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41.
In this study, we assessed the importance of cytoskeleton organization in the mammalian cells used to produce therapeutic proteins. Two cytoskeletal genes, Actin alpha cardiac muscle 1 (ACTC1) and a guanosine triphosphate GTPase-activating protein (TAGAP), were found to be upregulated in highly productive therapeutic protein-expressing Chinese hamster ovary (CHO) cells selected by the deprivation of vitamin B5. We report here that the overexpression of the ACTC1 protein was able to improve significantly recombinant therapeutic production, as well as to decrease the levels of toxic lactate metabolic by-products. ACTC1 overexpression was accompanied by altered as well as decreased polymerized actin, which was associated with high protein production by CHO cell cultured in suspension. We suggest that the depolymerization of actin and the possible modulation of integrin signaling, as well as changes in basal metabolism, may be driving the increase of protein secretion by CHO cells.  相似文献   
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Explaining the evolution of cooperation among non-relatives is one of the major challenges for evolutionary biology. In this study, we experimentally examined human cooperation in the iterated Snowdrift game (ISD), which has received little attention so far, and compared it with human cooperation in the iterated Prisoner's Dilemma (IPD), which has become the paradigm for the evolution of cooperation. We show that iteration in the ISD leads to consistently higher levels of cooperation than in the IPD. We further demonstrate that the most successful strategies known for the IPD (generous Tit-for-Tat and Pavlov) were also successfully used in the ISD. Interestingly, we found that female players cooperated significantly more often than male players in the IPD but not in the ISD. Moreover, female players in the IPD applied Tit-for-Tat-like or Pavlovian strategies significantly more often than male players, thereby achieving significantly higher pay-offs than male players did. These data demonstrate that the willingness to cooperate does not only depend on the type of the social dilemma, but also on the class of individuals involved. Altogether, our study shows that the ISD can potentially explain high levels of cooperation among non-relatives in humans. In addition, the ISD seems to reflect the social dilemma more realistically than the IPD because individuals obtain immediate direct benefits from the cooperative acts they perform and costs of cooperation are shared between cooperators.  相似文献   
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Conventionally Surface‐enhanced Raman spectroscopy (SERS) is realized by adsorbing analytes onto nano‐roughened planar substrate coated with noble metals (silver or gold) or their colloidal nanoparticles (NPs). Nanoscale irregularities in such substrates/NPs could lead to SERS sensors with poor reproducibility and repeatability. Herein, we demonstrate a suspended core photonic crystal fiber (PCF) based SERS sensor with extremely high reproducibility and repeatability in measurement with a relative SD of only 1.5% and 4.6%, respectively, which makes it more reliable than any existing SERS sensor platforms. In addition, our platform could improve the detection sensitivity owing to the increased interaction area between the guided light and the analyte, which is incorporated into the holes that runs along the length of the PCF. Numerical calculation established the significance of the interplay between light coupling efficiency and evanescent field distribution, which could eventually determine the sensitivity and reliability of the developed SERS active‐PCF sensor. As a proof of concept, using this sensor, we demonstrated the detection of haptoglobin, a biomarker for ovarian cancer, contained within the ovarian cyst fluid, which facilitated in differentiating the stages of cancer. We envision that with necessary refinements, this platform could potentially be translated as a next‐generation highly sensitive SERS‐active opto‐fluidic biopsy needle for the detection of biomarkers in body fluids.  相似文献   
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