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BackgroundEndometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus causing chronic inflammation, severe pain, and infertility. However, the innate immunity of gamma-delta (γδ) T lymphocytes in endometriosis has not been characterized. Women with endometriosis present numerous endocrine and immune dysfunctions and elevated risk for endometrial, ovarian, and breast cancers. The tyrosine kinase EphA2 is often overexpressed in cancer including endometrial carcinoma.MethodsWe analyzed Vδ1 and Vδ2 γδ T cells in peripheral blood and paired peritoneal fluid samples in endometriosis patients (n = 19) and compared the counts with that of age- and sex-matched healthy donors (n = 33) using flow cytometry. Vδ1 and Vδ2 T cells isolated from healthy donors were used against KLE, RL-95, and Ishikawa endometrial tumor cells in 4 h flow cytometric cytotoxicity assays. The EphA2 blocking studies were performed using antibody, small-molecule inhibitor ALW-II-41-27, and the CRISPR/Cas9.ResultsWe determined Vδ1 T cells substantially reduced in patients’ peripheral blood (p p ConclusionsWe determined variable levels of Vδ1 and Vδ2 γδ T cells in endometriosis patients. We observed inherent cytotoxic reactivity of γδ T-cell subsets against endometrial cell lines. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of endometrial tumor killing mediated by Vδ1 γδ T cells. These results suggest that EphA2 is involved in tumor cell lysis and contributes to susceptibility to Vδ1 γδ T cells cytotoxic reactivity.

In this paper, we have introduced the extension of recently introduced notion of summability of lacunary statistical delta 2 quasi Cauchy sequences to double sequences and established some essential results using analogy.

Aims: To compare developmental changes of delta 1 (0.5-2.0 Hz) and delta 2 (2.25-3.75 Hz) power spectra between healthy monozygotic (MZ) and dizygotic (DZ) twin pairs and among MZ and DZ twin groups during active/REM (AS/REM) and quiet/NREM (QS/NREM) sleep stages at 38th, 46th, and 52nd weeks of postmenstrual age (PMA). Materials and methods: Electroencephalography (EEG) recordings were analyzed using fast Fourier transforms. Differences in the developmental changes of delta power within twin pairs and between twin groups were estimated by calculating mean absolute differences of relative spectral values in delta 1 (0.5-2 Hz) and delta 2 (2.25- 3.75 Hz) frequencies. Results: A review of electrodes showed that relative delta 1 power decreased, whereas delta 2 power increased from 38th toward 52nd week of PMA regardless of zygosity, sleep stages, and electrode position. Twin groups did not significantly differ (P > .05) in within-pair MZ and DZ similarity for delta 1 and delta 2 power spectra ; similarity between MZ twin partners for delta 1 and delta 2 power spectra was as high as that of DZ twin partners on each electrode position, sleep stage, and period of measurement. Conclusions: Developmental changes of delta 1 and delta 2 power spectra occurred equally in MZ and DZ twin groups during AS and QS sleep stages at 38th, 46th, and 52th PMA. The rhythm of EEG maturation evidenced by the maturation of delta 1 and delta 2 power spectra was not dependent on zygosity.

We use the finiteness of the triangle diagram in order to establish that certain critical exponents take on their mean-field values. We again rely on the differential inequalities developed in chapter 3, and complement them with a differential inequality involving the triangle diagram. We then prove that, under the triangle condition, the critical exponents \(\delta \) and \(\beta \) take on their mean-field values \(\delta \) = 2 and \(\beta \) = 1.

A plane graph $G$ is entirely $k$-colorable if $V(G)\cup E(G) \cup F(G)$ can be colored with $k$ colors such that any two adjacent or incident elements receive different colors. In 1993, Borodin proved that every plane graph $G$ with maximum degree $\Delta\ge 12$ is entirely $(\Delta+2)$-colorable. In this paper, we improve this result by showing that every plane graph $G$ with $\Delta\ge 9$ is entirely $(\Delta+2)$-colorable.

It was proved in [8,9] that every Lagrangian submanifold $M$ of a complex space form $\tilde M^{5}(4c)$ of constant holomorphic sectional curvature $4c$ satisfies the following optimal inequality: {align}\tag{A}\delta(2,2)\leq \text{\small${25}{4}$} H^{2}+8c,{align} where $H^{2}$ is the squared mean curvature and $\delta(2,2)$ is a $\delta$-invariant on $M$ introduced by the first author. This optimal inequality improves a special case of an earlier inequality obtained in [B.-Y. Chen, Japan. J. Math. 26 (2000), 105-127]. The main purpose of this paper is to classify Lagrangian submanifolds of $\tilde M^{5}(4c)$ satisfying the equality case of the improved inequality (A)., Comment: 25 pages; appeared in Publ. Math. Debrecen, 82 (2013), 193-217

Understanding what are the mechanisms that strengthen, stabilize and restrict synaptic innervation is a relevant topic in glutamate receptor delta 2 (GluR delta 2)-related research. It also involves targeting and selection of afferent input during formation of the neuronal circuitry in the cerebellar cortex and its functioning. This review will focus oil the role of GluR delta 2, one of the main players in this field. Special emphasis will be placed on the processes that regulate the rapid translocation from climbing fibres to parallel fibres of GluR delta 2 and the role of GluR delta 2 in the reduction of supernumerary climbing fibre contacts on a single Purkinje cell. Furthermore, GluR delta 2 knockout mice show ataxia and impaired motor coordination, suggesting that the presence of GluR delta 2 plays an important role in controlling cerebellar functioning. (c) 2007 Elsevier Ltd. All rights reserved.

