Obesity and post-prandial lipid metabolism. Feast or famine?

Both in Western countries and in third world countries there is an increasing incidence of obesity. Obesity per se or insulin resistance associated with obesity may increase cardiovascular risk factors including dyslipidemia, hypertension and Type 2 diabetes. Over the past decade the understanding has increased of specific mediators in the hypothalamus that are involved in regulating food intake and body weight. In obese humans fasting plasma lipids can be normal but postprandial lipid metabolism is abnormal with an accumulation of triglyceride-rich remnant lipoproteins. In viscerally obese men chylomicron remnant catabolism was markedly decreased when compared with lean individuals. The decreased clearance of chylomicron remnants in viscerally obese subjects may be explained by competition between chylomicron remnants and the increased hepatic production of VLDL for clearance by low density lipoprotein receptors. Increased food intake in rodent models of obesity was shown to be associated with a delay in the catabolism of remnant lipoprotein particles. Prevention of hyperphagia was found to correct the impairment in the metabolism of remnant lipoproteins. Under fasting and food restricted conditions the improvement of remnant metabolism was associated with an increased oxidation of remnant lipids as determined by a novel stable isotope breath test. Anti-obesity and lipid lowering drugs have been used for the treatment of obesity. Inhibitors of cholesterol synthesis inhibitors (statins) have been shown to be effective in treating dyslipidemia. Inhibition of cholesterol synthesis with Atorvastatin was shown to improve chylomicron metabolism by increasing chylomicron remnant catabolism in obese subjects as assessed by the newly developed stable isotope breath test.     

Integration of ethnobotany and phytochemistry. dream or reality?

The major challenge of this paper comprises an attempt to compare the wealth of folk-information based on "traditional knowledge" with the efficacy of a chemo-biological background based on scientific knowledge. Surprisingly, correlations between plant uses (as food and medicine) and evolutionary status according to morphology (as assigned by Sporne indices) and metabolism (as assigned by diversity of phytochemicals) obey strikingly uniform systematic and evolutionary trends. The resulting patterns suggest a dynamic chemical mechanism for the bioactivity in plants regulated by the antagonistic gallate/caffeate pair. This finding is an important step toward the construction of a coherent chemo-biological language by a dynamic holistic quantitative methodology, one of the most potent prospects for understanding the functioning of nature.     

A. A. Ukhtomskiĭ and I. P. Pavlov: a controversy or a dialogue?

Pavlov's concept of conditioned reflexes and Ukhtomskii theory of dominanta fall within the biological line in physiology. They unravel the integral adaptive and active nature of the organism behavior in the environment. It is impossible to develop modern concepts about the determinants of goal-directed behavior of animals and voluntary activity of humans without in-depth study of the achievements of these Russian physiological schools which not only formed the methodological basis for the current studies but also directed the way for their further development.     

Non-coding RNA and antisense RNA. Nature's trash or treasure?

Although control of cellular function has classically been considered the responsibility of proteins, research over the last decade has elucidated many roles for RNA in regulation of not only the proteins that control cellular functions but also for the cellular functions themselves. In parallel to this advancement in knowledge about the regulatory roles of RNA there has been an explosion of knowledge about the role that epigenetics plays in controlling not only long-term cellular fate but also the short-term regulatory control of genes. Of particular interest is the crossover between these two worlds, a world where RNA can act out its part and subsequently elicit chromatin modifications that alter cellular function. Two main categories of RNA are examined here, non-coding RNA and antisense RNA both of which perform vital functions in controlling numerous genes, proteins and RNA itself. As the activities of non-coding and antisense RNA in both normal and aberrant cellular function are elucidated, so does the number of possible targets for pharmacopeic intervention.     

Neanderthals and volcanic rocks. Opportunistic behaviour or optimized management?

