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1.
Muscle Nerve ; 67(4): 259-271, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36448457

RESUMO

Small-fiber neuropathy (SFN) is a disorder that exclusively affects the small nerve fibers, sparing the large nerve fibers. Thinly myelinated Aδ-fibers and unmyelinated C-fibers are damaged, leading to development of neuropathic pain, thermal dysfunction, sensory symptoms, and autonomic disturbances. Although many SFNs are secondary and due to immunological causes or metabolic disturbances, the etiology is unknown in up to half of the patients. Over the years, this proportion of "idiopathic SFN" has decreased, as familial and genetic causes have been discovered, thus shifting a proportion of once "idiopathic" cases to the genetic category. After the discovery of SCN9A-gene variants in 2012, SCN10A and SCN11A variants have been found to be pathogenic in SFN. With improved accessibility of SFN diagnostic tools and genetic tests, many non-SCN variants and genetically inherited systemic diseases involving the small nerve fibers have also been described, but only scattered throughout the literature. There are 80 SCN variants described as causing SFN, 8 genes causing hereditary sensory autonomic neuropathies (HSAN) described with pure SFN, and at least 7 genes involved in genetically inherited systemic diseases associated with SFN. This systematic review aims to consolidate and provide an updated overview on the genetic variants of SFN to date---SCN genes and beyond. Awareness of these genetic causes of SFN is imperative for providing treatment directions, prognostication, and management of expectations for patients and their health-care providers.


Assuntos
Neuralgia , Neuropatia de Pequenas Fibras , Humanos , Neuropatia de Pequenas Fibras/patologia , Neuralgia/etiologia , Fibras Nervosas Amielínicas/patologia , Testes Genéticos , Causalidade , Canal de Sódio Disparado por Voltagem NAV1.7/genética
2.
BMC Endocr Disord ; 23(1): 221, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821852

RESUMO

BACKGROUND: Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles. METHODS: This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman's correlation was done to determine the association between variables. RESULTS: Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal. CONCLUSION: The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal.


Assuntos
Autoanticorpos , Doença de Hashimoto , Hipertireoidismo , Hipotireoidismo , Feminino , Humanos , Autoanticorpos/sangue , Estudos Transversais , Hipertireoidismo/diagnóstico , Hipertireoidismo/epidemiologia , Iodo , Nepal/epidemiologia , Centros de Atenção Terciária , Doenças da Glândula Tireoide/epidemiologia , Tireotropina/sangue , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
3.
J Thromb Thrombolysis ; 55(1): 83-91, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36192663

RESUMO

Hypertrophic cardiomyopathy predisposes to acute cerebrovascular events including ischaemic stroke, transient ischaemic attack and systemic thromboembolism. Atrial fibrillation confers even higher risk. We aim to report the incidence of these complications and to investigate the impact of atrial fibrillation on the ischaemic risk in patients with hypertrophic cardiomyopathy. A literature search was performed on PubMed, Scopus, Embase/Ovid and Cochrane library from inception to 20th March 2021. We compared the incidence of ischaemic strokes, transient ischaemic attack, non-specified thromboembolism events and systemic thromboembolism in hypertrophic cardiomyopathy patients with or without atrial fibrillation. Non-specified thromboembolism events in our paper referred to thromboembolic events whereby types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I2 test. A total of 713 studies were identified. Thirty-five articles with 42,570 patients were included. The pooled incidence of stroke/ transient ischaemic attack was 7.45% (95% confidence interval [CI] 5.80-9.52, p < 0.001) across 24 studies with a total of 37,643 hypertrophic cardiomyopathy patients. Atrial fibrillation significantly increased the risk of total stroke/ transient ischaemic attack (Risk Ratio 3.26, 95% CI 1.75-6.08, p < 0.001, I2 = 76.0). The incidence of stroke/ transient ischaemic attack was 9.30% (95% CI 6.64-12.87, p = 0.316) in the apical hypertrophic cardiomyopathy subgroup. Concomitant atrial fibrillation in hypertrophic cardiomyopathy increases the risk of thromboembolic events including ischaemic stroke and transient ischaemic attack. The apical subgroup shows a similar risk of acute cerebrovascular events as the overall hypertrophic cardiomyopathy population.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , Cardiomiopatia Hipertrófica , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Tromboembolia , Humanos , Acidente Vascular Cerebral/etiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/complicações , Tromboembolia/etiologia , Tromboembolia/complicações , AVC Isquêmico/complicações , Cardiomiopatia Hipertrófica/complicações , Fatores de Risco
4.
BMC Womens Health ; 23(1): 208, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37118753

