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1.
IEEE Int Conf Rehabil Robot ; 2023: 1-6, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37941185

RESUMO

Electromyography (EMG) is a popular human-machine interface for hand gesture control of assistive and rehabilitative technology. EMG can be used to estimate motor intent even when an individual cannot physically move due to weakness or paralysis. EMG is traditionally recorded from the extrinsic hand muscles located in the forearm. However, the wrist has become an increasingly attractive recording location for commercial applications as EMG sensors can be integrated into wrist-worn wearables (e.g., watches, bracelets). Here we explored the impact that recording EMG from the wrist, instead of the forearm, has on stroke patients with upper-limb hemiparesis. We show that EMG signal-to-noise ratio is significantly worse at the paretic wrist relative to the paretic forearm and non-paretic wrist. Despite this, we also show that the ability to classify hand gestures from EMG was significantly better at the paretic wrist relative to the paretic forearm. Our results also provide guidance as to the ideal gestures for each recording location. Namely, single-digit gestures appeared easiest to classify from both forearm and wrist EMG on the paretic side. These results suggest commercialization of wrist-worn EMG would benefit stroke patients by providing more accurate EMG control in a more widely adopted wearable formfactor.


Assuntos
Acidente Vascular Cerebral , Punho , Humanos , Eletromiografia , Punho/fisiologia , Gestos , Músculo Esquelético/fisiologia
2.
Prehosp Disaster Med ; 38(4): 456-462, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37340758

RESUMO

INTRODUCTION: Treatment of seriously ill patients is often complicated by prolonged or complex transfers between hospitals in sub-Saharan Africa. Difficulties or inefficiency in these transfers can lead to poor outcomes for patients. "On-call" triage systems have been utilized to facilitate communication between facilities and to avoid poor outcomes associated with patient transfer. This study attempts to examine the effects of a pilot study to implement such a system in Rwanda. METHODS: Data collection occurred prospectively in two stages, pre-intervention and intervention, in the emergency department (ED) at Kigali University Teaching Hospital (CHUK). All patients transferred during the pre-determined timeframe were enrolled. Data were collected by ED research staff via a standardized form. Statistical analysis was performed using STATA version 15.0. Differences in characteristics were assessed using χ2 or Fisher's exact tests for categorical variables and independent sample t-tests for normally distributed continuous variables. RESULTS: During the "on call" physician intervention, the indication for transfer was significantly more likely to be for critical care (P <.001), transfer times were faster (P <.001), patients were more likely to be displaying emergency signs (P <.001), and vital signs were more likely to be collected prior to transport (P <.001) when compared to the pre-interventional phase. CONCLUSION: The "[Emergency Medicine] EM Doc On Call" intervention was associated with improved timely interhospital transfer and clinical documentation in Rwanda. While these data are not definitive due to multiple limitations, it is extremely promising and worthy of further study.


Assuntos
Serviço Hospitalar de Emergência , Transferência de Pacientes , Humanos , Projetos Piloto , Ruanda , Hospitais
3.
Pediatr Neurol ; 137: 22-29, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36208614

RESUMO

BACKGROUND: Determine the prevalence of seizure clusters (two or more seizures in six hours), use of rescue medications, and adverse outcomes associated with seizure clusters in pediatric patients with a range of epilepsy severities, and identify risk factors predictive of seizure clusters. METHODS: Prospective observational two-center study, including phone call and seizure diary follow-up for 12 months in patients with epilepsy aged one month to 18 years. We classified patients into three risk groups based on seizures within the prior year: high, seizure cluster (two or more seizures within one day); intermediate, at least one seizure but no days with two or more seizures; low, no seizures. RESULTS: One-third (32.3%; high risk, 72.4%; intermediate risk, 30.4%; low risk, 3.1%) of 297 patients had a seizure cluster during the study, including half (46.2%) of the patients with active seizures at baseline (intermediate- and high-risk groups combined). Emergency room visits or injuries were no more likely due to a seizure cluster than an isolated seizure. Rescue medications were utilized in 15.8% of patients in the high-risk group and 19.2% in the intermediate-risk group. History of status epilepticus (adjusted odds ratio [aOR], 2.13; confidence interval [CI], 1.09 to 4.16]), seizure frequency greater than four per month (aOR, 4.27; CI, 1.92 to 9.50), and high-risk group status (aOR, 6.42; CI, 2.97 to 13.87) were associated with greater odds of seizure cluster. CONCLUSIONS: Seizure clusters are common in pediatric patients with epilepsy. High seizure frequency was the strongest predictor of clusters. Rescue medications were underutilized. Future studies should evaluate the applicability and effectiveness of these medications for optimization of pediatric seizure cluster treatment and reduction of seizure-related emergency department visits, injuries, and mortality.


