Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris.

Human T-cell-mediated autoimmune diseases are genetically linked to particular alleles of MHC class II genes. Susceptibility to pemphigus vulgaris (PV), an autoimmune disease of the skin, is linked to a rare subtype of HLA-DR4 (DRB1*0402, 1 of 22 known DR4 subtypes). The PV-linked DR4 subtype differs from a rheumatoid arthritis-associated DR4 subtype (DRB1*0404) only at three residues (DR beta 67, 70, and 71). The disease is caused by autoantibodies against desmoglein 3 (DG), and T cells are thought to trigger the autoantibody production against this keratinocyte adhesion molecule. Based on the DRB1*0402 binding motif, seven candidate peptides of the DG autoantigen were identified. T cells from four PV patients with active disease responded to one of these DG peptides (residues 190-204); two patients also responded to DG-(206-220). T-cell clones specific for DG-(190-204) secreted high levels of interleukins 4 and 10, indicating that they may be important in triggering the production of DG-specific autoantibodies. The DG-(190-204) peptide was presented by the disease-linked DRB1*0402 molecule but not by other DR4 subtypes. Site-directed mutagenesis of DRB1*0402 demonstrated that selective presentation of DG-(190-204), which carries a positive charge at the P4 position, was due to the negatively charged residues of the P4 pocket (DR beta 70 and 71). DR beta 71 has a negative charge in DRB1*0402 but a positive charge in other DR4 subtypes, including the DR4 subtypes linked to rheumatoid arthritis. The charge of the P4 pocket in the DR4 peptide binding site therefore appears to be a critical determinant of MHC-linked susceptibility to PV and rheumatoid arthritis.

Mutation of conserved negatively charged residues in the S2 and S3 transmembrane segments of a mammalian K+ channel selectively modulates channel gating.

Voltage-gated channel proteins sense a change in the transmembrane electric field and respond with a conformational change that allows ions to diffuse across the pore-forming structure. Site-specific mutagenesis combined with electrophysiological analysis of expressed mutants in amphibian oocytes has previously established the S4 transmembrane segment as an element of the voltage sensor. Here, we show that mutations of conserved negatively charged residues in S2 and S3 of a brain K+ channel, thought of as countercharges for the positively charged residues in S4, selectively modulate channel gating without modifying the permeation properties. Mutations of Glu235 in S2 that neutralize or reverse charge increase the probability of channel opening and the apparent gating valence. In contrast, replacements of Glu272 by Arg or Thr268 by Asp in S3 decrease the open probability and the apparent gating valence. Residue Glu225 in S2 tolerated replacement only by acidic residues, whereas Asp258 in S3 was intolerant to any attempted change. These results imply that S2 and S3 are unlikely to be involved in channel lining, yet, together with S4, may be additional components of the voltage-sensing structure.

Tunable Raman photons in singly charged p-doped quantum dots

The obtention of spontaneous Raman photons is analyzed in singly charged p-doped quantum dots in the absence of an external magnetic field. The use of a far detuned single driving laser allows to obtain a Raman photon line which exhibits subnatural linewidth, and whose center can be tuned by changing the detuning and/or the Rabi frequency of the driving field. The Raman photons are produced along the undriven transition and they arise from the weak interaction of the trion states with the nuclear spins. The operating point for the gate voltage of the heterostructure can also be used to modify the linewidth and the peak value of the fluorescent signal.

Measurement of the muon neutrino inclusive charged-current cross section in the energy range of 1–3 GeV with the T2K INGRID detector

We report a measurement of the νµ-nucleus inclusive charged current cross section (=σ cc) on ironusing data from exposed to the J-PARC neutrino beam. The detector consists of 14 modules in total, which are spread over a range of off-axis angles from 0◦ to 1.1◦. The variation in the neutrino energy spectrum as a function of the off-axis angle, combined with event topology information, is used to calculate this cross section as a function of neutrino energy. The cross section is measured to be σcc(1.1 GeV) = 1.10±0.15 (10^−38cm^2/nucleon), σcc(2.0 GeV) = 2.07±0.27 (10^−38cm^2/nucleon), and σcc(3.3 GeV) = 2.29 ± 0.45 (10^−38cm^2/nucleon), at energies of 1.1, 2.0, and 3.3 GeV, respectively. These results are consistent with the cross section calculated by the neutrino interaction generators currently used by T2K. More importantly, the method described here opens up a new way to determine the energy dependence of neutrino-nucleus cross sections.

Ion chromatography of anions /

"March 1980."

An introduction to the theory of multiply periodic functions /

Spine title: Multiply periodic functions.

Trial of twenty-four journeymen tailors, charged with a conspiracy before the Mayor's Court of the city of Philadelphia, September sessions, 1827 /

"An account of one of the earliest labor trials resulting from a strike. The first count of the indictment charges corrupt conspiracy to demand greater than customary wages." Cf. Adams.

Interplanetary charged particle models (1974).

Cover title.

Microfilms, their use or abuse ... A challenge to those charged with preserving the records of contemporary history for future generations, the paramount remedy, a timely analysis of the problem,

Mode of access: Internet.

The human equation in aircraft accidents; an analysis of 758 fatal accidents charged to "pilot error" which occurred in non-air carrier flying during the year 1948.

Mode of access: Internet.

Banking and currency reform : hearings before the subcommittee of the Committee on banking and currency, House of representatives, charged with investigating plans of banking and currency reform and reporting constructive legislation thereon.

Issued in 13 parts.

A vindication of the Church of England from the aspersions of a late libel intituled, Priestcraft in perfection, &c. : Wherein the controverted clause of the church's power in the XXth article is shewn to be of equal authority with all the rest of the articles; and the fraud and forgery, charged upon the clergy on the account of that clause, are retorted upon their accusers. With a preface containing some remarks upon the Reflections on that pamphlet. /

By Hilkiah Bedford. Cf. ESTC.