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1.
Anal Chem ; 96(11): 4446-4454, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38451777

RESUMO

Microfluidic isotachophoresis (ITP) is a powerful technique that can significantly increase the reaction rate of homogeneous chemical reactions by cofocusing reactants in a narrow sample zone. Correspondingly, ITP has been utilized to reduce the reaction time in various bioanalytical assays. However, in conventional ITP, it is hardly possible to control the reaction rate in real time, i.e., speeding up or slowing down a reaction on demand. Here, we experimentally demonstrate a new mode of ITP that allows the spatial overlap of two ITP zones to be precisely controlled over time, which is a crucial first step toward controlling reaction rates. Two nonreactive samples are initially focused and separated by a spacer using a DC electric field. By superimposing an oscillating field component with sufficiently high amplitude on the DC field, the spatial overlap of their concentration profiles is temporarily increased due to electromigration dispersion. The time-average of this overlap can be precisely controlled by varying the frequency and amplitude of the oscillation. We suggest that this scheme can be transferred to chemical reactions between ionic species with sufficiently different electrophoretic mobilities. Tuning the parameters of the oscillatory electric field should allow direct control of the corresponding reaction rate.

2.
BMC Public Health ; 24(1): 676, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439011

RESUMO

BACKGROUND: Reproductive span is the foundation of every woman's health in later life. India is currently facing a growing burden of multiple morbidities among the women in their reproductive age group which may further increase over the coming decades. The purpose of the present study aimed to identify different modifiable and non-modifiable risk factors affecting multimorbidity among the women in reproductive age group in Indian context. METHODS: Secondary data were obtained from the Demography and Health Survey (DHS), conducted in India during 2019-2021. A total of 671,967 women aged 15-49 years were selected for this present study. Descriptive, association studies and multinominal logistic regression analyses were performed to accomplish the objectives. RESULTS: Currently, 6.3% of total study participant's reproductive age group women suffered from multimorbidity in India. Never consuming protein, fruits, vegetables and milk increase the chances of developing multimorbidity. Consumption of fried foods, aerated drinks and addiction towards tobacco and alcohol also has a greater influence on the prevalence of multimorbidity. The prevalence of multimorbidity is sharply increased with increasing age and Body Mass Index (BMI). Regionally, the prevalence of multimorbidity was found more among the women hailed from eastern and north-eastern India. CONCLUSION: To reduce the risk of developing multimorbidity, targeted interventions are needed in the form of educating every woman concerning the importance of having minimum health-related knowledge, maintaining healthy lifestyle, weight management and having proper and balanced diet.


Assuntos
Comportamento Aditivo , Multimorbidade , Adulto , Feminino , Humanos , Povo Asiático , Frutas , Índia/epidemiologia , Adolescente , Adulto Jovem , Pessoa de Meia-Idade
3.
J Ethn Subst Abuse ; : 1-24, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613768

RESUMO

BACKGROUND: Alcohol consumption among tribal male adolescents in India is a significant social concern. Tribal adolescents are particularly vulnerable and tend to lean toward alcohol addiction. Therefore, it is crucial to introduce some necessary footsteps to reduce alcohol consumption. The primary objective of this study is to investigate the association of various latent factors with the alcohol-drinking behavior of tribal adolescents. METHODS: The study collected data from 600 tribal adolescents from the Dooars region, with 241 of them reported consuming alcohol. The study aimed to confirm the theoretical development of hypotheses regarding peer pressure, parental discord, stress, attitude toward alcohol, and food insecurity as exogenous latent factors influencing the alcohol-drinking behavior of tribal adolescents. In this context, the study adopted both measurement and structural models using Partial Least Squares-Structural Equation Modeling (PLS-SEM). RESULTS: The findings revealed a significant path relationship between alcohol drinking behavior and various exogenous factors like peer pressure (ß = 0.214, p = .000), parental discord (ß = 0.121, p = .009), stress (ß = 0.170, p = .000), attitude toward alcohol (ß = 0.110, p = .004), and food insecurity (ß = 0.510, p = .000). This study developed a reflective measurement model, and the evaluation of reflective measurement models was conducted, assessing internal consistency, convergent validity, and discriminant validity, yielding satisfactory results. CONCLUSION: To tackle alcohol issues among tribal adolescents in the Dooars region, effective strategies should be employed. These include educating in schools, highlighting tribal role models, aiding peers with alcohol dependence, providing life skills training, and addressing parental discord and food insecurity through awareness campaigns, workshops, and better infrastructure.

