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Alessandra Govoni Francesca Magri Simona Brajkovic Chiara Zanetta Irene Faravelli Stefania Corti Nereo Bresolin Giacomo P. Comi 《Cellular and molecular life sciences : CMLS》2013,70(23):4585-4602
Muscular dystrophy is a heterogeneous group of genetic disorders characterised by progressive muscle tissue degeneration. No effective treatment has been discovered for these diseases. Preclinical and clinical studies aimed at the development of new therapeutic approaches have been carried out, primarily in subjects affected with dystrophinopathies (Duchenne and Becker muscular dystrophy). In this review, we outline the current therapeutic approaches and past and ongoing clinical trials, highlighting both the advantages and limits of each one. The experimental designs of these trials were based on different rationales, including immunomodulation, readthrough strategies, exon skipping, gene therapy, and cell therapy. We also provide an overview of available outcome measures, focusing on their reliability in estimating meaningful clinical improvement in order to aid in the design of future trials. This perspective is extremely relevant to the field considering the recent development of novel therapeutic approaches that will result in an increasing number of clinical studies over the next few years. 相似文献
23.
Matthias Samereier Otto Baumann Irene Meyer Ralph Gräf 《Cellular and molecular life sciences : CMLS》2011,68(2):275-287
We have localized TACC to the microtubule-nucleating centrosomal corona and to microtubule plus ends. Using RNAi we proved
that Dictyostelium TACC promotes microtubule growth during interphase and mitosis. For the first time we show in vivo that both TACC and XMAP215
family proteins can be differentially localized to microtubule plus ends during interphase and mitosis and that TACC is mainly
required for recruitment of an XMAP215-family protein to interphase microtubule plus ends but not for recruitment to centrosomes
and kinetochores. Moreover, we have now a marker to study dynamics and behavior of microtubule plus ends in living Dictyostelium cells. In a combination of live cell imaging of microtubule plus ends and fluorescence recovery after photobleaching (FRAP)
experiments of GFP-α-tubulin cells we show that Dictyostelium microtubules are dynamic only in the cell periphery, while they remain stable at the centrosome, which also appears to harbor
a dynamic pool of tubulin dimers. 相似文献
24.
In most populations of mountain goats ( Oreamnos americanus ), mineral lick use is an essential part of the ecology of the species. In many areas, the distribution and use of licks in the landscape is poorly known, rendering planning for resource development difficult. We examined lick use by 28 GPS radio-collared mountain goats in 2 study areas in southeastern British Columbia during 2004–2005. Viewing collar-location movements on digital orthophotos, we assumed goat use of 6 previously known and 10 suspected mineral licks. Field visits verified that 9 of the 10 suspected sites were mineral licks. Thirteen of the 15 licks used by collared goats were within forests with commercial harvesting potential. All but 3 of the licks were ≤600 m from the closest logging block, and 5 licks were <100 m away. Number of annual visits to licks by individual goats ranged from 0 to 9. Goats often moved considerable distances (up to 17.3 km) to visit licks. Most visits by males occurred between early May and late June (median 9 June), and most visits by females occurred between early June and mid-July (median 21 June). Mean time spent at licks on each visit was 1.5 days for females and 1.6 days for males. Most of the licks were characterized by numerous cavities dug under trees (which we term “lick trees”). Using GPS collars, we were able to collect data on lower-elevation mineral licks not previously known to researchers. 相似文献
25.
Fungi are the principal degraders of biomass in terrestrial ecosystems and establish important interactions with plants and animals. However, our current understanding of fungal evolutionary diversity is incomplete and is based upon species amenable to growth in culture. These culturable fungi are typically yeast or filamentous forms, bound by a rigid cell wall rich in chitin. Evolution of this body plan was thought critical for the success of the Fungi, enabling them to adapt to heterogeneous habitats and live by osmotrophy: extracellular digestion followed by nutrient uptake. Here we investigate the ecology and cell biology of a previously undescribed and highly diverse form of eukaryotic life that branches with the Fungi, using environmental DNA analyses combined with fluorescent detection via DNA probes. This clade is present in numerous ecosystems including soil, freshwater and aquatic sediments. Phylogenetic analyses using multiple ribosomal RNA genes place this clade with Rozella, the putative primary branch of the fungal kingdom. Tyramide signal amplification coupled with group-specific fluorescence in situ hybridization reveals that the target cells are small eukaryotes of 3-5?μm in length, capable of forming a microtubule-based flagellum. Co-staining with cell wall markers demonstrates that representatives from the clade do not produce a chitin-rich cell wall during any of the life cycle stages observed and therefore do not conform to the standard fungal body plan. We name this highly diverse clade the cryptomycota in anticipation of formal classification. 相似文献
26.
Résumé L'imposition de conditions hypothermiques augmente l'incorporation de28Mg dans le cerveau et la glande pituitaire du rat.
Research for this paper was supported by NSF No. GB 27740 X. The authors are grateful for the technical assistance of Mrs.M. Turner, Mrs.E. Rovner and Mrs. L. Macko. 相似文献
Research for this paper was supported by NSF No. GB 27740 X. The authors are grateful for the technical assistance of Mrs.M. Turner, Mrs.E. Rovner and Mrs. L. Macko. 相似文献
27.
Summary The variations undergone by chlorogenic acid, cynarine, cynazoside and scolymoside during the biological cycle of the artichoke plant were studied. Furthermore, the differences in the composition of the orthodiphenolic fraction between different organs of the plant were studied. 相似文献
28.
Irene Faravelli Giulietta Riboldi Monica Nizzardo Chiara Simone Chiara Zanetta Nereo Bresolin Giacomo P. Comi Stefania Corti 《Cellular and molecular life sciences : CMLS》2014,71(17):3257-3268
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by degeneration of upper and lower motor neurons. There are currently no clinically impactful treatments for this disorder. Death occurs 3–5 years after diagnosis, usually due to respiratory failure. ALS pathogenesis seems to involve several pathological mechanisms (i.e., oxidative stress, inflammation, and loss of the glial neurotrophic support, glutamate toxicity) with different contributions from environmental and genetic factors. This multifaceted combination highlights the concept that an effective therapeutic approach should counteract simultaneously different aspects: stem cell therapies are able to maintain or rescue motor neuron function and modulate toxicity in the central nervous system (CNS) at the same time, eventually representing the most comprehensive therapeutic approach for ALS. To achieve an effective cell-mediated therapy suitable for clinical applications, several issues must be addressed, including the identification of the most performing cell source, a feasible administration protocol, and the definition of therapeutic mechanisms. The method of cell delivery represents a major issue in developing cell-mediated approaches since the cells, to be effective, need to be spread across the CNS, targeting both lower and upper motor neurons. On the other hand, there is the need to define a strategy that could provide a whole distribution without being too invasive or burdened by side effects. Here, we review the recent advances regarding the therapeutic potential of stem cells for ALS with a focus on the minimally invasive strategies that could facilitate an extensive translation to their clinical application. 相似文献
29.
Apiruck Watthanasurorot Kenneth Söderhäll Pikul Jiravanichpaisal Irene Söderhäll 《Cellular and molecular life sciences : CMLS》2011,68(2):315-323
Invertebrate circulating hemocytes are key players in the innate immune defense and their continuous renewal from hematopoietic
tissues is tightly regulated in crustaceans by astakine, a new family of cytokines sharing a prokineticin (PROK) domain. In
vertebrates, brain PROKs function as transmitters of circadian rhythms and we present evidence that hemocyte release from
hematopoietic tissues in crayfish is under circadian regulation, a direct result of rhythmic expression of astakine. We demonstrate
that the observed variation in astakine expression has an impact on innate immunity assessed as susceptibility to a pathogenic
Pseudomonas species. These findings enlighten the importance of comparing immune responses at fixed times not to neglect circadian regulation
of innate immunity. Moreover, our results entail an evolutionary conserved function for prokineticins as mediators of circadian
rhythm, and for the first time show a role for this domain in circadian regulation of hematopoiesis that may have implications
also in vertebrates. 相似文献
30.
Smith UM Consugar M Tee LJ McKee BM Maina EN Whelan S Morgan NV Goranson E Gissen P Lilliquist S Aligianis IA Ward CJ Pasha S Punyashthiti R Malik Sharif S Batman PA Bennett CP Woods CG McKeown C Bucourt M Miller CA Cox P Algazali L Trembath RC Torres VE Attie-Bitach T Kelly DA Maher ER Gattone VH Harris PC Johnson CA 《Nature genetics》2006,38(2):191-196
Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin. 相似文献