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1.
Nano Lett ; 24(1): 215-221, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38117702

RESUMO

Closing the band gap of a semiconductor into a semimetallic state gives a powerful potential route to tune the electronic energy gains that drive collective phases like charge density waves (CDWs) and excitonic insulator states. We explore this approach for the controversial CDW material monolayer (ML) TiSe2 by engineering its narrow band gap to the semimetallic limit of ML-TiTe2. Using molecular beam epitaxy, we demonstrate the growth of ML-TiTe2xSe2(1-x) alloys across the entire compositional range and unveil how the (2 × 2) CDW instability evolves through the normal state semiconductor-semimetal transition via in situ angle-resolved photoemission spectroscopy. Through model electronic structure calculations, we identify how this tunes the relative strength of excitonic and Peierls-like coupling, demonstrating band gap engineering as a powerful method for controlling the microscopic mechanisms underpinning the formation of collective states in two-dimensional materials.

2.
Phys Rev Lett ; 133(1): 016401, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39042805

RESUMO

The magnetic skyrmions generated in a centrosymmetric crystal were recently first discovered in Gd_{2}PdSi_{3}. In light of this, we observe the electronic structure by angle-resolved photoemission spectroscopy and unveil its direct relationship with the magnetism in this compound. The Fermi surface and band dispersions are demonstrated to have a good agreement with the density functional theory calculations carried out with careful consideration of the crystal superstructure. Most importantly, we find that the three-dimensional Fermi surface has extended nesting which matches well the q vector of the magnetic order detected by recent scattering measurements. The consistency we find among angle-resolved photoemission spectroscopy, density functional theory, and the scattering measurements suggests the Ruderman-Kittel-Kasuya-Yosida interaction involving itinerant electrons to be the formation mechanism of skyrmions in Gd_{2}PdSi_{3}.

3.
Br J Neurosurg ; : 1-8, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584489

RESUMO

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

4.
Nano Lett ; 23(11): 5201-5208, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37235208

RESUMO

Diverse emergent correlated electron phenomena have been observed in twisted-graphene layers. Many electronic structure predictions have been reported exploring this new field, but with few momentum-resolved electronic structure measurements to test them. We use angle-resolved photoemission spectroscopy to study the twist-dependent (1° < θ < 8°) band structure of twisted-bilayer, monolayer-on-bilayer, and double-bilayer graphene (tDBG). Direct comparison is made between experiment and theory, using a hybrid k·p model for interlayer coupling. Quantitative agreement is found across twist angles, stacking geometries, and back-gate voltages, validating the models and revealing field-induced gaps in twisted graphenes. However, for tDBG at θ = 1.5 ± 0.2°, close to the magic angle θ = 1.3°, a flat band is found near the Fermi level with measured bandwidth Ew = 31 ± 5 meV. An analysis of the gap between the flat band and the next valence band shows deviations between experiment (Δh = 46 ± 5 meV) and theory (Δh = 5 meV), indicative of lattice relaxation in this regime.

5.
Nano Lett ; 23(3): 1068-1076, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36637381

RESUMO

The integration of metallic contacts with two-dimensional (2D) semiconductors is routinely required for the fabrication of nanoscale devices. However, nanometer-scale variations in the 2D/metal interface can drastically alter the local optoelectronic properties. Here, we map local excitonic changes of the 2D semiconductor MoS2 in contact with Au. We utilize a suspended and epitaxially grown 2D/metal platform that allows correlated electron energy-loss spectroscopy (EELS) and angle resolved photoelectron spectroscopy (nanoARPES) mapping. Spatial localization of MoS2 excitons uncovers an additional EELS peak related to the MoS2/Au interface. NanoARPES measurements indicate that Au-S hybridization decreases substantially with distance from the 2D/metal interface, suggesting that the observed EELS peak arises due to dielectric screening of the excitonic Coulomb interaction. Our results suggest that increasing the van der Waals distance could optimize excitonic spectra of mixed-dimensional 2D/3D interfaces and highlight opportunities for Coulomb engineering of exciton energies by the local dielectric environment or moiré engineering.

6.
Nano Lett ; 23(17): 8035-8042, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37638737

RESUMO

Engineering surfaces and interfaces of materials promises great potential in the field of heterostructures and quantum matter designers, with the opportunity to drive new many-body phases that are absent in the bulk compounds. Here, we focus on the magnetic Weyl kagome system Co3Sn2S2 and show how for the terminations of different samples the Weyl points connect differently, still preserving the bulk-boundary correspondence. Scanning tunneling microscopy has suggested such a scenario indirectly, and here, we probe the Fermiology of Co3Sn2S2 directly, by linking it to its real space surface distribution. By combining micro-ARPES and first-principles calculations, we measure the energy-momentum spectra and the Fermi surfaces of Co3Sn2S2 for different surface terminations and show the existence of topological features depending on the top-layer electronic environment. Our work helps to define a route for controlling bulk-derived topological properties by means of surface electrostatic potentials, offering a methodology for using Weyl kagome metals in responsive magnetic spintronics.

7.
Gene Ther ; 30(5): 407-410, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35264741

RESUMO

Optimizing viral vectors and their properties will be important for improving the effectiveness and safety of clinical gene therapy. However, such research may generate dual-use insights relevant to the enhancement of pandemic pathogens. In particular, reliable and generalizable methods of immune evasion could increase viral fitness sufficient to cause a new pandemic. High potential for misuse is associated with (1) the development of universal genetic elements for immune modulation, (2) specific insights on capsid engineering for antibody evasion applicable to viruses with pandemic potential, and (3) the development of computational methods to inform capsid engineering. These risks may be mitigated by prioritizing non-viral delivery systems, pharmacological immune modulation methods, non-genetic vector surface modifications, and engineering methods specific to AAV and other viruses incapable of unassisted human-to-human transmission. We recommend that computational vector engineering and the publication of associated code and data be limited to AAV until a technical solution for preventing malicious access to viral engineering tools has been established.


Assuntos
Proteínas do Capsídeo , Vetores Genéticos , Humanos , Vetores Genéticos/genética , Proteínas do Capsídeo/genética , Capsídeo , Dependovirus/genética
8.
Phys Rev Lett ; 130(9): 096401, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930931

RESUMO

We report the evolution of the electronic structure at the surface of the layered perovskite Sr_{2}RuO_{4} under large in-plane uniaxial compression, leading to anisotropic B_{1g} strains of ϵ_{xx}-ϵ_{yy}=-0.9±0.1%. From angle-resolved photoemission, we show how this drives a sequence of Lifshitz transitions, reshaping the low-energy electronic structure and the rich spectrum of van Hove singularities that the surface layer of Sr_{2}RuO_{4} hosts. From comparison to tight-binding modeling, we find that the strain is accommodated predominantly by bond-length changes rather than modifications of octahedral tilt and rotation angles. Our study sheds new light on the nature of structural distortions at oxide surfaces, and how targeted control of these can be used to tune density of state singularities to the Fermi level, in turn paving the way to the possible realization of rich collective states at the Sr_{2}RuO_{4} surface.

9.
Proc Natl Acad Sci U S A ; 117(25): 14602-14608, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32522869

RESUMO

Bioinspired actuators with stimuli-responsive and deformable properties are being pursued in fields such as artificial tissues, medical devices and diagnostics, and intelligent biosensors. These applications require that actuator systems have biocompatibility, controlled deformability, biodegradability, mechanical durability, and stable reversibility. Herein, we report a bionic actuator system consisting of stimuli-responsive genetically engineered silk-elastin-like protein (SELP) hydrogels and wood-derived cellulose nanofibers (CNFs), which respond to temperature and ionic strength underwater by ecofriendly methods. Programmed site-selective actuation can be predicted and folded into three-dimensional (3D) origami-like shapes. The reversible deformation performance of the SELP/CNF actuators was quantified, and complex spatial transformations of multilayer actuators were demonstrated, including a biomimetic flower design with selective petal movements. Such actuators consisting entirely of biocompatible and biodegradable materials will offer an option toward constructing stimuli-responsive systems for in vivo biomedicine soft robotics and bionic research.


Assuntos
Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Biônica/métodos , Celulose/química , Elastina/química , Elastina/genética , Hidrogéis/química , Conformação Molecular , Nanofibras/química , Engenharia de Proteínas , Robótica/métodos , Seda/química , Seda/genética
10.
Proc Natl Acad Sci U S A ; 117(27): 15524-15529, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32576687

RESUMO

The interplay between spin-orbit coupling and structural inversion symmetry breaking in solids has generated much interest due to the nontrivial spin and magnetic textures which can result. Such studies are typically focused on systems where large atomic number elements lead to strong spin-orbit coupling, in turn rendering electronic correlations weak. In contrast, here we investigate the temperature-dependent electronic structure of [Formula: see text], a [Formula: see text] oxide metal for which both correlations and spin-orbit coupling are pronounced and in which octahedral tilts and rotations combine to mediate both global and local inversion symmetry-breaking polar distortions. Our angle-resolved photoemission measurements reveal the destruction of a large hole-like Fermi surface upon cooling through a coupled structural and spin-reorientation transition at 48 K, accompanied by a sudden onset of quasiparticle coherence. We demonstrate how these result from band hybridization mediated by a hidden Rashba-type spin-orbit coupling. This is enabled by the bulk structural distortions and unlocked when the spin reorients perpendicular to the local symmetry-breaking potential at the Ru sites. We argue that the electronic energy gain associated with the band hybridization is actually the key driver for the phase transition, reflecting a delicate interplay between spin-orbit coupling and strong electronic correlations and revealing a route to control magnetic ordering in solids.

11.
J Perianesth Nurs ; 38(1): 139-147, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35985972

RESUMO

PURPOSE: To evaluate the efficacy of ketamine in total knee and hip arthroplasty. DESIGN: Evidence-based review. METHODS: Following the guidelines outlined in the PRISMA statement, a comprehensive search was conducted using Google Scholar, PubMed, CINAHL, Cochrane Collaboration, and other grey literature. Only randomized controlled studies and pre-appraised evidence such as systematic review and meta-analysis examining the effects of ketamine in total knee and hip arthroplasty were included. The quality appraisal of the literature was conducted using the proposed algorithm described in the Johns Hopkins Nursing Evidence-Based Practice Evidence Level and Quality Guide. FINDINGS: Three systematic reviews and meta-analyses and 2 randomized controlled trials involving 1284 patients were included in this review. The use of ketamine reduced pain scores within the 24 hours after surgery. In addition, evidence suggests that patients who were treated with ketamine consumed fewer opioids 24 and 48 hours after surgery. Furthermore, ketamine reduced the incidence of postoperative nausea and vomiting with no effects on the incidence of hallucinations and central nervous system side effects. All studies included in the review were categorized as Level I and rated Grade A implying strong confidence in the true effects of ketamine in all outcome measures in the review. CONCLUSIONS: The current evidence demonstrates the viability of ketamine as a safe and effective alternative to opioids in the perioperative setting with major total joint arthroplasty surgery. Decreased pain scores and opioid consumption up to 48 hours into the postoperative period were observed in a number of the appraised articles.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Ketamina , Humanos , Analgésicos Opioides , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Articulação do Quadril , Ketamina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Support Care Cancer ; 30(1): 167-176, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34245360

RESUMO

PURPOSE: Sleep problems reported by hematological cancer patients are usually linked to higher levels of cancer-related fatigue. Although the awareness of sleep problems in solid cancer patients is rising, there has been less attention to the issue in hematological cancer patients. The present study assesses the differences in sleep by comparing physical activity and fatigue levels among hematological cancer patients during the onset of chemotherapy. Furthermore, it investigates the relationship between sleep, physical activity, and fatigue through mediation analysis. METHODS: The recruited sample consists of 58 newly diagnosed hematological cancer patients (47.1 ± 15.4 yrs; 51.7% males). Subjects completed questionnaires assessing sleep (PSQI), physical activity (visual analogue scale), fatigue (MFI-20), anxiety, depression (HADS), and quality of life (EORTC QLQ-C30) within two weeks from starting treatment. RESULTS: The sample reported more sleep problems in comparison to the German population norm. The classification as good (ca 25%) or bad sleepers (ca 75%) showed less frequent physical activity (p = .04), higher fatigue (p = .032), anxiety (p = .003), depression (p = .011) and pain (p = .011) in bad sleepers. The mediation analysis revealed significant indirect effects of sleep on fatigue through physical activity habits. CONCLUSIONS: This study highlights the combined action of sleep problems and physical activity on fatigue during the onset of induction chemotherapy. These two parameters could represent meaningful intervention targets to improve a patient's status during chemotherapy. TRIAL REGISTRATION: The study was registered on the WHO trial register (DRKS00007824).


Assuntos
Neoplasias Hematológicas , Transtornos do Sono-Vigília , Exercício Físico , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Qualidade de Vida , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia
13.
BMC Fam Pract ; 22(1): 239, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847874

RESUMO

BACKGROUND: Despite recent incentives through Medicare (Australia's universal health insurance scheme) to increase retinal screening rates in primary care, comprehensive diabetic retinopathy (DR) screening has not been reached in Australia. The current study aimed to identify key factors affecting the delivery of diabetic retinopathy (DR) screening in Australian general practices. METHODS: A descriptive qualitative study involving in-depth interviews was carried out from November 2019 to March 2020. Using purposive snowballing sampling, 15 general practitioners (GPs) were recruited from urban and rural general practices in New South Wales and Western Australia. A semi-structured interview guide was used to collect data from participants. All interviews were conducted over the phone by one facilitator, and each interview lasted up to 45 min. The Socio-Ecological Model was used to inform the content of the interview topic guides and subsequent data analysis. Recorded data were transcribed verbatim, and thematic analysis was conducted to identify and classify recurrent themes. RESULTS: Of 15 GPs interviewed, 13 were male doctors, and the mean age was 54.7 ± 15.5 years. Seven participants were practising in urban areas, while eight were practising in regional or remote areas. All participants had access to a direct ophthalmoscope, but none owned retinal cameras. None of the participants reported performing DR screening. Only three participants were aware of the Medicare Benefits Schedule (MBS) items 12,325 and 12,326 that allow GPs to bill for retinal screening. Seven themes, a combination of facilitators and barriers, emerged from interviews with the GPs. Despite the strong belief in their role in managing chronic diseases, barriers such as costs of retinal cameras, time constraints, lack of skills to make DR diagnosis, and unawareness of Medicare incentives for non-mydriatic retinal photography made it difficult to conduct DR screening in general practice. However, several enabling strategies to deliver DR screening within primary care include increasing GPs' access to continuing professional development, subsidising the cost of retinal cameras, and the need for a champion ace to take the responsibility of retinal photography. CONCLUSION: This study identified essential areas at the system level that require addressing to promote the broader implementation of DR screening, in particular, a nationwide awareness campaign to maximise the use of MBS items, improve GPs' competency, and subsidise costs of the retinal cameras for small and rural general practices.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Adulto , Idoso , Austrália , Retinopatia Diabética/diagnóstico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Atenção Primária à Saúde
14.
Proc Natl Acad Sci U S A ; 115(47): 11964-11969, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30301810

RESUMO

Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.


Assuntos
Histonas/química , Histonas/metabolismo , Animais , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/fisiologia , DNA/química , Proteínas de Ligação a DNA , Humanos , Espectroscopia de Ressonância Magnética , Conformação de Ácido Nucleico , Fosforilação , Ligação Proteica , Conformação Proteica , Processamento de Proteína Pós-Traducional
15.
Curr Top Microbiol Immunol ; 424: 1-20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31463536

RESUMO

Predicting which pathogen will confer the highest global catastrophic biological risk (GCBR) of a pandemic is a difficult task. Many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. In this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. This paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities.


Assuntos
Planejamento em Desastres/métodos , Monitoramento Epidemiológico , Microbiologia , Pandemias , Humanos , Medição de Risco
16.
Biochem J ; 476(7): 1121-1135, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30898848

RESUMO

Late embryogenesis abundant (LEA) proteins comprise a diverse family whose members play a key role in abiotic stress tolerance. As intrinsically disordered proteins, LEA proteins are highly hydrophilic and inherently stress tolerant. They have been shown to stabilise multiple client proteins under a variety of stresses, but current hypotheses do not fully explain how such broad range stabilisation is achieved. Here, using neutron reflection and surface tension experiments, we examine in detail the mechanism by which model LEA proteins, AavLEA1 and ERD10, protect the enzyme citrate synthase (CS) from aggregation during freeze-thaw. We find that a major contributing factor to CS aggregation is the formation of air bubbles during the freeze-thaw process. This greatly increases the air-water interfacial area, which is known to be detrimental to folded protein stability. Both model LEA proteins preferentially adsorb to this interface and compete with CS, thereby reducing surface-induced aggregation. This novel surface activity provides a general mechanism by which diverse members of the LEA protein family might function to provide aggregation protection that is not specific to the client protein.


Assuntos
Crioprotetores/química , Proteínas Intrinsicamente Desordenadas/química , Adsorção , Ar , Animais , Proteínas de Arabidopsis/química , Fenômenos Biofísicos , Citrato (si)-Sintase/química , Congelamento , Proteínas de Helminto/química , Difração de Nêutrons , Agregados Proteicos , Dobramento de Proteína , Estabilidade Proteica , Proteínas Recombinantes/química , Rabditídios/química , Espalhamento a Baixo Ângulo , Estresse Fisiológico , Suínos , Água
17.
J Sport Rehabil ; 30(3): 521-524, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871550

RESUMO

CONTEXT: A recent report demonstrated moderate to strong relationships between seated single-arm shot-put (SSASP) test performance and isokinetic pushing forces at varying velocities, directly supporting the SSASP test as a reflection of multijoint upper-extremity strength. Yet, no previous work appears to have assessed whether the SSASP test is more reflective of shoulder flexion or elbow extension strength. OBJECTIVE: To examine the relationship between isokinetic shoulder flexion and elbow extension strength and SSASP test performance and to compare limb symmetry indices (LSI) between the 2 tests. DESIGN: Correlational design. SETTING: Biomechanics laboratory. Patients (or Other Participants): A total of 30 healthy and physically active young adults. INTERVENTION(S): Participants completed the SSASP test and concentric isokinetic (60°/s and 180°/s) shoulder flexion and elbow extension using their dominant and nondominant arms. MAIN OUTCOME MEASURES: SSASP test performance and isokinetic shoulder flexion and elbow extension peak torques as well as LSI between the 2 tests. RESULTS: Strong relationships were observed between SSASP ranges and isokinetic peak torques at each velocity for both shoulder and elbow (r ≥ .804, P < .001). While the Bland-Altman results on the LSI only demonstrated a significant bias for the shoulder (60°/s, P = .009), limits of agreement results demonstrated extremely wide intervals (32.5%-52.1%). CONCLUSIONS: The SSASP test is a multijoint upper-extremity functional performance test that is reflective of equal shoulder flexion and elbow extension contributions; however, there was large variability regarding the agreement between the SSASP LSI and isokinetic shoulder and elbow strength LSI.


Assuntos
Cotovelo/fisiologia , Teste de Esforço/normas , Força Muscular/fisiologia , Desempenho Físico Funcional , Ombro/fisiologia , Adulto , Feminino , Humanos , Masculino , Torque , Adulto Jovem
18.
Biochemistry ; 58(35): 3630-3633, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31424918

RESUMO

Parkinson's disease etiology involves amyloid formation by α-synuclein (αSyn). In vivo, αSyn is constitutively acetylated at the α-amino N-terminus. Here, we find N-terminally acetylated αSyn (Ac-αSyn) aggregates more slowly than non-acetylated αSyn (NH3-αSyn) with significantly reduced sensitivity to thioflavin T (ThT). Fibril differences were characterized by transmission electron microscopy, circular dichroism spectroscopy, and limited proteolysis. Interestingly, the low-ThT Ac-αSyn fibrils seed both acetylated and non-acetylated αSyn and faithfully propagate the low-ThT character through several generations, indicating a stable fibril polymorph. In contrast, the high-ThT NH3-αSyn seeds lose fidelity over subsequent generations. Despite it being outside of the amyloid core, the chemical nature of the N-terminus modulates αSyn aggregation and fibril polymorphism.


Assuntos
Amiloide/genética , Amiloide/metabolismo , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Acetilação , Amiloide/química , Proteínas Amiloidogênicas/genética , Proteínas Amiloidogênicas/metabolismo , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Polimorfismo Genético , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Domínios Proteicos , Processamento de Proteína Pós-Traducional/fisiologia , Estrutura Secundária de Proteína/genética , alfa-Sinucleína/genética
19.
Am J Physiol Heart Circ Physiol ; 317(7): H26-H36, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30951363

RESUMO

The lack of pharmaceutical targets available to treat patients with calcific aortic valve disease (CAVD) necessitates further research into the specific mechanisms of the disease. The significant changes that occur to the aortic valves extracellular matrix (ECM) during the progression of CAVD suggests that these proteins may play an important role in calcification. Exploring the relationship between valve interstitial cells (VICs) and the ECM may lead to a better understand of CAVD mechanisms and potential pharmaceutical targets. In this study, we look at the effect of two ECM components, collagen and hyaluronic acid (HA), on the mineralization of VICs within the context of a two-dimensional, polyacrylamide (PAAM) model system. Using a novel, nondestructive imaging technique, we were able to track calcific nodule development in culture systems over a 3-wk time frame. We saw a significant increase in the size of the nodules grown on HA PAAM gels as compared with collagen PAAM gels, suggesting that HA has a direct effect on mineralization. Directly looking at the two known receptors of HA, CD44 and receptor for HA-mediated motility (RHAMM), and using siRNA knockdown revealed that a decrease in CD44 expression resulted in a reduction of calcification. A decrease in CD44, through siRNA knockdown, reduces mineralization on HA PAAM gels, suggesting a potential new target for CAVD treatment. NEW & NOTEWORTHY Our in vitro model of calcific aortic valve disease shows an interaction between the hyaluronic acid binding protein CD44 with the osteogenic factor OPN as a potential mechanism of aortic valve calcification. Using siRNA knockdown of CD44, we show an upregulation of OPN expression with a decrease in overall mineralization.


Assuntos
Valva Aórtica/metabolismo , Calcinose/genética , Doenças das Valvas Cardíacas/genética , Receptores de Hialuronatos/genética , Animais , Valva Aórtica/citologia , Calcinose/metabolismo , Movimento Celular , Células Cultivadas , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Doenças das Valvas Cardíacas/metabolismo , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Masculino , Osteopontina/genética , Osteopontina/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Phys Rev Lett ; 123(21): 216404, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809140

RESUMO

Quasiparticle interference (QPI) provides a wealth of information relating to the electronic structure of a material. However, it is often assumed that this information is constrained to two-dimensional electronic states. We show that this is not necessarily the case. For FeSe, a system dominated by surface defects, we show that it is actually all electronic states with negligible group velocity in the z axis that are contained within the experimental data. By using a three-dimensional tight-binding model of FeSe, fit to photoemission measurements, we directly reproduce the experimental QPI scattering dispersion, within a T-matrix formalism, by including both k_{z}=0 and k_{z}=π electronic states. This result unifies both tunnelling based and photoemission based experiments on FeSe and highlights the importance of k_{z} within surface sensitive measurements of QPI.

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