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1.
Sci Rep ; 13(1): 17733, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853114

RESUMO

Lactate accumulation and acidification in tumours are a cancer hallmark associated with the Warburg effect. Lactic acidosis correlates with cancer malignancy, and the benefit it offers to tumours has been the subject of numerous hypotheses. Strikingly, lactic acidosis enhances cancer cell survival to environmental glucose depletion by repressing high-rate glycolysis and lactic fermentation, and promoting an oxidative metabolism involving reactivated respiration. We used real-time NMR to evaluate how cytosolic lactate accumulation up to 40 mM and acidification up to pH 6.5 individually impact glucose consumption, lactate production and pyruvate evolution in isolated cytosols. We used a reductive cell-free system (CFS) to specifically study cytosolic metabolism independently of other Warburg-regulatory mechanisms found in the cell. We assessed the impact of lactate and acidification on the Warburg metabolism of cancer cytosols, and whether this effect extended to different cytosolic phenotypes of lactic fermentation and cancer. We observed that moderate acidification, independently of lactate concentration, drastically reduces the glucose consumption rate and halts lactate production in different lactic fermentation phenotypes. In parallel, for Warburg-type CFS lactate supplementation induces pyruvate accumulation at control pH, and can maintain a higher cytosolic pyruvate pool at low pH. Altogether, we demonstrate that intracellular acidification accounts for the direct repression of lactic fermentation by the Warburg-associated lactic acidosis.


Assuntos
Acidose Láctica , Neoplasias , Humanos , Ácido Láctico/metabolismo , Acidose Láctica/metabolismo , Fermentação , Sistema Livre de Células/metabolismo , Glicólise , Neoplasias/patologia , Piruvatos/metabolismo , Glucose/metabolismo , Concentração de Íons de Hidrogênio
2.
Org Biomol Chem ; 21(30): 6115-6119, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37462469

RESUMO

The synthesis of difluoromethyl-containing compounds exploiting the deoxofluorination reaction of aromatic aldehydes using XtalFluor-E is described. This transformation occurs at room temperature under highly concentrated conditions, i.e., with no added solvent. A wide range of difluoromethyl-containing compounds was obtained in 21 to 87% isolated yields.

3.
Org Lett ; 25(14): 2487-2491, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37017585

RESUMO

The synthesis of trifluoromethyl (CF3)- and pentafluorosulfanyl (SF5)-substituted cyclopropane-fused γ-lactones was carried out through Rh2(esp)2-catalyzed intramolecular cyclopropanation in up to 99% yields. Twelve examples of this interesting scaffold are reported, as well as postfunctionalizations that provide access to highly functionalized CF3- and SF5-substituted cyclopropanes. These novel SF5-substituted analogues join the very short list of available pentafluorosulfanyl intermediates.

4.
J Clin Med ; 12(3)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36769648

RESUMO

OBJECTIVES: The objective of this prospective, single-center study was to explore the mid-term outcomes 6 to 9 months after hospitalization in an Intensive Care Unit (ICU) for severe COVID-19 infection. METHODS: Patients systematically underwent biological tests, pulmonary function tests, chest computed tomography (CT) scan, and psychological tests. RESULTS: Among 86 patients, including 71 (82.6%) men, median age of 65.8 years (56.7; 72.4), 57 (71.3%) patients presented post-COVID-19 asthenia, 39 (48.1%) muscle weakness, and 30 (36.6%) arthralgia. Fifty-two (64.2%) patients had a decreased diffusion capacity for carbon monoxide (DLCO) <80% and 16 (19.8%) had DLCO <60%. Chest CT-scans showed ground glass opacities in 35 (40.7%) patients, and reticular changes in 28 patients (33.7%), including fibrosis-like changes in 18 (21.7%) patients. Reticular changes and DLCO <60% were associated with length of stay in ICU, and reticular changes with higher maximal CRP level. The psychological questionnaires found 37.7% suffered from depression, 23.5% from anxiety, 42.4% from insomnia, and 9.4% from post-traumatic stress. Being female was associated with a higher frequency of depression and anxiety, with depression scores being associated with obesity. CONCLUSIONS: Many patients hospitalized in ICU for severe COVID-19 infection have mid-term sequelae. Additional studies on the prognostic factors seem necessary.

