence to cloud cover and independence to incoming solar radiation, but is limited by its coarse spatial resolution. The study aims to create an improved SCA product from blended passive microwave (AMSR-E daily L3 Brightness Temperature) and optical (MODIS Terra and Aqua daily snow cover L3) remote sensing data in order to improve estimation of river streamflow caused by snowmelt with Québec's operational MOHYSE hydrological model through direct-insertion of the blended SCA product in a coupled snowmelt module (SPH-AV). SCA estimated from AMSR-E data is first compared with SCA estimated with MODIS, as well as with in situ snow depth measurements. Results show good agreement (+95%) between AMSR-E-derived and MODIS-derived SCA products in spring but comparisons with Environment Canada ground stations and SCA derived from Advanced Very High Resolution Radiometer (AVHRR) data show lesser agreements (83 % and 74% respectively). Results also show that AMSR-E generally underestimates SCA. Assimilating the blended snow product in SPH-AV coupled with MOHYSE yields significant improvement of simulated streamflow for the aux Écorces et au Saumon rivers overall when compared with simulations with no update during thaw events, These improvements are similar to results driven by biweekly ground data. Assimilation of remotely-sensed passive microwave data was also found to have little positive impact on springflood forecast due to the difficulty in differentiating melting snow from snow-free surfaces. Considering the direct-insertion and Newtonian nudging assimilation methods, the study also shows the latter method to be superior to the former, notably when assimilating noisy data. Keywords: Snow cover, spring streamflow, MODIS, AMSR-E, hydrological model.

Underestimation of Risk of Carotid Subclinical Atherosclerosis by Cardiovascular Risk Scores in Patients with Psoriatic Arthritis.

PubMed

Shen, Jiayun; Lam, Steven H; Shang, Qing; Wong, Chun-Kwok; Li, Edmund K; Wong, Priscilla; Kun, Emily W; Cheng, Isaac T; Li, Martin; Li, Tena K; Zhu, Tracy Y; Lee, Jack Jock-Wai; Chang, Mimi; Lee, Alex Pui-Wai; Tam, Lai-Shan

2018-02-01

To test the performances of established cardiovascular (CV) risk scores in discriminating subclinical atherosclerosis (SCA) in patients with psoriatic arthritis. These scores were calculated: Framingham risk score (FRS), QRISK2, Systematic COronary Risk Evaluation (SCORE), 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD) from the American College of Cardiology and the American Heart Association, and the European League Against Rheumatism (EULAR)-recommended modified versions (by 1.5 multiplication factor, m-). Carotid intima-media thickness > 0.9 mm and/or the presence of plaque determined by ultrasound were classified as SCA+. We recruited 146 patients [49.4 ± 10.2 yrs, male: 90 (61.6%)], of whom 142/137/128/118 patients were eligible to calculate FRS/QRISK2/SCORE/ASCVD. Further, 62 (42.5%) patients were SCA+ and were significantly older, with higher systolic blood pressure and higher low-density lipoprotein cholesterol (all p < 0.05). All CV risk scores were significantly higher in patients with SCA+ [FRS: 7.8 (3.9-16.5) vs 2.7 (1.1-7.8), p < 0.001; QRISK2: 5.5 (3.1-10.2) vs 2.9 (1.2-6.3), p < 0.001; SCORE: 1 (0-2) vs 0 (0-1), p < 0.001; ASCVD: 5.6 (2.6-12.4) vs 3.4 (1.4-6.1), p = 0.001]. The Hosmer-Lemeshow test revealed moderate goodness of fit for the 4 CV scores (p ranged from 0.087 to 0.686). However, of the patients with SCA+, those identified as high risk were only 44.1% (by FRS > 10%), 1.8% (QRISK2 > 20%), 10.9% (SCORE > 5%), and 43.6% (ASCVD > 7.5%). By applying the EULAR multiplication factor, 50.8%/14.3%/14.5%/54.5% of the patients with SCA+ were identified as high risk by m-FRS/m-QRISK2/m-SCORE/m-ASCVD, respectively. EULAR modification increased the sensitivity of FRS and ASCVD in discriminating SCA+ from 44% to 51%, and 44% to 55%, respectively. All CV risk scores underestimated the SCA+ risk. EULAR-recommended modification improved the sensitivity of FRS and ASCVD only to a moderate level.

Sudden Cardiac Arrest (SCA)

MedlinePlus

... attacks often have previous signs and symptoms. SCArisk.org The SCA Risk Assessment is an interactive tool ... 3400 F: 202-464-3401 E: info@HRSonline.org © Heart Rhythm Society 2018 Privacy Policy | Linking Policy | ...

The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin-Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk Domain

PubMed Central

Ito, Morihiro; Ohtsuka, Junpei; Hara, Kenichiro; Komada, Hiroshi; Nishio, Machiko; Nosaka, Tetsuya

2015-01-01

ABSTRACT Virus-specific interaction between the attachment protein (HN) and the fusion protein (F) is prerequisite for the induction of membrane fusion by parainfluenza viruses. This HN-F interaction presumably is mediated by particular amino acids in the HN stalk domain and those in the F head domain. We found in the present study, however, that a simian virus 41 (SV41) F-specific chimeric HPIV2 HN protein, SCA, whose cytoplasmic, transmembrane, and stalk domains were derived from the SV41 HN protein, could not induce cell-cell fusion of BHK-21 cells when coexpressed with an SV41 HN-specific chimeric PIV5 F protein, no. 36. Similarly, a headless form of the SV41 HN protein failed to induce fusion with chimera no. 36, whereas it was able to induce fusion with the SV41 F protein. Interestingly, replacement of 13 amino acids of the SCA head domain, which are located at or around the dimer interface of the head domain, with SV41 HN counterparts resulted in a chimeric HN protein, SCA-RII, which induced fusion with chimera no. 36 but not with the SV41 F protein. More interestingly, retroreplacement of 11 out of the 13 amino acids of SCA-RII with the SCA counterparts resulted in another chimeric HN protein, IM18, which induced fusion either with chimera no. 36 or with the SV41 F protein, similar to the SV41 HN protein. Thus, we conclude that the F protein specificity of the HN protein that is observed in the fusion event is not solely defined by the primary structure of the HN stalk domain. IMPORTANCE It is appreciated that the HN head domain initially conceals the HN stalk domain but exposes it after the head domain has bound to the receptors, which allows particular amino acids in the stalk domain to interact with the F protein and trigger it to induce fusion. However, other regulatory roles of the HN head domain in the fusion event have been ill defined. We have shown in the current study that removal of the head domain or amino acid substitutions in a particular region of the head domain drastically change the F protein specificity of the HN protein, suggesting that the ability of a given HN protein to interact with an F protein is defined not only by the primary structure of the HN stalk domain but also by its conformation. This notion seems to account for the unidirectional substitutability among rubulavirus HN proteins in triggering noncognate F proteins. PMID:26423949

Cell Growth Characteristics, Differentiation Frequency, and Immunophenotype of Adult Ear Mesenchymal Stem Cells

PubMed Central

Staszkiewicz, Jaroslaw; Frazier, Trivia P.; Rowan, Brian G.; Bunnell, Bruce A.; Chiu, Ernest S.; Gimble, Jeffrey M.

2010-01-01

Ear mesenchymal stem cells (EMSCs) represent a readily accessible population of stem-like cells that are adherent, clonogenic, and have the ability to self-renew. Previously, we have demonstrated that they can be induced to differentiate into adipocyte, osteocyte, chondrocyte, and myocyte lineages. The purpose of the current study was to characterize the growth kinetics of the cells and to determine their ability to form colonies of fibroblasts, adipocytes, osteocytes, and chondrocytes. In addition, the immunophenotypes of freshly isolated and culture-expanded cells were evaluated. From 1 g of tissue, we were able to isolate an average of 7.8 × 106 cells exhibiting a cell cycle length of ∼2–3 days. Colony-forming unit (CFU) assays indicated high proliferation potential, and confirmed previously observed multipotentiality of the cells. Fluorescence-activated cell sorting (FACS) showed that EMSCs were negative for hematopoietic markers (CD4, CD45), proving that they did not derive from circulating hematopoietic cells. The FACS analyses also showed high expression of stem cell antigen-1 (Sca-1) with only a minor population of cells expressing CD117, thus identifying Sca-1 as the more robust stem cell biomarker. Additionally, flow cytometry data revealed that the expression patterns of hematopoietic, stromal, and stem cell markers were maintained in the passaged EMSCs, consistent with the persistence of an undifferentiated state. This study indicates that EMSCs provide an alternative model for in vitro analyses of adult mesenchymal stem cells (MSCs). Further studies will be necessary to determine their utility for tissue engineering and regenerative medical applications. PMID:19400629

Development of NASA's Sample Cartridge Assembly: Summary of GEDS Design, Development Testing, and Thermal Analyses

NASA Technical Reports Server (NTRS)

O'Connor, Brian; Hernandez, Deborah; Hornsby, Linda; Brown, Maria; Horton-Mullins, Kathryn

2017-01-01

NASA's Sample Cartridge Assembly (SCA) project is responsible for designing and validating a payload that contains materials research samples in a sealed environment. The SCA will be heated in the European Space Agency's (ESA) Low Gradient Furnace (LGF) that is housed inside the Material Science Research Rack (MSRR) located on the International Space Station (ISS). The first Principle Investigator (PI) to utilize the SCA will focus on Gravitational Effects on Distortion in Sintering (GEDS) research. This paper will give a summary of the design and development test effort for the GEDS SCA and will discuss the role of thermal analysis in developing test profiles to meet the science and engineering requirements. Lessons learned will be reviewed and salient design features that may differ for each PI will be discussed.

Large pathogenic expansions in the SCA2 and SCA7 genes can be detected by fluorescent repeat-primed polymerase chain reaction assay.

PubMed

Cagnoli, Claudia; Stevanin, Giovanni; Michielotto, Chiara; Gerbino Promis, Giovanni; Brussino, Alessandro; Pappi, Patrizia; Durr, Alexandra; Dragone, Elisa; Viemont, Michelle; Gellera, Cinzia; Brice, Alexis; Migone, Nicola; Brusco, Alfredo

2006-02-01

Large expansions in the SCA2 and SCA7 genes (>100 CAG repeats) have been associated with juvenile and infantile forms of cerebellar ataxias that cannot be detected using standard polymerase chain reaction (PCR). Here, we describe a successful application of the fluorescent short tandem repeat-primed PCR method for accurate identification of these expanded repeats. The test is robust, reliable, and inexpensive and can be used to screen large series of patients, although it cannot give a precise evaluation of the size of the expansion. This test may be of practical value in prenatal diagnoses offered to affected or pre-symptomatic at-risk parents, in which a very large expansion inherited from one of the parents can be missed in the fetus by standard PCR.

Large Pathogenic Expansions in the SCA2 and SCA7 Genes Can Be Detected by Fluorescent Repeat-Primed Polymerase Chain Reaction Assay

PubMed Central

Cagnoli, Claudia; Stevanin, Giovanni; Michielotto, Chiara; Gerbino Promis, Giovanni; Brussino, Alessandro; Pappi, Patrizia; Durr, Alexandra; Dragone, Elisa; Viemont, Michelle; Gellera, Cinzia; Brice, Alexis; Migone, Nicola; Brusco, Alfredo

2006-01-01

Large expansions in the SCA2 and SCA7 genes (>100 CAG repeats) have been associated with juvenile and infantile forms of cerebellar ataxias that cannot be detected using standard polymerase chain reaction (PCR). Here, we describe a successful application of the fluorescent short tandem repeat-primed PCR method for accurate identification of these expanded repeats. The test is robust, reliable, and inexpensive and can be used to screen large series of patients, although it cannot give a precise evaluation of the size of the expansion. This test may be of practical value in prenatal diagnoses offered to affected or pre-symptomatic at-risk parents, in which a very large expansion inherited from one of the parents can be missed in the fetus by standard PCR. PMID:16436644

Space Communications and Navigation (SCaN) Network Simulation Tool Development and Its Use Cases

NASA Technical Reports Server (NTRS)

Jennings, Esther; Borgen, Richard; Nguyen, Sam; Segui, John; Stoenescu, Tudor; Wang, Shin-Ywan; Woo, Simon; Barritt, Brian; Chevalier, Christine; Eddy, Wesley

2009-01-01

In this work, we focus on the development of a simulation tool to assist in analysis of current and future (proposed) network architectures for NASA. Specifically, the Space Communications and Navigation (SCaN) Network is being architected as an integrated set of new assets and a federation of upgraded legacy systems. The SCaN architecture for the initial missions for returning humans to the moon and beyond will include the Space Network (SN) and the Near-Earth Network (NEN). In addition to SCaN, the initial mission scenario involves a Crew Exploration Vehicle (CEV), the International Space Station (ISS) and NASA Integrated Services Network (NISN). We call the tool being developed the SCaN Network Integration and Engineering (SCaN NI&E) Simulator. The intended uses of such a simulator are: (1) to characterize performance of particular protocols and configurations in mission planning phases; (2) to optimize system configurations by testing a larger parameter space than may be feasible in either production networks or an emulated environment; (3) to test solutions in order to find issues/risks before committing more significant resources needed to produce real hardware or flight software systems. We describe two use cases of the tool: (1) standalone simulation of CEV to ISS baseline scenario to determine network performance, (2) participation in Distributed Simulation Integration Laboratory (DSIL) tests to perform function testing and verify interface and interoperability of geographically dispersed simulations/emulations.

Identification and evaluation of two diagnostic markers linked to Fusarium wilt resistance (race 4) in banana (Musa spp.).

PubMed

Wang, Wei; Hu, Yulin; Sun, Dequan; Staehelin, Christian; Xin, Dawei; Xie, Jianghui

2012-01-01

Fusarium wilt caused by the fungus Fusarium oxysporum f. sp. cubense race 4 (FOC4) results in vascular tissue damage and ultimately death of banana (Musa spp.) plants. Somaclonal variants of in vitro micropropagated banana can hamper success in propagation of genotypes resistant to FOC4. Early identification of FOC4 resistance in micropropagated banana plantlets is difficult, however. In this study, we identified sequence-characterized amplified region (SCAR) markers of banana associated with resistance to FOC4. Using pooled DNA from resistant or susceptible genotypes and 500 arbitrary 10-mer oligonucleotide primers, 24 random amplified polymorphic DNA (RAPD) products were identified. Two of these RAPD markers were successfully converted to SCAR markers, called ScaU1001 (GenBank accession number HQ613949) and ScaS0901 (GenBank accession number HQ613950). ScaS0901 and ScaU1001 could be amplified in FOC4-resistant banana genotypes ("Williams 8818-1" and Goldfinger), but not in five tested banana cultivars susceptible to FOC4. The two SCAR markers were then used to identify a somaclonal variant of the genotype "Williams 8818-1", which lost resistance to FOC4. Hence, the identified SCAR markers can be applied for a rapid quality control of FOC4-resistant banana plantlets immediately after the in vitro micropropagation stage. Furthermore, ScaU1001 and ScaS0901 will facilitate marker-assisted selection of new banana cultivars resistant to FOC4.

Use of whole body CT to detect patterns of CPR-related injuries after sudden cardiac arrest.

PubMed

Dunham, Gregor M; Perez-Girbes, Alexandre; Bolster, Ferdia; Sheehan, Kellie; Linnau, Ken F

2017-11-09

We have recently implemented a dedicated sudden cardiac arrest (SCA) - whole-body computed tomography (WBCT) protocol to evaluate SCA patients with return of spontaneous circulation (ROSC) following cardiopulmonary resuscitation (CPR). The aim of this study is to evaluate the number and pattern of CPR-related injuries in ROSC patients with SCA-WBCT. Single-centre retrospective review of 39 patients (13 female; 20 male, mean age 51.8 years) with non-traumatic, out-of-hospital SCA and ROSC and evaluation with dedicated SCA-WBCT over a 10-month period. In-hospital mortality was 54%. CPR-related injuries were detected in 85% (33/39). Chest injuries were most common on WBCT: 85% (33) subjects had rib fractures (mean of 8.5 fractures/subject); 31% (12) sternal fractures; 13% (5) mediastinal haematoma; 10% (4) pneumothorax; 8% (3) pneumomediastinum and 3% (1) haemothorax. Three subjects (8%) had abdominal injuries on WBCT, including one hepatic haematoma with active haemorrhage. CPR-related injuries on WBCT after ROSC are common, with serial rib fractures detected most commonly. An unexpectedly high rate of abdominal injuries was detected on SCA-WBCT. Radiologists need to be attuned to the spectrum of CPR-related injuries in WBCT, including abdominal injuries and subtle rib fractures. • CPR frequently causes injuries. • Radiologists should be aware of the spectrum of CPR related injuries. • Rib fractures are frequent and radiologic findings often subtle. • Clinically unexpected abdominal injuries may be present.

Cancer in Machado-Joseph disease patients-low frequency as a cause of death.

PubMed

Souza, Gabriele Nunes; Kersting, Nathália; Gonçalves, Thomaz Abramsson; Pacheco, Daphne Louise Oliveira; Saraiva-Pereira, Maria-Luiza; Camey, Suzi Alves; Saute, Jonas Alex Morales; Jardim, Laura Bannach

2017-04-01

Since polyglutamine diseases have been related to a reduced risk of cancer, we aimed to study the 15 years cumulative incidence of cancer (CIC) (arm 1) and the proportion of cancer as a cause of death (arm 2) in symptomatic carriers of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). SCA3/MJD and control individuals from our state were invited to participate. A structured interview was performed. CIC as published by the Brazilian National Institute of Cancer, was used as populational control. Causes of death were obtained from the Public Information System on Mortality. We interviewed 154 SCA3/MJD patients and 80 unrelated controls: CIC was 7/154 (4.5%) and 5/80 (6.3%), respectively. The interim analysis for futility showed that the number of individuals required to detect a significant difference between groups (1938) would be three times larger than the existing local SCA3/MJD population (625), for an absolute risk reduction of 1.8%. Then this study arm was discontinued due to lack of power. In the same period, cancer was a cause of death in 9/101 (8.9%) SCA3/MJD and in 52/202 (26.2%) controls, with an absolute reduction risk of 17.3% (OR 0.27, 95%CI 0.13 to 0.58, p = 0.01). A significant reduction of cancer as cause of death was observed in SCA3/MJD, suggesting a common effect to all polyglutamine diseases. Copyright © 2017. Published by Elsevier Inc.

Quantitative assessment of cerebral blood flow in genetically confirmed spinocerebellar ataxia type 6.

