Klinik und Genetik des familiären Darmkrebses

Familial clustering of colorectal cancer (CRC) and early disease onset are indicators of an inherited tumour syndrome. Monogenic dispositions account for 3–5% of all CRC cases and are subdivided into hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome) and various gastrointestinal polyposis syndromes. Many of these syndromes are characterised by a broad spectrum of extracolonic tumours. Early detection and accurate classification are essential in providing effective surveillance and treatment. Initial diagnosis is based on endoscopic and histological findings as well as on the presence of extracolonic manifestations and family history. Molecular genetic examination is important for the differential diagnosis, evaluation of recurrence risk, and predictive testing of asymptomatic at risk individuals; it is performed according to largely standardised algorithms. Diagnostic difficulties are common among the hamartomatous polyposes due to their broad phenotypic overlap and frequent uncertainties in histological evaluation, as well as among patients with few adenomas. Risk-adapted surveillance guidelines have been established for HNPCC and for the more frequently observed polyposis syndromes. Beyond established tumour syndromes, familial clustering of CRC (which is often of late onset) or the occurrence of few adenomas is likely to be based upon a multifactorial (complex) etiology. Although identification of the underlying genetic risk factors and biological pathways is still in the early stages, rapid progress is being made due to methodical developments such as genome-wide association studies and CNV analysis.     

Test Based on Independent,but Non-identically Distributed Random Variables

The binomial test is applied for the problem of testing a hypothesis based on a sample of independent, but non-identically distributed random variables. The used basic idea is that each random variable indicates the presence of the hypothesis. Hence each random variable is transformed such that the binomial test can be used as a simple procedure.     

BioTRIZ Suggests Radiative Cooling of Buildings Can Be Done Passively by Changing the Structure of Roof Insulation to Let Longwave Infrared Pass

This paper demonstrates the application of a design tool called BioTRIZ. Its developers claim that it can be used to access biological strategies for solving engineering problems. Our aim is to design a roof for hot climates that gets free cooling through radiant coupling with the sky. The insulation in a standard roof stops the sun and convection from warming the thermal mass. But it also restricts the mass＇s longwave view of the cool sky. Different solutions to this conflict are offered by BioTRIZ. The chosen solution is to replace the standard insulation component with an open cell honeycomb. The vertical cells would allow longwave radiation to pass, while arresting convection. The solutions offered by BioTRIZ＇s technological counterpart include no such changes in structure. It is estimated that the thermal mass in the biomimetic roof would remain on average 4.5℃ cooler than in a standard roof over a year in Riyadh, Saudi Arabia.     

Pränatale Detektion fetaler chromosomaler Aberrationen im 1. und 2. Trimenon

Modern noninvasive methods of prenatal medicine, in particular first-trimester-screening, enable early risk evaluation of the most common forms of aneuploidy. With over 4000 certified gynecologists in Germany, this method nowadays represents the standard in prenatal risk evaluation. The importance of classic genetic sonography during the second trimester by detection of soft markers for aneuploidy has declined. However, detailed sonography during the second trimester remains the gold standard for the detection of congenital anomalies. Therefore, the specialist in prenatal medicine must be able to recognize soft markers during this examination in order to re-evaluate the maternal risk for aneuploidy.     

In vivo properties of the disaggregase function of J‐proteins and Hsc70 in Caenorhabditis elegans stress and aging

Protein aggregation is enhanced upon exposure to various stress conditions and aging, which suggests that the quality control machinery regulating protein homeostasis could exhibit varied capacities in different stages of organismal lifespan. Recently, an efficient metazoan disaggregase activity was identified in vitro, which requires the Hsp70 chaperone and Hsp110 nucleotide exchange factor, together with single or cooperating J‐protein co‐chaperones of classes A and B. Here, we describe how the orthologous Hsp70s and J‐protein of Caenorhabditis elegans work together to resolve protein aggregates both in vivo and in vitro to benefit organismal health. Using an RNAi knockdown approach, we show that class A and B J‐proteins cooperate to form an interactive flexible network that relocalizes to protein aggregates upon heat shock and preferentially recruits constitutive Hsc70 to disaggregate heat‐induced protein aggregates and polyQ aggregates that form in an age‐dependent manner. Cooperation between class A and B J‐proteins is also required for organismal health and promotes thermotolerance, maintenance of fecundity, and extended viability after heat stress. This disaggregase function of J‐proteins and Hsc70 therefore constitutes a powerful regulatory network that is key to Hsc70‐based protein quality control mechanisms in metazoa with a central role in the clearance of aggregates, stress recovery, and organismal fitness in aging.     

Osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most frequently occurring congenital disorder with an increased fracture rate and systemic skeletal involvement. The vast majority of patients have an autosomal dominant form of OI resulting from a mutation in one of the two type I collagen genes COL1A1 or COL1A2. Since 2006, eight genes for autosomal recessive forms of the disorder have been identified, as well as one additional gene for autosomal dominant OI. Our knowledge concerning molecular pathophysiology has been substantially broadened, such that the paradigm of OI as a pure ??collagenopathy?? no longer applies and the clinical classification system will have to be revised. Standard therapy for the more severe forms of OI comprises intravenous administration of bisphosphonates. Additional elements of a multimodal therapeutic concept include surgical intervention for bone deformities or fractures and physiotherapy.     

Mud mounds: A polygenetic spectrum of fine-grained carbonate buildups

Summary This research report contains nine case studies (part II to X) dealing with Palaeozoic and Mesozoic mud mounds, microbial reefs, and modern zones of active micrite production, and two parts (I and XI) summarizing the major questions and results. The formation of different types ofin situ formed micrites (automicrites) in close association with siliceous sponges is documented in Devonian, Carboniferous, Triassic, Jurassic and Cretaceous mounds and suggests a common origin with a modern facies found within reef caves. Processes involved in the formation of autochthonous micrites comprise: (i) calcifying mucus enriched in Asp and Glu, this type presumably is linked to the formation of stromatolites, thrombolites and massive fabrics; (ii) protein-rich substances within confined spaces (e.g. microcavities) result in peloidal pockets, peloidal coatings and peloidal stromatolites, and (iii) decay of sponge soft tissues, presumably enriched with symbiotic bacteria, lead to the micropeloidal preservation of parts of former sponge bodies. As a consequence, there is strong evidence that the primary production of micrite in place represents the initial cause for buildup development. The mode of precipitation corresponds to biologically-induced, matrix-mediated mineralization which results in high-Mg-calcites, isotopically balanced with inorganic cements or equilibrium skeletal carbonates, respectively. If distinct automicritic fabrics are absent, the source or origin of micrite remains questionable. However, the co-occurring identifiable components are inadequate, by quantity and physiology, to explain the enhanced accumulation of fine-grained calcium carbonate. The stromatolite reefs from the Permian Zechstein Basin are regarded as reminiscent of ancestral (Precambrian) reef facies, considered the precursor of automicrite/sponge buildups. Automicrite/sponge buildups represent the basic Phanerozoic reef type. Analogous facies are still present within modern cryptic reef habitats, where the biocalcifying carbonate factory is restricted in space.