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861.
862.
Engineered selective plant male sterility through pollen‐specific expression of the EcoRI restriction endonuclease 下载免费PDF全文
Reginald J. Millwood Hong S. Moon Charleson R. Poovaiah Balasubramaniam Muthukumar John Hollis Rice Jason M. Abercrombie Laura L. Abercrombie William Derek Green Charles Neal Stewart Jr 《Plant biotechnology journal》2016,14(5):1281-1290
Unintended gene flow from transgenic plants via pollen, seed and vegetative propagation is a regulatory concern because of potential admixture in food and crop systems, as well as hybridization and introgression to wild and weedy relatives. Bioconfinement of transgenic pollen would help address some of these concerns and enable transgenic plant production for several crops where gene flow is an issue. Here, we demonstrate the expression of the restriction endonuclease EcoRI under the control of the tomato pollen‐specific LAT52 promoter is an effective method for generating selective male sterility in Nicotiana tabacum (tobacco). Of nine transgenic events recovered, four events had very high bioconfinement with tightly controlled EcoRI expression in pollen and negligible‐to‐no expression other plant tissues. Transgenic plants had normal morphology wherein vegetative growth and reproductivity were similar to nontransgenic controls. In glasshouse experiments, transgenic lines were hand‐crossed to both male‐sterile and emasculated nontransgenic tobacco varieties. Progeny analysis of 16 000–40 000 seeds per transgenic line demonstrated five lines approached (>99.7%) or attained 100% bioconfinement for one or more generations. Bioconfinement was again demonstrated at or near 100% under field conditions where four transgenic lines were grown in close proximity to male‐sterile tobacco, and 900–2100 seeds per male‐sterile line were analysed for transgenes. Based upon these results, we conclude EcoRI‐driven selective male sterility holds practical potential as a safe and reliable transgene bioconfinement strategy. Given the mechanism of male sterility, this method could be applicable to any plant species. 相似文献
863.
864.
High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model 下载免费PDF全文
Irit Lubitz Jan Ricny Dana Atrakchi‐Baranes Chen Shemesh Efrat Kravitz Sigal Liraz‐Zaltsman Anna Maksin‐Matveev Itzik Cooper Avshalom Leibowitz Jaime Uribarri James Schmeidler Weijing Cai Zdena Kristofikova Daniela Ripova Derek LeRoith Michal Schnaider‐Beeri 《Aging cell》2016,15(2):309-316
There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic. 相似文献
865.
Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient 下载免费PDF全文
Andrew M. Cobb Delphine Larrieu Derek T. Warren Yiwen Liu Sonal Srivastava Andrew J. O. Smith Richard P. Bowater Stephen P. Jackson Catherine M. Shanahan 《Aging cell》2016,15(6):1039-1050
The nuclear lamina is essential for the proper structure and organization of the nucleus. Deregulation of A‐type lamins can compromise genomic stability, alter chromatin organization and cause premature vascular aging. Here, we show that accumulation of the lamin A precursor, prelamin A, inhibits 53BP1 recruitment to sites of DNA damage and increases basal levels of DNA damage in aged vascular smooth muscle cells. We identify that this genome instability arises through defective nuclear import of 53BP1 as a consequence of abnormal topological arrangement of nucleoporin NUP153. We show for the first time that this nucleoporin is important for the nuclear localization of Ran and that the deregulated Ran gradient is likely to be compromising the nuclear import of 53BP1. Importantly, many of the defects associated with prelamin A expression were significantly reduced upon treatment with Remodelin, a small molecule recently reported to reverse deficiencies associated with abnormal nuclear lamina. 相似文献
866.
Shahriar?Dabiri Ashraf?KariminikEmail author Derek?Kennedy 《European cytokine network》2016,27(2):34-40
Chemokines and their corresponding receptors serve as pro-inflammatory and migratory signals for immune cells. CXCR3 and its corresponding ligands, CXCL9, CXCL10 and CXCL11, participate in the induction of immune responses against several foreign antigens. Numerous cells, including macrophages, NK cells and T lymphocytes, express CXCR3 and thus, expression of the receptor and its ligands can induce activity of these important immune cells against foreign antigens, including allogeneic grafts. Several parameters of the immune system participate in the induction and stimulation of powerful immune responses against allogeneic grafts. A thorough understanding of the parameters that regulate these responses can provide insights into new methods for immunotherapy during organ transplantation. The aim of this review is to address the most recent information regarding the roles played by CXCR3 and its corresponding ligands in the outcome of renal transplantation. 相似文献
867.
Binge‐type eating disrupts dopaminergic and GABAergic signaling in the prefrontal cortex and ventral tegmental area 下载免费PDF全文
868.
Techniques to expand human hematopoietic stem cells ex-vivo could be beneficial to the fields of clinical hematopoietic stem cell transplantation and gene therapy targeted at hematopoietic stem cells. NUP98-HOXA10HD is a relatively newly discovered fusion gene that in mouse transplant experiments has been shown to increase numbers of hematopoietic stem cells. We evaluated whether this fusion gene could be used to expand engrafting human primitive CD34+ cells in an immunodeficient mouse model. Gene transfer was achieved using a lentiviral based vector. The engraftment of mobilized peripheral blood human CD34+ cells grown in culture for one week after gene transfer was evaluated 3–4 months after transplant and found to be 2–3 fold higher in the NUP98-HOXA10HD groups as compared to controls. These data suggest an expansive effect at least at the short term human repopulating cell level. Further evaluation in long term repopulating models and investment in a NUP98-HOXA10HD protein seems worthy of consideration. Additionally, the results here provide strong impetus to utilize NUP98-HOXA10HD as a tool to search for underlying genes and pathways involved in hematopoietic stem cell expansion that can be enhanced and have an even more potent expansive effect. 相似文献
869.
Brahim Redouane Eyal Cohen Derek Stephens Krista Keilty Marialena Mouzaki Unni Narayanan Theo Moraes Reshma Amin 《PloS one》2016,11(2)
Objective
Health related quality of life (HRQL) of children using medical technology at home is largely unknown. Our aim was to examine the HRQL in children on long-term ventilation at home (LTHV) in comparison to a cohort using an enterostomy tube.Study Design
Participants were divided into three groups: 1) LTHV without an enterostomy tube (LTHV cohort); 2) Enterostomy tube (GT cohort); 3) LTHV with an enterostomy tube (LTHV+GT cohort). Caregivers of children ≥ 5 years and followed at SickKids, Toronto, Canada, completed three questionnaires: Health Utilities Index 2/3 (HUI2/3), Caregiver Priorities Caregiver Health Index (CPCHILD), and the Paediatric Quality of Life Inventory (PedsQL). The primary outcome was the difference in utility (HUI2/3) scores between the cohorts.Results
One hundred and nineteen children were enrolled; 47 in the LTHV cohort, 44 in the GT cohort, and 28 in the LTHV+GT cohort. In univariate analysis, HUI2 mean (SE) scores were lowest for the GT cohort, 0.4 (0.04) followed by the LTHV+GT, 0.42 (0.05) and then the LTHV cohort, 0.7 (0.04), p = 0.001. A similar trend was seen for the HUI3 mean (SE) scores: GT cohort, 0.1 (0.06), followed by the LTHV +GT cohort, 0.2 (0.08) and then the LTHV cohort, 0.5 (0.06), p = 0.0001. Technology cohort, nursing hours and the severity of health care needs predicted HRQL as measured by the HUI2/3.Conclusion
The HRQL of these children is low. Children on LTHV had higher HRQL than children using enterostomy tubes. Further work is needed to identify modifiable factors that can improve HRQL. 相似文献870.
Markus?RiesterEmail authorView authors OrcID profile Angad?P.?Singh A.?Rose?Brannon Kun?Yu Catarina?D.?Campbell Derek?Y.?Chiang Michael?P.?Morrissey 《Source code for biology and medicine》2016,11(1):13