Assuntos
Epilepsia Generalizada , Epilepsia , Estado Epiléptico , Criança , Humanos , Prevalência , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia Generalizada/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Dano Encefálico Crônico , Fatores de Risco , Anticonvulsivantes/uso terapêutico
4.
PLoS One ; 17(1): e0262904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35077501

RESUMO

BACKGROUND: Although evidence from high-resource settings indicates that women with HIV are at higher risk of acquiring high-risk HPV and developing cervical cancer, data from cervical cancer "screen and treat" programs using visual inspection with acetic acid (VIA) in lower-income countries have found mixed evidence about the association between HIV status and screening outcomes. Moreover, there is limited evidence regarding the effect of HIV-related characteristics (e.g., viral suppression, treatment factors) on screening outcomes in these high HIV burden settings. METHODS: This study aimed to evaluate the relationship between HIV status, HIV treatment, and viral suppression with cervical cancer screening outcomes. Data from a "screen and treat" program based at a large, free antiretroviral therapy (ART) clinic in Lilongwe, Malawi was retrospectively analyzed to determine rates of abnormal VIA results and suspected cancer, and coverage of same-day treatment. Multivariate logistic regression assessed associations between screening outcomes and HIV status, and among women living with HIV, viremia, ART treatment duration and BMI. RESULTS: Of 1405 women receiving first-time VIA screening between 2017-2019, 13 (0.9%) had suspected cancer and 68 (4.8%) had pre-cancerous lesions, of whom 50 (73.5%) received same-day lesion treatment. There was no significant association found between HIV status and screening outcomes. Among HIV+ women, abnormal VIA was positively associated with viral load ≥ 1000 copies/mL (aOR 3.02, 95% CI: 1.22, 7.49) and negatively associated with ART treatment duration (aOR 0.88 per additional year, 95% CI: 0.80, 0.98). CONCLUSION: In this population of women living with HIV with high rates of ART coverage and viral suppression, HIV status was not significantly associated with abnormal cervical cancer screening results. We hypothesize that ART treatment and viral suppression may mitigate the elevated risk of cervical cancer for women living with HIV, and we encourage further study on this relationship in high HIV burden settings.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV , HIV-1 , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Malaui/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/epidemiologia
5.
Int J STD AIDS ; 32(10): 933-939, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33910402

RESUMO

Malawi has the highest incidence of and mortality rate due to cervical cancer in the world. This is largely because of inadequate screening and high rates of human immunodeficiency virus (HIV) infection, which greatly increases cervical cancer risk. We describe the implementation of a quality improvement program to increase use of cervical cancer screening at a non-government medical center in Lilongwe, Malawi. The intervention, developed and launched from March to August 2017, aimed to promote education among patients and clinicians about the importance of cervical cancer screening and improve accessibility of screening information within medical records. Visual inspection with acetic acid (VIA) was used to screen for cervical cancer. Women with a positive VIA were offered treatment using thermocoagulation. The number of VIA screenings conducted in 2016 (pre-intervention), 2017 (intervention), and 2018 (post-intervention) was 125, 234 and 456, respectively. Of the 815 women screened during this period, 36 (4.4%) had a VIA-positive result and 12 (1.5%) had suspect cancer. Of the VIA-positive women, 13 (36.1%) received same-day treatment with thermocoagulation. An interrupted time series regression revealed that there was a sustained increase in monthly screenings between the pre- and post-intervention period (ß = 30.84; p = 0.006; 95% CI 9.72-51.97), suggesting that the intervention likely was effective in increasing cervical cancer screening. Our results demonstrate that focusing on developing sustainable solutions and improving system processes, without additional equipment or funding, significantly increased the number of women screened and should be considered in other settings to enhance cervical cancer prevention services.


