Nesprin interchain associations control nuclear size

Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and associates instead to plectin, which binds intermediate filaments. Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH-domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3 association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH-domain but lacks the massive nesprin-2 giant rod segment) expression yields smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co-expression or microfilament depolymerization. Our findings suggest that multivariate intermolecular nesprin interactions with the cytoskeleton form a lattice-like filamentous network covering the outer nuclear membrane, which determines nuclear size.     

Reductive dehalogenation of chlorinated dioxins by an anaerobic bacterium

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) are among the most notorious environmental pollutants. Some congeners, particularly those with lateral chlorine substitutions at positions 2, 3, 7 and 8, are extremely toxic and carcinogenic to humans. One particularly promising mechanism for the detoxification of PCDDs and PCDFs is microbial reductive dechlorination. So far only a limited number of phylogenetically diverse anaerobic bacteria have been found that couple the reductive dehalogenation of chlorinated compounds--the substitution of a chlorine for a hydrogen atom--to energy conservation and growth in a process called dehalorespiration. Microbial dechlorination of PCDDs occurs in sediments and anaerobic mixed cultures from sediments, but the responsible organisms have not yet been identified or isolated. Here we show the presence of a Dehalococcoides species in four dioxin-dechlorinating enrichment cultures from a freshwater sediment highly contaminated with PCDDs and PCDFs. We also show that the previously described chlorobenzene-dehalorespiring bacterium Dehalococcoides sp. strain CBDB1 (ref. 3) is able to reductively dechlorinate selected dioxin congeners. Reductive dechlorination of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD) demonstrates that environmentally significant dioxins are attacked by this bacterium.     

Nitride semiconductors free of electrostatic fields for efficient white light-emitting diodes

Compact solid-state lamps based on light-emitting diodes (LEDs) are of current technological interest as an alternative to conventional light bulbs. The brightest LEDs available so far emit red light and exhibit higher luminous efficiency than fluorescent lamps. If this luminous efficiency could be transferred to white LEDs, power consumption would be dramatically reduced, with great economic and ecological consequences. But the luminous efficiency of existing white LEDs is still very low, owing to the presence of electrostatic fields within the active layers. These fields are generated by the spontaneous and piezoelectric polarization along the [0001] axis of hexagonal group-III nitrides--the commonly used materials for light generation. Unfortunately, as this crystallographic orientation corresponds to the natural growth direction of these materials deposited on currently available substrates. Here we demonstrate that the epitaxial growth of GaN/(Al,Ga)N on tetragonal LiAlO2 in a non-polar direction allows the fabrication of structures free of electrostatic fields, resulting in an improved quantum efficiency. We expect that this approach will pave the way towards highly efficient white LEDs.     

Redundant and unique roles of coronin proteins in <Emphasis Type="Italic">Dictyostelium</Emphasis>

Dictyostelium discoideum harbors a short (CRN12) and a long coronin (CRN7) composed of one and two beta-propellers, respectively. They are primarily present in the cell cortex and cells lacking CRN12 (corA ⁻) or CRN7 (corB ⁻) have defects in actin driven processes. We compared the characteristics of a mutant cell line (corA ⁻ /corB ⁻) lacking CRN12 and CRN7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. Cytokinesis, uptake of small particles, and developmental defects were not enhanced in the corA ⁻ /corB ⁻ strain as compared to the single mutants, whereas motility and phagocytosis of yeast particles were more severely impaired. It appears that although both proteins affect the same processes they do not act in a redundant manner. Rather, they often act antagonistically, which is in accordance with their proposed roles in the actin cytoskeleton where CRN12 acts in actin disassembly whereas CRN7 stabilizes actin filaments and protects them from disassembly.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.     

Zeitgeber-schedule dependent resynchronization of circadian rhythms in nocturnal mammals (Primates and Chiroptera)

Summary Changing the L: D time ratio of an entraining light-dark regime leads to characteristic alterations of the resynchronization behaviour of the circadian activity rhythms in night monkeys (Aotus trivirgatus) and African fruit bats (Rousettus aegyptiacus) after 8 h advance and delay shifts of the LD-Zeitgeber. Reduced speed of re-entrainment and occurrence of antidromic resynchronization point to a lower Zeitgeber strength of 24-h LD-cycles with a prolonged D-phase.Supported by the Deutsche Forschungsgemeinschaft (Er 59/8).     

Structure-dependent,selective localization of chlorinated xenobiotics in the cerebellum and other brain structures

Summary Remarkable regional distribution patterns of some chlorinated xenobiotics in the CNS are described.We thank Dr Åke Bergman, Wallenberg Laboratory, University of Stockholm, Stockholm, for the synthesis of compounds IV and V. The studies were supported by the Swedish Work Environment Fund (grants nos 73/169 and 74/181) and by the Research Committee of the National Swedish Environment Protection Board (grant no. 7-27/79).     

Rapid growth of black holes in massive star-forming galaxies

The tight relationship between the masses of black holes and galaxy spheroids in nearby galaxies implies a causal connection between the growth of these two components. Optically luminous quasars host the most prodigious accreting black holes in the Universe, and can account for greater than or approximately equal to 30 per cent of the total cosmological black-hole growth. As typical quasars are not, however, undergoing intense star formation and already host massive black holes (> 10(8)M(o), where M(o) is the solar mass), there must have been an earlier pre-quasar phase when these black holes grew (mass range approximately (10(6)-10(8))M(o)). The likely signature of this earlier stage is simultaneous black-hole growth and star formation in distant (redshift z > 1; >8 billion light years away) luminous galaxies. Here we report ultra-deep X-ray observations of distant star-forming galaxies that are bright at submillimetre wavelengths. We find that the black holes in these galaxies are growing almost continuously throughout periods of intense star formation. This activity appears to be more tightly associated with these galaxies than any other coeval galaxy populations. We show that the black-hole growth from these galaxies is consistent with that expected for the pre-quasar phase.