Allenpilgaard1863

Traditional teaching and assessment of clinical reasoning has focused on the individual clinician because of the preeminence of the information processing (IP) theory perspective. The clinician's mind has been viewed as the main source of effective or ineffective reasoning, and other participants, the environment and their interactions have been largely ignored. A social cognitive theoretical lens could enhance our understanding of how reasoning and error and the environment are linked. Therefore, a new approach in which the clinical reasoning process is situated and examined within the context may be required. The theories of embodied cognition, ecological psychology, situated cognition (SitCog) and distributed cognition (DCog) offer new insights to help the teacher and assessor enhance the quality of clinical reasoning instruction and assessment. We describe the teaching and assessment implications of clinical reasoning and error through the lens of this family of theories. Direct observation in different contexts focused on individual and team performance, simulation (with or without enhancement of technology), stimulated recall, think-aloud, and modeling are examples of teaching and assessment strategies grounded in this family of social cognitive theories. Educators may consider the instructional design of learning environments and educational tools that promote a situated educational approach to the teaching and assessment of clinical reasoning.Increasing evidences suggested that insufficient radiofrequency ablation (IRFA) can paradoxically promote tumor invasion and metastatic processes, while the effects of moderate hyperthermia on cancer progression are not well illustrated. Our study found that IRFA can increase the in vitro migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells via induction of Snail, a master regulator of EMT events. Among measured miRNAs, IRFA can decrease the expression of miR-148a-5p in HCC cells. While over expression of miR-148a-5p can reverse IRFA induced migration of HCC cells and upregulation of Snail. Mechanistically, over expression of miR-148a-5p can directly target and decrease the expression of protein kinase ATM (ataxia telangiectasia mutated), which can increase protein stability of Snail. Collectively, our data suggested that IRFA can regulate the miR-148a-5p/ATM/Snail axis to trigger migration of HCC cells.The respiratory pathway of mitochondria is composed of four electron transfer complexes and the ATP synthase. In this article we review evidence from studies of Saccharomyces cerevisiae that both ATP synthase and cytochrome oxidase (COX) are assembled from independent modules that correspond to structurally and functionally identifiable components of each complex. Biogenesis of the respiratory chain requires a coordinate and balanced expression of gene products that become partner subunits of the same complex, but are encoded in the two physically separated genomes. Current evidence indicates that synthesis of two key mitochondrial encoded subunits of ATP synthase is regulated by the F1 module. Expression of COX1 that codes for a subunit of the COX catalytic core, is also regulated by a mechanism that restricts synthesis of this subunit to the availability of a nuclear-encoded translational activator. The respiratory chain must maintain a fixed stoichiometry of the component enzyme complexes during cell growth. We propose that high molecular weight complexes composed of Cox6, a subunit of cytochrome oxidase, and of the Atp9 subunit of ATP synthase, play a key role in establishing the ratio of the two complexes during their assembly.Mitochondrial protein import is one of the key processes during mitochondrial biogenesis that involves a series of events necessary for recognition and delivery of nucleus-encoded/cytosolsynthesized mitochondrial proteins into the organelle. The past research efforts have mainly unraveled how membrane translocases ensure the correct protein sorting within the different mitochondrial subcompartments. However, early steps of recognition and delivery remain relatively uncharacterized. In this review we discuss our current understanding about the signals on mitochondrial proteins as well as in the mRNAs encoding them, that with the help of cytosolic chaperones and membrane receptors, support protein targeting to the organelle in order to avoid improper localization. In addition, we discuss recent findings that illustrate how mistargeting of mitochondrial proteins triggers stress responses, aiming to restore cellular homeostasis.The proteome of the mitochondrial intermembrane space (IMS) contains more than 100 proteins, all of which are synthesized on cytosolic ribosomes and consequently need to be imported by dedicated machineries. The mitochondrial disulfide relay is the major import machinery for soluble proteins in the IMS. Its major component, the oxidoreductase MIA40, interacts with incoming substrates, retains them in the IMS and oxidatively folds them. After this reaction, MIA40 is reoxidized by the sulfhydryl oxidase ALR, which couples disulfide formation by this machinery to the activity of the respiratory chain. In this review, we will discuss the import of IMS proteins with a focus on recent findings showing the diversity of disulfide relay substrates, describing the cytosolic control of this import system and highlighting the physiological relevance of the disulfide relay machinery in higher eukaryotes.Biogenesis of mitochondria relies on import of more than 1000 different proteins from the cytosol. Approximately 70% of these proteins follow the presequence pathway - they are synthesized with cleavable N-terminal extensions called presequences and reach the final place of their function within the organelle with the help of the TOM and TIM23 complexes in the outer and inner membranes, respectively. The translocation of proteins along the presequence pathway is powered by the import motor of the TIM23 complex. The import motor of the TIM23 complex is localized at the matrix face of the inner membrane and is likely the most complicated Hsp70-based system identified to date. How it converts the energy of ATP hydrolysis into unidirectional translocation of proteins into mitochondria remains one of the biggest mysteries of this translocation pathway. Sodium L-lactate Here, the knowns and the unknowns of the mitochondrial protein import motor are discussed.