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Tubulointerstitial injury and proximal tubule albumin transport in early diabetic nephropathy induced by type 1 diabetes mellitus

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BIOCELL 2017年第1期41卷 1-12页

作者： maximiliano giraud-billoud Fernando EZQUER Javiera BAHAMONDE Marcelo EZQUER IHEM Universidad Nacional de CuyoCONICETFacultad de Ciencias MédicasMendozaArgentina Centro de Medicina Regenerativa Facultad de Medicina Clínica AlemanaUniversidad del DesarrolloAvenida Las Condes 12438SantiagoChile

A decrease in the tubular expression of albumin endocytic transporters megalin and cubilin has been associated with diabetic nephropathy,but there are no comprehensive studies to date relating early tubulointerstitial injury and the effect of the disease on both transporters in type 1 diabetes mellitus(T1DM).We used eight-week-old male C57BL/6 mice divided into two groups;one of them received the vehicle(control group),while the other received the vehicle+200 mg/kg streptozotocin(T1DM).Ten weeks after the injection,we evaluated plasma insulin,enzymuria,urinary vitamin D-binding protein(VDBP),tubulointerstitial fibrosis and proximal tubule histology,markers of autophagy,and megalin and cubilin levels.We found a reduction in tubular protein reabsorption(albumin and VDBP as specific substances carried by both transporters)with increased tubulointerstitial injury,development of fibrosis,thickening of tubular basement membrane,and an increase in tubular cell metalloproteases.This was associated with a decrease in the renal expression of megalin and cubilin.We also observed an increase in the amount of cellular vesicles of the phagocytic system in the tubules,which could be linked to an alteration of normal intracellular trafficking of both receptors,thus affecting the normal function of transporters in early stages of diabetic nephropathy.In diabetic animals,the added effects of tubulointerstitial injury,the decreases in megalin and cubilin expression,and an altered intracellular trafficking of these receptors,seriously affect protein reabsorption.

关键词： Albuminuria Megalin Cubilin Autophagy

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Diabetic nephropathy,autophagy and proximal tubule protein endocytic transport:A potentially harmful relationship

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BIOCELL 2018年第2期42卷 35-40页

作者： maximiliano giraud-billoud Claudio M.FADER Rocío AGÜERO Fernando EZQUER Marcelo EZQUER IHEM Universidad Nacional de CuyoCONICETMendozaArgentina Universidad Nacional de Cuyo Facultad de Ciencias MédicasInstituto de FisiologíaCasilla de Correo 335500-MendozaArgentina Universidad Nacional de Cuyo Facultad de OdontologíaCasilla de Correo 335500-MendozaArgentina Centro de Medicina Regenerativa Facultad de Medicina Clínica AlemanaUniversidad del DesarrolloAvenida Las Condes 12438SantiagoChile

Diabetic nephropathy(DN)is the most frequent cause of chronic renal failure.Until now,the pathophysiological mechanisms that determine its development and progression have not yet been elucidated.In the present study,we evaluate the role of autophagy at early stages of DN,induced in type 2 diabetes mellitus(T2DM)mouse,and its association with proximal tubule membrane endocytic receptors,megalin and cubilin.In T2DM animals we observed a tubule-interstitial injury with significantly increased levels of urinary GGT and ALP,but an absence of tubulointerstitial fibrosis.Kidney proximal tubule cells of T2DM animals showed autophagic vesicles larger than those observed in the control group,and an increase in the number of these vesicles marked with LBPA by immunofluorescence.Furthermore,a significant decrease in the ratio of LC3II/LC3I isoforms and in p62 protein expression in DN affected animals is shown.Finally,we observed a marked increase in urinary albumin and vitamin D binding-protein levels in T2DM animals as well as a significant decrease in expression of megalin in the renal cortex.These results indicate an alteration of the tubular endocytic transporters in DN,which could be related to autophagic dysfunction,which would in turn result in impaired organelle recycling,thus contributing to the progression of this disease.

