Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules

Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study reveals an additional level of plasticity modulating the resolution of inflammation.     

Effects of elevation on litter-size variation among lizard populations in the Sceloporus grammicus complex (Phrynosomatidae) in Mexico

We examined the effect of elevation on litter-size variation in viviparous lizards of the Sceloporus grammicus complex in 10 states of Mexico. Female snout–vent length (SVL) decreased with increasing elevation, and absolute litter size based on embryos also tended to de crease with increasing elevation. However, after controlling for variation in female body size, we found that litter sizes tended to be relatively larger at higher elevation. Elevation therefore appears to influence litter size in these lizards; however, relatively little of the variation is explained by elevation; thus, other factors are likely making substantial contributions to the observed litter-size variation. The S. grammicus complex appears to be a good model system for examining the underlying causes of geographic and elevational variation in lizard life histories. Examinamos el efecto del altitud en la variación del tamaño de camada de las lagartijas vivíparas del complejo Sceloporus grammicus en 10 estados de México. La LHC de las hembras disminuyó con la altitud, y el tamaño absoluto de camada, calculado con base en el número de embriones, también tendió a disminuir. No obstante, después de controlar la variación en el tamaño corporal de las hembras, encontramos que los tamaños de camada tendieron a ser relativamente más grandes en altitudes mayores. La altitud, por tanto, parece influir en el tamaño de camada de estas lagartijas; sin embargo, la altitud explica relativamente poco de la variación, por lo que, es probable que otros factores contribuyan substancialmente a la variación observada en el tamaño de camada. El complejo S. grammicus parece ser un buen sistema para estudiar las causas fundamentales de la variación geográfica y altitudinal en la historia de vida de las lagartijas.     

On the Persuasiveness of Visual Arguments in Mathematics

Two experiments are reported which investigate the factors that influence how persuaded mathematicians are by visual arguments. We demonstrate that if a visual argument is accompanied by a passage of text which describes the image, both research-active mathematicians and successful undergraduate mathematics students perceive it to be significantly more persuasive than if no text is given. We suggest that mathematicians’ epistemological concerns about supporting a claim using visual images are less prominent when the image is described in words. Finally we suggest that empirical studies can make a useful contribution to our understanding of mathematical practice.     

The genome sequence and structure of rice chromosome 1

The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.