The semirigid binuclear ruthenium complex Delta,Delta-[mu-(11,11'-bidppz)(phen)(4)Ru(2)](4+) has been shown to rearrange slowly from an initial groove-bound nonluminescent state to a final intercalated emissive state by threading one of its bulky Ru(phen)(2) moieties through the DNA base stack. When this complex binds to poly[d(A-T)(2)], a further increase in emission from the complex is observed after completion of the intercalation, assigned to reorganization of the intercalated complex. We here report a study of the threading process in poly[d(A-T)(2)], in which the minor groove binding dye DAPI is used as an energy transfer probe molecule to assess the distribution of ruthenium complex during and also after the actual threading phase. The emission from DAPI is found to change with the same rate as the emission from the ruthenium complex, and furthermore, DAPI does not disturb the binding kinetics of the latter, justifying it as a good probe of both the threading and the reorganization processes. We conclude from the change in the emission from both DAPI and the ruthenium complex with time that DAPI-ruthenium interactions are most pronounced during the process of threading of the complex, suggesting that the complexes are initially threaded slightly anticooperatively and thereafter redistribute along the DNA to reach their thermodynamically most favorable distribution. The final distribution is characterized by a small but significant binding cooperativity, probably as a result of hydrophobic interactions between the complex ions despite their tetravalent positive charges. The mechanism of "shuffling" the complex along the DNA chain is discussed, i.e., whether the ruthenium complex remains threaded (requiring sequential base-pair openings) or if unthreading followed by lateral diffusion within the ionic atmosphere of the DNA and rethreading occurs.

Epoxidation and cis-hydroxylation of C-phenyl-delta(2,3)-glycopyranosides have been carried out with a view to developing C-aryl glycoside synthesis. Epoxidation of (2,3- and (6-O-tert-butyldimethylsilyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl)benzenedideoxy-D-erythro-hex-2-enopyranosyl)benzene gave predominantly the allo-adducts whatever the configuration at the anomeric center. Epoxidation of (4,6-di-O-tert-butyl-dimethylsilyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl)benzene gave the manno- and allo-adducts in a 89:11 and 40:60 ratios for the alpha- and beta-anomers, respectively. Hydroxylation of alpha-C-phenyl-(2,3)-glycopyranosides using OsO4 afforded the manno-adduct only, whatever the substituents at positions 4 and 6, whereas hydroxylation of (2,3-dideoxy-beta-D-erythro-hex-2-enopyranosyl)benzene and (4,6-di-O-tert-butyldimethylsilyl-2,3-dideoxy- beta-D-erythro-hex-2-enopyranosyl)benzene gave the manno- and allo-adducts in 25:75 and 80:20 ratios, respectively.

In early December 2003, the first Delta IV Heavy launch vehicle was successfully rolled out of the Horizontal Integration Facility (HIF) and erected on Space Launch Complex (SLC) 37 at Cape Canaveral Air Force Station, Florida. The vehicle remains on the launch pad, undergoing a series of launch readiness tests in preparation for liftoff on a qualification flight in the fall of 2004. The Heavy launch vehicle represents the largest of the five vehicles of the Delta IV family, which consists of the Delta IV Medium, three Delta IV Medium vehicles with solid strap-on rocket motors (Medium-Plus variants), and the Delta IV Heavy. All vehicle configurations utilize a common booster core (CBC). The Heavy employs two additional CBCs, serving as liquid rocket boosters for added payload capability. The vehicle measures 71.7 m in height when fully stacked with a payload. This paper describes in detail the Delta IV Heavy launch vehicle and summarizes the flight readiness process in preparation for a successful flight, including wet dress rehearsals. A summary of the sequence of events of the Heavy qualification flight is also included.

We have obtained the carbon-13 nuclear magnetic resonance spectra of a series of tryptophan-containing peptides and model systems, together with their X-ray crystallographic structures, and used quantum chemical methods to predict the (13)C NMR shifts (or shieldings) of all nonprotonated aromatic carbons (C(gamma), C(delta 2) and C(epsilon 2). Overall, there is generally good accord between theory and experiment. The chemical shifts of Trp C(gamma) in several proteins, hen egg white lysozyme, horse myoglobin, horse heart cytochrome c, and four carbonmonoxyhemoglobins, are also well predicted. The overall Trp C(gamma) shift range seen in the peptides and proteins is 11.4 ppm, and individual shifts (or shieldings) are predicted with an rms error of approximately 1.4 ppm (R value = 0.86). Unlike C(alpha) and N(H) chemical shifts, which are primarily a function of the backbone phi,psi torsion angles, the Trp C(gamma) shifts are shown to be correlated with the side-chain torsion angles chi(1) and chi(2) and appear to arise, at least in part, from gamma-gauche interactions with the backbone C' and N(H) atoms. This work helps solve the problem of the chemical shift nonequivalences of nonprotonated aromatic carbons in proteins first identified over 30 years ago and opens up the possibility of using aromatic carbon chemical shift information in structure determination.

We investigated the applicability of Raman microprobe spectroscopy for determining the density of CO2 in fluid inclusions in minerals of mantle-derived xenolith samples. A separation (delta) between two Raman bands of CO2 due to Fermi resonance can be a reliable densimeter for CO2 fluid. The relationship between the density of CO2 (g/cm3) and delta (cm-1) can be expressed as: d = -0.03238697 delta 3 + 10.08428 delta 2 - 1046.189 delta + 36163.67. This equation was obtained from the Raman data on CO2 fluid with densities from 0.1 to 1.21 g/cm3, including super critical fluids at 58-59 degrees C. The delta value was constant with increasing temperature from room temperature to 200 degrees C. This indicates that the Raman densimeter is not affected by a possible rise in temperature, an artifact induced by the high flux of the incident laser. The minimum size of measurable inclusions is 1 micron, and the precision in the determination of delta is 0.1 cm-1, corresponding to 0.02 g/cm3 for inclusions of 1 micron in size. The precision can be better for larger inclusions. The micro-Raman densimeter can determine the density of CO2 fluid inclusions over a wide range. In particular, densities of gas and mixtures of gas and liquid phases, which cannot be measured by microthermometry, can be determined.

The standard products of V(D)J recombination of immunoglobulin and T cell receptor genes are two kinds of DNA junction, a coding joint and a signal joint. TCR delta V-D and D-D signal joints in adult mouse thymocytes were sequenced following PCR amplification. We observed differential nucleotide insertions at the V delta-D delta signal joints, depending on the V delta and D delta gene usage in the developmental stage. Nucleotide insertions at the V delta-D delta 1 signal joints were less frequent for the V delta 4, 5 genes preferentially utilized in adult thymocytes than for the V delta 3, 6 genes, infrequently rearranged to D delta 1. In addition to standard signal joints, unexpectedly, novel nonstandard products, "replacement joints" of D delta 1 substituted downstream by the recombination signal sequence of V delta were also found. However, no D delta 2-associated replacement joints other than V delta 5 were found. The other replacement joints of D delta 1-D delta 2 recombination were also observed. The mutation in TCR beta gene affected the frequency of nucleotide insertions at the V delta-D delta signal joints and inhibited the formation of replacement joint. Recombination mechanism generating the replacement joint and the possible role of TCR beta in up-regulation of TCR delta gene rearrangements are discussed.

Assuming V=L(R)+AD, using methods from inner model theory, we give a new proof of the strong partition property for δ∼12. The result was originally proved by Kechris et al.

The Expendable Launch Systems division of The Boeing Company is well into the development of the new family of Delta IV launch vehicles to support commercial and government missions. The Delta IV adds to the existing Delta family of vehicles, the Delta II in four configurations and the Delta III with twice the performance of the Delta II. The addition of the Delta IV adds five vehicles to the Delta family: the Delta IV medium, three Delta IV Medium-Plus vehicles with solid rocket augmentation, and the Delta IV Heavy vehicles. This family now addresses the full market range of payload requirements from 2,000 to 29,000 pounds to geosynchronous transfer orbit (GTO). Full-scale commercial development was initiated in 1997, with the first Delta flight planned for the second quarter of 2001. This paper presents the status of the development program of the launch vehicles, the new green field, focused factory for common booster core production at Decatur, Alabama, the new launch facility construction at Cape Canaveral Air Force Station and Vandenberg Air Force Base, and the new LO2/LH2 RS-68 common booster core engine. The status of the Delta III return to flight is also presented.

We recently reported that the number of gamma delta T cells was increased after infection with Escherichia coli in C3H/HeN mice. We here showed that an i.p. injection with native lipid A derived from E. coli induced an increase of gamma delta T cells in the peritoneal cavity of LPS-responsive C3H/HeN mice and, albeit to a lesser degree, also in LPS-hyporesponsive C3H/HeJ mice. The purified gamma delta T cells from C3H/HeN and C3H/HeJ mice expressed a canonical TCR repertoire encoded by V gamma 6-J gamma 1/V delta 1-D delta 2-J delta 2 gene segments and proliferated in response to the native lipid A derived from E. coli in a TCR-independent manner. The lipid A-reactive gamma delta T cells bearing canonical V gamma 6/V delta 1 expressed Toll-like receptor (TLR) 2 mRNA, while TLR4 mRNA was undetectable. Treatment with a TLR2 anti-sense oligonucleotide resulted in hyporesponsiveness of the gamma delta T cells to the native lipid A. TLR2-deficient mice showed an impaired increase of the gamma delta T cells following injection of native lipid A. These results suggest that TLR2 is involved in the activation of canonical V gamma 6/V delta 1 T cells by native E. coli lipid A.

Kerr-gated picosecond time-resolved resonance Raman spectra of an enantiomerically pure ruthenium(II) diimine intercalator complex in water and acetonitrile are reported, affording the first direct temporally resolved evidence that its excited state is structurally different in the two solvents. Copyright © 2000 John Wiley & Sons, Ltd.

The differentiation mechanisms that force thymocytes into the T-cell receptor (TCR)-alpha beta or TCR-gamma delta lineage are poorly understood, but rearrangement processes in the TCR-alpha/delta locus are likely to play an important role. It is assumed that the TCR-delta gene is deleted prior to V alpha-J alpha rearrangements by rearrangement of the so-called TCR-delta-deleting elements delta Rec and psi J alpha. However, the TCR-delta gene can also be deleted via V delta-J alpha rearrangements. We studied the different TCR-delta-deleting rearrangements of V delta 1, delta Rec, V delta 2 and V delta 3 to J alpha gene segments in human thymocytes and peripheral blood using polymerase chain reaction analysis. The V delta 1 gene segment is the most upstream V delta gene segment tested and appears to rearrange to almost all J alpha gene segments. In contrast, the delta Rec and V delta 2 gene segments only rearrange to the 5'-located J alpha gene segments, thereby preserving an extensive TCR-alpha combinatorial diversity, because most J alpha gene segments are kept available for subsequent V alpha-J alpha rearrangements. Based on our combined data we hypothesize that the different V delta gene segments and the delta Rec gene segment play different roles in T-cell development with regard to TCR-delta deletion.

Treatment of p-tert-butylphenyl 4,6-di-O-benzyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside (1aα) or the 4,6-di-O-(tert-butyldimethylsilyl) analogue (1bα) with various functionalized arylmagnesium bromides in the presence of a catalytic amount of PdCl2(dppf) at 25 °C in THF afforded the corresponding unsaturated C-arylglycosides 2−14 having the α-configuration in quite good yields. Benzyl-, allyl-, and vinylmagnesium bromides gave also the corresponding unsaturated α-C-glycosides 15−18, although in lower yields. When the same reaction was performed in the presence of NiCl2(dppe) as the catalyst at −40 °C, only the formation of the corresponding unsaturated C-arylglycosides having the β-configuration was observed. As expected, reaction of phenylmagnesium bromide with p-tert-butylphenyl 4,6-di-O-benzyl-2,3-dideoxy-β-d-erythro-hex-2-enopyranoside (1aβ) in the presence of NiCl2(dppe) gave only the unsaturated β-C-phenylglycoside 2aβ, while palladium-catalyzed reaction led to the preponderant formation of C-ph...

