Is International Qualified Teacher Status (iQTS) A Solution to the Growing Demand for Teachers Globally?

Is International Qualified Teacher Status (iQTS) A Solution to the Growing Demand for Teachers Globally

On the modulation of the effects of some 5 - HT - related agents in axiety models

The results of an investigation into how stressors interact with the action of serotonergic agents in animal models of anxiety are presented. Water deprivation and restraint both increased plasma corticosterone concentrations and elevated 5-HT turnover. In the elevated X-maze, water deprivation had a duration-dependent "anxiolytic" effect. The effect of restraint was dependent on the duration of restraint and was to inhibit maze exploration. Water-deprivation did not influence the action of diazepam or any 5-HT1A ligand in the X-maze. Restraint switched the "anxiogenic" effect of 8-0H-DPAT to either "anxiolytic" or inactive, depending on the time after the restraint when testing was performed. The Vogel conflict test detected an "anxiolytic" "anxiolytic"V"anxiolytic""anxiolytic" effect of buspirone which was additive with "anxiolytic" effects of pindolol and propranolol. Diazepam and fluoxetine were also active, but 8-0H-DPAT, ipsapirone, gepirone and yohimbine were inactive. In the elevated X-maze, "anxiogenic" responses to picrotoxin, flumazenil, RU 24969, CGS 12066B, fluoxetine and 8-0H-DPAT were detected. Other 5-HT1A ligands were inactive. Diazepam and corticosterone had "anxiolytic" effects. Increasing light intensity did not change behaviour on the elevated X-maze, but was able to reverse the effect of 8- OH-DPAT to an "anxiolytic" action. This effect was attributed to a presynaptic mechanism, because it was abolished by pCPA. The occurence of different behaviours in different reglons of the maze was shown to be susceptible to modulation by "anxiolytic" and "anxiogenic" drugs. These results are discussed in the context of there being at least two separate 5-HT mechanisms which are involved in the control of anxiety

Corporeal ontology: Merleau-Ponty, flesh, and posthumanism

As posthumanism has developed in the last twenty-five years there has been hesitation in elucidating a robust posthumanist engagement with the body. My thesis redresses this gap in the literature in three intertwined ways. First, it is a critical assessment of posthumanism broadly, focusing on how the body is read in its discourse and how there is a continuation of a humanist telos in terms which revolve around the body. Second, it is a philosophical interrogation, adaptation, and transformation of aspects of the work of Maurice Merleau-Ponty, focusing its reading on Phenomenology of Perception and The Visible and the Invisible, with additional material drawn from his works on language, aesthetics, and ontology. Third, it is a critical analysis of four films drawn from that seemingly most posthumanist of genres, science fiction: Cronenberg's eXistenZ, Spielberg's A.I.: Artificial Intelligence, Rusnak's The Thirteenth Floor, and Oshii's Ghost in the Shell. Science fiction is the meeting place of popular and critical posthumanist imaginaries as the vast majority of texts on posthumanism (in whatever form) ground their analyses in a science fiction of some kind. By reading posthumanism through the work of Merleau-Ponty I outline a posthumanist ontology of corporeality which both demonstrates the limitations of how posthumanism has done its analyses of the body and elucidates an opening and levelling not adequately considered in posthumanist analyses of the body. Following Merleau-Ponty I argue that there is a ‘belongingness of the body to being and the corporeal relevance of every being’, yet, the body is not the singular purview of the human. There are alternative embodiments and bodies which have been previously overlooked and that all bodies (be they embodied organically, technologically, virtually or otherwise) are corporeal

Initiation of V(D)J recombination in a cell-free system

Cells performing V(D)J recombination make specific cuts in DNA at recombination signal sequences. Here, we show that nuclear extracts of pre-B cell lines carry out this specific cleavage. The products of cleavage are the same as found previously in thymocytes: full-length, blunt, 5'-phosphorylated signal ends, and covalently sealed (hairpin) coding ends. A complete signal sequence is required. Recombinant RAG1 protein greatly increases activity and complements an inactive extract from a RAG1 (-/-) pre-B cell line. When the extracts are fractionated, cleavage activity correlates with the presence of RAG2 protein. These results suggest that RAG1 and RAG2 are components of the V(D)J recombinase

