Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.362
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
RNA ; 30(9): 1151-1163, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38834242

RESUMO

The 3' end of the hepatitis C virus genome is terminated by a highly conserved, 98 nt sequence called 3'X. This untranslated structural element is thought to regulate several essential RNA-dependent processes associated with infection. 3'X has two proposed conformations comprised of either three or two stem-loop structures that result from the different base-pairing interactions within the first 55 nt. Here, we used single-molecule Förster resonance energy transfer spectroscopy to monitor the conformational status of fluorescently labeled constructs that isolate this region of the RNA (3'X55). We observed that 3'X55 can adopt both proposed conformations and the relative abundance of them can be modulated by either solution conditions or nucleotide deletions. Furthermore, interconversion between the two conformations takes place over the course of several hours. The simultaneous existence of two slowly interconverting conformations may help prime individual copies of the viral genome for either viral protein or RNA synthesis, thereby minimizing conflicts between these two competing processes.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Hepacivirus , Conformação de Ácido Nucleico , RNA Viral , Hepacivirus/genética , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo , Pareamento de Bases , Regiões 3' não Traduzidas , Genoma Viral , Sequência de Bases
2.
Proc Natl Acad Sci U S A ; 117(24): 13490-13498, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32461356

RESUMO

The voltage-gated Hv1 proton channel is a ubiquitous membrane protein that has roles in a variety of cellular processes, including proton extrusion, pH regulation, production of reactive oxygen species, proliferation of cancer cells, and increased brain damage during ischemic stroke. A crystal structure of an Hv1 construct in a putative closed state has been reported, and structural models for the channel open state have been proposed, but a complete characterization of the Hv1 conformational dynamics under an applied membrane potential has been elusive. We report structural models of the Hv1 voltage-sensing domain (VSD), both in a hyperpolarized state and a depolarized state resulting from voltage-dependent conformational changes during a 10-µs-timescale atomistic molecular dynamics simulation in an explicit membrane environment. In response to a depolarizing membrane potential, the S4 helix undergoes an outward displacement, leading to changes in the VSD internal salt-bridge network, resulting in a reshaping of the permeation pathway and a significant increase in hydrogen bond connectivity throughout the channel. The total gating charge displacement associated with this transition is consistent with experimental estimates. Molecular docking calculations confirm the proposed mechanism for the inhibitory action of 2-guanidinobenzimidazole (2GBI) derived from electrophysiological measurements and mutagenesis. The depolarized structural model is also consistent with the formation of a metal bridge between residues located in the core of the VSD. Taken together, our results suggest that these structural models are representative of the closed and open states of the Hv1 channel.


Assuntos
Ativação do Canal Iônico , Canais Iônicos/química , Canais Iônicos/metabolismo , Cristalografia por Raios X , Guanidinas/metabolismo , Humanos , Ligação de Hidrogênio , Canais Iônicos/genética , Potenciais da Membrana , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação , Conformação Proteica , Prótons
3.
Rep Prog Phys ; 85(1)2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34814127

RESUMO

Positron emission particle tracking (PEPT) is a technique which allows the high-resolution, three-dimensional imaging of particulate and multiphase systems, including systems which are large, dense, and/or optically opaque, and thus difficult to study using other methodologies. In this work, we bring together researchers from the world's foremost PEPT facilities not only to give a balanced and detailed overview and review of the technique but, for the first time, provide a rigorous, direct, quantitative assessment of the relative strengths and weaknesses of all contemporary PEPT methodologies. We provide detailed explanations of the methodologies explored, including also interactive code examples allowing the reader to actively explore, edit and apply the algorithms discussed. The suite of benchmarking tests performed and described within the document is made available in an open-source repository for future researchers.