We report a detailed neutron-scattering study of the ordering of spins and holes in oxygen-doped La{sub 2}NiO{sub 4.133}. The single-crystal sample exhibits the same oxygen-interstitial order but better defined charge-stripe order than that studied previously in crystals with {delta}=0.125. In particular, charge order is observed up to a temperature at least twice that of the magnetic transition, T{sub m}=110.5 K. On cooling through T{sub m}, the wave vector {epsilon}, equal to half the charge-stripe density within an NiO{sub 2} layer, jumps discontinuously from (1) /(3) to 0.2944. It continues to decrease with further cooling, showing several lock-in transitions on the way down to low temperature. To explain the observed lock-ins, a model is proposed in which each charge stripe is centered on either a row of Ni or a row of O ions. The model is shown to be consistent with the l dependence of the magnetic peak intensities and with the relative intensities of the higher-order magnetic satellites. Analysis of the latter also provides evidence that the magnetic domain walls (charge stripes) are relatively narrow. In combination with a recent study of magnetic-field-induced effects, we find that the charge stripes are all O centered at T{gt}T{sub m}, with amore » shift towards Ni centering at T{lt}T{sub m}. Inferences concerning the competing interactions responsible for the temperature dependence of {epsilon} and the localization of charge within the stripes are discussed. {copyright} {ital 1998} {ital The American Physical Society}« less

The molecular model of IL-4 delta 2, a naturally occurring splice variant of human IL-4 with exons 1, 3, and 4 in an open reading frame, is described. The second exon codes the main part of the long loop AB connected the helices A and B in parallel superposition. Therefore the hydrophobic core and the native fold of the rest part of IL-4 delta 2 molecule could be preserved without any significant changes only in the case of revolution of the helix A relative to other helices. In the result, the dominated a left-handed four-helix bundle structure of IL-4 with an up-up-down-down structural pattern is transformed to the IL-4 delta 2 structure with a down-up-down-down structural pattern.

Yu, W.-Z. and R. J. Bodnar. Interactions between Angiotensin Ii and delta opioid receptor subtype agonists upon water intake in rats. Peptides 18(2) 241–245, 1997.—Delta opioid receptor agonists, like those of mu and kappa receptors, stimulate water intake. To assess the relative contributions of delta 1 and delta 2 receptors in the modulation of water intake stimulated by Angiotensin II (AII), the present study examined the respective actions of [D-Pen 2 , D-Pen 5 ]-enkephalin (DPDPE: 5–20 ug, icv) and [D-Ala 2 , Glu 4 ]-Deltorphin (Delt II: 5–20 ug, icv) upon water intake per se, and upon AII (0.02–20 ng, icv)-induced hyperdipsia in rats. Both DPDPE and Delt II dose-dependently stimulated spontaneous water intake. An ineffective (5 ug) dose of DPDPE differentially altered water intake when paired with AII, significantly increasing intake at the 0.02 ng dose, not changing intake at the 0.2 ng dose and significantly decreasing intake at the 2 ng dose. In contrast, pairing ineffective doses of Delt II (5 ug) and AII (0.2 ng) significantly increased water intake that persisted when either the Delt II dose (1 ug) or the AII dose (0.02 ng) was lowered. However, neither delta 1 nor delta 2 opioid agonists significantly altered the ED 50 for AII-induced drinking. Thus, delta 2 opioid agonism appeared more consistent and reliable than delta 1 opioid agonism in stimulating water intake when paired with AII, and these data indicate interactions between delta 1 and delta 2 agonists and AII in mediating water intake.

Despite the potential for extensive diversity of gamma delta TCR, especially for delta-chains, expression of the gamma delta TCR repertoire in various mouse epithelial tissues is highly restricted. This implies that the recognition of antigen by gamma delta T cells may also be limited. To date, however, few studies have examined gamma delta TCR diversity in peripheral lymphoid tissue. This report presents the V delta usage and junctional region sequences of TCR delta-chain transcripts derived from the lymph nodes of normal (PL/J x SJ/L) F1 mice. Rearranged TCR V delta-C delta transcripts were amplified by PCR for TCR delta-chain cDNA using oligonucleotide primers specific for the murine V delta 1 to V delta 7 genes and the C delta region. Following cloning of the polymerase chain reaction-amplified TCR delta cDNA, the extent of junctional diversity was assessed by nucleotide sequencing of the V-D-J junctions of individual TCR cDNA clones. With the exception of V delta 3, all V delta genes were expressed in mouse lymph node. Furthermore, predominant usage of J delta 1 was found in cDNA clones expressing V delta 2, V delta 4, V delta 5, V delta 6 and V delta 7 gene segments but despite this there was extensive junctional diversity of delta-chains primarily due to the usage of multiple D delta segments and N-nucleotide sequence addition. In contrast, the V delta 1 cDNA clones had limited heterogeneity consisting mostly of V delta 1 directly spliced to C delta gene rearrangements. These results show that the expressed murine peripheral TCR delta-chain repertoire is extremely diverse indicating that gamma delta T cells may potentially recognize a large number of antigens, and play an important role in contributing to host immune responses.

The blood clam Barbatia lima subsp. from Amami-Oshima, Japan, expresses three types of haemoglobins in erythrocytes: a tetramer (alpha 2 beta 2), a homodimer (delta 2) and a polymer consisting of two kinds of chains, a 34 kDa two-domain (2D) globin and a delta chain. This is in sharp contrast to the congeneric clams B. reeveana (a North American species) and B. lima from Kochi, Japan, each containing a tetramer and a polymer consisting of the 2D globin, but not the delta chain. We have determined the cDNA-derived amino acid sequences of all four chains, alpha (163 residues), beta (155 residues), delta (152 residues) and 2D (308 residues) of B. lima (Amami-Oshima). The alpha chain has an extremely long N-terminal extension of 20 residues that may form a 'pre-A helix', and this makes the alpha chain the longest known globin. B. lima alpha and beta chains show about 50% sequence identity with the alpha and beta chains, respectively, of tetrameric haemoglobin from a related clam, Anadara trapezia. The B. lima homodimeric delta chain shows 71-74% identity with each of the two domains of the 2D chain, but only 39% identity with the homodimeric gamma chain of Anadara. In addition, the alignment of amino acid sequences of the delta chain and the two domains of the 2D chain revealed that the delta chain lacks one amino acid (Lys) at the C-terminus, suggesting that the C-terminal Lys (codon AAA or AAG) of the two domains of 2D chain could result from the stop codon TAA in the delta chain by nucleotide substitutions. These results, together with the fact that the delta and 2D chains form a polymeric haemoglobin, indicates that the delta chain is the ancestral single-domain globin for the 2D globin. The delta chain is expressed only in B. lima (Amami-Oshima), and appears to be a relic of molecular evolution.