RESUMO

BACKGROUND: Polycystic Ovarian Syndrome (PCOS) is a common endocrinopathy in women of reproductive age group and is highly associated with an increased risk of diabetes, hypertension, cardiovascular disease, and hyper estrogen-related malignancies in women with PCOS. This study was intended to assess the metabolic and hormonal profile of the patients with polycystic ovarian syndrome attending a tertiary care hospital. METHODOLOGY: A descriptive cross-sectional study was conducted among 107 women diagnosed with polycystic ovarian syndrome from the Department of Clinical Biochemistry of Tribhuvan University and Teaching Hospital. Descriptive analysis was performed to determine the socio-demographic characteristics of the participants. Bivariate analysis was conducted to determine using a t-test for comparing means between two groups and ANOVA for comparing the hormonal and metabolic parameters. RESULTS: The mean age of the participants was 27 ± 4 years. This study showed that blood pressure was significantly higher in overweight and obese women (p = 0.001). The obese group had significantly higher serum TSH than the normal group (10.04 vs. 2.73, p = 0.001). Abnormal glucose and hyperinsulinemia were present in 4% of the patients, while 40% had Vitamin D deficiency. Hypothyroidism (TSH ≥ 4.5 mIU/ml) was found in 11% of the PCOS participants with a mean value of 6.65 ± 21.17 mIU/ml. Hyperprolactinemia ≥ 26.8 ng/ml was depicted in 21% of the study population with a mean value of 37.25 ± 21.86 ng/ml. CONCLUSION: Our study demonstrated that PCOS is most commonly prevalent in young women of the reproductive age group which can lead to reproductive, metabolic, and oncological complications in the long term. LH/ FSH ratio was found to be significantly deranged indicating that PCOS should be diagnosed and treated early in the adolescent age group.


Assuntos
Síndrome do Ovário Policístico , Adolescente , Humanos , Feminino , Adulto Jovem , Adulto , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Centros de Atenção Terciária , Estudos Transversais , Nepal/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Tireotropina
5.
Heart Lung Circ ; 32(10): 1230-1239, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37743221

RESUMO

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Feminino , Humanos , Doenças Cardiovasculares/epidemiologia , Cálcio , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Suplementos Nutricionais
6.
Trop Anim Health Prod ; 55(6): 370, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37864597

RESUMO

The current research was undertaken to scrutinize the effect of leaf meal mixture as concentrate mixture in the ration of goats. Leaf meal mixture (LMM) was prepared using equal quantities of ten top-foliages namely Acacia nilotica, Celtis australis, Ficus palmata, Ficus religiosa, Grewia optiva, Melia azadarach, Morus alba, Quercus incana, Salix alba and Zizyphus jujube obtained from district Poonch of Jammu region in western Himalayas. The LMM prepared was substituted for 15% in the concentrate mixture being fed to the goats. The study constituted of two trials. Concentrate mixture offered to the animals was in mash and multi-nutrient block in first and second trial respectively. A total of twelve non-descript, adult male goats were selected for each trial. Goats of 0-14 months age (27.71 ± 2.96 kg live body weight) of for first trial while goats of 12-16 months age (27.02 ± 2.93 kg live weight) for second trial were divided into control and treatment groups as per randomized block design and fed ad-lib wheat straw and concentrate mixture @ (20 g/kgW0.75). No significant variation was observed (p > 0.05) in body weight, feed and DM intake among all groups in both trials. Comparable intake as well as digestibility of various nutrients like DM, OM, CP, EE, CF, NFE, NDF, ADF and TDN were found between the two groups during individual trials. There was a positive nitrogen, calcium and phosphorus balance among all experimental animals in both the trials. Serum enzymes ALT, AST and haemato-biochemical parameters like total protein, albumin, globulin, albumin: globulin and blood urea nitrogen (BUN) showed no significant differences during both trials in all groups, being within normal physiological levels. However, haemoglobin concentration was significantly higher (P < 0.05) in treatment group with respect to the control group in first trial. On the basis of current results, it can be established that leaf meal mixture can successfully be used to replace concentrate mixture up to 15% in the ration of goats without expecting any adverse impacts on their growth and overall health.


