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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： antonio masone Chiara Zucchelli Enrico Caruso Giovanna musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NmR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life sciences University of InsubriaVareseItaly

PrPsc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Oleogels for development of health-promoting food products

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Food science and Human Wellness 2020年第1期9卷 31-39页

作者： Artur J.martins antonio A.Vicente lorenzo m.Pastrana miguel A.Cerqueira International Iberian Nanotechnology Laboratory Av.Mestre JoséVeiga s/n4715-330BragaPortugal Centre of Biological Engineering University of MinhoCampus de Gualtar4710-057BragaPortugal

metabolic health and the maintenance of good levels of triglycerides,high-density lipoprotein cholesterol,blood pressure and glucose levels are concerns that can greatly impact human quality of *** consumers’demands,together with technological innovations,have led to a diversification of the food *** fostering of off-the-shelf available and affordable healthy food products is necessary,as detrimental effects on human health from the ingestion of saturated fat sources urge the efforts to find *** can be tailored using specific triglycerides and oleogelators,that can be selected to yield targeted fatty acids,reduce higher levels of cholesterol with competing binding-molecules(***),reduce saturated fat content,lessen appetite(*** the shape of foods)or carry exclusive bioactive compounds to be absorbed in the digestive *** are foreseen as an important technological advance in food science due to their versatility,easy processing and *** review explored the strategies in place to develop and produce oleogels,foreseeing their introduction in foods and how they might represent an important source of functionality through the use of healthy *** also explored how oleogels can act on the human overall metabolic health if they are used in human diet.

关键词： Oleogel Vagal pathway Nutrition Fatty acids metabolism Gut-brain axis

Effect of Noisy Fitness in Real-Time strategy Games Player Behaviour Optimisation Using Evolutionary Algorithms

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Journal of Computer science & Technology 2012年第5期27卷 1007-1023页

作者： antonio m. mora antonio Fernndez-Ares Juan J. merelo Pablo García-snchez Carlos m. Fernandes Computer Architecture and Technology Department University of Granada Institute for systems and Robotics Technical University of Lisbon

This paper investigates the performance and the results of an evolutionary algorithm （EA） specifically designed for evolving the decision engine of a program （which, in this context, is called bot） that plays Planet Wars. This game, which was chosen for the Google Artificial Intelligence Challenge in 2010, requires the bot to deal with multiple target planets, while achieving a certain degree of adaptability in order to defeat different opponents in different scenarios. The decision engine of the bot is initially based on a set of rules that have been defined after an empirical study, and a genetic algorithm （GA） is used for tuning the set of constants, weights and probabilities that those rules include, and therefore, the general behaviour of the bot. Then, the bot is supplied with the evolved decision engine and the results obtained when competing with other bots （a bot offered by Google as a sparring partner, and a scripted bot with a pre-established behaviour） are thoroughly analysed. The evaluation of the candidate solutions is based on the result of non-deterministic battles （and environmental interactions） against other bots, whose outcome depends on random draws as well as on the opponents＇ actions. Therefore, the proposed GA is dealing with a noisy fitness function. After analysing the effects of the noisy fitness, we conclude that tackling randomness via repeated combats and reevaluations reduces this effect and makes the GA a highly valuable approach for solving this problem.

关键词： real-time strategy game genetic algorithm noisy fitness player behaviour optimisation parameter adaptation

Autoimmune pancreatitis not otherwise specified(NOs): Clinical features and outcomes of the forgotten type

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 576-579页

作者： Nicolò de Pretis Filippo Vieceli Alessandro Brandolese lorenzo Brozzi antonio Amodio Luca Frulloni Gastroenterology Unit Pancreas Center University of Verona

Background:Autoimmune pancreatitis(AIP)is a well-recognized fibroinflammatory disease of the *** the significant number of studies published on AIP type 1 and 2,no studies have been focused on AIP type not otherwise specified(NOs)and therefore very little is known about clinical features and long-term outcomes of these *** aim of this study was to investigate clinical and radiological features of AIP type ***:Patients classified as AIP type NOs at clinical onset included in our database prospectively maintained since 1995 were ***,clinical data were collected and ***:Forty-six patients were included in the *** clinical onset was mainly characterized by weight loss,jaundice and acute *** patients(17.4%)were reclassified as AIP type 2 during follow-up because of the development of ulcerative *** patients(15.2%)experienced relapse after steroid treatment but only one(2.2%)needed immunosuppressive drugs because of recurrent ***:AIP type NOs shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative *** risk of relapse is low but not irrelevant.

