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.     

FISH in der Diagnostik hämatologischer Neoplasien

All hematological malignancies are characterized by considerable clinical heterogeneity. The diverse entities can be subdivided into a variety of prognosis-defining subtypes on the basis of cytogenetic aberrations and molecular mutations. To adapt the intensity of treatment to the patient’s individual risk profile, an exact classification of the subtypes on the basis of genetic markers is essential. Diverse fluorescent in situ hybridization (FISH) techniques thereby play a central role in interaction with classic chromosome banding analyses for clarifying findings of chromosome analyses, such as in the acute leukemias, or for classifying the diverse subtypes, as in the non-Hodgkin’s lymphomas. Depending on the disease, the clinical impact of FISH varies. It is used as the method of choice for genetic characterization (e.g., in multiple myeloma) or is used in combination with chromosome banding analysis. Furthermore, interphase FISH is essential when rapid confirmation of the diagnosis is needed, as in acute promyelocytic leukemia with the t(15;17)/PML-RARA rearrangement, for which therapy with all-trans retinoic acid (ATRA) should be immediately started.     

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.     

Ionenkanalerkrankungen des Gehirns – monogene Migräneformen

As opposed to the common, genetically complex types of migraine, there are a few rare monogenic migraine variants. The prototype is familial hemiplegic migraine (FHM), a severe subtype of migraine with aura, for which three causative genes (FHM1–3), all of which are involved in ion translocation in the CNS, have been identified. This review summarizes the current knowledge about the clinical symptomatology, (differential) diagnosis, treatment, genetics, and pathophysiology of FHM. Clinically and genetically overlapping disorders, such as episodic ataxia type 2 (EA-2), spinocerebellar ataxia type 6 (SCA-6) and alternating hemiplegia of childhood (AHC) are briefly discussed, and novel genes which have been occasionally associated with HM or migraine are critically evaluated. Finally, monogenic (vascular) syndromes, in which migraine is part of the phenotypic spectrum, are discussed.     

A GWAS Study on Liver Function Test Using eMERGE Network Participants

Introduction

Liver enzyme levels and total serum bilirubin are under genetic control and in recent years genome-wide population-based association studies have identified different susceptibility loci for these traits. We conducted a genome-wide association study in European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) Network dataset of patient medical records with available genotyping data in order to identify genetic contributors to variability in serum bilirubin levels and other liver function tests and to compare the effects between adult and pediatric populations.

Methods

The process of whole genome imputation of eMERGE samples with standard quality control measures have been described previously. After removing missing data and outliers based on principal components (PC) analyses, 3294 samples from European ancestry were used for the GWAS study. The association between each single nucleotide polymorphism (SNP) and total serum bilirubin and other liver function tests was tested using linear regression, adjusting for age, gender, site, platform and ancestry principal components (PC).

Results

Consistent with previous results, a strong association signal has been detected for UGT1A gene cluster (best SNP rs887829, beta = 0.15, p = 1.30x10^-118) for total serum bilirubin level. Indeed, in this region more than 176 SNPs (or indels) had p<10⁻⁸ spanning 150Kb on the long arm of chromosome 2q37.1. In addition, we found a similar level of magnitude in a pediatric group (p = 8.26x10^-47, beta = 0.17). Further imputation using sequencing data as a reference panel revealed association of other markers including known TA7 repeat indels (rs8175347) (p = 9.78x10^-117) and rs111741722 (p = 5.41x10^-119) which were in proxy (r2 = 0.99) with rs887829. Among rare variants, two Asian subjects homozygous for coding SNP rs4148323 (G71R) were identified. Additional known effects for total serum bilirubin were also confirmed including organic anion transporters SLCO1B1-SLCO1B3, TDRP and ZMYND8 at FDR<0.05 with no gene-gene interaction effects. Phenome-wide association studies (PheWAS) suggest a protective effect of TA7 repeat against cerebrovascular disease in an adult cohort (OR = 0.75, p = 0.0008). Among other liver function tests, we also confirmed the previous effect of the ABO blood group locus for variation in serum alkaline phosphatase (rs579459, p = 9.44x10^-15).

Conclusions

Taken together, our data present interesting findings with strong confirmation of previous effects by simply using the eMERGE electronic health record phenotyping. In addition, our findings indicate that similar to the adult population, the UGT1A1 is the main locus responsible for normal variation of serum bilirubin in pediatric populations.     

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.     

Evolutionary relationships among the male and female mitochondrial DNA lineages in the Mytilus edulis species complex

A novel form of mitochondrial DNA (mtDNA) inheritance has previously been documented for the blue mussel (Mytilus edulis). Female mussels inherit their mtDNA solely from their mother while males inherit mtDNA from both their mother and their father. In males, the paternal mtDNA is preferentially amplified so that the male gonad is highly enriched for the paternal mtDNA that is then transmitted from fathers to sons. We demonstrate that this mode of mtDNA inheritance also operates in the closely related species M. galloprovincialis and M. trossulus. The evolutionary relationship between the male and female mtDNA lineages is estimated by phylogenetic analysis of 455 nucleotides from the large subunit ribosomal RNA gene. We have found that the male and female lineages are highly divergent; the divergence of these lineages began prior to the speciation of the three species of blue mussels. Further, the separation between the male and female lineages is estimated to have occurred between 5.3 and 5.7 MYA.      

