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1.
Nature ; 612(7940): 442-447, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36517713

RESUMO

Hybrid semiconductor-superconductor devices hold great promise for realizing topological quantum computing with Majorana zero modes1-5. However, multiple claims of Majorana detection, based on either tunnelling6-10 or Coulomb blockade (CB) spectroscopy11,12, remain disputed. Here we devise an experimental protocol that allows us to perform both types of measurement on the same hybrid island by adjusting its charging energy via tunable junctions to the normal leads. This method reduces ambiguities of Majorana detections by checking the consistency between CB spectroscopy and zero-bias peaks in non-blockaded transport. Specifically, we observe junction-dependent, even-odd modulated, single-electron CB peaks in InAs/Al hybrid nanowires without concomitant low-bias peaks in tunnelling spectroscopy. We provide a theoretical interpretation of the experimental observations in terms of low-energy, longitudinally confined island states rather than overlapping Majorana modes. Our results highlight the importance of combined measurements on the same device for the identification of topological Majorana zero modes.

2.
Nano Lett ; 24(22): 6553-6559, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38775731

RESUMO

New approaches such as selective area growth (SAG), where crystal growth is lithographically controlled, allow the integration of bottom-up grown semiconductor nanomaterials in large-scale classical and quantum nanoelectronics. This calls for assessment and optimization of the reproducibility between individual components. We quantify the structural and electronic statistical reproducibility within large arrays of nominally identical selective area growth InAs nanowires. The distribution of structural parameters is acquired through comprehensive atomic force microscopy studies and transmission electron microscopy. These are compared to the statistical distributions of the cryogenic electrical properties of 256 individual SAG nanowire field effect transistors addressed using cryogenic multiplexer circuits. Correlating measurements between successive thermal cycles allows distinguishing between the contributions of surface impurity scattering and fixed structural properties to device reproducibility. The results confirm the potential of SAG nanomaterials, and the methodologies for quantifying statistical metrics are essential for further optimization of reproducibility.

3.
J Exp Zool B Mol Dev Evol ; 342(4): 350-367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38155515

RESUMO

In anurans, the vertebral column diverges widely from that of other tetrapods; yet the molecular mechanisms underlying its morphogenesis remain largely unexplored. In this study, we investigate the role of the homeologous uncx.L and uncx.S genes in the vertebral column morphogenesis of the allotetraploid frog Xenopus laevis. We initiated our study by cloning the uncx orthologous genes in the anuran Xenopus and determining their spatial expression patterns using in situ hybridization. Additionally, we employed gain-of-function and loss-of-function approaches through dexamethasone-inducible uncx constructs and antisense morpholino oligonucleotides, respectively. Comparative analysis of the messenger RNA sequences of homeologous uncx genes revealed that the uncx.L variant lacks the eh1-like repressor domain. Our spatial expression analysis indicated that in the presomitic mesoderm and somites, the transcripts of uncx.L and uncx.S are located in overlapping domains. Alterations in the function of uncx genes significantly impact the development and differentiation of the sclerotome and myotome, resulting in axial skeleton malformations. Our findings suggest a scenario where the homeologous genes uncx.L and uncx.S exhibit antagonistic functions during somitogenesis. Specifically, uncx.S appears to be crucial for sclerotome development and differentiation, while uncx.L primarily influences myotome development. Postallotetraploidization, the uncx.L gene in X. laevis evolved to lose its eh1-like repressor domain, transforming into a "native dominant negative" variant that potentially competes with uncx.S for the same target genes. Finally, the histological analysis revealed that uncx.S expression is necessary for the correct formation of pedicles and neural arch of the vertebrae, and uncx.L is required for trunk muscle development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio , Proteínas de Xenopus , Xenopus laevis , Animais , Evolução Biológica , Somitos/metabolismo , Coluna Vertebral/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
4.
Ophthalmology ; 131(3): 277-287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37802392

RESUMO

PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Ceratite por Acanthamoeba , Benzamidinas , Biguanidas , Humanos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Produção de Droga sem Interesse Comercial , Estudos Prospectivos
5.
J Pathol ; 261(4): 427-441, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37776271

RESUMO

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca2+ ) handling alterations. Next, we investigated the role of the TWEAK-Fn14 axis in cardiomyocyte function following renal ischaemia-reperfusion (I/R) injury in mice. We observed that TWEAK-Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca2+ handling and arrhythmogenic Ca2+ events through an impairment in sarcoplasmic reticulum Ca2+ -adenosine triphosphatase 2a pump (SERCA2a ) and ryanodine receptor (RyR2 ) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca2+ cycling and arrhythmogenic events and prevented SERCA2a and RyR2 modifications. In conclusion, this study establishes the relevance of the TWEAK-Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Injúria Renal Aguda , Cálcio , Humanos , Camundongos , Animais , Cálcio/metabolismo , Receptor de TWEAK/metabolismo , Estudos Retrospectivos , Citocina TWEAK/metabolismo , Fatores de Necrose Tumoral/metabolismo , Miócitos Cardíacos/metabolismo , Injúria Renal Aguda/metabolismo
6.
Environ Manage ; 73(4): 697-712, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38263340

RESUMO

In recent decades, there has been a discernible reduction in temperate and Mediterranean grasslands with consequences on the decline of biodiversity and landscape heterogeneity. When this decline is due to agricultural abandonment, a renewed joint management, combining bush clearing by conservationists and grazing by farmers, should favor the maintenance of grasslands, their protected habitats and species and forage production. Rainfall irregularity explains part of the variation of these parameters. To verify these hypotheses, we conduct a comprehensive, multi-scale, multi-taxa study over a ten-year period in a Mediterranean protected area. At the regional scale, experimental plots in which this joint management was implemented are representative of residual managed grasslands of the protected area. At the mesoscale, rainfall irregularity is the main factor explaining inter-annual differences in the biomass of open landscapes, while fauna depends on management, tree cover and trophic resources. At the local scale, in a representative experimental plot, clearing had an immediate negative impact on plant richness and bird and positive on forage. Over a decade, plant biodiversity increased while forage, specialist plants and bird maintained, despite the regrowth of bush. Drought had a negative impact on richness, plant and forage abundance and phenological asynchrony on butterflies. In conclusion, joint management has positive, neutral and negative impacts to be considered before implementing this strategy. This long-term monitoring study draws important lessons for designing a sustainable management of grasslands under abandonment and irregular climate, that should be applied in temperate and Mediterranean regions that are increasingly vulnerable to these trends.


Assuntos
Borboletas , Pradaria , Animais , Humanos , Fazendeiros , Biodiversidade , Ecossistema , Plantas
7.
Small ; : e2306045, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009519

RESUMO

Plexcitonic nanoparticles exhibit strong light-matter interactions, mediated by localized surface plasmon resonances, and thereby promise potential applications in fields such as photonics, solar cells, and sensing, among others. Herein, these light-matter interactions are investigated by UV-visible and surface-enhanced Raman scattering (SERS) spectroscopies, supported by finite-difference time-domain (FDTD) calculations. Our results reveal the importance of combining plasmonic nanomaterials and J-aggregates with near-zero-refractive index. As plexcitonic nanostructures nanorattles are employed, based on J-aggregates of the cyanine dye 5,5,6,6-tetrachloro-1,1-diethyl-3,3-bis(4-sulfobutyl)benzimidazolocarbocyanine (TDBC) and plasmonic silver-coated gold nanorods, confined within mesoporous silica shells, which facilitate the adsorption of the J-aggregates onto the metallic nanorod surface, while providing high colloidal stability. Electromagnetic simulations show that the electromagnetic field is strongly confined inside the J-aggregate layer, at wavelengths near the upper plexcitonic mode, but it is damped toward the J-aggregate/water interface at the lower plexcitonic mode. This behavior is ascribed to the sharp variation of dielectric properties of the J-aggregate shell close to the plasmon resonance, which leads to a high opposite refractive index contrast between water and the TDBC shell, at the upper and the lower plexcitonic modes. This behavior is responsible for the high SERS efficiency of the plexcitonic nanorattles under both 633 nm and 532 nm laser illumination. SERS analysis showed a detection sensitivity down to the single-nanoparticle level and, therefore, an exceptionally high average SERS intensity per particle. These findings may open new opportunities for ultrasensitive biosensing and bioimaging, as superbright and highly stable optical labels based on the strong coupling effect.

8.
Nucleic Acids Res ; 49(D1): D1130-D1137, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-32990755

RESUMO

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variability worldwide. CSVS is also part of the GA4GH Beacon network. CSVS can be accessed at: http://csvs.babelomics.org/.


Assuntos
Crowdsourcing , Bases de Dados Genéticas , Genética Populacional/métodos , Genoma Humano , Software , Alelos , Mapeamento Cromossômico , Exoma , Frequência do Gene , Variação Genética , Genômica , Humanos , Internet , Medicina de Precisão/métodos , Espanha
9.
BMC Biol ; 20(1): 149, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761233

RESUMO

BACKGROUND: Fungi use light as an environmental signal to regulate developmental transitions that are key aspects of their biological cycles and that are also relevant for their dispersal and infectivity as plant or animal pathogens. In addition, light regulates the accumulation of photoprotective pigments, like carotenoids, and other secondary metabolites. Most fungal light responses occur after changes in gene transcription and we describe here a novel effect of light in the regulation of degradation of VE-1, a key component of the velvet complex, in the model fungus Neurospora crassa. The velvet complex is a fungal-specific protein complex that coordinates fungal development, secondary metabolism, and light regulation by interacting with other regulators and photoreceptors and modifying gene expression. RESULTS: We have characterized the role of VE-1 during conidiation in N. crassa. In vegetative mycelia, VE-1 is localized in the cytoplasm and nuclei and is required for light-dependent transcription but does not interact with the photoreceptor and transcription factor WC-1. VE-1 is more stable in light than in darkness during asexual development (conidiation). We have shown that this light effect requires the blue-light photoreceptor WC-1. We have characterized the role of the proteasome, the COP9 signalosome (CSN), and the adaptor component of cullin-RING ubiquitin ligases, FWD-1, in the degradation of VE-1. CONCLUSIONS: We propose that this new effect of light allows the fungal cell to adapt quickly to changes in light exposure by promoting the accumulation of VE-1 for the regulation of genes that participate in the biosynthesis of photoprotective pigments.


Assuntos
Neurospora crassa , Animais , Núcleo Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Neurospora crassa/metabolismo , Metabolismo Secundário , Fatores de Transcrição/genética
10.
Int J Mol Sci ; 24(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36769052

RESUMO

Plant phytoprostanes (PhytoPs) are lipid oxidative stress mediators that share structural similarities with mammal prostaglandins (PGs). They have been demonstrated to modulate inflammatory processes mediated by prostaglandins. The present study aims to test the effects of the most abundant oxylipin from Gracilaria longissima, ent-9-D1t-Phytoprostane (9-D1t-PhytoP), on platelet activation and vascular cells as well as clarify possible interactions with platelets and the endothelial EP3 receptor Platelet and monocyte activation was assessed by flow cytometry in the presence of purified 9-D1t-PhytoP. Cell migration was studied using the human Ea.hy926 cell line by performing a scratch wound healing assay. The RNA expression of inflammatory markers was evaluated by RT-PCR under inflammatory conditions. Blind docking consensus was applied to the study of the interactions of selected ligands against the EP3 receptor protein. The 9D1t-PhytoP exerts several pharmacological effects; these include prothrombotic and wound-healing properties. In endothelial cells, 9D1t-PhytP mimics the migration stimulus of PGE2. Computational analysis revealed that 9D1t-PhytP forms a stable complex with the hydrophobic pocket of the EP3 receptor by interaction with the same residues as misoprostol and prostaglandin E2 (PGE2), thus supporting its potential as an EP3 agonist. The potential to form procoagulant platelets and the higher endothelial migration rate of the 9-D1t-PhytoP, together with its capability to interact with PGE2 main target receptor in platelets suggest herein that this oxylipin could be a strong candidate for pharmaceutical research from a multitarget perspective.


Assuntos
Gracilaria , Animais , Humanos , Receptores de Prostaglandina , Células Endoteliais/metabolismo , Oxilipinas/farmacologia , Ativação Plaquetária , Dinoprostona/metabolismo , Prostaglandinas , Movimento Celular , Receptores de Prostaglandina E Subtipo EP3 , Leucócitos/metabolismo , Mamíferos/metabolismo
11.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674838

RESUMO

Acute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated with an alteration in the anti-aging factor klotho expression. However, it is unknown whether a klotho deficiency might aggravate cardiac damage after AKI. We examined intracellular calcium (Ca2+) handling in native ventricular isolated cardiomyocytes from wild-type (+/+) and heterozygous hypomorphic mice for the klotho gene (+/kl) in which an overdose of folic acid was administered to induce AKI. Twenty-four hours after AKI induction, cardiomyocyte contraction was decreased in mice with the partial deletion of klotho expression (heterozygous hypomorphic klotho named +/kl). This was accompanied by alterations in Ca2+ transients during systole and an impairment of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) function in +/kl mice after AKI induction. Moreover, Ca2+ spark frequency and the incidence of Ca2+ pro-arrhythmic events were greater in cardiomyocytes from heterozygous hypomorphic klotho compared to wild-type mice after AKI. A decrease in klotho expression plays a role in cardiorenal damage aggravating cardiac Ca2+ mishandling after an AKI, providing the basis for future targeted approaches directed to control klotho expression as novel therapeutic strategies to reduce the cardiac burden that affects AKI patients.


Assuntos
Injúria Renal Aguda , Glucuronidase , Camundongos , Animais , Glucuronidase/genética , Glucuronidase/metabolismo , Cálcio/metabolismo , Injúria Renal Aguda/etiologia , Miócitos Cardíacos/metabolismo , Cálcio da Dieta
12.
J Pathol ; 254(1): 5-19, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33512736

RESUMO

There is a complex relationship between cardiac and renal disease, often referred to as the cardiorenal syndrome. Heart failure adversely affects kidney function, and both acute and chronic kidney disease are associated with structural and functional changes to the myocardium. The pathological mechanisms and contributing interactions that surround this relationship remain poorly understood, limiting the opportunities for therapeutic intervention. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (Fn14), are abundantly expressed in injured kidneys and heart. The TWEAK-Fn14 axis promotes responses that drive tissue injury such as inflammation, proliferation, fibrosis, and apoptosis, while restraining the expression of tissue protective factors such as the anti-aging factor Klotho and the master regulator of mitochondrial biogenesis peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). High levels of TWEAK induce cardiac remodeling, and promote inflammation, tubular and podocyte injury and death, fibroblast proliferation, and, ultimately, renal fibrosis. Accordingly, targeting the TWEAK-Fn14 axis is protective in experimental kidney and heart disease. TWEAK has also emerged as a biomarker of kidney damage and cardiovascular outcomes and has been successfully targeted in clinical trials. In this review, we update our current knowledge of the roles of the TWEAK-Fn14 axis in cardiovascular and kidney disease and its potential contribution to the cardiorenal syndrome. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Síndrome Cardiorrenal/metabolismo , Citocina TWEAK/metabolismo , Receptor de TWEAK/metabolismo , Animais , Síndrome Cardiorrenal/patologia , Coração , Humanos , Rim/metabolismo , Rim/patologia
13.
Int J Mol Sci ; 23(3)2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35163794

RESUMO

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin-CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.


Assuntos
Antibacterianos/farmacologia , Endopeptidases/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/crescimento & desenvolvimento , Silanos/farmacologia , Antibacterianos/química , Bacteriófagos/metabolismo , Biofilmes/efeitos dos fármacos , Dendrímeros , Composição de Medicamentos , Sinergismo Farmacológico , Interferometria , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia de Fluorescência , Plâncton/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Silanos/química
14.
Plant Foods Hum Nutr ; 77(4): 521-528, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36048356

RESUMO

High-fructose diet is associated with an increased risk of dyslipidemia, metabolic syndrome, and the development of non-alcoholic fatty liver disease (NAFLD) through chronic inflammation. The present study aimed to elucidate the potential benefit of daily consumption of Smallanthus sonchifolius (yacon) roots, rich in fructooligosaccharides (FOS), on the progression to liver fibrosis, in a rat model of NAFLD induced by a high-fructose diet. Male Wistar rats were fed a standard diet (CD, n = 6) or a standard diet plus 10% fructose solution (FD; n = 18). After 20 weeks, FD rats were randomly separated into the following groups (n = 6, each): FD; FD treated with yacon flour (340 mg FOS/body weight; FD + Y) and FD treated with fenofibrate (30 mg/kg body weight; FD + F), for 16 weeks. Daily intake of yacon flour significantly reduced body weight gain, plasma lipid levels, transaminase activities, and improved systemic insulin response in FD rats. In the liver, yacon treatment decreased fructose-induced steatosis and inflammation, and reduced total collagen deposition (64%). Also, yacon decreased TGF-ß1 mRNA expression (78%), followed by decreased nuclear localization of p-Smad2/3 in liver tissue. Yacon significantly reduced the expression of α-smooth muscle actin (α-SMA), Col1α1, and Col3α1 mRNAs (85, 44, and 47%, respectively), inhibiting the activation of resident hepatic stellate cells (HSCs). These results suggested that yacon roots have the potential to ameliorate liver damage caused by long-term consumption of a high-fructose diet, being a promising nutritional strategy in NAFLD management.


Assuntos
Asteraceae , Fenofibrato , Hepatopatia Gordurosa não Alcoólica , Animais , Ratos , Actinas/metabolismo , Dieta , Fenofibrato/metabolismo , Frutose/efeitos adversos , Inflamação , Insulina/metabolismo , Lipídeos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ratos Wistar , RNA Mensageiro , Transaminases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Aumento de Peso
15.
Ann Vasc Surg ; 71: 533.e1-533.e6, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32927047

RESUMO

We report a case of a 38-year-old male diagnosed with fibromuscular dysplasia (FMD) and a dissection of both common iliac arteries without aortic involvement. It was revealed after an inguinal hematoma and a pelvic pain, which are not the typical FMD presentation. Surgical treatment was performed after a rapid iliac growth in the first month control computed tomography angiography. Although the clinical course of this entity is relatively benign, rupture of the common iliac artery has also been described.


Assuntos
Dissecção Aórtica/etiologia , Displasia Fibromuscular/complicações , Aneurisma Ilíaco/etiologia , Artéria Ilíaca , Adulto , Dissecção Aórtica/diagnóstico por imagem , Implante de Prótese Vascular , Angiografia por Tomografia Computadorizada , Dilatação Patológica , Progressão da Doença , Displasia Fibromuscular/diagnóstico por imagem , Displasia Fibromuscular/cirurgia , Hematoma/etiologia , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/cirurgia , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/cirurgia , Masculino , Dor Pélvica/etiologia , Resultado do Tratamento
16.
Sensors (Basel) ; 21(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207883

RESUMO

Surveillance cameras are being installed in many primary daily living places to maintain public safety. In this video-surveillance context, anomalies occur only for a very short time, and very occasionally. Hence, manual monitoring of such anomalies may be exhaustive and monotonous, resulting in a decrease in reliability and speed in emergency situations due to monitor tiredness. Within this framework, the importance of automatic detection of anomalies is clear, and, therefore, an important amount of research works have been made lately in this topic. According to these earlier studies, supervised approaches perform better than unsupervised ones. However, supervised approaches demand manual annotation, making dependent the system reliability of the different situations used in the training (something difficult to set in anomaly context). In this work, it is proposed an approach for anomaly detection in video-surveillance scenes based on a weakly supervised learning algorithm. Spatio-temporal features are extracted from each surveillance video using a temporal convolutional 3D neural network (T-C3D). Then, a novel ranking loss function increases the distance between the classification scores of anomalous and normal videos, reducing the number of false negatives. The proposal has been evaluated and compared against state-of-art approaches, obtaining competitive performance without fine-tuning, which also validates its generalization capability. In this paper, the proposal design and reliability is presented and analyzed, as well as the aforementioned quantitative and qualitative evaluation in-the-wild scenarios, demonstrating its high sensitivity in anomaly detection in all of them.


Assuntos
Algoritmos , Redes Neurais de Computação , Gravação em Vídeo , Reprodutibilidade dos Testes
17.
Nano Lett ; 20(1): 456-462, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31769993

RESUMO

Nanowires can serve as flexible substrates for hybrid epitaxial growth on selected facets, allowing for the design of heterostructures with complex material combinations and geometries. In this work we report on hybrid epitaxy of freestanding vapor-liquid-solid grown and in-plane selective area grown semiconductor-ferromagnetic insulator-superconductor (InAs/EuS/Al) nanowire heterostructures. We study the crystal growth and complex epitaxial matching of wurtzite and zinc-blende InAs/rock-salt EuS interfaces as well as rock-salt EuS/face-centered cubic Al interfaces. Because of the magnetic anisotropy originating from the nanowire shape, the magnetic structure of the EuS phase is easily tuned into single magnetic domains. This effect efficiently ejects the stray field lines along the nanowires. With tunnel spectroscopy measurements of the density of states, we show that the material has a hard induced superconducting gap, and magnetic hysteretic evolution which indicates that the magnetic exchange fields are not negligible. These hybrid nanowires fulfill key material requirements for serving as a platform for spin-based quantum applications, such as scalable topological quantum computing.

18.
Acc Chem Res ; 52(7): 1855-1864, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31243968

RESUMO

For decades, plasmonic nanoparticles have been extensively studied due to their extraordinary properties, related to localized surface plasmon resonances. A milestone in the field has been the development of the so-called seed-mediated growth method, a synthetic route that provided access to an extraordinary diversity of metal nanoparticles with tailored size, geometry and composition. Such a morphological control came along with an exquisite definition of the optical response of plasmonic nanoparticles, thereby increasing their prospects for implementation in various fields. The susceptibility of surface plasmons to respond to small changes in the surrounding medium or to perturb (enhance/quench) optical processes in nearby molecules, has been exploited for a wide range of applications, from biomedicine to energy harvesting. However, the possibilities offered by plasmonic nanoparticles can be expanded even further by their careful assembly into either disordered or ordered structures, in 2D and 3D. The assembly of plasmonic nanoparticles gives rise to coupling/hybridization effects, which are strongly dependent on interparticle spacing and orientation, generating extremely high electric fields (hot spots), confined at interparticle gaps. Thus, the use of plasmonic nanoparticle assemblies as optical sensors have led to improving the limits of detection for a wide variety of (bio)molecules and ions. Importantly, in the case of highly ordered plasmonic arrays, other novel and unique optical effects can be generated. Indeed, new functional materials have been developed via the assembly of nanoparticles into highly ordered architectures, ranging from thin films (2D) to colloidal crystals or supercrystals (3D). The progress in the design and fabrication of 3D supercrystals could pave the way toward next generation plasmonic sensors, photocatalysts, optomagnetic components, metamaterials, etc. In this Account, we summarize selected recent advancements in the field of highly ordered 3D plasmonic superlattices. We first analyze their fascinating optical properties for various systems with increasing degrees of complexity, from an individual metal nanoparticle through particle clusters with low coordination numbers to disordered self-assembled structures and finally to supercrystals. We then describe recent progress in the fabrication of 3D plasmonic supercrystals, focusing on specific strategies but without delving into the forces governing the self-assembly process. In the last section, we provide an overview of the potential applications of plasmonic supercrystals, with a particular emphasis on those related to surface-enhanced Raman scattering (SERS) sensing, followed by a brief highlight of the main conclusions and remaining challenges.

19.
BMC Biol ; 17(1): 88, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711484

RESUMO

BACKGROUND: Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. RESULTS: We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10-11 (A. flavus), 1.1 × 10-11 (A. fumigatus) and 4.1 × 10-11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10-11 (A. flavus), 2.2 × 10-11 (A. fumigatus) and 4.5 × 10-11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5-6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. CONCLUSIONS: We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.


Assuntos
Aspergillus flavus/genética , Genoma Fúngico , Mutação , Mapeamento Cromossômico
20.
Nano Lett ; 19(6): 3396-3408, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31039314

RESUMO

The lack of mirror symmetry in binary semiconductor compounds turns them into polar materials, where two opposite orientations of the same crystallographic direction are possible. Interestingly, their physical properties (e.g., electronic or photonic) and morphological features (e.g., shape, growth direction, and so forth) also strongly depend on the polarity. It has been observed that nanoscale materials tend to grow with a specific polarity, which can eventually be reversed for very specific growth conditions. In addition, polar-directed growth affects the defect density and topology and might induce eventually the formation of undesirable polarity inversion domains in the nanostructure, which in turn will affect the photonic and electronic final device performance. Here, we present a review on the polarity-driven growth mechanism at the nanoscale, combining our latest investigation with an overview of the available literature highlighting suitable future possibilities of polarity engineering of semiconductor nanostructures. The present study has been extended over a wide range of semiconductor compounds, covering the most commonly synthesized III-V (GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb) and II-VI (ZnO, ZnTe, CdS, CdSe, CdTe) nanowires and other free-standing nanostructures (tripods, tetrapods, belts, and membranes). This systematic study allowed us to explore the parameters that may induce polarity-dependent and polarity-driven growth mechanisms, as well as the polarity-related consequences on the physical properties of the nanostructures.

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