Dapper Antagonist of Catenin-1 Cooperates with Dishevelled-1 during Postsynaptic Development in Mouse Forebrain GABAergic Interneurons

Synaptogenesis has been extensively studied along with dendritic spine development in glutamatergic pyramidal neurons, however synapse development in cortical interneurons, which are largely aspiny, is comparatively less well understood. Dact1, one of 3 paralogous Dact (Dapper/Frodo) family members in mammals, is a scaffold protein implicated in both the Wnt/β-catenin and the Wnt/Planar Cell Polarity pathways. We show here that Dact1 is expressed in immature cortical interneurons. Although Dact1 is first expressed in interneuron precursors during proliferative and migratory stages, constitutive Dact1 mutant mice have no major defects in numbers or migration of these neurons. However, cultured cortical interneurons derived from these mice have reduced numbers of excitatory synapses on their dendrites. We selectively eliminated Dact1 from mouse cortical interneurons using a conditional knock-out strategy with a Dlx-I12b enhancer-Cre allele, and thereby demonstrate a cell-autonomous role for Dact1 during postsynaptic development. Confirming this cell-autonomous role, we show that synapse numbers in Dact1 deficient cortical interneurons are rescued by virally-mediated re-expression of Dact1 specifically targeted to these cells. Synapse numbers in these neurons are also rescued by similarly targeted expression of the Dact1 binding partner Dishevelled-1, and partially rescued by expression of Disrupted in Schizophrenia-1, a synaptic protein genetically implicated in susceptibility to several major mental illnesses. In sum, our results support a novel cell-autonomous postsynaptic role for Dact1, in cooperation with Dishevelled-1 and possibly Disrupted in Schizophrenia-1, in the formation of synapses on cortical interneuron dendrites.     

Detection of myocardial ischemia by epicardial detection of potassium ion activity]

Early detection of myocardial ischaemia is a central problem in cardiological and cardiosurgical intensive care. A new approach is the use of ion-selective electrodes implanted directly on the myocardium, enabling detection of increased potassium activity as an indication of general hypoxia. After a comprehensive study of the electrode parameters, an animal experiment was carried out, in which it was found that respiration-induced hypoxia resulted in an increase in epicardial potassium activity (p < 0.01). Blood gas analysis performed simultaneously revealed reduced arterial pO2, but no acidosis. Haemodynamic data evidenced hypoxic depression of circulatory parameters. Histological examinations of the myocardium beneath the electrodes revealed typical lymphocytic infiltration. Electron microscopy demonstrated crystolysis in the mitochondria as an early sign of hypoxia, thus confirming the sensitivity of these electrodes. This underscores the potential of ion-selective electrodes for the detection of myocardial ischaemia, and they should now be investigated in the clinical setting.     

Aluminum,Fe, Ca,Mg, K,Mn, Cu,Zn and P in above- and belowground biomass. I.Abies amabilis andTsuga mertensiana

In a mature mixed subalpine stand ofTsuga mertensiana andAbies amabilis, significantly higher Al levels were found in foliage, branch and root tissues ofT. mertensiana.Tsuga mertensiana had significant increases in Al, Ca and Mn levels with increasing foliage age. In current foliage,T. mertensiana had lower levels of Ca, similar levels of Mg and P, and higher levels of Mn thanA. amabilis. Both tree species had Cu and Fe present at higher levels in branch than foliage tissues. Fine roots had the highest concentrations of Al, Fe and Cu but the lowest Ca and Mn concentrations of all tissues analyzed. In the roots of both species, phloem tissues always had significantly higher Al levels than xylem. Fine roots (< 1 and 1–2 mm) ofT. mertensiana had higher Al levels than were found inA. amabilis. Roots greater than 2 mm in diameter exhibited no significant differences in Al levels in phloem or xylem tissue betweenA. amabilis andT. mertensiana. The two species show a clear difference in their ability to accumulate specific elements from the soil.     

The electrochemical proton potential generated by the sulphur respiration of Wolinella succinogenes

Wolinella succinogenes grown on formate and elemental sulphur was found to use the polysulphide derivatives 2,2-tetrathiobispropionate (R₂S₄) or pentathionate (S₅O ₆ ⁼ ) as acceptors for formate oxidation. The specific activities of formate oxidation with these acceptors were similar to those with elemental sulphur. The main reaction products of R₂S₄ reduction were 2,2-dithiobispropionate (R₂S₂) and sulphide. Pentathionate was converted to thiosulphate and some elemental sulphur. The electrochemical proton potential across the cytoplasmic membrane of the bacterium was measured in the steady state of electron transport from formate to R₂S₄. The electrical proportion () of the determined through the distribution of labeled tetraphenylphosphonium cation was obtained as 0.17 Volt. The was zero, when a protonophore was present. The pH-difference across the membrane was negligible. Thus the generated by sulphur respiration is close to that measured earlier with fumarate as the terminal acceptor of electron transport.Abbreviations DMO 5,5-dimethyloxazolidine-2,4-dione - R₂S_n (n=2–5) 2,2-polythiobispropionate - TTFB 4,5,6,7-tetrachloro-2-trifluoromethylbenzimidazol - TPP tetraphenylphosphonium cation     

Preface

Goldman Festschrift

Preface     

Fish oil affects phosphoinositide turnover and thromboxane A metabolism in cultured vascular muscle cells

