Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Background. Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. Methods. In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1 -seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1 -seronegative individuals (control group). Results. Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor a and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1 beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. Conclusions. HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Plasmodium falciparum Accompanied the Human Expansion out of Africa

Plasmodium falciparum is distributed throughout the tropics and is responsible for an estimated 230 million cases of malaria every year, with a further 1.4 billion people at risk of infection [1-3]. Little is known about the genetic makeup of P. falciparum populations, despite variation in genetic diversity being a key factor in morbidity, mortality, and the success of malaria control initiatives. Here we analyze a worldwide sample of 519 P. falciparum isolates sequenced for two housekeeping genes (63 single nucleotide polymorphisms from around 5000 nucleotides per isolate). We observe a strong negative correlation between within-population genetic diversity and geographic distance from sub-Saharan Africa (R(2) = 0.95) over Africa, Asia, and Oceania. In contrast, regional variation in transmission intensity seems to have had a negligible impact on the distribution of genetic diversity. The striking geographic patterns of isolation by distance observed in P. falciparum mirror the ones previously documented in humans [4-7] and point to a joint sub-Saharan African origin between the parasite and its host. Age estimates for the expansion of P. falciparum further support that anatomically modern humans were infected prior to their exit out of Africa and carried the parasite along during their colonization of the world.

Molecular characterization of human polyomavirus JC in Brazilian AIDS patients with and without progressive multifocal leukoencephalopathy

Background: JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), is classified in 8 different genotypes. Previous reports have suggested a positive association between specific genotypes and PML. Objective: To compare genotypes and adaptive mutations of JCV strains from Brazilian AIDS patients with and without PML. Study design: The VP1 region of JCV was amplified by polymerase chain reaction from cerebrospinal fluid samples from 51 patients with PML and from urine samples of 47 patients with AIDS without central nervous system disease. Genotyping was done by phylogenetic analysis. Amino acid replacement and selection pressures were also investigated. Results: JCV genotype frequency distributions showed that genotypes 2 (32.7%), 1 (26.5%) and 3 (23.5%) were the most prevalent. Genotype 1 had a positive association (p < 0.0001) and genotype 3 showed an inverse association (p < 0.001) with PML. A previously undescribed point mutation at residue 91 (L/I or L/V) and (L/P), non-genotype-associated, was found in 5/49 (10.2%) and 2/47 (4.3%) JCV sequences from PML and non-PML patients, respectively. This mutation was under positive selection only in PML patients. A previously described substitution of T-A in position 128 showed a significant difference between PML and non-PML cases (70% versus 16%, respectively, p < 0.0005). Conclusion: In Brazilian patients with AIDS, JCV genotype 1 showed a strong association with PML (p < 0.0001) and JCV genotype 3 showed an inverse association with PML. The possible association of aminoacids substitution in residues 91 and 128 with PML in patients with AIDS must be further investigated. (C) 2010 Elsevier B.V. All rights reserved.

Base Excision Repair Activities Differ in Human Lung Cancer Cells and Corresponding Normal Controls

Oxidative damage to DNA is thought to play a role in carcinogenesis by causing Mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway for the repair of oxidized modifications both in nuclear and mitochondrial, DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three cell lines used. However, the specific activities and cancer versus control comparison differed significantly between the nuclear and mitochondrial compartments. OGG1 activity, as measured by 8-oxodA incision, was upregulated in cancer cell mitochondria but down-regulated in the nucleus when compared to control cells. Similarly, NTH1 activity was also up-regulated in mitochondrial extracts from cancer cells but did not change significantly in the nucleus. Together, these results support the idea that alterations in BER capacity are associated with carcinogenesis.

Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci

It has been postulated that noncoding RNAs (ncRNAs) are involved in the posttranscriptional control of gene expression, and may have contributed to the emergence of the complex attributes observed in mammalians. We show here that the complement of ncRNAs expressed from intronic regions of the human and mouse genomes comprises at least 78,147 and 39,660 transcriptional units, respectively. To identify conserved intronic sequences expressed in both humans and mice, we used custom-designed human cDNA microarrays to separately interrogate RNA from mouse and human liver, kidney, and prostate tissues. An overlapping tissue expression signature was detected for both species, comprising 198 transcripts; among these, 22 RNAs map to intronic regions with evidence of evolutionary conservation in humans and mice. Transcription of selected human-mouse intronic ncRNAs was confirmed using strand-specific RT-PCR. Altogether, these results support an evolutionarily conserved role of intronic ncRNAs in human and mouse, which are likely to be involved in the fine tuning of gene expression regulation in different mammalian tissues. (C) 2008 Elsevier Inc. All rights reserved.

