ANÁLISE DA INFLUÊNCIA DO ALELO T DO POLIMORFISMO T102C DO GENE 5-HT2A NA LONGEVIDADE DOS SERES HUMANOS

A mudança no perfil de envelhecimento populacional e o aumento da expectativa de vida encontram-se em fases diferenciadas em diversas regiões do mundo. Todavia, o aumento exponencial na proporção de idosos na população mundial é algo notável. O gene 5-HT2A, com o seu polimorfismo T102C, pode estar relacionado ao tempo de sobrevida de uma população, já que pesquisas têm demonstrado sua associação com maior ou menor suscetibilidade ao desenvolvimento de patologias e comportamentos de risco que diminuem o tempo de vida. O objetivo deste estudo foi analisar a distribuição do polimorfismo T102C do gene 5-HT2A em diferentes componentes etários representados por indivíduos de um a 104 anos. O DNA foi extraído dos descartes de amostras de sangue de 638 indivíduos do Oeste de Santa Catarina que realizaram exames de rotina no Laboratório Escola de Análises Clínicas da Unoesc de São Miguel do Oeste. A técnica de PCR-RLFP foi utilizada para a genotipagem e os resultados foram categorizados de acordo com a faixa etária dos indivíduos: “jovens”, “adulto jovem”, “adulto (meia-idade)”, “idoso jovem” e “idoso longevo”. Foram observadas diferenças relevantes entre a distribuição dos alelos do polimorfismo T102C do gene 5-HT2A entre a população de idosos longevos (> 80anos) com os demais grupos. Esses resultados sugerem que o polimorfismo T102C do gene 5-HT2A pode desempenhar algum papel na longevidade humana.Palavras-Chave: Envelhecimento. Longevidade. Gene 5-HT2A. Polimorfismo T102C

Grau de incapacidade, níveis de dor, força muscular e função eletromiográfica em portadores de hanseníase com lesão do nervo fibular comum

INTRODUCTION: This study evaluated the degree of disability, pain levels, muscle strength, and electromyographic function (RMS) in individuals with leprosy. METHODS: We assessed 29 individuals with leprosy showing common peroneal nerve damage and grade 1 or 2 disability who were referred for physiotherapeutic treatment, as well as a control group of 19 healthy participants without leprosy. All subjects underwent analyses of degree of disability, electromyographic tests, voluntary muscle force, and the Visual Analog Pain Scale. RESULTS: McNemar's test found higher levels of grade 2 of disability (Δ = 75.9%; p = 0.0001) among individuals with leprosy. The Mann-Whitney test showed greater pain levels (Δ = 5.0; p = 0.0001) in patients with leprosy who had less extension strength in the right and left extensor hallucis longus muscles (Δ = 1.28, p = 0.0001; Δ = 1.55, p = 0.0001, respectively) and dorsiflexion of the right and left feet (Δ = 1.24, p = 0.0001; Δ = 1.45, p = 0.0001, respectively) than control subjects. The Kruskal-Wallis test showed that the RMS score for dorsiflexion of the right (Δ = 181.66 m·s-2, p = 0.001) and left (Δ = 102.57m·s-2, p = 0.002) feet was lower in patients with leprosy than in control subjects, but intragroup comparisons showed no difference. CONCLUSIONS: Leprosy had a negative influence on all of the study variables, indicating the need for immediate physiotherapeutic intervention in individuals with leprosy. This investigation opens perspectives for future studies that analyze leprosy treatment with physical therapeutic intervention.INTRODUÇÃO: O objetivo do estudo foi avaliar o grau de incapacidade, níveis de dor, força muscular e a função eletromiográfica (RMS) em indivíduos portadores de hanseníase. MÉTODOS: A amostra foi composta de um grupo de 29 sujeitos portadores de hanseníase, apresentando lesão do nervo fibular comum e grau 1 ou 2 de incapacidade, com indicação ao tratamento fisioterapêutico, e um grupo controle de 19 indivíduos saudáveis, sem hanseníase. Os sujeitos foram submetidos à análise do grau de incapacidade, testes de eletromiografia, de força muscular voluntária e da Escala Visual Analógica (EVA) para a dor. RESULTADOS: O teste de McNemar mostrou maior prevalência do grau dois de incapacidade (Δ=75,9%; p=0,0001) entre os indivíduos com hanseníase. O teste de Mann-Whitney revelou maiores níveis de dor (Δ=5,0; p=0,0001) nos pacientes com hanseníase apresentando menores níveis de força muscular da extensão do hálux direito e esquerdo (Δ=1,28, p=0,0001; Δ=1,55, p=0,0001) e flexão dorsal do pé direito e esquerdo (Δ=1,24, p=0,0001; Δ=1,45, p=0,0001) do que os indivíduos sem hanseníase. O teste de Kruskal-Wallis revelou que os valores do RMS da flexão dorsal dos pés direito (Δ=181,66m.s-², p=0,001) e esquerdo (Δ=102,57m.s-2, p=0,002) apresentaram menores valores que o grupo controle em ambos os lados, mas as comparações intragrupos não mostraram diferenças. CONCLUSÕES: Conclui-se que a hanseníase altera todas as variáveis analisadas na pesquisa, indicando a necessidade de intervenção fisioterapêutica imediata nos sujeitos com Hanseníase. Esta investigação abre perspectivas de futuras pesquisas que analisem o tratamento da hanseníase com intervenção fisioterapêutica.Universidade Estadual do Piauí Centro de Ciências da SaúdeUniversidade Federal do Estado do Rio de Janeiro Laboratório de Biociências da Motricidade HumanaHospital Getúlio Vargas Clínica DermatológicaEscola de Educação Física do Exército BrasileiroFundação Oswaldo Cruz, Rio de Janeiro Laboratório de Doenças ParasitáriasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade do Oeste de Santa Catarina Laboratório de Aspectos Moleculares Associados a Doenças GenéticasUniversidade Federal do Rio Grande do SulUniversidade Federal do Estado do Rio de JaneiroUNIFESP, EPMSciEL

