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Pharmacological intervention for chronic phase of spinal cord injury

Neural Regeneration Research 2025年第5期20卷 1377-1389页

作者： Chihiro Tohda section of Neuromedical Science Institute of Natural MedicineUniversity of ToyamaToyamaJapan

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidat

关键词： axonal growth chronic phase clinical study pharmacotherapy spinal cord injury

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Molecular evolution of Na^(+) channels in teleost fishes

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Integrative Zoology 2009年第1期4卷 64-74页

作者： Harold H.ZAKON Manda C.JOST Derrick J.ZWICKL Ying LU David M.HILLIS section of Neurobiology section of Integrative biology The University of TexasAustinTXUSA

Voltage-dependent sodium channels are critical for electrical *** possess a single sodium channel gene;two rounds of genome duplication early in vertebrates increased the number to *** the teleost-tetrapod split,independent gene duplications in each lineage have further increased the number of sodium channel genes to 10 in tetrapods and 8 in *** we review how the occurrence of multiple sodium channel paralogs has influenced the evolutionary history of three groups of fishes:pufferfish,gymnotiform and mor-myriform electric ***(tetraodontidae)produce a neurotoxin,tetrodotoxin,that binds to and blocks the pore of sodium *** evolved resistance to their own toxins by amino acid substitutions in the pore of their sodium *** substitutions had to occur in parallel across multiple paralogs for organismal re-sistance to *** and mormyriform fishes independently evolved electric organs to generate elec-tricity for communication and object *** sodium channel genes are expressed in muscle in most *** both groups of weakly electric fishes,one gene lost its expression in muscle and became compartmen-talized in the evolutionary novel electric organ,which is a muscle *** gene then evolved at elevated rates,whereas the gene that is still expressed in muscle does not show elevated rates of *** the electric organ-expressing gene,amino acid substitutions occur in parts of the channel involved in determining how long the channel will be open or *** enhanced rate of sequence evolution of this gene likely underlies the spe-cies-level variations in the electric signal.

关键词： electric fish molecular evolution pufferfish sodium channels tetrodotoxin.

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Infectivity of Arbuscular Mycorrhizal Fungi in Naturally Regenerating,Unmanaged and Clear-Cut Beech Forests

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Pedosphere 2011年第1期21卷 65-74页

作者： I.CLOSA N.GOICOECHEA Department of Plant biology Section of Plant BiologySchool of SciencesUniversity of Navarra

Clear-cutting, a management practice applied to many beech forests in the North of Spain, modifies microclimate and, consequently, the composition of the understory plant community in the disturbed areas. The objectives of this study were to assess if changes in the understory vegetation caused by altered light microclimate after clear-cutting affect the infectivity of arbuscular mycorrhizal fungi （AMF） on herbaceous plant species in beech （Fagus sylvatica L.） forests naturally regenerating from clear-cutting and to test if the use of bioassays for studying the infectivity of native AMF could provide useful information to improve the management of clear-cut areas. Three nearby beech forests in northwest Navarra, Spain, a region in the northwest part of the Pyrenees, were selected： an unmanaged forest, a forest clear-cut in 1996, and another forest clear-cut in 2001. High stem density in the forest clear-cut in 1996 （44 000 trees ha-1） attenuated photosynthetic active radiation （PAR） and impaired the growth of herbaceous species within the ecosystem. The percentage of AMF colonization of plants in bioassays performed on soil samples collected from the forest clear-cut in 1996 was always lower than 10S. In the forest clear-cut in 2001, where soil was covered by perennial grasses, PAR was high and the infectivity of native AMF achieved minimum values in spring and autumn and a maximum value in summer. In contrast, the infectivity of native AMF in the unmanaged forest remained similar across the seasons. Our results demonstrated that changes in the composition of understory vegetation within beech forests strongly affected the infectivity of native AMF in clear-cut areas and suggested that the assessment of the infectivity of native AMF through bioassays could provide helpful information for planning either the removal of overstory when the tree density is so high that it impairs the correct development of herbaceous species or the plantation of new seedlings when high

关键词： bioassays herbaceous plant species photosynthetic active radiation tree density understory vegetation

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Digital Identification of Ecosystem Structure in the FIrtIna Valley of the Kakar Mountains in the Rize City of Turkey

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Journal of Mountain Science 2014年第2期11卷 421-428页

作者： Cagasan KARACAOGLU Selim Sualp CAGLAR Department of biology Faculty of Science Biology Department Ecology Section EBAL Laboratories Hacettepe University

Identifying the structure of protected mountain ecosystems is an important task for understanding conservation sustainability. The study area, the Firtina Valley, located in the Rize City on the Eastern Blacksea Coast, is one of the biological hotspots and a National Park of Turkey. In order to identify the structure of mountain ecosystems, we generated a GIS database for the main environmental parameters of the study area, including elevation,slope and aspect layers for topographic structure, 10year mean values of Normalized Difference Vegetation Index(NDVI), data for vegetation structure, annual mean temperature and precipitation layers for climatic structure, main soil groups for soil structure and stream flow accumulation, stream flow length and stream order layers for hydrological *** identify the complex relations among environmental factors in the study area a data reduction method is applied with Principal Component Analysis(PCA). PCA is performed using data of 16 layers from Geographical Information Systems(GIS). PCA analysis reduced 16 dimensions into 5 dimensions containing 75% of the variation in all data. It is also revealed that the topographic structure, mainly altitude, dominates the ecosystems of the Firtina Valley, but it should be considered that the interactions of environmental factors in an ecosystem dynamics are very complex. The ecosystem structure is determined by the environmental factors direct or indirect effects on energy regulation of an ecosystem. Therefore the relationship between topographic elements and other abiotic-biotic elements in the Firtina Valley are important for environmental assessment and sustainability of a protected area, and these effects are explained in this study.

关键词： PCA GIS Firtina Valley Ecosystem structure Protected areas

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Genetic signatures of ERCC1 and ERCC2 expression,along with SNPs variants,unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology Research 2025年第1期33卷 45-55页

作者： ENRICO CALIMAN SARA FANCELLI FEDERICO SCOLARI ADRIANO PASQUI CLARA MANNESCHI DANIELE LAVACCHI FRANCESCA MAZZONI FRANCESCA GENSINI VALERIA PASINI CAMILLA EVA COMIN LUCA VOLTOLINI SERENA PILLOZZI LORENZO ANTONUZZO Clinical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence50134Italy Department of Health Sciences University of FlorenceFlorence50134Italy Medical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Biomedical Sciences“Mario Serio” University of FlorenceFlorence50134Italy section of Anatomic Pathology Department of Health SciencesUniversity of FlorenceFlorence50139Italy section of Surgery Histopathology and Molecular PathologyUniversity of FlorenceFlorence50139Italy Thoracic Surgery Unit Careggi University HospitalFlorence50134Italy

Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum *** in this repair mechanism may affect patients’*** and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to *** expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor ***:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy *** with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant ***:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： Small cell lung cancer(SCLC) Nucleotide excision repair(NER)pathway ERCC genes Single nucleotide polymorphisms(SNPs) Platinumchemotherapy(CT)

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Today’s protected areas:supporting a more sustainable future for humanity

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Integrative Zoology 2020年第6期15卷 603-616页

作者： Jeffrey A.MCNEELY Society for Conservation biology Asia section Cha-AmPetchburiThailand

Nature provides significant benefits to people,especially those living in and around protected *** services from protected areas include producing wild food,supporting biodiversity and water cycles,regulating climate,and providing cultural services like better health,tourism,and legacy for future *** economic terms,the flows of ecosystem services provided by protected areas are worth hundreds of billions of dollars each year,well justifying the costs of managing these sites,but protected areas are suffering from environmental problems such as impacts from human population growth,rural poverty,growing demands for natural resources,land use change that degrades ecosystem productivity,invasive non-native species that harm natural ecosystems,and climate change that is affecting all *** these linked challenges will require mobilizing all parts of the economy,including the protected area *** example,protected areas can take a leadership role in rural development,expand the conservation estate to half of the planet through connectivity and improved management of more of the non-agricultural land,enhance the prominent role of protected areas in contributing to climate change mitigation and adaptation,encourage productive research on applying modern technology to protected areas management,seek broader private sector participation in conserving biodiversity and ecosystem services,and include protected areas as relevant parties in relevant trade and other international *** protected area managers embrace this broader role,they will find enthusiastic public support for this contribution to a sustainable human society.

关键词： Aichi target climate change economic benefit ecosystem service landscape conservation protected area

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The Application of CRISPR-Cas9 Genome Editing in Caenorhabditis elegans

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Journal of Genetics and Genomics 2015年第8期42卷 413-421页

作者： Suhong Xu Division of Biological Sciences Section of Cell and Developmental Biology University of California

Genome editing using the Cas9 endonuclease of Streptococcus pyogenes has demonstrated unparalleled efficacy and facility for modifying genomes in a wide variety of organisms. Caenorhabditis elegans is one of the most convenient multicellular organisms for genetic analysis, and the application of this novel genome editing technique to this organism promises to revolutionize analysis of gene function in the future. CRISPR-Cas9 has been successfully used to generate imprecise insertions and deletions via non-homologous end-joining mechanisms and to create precise mutations by homology-directed repair from donor templates. Key variables are the methods used to deliver the Cas9 endonuclease and the efficiency of the single guide RNAs. CRISPR-Cas9-mediated editing appears to be highly specific in C. elegans, with no reported off-target effects. In this review, 1 briefly summarize recent progress in CRISPR-Cas9-based genome editing in C. elegans, highlighting technical improvements in mutagenesis and mutation detection, and discuss potential future appli- cations of this technique.

关键词： Genome editing CRISPR: Cas9 Non-homologous end-joining (NHEJ) Homology-directed repair (HDR) Somatic mutation C. elegans

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Patterns of morphometric variation in the alpine newt (Mesotriton alpestris) at the southern limit of its distribution: environmental correlates

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Integrative Zoology 2008年第2期3卷 123-133页

作者： Konstantinos SOTIROPOULOS Anastasios LEGAKIS Rosa Maria POLYMENI section of Zoology-Marine biology Zoological Museum Department of BiologyUniversity of AthensAthensGreece

We applied multivariate analyses to an array of body measures of alpine newt specimens derived from 11 localpopulations in Greece to describe, analyse and detect patterns and putative causes of within-population andamong-population morphometric variation. The observed morphometric variation was partitioned into several independentlyvarying aspects of the external phenotype, frequently following variation patterns in different environmentalfactors. The size and features of the aquatic habitat were found to affect body size, while altitude was foundto affect head-shape variation in both sexes. At the intra-population level, variation in generalized body size andshape was found to be significantly lower when competitive newt species were present in the habitat, indicatingstabilizing selection towards a decrease in inter-specific competition. No clear discrimination on body size andshape proportions was detected between the two genetic lineages examined, implying ecogenetic or environmentallyinduced variation rather than phylogeny.

关键词： body size/shape environment Greece Mesotriton alpestris morphometrics

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Oxylipin Pathway in Rice and Arabidopsis

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Journal of Integrative Plant biology 2007年第1期49卷 43-51页

作者： E. Wassim Chehab John V. Perea Banu Gopalan Steve Theg Katayoon Dehesh section of Plant biology University of California-Davis Davis CA 95616 USA

Plants have evolved complex signaling pathways to coordinate responses to developmental and environmental Information. The oxylipin pathway Is one pivotal lipid-based signaling network, composed of several competing branch pathways, that determines the plant＇s ability to adapt to various stimuli. Activation of the oxyllpln pathway Induces the de novo synthesis of biologically active metabolltes called ＂oxyllplns＂. The relative levels of these metabolltes are a distinct indicator of each plant species and determine the ability of plants to adapt to different stimuli. The two major branches of the oxyllpln pathway, allene oxide synthase （AOS） and hydroperoxlde lyase （HPL） are responsible for production of the signaling compounds, jasmonates and aldehydes respectively. Here, we compare and contrast the regulation of AOS and HPL branch pathways In rice and Arabidopsis as model monocotyledonous and dicotyledonous systems. These analyses provide new Insights Into the evolution of JAs and aldehydes signaling pathways, and the complex network of processes responsible for stress adaptations In monocots and dicots.

关键词： aldehydes allene oxide synthase Arabidopsis hydroperoxide lyase jasmonates oxylipin pathway rice

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MAX2 Affects Multiple Hormones to Promote Photomorphogenesis

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Molecular Plant 2012年第3期5卷 750-762页

作者： Hui Shen Ling Zhu Qing-Yun Bu Enamul Huq section of Molecular Cell and Developmental biology and the Institute for Cellular and Molecular biology University of Texas at Austin Austin TX 78712 USA

Ubiquitin-26S proteasome system （UPS） has been shown to play central roles in light and hormone-regulated plant growth and development. Previously, we have shown that MAX2, an F-box protein, positively regulates facets of photomorphogenic development in response to light. However, how MAX2 controls these responses is still unknown. Here, we show that MAX2 oppositely regulates GA and ABA biosynthesis to optimize seed germination in response to light. Dose-response curves showed that max2 seeds are hyposensitive to GA and hypersensitive to ABA in seed ger- mination responses. RT-PCR assays demonstrated that the expression of GA biosynthetic genes is down-regulated, while the expression of GA catabolic genes is up-regulated in the rnax2 seeds compared to wild-type. Interestingly, expression of both ABA biosynthetic and catabolic genes is up-regulated in the max2 seeds compared to wild-type. Treatment with an auxin transport inhibitor, NPA, showed that increased auxin transport in max2 seedlings contributes to the long hypocotyl phenotype under light. Moreover, light-signaling phenotypes are restricted to max2, as the biosynthetic mutants in the strigolactone pathway, max1, max3, and rnax4, did not display any defects in seed germination and seedling de-etiolation compared to wild-type. Taken together, these data suggest that MAX2 modulates multiple hormone pathways to affect photomorphogenesis.

关键词： Arabidopsis F-box protein photomorphogenesis protein degradation strigolactone SCF complex

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