Search results for "Modeling"

2016

Introduction: cognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults. Methods: this cross-sectional study included 225 old (52% women, mean age: 74.4 ± 3.3 years) and 134 young (52% women, mean age: 23.4 ± 2.7 years) adult participants from the MyoAge project. Whole body bone mineral density was measured by dualenergy X-ray absorptiometry. Blood analyses included a panel of bone-related peptides (dickkopf-1, osteoprotegerin, osteocalcin (OC), osteopontin, sclerostin, parathyroid hormone and fibroblast growth factor …

2016

Orthopedic implant failure due to aseptic loosening and mechanical instability remains a major problem in total joint replacement. Improving osseointegration at the bone-implant interface may reduce micromotion and loosening. Bone sialoprotein (BSP) has been shown to enhance bone formation when coated onto titanium femoral implants and in rat calvarial defect models. However, the most appropriate method of BSP coating, the necessary level of BSP coating, and the effect of BSP coating on cell behavior remain largely unknown. In this study, BSP was covalently coupled to titanium surfaces via an aminosilane linker (APTES), and its properties were compared to BSP applied to titanium via physiso…

2019

Precise temporal and spatial regulation of gene expression in the brain is a prerequisite for cognitive processes such as learning and memory. Epigenetic mechanisms that modulate the chromatin structure have emerged as important regulators in this context. While posttranslational modification of histones or the modification of DNA bases have been examined in detail in many studies, the role of ATP-dependent chromatin remodeling factors (ChRFs) in learning- and memory-associated gene regulation has largely remained obscure. Here we present data that implicate the highly conserved chromatin assembly and remodeling factor Chd1 in memory formation and the control of immediate early gene (IEG) r…

Persistent immune stimulation exacerbates genetically driven myeloproliferative disorders via stromal remodeling

2017

Abstract Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with downregulation of secreted protein acidic and rich in cysteine (SPARC) and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal …

Epigenetic Regulation of TRAIL Signaling: Implication for Cancer Therapy

2019

International audience; One of the main characteristics of carcinogenesis relies on genetic alterations in DNA and epigenetic changes in histone and non-histone proteins. At the chromatin level, gene expression is tightly controlled by DNA methyl transferases, histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyl-binding proteins. In particular, the expression level and function of several tumor suppressor genes, or oncogenes such as c-Myc, p53 or TRAIL, have been found to be regulated by acetylation. For example, HATs are a group of enzymes, which are responsible for the acetylation of histone proteins, resulting in chromatin relaxation and transcriptional activation,…

Guanxin Danshen Formulation Protects against Myocardial Ischemia Reperfusion Injury-Induced Left Ventricular Remodeling by Upregulating Estrogen Rece…

2017

Background: Guanxin Danshen formulation (GXDSF) is a traditional Chinese herbal recipe recorded in the Chinese Pharmacopoeia since 1995 edition, which consists of Salviae miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Dalbergiae odoriferae Lignum. Our previous research suggested GXDSF had positive effect on cardiovascular disease. Therefore, the aim of this study was to elucidate the effects of GXDSF on myocardial ischemia reperfusion injury-induced left ventricular remodelling (MIRI-LVR). Methods: The effects of GXDSF on cardiac function were detected by haemodynamics and echocardiograms. The effects of GXDSF on biochemical parameters (AST, LDH and CK-MB) were analysed. H…

Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament trans…

2016

[EN] Context: The efficacy of the combination chondroitin sulfate-glucosamine (CS-GlcN) in the treatment of knee osteoarthritis (OA) has been suggested in recent clinical studies. In vitro reports have also suggested anti-inflammatory and anti-resorptive effects of this combination. Objective: The aim of this study was to characterize the effects of CS-GlcN on joint degradation in vivo including the assessment of inflammation and bone metabolism in a model of OA. Materials and methods: We have used the OA model induced by anterior cruciate ligament transection (ACLT) in ovariectomised rats. CS-GlcN was administered daily (oral gavage) from week 0 until week 12 after ovariectomy at the dose …

2019

As rats learn to search for multiple sources of food or water in a complex environment, they generate increasingly efficient trajectories between reward sites. Such spatial navigation capacity involves the replay of hippocampal place-cells during awake states, generating small sequences of spatially related place-cell activity that we call "snippets". These snippets occur primarily during sharp-wave-ripples (SWRs). Here we focus on the role of such replay events, as the animal is learning a traveling salesperson task (TSP) across multiple trials. We hypothesize that snippet replay generates synthetic data that can substantially expand and restructure the experience available and make learni…

SpCLUST: Towards a fast and reliable clustering for potentially divergent biological sequences

2019

International audience; This paper presents SpCLUST, a new C++ package that takes a list of sequences as input, aligns them with MUSCLE, computes their similarity matrix in parallel and then performs the clustering. SpCLUST extends a previously released software by integrating additional scoring matrices which enables it to cover the clustering of amino-acid sequences. The similarity matrix is now computed in parallel according to the master/slave distributed architecture, using MPI. Performance analysis, realized on two real datasets of 100 nucleotide sequences and 1049 amino-acids ones, show that the resulting library substantially outperforms the original Python package. The proposed pac…

Molecular basis of SARS-CoV-2 infection and rational design of potential antiviral agents: Modeling and simulation approaches

2020

International audience; The emergence in late 2019 of the coronavirus SARS-CoV-2 has resulted in the breakthrough of the COVID-19 pandemic that is presently affecting a growing number of countries. The development of the pandemic has also prompted an unprecedented effort of the scientific community to understand the molecular bases of the virus infection and to propose rational drug design strategies able to alleviate the serious COVID-19 morbidity. In this context, a strong synergy between the structural biophysics and molecular modeling and simulation communities has emerged, resolving at the atomistic level the crucial protein apparatus of the virus and revealing the dynamic aspects of k…