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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

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

systemic epigallocatechin gallate protects against retinal degeneration and hepatic oxidative stress in the P23H-1 rat

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Neural Regeneration Research 2022年第3期17卷 625-631页

作者： lorena Perdices lorena Fuentes-Broto Francisco segura Ana Cavero Elvira Orduna-Hospital Gema Insa-sánchez Ana Isabel sánchez-Cano Laura Fernández-sánchez Nicolás Cuenca Isabel Pinilla Aragón Institute for Health Research(IIs Aragón) ZaragozaSpain Pharmacology Physiology&Legal and Forensic MedicineUniversity of ZaragozaZaragozaSpain department of Applied Physics University of ZaragozaZaragozaSpain Health sciences Faculty San Jorge UniversityVillanueva de GállegoSpain department of Ophthalmology Miguel Servet University HospitalZaragozaSpain department of Physiology Genetics and MicrobiologyUniversity of AlicanteAlicanteSpain department of surgery Gynecology and ObstetricsUniversity of ZaragozaZaragozaSpain/Department of OphthalmologyLozano Blesa University HospitalZaragozaSpain

Retinitis pigmentosa(RP) is a group of inherited retinal disorders that lead to photoreceptor *** has been reported to be related to oxidative stress,autophagy,and inflammation.(-)-Epigallocatechin gallate(EGCG),the most abundant catechin-based flavonoid in green tea leaves,has significant antioxidant,anti-carcinogenic,antimicrobial,and neuroprotective ***,given its low molecular weight and hydrophilic properties,can cross the blood-retinal barrier and is able to reach different ocular tissues such as the lens,cornea,and *** has been shown to provide retinal protection against ischemia;sodium nitroprusside-,N-methyl-d-aspartate-,lipopolysaccharide-,light-,sodium iodate-,or H2 O2-induced damage and diabetic *** suggests that systemic EGCG administration has the potential to protect against retinal degenerative or neurodegenerative diseases such as *** aim of this work was to investigate whether EGCG can protect against RP progression in the animal P23 H line 1,the model of *** P23 H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical features of *** P23 H rats were treated via intraperitoneal injection with saline or EGCG at a dose of 25 mg/kg every week from P100 to P160 and then compared to wild-type Long Evans *** treated with EGCG showed better visual and retinal electrical function with increased contrast sensitivity and b-wave values compared with those observed in P23 H rats treated with *** reduced lipid peroxidation and increased total antioxidant capacity and catalase and superoxide dismutase *** differences were observed in visual acuity,nitrate levels,nitrite levels or glutathione s-transferase *** conclusion,EGCG not only reduced the loss of visual function in P23 H rats but also improved the levels of antioxidant enzymes and reduced oxidative *** study was approved by the Institutional Animal Care and Use Committee(CE

关键词： antioxidants contrast sensitivity electroretinogram green tea neurodegeneration oxidative stress retinal degeneration retinitis pigmentosa systemic visual acuity

Basic and clinical aspects of osteoporosis in inflammatory bowel disease

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World Journal of Gastroenterology 2007年第46期13卷 6156-6165页

作者： lorena Rodríguez-Bores JosuéBarahona-Garrido Jesús K Yamamoto-Furusho IBd Clinic Department of GastroenterologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.Vasco de Quiroga 15 colonia Sección ⅩⅥTlalpanCP 14000México

Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBd） has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBd. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBd and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBd are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin d receptors （VdRs） and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B （RANK）, RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBd patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMd include single energy x-ray absorptiometry, dXA, quantitative computed tomography （QCT）, radiographic absorptiometry, and *** is the establish method to determine BMd, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have

关键词： Inflammatory bowel disease Osteoporosis

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

Novel genetic markers in inflammatory bowel disease

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World Journal of Gastroenterology 2007年第42期13卷 5560-5570页

作者： lorena Rodríguez-Bores Gabriela C Fonseca Marco A Villeda Jesús K Yamamoto-Furusho IBd Clinic Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Vasco de Quiroga 15 colonia Sección XVI Tlalpan CP 14000 México

Genetic factors play a significant role in determining inflammatory bowel disease(IBd)*** data support genetic contribution to the pathogenesis of IBd,which include familial aggregation,twin studies,racial and ethnic differences in disease *** studies have identified several susceptibility genes contained in different genomic regions named IBd1 to *** oligomerization domain(NOd2)and human leukocyte antigen(HLA)genes are the most extensively studied genetic regions(IBd1 and IBd3 respectively)in *** of the NOd2 gene are associated with Crohn's disease(Cd)and several HLA genes are associated with ulcerative colitis(UC)and *** like receptors(TLRs)have an important role in the innate immune response against infections by mediating recognition of pathogen-associated microbial *** single-nucleotide polymorphisms(sNPs)in molecules involved in bacterial recognition seems to be essential to define genetic backgrounds at risk of ***,numerous new genes have been identified to be involved in the genetic susceptibility to IBd:NOd1/Caspase-activation recruitment domains 4(CARd4),Chemokine ligand 20(CCL20),IL-11,and IL-18 among *** characterization of these novel genes potentially will lead to the identification of therapeutic agents and clinical assessment of phenotype and prognosis in patients with IBd.

关键词： Genetic Inflammatory bowel disease Human leukocyte antigen Nucleotide oligomerizationdomain Toll like receptors susceptibility

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

Wnt signaling in the nervous system and in Alzheimer＇s disease

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Journal of Molecular Cell Biology 2014年第1期8卷 64-74页

作者： Nibaldo C. Inestrosa lorena Varela-Nallar Center for Aging and Regeneration (CARE) Department of Cell and Molecular Biology Faculty of Biological Sciences Pontifical Catholic University of ChileSantiago Chile Center for Biomedical Research Faculty of Biological Sciences and Faculty of Medicine AndrOs Bello University Santiago Chile

Wnts comprise a large family of proteins that have shown to be part of a signaling cascade that regulates several aspects of develop- ment including organogenesis, mid brain development as welt as stem cell proliferation. Wnt signaling pathway plays different roles in the development of neuronal circuits and also in the adult brain, where it regulates synaptic transmission and plasticity. It has been also implicated in various diseases including cancer and neurodegenerative diseases, reflecting its relevance in fundamental biological pro- cesses. This review summarizes the progress about Wnts function in mature nervous system with a focus on Alzheimer＇s disease （Ad）. We discuss the prospects of modulating canonical and non-canonical Wnt signaling as a strategy for neuroprotection. This will include the potential of Wnts to：（i） act as potent regulators of hippocampai synapses and impact in learning and memory; （ii） regulate adult neurogenesis; and finally （iii） control Ad pathogenesis.

关键词： Wnt glutamate Alzheimer's disease synapses dendritic spines neuroprotection