关键词： Megalin Cubilin Type 2 diabetes mellitus

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Excess dietary Lys reduces feed intake, stimulates jejunal CCK secretion and alters essential and non‑essential blood AA profile in pigs

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1336-1346页

作者： maximiliano Muller Elout Van Liefferinge Alan Tilbrook Robert van Barneveld Eugeni Roura Centre for Nutrition and Food Sciences Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandBrisbaneQueensland 4072Australia Laboratory of Animal Nutrition and Animal Product Quality(LANUPRO) Department of Animal Sciences and Aquatic EcologyGhent University339000 GhentFlandersBelgium Centre for Animal Science Queensland Alliance for Agriculture and Food Innovation and the School of Veterinary ScienceThe University of QueenslandBrisbaneQueensland 4072Australia SunPork Group BrisbaneQueensland 4009Australia

Background Commercial diets are frequently formulated to meet or exceed nutrient levels including those of lim-iting essential amino acids(AA)covering potential individual variations within the herd.However,the provision of dietary excess of AA,such as Lys,may lead to reduced appetite and growth in pigs.The mechanisms modulat-ing these responses have not been extensively investigated.This study evaluated the effect of Lys dietary excesses on performance and satiety biomarkers in post weaning pigs.Methods Twenty-four pigs aged 21 d and weighing 6.81±0.12kg(mean±SEM)were individually housed and offered 1 of 4 dietary treatments for 3weeks:a diet containing a standardized ileal digestible Lys reaching 100%(T0),120%(T1),150%(T2)or 200%(T3)of the NRC(2012)requirements.At the end of the experiment,blood samples from the cephalic vein of the T0 and T3 groups were obtained for AA analysis.In addition,primary intestinal cultures from T0 pigs were used,following their humane killing,to evaluate the effect of Lys on gut hormone secretion and AA sensors gene expression under ex vivo conditions.Results Feed intake was linearly reduced(P<0.001)and the weight gain to feed ratio reduced(P<0.10)with increased dietary levels of Lys during the third-and first-week post weaning,respectively.Cholecystokinin con-centration(P<0.05)and the metabotropic glutamate receptor 1 and the solute carrier family 7 member 2(P<0.10)gene expression was enhanced in proximal jejunum tissues incubated with Lys at 20mmol/L when compared to the control(Lys 0mmol/L).Plasma Lys and Glu(P<0.05)concentration increased in the T3 compared to T0 pigs.In contrast,plasma levels of His,Val,Thr,Leu(P<0.05)and Gln(P<0.10)were lower in T3 than T0 pigs.Conclusion The present results confirm that excess dietary Lys inhibits hunger in pigs.Moreover,the results provide evidence of pre-and post-absorptive mechanisms modulating these responses.Lys dietary excesses should be nar-rowed,when possible,to avoid negative effects of the AA on appetite in pigs.

关键词： Amino acid Blood Cholecystokinin Feed intake Lysine Pig Satiety

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Globe penetration during loco-regional anesthesia: prevalence and review of cases

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1683-1690页

作者： Alba Gómez-Benlloch maximiliano Olivera Jeroni Nadal Gemma Julio Javier Elizalde Centro de Oftalmología Barraquer Barcelona 08021Spain Institut Universitari Barraquer Universitat Autònoma de BarcelonaBarcelona 08021Spain School of Medicine Universitat Internacional de CatalunyaBarcelona 08017Spain

AIM: To describe prevalence and different clinical signs and management of cases with penetrating eye injuries during loco-regional anesthesia for ophthalmic surgery. METHODS: A retrospective review of clinical records was carried out, identifying cases of globe penetration secondary to peribulbar anesthesia injection during 5 y activity in Centro de Oftalmología Barraquer. RESULTS: A total of 17 460 needle-based ocular anesthesia procedures were performed in our centre and 4 cases of globe penetration were recorded with an estimated prevalence of 0.024%. Globe penetrations were always detected in the first 24 h after surgery. Vitreous haemorrhage was found in all the cases. Two eyes presented retinal detachment and two eyes choroidal detachment(CD). The initial surgical approach was performed within the first 48 h. Silicone oil was used as tamponade in three eyes and the fourth case remained only with air. Detachments were solved successfully in all the cases. Functional results varied among cases, depending on ocular remarkable antecedent and globe penetration with or without retinal or CD.CONCLUSION: Prevalence of globe penetration during loco-regional anesthesia is low in our centre. Physicians should consider the possibility of globe penetration in eyes with postoperative atypical appearance after locoregional anesthesia. Immediate B-scan ultrasonography is recommended in suspicious cases with a dense vitreous haemorrhage. An early vitrectomy surgery in conjunction with laser or cryotherapy at the penetration sites is essential for good anatomical and functional results.

