7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: design, synthesis, and biological activity

A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR of the series are discussed.     

Discovery of novel 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes as dual inhibitors of EGFR and ErbB-2 protein tyrosine kinases

We herein disclose a novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases, with IC(50) values in the nanomolar range. Structure-activity relationship (SAR) studies elucidated a critical role for the 4-amino and C-6 arylamino moieties. The X-ray co-crystal structure of EGFR with 37 was determined and validated our design rationale.     

Photochemistry of dyes and fluorochromes used in biology and medicine: some physicochemical background and current applications

An overview of the basic principles of photochemistry is presented to facilitate discussion of fluorescence, quenching and quantum yields. These topics in turn provide the foundation for an account of fluorescence spectroscopy and its application to microscopy. A brief overview of light microscopy and the application of fluorescence microscopy is given. The influences of molecular features, such as aromatic character and substitution patterns, on color and fluorescence are described. The concept of color fading is considered with particular reference to its effect on microscopic preparations. A survey of representative fluorescent probes is provided, and their sensitivity, application, and limitations are described. The phototoxicity of fluorescent molecules is discussed using biomembranes and DNA as examples of targets of toxicity. Photodynamic therapy, a relatively new clinical application of phototoxicity, is described. Both anticancer and antimicrobial applications are noted, and an assessment is given of the current ideas on the ideal physicochemical properties of the sensitizing agents for such applications.     

Differential binding of chemokines to macrophages and neutrophils in the human inflamed synovium

In chronic inflammatory foci, such as the rheumatoid joint, there is enhanced recruitment of phagocytes from the blood into the tissues. Chemokines are strongly implicated in directing the migration of these cells, although little is known regarding the chemokine receptors that could mediate their chemotaxis into the joint tissue. Therefore the objective of the study was to identify chemokine binding sites on macrophages and neutrophils within the rheumatoid synovium using radiolabeled ligand binding and in situ autoradiography. Specific binding sites for CCL3 (macrophage inflammatory protein-1α), CCL5 (RANTES), CCL2 (monocyte chemoattractant protein-1) and CXCL8 (IL-8) were demonstrated on CD68⁺ macrophages in the subintimal and intimal layers. The number and percentage of intimal cells that bound chemokines were greater in inflamed regions compared to noninflamed regions. The intensity of intimal binding varied between chemokines with the rank order, CCL3 > CCL5 > CCL2 > CXCL8. Neutrophils throughout the synovium bound CXCL8 but did not show any signal for binding CCL2, CCL3 or CCL5.     

Plant collecting spread and densities: their potential impact on biogeographical studies in Thailand

Aims To produce representative aggregate maps of plant collection locations in Thailand and discuss their impact on biogeographical studies in Thailand and the surrounding region. Location Thailand. Methods A representative data set comprising 6593 plant specimen records for Thailand has been assembled. The data set contains ± all known collections for fifteen representative plant families and further records for another 104. All records are localized to Changwat (province), 6441 to at least quarter degree square. Results Analysis shows that the spread of collecting activity in Thailand is markedly uneven; 20% of collections come from a single Changwat (Chiang Mai) and 53% of Changwat have fifty or fewer collections. The distribution of collections by Changwat and by quarter degree square is erratic with most squares and Changwat having few collections, both in proportionate and absolute terms. Some of the most densely forested Changwats and squares appear undercollected. Distribution maps for common, easily recognized tree species in the genus Syzygium show distributional gaps. Conclusions Thailand is defined as an undercollected country. Even within the few well‐collected quarter degree squares the spread of collecting is still poor; almost all collections being localized to one of three mountain ranges or their foothills. There are many gaps in collecting activity which make impossible a straightforward interpretation of biogeographical pattern. It is argued that targeted collecting activity is needed, that assembly of this type of data set is therefore essential and that our data set and its interpretation is a model for all countries in the region.     

Festschrift: Short Shrift?

Book reviewed in this article:
From Tzintzuntan to the "Image of Limited Good": Essays in Honor of George M. Foster. M. Clark, R. Kemper , and C. Nelson .
Essays in Humanistic Anthropology: A Festschrift in Honor of David Bidney. Bruce T. Grindal and Dennis M. Warren .
Cross-Examinations. P. H. Gulliver .
Currents in Anthropology: Essays in Honor of Sol Tax. Robert Hinshaw .     

Climatic seasonality, resource bottlenecks, and abundance of rainforest birds: implications for global climate change

We demonstrate that within-year climatic variability, particularly rainfall seasonality, is the most significant variable explaining spatial patterns of bird abundance in Australian tropical rainforest. The likely mechanism causing this pattern is a resource bottleneck (insects, nectar, and fruit) during the dry season that limits the population size of many species. The patterns support both the diversity–climatic–stability hypothesis and the species–energy hypothesis but clearly show that seasonality in energy availability may be a more significant factor than annual totals or means. An index of dry season severity is proposed that quantifies the combined effect of the degree of dryness and the duration of the dry season. We suggest that the predicted increases in seasonality due to global climate change could produce significant declines in bird abundance, further exacerbating the impacts of decreased range size, increased fragmentation, and decreased population size likely to occur as a result of increasing temperature. We suggest that increasing climatic seasonality due to global climate change has the potential to have significant negative impacts on tropical biodiversity.