Die organogenetische und transitorische rolle der vitellophagen in der darmentwicklung von Galathea (Crustacea,Anomura)

The present study of the development of the different organs of the gut, the vitellophags (primary yolk cells) and the other cell-types concerned with the resorption of the yolk gives the first detailed analysis of an Anomuran development.

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Verzeichnis der Abkürzungen in den Abbilduugen A ₁ 1. Antenne - A ₂ 2. Antenne - Ab Abdomen - Au Auge - B Blastoderm - Bb Blastodermbildung - Bl Blutlakunensystem - Bm Blastomer (Furchungszelle) - Bp Blastoporus - BZ Blutzelle - Ca Cardiamagen - Cf Carapaxfalte - Cp Caudalpapille - DI Drüsenfilter (Magen) - zDk zentraler Dotterkörper - Do Dorsalorgan - pDp primare Dotterpyramide - tDp tertiare Dotterpyramide (Vitellophagenepithel) - DR Rest des intraembryonalen Dottersackes - ieDS intraembryonaler Dottersack - bDv blastodermale Dottervakuole - sDZ sekunddre Dotterzelle - tDZ tertiare Dotterzelle - sE sekunddre Epithelialisierung (der Vitellophagen) - Ec Ectoderm - Ed Enddarm - Eh Eihiille (Chorion) - Ep Entodermplatte - Et Entodermtrichter - Ex Extremitdt (bsw. Extremitätenanlage) - Fsp Furchungsspindel (Teilungsspindel) - H Herz - ID Innendotter - Im Immigration (des Mesentoderms) - In Invagination (des Mesentoderms) - Ke Kern - KL Kopflappen (optischer Lobus) - KM Kaumuskulatur - L Darmlumen - M Mitose - Ma Magen - Md Mitteldarm - dMd dorsaler Mitteldarmdivertikel (dorsaler Mitteldarmblindsack) - Me Mesoderm - McEn Mesentoderm - Mddr Mitteldarmdrüse - Ml Mandibel - Mp ₁ 1. Maxilliped (1. Kieferfuß) - Mp ₂ 2. Maxilliped (2. Kieferfuß) - Mp ₃ 3. Maxilliped (3. Kieferfuß) - Mu Muskulatur - M₁ 1. Maxille - M₂ 2. Maxille - N Ganglien des Nervensystems - Ni Niere (Antennendrüse) - Oe Oesophagus - Ol Oberlippe - Pl Plasma - Py Pylorusmagen - Qv Querverbindung zwischen den Kopflappen - pR perivitelliner Raum - Seg Segment - Sf Sternalfurche - Sto Stomodaeum (Anlage des Vorderdarmes) - TA Thoracoabdominalanlage - Te Telson - Ul Urdarmlumen - V Vitellophage (primare Dotterzelle) - V ₁ Vitellophage 1 (1. Vitellophagengeneration) - V ₂ Vitellophage 2 (2. Vitellophagengeneration) - dV degenerierende Vitellophage - V intravitelline Vitellophage - IV Initialvitellophage (Lumenbildung) - pV perivitelline Vitellophage - Va Vakuole - Vi gelöster Dotter (im Darmlumen) - fZ freie Zellen (im perivitellinen Raum) Ausgeführt mit Mitteln des Schweizerischen Nationalfonds zur Förderung der wissenschaftlichen Forschung and der Freiwillig Akademischen Gesellschaft der Stadt Basel.     

Ultrahistochemical and autoradiographic evidence for epithelial transport in the uterus of the ovoviviparous salamander,Salamandra salamandra (L.) (Amphibia,Urodela)

Summary The uterine epithelium of pregnant females of the terrestrial ovoviviparous Salamandra salamandra is characterized by a considerable enlargement of its basolateral surface. Chloride and cations (among others sodium), preferentially within the intercellular spaces, can be demonstrated ultrahistochemically. There is indirect evidence of Na⁺-K⁺-ATPase activity along the basolateral plasma membranes of the epithelial cells using the Sr-technique for demonstration of a K⁺-NPPase and ³H-ouabain autoradiography. Preliminary measurements reveal a potential difference across the uterine wall of 15–25mV, the lumenal (mucosal) surface being negative with respect to the coelomic (serosal) surface, and a short circuit current of 200–300 A. The possibly electrogenic ion transport is ouabain-sensitive. The results are in agreement with the model of a forward transporting, i.e. absorptive epithelium. An active transport of solute out of the uterine lumen across the epithelium to the subjacent connective tissue and the blood vessels may be involved in the regulation of an intrauterine milieu appropriate for the development of the offspring.I am indebted to Miss Dr. U. Beigel, Zoologisches Institut der Universität Münster, for linguistic help