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Auswahl der wissenschaftlichen Literatur zum Thema „Chimeric competency“
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Zeitschriftenartikel zum Thema "Chimeric competency"
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Strell, Phoebe, Anala Shetty, Clifford J. Steer und Walter C. Low. „Interspecies Chimeric Barriers for Generating Exogenic Organs and Cells for Transplantation“. Cell Transplantation 31 (Januar 2022): 096368972211105. http://dx.doi.org/10.1177/09636897221110525.
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A growing need for organs and novel cell-based therapies has provided a niche for approaches like interspecies chimeras. To generate organs from one donor species in another host species requires techniques such as blastocyst complementation and gene editing to successfully create an embryo that has cells from both the donor and the host. However, the task of developing highly efficacious and competent interspecies chimeras is met by many challenges. These interspecies chimeric barriers impede the formation of chimeras, often leading to lower levels of chimeric competency. The barriers that need to be addressed include the evolutionary distance between species, stage-matching, temporal and spatial synchronization of developmental timing, interspecies cell competition and the survival of pluripotent stem cells and embryos, compatibility of ligand–receptor signaling between species, and the ethical concerns of forming such models. By overcoming the interspecies chimera barriers and creating highly competent chimeras, the technology of organ and cellular generation can be honed and refined to develop fully functioning exogenic organs, tissues, and cells for transplantation.
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Lacadena Calero, Juan Ramón. „BIOÉTIC AS MACAQUE-HUMAN CHIMERAS: SCIENTIFIC ASPECTS AND BIOETHICAL REFLECTIONS“. Anales de la Real Academia Nacional de Farmacia, Nr. 87(02) (2021): 117–21. http://dx.doi.org/10.53519/anaesranf.2021.87.02.01.
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The obtention by Izpisua and collaborators (2021) of macaque-human chimeric embryos by microinjection of human pluripotent stem cells into early blastocysts of cynomolgus monkey is described. They studied the competency of human pluripotent stem cells in macaque embryos cultured ex vivo until 19 days post-fertilization. A reflection on these experiments is made from the bioethical point of view.
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Afanassieff, Marielle, Florence Perold, Wilhelm Bouchereau, Antoine Cadiou und Nathalie Beaujean. „Embryo-derived and induced pluripotent stem cells: Towards naive pluripotency and chimeric competency in rabbits“. Experimental Cell Research 389, Nr. 2 (April 2020): 111908. http://dx.doi.org/10.1016/j.yexcr.2020.111908.
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Hirabayashi, M., T. Goto, C. Tamura, M. Sanbo und S. Hochi. „202 EFFECT OF LEUKEMIA INHIBITORY FACTOR AND FORSKOLIN ON ESTABLISHMENT OF RAT EMBRYONIC STEM CELL LINES“. Reproduction, Fertility and Development 26, Nr. 1 (2014): 215. http://dx.doi.org/10.1071/rdv26n1ab202.
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Rat embryonic stem (ES) cell lines can be established in culture medium containing inhibitors for glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase (MEK). We confirmed reproducibility of the 2i culture system in establishing rat ES cell lines (Hirabayashi et al. 2010 Mol. Reprod. Dev. 77, 94) and the likelihood of successful germline transmission (genuine) of rat ES cell lines established in leukemia inhibitory factor (LIF)- and forskolin (FK)-supplemented 2i medium (Hirabayashi et al. 2013 Transgenic Res. 22, 411–416). This study was designed to investigate whether LIF and/or FK supplemented to the 2i medium support establishment of germline-competent rat ES cell lines. E4.5 blastocysts were recovered from BLK rat females, and zona-free embryos were plated on mitomycin-treated mouse embryonic fibroblasts in N2B27 medium containing 1 mM MEK inhibitor PD0325901 and 3 mM GSK3 inhibitor CHIR99021, with rat 1000 U mL–1 LIF and/or 10 μM FK. Outgrowth rate of the blastocysts after 1 wk culture and establishment efficiency of ES cell lines after third passage were analyzed by Fisher's exact probability test. Arcsin-transformed percentage data on full-term development of ES cell-injected blastocysts, chimeric rat production, and germline-competent chimeras were analyzed by Fisher's least significant difference test after one-way ANOVA. Because of the higher outgrowth rates of blastocysts, supplementation of rat LIF, FK, or both contributed to the higher (P < 0.05) establishment efficiency of ES cell lines in BLK rat strain (76% to 92% v. 50% in LIF/FK-free 2i medium). Neither efficiency of producing chimeric rats (14% to 39% of blastocysts injected) nor germline transmission competency of the chimeric rats (67% to 100% of cell lines analyzed) was influenced by the pre-treatment of ES cell lines. When the LIF/FK-supplemented 2i medium was used, rat strain for blastocyst donor such as F344 or WI was a possible factor negatively influencing the establishment efficiency of ES cell lines. Once ES cell lines were established, however, all of them (9/9 in overall) were found to be germline-competent by progeny test of chimeric rats. In conclusion, both LIF and FK are not essential, but can play a beneficial role, for the establishment of genuine rat ES cell lines. This work was supported by a grant-in-aid for basic research from Japan Society for the Promotion of Science (No. 25290037; to M.H.).
