Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Colour assessment outcomes – a new approach to grading the severity of color vision loss

INTRODUCTION: Recent studies have shown that a significant percentage of subjects with anomalous, congenital trichromacy can perform the suprathreshold, colour-related tasks encountered in many occupations with the same accuracy as normal trichromats. In the absence of detailed, occupation-specific studies, an alternative approach is to make use of new findings and the statistical outcomes of past practices that have been considered safe to produce graded, justifiable categories of colour vision that can be enforced. METHODS: We analyzed traditional color assessment outcomes and measured severity of colour vision loss using the CAD test in 1363 subjects (336 normals, 705 deutan, 319 protan and 3 tritan). The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. RESULTS: The correlation between the number of Ishihara (IH) test plates subjects fail and the severity of RG colour vision loss was very poor. The 38 plates IH test has high sensitivity when no errors are allowed (i.e., only 0.71% deutans and 0.63% protans pass). Protocols based on zero errors are uncommon since 18.15% of normal trichromats fail. The most common protocols employ either the 24 or the 14 plates editions with two or less errors. These protocols pass almost all normal trichromats, but the deutans and some protans that also pass (when two or less errors are allowed) can be severely deficient. This is simply because the most challenging plates have not been included in the 24 and 14 plates editions. As a result, normals no longer fail, but the deutans and protans that pass have more severe loss of colour vision since they fail less challenging plates. The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. DISCUSSION: Historical evidence and new findings that relate severity of loss to the effective use of colour signals in a number of tasks provide the basis for a new colour grading system based on six categories. A single colour assessment test is needed to establish the applicant’s Colour Vision category which can range from ‘supernormal’ (CV0), for the most stringent, colour-demanding tasks, to ‘severe colour deficiency’, when red / green colour vision is either absent or extremely weak (CV5)

Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon

<p>Abstract</p> <p>Background</p> <p>Peru is one of the Latin American countries with the highest malaria burden, mainly due to <it>Plasmodium vivax </it>infections. However, little is known about <it>P. vivax </it>transmission dynamics in the Peruvian Amazon, where most malaria cases occur. The genetic diversity and population structure of <it>P. vivax </it>isolates collected in different communities around Iquitos city, the capital of the Peruvian Amazon, was determined.</p> <p>Methods</p> <p><it>Plasmodium vivax </it>population structure was determined by multilocus genotyping with 16 microsatellites on 159 <it>P. vivax </it>infected blood samples (mono-infections) collected in four sites around Iquitos city. The population characteristics were assessed only in samples with monoclonal infections (n = 94), and the genetic diversity was determined by calculating the expected heterozygosity and allelic richness. Both linkage disequilibrium and the genetic differentiation (<it>θ</it>) were estimated.</p> <p>Results</p> <p>The proportion of polyclonal infections varied substantially by site (11% - 70%), with the expected heterozygosity ranging between 0.44 and 0.69; no haplotypes were shared between the different populations. Linkage disequilibrium was present in all populations (<it>I</it>_A^S0.14 - 0.61) but was higher in those with fewer polyclonal infections, suggesting inbreeding and a clonal population structure. Strong population differentiation (<it>θ </it>= 0.45) was found and the Bayesian inference cluster analysis identified six clusters based on distinctive allele frequencies.</p> <p>Conclusion</p> <p>The <it>P. vivax </it>populations circulating in the Peruvian Amazon basin are genetically diverse, strongly differentiated and they have a low effective recombination rate. These results are in line with the low and clustered pattern of malaria transmission observed in the region around Iquitos city.</p

An abrupt weakening of the subpolar gyre as trigger of Little Ice Age-type episodes

We investigate the mechanism of a decadal-scale weakening shift in the strength of the subpolar gyre (SPG) that is found in one among three last millennium simulations with a state-of-the-art Earth system model. The SPG shift triggers multicentennial anomalies in the North Atlantic climate driven by long-lasting internal feedbacks relating anomalous oceanic and atmospheric circulation, sea ice extent, and upper-ocean salinity in the Labrador Sea. Yet changes throughout or after the shift are not associated with a persistent weakening of the Atlantic Meridional Overturning Circulation or shifts in the North Atlantic Oscillation. The anomalous climate state of the North Atlantic simulated after the shift agrees well with climate reconstructions from within the area, which describe a transition between a stronger and weaker SPG during the relatively warm medieval climate and the cold Little Ice Age respectively. However, model and data differ in the timing of the onset. The simulated SPG shift is caused by a rapid increase in the freshwater export from the Arctic and associated freshening in the upper Labrador Sea. Such freshwater anomaly relates to prominent thickening of the Arctic sea ice, following the cluster of relatively small-magnitude volcanic eruptions by 1600 CE. Sensitivity experiments without volcanic forcing can nonetheless produce similar abrupt events; a necessary causal link between the volcanic cluster and the SPG shift can therefore be excluded. Instead, preconditioning by internal variability explains discrepancies in the timing between the simulated SPG shift and the reconstructed estimates for the Little Ice Age onset

Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery

Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. the role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. in this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease. Copyright (C) 2011 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed ABC UFABC, CCNH, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilUniv Fed Sao Carlos UFSCar, DFQM, Sorocaba, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilFAPESP: 10/16050-9FAPESP: 10/11475-1FAPESP: 08/51116-0Web of Scienc

From fuzzy to annotated semantic web languages

The aim of this chapter is to present a detailed, selfcontained and comprehensive account of the state of the art in representing and reasoning with fuzzy knowledge in Semantic Web Languages such as triple languages RDF/RDFS, conceptual languages of the OWL 2 family and rule languages. We further show how one may generalise them to so-called annotation domains, that cover also e.g. temporal and provenance extensions

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion of previously reactive serology, generally achieved many years post-treatment. The lack of reliable tests to ensure parasite clearance and to examine the effect of treatment is the main difficulty in evaluating treatment for chronic Chagas disease. Decreases of conventional and non-conventional serological titers can be useful tools to monitor the early impact of treatment. We serially measured changes in antibody levels, including seronegative conversion as well as declines in titers in 53 benznidazole-treated and 89 untreated chronically T. cruzi-infected subjects. Seronegative conversion as well as decreases of titers was significantly higher in treated compared with untreated patients. A strong concordance was found between decreases of titers of conventional and non-conventional serologic tests post-treatment, reaffirming the findings. When seronegative conversion plus decreases of titers were considered altogether, the impact of treatment was higher, in a shorter follow-up period than previously considered. New tools for monitoring the effectiveness of treatment of chronic Chagas disease are necessary, and the results showed in this study is a contribution to researchers and physicians who assist patients suffering from this disease

Evaluation of Analytical Methods to Study Aquifer Properties with Pumping Tests in Coastal Aquifers with Numerical Modelling (Motril-Salobreña Aquifer)

Two pumping tests were performed in the unconfined Motril-Salobreña detrital aquifer in a 250 m-deep well 300 m from the coastline containing both freshwater and saltwater. It is an artesian well as it is in the discharge zone of this coastal aquifer. The two observation wells where the drawdowns are measured record the influence of tidal fluctuations, and the well lithological columns reveal high vertical heterogeneity in the aquifer. The Theis and Cooper-Jacob approaches give average transmissivity (T) and storage coefficient (S) values of 1460 m2 /d and 0.027, respectively. Other analytical solutions, modified to be more accurate in the boundary conditions found in coastal aquifers, provide similar T values to those found with the Theis and Cooper-Jacob methods, but give very different S values or could not estimate them. Numerical modelling in a synthetic model was applied to analyse the sensitivity of the Theis and Cooper-Jacob approaches to the usual boundary conditions in coastal aquifers. The T and S values calculated from the numerical modelling drawdowns indicate that the regional flow, variable pumping flows, and tidal effect produce an error of under 10 % compared to results obtained with classic methods. Fluids of different density (freshwater and saltwater) cause an error of 20 % in estimating T and of over 100 % in calculating S. The factor most affecting T and S results in the pumping test interpretation is vertical heterogeneity in sediments, which can produce errors of over 100 % in both parameters.This research has been financed by Project CGL2012-32892 (Ministerio de Economía y Competitividad of Spain) and by the Research Group Sedimentary Geology and Groundwater (RNM-369) of the Junta de Andalucía