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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

Seismic response of continuous span bridges through fiber-based finite element analysis

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Earthquake Engineering and Engineering Vibration 2006年第1期5卷 119-131页

作者： chiara Casarotti Rui Pinho University of Pavia Structural Mechanics Dept. Via Ferrata 1 27100 Pavia Italy

It is widely recognized that nonlinear time-history analysis constitutes the most accurate way to simulate the response of structures subjected to strong levels of seismic excitation. This analytical method is based on sound underlying principles and has the capability to reproduce the intrinsic inelastic dynamic behavior of structures. Nonetheless, comparisons with experimental results from large-scale testing of structures are still needed, in order to ensure adequate levels of confidence in this numerical methodology. The fiber modelling approach employed in the current endeavor inherently accounts for geometric nonlinearities and material inelasticity, without a need for calibration of plastic hinges mechanisms, typical in concentrated plasticity models. The resulting combination of analysis accuracy and modelling simplicity, allows thus to overcome the perhaps not fully justifiable sense of complexity associated to nonlinear dynamic analysis. The fiber-based modelling approach is employed in the framework of a finite element program downloaded from the Intemet for seismic response analysis of framed structures. The reliability and accuracy of the program are demonstrated by numerically reproducing pseudo-dynamic tests on a four span continuous deck concrete bridge. Modelling assumptions are discussed, together with their implications on numerical results of the nonlinear time-history analyses, which were found to be in good agreement with experimental results.

关键词： bridges seismic response pseudo-dynamic testing nonlinear dynamic analysis fiber modelling

Quantifying Environmental Impacts of Temporary Housing at the Urban Scale: Intersection of Vulnerability and PostHurricane Relief in New Orleans

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International Journal of Disaster Risk Science 2019年第4期10卷 478-492页

作者： Claire McConnell chiara Bertolin Department of Architecture and Technology Norwegian University of Science and Technology(NTNU)7491 TrondheimNorway Department of Mechanical and Industrial Engineering Norwegian University of Science and Technology(NTNU)7491 TrondheimNorway

The increasing risk and exposure of people and assets to natural hazards and disasters suggests an increasing need for temporary housing following *** to natural hazards is dependent on the resources available to families or communities to prepare for and mitigate risk,influenced by social *** study seeks to quantify the total environmental impact of temporary housing deployment in New Orleans,using the catastrophic impact of Hurricane Katrina in southern Louisiana in August 2005 as a case *** employ a novel approach to estimate displacement period and take into account social vulnerability across New Orleans neighborhoods to better understand the scale of post-disaster relief and its global warming *** methodology implemented in this study comprises three steps:a risk assessment,a life cycle assessment,and a resulting total impact *** demonstrate the considerable risk of greenhouse gas emissions and energy impacts from temporary housing deployment linked to hurricane ***,we show that environmental impact is highly sensitive to displacement period and find the current methodology of anticipating temporary housing use by hazard alone to be ***,the approach presented in this article provides tools to politicians and disaster risk professionals that allow for resource investment planning to decrease social vulnerability,thus enhancing resilience and adaptive capacity in a more homogeneous way at the urban scale.

关键词： Disaster risk Global warming potential Hurricane Katrina Life cycle assessment New Orleans Social vulnerability Temporary housing

Focus on cardiac troponin complex:From gene expression to cardiomyopathy

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Genes & Diseases 2024年第6期11卷 115-134页

作者： Rosetta Ragusa chiara Caselli Institute of Clinical Physiology CNRvia Moruzzi 1Pisa 56124Italy Fondazione Toscana Gabriele Monasterio via Moruzzi 1Pisa 56124Italy