Assuntos
Elétrons , Tomografia por Emissão de Pósitrons , Algoritmos , Imageamento Tridimensional , Tomografia por Emissão de Pósitrons/métodos
4.
J Dairy Sci ; 105(2): 1131-1149, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34955268

RESUMO

Milk yield and composition are modified by level and chemical characteristics of dietary energy and protein. Those factors determine nutrient availability from a given diet, and once absorbed, they interact with the endocrine system and together determine availability of metabolites to the mammary gland. Four multiparous dairy cows in early lactation and subsequently in late lactation were fed 2 diets for 28 d in a changeover design that provided, within the same stage of lactation, similar amounts of rumen fermentable feed with either high (HS) or low starch (LS). All diets had similar dietary crude protein (15.5% dry matter) and rumen-undegradable protein (∼40% of crude protein) content. Profiles of AA were calculated to be similar to that of casein. On d 28, [1-13C] Leu was infused into one jugular vein with blood samples taken at 0, 2, 4, 6, and 8 h, and cows milked at 0, 2, 4, 5, 6, 7, and 8 h from start of infusion. Isotopic enrichments of plasma Leu, keto-isocaproic acid, and milk casein were determined for calculation of Leu kinetics. Data were subjected to ANOVA using the MIXED procedure of SAS (SAS Institute Inc.), with time as repeated factor and cow as the random effect. Dry matter intake within each stage of lactation was similar between groups. Feeding LS resulted in lower blood glucose and greater ratio of bovine somatotropin to insulin. This response was associated with greater blood concentrations of nonesterified fatty acids and ß-hydroxybutyrate, which might have contributed to greater milk fat content in LS-fed cows. Except for His, average concentrations of all AA in blood were higher in late than early lactation. Diet did not alter average plasma concentrations of AA. However, for most of the essential AA (particularly branched-chain), the HS diet led to a marked decrease in concentrations after the forage meal, resulting in significant differences between dietary groups in early lactation. In early-lactating cows fed HS, a greater reduction in plasma concentrations at 8 h relative to pre-feeding values (time zero) was observed for Met, Lys, and His, resulting in decreases of 27.9%, 33.6%, and 38.5%, respectively. A higher bovine somatotropin/insulin ratio in early lactation and in cows fed LS could possibly have led to greater breakdown and, consequently, higher AA flux from peripheral tissues. In LS-fed cows, higher mobilization of body fat and protein was confirmed by the greater body weight loss in both stages of lactation. Higher irreversible loss of [1-13C] Leu in early lactation suggested lower protein retention in peripheral tissues during early compared with late lactation. Milk yield, protein output, and composition were similar between groups at both stages of lactation, whereas milk coagulation was faster (lower curd firming rate) and with higher curd firmness in response to feeding HS in late lactation. Overall, data indicated that rate of carbohydrate fermentability in the rumen can modify the availability of metabolites to the mammary gland and consequently modify milk protein coagulation.


Assuntos
Aminoácidos , Lactação , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Feminino , Leite , Rúmen , Amido
5.
Nature ; 518(7540): 525-8, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25686601

RESUMO

The Martian limb (that is, the observed 'edge' of the planet) represents a unique window into the complex atmospheric phenomena occurring there. Clouds of ice crystals (CO2 ice or H2O ice) have been observed numerous times by spacecraft and ground-based telescopes, showing that clouds are typically layered and always confined below an altitude of 100 kilometres; suspended dust has also been detected at altitudes up to 60 kilometres during major dust storms. Highly concentrated and localized patches of auroral emission controlled by magnetic field anomalies in the crust have been observed at an altitude of 130 kilometres. Here we report the occurrence in March and April 2012 of two bright, extremely high-altitude plumes at the Martian terminator (the day-night boundary) at 200 to 250 kilometres or more above the surface, and thus well into the ionosphere and the exosphere. They were spotted at a longitude of about 195° west, a latitude of about -45° (at Terra Cimmeria), extended about 500 to 1,000 kilometres in both the north-south and east-west directions, and lasted for about 10 days. The features exhibited day-to-day variability, and were seen at the morning terminator but not at the evening limb, which indicates rapid evolution in less than 10 hours and a cyclic behaviour. We used photometric measurements to explore two possible scenarios and investigate their nature. For particles reflecting solar radiation, clouds of CO2-ice or H2O-ice particles with an effective radius of 0.1 micrometres are favoured over dust. Alternatively, the plume could arise from auroral emission, of a brightness more than 1,000 times that of the Earth's aurora, over a region with a strong magnetic anomaly where aurorae have previously been detected. Importantly, both explanations defy our current understanding of Mars' upper atmosphere.

