I processi di attivazione dei sistemi enzimatici ossidasici dei grassi. I

Résumé Dans le foie de cobaye, l'activité du système enzymatique oxydasique des acides gras est en rapport avec la quantité d'A.T.P. qui y est directement introduit ou qui se forme par l'oxydation de l'acide fumarique. Tandis que l'acide -cétoglutarique active l'oxydation des acides gras beaucoup plus fortement que l'A.T.P. formé par l'oxydation du même acide -cétoglutarique.     

Meccanismo dell'azione attivatrice esplicata dal Guanosintrifosfato (G.T.P.) sui sistemi enzimatici ossidasici dei grassi. Nota IV

Résumé Dans le foie de cobaye l'arseniate ne modifie pas l'activation provoquée par le G. T. P. sur le système enzymatique des acides gras. De ces résultats on peut conclure que le G. T. P. donne directement l'énergie pour la synth`ese des acyl-CoA.      

Il guanosintrifosfato quale attivatore dei sistemi enzimatici ossidasici dei grassi Nota III

Summary In guinea-pig liver, G.T.P. and -ketoglutarate both activate enzyme systems of fatty acid oxidation in the same way, and both act independently of A.T.P.     

A radiometric method for the quantitation of experimental inflammation and anti-inflammatory activity

Zusammenfassung Nach Einspritzung von 5-Hydroxy-tryptamin in den einen Fuss einer Maus und physiologischer Salzlösung in den anderen, wurde die Radioaktivität beider Füsse verglichen. Mit radioaktivem Jod (I¹³¹) behandeltes Serumalbumin wurde dazu benutzt, den Umfang des Plasmaexsudates zu bestimmen. Das Ausmass der Hemmung der durch 5-HT induzierten Entzündung ist von der Dosis der physiologischen NaCl-Lösung abhängig.

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This study was supported in part by a grant from Sunkist Growers, Ontario (California).     

Reduced tuberoinfundibular dopaminergic neuronal function in rats after long-term withdrawal of estrogen treatment

Summary Hypothalamic fragments from female rats treated repeatedly with estradiol valerate (EV) and bearing prolactin (PRL)-secreting tumors contained, seven months after the last EV injection, lower concentrations of dopamine (DA) than age-matched controls. Depolarizing concentrations of K⁺ (35 mM) and amphetamine (50 M) evoked in PRL-secreting tumor bearing rats an endogenous DA release significantly lower than in controls.     

The unusual gamma-ray burst GRB 101225A explained as a minor body falling onto a neutron star

The tidal disruption of a solar-mass star around a supermassive black hole has been extensively studied analytically and numerically. In these events, the star develops into an elongated banana-shaped structure. After completing an eccentric orbit, the bound debris falls into the black hole, forming an accretion disk and emitting radiation. The same process may occur on planetary scales if a minor body passes too close to its star. In the Solar System, comets fall directly into our Sun or onto planets. If the star is a compact object, the minor body can become tidally disrupted. Indeed, one of the first mechanisms invoked to produce strong gamma-ray emission involved accretion of comets onto neutron stars in our Galaxy. Here we report that the peculiarities of the 'Christmas' gamma-ray burst (GRB 101225A) can be explained by a tidal disruption event of a minor body around an isolated Galactic neutron star. This would indicate either that minor bodies can be captured by compact stellar remnants more frequently than occurs in the Solar System or that minor-body formation is relatively easy around millisecond radio pulsars. A peculiar supernova associated with a gamma-ray burst provides an alternative explanation.     

Analysis of the coding genome of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular pathways, remains unknown. By combining next-generation sequencing and copy number analysis, we show that the DLBCL coding genome contains, on average, more than 30 clonally represented gene alterations per case. This analysis also revealed mutations in genes not previously implicated in DLBCL pathogenesis, including those regulating chromatin methylation (MLL2; 24% of samples) and immune recognition by T cells. These results provide initial data on the complexity of the DLBCL coding genome and identify novel dysregulated pathways underlying its pathogenesis.     

Stratified prokaryote network in the oxic-anoxic transition of a deep-sea halocline

The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling. Here we report a 2.5-m-thick chemocline with a steep NaCl gradient at 3.3 km within the water column betweeen Bannock anoxic hypersaline brine and overlying sea water. The chemocline supports some of the most biomass-rich and active microbial communities in the deep sea, dominated by Bacteria rather than Archaea, and including four major new divisions of Bacteria. Significantly higher metabolic activities were measured in the chemocline than in the overlying sea water and underlying brine; functional analyses indicate that a range of biological processes is likely to occur in the chemocline. Many prokaryotic taxa, including the phylogenetically new groups, were confined to defined salinities, and collectively formed a diverse, sharply stratified, deep-sea ecosystem with sufficient biomass to potentially contribute to organic geological deposits.     

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy.