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1.
Nano Lett ; 24(36): 11149-11155, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39197107

RESUMEN

The energy landscape of multiply connected superconducting structures is ruled by fluxoid quantization due to the implied single-valuedness of the complex wave function. The transitions and interaction between these energy states, each defined by a specific phase winding number, are governed by classical and/or quantum phase slips. Understanding these events requires the ability to probe, noninvasively, the state of the ring. Here, we employ a niobium resonator to examine the superconducting properties of an aluminum loop. By applying a magnetic field, adjusting temperature, and altering the loop's dimensions via focused ion beam milling, we correlate resonance frequency shifts with changes in the loop's kinetic inductance. This parameter is an indicator of the superconducting condensate's state, facilitating the detection of phase slips in nanodevices and providing insights into their dynamics. Our method presents a proof-of-principle spectroscopic technique with promising potential for investigating Cooper pair density in inductively coupled superconducting nanostructures.

2.
bioRxiv ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39185176

RESUMEN

The absence of dystrophin protein causes cardiac dysfunction in boys with Duchenne Muscular Dystrophy (DMD). However, the common mouse model of DMD (B10-mdx) does not manifest cardiac deficits until late adulthood limiting our understanding of the mechanism and therapeutic approaches to target the pediatric-onset cardiac pathology in DMD. We show the mdx mouse model on the DBA/2J genetic background (D2-mdx) displays juvenile-onset cardiomyopathy. Molecular and histological analysis revealed heightened leukocyte chemotactic signaling and failure to resolve inflammation, leading to chronic inflammation and extracellular matrix (ECM) fibrosis, causing cardiac pathology in juvenile D2-mdx mice. We show that pharmacologically activating the N-formyl peptide receptor 2 (FPR2) - a receptor that physiologically resolves acute inflammation, mitigated chronic cardiac inflammation and fibrosis, and prevented juvenile onset cardiomyopathy in the D2-mdx mice. These studies offer insights into pediatric onset of cardiac damage in DMD, a new therapeutic target, and identify a drug-based potential therapy.

3.
Adv Sci (Weinh) ; 11(33): e2402464, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38952077

RESUMEN

Phase transitions are typically quantified using order parameters, such as crystal lattice distances and radial distribution functions, which can identify subtle changes in crystalline materials or high-contrast phases with large structural differences. However, the identification of phases with high complexity, multiscale organization and of complex patterns during the structural fluctuations preceding phase transitions, which are essential for understanding the system pathways between phases, is challenging for those traditional analyses. Here, it is shown that for two model systems- thermotropic liquid crystals and a lyotropic water/surfactant mixtures-graph theoretical (GT) descriptors can successfully identify complex phases combining molecular and nanoscale levels of organization that are hard to characterize with traditional methodologies. Furthermore, the GT descriptors also reveal the pathways between the different phases. Specifically, centrality parameters and node-based fractal dimension quantify the system behavior preceding the transitions, capturing fluctuation-induced breakup of aggregates and their long-range cooperative interactions. GT parameterization can be generalized for a wide range of chemical systems and be instrumental for the growth mechanisms of complex nanostructures.

4.
Endocrine ; 84(3): 1116-1124, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703329

RESUMEN

PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.


Asunto(s)
Hormona de Crecimiento Humana , Piel , Humanos , Masculino , Femenino , Adulto , Piel/metabolismo , Hormona de Crecimiento Humana/deficiencia , Persona de Mediana Edad , Neoplasias Cutáneas , Envejecimiento de la Piel/fisiología , Adulto Joven , Fenómenos Fisiológicos de la Piel , Enanismo Hipofisario/epidemiología , Adolescente
5.
J Neuromuscul Dis ; 11(2): 315-326, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38217607

