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31.
The continuing interest in the biology of stem cells is enhanced by new discoveries surrounding developmental plasticity of both embryonic and adult stem cells. Adoptive transfer of concepts and definitions from the hematopoietic system to other tissue stem cells suggests inclusion of characteristics such as ability to self-renew and differentiate to functionally reconstitute a tissue/organ of origin. How adequate and accurate are these definitions? Within the great unknown of how these cells function, modulate their gene expression patterns and respond to extrinsic signals, it is apparent that there are numerous levels of stemness. We may envision a scale of developmental flexibility. At one end of the scale are positioned the embryonic stem cells, and at the other end are positioned partially-differentiated, differentiation restricted (committed) tissue/organ stem cells. There is evidence that some stem cells in the adult are pluripotent, thus positioned close to the embryonic end of the stem scale. It is uncertain yet to what extent stem cells can move back and forth along the stem scale. 相似文献
32.
Shimon Slavin Aliza Ackerstein Reuven Or Michael Y. Shapira Benjamin Gesundheit Nadir Askenasy Shoshana Morecki 《Cancer immunology, immunotherapy : CII》2010,59(10):1511-1519
The feasibility and safety of immunotherapy mediated by intentionally mismatched rIL-2 activated killer lymphocytes (IMAK)
with no prior stem cell engraftment was investigated in patients with advanced chemotherapy-resistant hematological malignancies
and metastatic solid tumors. Our goals were to maximize anti-cancer activity by using intentionally mismatched donor lymphocytes;
amplify killing of target cancer cells by rIL-2 activation of killer cells in vitro and in vivo, and avoid the risk of graft-versus-host
disease (GVHD) by anticipated rejection of alloreactive donor lymphocytes. Conditioning consisted of 5 days of fludarabine
25 mg/m2 or a single dose of cyclophosphamide 1,000 mg/m2, 2 subcutaneous injections of alpha interferon (IFN) 3 × 106 and COX2 inhibitors, followed by administration of IMAK (65 ± 5 CD3+CD56−; 17 ± 5 CD3−CD56+) in conjunction with low dose subcutaneous rIL-2 (6 × 106 IU/m2/day) for 5 days for continuous activation of alloreactive donor lymphocytes prior to their anticipated rejection. Here, we
present our phase 1 clinical study data in a cohort of 40 high-risk patients with metastatic solid tumors and hematological
malignancies. Treatment was accompanied by some malaise and occasional self-limited fever but otherwise well tolerated on
an outpatient basis. Transient engraftment of donor cells was documented in two patients and only one developed self-limited
grade 1 GVHD. Among patients with chemotherapy-resistant disease, long-term progression-free survival was recorded in 5 of
21 evaluable patients with metastatic solid tumors and in four of five patients with hematological malignancies. We conclude
that the proposed procedure is feasible, safe, and potentially effective, with some otherwise resistant cancer patients long-term
disease-free, thus justifying larger Phase II studies in patients with hematological malignancies and metastatic solid tumors,
preferably at a stage of minimal residual disease with the goal in mind to eradicate all malignant cells at an early stage
of the disease. 相似文献
33.
Espert L Eldin P Gongora C Bayard B Harper F Chelbi-Alix MK Bertrand E Degols G Mechti N 《Journal of cellular biochemistry》2006,98(5):1320-1333
We have previously shown that ISG20, an interferon (IFN)-induced gene, encodes a 3' to 5' exoribonuclease member of the DEDD superfamily of exonucleases. ISG20 specifically degrades single-stranded RNA. In this report, using immunofluorescence analysis, we demonstrate that in addition to a diffuse cytoplasmic and nucleoplasmic localization, the endogenous ISG20 protein was present in the nucleus both in the nucleolus and in the Cajal bodies (CBs). In addition, we show that the ectopic expression of the CBs signature protein, coilin, fused to the red fluorescent protein (coilin-dsRed) increased the number of nuclear dots containing both ISG20 and coilin-dsRed. Using electron microcopy analysis, ISG20 appeared principally concentrated in the dense fibrillar component of the nucleolus, the major site for rRNA processing. We also present evidences that ISG20 was associated with survival of motor neuron (SMN)-containing macromolecular nuclear complexes required for the biogenesis of various small nuclear ribonucleoproteins. Finally, we demonstrate that ISG20 was associated with U1 and U2 snRNAs, and U3 snoRNA. The accumulation of ISG20 in the CBs after IFN treatment strongly suggests its involvement in a new route for IFN-mediated inhibition of protein synthesis by modulating snRNA and rRNA maturation. 相似文献
34.
35.
Jay F Manel S Alvarez N Durand EY Thuiller W Holderegger R Taberlet P François O 《Molecular ecology》2012,21(10):2354-2368
Species range shifts in response to climate and land use change are commonly forecasted with species distribution models based on species occurrence or abundance data. Although appealing, these models ignore the genetic structure of species, and the fact that different populations might respond in different ways because of adaptation to their environment. Here, we introduced ancestry distribution models, that is, statistical models of the spatial distribution of ancestry proportions, for forecasting intra-specific changes based on genetic admixture instead of species occurrence data. Using multi-locus genotypes and extensive geographic coverage of distribution data across the European Alps, we applied this approach to 20 alpine plant species considering a global increase in temperature from 0.25 to 4 °C. We forecasted the magnitudes of displacement of contact zones between plant populations potentially adapted to warmer environments and other populations. While a global trend of movement in a north-east direction was predicted, the magnitude of displacement was species-specific. For a temperature increase of 2 °C, contact zones were predicted to move by 92 km on average (minimum of 5 km, maximum of 212 km) and by 188 km for an increase of 4 °C (minimum of 11 km, maximum of 393 km). Intra-specific turnover-measuring the extent of change in global population genetic structure-was generally found to be moderate for 2 °C of temperature warming. For 4 °C of warming, however, the models indicated substantial intra-specific turnover for ten species. These results illustrate that, in spite of unavoidable simplifications, ancestry distribution models open new perspectives to forecast population genetic changes within species and complement more traditional distribution-based approaches. 相似文献
36.
Nancy E. Gillette E. Matthew Hansen Constance J. Mehmel Sylvia R. Mori Jeffrey N. Webster Nadir Erbilgin David L. Wood 《Agricultural and Forest Entomology》2012,14(4):367-375
- 1 DISRUPT Micro‐Flake Verbenone Bark Beetle Anti‐Aggregant flakes (Hercon Environmental, Inc., Emigsville, Pennsylvania) were applied in two large‐scale tests to assess their efficacy for protecting whitebark pine Pinus albicaulis Engelm. from attack by mountain pine beetle Dendroctonus ponderosae Hopkins (Coleoptera: Scolytinae) (MPB). At two locations, five plots of equivalent size and stand structure served as untreated controls. All plots had early‐ to mid‐outbreak beetle populations (i.e. 7.1–29.2 attacked trees/ha). Verbenone was applied at 370 g/ha in both studies. Intercept traps baited with MPB aggregation pheromone were placed near the corners of each plot after the treatment in order to monitor beetle flight within the plots. Trap catches were collected at 7‐ to 14‐day intervals, and assessments were made at the end of the season of stand structure, stand composition and MPB attack rate for the current and previous years.
- 2 Applications of verbenone flakes significantly reduced the numbers of beetles trapped in treated plots compared with controls at both sites by approximately 50% at the first collection date.
- 3 The applications also significantly reduced the proportion of trees attacked in both Wyoming and Washington using the proportion of trees attacked the previous year as a covariate in the model for analysis of current year attack rates; in both sites, the reduction was ≥ 50%.
- 4 The flake formulation of verbenone appears to have promise for area‐wide treatment by aerial application when aiming to control the mountain pine beetle in whitebark pine forests.
37.
Kyrre Kausrud Bjørn Økland Olav Skarpaas Jean‐Claude Grégoire Nadir Erbilgin Nils Chr. Stenseth 《Biological reviews of the Cambridge Philosophical Society》2012,87(1):34-51
In recent decades we have seen rapid and co‐occurring changes in landscape structure, species distributions and even climate as consequences of human activity. Such changes affect the dynamics of the interaction between major forest pest species, such as bark beetles (Coleoptera: Curculionidae, Scolytinae), and their host trees. Normally breeding mostly in broken or severely stressed spruce; at high population densities some bark beetle species can colonise and kill healthy trees on scales ranging from single trees in a stand to multi‐annual landscape‐wide outbreaks. In Eurasia, the largest outbreaks are caused by the spruce bark beetle, Ips typographus (Linnaeus), which is common and shares a wide distribution with its main host, Norway spruce (Picea abies Karst.). A large literature is now available, from which this review aims to synthesize research relevant for the population dynamics of I. typographus and co‐occurring species under changing conditions. We find that spruce bark beetle population dynamics tend to be metastable, but that mixed‐species and age‐heterogeneous forests with good site‐matching tend to be less susceptible to large‐scale outbreaks. While large accumulations of logs should be removed and/or debarked before the next swarming period, intensive removal of all coarse dead wood may be counterproductive, as it reduces the diversity of predators that in some areas may play a role in keeping I. typographus populations below the outbreak threshold, and sanitary logging frequently causes edge effects and root damage, reducing the resistance of remaining trees. It is very hard to predict the outcome of interspecific interactions due to invading beetle species or I. typographus establishing outside its current range, as they can be of varying sign and strength and may fluctuate depending on environmental factors and population phase. Most research indicates that beetle outbreaks will increase in frequency and magnitude as temperature, wind speed and precipitation variability increases, and that mitigating forestry practices should be adopted as soon as possible considering the time lags involved. 相似文献
38.
Cristina Capanni Stefano Squarzoni Vittoria Cenni Maria Rosaria D’Apice Alessandra Gambineri Giuseppe Novelli Manfred Wehnert Renato Pasquali Nadir M. Maraldi Giovanna Lattanzi 《Cell cycle (Georgetown, Tex.)》2012,11(19):3568-3577
Prelamin A processing impairment is a common feature of a restricted group of rare genetic alterations/disorders associated with a wide range of clinical phenotypes. Changes in histone posttranslational modifications, alterations in non-histone chromatin proteins and chromatin disorganization have been specifically linked to impairment of specific, distinct prelamin A processing steps, but the molecular mechanism involved in these processes is not yet understood . In this study, we show that the accumulation of wild-type prelamin A detected in restrictive dermopathy (RD), as well as the accumulation of mutated forms of prelamin A identified in familial partial lipodystrophy (FPLD) and mandibuloacral dysplasia (MADA), affect the nuclear localization of barrier-to-autointegration factor (BAF), a protein able to link lamin A precursor to chromatin remodeling functions. Our findings, in accordance with previously described results, support the hypothesis of a prelamin A involvement in BAF nuclear recruitment and suggest BAF-prelamin A complex as a protein platform usually activated in prelamin A-accumulating diseases. Finally, we demonstrate the involvement of the inner nuclear membrane protein emerin in the proper localization of BAF-prelamin A complex. 相似文献
39.
Sara Benedetti Pia Bernasconi Enrico Bertini Elena Biagini Giuseppe Boriani Cristina Capanni Nicola Carboni Giovanna Cenacchi Marta Columbaro Monica D’Adamo Adele D’Amico Maria Rosaria D’Apice Marianna Fontana Alessandra Gambineri Giovanna Lattanzi Rocco Liguori Nadir M Maraldi Laura Mazzanti Eugenio Mercuri Tiziana Mongini Lucia O Morandi Iria Neri Giovanni Nigro Giuseppe Novelli Michela Ortolani Renato Pasquali Antonella Pini Stefania Petrini Luisa Politano Stefano Previtali Lisa Pucci Claudio Rapezzi Giulia Ricci Carmelo Rodolico Paolo Sbraccia Emanuela Scarano Gabriele Siciliano Stefano Squarzoni Antonio Toscano Liliana Vercelli Matteo Ziacchi 《Orphanet journal of rare diseases》2012,7(1):1-3
The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy. 相似文献
40.