Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Chem Rev ; 124(9): 5227-5420, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38661578

RESUMO

Ionic liquids (ILs) have unique physicochemical properties that make them advantageous for catalysis, such as low vapor pressure, non-flammability, high thermal and chemical stabilities, and the ability to enhance the activity and stability of (bio)catalysts. ILs can improve the efficiency, selectivity, and sustainability of bio(transformations) by acting as activators of enzymes, selectively dissolving substrates and products, and reducing toxicity. They can also be recycled and reused multiple times without losing their effectiveness. ILs based on imidazolium cation are preferred for structural organization aspects, with a semiorganized layer surrounding the catalyst. ILs act as a container, providing a confined space that allows modulation of electronic and geometric effects, miscibility of reactants and products, and residence time of species. ILs can stabilize ionic and radical species and control the catalytic activity of dynamic processes. Supported IL phase (SILP) derivatives and polymeric ILs (PILs) are good options for molecular engineering of greener catalytic processes. The major factors governing metal, photo-, electro-, and biocatalysts in ILs are discussed in detail based on the vast literature available over the past two and a half decades. Catalytic reactions, ranging from hydrogenation and cross-coupling to oxidations, promoted by homogeneous and heterogeneous catalysts in both single and multiphase conditions, are extensively reviewed and discussed considering the knowledge accumulated until now.

2.
BMC Plant Biol ; 24(1): 858, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39266956

RESUMO

BACKGROUND: African mahogany species (Khaya sp.) have been introduced to Brazil gaining increasing economic interest over the last years, as they produce high quality wood for industrial applications. To this date, however, the knowledge available on the genetic basis of African mahogany plantations in Brazil is limited, which has driven this study to examine the extent of genetic diversity and structure of three cultivated species (Khaya grandifoliola, Khaya senegalensis and Khaya ivorensis) and their prospects for forest breeding. RESULTS: In total, 115 individuals were genotyped (48 of K. grandifoliola, 34 of K. senegalensis and 33 of K. ivorensis) for 3,330 filtered neutral loci obtained from genotyping-by-sequencing for the three species. The number of SNPs varied from 2,951 in K. ivorensis to 4,754 in K. senegalensis. Multiloci clustering, principal component analysis, Bayesian structure and network analyses showed a clear genetic separation among the three species. Structure analysis also showed internal structure within each species, highlighting genetic subgroups that could be sampled for selecting distinct genotypes for further breeding, although the genetic distances are moderate to low. CONCLUSION: In our study, SNP markers efficiently assessed the genomic diversity of African mahogany forest plantations in Brazil. Our genetic data clearly separated the three Khaya species. Moreover, pairwise estimates of genetic distances among individuals within each species showed considerable genetic divergence among individuals. By genotyping 115 pre-selected individuals with desirable growth traits, allowed us not only to recommend superior genotypes but also to identify genetically distinct individuals for use in breeding crosses.


Assuntos
Florestas , Variação Genética , Brasil , Meliaceae/genética , Polimorfismo de Nucleotídeo Único , Melhoramento Vegetal , Genótipo , Genoma de Planta
3.
Mol Ecol ; : e17437, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887167

RESUMO

Environmental stress is a fundamental facet of life and a significant driver of natural selection in the wild. Gene expression diversity may facilitate adaptation to environmental changes, without necessary genetic change, but its role in adaptive divergence remains largely understudied in Neotropical systems. In Amazonian riparian forests, species distribution is predominantly influenced by species' waterlogging tolerance. The flooding gradient delineates distinct wetland forest types, shaping habitats and species characteristics. Here we investigated the molecular basis of environmental stress response in a tropical ground-herb species (Ischnosiphon puberulus) to environmental variation in Amazonian riparian forests. We compared environmental variables and gene expression profiles from individuals collected in two forest types: Igapó and Terra firme in the Amazonian riparian forests. Predictable seasonal flooding poses a significant challenge in Igapó compared to Terra firme environments, with the former presenting higher water column height and longer flooding duration. Our findings suggest that contrasting environmental conditions related to flooding regimes are important drivers of population genetic differentiation and differential gene expression in I. puberulus. Enriched gene ontology terms highlight associations with environmental stresses, such as defence response, water transport, phosphorylation, root development, response to auxin, salicylic acid and oxidative stress. By uncovering key environmental stress response pathways conserved across populations, I. puberulus offers novel genetic insights into the molecular basis of plant reactions to environmental constraints found in flooded areas of this highly biodiverse neotropical ecosystem.

4.
Heredity (Edinb) ; 127(2): 203-218, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33953353

RESUMO

Both genetic drift and divergent selection are predicted to be drivers of population differentiation across patchy habitats, but the extent to which these forces act on natural populations to shape traits is strongly affected by species' ecological features. In this study, we infer the genomic structure of Pitcairnia lanuginosa, a widespread herbaceous perennial plant with a patchy distribution. We sampled populations in the Brazilian Cerrado and the Central Andean Yungas and discovered and genotyped SNP markers using double-digest restriction-site associated DNA sequencing. In addition, we analyzed ecophysiological traits obtained from a common garden experiment and compared patterns of phenotypic and genetic divergence (PST-FST comparisons) in a subset of populations from the Cerrado. Our results from molecular analyses pointed to extremely low genetic diversity and a remarkable population differentiation, supporting a major role of genetic drift. Approximately 0.3% of genotyped SNPs were flagged as differentiation outliers by at least two distinct methods, and Bayesian generalized linear mixed models revealed a signature of isolation by environment in addition to isolation by distance for high-differentiation outlier SNPs among the Cerrado populations. PST-FST comparisons suggested divergent selection on two ecophysiological traits linked to drought tolerance. We showed that these traits vary among populations, although without any particular macro-spatial pattern, suggesting local adaptation to differences in micro-habitats. Our study shows that selection might be a relevant force, particularly for traits involved in drought stress, even for populations experiencing strong drift, which improves our knowledge on eco-evolutionary processes acting on non-continuously distributed species.


Assuntos
Deriva Genética , Genética Populacional , Aclimatação , Adaptação Fisiológica/genética , Teorema de Bayes , Variação Genética , Seleção Genética
5.
BMC Plant Biol ; 20(1): 554, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302865

RESUMO

BACKGROUND: Closely related hybridizing species are ideal systems for identifying genomic regions underlying adaptive divergence. Although gene expression plays a central role in determining ecologically-based phenotypic differences, few studies have inferred the role of gene expression for adaptive divergence in Neotropical systems. In this study, we conduct genome-wide expression analysis alongside soil elemental analysis in sympatric and allopatric populations of Epidendrum fulgens and E. puniceoluteum (Orchidaceae), which occur in contrasting adjacent habitats in the Neotropical coastal plains. RESULTS: These species were highly differentiated by their gene expression profiles, as determined by 18-21% of transcripts. Gene ontology (GO) terms associated with reproductive processes were enriched according to comparisons between species in both allopatric and sympatric populations. Species showed differential expression in genes linked to salt and waterlogging tolerance according to comparisons between species in sympatry, and biological processes related to environmental stimulus appeared as representative among those transcripts associated with edaphic characteristics in each sympatric zone. Hybrids, in their turn, were well differentiated from E. fulgens, but exhibited a similar gene expression profile to flooding-tolerant E. puniceolutem. When compared with parental species, hybrids showed no transcripts with additive pattern of expression and increased expression for almost all transgressive transcripts. CONCLUSIONS: This study sheds light on general mechanisms promoting ecological differentiation and assortative mating, and suggests candidate genes, such as those encoding catalase and calcium-dependent protein kinase, underling adaptation to harsh edaphic conditions in the Neotropical coastal plains. Moreover, it demonstrates that differential gene expression plays a central role in determining ecologically-based phenotypic differences among co-occurring species and their hybrids.


Assuntos
Ecossistema , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Orchidaceae/genética , Clima Tropical , Áreas Alagadas , Adaptação Fisiológica/genética , Brasil , Ontologia Genética , Interação Gene-Ambiente , Especiação Genética , Geografia , Hibridização Genética , Orchidaceae/classificação , Análise de Componente Principal , Especificidade da Espécie
6.
Heredity (Edinb) ; 125(5): 353-370, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32681156

RESUMO

Geographic isolation and reduced population sizes can lead to local extinction, low efficacy of selection and decreased speciation. However, population differentiation is an essential step of biological diversification. In allopatric speciation, geographically isolated populations differentiate and persist until the evolution of reproductive isolation and ecological divergence completes the speciation process. Pitcairnia flammea allows us to study the evolutionary consequences of habitat fragmentation on naturally disjoint rock-outcrop species from the Brazilian Atlantic Rainforest (BAF). Our main results showed low-to-moderate genetic diversity within populations, and deep population structuring caused by limited gene flow, low connectivity, genetic drift and inbreeding of long-term isolation and persistence of rock-outcrop populations throughout Quaternary climatic oscillations. Bayesian phylogenetic and model-based clustering analyses found no clear northern and southern phylogeographic structure commonly reported for many BAF organisms. Although we found two main lineages diverging by ~2 Mya during the early Pleistocene, species' delimitation analysis assigned most of the populations as independent evolving entities, suggesting an important role of disjoint rock outcrops in promoting high endemism in this rich biome. Lastly, we detected limited gene flow in sympatric populations although some hybridization and introgression were observed, suggesting a continuous speciation process in this species complex. Our data not only inform us about the extensive differentiation and limited gene flow found among Pitcairnia flammea species complex, but they also contain information about the mechanisms that shape the genetic architecture of small and fragmented populations of isolated rock outcrop of recently radiated plants.


Assuntos
Bromeliaceae/genética , Fluxo Gênico , Variação Genética , Genética Populacional , Teorema de Bayes , Brasil , Deriva Genética , Especiação Genética , Endogamia , Filogenia , Filogeografia
7.
8.
Int J Neurosci ; 130(9): 892-897, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31877079

RESUMO

Background: Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE e4 is an isoform of ApoE with altered function, and was previously associated with early onset epilepsy and refractoriness, both in animal models and in patients with focal epilepsies. There is a limited knowledge on ApoE's role in Genetic Generalized Epilepsies (GGE).Aim: To determine if ApoE isoforms are risk factors for GGE development.Methods: A group of 337 GGE patients (193 F, 144 M, 33.6 ± 14.2 years) was compared with a group of 342 healthy individuals in a case-control genetic association study. ApoE genotyping was performed using PCR-RFLP.Results: The genotypic frequency of ApoE e3/e2 was lower in GGE patients relative to controls (6.5% in GGE vs. 11.7% in controls, p = 0.019, OR (95% CI) = 0.53 (0.305-0.905). No associations with other clinical data such as photosensitivity or age at disease onset were observed.Conclusion: Our results show that ApoE e3/e2 genotype may be a protective factor for GGE development. There is evidence that this genotype could be neuroprotective, preventing oxidative damage and promoting neuronal survival. Although replication studies are warranted, our data suggest that ApoE isoforms have a role in epileptogenic mechanisms regardless of the specific epileptic manifestations.


Assuntos
Apolipoproteína E2/genética , Apolipoproteína E3/genética , Apolipoproteínas E/genética , Epilepsia Generalizada/genética , Síndromes Epilépticas/genética , Predisposição Genética para Doença/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Isoformas de Proteínas , Adulto Jovem
10.
Ann Bot ; 124(3): 499-512, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31219156

RESUMO

BACKGROUND AND AIMS: Isolated populations constitute an ideal laboratory to study the consequences of intraspecific divergence, because intrinsic incompatibilities are more likely to accumulate under reduced gene flow. Here, we use a widespread bromeliad with a patchy distribution, Pitcairnia lanuginosa, as a model to infer processes driving Neotropical diversification and, thus, to improve our understanding of the origin and evolutionary dynamics of biodiversity in this highly speciose region. METHODS: We assessed the timing of lineage divergence, genetic structural patterns and historical demography of P. lanuginosa, based on microsatellites, and plastid and nuclear sequence data sets using coalescent analyses and an Approximate Bayesian Computation framework. Additionally, we used species distribution models (SDMs) to independently estimate potential changes in habitat suitability. KEY RESULTS: Despite morphological uniformity, plastid and nuclear DNA data revealed two distinct P. lanuginosa lineages that probably diverged through dispersal from the Cerrado to the Central Andean Yungas, following the final uplift of the Andes, and passed through long-term isolation with no evidence of migration. Microsatellite data indicate low genetic diversity and high levels of inbreeding within populations, and restricted gene flow among populations, which are likely to be a consequence of bottlenecks (or founder events), and high selfing rates promoting population persistence in isolation. SDMs showed a slight expansion of the suitable range for P. lanuginosa lineages during the Last Glacial Maximum, although molecular data revealed a signature of older divergence. Pleistocene climatic oscillations thus seem to have played only a minor role in the diversification of P. lanuginosa, which probably persisted through adverse conditions in riparian forests. CONCLUSIONS: Our results imply drift as a major force shaping the evolution of P. lanuginosa, and suggest that dispersal events have a prominent role in connecting Neotropical open and forest biomes.


Assuntos
Fluxo Gênico , Variação Genética , Teorema de Bayes , Filogenia , Filogeografia
11.
BMC Vet Res ; 15(1): 325, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506083

RESUMO

BACKGROUND: Estrogens are essential for the development and proper function of several hormone-dependent organs. There are, however, several lines of evidence associating estrogens with mammary carcinogenesis. A marked individual genetic variability concerning estrogens biosynthesis, metabolism and mechanism of action was recognized and associated with human breast cancer susceptibility, clinical features and progression. Although some genetic variations in canine ESR1 gene were reported, their influence in clinicopathological features and progression of canine mammary tumors has not been fully evaluated. This study aims to assess the influence of SNPs in ESR1 gene (rs397512133, rs397510462, rs851327560, rs397510612, rs852887655, rs852684753 and rs852398698) in canine mammary tumors characteristics and progression. A group of 155 non-neutered bitches with mammary tumors was included in the study. Follow-up information was assessed 24 months after surgery. RESULTS: Genetic profiles associated with a later onset of mammary tumors and less aggressive clinicopathological features, namely smaller tumor size (≤ 3 cm) with extensive tubular differentiation and low canine-adapted prognostic index (vet-NPI), were identified in this study. CONCLUSIONS: Our data suggest that the ESR1 genetic profile may help on the decision regarding the selection of individual tailored preventive measures against canine mammary tumors development, such as early neutering.


Assuntos
Doenças do Cão/genética , Neoplasias Mamárias Animais/genética , Receptores de Estrogênio/genética , Animais , Cães , Feminino , Genótipo , Neoplasias Mamárias Animais/metabolismo , Polimorfismo de Nucleotídeo Único
12.
Am J Bot ; 105(10): 1725-1734, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30324691

RESUMO

PREMISE OF THE STUDY: Historical abiotic and biotic factors have strongly affected species diversification and speciation. Although pre-Pleistocene events have been linked to the divergence of several Neotropical organisms, studies have highlighted a more prominent role of Pleistocene climatic oscillations in shaping current patterns of genetic variation of plants. METHODS: We performed phylogeographic analyses based on plastidial markers and modeled the current distribution and paleodistribution of Bromelia balansae (Bromeliaceae), an herbaceous species with a wide geographical distribution in South America, to infer the processes underlying its evolutionary history. KEY RESULTS: Combined molecular and paleodistributional modeling analyses indicated retraction during the Last Glacial Maximum followed by interglacial expansion. Populations occurring in the semideciduous Atlantic Forest and the Cerrado formed two distinct genetic clusters, which have been historically or ecologically isolated since late Pliocene to early Pleistocene. Populations located in the transition zone had higher levels of genetic diversity, as expected by the long-term climatic stability in the region detected in our ecological niche models. CONCLUSIONS: Our study adds important information on how herbaceous species have been affected by past climate in Central and Southeast Brazil, helping to disentangle the complex processes that have triggered the evolution of Neotropical biota.


