Osaka University

Abstract: We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.

Abstract: The presence in mammalian liver microsomes of a carbon monoxide-binding pigment has been reported by Klingenberg (1) and by Garfinkel (2). The CO compound of the reduced pigment has an intense absorption band at 450 rnl.c and thus can be readily detected in dithionite-treated microsomes by difference spectrophotometry. The CO difference spectrum of reduced microsomes is, however, unusual in that it shows no peaks other than that at 450 rnp and, therefore, provides no clue to the nature of the pigment. The elucidation of its nature has further been hampered by the reported lability of the microsomal pigment to detergents, low pH, and enzymatic digestion (1,2). In addition, the CO compound has been reported as not photodissociable (1). In preliminary communications (3, 4), we have reported evidence for the hemoprotein nature of the microsomal CObinding pigment, provisionally called “P-450,” and shown that it can be converted into a solubilised form, which we term “P420,” by treatment of microsomes anaerobically with snake venom or deosycholate. The solubiliaation is accompanied by an unusual change in the spectral properties of the pigment. Further, the solubilized pigment has been partly purified, free from cytochrome 55, and shown to possess absorption spectra characteristic of hemoproteins (5). The present paper gives a detailed account of the investigations on rabbit liver microsomes and crude microsomal digests, which have led us to postulate the hemoprotein nature of the pigment. Purification and properties of the solubilized hemoprotein will be reported in the accompanying paper (6).

Abstract: Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs). Several classes of PRRs, including Toll-like receptors and cytoplasmic receptors, recognize distinct microbial components and directly activate immune cells. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.

Abstract: A search for the Standard Model Higgs boson in proton–proton collisions with the ATLAS detector at the LHC is presented. The datasets used correspond to integrated luminosities of approximately 4.8 fb−1 collected at View the MathML source in 2011 and 5.8 fb−1 at View the MathML source in 2012. Individual searches in the channels H→ZZ(⁎)→4l, H→γγ and H→WW(⁎)→eνμν in the 8 TeV data are combined with previously published results of searches for H→ZZ(⁎), WW(⁎), View the MathML source and τ+τ− in the 7 TeV data and results from improved analyses of the H→ZZ(⁎)→4l and H→γγ channels in the 7 TeV data. Clear evidence for the production of a neutral boson with a measured mass of View the MathML source is presented. This observation, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9, is compatible with the production and decay of the Standard Model Higgs boson.

Abstract: One of the mechanisms by which the innate immune system senses the invasion of pathogenic microorganisms is through the Toll-like receptors (TLRs), which recognize specific molecular patterns that are present in microbial components. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also instructs the development of antigen-specific acquired immunity. Here, we review the rapid progress that has recently improved our understanding of the molecular mechanisms that mediate TLR signalling.