Microring-Assisted Coupling Between Dissimilar Waveguides

The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators.     

Failure of calcium to stimulate Na,K-ATPase in the presence of EDTA

Summary The effect of calcium on Na, K-ATPase activity of rat brain homogenates and its modification by the chelating agent EDTA has been investigated. In the absence of EDTA, free calcium (approximately 10^–6mol/l) stimulates Na,K-ATPase activity; in the presence of EDTA the same concentration of free calcium is without effect on the enzyme. In the absence of EDTA the stimulation by calcium of Na,-K-ATPase activity is enhanced by the additional presence of calmodulin but in the presence of EDTA, even when calmodulin is added to excess, calcium still fails to stimulate the enzyme. The possibility that EDTA interferes with an interaction between a calcium-calmodulin complex and Na,K-ATPase is discussed.The expert technical assistance of Mrs Paula Jarvie is gratefully acknowledged. Thanks are due also to Professor Philip Kuchel for assistance with the calculations to determine the concentrations of metal-ligand complexes in the experimental media.     

A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC

It is now possible to paint a detailed picture of how cytoplasmic proteins are handled by the immune system. They are apparently degraded in the cytoplasm into peptides. These are then transported into the endoplasmic reticulum where they encounter class I major histocompatibility complex (MHC) molecules. Once loaded with peptide, the HLA molecules move through the Golgi apparatus to the cell membrane. Until recently, it had not been established how peptides without signal sequences cross the ER membrane. However, a number of papers have now described a pair of membrane transporter genes of the ABC (ATP-binding cassette) super-family which are attractive candidates for this function. Both transporter genes, which may encode two halves of a heterodimer, are situated in the class II region of the MHC. There is evidence that other putative components of the processing machinery, the LMPs (low molecular mass polypeptides), are also encoded in the MHC. Similarities between the properties of the LMPs and a large intracellular protease complex, called proteasome, have led to the suggestion that LMPs are involved in processing antigens. We have now identified a human gene with sequence homology to proteasome components. Remarkably, this gene maps between the two putative peptide transporter genes.     

Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex.

Presentation of cytoplasmic antigens to class I-restricted cytotoxic T cells implied the existence of a specialized peptide transporter. For most class I heavy chains, association with peptides of the appropriate length is required for stable assembly with beta 2-microglobulin. Mutant cells RMA-S and .174/T2 neither assemble stable class I molecules nor present intracellular antigens, and we have suggested that they have lost a function required for the transport of short peptides from the cytosol to the endoplasmic reticulum. The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex, within which two genes (RING4 and RING11) have been identified that code for 'ABC' (ATP-binding cassette) transporters. We report here that the protein products of these two genes assemble to form a complex. Defects in either protein result in the formation of unstable class I molecules and loss of presentation of intracellular antigens. The molecular defect in a new mutant, BM36.1, is shown to be in the ATP-binding domain of the RING11/PSF2 protein. This is in contrast to the mutant .134, which lacks the RING4/PSF1 protein.     

Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule.

Short antigenic peptides bound in the groove of class I major histocompatibility complex molecules enable T cells to detect intracellular pathogens. It has been assumed that structural features of the class I molecule alone select which peptides are bound. It is now demonstrated that a complex polymorphism in one of the major histocompatibility complex-encoded putative peptide-transporter genes is associated with an altered spectrum of bound peptides.     

Cacao usage by the earliest Maya civilization

The Maya archaeological site at Colha in northern Belize, Central America, has yielded several spouted ceramic vessels that contain residues from the preparation of food and beverages. Here we analyse dry residue samples by using high-performance liquid chromatography coupled to atmospheric-pressure chemical-ionization mass spectrometry, and show that chocolate (Theobroma cacao) was consumed by the Preclassic Maya as early as 600 bc, pushing back the earliest chemical evidence of cacao use by some 1,000 years. Our application of this new and highly sensitive analytical technique could be extended to the identification of other ancient foods and beverages.     

Second proteasome-related gene in the human MHC class II region

Antgen processing involves the generation of peptides from cytosolic proteins and their transport into the endoplasmic reticulum where they associate with major histocompatibility complex (MHC) class I molecules. Two genes have been identified in the MHC class II region, RING4 and RING11 in humans, which are believed to encode the peptide transport proteins. Attention is now focused on how the transporters are provided with peptides. The proteasome, a large complex of subunits with multiple proteolytic activities, is a candidate for this function. Recently we reported a proteasome-related sequence, RING10, mapping between the transporter genes. Here we describe a second human proteasome-like gene, RING12, immediately centromeric of the RING4 locus. Therefore RING12, 4, 10 and 11 form a tightly linked cluster of interferon-inducible genes within the MHC with an essential role in antigen processing.     

Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation.

Major histocompatibility complex (MHC) class I molecules bind and deliver peptides derived from endogenously synthesized proteins to the cell surface for survey by cytotoxic T lymphocytes. It is believed that endogenous antigens are generally degraded in the cytosol, the resulting peptides being translocated into the endoplasmic reticulum where they bind to MHC class I molecules. Transporters containing an ATP-binding cassette encoded by the MHC class II region seem to be responsible for this transport. Genes coding for two subunits of the '20S' proteasome (a multicatalytic proteinase) have been found in the vicinity of the two transporter genes in the MHC class II region, indicating that the proteasome could be the unknown proteolytic entity in the cytosol involved in the generation of MHC class I-binding peptides. By introducing rat genes encoding the MHC-linked transporters into a human cell line lacking both transporter and proteasome subunit genes, we show here that the MHC-encoded proteasome subunit are not essential for stable MHC class I surface expression, or for processing and presentation of antigenic peptides from influenza virus and an intracellular protein.     

Failure of calcium to stimulate Na,K-ATPase in the presence of EDTA

The effect of calcium on Na,K-ATPase activity of rat brain homogenates and its modification by the chelating agent EDTA has been investigated. In the absence of EDTA, free calcium (approximately 10(-6) mol/l) stimulates Na,K-ATPase activity; in the presence of EDTA the same concentration of free calcium is without effect on the enzyme. In the absence of EDTA the stimulation by calcium of Na,K-ATPase activity is enhanced by the additional presence of calmodulin but in the presence of EDTA, even when calmodulin is added to excess, calcium still fails to stimulate the enzyme. The possibility that EDTA interferes with an interaction between a calcium-calmodulin complex and Na,K-ATPase is discussed.     

Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter.

In mammalian cells, short peptides derived from intracellular proteins are displayed on the cell membrane associated with class I molecules of the major histocompatibility complex (MHC). The surface presentation of class I-peptide complexes presumably alerts the immune system to intracellular viral protein synthesis. Peptides derived from the cytosol must reach the cisternae of the endoplasmic reticulum where they are required for the assembly of stable class I molecules, and it has been proposed that the products of the two MHC-encoded ATP-binding cassette (ABC) transporter genes function to deliver the peptides across the membrane of the endoplasmic reticulum. This idea is supported by experiments in which transfection of a human cell line defective in class I expression with a complementary DNA of one of these genes restored cell surface expression levels. Here we show that the complete phenotype of the mouse mutant cell line RMA-S, in which lack of surface expression of stable class I molecules correlates with an inability to present viral peptides originating in the cytosol, is repaired by the cDNA of the other transporter gene. These results are consistent with the possibility that the two transporter polypeptides form a heterodimer.