5.
J Med Virol ; 95(1): e28209, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36226380

RESUMO

In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.


Assuntos
COVID-19 , Armadilhas Extracelulares , Humanos , Estudos Prospectivos , Anticorpos Anticardiolipina , COVID-19/patologia , Imunoglobulina G , Imunoglobulina M , Neutrófilos
6.
J Fungi (Basel) ; 8(7)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35887435

RESUMO

Whether severe COVID-19 is by itself a significant risk factor for the development of candidemia currently remains an open question as conflicting results have been published. We aim to assess the occurrence of candidemia in patients with severe COVID-19 admitted to the intensive care unit (ICU). We conducted a retrospective study on patients with severe SARS-CoV-2-related pneumonia admitted to 5 ICUs in France who were specifically screened for fungal complications between March 2020 and January 2021. The study population included a total of 264 patients; the median age was 56 years old and most of them were male (n = 186; 70.5%) and immunocompetent (n = 225; 87.5%), and 62.7% (n = 153/244) were on extracorporeal membrane oxygenation support. Microbiological analysis included 4864 blood culture samples and beta-glucan test performed on 975 sera. Candidemia was diagnosed in 13 (4.9%) patients. The species involved were mainly C. albicans (n = 6) and C. parapsilosis (n = 5). Almost all patients (12/13; 92.3%) had a colonization by yeasts. ICU mortality was not significantly impacted by the occurrence of candidemia. Unrelated positive beta-glucan tests were observed in 49 patients (23.4%), including 6 with mold infections and 43 with false positive results. In our series, patients with severe SARS-CoV-2-related pneumonia seemed at low risk of developing invasive candidiasis.

7.
Int J Comput Assist Radiol Surg ; 17(8): 1391-1398, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35639203

RESUMO

PURPOSE: Realistic fluid-structure interaction (FSI) simulation of the mitral valve opens the way toward planning for surgical repair. In the literature, blood leakage is identified by measuring the flow rate, but detailed information about closure efficiency is missing. We present in this paper an FSI model that improves the detection of blood leakage by building a map of contact. METHODS: Our model is based on the immersed boundary method that captures a map of contact and perfect closure of the mitral valve, without the presence of orifice holes, which often appear with existing methods. We also identified important factors influencing convergence issues. RESULTS: The method is demonstrated in three typical clinical situations: mitral valve with leakage, bulging, and healthy. In addition to the classical ways of evaluating MV closure, such as stress distribution and flow rate, the contact map provides easy detection of leakage with identification of the sources of leakage and a quality assessment of the closure. CONCLUSIONS: Our method significantly improves the quality of the simulation and allows the identification of regurgitation as well as a spatial evaluation of the quality of valve closure. Comparably fast simulation, ability to simulate large deformation, and capturing detailed contact are the main aspects of the study.


Assuntos
Insuficiência da Valva Mitral , Valva Mitral , Simulação por Computador , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Modelos Cardiovasculares
8.
Front Plant Sci ; 12: 792981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970289

RESUMO

The proportion and composition of plant tissues in maize stems vary with genotype and agroclimatic factors and may impact the final biomass use. In this manuscript, we propose a quantitative histology approach without any section labelling to estimate the proportion of different tissues in maize stem sections as well as their chemical characteristics. Macroscopic imaging was chosen to observe the entire section of a stem. Darkfield illumination was retained to visualise the whole stem cellular structure. Multispectral autofluorescence images were acquired to detect cell wall phenolic compounds after UV and visible excitations. Image analysis was implemented to extract morphological features and autofluorescence pseudospectra. By assimilating the internode to a cylinder, the relative proportions of tissues in the internode were estimated from their relative areas in the sections. The approach was applied to study a series of 14 maize inbred lines. Considerable variability was revealed among the 14 inbred lines for both anatomical and chemical traits. The most discriminant morphological descriptors were the relative amount of rind and parenchyma tissues together with the density and size of the individual bundles, the area of stem and the parenchyma cell diameter. The rind, as the most lignified tissue, showed strong visible-induced fluorescence which was line-dependant. The relative amount of para-coumaric acid was associated with the UV-induced fluorescence intensity in the rind and in the parenchyma near the rind, while ferulic acid amount was significantly correlated mainly with the parenchyma near the rind. The correlation between lignin and the tissue pseudospectra showed that a global higher amount of lignin resulted in a higher level of lignin fluorescence whatever the tissues. We demonstrated here the potential of darkfield and autofluorescence imaging coupled with image analysis to quantify histology of maize stem and highlight variability between different lines.

