Aromatic peptides such as diphenylalanine (FF) have the characteristic capacity to self-assemble into ordered nanostructures such as peptide nanotubes, which are biocompatible, thermally and chemically stable, and have strong piezoelectric activity and high mechanical strength. The physical properties of FF aggregates open up a variety of potential biomedical applications. Electric fields are commonly applied to align FF nanotubes, yet little is known about the effect of the electric field on the assembly process. Using all-atom molecular dynamics with explicit water molecules, we probe the conformational dynamics of individual, solvated FF molecules with both charged and neutral ends, to account for different possible pH conditions. With charged ends, the FF molecules show more complex dynamics, experiencing three main conformational states (cis, trans and extended). We first examine the structural response of FF monomers to the application of a constant external electric field over a range of intensities. We also probe the aggregation mechanism of FF peptides, both with and without an externally applied electric field, and find that the presence of even relatively weak fields can accelerate the formation of ordered FF aggregates, primarily by facilitating the alignment of individual molecular dipole moments. The correlation between the strength of the external electric field and the local dipolar interactions is modulated both by the conformational response of individual FF peptides (e.g. backbone stretching, hydrogen bonds and relative alignment of aromatic sidechains) and by the response of neighboring FF and water molecules. These field-dependent observations may facilitate future studies on the controlled formation of nano-structured aggregates of piezoelectric peptides and the understanding of their specific electromechanical properties.
Basal cell carcinoma (BCC) is the most common non-melanomatous skin cancer, typically arising in sun-exposed areas such as the head and neck. Defective signaling through the Hedgehog (HH) signaling pathway forms the molecular basis for BCC. Surgery remains the mainstay of treatment. Basal cell carcinoma of the genital tract is rare as is metastatic BCC. We report a case of metastatic BCC in a young woman with previously resected vulval BCC presenting six years later with inguinal nodal recurrence and multiple lung metastases.
In this article, we propose that T cell help for B cells can occur via an unusual three-cell cluster, with recipient CD4+ T helper cells interacting via direct allorecognition with donor dendritic cell class II MHC antigens, recipient B cells interacting with MHC class I (or any other) antigen on the donor dendritic cell surface, and noncognate (i.e., antigen nonspecific) T-B collaboration. In this noncognate pathway, antigen processing by B cells is not required and T cell help is potent because of the high precursor T cell frequency for direct recognition of allogeneic class II MHC molecules. The data supporting this hypothesis are: 1. LEW rat strain recipients of interstitial dendritic cell-free (DAxLEW)F1 kidney allografts were shown to have no detectable antibody to donor class I MHC antigens at day 7 after grafting. By contrast, LEW recipients of normal (DAxLEW)F1 kidneys had strong antibody responses. 2. Consistent wih important role for donor dendritic cells in the early antibody response to donor class I MHC antigens was the finding that it was dependent on donor class II MHC antigens. PVG recipients, previously immunized with pure DA RT1.B class II MHC antigens, had virtually no antibody response to the class I MHC antigens of DA kidney allografts. 3. We confirmed the low and high responder status of PVG and LEW rats, respectively, to DA class I antigens by studying antibody responses to pure DA class I antigens. However, PVG and LEW recipients of DA kidney allografts did not differ in their antibody response to the donor DA class I MHC antigens. This is consistent with this response not requiring the processing and presentation of DA class I antigen by PVG recipients. 4. LEW recipients of interstitial dendritic cell-free (DAxLEW)F1 kidney allografts did eventually develop a strong antibody response to DA class I antigens, but this was delayed by several weeks. That this delayed antibody response was probably mediated by conventional T-B collaboration and that T help was rate limiting in this situation, was demonstrated by immunizing LEW recipients with a DA class I peptide. This markedly accelerated the kinetics of the antibody response to the dendritic cell-free (DAxLEW)F1 kidneys.
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