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Cryptic exon inclusion in TDP-43 proteinopathies:opportunities and challenges

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Neural Regeneration Research 2025年第7期20卷 2003-2004页

作者： lorena Decker Sonja Menge Axel Freischmidt Department of Neurology Ulm UniversityUlmGermany

TDP-43 proteinopathies and cryptic exons:Transactive response DNA binding protein of 43 kDa(TDP-43)is a ubiquitously expressed RNA/DNA binding protein crucial for coding and non-coding RNA metabolism including transcription,splicing,transport,translation,and ***-43 shuttles between the nucleus and cytoplasm,but is predominantly localized in the *** diseases(NDs)may be accompanied by nuclear loss and possible cytoplasmic accumulation and aggregation of TDP-43 in vulnerable neurons and *** neuropathology is the hallmark of most individuals suffering from amyotrophic lateral sclerosis(ALS),frontotemporal dementia(FTD)with TDP-43-immunoreactive pathology(FTD-TDP),limbic-predominant age-related TDP-43 encephalopathy(LATE)and Perry syndrome,but also coexists with the primary pathology in subsets of patients suffering from other NDs,such as Alzheimer’s disease,Lewy body dementias,or Huntington’s *** in the gene encoding TDP-43(TARDBP)are the cause of ALS and/or FTD in some rare cases substantiating the importance of this protein in aging *** is still controversial if loss of nuclear,or increased cytoplasmic and/or aggregating TDP-43 is more harmful to neurons(Nag and Schneider,2023).Recently,the role of nuclear TDP-43 in repressing the inclusion of intronic sequences,named cryptic exons(CEs),into mature mRNAs gained much attention.

关键词： Huntington metabolism TDP

Computational studies on the seismic response of the State Route 99 bridge in Seattle with SMA/ECC plastic hinges

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Frontiers of Structural and Civil Engineering 2019年第1期13卷 149-164页

作者： Jiping GE M.Saiid SAIIDI Sebastian varela School of Urban Construction and Safety Engineering Shanghai Institute of TechnologyShanghai 201418China Department of Civil and Environmental Engineering University of NevadaRenoNV 89557USA Structural Engineering Group Freese and Nichols Inc.Fort WorthTX 76109USA

This paper reports a computational study on the seismic response of a three-span highway bridge system incorporating conventional and novel substructure details for improved seismic *** bridge has three continuous spans supported by two single-column piers and integral abutments founded on drilled *** will be the first full-scale highway bridge to use superelastic shape memory alloy bars (SMA)and engineered cementitious composite (ECC)to mitigate column plastic hinge damage and minimize residual displacements after a strong earthquake. A three-dimensional computational model capturing the nonlinear constitutive response of the novel materials and the effects of dynamic soil-structure interaction was developed to assess the seismic response of the bridge in finite-element software *** versions of the same bridge were analyzed and compared,one with conventional cast-in-place reinforced concrete columns,and the other with top plastic hinges incorporating Nickel-Titanium (NiTi)SMA reinforcing bars and *** novel SMA/ECC plastic hinges were found to substantially reduce damage and post-earthquake residual displacements in the bridge substructure,but led to larger maximum drifts relative to the bridge with conventional reinforced concrete plastic *** analysis results suggested that the novel plastic hinges could lead to improved post-earthquake serviceability of bridges after intense earthquakes.

关键词： seismic design analytical simulation near-fault earthquakes shape memory alloy engineered cementitious composite self-centering

Restoring expression of Stathmin-2:a novel strategy to treat TDP-43 proteinopathies

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3553-3554页

作者： Sonja Menge lorena Decker Axel Freischmidt Department of Neurology Ulm University89081 UlmGermany

In a recent study published in Science,Baughn et *** that TDP-43 acts as a steric block in STMN2 pre-mRNA processing preventing inclusion of a deleterious cryptic exon,and present strategies for substituting this function to compensate for the loss of nuclear TDP-43 in a variety of neurodegenerative diseases(NDs)including amyotrophic lateral sclerosis(ALS).1 Stathmin-2(STMN2)is a microtubule-associated protein speci-fically expressed in neurons and required for axon outgrowth and maintenance,as well as for axon regeneration after injury in vitro.

关键词： Stathmin diseases

Baculovirus RNA Polymerase: Activities, Composition, and Evolution

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中国病毒学 2007年第2期22卷 94-107页

作者： A.lorena Passarelli Molecular Cellular and Developmental Biology Program Division of Biology 116 Ackert Hall Kansas State University Manhattan KS 66506-4901 USA

Baculoviruses are the only nuclear replicating DNA-containing viruses that encode their own DNA-directed RNA polymerase (RNAP). The baculovirus RNAP is specific for the transcription of genes expressed after virus DNA replication. It is composed of four subunits, making it the simplest multisubunit RNAP known. Two subunits contain motifs found at the catalytic center of other RNAPs and a third has capping enzyme functions. The function of the fourth subunit is not known. Structural studies on this unique RNAP will provide new insights into the functions of this enzyme and the regulation of viral genes and may be instrumental to optimize the baculovirus gene expression system.