9.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1866(12): 159030, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34419589

RESUMO

In the liver, contact sites between the endoplasmic reticulum (ER) and mitochondria (named MAMs) may be crucial hubs for the regulation of lipid metabolism, thus contributing to the exacerbation or prevention of fatty liver. We hypothesized that tether proteins located at MAMs could play a key role in preventing triglyceride accumulation in hepatocytes and nonalcoholic fatty liver disease (NAFLD) occurrence. To test this, we explored the role of two key partners in building MAM integrity and functionality, the glucose-regulated protein 75 (Grp75) and mitofusin 2 (Mfn2), which liver contents are altered in obesity and NAFLD. Grp75 or Mfn2 expression was either silenced using siRNA or overexpressed with adenoviruses in Huh7 cells. Silencing of Grp75 and Mfn2 resulted in decreased ER-mitochondria interactions, mitochondrial network fusion state and mitochondrial oxidative capacity, while overexpression of the two proteins induced mirror impacts on these parameters. Furthermore, Grp75 or Mfn2 silencing decreased cellular cholesterol content and enhanced triglyceride secretion in ApoB100 lipoproteins, while their overexpression led to reverse effects. Cellular phosphatidylcholine/phosphatidylethanolamine ratio was decreased only upon overexpression of the proteins, potentially contributing to altered ApoB100 assembly and secretion. Despite the opposite differences, both silencing and overexpression of Grp75 or Mfn2 induced triglyceride storage, although a fatty acid challenge was required to express the alteration upon protein silencing. Among the mechanisms potentially involved in this phenotype, ER stress was closely associated with altered triglyceride metabolism after Grp75 or Mfn2 overexpression, while blunted mitochondrial FA oxidation capacity may be the main defect causing triglyceride accumulation upon Grp75 or Mfn2 silencing. Further studies are required to decipher the link between modulation of Grp75 or Mfn2 expression, change in MAM integrity and alteration of cholesterol content of the cell. In conclusion, Grp75 or Mfn2 silencing and overexpression in Huh7 cells contribute to altering MAM integrity and cholesterol storage in opposite directions, but all promote triglyceride accumulation through distinct cellular pathways. This study also highlights that besides Mfn2, Grp75 could play a central role in hepatic lipid and cholesterol metabolism in obesity and NAFLD.


Assuntos
Apolipoproteína B-100/genética , Colesterol/metabolismo , GTP Fosfo-Hidrolases/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas Mitocondriais/genética , Hepatopatia Gordurosa não Alcoólica/genética , Linhagem Celular , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , GTP Fosfo-Hidrolases/antagonistas & inibidores , Mutação com Ganho de Função/genética , Regulação da Expressão Gênica/genética , Inativação Gênica , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Mutação com Perda de Função/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismo
10.
Autoimmun Rev ; 20(9): 102891, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34229047

RESUMO

BACKGROUND AND OBJECTIVE: Cardiovascular diseases (CVD) are the leading causes of death in chronic inflammatory rheumatic diseases and are not solely explained by the increased prevalence of cardiovascular (CV) risk factors in this population. Arterial stiffness, assessed primarily by pulse wave velocity (PWV) and more indirectly by augmentation index (AIx), is a surrogate marker of CVD that should be considered. The objective of this review was to investigate the relationship between arterial stiffness and chronic inflammatory and/or autoimmune diseases. METHODS: We performed a systemic literature review of articles published in Medline from January 2012 to April 2020 restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and rheumatoid arthritis, systemic lupus erythematosus, psoriasis, Sjogren's syndrome and ankylosing spondylitis. For each selected article, data on PWV and AIx were extracted and factors that may have an impact on arterial stiffness were identified. RESULTS: A total of 214 references were identified through database searching and 82 of them were retained for analysis. Arterial stiffness is increased in chronic inflammatory and autoimmune diseases. Traditional CV risk factors such as hypertension and dyslipidemia accentuate this relationship. Current data are insufficient to determine whether disease activity significantly influences arterial stiffness, whereas disease duration seems rather critical. TNF-alpha inhibitors and cardiorespiratory fitness tend to decrease arterial stiffness. Finally, increased arterial stiffness leads to diastolic dysfunction, which is the main mechanism of heart failure in chronic inflammatory rheumatic diseases. CONCLUSION: CV risk assessment in chronic inflammatory and autoimmune diseases should also rely on PWV and AIx.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Rigidez Vascular , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Análise de Onda de Pulso , Fatores de Risco
11.
Int J Comput Assist Radiol Surg ; 16(5): 709-720, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33978895

