iMedical Hypotheses, Vol. 71, No. 6. (December 2008), pp. 839-850./ibr /br /Cancer is usually considered to be a by-product of design limitations of a multicellular organism and its intrinsic fallibility. However, recent data prompt a revision of some established notions about carcinogenesis and form a new paradigm of carcinogenesis as a highly conserved biological phenomenon – a programmed death of an organism. This altruistic program, which is unleashed when mutagenesis surpasses a certain critical threshold, gives a population the important benefit acting as a guardian of the gene pool against the spread of certain mutant genes. A growing body of evidence supports this point of view: (i) epigenetic changes leading to cancer arise early, simultaneously in many cells and look like deterministic regulation; (ii) concept of cancer stem cell suggests a view of carcinogenesis not as vague transformation but as well known differentiation; (iii) tumor/host relations usually perceived as antagonistic are, in reality, synergistic; (iv) death of an individual from cancer is predetermined and results apparently from a specific activity (killer function) of cancer cell and (v) evolutionary conservation indicates that cancer comes with a general advantage that explains its evolutionary success. A holistic approach to carcinogenesis suggests new avenues of research and new therapeutic strategy.

Publication Date: 2008 Nov 19 PMID: 19020048br/Authors: McGraw, H. F. - Nechiporuk, A. - Raible, D. W.br/Journal: J Neuroscibr/br/The proneural transcription factor neurogenin 1 (neurog1) has been shown to be a key regulator of dorsal root ganglion (DRG) neuron development. Here we use a novel transgenic zebrafish line to demonstrate that the neural crest population that gives rise to DRG neurons becomes fate restricted to a neuronal/glial precursor before the onset of neurog1 function. We generated a stable transgenic zebrafish line that carries a modified bacterial artificial chromosome that expresses green fluorescent protein (GFP) under the control of the neurog1 promoter [Tg(neurog1:EGFP)]. In contrast to previously described neurog1 transgenic lines, Tg(neurog1:EGFP) expresses GFP in DRG neuronal precursors cells as they migrate ventrally and after their initial differentiation as neurons. Using this line, we are able to track the fate of DRG neuronal precursor cells during their specification. When Neurog1 function is blocked, either by neurog1 morpholino antisense oligonucleotide injection or in neurog1 mutants, GFP expression initiates in neural crest cells, although they fail to form DRG neurons. Rather, these cells take on a glial-like morphology, retain proliferative capacity, and express glial markers and become associated with the ventral motor root. These results suggest that, within the zebrafish neural crest, there is a fate-restricted lineage that is limited to form either sensory neurons or glia in the developing DRG. Neurog1 acts as the key factor in this lineage to direct the formation of sensory neurons.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19020048title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 19 PMID: 19020039br/Authors: Zhu, G. - Okada, M. - Yoshida, S. - Ueno, S. - Mori, F. - Takahara, T. - Saito, R. - Miura, Y. - Kishi, A. - Tomiyama, M. - Sato, A. - Kojima, T. - Fukuma, G. - Wakabayashi, K. - Hase, K. - Ohno, H. - Kijima, H. - Takano, Y. - Mitsudome, A. - Kaneko, S. - Hirose, S.br/Journal: J Neuroscibr/br/Mutations of genes encoding alpha4, beta2, or alpha2 subunits (CHRNA4, CHRNB2, or CHRNA2, respectively) of nAChR [neuronal nicotinic ACh (acetylcholine) receptor] cause nocturnal frontal lobe epilepsy (NFLE) in human. NFLE-related seizures are seen exclusively during sleep and are characterized by three distinct seizure phenotypes: paroxysmal arousals, paroxysmal dystonia, and episodic wandering. We generated transgenic rat strains that harbor a missense mutation S284L, which had been identified in CHRNA4 in NFLE. The transgenic rats were free of biological abnormalities, such as dysmorphology in the CNS, and behavioral abnormalities. The mRNA level of the transgene (mutant Chrna4) was similar to the wild type, and no distorted expression was detected in the brain. However, the transgenic rats showed epileptic seizure phenotypes during slow-wave sleep (SWS) similar to those in NFLE exhibiting three characteristic seizure phenotypes and thus fulfilled the diagnostic criteria of human NFLE. The therapeutic response of these rats to conventional antiepileptic drugs also resembled that of NFLE patients with the S284L mutation. The rats exhibited two major abnormalities in neurotransmission: (1) attenuation of synaptic and extrasynaptic GABAergic transmission and (2) abnormal glutamate release during SWS. The currently available genetically engineered animal models of epilepsy are limited to mice; thus, our transgenic rats offer another dimension to the epilepsy research field.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19020039title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 19 PMID: 19020038br/Authors: Reiterer, V. - Maier, S. - Sitte, H. H. - Kriz, A. - Ruegg, M. A. - Hauri, H. P. - Freissmuth, M. - Farhan, H.br/Journal: J Neuroscibr/br/The GABA transporter-1 (GAT1) is a prototypical protein of the synaptic specialization. Export of GAT1 from the endoplasmic reticulum (ER) is contingent on its interaction with the COPII (coatomer protein-II) coat subunit Sec24D. Here we show that silencing all four Sec24 isoforms strongly inhibits transport of GAT1 to the cell surface. In contrast, transport of GAT1-RL/AS, a mutant that is deficient in Sec24D recruitment, was not inhibited, suggesting a nonconventional, COPII-independent pathway. However, ARFGAP1 bound directly to the C terminus of both GAT1-RL/AS and wild-type GAT1. Surface expression of GAT1-RL/AS involved ARFGAP1. GAT1-RL/AS appeared to bypass the ER-Golgi-intermediate compartment, but its pathway to the plasma membrane still involved passage through the Golgi. Thus, the GAT1-RL/AS mutant allowed to test whether COPII-dependent ER-export is required for correct sorting of GAT1 to the axon terminal in neuronal cells. In contrast to wild-type GAT1, GAT1-RL/AS failed to be specifically enriched at the tip of neurite extensions of CAD.a cells (a neuroblastoma cell line that can be differentiated into a neuron-like phenotype) and in the axon terminals of hippocampal neurons. These findings indicate that correct sorting to the axon is contingent on ER export via the COPII machinery and passage through the ER-Golgi-intermediate compartment.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19020038title=Entrez+PubmedCiteULike/a

Newly released today



features
Co-op redefined: This new action title from Valve, creators of the Counter-Strike and Half-Life games, promises to redefine the co-operative genre as those titles did for multiplayer and single player action games.
A.I. technology: The advanced artificial intelligence drives both friendly and unfriendly creatures to dynamically create intense single-player, co-op, and multiplayer experiences every time the game is played.
Expansive environments: Battle across twenty different maps with ten distinct weapons across four sprawling campaigns.
Online matchmaking: The matchmaking, stats, rankings, and awards system drive collaborative play.
Designer's Commentary mode: Activate this mode for a unique "behind the scenes" look at the development of the game.

description
Set in a modern day survival-horror universe, the co-operative gameplay of Left 4 Dead™ casts four "Survivors" in an epic struggle against hordes of swarming zombies and terrifying "Boss Infected" mutants.

The Survivor Co-op Game Mode is played out across four sprawling campaigns, set in urban and rural environments. The team of four Survivors may be comprised of one to four human players, allowing for single player and multiplayer co-op games.

The next-generation A.I. technology of all non-player Survivor and zombie characters is a pool of systems used to procedurally generate a unique experience by monitoring the players' experiences and tailoring the pacing and difficulty of action for each game. This makes for a different experience each time the game is played.

In the Left 4 Dead Vs. Mode, play as a Survivor or as one of four types of "Boss Infected." Each of the "Boss Infected" possesses an exceptional mutant ability -- such as a 50-foot tongue lasso or a giant belly full of explosive methane gas -- instead of traditional firearms.

http://www.play-asia.com/SOap-23-83-...j-70-23dt.html