Design,synthesis, and in vitro evaluation of BP-1-102 analogs with modified hydrophobic fragments for STAT3 inhibition

Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel compounds was evaluated using several human and two mouse cancer cell lines. BP-1-102 and its two analogs emerged as effective cytotoxic agents and were further tested in additional six human and two murine cancer cell lines, in all of which they manifested the cytotoxic effect in a micromolar range. Reference compound S3I-201.1066 was found ineffective in all tested cell lines, in contrast to formerly published data. The ability of selected BP-1-102 analogs to induce apoptosis and inhibition of STAT3 receptor-mediated phosphorylation was confirmed. The structure–activity relationship confirmed a demand for two hydrophobic substituents, i.e. the pentafluorophenyl moiety and another spatially bulky moiety, for effective cytotoxic activity and STAT3 inhibition.     

Altitudinal distribution and diversity of insects in miombo woodlands in Inhamacari,Manica Province,central Mozambique

To evaluate the role of altitude on distribution pattern and diversity of entomofauna on miombo woodlands, four altitudes (850, 1,000, 1,250 and 1,400 m) were selected in a characteristic mountainous forest of Inhamacari in Mozambique in July 2015. In each sampling altitude, a linear transect with 16 yellow pan traps spaced 2 m apart was established for insect capture. Capture results allowed assessment of insect distribution by determination of insect abundance and relative frequency. Insect diversity estimates were determined by Shannon–Wiener and Simpson indices. Altitude similarity was assessed by the Jaccard coefficient. The chi-square test () was used to compare insect abundance and distribution along the altitudinal gradient. Altitude significantly affected insect abundance, relative frequency and distribution, with a nonlinear decrease with increasing altitude. Families Formicidae (Hymenoptera) and Cecidomyiidae (Diptera) were most dominant. Highest diversity and more families confined to unique altitudinal positions were found at 1,250 m while the lowest diversity was observed at 1,000 m.a.s.l. Among the altitudes, greater similarity was found between 1,000 and 1,400 m. In conclusion, altitude had a significant effect on insect family's distribution. However, further research is recommended in order to understand effect of vegetation composition and structure on insect diversity at different altitudes.     

Impaired leptin activity in New Zealand Obese mice: model of angiogenesis

Leptin is prompt to drive angiogenesis, effecting proper vascularisation. Tissue remodeling (including adipose organ) is associated with the angiogenic response. The aim of this study was to investigate the effect of hyperleptinemia on angiogenesis in subcutaneous (s.c.) in vivo matrigel model in mice on a high fat (HF) diet. HF promoted adipose tissue accumulation and biochemical changes resembling metabolic syndrome. However, the impact of this dietary treatment on angiogenesis, measured in s.c. matrigel model was not significant. Changes in leptin concentration were not accompanied by significant angiogenic response. This lack of leptin activity and impaired signal transduction at the molecular level suggests malfunction of the leptin receptor in NZO mice.     

The cps gene cluster of Salmonella strain LT2 includes a second mannose pathway: sequence of two genes and relationship to genes in the rfb gene cluster

Summary We report the presence in Salmonella enterica strain LT2 (serovar thyphimurium) of duplicate genes for two steps in the synthesis of GDP-mannose. The previously known genes, rfbK (phosphomannomutase) and rfbM (mannose-l-phosphate guanyltransferase), are part of the gene cluster for the O antigen. The two new genes, cpsB and cpsG, respectively, are thought to be part of the gene cluster for the M antigen capsular polysaccharide, present in many Enterobacteriaceae. The two genes have been sequenced and have a GC content of 0.61, suggesting an origin outside of Salmonella. Comparison of the inferred protein sequences for cpsB and rfbM shows 57% identity of amino acids whereas for cpsG and rfbK there is only 19% identity. It is suggested that the greater divergence between cpsG and rfbK may be due to a period of accelerated evolution, perhaps precipitated by transfer of the genes from another species.