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31.
A fundamental puzzle about human behavior is low investment in preventive health inputs. Present-biased preferences have frequently been put forth as a theoretical explanation for this, but with limited empirical evidence supporting it, especially in developing countries. We extend our previous analysis of a field experiment testing advertising strategies to increase demand for a potentially life-saving preventive health technology, voluntary medical male circumcision. Offering compensation of US$10 conditional on a complement to the procedure, a short counseling session at a providing clinic, tripled uptake of the procedure. This is consistent with the idea that subsidizing a complement encouraged procrastinating men with latent demand to invest in preventive health. In addition, framing the basic advertisement using the statement “Are you tough enough?” doubled uptake. 相似文献
32.
Based on the conjugate strategy, two neutral 99mTc labeled 2-(1-(6-(dialkylamino)naphthalen-2-yl)ethylidene)malononitrile (DDNP) and 1-(6-(dialkylamino)naphthalen-2-yl)ethanone (ENE) derivatives, and their corresponding rhenium complexes were synthesized. In vitro fluorescent staining indicated that the corresponding rhenium derivatives selectively stained the β-amyloid (Aβ) plaques in the brain sections of AD model mice with low background. Compared with FDDNP and FENE, the affinities of the corresponding rhenium derivatives to Aβ aggregates decreased about 10-14-fold. In vivo biodistribution experiments in normal mice showed that 99mTc-MAMA-ENE displayed medium initial brain uptake (0.65 %ID/g at 2 min) with a reasonable washout from the brain (0.19 %ID/g at 2 h) while 99mTc-MAMA-DDNP showed a low brain uptake (0.28 %ID/g at 2 min). Further optimize these 99mTc-labeled tracers in order to improve their binding affinities to Aβ plaques and diffusion through the blood brain barrier may generate useful imaging agents for SPECT. 相似文献
33.
It has been proposed that proteins fold by a process called \"Zipping and Assembly\" (Z&A). Zipping refers to the growth of local substructures within the chain, and assembly refers to the coming together of already-formed pieces. Our interest here is in whether Z&A is a general method that can fold most of sequence space, to global minima, efficiently. Using the HP model, we can address this question by enumerating full conformation and sequence spaces. We find that Z&A reaches the global energy minimum native states, even though it searches only a very small fraction of conformational space, for most sequences in the full sequence space. We find that Z&A, a mechanism-based search, is more efficient in our tests than the replica exchange search method. Folding efficiency is increased for chains having: (a) small loop-closure steps, consistent with observations by Plaxco et al. 1998;277;985-994 that folding rates correlate with contact order, (b) neither too few nor too many nucleation sites per chain, and (c) assembly steps that do not occur too early in the folding process. We find that the efficiency increases with chain length, although our range of chain lengths is limited. We believe these insights may be useful for developing faster protein conformational search algorithms. 相似文献
34.
Margaux Bieuville Tazzio Tissot Alexandre Robert Pierre-Yves Henry Samuel Pavard 《Evolutionary Applications》2023,16(3):609-624
Current oncogenic theories state that tumors arise from cell lineages that sequentially accumulate (epi)mutations, progressively turning healthy cells into carcinogenic ones. While those models found some empirical support, they are little predictive of intraspecies age-specific cancer incidence and of interspecies cancer prevalence. Notably, in humans and lab rodents, a deceleration (and sometimes decline) of cancer incidence rate has been found at old ages. Additionally, dominant theoretical models of oncogenesis predict that cancer risk should increase in large and/or long-lived species, which is not supported by empirical data. Here, we explore the hypothesis that cellular senescence could explain those incongruent empirical patterns. More precisely, we hypothesize that there is a trade-off between dying of cancer and of (other) ageing-related causes. This trade-off between organismal mortality components would be mediated, at the cellular scale, by the accumulation of senescent cells. In this framework, damaged cells can either undergo apoptosis or enter senescence. Apoptotic cells lead to compensatory proliferation, associated with an excess risk of cancer, whereas senescent cell accumulation leads to ageing-related mortality. To test our framework, we build a deterministic model that first describes how cells get damaged, undergo apoptosis, or enter senescence. We then translate those cellular dynamics into a compound organismal survival metric also integrating life-history traits. We address four different questions linked to our framework: can cellular senescence be adaptive, do the predictions of our model reflect epidemiological patterns observed among mammal species, what is the effect of species sizes on those answers, and what happens when senescent cells are removed? Importantly, we find that cellular senescence can optimize lifetime reproductive success. Moreover, we find that life-history traits play an important role in shaping the cellular trade-offs. Overall, we demonstrate that integrating cellular biology knowledge with eco-evolutionary principles is crucial to solve parts of the cancer puzzle. 相似文献
35.
