Newly discovered endocrine functions of white adipose tissue: possible relevance in obesity-related diseases

During recent years our view of adipose tissue has been revolutionized. White adipose tissue (WAT) is no longer seen as mere energy store or provider of thermal and mechanical insulation. Neglect of WAT has been overcome by surprising discoveries in recent years, changing the view of this tissue towards a highly endocrine organ that is involved in a wide variety of physiological and pathophysiological processes. In this brief article we will focus on new developments in adipocyte and WAT biology. The appreciation of WAT as an endocrine organ will provide the basis for new and promising perspectives in the management of obesity and obesity-related diseases including diabetes, mellitus type II and arterial hypertension.     

Cytophotometric investigations on the influence of heavy water upon the nucleic acid content of tumour cells

Zusammenfassung Nach zweistündiger Inkubation von Tumorzellen mit schwerem Wasser nimmt die zytophotometrisch gemessene Feulgenreaktivität ab, während die Gallocyaninchromalaunfärbung, die auf Phosphatgruppen beruht, erhalten bleibt. Auch nach der D₂O-Behandlung blieben die Tumoren transplantabel.     

Relaxor ferroelectricity and colossal magnetocapacitive coupling in ferromagnetic CdCr2S4

Materials in which magnetic and electric order coexist--termed 'multiferroics' or 'magnetoelectrics'--have recently become the focus of much research. In particular, the simultaneous occurrence of ferromagnetism and ferroelectricity, combined with an intimate coupling of magnetization and polarization via magnetocapacitive effects, holds promise for new generations of electronic devices. Here we present measurements on a simple cubic spinel compound with unusual, and potentially useful, magnetic and electric properties: it shows ferromagnetic order coexisting with relaxor ferroelectricity (a ferroelectric cluster state with a smeared-out phase transition), both having sizable ordering temperatures and moments. Close to the ferromagnetic ordering temperature, the magnetocapacitive coupling (characterized by a variation of the dielectric constant in an external magnetic field) reaches colossal values, approaching 500 per cent. We attribute the relaxor properties to geometric frustration, which is well known for magnetic moments but here is found to impede long-range order of the structural degrees of freedom that drive the formation of the ferroelectric state.     

The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA

Influenza A viruses pose a serious threat to world public health, particularly the currently circulating avian H5N1 viruses. The influenza viral nucleoprotein forms the protein scaffold of the helical genomic ribonucleoprotein complexes, and has a critical role in viral RNA replication. Here we report a 3.2 A crystal structure of this nucleoprotein, the overall shape of which resembles a crescent with a head and a body domain, with a protein fold different compared with that of the rhabdovirus nucleoprotein. Oligomerization of the influenza virus nucleoprotein is mediated by a flexible tail loop that is inserted inside a neighbouring molecule. This flexibility in the tail loop enables the nucleoprotein to form loose polymers as well as rigid helices, both of which are important for nucleoprotein functions. Single residue mutations in the tail loop result in the complete loss of nucleoprotein oligomerization. An RNA-binding groove, which is found between the head and body domains at the exterior of the nucleoprotein oligomer, is lined with highly conserved basic residues widely distributed in the primary sequence. The nucleoprotein structure shows that only one of two proposed nuclear localization signals are accessible, and suggests that the body domain of nucleoprotein contains the binding site for the viral polymerase. Our results identify the tail loop binding pocket as a potential target for antiviral development.     

Tricellulin forms homomeric and heteromeric tight junctional complexes

Sealing of the paracellular cleft by tight junctions is of central importance for epithelia and endothelia to function as efficient barriers between the extracellular space and the inner milieu. Occludin and claudins represent the major tight junction components involved in establishing this barrier function. A special situation emerges at sites where three cells join together. Tricellulin, a recently identified tetraspan protein concentrated at tricellular contacts, was reported to organize tricellular as well as bicellular tight junctions. Here we show that in MDCK cells, the tricellulin C-terminus is important for the basolateral translocation of tricellulin, whereas the N-terminal domain appears to be involved in directing tricellulin to tricellular contacts. In this respect, identification of homomeric tricellulin-tricellulin and of heteromeric tricellulin-occludin complexes extends a previously published model and suggests that tricellulin and occludin are transported together to the edges of elongating bicellular junctions and get separated when tricellular contacts are formed.     

Cytophotometric studies of the course of the S phase in PHA stimulated lymphocytes

Zusammenfassung Karyologische und zytophotometrische Untersuchungen an PHA-stimulierten menschlichen Lymphozyten ergaben nach 76 h im DNS-Karyogramm einen weiteren Gipfel zwischen diploiden und tetraploiden Werten. Daraus wird geschlossen, dass bei Lymphozyten in der Kultur die DNS-Synthese in der S-Phase diskontinuierlich verläuft.     

Claudin-17 forms tight junction channels with distinct anion selectivity

Barrier properties of tight junctions are determined by the claudin protein family. Many claudins seal this barrier, but others form paracellular channels. Among these, no claudins with general and clear-cut anion selectivity have yet been described, while for claudin-10a and claudin-4, only circumstantial or small anion selectivities have been shown. A claudin with unknown function and tissue distribution is claudin-17. We characterized claudin-17 by overexpression and knock-down in two renal cell lines. Overexpression in MDCK C7 cell layers caused a threefold increase in paracellular anion permeability and switched these cells from cation- to anion-selective. Knockdown in LLC-PK(1) cells indorsed the finding of claudin-17-based anion channels. Mutagenesis revealed that claudin-17 anion selectivity critically depends on a positive charge at position 65. Claudin-17 expression was found in two organs: marginal in brain but abundant in kidney, where expression was intense in proximal tubules and gradually decreased towards distal segments. As claudin-17 is predominantly expressed in proximal nephrons, which exhibit substantial, though molecularly not defined, paracellular chloride reabsorption, we suggest that claudin-17 has a unique physiological function in this process. In conclusion, claudin-17 forms channels within tight junctions with distinct anion preference.