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1.
ACS Nano ; 17(17): 16960-16967, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37410703

RESUMO

The resistance of an ordered 3D-Bi2Te3 nanowire nanonetwork was studied at low temperatures. Below 50 K the increase in resistance was found to be compatible with the Anderson model for localization, considering that conduction takes place in individual parallel channels across the whole sample. Angle-dependent magnetoresistance measurements showed a distinctive weak antilocalization characteristic with a double feature that we could associate with transport along two perpendicular directions, dictated by the spatial arrangement of the nanowires. The coherence length obtained from the Hikami-Larkin-Nagaoka model was about 700 nm across transversal nanowires, which corresponded to approximately 10 nanowire junctions. Along the individual nanowires, the coherence length was greatly reduced to about 100 nm. The observed localization effects could be the reason for the enhancement of the Seebeck coefficient observed in the 3D-Bi2Te3 nanowire nanonetwork compared to individual nanowires.

2.
Nanomaterials (Basel) ; 12(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36558282

RESUMO

Recently, polymers have been attracted great attention because of their thermoelectric materials' excellent mechanical properties, specifically their cost-effectiveness and scalability at the industrial level. In this study, the electropolymerization conditions (applied potential and deposition time) of PEDOT films were investigated to improve their thermoelectric properties. The morphology and Raman spectroscopy of the PEDOT films were analyzed according to their applied potential and deposition time. The best thermoelectric properties were found in films grown at 1.3 V for 10 min, with an electrical conductivity of 158 ± 8 S/cm, a Seebeck coefficient of 33 ± 1 µV/K, and a power factor of 17 ± 2 µW/K·m2. This power factor value is three times higher than the value reported in the literature for electropolymerized PEDOT films in acetonitrile using lithium perchlorate as a counter-ion. The thermal conductivity was found to be (1.3 ± 0.3) × 10-1 W/m·K. The highest figure of merit obtained at room temperature was (3.9 ± 1.0) × 10-2 using lithium perchlorate as a counter-ion. In addition, three-dimensional (3D) PEDOT nanonetworks were electropolymerized inside 3D anodic aluminum oxide (3D AAO), obtaining lower values in their thermoelectric properties.

3.
Nanoscale ; 14(8): 3179-3190, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35142756

RESUMO

The use of metallic nanostructures in the fabrication of bioelectrodes (e.g., neural implants) is gaining attention nowadays. Nanostructures provide increased surface area that might benefit the performance of bioelectrodes. However, there is a need for comprehensive studies that assess electrochemical performance of nanostructured surfaces in physiological and relevant working conditions. Here, we introduce a versatile scalable fabrication method based on magnetron sputtering to develop analogous metallic nanocolumnar structures (NCs) and thin films (TFs) from Ti, Au, and Pt. We show that NCs contribute significantly to reduce the impedance of metallic surfaces. Charge storage capacity of Pt NCs is remarkably higher than that of Pt TFs and that of the other metals in both morphologies. Circuit simulations of the electrode/electrolyte interface show that the signal delivered in voltage-controlled systems is less filtered when nanocolumns are used. In a current-controlled system, simulation shows that NCs provide safer stimulation conditions compared to TFs. We have assessed the durability of NCs and TFs for potential use in vivo by reactive accelerated aging test, mimicking one-year in vivo implantation. Although each metal/morphology reveals a unique response to aging, NCs show overall more stable electrochemical properties compared to TFs in spite of their porous structure.

4.
Nanomaterials (Basel) ; 13(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36616063

RESUMO

The 1D nanowire arrays and 3D nanowire networks of topological insulators and metals have been fabricated by template-assisted deposition of Bi2Te3 and Ni inside anodic aluminum oxide (AAO) templates, respectively. Despite the different origins of the plasmon capabilities of the two materials, the results indicate that the optical response is determined by plasmon resonances, whose position depends on the nanowire interactions and material properties. Due to the thermoelectric properties of Bi2Te3 nanowires, these plasmon resonances could be used to develop new ways of enhancing thermal gradients and their associated thermoelectric power.

5.
Aging (Albany NY) ; 13(21): 23936-23952, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731089

RESUMO

Evidence suggests that aging-related dysfunctions of adipose tissue and metabolic disturbances increase the risk of diabetes and metabolic syndrome (MtbS), eventually leading to cognitive impairment and dementia. However, the neuroprotective role of adipocytokines in this process has not been specifically investigated. The present study aims to identify metabolic alterations that may prevent adipocytokines from exerting their neuroprotective action in normal ageing. We hypothesize that neuroprotection may occur under insulin resistance (IR) conditions as long as there are no other metabolic alterations that indirectly impair the action of adipocytokines, such as hyperglycemia. This hypothesis was tested in 239 cognitively normal older adults (149 females) aged 52 to 87 years (67.4 ± 5.9 yr). We assessed whether the homeostasis model assessment-estimated insulin resistance (HOMA-IR) and the presence of different components of MtbS moderated the association of plasma adipocytokines (i.e., adiponectin, leptin and the adiponectin to leptin [Ad/L] ratio) with cognitive functioning and cortical thickness. The results showed that HOMA-IR, circulating triglyceride and glucose levels moderated the neuroprotective effect of adipocytokines. In particular, elevated triglyceride levels reduced the beneficial effect of Ad/L ratio on cognitive functioning in insulin-sensitive individuals; whereas under high IR conditions, it was elevated glucose levels that weakened the association of the Ad/L ratio with cognitive functioning and with cortical thickness of prefrontal regions. Taken together, these findings suggest that the neuroprotective action of adipocytokines is conditioned not only by whether cognitively normal older adults are insulin-sensitive or not, but also by the circulating levels of triglycerides and glucose, respectively.


Assuntos
Adipocinas , Glicemia , Cognição/fisiologia , Resistência à Insulina/fisiologia , Neuroproteção/fisiologia , Adipocinas/sangue , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Glicemia/análise , Glicemia/metabolismo , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Fármacos Neuroprotetores/sangue , Fármacos Neuroprotetores/metabolismo , Triglicerídeos/sangue
6.
Nanoscale ; 13(4): 2227-2265, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33480949

RESUMO

Anodic porous alumina, -AAO- (also known as nanoporous alumina, nanohole alumina arrays, -NAA- or nanoporous anodized alumina platforms, -NAAP-) has opened new opportunities in a wide range of fields, and is used as an advanced photonic structure for applications in structural coloration and advanced optical biosensing based on the ordered nanoporous structure obtained and as a template to grow nanowires or nanotubes of different materials giving rise to metamaterials with tailored properties. Therefore, understanding the structure of nanoporous anodic alumina templates and knowing how they are fabricated provide a tool for the further design of structures based on them, such as 3D nanoporous structures developed recently. In this work, we review the latest developments related to nanoporous alumina, which is currently a very active field, to provide a solid and thorough reference for all interested experts, both in academia and industry, on these nanostructured and highly useful structures. We present an overview of theories on the formation of pores and self-ordering in alumina, paying special attention to those presented in recent years, and different nanostructures that have been developed recently. Therefore, a wide variety of architectures, ranging from ordered nanoporous structures to diameter changing pores, branched pores, and 3D nanostructures will be discussed. Next, some of the most relevant results using different nanostructured morphologies as templates for the growth of different materials with novel properties and reduced dimensionality in magnetism, thermoelectricity, etc. will be summarised, showing how these structures have influenced the state of the art in a wide variety of fields. Finally, a review on how these anodic aluminium membranes are used as platforms for different applications combined with optical techniques, together with principles behind these applications will be presented, in addition to a hint on the future applications of these versatile nanomaterials. In summary, this review is focused on the most recent developments, without neglecting the basis and older studies that have led the way to these findings. Thus, it gives an updated state-of-the-art review that should be useful not only for experts in the field, but also for non-specialists, helping them to gain a broad understanding of the importance of anodic porous alumina, and most probably, endow them with new ideas for its use in fields of interest or even developing the anodization technique.

7.
Gerontology ; 67(3): 281-289, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33429394

RESUMO

BACKGROUND: The older population has been especially affected by the severe acute respiratory syndrome coronavirus 2 pandemic (COVID-19). OBJECTIVE: The aim of the study was to explore the incidence, severity, mortality rate, clinical features, and risk factors of symptoms of COVID-19 in home-dwelling older people, and its association with type of residence, cognitive deterioration, and neurodegenerative diseases. METHODS: Data about symptoms of COVID-19 were collected through a telephone survey in the cohort of 913 older volunteers of the Vallecas Project, aged 75-90 years, most of them (902) home-dwelling, in Madrid, Spain. The association of demographic and anthropometric measures, genetic polymorphisms, comorbidities, life habits, type of residence, and frailty surrogates were explored as potential risk factors for the incidence, severity, and mortality of COVID-19 in the older population. FINDINGS: Sixty-two cases reported symptoms compatible with COVID-19; 6 of them had died, 4 in their home and 2 in the nursing home. Moderate/severe cases were significantly older and more frequently males. The APOE ε4 allele was associated with the presence of symptoms of COVID-19. Higher systolic blood pressure, more intense smoking habit, more alcohol intake, lower consumption of coffee and tea, and cognitive impairment were associated with disease severity. CONCLUSIONS: The estimated incidence of symptomatic COVID-19 in this older cohort of Madrid was 6.8%, with an overall mortality rate of 0.7% (18.2% in those living in a nursing home) and a fatality rate of 9.9%. Our exploratory study indicates that life habits, other clinical conditions and, the ε4 variant of the APOE gene are associated with the presence and clinical severity of coronavirus infection.


Assuntos
COVID-19/epidemiologia , Disfunção Cognitiva/epidemiologia , Vida Independente , Doenças Neurodegenerativas/epidemiologia , Casas de Saúde , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , COVID-19/mortalidade , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fumar/epidemiologia , Espanha/epidemiologia , Inquéritos e Questionários
8.
Antioxidants (Basel) ; 10(1)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467040

RESUMO

Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, xenobiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and neurodegeneration related to its capabilities as an antioxidant and scavenging of harmful molecules, versus its involvement in oxidative stress and aberrant immune response, depending on NM saturation state and its extracellular release.

9.
ACS Appl Energy Mater ; 4(12): 13556-13566, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35647490

RESUMO

3D interconnected nanowire scaffoldings are shown to increase the thermoelectric efficiency in comparison to similar diameter 1D nanowires and films grown under similar electrodeposition conditions. Bi2Te3 3D nanonetworks offer a reduction in thermal conductivity (κT) while preserving the high electrical conductivity of the films. The reduction in κT is modeled using the hydrodynamic heat transport equation, and it can be understood as a heat viscosity effect due to the 3D nanostructuration. In addition, the Seebeck coefficient is twice that of nanowires and films, and up to 50% higher than in a single crystal. This increase is interpreted as a nonequilibrium effect that the geometry of the structure induces on the distribution function of the phonons, producing an enhanced phonon drag. These thermoelectric metamaterials have higher performance and are fabricated with large areas by a cost-effective method, which makes them suitable for up-scale production.

10.
Lancet Neurol ; 19(10): 840-848, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32949544

RESUMO

BACKGROUND: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. METHODS: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. FINDINGS: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. INTERPRETATION: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. FUNDING: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.


Assuntos
Síndrome de Creutzfeldt-Jakob/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Predisposição Genética para Doença/epidemiologia , Humanos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
11.
Medicentro (Villa Clara) ; 24(2): 305-319, abr.-jun. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1124994

RESUMO

RESUMEN Introducción: el cáncer de piel es una afección común en las zonas expuestas a la luz solar; es la neoplasia maligna más frecuente a nivel mundial y su incidencia ha aumentado en las últimas décadas. Objetivo: describir las características clínico-epidemiológicas en pacientes con lesiones malignas en la piel. Métodos: se realizó un estudio descriptivo-transversal en los pacientes atendidos en la consulta de Dermatología del Policlínico Docente «Octavio de la Concepción y la Pedraja, Camajuaní, Villa Clara, año 2016. La muestra estuvo conformada por el total de pacientes diagnosticados clínicamente y por biopsia (160). La información se recopiló a través de un cuestionario y se procesó estadísticamente. Resultados: en las lesiones malignas de la piel: el 52,50 % perteneció al sexo masculino y se incrementó con la edad en ambos sexos. Se observó que la mayoría de los pacientes recibían exposición solar prolongada (61,40 %), durante cuatro o más horas diarias, principalmente los hombres obreros agrícolas (28,75 %), con predominio del fototipo cutáneo III (48,75 %). Las sombrillas son uno de los medios de protección solar más utilizados (16,87 %); mientras que el 32,50 % de los pacientes no utilizaban ninguno. Se constató que la mayoría de estas lesiones estaban localizadas en la región de la nariz (21,25 %). Conclusiones: las lesiones malignas de la piel se incrementan con la edad en ambos sexos. Están relacionadas con la exposición solar prolongada, principalmente en los hombres. Se evidenció un predominio del fototipo cutáneo III en los trabajadores agrícolas.


ABSTRACT Introduction: skin cancer is a common condition in areas exposed to sunlight; it is the most common malignancy worldwide and its incidence has increased in recent decades. Objective: to describe the clinical and epidemiological characteristics in patients with malignant skin lesions. Methods: a descriptive, cross-sectional study was conducted in patients seen in the Dermatology consultation at "Octavio de la Concepción y la Pedraja" Teaching Polyclinic, Camajuaní, Villa Clara during 2016. The total number of patients diagnosed clinically and by biopsy (160) constituted the sample. The information was collected through a questionnaire and processed statistically. Results: in malignant skin lesions: 52.50% belonged to male gender and increased with age in both genders. It was observed that most patients received prolonged sun exposure (61.40%), for four or more hours a day, mainly male agricultural workers (28.75%), with predominance of skin phototype III (48.75%). Umbrellas are one of the most used means of sun protection (16.87%); while 32.50% of the patients did not use any. It was found that most of these lesions were located in the region of the nose (21.25%). Conclusions: malignant skin lesions increase with age in both genders. They are related to prolonged sun exposure, mainly in men. A predominance of skin phototype III was evidenced in agricultural workers.


Assuntos
Atenção Primária à Saúde , Neoplasias Cutâneas/epidemiologia
12.
Biomolecules ; 10(2)2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32059611

RESUMO

Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. At this point, we sought to characterise the biomarker profile of iCJD and compare it to that of sporadic CJD (sCJD) for determining the value of available diagnostic tools in promptly recognising iCJD cases. To that end, we collected 23 iCJD samples from seven national CJD surveillance centres and analysed the electroencephalogram and neuroimaging data together with a panel of seven CSF biomarkers: 14-3-3, total tau, phosphorylated/total tau ratio, alpha-synuclein, neurofilament light, YKL-40, and real-time quaking induced conversion of prion protein. Using the cut-off values established for sCJD, we found the sensitivities of these biomarkers for iCJD to be similar to those described for sCJD. Given the limited relevant information on this issue to date, the present study validates the use of current sCJD biomarkers for the diagnosis of future iCJD cases.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Encefalopatia Espongiforme Bovina/líquido cefalorraquidiano , Encefalopatia Espongiforme Bovina/diagnóstico por imagem , Doenças Priônicas/líquido cefalorraquidiano , Doenças Priônicas/diagnóstico por imagem , Proteínas Priônicas/metabolismo , Adulto , Idoso , Transplante de Córnea/efeitos adversos , Síndrome de Creutzfeldt-Jakob/epidemiologia , Dura-Máter/transplante , Eletroencefalografia , Encefalopatia Espongiforme Bovina/epidemiologia , Feminino , Homozigoto , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Doença Iatrogênica , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Metionina/genética , Pessoa de Meia-Idade , Neuroimagem , Fenótipo , Polimorfismo Genético , Sistema de Registros , Reprodutibilidade dos Testes , Fatores Sexuais , Fatores de Tempo
13.
Biomolecules ; 9(12)2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795176

RESUMO

The exploration of accurate diagnostic markers for differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous study on cerebrospinal fluid (CSF)-mitochondrial malate dehydrogenase 1 (MDH1) in sporadic Creutzfeldt-Jakob disease (sCJD) patients revealed a highly significant upregulation of MDH1. Here, we measured the CSF levels of MDH1 via enzyme-linked immunosorbent assay in a cohort of rare genetic prion disease cases, such as genetic CJD (gCJD) cases, exhibiting the E200K, V210I, P102L (Gerstmann-Sträussler-Scheinker syndrome (GSS)), or D178N (fatal familial insomnia (FFI)) mutations in the PRNP. Interestingly, we observed enhanced levels of CSF-MDH1 in all genetic prion disease patients compared to neurological controls (without neurodegeneration). While E200K and V210I carriers showed highest levels of MDH1 with diagnostic discrimination from controls of 0.87 and 0.85 area under the curve (AUC), FFI and GSS patients exhibited only moderately higher CSF-MDH1 levels than controls. An impact of the PRNP codon 129 methionine/valine (MV) genotype on the amount of MDH1 could be excluded. A correlation study of MDH1 levels with other neurodegenerative marker proteins revealed a significant positive correlation between CSF-MDH1 concentration with total tau (tau) but not with 14-3-3 in E200K, as well as in V210I patients. In conclusion, our study indicated the potential use of MDH1 as marker for gCJD patients which may complement the current panel of diagnostic biomarkers.


Assuntos
Malato Desidrogenase/líquido cefalorraquidiano , Doenças Priônicas/líquido cefalorraquidiano , Proteínas 14-3-3/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Proteínas tau/líquido cefalorraquidiano
14.
Mol Neurobiol ; 56(4): 2811-2821, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30062673

RESUMO

Cerebrospinal fluid (CSF) total prion protein (t-PrP) is decreased in sporadic Creutzfeldt-Jakob disease (sCJD). However, data on the comparative signatures of t-PrP across the spectrum of prion diseases, longitudinal changes during disease progression, and levels in pre-clinical cases are scarce. T-PrP was quantified in neurological diseases (ND, n = 147) and in prion diseases from different aetiologies including sporadic (sCJD, n = 193), iatrogenic (iCJD, n = 12) and genetic (n = 209) forms. T-PrP was also measured in serial lumbar punctures obtained from sCJD cases at different symptomatic disease stages, and in asymptomatic prion protein gene (PRNP) mutation carriers. Compared to ND, t-PrP concentrations were significantly decreased in sCJD, iCJD and in genetic prion diseases associated with the three most common mutations E200K, V210I (associated with genetic CJD) and D178N-129M (associated with fatal familial insomnia). In contrast, t-PrP concentrations in P102L mutants (associated with the Gerstmann-Sträussler-Scheinker syndrome) remained unaltered. In serial lumbar punctures obtained at different disease stages of sCJD patients, t-PrP concentrations inversely correlated with disease progression. Decreased mean t-PrP values were detected in asymptomatic D178-129M mutant carriers, but not in E200K and P102L carriers. The presence of low CSF t-PrP is common to all types of prion diseases regardless of their aetiology albeit with mutation-specific exceptions in a minority of genetic cases. In some genetic prion disease, decreased levels are already detected at pre-clinical stages and diminish in parallel with disease progression. Our data indicate that CSF t-PrP concentrations may have a role as a pre-clinical or early symptomatic diagnostic biomarker in prion diseases as well as in the evaluation of therapeutic interventions.


Assuntos
Doenças Priônicas/líquido cefalorraquidiano , Proteínas Priônicas/líquido cefalorraquidiano , Idoso , Códon/genética , Progressão da Doença , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Doenças Priônicas/patologia , Proteínas Priônicas/genética
15.
Front Neurosci ; 12: 464, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30026686

RESUMO

Despite aging being by far the greatest risk factor for highly prevalent neurodegenerative disorders, the molecular underpinnings of age-related brain changes are still not well understood, particularly the transition from normal healthy brain aging to neuropathological aging. Aging is an extremely complex, multifactorial process involving the simultaneous interplay of several processes operating at many levels of the functional organization. The buildup of potentially toxic protein aggregates and their spreading through various brain regions has been identified as a major contributor to these pathologies. One of the most striking morphologic changes in neurons during normal aging is the accumulation of lipofuscin (LF) aggregates, as well as, neuromelanin pigments. LF is an autofluorescent lipopigment formed by lipids, metals and misfolded proteins, which is especially abundant in nerve cells, cardiac muscle cells and skin. Within the Central Nervous System (CNS), LF accumulates as aggregates, delineating a specific senescence pattern in both physiological and pathological states, altering neuronal cytoskeleton and cellular trafficking and metabolism, and being associated with neuronal loss, and glial proliferation and activation. Traditionally, the accumulation of LF in the CNS has been considered a secondary consequence of the aging process, being a mere bystander of the pathological buildup associated with different neurodegenerative disorders. Here, we discuss recent evidence suggesting the possibility that LF aggregates may have an active role in neurodegeneration. We argue that LF is a relevant effector of aging that represents a risk factor or driver for neurodegenerative disorders.

16.
Methods Mol Biol ; 1779: 497-512, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29886553

RESUMO

The study of brain pathology by fluorescence microscopy finds in the autofluorescence of the tissue an additional difficulty for the recognition of markers of interest. In particular, in the immunofluorescence study of brains from Alzheimer's disease (AD) patients, several approaches have been attempted to eliminate or mask the presence of autofluorescent aggregates. In the present work, we propose a method to characterize by fluorescent microscopy senile plaques discriminating them from autofluorescent aggregates, such as lipofuscin granules.This work describes four protocols carried out in human brain tissue of patients with AD, covering adequate tissue preparation, immunofluorescence acquisition, and data analysis: 1. Tissues processing of frozen samples for optimal epitope conservation. 2. Analysis of the fluorescence emission spectrum of the tissue by performing a confocal microscopy λ-scan. 3. Analysis of fluorescence emission of both intact and formic acid-treated tissues in four channels corresponding to the emission in blue, green, near red, and far-red regions. 4. Analysis a specific immunostaining of amyloid beta in senile plaques, using fluorescent-labeled antibodies by using specific emission channels to avoid detection of tissue autofluorescence.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lipofuscina/química , Placa Amiloide/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Imunofluorescência , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Placa Amiloide/metabolismo , Preservação de Tecido
17.
Nanomaterials (Basel) ; 8(5)2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29783697

RESUMO

Self-standing Bi2Te3 networks of interconnected nanowires were fabricated in three-dimensional porous anodic alumina templates (3D⁻AAO) with a porous structure spreading in all three spatial dimensions. Pulsed electrodeposition parameters were optimized to grow highly oriented Bi2Te3 interconnected nanowires with stoichiometric composition inside those 3D⁻AAO templates. The nanowire networks were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and Raman spectroscopy. The results are compared to those obtained in films and 1D nanowires grown under similar conditions. The crystalline structure and composition of the 3D Bi⁻Te nanowire network are finely tuned by controlling the applied voltage and the relaxation time off at zero current density during the deposition. With this fabrication method, and controlling the electrodeposition parameters, stoichiometric Bi2Te3 networks of interconnected nanowires have been obtained, with a preferential orientation along [1 1 0], which makes them optimal candidates for out-of-plane thermoelectric applications. Moreover, the templates in which they are grown can be dissolved and the network of interconnected nanowires is self-standing without affecting its composition and orientation properties.

18.
Sci Rep ; 8(1): 5969, 2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29654261

RESUMO

Apolipoprotein E (apoE) is a 34 kDa glycoprotein involved in lipid metabolism. The human APOE gene encodes for three different apoE protein isoforms: E2, E3 and E4. The interest in apoE isoforms is high for epidemiological research, patient stratification and identification of those at increased risk for clinical trials and prevention. The isoform apoE4 is associated with increased risk for coronary heart and Alzheimer's diseases. This paper describes a method for specifically detecting the apoE4 isoform from biological fluids by taking advantage of the capacity of apoE to bind "specifically" to polystyrene surfaces as capture and a specific anti-apoE4 monoclonal antibody as reporter. Our results indicate that the apoE-polystyrene binding interaction is highly stable, resistant to detergents and acid and basic washes. The methodology here described is accurate, easily implementable, fast and cost-effective. Although at present, our technique is unable to discriminate homozygous APOE ε4/ε4 from APOE ε3/ε4 and ε2/ε4 heterozygous, it opens new avenues for the development of inexpensive, yet effective, tests for the detection of apoE4 for patients' stratification. Preliminary results indicated that this methodology is also adaptable into turbidimetric platforms, which make it a good candidate for clinical implementation through its translation to the clinical analysis routine.


Assuntos
Apolipoproteínas E/genética , Doença de Alzheimer/genética , Anticorpos Monoclonais/metabolismo , Apolipoproteínas E/metabolismo , Estudos de Coortes , Doença das Coronárias/genética , Análise Custo-Benefício , Genótipo , Heterozigoto , Homozigoto , Humanos , Poliestirenos/metabolismo , Isoformas de Proteínas/genética
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