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1.
J Intell ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38392172

RESUMO

Our ability to think critically and our disposition to do so can have major implications for our everyday lives. Research across the globe has shown the impact of critical thinking on decisions about our health, politics, relationships, finances, consumer purchases, education, work, and more. This chapter will review some of that research. Given the importance of critical thinking to our everyday lives, the fair and unbiased assessment of critical thinking is useful for guiding educators in their classrooms, for the sake of self-improvement, and in employment decisions. This chapter will also review the psychometric properties of several critical thinking assessments, with a special emphasis on the everyday behaviors predicted by these assessments. The practical challenges faced by test adopters and future directions in the assessment of critical thinking will be discussed.

2.
Allergy ; 77(10): 3061-3069, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35960650

RESUMO

BACKGROUND: IgE-epitope profiling can accurately diagnose clinical peanut allergy. OBJECTIVE: We sought to determine whether sequential (linear) epitope-specific IgE (ses-IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double-blind, placebo-controlled food challenges utilizing PRACTALL dosing. METHODS: Sixty four ses-IgE antibodies were quantified in blood samples using a bead-based epitope assay. A pair of ses-IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope-based predictor was validated on 331 subjects from five independent cohorts (ages 4-25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated. RESULTS: In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho = 0.61, p < .05); this correlation was 0.51 (p < .05) in validation. Using the ses-IgE-based predictor, subjects were assigned into "high," "moderate," or "low" dose-reactivity groups. On average, subjects in the "high" group were four times more likely to tolerate a specific dose, compared with the "low" group. For example, predicted probabilities of tolerating 4, 14, 44, and 144 or 444 mg in the "low" group were 92%, 77%, 53%, 29%, and 10% compared with 98%, 95%, 94%, 88%, and 73% in the "high" group. CONCLUSIONS: Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study-specific challenge protocols. Despite these limitations, an epitope-based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges.


Assuntos
Arachis , Hipersensibilidade a Amendoim , Adolescente , Adulto , Alérgenos , Arachis/efeitos adversos , Criança , Pré-Escolar , Epitopos , Humanos , Imunoglobulina E , Hipersensibilidade a Amendoim/diagnóstico , Probabilidade , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-35589063

RESUMO

Early-life stage (ELS) avian toxicity tests have been proposed as a more ethical alternative to traditional standardized tests with adult birds. At the same time, 'omics approaches are gaining traction in the field of avian toxicology, but little has been done to characterize the metabolome and transcriptome at different life stages. The present study uses 'omics data from toxicity tests of 8 environmental chemicals in ELS and adult Japanese quail (Coturnix japonica) to address this data gap. Previous analyses of these data focused on responses to each of the individual chemicals. Here, we consider data from all studies to describe variation in the metabolome and transcriptome between life stages and across independent experiments, irrespective of chemical treatment. Of the 230 metabolites detected in liver, 163 were shared between the two life stages. However, many of the targeted bile acids that were present in the adult liver were absent from ELS samples. For the transcriptome, >90% of the 18,364 detected transcripts were common to both life stages. Based on the 213 genes solely detected in ELS liver, the neuroactive ligand-receptor interaction pathway was significantly enriched. Multivariate and hierarchical clustering analyses revealed that variability among independent experiments was higher for the adult than the ELS studies at both the metabolomic and transcriptomic levels. Our results indicate concordance of the two approaches, with less variation between independent experiments in the ELS metabolome and transcriptome than in adults, lending support for the use of ELS as an alternative toxicity testing strategy.


Assuntos
Coturnix , Transcriptoma , Animais , Coturnix/genética , Metaboloma , Metabolômica , Testes de Toxicidade
4.
Metabolites ; 11(12)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34940609

RESUMO

This proof-of-concept study characterizes the Japanese quail (Coturnix japonica) hepatic metabolome following exposure to benzo[a]pyrene, chlorpyrifos, ethinylestradiol, fluoxetine hydrochloride, hexabromocyclododecane, lead(II)nitrate, seleno-L-methionine, and trenbolone in embryos and adults. The analysis revealed effects on lipid metabolism following exposure to several chemicals at both life stages. The most pronounced effects were observed in embryos exposed to 41.1 µg/g chlorpyrifos. This work highlighted challenges and the need for further avian metabolomics studies.

5.
Environ Toxicol Chem ; 40(11): 3019-3033, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34293216

RESUMO

Modern 21st-century toxicity testing makes use of omics technologies to address critical questions in toxicology and chemical management. Of interest are questions relating to chemical mechanisms of toxicity, differences in species sensitivity, and translation of molecular effects to observable apical endpoints. Our study addressed these questions by comparing apical outcomes and multiple omics responses in early-life stage exposure studies with Japanese quail (Coturnix japonica) and double-crested cormorant (Phalacrocorax auritus), representing a model and ecological species, respectively. Specifically, we investigated the dose-dependent response of apical outcomes as well as transcriptomics and metabolomics in the liver of each species exposed to chlorpyrifos, a widely used organophosphate pesticide. Our results revealed a clear pattern of dose-dependent disruption of gene expression and metabolic profiles in Japanese quail but not double-crested cormorant at similar chlorpyrifos exposure concentrations. The difference in sensitivity between species was likely due to higher metabolic transformation of chlorpyrifos in Japanese quail compared to double-crested cormorant. The most impacted biological pathways after chlorpyrifos exposure in Japanese quail included hepatic metabolism, oxidative stress, endocrine disruption (steroid and nonsteroid hormones), and metabolic disease (lipid and fatty acid metabolism). Importantly, we show consistent responses across biological scales, suggesting that significant disruption at the level of gene expression and metabolite profiles leads to observable apical responses at the organism level. Our study demonstrates the utility of evaluating effects at multiple biological levels of organization to understand how modern toxicity testing relates to outcomes of regulatory relevance, while also highlighting important, yet poorly understood, species differences in sensitivity to chemical exposure. Environ Toxicol Chem 2021;40:3019-3033. © 2021 SETAC.


Assuntos
Clorpirifos , Coturnix , Animais , Clorpirifos/toxicidade , Coturnix/genética , Metabolômica , Especificidade da Espécie , Transcriptoma
6.
FASEB Bioadv ; 3(1): 36-48, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33490882

RESUMO

Chronic metabolic acidosis plays a role in cachexia by enhancing total proteolysis in skeletal muscle. Glucocorticoid also triggers proteolysis and plays a permissive role in the effect of acidosis. The System A amino acid transporter SNAT2/SLC38A2 is ubiquitously expressed in mammalian cells including muscle, performing Na+-dependent active import of neutral amino acids, and is strongly inhibited by low pH. Exposure of rat skeletal muscle cell line L6-G8C5 to low pH rapidly inhibits SNAT2 transport activity and enhances total proteolysis rate. Pharmacological inhibition or silencing of SNAT2 also enhances proteolysis. This study tests the hypothesis that the glucocorticoid dexamethasone (DEX), like low pH, inhibits SNAT2 activity in L6-G8C5 myotubes, thus contributing to total proteolysis. Incubation with 500 nM DEX for 4 h reduced the System A amino acid transport rate to half the rate in control cultures. This inhibition depended on glucocorticoid receptor-mediated gene transcription, but SNAT2 mRNA levels were unaffected by DEX. In contrast, the SNAT2 protein assessed by immunoblotting was significantly depleted. The co-inhibitory effects of DEX and low pH on System A transport activity were additive in stimulating total proteolysis. In keeping with this mechanism, DEX's inhibitory effect on SNAT2 transport activity was significantly blunted by the proteasome inhibitor MG132. Proof of principle was achieved in similar experiments using recombinant expression of a GFP-tagged SNAT2 fusion protein in HEK293A cells. It is concluded that DEX acutely depletes the SNAT2 transporter protein, at least partly through proteasome-dependent degradation of this functionally important transporter.

7.
Psychol Rep ; 120(4): 707-720, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28558538

RESUMO

Critical thinking is a kind of "good" thinking that integrates a set of cognitive skills and dispositions to use those skills with knowledge to increase the chances of success in academic settings, job market, and daily life. The impact of critical thinking on life events, in face of everyday decisions and challenges, is still unclear, and further research is needed. In this exploratory study, a sample of 230 first-year students of a Bachelor's Degree or a Master's Degree in Portugal completed an experimental Portuguese version of the Real-World Outcomes, a self-report inventory measuring everyday negative life events that are mediated by a lack of critical thinking. Based on exploratory factor analysis results and theoretical premises, changes were made to the Portuguese version of the inventory that was administered, and items were aggregated into six dimensions, creating a new version that is more familiar to Portuguese young adults in college. This original proposal of the inventory presents six types of negative life events resulting from a lack of critical thinking: health neglect, mismanagement, slackness, poor impulse control, academic negligence, and rashness. Both limitations and future potentialities of this version are presented.

8.
Aquat Toxicol ; 182: 102-112, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27886581

RESUMO

Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e. low-dose) effects, or differentiating between similar phenotypes induced by different chemicals. Inclusion of multi-omic analyses in studies investigating xenobiotic action provides improved characterization of biological response, thereby enhancing prediction of toxicological outcomes in whole animals in the absence of morphological effects. In the current study, we assessed perturbations in both the metabolome and transcriptome of zebrafish (Danio rerio; ZF) larvae exposed from 96 to 120h post fertilization to environmental concentrations of acetaminophen (APAP), diphenhydramine (DH), carbamazepine (CBZ), and fluoxetine (FLX); common pharmaceuticals with known mechanisms of action. Multi-omic responses were evaluated independently and integrated to identify molecular interactions and biological relevance of the responses. Results indicated chemical- and dose-specific changes suggesting differences in the time scale of transcript abundance and metabolite production. Increased impact on the metabolome relative to the transcriptome in FLX-treated animals suggests a stronger post-translational effect of the treatment. In contrast, the transcriptome showed higher sensitivity to perturbation in DH-exposed animals. Integration of 'omic' responses using multivariate approaches provided additional insights not obtained by independent 'omic' analyses and demonstrated that the most distinct overall response profiles were induced following low-dose exposure for all 4 pharmaceuticals. Importantly, changes in transcript abundance corroborated with predictions from metabolomic enrichment analyses and the identified perturbed biological pathways aligned with known xenobiotic mechanisms of action. This work demonstrates that a multi-omic toxicological approach, coupled with a sensitive animal model such as ZF larvae, can help characterize the toxicological relevance of acute low-dose chemical exposures.


Assuntos
Metaboloma/efeitos dos fármacos , Modelos Animais , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Xenobióticos/toxicidade , Peixe-Zebra/metabolismo , Acetaminofen/toxicidade , Animais , Carbamazepina/toxicidade , Difenidramina/toxicidade , Relação Dose-Resposta a Droga , Fluoxetina/toxicidade , Larva/efeitos dos fármacos , Testes de Toxicidade
9.
Environ Sci Technol ; 50(12): 6526-35, 2016 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-27232715

RESUMO

Sensitive and quantitative protocols for characterizing low-dose effects are needed to meet the demands of 21st century chemical hazard assessment. To test the hypothesis that xenobiotic exposure at environmentally relevant concentrations produces specific biochemical fingerprints in organisms, metabolomic perturbations in zebrafish (Danio rerio) embryo/larvae were measured following 24 h exposures to 13 individual chemicals covering a wide range of contaminant classes. Measured metabolites (208 in total) included amino acids, biogenic amines, fatty acids, bile acids, sugars, and lipids. The 96-120 h post-fertilization developmental stage was the most appropriate model for detecting xenobiotic-induced metabolomic perturbations. Metabolomic fingerprints were largely chemical- and dose-specific and were reproducible in multiple exposures over a 16-month period. Furthermore, chemical-specific responses were detected in the presence of an effluent matrix; importantly, in the absence of morphological response. In addition to improving sensitivity for detecting biological responses to low-level xenobiotic exposures, these data can aid the classification of novel contaminants based on the similarity of metabolomic responses to well-characterized "model" compounds. This approach is clearly of use for rapid, sensitive, and specific analyses of chemical effect on organisms, and can supplement existing methods, such as the Zebrafish Embryo Toxicity assay (OECD TG236), with molecular-level information.


Assuntos
Larva/efeitos dos fármacos , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/efeitos dos fármacos , Metabolômica , Poluentes Químicos da Água/toxicidade , Xenobióticos/metabolismo
10.
Sci Transl Med ; 5(207): 207ra142, 2013 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-24132637

RESUMO

Each year, millions of pulmonary nodules are discovered by computed tomography and subsequently biopsied. Because most of these nodules are benign, many patients undergo unnecessary and costly invasive procedures. We present a 13-protein blood-based classifier that differentiates malignant and benign nodules with high confidence, thereby providing a diagnostic tool to avoid invasive biopsy on benign nodules. Using a systems biology strategy, we identified 371 protein candidates and developed a multiple reaction monitoring (MRM) assay for each. The MRM assays were applied in a three-site discovery study (n = 143) on plasma samples from patients with benign and stage IA lung cancer matched for nodule size, age, gender, and clinical site, producing a 13-protein classifier. The classifier was validated on an independent set of plasma samples (n = 104), exhibiting a negative predictive value (NPV) of 90%. Validation performance on samples from a nondiscovery clinical site showed an NPV of 94%, indicating the general effectiveness of the classifier. A pathway analysis demonstrated that the classifier proteins are likely modulated by a few transcription regulators (NF2L2, AHR, MYC, and FOS) that are associated with lung cancer, lung inflammation, and oxidative stress networks. The classifier score was independent of patient nodule size, smoking history, and age, which are risk factors used for clinical management of pulmonary nodules. Thus, this molecular test provides a potential complementary tool to help physicians in lung cancer diagnosis.


Assuntos
Algoritmos , Proteômica , Nódulo Pulmonar Solitário/sangue , Nódulo Pulmonar Solitário/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas de Neoplasias/sangue , Reprodutibilidade dos Testes
11.
Clin J Pain ; 29(3): 265-75, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23369930

RESUMO

OBJECTIVES: This study examined the effect of pain interference and attentional interference on the anticipatory postural adjustments of trunk muscles in patients with nonspecific chronic low back pain. METHODS: Fifty-nine patients performed rapid flexion movements of the right arm under 6 conditions, namely a control condition and conditions with different attention demands. The latency between the activations of the shoulder and different trunk muscles, as measured with surface electromyography, was used as the outcome. Using repeated measures analysis of variance, attention conditions and group comparisons were tested between those who scored high and low on pain intensity, fear of movement, or pain catastrophizing. RESULTS: There were significant (although minimal) interactive effects but significant and potentially clinically relevant group and attention main effects. The group with the lowest scores showed delayed activity (14 to 29 ms) relative to those with higher scores. One attention-demanding condition delayed (20 to 35 ms) the latencies of some trunk muscles relative to the control condition, namely the one that was the most attention-demanding according to the reaction time results. DISCUSSION: These findings suggest that patients with chronic low back pain, who are characterized by higher scores on some pain-related variables (visual analog scale, Tampa Scale of Kinesiophobia, Pain Catastrophizing Scale), react favorably to protect the spine from further pain and injuries but would be at greater risk of injury when performing a complex physical task requiring more attention demand.


Assuntos
Atenção , Dor nas Costas/prevenção & controle , Dor nas Costas/fisiopatologia , Movimento , Contração Muscular , Músculo Esquelético/fisiologia , Mascaramento Perceptivo , Adolescente , Adulto , Antecipação Psicológica , Braço/fisiopatologia , Dor nas Costas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tempo de Reação , Adulto Jovem
12.
J Electromyogr Kinesiol ; 23(2): 369-77, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23200059

RESUMO

Evidence indicates that previous low back injury (LBI) is a strong predictor for re-injury. The purpose of this study was to examine whether neuromuscular patterns remain altered in a LBI group who were deemed recovered. Surface electromyograms from 12-abdominal and 12-back extensors sites and motion variables were recorded from 33 LBI individuals (sub-acute phase) and 54 asymptomatic controls. Pain-related variables were recorded and a clinical assessment performed for LBI participants. Subjects performed a symmetrical lift and replace task in two reaches. Pattern recognition techniques were applied to normalized activation amplitude patterns to extract key recruitment strategies. Mixed model ANOVAs tested for effects (p < 0.05). Despite similar task performance, significantly (p < 0.05) different recruitment strategies were observed for the LBI group. There were higher activation amplitudes for LBI subjects in all muscles (except posterior external oblique) and greater co-activation between abdominal and back extensor sites compared to controls. Local abdominal and back extensor sites showed altered responses to increased physical demands in the LBI group. Despite outcomes indicating recovery, the LBI group had altered neuromuscular patterns compared to asymptomatic controls supporting that residual alterations remain following recovery.


Assuntos
Eletromiografia/métodos , Dor Lombar/fisiopatologia , Dor Lombar/reabilitação , Contração Muscular , Músculo Esquelético/fisiopatologia , Recuperação de Função Fisiológica , Tronco/fisiopatologia , Adaptação Fisiológica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
13.
Hum Mov Sci ; 31(4): 863-79, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22406502

RESUMO

Muscle synergies are important for spinal stability, but few studies examine temporal responses of spinal muscles to dynamic perturbations. This study examined activation amplitudes and temporal synergies among compartments of the back extensor and among abdominal wall muscles in response to dynamic bidirectional moments of force. We further examined whether responses were different between men and women. 19 women and 18 men performed a controlled transfer task. Surface electromyograms from bilateral sites over 6 back extensor compartments and 6 abdominal wall muscle sites were analyzed using principal component analysis. Key features were extracted from the measured electromyographic waveforms capturing amplitude and temporal variations among muscle sites. Three features explained 97% of the variance. Scores for each feature were computed for each measured waveform and analysis of variance found significant (p<.05) muscle main effects and a sex by muscle interaction. For the back extensors, post hoc analysis revealed that upper and more medial sites were recruited to higher amplitudes, medial sites responded to flexion moments, and the more lateral sites responded to lateral flexion moments. Women had more differences among muscle sites than men for the lateral flexion moment feature. For the abdominal wall muscles the oblique muscles responded with synergies related to fiber orientation, with women having higher amplitudes and more responsiveness to the lateral flexion moment than men. Synergies between the abdominal and back extensor sites as the moment demands change are discussed. These findings illustrate differential activation among erector spinae compartments and abdominal wall muscle sites supporting a highly organized pattern of response to bidirectional external moments with asynchronies more apparent in women.


Assuntos
Músculos Abdominais/fisiologia , Dorso/fisiologia , Músculo Esquelético/fisiologia , Orientação/fisiologia , Equilíbrio Postural/fisiologia , Desempenho Psicomotor/fisiologia , Suporte de Carga/fisiologia , Adulto , Eletromiografia , Feminino , Lateralidade Funcional/fisiologia , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Junção Neuromuscular/fisiologia , Amplitude de Movimento Articular/fisiologia , Fatores Sexuais , Processamento de Sinais Assistido por Computador , Adulto Jovem
14.
Eur Spine J ; 19(9): 1508-16, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20473625

RESUMO

In chronic low back pain patients (CLBP), neuromuscular and pain intensity have been identified as contributing factors in the disability of the individual. However, it is unclear whether pain intensity influences neuromuscular activation and if directed attention mediates this relationship. Thus, the purpose of this study was to determine the effect of directed attention in individuals with different pain intensities on back extensor activation profiles. Fifty-four CLBP patients were separated into either high- or low-pain groups. Surface electromyograms were recorded from back muscles while the subjects performed a trunk flexion motion for four different attention conditions. Pattern recognition and repeated measures ANOVAs were used to examine the effect of sex, attention and pain intensity on temporal muscle activation patterns. The results showed that there was a significant sex x attention x pain interaction. The largest changes in muscle timing were observed in the low-pain group when their attention was focused on their pain, but the pattern of muscle activation differed between sexes. For males, a rapid decline in activation at mid-extension occurred, whereas females showed delayed activation at the beginning of extension. Overall, this study demonstrated that directed attention on pain had an effect on trunk muscle temporal recruitment, and that this relationship differed between sexes and pain groups. This suggests that sex-specific mechanisms may alter the neuromuscular control of the spine in CLBP patients for different pain levels.


Assuntos
Atenção/fisiologia , Dorso/fisiopatologia , Dor Lombar/fisiopatologia , Movimento/fisiologia , Músculo Esquelético/fisiologia , Adulto , Doença Crônica , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fatores Sexuais , Adulto Jovem
15.
Ergonomics ; 53(5): 685-95, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20432088

RESUMO

While the typical physical exposure to modern-day workers has changed from heavy to low level repetitive demands, there is limited research that examines light occupations. This study examined trunk muscle recruitment strategies in response to a simulated checkout operation. Surface electromyography and kinematic variables were recorded from 29 healthy subjects. Four principal patterns accounted for 95.3% of the variation. Significant differences in scores captured different strategies in response to reach conditions and external moment directions. Synergistic co-activation of ipsilateral back sites and differential activation among external oblique and erector spinae sites suggests that the central nervous system may control different regions of the trunk musculature to optimally account for asymmetrical demands. The strategy between the internal oblique and back extensor sites suggests that a specific co-activation strategy may be needed during lighter work. During low-load occupational tasks, several recruitment strategies were required to maintain spinal stability and account for changing external moments. STATEMENT OF RELEVANCE: Different recruitment strategies found in response to changing external moments offer new insights into neuromuscular control for lighter work. Specifically, multiple trunk muscle sites interact in a complex manner, taking into account task specificity and individual variation that are valuable in workstation design, evaluating injury risk and estimating spinal loads.


Assuntos
Eletromiografia/métodos , Movimento/fisiologia , Músculo Esquelético/fisiologia , Reconhecimento Automatizado de Padrão/métodos , Tórax/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Remoção , Masculino , Contração Muscular/fisiologia , Exposição Ocupacional/análise , Adulto Jovem
16.
Lab Invest ; 89(5): 498-512, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19308046

RESUMO

Indoleamine 2,3-dioxygenase (IDO) is the first enzyme in the kynurenine pathway. The kynurenines formed in this pathway chemically modify proteins and cause apoptosis in cells. Evidence suggests that kynurenines and their protein modifications are involved in cataract formation, but this has yet to be directly demonstrated. We generated transgenic (Tg) mouse lines that overexpress human IDO in the lens. Homozygous Tg (homTg) lenses had higher IDO immunoreactivity, approximately 4.5 times greater IDO mRNA, and approximately 8 times higher IDO activity compared to lenses from hemizygous Tg (hemTg) animals. The kynurenine content was threefold higher in homTg than in hemTg but was not detected in wild-type (Wt) lenses. Kynurenine modifications were approximately 2.6 times greater in homTg than in hemTg or Wt. HomTg lenses had vacuoles in the epithelium and cortical fiber cells. Kynurenine modifications coincided with apoptosis in the secondary fiber cells of homTg lenses. Caspase-3 and caspase-9 activities were markedly higher in homTg than in hemTg and Wt. The glutathione content was approximately 36% lower in homTg compared to hemTg and Wt lenses. HomTg animals also developed bilateral cataracts within 3 months of birth. Together these data demonstrate that IDO-mediated production of kynurenines results in defects in fiber cell differentiation and their apoptosis and suggest that IDO activity is kept low in the lens to prevent deleterious effects by kynurenines.


Assuntos
Apoptose , Catarata/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/metabolismo , Cristalino/crescimento & desenvolvimento , Animais , Glutationa/metabolismo , Camundongos , Camundongos Transgênicos , Triptofano/metabolismo
17.
Eur J Appl Physiol ; 106(1): 95-104, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19205724

RESUMO

It is assumed when lifting with the dominant hand that the relationship between contralateral and ipsilateral trunk muscle responses are similar to when lifting with the non-dominant hand. The purpose of this study was to quantify trunk muscle activation amplitude patterns during right- and left-handed lifts. Surface electromyography (EMG) and kinematic variables were recorded from 29 healthy subjects. Minimal trunk and pelvis motion was observed. Three principal patterns accounted for 95% of the variation in the EMG data indicating minimal variation in the pattern. Significant differences in scores captured different recruitment strategies for reach and hand. Selective and differential recruitment of back sites characterized lifts at greater distances from the body, whereas co-activation between internal oblique and back sites characterized lifts closer to the body. While the results showed no handedness effect for back muscles, the external oblique responded differently between right- and left-handed lifts. Specific recruitment strategies were used to account for subtle changes in reach and asymmetrical demands.


Assuntos
Músculos Abdominais/fisiologia , Lateralidade Funcional/fisiologia , Movimento/fisiologia , Músculo Esquelético/fisiologia , Levantamento de Peso/fisiologia , Adulto , Dorso/fisiologia , Feminino , Humanos , Masculino , Contração Muscular/fisiologia , Postura/fisiologia , Projetos de Pesquisa , Adulto Jovem
18.
J Proteome Res ; 8(3): 1594-609, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19216536

RESUMO

Macrophages were infected with virulent Brucella abortus strain 2308 or attenuated strain 19. Intracellular bacteria were recovered at different times after infection and their proteomes compared. The virulent strain initially reduced most biosynthesis and altered its respiration; adaptations reversed later in infection. The attenuated strain was unable to match the magnitude of the virulent strain's adjustments. The results provide insight into mechanisms utilized by Brucella to establish intracellular infections.


Assuntos
Proteínas de Bactérias/metabolismo , Brucella abortus/metabolismo , Macrófagos/microbiologia , Proteoma/metabolismo , Linhagem Celular , Cromatografia Líquida , Humanos , Espectrometria de Massas em Tandem
19.
Pain ; 141(1-2): 70-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19059719

RESUMO

This study examined the role of pain catastrophizing, fear of movement and depression as determinants of repetition-induced summation of activity-related pain. The sample consisted of 90 (44 women and 46 men) work-disabled individuals with chronic low back pain. Participants were asked to lift a series of 18 canisters that varied according to weight (2.9kg, 3.4kg, 3.9kg) and distance from the body. The canisters were arranged in a 3x6 matrix and the weights were distributed such that each 'column' of three canisters was equated in terms of physical demands. Participants rated their pain after each lift, and in a separate trial, estimated the weight of each canister. Mean activity-related pain ratings were computed for each Column of the task. An index of repetition-induced summation of pain was derived as the change in pain ratings across the six 'columns' of the task. Pain catastrophizing, fear of movement and depression were significantly correlated with condition-related pain (e.g., MPQ) and activity-related pain ratings. Women rated their pain as more intense than men, and estimated weights to be greater than men. A repetition-induced summation of pain effect was observed where pain ratings increased as participants lifted successive canisters. Fear of movement, but not pain catastrophizing or depression, was associated with greater repetition-induced summation of pain. The findings point to possible neurophysiological mechanisms that could help explain why fear of pain is a robust predictor of pain-related disability. Mechanisms of repetition-induced summation of activity-related pain are discussed.


Assuntos
Medo , Dor Lombar/complicações , Dor Lombar/psicologia , Movimento/fisiologia , Adulto , Análise de Variância , Doença Crônica , Depressão/etiologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Medição da Dor , Limiar da Dor , Postura/fisiologia , Testes Psicológicos , Índice de Gravidade de Doença , Estatística como Assunto , Inquéritos e Questionários , Adulto Jovem
20.
J Electromyogr Kinesiol ; 19(6): e505-12, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19041264

RESUMO

This study sought to determine the patterns of neuromuscular response from 24-trunk muscle sites during a symmetrical lift and replace task. Surface electromyograms (EMG) and kinematic variables were recorded from 29 healthy subjects. Pattern recognition techniques were used to examine how activation amplitude patterns changed with the different physical demands of the task (reach, phase of movement). The results indicated that there was very little trunk and pelvis motion during the task. Three principal patterns accounted for 95% of the total variation suggesting that the measured data had a simple underlying structure of variance. ANOVA results revealed significant differences in principal pattern scores. These differences captured subtle changes in muscle recruitment strategies that most likely reflect different stability and biomechanical demands. More balanced activations (bracing) between the abdominal and back sites were observed during the lighter demands, whereas differential recruitment among the back extensor sites was more predominant in the more demanding conditions. A pattern recognition technique offers a novel method to examine the relationships among a large number of muscles and test how different work characteristics change the relationships among the muscle sites.


Assuntos
Músculos Abdominais/fisiologia , Algoritmos , Eletromiografia/métodos , Remoção , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Reconhecimento Automatizado de Padrão/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
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