Assuntos
Digestão , Globulinas , Masculino , Animais , Cabras/fisiologia , Albuminas/metabolismo , Peso Corporal , Ração Animal/análise , Dieta/veterinária , Fenômenos Fisiológicos da Nutrição Animal
7.
J Neurosci ; 41(45): 9403-9418, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34635540

RESUMO

The neuronal and genetic bases of sleep, a phenomenon considered crucial for well-being of organisms, has been under investigation using the model organism Drosophila melanogaster Although sleep is a state where sensory threshold for arousal is greater, it is known that certain kinds of repetitive sensory stimuli, such as rocking, can indeed promote sleep in humans. Here we report that orbital motion-aided mechanosensory stimulation promotes sleep of male and female Drosophila, independent of the circadian clock, but controlled by the homeostatic system. Mechanosensory receptor nanchung (Nan)-expressing neurons in the chordotonal organs mediate this sleep induction: flies in which these neurons are either silenced or ablated display significantly reduced sleep induction on mechanosensory stimulation. Transient activation of the Nan-expressing neurons also enhances sleep levels, confirming the role of these neurons in sleep induction. We also reveal that certain regions of the antennal mechanosensory and motor center in the brain are involved in conveying information from the mechanosensory structures to the sleep centers. Thus, we show, for the first time, that a circadian clock-independent pathway originating from peripherally distributed mechanosensors can promote daytime sleep of flies Drosophila melanogasterSIGNIFICANCE STATEMENT Our tendency to fall asleep in moving vehicles or the practice of rocking infants to sleep suggests that slow rhythmic movement can induce sleep, although we do not understand the mechanistic basis of this phenomenon. We find that gentle orbital motion can induce behavioral quiescence even in flies, a highly genetically tractable system for sleep studies. We demonstrate that this is indeed true sleep based on its rapid reversibility by sensory stimulation, enhanced arousal threshold, and homeostatic control. Furthermore, we demonstrate that mechanosensory neurons expressing a TRPV channel nanchung, located in the antennae and chordotonal organs, mediate orbital motion-induced sleep by communicating with antennal mechanosensory motor centers, which in turn may project to sleep centers in the brain.


Assuntos
Encéfalo/fisiologia , Proteínas de Drosophila/metabolismo , Mecanorreceptores/fisiologia , Sono/fisiologia , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Drosophila melanogaster , Feminino , Masculino
8.
Indian J Clin Biochem ; 37(2): 212-217, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35463114

RESUMO

Idiopathic retinal vasculitis is a chronic disease of unknown aetiology which results in ocular morbidity in patients of productive age group. Homocysteine has been implicated in various ocular conditions like age-related macular degeneration, retinal vein occlusions, diabetic retinopathy, and optic nerve diseases. We conducted a study to investigate the relation between serum homocysteine levels and retinal vasculitis at a tertiary care centre in North India. In this case-control study, 32 cases and 64 controls were included and the duration was from June 2017 to March 2019. Serum homocysteine of cases and controls was detected by reflectance photometry using VITROS Chemistry Products HCY 2 (Homocysteine) and the normal range of serum homocysteine as per this method was 6.60 to 14.80 micro mol per litre. Our study found that of the total 32 retinal vasculitis patients, serum homocysteine was raised in 65.62% (21 cases out of 32) and in 70.31% of control group (45 out of 64). Chi square test results showed that there was no significant association found between S. homocysteine levels and Reticular vasculitis (P: 0.64). The two groups were comparable in terms of the age with mean ± SD in cases being 33.47 ± 8.336 years and controls being 35.16 ± 8.568 years with a P value of 0.37 being statistically insignificant. The data collected was analysed using SSPS-16 (Statistical Package for Social Sciences Version 16) software and test of association was Odd's ratio. Power of study was 80% and P < 0.05 is considered statistically significant. We found that there is no significant association between raised serum homocysteine and retinal vasculitis (with P < 0.64). Odds ratio was 0.80(0.33-1.99) implying that the cases and controls were statistically significantly different with respect to homocysteine levels.