Solving the non-convexity problem in some shopping-time and human-capital models

Several works in the shopping-time and in the human-capital literature, due to the nonconcavity of the underlying Hamiltonian, use Örst-order conditions in dynamic optimization to characterize necessity, but not su¢ ciency, in intertemporal problems. In this work I choose one paper in each one of these two areas and show that optimality can be characterized by means of a simple aplication of Arrowís (1968) su¢ ciency theorem.

Global stabilizing feedback law for a problem of biological control of mosquito-borne diseases

The control of the spread of dengue fever by introduction of the intracellular parasitic bacterium Wolbachia in populations of the vector Aedes aegypti, is presently one of the most promising tools for eliminating dengue, in the absence of an efficient vaccine. The success of this operation requires locally careful planning to determine the adequate number of mosquitoes carrying the Wolbachia parasite that need to be introduced into the natural population. The latter are expected to eventually replace the Wolbachia-free population and guarantee permanent protection against the transmission of dengue to human. In this paper, we propose and analyze a model describing the fundamental aspects of the competition between mosquitoes carrying Wolbachia and mosquitoes free of the parasite. We then introduce a simple feedback control law to synthesize an introduction protocol, and prove that the population is guaranteed to converge to a stable equilibrium where the totality of mosquitoes carry Wolbachia. The techniques are based on the theory of monotone control systems, as developed after Angeli and Sontag. Due to bistability, the considered input-output system has multivalued static characteristics, but the existing results are unable to prove almost-global stabilization, and ad hoc analysis has to be conducted.

O princípio da vedação ao retrocesso social e o papel dos poderes públicos na efetivação dos direitos fundamentais sociais

The purpose of this dissertation is to analyze the role of Public Powers in the enforcement of fundamental social rights, according to the principle of prohibition to social regression. The Federal Constitution of Brazil, situated in a position normative hierarchical superior, disciplines the legal and political process of the country, determining how Public Powers (Legislative, Executive and Judiciary) should act to enforce fundamental rights (social). Thus, features a cast of fundamental rights that aim to ensure social justice, highlighting the concern to ensure social values aimed at reducing social inequalities. The will of the state should be prevented by controlling the constitutionality of measures which restrict fundamental social rights, assuming the principle of human dignity, pillar of Social and Democratic State of Right, a dual role in the brazilian legal system, acting as the presupposition of jurisdictional control of the constitutionality of restrictive acts and as supervisory of omission or insufficient action of the State in the fulfillment of their fundamental duties. The constitutional determinations remove from the legislator the option to create or not the law that prints effectiveness to the social rights, as well as from the Executive the option of to execute or not rules directed at realization of the constitutional parameters, and Judiciary to behave or not in accordance with the Constitution, being given to the Powers only the arbitrariness of "how" to do, so that all functions performed by public actors to use the Constitution as a repository of the foundational values of the collectivity. Any situation that does not conform the principle of proportionality in relation to the enforcement of fundamental rights, especially the social, represents an unacceptable social regression unconstitutional. The constitutional rules and principles postulated by the realization of the rights, freedoms and guarantees of the human person, acting the principle of prohibition to social regression to regulate a concrete situation, whenever it is intended to change, reducing or deleting, the content of a social right. This paper of limit of state action serves to provide to the society legal security and protection of trust, ensuring the core of every social right. This should be effected to be sheltered the existential minimum, as a guarantee of the inviolability of human life, respecting the constitutional will, not falling into social regression

Organic acids and/or compound with defined microorganisms to control Salmonella enterica serovar Enteritidis experimental infection in chickens

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

Control of Salmonella enterica serovar Enteritidis in laying hens by inactivated Salmonella Enteritidis vaccines

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

Human face verification based on multidimensional Polynomial Powers of Sigmoid (PPS)

In this paper, we described how a multidimensional wavelet neural networks based on Polynomial Powers of Sigmoid (PPS) can be constructed, trained and applied in image processing tasks. In this sense, a novel and uniform framework for face verification is presented. The framework is based on a family of PPS wavelets,generated from linear combination of the sigmoid functions, and can be considered appearance based in that features are extracted from the face image. The feature vectors are then subjected to subspace projection of PPS-wavelet. The design of PPS-wavelet neural networks is also discussed, which is seldom reported in the literature. The Stirling Universitys face database were used to generate the results. Our method has achieved 92 % of correct detection and 5 % of false detection rate on the database.

