PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk

Autophagy, a process in which cellular components are engulfed and degraded within double-membrane vesicles termed autophagosomes, has an important role in the response to oxidative damage. Here we identify a novel cascade of phosphorylation events, involving a network of protein and lipid kinases, as crucial components of the signaling pathways that regulate the induction of autophagy under oxidative stress. Our findings show that both the tumor-suppressor death-associated protein kinase (DAPk) and protein kinase D (PKD), which we previously showed to be phosphorylated and consequently activated by DAPk, mediate the induction of autophagy in response to oxidative damage. Furthermore, we map the position of PKD within the autophagic network to Vps34, a lipid kinase whose function is indispensable for autophagy, and demonstrate that PKD is found in the same molecular complex with Vps34. PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate (PI(3)P) formation, and autophagosome formation. Consistent with its identification as a novel inducer of the autophagic machinery, we show that PKD is recruited to LC3-positive autophagosomes, where it localizes specifically to the autophagosomal membranes. Taken together, our results describe PKD as a novel Vps34 kinase that functions as an effecter of autophagy under oxidative stress

Effective Application of Knowledge Management in Evidence-based Chinese Medicine: A Case Study

Chinese medicine (CM) practice, as a knowledge-based industry, has not embraced knowledge management (KM) techniques widely. However, KM may facilitate the adaptation and promotion of evidence-based CM. A KM framework was introduced to its activities in evidence-based CM through the development of a CM portal. A codification strategy was used to codify and store knowledge systematically in a database. Several approaches were developed and implemented to address specific needs for CM such as centralizing the information, encouraging collective efforts, promoting integration of explicit and tacit knowledge, and developing a flexible technology and support system. Following the established KM framework, the RMIT Chinese Medicine Portal (www.chinese-medicine.com.au) was built up with four major components: organizational knowledge, knowledge workers, KM processes and information technology. Knowledge on Chinese herbs was classified into core, advanced and innovative categories, which involved the development of the monograph template. A working group was organized including CM, pharmacology and information technology professionals to implement this proposal with following sequential development stages: knowledge creation/acquisition, storage/organization, distribution and application. User interface and web language were also defined and accomplished. This case study demonstrates the applicability of KM in evidence-based CM through a multidisciplinary collaboration, such as, an effective collaboration between CM and information technology. The study also shows the potential of KM application in other disciplines of complementary and alternative medicine

Costly third-party interventions: The role of incidental anger and attention focus in punishment of the perpetrator and compensation of the victim

publisher: Elsevier articletitle: Costly third-party interventions: The role of incidental anger and attention focus in punishment of the perpetrator and compensation of the victim journaltitle: Journal of Experimental Social Psychology articlelink: http://dx.doi.org/10.1016/j.jesp.2016.04.004 content_type: article copyright: © 2016 Elsevier Inc. All rights reserved

Más sobre Cervantes, Plutarco y los cínicos: una anécdota de Alcibíades y el Coloquio de los perros

En el marco de la intertextualidad clásica cervantina, se recuerdan primeramente los lazos de Cervantes con Plutarco para después tratar de poner en relación una anécdota de la biografía de Alcibíades (Vidas paralelas) contra la murmuración con la ficción del Coloquio de los perros, con la que comparte una serie de rasgos

Practice patterns of naturopathic physicians: results from a random survey of licensed practitioners in two US States

BACKGROUND: Despite the growing use of complementary and alternative medicine (CAM) by consumers in the U.S., little is known about the practice of CAM providers. The objective of this study was to describe and compare the practice patterns of naturopathic physicians in Washington State and Connecticut. METHODS: Telephone interviews were conducted with state-wide random samples of licensed naturopathic physicians and data were collected on consecutive patient visits in 1998 and 1999. The main outcome measures were: Sociodemographic, training and practice characteristics of naturopathic physicians; and demographics, reasons for visit, types of treatments, payment source and visit duration for patients. RESULT: One hundred and seventy practitioners were interviewed and 99 recorded data on a total of 1817 patient visits. Naturopathic physicians in Washington and Connecticut had similar demographic and practice characteristics. Both the practitioners and their patients were primarily White and female. Almost 75% of all naturopathic visits were for chronic complaints, most frequently fatigue, headache, and back symptoms. Complete blood counts, serum chemistries, lipids panels and stool analyses were ordered for 4% to 10% of visits. All other diagnostic tests were ordered less frequently. The most commonly prescribed naturopathic therapeutics were: botanical medicines (51% of visits in Connecticut, 43% in Washington), vitamins (41% and 43%), minerals (35% and 39%), homeopathy (29% and 19%) and allergy treatments (11% and 13%). The mean visit length was about 40 minutes. Approximately half the visits were paid directly by the patient. CONCLUSION: This study provides information that will help other health care providers, patients and policy makers better understand the nature of naturopathic care

mTOR inhibition increases cell viability via autophagy induction during endoplasmic reticulum stress - An experimental and modeling study

Unfolded or misfolded proteins in the endoplasmic reticulum (ER) trigger an adaptive ER stress response known as unfolded protein response (UPR). Depending on the severity of ER stress, either autophagy-controlled survival or apoptotic cell death can be induced. The molecular mechanisms by which UPR controls multiple fate decisions have started to emerge. One such molecular mechanism involves a master regulator of cell growth, mammalian target of rapamycin (mTOR), which paradoxically is shown to have pro-apoptotic role by mutually interacting with ER stress response. How the interconnections between UPR and mTOR influence the dynamics of autophagy and apoptosis activation is still unclear. Here we make an attempt to explore this problem by using experiments and mathematical modeling. The effect of perturbed mTOR activity in ER stressed cells was studied on autophagy and cell viability by using agents causing mTOR pathway inhibition (such as rapamycin or metyrapone). We observed that mTOR inhibition led to an increase in cell viability and was accompanied by an increase in autophagic activity. It was also shown that autophagy was activated under conditions of severe ER stress but that in the latter phase of stress it was inhibited at the time of apoptosis activation. Our mathematical model shows that both the activation threshold and temporal dynamics of autophagy and apoptosis inducers are sensitive to variation in mTOR activity. These results confirm that autophagy has cytoprotective role and is activated in mutually exclusive manner with respect to ER stress levels

Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes

Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis and autophagy. We present the 4.4 Å crystal structure of the 385 kDa endosomal complex II (PIK3C3-CII), consisting of Vps34, Vps15 (p150), Vps30/Atg6 (Beclin 1) and Vps38 (UVRAG). The subunits form a Y-shaped complex, centered on the Vps34 C2 domain. Vps34 and Vps15 intertwine in one arm where the Vps15 kinase domain engages the Vps34 activation loop to regulate its activity. Vps30 and Vps38 form the other arm that brackets the Vps15/Vps34 heterodimer, suggesting a path for complex assembly. Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) revealed conformational changes accompanying membrane binding and identified a Vps30 loop that is critical for the ability of complex II to phosphorylate giant liposomes on which complex I is inactive

Generalising tree traversals and tree transformations to DAGs:Exploiting sharing without the pain

We present a recursion scheme based on attribute grammars that can be transparently applied to trees and acyclic graphs. Our recursion scheme allows the programmer to implement a tree traversal or a tree transformation and then apply it to compact graph representations of trees instead. The resulting graph traversal or graph transformation avoids recomputation of intermediate results for shared nodes – even if intermediate results are used in different contexts. Consequently, this approach leads to asymptotic speedup proportional to the compression provided by the graph representation. In general, however, this sharing of intermediate results is not sound. Therefore, we complement our implementation of the recursion scheme with a number of correspondence theorems that ensure soundness for various classes of traversals. We illustrate the practical applicability of the implementation as well as the complementing theory with a number of examples

Post‐translationally‐modified structures in the autophagy machinery: an integrative perspective

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113777/1/febs13356_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113777/2/febs13356.pd