Paralysis and delayed Z-disc formation in the Xenopus tropicalis unc45b mutant dicky ticker

<p>Abstract</p> <p>Background</p> <p>The protein components of mature skeletal muscle have largely been characterized, but the mechanics and sequence of their assembly during normal development remain an active field of study. Chaperone proteins specific to sarcomeric myosins have been shown to be necessary in zebrafish and invertebrates for proper muscle assembly and function.</p> <p>Results</p> <p>The <it>Xenopus tropicalis </it>mutation <it>dicky ticker </it>results in disrupted skeletal muscle myofibrillogenesis, paralysis, and lack of heartbeat, and maps to a missense mutation in the muscle-specific chaperone <it>unc45b</it>. <it>Unc45b </it>is known to be required for folding the head domains of myosin heavy chains, and mutant embryos fail to incorporate muscle myosin into sarcomeres. Mutants also show delayed polymerization of α-actinin-rich Z-bodies into the Z-disks that flank the myosin-containing A-band.</p> <p>Conclusions</p> <p>The <it>dicky ticker </it>phenotype confirms that a requirement for myosin-specific chaperones is conserved in tetrapod sarcomerogenesis, and also suggests a novel role for myosin chaperone function in Z-body maturation.</p

The History and Prehistory of Natural-Language Semantics

Contemporary natural-language semantics began with the assumption that the meaning of a sentence could be modeled by a single truth condition, or by an entity with a truth-condition. But with the recent explosion of dynamic semantics and pragmatics and of work on non- truth-conditional dimensions of linguistic meaning, we are now in the midst of a shift away from a truth-condition-centric view and toward the idea that a sentence’s meaning must be spelled out in terms of its various roles in conversation. This communicative turn in semantics raises historical questions: Why was truth-conditional semantics dominant in the first place, and why were the phenomena now driving the communicative turn initially ignored or misunderstood by truth-conditional semanticists? I offer a historical answer to both questions. The history of natural-language semantics—springing from the work of Donald Davidson and Richard Montague—began with a methodological toolkit that Frege, Tarski, Carnap, and others had created to better understand artificial languages. For them, the study of linguistic meaning was subservient to other explanatory goals in logic, philosophy, and the foundations of mathematics, and this subservience was reflected in the fact that they idealized away from all aspects of meaning that get in the way of a one-to-one correspondence between sentences and truth-conditions. The truth-conditional beginnings of natural- language semantics are best explained by the fact that, upon turning their attention to the empirical study of natural language, Davidson and Montague adopted the methodological toolkit assembled by Frege, Tarski, and Carnap and, along with it, their idealization away from non-truth-conditional semantic phenomena. But this pivot in explana- tory priorities toward natural language itself rendered the adoption of the truth-conditional idealization inappropriate. Lifting the truth-conditional idealization has forced semanticists to upend the conception of linguistic meaning that was originally embodied in their methodology

Molecular Characterization of a Novel Intracellular ADP-Ribosyl Cyclase

Background. ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates. Methodology/Principal Findings. Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1) is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained. Conclusions/Significance. Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized

Analogical cognition: an insight into word meaning

Analogical cognition, extensively researched by Dedre Gentner and her colleagues over the past thirty five years, has been described as the core of human cognition, and it characterizes our use of many words. This research provides significant insight into the nature of word meaning, but it has been ignored by linguists and philosophers of language. I discuss some of the implications of the research for our account of word meaning. In particular, I argue that the research points to, and helps account for, a key explanatory role that linguistic meaning must play. The research also shows how words contribute to thought as opposed to merely being a means of conveying thought

A novel nucleotide receptor in Xenopus activates the cAMP second messenger pathway

AbstractWe describe a Xenopus P2Y receptor that shares only weak homology with members of the mammalian P2Y family, being most similar to human P2Y11. When activated by nucleotide analogs, it stimulates both calcium and cAMP mobilization pathways, a feature unique, among mammalian P2Y receptors, to P2Y11. Activity can be blocked by compounds known to act as antagonists of mammalian P2Y11. Genomic synteny between Xenopus and mammals suggests that the novel gene is a true ortholog of P2Y11. Xenopus P2Y11 is transcribed during embryonic development, beginning at gastrulation, and is enriched in the developing nervous system

Abstracts of the 22nd International Isotope Society (UK Group) Symposium: synthesis and applications of labelled compounds 2013

Meeting Summary The 22nd annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK, on Friday, 18 October 2013. The meeting was attended by 65 delegates from academia and industry; the life sciences; and chemical, radiochemical and scientific instrument suppliers.Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral and poster presentations on isotopic chemistry and applications of labelled compounds, or of chemistry with potential implications for isotopic synthesis. Both short‐lived and long‐lived isotopes were represented, as were stable isotopes. The symposium programme was divided into a morning session chaired by Dr Karl Cable (GlaxoSmithKline, UK) and afternoon sessions chaired by Mr Mike Chappelle (Quotient Biosciences, UK) and by Dr Nick Bushby (AstraZeneca, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK)