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1.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
2.
Schooling often rests uneasily on presumed dichotomies between coverage and inquiry, skill development, and creativity. By
drawing on the often under-recognized parallels between biological evolution and human learning, this essay argues that formal
education needs and ought not to forego the unconscious exploratory processes of informal learning. Rather than posit as natural
the cultural story that formal schooling must prepare students to integrate with given cultures and foreknowable futures,
the evolutionary perspective shows that education is better thought of as preparing students to create cultures and to change,
and foster change, in relation to unknown futures. The properties that distinguish formal from informal learning—conscious
reflection and a degree of collective consensus about what constitutes knowledge at any given time—are, we argue, useful not
as ends in themselves, but as tools for maximizing, sharing, and extending unconscious, evolutionary learning. Working with
them as such offers a way out of some of education’s persistent problems. Two autobiographical case studies provide examples
of these evolutionary changes and indicate pathways of inquiry by which to pursue them. 相似文献
3.
The dramatic clinical manifestations of toxigenic infections such as cholera and diphtheria occur without substantial bacterial invasion. Disease is mediated by the secretion of potent toxins that use ADP-ribosylation as the catalytic mechanism underlying their action. ADP-ribosylating toxins comprise a large family, including the cholera, diphtheria, pertussis and Escherichia coli heat-labile (LT) toxins, and all produce disease by altering key metabolic processes after transfer of an ADP-ribose moiety from NAD to specific host-cell target proteins. A new paradigm implicating ADP-ribosylation during intracellular pathogenesis is beginning to emerge from recent research in Salmonella. 相似文献
4.
5.
Steven T. Staben Timothy P. Heffron Daniel P. Sutherlin Seema R. Bhat Georgette M. Castanedo Irina S. Chuckowree Jenna Dotson Adrian J. Folkes Lori S. Friedman Leslie Lee John Lesnick Cristina Lewis Jeremy M. Murray Jim Nonomiya Alan G. Olivero Emile Plise Jodie Pang Wei Wei Prior Laurent Salphati Lionel Rouge Bing-Yan Zhu 《Bioorganic & medicinal chemistry letters》2010,20(20):6048-6051
Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model. 相似文献
6.
R Moriggi Jr HS Di Mauro SC Dias JM Matos MB Urtado NF Camar?o IV Sousa Neto DC Nascimento RA Tibana CO Assump??o J Prestes CB Urtado 《Biology of sport / Institute of Sport》2015,32(4):289-294
Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. 相似文献
7.
JY Xiong SC Li YX Sun XS Zhang ZZ Dong P Zhong XR Sun 《Biology of sport / Institute of Sport》2015,32(4):295-300
Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer''s disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of β-amyloid, brain-derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of β-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P < 0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation of β-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P > 0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect. 相似文献
8.
Maraganore DM de Andrade M Lesnick TG Strain KJ Farrer MJ Rocca WA Pant PV Frazer KA Cox DR Ballinger DG 《American journal of human genetics》2005,77(5):685-693
We performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, we individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, we individually genotyped 1,793 PD-associated SNPs (P<.01 in tier 1) and 300 genomic control SNPs in 332 matched case-unrelated control pairs. We identified 11 SNPs that were associated with PD (P<.01) in both tier 1 and tier 2 samples and had the same direction of effect. For these SNPs, we combined data from the case-unaffected sibling pair (tier 1) and case-unrelated control pair (tier 2) samples and employed a liberalization of the sibling transmission/disequilibrium test to calculate odds ratios, 95% confidence intervals, and P values. A SNP within the semaphorin 5A gene (SEMA5A) had the lowest combined P value (P=7.62 x 10(-6)). The protein encoded by this gene plays an important role in neurogenesis and in neuronal apoptosis, which is consistent with existing hypotheses regarding PD pathogenesis. A second SNP tagged the PARK11 late-onset PD susceptibility locus (P=1.70 x 10(-5)). In tier 2b, we also selected for genotyping additional SNPs that were borderline significant (P<.05) in tier 1 but that tested a priori biological and genetic hypotheses regarding susceptibility to PD (n=941 SNPs). In analysis of the combined tier 1 and tier 2b data, the two SNPs with the lowest P values (P=9.07 x 10(-6); P=2.96 x 10(-5)) tagged the PARK10 late-onset PD susceptibility locus. Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility. 相似文献
9.
Lesnick TG Sorenson EJ Ahlskog JE Henley JR Shehadeh L Papapetropoulos S Maraganore DM 《PloS one》2008,3(1):e1449
Background
We recently described a genomic pathway approach to study complex diseases. We demonstrated that models constructed using single nucleotide polymorphisms (SNPs) within axon guidance pathway genes were highly predictive of Parkinson disease (PD) susceptibility, survival free of PD, and age at onset of PD within two independent whole-genome association datasets. We also demonstrated that several axon guidance pathway genes represented by SNPs within our final models were differentially expressed in PD.Methodology/Principal Findings
Here we employed our genomic pathway approach to analyze data from a whole-genome association dataset of amyotrophic lateral sclerosis (ALS); and demonstrated that models constructed using SNPs within axon guidance pathway genes were highly predictive of ALS susceptibility (odds ratio = 1739.73, p = 2.92×10−60), survival free of ALS (hazards ratio = 149.80, p = 1.25×10−74), and age at onset of ALS (R2 = 0.86, p = 5.96×10−66). We also extended our analyses of a whole-genome association dataset of PD, which shared 320,202 genomic SNPs in common with the whole-genome association dataset of ALS. We compared for ALS and PD the genes represented by SNPs in the final models for susceptibility, survival free of disease, and age at onset of disease and noted that 52.2%, 37.8%, and 34.9% of the genes were shared respectively.Conclusions/Significance
Our findings for the axon guidance pathway and ALS have prior biological plausibility, overlap partially with PD, and may provide important insight into the causes of these and related neurodegenerative disorders. 相似文献10.