关键词：杆状病毒聚合酶病毒复制病毒基因

New discriminant-function-based multidimensional discrimination of mid-ocean ridge and oceanic plateau

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Geoscience Frontiers 2020年第5期11卷 1681-1693页

作者： Surendra P.Verma lorena Diaz-Gonzalez Instituto de Energias Renovables Universidad Nacional Autonoma de MexicoPriv.Xochicalco S/no.Col.CentroApartado Postal 34TemixcoMor62580Mexico Centro de Investigacion en Ciencias Universidad Autonoma de Estado de MorelosCuernavacaMorelos62209Mexico

From a compilation of geochemical data for the discrimination of the tectonic settings of mid-ocean ridge(MOR;3730 samples)and oceanic plateau(OP;3656 samples),we present two new discriminant functions and diagrams obtained from censored multivariate discordant outlier-free *** different sets of data(original concentrations as well as isometric log-ratio transformed(ilr)variables;all 10 major(M)elements as well as all 10 major and 6 trace elements MT)were used to evaluate the quality of discrimination from linear discriminant analysis(LDA)and canonical *** selected multidimensional models ilrM(9 ilr transformed variables of multi-normally distributed 10 major elements)and ilrMT(15 ilr transformed variables of multi-normally distributed combined 10 major and 6 trace elements),considered as the best or most representative(total of5650 samples for ilrM and 2858 for ilrMT),provided percent success values,respectively,of 80.9%for the MOR and 81.1%for the OP(ilrM)and 88.5%for the MOR and 90.1%for the OP(ilrMT).Both processes(log-ratio transformation and multi-normality)rendered the percent success values similar for both groups(MOR and OP).The respective discriminant functions were successfully used for four tests from known tectonic settings and four application cases(two for ophiolites and two for Precambrian rocks),documenting thus the utility of the new discrimination procedure for the MOR and OP tectonic ***,we showed that our multidimensional procedure is robust against analytical errors or uncertainties,as well as post-emplacement compositional changes caused by element mobility from both low or high temperature *** robustness against the gain or loss of a single element at a time was also documented,from which the ilrMT model was evaluated as more robust than the ilrM model.A new online computer program MOROPdisc was written in Java Framework ZK,which is freely available for use at our web portal http://***

关键词： MORB Multivariate discordant outliers Log-ratio transformation Multidimensional discrimination Analytical uncertainties Post-emplacement changes

Chemical-Abrasion U-Pb zircon geochronology reveals 150 Myr of partial melting events in the Archean crust of the São Francisco Craton

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Geoscience Frontiers 2022年第5期13卷 169-189页

作者： lorena Martins Cristiano Lana Ariela Mazoz Tiago Novo Applied Isotope Research Group Departamento de GeologiaEscola de MinasUniversidade Federal de Ouro PretoMorro do CruzeiroOuro PretoMG35400-000Brazil Universidade Federal de Minas Gerais Programa de Pós-Graduação em GeologiaIGC-CPMTCCampus PampulhaAv.Antônio Carlos 6627Belo HorizonteMG31270-901Brazil

Field observations and CA-LA-ICP-MS U–Pb zircon ages and Hf isotope compositions obtained from migmatitic orthogneisses and granitoids from the Belo Horizonte Complex,southern São Francisco Craton,indicate a major period of partial melting and production of felsic rocks in the *** observations show that the complex is an important site for studying partial melting processes of Archean crystalline *** of the complex exposes fine-grained stromatic migmatites that are intruded by multiple leucogranitic veins and sheeted *** migmatites and leucogranite sheets are crosscut by several phases of granitoid batholiths and small granitic bodies;both of which are closely associated with the host banded *** abrasion followed by detailed cathodoluminescence imaging revealed a wide variety of zircon textures that are consistent with a long-lived period of partial melting and crustal *** of U-Pb and Hf isotopes disclose the complex as part of a much wider crustal segment,encompassing the entire southern part of the São Francisco *** of available U-Pb ages suggests that this crustal segment was consolidated sometime between 3000 Ma and 2900 Ma and that it experienced three main episodes of partial melting before stabilization at 2600 *** partial melting episodes took place between 2750 Ma and 2600 Ma as a result of tectonic accretion and peeling off the lithospheric mantle and lower *** process is likely responsible for the emplacement of voluminous potassic granitoids across the entire São Francisco *** believe that the partial melting of Meso-Archean crystalline crust and production of potassic granitoids are linked to a fundamental shift in the tectonics of the craton,which was also responsible for the widespread intrusion of large syenitic bodies in the northern part of the craton,and the construction of layered mafic–ultramafic intrusions to the south of the BHC.