RESUMEN

Background: Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of muscle mass and muscle function. Previous work from our lab demonstrated that skeletal muscles from a mouse model of ALS show elevated intracellular calcium (Ca2+) levels and heightened endoplasmic reticulum (ER) stress. Objective: To investigate whether overexpression of sarcoplasmic reticulum (SR) Ca2+ ATPase 1 (SERCA1) in skeletal muscle would improve intracellular Ca2+ handling, attenuate ER stress, and improve motor function ALS transgenic mice. Methods: B6SJL-Tg (SOD1*G93A)1Gur/J (ALS-Tg) mice were bred with skeletal muscle α-actinin SERCA1 overexpressing mice to generate wild type (WT), SERCA1 overexpression (WT/+SERCA1), ALS-Tg, and SERCA1 overexpressing ALS-Tg (ALS-Tg/+SERCA1) mice. Motor function (grip test) was assessed weekly and skeletal muscles were harvested at 16 weeks of age to evaluate muscle mass, SR-Ca2+ ATPase activity, levels of SERCA1 and ER stress proteins - protein disulfide isomerase (PDI), Grp78/BiP, and C/EBP homologous protein (CHOP). Single muscle fibers were also isolated from the flexor digitorum brevis muscle to assess changes in resting and peak Fura-2 ratios. Results: ALS-Tg/+SERCA1 mice showed improved motor function, delayed onset of disease, and improved muscle mass compared to ALS-Tg. Further, ALS-Tg/+SERCA1 mice returned levels of SERCA1 protein and SR-Ca2+ ATPase activity back to levels in WT mice. Unexpectedly, SERCA-1 overexpression increased levels of the ER stress maker Grp78/BiP in both WT and ALS-Tg mice, while not altering protein levels of PDI or CHOP. Lastly, single muscle fibers from ALS-Tg/+SERCA1 had similar resting but lower peak Fura-2 levels (at 30 Hz and 100 Hz) compared to ALS-Tg mice. Conclusions: These data indicate that SERCA1 overexpression attenuates the progressive loss of muscle mass and maintains motor function in ALS-Tg mice while not lowering resting Ca2+ levels or ER stress.


Asunto(s)
Esclerosis Amiotrófica Lateral , Ratones , Animales , Chaperón BiP del Retículo Endoplásmico , Calcio/metabolismo , Fura-2/metabolismo , Músculo Esquelético , Ratones Transgénicos , Atrofia Muscular/metabolismo , ATPasas Transportadoras de Calcio/metabolismo
6.
Chemosphere ; 349: 140889, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081521

RESUMEN

The Parnaíba River is the main river in the Parnaíba Delta basin, the largest delta in the Americas. About 18 polycyclic aromatic hydrocarbons (PAHs) were identified and the environmental risk associated with the sediments was evaluated. The study found that PAHs levels ranged from 5.92 to 1521.17 ng g-1, which was classified as low to high pollution, and that there were multiple sources of pollution along the river, with pyrolytic sources predominating, mainly from urban activity such as trucking, although the influence of rural activity cannot be ruled out. PAHs correlated with black carbon and organic matter and showed high correlation with acenaphthylene, phenanthrene, pyrene, benzo(a)anthracene, chrysene, benzo(ghi)perylene, and ∑PAHs. The benzo(a)pyrene levels were classified as a risk to aquatic life because the threshold effect level and the probable effect level were exceeded. In addition, the sediments were classified as slightly contaminated with a benzo(a)pyrene toxicity equivalent value of 108.43 ng g-1. Thus, the priority level PAH exhibited carcinogenic and mutagenic activity that posed a potential risk to human health.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Humanos , Hidrocarburos Policíclicos Aromáticos/análisis , Monitoreo del Ambiente , Benzo(a)pireno/análisis , Brasil , Contaminación Ambiental , Sedimentos Geológicos , Contaminantes Químicos del Agua/análisis , Medición de Riesgo
7.
Endocr Connect ; 13(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38019109

RESUMEN

Individuals with untreated isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene from Itabaianinha Brazil have increased insulin sensitivity, normal life expectancy, and an extended health span, i.e. the period of life free from disabilities. We hypothesize that their prolonged health span is accompanied by a delayed cognitive decline in senescence. To test this hypothesis, we have administered the Literacy-Independent Cognitive Assessment (LICA) to 15 IGHD individuals aged over 50 years and 15 controls matched by age, sex, years of education, and percentage of illiteracy. All individuals were negative for HIV and syphilis serology, and there were no differences in serum levels of folate, vitamin B12 and TSH between the two groups, while free T4 was higher in the IGHD group. IGHD subjects had a higher total LICA score than controls, 215 (22.7) vs 204.2 (18.1), without reaching statistical significance. Scores of memory, visuoconstruction, language and calculation were similar between the two groups, with better attention (9.5 (1.4) vs 8.3 (1.1), P = 0.01) and executive function (38.3 (4.8) vs 35.1 (2.5), P = 0.03) scores in IGHD. MANCOVA revealed that group (but no age) had a significant effect on the LICA variables (partial eta squared of 0.455, power of 0.812, P = 0.02). This effect is verified on attention (partial eta squared 0.216, power of 0.749, P = 0.01) and executive function (partial eta squared 0.154, power of 0.570, P = 0.03. In conclusion, IGHD in senescence is associated with similar total cognitive performance but better attention and executive function than controls.

8.
iScience ; 26(8): 107479, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37599828

RESUMEN

Fibro/adipogenic progenitors (FAPs) are skeletal muscle stromal cells that support regeneration of injured myofibers and their maintenance in healthy muscles. FAPs are related to mesenchymal stem cells (MSCs/MeSCs) found in other adult tissues, but there is poor understanding of the extent of similarity between these cells. Using single-cell RNA sequencing (scRNA-seq) datasets from multiple mouse tissues, we have performed comparative transcriptomic analysis. This identified remarkable transcriptional similarity between FAPs and MeSCs, confirmed the suitability of PDGFRα as a reporter for FAPs, and identified extracellular proteolysis as a new FAP function. Using PDGFRα as a cell surface marker, we isolated FAPs from healthy and dysferlinopathic mouse muscles and performed scRNA-seq analysis. This revealed decreased FAP-mediated Wnt signaling as a potential driver of FAP dysfunction in dysferlinopathic muscles. Analysis of FAPs in dysferlin- and dystrophin-deficient muscles identified a relationship between the nature of muscle pathology and alteration in FAP gene expression.

9.
Cell Death Discov ; 9(1): 224, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37402716

RESUMEN

Lack of dystrophin expression is the underlying genetic basis for Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2-mdx is a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2-mdx muscles is associated with an enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports the excessive accumulation of fibroadipogenic progenitors (FAPs), leading to increased fibrosis. Unexpectedly, the extent of damage and degeneration in juvenile D2-mdx muscle is significantly reduced in adults, and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance regenerative myogenesis in the adult D2-mdx muscle, reaching levels comparable to the milder B10-mdx model of DMD. Ex vivo co-culture of healthy satellite cells (SCs) with juvenile D2-mdx FAPs reduces their fusion efficacy. Wild-type juvenile D2 mice also manifest regenerative myogenic deficit and glucocorticoid treatment improves their muscle regeneration. Our findings indicate that aberrant stromal cell responses contribute to poor regenerative myogenesis and greater muscle degeneration in juvenile D2-mdx muscles and reversal of this reduces pathology in adult D2-mdx muscle, identifying these responses as a potential therapeutic target for the treatment of DMD.

10.
bioRxiv ; 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37034785

RESUMEN

Lack of dystrophin is the genetic basis for the Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2- mdx is a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2- mdx muscles is associated with enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports excessive accumulation of fibroadipogenic progenitors (FAPs). Unexpectedly, the extent of damage and degeneration of juvenile D2- mdx muscle is reduced in adults and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance myogenesis in the adult D2- mdx muscle, reaching levels comparable to the milder (B10- mdx ) mouse model of DMD. Ex vivo co-culture of healthy satellite cells (SCs) with the juvenile D2- mdx FAPs reduced their fusion efficacy and in vivo glucocorticoid treatment of juvenile D2 mouse improved muscle regeneration. Our findings indicate that aberrant stromal cell response contributes to poor myogenesis and greater muscle degeneration in dystrophic juvenile D2- mdx muscles and reversal of this reduces pathology in adult D2- mdx mouse muscle, identifying these as therapeutic targets to treat dystrophic DMD muscles.

11.
Environ Monit Assess ; 194(8): 568, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35794258

RESUMEN

In this study, the multi-marker approach was used for the first time with a highly urbanized lake located in the city of Fortaleza, Brazil, to provide a comprehensive view of temporal trends in sources of pollutants and evaluate the relation between the influence of anthropogenic activities and socioeconomic development. Total concentrations of the markers analyzed ranged from 21.0 to 103.8 ng g-1, 450.2 to 2390.2 ng g-1, and 233.8 to 9827.3 ng g-1 for ∑PAHs, ∑n-alk, and ∑sterols, respectively. Concentrations and patterns of PAH, AH, and sterol ratio distribution changed over time and may be associated with different episodes in the history of the city of Fortaleza. The marker ratio distribution in the sediment core revealed an overlap of natural and anthropogenic sources, with degraded oil, biogenic inputs, pyrogenic processes, and fecal contamination from humans and animals in the past changing to petroleum fossil inputs and high contamination from sewage in the present day. The distribution of markers and the chronological history of Fortaleza revealed two distinct periods related to human activities during the development of the city. In the first period (prior to the 1950s), the main human activities were animal breeding and the use of biomass for domestic activities, public and cargo transportation, and commercial activities, especially food production. In the second period (after the 1950s), expansion of the city occurred due to the so-called Brazilian economic miracle and the main human activities were industrialization and urbanization processes, involving deforestation, paving, sewage discharge, and petroleum combustion.


Asunto(s)
Petróleo , Contaminantes Químicos del Agua , Animales , Efectos Antropogénicos , Brasil , Monitoreo del Ambiente , Sedimentos Geológicos , Aguas del Alcantarillado , Contaminantes Químicos del Agua/análisis
12.
Environ Monit Assess ; 194(8): 567, 2022 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-35792964

RESUMEN

The Jundiaí-Potengi Estuary (EJP) is located on the semi-arid coast of northeastern Brazil and is influenced by multiple sources of contamination. The sediment quality of EJP was assessed by using a multi-geochemical approach during the dry and wet seasons. Sediments were analyzed for concentrations of nutrients, metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, hormones (natural and synthetic), and sterols. The results were integrated by multivariate methods. The sediment was altered by the presence of contaminants from anthropogenic and natural sources. The middle and lower estuarine areas were considered more degraded in both seasons. In these regions, metals, hormones, sterols, and PAHs were found, indicating that these regions are severely affected by industrial, sanitary and aquaculture effluents, combustion of fossil fuels, and oil spills. The upstream region was contaminated by pesticides. The contamination pattern along the EJP shows the prevalence of local sources which continuously release the chemicals into the estuary. Worse conditions occurred during the rainy season, when the runoff from urban and rural areas is more intense and carries a greater load of contaminants to the EJP.


Asunto(s)
Plaguicidas , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Brasil , Monitoreo del Ambiente/métodos , Estuarios , Sedimentos Geológicos , Hormonas , Metales/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Esteroles , Contaminantes Químicos del Agua/análisis
13.
Skelet Muscle ; 12(1): 14, 2022 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-35733150

RESUMEN

BACKGROUND: A common polymorphism (R577X) in the ACTN3 gene results in the complete absence of the Z-disc protein α-actinin-3 from fast-twitch muscle fibres in ~ 16% of the world's population. This single gene polymorphism has been subject to strong positive selection pressure during recent human evolution. Previously, using an Actn3KO mouse model, we have shown in fast-twitch muscles, eccentric contractions at L0 + 20% stretch did not cause eccentric damage. In contrast, L0 + 30% stretch produced a significant ~ 40% deficit in maximum force; here, we use isolated single fast-twitch skeletal muscle fibres from the Actn3KO mouse to investigate the mechanism underlying this. METHODS: Single fast-twitch fibres are separated from the intact muscle by a collagenase digest procedure. We use label-free second harmonic generation (SHG) imaging, ultra-fast video microscopy and skinned fibre measurements from our MyoRobot automated biomechatronics system to study the morphology, visco-elasticity, force production and mechanical strength of single fibres from the Actn3KO mouse. Data are presented as means ± SD and tested for significance using ANOVA. RESULTS: We show that the absence of α-actinin-3 does not affect the visco-elastic properties or myofibrillar force production. Eccentric contractions demonstrated that chemically skinned Actn3KO fibres are mechanically weaker being prone to breakage when eccentrically stretched. Furthermore, SHG images reveal disruptions in the myofibrillar alignment of Actn3KO fast-twitch fibres with an increase in Y-shaped myofibrillar branching. CONCLUSIONS: The absence of α-actinin-3 from the Z-disc in fast-twitch fibres disrupts the organisation of the myofibrillar proteins, leading to structural weakness. This provides a mechanistic explanation for our earlier findings that in vitro intact Actn3KO fast-twitch muscles are significantly damaged by L0 + 30%, but not L0 + 20%, eccentric contraction strains. Our study also provides a possible mechanistic explanation as to why α-actinin-3-deficient humans have been reported to have a faster decline in muscle function with increasing age, that is, as sarcopenia reduces muscle mass and force output, the eccentric stress on the remaining functional α-actinin-3 deficient fibres will be increased, resulting in fibre breakages.


Asunto(s)
Actinina , Enfermedades Musculares , Actinina/genética , Actinina/metabolismo , Animales , Calcio/metabolismo , Cinética , Ratones , Ratones Noqueados , Contracción Muscular/fisiología , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Enfermedades Musculares/metabolismo
14.
Biol Sport ; 39(2): 231-236, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35309530

RESUMEN

The present study aimed to investigate the physiological response to CrossFit "workouts of the day" (WODs) based on two different structures of training session: 1) the "as many repetitions as possible" (AMRAP) "Cindy" and 2) the "round for time" (RFT) "Open 18.4" session. CrossFit athletes (11 men and 12 women) were divided into two groups: 1) one performing the WOD "Cindy" (GC) and 2) one performing the WOD "Open 18.4" (GO). Before, immediately after and 30 min after WODs, blood lactate (LAC), heart rate (HR) and systolic and diastolic blood pressures (SBP and DBP) were measured. A two-way ANOVA indicated differences in physiological responses between GC and GO. Both WODs increased HR to similar levels. Only GO significantly increased SBP immediately after exercise compared to the rest period (p < 0.01), with no difference to GC. GO presented higher levels of LAC immediately after exercise compared to GC (15.8 ± 4.9 mM [GO] vs 9.3 ± 2.3 mM [GC]; p < 0.01). LAC remained different between the groups 30 min after exercise (7.0 ± 3.9 mM [GO] vs 3.9 ± 0.9 mM [GC]; p < 0.01). The results suggest that the studied WODs do not differ in acute cardiovascular responses, but depend on different metabolic demands, with RFT structure relying more on glycolytic metabolism (indicated by greater LAC levels after exercise in GO). Such results are in agreement independent of gender.

15.
ISA Trans ; 129(Pt A): 169-178, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35144771

RESUMEN

The present paper is concerned with the robust and smooth attitude-position tracking control of fully actuated multirotor aerial vehicles equipped with fixed rotors and subject to matched model uncertainties and disturbances. The vehicle coupled dynamic equations representing the translational and rotational motions are thoroughly derived using the multibody approach, considering the external torque and force disturbances as well as the uncertainties in the inertia parameters of the airframe and the rotors. From this model, it is shown that the overall disturbances and uncertainties can be lumped into an additive-matched plant-model discrepancy. Then, based on a geometrically consistent description of the control error in SE(3), a novel joint geometric attitude-position control law is designed using a multi-input smooth second-order sliding mode strategy. The latter uses a high-order sliding mode disturbance observer to guarantee the overall system robustness. The second-order sliding mode is proved to exist using vector-field homogeneity, and the tracking error is shown to exponentially converge to the origin. The method is extensively evaluated via numerical simulations using a fully actuated hexacopter with tilted rotors, showing advantages with respect to state-of-the-art alternatives.

16.
ISA Trans ; 128(Pt B): 123-135, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34980480

RESUMEN

The present paper is concerned with the wayset-based guidance of underactuated multirotor aerial vehicles (MAVs). A hierarchical guidance and control structure is first established, in which the guidance is realized as a supervisory loop. The lower-level stabilizing attitude and position control laws are assumed to be available. On the other hand, the outer-loop guidance is designed based on a fixed-horizon tube-based robust model predictive control (MPC), which conducts the MAV to visit a given sequence of waysets, without violating their state and control bounds, and allowing the vehicle to rest in each wayset for a specified period. The MPC is designed using a reduced-order closed-loop dynamic model describing the vehicle's translation, which is derived considering the stabilizing position and attitude control laws and the assumption of a time-scale separation between the closed-loop translational and rotational dynamics. This model is put into a discrete-time linear state-space representation subject to additive bounded random disturbance and measurement noise. The properties of the proposed method, which includes the MPC recursive feasibility and robust stability as well as the overall guidance feasibility, are analytically studied. The method is also numerically evaluated using a realistic quadrotor dynamic model, showing its effectiveness and confirming its properties.

17.
Environ Pollut ; 296: 118709, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34942290

RESUMEN

We reviewed 20 years of levels, sources, and environmental risks related to the main petroleum hydrocarbons in the northeast region of Brazil. The aim of this study was to conduct a systematic review to serve as a comprehensive baseline for future monitoring programmes related to the oil spill disaster in 2019/2020. Most contamination levels of both PAHs and AHs were classified as low, except those in specific areas influenced by human activities, such as ports, highly urbanised mangroves, or rivers of medium-sized cities with inadequate liquid and solid waste treatment. Most hydrocarbons were linked to natural sources and burning processes, except in regions of extraction activities and petrochemical facilities as well as highly urbanised areas, where degraded petroleum and oil hydrocarbons predominated. Only 2.5% of the samples exceeded threshold effect levels for ∑16-PAHs and no samples exceeded probable effect levels. When regional threshold levels were used, however, the probable effect for the ∑16-PAHs measured was high, ranging from 5.8 to 6.1%. The few studies reporting biological responses showed that hydrocarbons from anthropogenic sources can induce adverse effects on marine organisms even at low to moderate levels. As the region has recently received a considerable quantity of crude oil, studies should be prioritised for a more precise assessment of the impact of this oil spill.


Asunto(s)
Contaminación por Petróleo , Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Brasil , Ecosistema , Monitoreo del Ambiente , Sedimentos Geológicos , Humanos , Hidrocarburos/análisis , Petróleo/análisis , Contaminación por Petróleo/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes Químicos del Agua/análisis
18.
Trends Mol Med ; 28(1): 8-11, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34750068

RESUMEN

Aside from myofibers, numerous mononucleated cells reside in the skeletal muscle. These include the mesenchymal cells called fibro-adipogenic progenitors (FAPs), that support muscle development and regeneration in adult muscles. Recent evidence shows that defects in FAP function contributes to chronic muscle diseases and targeting FAPs offers avenues for treating these diseases.


Asunto(s)
Adipogénesis , Células Madre Mesenquimatosas , Adulto , Diferenciación Celular , Humanos , Desarrollo de Músculos , Músculo Esquelético
19.
ISA Trans ; 126: 21-35, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34366122

RESUMEN

The present work is concerned with the wayset-based guidance of a very general class of fully-actuated multirotor aerial vehicles which can be equipped with fixed or vectorable rotors. The problem is tackled by means of a hierarchical guidance and control framework containing two nested loops. For the outer loop, a guidance strategy based on the nonlinear model predictive control paradigm is proposed. It steers the vehicle through a sequence of position-attitude waysets, while guaranteeing the satisfaction of the control allocation constraints. For the inner loop, a single multi-variable inverse-dynamic force-torque control law is designed to stabilize the translational and rotational dynamics, and an optimal control allocator is formulated, by means of a convex program, to distribute the required control efforts among the available actuators. The asymptotic stability of the inner and outer loop, the recursive feasibility of the guidance algorithm, as well as the feasibility of the control allocator are proved to hold. The proposed method is numerically illustrated with a quadrotor containing two-degrees-of-freedom vectorable rotors and shows to be effective to guide the vehicle while respecting all the rotor constraints.

20.
J Neuromuscul Dis ; 8(s2): S383-S402, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34569969

RESUMEN

Recently, the Food and Drug Administration granted accelerated approvals for four exon skipping therapies -Eteplirsen, Golodirsen, Viltolarsen, and Casimersen -for Duchenne Muscular Dystrophy (DMD). However, these treatments have only demonstrated variable and largely sub-therapeutic levels of restored dystrophin protein in DMD patients, limiting their clinical impact. To better understand variable protein expression and the behavior of truncated dystrophin protein in vivo, we assessed turnover dynamics of restored dystrophin and dystrophin glycoprotein complex (DGC) proteins in mdx mice after exon skipping therapy, compared to those dynamics in wild type mice, using a targeted, highly-reproducible and sensitive, in vivo stable isotope labeling mass spectrometry approach in multiple muscle tissues. Through statistical modeling, we found that restored dystrophin protein exhibited altered stability and slower turnover in treated mdx muscle compared with that in wild type muscle (∼44 d vs. ∼24 d, respectively). Assessment of mRNA transcript stability (quantitative real-time PCR, droplet digital PCR) and dystrophin protein expression (capillary gel electrophoresis, immunofluorescence) support our dystrophin protein turnover measurements and modeling. Further, we assessed pathology-induced muscle fiber turnover through bromodeoxyuridine (BrdU) labeling to model dystrophin and DGC protein turnover in the context of persistent fiber degeneration. Our findings reveal sequestration of restored dystrophin protein after exon skipping therapy in mdx muscle leading to a significant extension of its half-life compared to the dynamics of full-length dystrophin in normal muscle. In contrast, DGC proteins show constant turnover attributable to myofiber degeneration and dysregulation of the extracellular matrix (ECM) in dystrophic muscle. Based on our results, we demonstrate the use of targeted mass spectrometry to evaluate the suitability and functionality of restored dystrophin isoforms in the context of disease and propose its use to optimize alternative gene correction strategies in development for DMD.


Asunto(s)
Distroglicanos/metabolismo , Distrofina/metabolismo , Terapia Genética/métodos , Distrofia Muscular de Duchenne/terapia , Oligonucleótidos Antisentido/uso terapéutico , Animales , Exones , Ratones , Ratones Endogámicos mdx , Fibras Musculares Esqueléticas/metabolismo
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