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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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How to make the end of a gene,the simple way

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BIOCELL 2022年第6期46卷 1453-1457页

作者： KAREL H.M.VAN WELY centro nacional de biotecnología/csic Madrid28049Spain

Transcription termination of nearly all protein-coding genes in mammals requires 3’end processing by a multiprotein complex that will cleave and polyadenylate the messenger RNA *** a variety of enzyme complexes intervene,3’end processing was thought to be fundamentally complex and subject to a multitude of regulatory *** possibility to select just one out of several polyadenylation sites,in particular,has caused much questioning and *** appear to be separate mechanisms however can be combined into a defined set of rules,allowing for a relatively simple interpretation of 3’end ***,readiness of the terminal exon splice site determines when a transcript reaches the maturity to select a nearby polyadenylation *** pausing then acts in concert,extending the timeframe during which the transcription complex is close to polyadenylation *** RNA polymerase pausing is governed by the same type of sequences in bacteria and metazoans,mammalian transcription termination resembles its prokaryote counterpart more than generally thought.

关键词： RNA transcription RNA polymerase II pausing Splicing Termination Polyadenylation

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Reversible acetylation fine-tunes plant hormone signaling and immunity

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Molecular Plant 2022年第9期15卷 1415-1417页

作者： Selena Gimenez-Ibanez Loreto Espinosa-Cores Roberto Solano Plant Molecular Genetics department Centro Nacional de Biotecnología-CSIC(CNB-CSIC)28049 MadridSpain

Plant pests and diseases threaten food security by causing over 10%loss of global crops *** immunity relies on a complex hormonal signaling network in which jasmonates(JAs)play a central *** are fatty acid–derived hormones ubiquitous in the plant kingdom similar to animal prostaglandins,and are essential phytohormones regulating development,environmental adaptation and defense against necrotrophic pathogens and insects in plants.

关键词： immunity crops network

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The cold-induced factor CBF3 mediates root stem cell activity,regeneration,and developmental responses to cold

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Plant Communications 2023年第6期4卷 197-211页

作者： Pablo Perez-Garcia Ornella Pucciariello Alvaro Sanchez-Corrionero Javier Cabrera Cristina del Barrio Juan Carlos del Pozo Mariano Perales Krzysztof Wabnik Miguel A.Moreno-Risueno centro de biotecnologíay Genómica de Plantas(Universidad Politécnica de Madrid(UPM)–Instituto nacional de Investigacióny Tecnología Agraria y Alimentaria–csic(INIA-csic)) MadridSpain

Plant growth and development involve the specification and regeneration of stem cell niches(SCNs).Although plants are exposed to disparate environmental conditions,how environmental cues affect developmental programs and stem cells is not well *** stem cells are accommodated in meristems in SCNs around the quiescent center(QC),which maintains their *** a combination of genetics and confocal microscopy to trace morphological defects and correlate them with changes in gene expression and protein levels,we show that the cold-induced transcription factor(TF)C-REPEAT BINDING FACTOR 3(CBF3),which has previously been associated with cold acclimation,regulates root development,stem cell activity,and ***3 is integrated into the SHORT-ROOT(SHR)regulatory network,forming a feedback loop that maintains SHR ***3 is primarily expressed in the root endodermis,whereas the CBF3 protein is localized to other meristematic tissues,including root *** of cbf3-1 using a wild-type CBF3 gene and a CBF3 fusion with reduced mobility show that CBF3 movement capacity is required for SCN patterning and regulates root ***,cold induces CBF3,affecting QC ***,exposure to moderate cold around 10℃–12℃promotes root regeneration and QC respecification in a CBF3-dependent manner during the recuperation *** contrast,CBF3 does not appear to regulate stem cell survival,which has been associated with recuperation from more acute cold(-4℃).We propose a role for CBF3 in mediating the molecular interrelationships among the cold response,stem cell activity,and development.

关键词： stem cells regeneration organ patterning protein movement cell fate low temperature

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Roles of Ubiquitination in the Control of Phosphate Starvation Responses in Plants

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Journal of Integrative Plant Biology 2013年第1期55卷 40-53页

作者： Mónica Rojas-Triana Regla Bustos Ana Espinosa-Ruiz Salom Prat Javier Paz-Ares Vicente Rubio The Samuel Roberts Noble Foundation Department of Plant Biology 2510 Sam Noble Parkway Ardmore CBGP (INIA-UPM) Departamento de Biotecnología Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Campus de Montegancedo centro nacional de biotecnología (CNB-csic) Darwin

Throughout evolution, plants have evolved sophisticated adaptive responses that allow them to grow with a limited supply of phos-phate, the preferential form in which the essential macronutrient phosphorus is absorbed by plants. Most of these responses are aimed to increase phosphate availability and acquisition through the roots, to optimize its usage in metabolic processes, and to protect plants from the deleterious effects of phosphate deficiency stress. Regulation of these adaptive responses requires fine percep- tion of the external and internal phosphate levels, and a complex signal transduction pathway that integrates information on the phosphate status at the whole-plant scale. The molecular mecha-nisms that participate in phosphate homeostasis include transcriptional control of gene expression, RNA silencing mediated by microRNAs, regulatory non-coding RNAs of miRNA activity, phosphate transporter trafficking, and post-translational modification of proteins, such as phosphorylation, sumoylation and ubiquitination. Such a varied regulatory repertoire reflects the complexity intrinsic to phosphate surveying and signaling pathways. Here, we describe these regulatory mechanisms, emphasizing the increasing importance of ubiquitination in the control of phosphate starvation responses.

关键词： Phosphate homeostasis phosphate signaling phosphate starvation post-translational control ubiquitin.

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Propagation of Recombinant Genes through Complex Microbiomes with Synthetic Mini-RP4 Plasmid Vectors

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Biodesign Research 2022年第1期2022卷 193-207页

作者： Tomás Aparicio Jillian Silbert Sherezade Cepeda Víctor de Lorenzo Systems and Synthetic Biology department Centro Nacional de Biotecnología(CNB-CSIC)Campus de Cantoblanco Madrid 28049Spain

The promiscuous conjugation machinery of the Gram-negative plasmid RP4 has been reassembled in a minimized, highlytransmissible vector for propagating genetically encoded traits through diverse types of naturally occurring microbialcommunities. To this end, the whole of the RP4-encoded transfer determinants (tra, mob genes, and origin of transfer oriT)was excised from their natural context, minimized, and recreated in the form of a streamlined DNA segment borne by anautoselective replicon. The resulting constructs (the pMATING series) could be self-transferred through a variety ofprokaryotic and eukaryotic recipients employing such a rationally designed conjugal delivery device. Insertion of GFP reporterinto pMATING exposed the value of this genetic tool for delivering heterologous genes to both specific mating partners andcomplex consortia (e.g., plant/soil rhizosphere). The results accredited the effective and functional transfer of the recombinantplasmids to a diversity of hosts. Yet the inspection of factors that limit interspecies DNA transfer in such scenarios uncoveredtype VI secretion systems as one of the factual barriers that check otherwise high conjugal frequencies of tested RP4derivatives. We argue that the hereby presented programming of hyperpromiscuous gene transfer can become a phenomenalasset for the propagation of beneficial traits through various scales of the environmental microbiome.

关键词： otherwise rational transferred

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The strigolactone receptor D14 targets SMAX1 for degradation in response to GR24 treatment and osmotic stress

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Plant Communications 2022年第2期3卷 76-91页

作者： Qingtian Li Elena Sánchez Martín-Fontecha Aashima Khosla Alexandra R.F.White Sunhyun Chang Pilar Cubas David C.Nelson department of Botany and Plant Sciences University of CaliforniaRiversideCA 92521USA Plant Molecular Genetics department Centro Nacional de Biotecnología/CSICCampus Universidad Autόnoma de MadridMadridSpain

The effects of the phytohormone strigolactone(SL)and smoke-derived karrikins(KARs)on plants are generally distinct,despite the fact that they are perceived through very similar *** homologous receptors DWARF14(D14)and KARRIKIN-INSENSITIVE2(KAI2),together with the F-box protein MORE AXILLARY GROWTH2(MAX2),mediate SL and KAR responses,respectively,by targeting different SMAX1-LIKE(SMXL)family proteins for *** mechanisms are putatively well-insulated,with D14-MAX2 targeting SMXL6,SMXL7,and SMXL8 and KAI2-MAX2 targeting SMAX1 and SMXL2 in Arabidopsis *** evidence challenges this *** investigated whether D14 can target SMAX1 and whether this occurs *** analysis indicates that the SL analog GR24 promotes D14-SMAX1 *** D14 shows weaker interactions with SMAX1 than with SMXL2 or SMXL7,D14 mediates GR24-induced degradation of SMAX1 in *** stress triggers SMAX1 degradation,which is protective,through SL biosynthesis and signaling ***,D14-SMAX1 crosstalk may be beneficial and not simply a vestige of the evolution of the SL pathway.

关键词： phytohormone signaling proteolysis crosstalk

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DNA features beyond the transcription factor binding site specify target recognition by plant MYC2-related bHLH proteins

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Plant Communications 2021年第6期2卷 27-43页

作者： Irene Lopez-Vidriero Marta Godoy Joaquin Grau Maria Penuelas Roberto Solano Jose M.Franco-Zorrilla Genomics Unit Centro Nacional de BiotecnologiaCSICC/Darwin 328049 MadridSpain department of Plant Molecular Genetics Centro Nacional de BiotecnologiaCSICC/Darwin 328049 MadridSpain

Transcription factors(TFs)regulate gene expression by binding to cis-regulatory sequences in the promoters of target *** research is helping to decipher in part the cis-regulatory code in eukaryotes,including plants,but it is not yet fully understood how paralogous TFs select their *** we addressed this question by studying several proteins of the basic helix-loop-helix(bHLH)family of plant TFs,all of which recognize the same DNA *** focused on the MYC-related group of bHLHs,that redundantly regulate the jasmonate(JA)signaling pathway,and we observed a high correspondence between DNA-binding profiles in vitro and MYC function in *** demonstrated that A/T-rich modules flanking the MYC-binding motif,conserved from bryophytes to higher plants,are essential for TF recogni*** observed particular DNA-shape features associated with A/T modules,indicating that the DNA shape may contribute to MYC DNA *** extended this analysis to 20 additional bHLHs and observed correspondence between in vitro binding and protein function,but it could not be attributed to A/T modules as in *** conclude that different bHLHs may have their own codes for DNA binding and specific selection of targets that,at least in the case of MYCs,depend on the TF-DNA interplay.

关键词： transcription factor bHLH target specificity plants

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Plant adaptation to low phosphorus availability:Core signaling,crosstalks,and applied implications

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Molecular Plant 2022年第1期15卷 104-124页

作者： Javier Paz-Ares Maria Isabel Puga Monica Rojas-Triana Iris Martinez-Hevia Sergio Diaz Cesar Poza-Carrión Miguel Mi(n)ambres Antonio Leyva department of Plant Molecular Genetics Centro Nacional de Biotecnología(CNB-CSIC)Darwin 3Campus Universidad Autónoma28049 MadridSpain Institute of Plant Biochemistry Institute of Synthetic Biology and CEPLASUniversity of Düsseldorf40225 DüsseldorfGermany

Phosphorus(P)is an essential nutrient for plant growth and *** preferentially absorb P as orthophosphate(Pi),an ion that displays low solubility and that is readily fixed in the soil,making P limita-tion a condition common to many soils and Pi fertilization an inefficient *** cope with Pi limitation,plants have evolved a series of developmental and physiological responses,collectively known as the Pi starvation rescue system(PSR),aimed to improve Pi acquisition and use efficiency(PUE)and protect from Pi-starvation-induced *** research has been carried out during the last 20 years to un-ravel the mechanisms underlying the control of the PSR in *** we review the results of this research effort that have led to the identification and characterization of several core Pi starvation signaling components,including sensors,transcription factors,microRNAs(miRNAs)and miRNA inhibitors,kinases,phosphatases,and components of the proteostasis *** also refer to recent results revealing the existence of intricate signaling interplays between Pi and other nutrients and antagonists,N,Fe,Zn,and As,that have changed the initial single-nutrient-centric view to a more integrated view of nutrient ***,we discuss advances toward improving PUE and future research priorities.

关键词： inositol pyrophosphate plant nutrient PHR1 transcription factor PUE(phosphorus acquisition and use efficiency) SPX sensor and STOP1 transcription factor

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Plant cell wall-mediated disease resistance:Current understanding and future perspectives

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Molecular Plant 2024年第5期17卷 699-724页

作者： Antonio Molina Lucıa Jorda Miguel Angel Torres Marina Martın-Dacal Diego Jose Berlanga Patricia Fernandez-Calvo Elena Gomez-Rubio Sonsoles Martın-Santamarıa centro de biotecnología y Genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain departamento de biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain centro de Investigaciones Biologicas Margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain Misión Biológica de Galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental *** walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental *** wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress *** cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease ***,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI *** number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent ***,the structural mechanisms underlying glycan recognition by plant PRRs remain ***,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological ***,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide *** include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and *** characterization of structural basis of glycans recogniti

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAMPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

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