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Leptin Signaling Modulates Expression of Polycomb and Trithorax Complexes in the Brain of Fat Tissue Implanted Polycystic Ovarian Sindrome Mice

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American Journal of Molecular Biology 2014年第4期4卷 177-192页

作者： Eduardo Henrique da Silva Freitas Samuel Marcos Ribeiro de Noronha Maria Nazareth Gamboa Ritto carlos fernandes baptista Ismael Dale Cotrim Guerreiro da Silva Silvana Aparecida Alves Correa-Noronha Ivaldo da Silva Gynecology Department Federal University of Sao Paulo Paulista School of Medicine (UNIFESP-EPM) Sao Paulo Brazil General Medicine Department Federal University of Rio de Janeiro State (UNIRIO) Rio de Janeiro Brazil Translacional Surgery Division Surgery Department Federal University of Sao Paulo Paulista School of Medicine (UNIFESP-EPM) Sao Paulo Brazil General and Specialized Surgery Department Federal University of Rio de Janeiro State (UNIRIO) Rio de Janeiro Brazil

The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus. The aim is to assess the expression of the Polycomb & Trithorax Complexes genes in brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS. Three B6 V-Lepob/J mouse groups: Normal weight, obese and seven-day-treatment obese had their brain RNA extracted and submitted to an 84 Polycomb & Trithorax Complexes genes PCR Array plate and MetacoreTM pathways localization. Genomic profiles obtained were compared to the ones of the normal-weight-mice group. Differentially expressed genes were 13% and 26% respectively to control and treatment. Major changes were in genes: Snai1/31;Smarca1/?17;Dnmt3b/4.7;Ezh1/ 15. Altered genes were associated to canonical pathways and provided 3 networks related to epigenetics. Underlying neuronal changes caused by leptin in obese mice brain, there is an important role being played by the histone code. Here there is evidence that leptin drives the chromatin packing to a more condensed pattern. Upregulation of methyltransferase genes, like Ezh1, favors this thought. In summary the Polycomb & Trithorax complexes might answer for the silencing of some downregulated genes in the obese mice brain when exposed to leptin.

关键词： Polycistic Ovarian Sindrome Obesity Polycomb and Trithorax Complexes Leptin Fat Mouse

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Leptin Causes the Early Inhibition of Glycolysis-and TCA Cycle-Related Genes in the Brain of Ob/Ob Mice to Restore Fertility

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American Journal of Molecular Biology 2014年第3期4卷 105-113页

作者： carlos fernandes baptista Samuel Marcos Ribeiro de Noronha Maria de Nazareth Gamboa Ritto Eduardo Henrique da Silva Freitas Melquíades Pereira Júnior Mauro Abi Haidar Ismael Dale Cotrim Guerreiro da Silva Silvana Aparecida Alves Corrêa de Noronha Marisa Teresinha Patriarca Gynecology Department Escola Paulista de Medicina/Universidade Federal de Sao Paulo(EPM-UNIFESP)São PauloBrazil Departmento de Cirurgia Geral e Especializada Universidade Federal do Rio de Janeiro(UNIRIO)Rio de JaneiroBrazil Surgery Department Escola Paulista de Medicina/Universidade Federal de Sao Paulo(EPM-UNIFESP)Sao PauloBrazil Departmento de Medicina Geral Universidade Federal do Rio de Janeiro(UNIRIO)Rio de JaneiroBrazil

Introduction: Polycystic ovarian syndrome (PCOS) is undoubtedly the commonest androgen disorder in woman’s fertile period and certainly one of the most prevalent causes of anovulation. The syndrome has an estimated prevalence of 4% - 10% among women of childbearing age. Previously, our group demonstrated the effect of gonadal white adipose tissue transplantation from wild-type lean and fertile female mice to isogenic obese anovulatory ob/ob mice. These complex metabolic interrelationships between obesity and PCOS have yet to be fully understood. The aim of this study was to evaluate the effect of gonadal white adipose tissue (WAT) transplantation from the wild-type lean and fertile female mice to isogenic obese, anovulatory mice (Lep ob/Lep ob) on the expression of glycolysis- and TCA cycle-related genes and obtain a general view of the glucose metabolism in the brain of these animals. Methods: Fifteen ob/ob mice ranging from 2 to 3 months of age were divided into 3 experimental groups: control normal weight (n = 5), obese control (n = 5) and obese 7 days leptin treated (n = 5). The whole brains of the mice were processed for RNA extraction. The samples from each group were used to perform PCR assays using an array plate containing 84 primers to study the glucose metabolism-related genes. Results: The glycolysis- and TCA cycle-related genes were significantly downregulated. The most significantly affected genes were as follows: for glycolysis (fold regulation with p < 0.05):Pgm1,Bpgm,Aldob, andEno3 (119, 45, 18, and 28 times less, respectively);and for the TCA cycle (fold regulation with p < 0.05):Cs,Idh3b, andMdh2 (84, 27, and 37 times less, respectively).Conclusion: The seven-day leptin treated mice show a decrease in the glucose metabolism. These results confirm the ability of the adipose tissue-derived hormone leptin to regulate early crucial genes that are related to glycolysis mechanisms and to the TCA cycle. This hormone seems to revert early the central phys

关键词： PCOS Obesity Leptin Glycolysis TCA Cycle Gene Expression

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Phenomenological model for torsional galloping of an elastic flat plate due to hydrodynamic loads

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Journal of Hydrodynamics 2014年第1期26卷 57-65页

作者： fernandes Antonio carlos ARMANDEI Mohammadmehdi Department of Naval and Ocean Engineering COPPE/UFRJ

This study investigates the torsional galloping phenomenon, an instability type flow-induced oscillation, in an elastic stru-cture due to hydrodynamic loads into the water current. The structure applied here is a rectangular flat plate with an elastic axis in its mid-chord length. The elasticity is provided by torsion spring. The flat plate has only one degree of freedom which is rotation in pure yaw about its axis. It is observed that as the current speed is higher than a critical velocity, the flat plate becomes unstable. The instability leads to torsional galloping occurrence, as a result of which the flat plate begins to yaw about the elastic axis. By testing two different chord lengths each with several torsion spring rates, the flat plate behavior is investigated and three different responses are recognized. Then, a phenomenological model is developed with the original kernel in the form of the van der Pol-Duffing equa-tion. The model explains these three responses observed experimentally.

关键词： torsional galloping flow-induced oscillation phenomenological model van der Pol-Duffing equation

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Stability analysis of the fluttering and autorotation of flow-induced rotation of a hinged flat plate

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Journal of Hydrodynamics 2013年第5期25卷 755-762页

作者： MIRZAEISEFAT Sina fernandes Antonio carlos Department of Naval Architecture and Marine Engineering University of Michigan COPPE/UFRJ Federal University of Rio de Janeiro

This work describes investigations performed on the interaction of uniform current and freely rotating plate about a fixed vertical axis. Fluttering and autorotation are two different motions that may occur during the flow induced rotation. The dimensional analysis proves that the motion in flow induced rotation motion is governed essentially by the dimensionless moment of inertia and Reynolds number. Certain combinations define the stability boundaries between fluttering and autorotation. Fluttering is oscillation of body about a vertical axis and the autorotation is a name given to the case when the body turns continuously about the vertical axis First, the loads and moment coefficients are calculated by experiments and streamline theory for different angles of attack for a fixed fiat plate. Then for dynamic case, a bifurcation diagram is presented based on experiments to classify different motion states of flow induced rotation. Finally, a dynamical model is proposed for stability analysis of flow induced rotation of a flat plate.

关键词： flow-induced rotation autorotation fluttering stability analysis

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Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration

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Neural Regeneration Research 2018年第1期13卷 100-104页

作者： Marcela fernandes Sandra Gomes Valente Rodrigo Guerra Sabongi Joao baptista Gomes dos Santos Vilnei Mattioli Leite Henning Ulrich Arthur Andrade Nery Maria José da Silva fernandes Division of Hand and Upper Limb Surgery Department of Orthopedics and Traumatology Universidade Federal de Sao Paulo Sao Paulo Brazil Department of Biochemistry Institute of Chemistry Universidade de Sao Paulo Sao Paulo Brazil Division of Neurosciences Department of Neurology and Neurosurgery Universidade Federal de Sao Paulo Sao Paulo Brazil

Studies have confirmed that bone marrow-derived mesenchymal stem cells （MSCs） can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs （BMSCs） is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs （ADSCs） have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups： sham （only sciatic nerve exposed）, Matrigel （MG; sciatic nerve injury ＋ intravenous transplantation of MG vehicle）, ADSCs （sciatic nerve injury ＋ intravenous MG containing ADSCs）, and BMSCs （sciatic nerve injury ＋ intravenous MG containing BMSCs） groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury,increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios （axonal diameter/fiber diameter ratios） in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for engraftment.

关键词： nerve regeneration mesenchymal stem cells adipose-derived mesenchmal stem cells sciatic nerve Matrigel sciatic functional index neural regeneration

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Mapping of quantitative trait loci using the skew-normal distribution

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2007年第11期8卷 792-801页

作者： fernandes Elisabete PACHECO António PENHA-GONALVES carlos Centre for Mathematics and Its Applications IST-Technical University of Lisbon1049-001 LisboaPortugal Department of Statistics and Operational ResearchFaculty of SciencesUniversity of Lisbon1749-016 LisboaPortugal Gulbenkian Institute of ScienceP-2781-901 OeirasPortugal Department of Mathematics and Centre for Mathematics and Its Applications IST-Technical University of Lisbon1049-001 LisboaPortugal Gulbenkian Institute of Science P-2781-901 OeirasPortugal

In standard interval mapping (IM) of quantitative trait loci (QTL), the QTL effect is described by a normal mixture model. When this assumption of normality is violated, the most commonly adopted strategy is to use the previous model after data transformation. However, an appropriate transformation may not exist or may be difficult to find. Also this approach can raise interpretation issues. An interesting alternative is to consider a skew-normal mixture model in standard IM, and the resulting method is here denoted as skew-normal IM. This flexible model that includes the usual symmetric normal distribution as a special case is important, allowing continuous variation from normality to non-normality. In this paper we briefly introduce the main peculiarities of the skew-normal distribution. The maximum likelihood estimates of parameters of the skew-normal distribution are obtained by the expectation-maximization (EM) algorithm. The proposed model is illustrated with real data from an intercross experiment that shows a significant departure from the normality assumption. The performance of the skew-normal IM is assessed via stochastic simulation. The results indicate that the skew-normal IM has higher power for QTL detection and better precision of QTL location as compared to standard IM and nonparametric IM.

关键词： Interval mapping (IM) Quantitative trait loci (QTL) Skew-normal distribution Expectation-maximization (EM)algorithm

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Liquid biopsies in myeloid malignancies

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Cancer Drug Resistance 2019年第4期2卷 1044-1061页

作者： Bilal Abdulmawjood Catarina Roma-Rodrigues Alexandra R.fernandes Pedro V.baptista UCIBIO Department of Life SciencesFaculdade de Ciências e TecnologiaUniversidade NOVA de LisboaCampus CaparicaCaparica 2829-516Portugal

Hematologic malignancies are the most common type of cancer affecting children and young adults,and encompass diseases,such as leukemia,lymphoma,and myeloma,all of which impact blood associated tissues such as the bone marrow,lymphatic system,and blood *** diagnostics of these malignancies relies heavily on the use of bone marrow samples,which is painful,debilitating,and not free from risks for leukemia *** biopsies are based on minimally invasive assessment of markers in the blood(and other fluids)and have the potential to improve the efficacy of diagnostic/therapeutic strategies in leukemia patients,providing a useful tool for the real time molecular profiling of *** most promising noninvasive biomarkers are circulating tumor cells,circulating tumor DNA,microRNAs,and ***,we discuss the role of assessing these circulating biomarkers for the understanding of tumor progression and metastasis,tumor progression dynamics through treatment and for follow-up.

关键词： Liquid biopsy circulating tumor cells circulating tumor DNA exosomes microRNAs leukemia

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Evaluation of bearing, gears and gearboxes performance with different wind turbine gear oils

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Friction 2015年第4期3卷 275-286页

作者： Ramiro Carneiro MARTINS carlos M.C.G.fernandes Jorge H.O.SEABRA INEGI Universidade do PortoPortoPortugal Faculdade de Engenharia Universidade do PortoPortoPortugal

The oil viscosity specification for wind turbine gear oils is ISO VG 320,although there are quite different viscosity indexes oils for that viscosity *** work evaluates the behaviour of different base oil formulations,since polyalphaolefin(PAO),mineral,ester and polyalkeleneglycol(PAG)that withstand quite different viscosity *** oils evaluation was done in rolling bearing tests and gear *** behaviour was compared for operating conditions in the range observable in a wind turbine *** experimental results showed considerable differences between the different oils and it was observed that depending on the contact type the relative behaviour of the lubricants would change,i.e.,the best lubricant for the rolling bearing would not imply the best result on the gear *** gear geometry is also very important toward the transmission efficiency,once using a low loss gear concept a decrease of up to 25%in torque loss could be *** models were implemented with the purpose of performing a better simulation of the mechanical system and also to obtain the friction coefficient promoted by the tested oils.

关键词： gears rolling bearings friction coefficient lubricants efficiency

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Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 234-243页

作者： João Gramaça Isabel Gomes fernandes Carolina Trabulo Joana Gonçalves Rita Gameiro dos Santos Adriano baptista Idília Pina Centro Hospitalar Barreiro Montijo Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal Medical Oncology Unit Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational *** RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT *** the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR *** SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May *** the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and *** neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

关键词： Metastatic colorectal cancer Rat sarcoma virus mutational status Liquid biopsy Rat sarcoma virus wild-type Neo-rat sarcoma virus wild-type Anti-epidermal growth factor receptor therapy Case report

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Peripheral nerve regeneration with conduits:use of vein tubes

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Neural Regeneration Research 2015年第4期10卷 529-533页

作者： Rodrigo Guerra Sabongi Marcela fernandes Joao baptista Gomes dos Santos Department of Orthopedics and Traumatology Escola Paulista de MedicinaFederal University of Sao Paulo Division of Hand Surgery Department of Orthopedics and TraumatologyEscola Paulista de MedicinaFederal University of Sao Paulo

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the com-plexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the au-tologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.

关键词： peripheral nerve injury nerve graft nerve conduit Wallerian degeneration neurotrophic factors veins autografts nerve regeneration

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