The cardiac troponin complex(cTn)is a regulatory component of *** consists of three subunits:cardiac troponin C(cTnC),which confers Ca2+sensitivity to muscle;cTnl,which inhibits the interaction of cross-bridge of myosin with thin filament during dias-tole;and cTnT,which has multiple roles in sarcomere,such as promoting the link between the cTnl-cTnC complex and tropomyosin within the thin filament and influencing Ca2+sensi-tivity of cTn and force development during *** that interfere with inter-actions within cTn and/or other thin filament proteins can be key factors in the regulation of cardiac *** conditions include alterations in myoflament Caz+sensitivity,direct changes in cTn function,and triggering downstream events that lead to adverse cardiac remodeling and impairment of heart *** review describes gene expression and post-translational modifications of cTn as well as the conditions that can adversely affect the deli-cate balance among the components of cTn,thereby promoting contractile dysfunction.

关键词： Cardiac troponin Cardiomyopathy Genemutation Post-translational modification Therapy

Comparison of laboratory and field electrical resistivity measurements of a gypsum rock for mining prospection applications

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International Journal of Mining Science and Technology 2019年第6期29卷 841-849页

作者： chiara Caselle Sabrina Bonetto Cesare Comina Department of Earth Science (DST) Torino University

Geophysical surveys are frequently applied in mining prospection to detect the presence and volume of ore bodies of different ***,in gypsum ore bodies exploitation,electrical resistivity measurements are usually the most used ***,it has been observed that different electrical resistivity values can be obtained depending on geometrical features and composition of ***,electrical resistivity of gypsum rocks depends on several parameters,such as gypsum purity,nature of secondary minerals,porosity,saturation and interstitial fluid *** and hydrogeological setting,in particular,were recognized as the most influencing *** conditions of gypsum rock masses are also very relevant for exploitability,safety conditions and economic feasibility and should be accurately known during the prospection and planning phases of the *** this work,a relationship between electrical resistivity and saturation degree of gypsum is *** possibility to estimate gypsum porosity with the use of this relationship is also *** reliability of laboratory measurements is finally verified in comparison with field and modelled resistivity *** reported results underline the potentiality of the proposed approach to obtain a reliable characterization of the studied ore body.

关键词： Gypsum rock Electrical resistivity Saturation Porosity Archie ERT Quarry

Stem cells, a two-edged sword: Risks and potentials of regenerative medicine

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World Journal of Gastroenterology 2008年第27期14卷 4273-4279页

作者： Anna chiara Piscaglia Department of Internal Medicine and Gastroenterology "GI & Liver Stem Cell Research Group" Catholic University of Rome

The recent advancements in stem cell (SC) biology have led to the concept of regenerative medicine, which is based on the potential of SC for therapies aimed to facilitate the repair of degenerating or injured tissues. Nonetheless, prior to large scale clinical appli- cations, critical aspects need to be further addressed, including the long-term safety, tolerability, and efficacy of SC-based treatments. Most problematic among the risks of SC-based therapies, in addition to the pos- sible rejection or loss of function of the infused cells, is their potential neoplastic transformation. Indeed, SCs may be used to cure devastating diseases, but their specific properties of self-renewal and clonogenicity may render them prone to generate cancers. In this respect, ‘Stemness’ might be seen as a two-edged sword, its bright side being represented by normal SCs, its dark side by cancer SCs. A better understand- ing of SC biology will help fulfill the promise of regen- erative medicine aimed at curing human pathologies and fighting cancer from its roots.

关键词： Stem cells Regenerative medicine Gastrointestinal diseases Chronic liver diseases Cell-basedtherapy

In vitro rumen fermentation of feed substrates added with chestnut tannins or an extract from Stevia rebaudiana Bertoni

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Animal Nutrition 2020年第1期6卷 54-60页

作者： chiara Sarnataro Mauro Spanghero Department of Agricultural FoodEnvironmental and Animal SciencesUniversity of UdineVia Sondrio2/A33100UdineItaly

Rumen fermentation parameters and microbiota were evaluated in 3 in vitro rumen fermentation experiments after addition of chestnut tannins(CWT)or an extract from Stevia rebaudiana Bertoni(SB)to substrates.A control(CTR)substrate was fermented alone or added with 1.5%of CWT or SB extracts in a batch culture system(Exp.1,fermentation in 500 mL for 24 h)and in a subsequent continuous culture system(Exp.2,fermentation in 2 L bottles for 9 d).Experiment 3 used the fermentation system of Exp.1 and tested 7 doses of each extract added to CTR(additions of 0.2%,0.4%,0.6%,0.8%,1.0%,1.2%and 1.4%for48 h).The addition of CWT lowered(P<0.01)the in vitro rumen ammonia concentration in all experiments and reduced the protozoa counts in Exp.1(P<0.05).In contrast,the SB extract did not modify the ammonia concentrations,but significantly lowered the protozoa counts in all 3 experiments(reduction of 47%and 20%in Exp.1 and 2,P<0.05;and a quadratic reduction in Exp.3,R^2=0.63,P<0.01).Neither extract affected the fermentation in terms of gas production(Exp.1 and 3)nor volatile fatty acids(VFA)yield(Exp.1 and 2),if we exclude a reduction at the highest CWT concentration in *** in VFA profile were induced by CWT and were limited to reductions in the iso-valerate(P<0.01,in Exp.2)and iso-butyrate levels(P<0.01,Exp.2).The CWT increased the abundance of Prevotella ruminicola and Selenomonas ruminantium and decreased that of Ruminobacter amylophilus(P<0.01,P<0.05 and P<0.05,respectively).The SB extract increased the relative abundance of Treponema saccarophylum(P<0.05).Both of the studied substances had an impact on rumen metabolism,with SB reducing protozoa counts and CWT lowering the rumen ammonia *** effects of both extracts on the rumen were appreciable at low dietary doses,and the negative impacts on fermentation were limited to the reduction in protein degradation with the addition of CWT.

关键词： Rumen Ammonia Protozoa Chestnut tannin Stevia rebaudiana Bertoni

Gene Duplication and the Evolution of Plant MADS-box Transcription Factors

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Journal of Genetics and Genomics 2012年第4期39卷 157-165页

作者： chiara A.Airoldi Brendan Davies Centre for Plant Sciences University of Leeds

Since the first MADS-box transcription factor genes were implicated in the establishment of floral organ identity in a couple of model plants, the size and scope of this gene family has begun to be appreciated in a much wider range of species. Over the course of millions of years the number of MADS-box genes in plants has increased to the point that the Arabidopsis genome contains more than 100. The understanding gained from studying the evolution, regulation and function of multiple MADS-box genes in an increasing set of species, makes this large plant transcription factor gene family an ideal subject to study the processes that lead to an increase in gene number and the selective birth, death and repurposing of its component members. Here we will use examples taken from the MADS-box gene family to review what is known about the factors that influence the loss and retention of genes duplicated in different ways and examine the varied fates of the retained genes and their associated biological outcomes.

关键词： Flower development MADS-box transcription factor Gene duplication Evolution

Genetic testing in neurology exploiting next generation sequencing:state of art

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Neural Regeneration Research 2020年第2期15卷 265-266页

作者： chiara Di Resta Maurizio Ferrari Vita-Salute San Raffaele University MilanItaly Unit of Genomics for Human Disease Diagnosis Division of Genetics and Cell BiologyIRCCS San Raffaele Scientific InstituteMilanItaly Clinical Molecular Biology Laboratory IRCCS San Raffaele HospitalMilanItaly

Next generations sequencing (NGS) is definitely one of the most revolutionary technology of the last years in genetic and medical field (Kricka and Di Resta, 2013). It brought important changes in genetic testing of inherited human disorders, in particular in neurological Mendelian forms, such as inherited neuropathies, ataxias or monogenic form of epilepsy, where “diagnostic odyssey” is quite common.

关键词： Genetic testing NGS diagnostic odyssey