Assuntos
Neoplasias do Colo do Útero , Detecção Precoce de Câncer , Feminino , Humanos , Malaui/epidemiologia , Programas de Rastreamento , Neoplasias do Colo do Útero/diagnóstico
6.
BMC Public Health ; 20(1): 1494, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008344

RESUMO

BACKGROUND: In Malawi, numerous barriers may prevent women from accessing cervical cancer screening services - including social factors such as male partner involvement. We conducted surveys that included open- and closed-ended questions with married Malawian men to evaluate their knowledge and beliefs about cervical cancer. METHODS: HIV-positive adult (≥18 years) men (married or in a stable relationship) were recruited from an antiretroviral therapy clinic in Lilongwe, Malawi. Men were asked a series of survey questions to assess their knowledge about cervical cancer, experience with cervical cancer, their female partner's screening history, and their beliefs about gender norms and household decision-making. Following the survey, participants responded to a set of open-ended interview questions about cervical cancer screening, and men's role in prevention. RESULTS: One hundred-twenty men were enrolled with average age 44 years and 55% having completed secondary school or higher education. Despite only moderate knowledge about cervical cancer and screening (average assessment score of 62% correct), all men expressed support of cervical cancer screening, and most (86%) believed they should be involved in their female partner's decision to be screened. Over half (61%) of men said their female partner had previously been screened for cervical cancer, and this was positively correlated with the male respondent having more progressive gender norms around sexual practices. Some men expressed concerns about the screening process, namely the propriety of vaginal exams when performed by male clinicians, and whether the procedure was painful. CONCLUSIONS: Male partners in Malawi want to be involved in decisions about cervical cancer screening, but have limited knowledge about screening, and hold rigid beliefs about gender norms that may affect their support for screening. Messaging campaigns addressing men's concerns may be instrumental in improving women's adoption of cervical cancer screening services in Malawi and similar settings.


Assuntos
Neoplasias do Colo do Útero , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Malaui , Masculino , Homens , Comportamento Sexual , Neoplasias do Colo do Útero/diagnóstico
7.
Circ Genom Precis Med ; 13(6): e003030, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33125268

RESUMO

BACKGROUND: Spontaneous coronary artery dissection (SCAD) occurs when an epicardial coronary artery is narrowed or occluded by an intramural hematoma. SCAD mainly affects women and is associated with pregnancy and systemic arteriopathies, particularly fibromuscular dysplasia. Variants in several genes, such as those causing connective tissue disorders, have been implicated; however, the genetic architecture is poorly understood. Here, we aim to better understand the diagnostic yield of rare variant genetic testing among a cohort of SCAD survivors and to identify genes or gene sets that have a significant enrichment of rare variants. METHODS: We sequenced a cohort of 384 SCAD survivors from the United Kingdom, alongside 13 722 UK Biobank controls and a validation cohort of 92 SCAD survivors. We performed a research diagnostic screen for pathogenic variants and exome-wide and gene-set rare variant collapsing analyses. RESULTS: The majority of patients within both cohorts are female, 29% of the study cohort and 14% validation cohort have a remote arteriopathy. Four cases across the 2 cohorts had a diagnosed connective tissue disorder. We identified pathogenic or likely pathogenic variants in 7 genes (PKD1, COL3A1, SMAD3, TGFB2, LOX, MYLK, and YY1AP1) in 14/384 cases in the study cohort and in 1/92 cases in the validation cohort. In our rare variant collapsing analysis, PKD1 was the highest-ranked gene, and several functionally plausible genes were enriched for rare variants, although no gene achieved study-wide statistical significance. Gene-set enrichment analysis suggested a role for additional genes involved in renal function. CONCLUSIONS: By studying the largest sequenced cohort of SCAD survivors, we demonstrate that, based on current knowledge, only a small proportion have a pathogenic variant that could explain their disease. Our findings strengthen the overlap between SCAD and renal and connective tissue disorders, and we highlight several new genes for future validation.


