Identification and design of a novel series of MGAT2 inhibitors

[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to na?ve, p <0.01) in plasma triacylglycerol (TAG) concentration.     

Ultrastructural changes of the midgut epithelial cells in feeding and moulting nymphs of the tick Haemaphysalis longicornis

The midgut epithelial cells in nymphs fed on laboratory rabbits were examined during feeding and after detachment. The midgut epithelium at the unfed stage consisted of digestive cells of lower activity, containing such nutritive substances as protein, lipid and glycogen. As feeding proceeded, the cells became active in intracellular digestion. At the middle of the feeding stage, the spent digestive cells derived from the active digestive cells began to be replaced by the new digestive cells of lower activity. After detachment, the pinocytotic activity of the above cells increased greatly, and the digestive activity increased to some extent. As a result, many large endosomes were formed by fusion of numerous pinosomes. Thereafter, endosomes decreased in size as digestion proceeded and there was an increase of haematin granules. On day 7 after detachment, the new digestive cells of lower activity, belonging to the 'nutritional reserve' type, appeared adjacent to the spent digestive cells which had almost exhausted all endosomes, and these new cells had completely replaced the spent cells by day 3 after moulting.     

Delimitation of morphologically similar sponge crab species of the genus Pseudodromia (Crustacea, Decapoda, Dromiidae) from South Africa

Stewart, B. A., Gouws, G., Daniels, S. R. & Matthee, C. A. (2004). Delimitation of morphologically similar sponge crab species of the genus Pseudodromia (Crustacea, Decapoda, Dromiidae) from South Africa. — Zoologica Scripta , 33 , 45–55.
Presently, three Pseudodromia sponge crab species are recognized, all of which are endemic to the continental shelf off the coast of South Africa. Two of these differ only in the morphology of their rostral teeth, making them difficult to distinguish, and can thus be considered as cryptic species. In addition they have very similar distribution ranges, thus raising doubts as to their specific status. Discriminant function analysis of morphometric data, differentiation at 10 allozyme loci, and sequence data derived from the 12S rRNA mitochondrial gene were used to test whether specimens identified as P. latens and P. rotunda are morphological forms of a single, widespread species, or represent two, distinct, reproductively isolated species, and to establish whether these two taxa are sister species, and thus form a monophyletic entity. The presence of fixed allele differences at three, and strong genetic heterogeneity at five other allozyme loci, indicating no gene flow occurring between sympatric populations, as well as the relatively high degree of 12S rRNA and allozyme genetic differentiation observed, supported the recognition of P. latens and P. rotunda as separate species. The 12S rRNA topology suggested that the genus Pseudodromia , as presently constituted, is paraphyletic, thus inferring that the morphological characters used to define this taxon might not be useful for phylogenetic inferences. It was concluded that in view of the uncertainties raised regarding the designation and composition of certain genera within the family Dromiidae, further rigorous analyses of morphological and genetic data are needed to further our understanding of the taxonomy of the sponge crabs.     

Decreased brown adipose tissue thermogenic activity following a reduction in brain serotonin by intraventricular p-chlorophenylalanine

The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fedad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake.     

Action Spectra for Inhibition by Light of Accumulation of Bacteriochlorophyll and Carotenoid during Aerobic Growth of Photosynthetic Bacteria

Action spectra for the inhibition by light of the accumulationof photosynthetic pigments during the aerobic growth of a photosyntheticbacterium, Rhodobacter sphaeroides, and an aerobic photosyntheticbacterium, Erythrobacter sp. strain OCh 114, were determinedover the range of wavelengths from 380 to 870 nm. The actionspectra for the inhibition of accumulation of bacteriochlorophyllin both R. sphaeroides and Erythrobacter sp. strain OCh 114indicated that the maximum inhibition occurred at approximately400 nm and a low level of inhibition occurred at 575 and 770nm. In R. sphaeroides, the action spectrum for the inhibitionof accumulation of carotenoid paralleled that for the inhibitionof accumulation of bacteriochlorophyll over the same range ofwavelengths. These results indicate that in both species, grownunder aerobic conditions, the same photoreceptor is involvedin the inhibition. One possible candidate for the relevant photoreceptormay be the precursor(s) to bacteriochlorophyll. It is possiblethat the photoreceptor is decomposed by light absorbed by itselfor by an unidentified photoreceptor that absorbs blue light(a photo-sensitizer). It is suggested that the accumulationof carotenoid is dependent on the stability of the bacteriochlorophyll. (Received September 16, 1988; Accepted March 2, 1989)