Accumulation of (5 ` S)-8,5 `-cyclo-2 `-deoxyadenosine in organs of Cockayne syndrome complementation group B gene knockout mice

Cockayne syndrome (CS) is a human genetic disorder characterized by sensitivity to UV radiation, neurodegeneration, premature aging among other phenotypes. CS complementation group B (CS-B) gene (csb) encodes the CSB protein (CSB) that is involved in base excision repair of a number of oxidatively induced lesions in genomic DNA in vivo. We hypothesized that CSB may also play a role in cellular repair of the DNA helix-distorting tandem lesion (5`S)-8,5`-cyclo-2`-deoxyadenosine (S-cdA). Among many DNA lesions. S-cdA is unique in that it represents a concomitant damage to both the sugar and base moieties of the same nucleoside. Because of the presence of the C8-C5` covalent bond, S-cdA is repaired by nucleotide excision repair unlike most of other oxidatively induced lesions in DNA, which are subject to base excision repair. To test our hypothesis, we isolated genomic DNA from brain, kidney and liver of wild type and csb knockout (csb(-/-)) mice. Animals were not exposed to any exogenous oxidative stress before the experiment. DNA samples were analysed by liquid chromatography/mass spectrometry with isotope-dilution. Statistically greater background levels of S-cdA were observed in all three organs of csb(-/-) mice than in those of wild type mice. These results suggest the in vivo accumulation of S-cdA in genomic DNA due to lack of its repair in csb(-/-) mice. Thus, this study provides, for the first time, the evidence that CSB plays a role in the repair of the DNA helix-distorting tandem lesion S-cdA. Accumulation of unrepaired S-cdA in vivo may contribute to the pathology associated with CS. Published by Elsevier B.V.

Education and Earnings for Poverty Reduction : Short-Term Evidence of Pro-Poor Growth from the Mexican Oportunidades Program

Education, as an indispensable component of human capital, has been acknowledged to play a critical role in economic growth, which is theoretically elaborated by human capital theory and empirically confirmed by evidence from different parts of the world. The educational impact on growth is especially valuable and meaningful when it is for the sake of poverty reduction and pro-poorness of growth. The paper re-explores the precious link between human capital development and poverty reduction by investigating the causal effect of education accumulation on earnings enhancement for anti-poverty and pro-poor growth. The analysis takes the evidence from a well-known conditional cash transfer (CCT) program — Oportunidades in Mexico. Aiming at alleviating poverty and promoting a better future by investing in human capital for children and youth in poverty, this CCT program has been recognized producing significant outcomes. The study investigates a short-term impact of education on earnings of the economically disadvantaged youth, taking the data of both the program’s treated and untreated youth from urban areas in Mexico from 2002 to 2004. Two econometric techniques, i.e. difference-in-differences and difference-in-differences propensity score matching approach are applied for estimation. The empirical analysis first identifies that youth who under the program’s schooling intervention possess an advantage in educational attainment over their non-intervention peers; with this identification of education discrepancy as a prerequisite, further results then present that earnings of the education advantaged youth increase at a higher rate about 20 percent than earnings of their education disadvantaged peers over the two years. This result indicates a confirmation that education accumulation for the economically disadvantaged young has a positive impact on their earnings enhancement and thus inferring a contribution to poverty reduction and pro-poorness of growth.

Cell cycle arrest evidence, parasiticidal and bactericidal properties induced by L-amino acid oxidase from Bothrops atrox snake venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differentiation of the XY Sex Chromosomes in the Fish Hoplias malabaricus (Characiformes, Erythrinidae): Unusual Accumulation of Repetitive Sequences on the X Chromosome

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Distinct localization of T cell Agrin during antigen presentation - evidence for the expression of Agrin receptor(s) in antigen-presenting cells

Agrin is over-expressed by activated and autoimmune T cells, and synergizes with the T cell receptor (TCR) to augment cell activation. In the present study, we show that Agrin accumulates to distinct areas of the plasma membrane and that cell activation causes its redistribution. During antigen presentation, Agrin primarily accumulates to the periphery of the mature immunological synapse, mostly in lamellipodia-like protrusions that wrap around the antigen-presenting cell and, conversely, anti-Agrin sera induced a significant redistribution of TCR at the plasma membrane. We also provide evidence for the expression of Agrin receptors in peripheral blood monocytes, dendritic cells and a fraction of B cells. Interestingly, interferon-a treatment, which induces the expression of Agrin in T cells, also augmented Agrin binding to monocytes. Stimulation of monocytes with recombinant Agrin induced the clustering of surface receptors, including major histocompatibility complex class II, activation of intracellular signalling cascades, as well as enhanced dsRNA-induced expression of pro-inflammatory cytokines interleukin-6 and tumour necrosis factor-a. Collectively, these results confirm the location of Agrin at the immunological synapse between T cells and antigen-presenting cells and justify further characterization of its receptors in the immune system.