Previous studies have suggested that gamma delta T cells can be increased in HIV-1-seropositive individuals, although characterization of gamma delta T cell subtypes and correlation with clinical status of these patients have not been performed. We investigated groups of HIV-seropositive persons to determine the prevalence of elevated levels of gamma delta T cells and whether any gamma delta T cell subtypes were preferentially expressed. Since a large proportion of human gamma delta T cells appear to be reactive to proteins encoded by mycobacteria, we also examined our patients for the incidence of mycobacterial infection. Our results show that a significant number of HIV-positive patients have an elevated number of gamma delta T cells in their peripheral blood as compared to normal controls. HIV-seropositive patients with clinical or laboratory evidence of mycobacterial infection had statistically significant increases in the percentage and total numbers of gamma delta T cells over the HIV-positive persons without mycobacterial infection. An examination of the subtypes of gamma delta T cells revealed that certain subtypes such as V gamma 9+ and V delta 2+ T cells were preferentially elevated in the mycobacteria-positive patients. These results suggest that an increased number of gamma delta T cells in HIV-positive patients is most often seen in the setting of an opportunistic mycobacterial infection and that specific gamma delta T cell subtypes are stimulated under these conditions. The role of these increased number of gamma delta T cells in HIV-associated disease is unclear but is likely a component of the response and degree of host resistance to this organism.

A 7 month old Japanese boy was diagnosed to have Wiskott-Aldrich syndrome (WAS) because of eczema, thrombocytopenia, progressive immune defect and CD43 (sialophorin) abnormality. He had developed repeated infections since 16 months of age. Gamma delta T cell-receptor positive T cells in the peripheral blood were gradually increased from 3.1% (7 months of age) to 5.6% (12 months), 19.6% (18 months) and 56.7% (25 months). The phenotypes of expanded gamma delta T cells were delta TCS1-positive (V delta 1-J delta 1/J delta 2) and CD8 dim-positive. The proportion of increased granular lymphocytes correlated well with that of gamma delta T cells. The significance of peripheral expansion of gamma delta T cells and granular lymphocytes in WAS is discussed.

An antibody was made to a C-terminus peptide of the glutamate receptor delta 2 subunit and used to study the distribution, biochemical properties, and developmental expression of the delta receptor in rat brain. The antibody recognizes both delta 1 and delta 2 but not AMPA, kainate, NMDA, and mGluR1 alpha glutamate receptor subunits based on Western blot analysis of transfected HEK-293 cells. Western blot analysis of brain showed a single immunoreactive band, migrating at M(r) = 114,000. Immunoprecipitation of detergent-solubilized cerebellar membranes was done to determine if delta is associated with other glutamate receptor subunits and if it binds any of the common excitatory amino acid ligands. Based on results of these studies, AMPA, kainate, NMDA, and mGluR1 alpha subunits do not coassemble with delta subunits, and 3H-glutamate, 3H-AMPA and 3H-kainate do not bind to the delta receptor complex. Western blot and immunocytochemical analyses showed marked expression of delta in the cerebellum while lower levels were detected in other regions of the brain. A dramatic increase of delta 1/2 immunoreactivity was observed in the cerebellum between the ages of 10 and 15 d postnatal. Light and electron microscopy, respectively, demonstrated dense immunostaining in Purkinje cells and in postsynaptic densities of the adult parallel fiber-Purkinje spine synapse. The prominent delta 1/2 immunoreactivity found in the parallel fiber-Purkinje spine synapse, and the temporal correlation of the development of this synapse with the major increase in delta 1/2 immunoreactivity, suggest a major functional role for the delta subunits in cerebellar circuitry.

Histidine usually exists in three different forms (including biprotonated species, neutral tau and pi tautomers) at physiological pH in biological systems. The different protonation and tautomerization states of histidine can be characteristically determined by C-13 and N-15 chemical shifts of imidazole ring. In this work, solid-state NMR techniques were developed for spectral editing of C-13 and N-15 sites in histidine imidazole ring, which provides a benchmark to distinguish the existing forms of histidine. The selections of C-13(gamma), C-13(delta 2), N-15(delta 1), and N-15(epsilon 2) sites were successfully achieved based on one-bond homo- and hetero-nuclear dipole interactions. Moreover, it was demonstrated that H-1, C-13, and 15 chemical shifts were roughly linearly correlated with the corresponding atomic charge in histidine imidazole ring by theoretical calculations. Accordingly, the H-1, C-13 and N-15 chemical shifts variation in different protonation and tautomerization states could be ascribed to the atomic charge change due to proton transfer in biological process. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.

The formation of kinetic, transient microstructures in structural phase transitions is analysed within the framework of time-dependent Landau-Ginzburg theories. The mesoscopic rate equation is delta phi / delta t= phi - phi 3+ delta 2 phi / delta x2- gamma delta 2 phi / delta x4+ delta delta 6 phi / delta x6. A front of a stable state phi =1 can grow into an unstable region with phi =0 in an oscillatory manner. It will then leave behind a transient domain structure with quasi-periodic walls. Such domain structures occur for positive and negative values of gamma with sufficiently large values of mod gamma mod . The phase diagram in ( gamma , delta ) space is explored using computer simulation. The repetition length does not diverge at the bifurcation between an oscillatory and solitonic regime except at the point gamma =1/12. delta =0 studied previously. It is shown that recent computer simulation studies of realistic microstructures used implicit values of gamma and delta close to the bifurcation condition.