PubMed

Honjo, Kie; Ohshita, Tomohiko; Kawakami, Hideshi; Naka, Hiromitsu; Imon, Yukari; Maruyama, Hirofumi; Mimori, Yasuyo; Matsumoto, Masayasu

2004-06-01

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by CAG trinucleotide expansion. The characteristics of regional cerebral blood flow (rCBF) in SCA6 patients have not been established, whereas it has been reported that decreased rCBF in the cerebrum seems to be a remote effect of cerebellar impairment in other cerebellar disorders. To clarify the characteristics of rCBF, including cerebro-cerebellar relationship, and its correlation with clinical manifestations in patients with genetically confirmed SCA6 using quantitative assessment of rCBF by brain single-photon emission computed tomography (SPECT). Technetium Tc 99m ethyl cysteinate dimer SPECT study using a Patlak plot. Patients Hiroshima University Hospital, Hiroshima, Japan. Ten patients with SCA6 and 9 healthy controls. Main Outcome Measure The rCBF of the cerebellar vermis, cerebellar hemisphere, and frontal lobes. In SCA6 patients, rCBF was decreased only in the cerebellar vermis and hemisphere compared with healthy controls, and this was inversely correlated with duration of illness. The rCBF in the frontal lobes was slightly correlated with duration of illness without statistical significance. The rCBF in the vermis was inversely correlated with severity of dysarthria, but there was no significant correlation with CAG repeated expansions. Decrease in rCBF was found only in the cerebellum and was associated with duration of illness, dysarthria and ataxia, and cerebellar atrophy. No remote effect of cerebellar hypoperfusion was found in the SCA6 patients.

Sickle cell anemia induces changes in peripheral lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in patients under treatment.

PubMed

Castilhos, Lívia G; Doleski, Pedro H; Bertoldo, Tatiana M D; Passos, Daniela F; Bertoncheli, Claudia de M; Rezer, João F P; Schlemmer, Josiane B; Leal, Daniela B R

2015-07-01

Sickle cell anemia (SCA) is characterized by hemoglobin polymerization that results in sickle-shaped red blood cells. The vascular obstruction by sickle erythrocytes is often inflammatory, and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune response. This study aimed to evaluate the E-NTPDase and E-ADA activities in lymphocytes of SCA treated patients, as well as verify the cytokine profile in this population. Fifteen SCA treated patients and 30 health subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated from clot formation for the cytokines quantification. E-NTPDase (ATP and ADP as substrate) and E-ADA (adenosine as substrate) activities were increased in lymphocytes from SCA patients (P<0.001). The TNF-α and IL-6 serum cytokines showed decreased on SCA patients comparing to control (P<0.001). The regulation of extracellular nucleotides released in response to hypoxia and inflammation through E-NTPDase and E-ADA enzymes represent an important control of purine-mediated in the SCA disease, avoiding elevated adenosine levels in the extracellular medium and consequent organ injuries in these patients. The pro-inflammatory cytokines decreased levels by use of hydroxyurea occur in attempt to reduce the pro-inflammatory response and prevent vaso-oclusive crisis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Snow cover dynamics in Andean watersheds of Chile (32.0-39.5° S) during the years 2000-2016

NASA Astrophysics Data System (ADS)

Stehr, Alejandra; Aguayo, Mauricio

2017-10-01

Andean watersheds present important snowfall accumulation mainly during the winter, which melts during the spring and part of the summer. The effect of snowmelt on the water balance can be critical to sustain agriculture activities, hydropower generation, urban water supplies and wildlife. In Chile, 25 % of the territory between the region of Valparaiso and Araucanía comprises areas where snow precipitation occurs. As in many other difficult-to-access regions of the world, there is a lack of hydrological data of the Chilean Andes related to discharge, snow courses, and snow depths, which complicates the analysis of important hydrological processes (e.g. water availability). Remote sensing provides a promising opportunity to enhance the assessment and monitoring of the spatial and temporal variability of snow characteristics, such as the snow cover area (SCA) and snow cover dynamic (SCD). With regards to the foregoing questions, the objective of the study is to evaluate the spatiotemporal dynamics of the SCA at five watersheds (Aconcagua, Rapel, Maule, Biobío and Toltén) located in the Chilean Andes, between latitude 32.0 and 39.5° S, and to analyse its relationship with the precipitation regime/pattern and El Niño-Southern Oscillation (ENSO) events. Those watersheds were chosen because of their importance in terms of their number of inhabitants, and economic activities depending on water resources. The SCA area was obtained from MOD10A2 for the period 2000-2016, and the SCD was analysed through a number of statistical tests to explore observed trends. In order to verify the SCA for trend analysis, a validation of the MOD10A2 product was done, consisting of the comparison of snow presence predicted by MODIS with ground observations. Results indicate that there is an overall agreement of 81 to 98 % between SCA determined from ground observations and MOD10A2, showing that the MODIS snow product can be taken as a feasible remote sensing tool for SCA estimation in southern-central Chile. Regarding SCD, no significant reduction in SCA for the period 2000-2016 was detected, with the exception of the Aconcagua and Rapel watersheds. In addition to that, an important decline in SCA in the five watersheds for the period of 2012 and 2016 was also evident, which is coincidental with the rainfall deficit for the same years. Findings were compared against ENSO episodes that occurred during 2010-2016, detecting that Niña years are coincident with maximum SCA during winter in all watersheds.

Prevalence of pure versus mixed snow cover pixels across spatial resolutions in alpine environments: implications for binary and fractional remote sensing approaches

USGS Publications Warehouse

Selkowitz, David J.; Forster, Richard; Caldwell, Megan K.

2014-01-01

Remote sensing of snow-covered area (SCA) can be binary (indicating the presence/absence of snow cover at each pixel) or fractional (indicating the fraction of each pixel covered by snow). Fractional SCA mapping provides more information than binary SCA, but is more difficult to implement and may not be feasible with all types of remote sensing data. The utility of fractional SCA mapping relative to binary SCA mapping varies with the intended application as well as by spatial resolution, temporal resolution and period of interest, and climate. We quantified the frequency of occurrence of partially snow-covered (mixed) pixels at spatial resolutions between 1 m and 500 m over five dates at two study areas in the western U.S., using 0.5 m binary SCA maps derived from high spatial resolution imagery aggregated to fractional SCA at coarser spatial resolutions. In addition, we used in situ monitoring to estimate the frequency of partially snow-covered conditions for the period September 2013–August 2014 at 10 60-m grid cell footprints at two study areas with continental snow climates. Results from the image analysis indicate that at 40 m, slightly above the nominal spatial resolution of Landsat, mixed pixels accounted for 25%–93% of total pixels, while at 500 m, the nominal spatial resolution of MODIS bands used for snow cover mapping, mixed pixels accounted for 67%–100% of total pixels. Mixed pixels occurred more commonly at the continental snow climate site than at the maritime snow climate site. The in situ data indicate that some snow cover was present between 186 and 303 days, and partial snow cover conditions occurred on 10%–98% of days with snow cover. Four sites remained partially snow-free throughout most of the winter and spring, while six sites were entirely snow covered throughout most or all of the winter and spring. Within 60 m grid cells, the late spring/summer transition from snow-covered to snow-free conditions lasted 17–56 days and averaged 37 days. Our results suggest that mixed snow-covered snow-free pixels are common at the spatial resolutions imaged by both the Landsat and MODIS sensors. This highlights the additional information available from fractional SCA products and suggests fractional SCA can provide a major advantage for hydrological and climatological monitoring and modeling, particularly when accurate representation of the spatial distribution of snow cover is critical.

Prevalence of spinocerebellar ataxia 36 in a US population

PubMed Central

Valera, Juliana M.; Diaz, Tatyana; Petty, Lauren E.; Quintáns, Beatriz; Yáñez, Zuleima; Boerwinkle, Eric; Muzny, Donna; Akhmedov, Dmitry; Berdeaux, Rebecca; Sobrido, Maria J.; Gibbs, Richard; Lupski, James R.; Geschwind, Daniel H.; Perlman, Susan; Below, Jennifer E.

2017-01-01

Objective: To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States. Methods: A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the NOP56 gene. Results: Fragment analysis of triplet repeat primed PCR products identified a GGCCTG hexanucleotide repeat expansion in intron 1 of NOP56 in 4 index cases. These 4 SCA36-positive families comprised 2 distinct ethnic groups: white (European) (2) and Asian (Japanese [1] and Vietnamese [1]). Individuals affected by SCA36 exhibited typical clinical features with gait ataxia and age at onset ranging between 35 and 50 years. Patients also suffered from ataxic or spastic limbs, altered reflexes, abnormal ocular movement, and cognitive impairment. Conclusions: In a US population, SCA36 was observed to be a rare disorder, accounting for 0.7% (4/577 index cases) of disease in a large undiagnosed ataxia cohort. PMID:28761930

Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6.

PubMed

Rochester, Lynn; Galna, Brook; Lord, Sue; Mhiripiri, Dadirayi; Eglon, Gail; Chinnery, Patrick F

2014-02-01

Spinocerebellar ataxia type 6 (SCA6) is an inherited ataxia with no established treatment. Gait ataxia is a prominent feature causing substantial disability. Understanding the evolution of the gait disturbance is a key step in developing treatment strategies. We studied 9 gait variables in 24 SCA6 (6 presymptomatic; 18 symptomatic) and 24 controls and correlated gait with clinical severity (presymptomatic and symptomatic). Discrete gait characteristics precede symptoms in SCA6 with significantly increased variability of step width and step time, whereas a more global gait deficit was evident in symptomatic individuals. Gait characteristics discriminated between presymptomatic and symptomatic individuals and were selectively associated with disease severity. This is the largest study to include a detailed characterization of gait in SCA6, including presymptomatic subjects, allowing changes across the disease spectrum to be compared. Selective gait disturbance is already present in SCA6 before clinical symptoms appear and gait characteristics are also sensitive to disease progression. Early gait disturbance likely reflects primary pathology distinct from secondary changes. These findings open the opportunity for early evaluation and sensitive measures of therapeutic efficacy using instrumented gait analysis which may have broader relevance for all degenerative ataxias. © 2013 Movement Disorder Society.

Spinocerebellar ataxia type 6.

PubMed

Solodkin, Ana; Gomez, Christopher M

2012-01-01

The autosomal dominant spinocerebellar ataxias (SCA) are a genetically heterogeneous group of neurodegenerative disorders characterized by progressive motor incoordination, in some cases with ataxia alone and in others in association with additional progressive neurological deficits. Spinocerebellar ataxia type 6 (SCA6) is the prototype of a pure cerebellar ataxia, associated with a severe form of progressive ataxia and cerebellar dysfunction. SCA6, originally classified as such by Zhuchenko et al. (1997), is caused by a CAG repeat expansion in the CACNA1A gene which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel. SCA6 is one of ten polyglutamine-encoding CAG nucleotide repeat expansion disorders comprising other neurodegenerative disorders such as Huntington's disease. The present review describes clinical, genetic, and pathological manifestations associated with this illness. Currently, there is no treatment for this neurodegenerative disease. Successful therapeutic strategies must target a valid pathological mechanism; thus, understanding the underlying mechanisms of disease is crucial to finding a proper treatment. Hence, this chapter will discuss as well the molecular mechanisms possibly associated with SCA6 pathology and their implication for the development of future treatment. 2012 Elsevier B.V. All rights reserved.

Visual Suppression is Impaired in Spinocerebellar Ataxia Type 6 but Preserved in Benign Paroxysmal Positional Vertigo

PubMed Central

Kishi, Masahiko; Sakakibara, Ryuji; Yoshida, Tomoe; Yamamoto, Masahiko; Suzuki, Mitsuya; Kataoka, Manabu; Tsuyusaki, Yohei; Tateno, Akihiko; Tateno, Fuyuki

2012-01-01

Positional vertigo is a common neurologic emergency and mostly the etiology is peripheral. However, central diseases may mimic peripheral positional vertigo at their initial presentation. We here describe the results of a visual suppression test in six patients with spinocerebellar ataxia type 6 (SCA6), a central positional vertigo, and nine patients with benign paroxysmal positional vertigo (BPPV), the major peripheral positional vertigo. As a result, the visual suppression value of both diseases differed significantly; e.g., 22.5% in SCA6 and 64.3% in BPPV (p < 0.001). There was a positive correlation between the visual suppression value and disease duration, cerebellar atrophy, and CAG repeat length of SCA6 but they were not statistically significant. In conclusion, the present study showed for the first time that visual suppression is impaired in SCA6, a central positional vertigo, but preserved in BPPV, the major peripheral positional vertigo, by directly comparing both groups. The abnormality in the SCA6 group presumably reflects dysfunction in the central visual fixation pathway at the cerebellar flocculus and nodulus. This simple test might aid differential diagnosis of peripheral and central positional vertigo at the earlier stage of disease. PMID:26859398

The effect of 3,4-diaminopyridine on the patients with hereditary pure cerebellar ataxia.

PubMed

Tsunemi, Taiji; Ishikawa, Kinya; Tsukui, Kei; Sumi, Takuro; Kitamura, Ken; Mizusawa, Hidehiro

2010-05-15

Downbeat nystagmus (DBN) is often seen in patients with pure cerebellar type of spinocerebellar ataxia (SCA) like spinocerebellar ataxia type 6 (SCA6). DBN frequently presents with other cerebellar symptoms such as postural imbalance or ataxia. A potassium channel blocker 3,4-diaminopyridine (3,4-DAP) has been reported to reduce DBN by increasing the excitability of Purkinje cells. The objective of this study is to determine whether 3,4-DAP has a beneficial effect on DBN along with postural imbalance and ataxic symptoms in 10 patients with SCA6 and five patients with chromosome 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA). The patients took 20mg of 3,4-DAP twice a day for a week. DBN was observed in seven patients with SCA6 and two with 16q-ADCA. Although 3,4-DAP significantly reduced DBN (P<0.05), other ataxic symptoms did not improved. However, 3,4-DAP showed benefit in two patients with oscillopsia. 3,4-DAP may be effective on DBN and oscillopsia, although it was not proved to be effective on other symptoms of ataxia in SCA patients. Copyright 2010 Elsevier B.V. All rights reserved.

Detection of Impaired Cerebral Autoregulation Using Selected Correlation Analysis: A Validation Study

PubMed Central

Brawanski, Alexander

2017-01-01

Multimodal brain monitoring has been utilized to optimize treatment of patients with critical neurological diseases. However, the amount of data requires an integrative tool set to unmask pathological events in a timely fashion. Recently we have introduced a mathematical model allowing the simulation of pathophysiological conditions such as reduced intracranial compliance and impaired autoregulation. Utilizing a mathematical tool set called selected correlation analysis (sca), correlation patterns, which indicate impaired autoregulation, can be detected in patient data sets (scp). In this study we compared the results of the sca with the pressure reactivity index (PRx), an established marker for impaired autoregulation. Mean PRx values were significantly higher in time segments identified as scp compared to segments showing no selected correlations (nsc). The sca based approach predicted cerebral autoregulation failure with a sensitivity of 78.8% and a specificity of 62.6%. Autoregulation failure, as detected by the results of both analysis methods, was significantly correlated with poor outcome. Sca of brain monitoring data detects impaired autoregulation with high sensitivity and sufficient specificity. Since the sca approach allows the simultaneous detection of both major pathological conditions, disturbed autoregulation and reduced compliance, it may become a useful analysis tool for brain multimodal monitoring data. PMID:28255331

Detection of Impaired Cerebral Autoregulation Using Selected Correlation Analysis: A Validation Study.

PubMed

Proescholdt, Martin A; Faltermeier, Rupert; Bele, Sylvia; Brawanski, Alexander

2017-01-01

Multimodal brain monitoring has been utilized to optimize treatment of patients with critical neurological diseases. However, the amount of data requires an integrative tool set to unmask pathological events in a timely fashion. Recently we have introduced a mathematical model allowing the simulation of pathophysiological conditions such as reduced intracranial compliance and impaired autoregulation. Utilizing a mathematical tool set called selected correlation analysis (sca), correlation patterns, which indicate impaired autoregulation, can be detected in patient data sets (scp). In this study we compared the results of the sca with the pressure reactivity index (PRx), an established marker for impaired autoregulation. Mean PRx values were significantly higher in time segments identified as scp compared to segments showing no selected correlations (nsc). The sca based approach predicted cerebral autoregulation failure with a sensitivity of 78.8% and a specificity of 62.6%. Autoregulation failure, as detected by the results of both analysis methods, was significantly correlated with poor outcome. Sca of brain monitoring data detects impaired autoregulation with high sensitivity and sufficient specificity. Since the sca approach allows the simultaneous detection of both major pathological conditions, disturbed autoregulation and reduced compliance, it may become a useful analysis tool for brain multimodal monitoring data.

Alpha-thalassaemia promotes frequent vaso-occlusive crises in children with sickle cell anaemia through haemorheological changes.

PubMed

Renoux, Céline; Connes, Philippe; Nader, Elie; Skinner, Sarah; Faes, Camille; Petras, Marie; Bertrand, Yves; Garnier, Nathalie; Cuzzubbo, Daniela; Divialle-Doumdo, Lydia; Kebaïli, Kamila; Renard, Cécile; Gauthier, Alexandra; Etienne-Julan, Maryse; Cannas, Giovanna; Martin, Cyril; Hardy-Dessources, Marie-Dominique; Pialoux, Vincent; Romana, Marc; Joly, Philippe

2017-08-01

Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic clinical complications. While β S -haplotypes and alpha-thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA. Steady-state haemorheological profile, biological parameters, β S -haplotypes, alpha-globin status, vaso-occlusive crisis (VOC) and acute chest syndrome frequencies were analysed in 128 children (aged 5 to 18 years) with SCA. Patients with alpha-thalassaemia showed increased red blood cell (RBC) deformability and aggregation compared to those without. Median VOC rate was higher in patients with homozygous alpha-thalassaemia compared to those with a normal alpha genotype. Conversely, the haemorheological profile and clinical complications were not influenced by the β S -haplotypes in our study. Our results demonstrate that alpha-thalassaemia is associated with higher risk for VOC events in children with SCA, which may be due in part to its effects on RBC deformability and aggregation. © 2017 Wiley Periodicals, Inc.

Genetics Home Reference: spinocerebellar ataxia type 6

MedlinePlus

... Twitter Home Health Conditions SCA6 Spinocerebellar ataxia type 6 Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Spinocerebellar ataxia type 6 ( SCA6 ) is a condition characterized by progressive problems ...

SCaN Network Ground Station Receiver Performance for Future Service Support

NASA Technical Reports Server (NTRS)

Estabrook, Polly; Lee, Dennis; Cheng, Michael; Lau, Chi-Wung

2012-01-01

Objectives: Examine the impact of providing the newly standardized CCSDS Low Density Parity Check (LDPC) codes to the SCaN return data service on the SCaN SN and DSN ground stations receivers: SN Current Receiver: Integrated Receiver (IR). DSN Current Receiver: Downlink Telemetry and Tracking (DTT) Receiver. Early Commercial-Off-The-Shelf (COTS) prototype of the SN User Service Subsystem Component Replacement (USS CR) Narrow Band Receiver. Motivate discussion of general issues of ground station hardware design to enable simple and cheap modifications for support of future services.

Spinocerebellar ataxia: a rational approach to aetiological diagnosis.