Nicholas A. Azzolina Edward F. Neuhauser Bruce D. Coulombe 《Soil & Sediment Contamination》2015,24(7):744-770
The sediment quality triad (SQT) assumes that three measurements (sediment chemistry, laboratory bioassay, and benthic macroinvertebrate counts) comprise an independent assessment of impact, which when integrated using a weight-of-evidence approach provides a comprehensive assessment of risk. An SQT assessment was conducted on 41 sediment samples collected adjacent to a manufactured gas plant site on the freshwater reach of the Hudson River in New York State. The assessment shows that the benthic macroinvertebrate data did not correlate with either sediment or pore water polycyclic aromatic hydrocarbon (PAH) concentrations, nor did these data show consistent relationships to the results of laboratory bioassay testing (Hyalella azteca 28-day survival or biomass). The benthic community across the site and reference areas was comprised of few taxa, all of which were pollution-tolerant organisms with tolerance values greater than or equal to five. Only in significantly impacted sediment samples with PAH concentrations in the thousands of milligrams per kilogram, pore water concentrations above 100 toxic units, and visible non-aqueous phase liquid present in the sample did the benthic macroinvertebrate data show a response. In contrast, sediment and pore water PAH measurements and H. azteca toxicity testing provided consistent interpretation of impact. These results illustrate that benthic macroinvertebrate data may contain less information value and be a more challenging line of evidence to interpret in triad studies conducted in certain ecological settings; in this case, a large-order river with a relatively depauperate benthic community dominated by species tolerant of PAHs. 相似文献
36.
Hugo R. Arias Dominik Feuerbach Katarzyna M. Targowska-Duda Shaili Aggarwal David J. Lapinsky Krzysztof Jozwiak 《Neurochemistry international》2012
The pharmacological properties of (±)-2-(N-tert-butylamino)-3′-iodo-4′-azidopropiophenone [(±)-SADU-3-72], a photoreactive analog of bupropion (BP), were characterized at different muscle nicotinic acetylcholine receptors (AChRs) by functional and structural approaches. Ca2+ influx results indicate that (±)-SADU-3-72 is 17- and 6-fold more potent than BP in inhibiting human (h) embryonic (hα1β1γδ) and adult (hα1β1εδ) muscle AChRs, respectively. (±)-SADU-3-72 binds with high affinity to the [3H]TCP site within the resting or desensitized Torpedo AChR ion channel, whereas BP has higher affinity for desensitized AChRs. Molecular docking results indicate that both SADU-3-72 enantiomers interact with the valine (position 13′) and serine (position 6′) rings. However, an additional domain, between the outer (position 20′) and valine rings, is observed in Torpedo AChR ion channels. Our results indicate that the azido group of (±)-SADU-3-72 may enhance its interaction with polar groups and the formation of hydrogen bonds at AChRs, thus supporting the observed higher potency and affinity of (±)-SADU-3-72 compared to BP. Collectively our results are consistent with a model where BP/SADU-3-72 and TCP bind to overlapping sites within the lumen of muscle AChR ion channels. Based on these results, we believe that (±)-SADU-3-72 is a promising photoprobe for mapping the BP binding site, especially within the resting AChR ion channel. 相似文献
37.
We describe a recently developed method to measure mechanical properties of the surfaces of plant tissues using atomic force microscopy (AFM) micro/nano-indentations, for a JPK AFM. Specifically, in this protocol we measure the apparent Young’s modulus of cell walls at subcellular resolutions across regions of up to 100 µm x 100 µm in floral meristems, hypocotyls, and roots. This requires careful preparation of the sample, the correct selection of micro-indenters and indentation depths. To account for cell wall properties only, measurements are performed in highly concentrated solutions of mannitol in order to plasmolyze the cells and thus remove the contribution of cell turgor pressure.In contrast to other extant techniques, by using different indenters and indentation depths, this method allows simultaneous multiscale measurements, i.e. at subcellular resolutions and across hundreds of cells comprising a tissue. This means that it is now possible to spatially-temporally characterize the changes that take place in the mechanical properties of cell walls during development, enabling these changes to be correlated with growth and differentiation. This represents a key step to understand how coordinated microscopic cellular changes bring about macroscopic morphogenetic events.However, several limitations remain: the method can only be used on fairly small samples (around 100 µm in diameter) and only on external tissues; the method is sensitive to tissue topography; it measures only certain aspects of the tissue’s complex mechanical properties. The technique is being developed rapidly and it is likely that most of these limitations will be resolved in the near future. 相似文献
38.
Corchero JL Mendoza R Lorenzo J Rodríguez-Sureda V Domínguez C Vázquez E Ferrer-Miralles N Villaverde A 《Biotechnology progress》2011,27(5):1206-1217
Successful production of recombinant proteins (r-proteins) by transient gene expression (TGE) depends on several parameters (including producer cells, culture conditions, transfection procedure, or expression vector) that should be optimized when producing any recombinant product. In this work, TGE-based production of human α-galactosidase A (GLA) is described. Producer cells, expression vectors, and parameters influencing cell metabolism after transfection have been tested. The enzyme is secreted, has the right molecular weight, and is enzymatically active. Productivities of up to 30-40 mg/L have been achieved, with a simple, fast procedure. A 6 × His tag allows enzyme purification in a single step, rendering a highly pure product. We propose a TGE-based protocol able to produce up to several milligrams per liter of highly pure, active GLA in a time as short as a few days. By this, enough amounts of engineered versions of the enzyme can be easily produced to be tested in vitro or in preclinical trials. 相似文献
39.
Abdallah Atia Ahmed Debez Zouhaier Barhoumi Abderrazak Smaoui Chedly Abdelly 《Comptes rendus biologies》2009,332(8):704-710
Impaired germination is common among halophyte seeds exposed to salt stress, partly resulting from the salt-induced reduction of the growth regulator contents in seeds. Thus, the understanding of hormonal regulation during the germination process is a main key: (i) to overcome the mechanisms by which NaCl-salinity inhibit germination; and (ii) to improve the germination of these species when challenged with NaCl. In the present investigation, the effects of ABA, GA3, NO−3, and NH+4 on the germination of the oilseed halophyte Crithmum maritimum (Apiaceae) were assessed under NaCl-salinity (up to 200 mM NaCl). Seeds were collected from Tabarka rocky coasts (N-W of Tunisia). The exogenous application of GA3, nitrate (either as NaNO3 or KNO3), and NH4Cl enhanced germination under NaCl salinity. The beneficial impact of KNO3 on germination upon seed exposure to NaCl salinity was rather due to NO−3 than to K+, since KCl failed to significantly stimulate germination. Under optimal conditions for germination (0 mM NaCl), ABA inhibited germination over time in a dose dependent manner, but KNO3 completely restored the germination parameters. Under NaCl salinity, the application of fluridone (FLU) an inhibitor of ABA biosynthesis, stimulated substantially seed germination. Taken together, our results point out that NO−3 and GA3 mitigate the NaCl-induced reduction of seed germination, and that NO−3 counteracts the inhibitory effect of ABA on germination of C. maritimum. To cite this article: A. Atia et al., C. R. Biologies 332 (2009). 相似文献
40.
Kuei‐Hua Chang Yolanda De Pablo Hyun‐pil Lee Hyoung‐gon Lee Mark A. Smith Kavita Shah 《Journal of neurochemistry》2010,113(5):1221-1229