On theories of enhanced CP violation in B_s,d meson mixing

The DO collaboration has measured a deviation from the standard model (SM) prediction in the like sign dimuon asymmetry in semileptonic b decay with a significance of 3.2 sigma. We discuss how minimal flavour violating (MFV) models with multiple scalar representations can lead to this deviation through tree level exchanges of new MFV scalars. We review how the two scalar doublet model can accommodate this result and discuss some of its phenomenology. Limits on electric dipole moments suggest that in this model the coupling of the charged scalar to the right handed u-type quarks is suppressed while its coupling to the d-type right handed quarks must be enhanced. We construct an extension of the MFV two scalar doublet model where this occurs naturally.Comment: 10 pages, 7 figures, v3 final JHEP versio

The Complete Genome Sequence of the Pathogenic Intestinal Spirochete Brachyspira pilosicoli and Comparison with Other Brachyspira Genomes

Background: The anaerobic spirochete Brachyspira pilosicoli colonizes the large intestine of various species of birds and mammals, including humans. It causes ''intestinal spirochetosis'', a condition characterized by mild colitis, diarrhea and reduced growth. This study aimed to sequence and analyse the bacterial genome to investigate the genetic basis of its specialized ecology and virulence. Methodology/Principal Findings: The genome of B. pilosicoli 95/1000 was sequenced, assembled and compared with that of the pathogenic Brachyspira hyodysenteriae and a near-complete sequence of Brachyspira murdochii. The B. pilosicoli genome was circular, composed of 2,586,443 bp with a 27.9 mol% G+C content, and encoded 2,338 genes. The three Brachyspira species shared 1,087 genes and showed evidence of extensive genome rearrangements. Despite minor differences in predicted protein functional groups, the species had many similar features including core metabolic pathways. Genes distinguishing B. pilosicoli from B. hyodysenteriae included those for a previously undescribed bacteriophage that may be useful for genetic manipulation, for a glycine reductase complex allowing use of glycine whilst protecting from oxidative stress, and for aconitase and related enzymes in the incomplete TCA cycle, allowing glutamate synthesis and function of the cycle during oxidative stress. B. pilosicoli had substantially fewer methyl-accepting chemotaxis genes than B. hyodysenteriae and hence these species are likely to have different chemotactic responses that may help to explain their different host range and colonization sites. B. pilosicoli lacked the gene for a new putative hemolysin identified in B. hyodysenteriae WA1. Both B. pilosicoli and B. murdochii lacked the rfbBADC gene cluster found on the B. hyodysenteriae plasmid, and hence were predicted to have different lipooligosaccharide structures. Overall, B. pilosicoli 95/1000 had a variety of genes potentially contributing to virulence. Conclusions/Significance: The availability of the complete genome sequence of B. pilosicoli 95/1000 will facilitate functional genomics studies aimed at elucidating host-pathogen interactions and virulence

Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

Vasoactive intestinal peptide (VIP) is an anti-inflammatory neuropeptide recently identified as a potential antimicrobial peptide. To overcome the metabolic limitations of VIP, we modified the native peptide sequence and generated two stable synthetic analogues (VIP51 and VIP51(6–30)) with better antimicrobial profiles. Herein we investigate the effects of both VIP analogues on cell viability, membrane integrity, and ultrastructure of various bacterial strains and Leishmania species. We found that the two VIP derivatives kill various non-pathogenic and pathogenic Gram-positive and Gram-negative bacteria as well as the parasite Leishmania major through a mechanism that depends on the interaction with certain components of the microbial surface, the formation of pores, and the disruption of the surface membrane. The cytotoxicity of the VIP derivatives is specific for pathogens, because they do not affect the viability of mammalian cells. Docking simulations indicate that the chemical changes made in the analogues are critical to increase their antimicrobial activities. Consequently, we found that the native VIP is less potent as an antibacterial and fails as a leishmanicidal. Noteworthy from a therapeutic point of view is that treatment with both derivatives increases the survival and reduces bacterial load and inflammation in mice with polymicrobial sepsis. Moreover, treatment with VIP51(6–30) is very effective at reducing lesion size and parasite burden in a model of cutaneous leishmaniasis. These results indicate that the VIP analogues emerge as attractive alternatives for treating drug-resistant infectious diseases and provide key insights into a rational design of novel agents against these pathogens.This work was supported, in whole or in part, by National Institutes of Health Grant RO1 AI031078 (to S. M. B.). This work was also supported by Excellence Grants from Junta de Andalucia (P09/CTS-4705) (to E. G.-R.) and European Cost Action (BM0802) (to E. G.-R.).Peer reviewe

Syrian hamster dermal cell immortalization is not enhanced by power line frequency electromagnetic field exposure

Several epidemiological studies have suggested associations between exposure to residential power line frequency electromagnetic fields and childhood leukaemia, and between occupational exposure and adult leukaemia. A variety of in vitro studies have provided limited supporting evidence for the role of such exposures in cancer induction in the form of acknowledged cellular end points, such as enhanced mutation rate and cell proliferation, though the former is seen only with extremely high flux density exposure or with co-exposure to ionizing radiation. However, in vitro experiments on a scale large enough to detect rare cancer-initiating events, such as primary cell immortalization following residential level exposures, have not thus far been reported. In this study, large cultures of primary Syrian hamster dermal cells were continuously exposed to power line frequency electromagnetic fields of 10 100 and 1000 μT for 60 h, with and without prior exposure to a threshold (1.5 Gy), or sub-threshold (0.5 Gy), immortalizing dose of ionizing radiation. Electromagnetic field exposure alone did not immortalize these cells at a detectable frequency (≥ 1 × 10−7); furthermore, such exposure did not enhance the frequency of ionizing radiation-induced immortalization. © 1999 Cancer Research Campaig

Vacuum Instabilities with a Wrong-Sign Higgs-Gluon-Gluon Amplitude

The recently discovered 125 GeV boson appears very similar to a Standard Model Higgs, but with data favoring an enhanced h to gamma gamma rate. A number of groups have found that fits would allow (or, less so after the latest updates, prefer) that the h-t-tbar coupling have the opposite sign. This can be given meaning in the context of an electroweak chiral Lagrangian, but it might also be interpreted to mean that a new colored and charged particle runs in loops and produces the opposite-sign hGG amplitude to that generated by integrating out the top, as well as a contribution reinforcing the W-loop contribution to hFF. In order to not suppress the rate of h to WW and h to ZZ, which appear to be approximately Standard Model-like, one would need the loop to "overshoot," not only canceling the top contribution but producing an opposite-sign hGG vertex of about the same magnitude as that in the SM. We argue that most such explanations have severe problems with fine-tuning and, more importantly, vacuum stability. In particular, the case of stop loops producing an opposite-sign hGG vertex of the same size as the Standard Model one is ruled out by a combination of vacuum decay bounds and LEP constraints. We also show that scenarios with a sign flip from loops of color octet charged scalars or new fermionic states are highly constrained.Comment: 20 pages, 8 figures; v2: references adde

Structural insights into the production of 3-hydroxypropionic acid by aldehyde dehydrogenase from Azospirillum brasilense

3-Hydroxypropionic acid (3-HP) is an important platform chemical to be converted to acrylic acid and acrylamide. Aldehyde dehydrogenase (ALDH), an enzyme that catalyzes the reaction of 3-hydroxypropionaldehyde (3-HPA) to 3-HP, determines 3-HP production rate during the conversion of glycerol to 3-HP. To elucidate molecular mechanism of 3-HP production, we determined the first crystal structure of a 3-HP producing ALDH, alpha-ketoglutarate-semialdehyde dehydrogenase from Azospirillum basilensis (AbKGSADH), in its apo-form and in complex with NAD(+). Although showing an overall structure similar to other ALDHs, the AbKGSADH enzyme had an optimal substrate binding site for accepting 3-HPA as a substrate. Molecular docking simulation of 3-HPA into the AbKGSADH structure revealed that the residues Asn159, Gln160 and Arg163 stabilize the aldehyde-and the hydroxyl-groups of 3-HPA through hydrogen bonds, and several hydrophobic residues, such as Phe156, Val286, Ile288, and Phe450, provide the optimal size and shape for 3-HPA binding. We also compared AbKGSADH with other reported 3-HP producing ALDHs for the crucial amino acid residues for enzyme catalysis and substrate binding, which provides structural implications on how these enzymes utilize 3-HPA as a substrate