PubMed

Degardin, Adrian; Dobbelaere, Dries; Vuillaume, Isabelle; Defoort-Dhellemmes, Sabine; Hurtevent, Jean-François; Sablonnière, Bernard; Destée, Alain; Defebvre, Luc; Devos, David

2012-03-01

The objective of this study was to determine the main causal diagnosis for spinocerebellar ataxia (SCA) in a geographically defined population of ataxia patients and to suggest a rational basis for choosing appropriate clinical and paraclinical assessments. Given the many aetiologies responsible for SCA, the diagnosis requires the performance of a wide range of paraclinical analyses. At present, there is no consensus on the diagnostic value of these examinations. Furthermore, most of the currently available data gathered by reference centres suffer from selection bias. We performed a prospective study of consecutive cerebellar ataxia patients referred by their family doctors to a university hospital in northern France. Multiple system atrophy and obvious secondary causes (e.g. alcoholism) were excluded by our screening process. The patient's family members were also assessed. Of the 204 patients examined, 47% presented autosomal dominant ataxia and 33% presented sporadic ataxia. Autosomal recessive ataxia was rare (8%) and age at onset was significantly earlier for this condition than for other forms. An aetiological diagnosis was established in 44% of patients, a plausible hypothesis could be formed in 13% of cases, and no diagnosis was made in the remaining 44%. Established diagnoses included SCA1, SCA2, SCA3 and SCA6 mutations, Friedreich's ataxia, and one rare case of ataxia associated with anti-glutamic acid decarboxylase antibodies. Two families presented ataxia associated with autosomal, dominant, optic atrophy with an OPA1 mutation. Mitochondrial diseases were suspected in about 10% of patients. In SCA, reliable determination of the transmission mode always requires the assessment of family members. Mitochondrial disease may be an emerging cause of ataxia. Metabolite assays appeared to be of little value when systematically performed and so should be prescribed only by metabolic disorder specialists in selected cases of sporadic and recessive ataxia. Ophthalmological examination was the most helpful physiological assessment.

Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population

PubMed Central

Faruq, Mohammed; Srivastava, Achal Kumar; Singh, Suman; Gupta, Rohit; Dada, Tanuj; Garg, Ajay; Behari, Madhuri; Mukerji, Mitali

2015-01-01

Background & objectives: Spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies. Methods: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location). Results: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that<49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population. Interpretations & conclusion: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7. PMID:25900954

The indole compound NC009-1 inhibits aggregation and promotes neurite outgrowth through enhancement of HSPB1 in SCA17 cells and ameliorates the behavioral deficits in SCA17 mice.

PubMed

Chen, Chiung-Mei; Chen, Wan-Ling; Hung, Chen-Ting; Lin, Te-Hsien; Chao, Chih-Ying; Lin, Chih-Hsin; Wu, Yih-Ru; Chang, Kuo-Hsuan; Yao, Ching-Fa; Lee-Chen, Guey-Jen; Su, Ming-Tsan; Hsieh-Li, Hsiu Mei

2018-06-21

Spinocerebellar ataxia type 17 (SCA17) is caused by the expansion of translated CAG repeat in the TATA box binding protein (TBP) gene encoding a long polyglutamine (polyQ) tract in the TBP protein, which leads to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On cells with inducible SCA17 TBP/Q 79 -GFP expression to test five in-house NC009 indole compounds for neuroprotection. We found that both aggregation and polyQ-induced reactive oxygen species can be significantly prohibited by the tested NC009 compounds in Tet-On TBP/Q 79 293 cells. Among the five indole compounds, NC009-1 up-regulated expression of heat shock protein family B (small) member 1 (HSPB1) chaperone to reduce polyQ aggregation and promote neurite outgrowth in neuronal differentiated TBP/Q 79 SH-SY5Y cells. The increased HSPB1 thus ameliorated the increased BH3 interacting domain death agonist (BID), cytochrome c (CYCS) release, and caspase 3 (CASP3) activation which result in apoptosis. Knock down of HSPB1 attenuated the effects of NC009-1 on TBP/Q 79 SH-SY5Y cells, suggesting that HSPB1 might be one of the major pathways involved for NC009-1 effects. NC009-1 further reduced polyQ aggregation in Purkinje cells and ameliorated behavioral deficits in SCA17 TBP/Q 109 transgenic mice. Our results suggest that NC009-1 has a neuroprotective effect on SCA17 cell and mouse models to support its therapeutic potential in SCA17 treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Utility of T-wave amplitude as a non-invasive risk marker of sudden cardiac death in hypertrophic cardiomyopathy.

PubMed

Sugrue, Alan; Killu, Ammar M; DeSimone, Christopher V; Chahal, Anwar A; Vogt, Josh C; Kremen, Vaclav; Hai, JoJo; Hodge, David O; Acker, Nancy G; Geske, Jeffrey B; Ackerman, Michael J; Ommen, Steve R; Lin, Grace; Noseworthy, Peter A; Brady, Peter A

2017-01-01

Sudden cardiac arrest (SCA) is the most devastating outcome in hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the surface electrocardiogram (ECG) to identify the potential risk factors for SCA. Data was collected from 52 patients with HCM who underwent implantable cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG closest to the time of ICD implant were utilised for measuring the Tpeak-Tend interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude. The presence of the five traditional SCA-associated risk factors was assessed, as well as the HCM risk-SCD score. 16 (30%) patients experienced aborted cardiac arrest over 8.5±4.1 years, with 9 receiving an ICD shock and 7 receiving ATP. On univariate analysis, T-wave amplitude was associated with appropriate ICD therapy (HR per 0.1 mV 0.79, 95% CI 0.56 to 0.96, p=0.02). Aborted SCA was not associated with a greater mean QTc duration, Tpeak-Tend interval, T-wave duration, or Tpe/QT ratio. Multivariate analysis (adjusting for cardinal HCM SCA-risk factors) showed T-wave amplitude in Lead V2 was an independent predictor of risk (adjusted HR per 0.1 mV 0.74, 95% CI 0.57 to 0.97, p=0.03). Addition of T-wave amplitude in Lead V2 to the traditional risk factors resulted in significant improvement in risk stratification (C-statistic from 0.65 to 0.75) but did not improve the performance of the HCM SCD-risk score. T-wave amplitude is a novel marker of SCA in this high risk HCM population and may provide incremental predictive value to established risk factors. Further work is needed to define the role of repolarisation abnormalities in predicting SCA in HCM.

Sex chromosome aneuploidies and copy-number variants: a further explanation for neurodevelopmental prognosis variability?

PubMed

Le Gall, Jessica; Nizon, Mathilde; Pichon, Olivier; Andrieux, Joris; Audebert-Bellanger, Séverine; Baron, Sabine; Beneteau, Claire; Bilan, Frédéric; Boute, Odile; Busa, Tiffany; Cormier-Daire, Valérie; Ferec, Claude; Fradin, Mélanie; Gilbert-Dussardier, Brigitte; Jaillard, Sylvie; Jønch, Aia; Martin-Coignard, Dominique; Mercier, Sandra; Moutton, Sébastien; Rooryck, Caroline; Schaefer, Elise; Vincent, Marie; Sanlaville, Damien; Le Caignec, Cédric; Jacquemont, Sébastien; David, Albert; Isidor, Bertrand

2017-08-01

Sex chromosome aneuploidies (SCA) is a group of conditions in which individuals have an abnormal number of sex chromosomes. SCA, such as Klinefelter's syndrome, XYY syndrome, and Triple X syndrome are associated with a large range of neurological outcome. Another genetic event such as another cytogenetic abnormality may explain a part of this variable expressivity. In this study, we have recruited fourteen patients with intellectual disability or developmental delay carrying SCA associated with a copy-number variant (CNV). In our cohort (four patients 47,XXY, four patients 47,XXX, and six patients 47,XYY), seven patients were carrying a pathogenic CNV, two a likely pathogenic CNV and five a variant of uncertain significance. Our analysis suggests that CNV might be considered as an additional independent genetic factor for intellectual disability and developmental delay for patients with SCA and neurodevelopmental disorder.

Heme-mediated cell activation: the inflammatory puzzle of sickle cell anemia.

PubMed

Guarda, Caroline Conceição da; Santiago, Rayra Pereira; Fiuza, Luciana Magalhães; Aleluia, Milena Magalhães; Ferreira, Júnia Raquel Dutra; Figueiredo, Camylla Vilas Boas; Yahouedehou, Setondji Cocou Modeste Alexandre; Oliveira, Rodrigo Mota de; Lyra, Isa Menezes; Gonçalves, Marilda de Souza

2017-06-01

Hemolysis triggers the onset of several clinical manifestations of sickle cell anemia (SCA). During hemolysis, heme, which is derived from hemoglobin (Hb), accumulates due to the inability of detoxification systems to scavenge sufficiently. Heme exerts multiple harmful effects, including leukocyte activation and migration, enhanced adhesion molecule expression by endothelial cells and the production of pro-oxidant molecules. Area covered: In this review, we describe the effects of heme on leukocytes and endothelial cells, as well as the features of vascular endothelial cells related to vaso-occlusion in SCA. Expert commentary: Free Hb, heme and iron, potent cytotoxic intravascular molecules released during hemolysis, can exacerbate, modulate and maintain the inflammatory response, a main feature of SCA. Endothelial cells in the vascular environment, as well as leukocytes, can become activated via the molecular signaling effects of heme. Due to the hemolytic nature of SCA, hemolysis represents an interesting therapeutic target for heme-scavenging purposes.

Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry

NASA Astrophysics Data System (ADS)

Shaked, Natan T.; Satterwhite, Lisa L.; Telen, Marilyn J.; Truskey, George A.; Wax, Adam

2011-03-01

We have applied wide-field digital interferometry (WFDI) to examine the morphology and dynamics of live red blood cells (RBCs) from individuals who suffer from sickle cell anemia (SCA), a genetic disorder that affects the structure and mechanical properties of RBCs. WFDI is a noncontact, label-free optical microscopy approach that can yield quantitative thickness profiles of RBCs and measurements of their membrane fluctuations at the nanometer scale reflecting their stiffness. We find that RBCs from individuals with SCA are significantly stiffer than those from a healthy control. Moreover, we show that the technique is sensitive enough to distinguish classes of RBCs in SCA, including sickle RBCs with apparently normal morphology, compared to the stiffer crescent-shaped sickle RBCs. We expect that this approach will be useful for diagnosis of SCA and for determining efficacy of therapeutic agents.

Long Term Performance Metrics of the GD SDR on the SCaN Testbed: The First Year on the ISS

NASA Technical Reports Server (NTRS)

Nappier, Jennifer; Wilson, Molly C.

2014-01-01

The General Dynamics (GD) S-Band software defined radio (SDR) in the Space Communications and Navigation (SCaN) Testbed on the International Space Station (ISS) provides experimenters an opportunity to develop and demonstrate experimental waveforms in space. The SCaN Testbed was installed on the ISS in August of 2012. After installation, the initial checkout and commissioning phases were completed and experimental operations commenced. One goal of the SCaN Testbed is to collect long term performance metrics for SDRs operating in space in order to demonstrate long term reliability. These metrics include the time the SDR powered on, the time the power amplifier (PA) is powered on, temperature trends, error detection and correction (EDAC) behavior, and waveform operational usage time. This paper describes the performance of the GD SDR over the first year of operations on the ISS.

Episodic ataxia and SCA6 within the same family due to the D302N CACNA1A gene mutation.

PubMed

Pradotto, Luca; Mencarelli, Monica; Bigoni, Matteo; Milesi, Alessandra; Di Blasio, Anna; Mauro, Alessandro

2016-12-15

Several dominant mutations of CACNA1A gene were associated with at least three different allelic disorders: spino-cerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2), and familial hemiplegic migraine-1 (FHM1). It is generally thought that loss-of-function mutations are associated with EA2, gain-of-function missense mutations with FHM1, and abnormal CAG expansions with SCA6. But, overlapping features, atypical symptoms and co-occurrence of distinct phenotypes within the same family were reported. We describe a four generation family showing different phenotypes ranging from EA2 to SCA6 and carrying the p.D302N CACNA1A gene mutation. In our family the phenotypes maintained separate and gender differences corresponding to different phenotypes were observed. Copyright © 2016 Elsevier B.V. All rights reserved.

Heat shock proteins as potential targets for protective strategies in neurodegeneration.

PubMed

Kampinga, Harm H; Bergink, Steven

2016-06-01

Protein aggregates are hallmarks of nearly all age-related neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and several polyglutamine diseases such as Huntington's disease and different forms of spinocerebellar ataxias (SCA; SCA1-3, SCA6, and SCA7). The collapse of cellular protein homoeostasis can be both a cause and a consequence of this protein aggregation. Boosting components of the cellular protein quality control system has been widely investigated as a strategy to counteract protein aggregates or their toxic consequences. Heat shock proteins (HSPs) play a central part in regulating protein quality control and contribute to protein aggregation and disaggregation. Therefore, HSPs are viable targets for the development of drugs aimed at reducing pathogenic protein aggregates that are thought to contribute to the development of so many neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

SBIR Technology Applications to Space Communications and Navigation (SCaN)

NASA Technical Reports Server (NTRS)

Liebrecht, Phil; Eblen, Pat; Rush, John; Tzinis, Irene

2010-01-01

This slide presentation reviews the mission of the Space Communications and Navigation (SCaN) Office with particular emphasis on opportunities for technology development with SBIR companies. The SCaN office manages NASA's space communications and navigation networks: the Near Earth Network (NEN), the Space Network (SN), and the Deep Space Network (DSN). The SCaN networks nodes are shown on a world wide map and the networks are described. Two types of technologies are described: Pull technology, and Push technologies. A listing of technology themes is presented, with a discussion on Software defined Radios, Optical Communications Technology, and Lunar Lasercom Space Terminal (LLST). Other technologies that are being investigated are some Game Changing Technologies (GCT) i.e., technologies that offer the potential for improving comm. or nav. performance to the point that radical new mission objectives are possible, such as Superconducting Quantum Interference Filters, Silicon Nanowire Optical Detectors, and Auto-Configuring Cognitive Communications

Spinocerebellar ataxia in monozygotic twins.

PubMed

Anderson, John H; Christova, Peka S; Xie, Ting-dong; Schott, Kelly S; Ward, Kenneth; Gomez, Christopher M

2002-12-01

Although phenotypic heterogeneity in autosomal dominant spinocerebellar ataxia (SCA) has been explained in part by genotypic heterogeneity, clinical observations suggest the influence of additional factors. To demonstrate, quantitate, and localize physiologic abnormalities attributable to nongenetic factors in the development of hereditary SCA. Quantitative assessments of ocular motor function and postural control in 2 sets of identical twins, one with SCA type 2 and the other with episodic ataxia type 2. University laboratory. Saccadic velocity and amplitude, pursuit gain, and dynamic posturography. We found significant differences in saccade velocity, saccade metrics, and postural stability between each monozygotic twin. The differences point to differential involvement between twins of discrete regions in the cerebellum and brainstem. These results demonstrate the presence of quantitative differences in the severity, rate of progression, and regional central nervous system involvement in monozygotic twins with SCA that must be owing to the existence of nongermline or external factors.

Parental decisions following prenatal diagnosis of sex chromosome aneuploidy in Hong Kong.

PubMed

So, Po Lam; Cheng, Kwun Yue Yvonne; Cheuk, Kwan Yiu; Chiu, Wan Kam; Mak, Shui Lam; Mok, Sau Lan; Lo, Tsz Kin; Yung, Wai Kuen; Lo, Fai Man; Chung, Hon Yin Brian; Kan, Sik Yau Anita; Lee, Chin Peng; Tang, Hoi Yin Mary

2017-12-01

According to the published work, pregnancy termination rates due to prenatal diagnosis of fetal sex chromosome aneuploidies (SCA) vary widely. Some potentially modifiable and non-modifiable factors have been reported to be associated with parental decision. This study aimed to evaluate the rate of pregnancy termination for fetal SCA and the factors influencing parents' decisions in Hong Kong. This was a 21-year retrospective cohort study of parents' decisions following prenatal diagnosis of SCA. Univariate and multivariate analyses for the association between demographic factors, prenatal factors, or counseling provided and decision-making were conducted. The study included 399 pregnancies with prenatal diagnosis of SCA and the overall termination rate was 55.6% (91.7%, 48.0%, 23.4%, 4.8%, and 22.7% for 45,X, 47,XXY, 47,XXX, 47,XYY, and mosaicism, respectively). Pregnancies with ultrasound abnormalities were associated with higher termination rates than pregnancies with normal ultrasound findings (91.3% vs 28.3%, P < 0.0001). From multivariate regression analysis on 226 pregnancies with normal ultrasound examination, a higher likelihood to terminate was found in pregnancies affected by 45,X and 47,XXY (adjusted odds ratio, 4.72, P < 0.0001). Increased maternal age and history of infertility were associated with lower likelihood to terminate (adjusted odds ratio, 0.9, P = 0.012; and 5.12, P = 0.038, respectively). The pregnancy termination rate declined over time. A significant correlation was found between the termination of SCA-affected pregnancy and the presence of fetal sonographic abnormalities, type of SCA, maternal age, and presence of infertility. © 2017 Japan Society of Obstetrics and Gynecology.

Histological features of bone marrow in paediatric patients during the asymptomatic phase of early-stage Black African sickle cell anaemia.

PubMed

Mauriello, Alessandro; Giacobbi, Erica; Saggini, Andrea; Isgrò, Antonella; Facchetti, Simone; Anemona, Lucia

2017-04-01

Bone marrow histological features of sickle cell anaemia (SCA) patients during early stages and in the asymptomatic phase of the disease appear an interesting area of study, representing early-stage consequences of SCA with a close relation to its pathophysiology. Unfortunately, this field of research has never been specifically addressed before. Bone marrow biopsies from 26 consecutive Black African SCA patients (M:F=1.6:1; age 2-17 years), free of clinical signs of chronic bone marrow damage, with no recent history of symptomatic vaso-occlusive episodes, and waiting for haematopoietic stem cell transplantation (HSCT), underwent morphological, immunohistochemical and electron microscopy evaluation. Additional comparison with three bone marrow specimens from post-HSCT SCA patients and 10 bone marrow specimens from AS healthy carriers was performed. Bone marrow of SCA patients was normocellular or slighly hypercellular in all cases. Erythroid hyperplasia was a common feature. Myeloid lineage was slightly decreased with normal to slightly diminished neutrophilic granulocytes; CD68 positive monocytic-macrophagic cells appeared slightly increased, with a predominant CD163 positive M2/M(Hb) phenotype. A positive correlation was found between haemoglobin values and number of bone marrow erythroid cells (R 2 =0.15, p=0.05). Intravascular and interstitial clusters of erythroid sickle cells were found in bone marrow of pre-HSCT homozygous SS SCA patients, as well as heterozygous AS healthy carriers, and the single post-HSCT patient matched to an AS health carrier donor. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Evaluation of gridded snow water equivalent and satellite snow cover products for mountain basins in a hydrologic model

USGS Publications Warehouse

Dressler, K.A.; Leavesley, G.H.; Bales, R.C.; Fassnacht, S.R.