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Allelic Frequencies of HPA-1 to 5 Human Platelet Antigens in Patients Infected With Hepatitis C Virus

Studies have suggested that hepatitis C virus (HCV) may infect not only hepatocytes but may also be carried by platelets. Platelets express more than 20 polymorphic antigenic determinants on their surface, which are called human platelet antigens (HPA), To determine the allele frequency of the HPA-1 to -5 in patients infected with HCV, blood samples were collected from 257 blood donors for the control group and from 191 patients infected with HCV. DNA was isolated and amplified for genes HPA-1 to -4 using PCR Sequence Specific Primers (PCR-SSP) and HPA-5 using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP). The allelic and genotypic frequency of HPA-5a in patients infected with HCV was found to be significantly lower(P < 0.05) than in the controls, and HPA-5b from patients infected with HCV was significantly higher (P < 0.05) than in controls. The increase in HPA5b allelic frequency in HCV infection may indicate a possible association between HCV infection and HPAs. J. Med. Virol. 81:757-759, 2009. (C) 2009 Wiley-Liss, Inc.

Genotoxicity in primary human peripheral lymphocytes after exposure to radiopacifiers in vitro

Taking into consideration that DNA damage plays an important role in carcinogenesis, the purpose of this study was to evaluate whether some radiopacifiers widely used in clinical practice are able to induce genetic damage in primary human cells in vitro. Human peripheral lymphocytes obtained from 10 healthy volunteers were exposed to barium sulphate (BaSO(4)), zirconium oxide (ZnO(2)) and bismuth oxide (Bi(2)O(3)) at final concentrations ranging from 1 to 1000 mu g/mL for 1 h at 37 degrees C. The negative control group was treated with vehicle control (phosphate buffer solution) for 1 h at 37 degrees C and the positive control group was treated with hydrogen peroxide (at 100 mu M) for 5 min on ice. Results were analyzed by the Friedman non-parametric test. The results pointed all compounds tested out did not induce DNA breakage in human peripheral lymphocytes as depicted by the mean tail moment and tail intensity in all concentrations tested. In summary, our results indicate that exposure to these radiopacifiers may not be a factor that increases the level of DNA lesions in human peripheral lymphocytes as detected by single cell gel (comet) assay.

MicroRNA-100 Acts as a Tumor Suppressor in Human Bladder Carcinoma 5637 Cells

Bladder carcinoma is one of the most common tumors in the world and, despite the therapy currently available, most of the patients relapse. Better understanding of the factors involved in disease pathogenesis would provide insights for the development of more effective strategies in treatment. Recently, differential miRNA expression profiles in bladder urothelial carcinomas identified miR-100 down-regulation and miR-708 up-regulation among the most common alterations, although the possible influence of these miRNAs in the control of basic mechanisms in bladder tumors has not been addressed. In this context, the present study aimed to evaluate the in vitro effects of miR-100 forced expression and miR-708 inhibition in the bladder carcinoma cell line 5637. Our results showed that overexpression of miR-100 significantly inhibited growth when compared to controls at both times tested (72 and 96 hours, p<0.01) with a maximum effect at 72 hours reducing proliferation in 29.6 %. Conversely, no effects on cell growth were observed after inhibition of miR-708. MiR-100 also reduced colony formation capacity of 5637 cells by 24.4%. No alterations in cell cycle progression or apoptosis induction were observed. The effects of miR-100 on growth and clonogenicity capacity in 5637 cells evince a possible role of this miRNA in bladder carcinoma pathogenesis. Further studies are necessary to corroborate our findings and examine the potential use of this microRNA in future therapeutic interventions.