关键词： loco-regional anesthesia peribulbar retrobulbar globe penetration retina

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Determining the spatial distribution of environmental and socio-economic suitability for human leptospirosis in the face of limited epidemiological data

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Infectious Diseases of Poverty 2022年第4期11卷 99-100页

作者： maximiliano A.Cristaldi Thibault Catry Aurea Pottier Vincent Herbreteau Emmanuel Roux Paulina Jacob M.Andrea Previtali Department of Natural Sciences College of Humanities and SciencesNational University of LitoralSanta FeArgentina 不详

Background:Leptospirosis is among the leading zoonotic causes of morbidity and mortality worldwide.Knowledge about spatial patterns of diseases and their underlying processes have the potential to guide intervention efforts.However,leptospirosis is often an underreported and misdiagnosed disease and consequently,spatial patterns of the disease remain unclear.In the absence of accurate epidemiological data in the urban agglomeration of Santa Fe,we used a knowledge-based index and cluster analysis to identify spatial patterns of environmental and socioeconomic suitability for the disease and potential underlying processes that shape them.Methods:We geocoded human leptospirosis cases derived from the Argentinian surveillance system during the period 2010 to 2019.Environmental and socioeconomic databases were obtained from satelite images and publicly available platforms on the web.Two sets of human leptospirosis determinants were considered according to the level of their support by the literature and expert knowledge.We used the Zonation algorithm to build a knowledge-based index and a clustering approach to identify distinct potential sets of determinants.Spatial similarity and correlations between index,clusters,and incidence rates were evaluated.Results:We were able to geocode 56.36%of the human leptospirosis cases reported in the national epidemiological database.The knowledge-based index showed the suitability for human leptospirosis in the UA Santa Fe increased from downtown areas of the largest cities towards peri-urban and suburban areas.Cluster analysis revealed downtown areas were characterized by higher levels of socioeconomic conditions.Peri-urban and suburban areas encompassed two clusters which differed in terms of environmental determinants.The highest incidence rates overlapped areas with the highest suitability scores,the strength of association was low though(CSc r=0.21,P<0.001 and ESc r=0.19,P<0.001).Conclusions:We present a method to analyze the environmental and socioeconomic suitability for hu

关键词： Spatial epidemiology Underreported misdiagnosed diseases Environmental conditions Socioeconomic groups Knowledge-based index Cluster analysis

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Assessing the impact of conceptual mineral systems uncertainty on prospectivity predictions

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Geoscience Frontiers 2022年第6期13卷 182-207页

作者： Mark D Lindsay Agnieszka M.Piechocka Mark W Jessell Richard Scalzo Jeremie giraud Guillaume Pirot Edward Cripps Commonwealth Scientific and Industrial Research Organisation Mineral Resources Australian Resources Research CentreWA 6151Australia Mineral Exploration Cooperative Research Centre Centre for Exploration TargetingSchool of Earth SciencesThe University of Western AustraliaPerthWA 6009Australia ARC Centre for Data Analytics for Resources and Environments(DARE) Perth and SydneyAustralia University of Sydney School of Mathematics and StatisticsSydneyAustralia Universitéde Lorraine GeoRessourcesCNRS54000 NancyFrance The University of Western Australia Department of Mathematics and StatisticsPerthAustralia

The past two decades have seen a rapid adoption of artificial intelligence methods applied to mineral exploration. More recently, the easier acquisition of some types of data has inspired a broad literature that has examined many machine learning and modelling techniques that combine exploration criteria,or ’features’, to generate predictions for mineral prospectivity. Central to the design of prospectivity models is a ’mineral system’, a conceptual model describing the key geological elements that control the timing and location of economic mineralisation. The mineral systems model defines what constitutes a training set, which features represent geological evidence of mineralisation, how features are engineered and what modelling methods are used. Mineral systems are knowledge-driven conceptual models, thus all parameter choices are subject to human biases and opinion so alternative models are possible.However, the effect of alternative mineral systems models on prospectivity is rarely compared despite the potential to heavily influence final predictions. In this study, we focus on the effect of conceptual uncertainty on Fe ore prospectivity models in the Hamersley region, Western Australia. Four important considerations are tested.(1) Five different supergene and hypogene conceptual mineral systems models guide the inputs for five forest-based classification prospectivity models model.(2) To represent conceptual uncertainty, the predictions are then combined for prospectivity model comparison.(3)Representation of three-dimensional objects as two-dimensional features are tested to address commonly ignored thickness of geological units.(4) The training dataset is composed of known economic mineralisation sites(deposits) as ’positive’ examples, and exploration drilling data providing ’negative’sampling locations. Each of the spatial predictions are assessed using independent performance metrics common to AI-based classification methods and subjected to geological plausibility testing. We find that different conce

