Tracing Photoinduced Hydrogen Migration in Alcohol Dications from Time-Resolved Molecular-Frame Photoelectron Angular Distributions.

The recent implementation of attosecond and few-femtosecond X-ray pump/X-ray probe schemes in large-scale free-electron laser facilities has opened the way to visualize fast nuclear dynamics in molecules with unprecedented temporal and spatial resolution. Here, we present the results of theoretical calculations showing how polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) can be used to visualize the dynamics of hydrogen migration in methanol, ethanol, propanol, and isopropyl alcohol dications generated by X-ray irradiation of the corresponding neutral species. We show that changes in the PA-MFPADs with the pump-probe delay as a result of intramolecular photoelectron diffraction carry information on the dynamics of hydrogen migration in real space. Although visualization of this dynamics is more straightforward in the smaller systems, methanol and ethanol, one can still recognize the signature of that motion in propanol and isopropyl alcohol and assign a tentative path to it. A possible pathway for a corresponding experiment requires an angularly resolved detection of photoelectrons in coincidence with molecular fragment ions used to define a molecular frame of reference. Such studies have become, in principle, possible since the first XFELs with sufficiently high repetition rates have emerged. To further support our findings, we provide experimental evidence of H migration in ethanol-OD from ion-ion coincidence measurements performed with synchrotron radiation.

Femtosecond charge and molecular dynamics of I-containing organic molecules induced by intense X-ray free-electron laser pulses.

We studied the electronic and nuclear dynamics of I-containing organic molecules induced by intense hard X-ray pulses at the XFEL facility SACLA in Japan. The interaction with the intense XFEL pulse causes absorption of multiple X-ray photons by the iodine atom, which results in the creation of many electronic vacancies (positive charges) via the sequential electronic relaxation in the iodine, followed by intramolecular charge redistribution. In a previous study we investigated the subsequent fragmentation by Coulomb explosion of the simplest I-substituted hydrocarbon, iodomethane (CH3I). We carried out three-dimensional momentum correlation measurements of the atomic ions created via Coulomb explosion of the molecule and found that a classical Coulomb explosion model including charge evolution (CCE-CE model), which accounts for the concerted dynamics of nuclear motion and charge creation/charge redistribution, reproduces well the observed momentum correlation maps of fragment ions emitted after XFEL irradiation. Then we extended the study to 5-iodouracil (C4H3IN2O2, 5-IU), which is a more complex molecule of biological relevance, and confirmed that, in both CH3I and 5-IU, the charge build-up takes about 10 fs, while the charge is redistributed among atoms within only a few fs. We also adopted a self-consistent charge density-functional based tight-binding (SCC-DFTB) method to treat the fragmentations of highly charged 5-IU ions created by XFEL pulses. Our SCC-DFTB modeling reproduces well the experimental and CCE-CE results. We have also investigated the influence of the nuclear dynamics on the charge redistribution (charge transfer) using nonadiabatic quantum-mechanical molecular dynamics (NAQMD) simulation. The time scale of the charge transfer from the iodine atomic site to the uracil ring induced by nuclear motion turned out to be only ∼5 fs, indicating that, besides the molecular Auger decay in which molecular orbitals delocalized over the iodine site and the uracil ring are involved, the nuclear dynamics also play a role for ultrafast charge redistribution. The present study illustrates that the CCE-CE model as well as the SCC-DFTB method can be used for reconstructing the positions of atoms in motion, in combination with the momentum correlation measurement of the atomic ions created via XFEL-induced Coulomb explosion of molecules.

Functional roles of two polypeptide chains that compose an antigen-specific suppressor T cell factor.

The functional roles of the two polypeptide chains that compose the T cell suppressor factor (TsF) that mediates the antigen-specific and genetically restricted suppressor function were studied by using the heavy or light chains isolated from the conventional TsF or the 11S and 13S mRNA translation products of TsF. Either the heavy or the light chain of mRNA translation products reconstitutes the active TsF that suppresses the antibody response in an antigen-specific and genetically restricted manner when it is combined with the isolated heavy or light chain from the conventional TsF. As a consequence, the antigen-binding heavy chain mediates the antigen specificity of TsF. On the other hand, the I-J-positive light chain works as an element to determine the genetic restriction specificity. Thus, the identity of the histocompatibility between the I-J haplotypes on the light chain and the responding cell is essential for the functional expression of TsF. No genetic preference, however, was observed, in the association of the heavy and light chains of TsF.

Monoclonal antibodies that recognize the product controlled by a gene in the I-J subregion of the mouse H-2 complex.