Assuntos
Anomalias dos Vasos Coronários/genética , Sequenciamento do Exoma , Variação Genética , Genoma Humano , Doenças Vasculares/congênito , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Reino Unido , Doenças Vasculares/genética , Adulto Jovem
8.
PLoS Genet ; 16(6): e1008864, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32584820

RESUMO

Cytosine methylation is an ancient epigenetic modification yet its function and extent within genomes is highly variable across eukaryotes. In mammals, methylation controls transposable elements and regulates the promoters of genes. In insects, DNA methylation is generally restricted to a small subset of transcribed genes, with both intergenic regions and transposable elements (TEs) depleted of methylation. The evolutionary origin and the function of these methylation patterns are poorly understood. Here we characterise the evolution of DNA methylation across the arthropod phylum. While the common ancestor of the arthropods had low levels of TE methylation and did not methylate promoters, both of these functions have evolved independently in centipedes and mealybugs. In contrast, methylation of the exons of a subset of transcribed genes is ancestral and widely conserved across the phylum, but has been lost in specific lineages. A similar set of genes is methylated in all species that retained exon-enriched methylation. We show that these genes have characteristic patterns of expression correlating to broad transcription initiation sites and well-positioned nucleosomes, providing new insights into potential mechanisms driving methylation patterns over hundreds of millions of years.


Assuntos
Artrópodes/genética , Metilação de DNA , Epigênese Genética , Evolução Molecular , Animais , Ilhas de CpG/genética , Elementos de DNA Transponíveis/genética , Éxons/genética , Filogenia , Regiões Promotoras Genéticas/genética
9.
J Heart Lung Transplant ; 37(6): 763-769, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29530322

RESUMO

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS: At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS: In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.


Assuntos
Antivirais/uso terapêutico , Transplante de Coração , Hepatite C Crônica/tratamento farmacológico , Obtenção de Tecidos e Órgãos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento
10.
Nat Ecol Evol ; 2(1): 174-181, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29203920

RESUMO

In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders and scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.


Assuntos
Artrópodes/genética , Elementos de DNA Transponíveis/fisiologia , Evolução Molecular , RNA Mensageiro/fisiologia , RNA Interferente Pequeno/genética , Animais , RNA Interferente Pequeno/metabolismo
11.
Genetics ; 204(2): 757-769, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27535930

RESUMO

Argonaute2 (Ago2) is a rapidly evolving nuclease in the Drosophila melanogaster RNA interference (RNAi) pathway that targets viruses and transposable elements in somatic tissues. Here we reconstruct the history of Ago2 duplications across the D. obscura group and use patterns of gene expression to infer new functional specialization. We show that some duplications are old, shared by the entire species group, and that losses may be common, including previously undetected losses in the lineage leading to D. pseudoobscura We find that while the original (syntenic) gene copy has generally retained the ancestral ubiquitous expression pattern, most of the novel Ago2 paralogs have independently specialized to testis-specific expression. Using population genetic analyses, we show that most testis-specific paralogs have significantly lower genetic diversity than the genome-wide average. This suggests recent positive selection in three different species, and model-based analyses provide strong evidence of recent hard selective sweeps in or near four of the six D. pseudoobscura Ago2 paralogs. We speculate that the repeated evolution of testis specificity in obscura group Ago2 genes, combined with their dynamic turnover and strong signatures of adaptive evolution, may be associated with highly derived roles in the suppression of transposable elements or meiotic drive. Our study highlights the lability of RNAi pathways, even within well-studied groups such as Drosophila, and suggests that strong selection may act quickly after duplication in RNAi pathways, potentially giving rise to new and unknown RNAi functions in nonmodel species.