While V gamma 9/V delta 2 cells dominate among peripheral blood gamma delta T cells in healthy adults, the majority of gamma delta T cells in most HIV-1-infected individuals express V delta 1. We asked whether these elevated levels of V delta 1 T cells were due to clonal expansion. Three-color flow cytometry with monoclonal antibodies against V gamma 2/V gamma 3/V gamma 4, V gamma 4 and V gamma 9 was used to investigate V gamma usage in 27 patients with elevated numbers of V delta 1 T cells. While the relative proportion of V gamma 9 cells among gamma delta T cells was significantly reduced in HIV-1+ individuals (10 +/- 11% vs. 80 +/- 17%, p < 0.001), the fraction of gamma delta T cells using V gamma 5 or V gamma 8 was significantly increased (54 +/- 15% vs. 7 +/- 11%, p < 0.001). In 1 patient, 76% of the V delta 1 cells expressed V gamma 2 or V gamma 3, suggesting clonality of the V delta 1 population. In line with this assumption, analysis of the V delta 1-J delta junctional regions by reverse transcription-polymerase chain reaction (RT-PCR) resulted in products of only one junctional length, as demonstrated by electrophoresis on denaturing gels, and 12 out of 16 (75%) in-frame junctional sequences were identical in this patient. In other HIV-1+ patients, RT-PCR resulted in products of several distinct sizes, also indicating a highly restricted repertoire. After sequencing the V delta 1-J delta junctional regions of 3 additional patients, we found repeated but patient-specific in-frame junctions accounting for 10-30% of the sequenced clones. However, limited V delta 1-J delta junctional diversity was also seen in healthy donors. RT-PCR products from 10 healthy individuals resulted in distinct bands on denaturing gels. In 1 of them exhibiting a single prominent band, 10 out of 17 (58%) sequenced junctions were identical. Two other healthy donors displayed 2/14 and 5/18 identical junctional sequences, respectively. Taken together, our results reveal significant alterations of V gamma usage in HIV-1+ patients, while the V delta 1 junctional repertoire is similarly restricted in HIV-1+ and HIV-1- individuals. Therefore, these data argue against an obligatory clonal expansion of V delta 1-expressing cells during HIV-1 infection.

SLE is an autoimmune connective tissue disorder affecting multiple organs, in which T cells may play a central role. This study investigated T cell receptor (TCR) gamma/delta repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individuals using variable (V) gene family-specific polymerase chain reaction (PCR) amplification of TCR cDNA. The expressed V gamma repertoires were diverse in SLE and control PBMC, although V gamma IV gene rearrangements were barely detectable or not expressed in some patients. In contrast, delta chain expression was limited in all SLE patients, with delta transcripts rearranged primarily to the V delta 1 and V delta 2 genes, as opposed to control PBMC, in which all six V delta genes were detected. To assess the clonality of TCR populations, cDNA clones containing rearranged V delta 1, V delta 2 and V gamma 9 transcripts were sequenced from PBMC of both patients and controls. For controls, delta chain junctional region sequences showed extensive molecular heterogeneity, since virtually all 34 V delta 1 and 32 V delta 2 cDNA clones analysed were unique. A few V gamma 9 cDNA clones (3/21) had the same junctional region sequence motif (EVQEL) encoded largely by the V gamma 9 and joining (J) gamma P gene segments. Identical V gamma 9 junctional sequences were found in SLE patients that did not contain the EVQEL motif present in normal peripheral blood gamma/delta lymphocytes. Moreover, the predominant V delta 1-J delta -constant (C) delta and V delta 2-J delta-C delta gene rearrangements expressed in SLE PBMC showed restricted junctional diversity, but the oligoclonal delta transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of gamma/delta T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether gamma/delta T cells contribute to the development of systemic autoimmunity remains to be investigated.

Separate genetic elements (V, D, and J) encode the variable regions of lymphocyte antigen receptors. During early lymphocyte differentiation, these elements rearrange to form contiguous coding segments (VJ and VDJ) for a diverse array of variable regions. Rearrangement is mediated by a recombinase that recognizes short DNA sequences (signals) flanking V, D, and J elements. Signals flank both the 5' and 3' sides of each D element, thereby allowing assembly of a functional VDJ gene. However, in rearrangements involving the D delta 2 and J delta 1 elements of the mouse T-cell receptor delta (TCR delta) locus, we unexpectedly found that the D delta 2 element and a portion of its 5' signal are often deleted. Approximately 50% of recovered D delta 2 to J delta 1 rearrangements from thymocytes of adult wild-type mice showed such deletions. An additional 20% of the rearrangements contained standard D delta 2-J delta 1 coding junctions but showed some loss of nucleotides from the 5' D delta 2 signal. This loss was clearly associated with another event involving a site-specific cleavage at the 5' signal/coding border of D delta 2 and rejoining of the modified signal and coding ends. The abnormal loss of D delta 2 and a portion of the 5' D delta 2 signal was infrequently observed in D delta 2-to-J delta 1 rearrangements recovered from neonatal mice. The possible basis and significance of this age-dependent phenomenon are discussed.

Acoustic measurements from 10-2 to 107 Hz show that phase-like transitions (PLTs) characterized by a small jump of lattice parameters in the range 100-300 K always exist in high-Tc (near 100 K) superconducting Y-Ba-Cu-O, Bi-Sr-Ca-Cu-O and Tl-Ba-Ca-Cu-O. Ferroelastic loops associated with the elastic softening of C'=((C11+C22)/2-C12)/2 and C66 invariably occur at the PLT temperatures, and in some cases the shape memory effect may be observed. For various samples of Bi-Sr-Ca-Cu-O and Tl-Ba-Ca-Cu-O with different Tc, the acoustic attenuation (Q-1, alpha ) from the kilohertz to megahertz range reveals a plateau (Qp-1, alpha p) above Tc and drops obviously below Tc with the turning point at Tc. This kind of anomaly has not been observed for non-superconducting samples. Qp-1 is found to be closely related to the carrier density for YBa2Cu3O7- delta , Y1-xPrxBa2Cu3O7 and Gd1-xPrxBa2Cu3O7, and the drop of Q-1 and a below Tc is considered to be caused by superconducting condensation. The energy dissipation (Qp-1 and alpha p) related to carriers can be explained reasonably by using a coupling model of carriers with local dynamic distortion. Furthermore, taking account of the smearing of the superconducting gap structure and by using the modified Bardeen-Cooper-Schrieffer (BCS) relative jump rate, S(E, E', Gamma )=Re(1- Delta 2/((E-i Gamma )(E'-i Gamma ))), the calculated results of acoustic attenuation below Tc are in fairly good agreement with the experimental data. The superconducting gap Delta and the damping rate Gamma for both Bi-Sr-Ca-Cu-O and TI-Ba-Ca-Cu-O have also been obtained.

