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Various Targets (various + target)
Selected AbstractsTranscriptional regulation of nonfermentable carbon utilization in budding yeastFEMS YEAST RESEARCH, Issue 1 2010Bernard Turcotte Abstract Saccharomyces cerevisiae preferentially uses glucose as a carbon source, but following its depletion, it can utilize a wide variety of other carbons including nonfermentable compounds such as ethanol. A shift to a nonfermentable carbon source results in massive reprogramming of gene expression including genes involved in gluconeogenesis, the glyoxylate cycle, and the tricarboxylic acid cycle. This review is aimed at describing the recent progress made toward understanding the mechanism of transcriptional regulation of genes responsible for utilization of nonfermentable carbon sources. A central player for the use of nonfermentable carbons is the Snf1 kinase, which becomes activated under low glucose levels. Snf1 phosphorylates various targets including the transcriptional repressor Mig1, resulting in its inactivation allowing derepression of gene expression. For example, the expression of CAT8, encoding a member of the zinc cluster family of transcriptional regulators, is then no longer repressed by Mig1. Cat8 becomes activated through phosphorylation by Snf1, allowing upregulation of the zinc cluster gene SIP4. These regulators control the expression of various genes including those involved in gluconeogenesis. Recent data show that another zinc cluster protein, Rds2, plays a key role in regulating genes involved in gluconeogenesis and the glyoxylate pathway. Finally, the role of additional regulators such as Adr1, Ert1, Oaf1, and Pip2 is also discussed. [source] Structural basis of target recognition by Atg8/LC3 during selective autophagyGENES TO CELLS, Issue 12 2008Nobuo N. Noda Autophagy is a non-selective bulk degradation process in which isolation membranes enclose a portion of cytoplasm to form double-membrane vesicles, called autophagosomes, and deliver their inner constituents to the lytic compartments. Recent studies have also shed light on another mode of autophagy that selectively degrades various targets. Yeast Atg8 and its mammalian homologue LC3 are ubiquitin-like modifiers that are localized on isolation membranes and play crucial roles in the formation of autophagosomes. These proteins are also involved in selective incorporation of specific cargo molecules into autophagosomes, in which Atg8 and LC3 interact with Atg19 and p62, receptor proteins for vacuolar enzymes and disease-related protein aggregates, respectively. Using X-ray crystallography and NMR, we herein report the structural basis for Atg8,Atg19 and LC3,p62 interactions. Remarkably, Atg8 and LC3 were shown to interact with Atg19 and p62, respectively, in a quite similar manner: they recognized the side-chains of Trp and Leu in a four-amino acid motif, WXXL, in Atg19 and p62 using hydrophobic pockets conserved among Atg8 homologues. Together with mutational analyses, our results show the fundamental mechanism that allows Atg8 homologues, in association with WXXL-containing proteins, to capture specific cargo molecules, thereby endowing isolation membranes and/or their assembly machineries with target selectivity. [source] Immune response inspired spatial,temporal target detection algorithms with CNN-UMINTERNATIONAL JOURNAL OF CIRCUIT THEORY AND APPLICATIONS, Issue 1 2006György Cserey Abstract In this paper we show that, similar to the nervous system and the genetic system, the immune system provides a prototype for a ,computing mechanism.' We are presenting an immune response inspired algorithmic framework for spatial,temporal target detection applications using CNN technology (IEEE Trans. Circuits Syst. II 1993; 40(3):163,173; Foundations and Applications. Cambridge University Press: Cambridge, 2002). Unlike most analogic CNN algorithms (IEEE Trans. Circuits Syst. 1988; 35(10):1257,1290; Foundations and Applications. Cambridge University Press: Cambridge, 2002) here we will detect various targets by using a plethora of templates. These algorithms can be implemented successfully only by using a computer upon which thousands of elementary, fully parallel spatial,temporal actions can be implemented in real time. In our tests the results show a statistically complete success rate, and we are presenting a special example of recognizing dynamic objects. Results from tests in a 3D virtual world with different terrain textures are also reported to demonstrate that the system can detect unknown patterns and dynamical changes in image sequences. Applications of the system include in explorer systems for terrain surveillance. Copyright © 2006 John Wiley & Sons, Ltd. [source] Disease modifying therapy for AD?,JOURNAL OF NEUROCHEMISTRY, Issue 3 2006Todd E. Golde Alzheimer's disease (AD) is the most common form of dementia in industrialized nations. If more effective therapies are not developed that either prevent AD or block progression of the disease in its very early stages, the economic and societal cost of caring for AD patients will be devastating. Only two types of drugs are currently approved for the treatment of AD: inhibitors of acetyl cholinesterase, which symptomatically enhance cognitive state to some degree but are not disease modifying; and the adamantane derivative, memantine. Memantine preferentially blocks excessive NMDA receptor activity without disrupting normal receptor activity and is thought to be a neuroprotective agent that blocks excitotoxicty. Memantine therefore may have a potentially disease modifying effect in multiple neurodegenerative conditions. An improved understanding of the pathogeneses of AD has now led to the identification of numerous therapeutic targets designed to alter amyloid , protein (A,) or tau accumulation. Therapies that alter A, and tau through these various targets are likely to have significant disease modifying effects. Many of these targets have been validated in proof of concept studies in preclinical animal models, and some potentially disease modifying therapies targeting A, or tau are being tested in the clinic. This review will highlight both the promise of and the obstacles to developing such disease modifying AD therapies. [source] Front and Back Covers, Volume 24, Number 5.ANTHROPOLOGY TODAY, Issue 5 2008June 200 Front & Back cover caption, volume 24 issue 5 Iron Mike (see back cover) represents a generic soldier at Fort Bragg, one