Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients

Background: A novel gammaretrovirus named xenotropic murine leukemia virus-related virus (XMRV) has been recently identified and found to have a prevalence of 40% in prostate tumor samples from American patients carrying a homozygous R462Q mutation in the RNaseL gene. This mutation impairs the function of the innate antiviral type I interferon pathway and is a known susceptibility factor for prostate cancer. Here, we attempt to measure the prevalence of XMRV in prostate cancer cases in Germany and determine whether an analogous association with the R462Q polymorphism exists. Results: 589 prostate tumor samples were genotyped by real-time PCR with regard to the RNaseL mutation. DNA and RNA samples from these patients were screened for the presence of XMRV-specific gag sequences using a highly sensitive nested PCR and RT-PCR approach. Furthermore, 146 sera samples from prostate tumor patients were tested for XMRV Gag and Env antibodies using a newly developed ELISA assay. In agreement with earlier data, 12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV specific sequences were detected at neither the DNA nor the RNA level. Consistent with this result, none of the sera analyzed from prostate cancer patients contained XMRV-specific antibodies. Conclusion: Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections

Caracterização ambiental da bacia do córrego do Cedrinho no município de Presidente Prudente e propostas para recuperação da área

O presente artigo apresenta o resultado do Trabalho de Graduação em Engenharia Ambiental da F.C.T. - UNESP atualizado com parte dos conhecimentos adquiridos pelos autores no Mestrado em Engenharia Civil da UNICAMP e as contribuições do Prof. Dr. Antonio Cezar Leal. O trabalho é aplicado à bacia do Córrego do Cedrinho no município de Presidente Prudente e tem por objetivo principal a caracterização ambiental do meio físico. A base da metodologia de trabalho foi o mapeamento, por meio de dados secundários, de vários temas sobre o meio físico da área amparados por trabalhos de campo como forma de verificação. A ferramenta principal para a aplicação do método foi o SIG SPRING. Como resultado o trabalho apresentou uma série de mapas e tabelas sobre o meio físico da bacia servindo de suporte para a elaboração de critérios para a recuperação ambiental da área. No final do trabalho são apresentadas algumas propostas de recuperação da área, porém caso ocorram tais intervenções na bacia, estas devem estar amparadas por projetos específicos mais detalhados para cada ação.   Palavras-Chave: caracterização ambiental . recursos hídricos . áreas degradadas.   Abstract   This paper presents results of the under graduation final task in Environmental Engineering from FCT - UNESP updated with some knowledge acquired by the authors during the Master's degree in Civil Engineering from UNICAMP, as well as, contributions of Prof. Dr. Cezar Antonio Leal. The task is applied to the basin of the Cedrinho stream in the city of Presidente Prudente and it has as main objective, the environmental characterization of the physical environment. The basis of the methodology of the task was the mapping, through secondary data, several issues on the physical environment of the area supported by field work as a mean of verification. The main tool for the application of the method was the GIS SPRING. As a result, the work presented a series of maps and tables on the physical environment of the basin which served as support for the development of criteria for the environmental recovery of the area. At the end of the paper, it's presented some proposals for recuperation of the area, however if such interventions occur in the basin, these must be supported by more detailed specific projects for each action.   Keywords: Environmental characterization . water resources . degraded areas

Reliability and Validity of the Severe Impairment Battery (SIB) in Korean Dementia Patients

This study was conducted to examine the reliability, validity and clinical utility of the Severe Impairment Battery (SIB) for a Korean population. 69 dementia patients with Clinical Dementia Rating (CDR) stages 2 or 3 were participated in this study. The SIB, Korean version-Mini Mental State Examination (K-MMSE), CDR, and Seoul-Activities of Daily Living (S-ADL) were administered. The validity of the SIB was confirmed by evaluating the correlation coefficients between the SIB and K-MMSE, CDR, S-ADL, which were found to be significant. Cronbach's alpha for the total SIB score and each subscale score showed high significance, and the item-total correlation for each subscale was also acceptable. The test-retest correlation for the total SIB score and subscale scores were significant, except for the praxis and orienting to name. The total SIB score and subscale scores were examined according to CDR. The results suggest that the SIB can differentiate the poor performances of severely impaired dementia patients. On the basis of the receiver operating characteristic (ROC), it can be concluded that the SIB is able to accurately discriminate between CDR 2 and 3 patients. The results of this study suggest that the SIB is a reliable and valid instrument for evaluating severe dementia patients in Korean population

Structural connectivity in a single case of progressive prosopagnosia: The role of the right inferior longitudinal fasciculus

Progressive prosopagnosia (PP) is a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people. Here we report a patient (G.S.) with PP, mainly related to a prominent deficit in recognition of familiar faces, without a semantic (cross-modal) impairment. An in-depth evaluation showed that his deficit extended to other classes of objects, both living and non-living. A follow-up neuropsychological assessment did not reveal substantial changes after about 1 year. Structural MRI showed predominant right temporal lobe atrophy. Diffusion tensor imaging was performed to elucidate structural connectivity of the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), the two major tracts that project through the core fusiform region to the anterior temporal and frontal cortices, respectively. Right ILF was markedly reduced in G.S., while left ILF and IFOFs were apparently preserved. These data are in favour of a crucial role of the neural circuit subserved by right ILF in the pathogenesis of PP

miROrtho: computational survey of microRNA genes

MicroRNAs (miRNAs) are short, non-protein coding RNAs that direct the widespread phenomenon of post-transcriptional regulation of metazoan genes. The mature ∼22-nt long RNA molecules are processed from genome-encoded stem-loop structured precursor genes. Hundreds of such genes have been experimentally validated in vertebrate genomes, yet their discovery remains challenging, and substantially higher numbers have been estimated. The miROrtho database (http://cegg.unige.ch/mirortho) presents the results of a comprehensive computational survey of miRNA gene candidates across the majority of sequenced metazoan genomes. We designed and applied a three-tier analysis pipeline: (i) an SVM-based ab initio screen for potent hairpins, plus homologs of known miRNAs, (ii) an orthology delineation procedure and (iii) an SVM-based classifier of the ortholog multiple sequence alignments. The web interface provides direct access to putative miRNA annotations, ortholog multiple alignments, RNA secondary structure conservation, and sequence data. The miROrtho data are conceptually complementary to the miRBase catalog of experimentally verified miRNA sequences, providing a consistent comparative genomics perspective as well as identifying many novel miRNA genes with strong evolutionary support

CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer

The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk

MicroRNA-296 is enriched in cancer cells and downregulates p21WAF1 mRNA expression via interaction with its 3′ untranslated region

MicroRNAs (miRNAs) are a class of noncoding small RNAs that act as negative regulators of gene expression. To identify miRNAs that may regulate human cell immortalization and carcinogenesis, we performed comparative miRNA array profiling of human normal and SV40-T antigen immortalized cells. We found that miR-296 was upregulated in immortalized cells that also had activation of telomerase. By an independent experiment on genomic analysis of cancer cells we found that chromosome region (20q13.32), where miR-296 is located, was amplified in 28/36 cell lines, and most of these showed enriched miR-296 expression. Overexpression of miR-296 in human cancer cells, with and without telomerase activity, had no effect on their telomerase function. Instead, it suppressed p53 function that is frequently downregulated during human cell immortalization and carcinogenesis. By monitoring the activity of a luciferase reporter connected to p53 and p21WAF1 (p21) untranslated regions (UTRs), we demonstrate that miR-296 interacts with the p21-3′UTR, and the Hu binding site of p21-3′UTR was identified as a potential miR-296 target site. We demonstrate for the first time that miR-296 is frequently upregulated during immortalization of human cells and contributes to carcinogenesis by downregulation of p53-p21WAF1 pathway

MicroRNA Fingerprints Identify miR-150 as a Plasma Prognostic Marker in Patients with Sepsis

BACKGROUND: The physiopathology of sepsis continues to be poorly understood, and despite recent advances in its management, sepsis is still a life-threatening condition with a poor outcome. If new diagnostic markers related to sepsis pathogenesis will be identified, new specific therapies might be developed and mortality reduced. Small regulatory non-coding RNAs, microRNAs (miRNAs), were recently linked to various diseases; the aim of our prospective study was to identify miRNAs that can differentiate patients with early-stage sepsis from healthy controls and to determine if miRNA levels correlate with the severity assessed by the Sequential Organ Failure Assessment (SOFA) score. METHODOLOGY/PRINCIPAL FINDINGS: By using genome-wide miRNA profiling by microarray in peripheral blood leukocytes, we found that miR-150, miR-182, miR-342-5p, and miR-486 expression profiles differentiated sepsis patients from healthy controls. We also proved by quantitative reverse transcription-polymerase chain reaction that miR-150 levels were significantly reduced in plasma samples of sepsis patients and correlated with the level of disease severity measured by the SOFA score, but were independent of the white blood counts (WBC). We found that plasma levels of tumor necrosis factor alpha, interleukin-10, and interleukin-18, all genes with sequence complementarity to miR-150, were negatively correlated with the plasma levels of this miRNA. Furthermore, we identified that the plasma levels ratio for miR-150/interleukin-18 can be used for assessing the severity of the sepsis. CONCLUSIONS/SIGNIFICANCE: We propose that miR-150 levels in both leukocytes and plasma correlate with the aggressiveness of sepsis and can be used as a marker of early sepsis. Furthermore, we envision miR-150 restoration as a future therapeutic option in sepsis patients

Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer

BACKGROUND: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker. METHODS: The 5-aza-2'-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. RESULTS: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P=0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P=0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P=0.561. CONCLUSIONS: These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker