Balanced polymorphism in bottlenecked populations: The case of the CCR5 5 ` cis-regulatory region in Amazonian Amerindians

The 5` cis-regulatory region of the CCR5 gene exhibits a strong signature of balancing selection in several human populations. Here we analyze the polymorphism of this region in Amerindians from Amazonia, who have a complex demographic history, including recent bottlenecks that are known to reduce genetic variability. Amerindians show high nucleotide diversity (pi = 0.27%) and significantly positive Tajima`s D, and carry haplotypes associated with weak and strong gene expression. To evaluate whether these signatures of balancing selection could be explained by demography, we perform neutrality tests based on empiric and simulated data. The observed Tajima`s D was higher than that of other world populations: higher than that found for 18 noncoding regions of South Amerindians, and higher than 99.6% of simulated genealogies, which assume nonequilibrium conditions. Moreover, comparing Amerindians and Asians, the Fst for CCR5 cis-regulatory region was unusually low, in relation to neutral markers. These findings indicate that, despite their complex demographic history, South Amerindians carry a detectable signature of selection on the CCR5 cis-regulatory region. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Craniometric Similarities Within and Between Human Populations in Comparison with Neutral Genetic Data

The statement that pairs of individuals from different populations are often more genetically similar than pairs from the same population is a widespread idea inside and outside the scientific community. Witherspoon et al. [""Genetic similarities within and between human populations,"" Genetics 176:351-359 (2007)] proposed an index called the dissimilarity fraction (omega) to access in a quantitative way the validity of this statement for genetic systems. Witherspoon demonstrated that, as the number of loci increases, omega decreases to a point where, when enough sampling is available, the statement is false. In this study, we applied the dissimilarity fraction to Howells`s craniometric database to establish whether or not similar results are obtained for cranial morphological traits. Although in genetic studies thousands of loci are available, Howells`s database provides no more than 55 metric traits, making the contribution of each variable important. To cope with this limitation, we developed a routine that takes this effect into consideration when calculating. omega Contrary to what was observed for the genetic data, our results show that cranial morphology asymptotically approaches a mean omega of 0.3 and therefore supports the initial statement-that is, that individuals from the same geographic region do not form clear and discrete clusters-further questioning the idea of the existence of discrete biological clusters in the human species. Finally, by assuming that cranial morphology is under an additive polygenetic model, we can say that the population history signal of human craniometric traits presents the same resolution as a neutral genetic system dependent on no more than 20 loci.

Population genetic analysis of large sequence polymorphisms in Plasmodium falciparum blood-stage antigens

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates. Members of the multi-gene PfRh family are surface antigens that have been shown to play a central role in directing merozoites to alternative erythrocyte receptors for invasion. Recently, we identified a large structural polymorphism, a 0.58 Kb deletion, in the C-terminal region of the PfRh2b gene, present at a high frequency in parasite populations from Senegal. We hypothesize that this region is a target of humoral immunity. Here, by analyzing 371 P. falciparum isolates we show that this major allele is present at varying frequencies in different populations within Senegal, Africa, and throughout the world. For allelic dimorphisms in the asexual stage antigens, Msp-2 and EBA-175, we find minimal geographic differentiation among parasite populations from Senegal and other African localities, suggesting extensive gene flow among these populations and/or immune-mediated frequency-dependent balancing selection. In contrast, we observe a higher level of inter-population divergence (as measured by F(st)) for the PfRh2b deletion, similar to that observed for SNPs from the sexual stage Pfs45/48 loci, which is postulated to be under directional selection. We confirm that the region containing the PfRh2b polymorphism is a target of humoral immune responses by demonstrating antibody reactivity of endemic sera. Our analysis of inter-population divergence suggests that in contrast to the large allelic dimorphisms in EBA-175 and Msp-2, the presence or absence of the large PfRh2b deletion may not elicit frequency-dependent immune selection, but may be under positive immune selection, having important implications for the development of these proteins as vaccine candidates. (C) 2009 Elsevier B.V. All rights reserved.

Population dynamics of genetically diverse Plasmodium falciparum lineages: community-based prospective study in rural Amazonia

Temporal changes in the prevalence of antigenic variants in Plasmodium falciparum populations have been interpreted as evidence of immune-mediated frequency-dependent selection, but evolutively neutral processes may generate similar patterns of serotype replacement. Over 4 years, we investigated the population dynamics of P. falciparum polymorphisms the community level by using 11 putatively neutral microsatellite markers. Plasmodium falciparum Populations were less diverse than sympatric P. vivax isolates, with less multiple-clone infections, lower number of alleles per locus and lower Virtual heterozygosity, but both species showed significant multilocus linkage disequilibrium. Evolutively neutral P. falciparum polymorphisms showed a high turnover rate, with few lineages persisting for several months in the population. Similar results had previously been obtained, in the same community, for sympatric P. vivax isolates. In contrast, the prevalence of the 2 dimorphic types of a major antigen, MSP-2, remained remarkably stable throughout the Study period. We Suggest that the relatively fast turnover of parasite lineages represents the typical population dynamics of neutral polymorphisms in small populations, with clear implications for the detection of frequency-dependent selection of polymorphisms.

Motor Nerve-Conduction Studies in Obstetric Brachial Plexopathy for a Selection of Patients with a Poor Outcome

Background: The criteria and timing for nerve surgery in infants with obstetric brachial plexopathy remain controversial. Our aim was to develop a new method for early prognostic assessment to assist this decision process. Methods: Fifty-four patients with unilateral obstetric brachial plexopathy who were ten to sixty days old underwent bilateral motor-nerve-conduction studies of the axillary, musculocutaneous, proximal radial, distal radial, median, and ulnar nerves. The ratio between the amplitude of the compound muscle action potential of the affected limb and that of the healthy side was called the axonal viability index. The patients were followed and classified in three groups according to the clinical outcome. We analyzed the receiver operating characteristic curve of each index to define the best cutoff point to detect patients with a poor recovery. Results: The best cutoff points on the axonal viability index for each nerve (and its sensitivity and specificity) were <10% (88% and 89%, respectively) for the axillary nerve, 0% (88% and 73%) for the musculocutaneous nerve, <20% (82% and 97%) for the proximal radial nerve, <50% (82% and 97%) for the distal radial nerve, and <50% (59% and 97%) for the ulnar nerve. The indices from the proximal radial, distal radial, and ulnar nerves had better specificities compared with the most frequently used clinical criterion: absence of biceps function at three months of age. Conclusions: The axonal viability index yields an earlier and more specific prognostic estimation of obstetric brachial plexopathy than does the clinical criterion of biceps function, and we believe it may be useful in determining surgical indications in these patients.

Chaotic phase synchronization and desynchronization in an oscillator network for object selection

Object selection refers to the mechanism of extracting objects of interest while ignoring other objects and background in a given visual scene. It is a fundamental issue for many computer vision and image analysis techniques and it is still a challenging task to artificial Visual systems. Chaotic phase synchronization takes place in cases involving almost identical dynamical systems and it means that the phase difference between the systems is kept bounded over the time, while their amplitudes remain chaotic and may be uncorrelated. Instead of complete synchronization, phase synchronization is believed to be a mechanism for neural integration in brain. In this paper, an object selection model is proposed. Oscillators in the network representing the salient object in a given scene are phase synchronized, while no phase synchronization occurs for background objects. In this way, the salient object can be extracted. In this model, a shift mechanism is also introduced to change attention from one object to another. Computer simulations show that the model produces some results similar to those observed in natural vision systems.

A network of integrate and fire neurons for visual selection

Biological systems have facility to capture salient object(s) in a given scene, but it is still a difficult task to be accomplished by artificial vision systems. In this paper a visual selection mechanism based on the integrate and fire neural network is proposed. The model not only can discriminate objects in a given visual scene, but also can deliver focus of attention to the salient object. Moreover, it processes a combination of relevant features of an input scene, such as intensity, color, orientation, and the contrast of them. In comparison to other visual selection approaches, this model presents several interesting features. It is able to capture attention of objects in complex forms, including those linearly nonseparable. Moreover, computer simulations show that the model produces results similar to those observed in natural vision systems.

Effect of ultrasonic instrumentation on the bond strength of crowns cemented with zinc phosphate cement to natural teeth. An in vitro study

Several studies have reported the benefits of sonic and/or ultrasonic instrumentation for root debridement, with most of them focusing on changes in periodontal clinical parameters. The present study investigated possible alterations in the tensile bond strength of crowns cemented with zinc phosphate cement to natural teeth after ultrasonic instrumentation. Forty recently extracted intact human third molars were selected, cleaned and stored in physiologic serum at 4°C. They received standard preparations, at a 16º convergence angle, and AgPd alloy crowns. The crowns were cemented with zinc phosphate cement and then divided into four groups of 10 teeth each. Each group was then subdivided into two subgroups, with one of the subgroups being submitted to 5,000 thermal cycles ranging from 55 ± 2 to 5 ± 2°C, while the other was not. Each group was submitted to ultrasonic instrumentation for different periods of time: group 1 - 0 min (control), group 2 - 5 min, group 3 - 10 min, and group 4 - 15 min. Tensile bond strength tests were performed with an Instron testing machine (model 4310). Statistical analysis was performed using ANOVA and Tukey's test at the 5% level of significance. A significant reduction in the tensile bond strength of crowns cemented with zinc phosphate and submitted to thermal cycles was observed at 15 min (196.75 N versus 0 min = 452.01 N, 5 min = 444.23 N and 10 min = 470.85 N). Thermal cycling and ultrasonic instrumentation for 15 min caused a significant reduction in tensile bond strength (p < .05).

Evolução morfométrica dos anexos embrionários e fetais bovinos obtidos por monta natural, com 10 a 70 dias da gestação

O período inicial da gestação de bovinos é caracterizado por grandes perdas embrionárias. Considerando a importância deste fator no âmbito da reprodução animal foram estudados os anexos embrionários e fetais bovinos fecundados por monta natural de 15-70 dias de gestação, com o objetivo de estabelecer parâmetros morfométricos da placenta na fase inicial da gestação. Com uso de um paquímetro foram realizadas mensurações do comprimento (crânio caudal), largura (latero lateral) e altura (dorso ventral) das membranas corioalantóide e amniótica. O início da formação dos cotilédones foi observado e quantificado, assim como, o peso placentário. O peso médio do saco gestacional aumentou com o evoluir da idade gestacional, entretanto, o crescimento foi acelerado a partir de 20-30 dias de gestação. O comprimento crânio caudal e dorso ventral da membrana corioalantóide e do âmnio apresentaram crescimento lento e gradual com o evoluir dos períodos gestacionais analisados. Com 30-40 dias de gestação, os primeiro cotilédones já eram visualizados e contatos com facilidade na superfície coriônica. Os períodos de crescimento coincidiram com os maiores índices de perdas gestacionais em bovinos. Os parâmetros aqui analisados poderão servir para futuras investigações dos anexos embrionários de organismos manipulados em laboratório.

Natural history and population data of fishes in caves of the Serra do Ramalho karst area, Middle São Francisco basin, northeastern Brazil

During the exploration and mapping of new caves in Serra do Ramalho karst area, southern Bahia state, cavers from the Grupo Bambuí de Pesquisas Espeleológicas - GBPE (Belo Horizonte) noticed the presence of troglomorphic catfishes (species with reduced eyes and/or melanic pigmentation), which we intensively investigated with regards to their ecology and behavior since 2005. Non-troglomorphic fishes regularly found in the studied caves were included in this investigation. We present here data on the natural history of two troglobitic (exclusively subterranean troglomorphic species) fishes - Rhamdia enfurnada Bichuette & Trajano, 2005 (Heptapteridae; Gruna do Enfurnado) and Trichomycterus undescribed species (Trichomycteridae; Lapa dos Peixes and Gruna da Água Clara), and non-troglomorphic Hoplias cf. malabaricus, probably a troglophile (able to form populations both in epigean and subterranean habitats) in the Gruna do Enfurnado, and Pimelodella sp., a species with a sink population in the Lapa dos Peixes.

Ecology and natural history of Akodon lindberghi (Rodentia, Sigmodontinae) in southeastern Brazil

We studied the ecology and natural history of the globally threatened and poorly known Akodon lindberghi Hershkovitz, 1990 in Parque Nacional da Serra da Canastra (PNSC) and Juiz de Fora (JF), southeastern Brazil. From November 1998 to September 2001 a total of 131 individuals were captured in wire-cage live-traps and 52 by pitfalls traps. They were all marked and released at the site. The largest abundances were registered during the dry season, and most of the captures occurred in open habitats. The mean body mass of the two populations was significantly different (18.1 g at PNSC versus 13.1 g at JF; H = 46.2678, g.l.=2, p<0.001). In PNSC, individuals were reproductively active from August to February, and juveniles were present from May to August. The results suggest that the changes in vegetation structure caused by deforestation and intensive agricultural activities could increase the predation rate, affecting the mean body mass of the population.

Metronidazole release using natural rubber latex as matrix

Natural Rubber Latex (NRL) can be used successfully in controlled release drug delivery due to their excellent matrix forming properties. Recently, NRL has shown to stimulate angiogenesis, cellular adhesion and the formation of extracellular matrix, promoting the replacement and regeneration of tissue. A dermatological delivery system comprising a topically acceptable, inert support impregnated with a metronidazole (MET) solution was developed. MET 2-(2- methyl- 5-nitro- 1H- imidazol- 1-yl) ethanol, has been widely used for the treatment of protozoa and anaerobic bacterial infections. MET is a nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. In a previous study, we have tested NRL as an occlusive membrane for GBR with promising results. One possible way to decrease the inflammatory process, it was incorporated the MET in NRL. MET was incorporated into the NRL, by mixing it in solution for in vitro protein delivery experiments. The solutions of latex and MET were polymerized at different temperatures, from -100 to 40 °C, in order to control the membrane morphology. SEM microscopy analysis showed that the number, size and distribution of pores in NRL membranes varied depending on polymerization temperature, as well as its overall morphology. Results demonstrated that the best drug-delivery system was the membrane polymerized at -100 °C, which does release 77,1% of its MET content for up 310 hours.

Natural rubber latex used as drug delivery system in guided bone regeneration (GBR)

In this work, we propose natural rubber latex (NRL) membranes as a protein delivery system. For this purpose Bovine Serum Albumin (BSA) was incorporated into the latex solution for in vitro protein delivery experiments. Different polymerization temperatures were used, from -10 to 27 °C, in order to control the membrane morphology. These membranes were characterized by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), as well as the Lowry Method to measure the BSA release. SEM and AFM microscopy analysis showed that the number, size and distribution of pores in NRL membranes can be varied, as well as its overall morphology. We have found that the morphology of the membrane is the predominant factor for higher protein release, compared with pore size and number of pores. Results demonstrated that the best drug-delivery system was the membrane polymerized at RT (27 °C), which does release 66% of its BSA content for up to 18 days. Our results indicate that NRLb could be used in the future as an active membrane that could accelerate bone healing in GBR.

Caracterização mecânica e térmica da borracha natural formulada e vulcanizada dos clones: GT 1, IAN 873, PB 235 e RRIM 600

Neste trabalho estudou-se o desempenho mecânico e térmico de compostos de borracha natural (Hevea brasiliensis) de 4 diferentes clones (GT 1, IAN 873, PB 235 e RRIM 600) cultivados no Estado de São Paulo, assim como de uma mistura destes clones e de uma borracha comercial, GEB-1. Estas borrachas foram formuladas e vulcanizadas com tempos de 5, 7 e 9 minutos. A caracterização foi realizada por calorimetria exploratória diferencial, termogravimetria, ensaios de resistência à tração, análise dinâmico-mecânica, medidas de dureza Shore A, microscopia eletrônica de varredura e espectroscopia na região do infravermelho. Os resultados permitiram concluir que o tempo de vulcanização e o tipo de clone não influenciaram na temperatura de transição vítrea (Tg) dos compostos. Os valores de Tg obtidos por DMA foram de cerca de -62 °C, e os resultados ensaios de dureza apresentaram valores próximos de 60 para todos os compostos estudados. Os ensaios de resistência à tração mostraram que o melhor desempenho mecânico foi obtido pelo clone RRIM 600. De acordo com os resultados obtidos neste trabalho, todos os clones atingiram as propriedades reportadas na literatura, podendo ser utilizados, em princípio, nas indústrias de artefatos de borracha separadamente ou na forma de mistura.

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.