1H-NMR spectra have been recorded for glucoamylases I and II from Aspergillus awamori var. X100 and from A. niger in the 9-15-ppm region. At least 17 distinct peaks, many of them arising from single protons, are observed. These are designated A-Q, A being the furthest downfield. At least 9 of these are lost rapidly by exchange when the enzyme is placed in D2O. Peaks A, B, E and H undergo distinct shifts with pH change in the pH region 3-7. Several others undergo smaller shifts. Small differences are also seen between the enzymes from the two different sources. Binding of the pseudotetrasaccharide inhibitor acarbose leads to a 0.50-ppm downfield shift of peak B, other smaller changes, and retention of two additional protons in D2O. delta-D-gluconolactone induces shifts in peaks E, H, and L. The slow substrate maltitol causes peak A to broaden and shift, peaks J and K to shift and a new or greatly shifted resonance to appear at 15.4 ppm. It disappears as the maltitol is hydrolyzed. Treatment with iodoacetamide or diethyl pyrocarbonate leads to disappearance of peak D at 12.3 ppm. When this peak was irradiated strong nuclear Overhauser effects (NOE) were observed at 8.01 ppm and 7.22 ppm, positions expected for the C epsilon 1 and C delta 2 protons of an uncharged imidazole ring. We identify D as arising from the N epsilon 2 proton of His254 which is uncharged except at the lowest pH values. Other NOE and two-dimensional NOE spectra have provided additional information. Three mutant forms of the A. niger enzyme, in which tryptophan residues have been replaced by phenylalanine, have been examined. Because of shifts induced by changes in ring current and other environmental effects it is hard to make a direct identification of the resonances from the replaced indole NH protons. However, on the basis of a distinct NOE between peaks E and H we have identified these resonances as arising from the indole NH protons of Trp52 and Trp120. Other possible assignments are considered. The NMR spectra of the glucoamylases I, which have a starch binding domain of about 104 residues at the carboxyl terminus, show four sharp resonances in the 9.7-10.6-ppm range that are not present in the glucoamylases II, which lack this domain. These resonances no doubt represent the four indole NH ring protons from Trp543, Trp562, Trp590 and Trp615. Three of these are very sharp suggesting a high mobility of this domain.

Recently, we and others have shown the occurrence of TCR delta gene rearrangements in acute myeloid leukaemia (AML). In this study we describe the molecular characteristics of these rearrangements by the polymerase chain reaction (PCR) and the direct sequencing of PCR products. 11 rearrangements were characterized in blast cell samples from six patients. We found a heterogenous pattern of TCR delta gene rearrangements with involvement of V delta 1-5 regions. These findings differ from observations in T-ALL and B-cell precursor ALL, where predominantly usage of V delta 1 and V delta 2 regions has been described. Furthermore, extensive diversity of junctional sites was observed, including addition of up to 37 N nucleotides, nucleotide deletions at junction sites of V delta and J delta segments and usage of up to three D delta segments. The D delta 3 fragment was the most frequently used diversity element and was found in 10 rearrangements. Nine of the 11 rearrangements were non-functional, either incomplete or out of the reading frame. Therefore a functional TCR delta cannot be expressed in these myeloid blast cells.

Clonality, in MDS, can only be assessed in patients with chromosomal rearrangements or in females heterozygote for X chromosome restricted polymorphisms. "Illegitimate" rearrangements of the immunoglobulin heavy chain (IgH) gene and incomplete rearrangements involving V delta 2 and D delta 3 segments of the T-cell receptor delta (TcR delta) gene are seen in some cases of AML, and AML post-SMD, and can be detected by a sensitive PCR method. In order to analyse clonality in additional cases in MDS, we looked for Ig H and TcR delta gene rearrangement by PCR in 95 cases of MDS. A rearrangement of the Ig H gene was seen in 2 of the 95 patients: in the circulating blood of 2 of the 36 cases of chronic myelomonocytic leukaemia (CMML) and in none of the marrow samples of the other 59 MDS. A rearrangement of the TcR delta gene (involving V delta 2 and D delta 3 segments) was seen in three cases (in the circulating blood of two other CMLL patients, and in the bone marrow of another MDS patient). Twenty-five of the 90 cases of MDS with negative PCR findings, in addition to the five cases with positive PCR findings underwent Southern blot analysis of Ig H and TcR delta genes, and PCR analysis of V delta 1 and J delta 1 segments of the TcR delta gene. Those examinations were normal in all the cases tested. In patients with positive PCR findings for Ig H or V delta 2 D delta 3 rearrangements, the proportion of rearranged cells was evaluated at 1-5% in four cases, and 5-10% in the remaining patient. Because the analysis was performed on total circulating leukocytes or total nucleated marrow cells, the nature of the clonal population in positive cases (lymphoid cells? myeloid cells? blasts?) could not be determined. From a practical point of view, Ig H and TcR delta gene rearrangements seem to very rare in MDS, and cannot be used as clonality markers in most cases.

The rearrangement and expression of T cell receptor (TCR) gene segments occurs in a highly ordered fashion during thymic ontogeny of T lymphocytes. To study the regulation of gene rearrangement within the TCR alpha/delta locus, we generated transgenic mice that carry a germline human TCR delta minilocus that includes V delta 1, V delta 2, D delta 3, J delta 1, J delta 3, and C delta segments, and either contains or lacks the TCR delta enhancer. We found that the enhancer-positive construct rearranges stepwise, first V to D, and then V-D to J. Construct V-D rearrangement mimics a unique property of the endogenous TCR delta locus. V-D-J rearrangement is T cell specific, but is equivalent in alpha/beta and gamma/delta T lymphocytes. Thus, either there is no commitment to the alpha/beta and gamma/delta T cell lineages before TCR delta gene rearrangement, or if precommitment occurs, it does not operate directly on TCR delta gene cis-acting regulatory elements to control TCR delta gene rearrangement. Enhancer-negative mice display normal V to D rearrangement, but not V-D to J rearrangement. Thus, the V-D to J step is controlled by the enhancer, but the V to D step is controlled by separate elements. The enhancer apparently controls access to J delta 1 but not D delta 3, suggesting that a boundary between two independently regulated domains of the minilocus lies between these elements. Within the endogenous TCR alpha/delta locus, this boundary may represent the 5' end of a chromatin regulatory domain that is opened by the TCR delta enhancer during T cell development. The position of this boundary may explain the unique propensity of the TCR delta locus to undergo early V to D rearrangement. Our results indicate that the TCR delta enhancer performs a crucial targeting function to regulate TCR delta gene rearrangement during T cell development.