V(D)J Recombination and the Evolution of the Adaptive Immune System

In order for the immune system to generate its vast numbers of receptors, B- and T-cell receptor genes are created by recombining preexisting gene segments. This well- coordinated set of reactions is explaine

RSSsite: a reference database and prediction tool for the identification of cryptic Recombination Signal Sequences in human and murine genomes

Recombination signal sequences (RSSs) flanking V, D and J gene segments are recognized and cut by the VDJ recombinase during development of B and T lymphocytes. All RSSs are composed of seven conserved nucleotides, followed by a spacer (containing either 12 ± 1 or 23 ± 1 poorly conserved nucleotides) and a conserved nonamer. Errors in V(D)J recombination, including cleavage of cryptic RSS outside the immunoglobulin and T cell receptor loci, are associated with oncogenic translocations observed in some lymphoid malignancies. We present in this paper the RSSsite web server, which is available from the address http://www.itb.cnr.it/rss. RSSsite consists of a web-accessible database, RSSdb, for the identification of pre-computed potential RSSs, and of the related search tool, DnaGrab, which allows the scoring of potential RSSs in user-supplied sequences. This latter algorithm makes use of probability models, which can be recasted to Bayesian network, taking into account correlations between groups of positions of a sequence, developed starting from specific reference sets of RSSs. In validation laboratory experiments, we selected 33 predicted cryptic RSSs (cRSSs) from 11 chromosomal regions outside the immunoglobulin and TCR loci for functional testing

Assessing the Safety of Stem Cell Therapeutics

Unprecedented developments in stem cell research herald a new era of hope and expectation for novel therapies. However, they also present a major challenge for regulators since safety assessment criteria, designed for conventional agents, are largely inappropriate for cell-based therapies. This article aims to set out the safety issues pertaining to novel stem cell-derived treatments, to identify knowledge gaps that require further research, and to suggest a roadmap for developing safety assessment criteria. It is essential that regulators, pharmaceutical providers, and safety scientists work together to frame new safety guidelines, based on “acceptable risk,” so that patients are adequately protected but the safety “bar” is not set so high that exciting new treatments are lost

Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps

Formation of double-strand breaks at recombination signal sequences is an early step in V(D)J recombination. Here we show that purified RAG1 and RAG2 proteins are sufficient to carry out this reaction. The cleavage reaction can be divided into two distinct steps. First, a nick is introduced at the 5' end of the signal sequence. The other strand is then broken, resulting in a hairpin structure at the coding end and a blunt, 5'-phosphorylated signal end. The hairpin is made as a direct consequence of the cleavage mechanism. Nicking and hairpin formation each require the presence of a signal sequence and both RAG proteins

The ESC: The Dangerous by-product of V(D)J Recombination

V(D)J recombination generates antigen receptor diversity by mixing and matching individual variable (V), diversity (D), and joining (J) gene segments. An obligate by-product of many of these reactions is the excised signal circle (ESC), generated by excision of the DNA from between the gene segments. Initially, the ESC was believed to be inert and formed to protect the genome from reactive broken DNA ends but more recent work suggests that the ESC poses a substantial threat to genome stability. Crucially, the recombinase re-binds to the ESC, which can result in it being re-integrated back into the genome, to cause potentially oncogenic insertion events. In addition, very recently, the ESC/recombinase complex was found to catalyze breaks at recombination signal sequences (RSSs) throughout the genome, via a “cut-and-run” mechanism. Remarkably, the ESC/recombinase complex triggers these breaks at key leukemia driver genes, implying that this reaction could be a significant cause of lymphocyte genome instability. Here, we explore these alternate pathways and discuss their relative dangers to lymphocyte genome stability