4.
Anal Chem ; 95(19): 7575-7583, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37133530

RESUMO

Lowering the limit of detection in chemical or biochemical analysis is key to extending the application scope of sensing schemes. Usually, this is related to an increased instrumentation effort, which in turn precludes many commercial applications. We demonstrate that the signal-to-noise ratio of isotachophoresis-based microfluidic sensing schemes can be substantially increased merely by postprocessing of recorded signals. This becomes possible by exploiting knowledge about the physics of the underlying measurement process. The implementation of our method is based on microfluidic isotachophoresis and fluorescence detection, for which we take advantage of the physics of electrophoretic sample transport and the structure of noise in the imaging process. We demonstrate that by processing only 200 images, the detectable concentration, compared to the detection from a single image, is already lowered by 2 orders of magnitude without any additional instrumentation effort. Furthermore, we show that the signal-to-noise ratio is proportional to the square root of the number of fluorescence images, which leaves room for further lowering of the detection limit. In the future, our results could be relevant for various applications where the detection of minute sample amounts plays a role.

5.
J Org Chem ; 88(8): 5078-5089, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36520948

RESUMO

A protocol for the carbonylative synthesis of acyl amidines from aryl halides, amidines, and carbon monoxide catalyzed by Pd(0) is reported herein. Notably, carbon monoxide is generated ex situ from a solid CO source, and several productive palladium ligands were identified with complementary benefits and substrate scope. Furthermore, sequential one-pot, two-step protocols for the synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles via acyl amidine intermediates are reported. In addition, this approach was extended to isotopic labeling using [11C]carbon monoxide to allow, for the first time, synthesis of 11C-labeled acyl amidines as well as a 11C-labeled 1,2,4-oxadiazole.

6.
Bioorg Med Chem ; 66: 116804, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35576659

RESUMO

Ligands comprising a benzimidazole rather than the imidazole ring that is common in AT2R ligands e.g. in the AT2R agonist C21, can provide both high affinity and receptor selectivity. In particular, compounds encompassing benzimidazoles, substituted in the 2-position with small bulky groups such as an isopropyl (Ki = 4.0 nM) or a tert-butyl (Ki = 5.3 nM) or alternatively a thiazole heterocycle (Ki = 5.1 nM) demonstrate high affinity and AT2R selectivity. An n-butyl chain, as found in the AT1R selective sartans, makes the ligand less receptor selective. The isobutyl group on the biaryl scaffold present in most AT2R selective ligands reported so far was originally derived from the nonselective potent AT1R/AT2R ligand L-162,313. Notably, in all ligands discussed herein, the isobutyl group was substituted by an n-propyl group and ligands with high affinity to AT2R were provided and in addition the majority of them demonstrate a favorable AT2R/AT1R selectivity. The introduction of fluoro atoms in various positions had no pronounced effect on the affinity data. Ligands with a thiazole or a tert-butyl group attached to the 2-position and with a terminal trifluoromethyl butoxycarbonyl sidechain exhibited a similar stability as C21 in human liver microsomes, while other ligands examined were less stable in the microsome assay.


Assuntos
Benzimidazóis , Receptor Tipo 2 de Angiotensina , Benzimidazóis/farmacologia , Humanos , Imidazóis , Ligantes , Receptor Tipo 2 de Angiotensina/agonistas , Sulfonamidas , Tiazóis , Tiofenos
7.
Oecologia ; 200(1-2): 89-106, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36181546