2006-01-01

The USGS precipitation-runoff modelling system (PRMS) hydrologic model was used to evaluate experimental, gridded, 1 km2 snow-covered area (SCA) and snow water equivalent (SWE) products for two headwater basins within the Rio Grande (i.e. upper Rio Grande River basin) and Salt River (i.e. Black River basin) drainages in the southwestern USA. The SCA product was the fraction of each 1 km2 pixel covered by snow and was derived from NOAA advanced very high-resolution radiometer imagery. The SWE product was developed by multiplying the SCA product by SWE estimates interpolated from National Resources Conservation Service snow telemetry point measurements for a 6 year period (1995-2000). Measured SCA and SWE estimates were consistently lower than values estimated from temperature and precipitation within PRMS. The greatest differences occurred in the relatively complex terrain of the Rio Grande basin, as opposed to the relatively homogeneous terrain of the Black River basin, where differences were small. Differences between modelled and measured snow were different for the accumulation period versus the ablation period and had an elevational trend. Assimilating the measured snowfields into a version of PRMS calibrated to achieve water balance without assimilation led to reduced performance in estimating streamflow for the Rio Grande and increased performance in estimating streamflow for the Black River basin. Correcting the measured SCA and SWE for canopy effects improved simulations by adding snow mostly in the mid-to-high elevations, where satellite estimates of SCA are lower than model estimates. Copyright ?? 2006 John Wiley & Sons, Ltd.

Spinocerebellar Ataxia 27: A Review and Characterization of an Evolving Phenotype

PubMed Central

Groth, Christopher L.; Berman, Brian D.

2018-01-01

Background Spinocerebellar ataxia (SCA) is an uncommon form of progressive cerebellar ataxia with multiple genetic causes and marked variability in phenotypic expression even across patients with identical genetic abnormalities. SCA27 is a recently identified SCA caused by mutations in the Fibroblast Growth Factor 14 gene, with a phenotypic expression that is only beginning to be fully appreciated. We report here a case of a 70-year-old male who presented with slowly worsening tremor and gait instability that began in his early adulthood along with additional features of parkinsonism on examination. Work-up revealed a novel pathogenic mutation in the Fibroblast Growth Factor 14 gene, and symptoms improved with amantadine and levodopa. We also provide a review of the literature in order to better characterize the phenotypic expression of this uncommon condition. Methods Case report and review of the literature. Results Review of the literature revealed a total of 32 previously reported clinical cases of SCA27. Including our case, we found that early-onset tremor (12.1 ± 10.5 years) was present in 95.8%, while gait ataxia tended to present later in life (23.7 ± 16.7 years) and was accompanied by limb ataxia, dysarthria, and nystagmus. Other features of SCA27 that may distinguish it from other SCAs include the potential for episodic ataxia, accompanying psychiatric symptoms, and cognitive impairment. Discussion Testing for SCA27 should be considered in individuals with ataxia who report tremor as an initial or early symptom, as well as those with additional findings of episodic ataxia, neuropsychiatric symptoms, or parkinsonism. PMID:29416937

White matter damage is related to ataxia severity in SCA3.

PubMed

Kang, J-S; Klein, J C; Baudrexel, S; Deichmann, R; Nolte, D; Hilker, R

2014-02-01

Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

Lack of association between some risk factors and hepatitis B surface antigenaemia in children with sickle cell anaemia.

PubMed

Angyo, I A; Yakubu, A M

2001-01-01

The risk factors for transmission of Hepatitis B virus (HBV) as well as the relationship between HBs Antigeneamia and some socio-cultural factors including socio-economic status of the families of the children, tribe, religion, rural or urban domicile and the number of persons per bedroom, were studied among 507 children with sickle cell anaemia (SCA) and 501 controls at the Jos University Teaching Hospital (JUTH). Twenty-three percent (22.7%) of the children with SCA were HBsAg positive compared with 19.6% among the control group. None of the risk factors studied, including blood transfusion, parenteral injections, intravenous infusions, hospitalization, ulcers, traditional uvulectomy, surgery, contact with case of known hepatitis, mass immunizations, circumcision, ear piercing and traditional scarifications was significantly associated with HBV infection in both children with SCA and control group and also between children with SCA compared with controls. There was also no association between HBs Antigenaemia and the number of blood transfusions, intravenous infusion or hospitalization in both children with SCA and controls. Similarly, there was no association between the socio-cultural factors studied and HBs Antigenaemia. The result of this study suggests that HBV infection is common in children in this environment and other factors yet to, be identified may play a very important role in the transmission of HBV infection. The high prevalence of HBsAg obtained in both children with SCA and controls, and the lack of identifiable association between the risk factos studied and HBsAntigenaemia suggest that these children may have equally been exposed earlier in life.

Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity.

PubMed

Torres-Ramos, Y; Montoya-Estrada, A; Cisneros, B; Tercero-Pérez, K; León-Reyes, G; Leyva-García, N; Hernández-Hernández, Oscar; Magaña, Jonathan J

2018-06-06

Spinocerebellar ataxia type 7 is a neurodegenerative inherited disease caused by a CAG expansion in the coding region of the ATXN7 gene, which results in the synthesis of polyglutamine-containing ataxin-7. Expression of mutant ataxin-7 disturbs different cell processes, including transcriptional regulation, protein conformation and clearance, autophagy, and glutamate transport; however, mechanisms underlying neurodegeneration in SCA7 are still unknown. Implication of oxidative stress in the pathogenesis of various neurodegenerative diseases, including polyglutamine disorders, has recently emerged. We perform a cross-sectional study to determine for the first time pheripheral levels of different oxidative stress markers in 29 SCA7 patients and 28 age- and sex-matched healthy subjects. Patients with SCA7 exhibit oxidative damage to lipids (high levels of lipid hydroperoxides and malondialdehyde) and proteins (elevated levels of advanced oxidation protein products and protein carbonyls). Furthermore, SCA7 patients showed enhanced activity of various anti-oxidant enzymes (glutathione reductase, glutathione peroxidase, and paraoxonase) as well as increased total anti-oxidant capacity, which suggest that activation of the antioxidant defense system might occur to counteract oxidant damage. Strikingly, we found positive correlation between some altered oxidative stress markers and disease severity, as determined by different clinical scales, with early-onset patients showing a more severe disturbance of the redox system than adult-onset patients. In summay, our results suggest that oxidative stress might contribute to SCA7 pathogenesis. Furthermore, oxidative stress biomarkers that were found relevant to SCA7 in this study could be useful to follow disease progression and monitor therapeutic intervention.

Importance of methodological standardization for the ektacytometric measures of red blood cell deformability in sickle cell anemia.

PubMed

Renoux, Céline; Parrow, Nermi; Faes, Camille; Joly, Philippe; Hardeman, Max; Tisdale, John; Levine, Mark; Garnier, Nathalie; Bertrand, Yves; Kebaili, Kamila; Cuzzubbo, Daniela; Cannas, Giovanna; Martin, Cyril; Connes, Philippe

2016-01-01

Red blood cell (RBC) deformability is severely decreased in patients with sickle cell anemia (SCA), which plays a role in the pathophysiology of the disease. However, investigation of RBC deformability from SCA patients demands careful methodological considerations. We assessed RBC deformability by ektacytometry (LORRCA MaxSis, Mechatronics, The Netherlands) in 6 healthy individuals and 49 SCA patients and tested the effects of different heights of the RBC diffraction patterns, obtained by altering the camera gain of the LORRCA, on the result of RBC deformability measurements, expressed as Elongation Index (EI). Results indicate that the pattern of RBCs from control subjects adopts an elliptical shape under shear stress, whereas the pattern of RBCs from individuals with SCA adopts a diamond shape arising from the superposition of elliptical and circular patterns. The latter represent rigid RBCs. While the EI measures did not change with the variations of the RBC diffraction pattern heights in the control subjects, we observed a decrease of EI when the RBC diffraction pattern height is increased in the SCA group. The differences in SCA EI values measured at 5 Pa between the different diffraction pattern heights correlated with the percent of hemoglobin S and the percent of sickled RBC observed by microscopy. Our study confirms that the camera gain or aperture of the ektacytometer should be used to standardize the size of the RBC diffraction pattern height when measuring RBC deformability in sickle cell patients and underscores the potential clinical utility of this technique.

Genetics Home Reference: spinocerebellar ataxia type 2

MedlinePlus

... are relatively rare. SCA2 is more common in Cuba, particularly in the Holguín province, where approximately 40 ... Cedeño H. Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin. Neurosci ...

Concentrating Solar Power Projects - Andasol-1 | Concentrating Solar Power

Science.gov Websites

: UTE CT Andasol-1: Cobra (80%) and Sener (20%) Operator(s): Cobra O&M Generation Offtaker(s # of Modules per SCA: 12 SCA Manufacturer (Model): UTE CT Andasol-1 (SKAL-ET) Mirror Manufacturer

Hormonal and echocardiographic abnormalities in adult patients with sickle-cell anemia in Bahrain

PubMed Central

Garadah, Taysir S; Jaradat, Ahmed A; Alalawi, Mohammed E; Hassan, Adla B

2016-01-01

Background Adrenal, thyroid, and parathyroid gland hormonal changes are recognized in children with homozygous (HbSS) sickle-cell anemia (SCA), but are not clear in adult patients with SCA. Aim To assess the metabolic and endocrine abnormalities in adult patients with SCA and evaluate left ventricular (LV) systolic and diastolic functions compared with patients with no SCA and further study the relationship between serum levels of cortisol, free thyroxine (T4), and testosterone with serum ferritin. Materials and methods The study was conducted on 82 patients with adult HbSS SCA compared with a sex- and age-matched control group. The serum levels of cortisol, parathyroid hormone (PTH), testosterone, thyroid-stimulating hormone (TSH), and free T4 were compared. Blood levels of hemoglobin, reticulocyte count, lactate dehydrogenase (LDH), calcium, alkaline phosphatase (ALP), vitamin D3, and ferritin were also compared. Pulsed Doppler echo was performed to evaluate the LV mass, wall thickness, and cavity dimensions with diastolic filling velocities of early (E) and atria (A) waves. Biometric data were analyzed as mean ± standard deviation between the two groups. Multiple regression analysis was performed between serum levels of ferritin as independent variable and testosterone, cortisol, and thyroid hormones. Results A total of 82 adult patients with HbSS SCA were enrolled who had a mean age of 21±5.7 years, with 51 males (62%). Patients with SCA compared with the control group had significantly lower hemoglobin, body mass index, cortisol, vitamin D3, testosterone, and T4. Furthermore, there were significantly high levels of reticulocyte count, PTH, TSH, ferritin, LDH, ALP, and uric acid. The incidence of subclinical hypothyroidism and adrenal insufficiency was 7% and 4.8%, respectively, with hypogonadism 9.8% and vitamin D3 deficiency 61%. There were inverse relationships between ferritin as independent variable and serum levels of testosterone, T4, and cortisol, with regression coefficients of −0.49 (P<0.001), −0.33 (P<0.001), and −0.11 (P<0.92), respectively. Conclusion Patients with adult SCA had a high prevalence of in vivo hypoadrenialism (4.8%), hypogonadism (9.8%), and hypothyroidism (7%). There were significant inverse relationships between serum ferritin as independent variable and cortisol, testosterone, and T4. Pulsed Doppler echocardiography showed increased LV mass, with a restrictive LV diastolic pattern suggestive of diastolic dysfunction. PMID:28008293

78 FR 5179 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... & Co. 20130257 G Equifax Inc.; Computer Sciences Corporation; Equifax Inc. 20130279 G Arsenal Capital.... 20130429 G Lagardere SCA; Excel Sports Management, LLC; Lagardere SCA. 12/19/2012 20130236 G Cisco Systems...

KSC-07pd1764

NASA Image and Video Library

2007-07-03

KENNEDY SPACE CENTER, FLA. -- On the KSC Shuttle Landing Facility, workers supervise the movement of the sling above the orbiter Atlantis. The sling will be attached and lift the orbiter away from the shuttle carrier aircraft (SCA) underneath. The SCA carried the orbiter piggyback from California. Atlantis landed at Edwards Air Force Base in California on June 22 to end mission STS-117. It returned to Kennedy atop the SCA on July 3 after a three-day, cross-country flight due to fuel stops and weather delays. Touchdown was at 8:27 a.m. EDT. Photo credit: NASA/Kim Shiflett

Endeavour, Orbiter Vehicle (OV) 105, atop SCA NASA 911 at Ellington Field

NASA Technical Reports Server (NTRS)

1991-01-01

Endeavour, Orbiter Vehicle (OV) 105, atop a Shuttle Carrier Aircraft (SCA) NASA 911, a modified Boeing 747, is parked on an Ellington Field runway during a stopover on its way to the Kennedy Space Center (KSC). A crowd gathers around the massive aircraft carrying the newest addition to the Space Shuttle fleet. This view is a good profile of SCA/OV-105 and shows the orbiter/aircraft attach points. The spacecraft and aircraft-tandem left Houston later on this day and headed for another stop in Mississippi before landing in Florida on 05-07-91.

Small Aircraft Transportation System Higher Volume Operations Concept

NASA Technical Reports Server (NTRS)

Abbott, Terence S.; Consiglio, Maria C.; Baxley, Brian T.; Williams, Daniel M.; Jones, Kenneth M.; Adams, Catherine A.

2006-01-01

This document defines the Small Aircraft Transportation System (SATS) Higher Volume Operations concept. The general philosophy underlying this concept is the establishment of a newly defined area of flight operations called a Self-Controlled Area (SCA). Within the SCA, pilots would take responsibility for separation assurance between their aircraft and other similarly equipped aircraft. This document also provides details for a number of off-nominal and emergency procedures which address situations that could be expected to occur in a future SCA. The details for this operational concept along with a description of candidate aircraft systems to support this concept are provided.

Transfusional iron overload in children with sickle cell anemia on chronic transfusion therapy for secondary stroke prevention.

PubMed

Kwiatkowski, Janet L; Cohen, Alan R; Garro, Julian; Alvarez, Ofelia; Nagasubramanian, Ramamorrthy; Sarnaik, Sharada; Thompson, Alexis; Woods, Gerald M; Schultz, William; Mortier, Nicole; Lane, Peter; Mueller, Brigitta; Yovetich, Nancy; Ware, Russell E

2012-02-01

Chronic transfusion reduces the risk of recurrent stroke in children with sickle cell anemia (SCA) but leads to iron loading. Management of transfusional iron overload in SCA has been reported as suboptimal [1], but studies characterizing monitoring and treatment practices for iron overload in children with SCA, particularly in recent years with the expansion of chelator options, are lacking. We investigated the degree of iron loading and treatment practices of 161 children with SCA receiving transfusions for a history of stroke who participated in the Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) trial. Data obtained during screening, including past and entry liver iron concentration (LIC) measurements, ferritin values, and chelation were analyzed. The mean age at enrollment was 12.9 ± 4 years and the mean duration of transfusion was 7 ± 3.8 years. Baseline LIC (median 12.94 mg/g dw) and serum ferritin (median 3,164 ng/mL) were elevated. Chelation therapy was initiated after a mean of 2.6 years of transfusions. At study entry, 137 were receiving chelation, most of whom (90%) were receiving deferasirox. This study underscores the need for better monitoring of iron burden with timely treatment adjustments in chronically transfused children with SCA.

Higher order scaffoldin assembly in Ruminococcus flavefaciens cellulosome is coordinated by a discrete cohesin-dockerin interaction.

PubMed

Bule, Pedro; Pires, Virgínia M R; Alves, Victor D; Carvalho, Ana Luísa; Prates, José A M; Ferreira, Luís M A; Smith, Steven P; Gilbert, Harry J; Noach, Ilit; Bayer, Edward A; Najmudin, Shabir; Fontes, Carlos M G A

2018-05-03

Cellulosomes are highly sophisticated molecular nanomachines that participate in the deconstruction of complex polysaccharides, notably cellulose and hemicellulose. Cellulosomal assembly is orchestrated by the interaction of enzyme-borne dockerin (Doc) modules to tandem cohesin (Coh) modules of a non-catalytic primary scaffoldin. In some cases, as exemplified by the cellulosome of the major cellulolytic ruminal bacterium Ruminococcus flavefaciens, primary scaffoldins bind to adaptor scaffoldins that further interact with the cell surface via anchoring scaffoldins, thereby increasing cellulosome complexity. Here we elucidate the structure of the unique Doc of R. flavefaciens FD-1 primary scaffoldin ScaA, bound to Coh 5 of the adaptor scaffoldin ScaB. The RfCohScaB5-DocScaA complex has an elliptical architecture similar to previously described complexes from a variety of ecological niches. ScaA Doc presents a single-binding mode, analogous to that described for the other two Coh-Doc specificities required for cellulosome assembly in R. flavefaciens. The exclusive reliance on a single-mode of Coh recognition contrasts with the majority of cellulosomes from other bacterial species described to date, where Docs contain two similar Coh-binding interfaces promoting a dual-binding mode. The discrete Coh-Doc interactions observed in ruminal cellulosomes suggest an adaptation to the exquisite properties of the rumen environment.

Spinocerebellum Ataxia Type 6: Molecular Mechanisms and Calcium Channel Genetics.

PubMed

Du, Xiaofei; Gomez, Christopher Manuel

2018-01-01

Spinocerebellar ataxia (SCA) type 6 is an autosomal dominant disease affecting cerebellar degeneration. Clinically, it is characterized by pure cerebellar dysfunction, slowly progressive unsteadiness of gait and stance, slurred speech, and abnormal eye movements with late onset. Pathological findings of SCA6 include a diffuse loss of Purkinje cells, predominantly in the cerebellar vermis. Genetically, SCA6 is caused by expansion of a trinucleotide CAG repeat in the last exon of longest isoform CACNA1A gene on chromosome 19p13.1-p13.2. Normal alleles have 4-18 repeats, while alleles causing disease contain 19-33 repeats. Due to presence of a novel internal ribosomal entry site (IRES) with the mRNA, CACNA1A encodes two structurally unrelated proteins with distinct functions within an overlapping open reading frame (ORF) of the same mRNA: (1) α1A subunit of P/Q-type voltage gated calcium channel; (2) α1ACT, a newly recognized transcription factor, with polyglutamine repeat at C-terminal end. Understanding the function of α1ACT in physiological and pathological conditions may elucidate the pathogenesis of SCA6. More importantly, the IRES, as the translational control element of α1ACT, provides a potential therapeutic target for the treatment of SCA6.

Identification of the physiological promoter for spinocerebellar ataxia 2 gene reveals a CpG island for promoter activity situated into the exon 1 of this gene and provides data about the origin of the nonmethylated state of these types of islands.

PubMed

Aguiar, J; Santurlidis, S; Nowok, J; Alexander, C; Rudnicki, D; Gispert, S; Schulz, W; Auburger, G

1999-01-19

In order to further use the spinocerebellar ataxia 2 (SCA2) promoter for transgenic mice models of "CAG repeat" neurodegeneration, different fragments of this 5' end were ligated into pGL3-Luc plasmid to obtain the better promoter-activity of the physiological promoter for SCA2. Base-par composition of the SCA2-5' region, and promoter prediction algorithms such as TSSW and TSSG, together with the high firefly luciferase expression after 48 hours of transient transfection in mammalian cells lines, showed a typical CpG island for promoter-activity. The promoter activity was specifically localized into the exon 1 of the SCA2 gene. The higher expression of firefly luciferase in the embryonal F9 cells by the use of SCA2 promoter, rather than by the use of CMV promoter may be related with the origin of the nonmethylated CpG island during the early embryogenesis. Analysis of the 5' region from HD gene revealed to a CpG island, which could be containing the physiological promoter for this gene. Copyright 1999 Academic Press.

Group Counseling: Health Related.

