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51.
Substantial progress has been made in the past decade in treating several primary immunodeficiency disorders (PIDs) with gene therapy. Current approaches are based on ex-vivo transfer of therapeutic transgene via viral vectors to patient-derived autologous hematopoietic stem cells (HSCs) followed by transplantation back to the patient with or without conditioning. The overall outcome from all the clinical trials targeting different PIDs has been extremely encouraging but not without caveats. Malignant outcomes from insertional mutagenesis have featured prominently in the adverse events associated with these trials and have warranted intense pre-clinical investigation into defining the tendencies of different viral vectors for genomic integration. Coupled with issues pertaining to transgene expression, the therapeutic landscape has undergone a paradigm shift in determining safety, stability and efficacy of gene therapy approaches. In this review, we aim to summarize the progress made in the gene therapy trials targeting ADA-SCID, SCID-X1, CGD and WAS, review the pitfalls, and outline the recent advancements which are expected to further enhance favourable risk benefit ratios for gene therapeutic approaches in the future. 相似文献
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LTRs are sequence elements in retroviruses and retrotransposons which are difficult to align due to their variability. One way of handling such cases is to use Hidden Markov Models (HMMs). In this work HMMs of LTRs were constructed for three groups of orthoretroviruses: the betaretroviruslike human MMTV-like (HML) endogenous retroviruses, the lentiviruses, including HIV, and gammaretroviruslike human endogenous retroviruses (HERVs). The HMM-generated LTR alignments and the phylogenetic trees constructed from them were compared with trees based on alignments of the pol gene at the nucleic acid level. The majority of branches in the LTR and pol based trees had the same order for the three retroviral genera, showing that HMM methods are successful in aligning and constructing phylogenies of LTRs. The HML LTR tree deviated somewhat from the pol tree for the groups HML3, HML7 and HML6. Among the gammaretroviruslike proviruses, the exogenous Mouse Leukemia Virus (MLV) was highly related to HERV-T in the pol based tree, but not in the LTR based tree. Aside from these differences, the similarity between the trees indicates that LTRs and pol coevolved in a largely monophyletic way. 相似文献
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Susan G. Larson 《Evolutionary anthropology》1998,6(3):87-99
The evolutionary history of the living hominoids has remained elusive despite years of exploration and the discovery of numerous Miocene fossil ape species. Part of the difficulty can be attributed to the changing nature of our views about the course of hominoid evolution. In the 1950s and 1960s, individual Miocene taxa were commonly viewed as the direct ancestors of specific living ape species, suggesting an early divergence of the modern lineages.1–5 However, in most cases, the Miocene forms were essentially “dental apes,” resembling extant species in dental and a few cranial features, but possessing more primitive postcranial features that suggested arboreal quadrupedalism rather than suspensory habits. With the introduction of molecular methods of phylogenetic reconstruction and the increasing use of cladistic analysis, it has become apparent that the radiation leading to the modern hominoids was somewhat more recent than had been believed, and that most of the Miocene hominoid species had little to do with the evolutionary history of the living apes. © 1998 Wiley-Liss, Inc. 相似文献
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Human uniqueness and theoretical content in paleoanthropology 总被引:1,自引:0,他引:1
Matt Cartmill 《International journal of primatology》1990,11(3):173-192
One of the things that distinguishes science from nonscientific discourse is the incorporation of its hypotheses into theoretical structures. Like parapsychology, the study of human evolution lacks theoretical content and connections. This lack is due, in part, to the collapse of the classical primatological synthesis in the 1970s. It is due in larger measure to a persistent anthropological focus on human uniqueness as the phenomenon to be explained. Such supposedly unique human features as large brains, language, conceptual thinking, and upright bipedalism are uniquely human by definition rather than as a matter of empirical fact. Much scientific effort and ingenuity has gone into redefining such characteristics whenever discoveries about other animals have posed a threat to human uniqueness. But since by definition qualitatively unique phenomena do not conform to overarching laws that apply to similar cases, they must remain theoretically inexplicable. Paleoanthropology should aim at increasing its theoretical content by reducing the list of qualitative human uniquenesses-and eliminating it altogether if possible.If man wants to set up a contest in resembling himself and award himself the prize, no one will quarrel with him. 相似文献
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Published data on milk composition for nonhuman primates, especially great apes, are lacking. Milk composition data are important for understanding the physiology and evolution of mammalian milk production, as well as the nutritional requirements of infants. For many primate species these data have added relevance because of the need to hand raise infants orphaned by poaching or separated from their mothers in captivity. The proximate composition (dry matter (DM), protein, fat, sugar) of free-ranging mountain gorilla (MG) (Gorilla beringei beringei) milk was characterized from samples (N = 10) collected opportunistically during field procedures. The mean values for mid-lactation (1-50 months) milk samples from healthy MGs (N = 7) were: 10.7% DM, 1.9% fat, 1.4% crude protein, 6.8% sugar, and 0.53 kcal/g. These results are lower in fat and total energy than most other Hominidae, including humans. One early-lactation sample was high in protein content while the composition of two samples from gorillas with poor health and suspected poor milk quality both deviated from the normal, mid-lactation pattern. This survey adds to the data available for primate milk composition and suggests that wild MG infants normally consume milk that is lower in fat and total energy than human milk. 相似文献
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Eiji Inoue Etienne François Akomo‐Okoue Chieko Ando Yuji Iwata Mariko Judai Shiho Fujita Shun Hongo Chimene Nze‐Nkogue Miho Inoue‐Murayama Juichi Yamagiwa 《American journal of physical anthropology》2013,151(4):583-588
The male dispersal patterns of western lowland gorillas (WLGs, Gorilla gorilla gorilla) are not well understood. To determine whether most silverbacks stay close to their relatives, we analyzed autosomal and Y‐chromosomal microsatellites (STRs) in wild WLGs at Moukalaba, Gabon. We obtained STR genotypes for 38 individuals, including eight silverbacks and 12 adult females in an approximately 40 km2 area. Among them, 20 individuals were members of one identified group (Group Gentil; GG), including one silverback and six adult females. The silverback sired all 13 of the offspring in GG and no Y‐STR polymorphism within GG was found, as expected in a one‐male group structure. Over all silverbacks sampled, Y‐STR diversity was high considering the limited sampling area, and silverbacks with similar Y‐STR haplotypes were not always located in nearby areas. Although the misclassification rate of kinship estimates in this study was not negligible, there were no kin dyads among all silverbacks sampled. These results suggest that silverbacks born in the same group do not stay close to each other after maturation. The Y‐STR diversity in this study was similar to that of a previous study conducted in an area that was approximately 150 times larger than our study area. Similarity of WLG Y‐STR diversity between studies at different sampling scales suggests that male gene flow may not be geographically limited. These results suggest that WLG males normally disperse from their natal areas after maturation, at least, in Moukalaba. Am J Phys Anthropol 151:583–588, 2013. © 2013 Wiley Periodicals, Inc. 相似文献