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Arrestins:structural disorder creates rich functionality

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Protein & Cell 2018年第12期9卷 986-1003页

作者： Vsevolod V.Gurevich eugenia V.Gurevich Vladimir N.Uversky Department of Pharmacology Vanderbilt UniversityNashvilleTN 37232USA Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute Morsani College of Medicine University of South FloridaTampaFL 33612USA Institute for Biological Instrumentation Russian Academy of SciencesPushchinoMoscow RegionRussia 142290

Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures. However, protein-protein interactions often involve highly flexible elements that can assume many distinct conformations upon binding to different partners. Existing evidence suggests that arrestins are no exception to this rule: their flexibility is necessary for functional versatility. The data on arrestins and many other multi-functional proteins indicate that in many cases, "order" might be artificially imposed by highly non-physiological crystallization conditions and/or crystal packing forces. In contrast, conformational flexibility (and its extreme case, intrinsic disorder) is a more natural state of proteins, representing true biological order that underlies their physiologically relevant functions.

关键词： EPR GPCR NMR arrestin crystal structure disorder protein-protein interactions

Alzheimer’s disease risk after COVID-19:a view from the perspective of the infectious hypothesis of neurodegeneration

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Neural Regeneration Research 2023年第7期18卷 1404-1410页

作者： eugenia Olivera Albany Sáez Lila Carniglia Carla Caruso Mercedes Lasaga Daniela Durand Instituto de Investigaciones Biomédicas INBIOMED UBA-CONICET Facultad de MedicinaUniversidad de Buenos AiresArgentina

In light of the rising evidence of the association between viral and bacterial infections and neurodegeneration,we aimed at revisiting the infectious hypothesis of Alzheimer’s disease and analyzing the possible implications of COVID-19 neurological sequelae in long-term *** wondered how SARS-CoV-2 could be related to the amyloid-βcascade and how it could lead to the pathological hallmarks of the *** also predict a paradigm change in clinical medicine,which now has a great opportunity to conduct prospective surveillance of cognitive sequelae and progression to dementia in people who suffered severe infections together with other risk factors for Alzheimer’s disease.

关键词： Alzheimer amyloid beta antimicrobial cognitive decline COVID-19 infectious hypothesis long-term sequelae neurodegeneration neuroinflammation neurological symptoms neurotropism SARS-CoV-2

Vector-valued operators, optimal weighted estimates and the C_p condition

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Science China Mathematics 2020年第7期63卷 1339-1368页

作者： María eugenia Cejas Kangwei Li Carlos Pérez Israel Pablo Rivera-Ríos BCAM—Basque Center for Applied Mathematics Bilbao 48009Spain CONICET Departamento de MatematicaFacultad de Ciencias ExactasUniversidad Nacional de La PlataLa Plata 1900Argentina Department of Mathematics University of the Basque CountryBilbao 48080Spain Ikerbasque Basque Foundation of ScienceBilbao 48013Spain INMABB CONICETDepartamento de MatematicaUniversidad Nacional del SurBahia Blanca 8000Argentina

In this paper some new results concerning the C_p classes introduced by Muckenhoupt(1981)and later extended by Sawyer(1983),are *** particular,we extend the result to the full expected range p>0,to the weak norm,to other operators and to their vector-valued *** of those results rely upon sparse domination,which in the vector-valued case are provided as *** will also provide sharp weighted estimates for vector-valued extensions relying on those sparse domination results.

关键词： A_p weights quantitative estimates C_p estimates vector-valued extensions sparse domination maximal functions Calderon-Zygmund operators commutators

A shape shifting organelle: unusual mitochondrial phenotype determined with three-dimensional electron microscopy reconstruction

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Neural Regeneration Research 2016年第6期11卷 900-901页

作者： eugenia Trushina Department of Neurology Mayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic

Mitochondria,the powerhouses of the cell,are dynamic organelles that constantly move and change their size and morphology to meet energetic demands of the cell（Wai and Langer,2016）.Recent studies demonstrated that energy production is dependent on the ability of mitochondria to undergo cycles of fission and fusion collectively termed“mitochondrial dynamics”（Youle and van der Bliek,2012）.

关键词： mitochondrial phenotype Langer constantly fission hippocampal neuronal unusual protective deprivation

Alcoholism and liver disease in Mexico:Genetic and environmental factors

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World Journal of Gastroenterology 2013年第44期19卷 7972-7982页

作者： Sonia Roman Eloy Alfonso Zepeda-Carrillo Laura eugenia Moreno-Luna Arturo Panduro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" and Health Sciences Center University of GuadalajaraGuadalajara Jalisco 44280 Mexico Universidad Autónoma de Nayarit and Hospital Civil Tepic "Antonio González Guevara" Tepic Nayarit 63000 Mexico

Alcoholism and cirrhosis,which are two of the most serious health problems worldwide,have a broad spectrum of clinical *** diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each *** contrast to other regions around the world,Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol *** has a unique history of alcohol consumption that is linked to profound anthropological and social *** Mexican population has an admixture genome inherited from different races,Caucasian,Amerindian and African,with a heterogeneous distribution within the ***,genes related to alcohol addiction,such as dopamine receptor D2 in the brain,or liver alcoholmetabolizing enzymes,such as alcohol dehydrogenase classⅠpolypeptide B,cytochrome P450 2E1 and aldehyde dehydrogenase class 2,may vary from one individual to ***,they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver ***,in this era of genomics,personalized medicine will benefit patients if it is directed according to individual or population-based *** association studies will be required to establish novel strategies for the prevention,care and treatment of liver disease in Mexico and worldwide.

关键词： Alcohol Genes Alcoholism Alcohol dependence Alcohol addiction Alcohol abuse Alcoholic liver cirrhosis Anthropology

Imbalance in T-cell differentiation as a biomarker of chronic diabetic foot ulceration

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Cellular & Molecular Immunology 2019年第10期16卷 833-834页

作者： Joao Moura Joao Rodrigues Marta Gonçalves Claudia Amaral Margarida Lima eugenia Carvalho Center for Neuroscience and Cell Biology(CNC) University of CoimbraCoimbraPortugal INEB-Instituto Nacional de Engenharia Biomedica University of PortoPortoPortugal I3S-Instituto de Investigaçao e Inovaçao em Saude University of PortoPortoPortugal Department of Hematology Hospital de Santo Antonio(HSA)Centro Hospitalar Universitario do Porto(CHUP)PortoPortugal Unidade Multidisciplinar de Investigaçao Biomedica(UMIB/ICBAS/UP) PortoPortugal Department of Endocrinology Hospital de Santo Antonio(HSA)Centro Hospitalar Universitário do Porto(CHUP)PortoPortugal Department of Geriatrics University of Arkansas for Medical Sciences(UAMS)and Arkansas Children’s Hospital Research Institute(ACHRI)Little RockArkansas 72202USA

Diabetes is a growing epidemic due to the systematic increase in overweight and obesity,and chronic diabetic foot ulcers(DFUs)are the most debilitating and costly complication of *** is still essential for DFU care,but early detection is limited because we do not have a good DFU ***,we report the preliminary results of a large longitudinal study to test the effectiveness of the use of T-cell phenotype and TCR repertoire diversity as DFU *** results show that the ratio of effector/naïve T-cells and the number of TCR expansions are valuable biomarkers of DFU prognosis.

关键词： diabetic chronic obesity

Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

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Neural Regeneration Research 2020年第9期15卷 1757-1766页

作者： Massimo Santoro Roberto Piacentini Alessia Perna eugenia Pisano Anna Severino Anna Modoni Claudio Grassi Gabriella Silvestri IRCCS Fondazione Don Carlo Gnocchi MilanItaly Department of Neuroscience Universita Cattolica del Sacro CuoreRomeItaly Department of Cardiovascular and Thoracic Sciences Universita Cattolica del Sacro CuoreRomeItaly Fondazione Policlinico Universitario A.Gemelli IRCCS RomeItaly

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

关键词： alternative splicing calcium homeostasis CUG-BP1 foci MBNL1 myotonic dystrophy type 1 myotubes resveratrol

Epidermal stem cells and skin tissue engineering in hair follicle regeneration

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World Journal of Stem Cells 2015年第4期7卷 711-727页

作者： María eugenia Balaná Hernán Eduardo Charreau Gustavo Jose Leirós Fundación Pablo Cassará-Instituto de Ciencia y Tecnología Dr.César Milstein Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Saladillo 2468 C1440FFXCiudad de Buenos AiresArgentina Technology Intelligence Unit ClarkeModet&C°Lavalle 1903°PisoC1047AAD Buenos AiresArgentina

The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide threedimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This fiel

关键词： Adult stem cells Skin grafts Epidermis Multipotential differentiation Tissue regeneration Dermal papilla Epithelial-mesenchymal interactions

Potential of the Arkhangelsk seismic network for European Arctic monitoring

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Earthquake Science 2024年第5期37卷 434-444页

作者： Galina Antonovskaya Yana Konechnaya Ekaterina Morozova Yana Mikhailova eugenia Shakhova N.Laverov Federal Center for Integrated Arctic Research of the Ural Branch of the Russian Academy of Sciences Arkhangelsk 163002Russia Geophysical Survey of the Russian Academy of Sciences ObninskKaluga region 249034Russia

The Arkhangelsk Seismic Network(ASN)of the *** Federal Center for Integrated Arctic Research of the Ural Branch of the Russian Academy of Sciences,founded in 2003,includes 10 permanent seismic stations located on the coasts of the White,Barents,and Kara Seas and on the Arctic archipelagos of Novaya Zemlya,Franz Josef Land,and Severnaya *** network is registered with the International Federation of Digital Seismograph Networks and the International Seismological *** used not only ASN data to process earthquakes but also the waveforms of various international seismic *** 13,000 seismic events were registered using ASN data for 2012-2022,and for 5,500 of them,we determined the parameters of the earthquake epicenters from the European *** spatial distribution of epicenters shows that the ASN monitors not only the main seismically active zones but also weak seismicity on the shelf of the Barents and Kara *** representative magnitude of ASN was ML,rep=*** level of microseismic noise has seasonal variations that affect the registration capabilities of each station included in the ASN and the overall sensitivity of the network as a *** summer,the sensitivity of the ASN decreased owing to the increasing microseismic and ambient noises,whereas in winter,the sensitivity of the ASN increased significantly because of the decrease.

关键词： European Arctic Arkhangelsk Seismic Network seismic monitoring seismic network registration capabilities