Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease

Background: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer’s disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation. Methodology/Principal Findings: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter was hypermethylated more in MCI than in advanced AD. The cytosine methylation of total genomic DNA was similar in AD, MCI, and control samples. Consistent with a notion that hypermethylation-mediated silencing of the nucleolar chromatin stabilizes rDNA loci, preventing their senescence-associated loss, genomic rDNA content was elevated in cerebrocortical samples from MCI and AD groups. Conclusions/Significance: In conclusion, rDNA hypermethylation could be a new epigenetic marker of AD. Moreover, silencing of nucleolar chromatin may occur during early stages of AD pathology and play a role in AD-related ribosoma

CyclinPred: A SVM-Based Method for Predicting Cyclin Protein Sequences

Functional annotation of protein sequences with low similarity to well characterized protein sequences is a major challenge of computational biology in the post genomic era. The cyclin protein family is once such important family of proteins which consists of sequences with low sequence similarity making discovery of novel cyclins and establishing orthologous relationships amongst the cyclins, a difficult task. The currently identified cyclin motifs and cyclin associated domains do not represent all of the identified and characterized cyclin sequences. We describe a Support Vector Machine (SVM) based classifier, CyclinPred, which can predict cyclin sequences with high efficiency. The SVM classifier was trained with features of selected cyclin and non cyclin protein sequences. The training features of the protein sequences include amino acid composition, dipeptide composition, secondary structure composition and PSI-BLAST generated Position Specific Scoring Matrix (PSSM) profiles. Results obtained from Leave-One-Out cross validation or jackknife test, self consistency and holdout tests prove that the SVM classifier trained with features of PSSM profile was more accurate than the classifiers based on either of the other features alone or hybrids of these features. A cyclin prediction server- CyclinPred has been setup based on SVM model trained with PSSM profiles. CyclinPred prediction results prove that the method may be used as a cyclin prediction tool, complementing conventional cyclin prediction methods

Mice with Different Susceptibility to Japanese Encephalitis Virus Infection Show Selective Neutralizing Antibody Response and Myeloid Cell Infectivity

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes public health problems in Asian countries. Only a limited number of JEV-infected individuals show symptoms and develop severe encephalitis, indicating host-dependent susceptibilities.C3H/HeN and DBA/2 mice, which exhibit different mortalities when infected by intraperitoneal inoculation with JEV, were used as experimental models to compare viral pathogenesis and host responses. One hundred infectious virus particles killed 95% of C3H/HeN mice whereas only 40% of DBA/2 mice died. JEV RNA was detected with similar low levels in peripheral lymphoid organs and in the sera of both mouse strains. High levels of viral and cytokine RNA were observed simultaneously in the brains of C3H/HeN and DBA/2 mice starting on days 6 and 9 post-infection, respectively. The kinetics of the cytokines in sera correlated with the viral replication in the brain. Significantly earlier and higher titers of neutralizing antibodies were detected in the DBA/2 strain. Primary embryonic fibroblasts, bone marrow-derived dendritic cells and macrophages from the two mouse strains were cultured. Fibroblasts displayed similar JEV replication abilities, whereas DBA/2-derived myeloid antigen-presenting cells had lower viral infectivity and production compared to the C3H/HeN–derived cells. may be elements associated with late and decreased mouse neuroinvasion

Regulation of inflammation in Japanese encephalitis

Uncontrolled inflammatory response of the central nervous system is a hallmark of severe Japanese encephalitis (JE). Although inflammation is necessary to mount an efficient immune response against virus infections, exacerbated inflammatory response is often detrimental. In this context, cells of the monocytic lineage appear to be important forces driving JE pathogenesis

Espondilite tuberculosa: uma revisão de 31 pacientes do Hospital Santa Marcelina Espondilitis tuberculosa: una revisión de 31 pacientes del Hospital Santa Marcelina Tuberculous spondylitis: a report of thirty one cases from Santa Marcelina Hospital

INTRODUÇÃO: a infecção da coluna vertebral pelo bacilo de Koch costuma ser devastadora, sendo necessários seu diagnóstico e tratamento precoce. OBJETIVO: avaliar o tratamento e o seguimento em relação à dor, cifose residual, imagem por ressonância magnética (RM), e a importância da biópsia correlacionando-a com o tratamento clínico. Métodos: estudo retrospectivo de 31 pacientes com diagnóstico de espondilite tuberculosa, fazendo uma análise estatística dos dados descritivos: sexo, idade, status neurológico, segmento vertebral acometido, presença de abscesso e cifose residual, e suas correlações clínicas importantes comparando nossos casos com a literatura e correlacionando seus dados, tais como sexo e faixa etária mais comum, se a presença do abscesso influencia no déficit neurológico ou na cifose residual. RESULTADOS: a amostra identificou uma incidência em 23 homens e 8 mulheres. Foi identificado abscesso frio em 4 pacientes, sendo os que apresentaram uma grave deformidade final: a biopsia percutânea foi realizada em 19 pacientes com positividade em 5, não influenciando o tratamento do paciente. A dor pós-tratamento clínico apresentou melhora importante; foi utilizado esquema tríplice por um ano. CONCLUSÃO: o tratamento clínico da tuberculose deve ser iniciado assim que se suspeitar da doença e tiver imagens compatíveis com: corpo vertebral, diminuição da altura do espaço discal e elevação do ligamento longitudinal anterior. Na presença de cifose, o uso de um colete rígido deve ser ponderado, sendo ele o de Boston ou um colete gessado. A avaliação neurológica deve ser acompanhada com um intervalo curto, quinzenalmente nos primeiros três meses, pois se o tratamento clínico for ineficaz e o paciente apresentar déficit neurológico, o tratamento cirúrgico deve ser considerado. A biopsia é um exame de alta especificidade, mas de baixa sensibilidade. Quando positiva, reforça o tratamento medicamentoso.<br>INTRODUCCIÓN: la infección de la columna vertebral por el bacilo de Koch acostumbra ser devastadora, siendo necesario el diagnóstico y tratamiento precoz. OBJETIVO: evaluar el tratamiento y el seguimiento en relación al dolor, cifosis residual, imagen en la resonancia magnética (RM) y la importancia de la biopsia correlacionándola con el tratamiento clínico. MÉTODOS: estudio retrospectivo de 31 pacientes con diagnóstico de espondilitis tuberculosa haciendo un análisis estadístico de los datos descriptivos: sexo, edad, estatus neurológico, segmento vertebral comprometido, presencia de absceso y cifosis residual, así como sus correlaciones clínicas importantes comparando nuestros casos con la literatura y correlacionando sus datos con lo referente al sexo y la tasa etaria donde fue más común, si la presencia del absceso influyó en el déficit neurológico o en la cifosis residual. RESULTADOS: la muestra identificó una incidencia en 23 hombres y 8 mujeres. Fue identificado absceso frío en cuatro pacientes, siendo los que presentaron una grave deformidad final; la biopsia percutánea fue realizada en 19 pacientes con positividad en 5, no influyendo en el tratamiento del paciente. El dolor post tratamiento clínico presentó una mejoría importante; fue utilizado un esquema triple por un año. CONCLUSIÓN: el tratamiento clínico de tuberculosis debe ser iniciado así que la enfermedad fuera sospechada y tuviera imágenes compatibles con: el cuerpo vertebral, la disminución de la altura del espacio discal, y con la elevación del ligamento longitudinal anterior. En la presencia del cifosis, el uso de un chaleco rígido debe ser ponderado, siendo un Chaleco de Boston o un chaleco de yeso. La evaluación neurológica debe ser acompañada de un intervalo pequeño, quincenalmente en los primeros tres meses, pues si el tratamiento clínico fuera ineficaz y el paciente presentara déficit neurológico, el tratamiento quirúrgico debería ser considerado. La biopsia es un examen de alta especificidad, pero de baja sensibilidad. Si fuera positiva, refuerza el tratamiento medicamentoso.<br>INTRODUCTION: the infection of the spine by the mycobacterium tuberculosis is often devastating, requiring early diagnosis and treatment. Objective: to assess the treatment and follow-up regarding the pain, residual kyphosis, image of magnetic resonance imaging (MRI), and importance of biopsy relating to the clinical treatment. METHODS: retrospective study of 31 patients with diagnosis tuberculous spondylitis making a statistical analysis, studying the data descrition: gender, age, neurological status, spinal segment and kyphosis abscess, presence of residual kyphosis and their clinical correlations, comparing our major cases with literature and relashionship, and if the presence of abscess can influence in on neurological deficit or residual kyphosis. RESULTS: the sample identified an incidence in 23 men and 8 women; cold abscess was identified in 4 patients, and how those with a severe deformity final percutaneous biopsy was performed in 19 patients with positivity in 5, with no influence patient treatment. The pain after treatment showed significant improvement and we used triple drug regimen for one year. CONCLUSIONS: the clinical treatment of tuberculosis should start once the disease is suspected and have compatible images with: vertebral body, decreased disc space height, and elevation of the anterior longitudinal ligament. In the presence of kyphosis using a weighted vest to be hard, being the Boston vest or a plaster cast. The neurological evaluation should be accompanied, and with a short interval, fortnightly during the first three months, because if the clinical treatment is ineffective and the patient has neurological deficit surgical treatment should be considered. The biopsy is a test of high specificity but low sensitivity. When the test is positive it reinforces drug treatment