关键词： Autoimmune pancreatitis Not otherwise specified Outcome Follow-up Therapy

Nanostructural Evolution of sugarcane Rind and Pith submitted to Hydrothermal Pretreatments

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Journal of Renewable materials 2018年第2期6卷 152-159页

作者： marcelo m.Oliveira antonio A.s.Curvelo Carlos Driemeier Brazilian Bioethanol science and Technology Laboratory(CTBE) Brazilian Center for Research in Energy and Materials(CNPEM)Caixa Postal 619213083-970CampinasSão PauloBrasil são Carlos school of Engineering(EEsC) University of São Paulo(USP)Caixa Postal 78013560-970São CarlosSão PauloBrasil são Carlos Institute of Chemistry(IQsC) University of São Paulo(USP)Caixa Postal 78013560-970São CarlosSão PauloBrasil

Lignocellulose conversion into cellulosic ethanol and coproducts starts with a pretreatment *** current industrial plants of cellulosic ethanol use thermochemical pretreatments under hydrothermal conditions,with or without addition of acid *** pretreatments modify biomass chemistry and morphology,particularly at the *** this work,we use X-ray diffraction,dynamic vapor sorption and calorimetric thermoporometry to investigate the biomass nanostructural changes promoted by hydrothermal *** compare and differentiate the rind and pith fractions of sugarcane stalks in order to contribute to the understanding of rind-pith contrasting ***,for both cane fractions our results point consistently to cellulose co-crystallization,lignin aggregation,and opening of nanoscale pores as the main nanostructural phenomena occurring during hydrothermal treatments.

关键词： Cellulose bagasse sugarcane cellulosic ethanol pretreatment

Infrastructure for collaborative science and societal applications in the Columbia River estuary

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Frontiers of Earth science 2015年第4期9卷 659-682页

作者： antonio m. BAPTIsTA NsF science and Technology Center for Coastal margin Observation & Prediction Oregon Health & science University Portland Oregon 97239 USA Oregon Health & science University Astoria Oregon 97103 USA Portland state University Portland Oregon 97201 USA Applied Physics Laboratory of the University of Washington Seattle Washington 98105 USA Oregon state University Corvallis Oregon 97331 USA Formerly University of maryland Center for Environmental studies Maryland 21613 USA

To meet societal needs, modem estuarine science needs to be interdisciplinary and collaborative, combine discovery with hypotheses testing, and be responsive to issues facing both regional and global stakeholders. such an approach is best conducted with the benefit of data-rich environments, where information from sensors and models is openly accessible within convenient timeframes. Here, we introduce the operational infrastruc- ture of one such data-rich environment, a collaboratory created to support （a） interdisciplinary research in the Columbia River estuary by the multi-institutional team of investigators of the science and Technology Center for Coastal margin Observation ＆ Prediction and （b） the integration of scientific knowledge into regional decision making. Core components of the operational infrastructure are an observation network, a modeling system and a cyber-infrastructure, each of which is described. The observation network is anchored on an extensive array of long-term stations, many of them interdisciplinary, and is complemented by on-demand deployment of temporary stations and mobile platforms, often in coordinated field campaigns. The modeling system is based on finite- element unstructured-grid codes and includes operational and process-oriented simulations of circulation, sediments and ecosystem processes. The flow of information is managed through a dedicated cyber-infrastructure, con- versant with regional and national observing systems.

关键词： estuaries observations numerical modeling,cyber-infrastructure Columbia River

Efficacy and safety of low-intensity shockwave therapy plus tadalafil 5 mg once daily in men with type 2 diabetes mellitus and erectile dysfunction:a matched-pair comparison study

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Asian Journal of Andrology 2020年第4期22卷 379-382页

作者： Paolo Verze marco Capece massimiliano Creta Roberto La Rocca Francesco Persico lorenzo spirito antonio Cardi Vincenzo mirone Department of Neurosciences Reproductive Sciences and OdontostomatologyUniversity of Naples“Federico II”Naples 80131Italy Department of Urology San Giovanni Addolorata HospitalRome 00184Italy

