Evaluating the current state of the art of Huntington disease research: a scientometric analysis

Huntington disease (HD) is an incurable neurodegenerative disorder caused by a dominant mutation on the 4th chromosome. We aim to present a scientometric analysis of the extant scientific undertakings devoted to better understanding HD. Therefore, a quantitative study was performed to examine the current state-of-the-art approaches that foster researchers' understandings of the current knowledge, research trends, and research gaps regarding this disorder. We performed literature searches of articles that were published up to September 2016 in the "ISI Web of Science™" (http://apps.webofknowledge.com/). The keyword used was "Huntington disease". Of the initial 14,036 articles that were obtained, 7732 were eligible for inclusion in the study according to their relevance. Data were classified according to language, country of publication, year, and area of concentration. The country leader regarding the number of studies published on HD is the United States, accounting for nearly 30% of all publications, followed by England and Germany, who have published 10 and 7% of all publications, respectively. Regarding the language in which the articles were written, 98% of publications were in English. The first publication to be found on HD was published in 1974. A surge of publications on HD can be seen from 1996 onward. In relation to the various knowledge areas that emerged, most publications were in the fields of neuroscience and neurology, likely because HD is a neurodegenerative disorder. Publications written in areas such as psychiatry, genetics, and molecular biology also predominated.

Clinical phenotype and genetic analysis of MED13L syndrome / 中国当代儿科杂志

A boy aged 4 years and 2 months was found to have delayed language and motor development, instability of gait, poor eye contact, stereotyped behavior, and seizure at the age of 3 years. Physical examination showed special facial features, including plagiocephaly, blepharoptosis, wide nasal bridge, down-turned mouth corners at both sides, and low-set ears. There were only two knuckles at the little finger of the left hand. The anteroposterior and lateral films of the spine showed scoliosis; echocardiography showed ventricular septal defect; the Gesell Developmental Scale showed delayed language development and moderate intellectual disability; there were no abnormalities in the karyotype; genome-wide SNP arrays found a duplication in 12q24.21 region with a size of 1.03 Mb in chromosome 12, while this was not seen in his parents. The boy was diagnosed with MED13L syndrome. Point mutation, deletion, and duplication in the MED13L gene can lead to MED13L syndrome. The patients with different genotypes may have different phenotypes. Genome-wide SNP arrays may help with the diagnosis of this disease.

Mortality from Alzheimer's disease in Brazil, 2000-2009 / Enfermedad de Alzheimer: estudio de la mortalidad en Brasil, 2000-2009 / Doença de Alzheimer: estudo da mortalidade no Brasil, 2000-2009

Alzheimer's disease is the most prevalent type of dementia in the elderly worldwide. To evaluate the mortality trend from Alzheimer's disease in Brazil, a descriptive study was conducted with the Mortality Information System of the Brazilian Ministry of Health (2000-2009). Age and sex-standardized mortality rates were calculated in Brazil's state capitals, showing the percentage variation by exponential regression adjustment. The state capitals as a whole showed an annual growth in mortality rates in the 60 to 79 year age bracket of 8.4% in women and 7.7% in men. In the 80 and older age group, the increase was 15.5% in women and 14% in men. Meanwhile, the all-cause mortality rate declined in both elderly men and women. The increase in mortality from Alzheimer's disease occurred in the context of chronic diseases as a proxy for increasing prevalence of the disease in the population. The authors suggest healthcare strategies for individuals with chronic non-communicable diseases.

La enfermedad de Alzheimer es la demencia más frecuente entre adultos mayores en el mundo. Para evaluar la evolución de la mortalidad por la enfermedad de Alzheimer en Brasil, se ha desarrollado un estudio con datos del Sistema de Información sobre Mortalidad del Ministerio de Salud, durante el período 2000-2009. Se calcularon las tasas de mortalidad estandarizadas por edad y sexo en las capitales brasileñas y se registró la variación porcentual mediante ajuste de la regresión exponencial. El conjunto de las capitales presentó un aumento anual de las tasas de mortalidad en el grupo de edad de 60 a 79 años, de un 8,4% en mujeres y un 7,7% en hombres. En el grupo de 80 o más años, el aumento fue de un 15,5% en mujeres y un 14% en hombres. No obstante, hubo una disminución en la tasa de mortalidad por todas las causas entre los adultos mayores de ambos sexos. Se destaca un aumento de la mortalidad por enfermedad de Alzheimer en el contexto de las enfermedades crónicas como un proxy para la prevalencia de la enfermedad en la población, y se indican estrategias de asistencia en el cuidado de pacientes con enfermedades de larga duración.

