Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34

Excess levels of circulating amino acids (AAs) play a causal role in specific human pathologies, including obesity and type 2 diabetes. Moreover, obesity and diabetes are contributing factors in the development of cancer, with recent studies suggesting that this link is mediated in part by AA activation of mammalian target of rapamycin (mTOR) Complex 1. AAs appear to mediate this response through class III phosphatidylinositol 3-kinase (PI3K), or human vacuolar protein sorting 34 (hVps34), rather than through the canonical class I PI3K pathway used by growth factors and hormones. Here we show that AAs induce a rise in intracellular Ca²⁺ ([Ca²⁺]_i), which triggers mTOR Complex 1 and hVps34 activation. We demonstrate that the rise in [Ca²⁺]_i increases the direct binding of Ca²⁺/calmodulin (CaM) to an evolutionarily conserved motif in hVps34 that is required for lipid kinase activity and increased mTOR Complex 1 signaling. These findings have important implications regarding the basic signaling mechanisms linking metabolic disorders with cancer progression.     

Idiopathic chronic diarrhea associated with dysbiosis in a captive cynomolgus macaque (Macaca fascicularis)

Chronic inflammatory enteric diseases occur commonly in humans and animals, especially in captive bred macaques. However, information about the etiology of idiopathic chronic inflammatory diarrhea in cynomolgus monkeys is limited. In this paper, we reported the unusual case of idiopathic chronic diarrhea in a captive cynomolgus monkey based on microbial, imaging, and microbiome examinations.     

Facile nitroxide-mediated oxidations of D-glucose to D-glucaric acid.

The oxidation of D-(+)-glucose to D-glucaric acid using the TEMPO-like nitroxide oxidation catalyst, 4-acetamido-2,2,6,6-tetramethyl-1-piperidinyloxy (4-acetamido-TEMPO) was carried out using several oxidizing agents and co-catalyst. The pH and temperature of the reactions were closely monitored to decrease degradations during the oxidation, and several isolation methods were explored.     

In vitro study of the effects of ELF electric fields on gene expression in human epidermal cells

An acceleration of differentiation, at the expense of proliferation, is observed after exposure of various biological models to low frequency and low amplitude electric and electromagnetic fields. Following these results showing significant modifications, we try to identify the biological mechanism involved at the cell level through microarray screening. For this study, we use epidermis cultures harvested from human abdominoplasty. Two platinum electrodes are used to apply the electric signal. The gene expressions of 38,500 well‐characterized human genes are analyzed using Affymetrix® microarray U133 Plus 2.0 chips. The protocol is repeated on three different patients. After three periods of exposure, a total of 24 chips have been processed. After the application of ELF electric fields, the microarray analysis confirms a modification of the gene expression of epidermis cells. Particularly, four up‐regulated genes (DKK1, TXNRD1, ATF3, and MME) and one down‐regulated gene (MACF1) are involved in the regulation of proliferation and differentiation. Expression of these five genes was also confirmed by real‐time rtPCR in all samples used for microarray analysis. These results corroborate an acceleration of cell differentiation at the expense of cell proliferation. Bioelectromagnetics 32:28–36, 2011. © 2010 Wiley‐Liss, Inc.     

Magical Flight and Monstrous Stress: Technologies of Absorption and Mental Wellness in Azeroth

Videogame players commonly report reaching deeply “immersive” states of consciousness, in some cases growing to feel like they actually are their characters and really in the game, with such fantastic characters and places potentially only loosely connected to offline selves and realities. In the current investigation, we use interview and survey data to examine the effects of such “dissociative” experiences on players of the popular online videogame, World of Warcraft (WoW). Of particular interest are ways in which WoW players’ emotional identification with in-game second selves can lead either to better mental well-being, through relaxation and satisfying positive stress, or, alternatively, to risky addiction-like experiences. Combining universalizing and context-dependent perspectives, we suggest that WoW and similar games can be thought of as new “technologies of absorption”—contemporary practices that can induce dissociative states in which players attribute dimensions of self and experience to in-game characters, with potential psychological benefit or harm. We present our research as an empirically grounded exploration of the mental health benefits and risks associated with dissociation in common everyday contexts. We believe that studies such as ours may enrich existing theories of the health dynamics of dissociation, relying, as they often do, on data drawn either from Western clinical contexts involving pathological disintegrated personality disorders or from non-Western ethnographic contexts involving spiritual trance.     

Adult neurogenesis: examples from the decapod crustaceans and comparisons with mammals

Defining evolutionary origins is a means of understanding an organism's position within the integrated web of living beings, and not only to trace characteristics back in time, but also to project forward in an attempt to reveal relationships with more recently evolved forms. Both the vertebrates and arthropods possess condensed nervous systems, but this is dorsal in the vertebrates and ventral in the arthropods. Also, whereas the nervous system in the vertebrates develops from a neural tube in the embryo, that of the arthropods comes from an ectodermal plate. Despite these apparently fundamental differences, it is now generally accepted that life-long neurogenesis, the generation of functionally integrated neurons from progenitor cells, is a common feature of the adult brains of a variety of organisms, ranging from insects and crustaceans to birds and mammals. Among decapod crustaceans, there is evidence for adult neurogenesis in basal species of the Dendrobranchiata, as well as in more recent terrestrial, marine and fresh-water species. The widespread nature of this phenomenon in decapod species may relate to the importance of the adult-born neurons, although their functional contribution is not yet known. The many similarities between the systems generating neurons in the adult brains of decapod crustaceans and mammals, reviewed in this paper, suggest that adult neurogenesis is governed by common ancestral mechanisms that have been retained in a phylogenetically broad group of species.