6.
J Comput Assist Tomogr ; 45(3): 374-382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33797439

RESUMO

ABSTRACT: Ectopic pregnancy (EP) is a known cause of maternal mortality and may be misdiagnosed in up to 50% of pregnant female individuals (Ann Emerg Med. 1996;28(1):10-17). Magnetic resonance imaging, with its superior soft tissue resolution, is a valuable alternative diagnostic modality to diagnose EP when transvaginal ultrasound results are inconclusive. Although an extrauterine gestational sac is the most specific finding, there are other key MRI findings that can aid in diagnosing EP. As availability of MRI access in the emergency department setting increases across the nation, its utility in women with a positive pregnancy test has also increased. Specific MRI findings that are diagnostic of EP include absence of intrauterine pregnancy, adnexal mass separate from the ovary, and hemoperitoneum. In addition, intrauterine ectopic locations, especially intramural, cornual, and cervical pregnancies, can be diagnosed with increased accuracy with the help of MRI. Magnetic resonance imaging is also useful in excluding potential mimics of EP, including adnexal cysts, ovarian neoplasms, and fibroids. In summary, providing an accurate diagnosis and determining the precise location of an EP, which is supported by the use of MRI, is imperative for guiding a patient's treatment to prevent a potentially fatal outcome.


Assuntos
Imageamento por Ressonância Magnética/métodos , Gravidez Ectópica/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Gravidez , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal , Adulto Jovem
7.
J Pharmacol Exp Ther ; 375(2): 296-307, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32958629

RESUMO

Infarct expansion can occur after myocardial infarction (MI), which leads to adverse left ventricular (LV) remodeling and failure. An imbalance between matrix metalloproteinase (MMP) induction and tissue inhibitors of MMPs (TIMPs) can accelerate this process. Past studies have shown different biologic effects of TIMP-3, which may depend upon specific domains within the TIMP-3 molecule. This study tested the hypothesis that differential effects of direct myocardial injections of either a full-length recombinant TIMP-3 (F-TIMP-3) or a truncated form encompassing the N-terminal region (N-TIMP-3) could be identified post-MI. MI was induced in pigs that were randomized for MI injections (30 mg) and received targeted injections within the MI region of F-TIMP-3 (n = 8), N-TIMP-3 (n = 9), or saline injection (MI-only, n = 11). At 14 days post-MI, LV ejection fraction fell post-MI but remained higher in both TIMP-3 groups. Tumor necrosis factor and interleukin-10 mRNA increased by over 10-fold in the MI-only and N-TIMP-3 groups but were reduced with F-TIMP-3 at this post-MI time point. Direct MI injection of either a full-length or truncated form of TIMP-3 is sufficient to favorably alter the course of post-MI remodeling. The functional and differential relevance of TIMP-3 domains has been established in vivo since the TIMP-3 constructs demonstrated different MMP/cytokine expression profiles. These translational studies identify a unique and more specific therapeutic strategy to alter the course of LV remodeling and dysfunction after MI. SIGNIFICANCE STATEMENT: Using different formulations of tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), when injected into the myocardial infarction (MI) region, slowed the progression of indices of left ventricular (LV) failure, suggesting that the N terminus of TIMP-3 is sufficient to attenuate early adverse functional events post-MI. Injections of full-length recombinant TIMP-3, but not of the N-terminal region of TIMP-3, reduced relative indices of inflammation at the mRNA level, suggesting that the C-terminal region affects other biological pathways. These unique proof-of-concept studies demonstrate the feasibility of using recombinant small molecules to selectively interrupt adverse LV remodeling post-MI.


Assuntos
Infarto do Miocárdio/patologia , Fragmentos de Peptídeos/farmacologia , Inibidor Tecidual de Metaloproteinase-3/química , Remodelação Ventricular/efeitos dos fármacos , Sequência de Aminoácidos , Colágeno/genética , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções , Metaloproteinases da Matriz/genética , Fragmentos de Peptídeos/química , Domínios Proteicos , RNA Mensageiro/genética , Inibidor Tecidual de Metaloproteinase-3/genética
8.
Oecologia ; 191(3): 531-540, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31535256

RESUMO

There are several hypotheses that could explain territory size in mammals, including the resource dispersion hypothesis (RDH), the intruder pressure hypothesis (IPH), and the intraguild predation hypothesis (IGPH). In this study, we tested predictions of these three hypotheses regarding territories of 19 packs of endangered African wild dogs (Lycaon pictus) over 2 years in the Kruger National Park, South Africa. If territory size was supported by the RDH, then we would observe (1) wild dog territories would be larger when resource patches were more dispersed, (2) pack sizes would be larger when resource patches were rich, and (3) pack size would not affect territory size. If supported by the IPH, then we would observe (4) larger territories would experience less intrusions, and (5) there would be an increase in territory overlap in areas of low resource dispersion. Finally, if supported by the IGPH, we would observe (6) territories would be larger in areas of higher lion (Panthera leo) density, as evidence of a spatial avoidance strategy. We found that the IGPH was fully supported (6), the IPH half supported (5), and the RDH partially supported (1 and 3), where we found spatial partitioning of wild dogs with lions, potentially mediated by resources and territory overlap with conspecifics. Ultimately, our results show that subordinate carnivores must balance a trade-off between dominant interspecific competitors and conspecifics to successfully coexist in areas with dominant carnivores.


Assuntos
Carnívoros , Leões , Animais , Ecossistema , Comportamento Predatório , África do Sul
9.
J Phys Chem A ; 123(32): 6886-6896, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31322887

RESUMO

Photodissociation of vibrationally and electronically excited sulfur dimer molecules (S2) has been studied in a combined experimental and computational quantum chemistry study in order to characterize bound-continuum transitions. Ab initio quantum chemistry calculations are carried out to predict the potential energy curves, spin-orbit coupling, transition moments, and bound-continuum spectra of S2 for comparison with the experimental data. The experiment uses velocity map imaging to measure S-atom production following S2 photoexcitation in the ultraviolet region (320-205 nm). A pulsed electric discharge in H2S produces ground-state S2 X3Σg-(v = 0-15) as well as electronically excited singlet sulfur and b1Σg+(v = 0, 1), and evidence is presented for the production and photodissociation of S2 a1Δg. In a previous paper, we reported threshold photodissociation of S2X3Σg-(v = 0) in the 282-266 nm region. In the present study, S(3PJ) fine structure branching and angular distributions for photodissociation of S2 (X3Σg-(v = 0), a1Δg and b1Σg+) via the B″3Πu, B3Σu- and 11Πu excited states are reported. In addition, photodissociation of the X3Σg-(v = 0) state of S2 to the second dissociation limit producing S(3P2) + S(1D) is characterized. The present results on S2 photodynamics are compared to those of the well-studied electronically isovalent O2 molecule.

10.
J Biol Chem ; 292(11): 4623-4637, 2017 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-28057757

RESUMO

The activity of the reversible decarboxylase enzyme Fdc1 is dependent on prenylated FMN (prFMN), a recently discovered cofactor. The oxidized prFMN supports a 1,3-dipolar cycloaddition mechanism that underpins reversible decarboxylation. Fdc1 is a distinct member of the UbiD family of enzymes, with the canonical UbiD catalyzing the (de)carboxylation of para-hydroxybenzoic acid-type substrates. Here we show that the Escherichia coli UbiD enzyme, which is implicated in ubiquinone biosynthesis, cannot be isolated in an active holoenzyme form despite the fact active holoFdc1 is readily obtained. Formation of holoUbiD requires reconstitution in vitro of the apoUbiD with reduced prFMN. Furthermore, although the Fdc1 apoenzyme can be readily reconstituted and activated, in vitro oxidation to the mature prFMN cofactor stalls at formation of a radical prFMN species in holoUbiD. Further oxidative maturation in vitro occurs only at alkaline pH, suggesting a proton-coupled electron transfer precedes formation of the fully oxidized prFMN. Crystal structures of holoUbiD reveal a relatively open active site potentially occluded from solvent through domain motion. The presence of a prFMN sulfite-adduct in one of the UbiD crystal structures confirms oxidative maturation does occur at ambient pH on a slow time scale. Activity could not be detected for a range of putative para-hydroxybenzoic acid substrates tested. However, the lack of an obvious hydrophobic binding pocket for the octaprenyl tail of the proposed ubiquinone precursor substrate does suggest UbiD might act on a non-prenylated precursor. Our data reveals an unexpected variation occurs in domain mobility, prFMN binding, and maturation by the UbiD enzyme family.


Assuntos
Carboxiliases/metabolismo , Escherichia coli/metabolismo , Mononucleotídeo de Flavina/metabolismo , Ubiquinona/metabolismo , Sítios de Ligação , Carboxiliases/química , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons , Escherichia coli/química , Modelos Moleculares , Oxirredução , Prenilação , Domínios Proteicos , Ubiquinona/química
11.
Mol Ecol ; 27(24): 4978-4990, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30447117

RESUMO

Animal species are able to acquire new genetic material via hybridization and subsequent introgression. However, little is known about how foreign genomic material is incorporated into a population over time and what genes are susceptible to introgression. Here, we follow the closely related mosquito sister species Anopheles coluzzii and Anopheles gambiae in a sympatric natural population in Mali at multiple time points spanning a period of 25 years. During this period, we observed the temporary breakdown of mating barriers, which allowed us to explore the fate of alleles that crossed the species boundary in a natural population. Whole genome sequencing of 74 individuals revealed introgression within only 34 genes (0.26% of total genes) from A. gambiae to A. coluzzii, the majority contained within a 4 Mb region on the 2L chromosome which includes the insecticide resistance gene (AGAP004707). We designed a genotyping assay to follow 25 of the 34 introgressed alleles over time and found that all A. gambiae alleles, except four, reached a frequency of 50% in the A. coluzzii population within 4 years (~50 generations) and increased to ~80% within 6 years (~75 generations). However, the frequency of all introgressed alleles, except three, decreased to ~60% in 2016. This suggests an ongoing process of purifying selection in the population against DNA of foreign ancestry, except for alleles that are under positive selection, resulting in a complex genomic landscape. This study shows that stable introgression is limited to only specific genes even within closely related species.


Assuntos
Anopheles/genética , Hibridização Genética , Resistência a Inseticidas/genética , Seleção Genética , Alelos , Animais , Fluxo Gênico , Genes de Insetos , Genética Populacional , Genótipo , Mali , Polimorfismo de Nucleotídeo Único , Simpatria
12.
Nature ; 487(7408): 482-5, 2012 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-22837004

RESUMO

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , Ácidos Hidroxâmicos/farmacologia , Latência Viral/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/sangue , HIV-1/genética , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/farmacologia , Histonas/efeitos dos fármacos , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/efeitos adversos , Provírus/efeitos dos fármacos , Provírus/genética , Provírus/crescimento & desenvolvimento , RNA Viral/biossíntese , RNA Viral/sangue , Medição de Risco , Regulação para Cima/efeitos dos fármacos , Viremia/tratamento farmacológico , Viremia/virologia , Vorinostat
13.
Nano Lett ; 17(3): 1642-1647, 2017 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-28140593

RESUMO

Combined scanning tunneling microscopy, spectroscopy, and local barrier height (LBH) studies show that low-temperature-cleaved optimally doped Ba(Fe1-xCox)2As2 crystals with x = 0.06, with Tc = 22 K, have complicated morphologies. Although the cleavage surface and hence the morphologies are variable, the superconducting gap maps show the same gap widths and nanometer size inhomogeneities irrelevant to the morphology. Based on the spectroscopy and LBH maps, the bright patches and dark stripes in the morphologies are identified as Ba- and As-dominated surface terminations, respectively. Magnetic impurities, possibly due to Co or Fe atoms, are believed to create local in-gap state and, in addition, suppress the superconducting coherence peaks. This study will clarify the confusion on the cleavage surface terminations of the Fe-based superconductors and its relation with the electronic structures.

14.
Hum Brain Mapp ; 38(2): 855-868, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27774721

RESUMO

Childhood maltreatment is associated with alterations in neural architecture that potentially put these children at increased risk for psychopathology. Alterations in white matter (WM) tracts have been reported, however no study to date has investigated WM connectivity in brain networks in maltreated children to quantify global and local abnormalities through graph theoretical analyses of DTI data. We aimed for a multilevel investigation examining the DTI-based structural connectome and its associations with basal cortisol levels of 25 children with documented maltreatment experiences before age 3, and 24 matched controls (age: 10.6 ± 1.75 years). On the global and lobar level, maltreated children showed significant reductions in global connectivity strength, local connectivity and increased path length, suggesting deviations from the small-world network architecture previously associated with psychopathology. Reductions in global connectivity were associated with placement instability, attenuated cortisol secretion and higher levels of internalizing and externalizing behaviours. Regional measures revealed lower connectivity strength especially in regions within the ventromedial prefrontal cortex (vMPFC) in maltreated children. These findings show that childhood maltreatment is associated with systemic global neurodevelopmental alterations in WM networks next to regional alterations in areas involved in the regulation of affect. These alterations in WM organization could underlie global functional deficits and multi-symptom patterns frequently observed in children with maltreatment experiences. Hum Brain Mapp 38:855-868, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Encéfalo/diagnóstico por imagem , Maus-Tratos Infantis , Imagem de Tensor de Difusão , Transtornos Mentais/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Mapeamento Encefálico , Criança , Maus-Tratos Infantis/psicologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Modelos Neurológicos , Fibras Nervosas Mielinizadas/fisiologia , Escalas de Graduação Psiquiátrica
15.
Cell Tissue Res ; 370(3): 513-521, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28948356

RESUMO

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS + semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P ≤ 0.0001) and placental weight (1.13-fold, P ≤ 0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P ≤ 0.05), JNK (2.4-fold, P ≤ 0.05) and p38 (2.1-fold, P ≤ 0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P ≤ 0.05) and IL-1ß (1.03-fold, P ≤ 0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P < 0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.


Assuntos
Retardo do Crescimento Fetal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Fumaça/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Trofoblastos/efeitos dos fármacos , Animais , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Phys Rev Lett ; 119(13): 132502, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29341725

RESUMO

Excited states in certain atomic nuclei possess an unusual structure, where the dominant degrees of freedom are those of α clusters rather than individual nucleons. It has been proposed that the diffuse 3α system of the ^{12}C Hoyle state may behave like a Bose-Einstein condensate, where the α clusters maintain their bosonic identities. By measuring the decay of the Hoyle state into three α particles, we obtained an upper limit for the rare direct 3α decay branch of 0.047%. This value is now at a level comparable with theoretical predictions and could be a sensitive probe of the structure of this state.

17.
Nature ; 475(7354): 71-4, 2011 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-21734704

RESUMO

Convective storms occur regularly in Saturn's atmosphere. Huge storms known as Great White Spots, which are ten times larger than the regular storms, are rarer and occur about once per Saturnian year (29.5 Earth years). Current models propose that the outbreak of a Great White Spot is due to moist convection induced by water. However, the generation of the global disturbance and its effect on Saturn's permanent winds have hitherto been unconstrained by data, because there was insufficient spatial resolution and temporal sampling to infer the dynamics of Saturn's weather layer (the layer in the troposphere where the cloud forms). Theoretically, it has been suggested that this phenomenon is seasonally controlled. Here we report observations of a storm at northern latitudes in the peak of a weak westward jet during the beginning of northern springtime, in accord with the seasonal cycle but earlier than expected. The storm head moved faster than the jet, was active during the two-month observation period, and triggered a planetary-scale disturbance that circled Saturn but did not significantly alter the ambient zonal winds. Numerical simulations of the phenomenon show that, as on Jupiter, Saturn's winds extend without decay deep down into the weather layer, at least to the water-cloud base at pressures of 10-12 bar, which is much deeper than solar radiation penetrates.

