Ataxins ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins ; genetics ; Spinocerebellar Ataxias ; genetics ; Trinucleotide Repeats

Objective To identify the specific genotype and analyze clinical features of spinocerebellar ataxias (SCAs) pedigree in the region of Yunnan Province.Methods Fourteen SCAs pedigrees and 183 blood samples of the family members were collected between January 2011 and July 2014 from Department of Neurology,First Affiliated Hospital of Kunming Medical College.Polymerase chain reaction (PCR) amplification,agarose gel electrophoresis and DNA sequencing technologies were utilized to identify the specific genotype of SCAs pedigree.Presymptomatic tests were carried out and the clinical features and genetic test results of patients were carefully analyzed.Results SCA3 was the most common subtype of SCAs in the Han nationality of Yunnan region.Nine of the 14 families were SCA3,only one family was SCA2.Additionally,there were four SCAs families that remained indeterminate.The patients with di-allele mutations (46/77) of SCA3 gene had early onset,rapid progression and serious clinical symptoms.Hereditary SCA3 and autonomic dominant polycystic kidney disease can happen simultaneously in a family.The proband SCA3 gene' s CAG repeat number is 28/76,and repetitions of the mutation allele are in all range.The PKD1 gene exon 23 is found to be in abnormal sequence.Conclusions SCA3 is the most common subtype of SCAs in the Han population of Yunnan region.There are 15/46 incomplete penetrance nutation and 46/77 di-allele mutations.It is possible that di-allele mutations make the disease worse and accelerate clinical course progression.SCA3 and polycystic kidney disease can uncommonly happen simultaneously in a family,which perhaps suggests there are interactions between the two disease-virulence genes.

Multiple sequence alignment is one of the basic techniques in bioinformatics, and it plays a vital role in structure modeling, functional site prediction, and phylogenetic analysis. In this paper, we review the methodologies and recent advances in the multiple protein sequence alignment, e.g., speeding up the calculation of distances among sequences and employing the iterative refinement and consistency-based scoring function, with emphasis on the use of additional sequence and structural information for improving alignment quality.
Algorithms ; Proteins ; chemistry ; Sequence Alignment ; methods ; Sequence Analysis, Protein ; methods

OBJECTIVETo investigate clinical features and genetic mutations of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease.

METHODSPolymerase chain reaction and DNA sequencing were employed to analyze exon 10 of the SCA3 gene, in addition with all exons and flanking sequences of PKD1 and PKD2 genes. The clinical features were also carefully analyzed.

RESULTSThe numbers of CAG repeat in the proband's SCA3 gene were 28/76, with the number of repeats in the mutant allele being in the full range. The sequence of exon 23 of the PKD1 gene was also found to be abnormal. Clinical symptoms of the proband were very serious, which were characterized by obvious ataxia, pyramidal signs, Meige syndrome, depression and high blood pressure.

CONCLUSIONHereditary spinocerebellar ataxia 3 and autonomic dominant polycystic kidney disease may co-occur, and genetic testing is the primary means of diagnosis.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Polycystic Kidney Diseases ; genetics ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; genetics

Objective:To explore the effect of functional electrical stimulation on cognition and on the expression of the brain-derived neurotrophic factor (BDNF), synaptophysin (SYN) and microtubule-associated protein 2 (MAP2) using a rat model of vascular dementia.Methods:Ninety pathogen-free male Wistar rats were randomly divided into a sham operation group, a placebo stimulation group and an electrical stimulation group. Both the placebo and electrical stimulation groups underwent bilateral occlusion of the common carotid artery to establish a model of vascular dementia. In the sham operation group the arteries were exposed without occlusion. Each group was then sub-divided into 3, 7 and 14 days subgroups with 10 rats in each subgroup. Beginning seven days after the surgery, the rats in the electrical stimulation group were given 30-minutes of stimulation every day while those in the sham operation group and the placebo stimulation group were given false electrical stimulation. After 3, 7 or 14 days the rats′ cognitive functioning was quantified using the Morris water maze test. The rats were then sacrificed and the expression of BDNF mRNA was measured using in situ hybridization. MAP2 and SYN levels were quantified immunohistochemically.Results:After 14 days the average latency in the placebo stimulation group was significantly longer than in the other groups. On the sixth day the average time in the target zone among the placebo stimulation group was significantly shorter than the other two groups′ averages. After only 3 days of simulation, the average expression of BDNF mRNA in the CA1 area of the hippocampus was significantly lower in the placebo stimulation group than among the others. After 7 days of stimulation the placebo group′s average was significantly lower than that of the sham operation group. The average expression of MAP2 had decreased significantly in the placebo stimulation group compared with the other two groups after 7 and 14 days of simulation. After 7 days the average expression of SYN in the placebo stimulation group was significantly lower than in the sham operation group, and after 14 days it was significantly lower than in the other two groups.Conclusions:Functional electrical stimulation may improve learning and memory in rats modelling vascular dementia through increasing BDNF, SYN and MAP2 expression levels.

Objective:To explore the features the gait of elderly persons with type 2 diabetes and peri-pheral neuropathy.Methods:Twenty patients no less than 60 years old with type 2 diabetes and peripheral neuropathy (DPN) formed a DPN group, while 20 counterparts with type 2 diabetes but without peripheral neuropathy composed the DM group, and another 20 healthy counterparts served as a control group. The three groups were tested using the Swedish Qualisys motion capture system and their walking speed, step length, step width, stride frequency and stride length, bipedal foot support phase time, single foot support phase time, peak plantar pressure, and regional-holding time were collected and compared.Results:The average walking speed, stride length and stepping frequency of the DPN group were all significantly lower than the other 2 groups′ averages. Their bipedal support phase was significantly longer, but their single foot support phase time was significantly shorter. And in the DPN group the average first and second peak plantar pressures and the second peak pressure time were significantly greater than the other groups′ averages.Conclusions:Elderly patients with type 2 diabetes and peripheral neuropathy have significant gait abnormalities, decreased walking stability, as well as increased plantar pressure and plantar compression time.