Gene therapy for global brain diseases: one small step for mice, one giant leap for humans.
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ABSTRACT:
SUBMITTER: Rahim AA
PROVIDER: S-EPMC7364739 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC9350584 | biostudies-literature
Project description:This article discusses the recently published EMPA-REG OUTCOME trial, which assessed cardiovascular outcomes with empagliflozin therapy in persons with type 2 diabetes mellitus and coexisting cardiovascular disease. The article describes the background and challenges of modern cardiovascular outcome trials, points out the strengths of the EMPA-REG OUTCOME study, and places the results in perspective. It highlights the significant impact that these results will have on cardiovascular preventive pharmacotherapy, and on future drug development in diabetes. At the same time, it reminds readers of the limitations of the results, and lists the questions raised by, or left unanswered by, the trial.
| S-EPMC4674475 | biostudies-literature
Project description:We explore humans' rule-based category learning using analytic approaches that highlight their psychological transitions during learning. These approaches confirm that humans show qualitatively sudden psychological transitions during rule learning. These transitions contribute to the theoretical literature contrasting single vs. multiple category-learning systems, because they seem to reveal a distinctive learning process of explicit rule discovery. A complete psychology of categorization must describe this learning process, too. Yet extensive formal-modeling analyses confirm that a wide range of current (gradient-descent) models cannot reproduce these transitions, including influential rule-based models (e.g., COVIS) and exemplar models (e.g., ALCOVE). It is an important theoretical conclusion that existing models cannot explain humans' rule-based category learning. The problem these models have is the incremental algorithm by which learning is simulated. Humans descend no gradient in rule-based tasks. Very different formal-modeling systems will be required to explain humans' psychology in these tasks. An important next step will be to build a new generation of models that can do so.
| S-EPMC4558046 | biostudies-literature
Project description:Genome driven precision oncology has transformed the landscape of multiple cancers. However, access barriers exist. A recent study exemplified a direct-to-patient outreach program via social media through the implementation of a global program that offered free tumor genomic testing with a focus on rare cancers. See related article by Doe-Tetteh et al., p. 2445.
| S-EPMC10330328 | biostudies-literature
Project description:Granulocyte macrophage-colony stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that is known to facilitate vaccine efficacy by promoting the development and prolongation of both humoral and cellular immunity. In the past years we have generated a novel codon-optimized GM-CSF gene as an adjuvant. The codon-optimized GM-CSF gene significantly increased protein expression levels in all cells tested and helped in generating a strong immune responses against HIV-1 Gag and HPV-associated cancer. Here, we review the literature dealing with the adjuvant activity of GM-CSF both in animal models and clinical trials. We anticipate that the codon-optimized GM-CSF gene offers a practical molecular strategy for potentiating immune responses to tumor cell-based vaccinations as well as other immunotherapeutic strategies.
| S-EPMC5215529 | biostudies-other
Project description:Biomolecule phosphorylation by protein kinases is a fundamental cell signaling process in all living cells. Following the comprehensive cataloguing of the protein kinase complement of the human genome (Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 1912-1934), this review will detail the state-of-the-art human and mouse kinase proteomes as provided in the UniProtKB/Swiss-Prot protein knowledgebase. The sequences of the 480 classical and up to 24 atypical protein kinases now believed to exist in the human genome and 484 classical and up to 24 atypical kinases within the mouse genome have been reviewed and, where necessary, revised. Extensive annotation has been added to each entry. In an era when a wealth of new databases is emerging on the Internet, UniProtKB/Swiss-Prot makes available to the scientific community the most up-to-date and in-depth annotation of these proteins with access to additional external resources linked from within each entry. Incorrect sequence annotations resulting from errors and artifacts have been eliminated. Each entry will be constantly reviewed and updated as new information becomes available with the orthologous enzymes in related species being annotated in a parallel effort and complete kinomes being completed as sequences become available. This ensures that the mammalian kinomes available from UniProtKB/Swiss-Prot are of a consistently high standard with each separate entry acting both as a valuable information resource and a central portal to a wealth of further detail via extensive cross-referencing.
| S-EPMC2500232 | biostudies-literature
Project description:Understanding larval duration and hence dispersal potential of the European oyster Ostrea edulis is crucial to inform restoration strategies. Laval duration has an obligatory period of maturity to pediveliger (when larvae are ready to settle), but also an unknown period until metamorphosis is triggered by a settlement cue. The extent to which larvae can prolong the pediveliger period and delay metamorphosis has not been studied. Here we show that O. edulis larvae can delay metamorphosis for a period of 11 days, while retaining the capability to settle in high proportions when presented with a suitable settlement cue. O. edulis larvae are likely to be able to delay metamorphosis even further, since 80% of larvae in the control treatment were still alive when the experiment was terminated at day 14. The results indicate the ability of O. edulis larvae to more than double pelagic duration and probably further delay metamorphosis. We discuss these findings in the context of larval mortality, and the importance of O. edulis' larval settlement requirements for dispersal potential, recruitment success and connectivity of restoration sites.
| S-EPMC8372959 | biostudies-literature
Project description:The anti-La mab 312B, which was established by hybridoma technology from human-La transgenic mice after adoptive transfer of anti-human La T cells, immunoprecipitates both native eukaryotic human and murine La protein. Therefore, it represents a true anti-La autoantibody. During maturation, the anti-La mab 312B acquired somatic hypermutations (SHMs) which resulted in the replacement of four aa in the complementarity determining regions (CDR) and seven aa in the framework regions. The recombinant derivative of the anti-La mab 312B in which all the SHMs were corrected to the germline sequence failed to recognize the La antigen. We therefore wanted to learn which SHM(s) is (are) responsible for anti-La autoreactivity. Humanization of the 312B ab by grafting its CDR regions to a human Ig backbone confirms that the CDR sequences are mainly responsible for anti-La autoreactivity. Finally, we identified that a single amino acid replacement (D > Y) in the germline sequence of the CDR3 region of the heavy chain of the anti-La mab 312B is sufficient for anti-La autoreactivity.
| S-EPMC8584381 | biostudies-literature
Project description: Not available
| S-EPMC3133615 | biostudies-literature
Project description:Recent technological improvements have made possible the development of lightweight GPS-tagging devices suitable to track medium-to-small sized animals. However, current inferences concerning GPS performance are based on heavier designs, suitable only for large mammals. Lightweight GPS-units are deployed close to the ground, on species selecting micro-topographical features and with different behavioural patterns in comparison to larger mammal species. We assessed the effects of vegetation, topography, motion, and behaviour on the fix success rate for lightweight GPS-collar across a range of natural environments, and at the scale of perception of feral cats (Felis catus). Units deployed at 20 cm above the ground in sites of varied vegetation and topography showed that trees (native forest) and shrub cover had the largest influence on fix success rate (89% on average); whereas tree cover, sky availability, number of satellites and horizontal dilution of position (HDOP) were the main variables affecting location error (±39.5 m and ±27.6 m before and after filtering outlier fixes). Tests on HDOP or number of satellites-based screening methods to remove inaccurate locations achieved only a small reduction of error and discarded many accurate locations. Mobility tests were used to simulate cats' motion, revealing a slightly lower performance as compared to the fixed sites. GPS-collars deployed on 43 cats showed no difference in fix success rate by sex or season. Overall, fix success rate and location error values were within the range of previous tests carried out with collars designed for larger species. Lightweight GPS-tags are a suitable method to track medium to small size species, hence increasing the range of opportunities for spatial ecology research. However, the effects of vegetation, topography and behaviour on location error and fix success rate need to be evaluated prior to deployment, for the particular study species and their habitats.
| S-EPMC3233555 | biostudies-literature