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2.
Gait Posture ; 109: 277-283, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38377744

RESUMO

BACKGROUND: Perinatal running participation has increased recently; however, pregnancy related symptoms can limit activity. Perinatal running biomechanics could inform interventions to help perinatal individuals maintain an active lifestyle. RESEARCH QUESTION: Are perinatal running biomaechanics and muscle activation different compared to nulligravida females? METHODS: Sixteen pregnant participants completed self-selected velocity running during second trimester (2 T), third trimester (3 T), and postpartum (PP) and 16 matched controls completed these procedures once in this case control study. Kinematic, kinetic, and electromyography (EMG) data were collected using a motion capture system, force plates, and EMG electrodes. Peak trunk, pelvis, hip, knee, and ankle kinematics and hip, knee, and ankle moments during stance phase, and average and peak erector spinae (ES), gluteus maximus (GMax), and gluteus medius (GMed) EMG amplitude and duration of activation during stance and swing phases were calculated. Independent t-tests were used to compare 2 T, 3 T, and PP to control participants (α < 0.05). RESULTS: Running velocity was slower during 3 T compared to control participants. At all pregnancy timepoints compared to the control group, peak trunk contralateral rotation was smaller. During 2 T and 3 T peak hip flexor moments were smaller. At 3 T pelvis contralateral rotation was smaller, ES average amplitude was greater during swing, GMax percent duration during stance and GMed percent duration during swing were smaller. At PP trunk flexion was smaller and knee abduction was greater (all p < 0.05). CONCLUSIONS: Decreased running velocity may help offset increased demand during pregnancy. During 3 T, greater ES activation, smaller trunk and pelvis motion, and altered gluteal activation could indicate trunk rigidity combined with modified hip stabilizer muscle utilization. During PP, the rigid trunk combined with greater knee abduction may indicate hip and trunk strength deficits. Altered trunk and hip motion and activation could be relevant to pathologies such as perinatal low back, pelvic girdle, or knee pain.


Assuntos
Articulação do Quadril , Corrida , Humanos , Feminino , Gravidez , Articulação do Quadril/fisiologia , Fenômenos Biomecânicos , Estudos de Casos e Controles , Músculo Esquelético/fisiologia , Eletromiografia/métodos , Nádegas
3.
Biomacromolecules ; 25(2): 829-837, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38173238

RESUMO

The mechanical and architectural properties of the three-dimensional (3D) tissue microenvironment can have large impacts on cellular behavior and phenotype, providing cells with specialized functions dependent on their location. This is especially apparent in macrophage biology where the function of tissue resident macrophages is highly specialized to their location. 3D bioprinting provides a convenient method of fabricating biomaterials that mimic specific tissue architectures. If these printable materials also possess tunable mechanical properties, they would be highly attractive for the study of macrophage behavior in different tissues. Currently, it is difficult to achieve mechanical tunability without sacrificing printability, scaffold porosity, and a loss in cell viability. Here, we have designed composite printable biomaterials composed of traditional hydrogels [nanofibrillar cellulose (cellulose) or methacrylated gelatin (gelMA)] mixed with porous polymeric high internal phase emulsion (polyHIPE) microparticles. By varying the ratio of polyHIPEs to hydrogel, we fabricate composite hydrogels that mimic the mechanical properties of the neural tissue (0.1-0.5 kPa), liver (1 kPa), lungs (5 kPa), and skin (10 kPa) while maintaining good levels of biocompatibility to a macrophage cell line.


Assuntos
Bioimpressão , Alicerces Teciduais , Porosidade , Engenharia Tecidual/métodos , Hidrogéis , Bioimpressão/métodos , Impressão Tridimensional , Materiais Biocompatíveis , Polímeros , Gelatina , Celulose , Técnicas de Cultura de Células em Três Dimensões
4.
Front Neurosci ; 17: 1130892, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37021140

RESUMO

In a natural acoustic environment, a preceding sound can suppress the perception of a succeeding sound which can lead to auditory phenomena such as forward masking and the precedence effect. The degree of suppression is dependent on the relationship between the sounds in sound quality, timing, and location. Correlates of such phenomena exist in sound-elicited activities of neurons in hearing-related brain structures. The present study recorded responses to pairs of leading-trailing sounds from ensembles of neurons in the rat's inferior colliculus. Results indicated that a leading sound produced a suppressive aftereffect on the response to a trailing sound when the two sounds were colocalized at the ear contralateral to the site of recording (i.e., the ear that drives excitatory inputs to the inferior colliculus). The degree of suppression was reduced when the time gap between the two sounds was increased or when the leading sound was relocated to an azimuth at or close to the ipsilateral ear. Local blockage of the type-A γ-aminobutyric acid receptor partially reduced the suppressive aftereffect when a leading sound was at the contralateral ear but not at the ipsilateral ear. Local blockage of the glycine receptor partially reduced the suppressive aftereffect regardless of the location of the leading sound. Results suggest that a sound-elicited suppressive aftereffect in the inferior colliculus is partly dependent on local interaction between excitatory and inhibitory inputs which likely involves those from brainstem structures such as the superior paraolivary nucleus. These results are important for understanding neural mechanisms underlying hearing in a multiple-sound environment.

5.
Biochem Soc Trans ; 51(1): 387-401, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36744644

RESUMO

The advent of 3D cell culture technology promises to enhance understanding of cell biology within tissue microenvironments. Whilst traditional cell culturing methods have been a reliable tool for decades, they inadequately portray the complex environments in which cells inhabit in vivo. The need for better disease models has pushed the development of effective 3D cell models, providing more accurate drug screening assays. There has been great progress in developing 3D tissue models in fields such as cancer research and regenerative medicine, driven by desires to recreate the tumour microenvironment for the discovery of new chemotherapies, or development of artificial tissues or scaffolds for transplantation. Immunology is one field that lacks optimised 3D models and the biology of tissue resident immune cells such as macrophages has yet to be fully explored. This review aims to highlight the benefits of 3D cell culturing for greater understanding of macrophage biology. We review current knowledge of macrophage interactions with their tissue microenvironment and highlight the potential of 3D macrophage models in the development of more effective treatments for disease.


Assuntos
Bioimpressão , Impressão Tridimensional , Medicina Regenerativa , Macrófagos , Técnicas de Cultura de Células em Três Dimensões , Técnicas de Cultura de Células , Engenharia Tecidual
6.
Gait Posture ; 97: 43-47, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35872482

RESUMO

BACKGROUND: Falls are common during pregnancy and present potential for injury to the pregnant individual and the baby. RESEARCH QUESTION: Do center of pressure characteristics during single leg stance differ between participants during and after pregnancy and nulligravida participants in the presence and absence of visual input? METHODS: Nineteen pregnant participants completed testing during the second trimester, the third trimester, and 4-6 months post-partum. Matched, nulligravida females completed testing once. All participants performed single leg stance on a force platform on each limb for up to 20 s with eyes open and with eyes closed. Center of pressure characteristics were compared between pregnant and nulligravida females using three separate 2 × 2 mixed way ANOVAs, one for each pregnancy time point (second trimester, third trimester, and post-partum) with Bonferroni correction. RESULTS: Pregnant females demonstrated smaller single leg stance time with eyes closed during the third trimester. During the second and third trimester, pregnant participants demonstrated smaller sway and sway velocity across eyes open and eyes closed conditions. During the third trimester and post-partum, pregnant participants demonstrated greater median frequency of the center of pressure data. Pregnant participants also demonstrated smaller sample entropy in the anteroposterior direction during the second and third trimesters and in the mediolateral direction during the second trimester. SIGNIFICANCE: The decreased total sway and sway velocity observed during pregnancy may reflect rigidity or a protective strategy during single limb stance. Additionally, center of pressure data were less smooth and more repetitive during pregnancy indicating robust differences in postural control strategies and potentially increased fall risk. Because single limb stance is a component of many activities of daily living, the single limb stance task may have clinical utility for testing or training balance in this population with a goal of decreasing falls.


Assuntos
Atividades Cotidianas , Perna (Membro) , Feminino , Humanos , Paridade , Equilíbrio Postural , Gravidez
7.
Nat Commun ; 13(1): 3387, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697699

RESUMO

COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don't understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.


Assuntos
COVID-19 , COVID-19/complicações , Humanos , Peptídeos , Proteoma , RNA Viral , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda
8.
Clin Biomech (Bristol, Avon) ; 97: 105705, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35763890

RESUMO

BACKGROUND: The purpose of this study was to compare gait kinematics, kinetics, and muscle activation between pregnant females with high and low scores for low back and/or pelvic girdle pain during and after pregnancy. METHODS: Twenty participants tested during second trimester, third trimester, and again post-partum. At each session, motion capture, force plates, and surface electromyography data were captured during self-selected velocity over-ground walking. Participants completed the Quebec Back Pain Disability Scale (QBPDS) and were assigned to high (QBPDS ≥15) or low pain groups (QBPDS <15) based on third trimester scores. Two-way mixed model ANOVAs were used to compare high and low pain groups over time. FINDINGS: Nine participants met the high pain group criteria and 11 were low pain. During second trimester the high pain group compared to the low pain group demonstrated smaller peak hip flexor moments, total hip work, percent hip contribution to work, and larger percent ankle contribution to work. Pregnant females demonstrated greater hip, knee, and ankle moments, ankle work, and gluteus maximus muscle activation third trimester than second trimester. INTERPRETATION: Reduced hip and greater ankle contribution to work in the high pain group during second trimester could indicate decreased hip utilization early in pregnancy and may contribute to disability as pregnancy progresses. It is also possible kinetic differences during second trimester reflect an early strategy to reduce pain by avoiding hip joint loading. Increased moments and work during third trimester indicate a clinical imperative to better prepare pregnant females to accommodate increased joint loading and muscular demand.


Assuntos
Dor da Cintura Pélvica , Fenômenos Biomecânicos , Feminino , Marcha/fisiologia , Articulação do Quadril/fisiologia , Humanos , Articulação do Joelho/fisiologia , Músculo Esquelético/fisiologia , Gravidez
9.
Biophys Chem ; 287: 106830, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35635892

RESUMO

Membrane-mediated assembly has been well characterised for toxic amyloid species such as the amyloid-ß peptide implicated in Alzheimer's disease. However, little is known about the membrane-mediated assembly of functional-amyloid forming peptides, recently identified as a natural storage state for neuropeptide hormones in vivo. Here, we study the aggregation of somatostatin-14 (SST-14) co-incubated with model lipid membranes. Atomic force microscopy (AFM) studies confirmed that nanofibrils formed in the presence of various lipid membranes display reduced fibrillogenesis and promote the formation of non-fibrillar oligomers. Both circular dichroism (CD) and intrinsic tryptophan fluorescence studies confirmed interaction between the peptide and the lipid bilayer; this interaction appears to drive changes in membrane-mediated aggregation kinetics. We show that both the surface charge of the membrane and chain packing drive changes in the electrostatic and hydrophobic interactions between the peptide and the membrane, and hence the rate of assembly. The similarities in the effect of the lipid membrane on aggregation of functional amyloids and the more well studied toxic amyloids suggest strong aggregation modifying lipid bilayer interactions are a ubiquitous feature of all amyloid fibrils and highlight the need for further investigation as to why this leads to toxicity in some systems and not others.


Assuntos
Amiloide , Amiloidose , Lipídeos de Membrana , Amiloide/química , Amiloide/metabolismo , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/química , Proteínas Amiloidogênicas/metabolismo , Amiloidose/metabolismo , Humanos , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Somatostatina
10.
Exp Brain Res ; 240(4): 1257-1266, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35199188

RESUMO

Self-motion perception refers to the ability to perceive how the body is moving through the environment. Perception of self-motion has been shown to depend upon the locomotor action patterns used to move the body through the environment. Two separate lines of enquiry have led to the establishment of two distinct theories regarding this effect. One theory has proposed that distances travelled during locomotion are perceived via higher order perceptual variables detected by the haptic perceptual system. This theory proposes that two higher order haptic perceptual variables exist, and that the implication of one of these variables depends upon the type of gait pattern that is used. A second theory proposes that self-motion is perceived via a higher order perceptual variable termed multimodally specified energy expenditure (MSEE). This theory proposes that the effect of locomotor actions patterns upon self-motion perception is related to changes in the metabolic cost of locomotion per unit of perceptually specified traversed distance. Here, we test the hypothesis that the development of these distinct theories is the result of different choices in methodology. The theory of gait type has been developed based largely on the results of homing tasks, whereas the effect of MSEE has been developed based on the results of distance matching tasks. Here we test the hypothesis that the seemly innocuous change in experimental design from using a homing task to using a distance matching task changes the type of perceptual variables implicated in self-motion perception. To test this hypothesis, we closely replicated a recent study of the effect of gait type in all details bar one-we investigated a distance matching task rather than a homing task. As hypothesized, this change yielded results consistent with the predictions of MSEE, and distinct from gait type. We further show that, unlike the effect of gait type, the effect of MSEE is unaffected by the availability of vision. In sum, our findings support the existence of two distinct types of higher order perceptual variables in self-motion perception. We discuss the roles of these two types of perceptual variables in supporting effective human wayfinding.


Assuntos
Locomoção , Percepção de Movimento , Metabolismo Energético , Marcha , Humanos , Visão Ocular
11.
Nat Commun ; 12(1): 2634, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976129

RESUMO

Realization of a self-assembled, nontoxic and eco-friendly piezoelectric device with high-performance, sensitivity and reliability is highly desirable to complement conventional inorganic and polymer based materials. Hierarchically organized natural materials such as collagen have long been posited to exhibit electromechanical properties that could potentially be amplified via molecular engineering to produce technologically relevant piezoelectricity. Here, by using a simple, minimalistic, building block of collagen, we fabricate a peptide-based piezoelectric generator utilising a radically different helical arrangement of Phe-Phe-derived peptide, Pro-Phe-Phe and Hyp-Phe-Phe, based only on proteinogenic amino acids. The simple addition of a hydroxyl group increases the expected piezoelectric response by an order of magnitude (d35 = 27 pm V-1). The value is highest predicted to date in short natural peptides. We demonstrate tripeptide-based power generator that produces stable max current >50 nA and potential >1.2 V. Our results provide a promising device demonstration of computationally-guided molecular engineering of piezoelectricity in peptide nanotechnology.


Assuntos
Fontes de Energia Bioelétrica , Materiais Biomiméticos/química , Biomimética/métodos , Engenharia Química/métodos , Oligopeptídeos/química , Materiais Biomiméticos/metabolismo , Colágeno/química , Desenho Assistido por Computador , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Oligopeptídeos/metabolismo , Conformação Proteica em alfa-Hélice , Reprodutibilidade dos Testes , Difração de Raios X
12.
Acta Biomater ; 129: 110-121, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34010693

RESUMO

Mesenchymal stem cell therapies show great promise in regenerative medicine. However, to generate clinically relevant numbers of these stem cells, significant in vitro expansion of the cells is required before transplantation into the affected wound or defect. The current gold standard protocol for recovering in vitro cultured cells involves treatment with enzymes such as trypsin which can affect the cell phenotype and ability to interact with the environment. Alternative enzyme free methods of adherent cell recovery have been investigated, but none match the convenience and performance of enzymatic detachment. In this work we have developed a synthetically simple, low cost cell culture substrate functionalized with gold nanorods that can support cell proliferation and detachment. When these nanorods are irradiated with biocompatible low intensity near infrared radiation (785 nm, 560 mWcm-2) they generate localized surface plasmon resonance induced nanoscale heating effects which trigger detachment of adherent mesenchymal stem cells. Through simulations and thermometry experiments we show that this localized heating is concentrated at the cell-nanorod interface, and that the stem cells detached using this technique show either similar or improved multipotency, viability and ability to differentiate into clinically desirable osteo and adipocytes, compared to enzymatically harvested cells. This proof-of-principle work shows that photothermally mediated cell detachment is a promising method for recovering mesenchymal stem cells from in vitro culture substrates, and paves the way for further studies to scale up this process and facilitate its clinical translation. STATEMENT OF SIGNIFICANCE: New non-enzymatic methods of harvesting adherent cells without damaging or killing them are highly desirable in fields such as regenerative medicine. Here, we present a synthetically simple, non-toxic, infra-red induced method of harvesting mesenchymal stem cells from gold nanorod functionalized substrates. The detached cells retain their ability to differentiate into therapeutically valuable osteo and adipocytes. This work represents a significant improvement on similar cell harvesting studies due to: its simplicity; the use of clinically valuable stem cells as oppose to immortalized cell lines; and the extensive cellular characterization performed. Understanding, not just if cells live or die but how they proliferate and differentiate after photothermal detachment will be essential for the translation of this and similar techniques into commercial devices.


Assuntos
Células-Tronco Mesenquimais , Nanotubos , Raios Infravermelhos , Ressonância de Plasmônio de Superfície
13.
Exp Brain Res ; 239(4): 1305-1316, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33630131

RESUMO

The visual, vestibular, and haptic perceptual systems are each able to detect self-motion. Such information can be integrated during locomotion to perceive traversed distances. The process of distance integration is referred to as odometry. Visual odometry relies on information in optic flow patterns. For haptic odometry, such information is associated with leg movement patterns. Recently, it has been shown that haptic odometry is differently calibrated for different types of gaits. Here, we use this fact to examine the relative contributions of the perceptual systems to odometry. We studied a simple homing task in which participants travelled set distances away from an initial starting location (outbound phase), before turning and attempting to walk back to that location (inbound phase). We manipulated whether outbound gait was a walk or a gallop-walk. We also manipulated the outbound availability of optic flow. Inbound reports were performed via walking with eyes closed. Consistent with previous studies of haptic odometry, inbound reports were shorter when the outbound gait was a gallop-walk. We showed that the availability of optic flow decreased this effect. In contrast, the availability of optic flow did not have an observable effect when the outbound gait was walking. We interpreted this to suggest that visual odometry and haptic odometry via walking are similarly calibrated. By measuring the decrease in shortening in the gallop-walk condition, and scaling it relative to the walk condition, we estimated a relative contribution of optic flow to odometry of 41%. Our results present a proof of concept for a new, potentially more generalizable, method for examining the contributions of different perceptual systems to odometry, and by extension, path integration. We discuss implications for understanding human wayfinding.


Assuntos
Percepção de Distância , Marcha , Humanos , Locomoção , Visão Ocular , Caminhada
14.
Nanoscale ; 12(44): 22680-22687, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33165459

RESUMO

Substance P neuropeptide is here reported to self-assemble into well-defined semi-flexible nanotubes. Using a blend of synchrotron small angle X-ray scattering, atomic force microscopy and other biophysical techniques, the natural peptide is shown to self-assemble into monodisperse 6 nm wide nanotubes, which can closely associate into nano-arrays with nematic properties. Using simple protocols, the nanotubes could be precipitated or mineralised while conserving their dimensions and core-shell morphology. Our discovery expands the small number of available monodisperse peptide nanotube systems for nanotechnology, beyond direct relevance to biologically functional peptide nanostructures since the substance P nanotubes are fundamentally different from typical amyloid fibrils.


Assuntos
Nanoestruturas , Nanotubos , Humanos , Microscopia de Força Atômica , Nanotecnologia , Substância P
15.
Gait Posture ; 81: 33-40, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659459

RESUMO

BACKGROUND: Low back, pelvic, and lower extremity pain are common during and after pregnancy. Understanding differences in mechanics between pregnant and non-pregnant females is a first step toward identifying potential pathological mechanisms. The primary purpose of this study was to compare joint kinetics and muscle activation during gait between females during and after pregnancy to nulliparous females. METHODS: Twenty pregnant females completed testing on three occasions (second trimester, third trimester, and post-partum), while 20 matched, nulliparous controls were tested once. Motion capture, force data, and surface electromyography were averaged across seven trials during gait. Lower extremity kinematics, lower extremity moments and work normalized to pre-pregnancy body mass, work distribution, and peak and average muscle activation amplitude were calculated. Independent t-tests were conducted between pregnant and nulliparous females at each time point. RESULTS: Compared to controls, peak hip abductor moments were greater throughout and after pregnancy. Females in second trimester also demonstrated greater sagittal negative ankle work and greater percent contribution of the ankle and smaller percent contribution of the hip to negative work. Compared to controls, during third trimester there were greater knee abductor, ankle plantarflexor, and ankle dorsiflexor moments and greater work at the ankle and total work. Several moment and work variables continued to be elevated post-partum compared to controls. Gluteus maximus muscle activation amplitude was smaller in second trimester and post-partum compared to controls. SIGNIFICANCE: While overall joint demands were greater during and after pregnancy, there was a smaller relative sagittal utilization of the hip early in pregnancy and smaller gluteus maximus muscle amplitude during second trimester and post-partum. Because the gluteus maximus muscle contributes to force closure and dynamic stability of the low back and pelvis, relative gluteus maximus disuse, concurrent with increased joint loads, could potentially contribute to pain during and after pregnancy.


Assuntos
Fenômenos Biomecânicos/fisiologia , Marcha/fisiologia , Extremidade Inferior/fisiologia , Músculo Esquelético/fisiologia , Adulto , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
16.
Biophys J ; 118(10): 2526-2536, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32311316

RESUMO

Several atomic structures have now been found for micrometer-scale amyloid fibrils or elongated microcrystals using a range of methods, including NMR, electron microscopy, and X-ray crystallography, with parallel ß-sheet appearing as the most common secondary structure. The etiology of amyloid disease, however, indicates nanometer-scale assemblies of only tens of peptides as significant agents of cytotoxicity and contagion. By combining solution X-ray with molecular dynamics, we show that antiparallel structure dominates at the first stages of aggregation for a specific set of peptides, being replaced by parallel at large length scales only. This divergence in structure between small and large amyloid aggregates should inform future design of molecular therapeutics against nucleation or intercellular transmission of amyloid. Calculations and an overview from the literature argue that antiparallel order should be the first appearance of structure in many or most amyloid aggregation processes, regardless of the endpoint. Exceptions to this finding should exist, depending inevitably on the sequence and on solution conditions.


Assuntos
Peptídeos beta-Amiloides , Amiloide , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Estrutura Secundária de Proteína
17.
ACS Appl Mater Interfaces ; 12(19): 21992-22001, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32307977

RESUMO

Phenylalanine was the minimalistic and first of numerous nonproteinaceous building blocks to be demonstrated to form amyloid-like fibrils. This unexpected organization of such a simple building block into canonical architecture, which was previously observed only with proteins and peptides, has numerous implications for medicine and supramolecular chemistry. However, the morphology of phenylalanine fibrils and their mechanical properties was never characterized in solutions. Here, using electron and atomic force microscopy, we analyze the morphological and mechanical properties of phenylalanine fibrils in both air and fluids. The fibrils demonstrate an exceptionally high Young's modulus (up to 30 GPa) and are found to be composed of intertwined protofilaments in a helical or twisted ribbon morphology. In addition, X-ray scattering experiments provide convincing evidence of an amyloidal cross-ß-like secondary structure within the nanoassemblies. Furthermore, increasing the phenylalanine concentration results in the formation of highly homogenous, noncrystalline, self-healing hydrogels that display storage and loss moduli significantly higher than similar noncovalently cross-linked biomolecular nanofibrillar scaffolds. These remarkably stiff nanofibrillar hydrogels can be harnessed for various technological and biomedical applications, such as self-healing, printable, structural, load-bearing 3D scaffolds. The properties of this simple but quite remarkable hydrogel open a possibility to utilize it in the biomaterial industry.


Assuntos
Amiloide/química , Hidrogéis/química , Nanofibras/química , Fenilalanina/química , Módulo de Elasticidade , Estrutura Quaternária de Proteína
18.
J Strength Cond Res ; 34(1): 145-151, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29210957

RESUMO

Russell, M, Reynolds, NA, Crewther, BT, Cook, CJ, and Kilduff, L. Physiological and performance effects of caffeine gum consumed during a simulated half-time by professional academy rugby union players. J Strength Cond Res 34(1): 145-151, 2020-Despite the prevalence of caffeine (CAF) as an ergogenic aid, few studies have examined the use of caffeinated gums, especially during half-time in team sports. The physiological (blood lactate and salivary hormone concentrations) and performance (repeated sprints and cognitive function) effects of consuming CAF gum during a simulated half-time were examined. Professional academy rugby union players (n = 14) completed this double-blind, randomized, counterbalanced study. After pre-exercise measurements, players chewed a placebo (PLC) gum for 5 minutes before a standardized warm-up and completing repeated sprint testing (RSSA1). Thereafter, during a 15-minute simulated half-time period, players chewed either CAF (400 mg; 4.1 ± 0.5 mg·kg) or PLC gum for 5 minutes before completing a second repeated sprint test (RSSA2). Blood lactate, salivary testosterone and cortisol concentrations, and indices of cognitive function (i.e., reaction time and Stroop test) were measured at baseline, pre-RSSA1, post-RSSA1, pre-RSSA2, and post-RSSA2. Sprint performance was not affected by CAF (p = 0.995) despite slower sprint times after the first sprint of both RSSA tests (all p < 0.002). After half-time, salivary testosterone increased by 70% (+97 ± 58 pg·ml) in CAF vs. PLC (p < 0.001), whereas salivary cortisol remained unchanged (p = 0.307). Cognitive performance was unaffected by time and trial (all p > 0.05). Although performance effects were absent, chewing CAF gum increased the salivary testosterone concentrations of professional rugby union players over a simulated half-time. Practitioners may, therefore, choose to recommend CAF gum between successive exercise bouts because of the increases in salivary testosterone observed; a variable associated with increased motivation and high-intensity exercise performance.


Assuntos
Desempenho Atlético/fisiologia , Cafeína/administração & dosagem , Futebol Americano/fisiologia , Substâncias para Melhoria do Desempenho/administração & dosagem , Adolescente , Goma de Mascar , Cognição , Estudos Cross-Over , Método Duplo-Cego , Humanos , Hidrocortisona/análise , Ácido Láctico/sangue , Masculino , Saliva/química , Testosterona/análise , Exercício de Aquecimento , Adulto Jovem
19.
Hear Res ; 385: 107846, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786442

RESUMO

Cochlear implantation leads to many structural changes within the cochlea which can impair residual hearing. In patients with preserved low-frequency hearing, a delayed hearing loss can occur weeks-to-years post-implantation. We explore whether stiffening of the basilar membrane (BM) may be a contributory factor in an animal model. Our objective is to map changes in morphology and Young's modulus of basal and apical areas of the BM after cochlear implantation, using quantitative nanomechanical atomic force microscopy (QNM-AFM) after cochlear implant surgery. Cochlear implantation was undertaken in the guinea pig, and the BM was harvested at four time-points: 1 day, 14 days, 28 days and 84 days post-implantation for QNM-AFM analysis. Auditory brainstem response thresholds were determined prior to implantation and termination. BM tissue showed altered morphology and a progressive increase in Young's modulus, mainly in the apex, over time after implantation. BM tissue from the cochlear base demonstrated areas of extreme stiffness which are likely due to micro-calcification on the BM. In conclusion, stiffening of the BM after cochlear implantation occurs over time, even at sites far apical to a cochlear implant.


Assuntos
Membrana Basilar/patologia , Calcinose/etiologia , Cicatriz/etiologia , Implante Coclear/efeitos adversos , Microscopia de Força Atômica , Nanotecnologia , Animais , Limiar Auditivo , Membrana Basilar/fisiopatologia , Calcinose/patologia , Calcinose/fisiopatologia , Cicatriz/patologia , Cicatriz/fisiopatologia , Implante Coclear/instrumentação , Implantes Cocleares , Módulo de Elasticidade , Potenciais Evocados Auditivos do Tronco Encefálico , Fibrose , Cobaias , Modelos Animais , Fatores de Tempo
20.
ACS Nano ; 13(12): 14477-14485, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31755683

RESUMO

The formation of ordered nanostructures by metabolites is gaining increased interest due to the simplicity of the building blocks and their natural occurrence. Specifically, aromatic amino acids possess the ability to form ordered supramolecular interactions due to their limited solubility in aqueous solution. Unexpectedly, l-tyrosine (l-Tyr) is almost 2 orders of magnitude less soluble in water compared to l-phenylalanine (l-Phe). However, the underlying mechanism is not fully understood as l-Tyr is more polar. Here, we explore the utilization of insoluble tyrosine assemblies for technological applications and their molecular basis by manipulating the basic building blocks of tightly packed dimers. We show that the addition of an amyloid inhibition agent increases l-Tyr solubility due to the disruption of the dimer formation. The molecular organization grants the l-Tyr crystal higher thermal stability and mechanical properties between three amino acids. Additionally, l-Tyr crystals are shown to generate high and stable piezoelectric power outputs under mechanical pressure in a sandwich device. By incorporating the rigid l-Tyr crystals into a soft polymer, a mechano-responsive bending composite was fabricated. Furthermore, the l-Tyr crystalline needles exhibit an active photowaveguiding property, making them promising candidates for the generation of photonic biomaterial-based devices. The present work exemplifies a feasible strategy to explore physical properties of supramolecular self-assemblies comprises minimalistic naturally occurring building blocks and their applications in energy harvesting, photonic devices, stretchable electronics, and soft robotics.

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