ERIC Educational Resources Information Center

McFadden, Johnnie

1979-01-01

Diabetes and sickle cell anemia (SCA) are two health-related characteristics that distinguish young people from their peers. This article outlines the problems of children with diabetes and SCA and presents the goals and format for group counseling of these populations and their parents. (Author/BEF)

Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs.

PubMed

Muguruma, Keiko

2018-02-01

Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that cerebellar tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable cerebellar disease.

Label-free screening of niche-to-niche variation in satellite stem cells using functionalized pores

NASA Astrophysics Data System (ADS)

Chapman, Matthew R.; Balakrishnan, Karthik; Conboy, Michael J.; Mohanty, Swomitra; Jabart, Eric; Huang, Haiyan; Hack, James; Conboy, Irina M.; Sohn, Lydia L.

2012-02-01

Combinations of surface markers are currently used to identify muscle satellite cells. Using pores functionalized with specific antibodies and measuring the transit time of cells passing through these pores, we discovered remarkable heterogeneity in the expression of these markers in muscle (satellite) stem cells that reside in different single myofibers. Microniche-specific variation in stem cells of the same organ has not been previously described, as bulk analysis does not discriminate between separate myofibers or even separate hind-leg muscle groups. We found a significant population of Sca-1+ satellite cells that form myotubes, thereby demonstrating the myogenic potential of Sca-1+ cells, which are currently excluded in bulk sorting. Finally, using our label-free pore screening technique, we have been able to quantify directly surface expression of Notch1 without activation of the Notch pathway. We show for the first time Notch1-expression heterogeneity in unactivated satellite cells. The discovery of fiber-to-fiber variations prompts new research into the reasons for such diversity in muscle stem cells.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke.

PubMed

Dowling, Michael M; Quinn, Charles T; Ramaciotti, Claudio; Kanter, Julie; Osunkwo, Ifeyinwa; Inusa, Baba; Iyer, Rathi; Kwiatkowski, Janet L; Johnson, Clarissa; Rhodes, Melissa; Owen, William; Strouse, John J; Panepinto, Julie A; Neumayr, Lynne; Sarnaik, Sharada; Plumb, Patricia A; Dlamini, Nomazulu; Kirkham, Fenella; Hynan, Linda S

2017-01-01

'Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6-4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA. © 2016 John Wiley & Sons Ltd.

Are sickle cell anaemia and sickle cell trait predictive factors for periodontal disease? A cohort study.

PubMed

de Carvalho, H L C C; Thomaz, E B A F; Alves, C M C; Souza, S F C

2016-10-01

Periodontal diseases are associated with bacterial challenge and the host immune response, and are also modulated by genetic factors. There is evidence that sickle cell anaemia (SCA) does not represent a risk factor for periodontal diseases. However, it is still unclear whether the heterozygous condition [sickle cell trait (SCT)] is associated with periodontal diseases. SCT is a genetic condition that can cause vaso-occlusive events, which may be associated with a propensity to bacterial infections. The aim of this study was to investigate the association of SCA and SCT with periodontal diseases by evaluating clinical and radiographic characteristics. The sample (n = 369) was selected and divided into two groups: exposed groups [HbSS (SCA genotype) and HbAS (SCT genotype) = 246] and a nonexposed group (HbAA = 123). HbAA consisted of individuals without SCA and SCT. The clinical parameters evaluated were plaque index, gingival index, calculus index, clinical probing depth, clinical attachment level, gingival recession, tooth mobility and furcation involvement. The percentage of alveolar bone loss was measured using a Schei ruler. Binomial and Poisson regressions were used to estimate correlations of interest (α = 0.05). None of the periodontal parameters was associated with SCA. SCT was associated with gingivitis (p = 0.041) and periodontitis (p = 0.002). Individuals with SCT had a lower plaque index (p = 0.044) but a higher calculus index (p = 0.003) and greater alveolar bone loss (p = 0.010) compared with subjects in the HbAA group. SCT can act as a predictor for establishment of periodontal diseases. There was no correlation between SCA and periodontal diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Wasting and stunting are still prevalent in children with sickle cell anaemia in Lagos, Nigeria.

PubMed

Esezobor, Christopher I; Akintan, Patricia; Akinsulie, Adebola; Temiye, Edamisan; Adeyemo, Titilope

2016-05-04

Sickle cell anaemia (SCA) is associated with growth failure. However, recent reports indicate high rates of overweight or obesity among children with SCA in developed countries. It is unclear whether overweight or obesity is also common in children with SCA in developing countries. The objectives of the study were to determine the prevalence of overweight or obesity, wasting and stunting and identify predictors of wasting and stunting among children with SCA in Nigeria. Children with SCA attending a public-funded tertiary hospital clinic were studied. Weight, height, haemoglobin, haemoglobin fractions and white cell count were measured. Anthropometric values were converted to z scores and referenced to the WHO Child Growth Standards and WHO Reference 2007. The proportions with wasting, stunting and overweight or obesity were determined. Regression analysis was used to identify the predictors of wasting and stunting. Two hundred and thirty-three children [mean (±SD) age of 9.0 (±4.0) years, 60.9 % males] participated in the study. Wasting, stunting and overweight or obesity rates were 22.7 %, 11.6 % and 1.7 %, respectively. Boys and children from low socioeconomic class were 3.25 (1.45-7.29) and 2.42 (1.14-5.18) times more likely to be wasted respectively, while both wasting and stunting were more common with increasing age [adjusted OR of 1.33 (1.18-1.51) and 1.15 (1.01-1.32) respectively]. Sickle cell-related complications and intake of oral penicillin and hydroxyurea were not associated with wasting and stunting. Overweight or obesity is uncommon while wasting and stunting are still prevalent in children with SCA in Lagos. The strongest predictors of wasting and stunting were older age, male gender and low socioeconomic status.

Prevalence of stroke in children admitted with sickle cell anaemia to Mulago Hospital.

PubMed

Munube, Deogratias; Katabira, Elly; Ndeezi, Grace; Joloba, Moses; Lhatoo, Samden; Sajatovic, Martha; Tumwine, James K

2016-09-17

Stroke is a major complication of sickle cell anaemia (SCA). It occurs commonly in childhood with about 10 % of children with sickle cell anaemia getting affected by this complication. In Uganda, there is paucity of data on the prevalence of stroke in children admitted in a tertiary institution. We determined the prevalence of stroke amongst children with SCA admitted to Mulago National Referral Hospital in Uganda and described the ir co-morbidities. We conducted a retrospective record review of children with SCA admitted from August 2012 to August 2014 to the Paediatric Haematology Ward of Mulago Hospital in Kampala, Uganda. The target population was SCA children age 6 months-17 years of age. A descriptive analysis was used to summarize the demographic characteristics and clinical diagnosis. There were 2,176 children with SCA admitted who were included in this study. There were 147 children with stroke. Their mean age 6.1, (SD 3), with a male to female ratio was 1:1 (71 males and 76 females). The M: F ratio of non-stroke children was 1.1:1 (1084 males and 945 females) with a mean age of 5.2, (SD 3). The prevalence of stroke was 6.8 % (147 of 2176). Amongst the children with stroke, 72.1 % (106 of 147) had co-morbidities which included severe anaemia 21.7 % (23 of 106), bacteraemia and vaso-occlusive crisis 17 % (18 of 106), pneumonia 8.4 % (9 of 106) and malaria 6.6 % (7 of 106). The prevalence of stroke in hospitalized Ugandan children with SCA was 6.8 %. Children with stroke were often admitted with other medical conditions such as severe anaemia, bacteraemia and vaso-occlusion.

Airway Hyperresponsiveness in Children With Sickle Cell Anemia

PubMed Central

Field, Joshua J.; Stocks, Janet; Kirkham, Fenella J.; Rosen, Carol L.; Dietzen, Dennis J.; Semon, Trisha; Kirkby, Jane; Bates, Pamela; Seicean, Sinziana; DeBaun, Michael R.; Redline, Susan

2011-01-01

Background: The high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained. Methods: To determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS. Results: Methacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV1 < 4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P < .001), IgE (P = .009), and lactate dehydrogenase (LDH) levels (P = .005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma (P = .986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction. Conclusions: In children with SCA, AHR to methacholine is prevalent. Younger age, serum IgE concentration, and LDH level, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies. PMID:20724735

Toxicity and aggregation of the polyglutamine disease protein, ataxin-3 is regulated by its binding to VCP/p97 in Drosophila melanogaster.

PubMed

Ristic, Gorica; Sutton, Joanna R; Libohova, Kozeta; Todi, Sokol V

2018-04-26

Among the nine dominantly inherited, age-dependent neurodegenerative diseases caused by abnormal expansion in the polyglutamine (polyQ) repeat of otherwise unrelated proteins is Spinocerebellar Ataxia Type 3 (SCA3). SCA3 is caused by polyQ expansion in the deubiquitinase (DUB), ataxin-3. Molecular sequelae related to SCA3 remain unclear. Here, we sought to understand the role of protein context in SCA3 by focusing on the interaction between this DUB and Valosin-Containing Protein (VCP). VCP is bound directly by ataxin-3 through an arginine-rich area preceding the polyQ repeat. We examined the importance of this interaction in ataxin-3-dependent degeneration in Drosophila melanogaster. Our assays with new isogenic fly lines expressing pathogenic ataxin-3 with an intact or mutated VCP-binding site show that disrupting the ataxin-3-VCP interaction delays the aggregation of the toxic protein in vivo. Importantly, early on flies that express pathogenic ataxin-3 with a mutated VCP-binding site are indistinguishable from flies that do not express any SCA3 protein. Also, reducing levels of VCP through RNA-interference has a similar, protective effect to mutating the VCP-binding site of pathogenic ataxin-3. Based on in vivo pulse-chases, aggregated species of ataxin-3 are highly stable, in a manner independent of VCP-binding. Collectively, our results highlight an important role for the ataxin-3-VCP interaction in SCA3, based on a model that posits a seeding effect from VCP on pathogenic ataxin-3 aggregation and subsequent toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Hydroxyurea Therapy for Children With Sickle Cell Anemia in Sub‐Saharan Africa: Rationale and Design of the REACH Trial

PubMed Central

Tshilolo, Léon; Santos, Brigida; Tomlinson, George A.; Stuber, Susan; Latham, Teresa; Aygun, Banu; Obaro, Stephen K.; Olupot‐Olupot, Peter; Williams, Thomas N.; Odame, Isaac; Ware, Russell E.

2015-01-01

Background Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease‐modifying therapy for SCA, and has proven safety and efficacy in high‐resource countries. In sub‐Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence‐based guidelines, and inexperience among healthcare providers. Procedure A partnership was established between investigators in North America and sub‐Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. Results The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open‐label dose escalation study of hydroxyurea that will treat a total of 600 children age 1–10 years with SCA: 150 at each of four different clinical sites within sub‐Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed‐dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose. Conclusions REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub‐Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. PMID:26275071

Hydroxyurea Therapy for Children With Sickle Cell Anemia in Sub-Saharan Africa: Rationale and Design of the REACH Trial.

PubMed

McGann, Patrick T; Tshilolo, Léon; Santos, Brigida; Tomlinson, George A; Stuber, Susan; Latham, Teresa; Aygun, Banu; Obaro, Stephen K; Olupot-Olupot, Peter; Williams, Thomas N; Odame, Isaac; Ware, Russell E

2016-01-01

Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries. In sub-Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence-based guidelines, and inexperience among healthcare providers. A partnership was established between investigators in North America and sub-Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open-label dose escalation study of hydroxyurea that will treat a total of 600 children age 1-10 years with SCA: 150 at each of four different clinical sites within sub-Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed-dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose. REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub-Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa. © 2015 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Spinocerebellar ataxia 36 (SCA36): «Costa da Morte ataxia».

PubMed

Arias, M; García-Murias, M; Sobrido, M J

To describe the history of the discovery of SCA36 and review knowledge of this entity, which is currently the most prevalent hereditary ataxia in Galicia (Spain) owing to a founder effect. SCA36 is an autosomal dominant hereditary ataxia with late onset and slow progression. It presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor neuron impairment (tongue atrophy with denervation, discrete pyramidal signs). SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da Morte ataxia). The condition is caused by a genetic mutation (intronic hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome 20 (20p13). Magnetic resonance image study initially shows cerebellar vermian atrophy that subsequently extends to the rest of the cerebellum and finally to the pontomedullary region of the brainstem without producing white matter lesions. Peripheral nerve conduction velocities are normal, and sensorimotor evoked potential studies show delayed conduction of stimuli to lower limbs. In patients with hearing loss, audiometric studies show a drop of >40dB in frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show lack of waves I and II. Costa da Morte ataxia or SCA36 is the most prevalent SCA in the Spanish region of Galicia. Given the region's history of high rates of emigration, new cases may be diagnosed in numerous countries, especially in Latin America. Genetic studies are now available to patients and asymptomatic carriers. Since many people are at risk for this disease, we will continue our investigations aimed at elucidating the underlying pathogenic molecular mechanisms and discovering effective treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

MODIS Snow Cover Recovery Using Variational Interpolation

NASA Astrophysics Data System (ADS)

Tran, H.; Nguyen, P.; Hsu, K. L.; Sorooshian, S.

2017-12-01

Cloud obscuration is one of the major problems that limit the usages of satellite images in general and in NASA's Moderate Resolution Imaging Spectroradiometer (MODIS) global Snow-Covered Area (SCA) products in particular. Among the approaches to resolve the problem, the Variational Interpolation (VI) algorithm method, proposed by Xia et al., 2012, obtains cloud-free dynamic SCA images from MODIS. This method is automatic and robust. However, computational deficiency is a main drawback that degrades applying the method for larger scales (i.e., spatial and temporal scales). To overcome this difficulty, this study introduces an improved version of the original VI. The modified VI algorithm integrates the MINimum RESidual (MINRES) iteration (Paige and Saunders., 1975) to prevent the system from breaking up when applied to much broader scales. An experiment was done to demonstrate the crash-proof ability of the new algorithm in comparison with the original VI method, an ability that is obtained when maintaining the distribution of the weights set after solving the linear system. After that, the new VI algorithm was applied to the whole Contiguous United States (CONUS) over four winter months of 2016 and 2017, and validated using the snow station network (SNOTEL). The resulting cloud free images have high accuracy in capturing the dynamical changes of snow in contrast with the MODIS snow cover maps. Lastly, the algorithm was applied to create a Cloud free images dataset from March 10, 2000 to February 28, 2017, which is able to provide an overview of snow trends over CONUS for nearly two decades. ACKNOWLEDGMENTSWe would like to acknowledge NASA, NOAA Office of Hydrologic Development (OHD) National Weather Service (NWS), Cooperative Institute for Climate and Satellites (CICS), Army Research Office (ARO), ICIWaRM, and UNESCO for supporting this research.

Social and Cultural Elements Associated with Neurocognitive Dysfunctions in Spinocerebellar Ataxia Type 2 Patients.

PubMed

Mercadillo, Roberto Emmanuele; Galvez, Víctor; Díaz, Rosalinda; Paredes, Lorena; Velázquez-Moctezuma, Javier; Hernandez-Castillo, Carlos R; Fernandez-Ruiz, Juan

2015-01-01

Spinocerebellar Ataxia Type 2 (SCA2) is a rare genetic disorder producing cerebellar degeneration and affecting motor abilities. Neuroimaging studies also show neurodegeneration in subcortical and cortical regions related to emotional and social processes. From social neuroscience, it is suggested that motor and social abilities can be influenced by particular cultural dynamics so, culture is fundamental to understand the effect of brain-related alterations. Here, we present the first analysis about the cultural elements related to the SCA2 disorder in 15 patients previously evaluated with neuroimaging and psychometric instruments, and their nuclear relationships distributed in six geographical and cultural regions in Mexico. Ethnographic records and photographic and video archives about the quotidian participant's routine were obtained from the patients, their relatives and their caregivers. The information was categorized and interpreted taking into consideration cultural issues and patients' medical files. Our analyses suggest that most of the participants do not understand the nature of the disease and this misunderstanding favors magic and non-medical explanations. Patients' testimonies suggest a decrease in pain perception as well as motor alterations that may be related to interoceptive dysfunctions. Relatives' testimonies indicate patients' lack of social and emotional interests that may be related to frontal, temporal, and cerebellar degeneration. In general, participants use their religious beliefs to deal with the disease and only a few of them trust the health system. Patients and their families are either openly rejected and ignored, tolerated or even helped by their community accordingly to different regional traits. We propose that ethnography can provide social representations to understand the patients' alterations, to formulate neurobiological hypotheses, to develop neurocognitive interventions, and to improve the medical approach to the disease.

Social and Cultural Elements Associated with Neurocognitive Dysfunctions in Spinocerebellar Ataxia Type 2 Patients

PubMed Central

Mercadillo, Roberto Emmanuele; Galvez, Víctor; Díaz, Rosalinda; Paredes, Lorena; Velázquez-Moctezuma, Javier; Hernandez-Castillo, Carlos R.; Fernandez-Ruiz, Juan

2015-01-01

Spinocerebellar Ataxia Type 2 (SCA2) is a rare genetic disorder producing cerebellar degeneration and affecting motor abilities. Neuroimaging studies also show neurodegeneration in subcortical and cortical regions related to emotional and social processes. From social neuroscience, it is suggested that motor and social abilities can be influenced by particular cultural dynamics so, culture is fundamental to understand the effect of brain-related alterations. Here, we present the first analysis about the cultural elements related to the SCA2 disorder in 15 patients previously evaluated with neuroimaging and psychometric instruments, and their nuclear relationships distributed in six geographical and cultural regions in Mexico. Ethnographic records and photographic and video archives about the quotidian participant’s routine were obtained from the patients, their relatives and their caregivers. The information was categorized and interpreted taking into consideration cultural issues and patients’ medical files. Our analyses suggest that most of the participants do not understand the nature of the disease and this misunderstanding favors magic and non-medical explanations. Patients’ testimonies suggest a decrease in pain perception as well as motor alterations that may be related to interoceptive dysfunctions. Relatives’ testimonies indicate patients’ lack of social and emotional interests that may be related to frontal, temporal, and cerebellar degeneration. In general, participants use their religious beliefs to deal with the disease and only a few of them trust the health system. Patients and their families are either openly rejected and ignored, tolerated or even helped by their community accordingly to different regional traits. We propose that ethnography can provide social representations to understand the patients’ alterations, to formulate neurobiological hypotheses, to develop neurocognitive interventions, and to improve the medical approach to the disease. PMID:26113822

KSC-2012-5024

NASA Image and Video Library

2012-09-12

CAPE CANAVERAL, Fla. - Jeff Moultrie, pilot of the Shuttle Carrier Aircraft, or SCA, speaks with news media at the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. The SCA will take space shuttle Endeavour from Florida to Los Angeles for public display. Photo credit: NASA/Kim Shiflett

Parental decisions regarding prenatally detected fetal sex chromosomal abnormality and the impact of genetic counselling: an analysis of 57 cases in Taiwan.

PubMed

Shaw, Sheng-Wen; Chueh, Ho-Yen; Chang, Shuenn-Dyh; Cheng, Po-Jen; Hsieh, T'sang-T'ang; Soong, Yung-Kuei

2008-04-01

To analyse parental decisions regarding pregnancies with sex chromosome abnormalities (SCA). Collected and reviewed records from our hospital for 1991-2005. Genetic counselling was provided by obstetricians or perinatologists. Among 57 fetuses with SCA were 36 non-mosaic cases (four of 36, 45,X; 12 of 36, 47,XXY; seven of 36, 47,XYY, 13 of 36, 47,XXX) and 21 mosaic cases (15 of 21, 45,X mosaicism). Only 20% of 45,X mosaic pregnancies were continued, whereas all other mosaic pregnancies (100%) were continued (P = 0.004). Of 32 SCA cases counselled by a perinatologist, 66% (21 of 32) were continued. In contrast, 36% (nine of 25) of cases counselled by a general obstetrician were continued, a barely significant difference (P = 0.048). More couples chose to continue pregnancies in recent years. Genetic counselling by well-trained specialists is valuable, and the trend towards fewer terminations at our centre suggests improved parental knowledge of pathology associated with SCA.

Architecture of a general purpose embedded Slow-Control Adapter ASIC for future high-energy physics experiments

NASA Astrophysics Data System (ADS)

Gabrielli, Alessandro; Loddo, Flavio; Ranieri, Antonio; De Robertis, Giuseppe

2008-10-01

This work is aimed at defining the architecture of a new digital ASIC, namely Slow-Control Adapter (SCA), which will be designed in a commercial 130-nm CMOS technology. This chip will be embedded within a high-speed data acquisition optical link (GBT) to control and monitor the front-end electronics in future high-energy physics experiments. The GBT link provides a transparent transport layer between the SCA and control electronics in the counting room. The proposed SCA supports a variety of common bus protocols to interface with end-user general-purpose electronics. Between the GBT and the SCA a standard 100 Mb/s IEEE-802.3 compatible protocol will be implemented. This standard protocol allows off-line tests of the prototypes using commercial components that support the same standard. The project is justified because embedded applications in modern large HEP experiments require particular care to assure the lowest possible power consumption, still offering the highest reliability demanded by very large particle detectors.

Spinocerebellar ataxia type 12 identified in two Italian families may mimic sporadic ataxia.

PubMed

Brussino, Alessandro; Graziano, Claudio; Giobbe, Dario; Ferrone, Marina; Dragone, Elisa; Arduino, Carlo; Lodi, Raffaele; Tonon, Caterina; Gabellini, Anna; Rinaldi, Rita; Miccoli, Sara; Grosso, Enrico; Bellati, Maria Cristina; Orsi, Laura; Migone, Nicola; Brusco, Alfredo

2010-07-15

SCA12 is an autosomal dominant cerebellar ataxia characterized by onset in the fourth decade of life with action tremor of arms and head, mild ataxia, dysmetria, and hyperreflexia. The disease is caused by an expansion of >or=51 CAGs in the 5' region of the brain- specific phosphatase 2 regulatory subunit B-beta isoform (PPP2R2B) gene. SCA12 is very rare, except for a single ethnic group in India. We screened 159 Italian ataxic patients for SCA12 and identified two families that segregated an expanded allele of 57 to 58 CAGs, sharing a common haplotype. The age at onset, phenotype, and variability of symptoms were compatible with known cases. In one family, the disease was apparently sporadic due to possible incomplete penetrance and/or late age at onset. Our data indicate that SCA12 is also present in Italian patients, and its genetic testing should be applied to both sporadic and familial ataxias.

Identification of IFRD1 variant in a Han Chinese family with autosomal dominant hereditary spastic paraplegia associated with peripheral neuropathy and ataxia.

PubMed

Lin, Pengfei; Zhang, Dong; Xu, Guangrun; Yan, Chuanzhu

2018-04-01

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant, clinically heterogeneous neurodegenerative disorders. SCA18 is a rare autosomal dominant sensory/motor neuropathy with ataxia (OMIM#607458) associated with a single missense variant c.514 A>G in the interferon related developmental regulator 1 (IFRD1) gene previously reported in a five-generation American family of Irish origin. However, to date, there have been no other reports of the IFRD1 mutation to confirm its role in SCA. Here, we report a Han Chinese family with SCA18; the family members presented with a slowly progressing gait ataxia, pyramidal tract signs, and peripheral neuropathy. We identified a missense variant (c.514 A>G, p.I172V) in IFRD1 gene in the family using targeted next-generation sequencing and Sanger direct sequencing with specific primers. Our results suggest that the IFRD1 gene may be the causative allele for SCA18.

From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

PubMed

Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

PubMed Central

Panas, Marios; Paraskevas, George P.; Bougea, Anastasia M.; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family. PMID:25349749

[A clinical trial of acetazolamide for SCA6].

PubMed

Yabe, I; Sasaki, H; Yamashita, I; Takei, A; Fukazawa, T; Hamada, T; Tashiro, K

1999-08-01

Spinocerebellar ataxia type 6 (SCA 6) is an allelic disorder of episodic ataxia type 2 (EA 2) and is caused by a small CAG repeat expansion in the gene encoding the alpha 1A-voltage-dependent-Ca channel subunit (CACNA 1 A) on chromosome 19p13.1. The disorder starts at adulthood with progressive cerebellar ataxia, and the symptoms often fluctuate at early stage. These clinical features overlap with those of EA 2, which has been known as acetazolamide-responsive ataxia. On this background, we studied the clinical effectiveness of acetazolamide for SCA 6 in 9 consecutive patients. Their clinical severity was serially evaluated by ARS (ataxia rating scale) and gravimetric test, over 32 weeks of oral administration of acetazolamide (250-500 mg/day). Consequently, a significant improvement was observed in ARS and postural sway. Our results indicate that acetazolamide is temporally effective for ameliorating the symptoms of SCA 6. However, its effects for the disease progression need to be examined in more large scales in number and duration.

KSC-2012-2347

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies out to the runway for a takeoff at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2447

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, begins takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

Atmospheric River Development and Effects on Southern California

NASA Astrophysics Data System (ADS)

Harris, S. M.; Carvalho, L. V.

2014-12-01

Throughout most of southern California (SCA) annual precipitation totals occur from relatively few storms per season. Any changes to storm frequency or intensity may dramatically impact the region, as its landscapes are prone to various rainfall-induced hazards including landslides and floods. These hazards become more frequent following drought or fire events, conditions also reliant on precipitation and common in SCA. Rainfall forecasts are especially difficult to determine as regional precipitation is affected by numerous phenomena. On synoptic timescales, atmospheric rivers (ARs) are one such phenomenon known to impact SCA rainfall. ARs are channels of high water vapor content found within the lower atmosphere that transport moisture towards midlatitudes. In areas with varying topography, ARs often produce high-intensity precipitation due to orographic forcing. Although much insight has been gained in understanding AR climatology affecting North America's western coast, the spatiotemporal characteristics and atmospheric forcings driving ARs to SCA need to be further addressed. The goal of this work is to understand the characteristics of ARs that impact SCA and to distinguish them from ARs that impact northern latitudes. We investigate AR characteristics as well as atmospheric features prior to plume initiation for ARs impacting different landfall regions along North America's western coast between 1998-2008. Dates of AR events are organized according to landfall region using total precipitable water (TPW) fields from the National Oceanic and Atmospheric Administration's Climate Forecast System Reanalysis (CFSR). Additional CFSR fields are used to create anomaly composites of moist static energy, geopotential height, as well as upper-level zonal and low-level meridional winds for each landfall region on the day of and prior to AR occurrence. ARs that impact SCA display different TPW plume characteristics as well as wave train patterns throughout the AR lifecycle (prior to plume initiation-AR landfall) compared to ARs that landfall further north. This suggests that ARs impacting SCA differ in initiation mechanisms as well as structural qualities from other ARs. Information from these analyses will assist in creating and validating an automatic tool for identifying AR occurrences.

Fatty acids in the de novo lipogenesis pathway and risk of coronary heart disease: the Cardiovascular Health Study.

PubMed

Wu, Jason H Y; Lemaitre, Rozenn N; Imamura, Fumiaki; King, Irena B; Song, Xiaoling; Spiegelman, Donna; Siscovick, David S; Mozaffarian, Dariush

2011-08-01

De novo lipogenesis (DNL) is an endogenous pathway whereby carbohydrates and proteins are converted to fatty acids. DNL could affect coronary heart disease (CHD) or sudden cardiac arrest (SCA) via generation of specific fatty acids. Whether these fatty acids are prospectively associated with SCA or other CHD events is unknown. The objective was to investigate the relations of 4 fatty acids in the DNL pathway-palmitic acid (16:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and cis-vaccenic acid (18:1n-7)-with incident CHD, including fatal CHD, nonfatal myocardial infarction (NFMI), and SCA. A community-based prospective study was conducted in 2890 men and women aged ≥65 y, who were free of known CHD at baseline and who were followed from 1992 to 2006. Cardiovascular disease risk factors and plasma phospholipid fatty acids were measured at baseline by using standardized methods. Incident CHD was ascertained prospectively and was centrally adjudicated by using medical records. Risk was assessed by using multivariable-adjusted Cox proportional hazards. During 29,835 person-years of follow-up, 631 CHD and 71 SCA events occurred. Both 18:1n-7 and 16:1n-9 were associated with a higher risk of SCA [multivariable-adjusted hazard ratio (95% CI) for the interquintile range: 7.63 (2.58, 22.6) for 18:1n-7 and 2.30 (1.16, 4.55) for 16:1n-9] but not of total CHD, fatal CHD, or NFMI. In secondary analyses censored to mid-follow-up (7 y) to minimize the effects of changes in concentrations over time, 16:1n-9 was also associated with a significantly higher risk of total CHD (2.11; 1.76, 2.54), including a higher risk of CHD death, NFMI, and SCA; 16:0 and 16:1n-7 were not associated with clinical CHD outcomes. Higher plasma phospholipid 18:1n-7 and 16:1n-9 concentrations were prospectively associated with an elevated risk of SCA but not of other CHD events, except in secondary analyses.

Fatty acids in the de novo lipogenesis pathway and risk of coronary heart disease: the Cardiovascular Health Study123

PubMed Central

Lemaitre, Rozenn N; Imamura, Fumiaki; King, Irena B; Song, Xiaoling; Spiegelman, Donna; Siscovick, David S; Mozaffarian, Dariush

2011-01-01

Background: De novo lipogenesis (DNL) is an endogenous pathway whereby carbohydrates and proteins are converted to fatty acids. DNL could affect coronary heart disease (CHD) or sudden cardiac arrest (SCA) via generation of specific fatty acids. Whether these fatty acids are prospectively associated with SCA or other CHD events is unknown. Objective: The objective was to investigate the relations of 4 fatty acids in the DNL pathway—palmitic acid (16:0), palmitoleic acid (16:1n−7), 7-hexadecenoic acid (16:1n−9), and cis-vaccenic acid (18:1n−7)—with incident CHD, including fatal CHD, nonfatal myocardial infarction (NFMI), and SCA. Design: A community-based prospective study was conducted in 2890 men and women aged ≥65 y, who were free of known CHD at baseline and who were followed from 1992 to 2006. Cardiovascular disease risk factors and plasma phospholipid fatty acids were measured at baseline by using standardized methods. Incident CHD was ascertained prospectively and was centrally adjudicated by using medical records. Risk was assessed by using multivariable-adjusted Cox proportional hazards. Results: During 29,835 person-years of follow-up, 631 CHD and 71 SCA events occurred. Both 18:1n−7 and 16:1n−9 were associated with a higher risk of SCA [multivariable-adjusted hazard ratio (95% CI) for the interquintile range: 7.63 (2.58, 22.6) for 18:1n−7 and 2.30 (1.16, 4.55) for 16:1n−9] but not of total CHD, fatal CHD, or NFMI. In secondary analyses censored to mid-follow-up (7 y) to minimize the effects of changes in concentrations over time, 16:1n−9 was also associated with a significantly higher risk of total CHD (2.11; 1.76, 2.54), including a higher risk of CHD death, NFMI, and SCA; 16:0 and 16:1n−7 were not associated with clinical CHD outcomes. Conclusion: Higher plasma phospholipid 18:1n−7 and 16:1n−9 concentrations were prospectively associated with an elevated risk of SCA but not of other CHD events, except in secondary analyses. PMID:21697077

KSC-2012-2294

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At the Shuttle Landing Facility at NASA’s Kennedy Space Center in Florida, no weather constraints to the planned flight plan are detected for departure tomorrow morning of the Shuttle Carrier Aircraft with space shuttle Discovery secured to its back. In the distance, at right, is the mate/demate device used to lift Discovery onto the aircraft. The device, also known as the MDD, is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the aircraft, or SCA. The SCA is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. The SCA designated NASA 905 is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian's National Air and Space Museum Steven F. Udvar-Hazy Center. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Jacobs The aircraft, also known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. The SCA designated NASA 905 is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian's National Air and Space Museum Steven F. Udvar-Hazy Center. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Jacobs

Comprehensive Assessment of Coronary Artery Disease in Sports-Related Sudden Cardiac Arrest.

PubMed

Karam, Nicole; Pechmajou, Louis; Dumas, Florence; Bougouin, Wulfran; Sharifzadehgan, Ardalan; Beganton, Frankie; Bonnet, Guillaume; Jost, Daniel; Lamhaut, Lionel; Varenne, Olivier; Aubry, Pierre; Sideris, Georgios; Spaulding, Christian; Cariou, Alain; Marijon, Eloi; Jouven, Xavier

2018-05-02

Despite the cardiovascular benefits of regular sports, sudden cardiac arrest (SCA) risk is increased during or shortly after exercise. Association with coronary artery disease (CAD) has been described in small studies, mainly autopsic with potential bias given the high sports-related SCA survival, and focusing on young competitive athletes, whereas sports-related SCA occurs mostly in recreational athletes. 1-5 Through the Paris Sudden Death Expertise Center prospective registry that includes all SCAs in Paris and suburbs since May 2011, we performed the first broad comprehensive CAD description in sports-related SCAs, with a comparison with matched non-sports-related SCAs.

KSC-2012-5021

NASA Image and Video Library

2012-09-12

CAPE CANAVERAL, Fla. - Henry Taylor, chief flight engineer on the Shuttle Carrier Aircraft, or SCA, speaks with news media at the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. The SCA will take space shuttle Endeavour from Florida to Los Angeles for public display. Photo credit: NASA/Kim Shiflett

KSC-2012-5022

NASA Image and Video Library

2012-09-12

CAPE CANAVERAL, Fla. - Henry Taylor, chief flight engineer on the Shuttle Carrier Aircraft, or SCA, speaks with news media at the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. The SCA will take space shuttle Endeavour from Florida to Los Angeles for public display. Photo credit: NASA/Kim Shiflett

Evaluating MODIS snow products for modelling snowmelt runoff: Case study of the Rio Grande headwaters

NASA Astrophysics Data System (ADS)

Steele, Caitriana; Dialesandro, John; James, Darren; Elias, Emile; Rango, Albert; Bleiweiss, Max

2017-12-01

Snow-covered area (SCA) is a key variable in the Snowmelt-Runoff Model (SRM) and in other models for simulating discharge from snowmelt. Landsat Thematic Mapper (TM), Enhanced Thematic Mapper (ETM +) or Operational Land Imager (OLI) provide remotely sensed data at an appropriate spatial resolution for mapping SCA in small headwater basins, but the temporal resolution of the data is low and may not always provide sufficient cloud-free dates. The coarser spatial resolution Moderate Resolution Imaging Spectroradiometer (MODIS) offers better temporal resolution and in cloudy years, MODIS data offer the best alternative for mapping snow cover when finer spatial resolution data are unavailable. However, MODIS' coarse spatial resolution (500 m) can obscure fine spatial patterning in snow cover and some MODIS products are not sensitive to end-of-season snow cover. In this study, we aimed to test MODIS snow products for use in simulating snowmelt runoff from smaller headwater basins by a) comparing maps of TM and MODIS-based SCA and b) determining how SRM streamflow simulations are changed by the different estimates of seasonal snow depletion. We compared gridded MODIS snow products (Collection 5 MOD10A1 fractional and binary SCA; SCA derived from Collection 6 MOD10A1 Normalised Difference Snow Index (NDSI) Snow Cover), and the MODIS Snow Covered-Area and Grain size retrieval (MODSCAG) canopy-corrected fractional SCA (SCAMG), with reference SCA maps (SCAREF) generated from binary classification of TM imagery. SCAMG showed strong agreement with SCAREF; excluding true negatives (where both methods agreed no snow was present) the median percent difference between SCAREF and SCAMG ranged between -2.4% and 4.7%. We simulated runoff for each of the four study years using SRM populated with and calibrated for snow depletion curves derived from SCAREF. We then substituted in each of the MODIS-derived depletion curves. With efficiency coefficients ranging between 0.73 and 0.93, SRM simulation results from the SCAMG runs yielded the best results of all the MODIS products and only slightly underestimated discharge volume (between 7 and 11% of measured annual discharge). SRM simulations that used SCA derived from Collection 6 NDSI Snow Cover also yielded promising results, with efficiency coefficients ranging between 0.73 and 0.91. In conclusion, we recommend that when simulating snowmelt runoff from small basins (<4000 km2) with SRM, we recommend that users select either canopy-corrected MODSCAG or create their own site-specific products from the Collection 6 MOD10A1 NDSI.

SCA17 repeat expansion: mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications.

PubMed

Chen, Chiung-Mei; Lee, Li-Ching; Soong, Bing-Wen; Fung, Hon-Chung; Hsu, Wen-Chuin; Lin, Pei-Ying; Huang, Hui-Ju; Chen, Fen-Lin; Lin, Cheng-Yueh; Lee-Chen, Guey-Jen; Wu, Yih-Ru

2010-03-01

Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad. We screened for triplet expansion in the TBP gene in Taiwanese Parkinson's disease (PD), Alzheimer's disease (AD) and atypical parkinsonism and investigated the functional implication of expanded alleles using lymphoblastoid cells as a model. A total of 6 mildly expanded alleles (44-46) were identified in patients group. The frequency of the individuals carrying expanded alleles in PD (3/602 [0.5%]), AD (2/245 [0.8%]) and atypical parkinsonism (1/44 [2.3%]) is not significant as compared to that in the control subjects (0/644 [0.0%]). In lymphoblastoid cells, HSPA5, HSPA8 and HSPB1 expression levels in cells with expanded TBP were significantly lower than that of the control cells. Although not significantly, the levels of PARK7 protein isoforms 6.1 and 6.4 are notably increased in SCA17 lymphoblastoid cells. Treatment of TBH (tert-butyl hydroperoxide) significantly increases cell death in the cells with mildly expanded TBP. Our findings expand the spectrum of SCA17 phenotype and may contribute to our understanding of the disease. Copyright 2009 Elsevier B.V. All rights reserved.

Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17.

