Novel susceptibility genes in inflammatory bowel disease

The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are polygenic disorders with important environmental interactions. To date, the most widely adopted approach to identifying susceptibility genes in complex diseases has involved genome wide linkage studies followed by studies of positional candidate genes in loci of interest. This review encompasses data from studies into novel candidate genes implicated in the pathogenesis of inflammatory bowel disease. Novel techniques to identify candidate genes-genome wide association studies, yeast-two hybrid screening, microarray gene expression studies and proteomic profiling, are also reviewed and their potential role in unravelling the pathogenesis of inflammatory bowel disease are discussed.

New genetic markers for male fertility

Studies in the last years deFmitively demonstrate the high prevalence of gen- etic causes of spermatogenic impairment. A large proportion of infertile males does not receive a dear diagnosis and are reported as idiopathic or unexplained, also because standard semen analysis cannot clearly distinguish fertile from infertile populations.

ACTN3 and AMPD1 Polymorphism and Genotype Combinations in Bulgarian Athletes Performing Wingate Test

The aim of the study was to investigate ACTN3 （ct-actinin-3） and AMPD1 （adenosine monophosphate deaminase） polymorphism and genotype combinations in Bulgarian athletes competing in various sports and the relation to peak power output. A mixed group of athletes （n = 52） competing at national and international level and a matching genetic control group （n = 109） of volunteers were recruited. Participants were genotyped for ACTN3 and AMPD1 by polymerase chain reaction. There were no significant differences in ACTN3 genotype distribution between athletes performing Wingate test （38% RR, 46% RX, 16% XX） and controls （41.2% RR, 46% RX, 12.8% XX）. AMPD1 distribution was （73% CC, 27% CT, 0% TT） and in controls （73.2% CC, 25% CT, 1.8% TT）. Athletes performing Wingate test showed equal 33% frequency of RR/CC and RX/CC combination, and 12% RX/CT. Significantly higher （P 〈 0.05） peak power output （11.10 W kg1） was found in athletes with RX/CT combination compared to other combinations （range： 8.83-9.71 W kg-1） and in R-power （RR ＋ RX） and C-power （CC ＋ CT） dominant models （9.91 W kgl）. Mean power was higher （P 〈 0.05） in RX/CT combination （8.93 W kg-1） compared to RR/CC （7.75 W kg-1） and RR/CT （7.95 W kgl）. In conclusion, the low frequency of T AMPD1 allele in Bulgarian athletes might indicate that this mutant allele is related to the physical performance. The prevalence of R ACTN3 and C AMPD1 alleles suggests that they could contribute to anaerobic performance. Higher peak power in Wingate test is associated with RX/CT genotype combination and R- and C-power dominant models.

TIFA suppresses hepatocellular carcinoma progression via MALT1-dependent and-independent signaling pathways

TIFA,also called T2BP,was first identified using yeast two-hybrid screening.Our previous work showed that TIFA suppresses hepatocellular carcinoma(HCC)progression via apoptosis and cell cycle arrest.However,the mechanism by which this TIFA suppression occurs remains unclear.Here we demonstrated that TIFA-induced apoptosis demonstrates two distinct time patterns(i.e.,at 48 h and 47 days)when TIFA reconstitution occurs.Moreover,we found that MALT1(a competitor of TIFA)plays a crucial role in short-duration TIFA reconstitution.In this regard,MALT1 silencing with shRNA markedly enhances TIFA-induced apoptosis in vitro and in vivo.In addition,TIFA overexpression triggers JNK and p38 activation in long-duration TIFA reconstitution through TRAF6 binding.In particular,JNK activation leads to TIFA-induced apoptosis while p38 activation governs TIFA-induced cell cycle arrest by p53-p21 signaling in vitro and in vivo.Our data suggest a novel mechanism by which TIFA suppresses HCC progression via both MALT1-dependent and MALT1-independent signaling pathways.This may provide insights into a novel targets where HCC progression may be vulnerable to clinical treatment.