Mitochondrial delta 3,5, delta 2,4-dienoyl-CoA isomerase, which catalyzes the conversion of 3,5-octadienoyl-CoA to 2,4-octadienoyl-CoA, was purified from rat liver 370-fold at almost 30% yield by a six-step purification procedure. The final preparation appeared to be homogeneous as judged by gel electrophoresis. The molecular weights of the native enzyme and its subunit(s) were estimated to be 126,000 and 32,000, respectively. The purification of delta 3,5, delta 2,4-dienoyl-CoA isomerase completes the characterization of the enzymes functioning in the NADPH-dependent pathway for the beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms. This novel pathway may not be operative in peroxisomes because delta 3,5, delta 2,4-dienoyl-CoA isomerase was only detected in mitochondria. Substrates of this pathway are 2,5-dienoyl-CoAs formed from 5-enoyl-CoAs by acyl-CoA dehydrogenase. Two sequential isomerization reactions catalyzed by delta 3, delta 2-enoyl-CoAs isomerase and delta 3,5, delta 2,4-dienoyl-CoA isomerase, respectively, convert 2,5-dienoyl-CoAs to 2,4-dienoyl-CoAs, which are reduced by NADPH-dependent 2,4-dienoyl-CoA reductase (EC 1.3.1.34) before reentering the beta-oxidation spiral.

The behaviour of drift waves localized in a narrow layer in a plasma with a density gradient is discussed. In zero order the plasma is assumed to be in a steady state in which ionization is balanced by a plasma transport process independent of the drift waves, which leads to a flux of plasma through the drift wave layer. It is shown that this plasma flux interacts with the drift wave to increase the damping rate by an amount inversely proportional to the density gradient. Thus as the drift wave amplitude increases, the density gradient flattens until the growth rate is reduced to zero. The theory leads to specific predictions of the saturated amplitude and the drift wave transport: the amplitude rises until the plasma excursion is equal to Delta , the half-thickness of the drift wave layer, and the additional diffusivity is 1/2 gamma Delta 2 where gamma is the linear growth rate at zero amplitude. This theory is shown to agree well with experimental results from the SHEILA heliac, while for comparison a fully nonlinear theory is shown to predict amplitudes much larger than those observed.

The majority (50-90%) of gamma delta T cells in the peripheral blood of adult individuals expresses a T-cell receptor (TCR) which uses V gamma 9 and V delta 2 as variable elements. Little is known about the distribution of other V gamma gene elements in the remaining 10-50% of gamma delta T cells. Here we have studied the V gamma gene expression in peripheral blood gamma delta T cells by 3-color flow cytometry analysis applying established monoclonal antibodies (mAb) directed against V gamma 9 and V gamma 4, as well as a novel mAb directed against V gamma 2, V gamma 3 and V gamma 4. On average, 79.9% of gamma delta T cells expressed V gamma 9, 11.9% V gamma 2/V gamma 3, 4.4% V gamma 4, and 7.5% one of the remaining V gamma 5, V gamma 8, V gamma 10 or V gamma 11 elements. There were remarkable variations in the gamma delta subset composition between individual donors. The majority (69.8%) of V gamma 2/V gamma 3/V gamma 4-bearing cells co-expressed V delta 1, while on average only 17.8% of V gamma 2/V gamma 3/V gamma 4-bearing cells co-expressed V delta 2. This is in contrast to V gamma 9-bearing gamma delta T cells, of which 83.1% used V delta 2 and only 12.7% V delta 1. Taken together, this data identifies V gamma 2/V gamma 3 as the second most frequently used set of V gamma elements in human peripheral blood gamma delta T cells.

In order to investigate the distribution and involvement of human gamma delta T-cell receptor-positive (TCR+) cells in delayed-type hypersensitivity reactions of the skin, we examined the occurrence and kinetics of gamma delta TCR+ cells during skin reactions of allergic contact dermatitis. In normal human skin sections, gamma delta TCR+ cells were scarce. In allergic contact dermatitis from DNCB, increased gamma delta TCR+ cells were observed both in the epidermis and in the dermis from 48 h after the challenge. Most of the gamma delta TCR+ cells were TCR delta 1+ delta TCS1- BB3+ Ti gamma A+ (V delta 1- V delta 2+ V gamma 9+). The percentage of gamma delta TCR+ cells in the peripheral blood remained unchanged and a few gamma delta TCR+ cells in the skin lesions proliferated in situ. It is suggested that the gamma delta TCR+ cells in skin lesions of allergic contact dermatitis may not be involved in initiation of delayed-type hypersensitivity but may have some other roles responding to factors induced in the reaction.

We have performed a phenotypic and molecular analysis of monoclonal TCR gamma/delta T-cell lines derived from jejunal and colonic biopsies of healthy individuals. Flow cytometric analysis employing a panel of 24 monoclonal antibodies (MoAbs) demonstrated that intestinal TCR gamma/delta intraepithelial lymphocytes (IEL) constitute a phenotypically heterogeneous population. Nucleotide sequence analysis of expressed TCR delta variable (V) regions revealed the dominant utilization of the V delta 2 and D delta 3 gene segments and frequent rearrangement of J delta 3. IEL V delta regions displayed extensive junctional diversity as a result of N and P insertion and the utilization of D delta 3 in all three reading frames. The results demonstrate that intestinal TCR gamma/delta T cells from healthy individuals constitute a phenotypically heterogeneous population expressing V delta regions that differ from their systemic counterparts.