Low-intensity extracorporeal shockwave therapy(LiEsWT)represents a promising treatment for patients with erectile dysfunction(ED).We investigated the efficacy of LiEsWT combined with tadalafil 5 mg once daily in men with type 2 diabetes mellitus(T2Dm)and ED and compared LiEsWT protocols administering different number of *** performed a retrospective matched-pair comparison using data from a prospectively maintained ***-eight patients who received tadalafil 5 mg once dai7ly for 12 weeks+LiEsWT performed with an electrohydraulic source for 3 weeks(Group A)were matched 1:1 to patients who received tadalafil 5 mg once daily alone for 12 weeks(Group B).A subgroup analysis was performed according to the number of shockwaves delivered during each session(1500,1800,and 2400 in subgroup A1,A2,and A3,respectively).The mean International Index of Erectile Function-5(IIEF-5)score variations with respect to baseline recorded at 4,12,and 24 weeks after the end of the treatment were investigated as treatment *** mean IIEF-5 scores significantly improved in all groups and subgroups at 4-week follow-up without intergroup *** 12-and 24-week follow-up,the mean IIEF-5 improvement was significantly higher among patients in the A3 subgroup(+5.0±2.1[Pspectively).The combined approach with tadalafil 5 mg once daily and LiEsWT with a protocol involving 2400 shockwaves provides significant advantages in terms of IIEF-5 improvement and durability compared to tadalafil 5 mg once daily alone in patients with T2Dm and ED.

关键词： diabetes mellitus erectile dysfunction low-intensity shockwave therapy tadalafil

A solution to Tingley's problem for isometries between the unit spheres of compact C~*-algebras and JB~*-triples

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science China mathematics 2019年第3期62卷 553-568页

作者： antonio m.Peralta Ryotaro Tanaka Departamento de Ana'lisis matem'atico Facultad de Ciencias Universidad de Granada Faculty of mathematics Kyushu University

Let f : s(E) → s(B) be a surjective isometry between the unit spheres of two weakly compact JB*-triples not containing direct summands of rank less than or equal to 3. suppose E has rank greater than or equal to 5. Applying techniques developed in JB*-triple theory, we prove that f admits an extension to a surjective real linear isometry T : E → B. Among the consequences, we show that every surjective isometry between the unit spheres of two compact C*-algebras A and B, without assuming any restriction on the rank of their direct summands(and in particular when A = K(H) and B = K(H′)), extends to a surjective real linear isometry from A into B. These results provide new examples of infinite-dimensional Banach spaces where Tingley's problem admits a positive answer.

关键词： Tingley’s problem extension of isometries JB*-triples compact operators

Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

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World Journal of Gastroenterology 2016年第11期22卷 3165-3174页

作者： antonio madejón míriam Romero ángela Hernández Araceli García-sánchez marta sánchez-Carrillo antonio Olveira Javier García-samaniego Hepatology section Gastroenterology Department Hospital Universitario La Paz 28046 Madrid Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas (CIBERehd) 28046 Madrid Spain Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ) 28046 Madrid Spain

AIm: To study the hepatitis B virus(HBV) and hepatitis D virus(HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV ***: We conducted a transversal study including 68 chronic hepatitis delta(CHD)(37 HIVpositive) patients and a control group of 49 chronic hepatitis B(CHB)(22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B(HBs Ag) serum titers were analyzed with the monolisa HBs Ag Ultra system(Bio-Rad), using as quantification standard a serial dilution curve of an international HBs Ag standard. serum HBV-DNA titers were analyzed using the Roche Cobas Taq man(Roche, Barcelona, spain), and the serum HDV-RNA using an in-house real-time q RT-PCR method, with Taq man probes. HBV genotype was determined with the line immunoassay Li PA HBV genotyping system(Innogenetics, Ghent, Belgium). In those patients negative for Li PA assay, a nested PCR method of complete HBs Ag coding region, followed by sequence analysis was ***: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median(IQR): 1.25(1.00-1.35) vs 2.95(2.07-3.93) log10(copies/m L), P = 0.013] and HIV positive patients [2.63(1.24-2.69) vs 7.25(4.61-7.55) log10(copies/m L), P s was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with Li PA assay. Finally, the HBs Ag titers reflected no significant differences in CHD patients infected with HBV-A or ***: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

关键词： Hepatitis D virus Hepatitis B virus Delta hepatitis Replication interference Viral replication