RESUMO

Size-selective mortality is common in fish populations and can operate either in a positive size-selective fashion by harvesting larger-than-average fish or be negatively size-selective by harvesting smaller-than-average fish. Through various mechanisms (like genetic correlations among behaviour and life-history traits or direct selection on behaviour co-varying with growth rate or size-at-maturation), size-selection can result in evolutionary changes in behavioural traits. Theory suggests that both positive and negative size-selection without additional selection on behaviour favours boldness, while evolution of shyness is possible if the largest fish are harvested. Here we examined the impact of size-selective mortality on collective boldness across ontogeny using three experimental lines of zebrafish (Danio rerio) generated through positive (large-harvested), negative (small-harvested) and random (control line) size-selective mortality for five generations and then relaxed selection for 10 generations to examine evolutionarily fixed outcomes. We measured collective risk-taking during feeding (boldness) under simulated aerial predation threat, and across four contexts in presence/absence of a cichlid. Boldness decreased across ontogeny under aerial predation threat, and the small-harvested line was consistently bolder than controls. The large and small-harvested lines showed higher behavioural plasticity as larvae and developed personality earlier compared to the controls. The large-harvested line showed increased variability and plasticity in boldness throughout ontogeny. In the presence of a live predator, fish did not differ in boldness in three contexts compared to the controls, but the large-harvested line showed reduced behavioural plasticity across contexts than controls. Our results confirmed theory by demonstrating that size-selective harvesting evolutionarily alters collective boldness and its variability and plasticity.


Assuntos
Comportamento Predatório , Peixe-Zebra , Animais , Comportamento Animal , Tamanho Corporal , Fenótipo , Assunção de Riscos , Peixe-Zebra/genética
8.
Langmuir ; 37(9): 2891-2899, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33635660

RESUMO

Liquid-jet impact on porous, relatively thin solids has a variety of applications in heat transfer, filtration, liquid-fuel atomization, incontinence products, and solid-substrate erosion, among others. Many prior studies focused on liquid-jet impact on impermeable substrates, and some have investigated the hydraulic jump phenomenon. In the present work, the liquid jet strikes a superhydrophobic, permeable, metal mesh orthogonally, and the radial spreading and throughflow of the liquid are characterized. The prebreakthrough hydraulic jump, the breakthrough velocity, and the postbreakthrough spatial distributions of the liquid are investigated by varying the liquid properties (density, surface tension, and viscosity) and the openness of the metal mesh. The hydraulic jump radius in the prebreakthrough regime increases with jet velocity and is independent of the liquid properties and mesh geometry (pore size, wire diameter and pitch). The breakthrough velocity increases with surface tension of the liquid and decreases with the mesh opening diameter and liquid viscosity. A simple analytical model predicts the jet breakthrough velocity; its predictions are in accordance with the experimental observations. In the postbreakthrough regime, as the jet velocity increases, the liquid flow rate penetrating the mesh shows an initially steep increase, followed by a plateau, which is attributed to a Cassie-Baxter-to-Wenzel transition at the impact area of the mesh.

9.
Child Youth Serv Rev ; 130: 106226, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34511676

RESUMO

Worldwide the incidents of intimate partner violence (IPV) have increased due to lockdowns related to the COVID-19 pandemic. This paper aims to identify the association between IPV and different socio-economic factors of women & their most recent partner during the COVID-19 pandemic in returnee migrant worker families in Balurghat Block (area 363.9 sq. km), Dakshin Dinajpur district, West Bengal, India. A total of 159 ever-married women were included in this present study, whose husbands were engaged as workers elsewhere at least two years before the lockdown. The result of the multinomial logistic regression model revealed that, after controlling for other variables, the women who had the poorest wealth background were 37% more likely (RRR: 1.37; 95% CI [1.18, 1.47]) to experience IPV almost every day in a week than those who had a middle wealth background. Conversely, the women who had the poorest wealth background were 37% (95% CI [0.57, 0.82]) less likely to experience IPV for three to four days in a week. Furthermore, the women whose partners were currently unemployed were 21% more likely (RRR: 1.21; 95% CI [1.16, 1.36]) to experience IPV almost every day in a week than those whose husbands were currently employed. The women whose husband's had a loan were 26% more likely (RRR: 1.26; 95% CI [1.25, 1.33]) to experience IPV for three to four days in a week than those whose husbands did not have any loans. The likelihood to experience IPV almost every day in a week is higher among those women whose husbands attain weekly (31%) loan instalment pattern and consume alcohol daily (31%). Interventions are needed at the grassroots level and some economic planning is required at an urgent basis.

10.
Langmuir ; 36(40): 11829-11835, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-32921058

RESUMO

Spreading of liquid droplets on wettability-confined paths has attracted considerable attention in the past decade. On the other hand, the inverse scenario of a gas bubble spreading on a submerged, wettability-confined track has rarely been studied. In the present work, an experimental investigation of the spreading of millimetric gas bubbles on horizontally submerged, textured, wettability-confined tracks is carried out. The width of the track is kept fixed along its entire length, and the spreading behavior of a gas bubble, dispensed at one end of the track, is studied. The effects of varying track width, bubble diameter, and ambient liquid are investigated. Post-contact, the gas bubble spreads along the track at a linear rate with time, while remaining pinned at its back end; the recorded spreading speed is O(0.5 m/s). An inertio-capillary force balance describes the experimentally observed spreading dynamics with excellent agreement.

