Dominant negative mutant Cyclin T1 proteins inhibit HIV transcription by specifically degrading Tat

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Evaluation of Rapid Immunochromatographic Tests for Norovirus in Neonatal and Infant Faecal Specimens

Objectives: To compare the diagnostic performance of two norovirus rapid immunochromatographic kits (QuickNavi(®)-Norovirus [QN] and QuickNavi®-Norovirus 2 [QN2]; Denka Seiken, Niigata, Japan) for neonatal and infant faecal specimens. Methods: Monthly faecal samples were collected from infants from birth to 12 months of age, and tested for norovirus using QN and QN2. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used as the gold standard for norovirus detection. The diagnostic performance of the kits was calculated. Results: A total of 343 specimens from 81 infants were analysed. In all samples, the specificity of QN and QN2 was 80% (275/343) and 99% (339/343), respectively. In infants aged Conclusions: QN2 offers improved performance and is more useful than QN for the diagnosis of norovirus infection in the neonatal and infant period

Parental rearing attitudes in childhood is associated with adult sleep disturbances independently from depression and life events: a cross-sectional survey in Japan

Sleep disturbance associated with depression and suicide is a serious public health concern. Previous studies have suggested that sleep disturbances increase the risk of suicide without going through depression. Adverse childhood experience, which has a long-term effect on mental health, is also a serious problem. We conducted a study to investigate the association between parental rearing attitudes in childhood and sleep disturbances in adulthood by performing a questionnaire survey. A cross-sectional survey performed with the residents of a provincial city in Japan. A total of 1,500 male (aged ≧ 30 years) subjects were randomly selected by a computer from the basic resident register after stratifying them by age. The subjects were assessed by personal characteristics, the Center for Epidemiologic Studies Depression Scale (CES-D), the Social Readjustment Rating Scale (SRRS), and the Parent Bonding Instrument (PBI). We obtained an answer from 400 people (26.7%) among 1,500 subjects. Their average age and standard deviation were 48.3±8.6 years at the time of the survey. According to performing a logistic regression analysis that assessed each parental bonding type compared with optimal bonding adjusted for CES-D and SRRS, “affectionless control” and “awaking during sleep,” and “affectionate constraint” and “a sense of insufficiency of the sleep” were significantly associated, even after controlling for age (OR 2.93, 95% CI: 1.46-5.87; OR 0.24, 95% CI: 0.07-0.79, respectively). Our study raises the possibility that the parental care of a child affects sleep disturbances in adulthood

Epigenetic biomarkers for prediction of sensitivity to chemotherapeutic drugs in multiple myeloma

Multiple myeloma continues to be a lethal malignancy despite the development of treatments such as high-dose chemotherapy combined with stem cell transplantation. Multiple myeloma arises through an accumulation of multiple genetic anges, including immunoglobulin gene rearrangements involved in Cyclin D. The main difficulties in multiple myeloma treatments are drug-resistance. DNA methylation of the5\u27 CpG islands of genes is often found in multiple myeloma. To screen for he genes involved in tumorigenesis of multiple myeloma, which are silenced by DNA methylation, we performed cDNA microarray analysis using multiple myeloma cell lines treated with demethylating agent5-aza-2-deoxycytidine (DAC), and entified RASD1, a dexamethasone (Dex)-inducible gene, as one of the targets of epigenetic changes. Inactivation of RASD1 was found to correlate with resistance to Dex, and treatment of multiple myeloma cells with DAC restored sensitivity to Dex. These findings suggest the involvement of epigenetic gene silencing in multiple myeloma progression and drug-resistance, and the usefulness of demethylation therapy for multiple myeloma treatment. Furthermore, DNA methylation can be an epigenetic biomarker for multiple myeloma

A diagnostic marker for superficial urothelial bladder carcinoma : lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n= 110) and ATBF1− (n=7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma

Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations

金沢大学医薬保健学総合研究科先進的地域医療研究講座 = Department of Advanced Research in Community MedicineTo clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions’ clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect

Researching peers and disaster vulnerable communities: an insider perspective

Conducting research among peers and communities that a researcher also serves may be both daunting and rewarding. Researching peers may make the researcher feel uncomfortable raising certain questions that are sensitive or that could be construed to be testing their competencies. This paper is inclined more towards showing that it is advantageous to be an insider, whose position can facilitate collection of information that could not have been accessed, or revealed to an outsider. The paper reports on fieldwork conducted in a low-income country in Sub-Sahara Africa as part of a doctoral study with communities affected by disasters and those that work with such communities. The paper demonstrates the complexities of conducting such research and provides some insights that may be useful to insiders, outsiders or “in-betweeners” embarking on fieldwork in low-income countries and among vulnerable population struggling with manifold stresses and shocks

Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer

Gastric cancer cells often show altered Ras signaling, though the underlying molecular mechanism is not fully understood. We examined the expression profile of eight ras-association domain family (RASSF) genes plus MST1/2 and found that RASSF2A is the most frequently downregulated in gastric cancer. RASSF2A was completely silenced in 6 of 10 gastric cancer cell lines as a result of promoter methylation, and expression was restored by treating the cells with 5-aza-2′-deoxycytidine. Introduction of RASSF2A into non-expressing cell lines suppressed colony formation and induced apoptosis. These effects were associated with the cytoplasmic localization of RASSF2A and morphological changes to the cells. Complementary DNA microarray analysis revealed that RASSF2A suppresses the expression of inflammatory cytokines, which may in turn suppress angiogenesis and invasion. In primary gastric cancers, aberrant methylation of RASSF2A was detected in 23 of 78 (29.5%) cases, and methylation correlated significantly with an absence of the lymphatic invasion, absence of venous invasion, absence of lymph node metastasis, less advanced stages, Epstein–Barr virus, absence of p53 mutations and the presence of the CpG island methylator phenotype-high. These results suggest that epigenetic inactivation of RASSF2A is required for tumorigenesis in a subset of gastric cancers