Assuntos
Proteínas Argonautas/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Evolução Molecular , Seleção Genética/genética , Animais , Elementos de DNA Transponíveis/genética , Drosophila melanogaster/crescimento & desenvolvimento , Duplicação Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento , Genética Populacional , Genoma de Inseto , Masculino , Especificidade de Órgãos/genética , Homologia de Sequência , Testículo/crescimento & desenvolvimento
12.
Evol Bioinform Online ; 12(Suppl 2): 13-25, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27375356

RESUMO

Drosophila melanogaster is an important laboratory model for studies of antiviral immunity in invertebrates, and Drosophila species provide a valuable system to study virus host range and host switching. Here, we use metagenomic RNA sequencing of about 1600 adult flies to discover 25 new RNA viruses associated with six different drosophilid hosts in the wild. We also provide a comprehensive listing of viruses previously reported from the Drosophilidae. The new viruses include Iflaviruses, Rhabdoviruses, Nodaviruses, and Reoviruses, and members of unclassified lineages distantly related to Negeviruses, Sobemoviruses, Poleroviruses, Flaviviridae, and Tombusviridae. Among these are close relatives of Drosophila X virus and Flock House virus, which we find in association with wild Drosophila immigrans. These two viruses are widely used in experimental studies but have not been previously reported to naturally infect Drosophila. Although we detect no new DNA viruses, in D. immigrans and Drosophila obscura, we identify sequences very closely related to Armadillidium vulgare iridescent virus (Invertebrate iridescent virus 31), bringing the total number of DNA viruses found in the Drosophilidae to three.

13.
Genome Biol Evol ; 8(3): 507-18, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-26868596

RESUMO

Genetic studies of Drosophila melanogaster have provided a paradigm for RNA interference (RNAi) in arthropods, in which the microRNA and antiviral pathways are each mediated by a single Argonaute (Ago1 and Ago2) and germline suppression of transposable elements is mediated by a trio of Piwi-subfamily Argonaute proteins (Ago3, Aub, and Piwi). Without a suitable evolutionary context, deviations from this can be interpreted as derived or idiosyncratic. Here we analyze the evolution of Argonaute genes across the genomes and transcriptomes of 86 Dipteran species, showing that variation in copy number can occur rapidly, and that there is constant flux in some RNAi mechanisms. The lability of the RNAi pathways is illustrated by the divergence of Aub and Piwi (182-156 Ma), independent origins of multiple Piwi-family genes in Aedes mosquitoes (less than 25Ma), and the recent duplications of Ago2 and Ago3 in the tsetse fly Glossina morsitans. In each case the tissue specificity of these genes has altered, suggesting functional divergence or innovation, and consistent with the action of dynamic selection pressures across the Argonaute gene family. We find there are large differences in evolutionary rates and gene turnover between pathways, and that paralogs of Ago2, Ago3, and Piwi/Aub show contrasting rates of evolution after duplication. This suggests that Argonautes undergo frequent evolutionary expansions that facilitate functional divergence.


Assuntos
Proteínas Argonautas/genética , Proteínas de Drosophila/genética , Evolução Molecular , Fatores de Iniciação de Peptídeos/genética , Aedes/genética , Animais , Drosophila melanogaster/genética , Variação Genética , Genoma de Inseto , Filogenia
14.
Nucleic Acids Res ; 42(14): 9436-46, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25053841

RESUMO

Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/genética , Ixodes/genética , Ixodes/virologia , Interferência de RNA , Animais , Proteínas Argonautas/fisiologia , Linhagem Celular , RNA Interferente Pequeno/química , Pequeno RNA não Traduzido/química , RNA Viral/química , Ribonuclease III/fisiologia
15.
Curr Opin Microbiol ; 20: 170-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25042205

RESUMO

The evolution of viral sensors is likely to be shaped by the constraint imposed through high conservation of viral Pathogen-Associated Molecular Patterns (PAMPs), and by the potential for 'arms race' coevolution with more rapidly evolving viral proteins. Here we review the recent progress made in understanding the evolutionary history of two types of viral sensor, RNA helicases and Toll-like receptors. We find differences both in their rates of evolution, and in the levels of positive selection they experience. We suggest that positive selection has been the primary driver of the rapid evolution of the RNA helicases, while selective constraint has been a stronger influence shaping the slow evolution of the Toll-like receptors.