The use of volcanic rocks by Neanderthals is frequently considered to be opportunistic, especially when good-quality stones were rare in the site neighbourhood. An analysis of the lithic series made of volcanic rocks discovered in the Middle Palaeolithic sites of Payre and Sainte-Anne I, located in the south part and at the southeastern margin of the Massif Central of France and dated back to MIS 7 up until the end of MIS 5, illustrates the capacity of Neanderthals to manage these raw materials and enables us to compare the strategies used in two different mineral environments. Shaping and flaking reduction sequences coexist in both sites in varying proportions, depending on the available rocks in the surroundings. At Payre, artefacts made of volcanic rocks are rarer in surroundings rich in flint while at Sainte-Anne I, the different series comprise a large quantity of artefacts made of different basalts and trachy-phonolites in an environment relatively poor in flint. Most of the reduction processes took place in situ. Activities outside the sites only appear to have concerned the shaping of some heavy-duty tools and some large flakes. It is likely that volcanic rocks were considered by Neanderthals as a geo-resource, either major or lesser in importance, to provide large flakes and both heavy-duty and light-duty tools, besides flint quartz and other rocks.     

F.G. syndrome: a rare and/or extremely polymorphic syndrome?

We report a case of mental retardation associated with multiple congenital anomalies suggesting an F.G. syndrome. We discuss problems concerning genetic counselling and the management of future pregnancies. Unfortunately, no concrete strategy, concerning prenatal diagnosis, can be proposed.     

I. THE EXPRESSION OF INSTABILITY IN N. TABACUM × N. PLUMBAGINIFOLIA

Moav , Rom (Hebrew U., Jerusalem), and D. R. Cameron . Genetic instability in Nicotiana hybrids. I. The expression of instability in N. tabacum × N. plumbaginifolia. Amer. Jour. Bot. 47(2): 87—93. 1960.—N. tabacum (n = 24) and N. plumbaginifolia (n=10) are distantly related species both from morphological and cytological points of view. Hybrids of these species with various genome dosages have exhibited somatic variegation when plumbaginifolia dominant characters were superimposed on an appropriate tabacum genetic background. Five loci were studied in this respect: Wh and Tg—for flower coloration; Ws—for chlorophyll production; Kl—for pollen abortion and Bs—for black shank resistance. All 5 were found to be unstable. Backcross progenies of the sesquidiploid hybrid (tbc-tbc-pbg) to tabacum showed a marked increase in intensity of variegation. This has been attributed to the breaking up of the plumbaginifolia genome into individual chromosomes. The evidence indicates that variegation was due to somatic chromosomal aberrations which probably characterized all the plumbaginifolia chromosomes. An hypothesis regarding the heterogeneity of F₁ hybrids of distantly related homozygous species is outlined and the occurrence of instability due to hybridization in other Nicotiana hybrids is discussed.     

Synthesis and antimicrobial activity of N¹-benzyl or N¹-benzyloxy-1,6-dihydro-1,3,5-triazine-2,4-diamines

The emergence and spread of multidrug-resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis are generating a threat to public health worldwide. In the current study, a series of N(1)-benzyl and N(1)-benzyloxy-1,6-dihydro-1,3,5-triazine-2,4-diamine derivatives were synthesized and investigated for their antimicrobial activity against S. aureus, and Mycobacterium smegmatis which is taxonomically related to M. tuberculosis. Most of the compounds exhibited good activity against M. smegmatis as determined by comparison of diameters of the zone of inhibition of test compounds and standard antibiotics. Compound 7o showed potent antimycobacterial activity against M. smegmatis without mammalian DHFR inhibition liability. The results from this study indicate that 1-benzyl derivatives of 1,6-dihydro-1,3,5-triazine-2,4-diamines may be used as lead compounds for the discovery of antimycobacterial agents.     

Causation and the Origin of Life. Metabolism or Replication First?

The conceptual gulf that separates the 'metabolism first' and 'replication first' mechanisms for the emergence of life continues to cloud the origin of life debate. In the present paper we analyze this aspect of the origin of life problem and offer arguments in favor of the 'replication first' school. Utilizing Wicken's two-tier approach to causation we argue that a causal connection between replication and metabolism can only be demonstrated if replication would have preceded metabolism. In conjunction with existing empirical evidence and theoretical reasoning, our analysis concludes that there is no substantive evidence for a 'metabolism first' mechanism for life's emergence, while a coherent case can be made for the 'replication first' group of mechanisms. The analysis reaffirms our conviction that life is an extreme expression of kinetic control, and that the emergence of metabolic pathways can be understood by considering life as a manifestation of 'replicative chemistry'.