PubMed

Gao, Rui; Matsuura, Tohru; Coolbaugh, Mary; Zühlke, Christine; Nakamura, Koichiro; Rasmussen, Astrid; Siciliano, Michael J; Ashizawa, Tetsuo; Lin, Xi

2008-02-01

Trinucleotide repeat expansions are dynamic mutations causing many neurological disorders, and their instability is influenced by multiple factors. Repeat configuration seems particularly important, and pure repeats are thought to be more unstable than interrupted repeats. But direct evidence is still lacking. Here, we presented strong support for this hypothesis from our studies on spinocerebellar ataxia type 17 (SCA17). SCA17 is a typical polyglutamine disease caused by CAG repeat expansion in TBP (TATA binding protein), and is unique in that the pure expanded polyglutamine tract is coded by either a simple configuration with long stretches of pure CAGs or a complex configuration containing CAA interruptions. By small pool PCR (SP-PCR) analysis of blood DNA from SCA17 patients of distinct racial backgrounds, we quantitatively assessed the instability of these two types of expanded alleles coding similar length of polyglutamine expansion. Mutation frequency in patients harboring pure CAG repeats is 2-3 folds of those with CAA interruptions. Interestingly, the pure CAG repeats showed both expansion and deletion while the interrupted repeats exhibited mostly deletion at a significantly lower frequency. These data strongly suggest that repeat configuration is a critical determinant for instability, and CAA interruptions might serve as a limiting element for further expansion of CAG repeats in SCA17 locus, suggesting a molecular basis for lack of anticipation in SCA17 families with interrupted CAG expansion.

Moderate endurance exercise in patients with sickle cell anaemia: effects on oxidative stress and endothelial activation.

PubMed

Faes, Camille; Balayssac-Siransy, Edwige; Connes, Philippe; Hivert, Ludovic; Danho, Clotaire; Bogui, Pascal; Martin, Cyril; Pialoux, Vincent

2014-01-01

Very few studies have investigated the effects of exercise on the biological parameters involved in vaso-occlusive events in sickle cell anaemia (SCA). The aim of this study was to test how a mild-moderate endurance exercise modulates oxidative stress, nitric oxide bioavailability and endothelial activation in SCA patients and healthy individuals. Eleven patients with SCA and 15 healthy subjects completed a 20-min duration submaximal cycling exercise at ≈45 Watts. Plasma markers of oxidative stress, antioxidant activity, endothelial activation and nitric oxide bioavailability were investigated before and after the exercise. Nitric oxide levels, anti-oxidant capacity, soluble (s)E-selectin and sP-selectin did not change in response to this exercise. Except for the malondialdehyde levels, which increased in the two groups, the other markers of oxidative stress remained unchanged in both groups in response to exercise. Soluble vascular cell adhesion molecule 1 levels were increased at the end of exercise in both groups. sL-selectin decreased and soluble intercellular adhesion molecule 1 increased with exercise in SCA patients only. The present data suggest that patients with SCA may undertake mild-moderate physical activities without any acute clinical complications, but care should be taken because oxidative stress and endothelial activation significantly increased in some patients. © 2013 John Wiley & Sons Ltd.

Substituting Sodium Hydrosulfite with Sodium Metabisulfite Improves Long-Term Stability of a Distributable Paper-Based Test Kit for Point-of-Care Screening for Sickle Cell Anemia.

PubMed

Torabian, Kian; Lezzar, Dalia; Piety, Nathaniel Z; George, Alex; Shevkoplyas, Sergey S

2017-09-20

Sickle cell anemia (SCA) is a genetic blood disorder that is particularly lethal in early childhood. Universal newborn screening programs and subsequent early treatment are known to drastically reduce under-five SCA mortality. However, in resource-limited settings, cost and infrastructure constraints limit the effectiveness of laboratory-based SCA screening programs. To address this limitation our laboratory previously developed a low-cost, equipment-free, point-of-care, paper-based SCA test. Here, we improved the stability and performance of the test by replacing sodium hydrosulfite (HS), a key reducing agent in the hemoglobin solubility buffer which is not stable in aqueous solutions, with sodium metabisulfite (MS). The MS formulation of the test was compared to the HS formulation in a laboratory setting by inexperienced users ( n = 3), to determine visual limit of detection (LOD), readout time, diagnostic accuracy, intra- and inter-observer agreement, and shelf life. The MS test was found to have a 10% sickle hemoglobin LOD, 21-min readout time, 97.3% sensitivity and 99.5% specificity for SCA, almost perfect intra- and inter-observer agreement, at least 24 weeks of shelf stability at room temperature, and could be packaged into a self-contained, distributable test kits comprised of off-the-shelf disposable components and food-grade reagents with a total cost of only $0.21 (USD).

Neuroimaging abnormalities in adults with sickle cell anemia

PubMed Central

Insel, Philip; Truran, Diana; Vichinsky, Elliot P.; Neumayr, Lynne D.; Armstrong, F.D.; Gold, Jeffrey I.; Kesler, Karen; Brewer, Joseph; Weiner, Michael W.

2014-01-01

Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = −2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = −3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Conclusions: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA. PMID:24523480

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles.

PubMed

Aleluia, Milena Magalhães; Fonseca, Teresa Cristina Cardoso; Souza, Regiana Quinto; Neves, Fábia Idalina; da Guarda, Caroline Conceição; Santiago, Rayra Pereira; Cunha, Bruna Laís Almeida; Figueiredo, Camylla Villas Boas; Santana, Sânzio Silva; da Paz, Silvana Sousa; Ferreira, Júnia Raquel Dutra; Cerqueira, Bruno Antônio Veloso; Gonçalves, Marilda de Souza

2017-01-01

In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the β S -globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α 3.7Kb -thal), as well as the occurrence of clinical events in both SCD genotypes. Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α 3.7Kb -thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

KSC-2012-2281

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. From the left, are Mission Specialists Alvin Drew, Nicole Stott, Michael Barrett and Steve Bowen, Pilot Eric Boe and Commander Steve Lindsay. In the background is the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2282

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. From the left, are Mission Specialists Alvin Drew, Nicole Stott, Michael Barrett and Steve Bowen, Pilot Eric Boe and Commander Steve Lindsay. In the background is the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2288

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. Commander Steve Lindsay visits with the media. Also present, but not in view, are Mission Specialists Nicole Stott, Michael Barrett, Steve Bowen and Alvin Drew, and Pilot Eric Boe. The crew arrived to view the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2287

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. Pilot Eric Boe visits with the media. Also present, but not in view, are Mission Specialists Nicole Stott, Michael Barrett, Steve Bowen and Alvin Drew, and Commander Steve Lindsay. The crew arrived to view the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2280

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. From the left, are Mission Specialists Nicole Stott, Michael Barrett and Alvin Drew facing away, Pilot Eric Boe and Commander Steve Lindsay. In the background is the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2289

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. Commander Steve Lindsay visits with the media. Also present, but not in view, are Mission Specialists Nicole Stott, Michael Barrett, Steve Bowen and Alvin Drew, and Pilot Eric Boe. The crew arrived to view the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

Localization of autosomal dominant cerebellar ataxia associated with retinal degeneration and anticipation to chromosome 3p12-p21.1.

PubMed

Holmberg, M; Johansson, J; Forsgren, L; Heijbel, J; Sandgren, O; Holmgren, G

1995-08-01

We present linkage analysis on a large Swedish five-generation family of 15 affected individuals with autosomal dominant cerebellar ataxia (ADCA) associated with retinal degeneration and anticipation. Common clinical signs in this family include ataxia, dysarthria and severely impaired vision with the phenotype ADCA type II. Different subtypes of ADCA have proven difficult to classify clinically due to extensive phenotypic variability within and between families. Genetic analysis of a number of ADCA type I families shows that heterogeneity exists also genetically. During the last few years several types of ADCA type I have been localized and to date six genetically distinct forms have been identified including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph disease (MJD) (14q), SCA4 (16q), and finally SCA5 (11). We performed a genome-wide search of the Swedish ADCA type II family using a total of 270 microsatellite markers. Positive lod scores were obtained with a number of microsatellite markers located on chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod score of 4.53 achieved with the marker D3S1600. The ADCA type II gene could be restricted to a region of 32 cM by the markers D3S1547 and D3S1274.

Sleep disorders in spinocerebellar ataxia type 2 patients.

PubMed

Velázquez-Pérez, Luis; Voss, Ursula; Rodríguez-Labrada, Roberto; Auburger, Georg; Canales Ochoa, Nalia; Sánchez Cruz, Gilberto; Galicia Polo, Lourdes; Haro Valencia, Reyes; Aguilera Rodríguez, Raúl; Medrano Montero, Jacqueline; Laffita Mesa, Jose M; Tuin, Inka

2011-01-01

Sleep disturbances are common features in spinocerebellar ataxias (SCAs). Nevertheless, sleep data on SCA2 come from scarce studies including few patients, limiting the evaluation of the prevalence and determinants of sleep disorders. To assess the frequency and possible determinants of sleep disorders in the large and homogeneous SCA2 Cuban population. Thirty-two SCA2 patients and their age- and sex-matched controls were studied by video-polysomnography and sleep interviews. The most striking video-polysomnography features were rapid eye movement (REM) sleep pathology and periodic leg movements (PLMs). REM sleep abnormalities included a consistent reduction of the REM sleep percentage and REM density as well as an increase in REM sleep without atonia (RWA). REM sleep and REM density decreases were closely related to the increase in ataxia scores, whereas the RWA percentage was influenced by the cytosine-adenine-guanine (CAG) repeats. PLMs were observed in 37.5% of cases. The PLM index showed a significant association with the ataxia score and disease duration but not with CAG repeats. REM sleep pathology and PLMs are closely related to SCA2 severity, suggesting their usefulness as disease progression markers. The RWA percentage is influenced by the CAG repeats and might thus be a sensitive parameter for reflecting polyglutamine toxicity. Finally, as PLMs are sensible to drug treatment, they represents a new therapeutic target for the symptomatic treatment of SCA2. Copyright © 2011 S. Karger AG, Basel.

Optimizing hydroxyurea therapy for sickle cell anemia.

PubMed

Ware, Russell E

2015-01-01

Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA. © 2015 by The American Society of Hematology. All rights reserved.

Regional climate of the Subtropical Central Andes using high-resolution CMIP5 models. Part II: future projections for the twenty-first century

NASA Astrophysics Data System (ADS)

Zazulie, Natalia; Rusticucci, Matilde; Raga, Graciela B.

2017-12-01

In Part I of our study (Zazulie et al. Clim Dyn, 2017, hereafter Z17) we analyzed the ability of a subset of fifteen high-resolution global climate models (GCMs) from the Coupled Model Intercomparison Project phase 5 to reproduce the past climate of the Subtropical Central Andes (SCA) of Argentina and Chile. A subset of only five GCMs was shown to reproduce well the past climate (1980-2005), for austral summer and winter. In this study we analyze future climate projections for the twenty-first century over this complex orography region using those five GCMs. We evaluate the projections under two of the representative concentration pathways considered as future scenarios: RCP4.5 and RCP8.5. Future projections indicate warming during the twenty-first century over the SCA region, especially pronounced over the mountains. Projections of warming at high elevations in the SCA depend on altitude, and are larger than the projected global mean warming. This phenomenon is expected to strengthen by the end of the century under the high-emission scenario. Increases in winter temperatures of up to 2.5 °C, relative to 1980-2005, are projected by 2040-2065, while a 5 °C warming is expected at the highest elevations by 2075-2100. Such a large monthly-mean warming during winter would most likely result in snowpack melting by late winter-early spring, with serious implication for water availability during summer, when precipitation is a minimum over the mountains. We also explore changes in the albedo, as a contributing factor affecting the net flux of energy at the surface and found a reduction in albedo of 20-60% at high elevations, related to the elevation dependent warming. Furthermore, a decrease in winter precipitation is projected in central Chile by the end of the century, independent of the scenario considered.

Detection of dual effects of degradation of perennial snow and ice covers on the hydrologic regime of a Himalayan river basin by stream water availability modeling

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Biswajit

2012-01-01

SummaryIn river basins where melt water from snow and ice constitutes a dominant component of stream discharge during summer, degradation or reduction of perennial snow and ice covered areas ( SCA P) has a profound effect on stream water availability in those basins. Degradation of SCA P that includes glaciers is a globally widespread phenomenon observed in the recently past decades; its cause has been attributed to global warming and its consequence is expected to dramatically alter the flow regimes of the rivers draining the terrains. The predicted change in flow regime is an initial increase in summer flows in the early decades of 21st century followed by sharp decline of the same during the later parts of the century. Estimation of SCA P within the Upper Indus Basin (UIB), straddling the western ranges of the Greater Himalayas, Karakoram Mountains, and the eastern mountain ranges of the Hindu Kush, shows that from 1992 to 2010 there has been about 2.15% reduction in SCA P. A spatially distributed basin-scale stream water availability model is presented to calculate monthly river discharges at critical hydrologic junctions within UIB. Model calculations for the years 1992, 2000, and 2008, show that due to the degradation of the SCA P within the basin, there has been significant decrease in summer discharges at various hydrologic junctions. The percentage decline in flows varies from 10% to 22%, depending on the locations of the junctions within the basin. The space-dependence of these variations reflects differential degradation of SCA P in various parts of the basin. Furthermore, the time of peak discharge at all of the hydrological junctions has shifted from middle/late summer to late spring/early summer as another outcome of SCA P reduction. Such temporal shifting of nival regimes to early part of warmer season has also been predicted by global warming models. However, the case study presented here for a major Himalayan river basin demonstrates that such shifting of peak discharge in the time domain can also take place simply due to retreat of the equilibrium line. Thus, the effects of a warming climate have possibly been already set within UIB. Instead of experiencing an increased pulse of summer flows for the next few decades, summer flows within this basin are expected to decline. Changes in the timing of peak flows can have adverse effects on multipurpose water resources management without appropriate adaptation and mitigation measures. Monthly average stream flow data with 35 year period of record from a key gauging station support the findings of the model results. Similarly, digital maps of SCA P at different time periods within a key catchment of UIB, containing one of the major glaciers, show retreat of glacial lobes and significant decrease in total SCA P taking place during the past decades.

Sugarcane aphid resistance in sorghum and a host range

USDA-ARS?s Scientific Manuscript database

The sugarcane aphid (SCA), Melanaphis sacchari, has been present in the United States primarily on sugarcane in Florida, Hawaii, and Louisiana until 2013 where it was found on grain sorghum near Beaumont, Texas. Since 2013, the SCA has been rapidly spreading and overwintering. Depending on the plant...

Emergency Response Systems for Outdoor Programming.

ERIC Educational Resources Information Center

Merrill, Kurt; Satz, Jay A.

The Student Conservation Association (SCA) runs backcountry programs in wilderness settings, providing both an educational experience for participants and badly needed conservation work on public lands. As part of its risk management efforts, SCA has developed an emergency response system that ties resources in the field to all the resources of…

Paliperidone palmitate once-monthly maintains improvement in functioning domains of the Personal and Social Performance scale compared with placebo in subjects with schizoaffective disorder.

PubMed

Fu, Dong-Jing; Turkoz, Ibrahim; Walling, David; Lindenmayer, Jean-Pierre; Schooler, Nina R; Alphs, Larry

2018-02-01

Evaluate the effect of paliperidone palmitate once-monthly (PP1M) injectable on the specific functioning domains of the Personal and Social Performance (PSP) scale in patients with schizoaffective disorder (SCA) participating in a long-term study. This study (NCT01193153) included both in- and outpatient subjects with SCA experiencing an acute exacerbation of psychotic and mood symptoms. Subjects were treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers during a 25-week open-label (OL) phase. Stabilized subjects were randomly assigned 1:1 (PP1M or placebo) into a 15-month double-blind (DB) relapse-prevention period. Functioning of the randomized subjects during OL and DB phases was evaluated using the PSP scale (four domains: socially useful activities, personal/social relationships, self-care, and disturbing/aggressive behaviors). Three statistical approaches were utilized to analyze PSP scores to assess robustness and consistency of findings. No adjustments were made for multiplicity. 334 of 667 enrolled subjects were stabilized with PP1M, randomly assigned to PP1M (n=164) or placebo (n=170) in the DB phase, and included in this analysis. Improvements in all PSP domain scores were observed during the OL phase and were maintained during the DB phase with PP1M, but decreased with placebo. Differences compared to placebo were significant in all four PSP domains during the DB phase (P≤0.008). The analysis in this study showed that PP1M improves functioning, as measured by the four PSP domain scores, in symptomatic subjects with SCA. Functioning was maintained compared with placebo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Only a minority of sex chromosome abnormalities are detected by a national prenatal screening program for Down syndrome.

PubMed

Viuff, Mette Hansen; Stochholm, Kirstine; Uldbjerg, Niels; Nielsen, Birgitte Bruun; Gravholt, Claus Højbjerg

2015-10-01

How does a national prenatal screening program for Down syndrome (DS) perform in detecting sex chromosome abnormalities (SCAs)-Turner syndrome (TS), Klinefelter syndrome, 47,XXX and 47,XYY syndromes. The SCA detection rate resulting from DS screening was below 50% for all four groups of SCAs. The detection rates of SCAs are higher in countries with DS screening. TS is associated with greater nuchal translucency (NT) and lower pregnancy-associated plasma protein-A (PAPP-A). However, specific detection rates of SCAs using prenatal DS screening have not been determined. No clear trend in PAPP-A, free beta human chorionic gonadotropin (β-hCG) and NT has been found in the remaining SCAs. Several lines of inquiry suggest that it would be advantageous for individuals with SCA to be detected early in life, leading to prevention or treatment of accompanying conditions. There is limited information about pre- and perinatal status that distinguishes SCA embryogenesis from normal fetal development. A register-based case-control study from the Danish Central Cytogenetic Register (DCCR), cross-linked with the Danish Fetal Medicine Database (DFMD), was performed from 2008 to 2012. Groups of SCAs were compared with DS and then matched with non-SCA controls to assess differences between these groups in prenatal markers and birth outcomes. We included cases with prenatal and post-natal SCA karyotypes (n = 213), DS (n = 802) and 168 056 controls. We screened 275 037 individuals examined prenatally. We retrieved information regarding maternal age, NT, β-hCG and PAPP-A, as well as details regarding maternal and newborn characteristics. The DS screening procedure detected 87 per 100 000 TS (42% of expected), 19 per 100 000 Klinefelter syndrome (13% of expected), 16 per 100 000 47,XXX (16% of cases) and 5 per 100 000 47,XYY (5% of expected) SCAs, with an overall detection rate of 27%. Compared with controls, all four SCA groups showed significantly higher NT and lower PAPP-A compared with controls (all P < 0.01) and similar to DS. The legal abortion rate was high for all four syndromes (47,XXX: 24%; 47,XYY: 29%; Klinefelter syndrome: 48%, TS: 84%). For SCA fetuses carried to term, only TS fetuses had consistently lower birthweights and placenta weights than non-SCA controls (both P = 0.0001). A few SCA cases localized in DCCR could not be found in DFMD (n = 16). Controls were matched on sex of the fetus of cases, meaning that all electively aborted fetuses (before week 12) were excluded, possibly reducing the diversity in the control group. We were not able to localize all diagnosed cases of SCA and DS in DFMD. Although these cases were present in DCCR, we were not able to account for the discrepancy. In addition, we suspect that several SCA children have not been diagnosed yet and future post-natal diagnosis of these cases would reduce the diagnostic yield reported here even further. The prenatal detection rate is below 50% for all SCAs. The approach used for detecting DS cannot be extended to also include SCAs. In addition, all SCAs have low PAPP-A and increased NT, thus probably reflecting an abnormal embryogenesis. Growth retardation of TS fetuses is if anything more pronounced than previously reported, both when evaluating fetus and placenta. This study received support from Aarhus University and the Novo Nordisk Foundation. The authors have no competing interests that may be relevant to the study. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cerebral vasculopathy in children with sickle cell anemia.

PubMed

Fasano, Ross M; Meier, Emily R; Hulbert, Monica L

2015-01-01

Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Shocking Statistics

ERIC Educational Resources Information Center

Bingham, Dave

2009-01-01

On a Friday night in 2000, high school football player Josh Miller collapsed as he ran off the field. Several minutes later, the 15-year-old was dead from sudden cardiac arrest (SCA). This is not an uncommon scenario in school athletics. According to the American Heart Association (AHA), SCA is the leading cause of death in young athletes and…

Paliperidone for the treatment of schizoaffective disorder.

PubMed

Alphs, Larry; Fu, Dong-Jing; Turkoz, Ibrahim

2016-01-01

Schizoaffective disorder (SCA) is a complex mental illness characterized by psychosis and affective symptoms. Treatment usually involves concomitant therapy with antipsychotics, mood stabilizers, and/or antidepressants. Effective treatment must address acute symptoms, maintain long-term stability, promote recovery, and improve patient functioning. Data from 3 pivotal studies evaluating the acute and maintenance treatment of SCA with paliperidone are reviewed. Two formulations of paliperidone have been studied for these indications: an extended-release oral formulation (NCT00397033, NCT00412373) and long-acting injectable once-monthly paliperidone palmitate (NCT01193153). The reported effects of these formulations on psychotic, depressive, and manic symptoms are discussed. Both formulations were found to be safe and effective for the acute and maintenance treatment of SCA. Of critical importance for this treatment population is that rapid improvement was seen in all major symptoms of SCA, including psychosis, depression, and mania. Mediation analyses suggest that the known antipsychotic effects of paliperidone occur independently of its antidepressant effects. Both formulations of the drug are effective when used as monotherapy or adjunctively with antidepressants or mood stabilizers. Beyond symptom control, both formulations improved patient functioning and increased patient satisfaction.

Heterogeneity of adult masseter muscle satellite cells with cardiomyocyte differentiation potential.

PubMed

Huang, Wei; Liang, Jialiang; Feng, Yuliang; Jia, Zhanfeng; Jiang, Lin; Cai, Wenfeng; Paul, Christian; Gu, Jianguo G; Stambrook, Peter J; Millard, Ronald W; Zhu, Xiao-Lan; Zhu, Ping; Wang, Yigang

2018-05-26

Although resident cardiac stem cells have been reported, regeneration of functional cardiomyocytes (CMs) remains a challenge. The present study identifies an alternative progenitor source for CM regeneration without the need for genetic manipulation or invasive heart biopsy procedures. Unlike limb skeletal muscles, masseter muscles (MM) in the mouse head are developed from Nkx2-5 mesodermal progenitors. Adult masseter muscle satellite cells (MMSCs) display heterogeneity in developmental origin and cell phenotypes. The heterogeneous MMSCs that can be characterized by cell sorting based on stem cell antigen-1 (Sca1) show different lineage potential. While cardiogenic potential is preserved in Sca1 + MMSCs as shown by expression of cardiac progenitor genes (including Nkx2-5), skeletal myogenic capacity is maintained in Sca1 - MMSCs with Pax7 expression. Sca1 + MMSC-derived beating cells express cardiac genes and exhibit CM-like morphology. Electrophysiological properties of MMSC-derived CMs are demonstrated by calcium transients and action potentials. These findings show that MMSCs could serve as a novel cell source for cardiomyocyte replacement. Copyright © 2018. Published by Elsevier Inc.

Performance Analysis of a NASA Integrated Network Array

NASA Technical Reports Server (NTRS)

Nessel, James A.

2012-01-01

The Space Communications and Navigation (SCaN) Program is planning to integrate its individual networks into a unified network which will function as a single entity to provide services to user missions. This integrated network architecture is expected to provide SCaN customers with the capabilities to seamlessly use any of the available SCaN assets to support their missions to efficiently meet the collective needs of Agency missions. One potential optimal application of these assets, based on this envisioned architecture, is that of arraying across existing networks to significantly enhance data rates and/or link availabilities. As such, this document provides an analysis of the transmit and receive performance of a proposed SCaN inter-network antenna array. From the study, it is determined that a fully integrated internetwork array does not provide any significant advantage over an intra-network array, one in which the assets of an individual network are arrayed for enhanced performance. Therefore, it is the recommendation of this study that NASA proceed with an arraying concept, with a fundamental focus on a network-centric arraying.

Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels

PubMed Central

Watase, Kei; Barrett, Curtis F.; Miyazaki, Taisuke; Ishiguro, Taro; Ishikawa, Kinya; Hu, Yuanxin; Unno, Toshinori; Sun, Yaling; Kasai, Sayumi; Watanabe, Masahiko; Gomez, Christopher M.; Mizusawa, Hidehiro; Tsien, Richard W.; Zoghbi, Huda Y.

2008-01-01

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by CAG repeat expansions within the voltage-gated calcium (CaV) 2.1 channel gene. It remains controversial whether the mutation exerts neurotoxicity by changing the function of CaV2.1 channel or through a gain-of-function mechanism associated with accumulation of the expanded polyglutamine protein. We generated three strains of knockin (KI) mice carrying normal, expanded, or hyperexpanded CAG repeat tracts in the Cacna1a locus. The mice expressing hyperexpanded polyglutamine (Sca684Q) developed progressive motor impairment and aggregation of mutant CaV2.1 channels. Electrophysiological analysis of cerebellar Purkinje cells revealed similar Ca2+ channel current density among the three KI models. Neither voltage sensitivity of activation nor inactivation was altered in the Sca684Q neurons, suggesting that expanded CAG repeat per se does not affect the intrinsic electrophysiological properties of the channels. The pathogenesis of SCA6 is apparently linked to an age-dependent process accompanied by accumulation of mutant CaV2.1 channels. PMID:18687887

KSC-2012-2349

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the midfield air traffic control tower. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2353

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the 525-foot-tall Vehicle Assembly Building. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2451

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies along the runway on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2453

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies past the midpoint on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2448

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, begins takeoff on runway 15 at 7 a.m. EDT. Discovery is on the way to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2348

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the midfield air traffic control tower. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2455

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies past the midpoint on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2357

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, begins to make the turn on runway 15 for a takeoff at 7 a.m. EDT to deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2450

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, is in the air after taking off from runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2362

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, begins takeoff from runway 15 at 7 a.m. EDT on its way to deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2355

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the 525-foot-tall Vehicle Assembly Building. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2351

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background are the midfield air traffic control tower and the 525-foot-tall Vehicle Assembly Building. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2291

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At the Shuttle Landing Facility at NASA’s Kennedy Space Center in Florida, the Shuttle Carrier Aircraft backs away from the mate/demate device with space shuttle Discovery secured to its back. The device, also known as the MDD, is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the aircraft, or SCA. The SCA is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. The SCA designated NASA 905 is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian's National Air and Space Museum Steven F. Udvar-Hazy Center. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Jacobs

KSC-2012-2356

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT to deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2454

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies past the midpoint on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2456

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies past the midpoint on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2354

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the 525-foot-tall Vehicle Assembly Building. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2359

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, completes the turn on runway 15 in preparation for a takeoff at 7 a.m. EDT to deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2445

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies past the midpoint on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2358

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, begins to make the turn on runway 15 for a takeoff at 7 a.m. EDT to deliver Discovery to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2350

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the midfield air traffic control tower. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

KSC-2012-2449

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, is in the air after taking off from runway 15 at 7 a.m. EDT. Discovery is on the way to its new home. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2452

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies past the midpoint on its way for a takeoff on runway 15 at 7 a.m. EDT. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Tim Powers and Rick Wetherington

KSC-2012-2352

NASA Image and Video Library

2012-04-17

CAPE CANAVERAL, Fla. – In the early morning hours at NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery secured atop, taxies down the runway for a takeoff at 7 a.m. EDT. In the background is the midfield air traffic control tower. The aircraft, known as an SCA, is a Boeing 747 jet, originally manufactured for commercial use, which was modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Glenn Benson

[Effects of a physical training program on quantitative neurological indices in mild stage type 2 spinocerebelar ataxia patients].

PubMed

Pérez-Avila, I; Fernández-Vieitez, J A; Martínez-Góngora, E; Ochoa-Mastrapa, R; Velázquez-Manresa, M G

Type 2 spinocerebelar ataxia (SCA2) is a neurodegenerative disease with higher prevalence and incidence in Holguín province, Cuba. At present, there is not any drug to counteract the loss of coordinative motor capacities of these patients. Thus physical training seems to be the only way to attenuate the course of disease. To evaluate the effectiveness of a physical training program on quantitative neurological indices in SCA2 patients. A samples of 87 SCA2 patients were studied. All subjects underwent a six month physical exercise program based on coordination, balance and muscular conditioning exercises. Quantitative tests were applied to all patients both before and after the application of the exercise program. Comparisons between pretest versus posttest values were made to evaluate the improvement in neurological indices. All neurological indices both with open eyes and closed eyes significantly improved from pretest to posttest. Static balance, evaluated by Romberg test, also enhanced with training. The exercise training program significantly improved the neurological indices in SCA2 patient with mild stage of disease.

Efficient and anonymous two-factor user authentication in wireless sensor networks: achieving user anonymity with lightweight sensor computation.

PubMed

Nam, Junghyun; Choo, Kim-Kwang Raymond; Han, Sangchul; Kim, Moonseong; Paik, Juryon; Won, Dongho

2015-01-01

A smart-card-based user authentication scheme for wireless sensor networks (hereafter referred to as a SCA-WSN scheme) is designed to ensure that only users who possess both a smart card and the corresponding password are allowed to gain access to sensor data and their transmissions. Despite many research efforts in recent years, it remains a challenging task to design an efficient SCA-WSN scheme that achieves user anonymity. The majority of published SCA-WSN schemes use only lightweight cryptographic techniques (rather than public-key cryptographic techniques) for the sake of efficiency, and have been demonstrated to suffer from the inability to provide user anonymity. Some schemes employ elliptic curve cryptography for better security but require sensors with strict resource constraints to perform computationally expensive scalar-point multiplications; despite the increased computational requirements, these schemes do not provide user anonymity. In this paper, we present a new SCA-WSN scheme that not only achieves user anonymity but also is efficient in terms of the computation loads for sensors. Our scheme employs elliptic curve cryptography but restricts its use only to anonymous user-to-gateway authentication, thereby allowing sensors to perform only lightweight cryptographic operations. Our scheme also enjoys provable security in a formal model extended from the widely accepted Bellare-Pointcheval-Rogaway (2000) model to capture the user anonymity property and various SCA-WSN specific attacks (e.g., stolen smart card attacks, node capture attacks, privileged insider attacks, and stolen verifier attacks).

Efficient and Anonymous Two-Factor User Authentication in Wireless Sensor Networks: Achieving User Anonymity with Lightweight Sensor Computation

PubMed Central

Nam, Junghyun; Choo, Kim-Kwang Raymond; Han, Sangchul; Kim, Moonseong; Paik, Juryon; Won, Dongho

2015-01-01

A smart-card-based user authentication scheme for wireless sensor networks (hereafter referred to as a SCA-WSN scheme) is designed to ensure that only users who possess both a smart card and the corresponding password are allowed to gain access to sensor data and their transmissions. Despite many research efforts in recent years, it remains a challenging task to design an efficient SCA-WSN scheme that achieves user anonymity. The majority of published SCA-WSN schemes use only lightweight cryptographic techniques (rather than public-key cryptographic techniques) for the sake of efficiency, and have been demonstrated to suffer from the inability to provide user anonymity. Some schemes employ elliptic curve cryptography for better security but require sensors with strict resource constraints to perform computationally expensive scalar-point multiplications; despite the increased computational requirements, these schemes do not provide user anonymity. In this paper, we present a new SCA-WSN scheme that not only achieves user anonymity but also is efficient in terms of the computation loads for sensors. Our scheme employs elliptic curve cryptography but restricts its use only to anonymous user-to-gateway authentication, thereby allowing sensors to perform only lightweight cryptographic operations. Our scheme also enjoys provable security in a formal model extended from the widely accepted Bellare-Pointcheval-Rogaway (2000) model to capture the user anonymity property and various SCA-WSN specific attacks (e.g., stolen smart card attacks, node capture attacks, privileged insider attacks, and stolen verifier attacks). PMID:25849359

From virtual clustering analysis to self-consistent clustering analysis: a mathematical study

NASA Astrophysics Data System (ADS)

Tang, Shaoqiang; Zhang, Lei; Liu, Wing Kam

2018-03-01

In this paper, we propose a new homogenization algorithm, virtual clustering analysis (VCA), as well as provide a mathematical framework for the recently proposed self-consistent clustering analysis (SCA) (Liu et al. in Comput Methods Appl Mech Eng 306:319-341, 2016). In the mathematical theory, we clarify the key assumptions and ideas of VCA and SCA, and derive the continuous and discrete Lippmann-Schwinger equations. Based on a key postulation of "once response similarly, always response similarly", clustering is performed in an offline stage by machine learning techniques (k-means and SOM), and facilitates substantial reduction of computational complexity in an online predictive stage. The clear mathematical setup allows for the first time a convergence study of clustering refinement in one space dimension. Convergence is proved rigorously, and found to be of second order from numerical investigations. Furthermore, we propose to suitably enlarge the domain in VCA, such that the boundary terms may be neglected in the Lippmann-Schwinger equation, by virtue of the Saint-Venant's principle. In contrast, they were not obtained in the original SCA paper, and we discover these terms may well be responsible for the numerical dependency on the choice of reference material property. Since VCA enhances the accuracy by overcoming the modeling error, and reduce the numerical cost by avoiding an outer loop iteration for attaining the material property consistency in SCA, its efficiency is expected even higher than the recently proposed SCA algorithm.

Nystagmus in SCA territory cerebellar infarction: pattern and a possible mechanism.

PubMed

Lee, Hyung; Kim, Hyun-Ah

2013-04-01

To investigate the frequency and pattern of nystagmus associated with isolated cerebellar infarction in the territory of the superior cerebellar artery (SCA) and to discuss its possible mechanism. We identified 41 consecutive patients with isolated SCA territory cerebellar infarction diagnosed by MRI. Each patient completed a standardised dizziness questionnaire and underwent neurotological evaluations. Eye movements were recorded using 3-dimensional video-oculography during the acute period. Approximately half (19/41) of the patients experienced true vertigo early in the course of the SCA distribution infarct. 11 (27%) of the 41 patients showed spontaneous nystagmus (SN) or direction changed bidirectional gaze-evoked nystagmus (GEN). SN was observed in 10 patients (24%) and the horizontal component of SN was predominant in most case (80%, 8/10) and always beat towards the lesion side. Direction changed bidirectional GEN was observed in five patients and was mostly (4/5) accompanied by SN. Lesion subtraction analyses revealed that damage to the rostral anterior cerebellum including the ala of the central lobule and part of the quadrangular lobule was more frequent in patients with nystagmus compared to patients without nystagmus (9/11, 82% vs 11/30, 37%) (p=0.015). In most (82%, 9/11) patients with SN or GEN, the nystagmus subsided within 1 week after hospitalisation. Vertigo and nystagmus in SCA territory cerebellar infarction are more common than previously thought. Ipsilesional SN may result from damage to the anterior lobe of the cerebellum, which transmits the vestibular output to the fastigial nucleus.

KSC-2012-2286

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. Mission Specialist Nicole Stott visits with the media. Also present, but not in view, are Mission Specialists Michael Barrett, Steve Bowen and Alvin Drew, Pilot Eric Boe and Commander Steve Lindsay. The crew arrived to view the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2290

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. From the left, are Mission Specialists Alvin Drew, Nicole Stott, Steve Bowen partially hidden and Michael Barrett, and Pilot Eric Boe. Also present, but not in view, is Commander Steve Lindsay. The crew arrived to view the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2284

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. Mission Specialists Michael Barrett foreground and Alvin Drew visit with the media. Also present, but not in view, are Mission Specialists Nicole Stott and Steve Bowen, Pilot Eric Boe and Commander Steve Lindsay. The crew arrived to view the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2285

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, have arrived. Mission Specialist Alvin Drew visits with the media. Also present, but not in view, are Mission Specialists Nicole Stott, Michael Barrett and Steve Bowen, Pilot Eric Boe and Commander Steve Lindsay. In the background is the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

KSC-2012-2283

NASA Image and Video Library

2012-04-16

CAPE CANAVERAL, Fla. – At NASA Kennedy Space Center’s Shuttle Landing Facility in Florida, crew members of space shuttle Discovery’s last mission, STS-133, visit with each other after arriving in T-38 jet aircraft. From the left, are Mission Specialists Alvin Drew, Nicole Stott, Michael Barrett and Steve Bowen, Pilot Eric Boe and Commander Steve Lindsay. In the background is the Shuttle Carrier Aircraft, or SCA, with space shuttle Discovery attached atop after being backed away from the mate/demate device. Known as the MDD, the devise is a large gantry-like steel structure used to hoist a shuttle off the ground and position it onto the back of the SCA. The SCA is a Boeing 747 jet that was originally manufactured for commercial use and modified by NASA to transport the shuttles between destinations on Earth. This SCA, designated NASA 905, is assigned to the remaining ferry missions, delivering the shuttles to their permanent public display sites. NASA 905 is scheduled to ferry Discovery to the Washington Dulles International Airport in Virginia on April 17, after which the shuttle will be placed on display in the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information on the SCA, visit http://www.nasa.gov/centers/dryden/news/FactSheets/FS-013-DFRC.html. For more information on shuttle transition and retirement activities, visit http://www.nasa.gov/transition. Photo credit: NASA/Dimitri Gerondidakis

ELOVL5 Mutations Cause Spinocerebellar Ataxia 38

PubMed Central

Di Gregorio, Eleonora; Borroni, Barbara; Giorgio, Elisa; Lacerenza, Daniela; Ferrero, Marta; Lo Buono, Nicola; Ragusa, Neftj; Mancini, Cecilia; Gaussen, Marion; Calcia, Alessandro; Mitro, Nico; Hoxha, Eriola; Mura, Isabella; Coviello, Domenico A.; Moon, Young-Ah; Tesson, Christelle; Vaula, Giovanna; Couarch, Philippe; Orsi, Laura; Duregon, Eleonora; Papotti, Mauro Giulio; Deleuze, Jean-François; Imbert, Jean; Costanzi, Chiara; Padovani, Alessandro; Giunti, Paola; Maillet-Vioud, Marcel; Durr, Alexandra; Brice, Alexis; Tempia, Filippo; Funaro, Ada; Boccone, Loredana; Caruso, Donatella; Stevanin, Giovanni; Brusco, Alfredo

2014-01-01

Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases. PMID:25065913