Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study.

Scand J Clin Lab Invest. 2007 Aug 1;:1-11 [Epub ahead of print]

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

FITOTOXICIDADE DE FUNGICIDAS, ACARICIDAS E INSETICIDAS, SOBRE O MAMOEIRO (Carica papaya L.) CULTIVAR SUNRISE SOLO IMPROVED LINE 72/12 EM CONDIÇÕES DE CAMPO

A presente pesquisa teve como objetivo estudar os efeitos fitotóxicos de fungicidas, acaricidas e inseticidas e algumas associações entre eles, em plantas de mamoeiros (Carica papaya L.) cv. Sunrise Solo Improved Line 72/12, em condições de campo, no município de São Mateus -- ES, pertencente à maior região produtora do Estado. O experimento foi arranjado em delineamento de blocos casualizados, com 4 repetições e 03 plantas úteis por parcela. Foram utilizados os seguintes produtos, com as respectivas doses, para cada 100 L de água: chlorothalonil (Daconil PM-200g); mancozeb (Dithane PM -- 200g); oxicloreto de cobre (Reconil -- 400g); thiabendazole (Tecto 450 -- 100ml); dicofol + tetradifon (Carbax -- 200ml); triazophós (Hostathion 400 BR -- 150ml); óxido de fenbutatina (Torque 500 SC -- 60ml); e abamectin (Vertimec 18 CE -- 50ml): Analisou-se a fitotoxicidade dos produtos testados, em relação à altura da planta, nº de folhas, número de flores e frutos ; diâmetro do caule e queimaduras ou injúrias foliares. As datas das avaliações foram: 01 dia antes das pulverizações, 15 dias e 30 dias após as mesmas. Os fungicidas Daconil BR, Reconil e Tecto 450; o fungicida acaricida Dithane PM; os acaricidas Carbax e Torque 500 SC; e o inseticida-acaricida Vertimec 18 CE, aplicados isoladamente, não afetaram o crescimento e a produção das plantas, nem causaram injúrias nas folhas das mesmas. A associação de fungicidas e fungicida-acaricida, com os acaricidas, ou inseticida-acaricida, não mostrou nenhum efeito fitotóxico sobre os parâmetros de crescimento avaliados, nem causaram queimaduras ou injúrias foliares.

Teores de nutrientes do mamoeiro 'Improved Sunrise Solo 72/12' sob diferentes lâminas de irrigação, no Norte Fluminense

Entre os fatores que limitam a produtividade do mamoeiro, destacam-se a disponibilidade de água e nutrientes minerais. Assim, o ajuste de uma lâmina de irrigação adequada para a cultura exige também o monitoramento do estado nutricional das plantas. O objetivo desse trabalho foi avaliar a resposta das diferentes lâminas de irrigação (0; 40; 80; 120; 160; 200 e 240% da ETo) sobre os teores de nutrientes nas folhas do mamoeiro 'Improved Sunrise Solo 72/12'. As avaliações dos teores de nutrientes no mamoeiro foram realizadas em junho de 1999, retirando-se amostras de duas plantas de cada tratamento, das quais foram analisados, separadamente, o limbo e o pecíolo foliar. Os resultados indicam que os teores de N, P, K, Ca, Mg, B, Na, Fe e Cu, no limbo, e os teores de N, P, Ca, Mg, S, B, Na e Fe, no pecíolo, variaram significativamente com a lâmina de água aplicada. A concentração desses nutrientes em função das lâminas de irrigação foi explicada, na maioria dos casos, por regressões lineares, decrescentes para N, K e Fe, e crescente para os demais nutrientes. A variação significativa dos teores de nutrientes, em função da irrigação, mostra a necessidade de estudos que permitam o ajuste da adubação à lâmina de irrigação empregada.

