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951.
Translational research using evidence-based and comparative effectiveness research continues to evolve, becoming a useful tool in improving informed
consent and decision-making in the clinical setting. While in development, emerging technologies, including cellular and molecular biology, are leading to
establishing evidence-based dental practices. One emerging technology, which conjoins bench proteomic findings to clinical decision-making for
treatment intervention, is the Translational Evidence Mechanism. This mechanism was developed to be a foundation for a compact between researcher,
translational researcher, clinician, and patient. The output of such a mechanism is the clinical practice guideline (CPG), an interactive tool for dentists and
patients to game evidence in reaching optimum clinical decisions that correspond to individual patient preferences and values. As such, the clinical
practice guideline requires the vesting of decision, utility, and cost best evidence. Evidence-based research provides decision data, a first attempt at
supporting decision-making by providing best outcome data. Since then comparative effectiveness research has emerged, using systematic review analysis
to compare similar treatments or procedures in maximizing the choice of the most effective cost/benefit option within the context of best evidence. With
innovation in the clinical practice guideline for optimizing efficacy and comparative effectiveness research, evidence-based practices will shape a new
approach to health-based systems that adhere to shared decision-making between bench scientists, healthcare providers and patients. 相似文献
952.
Carla Carluccio Francesco Salvatore Arianna Fornili 《Journal of biomolecular structure & dynamics》2016,34(3):497-507
The enzyme phenylalanine hydroxylase (PAH) is defective in the inherited disorder phenylketonuria. PAH, a tetrameric enzyme, is highly regulated and displays positive cooperativity for its substrate, Phe. Whether Phe binds to an allosteric site is a matter of debate, despite several studies worldwide. To address this issue, we generated a dimeric model for Phe–PAH interactions, by performing molecular docking combined with molecular dynamics simulations on human and rat wild-type sequences and also on a human G46S mutant. Our results suggest that the allosteric Phe-binding site lies at the dimeric interface between the regulatory and the catalytic domains of two adjacent subunits. The structural and dynamical features of the site were characterized in depth and described. Interestingly, our findings provide evidence for lower allosteric Phe-binding ability of the G46S mutant than the human wild-type enzyme. This also explains the disease-causing nature of this mutant. 相似文献
953.
954.
Tight control of mRNA expression is required for cell differentiation; imbalanced regulation may lead to developmental disorders and cancer. The activity of the translational machinery (including ribosomes and translation factors) regulates the rate (slow or fast) of translation of encoded proteins, and the quality of these proteins highly depends on which mRNAs are available for translation. Specific RNA-binding and ribosomal proteins seem to play a key role in controlling gene expression to determine the differentiation fate of the cell. This demonstrates the important role of RNA-binding proteins, specific ribosome-binding proteins and microRNAs as key molecules in controlling the specific proteins required for the differentiation or dedifferentiation of cells. This delicate balance between specific proteins (in terms of quality and availability) and post-translational modifications occurring in the cytoplasm is crucial for cell differentiation, dedifferentiation and oncogenic potential. In this review, we report how defects in the regulation of mRNA translation can be dependent on specific proteins and can induce an imbalance between differentiation and dedifferentiation in cell fate determination. 相似文献
955.
Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. 相似文献
956.
957.
Jesús Olivero John E. Fa Miguel A. Farfán Jerome Lewis Barry Hewlett Thomas Breuer Giuseppe M. Carpaneto María Fernández Francesco Germi Shiho Hattori Josephine Head Mitsuo Ichikawa Koichi Kitanaishi Jessica Knights Naoki Matsuura Andrea Migliano Barbara Nese Andrew Noss Dieudonné Ongbwa Ekoumou Pascale Paulin Raimundo Real Mike Riddell Edward G. J. Stevenson Mikako Toda J. Mario Vargas Hirokazu Yasuoka Robert Nasi 《PloS one》2016,11(1)
Pygmy populations occupy a vast territory extending west-to-east along the central African belt from the Congo Basin to Lake Victoria. However, their numbers and actual distribution is not known precisely. Here, we undertake this task by using locational data and population sizes for an unprecedented number of known Pygmy camps and settlements (n = 654) in five of the nine countries where currently distributed. With these data we develop spatial distribution models based on the favourability function, which distinguish areas with favourable environmental conditions from those less suitable for Pygmy presence. Highly favourable areas were significantly explained by presence of tropical forests, and by lower human pressure variables. For documented Pygmy settlements, we use the relationship between observed population sizes and predicted favourability values to estimate the total Pygmy population throughout Central Africa. We estimate that around 920,000 Pygmies (over 60% in DRC) is possible within favourable forest areas in Central Africa. We argue that fragmentation of the existing Pygmy populations, alongside pressure from extractive industries and sometimes conflict with conservation areas, endanger their future. There is an urgent need to inform policies that can mitigate against future external threats to these indigenous peoples’ culture and lifestyles. 相似文献
958.
959.
Luca Valzania Patrizia Romani Ling Tian Sheng Li Valeria Cavaliere Francesco Pennacchio Giuseppe Gargiulo 《PloS one》2014,9(4)
Polydnaviruses are obligate symbionts integrated as proviruses in the genome of some ichneumonoid wasps that parasitize lepidopteran larvae. Polydnavirus free viral particles, which are injected into the host at oviposition, express virulence factors that impair immunity and development. To date, most studies have focused on the molecular mechanisms underpinning immunosuppression, whereas how viral genes disrupt the endocrine balance remains largely uninvestigated. Using Drosophila as a model system, the present report analyzes the function of a member of the ankyrin gene family of the bracovirus associated with Toxoneuron nigriceps, a larval parasitoid of the noctuid moth Heliothis virescens. We found that the TnBVank1 expression in the Drosophila prothoracic gland blocks the larval-pupal molt. This phenotype can be rescued by feeding the larvae with 20-hydroxyecdysone. The localization of the TnBVANK1 is restricted to the cytoplasm where it interacts with Hrs and Alix marked endosomes. Collectively, our data demonstrate that the TnBVANK1 protein acts as a virulence factor that causes the disruption of ecdysone biosynthesis and developmental arrest by impairing the vesicular traffic of ecdysteroid precursors in the prothoracic gland steroidogenic cells. 相似文献
960.