The B cell hybridomas producing monoclonal antibodies (E10, D7, F4, H6, and D4) were established by the fusion of P3U1 or NS-1 murine myeloma cell lines and spleen cells of B10.A(5R) mice hyperimmunized with mitomycin C-treated B10.A(3R) spleen and thymus cells. Two types of monoclonal antibodies specific for the products controlled by a gene in the I-Jb subregion of the H-2 complex were characterized: one specific for the private type of I-Jb determinant, the other recognizing the cross-reactive determinant between the I-Jb and I-Jd products. By using these monoclonal reagents, the I-J-encoded product on the antigen-specific suppressor T cells was found to be expressed on their soluble suppressor factors. Furthermore, the I-Jb products were successfully detected not only on the T cell hybridoma with suppressor activity specific for keyhole limpet hemocyanin (KLH), but also on KLH-primed suppressor T cells enriched by antigen-coated petri dishes and concanavalin A-induced thymocyte blasts of C57BL/6 mice by complement-dependent cytotoxic assays and membrane fluorescence techniques.

Extrathymic development of V alpha 14-positive T cells.

It is known that rearrangement of the T cell antigen receptor (TCR) gene occurs in the thymus during T cell development and consequently results both in the deletion of DNA between the variable (V) and diversity/joining segments and in the formation of a circular DNA with recombination signal sequences. Here, we provide evidence that V alpha 14+ TCR gene rearrangements take place in extrathymic sites, such as bone marrow, liver, and intestine, but not in spleen, because we were able to detect frequent productive and nonproductive V alpha 14+ coding and signal sequences as a result of TCR rearrangements in extrathymic sites. Similar findings were also detected in athymic mice. Quantitative analysis shows that the relative amounts of V alpha 14 gene-mediated signal sequences in extrathymic tissues are higher than those in thymus. On the contrary, TCR rearrangements of V alpha 1.1 T cells, which are known to develop in the thymus, were mainly detected in the thymus, Peyer's patch, and spleen, but not in other extrathymic tissues, showing patterns distinct from V alpha 14 TCR rearrangements. These findings are evidence of extrathymic development of V alpha 14+ T cells. Differential characteristic TCR rearrangement patterns also indicate that distinct TCR repertoires are generated in different lymphoid tissues.

Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors.

A lymphocyte subpopulation, the Valpha14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the Valpha14 and Jalpha281 gene segments. Mice with a deletion of the Jalpha281 gene segment were found to exclusively lack this subpopulation. The Valpha14 NKT cell-deficient mice could no longer mediate the interleukin-12 (IL-12)-induced rejection of tumors. Although the antitumor effect of IL-12 was thought to be mediated through natural killer cells and T cells, Valpha14 NKT cells were found to be an essential target of IL-12, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.

Cloning of the 62-kilodalton component of basic transcription factor BTF2.

Cloning of the mammalian basic transcription factors serves as a major step in understanding the mechanism of transcription initiation. The 62-kilodalton component (p62) of one of these transcription factors, BTF2 was cloned and overexpressed. A monoclonal antibody to this polypeptide inhibited transcription in vitro. Immunoaffinity experiments demonstrated that the 62-kilodalton component is closely associated with the other polypeptides present in the BTF2 factor. Sequence similarity suggests that BTF2 may be the human counterpart of RNA polymerase II initiation factor b from yeast.

[A prosthetic ring annuloplasty with edge-to-edge repair for a treatment of severe tricuspid regurgitation].

A 59-year-old woman admitted to our hospital with shortness of breath and edema of the lower extremities was diagnosed with right ventricular failure stemming from severe tricuspid valve regurgitation (TR). She had undergone mitral valve replacement (MVR) with a mechanical valve at the age of 42. The approach to the heart was established via a right thoracotomy at the 4th intercostals space. A beating heart cardiopulmonary bypass procedure was performed in which tricuspid valve repair was performed with the edge-to-edge repair and MC3 annuloplasty system. The operative course was uneventful. This technique may be feasible and clinically effective in the treatment of severe TR.

Destabilization of neutrophil NADPH oxidase by ATP and other trinucleotides and its prevention by Mg(2+).

Neutrophil NADPH oxidase (O(2)(-) generating enzyme) activated in a cell-free system was deactivated by dilution. When ATP was included in dilution the deactivation was further accelerated. The deactivation by dilution was biphasic, and the half-life of the enzyme was significantly shortened by ATP in each phase. ADP and AMP had little effect on the enzyme longevity while GTP and CTP had a similar effect to ATP. Staurosporine, a wide-range inhibitor of protein kinases, had no effect on ATP-induced deactivation, suggesting that the effect was not due to a protein phosphorylation. Mg(2+) addition largely prevented the deactivation by ATP. Chemical crosslinking of the activated oxidase prevented the deactivation by dilution and ATP, suggesting that the deactivation is caused by dissociation of the oxidase complex. Estimation of actin filament (F-actin) showed that the F-actin level was markedly reduced by addition of ATP. The ATP effect on the deactivation was not prominent in a semi-recombinant system which does not contain cytosol. These results suggest that ATP-induced deactivation is largely due to the chelation of Mg(2+) and are consistent with the concept that Mg(2+) stabilizes the oxidase complex by stabilizing F-actin.