Assuntos
Evolução Biológica , Bromelia/fisiologia , Ecossistema , Filogeografia , Dispersão Vegetal , Brasil , Bromelia/genética , Modelos Biológicos , América do Sul
13.
Int J Neurosci ; 128(4): 305-310, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28675059

RESUMO

PURPOSE: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1ß and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1ß), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. METHODS: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case-control study. RESULTS: The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13-4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. CONCLUSION: The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1ß levels produced by this genotype. High IL-1ß levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.


Assuntos
Causalidade , Epilepsia do Lobo Temporal/genética , Cadeias HLA-DRB1/genética , Hipocampo/patologia , Interleucina-1alfa/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Epilepsia do Lobo Temporal/complicações , Feminino , Genótipo , Humanos , Imunogenética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose/etiologia , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
14.
Int J Neurosci ; 127(9): 800-804, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27875923

RESUMO

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most frequent pharmaco-resistant epilepsy. It has been associated with febrile seizures (FS) in childhood. Its aetiology remains unclear but genetic factors are involved. Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE ϵ4 is an isoform of ApoE with altered protein function, previously associated with refractoriness and early onset epilepsy. This study was undertaken to determine if ApoE isoforms are risk factors for MTLE-HS and influence clinical characteristics. METHODS: A group of 188 MTLE-HS patients (101 F, 87 M, mean age = 44.7 ± 11.6 years, 100 with FS antecedents) was studied and compared with a group of 342 healthy individuals in a case-control genetic association study. Data were analysed with Pearson Chi-squared Test or Student's t test, as appropriated. RESULTS: No differences in ApoE ϵ4 allelic frequencies between MTLE-HS patients and controls or between MTLE-HS subgroups were observed. Nevertheless, ApoE ϵ4 carriers had an earlier MTLE-HS onset (11.0 ± 7.9 years in ApoE ϵ4 carriers vs. 14.4 ± 11.2 years in ApoE ϵ4 non-carriers p < 0.05). Additionally, we observed that MTLE-HS patients with FS antecedents had a statistically significant early disease onset (11.5 ± 8.7 years in FS+ vs. 16.0 ± 12.1 years in FS-, p < 0.01). CONCLUSIONS: Our data show that ApoE ϵ4 and FS may not participate directly in etiopathogenic mechanisms of MTLE-HS but could hasten the disease development in predisposed individuals.


Assuntos
Apolipoproteína E4/genética , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/genética , Predisposição Genética para Doença/genética , Hipocampo/patologia , Adolescente , Adulto , Idade de Início , Idoso , Estudos de Casos e Controles , Eletroencefalografia , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Esclerose/etiologia , Estatísticas não Paramétricas , Adulto Jovem
15.
Inorg Chem ; 55(2): 865-70, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26741646

RESUMO

Interacting superparamagnetic iron(II) oxide nanoparticles (NPs) with sizes of 5.3 ± 1.6 nm were prepared by simple decomposition of [Fe(COT)2] (COT = 1,3,5,7-cyclooctatetraene) with 5 bar of H2 in 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI·NTf2) ionic liquid (IL). The static and dynamic magnetic characterization revealed a superparamagnetic behavior with weak dipolar interactions of these NPs. In situ structural studies by X-ray absorption spectroscopy demonstrated that they consist of nanostructured FeO. This approach is an appropriate method to prepare and stabilize nanostructured FeO particles, where the presence of an IL proved to be fundamental to suppress the aggregation and usual overoxidation of the FeO NPs.