A doença de Alzheimer é o tipo de demência que mais prevalece entre os idosos no mundo. Para avaliar a evolução da mortalidade por doença de Alzheimer no Brasil foi desenvolvido um estudo descritivo com os dados do Sistema de Informações sobre Mortalidade do Ministério da Saúde, no período de 2000 a 2009. Calcularam-se as taxas de mortalidade padronizadas por idade e sexo nas capitais brasileiras e se observou a variação percentual por meio de ajuste por regressão exponencial. Para o conjunto das capitais houve um crescimento anual nas taxas de mortalidade na faixa etária de 60 a 79 anos de 8,4% entre as mulheres e 7,7% entre os homens. No grupo etário de 80 anos e mais, o aumento foi de 15,5% entre as mulheres e 14% entre os homens. Contrariamente, verificou-se declínio da taxa de mortalidade por todas as causas entre os idosos em ambos os sexos. Destaca-se o aumento da mortalidade por doença de Alzheimer no contexto das doenças crônicas como um indicador aproximado da prevalência da doença na população, e são apontadas estratégias de assistência ao cuidado dos portadores de doenças de longa duração.

MED12 mutations in human diseases

The Mediator Complex plays key roles in activating gene transcription in eukaryotes. Mediator of RNA polymerase II transcription subunit 12 homolog (MED12) is a subunit of the Mediator Complex and regulates the activity of the complex. MED12 is involved in a variety of cellular activities, and mutations in MED12 gene impair MED12 activities and are associated with several diseases, including Opitz-Kaveggia syndrome, Lujan syndrome, uterine leiomyomas and prostate cancer. This review will discuss the biological function of MED12 and the relationship between MED12 mutations and diseases.

Structural flexibility and functional interaction of Mediator Cdk8 module

Mediator is a highly conserved large protein complex (25 proteins, >1000 kDa) and preeminently responsible for eukaryotic transcription, which contains a dissociable 'Cdk8 module'. Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation, the detailed structure, and subunit organization, molecular mechanism how it regulates transcription remain elusive. Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural flexibility. The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo. An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro, which is presumed to be an active functional state of Mediator. Taken together, our results illuminated the detailed architecture of Cdk8 module, and suggested the Cdk8 module could positively regulate transcription by modulating Mediator conformation.

Construction of the eukaryotic expression vector of MJD1 and its expression in SH-SY5Y cells / 中南大学学报(医学版)

OBJECTIVE@#To construct the eukaryotic expression vector of MJD1 with normal copies of CAG trinucleotide repetition and MJD1 with CAG trinucleotide repetition expansion mutation respectively, and to determine whether the polyglutamine expansion in ataxin-3 could lead to the formation of intranuclear aggregation.@*METHODS@#The coding sequence of wild-type MJD1 and mutant MJD1 was amplified by PCR from pAS2-1-MJD20Q and pAS2-1-MJD68Q respectively. After being digested with BamH I and Hind III, the PCR products were inserted into pcDNA3. 1-Myc-His(-) B. The recombinant plasmids pcDNA3.1-Myc-His(-) B-MJD20Q and pcDNA3.1-Myc-His(-) B-MJD68Q were identified by enzyme digestion analysis and DNA sequencing. The recombinant plasmid was transfected into SH-SYSY cells and the expression of MJD1 in the transfected cells was analyzed by Western blot. The immunofluorescence of the transfected cells was examined using a confocal microscope to observe the formation of intranuclear aggregation.@*RESULTS@#Enzyme digestion analysis and DNA sequencing showed that the target gene was cloned into pcDNA3. 1-Myc-His(-) B. The expression of MJD1 in the transfected cells was confirmed by Western blot; The SH-SY5Y cells transfected with pcDNA3. 1-Myc-His(-) B-MJD68Q showed the formation of intranuclear aggregation, but the cells transfected with pcDNA3.1-Myc-His(-) B-MJD20Q did not show such phenomenon.@*CONCLUSION@#The eukaryotic expression vectors of MJD1 has been successfully constructed; The polyglutamine expansion in ataxin-3 could lead to the formation of intranuclear aggregation.