关键词： Uncertainty Modelling Prospectivity Economic geology Geological plausibility Forest-based classification

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High density lipoprotein as a therapeutic target:Focus on its functionality

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BIOCELL 2023年第11期47卷 2361-2383页

作者： LEONARDO GÓMEZ ROSSO BELÉN DAVICO EZEQUIEL LOZANO CHIAPPE WALTER TETZLAFF LAURA BOERO FERNANDO BRITES maximiliano MARTÍN School of Pharmacy and Biochemistry Laboratory of Lipids and AtherosclerosisDepartment of Clinical BiochemistryUniversity of Buenos AiresNational Scientific and Technical Research Council(CONICET)Buenos Aires1113Argentina

Cardiovascular diseases(CVDs)are the leading cause of death globally.CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease among other conditions.There are multiple independent risk factors for CVD,including hypertension,age,smoking,insulin resistance,elevated low-density lipoprotein cholesterol(LDL-C)levels,and triglyceride levels.LDL-C levels have traditionally been the target for therapies aimed at reducing CVD risk.High density lipoprotein(HDL)constitutes the only lipoprotein fraction with atheroprotective functions.Early HDL-targeted therapies have focused on increasing HDL-C levels.However,clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction.A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition,leading to loss of functionality.As a result,targeting HDL-C levels would be insufficient to achieve CVD risk reduction,making HDL functionality a more desirable focus for HDL-directed therapies.There are several drugs which show the potential to improve HDL functionality.These drugs include molecules already approved for human use,such as statins and niacin,and particularly,compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL preparations.These therapies show promising potential to improve HDL functionality specifically.Future therapeutic strategies should incorporate HDL functionality as a main target of interest.

关键词： HDL Cholesterol efflux rHDL Apo A-I mimetics Statins Paraoxonase

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Biodegradation of polycyclic aromatic hydrocarbons(PAHs)by fungal enzymes:A review

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Journal of Environmental Sciences 2017年第1期29卷 52-74页

作者： Tayssir Kadri Tarek Rouissi Satinder Kaur Brar maximiliano Cledon Saurabhjyoti Sarma Mausam Verma INRS-ETE Universite du Quebec490 Rue de la CouronneQuebecQC G1K 9A9Canada CO2 Solutions Inc. 2300rue Jean-PerrinQuebecQC G2C 1T9Canada

Polycyclic aromatic hydrocarbons（PAHs） are a large group of chemicals.They represent an important concern due to their widespread distribution in the environment,their resistance to biodegradation,their potential to bioaccumulate and their harmful effects.Several pilot treatments have been implemented to prevent economic consequences and deterioration of soil and water quality.As a promising option,fungal enzymes are regarded as a powerful choice for degradation of PAHs.Phanerochaete chrysosporium,Pleurotus ostreatus and Bjerkandera adusta are most commonly used for the degradation of such compounds due to their production of ligninolytic enzymes such as lignin peroxidase,manganese peroxidase and laccase.The rate of biodegradation depends on many culture conditions,such as temperature,oxygen,accessibility of nutrients and agitated or shallow culture.Moreover,the addition of biosurfactants can strongly modify the enzyme activity.The removal of PAHs is dependent on the ionization potential.The study of the kinetics is not completely comprehended,and it becomes more challenging when fungi are applied for bioremediation.Degradation studies in soil are much more complicated than liquid cultures because of the heterogeneity of soil,thus,many factors should be considered when studying soil bioremediation,such as desorption and bioavailability of PAHs.Different degradation pathways can be suggested.The peroxidases are heme-containing enzymes having common catalytic cycles.One molecule of hydrogen peroxide oxidizes the resting enzyme withdrawing two electrons.Subsequently,the peroxidase is reduced back in two steps of one electron oxidation.Laccases are copper-containing oxidases.They reduce molecular oxygen to water and oxidize phenolic compounds.

