MAL64 c is a global regulator of α-glucoside fermentation: identification of a new gene involved in melezitose fermentation

Summary Maltase constitutive mutants at the MAL6 locus have been mapped to the newly identified regulatory gene MAL64 ^c. We show here that MAL64 ^c has in addition pleiotropic effects on sugar fermentation: MAL64 ^c strains constitutively synthesize an -methylglucosidase and can complement a new gene, MTP1, for the fermentation of melezitose and -methylglucoside. MTP1, maps near MAL1, and either encodes a permease which transports melezitose, -methylglucoside, and maltose or regulates the activity of such a permease. This work shows that MAL64 ^c, a trans-acting regulatory gene, is a global regulatory gene affecting several different pathways of -glucoside metabolism.     

Comparison of Self-Report Versus Sensor-Based Methods for Measuring the Amount of Upper Limb Activity Outside the Clinic

Objective

To compare self-reported with sensor-measured upper limb (UL) performance in daily life for individuals with chronic (≥6mo) UL paresis poststroke.

TIRAP C539T polymorphism contributes to tuberculosis susceptibility: Evidence from a meta-analysis

BackgroundToll-interleukin 1 receptor domain containing adaptor protein (TIRAP), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, is highly involved in the activation and coordination of the anti-mycobacterial immune response. We performed a meta-analysis to assess the association between TIRAP C539T polymorphism and tuberculosis (TB) risk.MethodsA systematic literature search for relevant studies up to February 27, 2014 was conducted in PUBMED, EMBASE, Web of science, CNKI, VIP, and Wanfang database. The association between gene and disease was assessed using odds ratios (ORs) with 95% confidence intervals (95%CIs) based on five genetic models.ResultsA total of 16 qualified studies were enrolled in this meta-analysis. The results of pooling all studies detected statistically resistance of TIRAP C539T mutants to TB risk (T vs. C: OR 0.80, 95%CI 0.65–0.97; TC vs. CC: OR 0.71, 95%CI 0.55–0.92; TT + TC vs. CC: OR 0.74, 95% CI 0.58–0.94). Further subgroup analyses by ethnicity also demonstrated reduced risk of TB in European population (T vs. C: OR 0.71, 95%CI 0.52–0.95; TC vs. CC: OR 0.56, 95%CI 0.35–0.91; TT + TC vs. CC: OR 0.61, 95%CI 0.40–0.92), whereas no such effects were observed in other ethnicities.ConclusionThis present meta-analysis suggests TIRAP C539T polymorphism is significantly correlated with reduced risk of TB infection, with stronger effect in European. Additional well-designed, larger-scale epidemiological studies among different ethnicities are needed.     

MAL基因与肿瘤

MAL基因是一个在T细胞分化中晚期表达的基因。许多研究表明MAL基因在食管癌、胃癌、结肠癌、头颈部鳞癌等多种肿瘤组织中表达下调或缺失，与肿瘤的发生发展过程有关。MAL基因要作为临床诊断、判断预后及指导治疗的指标而得到应用，还需要进一步研究。     

MAL promoter hypermethylation as a novel prognostic marker in gastric cancer

T-lymphocyte maturation associated protein, MAL, has been described as a tumour-suppressor gene with diagnostic value in colorectal and oesophageal cancers, and can be inactivated by promoter hypermethylation. The aim of this study was to analyse the prevalence of MAL promoter hypermethylation and the association with mRNA expression in gastric cancers and to correlate methylation status to clinicopathological data. Bisulphite-treated DNA isolated from formalin-fixed and paraffin-embedded samples of 202 gastric adenocarcinomas and 22 normal gastric mucosae was subjected to real-time methylation-specific PCR (Q-MSP). Two regions within the MAL promoter (M1 and M2) were analysed. In addition, 17 frozen gastric carcinomas and two gastric cancer cell lines were analysed both by Q-MSP and real-time RT–PCR. Methylation of M1 and M2 occurred in 71 and 80% of the gastric cancers, respectively, but not in normal gastric mucosa tissue. Hypermethylation of M2, but not M1, correlated with significantly better disease-free survival in a univariate (P=0.03) and multivariate analysis (P=0.03) and with downregulation of expression (P=0.01). These results indicate that MAL has a putative tumour-suppressor gene function in gastric cancer, and detection of promoter hypermethylation may be useful as a prognostic marker.     

MAL基因在胃癌组织中的甲基化及其mRNA的表达

目的:研究MAL基因在胃癌和癌旁组织中的甲基化状态及其mRNA表达.方法:应用甲基化特异性PCR(MSP)和实时荧光定量RT-PCR法检测37例人胃癌组织及对应癌旁5 cm组织中MAL基因的甲基化状态和mRNA表达,并分别将其与各临床病理指标进行统计学分析.结果:37例胃癌组织中MAL基因甲基化率为78.4%.对应37例癌旁组织中MAL基因甲基化率为5.4%.癌组织与癌旁组织的甲基化率差异有统计学意义(P<0.01).胃癌组织中MAL基因甲基化状态与患者年龄、性别、肿瘤大小、有无淋巴结转移、胃癌分化程度、临床分期无统计学意义(P>0.05).在胃癌组织与对应癌旁组织中MAL基因mRNA定量表达差异有统计学意义(P<0.05),胃癌组织中MAL基因mRNA定量表达与患者年龄、性别、肿瘤大小、胃癌分化程度、有无淋巴结转移、有无神经束浸润及肿瘤TNM分期无相关(P>0.05).结论:胃癌组织中MAL基因表达缺失或低下,并且存在高甲基化率,MAL基因发生甲基化可能与胃癌发生有关.     

MAL基因与肿瘤

MAL基因是一个在T细胞分化中晚期表达的基因.许多研究表明MAL基因在食管癌、胃癌、结肠癌、头颈部鳞癌等多种肿瘤组织中表达下调或缺失,与肿瘤的发生发展过程有关.MAL基因要作为临床诊断、判断预后及指导治疗的指标而得到应用,还需要进一步研究.     

Methyl aminolaevulinate photodynamic therapy for the treatment of hidradenitis suppurativa and pilonidal cysts

Hidradenitis suppurativa (HS) and pilonidal cysts are chronic, inflammatory skin conditions involving apocrine gland-bearing skin. Treatment is limited and unsatisfactory. Photodynamic therapy (PDT) has been reported to be safe and effective in the treatment of several off-label skin conditions. We report the case of a 29-year-old man affected by HS and pilonidal cysts since the age of 21. In the past, the patient was treated with antibiotics, corticosteroids and retinoids, without significant clinical improvement. Treatment with methyl aminolaevulinate (MAL)-PDT was started. A topical MAL cream (Metvix^®) was applied to the affected areas with an occlusive dressing for 3 h and irradiated with a red light source. Therapy was repeated every 15 days for a total of nine applications. The patient completed a 6-month follow-up and achieved an almost complete clinical remission of the skin lesions (80%) and complete resolution of the itching and discomfort. This is the first case of HS associated with pilonidal cysts treated with MAL-PDT. MAL-PDT was effective and well tolerated in our patient. The costs of this therapy represent an important limitation, taking into account the high number of sessions that were performed compared with non-melanoma skin cancers.