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Tapponnier, Yann, Marielle Afanassieff, Irène Aksoy, Maxime Aubry, Anaïs Moulin, Lucas Medjani, Wilhelm Bouchereau et al. „Reprogramming of rabbit induced pluripotent stem cells toward epiblast and chimeric competency using Krüppel-like factors“. Stem Cell Research 24 (Oktober 2017): 106–17. http://dx.doi.org/10.1016/j.scr.2017.09.001.
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Whitaker, Neal, Trista M. Berry, Nathan Rosenthal, Jay E. Gordon, Christian Gonzalez-Rivera, Kathy B. Sheehan, Hilary K. Truchan et al. „Chimeric Coupling Proteins Mediate Transfer of Heterologous Type IV Effectors through the Escherichia coli pKM101-Encoded Conjugation Machine“. Journal of Bacteriology 198, Nr. 19 (18.07.2016): 2701–18. http://dx.doi.org/10.1128/jb.00378-16.
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ABSTRACTBacterial type IV secretion systems (T4SSs) are composed of two major subfamilies, conjugation machines dedicated to DNA transfer and effector translocators for protein transfer. We show here that theEscherichia colipKM101-encoded conjugation system, coupled with chimeric substrate receptors, can be repurposed for transfer of heterologous effector proteins. The chimeric receptors were composed of the N-terminal transmembrane domain of pKM101-encoded TraJ fused to soluble domains of VirD4 homologs functioning inAgrobacterium tumefaciens,Anaplasma phagocytophilum, orWolbachia pipientis. A chimeric receptor assembled fromA. tumefaciensVirD4 (VirD4At) mediated transfer of a MOBQ plasmid (pML122) andA. tumefacienseffector proteins (VirE2, VirE3, and VirF) through the pKM101 transfer channel. Equivalent chimeric receptors assembled from the rickettsial VirD4 homologs similarly supported the transfer of known or candidate effectors from rickettsial species. These findings establish a proof of principle for use of the dedicated pKM101 conjugation channel, coupled with chimeric substrate receptors, to screen for translocation competency of protein effectors from recalcitrant species. Many T4SS receptors carry sequence-variable C-terminal domains (CTDs) with unknown function. While VirD4Atand the TraJ/VirD4Atchimera with their CTDs deleted supported pML122 transfer at wild-type levels, ΔCTD variants supported transfer of protein substrates at strongly diminished or elevated levels. We were unable to detect binding of VirD4At's CTD to the VirE2 effector, although other VirD4Atdomains bound this substratein vitro. We propose that CTDs evolved to govern the dynamics of substrate presentation to the T4SS either through transient substrate contacts or by controlling substrate access to other receptor domains.IMPORTANCEBacterial type IV secretion systems (T4SSs) display striking versatility in their capacity to translocate DNA and protein substrates to prokaryotic and eukaryotic target cells. A hexameric ATPase, the type IV coupling protein (T4CP), functions as a substrate receptor for nearly all T4SSs. Here, we report that chimeric T4CPs mediate transfer of effector proteins through theEscherichia colipKM101-encoded conjugation system. Studies with these repurposed conjugation systems established a role for acidic C-terminal domains of T4CPs in regulating substrate translocation. Our findings advance a mechanistic understanding of T4CP receptor activity and, further, support a model in which T4SS channels function as passive conduits for any DNA or protein substrates that successfully engage with and pass through the T4CP specificity checkpoint.