关键词： Polycyclic aromatic hydrocarbons （PAHs） Biodegradation Fungi Enzymes

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New Precipitation and Temperature Grids for Northern Patagonia： Advances in Relation to Global Climate Grids

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Journal of Meteorological Research 2016年第1期30卷 38-52页

作者： Emilio Bianchi Ricardo Villalba maximiliano Viale Fleur Couvreux Rocio Marticorena instituto nacional de tecnología agropecuaria estación experimental agropecuaria barilocheModesta Victoria 4450BarilocheArgentina consejo nacional de investigaciones científicas y tcnicas Argentina instituto argentino de nivología glaciología y ciencias ambientales-consejo nacional de investigaciones científicas y tcnicasMendozaRuiz LealMendozaArgentina centre national de recherches mtorologiques(cnrm-game) Mdtdo-FranceToulouseFrance autoridad interjurisdiccional de cuencas Argentina

Climate data of mean monthly temperature and total monthly precipitation compiled from different sources in northern Patagonia were interpolated to 20-km resolution grids over the period 1997-2010. This northern Patagonian climate grid （NPCG） improves upon previous gridded products in terms of its spatial resolution and number of contributing stations, since it incorporates 218 and 114 precipitation and temper- ature records, respectively. A geostatistical method using surface elevation from a Digital Elevation Model （DEM） as the ancillary variable was used to interpolate station data into even spaced points. The maps provided by NPCG are consistent with the broad spatial and temporal patterns of the northern Patagonian climate, showing a comprehensive representation of the latitudinal and altitudinal gradients in temperature and precipitation, as well as their related patterns of seasonality and continentality. We compared the per- formance of NPCG and various other datasets available to the climate community for northern Patagonia. The grids used for the comparison included those of the Global Precipitation Climatology Project, ERA- Interim, Climate Research Unit （University of East Anglia）, and University of Delaware. Based on three statistics that quantitatively assess the spatial coherence of gridded data against available observations （bias, MAE, and RMSE）, NPCG outperforms other global grids. NPCG represents a useful tool for understand- ing climate variability in northern Patagonia and a valuable input for regional models of hydrological and ecological processes. Its resolution is optimal for validating data from the general circulation models and working with raster data derived from remote sensing, such as vegetation indices.

关键词： northern Patagonia precipitation temperature co-kriging climate grids Cordillera de los Andes

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Collaterals of Life: Fistulous Communication of Vieussens’ Arterial Ring

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Case Reports in Clinical Medicine 2023年第9期12卷 333-338页

作者： Elba Palacios-Espinoza Javier Figueroa-Tataje Hugo maximiliano-Nieva Cardiology Department Cardiac Imaging Unit Hospital Nacional Alberto Sabogal Sologuren Lima Peru Association for the Development of Research in Health Sciences (ADIECS) National University of San Marcos Lima Peru

The Vieussens’ arterial ring (VAR) is a rare coronary anomaly that may be associated with a pulmonary fistula, and has been linked to ischemia, myocardial infarction, heart failure, arrhythmias, and sudden death. We present the case of a 54-year-old man who was admitted to the emergency room with angina and dyspnea on moderate exertion, in the context of atrial fibrillation and decompensated heart failure with left ventricular systolic dysfunction. In the study of its etiology, coronary computed tomography angiography (CCTA) identified an anomalous conal artery outflow (type C) as part of the VAR and a fistula to the pulmonary artery trunk (variant 1b), with an arterial flow linking the conal artery and the middle third of the left anterior descending artery (LAD), which then fistulized to the pulmonary artery trunk. The hemodynamic and clinical repercussions presented with signs of ischemia in the LAD territory and acute heart failure. In this case, CCTA identified the coronary anomaly and its trajectory with great precision through volume rendering reconstruction, as well as the dynamics of coronary flow in the presence of the pulmonary fistula. This anatomical variant is rarely described, and CCTA is of great utility in the therapeutic decision for fistula closure.

关键词： Vieussens’ Arterial Ring Pulmonary Fistula Coronary Artery Anomaly

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