9.
Trop Anim Health Prod ; 53(4): 430, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34363100

RESUMO

This research trial is aimed to study the nutritional qualities and significance of feeding spent marigold flower meal (SMFM) in goats. SMFM and diet containing iso-nitrogenous concentrate mixture with different levels of spent marigold flower meal (0-30%) were studied for in vitro degradation. Depending upon the in vitro results, concentrate mixture containing 15% level of SMFM was selected for in vivo trial. In vivo studies were conducted for a period of 60 days, and 12 local, non-descript, adult male goats (10-14 months age; 31.09 ± 2.91 kg body weight) were randomly assigned to two groups and were fed on ad libitum wheat straw with either conventional (control) or SMFM containing concentrate mixture (treatment). Results of the study showed that there was no variation in body weight of the goats between periods and between groups. DM and OM intake along with their digestibility were similar among the two groups. The digestibility of all other nutrients was comparable between the two groups. Nitrogen, calcium and phosphorus balance were positive in both the groups without any significant disparity. Moreover, experimental goats did not differ in biochemical parameters, without any significant difference between periods and dietary treatments except AST level which was significantly higher (P > 0.05) in treatment group. So, this study successfully demonstrates that SMFM could be incorporated in the concentrate mixture, up to 15% without any discernable difference in the performance of goats.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Cabras , Ração Animal/análise , Animais , Dieta/veterinária , Digestão , Flores , Masculino
10.
Pak J Pharm Sci ; 34(4): 1397-1401, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34799313

RESUMO

The current research was aimed to isolate newer phyto-metabolites from rhizomes of Alpinia galanga plant. Study involved preparation of Alpinia galanga rhizome methanolic extract, followed by normal phase column chromatography assisted isolation of new phytometabolites (using different combinations of chloroform and methanol), and characterization (by UV, FTIR, 13C-NMR, 1H-NMR, COSY, DEPT and Mass spectrometry). The isolation and characterization experiment offered two phytometabolites: an ester (Ag-1) and tetrahydronapthalene type lactone (Ag-2). Present study concludes and reports the two phytometabolites, benzyl myristate (Ag-1) and 3-Methyl-6α, 8ß-diol-7-carboxylic acid tetralin-11, 9ß-olide (Ag-2) for the first time in Alpinia galanga rhizome. The study recommends that these phytometabolites Ag-1 and Ag-2 can be utilized as effective analytical biomarkers for identification, purity and quality control of this plant in future.


Assuntos
Alpinia/química , Extratos Vegetais/isolamento & purificação , Rizoma/química , Compostos de Benzil/química , Compostos de Benzil/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Miristatos/química , Miristatos/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química
11.
Med J Armed Forces India ; 76(2): 166-171, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32476714

RESUMO

BACKGROUND: Endothelial keratoplasties have become the surgical procedure of choice over full thickness penetrating keratoplasty for corneal decompensation because of endothelial dysfunction. METHODS: A retrospective data review was performed from February 2016 to April 2017 for all the patients who underwent endothelial keratoplasty in a tertiary care center for Indian Armed Forces. RESULTS: A total of 161 corneal transplants were performed; endothelial keratoplasties accounted for 34 (21.1%) transplants. Most common indication was pseudophakic/aphakic bullous keratopathy followed by Ahmed glaucoma valve-related corneal decompensation and Fuchs' corneal dystrophy, respectively. Mean preoperative corneal thickness was 845.96 ± 106.9 microns. Mean lenticule thickness was 131.55 ± 42.47 microns with microkeratome for descemet stripping automated endothelial keratoplasty (DSAEK) and 174 ± 70.4 microns manually for descemet stripping endothelial keratoplasty (DSEK). Mean preoperative best-corrected visual acuity (BCVA) was 1.65 LogMAR (Snellen equivalent in meters 2/60 approx) which significantly improved to 0.82 LogMAR (Snellen equivalent in meters 6/36 approx) after surgery. In the DSAEK group, BCVA improved from 1.61 to 0.7 LogMAR, whereas in the DSEK group, the visual acuity improved from 1.7 to 0.94 LogMAR at one-month postoperative period. Postoperatively, two patients had graft detachment and had to undergo repeat DSAEK. CONCLUSION: Study results suggest the similar trends in our tertiary care hospital as in other most advanced ophthalmic centers around the world for adoption of newer techniques of lamellar corneal transplants and their outcomes.