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Kondoh, Gen, Yoichi Yamamoto, Kayo Yoshida, Yutaka Suzuki, Soh Osuka, Yuka Nakano, Takashi Morita und Junji Takeda. „Easy assessment of ES cell clone potency for chimeric development and germ-line competency by an optimized aggregation method“. Journal of Biochemical and Biophysical Methods 39, Nr. 3 (Mai 1999): 137–42. http://dx.doi.org/10.1016/s0165-022x(99)00008-1.
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Fields, Chris, und Michael Levin. „Competency in Navigating Arbitrary Spaces as an Invariant for Analyzing Cognition in Diverse Embodiments“. Entropy 24, Nr. 6 (12.06.2022): 819. http://dx.doi.org/10.3390/e24060819.
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One of the most salient features of life is its capacity to handle novelty and namely to thrive and adapt to new circumstances and changes in both the environment and internal components. An understanding of this capacity is central to several fields: the evolution of form and function, the design of effective strategies for biomedicine, and the creation of novel life forms via chimeric and bioengineering technologies. Here, we review instructive examples of living organisms solving diverse problems and propose competent navigation in arbitrary spaces as an invariant for thinking about the scaling of cognition during evolution. We argue that our innate capacity to recognize agency and intelligence in unfamiliar guises lags far behind our ability to detect it in familiar behavioral contexts. The multi-scale competency of life is essential to adaptive function, potentiating evolution and providing strategies for top-down control (not micromanagement) to address complex disease and injury. We propose an observer-focused viewpoint that is agnostic about scale and implementation, illustrating how evolution pivoted similar strategies to explore and exploit metabolic, transcriptional, morphological, and finally 3D motion spaces. By generalizing the concept of behavior, we gain novel perspectives on evolution, strategies for system-level biomedical interventions, and the construction of bioengineered intelligences. This framework is a first step toward relating to intelligence in highly unfamiliar embodiments, which will be essential for progress in artificial intelligence and regenerative medicine and for thriving in a world increasingly populated by synthetic, bio-robotic, and hybrid beings.
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Ugale, Amol Sanjay, Gudmundur Logi Norddahl, Martin Wahlestedt, Petter Säwén, Pekka Jaako, Cornelis J. H. Pronk, Shamit Soneji, Jorg Cammenga und David Bryder. „Hematopoietic Stem Cells Are Intrinsically Protected Against MLL-ENL Mediated Transformation“. Blood 124, Nr. 21 (06.12.2014): 839. http://dx.doi.org/10.1182/blood.v124.21.839.839.
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Abstract Studies on the developmental pathways of hematopoietic stem cells (HSCs) have led to roadmaps of differentiation and resulted in key information concerning lineage relationships and restriction points in the blood system. This knowledge is also central to understand the etiology of acute myeloid leukemia (AML), where recent work has proposed that the heterogeneity and aggressiveness of AML can associate with the developmental stage of transformation. Balanced chromosomal translocations that result in fusion proteins with aberrant transcriptional regulatory activities are frequent initiating events in acute myeloid leukemia, and a prototype family of such chimeric transcription factors is represented by fusions involving the mixed lineage leukemia-1 (MLL1) gene. Previous work using mouse models have suggested that at some stage of normal differentiation there is a loss of competence to induce AML. However discrepancies exists between these mouse models concerning the target cells of MLL fusion genes. While it is clear that cells can lose competence for leukemic transformation as part of their normal differentiation, the question remains whether the most primitive HSCs are always imbued with leukemogenic competency as part of their normal biology. To address this, we developed a Doxycycline inducible transgenic mouse model of the human chimeric transcription factor Mixed Lineage Leukemia-Eleven Nineteen Leukemia (MLL-ENL). Prospective isolations of candidate leukemia-initiating cells followed by adoptive transfers allowed us to detail leukemia-initiation and competence throughout the hematopoietic hierarchy. We show that AML can origin from multiple HPC subsets with intrinsic granulocytic/monocytic potential. Closely related myeloid progenitors displayed distinct leukemic- and functional capacity in response to physiological levels of MLL-ENL, highlighting the importance of a careful prospective isolation of progenitor populations. AML could also develop efficiently from common lymphoid progenitors, supporting a latent myeloid potential of these cells. By contrast, early commitment to the megakaryocytic/erythroid lineages was incompatible with leukemic development. By contrast, disease failed to arise from the most primitive progenitor subsets, including HSCs. Investigations of the immediate transcriptional responses to MLL-ENL showed evidence for a block in differentiation in both myeloid progenitors and HSCs, while MLL-ENL restricted cell cycle progression uniquely in HSCs. Our study highlights how an oncogene can exert unique functions depending on the developmental position of its cellular targets and demonstrate the existence of a mechanism, operational at the level of immature HSCs/progenitors, which act to prevent leukemic development. Figure 1 Graphical abstract Figure 1. Graphical abstract Disclosures No relevant conflicts of interest to declare.
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Zaslavsky, Alexander, Mackenzie Adams, Sandra Wissmueller, Douglas Campbell, Hans Klingemann, Brad Walsh und Ganesh S. Palapattu. „Glypican-1 as a novel immunotherapeutic target in prostate cancer.“ Journal of Clinical Oncology 36, Nr. 6_suppl (20.02.2018): 174. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.174.
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174 Background: New effective therapies for men with prostate cancer are desperately needed. Recently, cancer immunotherapy has emerged as an important new treatment strategy for prostate cancer and for castrate resistant prostate cancer (CRPC). Multiple studies have identified the heparan sulfate proteoglycan-1 Glypican 1 (GPC-1) as being overexpressed in different cancers, and also as being a possible marker of poor prognosis in several solid tumor cancers. GPC-1 has been recently identified as a potential marker for prostate cancer. The MIL-38 monoclonal antibody detects GPC-1 and an IgG1 chimeric version of this antibody has been developed for preclinical studies. Here we sought to examine MIL-38 binding to a panel of prostate cancer cell lines and examine its feasibility as a novel immunotherapeutic agent targeting GPC-1 in prostate cancer Methods: Expression of GPC-1 in CRPC cell lines was examined by Flow cytometry and Western Blotting using MIL-38 as the detector antibody. The competency of GPC-1 as an immunotherapeutic target was assessed via chimeric MIL-38 induced Antibody Dependent Cell Cytotoxicity (ADCC) using high affinity Natural Killer cells (haNKs) in vitro . Results: Flow cytometry and Western blot assessments of normal prostatic epithelial cells (i.e. RWPE-1) and cells from prostate cancer cell lines (i.e. PC-3, 22RV1, DU-145, VCaP, LNCaP, CWR-R1, and LAPC-4) revealed that only cancer cells expressed GPC-1. Enzalutamide resistant cell lines demonstrated higher expression of GPC-1 than their respective parental line. ADCC assays demonstrated enhanced haNK – prostate cancer cell cytotoxicity in the presence of chimeric MIL-38 anti-GPC-1 antibody, while the IgG1 isotype control had no effect. Conclusions: GPC-1 protein was expressed by most prostate cancer cell lines, including enhanced expression by enzalutamide resistant cells. Preliminary in vitro ADCC assay results revealed the potential utility of GPC-1 as an immunotherapeutic target in prostate cancer.
Dissertationen zum Thema "Chimeric competency"
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Pijoff, Yannicke. „Colonisation embryonnaire et compétence chimérique des cellules souches pluripotentes : étude chez la souris, le lapin et le chimpanzé“. Electronic Thesis or Diss., Lyon 1, 2024. http://www.theses.fr/2024LYO10255.
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Les cellules souches pluripotentes (PSC) naïves ont la capacité de réintégrer le développement embryonnaire normal et de produire des fœtus chimériques chez les rongeurs. Cependant, les PSC naïves provenant d'espèces autres que les rongeurs présentent une capacité nettement moins efficace à coloniser les embryons. Actuellement, notre compréhension des mécanismes impliqués dans la formation des chimères est limitée. Le projet avait pour objectif de mieux comprendre les mécanismes impliqués dans la capacité des PSC à coloniser l’embryon pré-implantatoire. Dans un premier temps, nous nous sommes intéressés aux caractéristiques spécifiques des PSC capables de coloniser. Au laboratoire nous avons obtenus des lignées de PSC de lapin et une lignée de PSC de chimpanzé capable de coloniser l’embryon pré-implantatoire de lapin. Nous avons alors séquencé et analysé le transcriptome de ces lignées de PSC de lapin et de chimpanzé pour identifier les caractéristiques moléculaires des PSC capables de coloniser. Ainsi, nous avons montré que les PSC capables de coloniser active la signalisation PI3K, répriment la signalisation Hippo et modulent les voies impliquées dans les interactions cellulaires et la régulation du cytosquelette. Dans un second temps, nous nous sommes intéressés aux mécanismes moléculaires intervenant durant la colonisation de l’embryon par les PSC. Pour cela, nous avons séquencé des embryons de lapin chimériques 48h après injection de PSC de chimpanzé ou de souris capables de coloniser. L’analyse du transcriptome des PSC injectées a révélé une augmentation de la signalisation PI3K/AKT ainsi que des voies de signalisations impliquées dans les jonctions cellulaires, les adhésions cellulaires et les régulations du cytosquelette, suggérant des interactions hôte-PSC injectés. De plus, l’analyse a également révélé qu’une partie de l’épiblaste de l’embryon hôte est composé de PSC injectées sans altération de l’identité de l’hôte. En conclusion, lors de la colonisation, les PSC et les cellules de l’embryon hôte interagissent et communiquent pour harmoniser leur développementNaïve pluripotent stem cells (PSC) possess the ability to re-enter normal development and generate chimeric fetuses in rodents. However, naïve PSCs from non-rodent species exhibit a significantly less efficient capacity to colonize embryos. Currently, our understanding of the mechanisms involved in chimera formation is limited. The project aimed to decipher these mechanisms. Firstly, we focused on hallmarks of chimeric competent PSCs. In the lab, we obtained chimeric competent PSCs in rabbit and chimpanzee that we analyzed by RNA sequencing analysis to identify the molecular signature of chimeric competent PSCs. We showed that rabbit, chimpanzee as well as mouse PSCs enhance PI3K/AKT signaling, downregulate Hippo signaling and modulate cellular interactions and regulation of cytoskeleton. Secondly, we investigated mechanisms taking place during embryo colonization by PSCs. To this aim, we performed a single-cell RNA sequencing analysis of rabbit embryos colonized by chimpanzee and mouse PSCs. The analysis revealed that injected PSCs increased PI3K/AKT signaling and other signaling pathways involved in cell junction, cell adhesion, and cytoskeleton regulations, suggesting interactions between host embryo cells and injected PSCs. This analysis also revealed that part of the host epiblast is replaced by injected PSCs without any changes of the host cells’ identity. To conclude, during colonization, PSC and cells from the host embryos interact and communicate for efficient colonization
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Mutungi, Evans Mulandi. „Humoral immune responses against novel recombinant replication-competent poxvirus candidate vaccines expressing full length and chimeric lyssavirus glycoprotein genes“. Diss., University of Pretoria, 2011. http://hdl.handle.net/2263/31290.
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Rabies is a neurological disease caused by viruses of the genus Lyssavirus belonging to the family Rhabdoviridae and order Mononegavirales. The Lyssavirus genus consists of eleven species namely rabies virus; Lagos bat virus; Mokola virus , Duvenhage virus; European bat lyssavirus virus type 1; European bat lyssavirus type 2; Australian bat lyssavirus; Aravan; Khujand; Irkut; West Caucasian bat viruses and recently isolated Shimoni bat virus. The prototype virus of the Lyssavirus genus is represented by rabies virus. The remaining lyssaviruses are collectively denoted as rabies-related viruses. It has been proposed that these lyssavirus genotypes/species could be divided into 2 and possibly 3 phylogroups, based on diversity and shared biological/pathogenicity properties.
Currently available vaccines have proven efficacy against viruses that would make up phylogroup I, but fail to cross-protect against those lyssaviruses belonging to phylogroup II and III. The potential public health burden associated with mortality due to rabies-related virus infection has prompted several vaccine studies to focus on the pan-lyssavirus vaccine cross-protection. The studies demonstrated that lyssaviruses glycoprotein domains (antigenic sites) can be exchanged to generate chimeric vaccine constructs and that combining antigenic sites II and III of different lyssaviruses raised virus neutralizing antibodies against different lyssaviruses. The objective of our study was to determine the cross protective capacity of similar constructs in a vaccinia virus Copenhagen strain based recombinant in proof of concept to ascertain cross protection in a murine model. The current study substantiates findings of preceding studies that chimeric lyssavirus glycoprotein vaccine constructs conferred protection against homologous and heterologous lyssaviruses. The replicating vaccinia virus based vector demonstrated the benefit of a replicating recombinant vaccine vector as illustrated by the high protective neutralizing antibody titers obtained. The value of administering a booster dose was also highlighted in the higher antibody titers obtained upon a vaccine boost. The study clearly demonstrated that glycoprotein antigenic site II and III are not equal in inducing protection and that site II confers better protection against a homologous virus.Dissertation (MSc)--University of Pretoria, 2011.
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Bücher zum Thema "Chimeric competency"
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Friedman, Jeffrey. Power without Knowledge. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780190877170.001.0001.
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Technocrats claim to know how to solve the social and economic problems of complex modern societies. But this would require predicting how people will act once technocrats impose their policy solutions. Power Without Knowledge argues that people’s ideas, w hich govern their deliberate actions, are too heterogeneous for their behavior to be reliably predicted. Thus, a technocracy of social-scientific experts cannot be expected to accomplish its objectives. The author also shows that a large part of contemporary mass politics, even populist mass politics, is technocratic, as members of the general public often assume that they are competent to decide which policies or politicians will be able to solve social and economic problems. How, then, do “citizen-technocrats” make these decisions? Drawing on political psychology and survey research, the author contends that people often assume that the solutions to social problems are self-evident, such that politics becomes a matter of vetting public officials for their good intentions and strong wills, not their knowledge. Turning to the more conventional meaning of technocracy, the author argues that social scientists, too, drastically oversimplify technocratic realities, but in an entirely different manner. Neoclassical economists, for example, theorize that people respond rationally to the incentives they face. This theory is simplistic, but it creates the appearance that people’s behavior is predictable. Without such oversimplifications, the author argues, technocracy would be seen by technocrats themselves to be chimerical.
Buchteile zum Thema "Chimeric competency"
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McGrath, Eoin, und Petr Machalik. „The Regulatory Framework for CAR-T Cells in Europe: Current Status and Foreseeable Changes AND Centre Qualification by Competent Authorities and Manufacturers“. In The EBMT/EHA CAR-T Cell Handbook, 191–98. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94353-0_37.
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AbstractUnder current European Union regulations, CAR-T cell therapies fall under the advanced therapy medicinal products (ATMPs) framework. ATMPs represent a category of medicinal products defined in EU Regulation 1394/2007 and subdivided into four categories, of which autologous or allogeneic CAR-T cells, among other therapies, are considered gene therapy medicinal products (GTMPs). ATMPs are subject to a centralized evaluation framework whereby one authorization is valid for all countries in the EU led by the European Medicines Agency’s Committee for Advanced Therapies (CAT). The framework includes different regulatory pathways for bringing ATMPs from clinical trials to market authorization, and the regulatory pathway taken will depend on a product’s characteristics and the target patient population. In 2018, two chimeric antigen receptor (CAR) T cell therapies, Yescarta and Kymriah, completed their authorization process via the priority medicines PRIME scheme to Marketing Authorization (Detela and Lodge 2019).
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Torres, Raul M., und Ralf Kühn. „ES cells - handling and use“. In Laboratory Protocols for Conditional Gene Targeting, 66–72. Oxford University PressOxford, 1997. http://dx.doi.org/10.1093/oso/9780199636778.003.0014.
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Abstract Pluripotent embryonic cells (ES cells) were first established directly from murine blastocysts in 1981 (136, 137) after unsuccessful early attempts to obtain germline chimerism with teratocarcinoma (EC) cells (138, 139 for review), and later shown to efficiently produce germline chimeras (140) even after transfection (141, 142). Since then, a fairly large number of ES cell lines have been generated and the lines currently often used for gene targeting experiments include D3 (143), E14 (144, 145), ABl (146), Rl (147), Jl (148) and CCE (140) which are all derived from 129 substrains or 129 hybrids. A germline competent hprt-negative line which can be used with HPRT as selection marker has also been described (149). There is a smaller number of less frequently used ES lines derived from other strains like ES623 (143) and B6-III (150) which were established from C57BL/6 mice. For the derivation and establishment of new ES cell lines see Robertson (14) and Abbondanzo, et al. (151).
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Boomsma, Jacobus J. „The multicellular organisms and colonial superorganisms“. In Domains and Major Transitions of Social Evolution, 130–63. Oxford University PressOxford, 2022. http://dx.doi.org/10.1093/oso/9780198746171.003.0006.
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Abstract Comparative data indicate that clades of differentiated multicellular organisms and colonial superorganisms always originated by somatic adherence to a diploid (zygotic) cell and by comparable loyalty of a worker caste to monogamous parents. However, the functional analogy remains ambiguous because multicellular animals ultimately die from somatic failure while single-queen colonies die from germline failure. This difference relates to the forms of corruption that plague the two levels of organizational complexity, metazoan cancers due to somatic mosaicicm and inquiline social parasites due to germline chimerism. Parental monogamy also shaped condition-dependent reproductive altruism in societies of cooperative breeders, which never became monogamous enough to evolve permanently altruistic castes. In addition to evidence for ultimate conjectures, I explore three proximate parallels between multicellular animals and colonial superorganisms. First, the ways in which germlines and soma segregate and differentiate in bodies and colonies; second, the principles by which superorganismal (but not society) immune defenses reached impressive efficiencies, particularly in ants and termites that defend non-overlapping territories; third, the extent of developmental similarity between cell differentiation in metazoan bodies and caste differentiation in superorganismal colonies. Early organismal biologists often appreciated these natural history parallels more than modern scientists, and even pre-Darwinian naturalists were remarkably competent observers of life’s organization. The empirical data appear consistent with expressions of condition-dependent somatic altruism by cells or multicellular individuals not being ancestral to obligate and unconditional reproductive altruism in (super)organismal clades. This challenges the reproductive bauplan concept for the origin of castes and suggests that the clarification of unique gene regulatory networks for obligate somatic altruism need to replace the reductionist identification of toolkit genes.
Berichte der Organisationen zum Thema "Chimeric competency"
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Dolja, Valerian V., Amit Gal-On und Victor Gaba. Suppression of Potyvirus Infection by a Closterovirus Protein. United States Department of Agriculture, März 2002. http://dx.doi.org/10.32747/2002.7580682.bard.
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The plant virus family Polyviridae is the largest and most destructive of all plant viruses. Despite the continuous effort to develop resistant plant varieties, there is a desperate need for novel approaches conferring wide-range potyvirus resistance. Based on experiments with the tobacco etch potyvirus (TEV)-derived gene expression vector, we suggested approach for screening of the candidate resistance genes. This approach relies on insertion of the genes into a virus vector and evaluation of the phenotypes of the resulting recombinant viruses. The genes which suppress infection by the recombinant virus are selected as candidates for engineering transgenic resistance. Our analysis of the TEV variants expressing proteins of the beet yellows closterovirus (BYV) revealed that one of those, the leader proteinase (L-Pro), strongly and specifically interfered with the hybrid TEV infection. Since closterovirus L-Pro is evolutionary related to potyviral helper component-proteinase (HC-Pro), we suggested that the L-Pro interfered with HC-Pro function via a trans-dominant inhibitory effect. Based on these findings, we proposed to test two major hypotheses. First, we suggested that L-Pro-mediated suppression of potyvirus infection is a general phenomenon effective against a range of potyviruses. The second hypothesis stated that the suppression effect can be reproduced in transgenic plants expressing L-Pro, and can be utilized for generation of resistance to potyviruses. In accord with these hypotheses, we developed two original objectives of our proposal: A) to determine the range of the closterovirus-derived suppression of potyviral infection, and B) to try and utilize the L-Pro-mediated suppression for the development of transgenic resistance to potyviruses. In the first phase of the project, we have developed all major tools and technologies required for successful completion of the proposed research. These included TEV and ZYMV vectors engineered to express several closteroviral L-Pro variants, and generation of the large collection of transgenic plants. To our satisfaction, characterization of the infection phenotypes exhibited by chimeric TEV and ZYMV variants confirmed our first hypothesis. For instance, similar to TEV-L- Pro(BYV) chimera, ZYMV-L-Pro(LIYV) chimera was debilitated in its systemic spread. In contrast, ZYMV-GUS chimera (positive control) was competent in establishing vigorous systemic infection. These and other results with chimeric viruses indicated that several closteroviral proteinases inhibit long-distance movement of the potyviruses upon co-expression in infected plants. In order to complete the second objective, we have generated ~90 tobacco lines transformed with closteroviral L-Pro variants, as well as ~100 lines transformed with BYV Hsp70-homolog (Hsp70h; a negative control). The presence and expression of the trans gene in each line was initially confirmed using RT-PCR and RNA preparations isolated from plants. However, since detection of the trans gene-specific RNA can not guarantee production of the corresponding protein, we have also generated L-Pro- and Hsp70h-specific antisera using corresponding synthetic peptides. These antisera allowed us to confirm that the transgenic plant lines produced detectable, although highly variable levels of the closterovirus antigens. In a final phase of the project, we tested susceptibility of the transgenic lines to TEV infection. To this end, we determined that the minimal dilution of the TEV inoculum that is still capable of infecting 100% of nontransgenic plants was 1:20, and used 10 plants per line (in total, ~2,000 plants). Unfortunately, none of the lines exhibited statistically significant reduction in susceptibility. Although discouraging, this outcome prompted us to expand our experimental plan and conduct additional experiments. Our aim was to test if closteroviral proteinases are capable of functioning in trans. We have developed agroinfection protocol for BYV, and tested if co- expression of the L-Pro is capable of rescuing corresponding null-mutant. The clear-cut, negative results of these experiments demonstrated that L-Pro acts only in cis, thus explaining the lack of resistance in our transgenic plants. We have also characterized a collection of the L-Pro alanine- scanning mutants and found direct genetic evidence of the requirement for L-Pro in virus systemic spread. To conclude, our research supported by BARD confirmed one but not another of our original hypotheses. Moreover, it provided an important insight into functional specialization of the viral proteinases and generated set of tools and data with which we will be able to address the molecular mechanisms by which these proteins provide a variety of critical functions during virus life cycle.
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Gurevitz, Michael, Michael E. Adams, Boaz Shaanan, Oren Froy, Dalia Gordon, Daewoo Lee und Yong Zhao. Interacting Domains of Anti-Insect Scorpion Toxins and their Sodium Channel Binding Sites: Structure, Cooperative Interactions with Agrochemicals, and Application. United States Department of Agriculture, Dezember 2001. http://dx.doi.org/10.32747/2001.7585190.bard.
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Integrated pest management in modern crop protection may combine chemical and biological insecticides, particularly due to the risks to the environment and livestock arising from the massive use of non-selective chemicals. Thus, there is a need for safer alternatives, which target insects more specifically. Scorpions produce anti-insect selective polypeptide toxins that are biodegradable and non-toxic to warm-blooded animals. Therefore, integration of these substances into insect pest control strategies is of major importance. Moreover, clarification of the molecular basis of this selectivity may provide valuable information pertinent to their receptor sites and to the future design of peptidomimetic anti-insect specific substances. These toxins may also be important for reducing the current overuse of chemical insecticides if they produce a synergistic effect with conventional pesticides. Based on these considerations, our major objectives were: 1) To elucidate the three-dimensional structure and toxic-site of scorpion excitatory, "depressant, and anti-insect alpha toxins. 2) To obtain an initial view to the sodium channel recognition sites of the above toxins by generating peptide decoys through a phage display system. 3) To investigate the synergism between toxins and chemical insecticides. Our approach was to develop a suitable expression system for toxin production in a recombinant form and for elucidation of toxin bioactive sites via mutagenesis. In parallel, the mode of action and synergistic effects of scorpion insecticidal toxins with pyrethroids were studied at the sodium channel level using electrophysiological methods. Objective 1 was achieved for the alpha toxin, LqhaIT Zilberberg et al., 1996, 1997; Tugarinov et al., 1997; Froy et al., 2002), and the excitatory toxin, Bj-xtrIT (Oren et al., 1998; Froy et al., 1999; unpublished data). The bioactive surface of the depressant toxin, LqhIT2, has been clarified and a crystal of the toxin is now being analyzed (unpublished). Objective 2 was not successful thus far as no phages that recognize the toxins were obtained. We therefore initiated recently an alternative approach, which is introduction of mutations into recombinant channels and creation of channel chimeras. Objective 3 was undertaken at Riverside and the results demonstrated synergism between LqhaIT or AaIT and pyrethroids (Lee et al., 2002). Furthermore, negative cross-resistance between pyrethroids and scorpion toxins (LqhaIT and AaIT) was demonstrated at the molecular level. Although our study did not yield a product, it paves the way for future design of selective pesticides by capitalizing on the natural competence of scorpion toxins to distinguish between sodium channels of insects and vertebrates. We also show that future application of anti-insect toxins may enable to decrease the amounts of chemical pesticides due to their synergism.