Fitotoxicidade de fungicidas, acaricidas e inseticidas sobre o mamoeiro (Carica papaya L.) cultivar sunrise solo improved line 72/12

Estudaram-se os efeitos fitotóxicos de fungicidas, acaricidas e inseticidas e algumas associações entre eles, em plantas de mamoeiros (Carica papaya L.) cv. Sunrise Solo Improved Line 72/12, em condições de verão, no município de São Mateus - ES, localizado na região produtora do Estado. O experimento foi arranjado em delineamento de blocos casualizados, com 4 repetições e 03 plantas úteis por parcela experimental. Foram utilizados os seguintes produtos, com as respectivas doses, para cada 100 l de água: abamectin (Vertimec 18 CE - 50 ml); dicofol + tetradiphon (Carbax - 200 ml), fenbutatin oxide (Torque 500 SC - 60 ml); mancozeb (Dithane PM - 200g); oxicloreto de cobre (Reconil - 400g) e thiabendazole (Tecto 450 - 100ml). Analisou-se a fitotoxicidade dos produtos em relação à altura da planta, nº de folhas, número de flores e frutos ; diâmetro do caule e queimaduras ou injúrias foliares. As medições e contagens foram feitas um dia antes das pulverizações, 15 e 30 dias após. Constatou-se que o Vertimec 18 CE, associado ao Reconil ou ao Tecto 450, ocasionou leves injúrias foliares, detectadas aos 15 dias após as pulverizações, que se tornaram praticamente imperceptíveis, aos 30 dias após as pulverizações; e que Dithane PM, Reconil, Tecto 450, Carbax, Torque 500 SC, Dithane PM + Carbax, Dithane PM + Torque 500 SC, Dithane PM + Vertimec 18 CE, Reconil + Carbax, Reconil + Torque 500 SC, Tecto 450 + Carbax e, Tecto 450 + + Torque 500 SC não interferiram nos parâmetros de desenvolvimento e de produção estudados, bem como não causaram injúrias ou queimaduras nas folhas dos mamoeiros.

A microsatellite library for Carica papaya L. cv. Sunrise solo

In experimental areas of the Education and Researches Ilha Solteira and Jaboticabal UNESP/Campus farms were selected and tagged 20 hermaphrodite plants and 20 feminine of cultivar Sunrise Solo, Improved Sunrise Solo cv.72/12 and Baixinho of Santa Amália.The seeds origined of the selected fruits were cropped to be analysed the self-pollination efficiency and frequency of the sex in the progenies. After that, samples of the young leaf of the matrix plants were colected for the extration of the DNA. It was built five library enriched of microsatellite sequencies, using probes (TCA)10, (TC)13, (GATA)4, (CAC)10 e (TGAG)8.It was possible the development of the primers only in the library that has utilized the probe (TCA)10. This probe allowed the design of 32 primer pairs. From these, 31 presented pattern of unique band in agarose Metaphor and in acrilamide. For primer S36 were observed 2 bands, but with no polymorphism to differentiation in the sexual form at papaya tree culture. However, these primers can be tested, in the futures, in the investigation of the others features in segregated populations of this specie and the related species, germoplasm analysis, cultivars identification, parent evolution and molecular markers for the assisted plant breeding programs.

Scrfl restriction fragment length polymorphism at the D7S23 locus (probe pKM.19), closely linked to cystic fibrosis

Source/Description: pKM.19 is a 1.0 kb EcoRI genomic fragment in pUC13 (ref. 1,2). pPl was isolated independently but contains the same fragment as pKM.19 (ref. 3)...

Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism.

Brain-derived neurotrophic factor (BDNF) polymorphism is associated with the pathophysiology of several neurodegenerative disorders, including Huntington"s disease. In view ofthese data andthe involvement of huntingtin in intracellular trafficking, we examined the intracellular transport and release of Val66Val BDNF (Val-BDNF) and Val66Met BDNF (Met-BDNF) in transfected striatal knock-in cells expressing wild-type or mutant full-length huntingtin. Colocalization studies with specific markers for endoplasmic reticulum showed no differences between the Val-BDNF and Met-BDNF and were not modified by mutant huntingtin. However, post-Golgi trafficking was altered by mutant huntingtin dependent on the BDNF form. Thus, fluorescence recovery after photobleaching (FRAP) and inverse FRAP analysis showed retention of Met-BDNF inthe Golgi apparatus with respectto Val-BDNF in wild-type cells. Strikingly, mutant huntingtin diminished post-Golgi trafficking of Val-BDNF, whereas Met-BDNF was not modified. Accordingly, a reduction in the number of transport vesicles was only observed in mutant huntingtin cells transfected with Val-BDNF but not Met-BDNF. Moreover, mutant huntingtin severely affectedthe KCl-evoked release of Val-BDNF, although it had little effect on Met-BDNF regulated release. The constitutive release of Val-BDNF or Met-BDNF in mutant cells was only slightly reduced. Interestingly, mutant huntingtin only perturbed post-Golgi trafficking of proteins that follow the regulated secretory pathway (epidermal growth factor receptor or atrial natriuretic factor), whereas it did not change those that follow the constitutive pathway (p75 NTR ). We conclude that mutant huntingtin differently affects intracellular transport and release of Val-BDNF and Met-BDNF. In addition, our findings reveal a new role for huntingtin in the regulation of the post-Golgi trafficking of the regulated secretory pathway.

Inversion polymorphism in two Serbian natural populations of Drosophila subobscura: Analysis of long-term changes

To study whether inversions (or arrangements) by themselves or karyotypes are the main global warming adaptive target of natural selection, two Drosophila subobscura Serbian populations (Apatin and Petnica) were re analyzed using different statistical approaches. Both populations were sampled in an approximately 15 years period: Apatin in 1994 and 2008 + 2009 and Petnica in 1995 and 2010. For all chromosomes, the four collections studied were in Hardy-Weinberg equilibrium. Thus, it seems that inversions (or arrangements) combined at random to constitute populations" karyotypes. However, there were differences in karyotypic fre quencies along the years, although they were significant only for Apatin population. It is possible to conclude that inversions (or arrangements) are likely the target of natural selection, because they presented long term changes, but combine at random to generate the corresponding karyotypic combinations. As a consequence, the frequencies of karyotypes also change along time.

Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report

Introduction: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. Case presentation: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77. Neuropathological findings showed: spongiform change in the patient"s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. Conclusion: Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies

Catechol-O-methyltransferase, dopamine, and sleep-wake regulation.

NlmCategory="UNASSIGNED">Sleep and sleep disorders are complex and highly variable phenotypes regulated by many genes and environment. The catechol-O-methyltransferase (COMT) gene is an interesting candidate, being one of the major mammalian enzymes involved in the catabolism of catecholamines. The activity of COMT enzyme is genetically polymorphic due to a guanine-to-adenine transition at codon 158, resulting in a valine (Val) to methionine (Met) substitution. Individuals homozygous for the Val allele show higher COMT activity, and lower dopaminergic signaling in prefrontal cortex (PFC) than subjects homozygous for the Met allele. Since COMT has a crucial role in metabolising dopamine, it was suggested that the common functional polymorphism in the COMT gene impacts on cognitive function related to PFC, sleep-wake regulation, and potentially on sleep pathologies. The COMT Val158Met polymorphism may predict inter-individual differences in brain electroencephalography (EEG) alpha oscillations and recovery processes resulting from partial sleep loss in healthy individuals. The Val158Met polymorphism also exerts a sexual dimorphism and has a strong effect on objective daytime sleepiness in patients with narcolepsy-cataplexy. Since the COMT enzyme inactivates catecholamines, it was hypothesized that the response to stimulant drugs differs between COMT genotypes. Modafinil maintained executive functioning performance and vigilant attention throughout sleep deprivation in subjects with Val/Val genotype, but less in those with Met/Met genotype. Also, homozygous Met/Met patients with narcolepsy responded to lower doses of modafinil compared to Val/Val carriers. We review here the critical role of the common functional COMT gene polymorphism, COMT enzyme activity, and the prefrontal dopamine levels in the regulation of sleep and wakefulness in normal subjects, in narcolepsy and other sleep-related disorders, and its impact on the response to psychostimulants.

A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease

The β site APP cleaving enzyme 1 (BACE1) is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer"s disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer"s and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players

Annonaceae substitution rates: a codon model perspective

The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these differences has led to inconsistent results when estimating the ages of clades in Annonaceae using molecular dating techniques. We ask whether these differences may be attributed to inappropriate modelling assumptions in the phylogenetic analyses. Specifically, we test for (clade-specific) differences in rates of non-synonymous and synonymous substitutions. A high ratio of nonsynonymous to synonymous substitutions may lead to similarity of DNA sequences due to convergence instead of common ancestry, and as a result confound phylogenetic analyses. We use a dataset of three chloroplast genes (rbcL, matK, ndhF) for 129 species representative of the family. We find that differences in branch lengths between major clades are not attributable to different rates of non-synonymous and synonymous substitutions. The differences in evolutionary rate between the major clades of Annonaceae pose a challenge for current molecular dating techniques that should be seen as a warning for the interpretation of such results in other organisms.