of the world's largest military bases, in Fayetteville, North Carolina. Here he appears to patrol streets under martial law, empty and grey. The Pawn Shop Target Practice (see front cover) is also in Fayetteville. At the back of the shop you can buy guns, bullets, jewellery and more, and also take aim at various targets , images of a woman in a bikini, an anonymous silhouette, a deer. Violence is found in Fayetteville as a symbol of protection, as entertainment, and certainly as a commodity. The absence of living people in these photographs underscores a clinical attitude cultivated in the military towards the largely dehumanized adversary other , a long way from the kind of engagement anthropologists seek through participant-observation. It may well be that the military would benefit from being ,anthropologized'. However, given Keenan's and Besteman's experiences in Africa, as described in this issue, what is the guarantee that the African peoples will actually benefit from militarization at this time of US military expansion? MILITARIZING THE DISCIPLINE? US Secretary of Defense Robert Gates approvingly cites Montgomery McFate: ,I'm frequently accused of militarizing anthropology. But we're really anthropologizing the military'.* This issue of ANTHROPOLOGY TODAY draws attention to the launch of two initiatives in October this year, both of which will have an impact on the peoples we work with and on anthropology as a discipline. The first is the launch of Minerva, a new Pentagon initiative to recruit social scientists for research, for which proposals are due this month. As Catherine Lutz argues in her editorial, this programme may soon outspend civilian funds within our discipline, and will thus undoubtedly influence our research agenda and restrict the public sphere in which we work. If the Pentagon wants high-quality research, why not commission this from reputable and experienced civilian research agencies, who should be able to manage peer review at arm's length from the Pentagon? The second initiative is AFRICOM, the newly unified regional US command for Africa. Although presented benignly as supporting development in Africa, it was originally cast in the security discourse of the global ,war on terror', with the aim of securing North America's oil supplies in Africa. In this issue, Africanist anthropologists Jeremy Keenan and Catherine Besteman criticize AFRICOM's destabilizing and militarizing effect on the regions in which they work, which collapses development into military security. Once deployed to the ends of military securitization, can anthropology remain non-partisan? Alf Hornborg, in his editorial, asks if we can continue to rely on the cornucopia of cheap energy, arguing that military intervention to securitize oil supplies, and academic discourse that mystifies the logic of the global system, benefit only a small minority of the world's population. In the light of developments such as Minerva and AFRICOM, can anthropology continue to offer an independent reflexive ,cultural critique' of the socio-political system from which our discipline has sprung? *Montgomery McFate, quoted by Robert M. Gates (,Nonmilitary work essential for long-term peace, Secretary of Defense says'. Manhattan, Kansas State University, Landon Lecture, 26.11.2007), as cited in Rohde, David, ,Army enlists anthropology in war zones' (New York Times, 05.10.2007). [source] An integrated database of flavonoidsBIOFACTORS, Issue 3 2006Takashi Kinoshita Abstract Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Some of these molecules exhibit various physiological activities. Among existing drugs, there are a huge number of compounds bearing a flavonoid-related skeleton. Because of the relevance for pharmaceutical research, it would be beneficial to collect these compounds into a database. Recently, various databases of chemicals were compiled to help biological and/or chemical research, but no comprehensive database of flavonoids with chemical structures and physicochemical parameters, supposedly related to their activity, is available yet. The aim of this research was to merge the information about flavonoids of plant origin and flavonoids used as medicines into a database. Moreover, predictions of activities against various targets were performed using a virtual screening procedure to demonstrate a possible application of the database for pharmaceutical research. [source] Traditional therapies: glucocorticoids, azathioprine, methotrexate, hydroxyureaCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 7 2002G. Belgi Summary The ,old favourites' used for treatment of inflammatory diseases, and hence, the original immunomodulators, include the glucocorticoids, azathioprine, methotrexate and hydroxyurea. Glucocorticoids are still one of the most effective anti-inflammatory agents because they work on several different intracellular processes and hence, block many components that contribute to inflammatory and immune responses. They bind to intracellular glucocorticoid receptors which transport them into the nucleus. Here the receptor/steroid complex may bind to many genes that interact with transcription factors including NF,B and AP-1, to inhibit their activation, thereby preventing activation of many genes encoding immune effector and pro-inflammatory cytokines. Also, protein kinases involved in intracellular signalling, are directly activated resulting in phosphorylation of various targets of which Annexin (AXA)-1 is critical in inhibiting biosynthesis of both purines and DNA. This results in reduced proliferation of B and T lymphocytes, reduced immune effector mechanisms and reduced recruitment of mononuclear cells including monocytes into sites of immune inflammation. Methotrexate also blocks DNA synthesis and hence cellular proliferation but also induces release of adenosine. This inhibits chemotaxis of polymorph neutrophils and release of critical cytokines such as TNF-, and Interleukins 6 and 8. Hydroxyurea also inhibits DNA synthesis with inhibitory effects on proliferation of lymphocytes and possibly kerationcytes. Even though many new agents with much greater selectivity are coming through into clinical use, this group of old agents still have an absolutely central position in the therapeutic armamentarium. Their value lies in the fact that they are not ,clean' drugs with narrow effects but they inhibit a wide range of mechanisms involved in immune and inflammatory processes. [source] | ||||||||||