16.
Physiol Plant ; 154(4): 500-10, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25271368

RESUMO

Physiological changes that increase plant performance during exposure to high temperatures may play an inverse role during exposure to low temperatures. The objective of this study was to test variations in photosystem II response to heat and cold stress in the leaves of a bromeliad with crassulacean acid metabolism submitted to high or low temperatures. Leaves were maintained under constant temperatures of 10 and 35°C and used to examine possible relationships among physiological responses to high and low temperatures and organic acid accumulation. We also tested if distinct parts of bromeliad leaves show differences in photosynthetic thermotolerance. The samples from leaves maintained at 35°C showed greater heat tolerance values, while those from leaves maintained at 10°C showed lower cold tolerance values. Our results identified a strong negative relationship between the organic acid accumulation and thermal tolerance of bromeliad leaves that largely explained the differences in thermal tolerance among groups. One of these differences occurred among regions of a single leaf, with the base showing critical heat values of up to 8°C higher than the top region, suggesting a possible partitioning of leaf response among its regions. Differences in thermal tolerance were also observed between sampling times, with higher values observed in the morning.


Assuntos
Ácidos/metabolismo , Bromeliaceae/fisiologia , Folhas de Planta/metabolismo , Temperatura , Bromeliaceae/metabolismo , Fotossíntese , Estresse Fisiológico
17.
Clin Exp Rheumatol ; 32(4 Suppl 84): S72-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25268662

RESUMO

OBJECTIVES: To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (BD) in a Portuguese population. METHODS: A total of 122 BD patients and 227 ethnically-matched controls were studied. Genotyping of the CCR5Δ32 polymorphisms was performed using polymerase chain reaction product sizing. RESULTS: No significant differences were observed in the allelic frequencies of CCR532 between patients and controls (OR=0.820; p=0.512). Stratification for gender and for the presence of HLA-B*51 did not reveal any significant differences. CONCLUSIONS: These results indicate that CCR5Δ32 is unlikely to contribute to susceptibility to BD in Portuguese patients. This may be explained by the known functional redundancy of this signalling system.


Assuntos
Síndrome de Behçet/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético , Receptores CCR5/genética , Adolescente , Adulto , Idoso , Síndrome de Behçet/metabolismo , Feminino , Deleção de Genes , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Receptores CCR5/metabolismo , Transdução de Sinais/genética , Adulto Jovem
18.
Brain ; 136(Pt 10): 3140-50, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24014518

RESUMO

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.


Assuntos
Epilepsia do Lobo Temporal/genética , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Esclerose/genética , Convulsões Febris/genética , Epilepsia do Lobo Temporal/etiologia , Estudo de Associação Genômica Ampla/métodos , Hipocampo/patologia , Humanos , Estudos Prospectivos , Convulsões Febris/diagnóstico , Lobo Temporal/patologia
19.
J Parkinsons Dis ; 14(2): 313-324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363619

RESUMO

Background: A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated. Objective: To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology. Methods: Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses. Results: rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates. Conclusions: Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Humanos , Receptores de Dopamina D3/genética , Doença de Parkinson/complicações , Doença de Parkinson/genética , Doença de Parkinson/tratamento farmacológico , Disfunção Cognitiva/genética , Disfunção Cognitiva/complicações , Polimorfismo Genético , Ansiedade/genética
20.
iScience ; 27(8): 110546, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39184445

RESUMO

Microglia play a crucial role in a range of neuropathologies through exacerbated activation. Microglial inflammatory responses can be influenced by prior exposures to noxious stimuli, like increased levels of extracellular adenosine and ATP. These are characteristic of brain insults like epileptic seizures and could potentially shape subsequent responses through epigenetic regulation. We investigated DNA methylation and expression changes in human microglia-like cells differentiated from monocytes following ATP-mediated preconditioning. We demonstrate that microglia-like cells display homeostatic microglial features, shown by surface markers, transcriptome, and DNA methylome. After exposure to ATP, TLR-mediated activation leads to an exacerbated pro-inflammatory response. These changes are accompanied by methylation and transcriptional reprogramming associated with enhanced immune-related functions. The reprogramming associated with ATP-mediated preconditioning leads to profiles found in microglial subsets linked to epilepsy. Purine-driven microglia immune preconditioning drives epigenetic and transcriptional changes that could contribute to altered functions of microglia during seizure development and progression.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA