Alessandro N. Vargas  Leonardo Acho  Gisela Pujol  Eduardo F. Costa  João Y. Ishihara  João B. R. do Val 《国际强度与非线性控制杂志
》2016,26(9):1980-1993

The note presents an output feedback control strategy for Markov jump linear systems with no mode observation. Based on minimizing a finite‐time quadratic cost, we derive an algorithm that generates output feedback gains that satisfy a necessary optimality condition. These gains can be computed off‐line relying only on the initial condition of the system. This result expands a previous one from the literature that considered state‐feedback only. To illustrate the usefulness of the approach, real‐time laboratory experiments were performed to control an automotive electronic throttle valve subject to Markov‐driven voltage fluctuations. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

    

Veronika Ozana  Karel Hruska  Leonardo A. Sechi 《International journal of molecular sciences》2022,23(7)

Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization, lifestyle changes and new technologies in the animal and plant industry are involved in frequent contact of people with mycobacteria. Type 1 diabetes is a multifactorial polygenic disease; its origin is conditioned by the mutual interaction of genetic and other factors. The environmental factors and certain pathogenetic pathways are shared by some immune mediated chronic inflammatory and autoimmune diseases, which are associated with triggers originating mainly from Mycobacterium avium subspecies paratuberculosis, an intestinal pathogen which persists in the environment. Type 1 diabetes and some other chronic inflammatory diseases thus pose the global health problem which could be mitigated by measures aimed to decrease the human exposure to this neglected zoonotic mycobacterium.  相似文献   

    

Leonardo Albarracin  Ramiro Ortiz Moyano  Juan Martin Vargas  Bruno G. N. Andrade  Juan Cortez Zamar  Stefania Dentice Maidana  Kohtaro Fukuyama  Shoichiro Kurata  María ngela Jure  Haruki Kitazawa  Julio Villena 《International journal of molecular sciences》2022,23(13)

In recent years, an increase in the prevalence hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) was detected in hospitals of Tucuman (Northwest Argentina). In this work, the virulence and the innate immune response to two K. pneumoniae ST25 strains (LABACER 01 and LABACER 27) were evaluated in a murine model after a respiratory challenge. In addition, comparative genomics was performed with K. pneumoniae LABACER01 and LABACER27 to analyze genes associated with virulence. Both LABACER01 and LABACER27 were detected in the lungs of infected mice two days after the nasal challenge, with LABACER01 counts significantly higher than those of LABACER27. Only LABACER01 was detected in hemocultures. Lactate dehydrogenase (LDH) and albumin levels in bronchoalveolar lavage (BAL) samples were significantly higher in mice challenged with LABACER01 than in LABACER27-infected animals, indicating greater lung tissue damage. Both strains increased the levels of neutrophils, macrophages, TNF-α, IL-1β, IL-6, KC, MCP-1, IFN-γ, and IL-17 in the respiratory tract and blood, with the effect of LABACER01 more marked than that of LABACER27. In contrast, LABACER27 induced higher levels of IL-10 in the respiratory tract than LABACER01. Genomic analysis revealed that K. pneumoniae LABACER01 and LABACER27 possess virulence factors found in other strains that have been shown to be hypervirulent, including genes required for enterobactin (entABCDEF) and salmochelin (iroDE) biosynthesis. In both strains, the genes of toxin–antitoxin systems, as well as regulators of the expression of virulence factors and adhesion genes were also detected. Studies on the genetic potential of multiresistant K. pneumoniae strains as well as their cellular and molecular interactions with the host are of fundamental importance to assess the association of certain virulence factors with the intensity of the inflammatory response. In this sense, this work explored the virulence profile based on genomic and in vivo studies of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 strains, expanding the knowledge of the biology of the emerging ST25 clone in Argentina.  相似文献   

    

Lara Alessandrini  Leonardo Franz  Marta Sbaraglia  Tommaso Saccardo  Filippo Cappello  Alessandro Drigo  Anna Chiara Frigo  Gino Marioni 《International journal of molecular sciences》2022,23(14)

Programmed cell death ligand 1 (PD-L1) seems to rely on close relations between neoplastic and immune cells in the tumor microenvironment. Tumor to stroma ratio (TSR) has been associated with prognosis in different malignancies. The aims of this exploratory investigation were to analyze for the first time the: (i) association between TSR, PD-L1 expression and other clinical–pathological features in laryngeal squamous cell carcinoma (LSCC) biopsies and paired surgical specimens; (ii) prognostic and predictive role of TSR and PD-L1. TSR, PD-L1 expression (in terms of combined positive score [CPS]), and other clinical–pathological features were analyzed in biopsies and surgical specimens of 43 consecutive LSCC cases. A CPS < 1 evaluated on surgical specimens was associated with a low TSR (stroma rich) on both biopsies and surgical specimens (p = 0.0143 and p = 0.0063). Low TSR showed a significant negative prognostic value when evaluated on both biopsies and surgical specimens (HR = 8.808, p = 0.0003 and HR = 11.207, p = 0.0002). CPS ≥ 1 appeared to be a favorable prognostic factor (HR = 0.100, p = 0.0265). The association between bioptic and surgical specimen TSR and PD-L1 expression should be further investigated for a potential impact on targeted treatments, also with regard to immunotherapeutic protocols.  相似文献   

    

Diane Cleydes Baía da Silva  Leonardo Oliveira Bittencourt  Daiane Claydes Baia-da-Silva  Victoria Santos Chemelo  Luciana Eir-Quirino  Priscila Cunha Nascimento  Mrcia Cristina Freitas Silva  Marco Aurelio M. Freire  Walace Gomes-Leal  Maria Elena Crespo-Lopez  Rafael Rodrigues Lima 《International journal of molecular sciences》2022,23(7)

Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects of maternal exposure to MeHg during gestation and lactation on the spinal cord of offspring. Pregnant rats received oral doses of MeHg (40 μg/kg/day) over a period of 42 days (21 gestation and 21 lactation). Control animals received the vehicle only. Total mercury concentration was measured in blood samples from offspring collected at the 41st postnatal day. Counting of motor neurons and immunoreactivity for myelin basic protein (MBP) were assessed in the spinal cords in both control and MeHg-intoxicated animals. Our results showed that MeHg promoted an increase in blood Hg levels. In addition, it caused a reduction in the number of spinal cord motor neurons as well as decreased MBP immunoreactivity in the cervical, thoracic and lumbar segments. Our present findings suggest that MeHg intoxication during rat pregnancy and lactation is associated with a pattern of motor neuron degeneration and downregulation of myelin basic protein in different segments of a developing spinal cord. Further studies are needed to establish the effect of MeHg intoxication in both young and adult rats.  相似文献   

    

Lorenzo Vannozzi  Alessandro Lucantonio  Arturo Castillo  Antonio De Simone  Leonardo Ricotti 《International journal of molecular sciences》2022,23(15)

In this work, an innovative model is proposed as a design tool to predict both the inner and outer radii in rolled structures based on polydimethylsiloxane bilayers. The model represents an improvement of Timoshenko’s formula taking into account the friction arising from contacts between layers arising from rolling by more than one turn, hence broadening its application field towards materials based on elastomeric bilayers capable of large deformations. The fabricated structures were also provided with surface topographical features that would make them potentially usable in different application scenarios, including cell/tissue engineering ones. The bilayer design parameters were varied, such as the initial strain (from 20 to 60%) and the bilayer thickness (from 373 to 93 µm). The model matched experimental data on the inner and outer radii nicely, especially when a high friction condition was implemented in the model, particularly reducing the error below 2% for the outer diameter while varying the strain. The model outperformed the current literature, where self-penetration is not excluded, and a single value of the radius of spontaneous rolling is used to describe multiple rolls. A complex 3D bioinspired hierarchical elastomeric microstructure made of seven spirals arranged like a hexagon inscribed in a circumference, similar to typical biological architectures (e.g., myofibrils within a sarcolemma), was also developed. In this case also, the model effectively predicted the spirals’ features (error smaller than 18%), opening interesting application scenarios in the modeling and fabrication of bioinspired materials.  相似文献   

    

Leonardo Oliveira Bittencourt  Victria Santos Chemelo  Walessa Alana Bragana Arago  Bruna Puty  Aline Dionizio  Francisco Bruno Teixeira  Mileni Silva Fernandes  Mrcia Cristina Freitas Silva  Luanna Melo Pereira Fernandes  Edivaldo Herculano Corrêa de Oliveira  Marilia Afonso Rabelo Buzalaf  Maria Elena Crespo-Lopez  Cristiane do Socorro Ferraz Maia  Rafael Rodrigues Lima 《International journal of molecular sciences》2022,23(1)

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl₂ or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.  相似文献   

    

Elena Dozio  Elisa Maffioli  Elena Vianello  Simona Nonnis  Francesca Grassi Scalvini  Leonardo Spatola  Paola Roccabianca  Gabriella Tedeschi  Massimiliano Marco Corsi Romanelli 《International journal of molecular sciences》2022,23(7)

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Davide Loizzo  Savio Domenico Pandolfo  Devin Rogers  Clara Cerrato  Nicola Antonio di Meo  Riccardo Autorino  Vincenzo Mirone  Matteo Ferro  Camillo Porta  Alessandro Stella  Cinzia Bizzoca  Leonardo Vincenti  Marco Spilotros  Monica Rutigliano  Michele Battaglia  Pasquale Ditonno  Giuseppe Lucarelli 《International journal of molecular sciences》2022,23(7)

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.  相似文献   

    

Natlia Lins da Silva-Gomes  Leonardo Alexandre de Souza Ruivo  Claudia Moreira  Marcelo Meuser-Batista  Cristiane Frana da Silva  Denise da Gama Jaen Batista  Stênio Fragoso  Gabriel Melo de Oliveira  Maria de Nazar Correia Soeiro  Otacilio C. Moreira 《International journal of molecular sciences》2022,23(23)

Ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes located on the surface of the T. cruzi plasma membrane, which hydrolyze a wide range of tri-/-diphosphate nucleosides. In this work, we used previously developed genetically modified strains of Trypanosoma cruzi (T. cruzi), hemi-knockout (KO +/−) and overexpressing (OE) the TcNTPDase-1 gene to evaluate the parasite infectivity profile in a mouse model of acute infection (n = 6 mice per group). Our results showed significantly higher parasitemia and mortality, and lower weight in animals infected with parasites OE TcNTPDase-1, as compared to the infection with the wild type (WT) parasites. On the other hand, animals infected with (KO +/−) parasites showed no mortality during the 30-day trial and mouse weight was more similar to the non-infected (NI) animals. In addition, they had low parasitemia (45.7 times lower) when compared with parasites overexpressing TcNTPDase-1 from the hemi-knockout (OE KO +/−) group. The hearts of animals infected with the OE KO +/− and OE parasites showed significantly larger regions of cardiac inflammation than those infected with the WT parasites (p < 0.001). Only animals infected with KO +/− did not show individual electrocardiographic changes during the period of experimentation. Together, our results expand the knowledge on the role of NTPDases in T. cruzi infectivity, reenforcing the potential of this enzyme as a chemotherapy target to treat Chagas disease (CD).  相似文献