New Insight into the Mechanism of Action of Wasp Mastoparan Peptides: Lytic Activity and Clustering Observed with Giant Vesicles

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Clustering of rare earth in glasses, aluminum effect: experiments and modeling

Luminescent spectra of Eu3+-doped sol-gel glasses have been analyzed during the densification process and compared according to the presence or not of aluminum as a codoping ion. A transition temperature from hydrated to dehydroxyled environments has been found different for doped and codoped samples. However, only slight modifications have been displayed from luminescence measurements beyond this transition. To support the experimental analysis, molecular dynamics simulations have been performed to model the doped and codoped glass structures. Despite no evidence of rare earth clustering reduction due to aluminum has been found, the modeled structures have shown that the luminescent ions are mainly located in aluminum-rich domains. The synthesis of both experimental and numerical analyses has lead us to interpret the aluminum effect as responsible for differences in structure of the luminescent sites rather than for an effective dispersion of the rare earth ions. (C) 2004 Elsevier B.V. All rights reserved.

Structure, mobility and clustering of interstitial O in La2CuO4+delta in the limit of small delta

Anelastic spectra (elastic energy absorption as a function of temperature) are reported which provide evidence that excess O in La2CuO4+delta starts forming two different types of defects already at very low concentrations, where no phase separation or changes in the type of O intercalation are believed to occur. The absorption peak with the lowest activation enthalpy, H/k(B) = 5600 K, is visible at lowest values of delta and is attributed to the hopping of single interstitial O2- ions. The second process, with a slightly slower dynamics, appears at higher values of delta and soon becomes preponderant over the former process. The latter process is proposed to be due to stable pairs of O atoms and is put in connection with the formation of partially covalent bonds between interstitial and apical oxygen; such bonds would reduce the doping efficiency of excess O at increasing delta. The geometry of the interstitial O defect is discussed. O 1998 Published by Elsevier B.V. B.V. All rights reserved.

Comparative phylogeography of Trypanosoma cruzi TCIIc: New hosts, association with terrestrial ecotopes, and spatial clustering

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Economic growth in Latin America in the late 20th century: evidence and interpretation

Includes bibliography

Conjugated Linoleic Acid Combined with Physical Activity Reduces Body Fat Accumulation But Does Not Modify Lean Body Mass in Male and Female Wistar Rats

Several biological and clinical studies have suggested that conjugated linoleic acid (CLA) prevents body fat accumulation and increases lean body mass. CLA is available as a concentrated dietary supplement and is purported to provide the aforementioned benefits for people who perform physical activity. This study was conducted to evaluate the effect of a CLA-supplemented diet combined with physical activity on the body composition of Wistar rats. Two groups of Wistar rats of both sexes, between 45 and 60 days old, were fed a diet containing 5.5% soybean oil (control group) or a CLA-supplemented diet (0.5% CLA and 5.0% soybean oil) (test group). Half the rats in both groups were assigned to exercise by running on a treadmill. The biochemical and anatomical body compositions were analyzed. In both groups, CLA had no effect on the dietary consumption or the weight of the liver, heart, and lungs. However, it did influence the overall weight gain of exercised male rats and the chemical and anatomical body composition in exercised and sedentary rats of both sexes. The results confirm that a CLA-supplemented diet with and without physical activity reduced body fat accumulation in rats of both sexes. However, there is no evidence of an increase in the lean body mass of the exercised rats.