关键词： Archean São Francisco Craton Crustal reworking U-Pb geochronology Lu-Hf isotopes

Endocytic Trafficking towards the Vacuole Plays a Key Role in the Auxin Receptor SCF^TIR-Independent Mechanism of Lateral Root Formation in A. thaliana

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Molecular Plant 2012年第6期5卷 1195-1209页

作者： Patricio Perez-Henrique Natasha V. Raikhel lorena Norambuena Plant Molecular Biology Laboratory Department of Biology Faculty of Sciences University of Chile Santiago Chile Millenium Nucleus in Plant Cell Biotechnology Chile Center for Plant Cell Biology and Department of Botany and Plant Sciences University of California Riverside CA 92521 USA

Plants＇ developmental plasticity plays a pivotal role in responding to environmental conditions. One of the most plastic plant organs is the root system. Different environmental stimuli such as nutrients and water deficiency may induce lateral root formation to compensate for a low level of water and/or nutrients. It has been shown that the hor- mone auxin tunes lateral root development and components for its signaling pathway have been identified. Using chemi- cal biology, we discovered an Arabidopsis thaliana lateral root formation mechanism that is independent of the auxin receptor SCFTM. The bioactive compound Sortin2 increased lateral root occurrence by acting upstream from the morpho- logical marker of lateral root primordium formation, the mitotic activity. The compound did not display auxin activity. At the cellular level, Sortin2 accelerated endosomal trafficking, resulting in increased trafficking of plasma membrane recy- cling proteins to the vacuole. Sortin2 affected Late endosome/PVC/MVB trafficking and morphology. Combining Sortin2 with well-known drugs showed that endocytic trafficking of Late E/PVC/MVB towards the vacuole is pivotal for Sortin2- induced SCFTm-independent lateral root initiation. Our results revealed a distinctive role for endosomal trafficking in the promotion of lateral root formation via a process that does not rely on the auxin receptor complex SCFTM.

关键词： lateral root development endocytic trafficking Sortin2 endosomes Arabidopsis.

RESIDENTIAL SOLAR ENERGY POTENTIAL FOR PUBLIC DISSEMINATION:A CASE STUDY IN CONCEPCION,CHILE

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Journal of Green Building 2016年第1期11卷 118-133页

作者： Rodrigo García Alvarado lorena Troncoso Pablo Campos University of Bio-Bío Department of Design and Theory of ArchitectureConcepciónChile University of Concepción Department of Mechanical EngineeringConcepciónChile

This paper presents a method for estimating the solar capture capacity of dwell-ings using the central urban area of Concepción,Chile,as a case study in order to promote self-generation of energy by *** method takes into account the growing domestic energy demand and the possibility of meeting this demand through integrated solar energy collection into buildings using different *** methodology considers a study of the potential incoming solar radiation on buildings according to their geographical location and the surrounding *** capacity for solar capture is then estimated for different dwelling types accord-ing to their ***,the energy contribution provided by differ-ent technologies(solar thermal,photovoltaic and hybrid)is identified in relation to the main average energy demands for electricity,water and space ***,systems for each dwelling are recommended in an urban map available *** development is based on climate information,cartography,aerial photo-graphs,surveys,housing models,technical standards,standardised calculations and dynamic simulations,implemented according to building layouts from an online Geographic Information System(GIS).The housing types are categorised in an urban map that relates household demands and the contribution of different solar energy *** to the estimates calculated,the residential units in the study offer sufficient solar capacity to supply between 40 and 60%of their energy consumption,especially in detached houses using roof-mounted hybrid systems.

关键词： solar energy urban area housing solar map Concepción Chile

A study on monoterpenoid-based natural deep eutectic solvents

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Green Chemical Engineering 2023年第1期4卷 99-114页

作者： Sara Rozas lorena Zamora Cristina Benito Mert Atilhan Santiago Aparicio Department of Chemistry University of BurgosBurgos09001Spain Department of Chemical and Paper Engineering Western Michigan UniversityKalamazooMI49008-5462USA

Herein,the synthesis and characterization methods of natural deep eutectic solvents based on monoterpenoids have been *** viscous fluids with suitable physicochemical properties are *** materials are non-toxic,biodegradable,and ***,they can be used to develop sustainable solvents for various processes and can find their applications in various fields.A theoretical study based on quantum chemistry and classical molecular dynamics is used for the nanoscopic characterization of structure,dynamics,and hydrogen *** reported results help analyze the properties of this new family of *** required information for developing structure–property relationships for proper solvent design to form a sustainable chemistry framework is obtained.

关键词： Natural deep eutectic solvents Terpenes DFT MD COSMO-RS CO_(2)solubility