RESUMO

PURPOSE: Mitral valve computational models are widely studied in the literature. They can be used for preoperative planning or anatomical understanding. Manual extraction of the valve geometry on medical images is tedious and requires special training, while automatic segmentation is still an open problem. METHODS: We propose here a fully automatic pipeline to extract the valve chordae architecture compatible with a computational model. First, an initial segmentation is obtained by sub-mesh topology analysis and RANSAC-like model-fitting procedure. Then, the chordal structure is optimized with respect to objective functions based on mechanical, anatomical, and image-based considerations. RESULTS: The approach has been validated on 5 micro-CT scans with a graph-based metric and has shown an [Formula: see text] accuracy rate. The method has also been tested within a structural simulation of the mitral valve closed state. CONCLUSION: Our results show that the chordae architecture resulting from our algorithm can give results similar to experienced users while providing an equivalent biomechanical simulation.


Assuntos
Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/anatomia & histologia , Valva Mitral/diagnóstico por imagem , Algoritmos , Animais , Fenômenos Biomecânicos , Simulação por Computador , Processamento de Imagem Assistida por Computador , Insuficiência da Valva Mitral/cirurgia , Modelos Anatômicos , Reconhecimento Automatizado de Padrão , Reprodutibilidade dos Testes , Suínos , Microtomografia por Raio-X
12.
Eur J Pharm Sci ; 159: 105730, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33493670

RESUMO

Monoclonal antibodies (mAbs) display numerous structural attributes, some of them may impact their safety and/or efficacy profiles. C-terminal lysine clipping is a common phenomenon occurring during the bioproduction of mAbs and leads to variable amounts of final process-related charge variants. If Fc-glycosylation has been by far the most documented critical quality attribute (CQA), the potential impacts of mAb C-terminal lysine content is far less reported, particularly on the ability of these basic variants to bind human Fc receptors. To address this question, three charge variant species having zero (K0), one (K1) and two (K2) C-terminal lysine(s) were isolated with high purity from an in-house human IgG1 by preparative strong-cation exchange (SCX) chromatography. A comprehensive biophysical characterization of these three fractions was undertaken, demonstrating their high similarity in terms of structural homogeneity, with a particular attention paid on their respective N-glycosylation profiles. The binding affinity of the fractions to human FcγRIIIa-Val176 was assessed both by affinity chromatography and surface plasmon resonance (SPR), and to human neonatal Fc receptor (FcRn) by affinity chromatography. Results demonstrate that the three charge variants did not show any significant binding difference for the two tested human Fc receptors, translating certainly to comparable biological properties. As a consequence, C-terminal lysine clipping of the present therapeutic IgG1 should not impact both FcRn-dependent pharmacokinetic profiles and FcγRIIIa-driven cytotoxic activities. The methods used in this study can be widely applied to other IgG1 to define criticality of the C-terminal lysine clipping as a CQA.


Assuntos
Imunoglobulina G , Lisina , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/metabolismo , Recém-Nascido , Ligação Proteica , Receptores Fc/metabolismo , Receptores de IgG/metabolismo
13.
Anal Bioanal Chem ; 412(22): 5453-5463, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32556564

RESUMO

Cellular metabolomics has become key to elucidate mechanistic aspects in various fields such as cancerology or pharmacology, and is rapidly becoming a standard phenotyping tool accessible to the broad biological community. Acquisition of reliable spectroscopic datasets, such as nuclear magnetic resonance (NMR) spectra, to characterize biological systems depends on the elaboration of robust methods for cellular metabolites extraction. Previous studies have addressed many issues raised by these protocols, however with little pondering on ergonomic and practical aspects of the methods that impact their scalability, reproducibility and hence their suitability to high-throughput studies or their use by non-metabolomics experts. Here, we optimize a fast and ergonomic protocol for extraction of metabolites from adherent mammalian cells for NMR metabolomics studies. The proposed extraction protocol, including cell washing, metabolism quenching and actual extraction of intracellular metabolites, was first optimized on HeLa cells. Efficiency of the protocol, in its globality and for the different individual steps, was assessed by NMR quantification of 27 metabolites from cellular extracts. We show that a single PBS wash provides a seemly compromise between contamination from growth medium and leakage of intracellular metabolites. In HeLa cells, extraction using pure methanol, without cell scraping, recovered a higher amount of intracellular metabolites than the reference methanol/water/chloroform method with cell scraping, with yields varying across metabolite classes. Optimized and reference protocols were further tested on eight cell lines of miscellaneous nature, and inter-operator reproducibility was demonstrated. Our results stress the need for tailored extraction protocols and show that fast protocols minimizing time-consuming steps, without compromising extraction yields, are suitable for high-throughput metabolomics studies. Graphical abstract.


Assuntos
Adesão Celular , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Animais , Linhagem Celular , Linhagem Celular Tumoral , Meios de Cultura , Ergonomia , Ensaios de Triagem em Larga Escala , Humanos , Mamíferos , Solventes/química , Água/química
14.
Sensors (Basel) ; 20(11)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471231

RESUMO

Collecting correlated scene images and camera poses is an essential step towards learning absolute camera pose regression models. While the acquisition of such data in living environments is relatively easy by following regular roads and paths, it is still a challenging task in constricted industrial environments. This is because industrial objects have varied sizes and inspections are usually carried out with non-constant motions. As a result, regression models are more sensitive to scene images with respect to viewpoints and distances. Motivated by this, we present a simple but efficient camera pose data collection method, WatchPose, to improve the generalization and robustness of camera pose regression models. Specifically, WatchPose tracks nested markers and visualizes viewpoints in an Augmented Reality- (AR) based manner to properly guide users to collect training data from broader camera-object distances and more diverse views around the objects. Experiments show that WatchPose can effectively improve the accuracy of existing camera pose regression models compared to the traditional data acquisition method. We also introduce a new dataset, Industrial10, to encourage the community to adapt camera pose regression methods for more complex environments.

15.
Ann Biomed Eng ; 48(1): 447-462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31549328

RESUMO

An automatic elastic registration method suited for vascularized organs is proposed. The vasculature in both the preoperative and intra-operative images is represented as a graph. A typical application of this method is the fusion of pre-operative information onto the organ during surgery, to compensate for the limited details provided by the intra-operative imaging modality (e.g. cone beam CT) and to cope with changes in the shape of the organ. Due to image modalities differences and organ deformation, each graph has a different topology and shape. The adaptive compliance graph matching (ACGM) method presented does not require any manual initialization, handles intra-operative nonrigid deformations of up to 65 mm and computes a complete displacement field over the organ from only the matched vasculature. ACGM is better than the previous biomechanical graph matching method (Garcia Guevara et al. IJCARS, 2018) (BGM) because it uses an efficient biomechanical vascularized liver model to compute the organ's transformation and the vessels bifurcations compliance. This allows to efficiently find the best graph matches with a novel compliance-based adaptive search. These contributions are evaluated on 10 realistic synthetic and 2 porcine automatically segmented datasets. ACGM obtains better target registration error (TRE) than BGM, with an average TRE in the real datasets of 4.2 mm compared to 6.5 mm, respectively. It also is up to one order of magnitude faster, less dependent on the parameters used and more robust to noise.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Animais , Fenômenos Biomecânicos , Elasticidade , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Modelos Teóricos , Período Perioperatório , Veia Porta/diagnóstico por imagem , Período Pré-Operatório , Suínos , Tomografia Computadorizada por Raios X
16.
Protein Sci ; 28(11): 1982-1992, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31583777

RESUMO

Human serum albumin (HSA) is the most abundant protein in plasma and presents the particularity, with IgG, to have an extraordinary long serum half-life conferred by its interaction with the neonatal Fc receptor (FcRn). If the impact of IgG post-translational modifications (PTMs) on FcRn binding is well documented, it is far less reported for HSA despite numerous PTMs occurring on the protein in plasma. HSA is susceptible to numerous degradation reactions in plasma, because of aging, oxidative stress or liver and pancreas related pathologies. In the present study, we combined FcRn affinity chromatography and mass spectrometry to investigate the impact of HSA PTMs upon FcRn binding. This methodology presents the advantage to distinguish the effect of a single modification from a plasma HSA preparation made of a mixture of different isoforms. Cys34 oxidation, Lys525 glycation, and Leu585 C-terminal truncation, which are modifications related to several pathological conditions, were demonstrated to act negatively on HSA-FcRn interaction. The HSA-FcRn binding alteration generated by these modifications is consistent with their vicinity with the interaction interface of the two proteins. Results were discussed regarding altered half-life of HSA observed in several disease states and pave the way toward new understandings of the hypoalbuminemia pathogenesis. SIGNIFICANCE STATEMENT: In this study, we investigated the impact of several post-translational modifications of HSA toward its ability to bind to the neonatal Fc receptor using in vitro affinity chromatography, mass spectrometry, and surface plasmon resonance. Cys34 oxidation, Lys525 glycation, and Leu585 C-terminal truncation were demonstrated to decrease HSA-FcRn binding. These modifications occurring in circulating HSA were discussed in relation to several pathologies as well as for the use of HSA as a therapeutic protein.


Assuntos
Antígenos de Histocompatibilidade Classe I/química , Receptores Fc/química , Albumina Sérica Humana/química , Cromatografia de Afinidade , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Ligação Proteica , Isoformas de Proteínas , Receptores Fc/metabolismo , Albumina Sérica Humana/metabolismo
17.
Glob Chang Biol ; 24(12): 5573-5589, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30155993

RESUMO

Climate change reshapes the physiology and development of organisms through phenotypic plasticity, epigenetic modifications, and genetic adaptation. Under evolutionary pressures of the sessile lifestyle, plants possess efficient systems of phenotypic plasticity and acclimation to environmental conditions. Molecular analysis, especially through omics approaches, of these primary lines of environmental adjustment in the context of climate change has revealed the underlying biochemical and physiological mechanisms, thus characterizing the links between phenotypic plasticity and climate change responses. The efficiency of adaptive plasticity under climate change indeed depends on the realization of such biochemical and physiological mechanisms, but the importance of sensing and signaling mechanisms that can integrate perception of environmental cues and transduction into physiological responses is often overlooked. Recent progress opens the possibility of considering plant phenotypic plasticity and responses to climate change through the perspective of environmental sensing and signaling. This review aims to analyze present knowledge on plant sensing and signaling mechanisms and discuss how their structural and functional characteristics lead to resilience or hypersensitivity under conditions of climate change. Plant cells are endowed with arrays of environmental and stress sensors and with internal signals that act as molecular integrators of the multiple constraints of climate change, thus giving rise to potential mechanisms of climate change sensing. Moreover, mechanisms of stress-related information propagation lead to stress memory and acquired stress tolerance that could withstand different scenarios of modifications of stress frequency and intensity. However, optimal functioning of existing sensors, optimal integration of additive constraints and signals, or memory processes can be hampered by conflicting interferences between novel combinations and novel changes in intensity and duration of climate change-related factors. Analysis of these contrasted situations emphasizes the need for future research on the diversity and robustness of plant signaling mechanisms under climate change conditions.


Assuntos
Aclimatação , Mudança Climática , Fenômenos Fisiológicos Vegetais , Plantas/genética
18.
Int J Comput Assist Radiol Surg ; 13(6): 805-813, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29616446

RESUMO

PURPOSE: Augmenting intraoperative cone beam computed tomography (CBCT) images with preoperative computed tomography data in the context of image-guided liver therapy is proposed. The expected benefit is an improved visualization of tumor(s), vascular system and other internal structures of interest. METHOD: An automatic elastic registration based on matching of vascular trees extracted from both the preoperative and intraoperative images is presented. Although methods dedicated to nonrigid graph matching exist, they are not efficient when large intraoperative deformations of tissues occur, as is the case during the liver surgery. The contribution is an extension of the graph matching algorithm using Gaussian process regression (GPR) (Serradell et al. in IEEE Trans Pattern Anal Mach Intell 37(3):625-638, 2015): First, an improved GPR matching is introduced by imposing additional constraints during the matching when the number of hypothesis is large; like the original algorithm, this extended version does not require a manual initialization of matching. Second, a fast biomechanical model is employed to make the method capable of handling large deformations. RESULTS: The proposed automatic intraoperative augmentation is evaluated on both synthetic and real data. It is demonstrated that the algorithm is capable of handling large deformations, thus being more robust and reliable than previous approaches. Moreover, the time required to perform the elastic registration is compatible with the intraoperative navigation scenario. CONCLUSION: A biomechanics-based graph matching method, which can handle large deformations and augment intraoperative CBCT, is presented and evaluated.


Assuntos
Algoritmos , Tomografia Computadorizada de Feixe Cônico/métodos , Hepatopatias/fisiopatologia , Fígado/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Humanos , Fígado/fisiopatologia , Fígado/cirurgia , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Suínos , Tomografia Computadorizada por Raios X
19.
Sci Rep ; 7: 44361, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28295058

RESUMO

The crystal structure of bulk SrTiO3(STO) transitions from cubic to tetragonal at around 105 K. Recent local scanning probe measurements of LaAlO3/SrTiO3 (LAO/STO) interfaces indicated the existence of spatially inhomogeneous electrical current paths and electrostatic potential associated with the structural domain formation in the tetragonal phase of STO. Here we report a study of temperature dependent electronic transport in combination with the polarized light microscopy of structural domains in mesoscopic LAO/STO devices. By reducing the size of the conductive interface to be comparable to that of a single tetragonal domain of STO, the anisotropy of interfacial electron conduction in relationship to the domain wall and its direction was characterized between T = 10-300 K. It was found that the four-point resistance measured with current parallel to the domain wall is larger than the resistance measured perpendicular to the domain wall. This observation is qualitatively consistent with the current diverting effect from a more conductive domain wall within the sample. Among all the samples studied, the maximum resistance ratio found is at least 10 and could be as large as 105 at T = 10 K. This electronic anisotropy may have implications on other oxide hetero-interfaces and the further understanding of electronic/magnetic phenomena found in LAO/STO.

20.
J Acoust Soc Am ; 139(2): 636-48, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26936548

RESUMO

Acquisition of dynamic articulatory data is of major importance for studying speech production. It turns out that one technique alone often is not enough to get a correct coverage of the whole vocal tract at a sufficient sampling rate. Ultrasound (US) imaging has been proposed as a good acquisition technique for the tongue surface because it offers a good temporal sampling, does not alter speech production, is cheap, and is widely available. However, it cannot be used alone and this paper describes a multimodal acquisition system which uses electromagnetography sensors to locate the US probe. The paper particularly focuses on the calibration of the US modality which is the key point of the system. This approach enables US data to be merged with other data. The use of the system is illustrated via an experiment consisting of measuring the minimal tongue to palate distance in order to evaluate and design Magnetic Resonance Imaging protocols well suited for the acquisition of three-dimensional images of the vocal tract. Compared to manual registration of acquisition modalities which is often used in acquisition of articulatory data, the approach presented relies on automatic techniques well founded from geometrical and mathematical points of view.


Assuntos
Acústica , Fenômenos Eletromagnéticos , Laringe/diagnóstico por imagem , Fonação , Medida da Produção da Fala/métodos , Língua/diagnóstico por imagem , Ultrassonografia/métodos , Acústica/instrumentação , Automação , Fenômenos Biomecânicos , Calibragem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Imagem Multimodal , Processamento de Sinais Assistido por Computador , Acústica da Fala , Medida da Produção da Fala/instrumentação , Medida da Produção da Fala/normas , Fatores de Tempo , Transdutores , Ultrassonografia/instrumentação , Ultrassonografia/normas , Qualidade da Voz
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