Fish oil has been reported as having beneficial effects on cardiovascular diseases. Elevated serum lipoproteins, prostaglandins and intracellular free calcium concentrations [( Ca2+]i) of the vasculature and thus the phosphoinositide (PI) turnover may be involved in the pathogenesis of these disorders. Therefore, the effect of fish oil on the potency of both low-density lipoprotein (LDL) and angiotensin II (AII) to stimulate the PI turnover in cultured rat vascular smooth muscle cells (VSMC) has been studied. Furthermore, a possible link between PI turnover activity and thromboxane A2 (TXA2) metabolism in these cells has been investigated. In VSMC cultured for up to 7 weeks with either fish oil or n-3 eicosapentaenoic acid (EPA) a decrease to 5-48% of the LDL-induced inositol trisphosphate (IP3) formation (= 100%) was found. A similar range of decreased IP3 synthesis was observed, when AII was used instead of LDL. Both LDL- and AII-stimulated TXA2 synthesis was suppressed concomitantly within the range 34-60%. Blockade of VSMC TXA2 biosynthesis with either indomethacin or TXA2 synthetase blocker (SQ-80338) inhibited LDL-induced formation of IP3 in a dose-dependent manner. Similar results were obtained, when TXA2 receptor coupling antagonists (SQ-27427 or BM-13177) were used. However, blockers of TXA2 synthesis and of TXA2 receptor binding failed to affect AII-induced formation of IP3.     

Brutbiologie des Turmfalken (Falco tinnunculus): 16j?hrige Untersuchungen in Westfalen

Zusammenfassung Anhand einer 16jährigen Untersuchung im Raum Ostwestfalen/Bielefeld wird der Bruterfolg des Turmfalken anhand von 439 Gelegen und 2256 Eiern beschrieben. Drei Brutplatztypen können unterschieden werden: A. Baumbruten in Nestern; B₁. Baumbruten in Nistkästen; B₂. Gebäudebruten in Nischen oder Nistkästen. Zwischen Baumbruten (A) und Nistkastenbruten (B_1/2) werden signifikante Unterschiede beschrieben, die für Nistkästen größere Gelege (ca. ein Ei mehr) und größeren Ausfliegeerfolg belegen. Zwischen Nistkästen in Bäumen (B₁) oder an Gebäuden (B₂) konnten keine signifikanten Unterschiede festgestellt werden. Weiterhin werden Lege- und Schlupftermine, Legerhythmus und oologische Daten aus dem Untersuchungsgebiet angegeben.

---

Breeding biology of Kestrels (Falco tinnunculus) in Eastern Westfalia 1972–1987

Summary The 16 years of study gave 439 clutches with 2,256 eggs. We separated three types of breeding sites: the use of (a) stick nests, mostly built by corvids (cf. Tab., Fig. 3), (b₁) nest boxes attached to trees or telegraph poles (Fig. 2) and (b₂) nest boxes or cavities at or in buildings (Fig. 1). Within these different types of breeding places we found some significant differences. Stick nests had less eggs and though less breeding success, which was possibly caused by predation of corvids, especially magpies. Within the two types of places with nest boxes no significant differences could be established. We concluded, that stick nests were marginal in Kestrels and nest boxes were optimal despite of their placement in trees, at poles or in buildings. Furthermore, the timing of breeding cycle was described (Fig. 4) and laying interval was determind to an average value of approximately two days (Fig. 5). Mean egg size was and average volume 21.2 cm². Two daily controlled clutches lost 15.5% and 16.1% of mass (Fig. 6) pressumably mostly due to water losses.

     

A “new” genetic polymorphism of a human serum protein: inter-alpha-trypsin-inhibitor

Summary A new genetic polymorphism of a human serum glycoprotein, the inter--trypsin-inhibitor (ITI), has been demonstrated by population and family studies. Sera were examined after neuraminidase treatment by isoelectric focusing on agarose gels followed by immunoblotting or by immunfixation with specific ITI-antiserum. Using this method, three common ITI phenotypes 1, 1–2 and 2, as well as two further rare ITI types 1–3 and 2–3 were disclosed. Genetically, these phenotypes are controlled by three allelic genes that determine a total of six phenotypes. These alleles are designated ITI^*1, ITI^*2 and ITI^*3. The homozygous form of the third allele ITI^*3 has not been found, as yet. The frequencies of ITI were examined in two population samples from Southern Germany (n=248) and from Tyrol, Austria (n=124). The gene frequencies of the common alleles ITI^*1 and ITI^*2 were 0.575 and 0.417, respectively, in Southern Germany, and 0.577 and 0.423, respectively, in Tyrol, Austria. The third allele ITI^*3 was found only in the sample from Southern Germany, thus far, and was calculated to be 0.008.     

Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus

Summary A basic problem in genetic counseling of families with Duchenne/Becker muscular dystrophy (DMD/BMD) concerns the carrier status of female relatives of an affected male. In about 60% of these patients, deletions of one or more exons of the dystrophin gene can be identified. These deletions preferentially include exon 45, which can be detected by multiplex polymerase chain reaction (PCR) and Southern blot analysis of genomic cosmid clones that map to this critical region. As a new approach for definitive carrier detection, we have performed chromosomal in situ suppression (CISS) hybridization with these cosmid clones in female relatives of four unrelated patients. In normal females, most metaphases showed signals on both×chromosomes, whereas only one×chromosome was labeled in carriers. Our results demonstrate that CISS hybridization can define the carrier status in female relatives of DMD patients exhibiting a deletion in the dystrophin gene.