11.
Langmuir ; 35(39): 12711-12721, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499000

RESUMO

The impact of liquid droplets on permeable substrates is important for a number of applications, such as fog collection, liquid atomization, and interaction of liquids with filters and textiles. When a water droplet impacts a wettable mesh, it penetrates the mesh easily with a part of the liquid remaining pinned. On the other hand, when striking a superhydrophobic mesh, part of the water droplet may penetrate and detach from the parent droplet, depending upon the impact velocity and the relative length scales of the droplet and the mesh. In most cases, the remaining droplet would rebound from the top of the superhydrophobic mesh. In this work, we study the impact of a water droplet on a wettability-patterned mesh, with the droplet centrally impacting the wettability-contrast line between the superhydrophobic and superhydrophilic semi-infinite domains. Half of the droplet seeing the superhydrophobic domain responds to it in a fashion that differs from the half hitting the superhydrophilic mesh side. This creates a wide range of post-impact scenarios, depending on the impact conditions and the relative characteristics of the droplet and the mesh. The difference in mesh wettability leads to a net unbalanced surface-tension force that makes the droplet rebound with a horizontal momentum component directed from the non-wettable to the wettable side. Some part of the droplet may even detach during such directional rebounding (i.e., vectoring). Along with the experimental results, a simplified analytical model is presented, which differentiates the cases of detachment or no detachment during vectoring.

12.
Soft Matter ; 14(38): 7926-7933, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30238941

RESUMO

We study the relaxation of surface-tethered polymers in microchannels under moderate confinement (i.e. h ∼ Rg, where h is the channel height and Rg is the radius of gyration of the polymer) by experiments with fluorescence-marked DNA molecules and coupled lattice-Boltzmann/molecular dynamics simulations. The determined scaling exponent suggests that the relaxation is dominated by Zimm-dynamics with significant intra-chain hydrodynamic interactions. The relaxation of the DNA molecules is slower in shallower channels, indicating a pronounced effect of confinement on the longest relaxation time. An experimental correlation is obtained for the longest relaxation time as a function of the molecular contour length and the channel height. Good agreement between the experimental and the simulation results is found.


Assuntos
Polímeros/química , DNA/química , Corantes Fluorescentes/química , Hidrodinâmica , Simulação de Dinâmica Molecular , Rotação , Propriedades de Superfície
13.
Learn Behav ; 46(2): 124-133, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29052112

RESUMO

Given its diverse ecological distribution, zebrafish has great potential for investigations on the effect of habitat characteristics on cognition. Studies were conducted on four wild-caught zebrafish populations to understand the role of native habitat, sex, and body size in determining learning through a novel task associated with a food reward. The habitat variables, namely, the relative abundances of zebrafish and predatory fish and the substrate and vegetation diversity, were quantified during fish sampling. Fish were subjected to a novel task to find a food reward in a maze over successive training trials followed by a test for memory. Performances of subjects were based on time taken to find the food reward and number of mistakes made during trials, and tests for memory. The experiments revealed significant differences in learning rates and memory across populations. Males made significantly fewer mistakes than females only within two populations. No relationship between performance and body size was observed. The differences in learning and memory among wild zebrafish could be due to differences in predation, complexity, and stability of the native habitats. These findings suggest the possible role of multiple interacting factors in determining learning and memory among populations and point to a need for incorporating effects of several factors in future studies.


Assuntos
Comportamento Animal/fisiologia , Tamanho Corporal/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Animais , Feminino , Masculino , Fatores Sexuais , Peixe-Zebra
14.
Soft Matter ; 13(36): 6189-6196, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28798968

RESUMO

We study the effect of pressure-driven flow on a single surface-tethered DNA molecule confined between parallel surfaces. The influence of flow and channel parameters as well as the length of the molecules on their extension and orientation is explored. In the experiments the chain conformations are imaged by laser scanning confocal microscopy. We find that the fractional extension of the tethered DNA molecules mainly depends on the wall shear stress, with effects of confinement being very weak. Experiments performed with molecules of different contour length show that the fractional extension is a universal function of the product of the wall shear stress and the contour length, a result that can be obtained from a simple scaling relation. The experimental results are in good agreement with results from coarse-grained molecular dynamics/Lattice-Boltzmann simulations.


