For whom the bell tolls? DING proteins in health and disease

DING proteins, identified mainly by their eponymous N-terminal sequences, are ubiquitous in living organisms. Amongst bacteria, they are common in pseudomonads, and have been characterised with respect to genetics and structure. They form part of a wider family of phosphate-binding proteins, with emerging roles in phosphate acquisition and pathogenicity. Many DING proteins have been isolated in eukaryotes, in which they have been associated with very diverse biological activities, often in the context of possible signalling roles. Disease states in which DING proteins have been implicated include rheumatoid arthritis, lithiasis, atherosclerosis, some tumours and tumour-associated cachexia, and bacterial and viral adherence. Complete genetic and structural characterisation of eukaryotic DING genes and proteins is still lacking, though the phosphate-binding site seems to be conserved. Whether as bacterial proteins related to bacterial pathogenicity, or as eukaryotic components of biochemical signalling systems, DING proteins require further study. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Dynamics of human adipose lipid turnover in health and metabolic disease

Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.     

Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.     

Migration of lymphocytes through the endothelium of venules in experimental allergic neuritis

Zusammenfassung Bei der experimentellen allergischen Neuritis verlassen die Lymphozyten das zirkulierende Blut der Venolen der peripheren Nerven, indem sie eher durch die als zwischen den Endothelzellen austreten. Der Durchtritt durch das Zytoplasma der Endothelzellen ist ein Beispiel von Emperipolesis.

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Supported by parts by NIH grant No. NB-03789-05, Inst. grant No. FRO5486-04, and a grant from the Swedish Medical Research Council. I thank Mr.L. Cherkas for help with the photography.     

Common mammals drive the evolutionary increase of hypsodonty in the Neogene

During the past 20 million years, herbivorous mammals of numerous lineages have evolved hypsodont, or high-crowned, cheek teeth. Hypsodonty is informative ecologically because it is well developed in mammals eating fibrous and abrasive foods that are most abundant in open and generally or seasonally dry environments. Here we report that in the Neogene of Europe mammals with the greatest locality coverages showed an increase in hypsodonty. We used a data set of 209 localities to measure whether large mammals occurring in many fossil localities show a similar increase in hypsodonty to mammals occurring in single or few localities. Taxonomic and morphological groupings show a low average hypsodonty in the early Miocene epoch. From the middle Miocene onwards, only the hypsodonty of commonly found mammals shows a marked increase. Therefore, in the drying Europe of the late Miocene, only increasingly hypsodont mammals may have been able to expand their share of habitats and food resources. These results suggest that the relatively small number of species known from multiple localities are palaeoecologically informative by themselves, irrespective of the rest of the known species.     

Cholinergic and adrenergic innervation of the penis artery of the bull: transmitter concentrations and synaptic vesicles.

The penile artery of the bull contained significant amounts of acetylcholine, noradrenaline and dopamine, and its axon profiles contained either numerous small granular or agranular vesicles, as well as some large granular vesicles. In the dorsal metatarsal artery, only noradrenaline and dopamine were detectable, and the axon profiles observed contained numerous small granular vesicles. In the penile artery, the axons with small agranular vesicles, probably cholinergic axons, were in close contact with axons containing small granular vesicles. It is suggested that, in the penile artery of the bull, one of the functions of the cholinergic nerves is suppression of excitatory adrenergic neurotransmission.     

High noradrenaline content in the vas deferens of the cock and the tortoise

Zusammenfassung Der Noradrenalingehalt des Samenleitergewebes von Hahn und Schildkröte ist gleich hoch wie bei Säugetieren.     

Release of plasminogen activator from normal and neoplastic endometrium

Summary In the medium of endometrial carcinoma cultures, anti-urokinase-reacting plasminogen activator was released in contrast to cultures of normal or hyperplastic endometrium.This investigation was supported by grants from Malmö General Hospital, the Council for Tobacco Research, USA and the Swedish Medical Research Council (B79-17X-04523-05B).     

Lipid accumulation in mouse hepatocytes after morphine exposure

Summary After morphine injection lipid accumulation in mouse hepatocytes begins within 2 h and continues for 24 h when most hepatocytes are filled with lipid droplets. In spite of morphine maintenance the liver recovers as the accumulated lipids are coupled with protein and subsequently transported and released into the perisinusoidal space of Disse.Supported by USPHS Grants GM 15490, 5 SO7 RR05386-16 and DA-01310.     

On short adrenergic neurons in the accessory male genital organs of the bull

Zusammenfassung Basierend auf dem speziellen Betragen der isolierten Noradrenalingranula der inneren männlichen Geschlechtsdrüsen, die von kurzen adrenergischen Neuronen innerviert sind, werden Definitionen für 4 «übergangsformen» der peripheren katecholamin-enthaltenden Zellen diskutiert: chromaffine Zellen der Adrenomedulla, kleine verzweigte, nicht adrenale chromaffine Zellen,kurze adrenergische Neurone undlange adrenergische Neurone.