Assuntos
Evolução Biológica , Imunidade Inata , Vírus/imunologia , Animais , RNA Helicases/genética , RNA Helicases/imunologia , RNA Helicases/metabolismo , Seleção Genética , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
16.
Neuropharmacology ; 63(3): 434-40, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22561751

RESUMO

Habenulo-interpeduncular nicotinic receptors, particularly those containing α3, ß4 and α5 subunits, have recently been implicated in the reinforcing effects of nicotine. Our laboratory has shown that injection of α3ß4 nicotinic receptor antagonists into the medial habenula (MHb) decreases self-administration of multiple abused drugs, including nicotine (Glick et al., 2006, 2008; 2011). However, it is unclear whether blockade of MHb nicotinic receptors has a direct effect on mesolimbic dopamine. Here, we performed in vivo microdialysis in female rats. Microdialysis probes were implanted into the nucleus accumbens (NAcc) and α3ß4 nicotinic receptor antagonists (18-methoxycoronaridine; 18-MC or α-conotoxin AuIB; AuIB), were injected into the ipsilateral MHb, just prior to systemic nicotine (0.4 mg/kg, s.c.). Dialysate samples were collected before and after drug administration and levels of extracellular dopamine and its metabolites were measured using HPLC. Acute nicotine administration increased levels of extracellular dopamine and its metabolites in the NAcc. Pre-treatment with intra-habenular AuIB or 18-MC prevented nicotine-induced increases in accumbal dopamine. Neither drug had an effect on nicotine-induced increases in dopamine metabolites, suggesting that α3ß4 receptors do not play a role in dopamine metabolism. The effect of intra-habenular blockade of α3ß4 receptors on NAcc dopamine was selective for acute nicotine: neither AuIB nor 18-MC prevented increases in NAcc dopamine stimulated by acute d-amphetamine or morphine. These results suggest the mesolimbic response to acute nicotine, but not to acute administration of other drugs of abuse, is directly modulated by α3ß4 nicotinic receptors in the MHb, and emphasize a critical role for habenular nicotinic receptors in nicotine's reinforcing effects.


Assuntos
Dopamina/fisiologia , Habenula/efeitos dos fármacos , Sistema Límbico/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/fisiologia , Animais , Cromatografia Líquida de Alta Pressão , Dextroanfetamina/farmacologia , Dopamina/metabolismo , Dopaminérgicos/farmacologia , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Feminino , Habenula/citologia , Ibogaína/análogos & derivados , Ibogaína/farmacologia , Microdiálise , Morfina/farmacologia , Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/efeitos dos fármacos
17.
J Forensic Sci ; 55(6): 1462-70, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20629909

RESUMO

Exposure to light or heat, or simply a dearth of fingerprint material, renders some latent fingerprints undetectable using conventional methods. We begin to address such elusive fingerprints using detection targeting photo- and thermally stable fingerprint constituents: surface-enhanced Raman spectroscopy (SERS). SERS can give descriptive vibrational spectra of amino acids, among other robust fingerprint constituents, and good sensitivity can be attained by improving metal-dielectric nanoparticle substrates. With SERS chemical imaging, vibrational bands' intensities recreate a visual of fingerprint topography. The impact of nanoparticle synthesis route, dispersal methodology-deposition solvent, and laser wavelength are discussed, as are data from enhanced vibrational spectra of fingerprint components. SERS and Raman chemical images of fingerprints and realistic contaminants are shown. To our knowledge, this represents the first SERS imaging of fingerprints. In conclusion, this work progresses toward the ultimate goal of vibrationally detecting latent prints that would otherwise remain undetected using traditional development methods.


