Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90

With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens.     

Genotypic analysis of Mycobacterium leprae isolates from Japan and other Asian countries reveals a global transmission pattern of leprosy

The genotype of single-nucleotide polymorphism type 3, CTC, at positions 14676, 164275, and 2935685, along with four copies of 6 bp repeats in the rpoT gene, was predominant for isolates originating in the Japanese mainland. Type 1, CGA, type 2, CTA, and type 3 were detected from Korea, Indonesia, and Myanmar. No isolates with four copies of 6 bp were detected from Myanmar, Okinawa, and Japanese Brazilian patients. Type 4, TTC, with three copies of 6 bp, was detected only from Japanese Brazilians. The results indicate that infection occurred in Brazil and the disease developed later in Japan.     

A new primate from the Eocene Pondaung Formation of Myanmar and the monophyly of Burmese amphipithecids

The family Amphipithecidae is one of the two fossil primate taxa from Asia that appear to be early members of the anthropoid clade. Ganlea megacanina, gen. et sp. nov., is a new amphipithecid from the late middle Eocene Pondaung Formation of central Myanmar. The holotype of Ganlea is distinctive in having a relatively enormous lower canine showing heavy apical wear, indicating an important functional role of the lower canine in food preparation and ingestion. A phylogenetic analysis of amphipithecid relationships suggests that Ganlea is the sister taxon of Myanmarpithecus, a relatively small-bodied taxon that has often, but not always, been included in Amphipithecidae. Pondaungia is the sister taxon of the Ganlea + Myanmarpithecus clade. All three Pondaung amphipithecid genera are monophyletic with respect to Siamopithecus, which is the most basal amphipithecid currently known. The inclusion of Myanmarpithecus in Amphipithecidae diminishes the likelihood that amphipithecids are specially related to adapiform primates. Extremely heavy apical wear has been documented on the lower canines of all three genera of Burmese amphipithecids. This distinctive wear pattern suggests that Burmese amphipithecids were an endemic radiation of hard object feeders that may have been ecological analogues of living New World pitheciin monkeys.     

Molecular phylogenetics and biogeography of the Neocellia Series of Anopheles mosquitoes in the Oriental Region

Molecular studies of population divergence and speciation across the Oriental Region are sparse, despite the region’s high biodiversity and extensive Pliocene and Pleistocene environmental change. A molecular phylogenetic study of the Neocellia Series of Anopheles mosquitoes was undertaken to identify patterns of diversification across the Oriental Region and to infer the role of Pleistocene and Pliocene climatic change. A robust phylogeny was constructed using CO2 and ND5 mitochondrial genes and ITS2 and D3 nuclear ribosomal markers. Bayesian analysis of mitochondrial genes was used to date divergence events. The repeated contraction and expansion of forest habitat resulting from Pleistocene climatic fluctuations appears to have had a substantial impact on intraspecific diversification, but has not driven speciation within this group. Primarily early to mid Pliocene speciation was detected within the Annularis Group, whereas speciation within the Maculatus and Jamesii Groups occurred during the mid and late Pliocene. Both allopatric divergence driven by late Pliocene environmental changes and ecological adaptation, involving altitudinal replacement and seasonality, are likely to have influenced speciation in the Maculatus Group.     

Estimating abundance with sparse data: tigers in northern Myanmar

As part of a national strategy for recovering tiger populations, the Myanmar Government recently proposed its first and the world’s largest tiger reserve in the Hukaung Valley, Kachin State. During November 2002–June 2004, camera-traps were used to record tigers, identify individuals, and, using capture–recapture approaches, estimate density in the reserve. Despite extensive (203 trap locations, 275–558 km² sample plots) and intensive (>4,500 trap nights, 9 months of sampling) survey efforts, only 12 independent detections of six individual tigers were made across three study sites. Due to the sparse data, estimates of tiger abundance generated by Program CAPTURE could not be made for all survey sites. Other approaches to estimating density, based on numbers of tigers caught, or derived from borrowed estimates of detection probability, offer an alternative to capture–recapture analysis. Tiger densities fall in the range of 0.2–2.2 tigers/100 km², with 7–71 tigers inside a 3,250 km² area of prime tiger habitat, where efforts to protect tigers are currently focused. Tiger numbers might be stabilized if strict measures are taken to protect tigers and their prey from seasonal hunting and to suppress illegal trade in wildlife. Efforts to monitor abundance trends in the tiger population will be expensive given the difficulty with which tiger data can be obtained and the lack of available surrogate indices of tiger density. Monitoring occupancy patterns, the subject of a separate ongoing study, may be more efficient.     

Dammarane-type saponins from Gynostemma pentaphyllum

Dammarane-type saponins, gypenosides VN1–VN7 (1–7), were isolated from the total saponin extract of Gynostemma pentaphyllum aerial parts, with their structures elucidated on the basis of spectroscopic and chemical methods. These compounds showed moderate cytotoxic activity against four human cancer cell lines, A549 (lung), HT-29 (colon), MCF-7 (breast), and SK-OV-3 (ovary), with IC₅₀ values ranging from 19.6 ± 1.1 to 43.1 ± 1.0 μM. Regarding the HL-60 (acute promyelocytic leukemia) cell line, compounds 1, 5, and 6 showed weakly active with IC₅₀ values of 62.8 ± 1.9, 72.6 ± 3.6, and 82.4 ± 3.2 nM, respectively, while 2, 3, 4, and 7 were less active with IC₅₀ values >100 μM.     

Metabolic pathways variability and sequence/networks comparisons

Background  

In this work a simple method for the computation of relative similarities between homologous metabolic network modules is presented. The method is similar to classical sequence alignment and allows for the generation of phenotypic trees amenable to be compared with correspondent sequence based trees. The procedure can be applied to both single metabolic modules and whole metabolic network data without the need of any specific assumption.     

Enzymatic synthesis of two novel non-reducing oligosaccharides using transfructosylation activity with β-fructofuranosidase from Arthrobacter globiformis

Two novel non-reducing oligosaccharides together with tri- and tetra-saccharides were synthesized by transfructosylation activity from sucrose as a donor and cellobiose or cellotriose as an acceptor with a purified beta-fructofuranosidase from Arthrobacter globiformis IFO 3062, and these oligosaccharides were identified as O-beta-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranosyl-(1-->2)-alpha,beta-D-fructofuranoside and O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranosyl-(1-->2)-alpha,beta-D-fructofuranoside by spectrometric analyses. Both oligosaccharides were stable under condition at 100 degrees C for 30 min, and showed no degradation at pH 2.     

OPTIMUM POLLEN AND FEMALE RECEPTOR SIZE FOR ANEMOPHILY

A set of mathematical models is developed to describe the relationship between the sizes of pollen grains and female receptors which result in maximum anemophilous pollen transfer. The models predict anemophilous plants should have Stokes numbers in the range of 1.0 to 2.72. The Stokes number is a function of both pollen size and effective receptive surface size. The models were tested with data gathered for 28 assumed anemophilous species and 20 known zoophilous species. The models identify anemophily with an accuracy of approximately 75%. If pollen size alone is used to determine anemophily, then accuracy drops to only 50%. The Stokes number criterion reported here could help in the determination of anemophily of extant and fossil plant taxa.