Assuntos
Polímeros/química , Pressão , DNA/química , Estresse Mecânico , Propriedades de Superfície
15.
J Chem Phys ; 147(3): 034902, 2017 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-28734293

RESUMO

We use mesoscopic lattice-Boltzmann/molecular dynamics simulations to study the stretching behavior of a single tethered polymer in micro- and nanochannels. In particular, we are interested in the connection between fluid flow properties and the force on the polymer chain. An analytical expression for the stretching force is proposed, which linearly depends on the number of monomers and the boundary shear rate. In agreement with theory, the numerical findings reveal that the influence of hydrodynamic interactions can be ignored, which is also supported by results of additional Langevin dynamics simulations. Our simulation data coincide with the analytical expression for the fractional extension of the chain and further indicate that even weak Poiseuille flow profiles induce a strong alignment of the chain along the channel walls. The numerical results are in good agreement with experimental data obtained by microfluidic stretching of tethered λ-DNA.

16.
Artigo em Inglês | MEDLINE | ID: mdl-39009927

RESUMO

BACKGROUND: Alcohol consumption is a significant social and health problem among tribal male adolescents. The Dooars region of West Bengal has the highest concentration of the tribal population. This study aimed to examine the role of various factors in the early initiation of alcohol consumption among tribal male adolescents. METHODS: This study relied on primary data and included 600 tribal adolescents. To fulfil the objective, the Cox regression hazard model was employed. Additionally, hazard rates were calculated to identify the changing hazard rates over a specific age. The Kaplan-Meier failure graph was also used to illustrate the occurrence of alcohol consumption events among different groups of tribal adolescents. FINDINGS: The risk of alcohol consumption was higher among tribal adolescents who dropped out of the educational system (HR: 2.94), did not participate in outdoor games (HR: 3.10), worked for pay (HR: 3.23), smoked (HR: 12.55), drank traditional liquor (HR: 3.61), and had siblings (HR: 4.27) or peers (HR: 3.60) who used substances or fathers who consumed alcohol (HR: 3.80). Unsupervised time with peers (HR: 3.61) and stress (HR: 3.61) also increased the risk of alcohol consumption. In contrast, self-esteem was found to be protective (HR: 0.93). CONCLUSIONS: The government has introduced various interventions and schemes to reduce alcohol consumption, but more targeted actions are needed at the household and individual levels. In the tea gardens of the Dooars region, NGOs and the government should promote education, organize extracurricular activities for adolescents' holistic development, and raise awareness in tribal communities about the harmful effects of alcohol consumption.

17.
Arch Public Health ; 82(1): 57, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664719

RESUMO

BACKGROUND: In the 21st century, people still use solid fuel for cooking at home, resulting in poor indoor air quality. Prolonged exposure to such conditions may negatively affect one's cognitive function. So, the present study examines the possible association between IAP and the cognitive function of individuals aged 45 years or above in India. METHODS: The study utilizes secondary data, procured from the longitudinal ageing study in India (2017-18). Treatment effects through regression-adjusted models were applied to represent the association between IAP and cognitive health and the results are represented by beta coefficient (ß). Three separate models with a 95% confidence interval adjusting with the other factors like housing environment, individual and behavioural were framed. RESULTS: The study revealed that households without a separate kitchen (ß = -0.64; 95%CI: -0.90 to -0.39) and electricity (ß = -0.97; 95%CI: -1.34 to -0.61) significantly affect cognitive strength. Cognitive decline is likely more pronounced among older adults (ß = -1.19; 95%CI: -1.42 to -0.96) than the middle-aged population. Moreover, the cognitive ability of rural residents (ß = -1.11; 95%CI: -1.49 to -0.73) and women (ß = -2.05; 95%CI: -2.29 to -1.81) is negatively associated with IAP exposure. Older adults with no reading habits (ß = -6.28; 95%CI: -6.72; to -5.85) and physical inactivity (ß = -0.96; 95%CI: -1.22 to -0.70) had a sign of notable decline in cognitive ability. CONCLUSIONS: Findings revealed that cognitive function is negatively associated with IAP, demanding a deep intervention plan to minimize the detrimental effect.

18.
Pediatr Neonatol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38692947

RESUMO

BACKGROUND: A newborn's birth weight ≥4000 g is defined as fetal macrosomia, which is recognized as a reproductive and serious child health concern. OBJECTIVES: Our study aims to reveal existence of any connection between maternal factors and newborn sex in giving birth to newborn ≥4000 g in an Indian context. METHODS: Data were drawn from the fifth round of National Family Health Survey (NFHS-5). A cross-sectional observational study was carried out with a total of 152,827 children born to women in reproductive age group (15-49) who had most recent live birth in the five years preceding the survey. Descriptive analyses, cross-tabulation, test of association and multivariate logistic regression analyses were performed. RESULTS: In India, the prevalence of macrosomia was found in 3.8% of the total study participants. Considering newborn characteristics, fetal macrosomia was more prevalent among male neonates than female (AOR: 0.730; 95% CI: 0.687-0.775). Regarding maternal characteristics, overweight (AOR: 1.468; 95% CI: 2.042-2.559) and obese (AOR: 2.764; 95% CI: 2.394-3.192) motherswith gestational diabetes (AOR: 1.731, 95% CI: 1.385-2.164) and hypertension (AOR: 1.288, 95% CI: 1.116-1.488) were more likely to giving birth of macrosomic babies. Multiparous mothers (AOR: 1.207, 95% CI: 1.128-1.293) and women who did not undergo proper antenatal care (ANC) follow up had also greater risk of developing fetal macrosomia. Muslim women (AOR: 1.223, 95% CI: 1.119-1.338), and women belonging to a tribe (AOR: 1.476, 95% CI: 0.922-2.361) were significantly associated with the risk of having newborn ≥4000 g. CONCLUSION: Emphasis should be given on counseling for mothers for desired weight management before and during pregnancy, gestational diabetes and hypertension screening, physical activity during pregnancy, adequate ANC follow up and balanced dietary intake among pregnant women.

19.
Chem Commun (Camb) ; 60(56): 7148-7151, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38860653

RESUMO

We report the use of DOTA as a chelator for titanium. The resulting complex is fully characterised and in vitro stability studies reveal its high kinetic inertness against transmetallation and transchelation. The radiolabeling of DOTA with 45Ti, via a guaiacol-based liquid-liquid extraction method, leads to a high radiochemical conversion up to 98%.


Assuntos
Compostos Heterocíclicos com 1 Anel , Compostos Radiofarmacêuticos , Titânio , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/síntese química , Titânio/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Compostos Aza/química , Compostos Aza/síntese química , Quelantes/química , Quelantes/síntese química , Estrutura Molecular
20.
Proc Natl Acad Sci U S A ; 107(49): 21146-51, 2010 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-21078990

RESUMO

Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and multidimensional liquid chromatography, in combination with tandem mass spectrometry, revealed 33 proteins that were increased and 21 proteins that were decreased in SOD1(G93A) rat spinal cord mitochondria compared with SOD1(WT) spinal cord mitochondria. Analysis of this group of proteins revealed a higher-than-expected proportion involved in complex I and protein import pathways. Direct import assays revealed a 30% decrease in protein import only in spinal cord mitochondria, despite an increase in the mitochondrial import components TOM20, TOM22, and TOM40. Recombinant SOD1(G93A) or SOD1(G85R), but not SOD1(WT) or a Parkinson's disease-causing, misfolded α-synuclein(E46K) mutant, decreased protein import by >50% in nontransgenic mitochondria from spinal cord, but not from liver. Thus, altered mitochondrial protein content accompanied by selective decreases in protein import into spinal cord mitochondria comprises part of the mitochondrial damage arising from mutant SOD1.


Assuntos
Esclerose Lateral Amiotrófica/enzimologia , Proteínas Mitocondriais/análise , Mutação , Superóxido Dismutase/fisiologia , Esclerose Lateral Amiotrófica/genética , Animais , Fígado/química , Fígado/ultraestrutura , Mitocôndrias/metabolismo , Transporte Proteico , Proteômica/métodos , Ratos , Medula Espinal/química , Medula Espinal/ultraestrutura , Superóxido Dismutase/genética , Superóxido Dismutase-1
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