Assuntos
Dermatoglifia , Análise Espectral Raman , Coloides , Elastômeros , Humanos , Microscopia Eletrônica de Varredura , Microscopia de Tunelamento , Nanopartículas , Nebulizadores e Vaporizadores , Prata/química , Suor
18.
J Forensic Sci ; 55(4): 962-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20487155

RESUMO

Photo- and thermal-degradation studies on eccrine fingerprint components are presented herein. Dilute distinct solutions of urea, lactic acid, and seven amino acids were deposited on steel coupons and Teflon disks, exposed to artificial sunlight or heat, extracted, and analyzed. This aim of this study was to determine whether the investigated eccrine components, previously determined to be Raman active for a parallel study, experienced photo- or thermally induced degradation, and if so, to determine the rate and identify any detectable products. Neither the amino acids nor urea exhibited photo-degradation; however, when heated for a period of three minutes, the onset of thermal-degradation was initiated at 100 degrees C for the amino acids and 100 degrees C for urea. Lactic acid, the major polymerization initiator of superglue fuming, showed photochemical and thermal-degradation. These results could be used for future development of new latent fingerprint visualization methods, especially when lactic acid is degraded.


Assuntos
Dermatoglifia , Temperatura Alta , Raios Ultravioleta , Aminoácidos/química , Cromatografia Líquida , Humanos , Ácido Láctico/química , Espectrometria de Massas , Ureia/química
19.
Anal Chem ; 81(7): 2575-80, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19267478

RESUMO

Landfill biogases are being utilized more frequently as a new source of fuel energy. Volatile siloxane compounds usually contained in landfill biogases will form siloxane residues when the gases are burned, which significantly increases abrasion of combustion engines. Research on detection of siloxanes in landfill gas has been active during recent years with the principal analytical technique being gas chromatography/mass spectrometry (GC/MS). In our present work, we introduce a less expensive, compact methodology that employs microcantilever (MC) arrays for sensitive nanomechanical-based gas-phase sensing of the siloxanes. The cantilevers on the MC array were differentially coated on the active, nanostructured side with different responsive phases, and composite responses (magnitude of siloxane-induced MC bending) for four siloxanes were collected that exhibited selective signatures to aid in recognizing each siloxane. Limits of detection (LODs) derived from linear calibration plots were down to the sub-parts-per-million range, a sensitivity that is comparable with that of GC/MS reported by other researchers. Studies were performed in rather inert helium environment and a realistic matrix, and the overall response profiles and LODs were similar for both matrixes. A 5 week long-term reproducibility study illustrates the stability of the MC array. Moreover, the portable character of the MC array setup makes our method a very promising way to facilitate in-field detection of siloxanes in landfill gas in the future.

20.
Anal Chem ; 75(11): 2753-60, 2003 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-12948146

RESUMO

The application of electrospray ionization mass spectrometry (ESI-MS) to trace-fiber color analysis is explored using acidic dyes commonly employed to color nylon-based fibers, as well as extracts from dyed nylon fibers. Qualitative information about constituent dyes and quantitative information about the relative amounts of those dyes present on a single fiber become readily available using this technique. Sample requirements for establishing the color identity of different samples (i.e., comparative trace-fiber analysis) are shown to be submillimeter. Absolute verification of dye mixture identity (beyond the comparison of molecular weights derived from ESI-MS) can be obtained by expanding the technique to include tandem mass spectrometry (ESI-MS/MS). For dyes of unknown origin, the ESI-MS/MS analyses may offer insights into the chemical structure of the compound-information not available from chromatographic techniques alone. This research demonstrates that ESI-MS is viable as a sensitive technique for distinguishing dye constituents extracted from a minute amount of trace-fiber evidence. A protocol is suggested to establish/refute the proposition that two fibers--one of which is available in minute quantity only--are of the same origin.

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