18.
J Chem Phys ; 147(1): 013909, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28688421

RESUMO

We investigate the laser ionization process taking place when the CO molecule is exposed to vacuum ultraviolet (VUV) radiation resonant with the CO A1Π(v = 0) ← X1Σ+(v = 0) transition around 154 nm, along with the ultraviolet (UV) and visible (Red) radiation used to generate VUV by four-wave difference-frequency mixing. By measuring the CO+ ion recoil and a room temperature gas spectrum, it is possible to assign the ionization process as 1 + 1' + 1'' REMPI where the one-photon steps refer to the VUV, UV, and Red radiation, respectively. Resonance enhanced ionization of rotational states around J = 12 arise due to the overlap of the fixed wavelength UV (∼250 nm) with the R band-head of a transition assigned to CO E1Π(v = 6) ← A1Π(v = 0) with a term value of 104 787.5 cm-1. The REMPI process is efficient and polarization sensitive and should be useful in a wide range of studies involving nascent CO.

19.
J Chem Phys ; 147(1): 013906, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28688406

RESUMO

Pathways for formation of C+ and O+ ions when applying (2 + 1) resonance enhanced multiphoton ionization (REMPI) of CO via the B1Σ+ and E1Π electronic states are characterized with the velocity map imaging technique. By employing an unskimmed pulsed valve, it was possible to obtain sharp images for a wide range of initial CO J-states. Most of the atomic ion production pathways could be assigned as one- or two-photon dissociation of a series of vibrational levels of the CO+ X2Σ+ and A2Π states. Large enhancements in dissociation of particular CO+ vibrational states in these progressions could be accurately assigned to accidental resonances of the REMPI laser with CO+ X2Σ+-B2Σ+ transitions.

20.
BMC Palliat Care ; 16(1): 33, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28521799

RESUMO

BACKGROUND: The purpose of this study was to compare the differences across occupational groups related to their end-of-life care-specific educational needs and reported intensity of interprofessional collaboration in long-term care (LTC) homes. METHODS: A cross-sectional survey, based on two questionnaires, was administered at four LTC homes in Ontario, Canada using a modified Dilman's approach. The first questionnaire, End of Life Professional Caregiver Survey, included three domains: patients and family-centered communication, cultural and ethical values, effective care delivery. The Intensity of Interprofessional Collaboration Scale included two subscales: care sharing activities, and interprofessional coordination. In total, 697 LTC staff were given surveys, including personal support workers, support staff (housekeeping, kitchen, recreation, laundry, dietician aids, office staff), and registered staff (licensed nurses, physiotherapists, social workers, pharmacists, physicians). RESULTS: A total of 317 participants completed the survey (126 personal support workers, 109 support staff, 82 registered staff) for a response rate of 45%. Significant differences emerged among occupational groups across all scales and subscales. Specifically, support staff rated their comfort of working with dying patients significantly lower than both nurses and PSWs. Support staff also reported significantly lower ratings of care sharing activities and interprofessional coordination compared to both registered staff and personal support workers. CONCLUSIONS: These study findings suggest there are differing educational needs and sense of interprofessional collaboration among LTC staff, specific to discipline group. Both the personal support workers and support staff groups appeared to have higher needs for education; support staff also reported higher needs related to integration on the interdisciplinary team. Efforts to build capacity within support staff related to working with dying residents and their families are needed. Optimal palliative care may require resources to increase the availability of support for all staff involved in the care of patients.


Assuntos
Avaliação das Necessidades , Ocupações , Cuidados Paliativos/métodos , Educação de Pacientes como Assunto/métodos , Adulto , Estudos Transversais , Feminino , Humanos , Relações Interprofissionais , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Ontário , Psicometria/instrumentação , Psicometria/métodos , Inquéritos e Questionários , Recursos Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA