Diagnostics of Inflammatory Bowel Disease Nikolaus, Susanna; Schreiber, Stefan
Gastroenterology (New York, N.Y. 1943),
11/2007, Letnik:
133, Številka:
5
Journal Article
Recenzirano
The diagnosis of inflammatory bowel disease (IBD) with its 2 main subforms, Crohn’s disease and ulcerative colitis, is based on clinical, endoscopic, radiologic, and histologic criteria. This ...paradigm remains unchanged despite the advent of new molecular technologies for the examination of serum proteins and genetic sequences, respectively. The main innovations in diagnostic technologies include the development of more sophisticated endoscopic and noninvasive imaging techniques with the aim of improving the identification of complications, in particular malignant diseases associated with IBD. The future will see further progress in the identification of genetic susceptibility factors and of protein biomarkers and their use to describe the molecular epidemiology of IBD. It can be expected that future diagnostic algorithms will include molecular parameters to detect early disease or guide therapies by predicting the individual course of disease.
Abstract
Almost seventy years after the discovery of the mechanisms of action potential generation, some aspects of their computational consequences are still not fully understood. Based on ...mathematical modeling, we here explore a type of action potential dynamics – arising from a saddle-node homoclinic orbit bifurcation - that so far has received little attention. We show that this type of dynamics is to be expected by specific changes in common physiological parameters, like an elevation of temperature. Moreover, we demonstrate that it favours synchronization patterns in networks – a feature that becomes particularly prominent when system parameters change such that homoclinic spiking is induced. Supported by in-vitro hallmarks for homoclinic spikes in the rodent brain, we hypothesize that the prevalence of homoclinic spikes in the brain may be underestimated and provide a missing link between the impact of biophysical parameters on abrupt transitions between asynchronous and synchronous states of electrical activity in the brain.
The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. ...A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987-13992. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans.
Chronic venous disease (CVD) is a multifactorial condition representing one of the most common disorders among populations of Western countries. The heritability of about 17% suggests genetic risk ...factors in CVD etiology. However, so far the genetic causes are unknown. We undertook the hitherto first genome-wide association study (GWAS) for CVD, analyzing more than 1.93 M SNPs in 4,942 German individuals, followed by replication in two independent German data sets. The combined analysis of discovery and replication stages (2,269 cases and 7,765 controls) yielded robust associations within the two genes EFEMP1 and KCNH8 (rs17278665, rs727139 with P < 5 × 10
), and suggestive association within gene SKAP2 (rs2030136 with P < 5 × 10
). Association signals of rs17278665 and rs727139 reside in regions of low linkage disequilibrium containing no other genes. Data from the ENCODE and Roadmap Epigenomics projects show that tissue specific marks overlap with the variants. SNPs rs17278665 and rs2030136 are known eQTLs. Our study demonstrates that GWAS are a valuable tool to study the genetic component of CVD. With our approach, we identified two novel genome-wide significant susceptibility loci for this common disease. Particularly, the extracellular matrix glycoprotein EFEMP1 is promising for future functional studies due to its antagonistic role in vessel development and angiogenesis.
The ability to attribute mental states to other individuals is crucial for human cognition. A milestone of this ability is reached around the age of 4, when children start understanding that others ...can have false beliefs about the world. The neural basis supporting this critical step is currently unknown. Here, we relate this behavioural change to the maturation of white matter structure in 3- and 4-year-old children. Tract-based spatial statistics and probabilistic tractography show that the developmental breakthrough in false belief understanding is associated with age-related changes in local white matter structure in temporoparietal regions, the precuneus and medial prefrontal cortex, and with increased dorsal white matter connectivity between temporoparietal and inferior frontal regions. These effects are independent of co-developing cognitive abilities. Our findings show that the emergence of mental state representation is related to the maturation of core belief processing regions and their connection to the prefrontal cortex.
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