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Plankton and benthos are popular concepts identifying two ways of life of aquatic organisms. Their spatial separation led to the development of different sampling techniques and to separate conceptualizations of the principles governing these subsets of the aquatic environment. Reciprocal connections between plankton and benthos, however, are very strong both from a functional (energy fluxes) and a structural (life cycle dynamics) point of view. A full appreciation of such links is forcing marine ecology towards a more integrated approach. 相似文献
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Effect of a high-intensity exercise training on the metabolism and function of macrophages and lymphocytes of walker 256 tumor bearing rats 总被引:1,自引:0,他引:1
Bacurau AV Belmonte MA Navarro F Moraes MR Pontes FL Pesquero JL Araújo RC Bacurau RF 《Experimental biology and medicine (Maywood, N.J.)》2007,232(10):1289-1299
Epidemiologic studies suggest that moderately intense training promotes augmented immune function, whereas strenuous exercise can cause immunosupression. Because the combat of cancer requires high immune function, high-intensity exercise could negatively affect the host organism; however, despite the epidemiologic data, there is a lack of experimental evidence to show that high-intensity training is harmful to the immune system. Therefore, we tested the influence of high-intensity treadmill training (10 weeks, 5 days/week, 30 mins/day, 85% VO(2)max) on immune system function and tumor development in Walker 256 tumor-bearing Wistar rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, in addition to some functional parameters such as hydrogen peroxide production, phagocytosis, and lymphocyte proliferative responses. The metabolism of Walker 256 cells was also investigated. Results demonstrated that high-intensity training increased the life span of tumor-bearing rats, promoted a reduction in tumor mass, and prevented indicators of cachexia. Several changes, such as a reduction in body weight and food intake and activation of glutamine metabolism in macrophages and lymphocytes induced by the presence of Walker 256 tumor, were prevented by high intensity training. The reduction in tumor growth was associated with an impairment of tumor cell glucose and glutamine metabolism. These data suggest that high-intensity exercise training may be a viable strategy against tumors. 相似文献
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Shelf Life Degradation of Bulk Heterojunction Solar Cells: Intrinsic Evolution of Charge Transfer Complex 下载免费PDF全文
Antonio Guerrero Hamed Heidari Teresa S. Ripolles Martin Pfannmöller Sara Bals Louis‐Dominique Kauffmann Juan Bisquert Germà Garcia‐Belmonte 《Liver Transplantation》2015,5(7)
Achievement of long‐term stability of organic photovoltaics is currently one of the major topics for this technology to reach maturity. Most of the techniques used to reveal degradation pathways are destructive and/or do not allow for real‐time measurements in operating devices. Here, three different, nondestructive techniques able to provide real‐time information, namely, film absorbance, capacitance–voltage (C–V), and impedance spectroscopy (IS), are combined over a period of 1 year using non‐accelerated intrinsic degradation conditions. It is discerned between chemical modifications in the active layer, physical processes taking place in the bulk of the blend from those at the active layer/contact interfaces. In particular, it is observed that during the ageing experiment, the main source for device performance degradation is the formation of donor–acceptor charge‐transfer complex (–) that acts as an exciton quencher. Generation of these radical species diminishes photocurrent and reduces open‐circuit voltage by the creation of electronic defect states. Conclusions extracted from absorption, C–V, and IS measurements will be further supported by a range of other techniques such as atomic force microscopy, X‐ray diffraction, and dark‐field imaging of scanning transmission electron microscopy on ultrathin cross‐sections. 相似文献
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In a recent landmark paper, the Huntington''s disease (HD) iPSC Consortium reports on the establishment and characterization of a panel of iPSC lines from HD patients, and more importantly, the successful modeling of HD in vitro. In the same issue of Cell Stem Cell, An et al. reports on the successful targeted gene correction of HD in human iPSCs. Both advances are exciting, provide new resources for current and future HD research, and uncover new challenges to better understand and, most importantly, treat this devastating disease in the near future.Modeling human diseases using induced pluripotent stem cells (iPSCs) has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. Combined with advanced gene correction technology, human iPSCs hold great promise to provide patient-specific and mutation-free cells for potential cell replacement therapy. Huntington''s disease (HD) is an autosomal dominant neurodegenerative disorder, which causes motor dysfunction, psychiatric disturbances and cognitive impairment1. HD is caused by an expanded cystosine adenine guanine (CAG) tri-nucleotide repeat encoding polyglutamine in the first exon of the Huntingtin (HTT) gene. To date, there is no effective therapy for preventing the onset or slowdown of this disorder. Preliminary clinical trials using fetal neural grafts had shown long-lasting functional benefits in patients2. Though only effective in limited cases, these results suggest that cell-based therapy could be a potential treatment if a reliable and consistent cell source is available. For this purpose, an alternative cell source to overcome the logistical and biological hurdles of this disease had been actively explored in the past decade. With recent advancement in human iPSCs technology, HD patient-specific iPSCs coupled with an efficient directed cell differentiation protocol offers hope for an unlimited supply of autologous cells. Since HD is a monogenic disease, with a very well-established correlation between the number of CAG repeats and the age of disease onset, it provides an ideal target for iPSC-based gene correction that will allow for the production of disease-free cells for potential autologous cell therapy, and at the same time provide a much needed, valuable platform to further study the pathogenesis of the disease3,4.This is in fact what has been recently accomplished in two reports published in Cell Stem Cell5,6. The HD iPSC Consortium reports on the generation of HD patient-specific iPSC lines that showed CAG-repeat-expansion-associated phenotypes5. The study from An et al.6 reports on the successful targeted correction of expanded CAG repeat in HD patient iPSCs and the reversion of disease phenotypes.In the study reported from the HD iPSC Consortium, the authors generated 14 iPSC lines from HD patients and controls (listed in Open in a separate window
Open in a separate windowHD, Huntington''s Disease; iPSC, induced pluripotent stem cell; NPC, neural progenitor cell; O, Oct4; S, Sox2; K, Klf4; M, Myc; N, Nanog; L, Lin28.Meanwhile, using a homologous recombination-based gene targeting strategy, An et al.6 reported on the successful correction of the CAG-repeat-expanded HTT allele in HD patient iPSCs. These corrected iPSCs shared the same genetic background as the disease iPSCs, thereby serving as non-biased controls for their uncorrected counterparts. By comparing gene expression profiles of corrected iPSCs versus disease iPSCs, An et al. found that the alterations of cadherin, TGF-β, and caspase-related pathways in HD were rescued in the non-expanded iPSCs. The authors further demonstrated that gene correction in HD iPSCs reversed disease phenotypes such as susceptibility to cell death and altered mitochondrial bioenergetics in NSCs. More importantly, when transplanted into a mouse model of HD, the corrected HD iPSC-derived NSCs could survive and differentiate into GABAergic neurons and DARPP-32-positive neurons in vivo.Taken together, these two studies present very significant advances for iPSC-based disease modeling of HD and provide a potential donor source for cell replacement therapy. Though exciting indeed, several important challenges remain unsolved.First, complete recapitulation of neuropathology phenotypes in the iPSC-based models in vitro remains a challenge in the field. As a neurodegenerative disease, pathologic development of HD usually takes several decades and may be influenced by several external factors. In the HD iPSC-based model, the derivation method, clonal discrepancy as well as the culture conditions may affect the manifestation of phenotypes. Indeed, in previously reported HD iPSC lines, only slight increases in caspase and lysosomal activity were observed7,8,9. Although in both reports of HD iPSCs, significant phenotypes in electrophysiology, energy metabolism and cell death were recorded, other typical HD-associated phenotypes such as oligomeric mutant HTT aggregation, formation of nuclear inclusions and preferential striatal degeneration were not observed.Second, it is still an open question whether neural cells derived from gene-corrected iPSCs are fully functional, that is, whether they may restore physiological functions after cell replacement therapy. Ma et al.10 have recently reported on a protocol to differentiate striatal projection neurons from human embryonic stem cells with a high efficiency. After transplantation, these cells survived, reconnected striatal circuitry, and restored motor function in a striatal neurodegenerative mouse model. In spite of these encouraging first attempts, further improvements of the methodology for the directed cell differentiation in vitro and cell transplantation in vivo are still needed.Third, HTT protein is ubiquitously expressed and functional in different tissue. It has been hypothesized that HD may also develop in a non-autonomous manner11. The current studies mainly focused on the phenotypes of HD iPSC-derived neurons. However, supporting cells such as astrocytes might also play direct or indirect roles in HD progression. Indeed, a vacuolation phenotype has been observed in HD iPSC-derived astrocytes12. Therefore, it will be interesting to expand the HD iPSC platform into other cell types with the goal to extend and uncover the various ethiopathological factors involved in HD.Finally, human iPSC models of monogenic disorders in general possess great potential for the mechanistic study of the disease. However, as is the case with many neuropsychiatric disorders, HD establishment and progression is linked to different genetic and epigenetic factors, including environmental change-induced epigenetic modification, multiple mutations, and genetic alternation in non-coding regions. To this end, although the successful generation of HD iPSCs as well as targeted gene correction would greatly facilitate the study of HD, a comprehensive understanding of HD pathogenesis will need to be achieved before trying to translate the recent results into the clinic.In summary, despite all of these open questions, the recent studies have uncovered the unlimited potential of iPSCs for modeling HD in vitro. These studies will promote and enhance HD research in various areas, including elucidation of HD cellular pathogenesis, development of HD-specific biomarkers, screening for small therapeutic molecules, and manipulation of HD iPSCs for stem cell replacement therapy, which together may ultimately fulfill the promise of using iPSCs as a tool for regenerative medicine and drug discovery for HD in the near future. 相似文献
Code | Number of iPSC line | CAG repeats | HD type | Age of sample procured | Reprogramming strategy | Phenotype detected cell type | Gene correction line available | Phenotype | References |
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HD 43 | 1 | 39/43 | Adult onset HD | 44 years | OSKM (lentivirus) | iPSCs | no | Increased Iysosomal activity | 7 |
HD 44 | 4 | 42/44 | Adult onset HD | 59 years | 2 lines:OSKM (lentivirus) 2 lines: OSK (lentivirus) | iPSCs | no | Increased Iysosomal activity | 7 |
HD 50 | 1 | 50 | Adult onset HD | unknown (father) | OSKM (retrovirus) | Astrocyte | no | Neural differentiation normal, Vacuolation in astrocyte | 12 |
HD109-1 | 1 | 109 | Juvenile HD | unknown (daughter) | OSKM (retrovirus) | Astrocyte | no | Similar to HD 50, more vacuolation in astrocyte | 12 |
HD 72 | 1 | 72 | Juvenile HD | 20 years | OSKM (retrovirus) | NPCs | yes | Elevated caspase activity; more vulnerable to cell death | 6,8,9 |
HD 60 | 3 | 60 | Adult onset HD | 29 years | 2 lines:OSKMNL (lentivirus) 1 line: OSKM (episomal) | NPCs, neurons | no | Altered cell adhesion, energetics, and electrophysiology; Increased cell death in long time neural differentiation | 5 |
HD109-2 | 1 | 109 | Juvenile HD | 9 years | OSKMNL (lentivirus) | NPCs, neurons | no | Similar to HD 60; higher risk to cell death in response to BDNF withdrawal | 5 |
HD180 | 4 | 180 | Juvenile HD | 6 years | 3 lines:OSKMNL (lentivirus) 1 line: OSKM (episomal) | NPCs, neurons | no | Similar to HD 60 and 109; Increased vulnerable to stress and toxicity | 5 |
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The antimicrobial activity of hemoglobin fragments (hemocidins) has been reported in a variety of models. The cattle tick Rhipicephalus (Boophilus) microplus is a blood sucking arthropod from where the first in vivo-generated hemocidin was characterized (Hb 33-61). In the present work we identified a novel antimicrobial peptide from the midgut of fully engorged R. (B.) microplus females, which comprises the amino acids 98-114 of the alpha subunit of bovine hemoglobin, and was designated Hb 98-114. This peptide was active against several yeast and filamentous fungi, although no activity was detected against bacteria up to 50μM of the synthetic peptide. Hb 98-114 was capable of permeabilizing Candida albicans cell membrane and had a fungicidal effect against this yeast. Circular dichroism (CD) and nuclear magnetic resonance (NMR) experiments showed that Hb 98-114 has a random conformation in aqueous solution but switches to an alpha-helical conformation in the presence of sodium dodecyl sulfate (SDS). This alpha helix adopts an amphipathic structure which may be the mechanism of cell membrane permeabilization. Importantly, Hb 98-114 may play an important role in defending the tick midgut against fungal pathogens and is the first hemocidin with specific antifungal activity to be characterized. 相似文献