13.
J Chem Phys ; 151(22): 224708, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31837672

RESUMO

The intentional incorporation of transition metal impurities into colloidal semiconductor nanocrystals allows an extension of the host material's functionality. While dopant incorporation has been extensively investigated in zero-dimensional quantum dots, the substitutional replacement of atoms in two-dimensional (2D) nanostructures by magnetic dopants has been reported only recently. Here, we demonstrate the successful incorporation of Co2+ ions into the shell of CdSe/CdS core/shell nanoplatelets, using these ions (i) as microscopic probes for gaining distinct structural insights and (ii) to enhance the magneto-optical functionality of the host material. Analyzing interatomic Co2+ ligand field transitions, we conclude that Co2+ is incorporated into lattice sites of the CdS shell, and effects such as diffusion of dopants into the CdSe core or diffusion of the dopants out of the heterostructure causing self-purification play a minor role. Taking advantage of the absorption-based technique of magnetic circular dichroism, we directly prove the presence of sp-d exchange interactions between the dopants and the band charge carriers in CdSe/Co2+:CdS heteronanoplatelets. Thus, our study not only demonstrates magneto-optical functionality in 2D nanocrystals by Co2+ doping but also shows that a careful choice of the dopant type paves the way for a more detailed understanding of the impurity incorporation process into these novel 2D colloidal materials.

14.
BMC Dev Biol ; 18(1): 21, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577765

RESUMO

BACKGROUND: Previous studies have implicated a role for circadian clocks in regulating pre-adult development of organisms. Among them two approaches are most notable: 1) use of insects whose clocks have different free-running periods and 2) imposition of artificial selection on either rate of development, timing of emergence or circadian period in laboratory populations. Using these two approaches, influence of clock on rate of development has been elucidated. However, the contribution of circadian clocks in determining time taken for pre-adult development has remained unclear. Here we present results of our studies aimed to understand this influence by examining populations of fruit flies carrying three different alleles of the period gene and hence having different free-running periods. We tried to achieve similarity of genetic background among the three strains while also ensuring that they harbored sufficient variation on loci other than period gene. RESULTS: We find that under constant conditions, flies with long period have slower development whereas in presence of light-dark cycles (LD) of various lengths, the speed of development for each genotype is influenced by whether their eclosion rhythms can entrain to them. Under LD 12:12 (T24), where all three strains entrain, they do not show any difference in time taken for emergence, whereas under LD 10:10 (T20) where long period flies do not entrain and LD 14:14 (T28) where short period flies do not entrain, they have slower and faster pre-adult development, respectively, compared to the controls. We also show that a prior stage in development namely pupation is not rhythmic though time taken for pupation is determined by both the environmental cycle and period allele. CONCLUSION: We discuss how in presence of daily time cues, interaction of the cyclic environmental factors with the clock determines the position and width of the gate available for a fly to emerge (duration of time within a cycle when adult emergence can occur) resulting in an altered developmental duration from that observed under constant conditions. We also discuss the relevance of genetic background influencing this regulation.


Assuntos
Relógios Circadianos/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/fisiologia , Meio Ambiente , Animais , Escuridão , Feminino , Masculino , Fotoperíodo , Pupa/fisiologia , Fatores de Tempo
15.
Biochim Biophys Acta Proteins Proteom ; 1865(6): 715-724, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28400297

RESUMO

EccA family proteins are conserved components of ESX secretion pathways in M. tuberculosis H37Rv. Here, we report the characterization of EccA3 (Rv0282), a CbbX family AAA (ATPases Associated with diverse cellular Activities) protein from the ESX-3 pathway that is required for in vitro growth of mycobacteria, secretion of virulence factors, and acquisition of iron and zinc. EccA3 is a thermostable ATPase with a molecular weight of ~68kDa. It exists as a dodecamer in the apo form and associates as a hexamer in the presence of ATP. Its C-terminal region consists of a CbbX-like AAA-domain while the N-terminal region contains a tetratricopeptide repeat (TPR) domain with lower homology to other EccA-type proteins. Further, the C-terminal domain functions as the oligomerization domain and also exhibits ATPase activity. Mutational analysis, steady state kinetics and molecular docking studies identify R573 as the important 'sensor arginine' and R505 as an 'arginine finger' in EccA3. Dynamic fluorescence quenching experiments suggest that the N-terminal domain moves closer to the C-terminal domain upon ATP-binding. The ATP-dependent 'open-close' relative movements of the two domains might help EccA3 interaction and secretion of essential virulence factors.


Assuntos
Adenosina Trifosfatases/metabolismo , Mycobacterium tuberculosis/enzimologia , Adenosina Trifosfatases/química , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Cromatografia em Gel , Dicroísmo Circular , Estabilidade Enzimática , Hidrólise , Simulação de Acoplamento Molecular , Ligação Proteica , Homologia de Sequência de Aminoácidos , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
16.
Cell Mol Life Sci ; 73(17): 3401-17, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26984196

RESUMO

Mycobacterium tuberculosis codes for a HAD-phosphatase, Rv3042c (MtSerB2), that has earlier been characterized as a metabolic enzyme. Here we demonstrate that MtSerB2 is secreted into the cytosol of infected macrophages and is found in bronchoalveolar lavage samples of tuberculosis patients. MtSerB2 induces significant cytoskeleton rearrangements through cofilin activation and affects the expression of genes that regulate actin dynamics. It specifically interacts with HSP90, HSP70 and HSP27 that block apoptotic pathways and not with other HSPs. It actively dephosphorylates MAPK-p38 and NF-kappa B p65 that play crucial roles in inflammatory and immune responses. This in turn leads to down-regulation of Interleukin 8, a chemotactic and inflammatory cytokine. Finally, during evaluation of inhibitors against MtSerB2 we found that Clofazimine, a drug being evaluated for XDR and MDR tuberculosis, inhibits MtSerB2 phosphatase activity and reverses the above effects and interactions with host proteins. Overall, the study identifies that MtSerB2 has new functions that might help the pathogen to evade the host's immune response.


Assuntos
Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Actinas/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Sítios de Ligação , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Linhagem Celular , Dimerização , Regulação para Baixo/efeitos dos fármacos , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/metabolismo , Humanos , Interleucina-8/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis/metabolismo , Monoéster Fosfórico Hidrolases/química , Monoéster Fosfórico Hidrolases/genética , Estrutura Quaternária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Fator de Transcrição RelA/metabolismo , Tuberculose/diagnóstico , Tuberculose/imunologia , Tuberculose/microbiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
BMC Evol Biol ; 16: 46, 2016 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-26922082

RESUMO

BACKGROUND: The hypothesis that circadian clocks confer adaptive advantage to organisms has been proposed based on its ubiquity across almost all levels of complexity and organization of life-forms. This thought has received considerable attention, and studies employing diverse strategies have attempted to investigate it. However, only a handful of them have examined how selection for circadian clock controlled rhythmic behaviors influences life-history traits which are known to influence Darwinian fitness. The 'early' and 'late' chronotypes are amongst the most widely studied circadian phenotypes; however, life-history traits associated with these chronotypes, and their consequences on Darwinian fitness remain largely unexplored, primarily due to the lack of a suitable model system. Here we studied several life-history traits of Drosophila melanogaster populations that were subjected to laboratory selection for morning (early) and evening (late) emergence. RESULTS: We report that the late eclosion chronotypes evolved longer pre-adult duration as compared to the early eclosion chronotypes both under light/dark (LD) and constant dark (DD) conditions, and these differences appear to be mediated by both clock dependent and independent mechanisms. Furthermore, longer pre-adult duration in the late chronotypes does not lead to higher body-mass at pupariation or eclosion, but the late females were significantly more fecund and lived significantly shorter as compared to the early females. CONCLUSIONS: Coevolution of multiple life-history traits in response to selection on timing of eclosion highlights correlations of the genetic architecture governing timing of eclosion with that of fitness components which suggests that timing ecologically relevant behaviors at specific time of the day might confer adaptive advantage.


Assuntos
Ritmo Circadiano , Drosophila melanogaster/fisiologia , Adaptação Biológica , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Estágios do Ciclo de Vida , Luz , Masculino , Fenótipo , Fotoperíodo , Fatores de Tempo
18.
Opt Lett ; 41(12): 2883-6, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27304313

RESUMO

Here we report CdSe nanoplatelets that are incorporated into color-converting CdSe/ZnS nanocrystals for InGaN/GaN light-emitting diodes. The critical role of CdSe nanoplatelets as an exciton donor for the color conversion was experimentally investigated. The power conversion efficiency of the hybrid light-emitting diode was found to increase by 23% with the incorporation of the CdSe nanoplatelets. The performance enhancement is ascribed to efficient exciton transfer from the donor CdSe nanoplatelet quantum wells to the acceptor CdSe/ZnS nanocrystal quantum dots through Förster-type nonradiative resonance energy transfer.

19.
Naturwissenschaften ; 103(9-10): 74, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27585442

RESUMO

Robustness is considered to be an important feature of biological systems which may evolve when the functionality of a trait is associated with higher fitness across multiple environmental conditions. Thus, the ability to maintain stable biological phenotypes across environments is thought to be of adaptive value. Previously, we have reported higher intrinsic activity levels (activity levels of free-running rhythm in constant darkness) and power of rhythm (as assessed by amplitude of the periodogram) in Drosophila melanogaster populations (stocks) reared in constant darkness (DD stocks) as compared to those reared in constant light (LL stocks) and 12:12-h light-dark cycles (LD stocks) for over 19 years (∼330 generations). In the current study, we intended to examine whether the enhanced levels of activity observed in DD stocks persist under various environments such as photoperiods, ambient temperatures, non-24-h light-dark (LD) cycles, and semi-natural conditions (SN). We found that DD stocks largely retain their phenotype of enhanced activity levels across most of the above-mentioned environments suggesting the evolution of robust circadian clocks in DD stocks. Furthermore, we compared the peak activity levels of the three stocks across different environmental conditions relative to their peaks in constant darkness and found that the change in peak activity levels upon entrainment was not significantly different across the three stocks for any of the examined environmental conditions. This suggests that the enhancement of activity levels in DD stocks is not due to differential sensitivity to environment. Thus, these results suggest that rearing in constant darkness (DD) leads to evolution of robust circadian clocks suggesting a possible adaptive value of possessing such rhythms under constant dark environments.


Assuntos
Evolução Biológica , Relógios Circadianos/fisiologia , Escuridão , Drosophila melanogaster/fisiologia , Atividade Motora/fisiologia , Animais , Meio Ambiente
20.
BMC Neurol ; 16: 46, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27067253

RESUMO

BACKGROUND: The predictive ability of National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol and Montreal Cognitive Assessment (MoCA) administered sub-acutely and at the convalescent phase after stroke for significant vascular cognitive impairment (VCI) at 1 year is unknown. We compared prognostic values of these tests. METHODS: Patients with ischemic stroke and transient ischemic attack (TIA) received MoCA sub-acutely (within 2 weeks) and 3-6 months after stroke followed by a formal neuropsychological evaluation at 1 year. The total score of NINDS-CSN 5-minutes protocol was derived from MoCA. Moderate-severe VCI was defined as neuropsychological impairment in ≥ 3 domains. Area under the receiver operating characteristic curve (AUC) analyses were conducted to establish the optimal cutoff points and discriminatory properties of the MoCA and NINDS-CSN 5-minute protocol in detecting moderate-severe VCI. RESULTS: Four hundre patients were recruited at baseline. Of these, 291 received a formal neuropsychological assessment 1 year after stroke. 19% patients had moderate-severe VCI. The MoCA was superior to the NINDS-CSN 5-minute protocol [sub-acute AUCs: 0.89 vs 0.80, p < 0.01; 3-6 months AUCs: 0.90 vs 0.83, p < 0.01] in predicting for moderate-severe VCI at 1 year. At respective cutoff points, MoCA had significantly higher sensitivity than the NINDS-CSN 5-minute protocol at baseline (p = 0.01) and 3-6 months (p = 0.04). CONCLUSIONS: MoCA administered sub-acutely and 3-6 months after stroke is superior to the NINDS-CSN 5-minute protocol in predicting moderate-severe VCI at 1 year.


Assuntos
Transtornos Cognitivos/diagnóstico , Ataque Isquêmico Transitório/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Idoso , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Curva ROC
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