622 research outputs found
Chastity, foreign theories, and national heritage reorganization: Hu Shi (1892-1962) addresses ‘the woman problem’
This article examines Hu Shi’s view of “The Woman Problem” (funü wenti) through his tripartite approach for achieving a Chinese Renaissance as enunciated in his 1919 article “The Significance of the New Tide” (Xinsichao de yiyi). Our reading of the 1919 article reveals that Hu conceived of the twentieth-century Chinese Renaissance as a meticulously planned reform project based on a tripartite approach that involved: (1) researching concrete problems (yanjiu wenti), (2) importing foreign theories (shuru xueli), and (3) reorganizing national heritage (zhengli guogu). The article aims to demonstrate how Hu applied each of these interconnected methods to “The Woman Problem.” Previous scholarship on Hu’s views on women has failed to notice that it was methodologically integrated into his overarching Chinese Renaissance project and simultaneously underpinned by his academic program to reorganize national heritage. This essay also probes the quality of Hu Shi’s ‘feminism’ by expounding how his analysis of “The Woman Problem” was integrated into his overarching program to achieve a Chinese Renaissance
Testing Methods to Enhance Longevity Awareness
Many people have only a vague notion of the concept of life expectancy and the longevity risk they face at older ages, which in turn implies that they are likely to undersave for retirement. This paper employs an online experiment to investigate alternative ways to describe both life expectancy and longevity risk, with the goal of assessing whether these can raise peoples’ awareness of possible retirement shortfalls. We also evaluate whether providing this information promotes interest in saving activity and demand for longevity insurance products. We find that providing longevity risk information impacts respondents’ subjective survival probabilities, while simply describing average life expectancy does not. Yet providing life expectancy or longevity information significantly affects financial decisions, mostly regarding annuitization. Interestingly, we also find that merely prompting people to think about financial decisions changes their perceptions regarding subjective survival probabilities
Longevity Perceptions and Saving Decisions During the COVID-19 Outbreak: An Experimental Investigation
We experimentally study individuals’ perceptions about and advice to others regarding retirement savings and annuitization during the pandemic. Many people recommend that others save more for retirement, but those most affected by the pandemic tell others to save and annuitize less. We investigate two possible channels for this result and show that the pandemic does not substantially alter optimism regarding survival probabilities. Hence, we conclude that economic factors are driving our results. Consequently, some financial ramifications of the COVID-19 outbreak are yet to be revealed, as the pandemic is having longer-term effects on peoples’ willingness to save and annuitize
De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints.
Molecular evolution has focused on the divergence of molecular functions, yet we know little about how structurally distinct protein folds emerge de novo. We characterized the evolutionary trajectories and selection forces underlying emergence of β-propeller proteins, a globular and symmetric fold group with diverse functions. The identification of short propeller-like motifs (<50 amino acids) in natural genomes indicated that they expanded via tandem duplications to form extant propellers. We phylogenetically reconstructed 47-residue ancestral motifs that form five-bladed lectin propellers via oligomeric assembly. We demonstrate a functional trajectory of tandem duplications of these motifs leading to monomeric lectins. Foldability, i.e., higher efficiency of folding, was the main parameter leading to improved functionality along the entire evolutionary trajectory. However, folding constraints changed along the trajectory: initially, conflicts between monomer folding and oligomer assembly dominated, whereas subsequently, upon tandem duplication, tradeoffs between monomer stability and foldability took precedence.We thank Michael Gurevitz (Tel Aviv University), John Finnerty (Boston University) and Adam Reitzel (Woodshole Oceanographic Institute) for providing N. vectensis cDNA, and Joseph Rogers (University of Cambridge) for discussion and assistance. We thank Liam Longo, Ron Milo and Balaji Santhanam for insightful comments on this manuscript. This work was supported by the Israel Science Foundation grant 980/14 (DST), the Weizmann - UK Joint Research Program (DST and JC), the Weizmann Koshland and Dean of Faculty fellowships (RGS) and an EMBO short-term fellowship (RGS). JC is a Wellcome Trust Fellow (WT 095195).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.cell.2015.12.02
On the Connection Between Metal Absorbers and Quasar Nebulae
We establish a simple model for the distribution of cold gas around L*
galaxies using a large set of observational constraints on the properties of
strong MgII absorber systems. Our analysis suggests that the halos of L*
galaxies are filled with cool gaseous clouds having sizes of order 1kpc and
densities of ~10^{-2} cm^{-3}. We then investigate the physical effects of
cloud irradiation by a quasar and study the resulting spectral signatures. We
show that quasar activity gives rise to (i) extended narrow-line emission on
~100kpc scales and (ii) an anisotropy in the properties of the absorbing gas
arising from the geometry of the quasar radiation field. Provided that quasars
reside in halos several times more massive than those of L* galaxies, our model
predictions appear to be in agreement with observations of narrow emission-line
nebulae around quasars and the recent detections of ~100kpc cold gaseous
envelopes around those objects, suggesting a common origin for these phenomena.
We discuss the implications of our results for understanding absorption
systems, probing quasar environments at high redshifts, and testing the quasar
unification scheme.Comment: 15 pages, 13 figures (ApJ submitted
HIV-1 Tat interacts with LIS1 protein
BACKGROUND: HIV-1 Tat activates transcription of HIV-1 viral genes by inducing phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Tat can also disturb cellular metabolism by inhibiting proliferation of antigen-specific T lymphocytes and by inducing cellular apoptosis. Tat-induced apoptosis of T-cells is attributed, in part, to the distortion of microtubules polymerization. LIS1 is a microtubule-associated protein that facilitates microtubule polymerization. RESULTS: We identified here LIS1 as a Tat-interacting protein during extensive biochemical fractionation of T-cell extracts. We found several proteins to co-purify with a Tat-associated RNAPII CTD kinase activity including LIS1, CDK7, cyclin H, and MAT1. Tat interacted with LIS1 but not with CDK7, cyclin H or MAT1 in vitro. LIS1 also co-immunoprecipitated with Tat expressed in HeLa cells. Further, LIS1 interacted with Tat in a yeast two-hybrid system. CONCLUSION: Our results indicate that Tat interacts with LIS1 in vitro and in vivo and that this interaction might contribute to the effect of Tat on microtubule formation
Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy.
The exosome complex is the most important RNA processing machinery within the cell. Mutations in its subunits EXOSC8 and EXOSC3 cause pontocerebellar hypoplasia, spinal muscular atrophy (SMA) and central nervous system demyelination. We present a patient with SMA-like phenotype carrying a homozygous mutation in RBM7-a subunit of the nuclear exosome targeting (NEXT) complex-which is known to bind and carry specific subtypes of coding and non-coding RNAs to the exosome. The NEXT complex with other protein complexes is responsible for the substrate specificity of the exosome. We performed RNA-sequencing (RNA-seq) analysis on primary fibroblasts of patients with mutations in EXOSC8 and RBM7 and gene knock-down experiments using zebrafish as a model system. RNA-seq analysis identified significantly altered expression of 62 transcripts shared by the two patient cell lines. Knock-down of rbm7, exosc8 and exosc3 in zebrafish showed a common pattern of defects in motor neurons and cerebellum. Our data indicate that impaired RNA metabolism may underlie the clinical phenotype by fine tuning gene expression which is essential for correct neuronal differentiation
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Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.
AimsIn this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril.Methods and resultsIn a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001).ConclusionsIn PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs
Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression
This report provides a global view of how gene expression is affected by DNA replication. We analyzed synchronized cultures of Saccharomyces cerevisiae under conditions that prevent DNA replication initiation without delaying cell cycle progression. We use a higher-order singular value decomposition to integrate the global mRNA expression measured in the multiple time courses, detect and remove experimental artifacts and identify significant combinations of patterns of expression variation across the genes, time points and conditions. We find that, first, ∼88% of the global mRNA expression is independent of DNA replication. Second, the requirement of DNA replication for efficient histone gene expression is independent of conditions that elicit DNA damage checkpoint responses. Third, origin licensing decreases the expression of genes with origins near their 3′ ends, revealing that downstream origins can regulate the expression of upstream genes. This confirms previous predictions from mathematical modeling of a global causal coordination between DNA replication origin activity and mRNA expression, and shows that mathematical modeling of DNA microarray data can be used to correctly predict previously unknown biological modes of regulation
Experimental myocarditis in rat can be detected and monitored by cardiac magnetic resonance imaging performed on a clinical 3.0 T scanner
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