A large Cervidae Holocene accumulation in Eastern Brazil: an example of extreme taphonomical control in a cave environment

A remarkable cervid bone accumulation occurs at a single passage (named Cervid Passage; CP) at Lapa Nova, a maze cave in eastern Brazil. CP lies away from cave entrances, is a typical pitfall passage and contains bone remains of at least 121 cervids, besides few bats, peccaries and rodents remains. There is no evidence of water (or sediment) flow at the site and in general bones lack post depositional alterations and display anatomical proximity, suggesting that the majority of the remains found inside CP (mainly cervids) are due to animals that after entering the cave got trapped in the site. Observations suggest that two entrances could have provided access to cervids (and the few other animals, besides bats), either by falling inside the cave or by entering by their own free will. Once inside the cave, the maze pattern would make route finding difficult, and of all passage intersections, only the one leading to CP would result in a non-return situation, starving the animal to death. Radiocarbon dates suggest that animal entrapment occurred during at least 5 thousand years, during the Holocene. The reasons why mainly cervids were found are unknown but they are probably related to the biology of this group coupled with the fact that caves provide several specific taphonomic processes that may account for a strong bias in bone accumulation. Indeed, the frequent occurrence of Cervidae in both the fossil and sub-fossil record in Brazilian caves may be related to an overall high faunal abundance or may suggest that these animals were especially prone to enter caves, perhaps in search of nutrients (as cave saltpetre) or water.

Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude

Background: Homeopathy is based on treatment by similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce 'typical' fractures in patients with osteoporosis, but recent studies report 'atypical' fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism. Method: Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event. Results: Several studies have described multiple cases of 'atypical' low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon. Conclusion: As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this 'unresolved' issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs. Homeopathy (2012) 101, 231-242.

Measure of Global Specialization and Spatial Clustering for the Identification of "Specialized" Agglomeration

The intensity of regional specialization in specific activities, and conversely, the level of industrial concentration in specific locations, has been used as a complementary evidence for the existence and significance of externalities. Additionally, economists have mainly focused the debate on disentangling the sources of specialization and concentration processes according to three vectors: natural advantages, internal, and external scale economies. The arbitrariness of partitions plays a key role in capturing these effects, while the selection of the partition would have to reflect the actual characteristics of the economy. Thus, the identification of spatial boundaries to measure specialization becomes critical, since most likely the model will be adapted to different scales of distance, and be influenced by different types of externalities or economies of agglomeration, which are based on the mechanisms of interaction with particular requirements of spatial proximity. This work is based on the analysis of the spatial aspect of economic specialization supported by the manufacturing industry case. The main objective is to propose, for discrete and continuous space: i) a measure of global specialization; ii) a local disaggregation of the global measure; and iii) a spatial clustering method for the identification of specialized agglomerations.

Premature Osteoblast Clustering by Enamel Matrix Proteins Induces Osteoblast Differentiation through Up-Regulation of Connexin 43 and N-Cadherin

In recent years, enamel matrix derivative (EMD) has garnered much interest in the dental field for its apparent bioactivity that stimulates regeneration of periodontal tissues including periodontal ligament, cementum and alveolar bone. Despite its widespread use, the underlying cellular mechanisms remain unclear and an understanding of its biological interactions could identify new strategies for tissue engineering. Previous in vitro research has demonstrated that EMD promotes premature osteoblast clustering at early time points. The aim of the present study was to evaluate the influence of cell clustering on vital osteoblast cell-cell communication and adhesion molecules, connexin 43 (cx43) and N-cadherin (N-cad) as assessed by immunofluorescence imaging, real-time PCR and Western blot analysis. In addition, differentiation markers of osteoblasts were quantified using alkaline phosphatase, osteocalcin and von Kossa staining. EMD significantly increased the expression of connexin 43 and N-cadherin at early time points ranging from 2 to 5 days. Protein expression was localized to cell membranes when compared to control groups. Alkaline phosphatase activity was also significantly increased on EMD-coated samples at 3, 5 and 7 days post seeding. Interestingly, higher activity was localized to cell cluster regions. There was a 3 fold increase in osteocalcin and bone sialoprotein mRNA levels for osteoblasts cultured on EMD-coated culture dishes. Moreover, EMD significantly increased extracellular mineral deposition in cell clusters as assessed through von Kossa staining at 5, 7, 10 and 14 days post seeding. We conclude that EMD up-regulates the expression of vital osteoblast cell-cell communication and adhesion molecules, which enhances the differentiation and mineralization activity of osteoblasts. These findings provide further support for the clinical evidence that EMD increases the speed and quality of new bone formation in vivo.