double negative t

The ability to directly detect double-stranded DNA (dsDNA) without sequence-preference continues to be a major challenge. Herein, we report an electrochemical method for the direct, highly sensitive detection of dsDNA based on the strand replacement of dsDNA by peptide nucleic acid (PNA) and the in situ growth of electroactive polymers through the surface-initiated electrochemically mediated atom transfer radical polymerization (SI-eATRP). Thiolated PNA molecules are firstly self-assembled onto gold electrode surface for the specific recognition of target dsDNA (dsDNA-T), which in turn leads to the formation of a high density of PNA/DNA heteroduplexes on the electrode surface for the subsequent attachment of ATRP initiators via the phosphate-Zr(4+)-carboxylate chemistry...

IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8(+) T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8(+) T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation...

Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These "double-negative" PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence...

Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly γδ DN T cells play a role in the control of immune activation in PHI. Since γδ T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI)...

We present a case of a 2-year-old female presenting with diffuse lymphadenopathy 2 years following orthotopic heart transplant. Initially, she was diagnosed with posttransplant lymphoproliferative disease based on clinical presentation and pathology and she was treated accordingly. Because of persistent lymphadenopathy following the completion of chemotherapy and new onset of autoimmune cytopenias, repeat flow of the lymph node showed an elevated double negative T-cell population prompting evaluation for autoimmune lymphoproliferative syndrome (ALPS)...

BACKGROUND/AIMS: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. METHODS: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression...

BACKGROUND: Prenatal mercury exposure has been related to reductions in anthropometry at birth. Levels of mercury have been reported as being relatively elevated in the Spanish population. OBJECTIVE: To investigate the relation between prenatal exposure to mercury and fetal growth. METHODS: Study subjects were pregnant women and their newborns (n:1867) participating in a population-based birth cohort study set up in four Spanish regions from the INMA Project...

Collisional energy transfer under cold conditions is of great importance from the fundamental and applicative point of view. Here, we investigate low temperature collisions of the SH(-) anion with He. We have generated a three-dimensional potential energy surface (PES) for the SH(-)(X(1)Σ(+))-He((1)S) van der Waals complex. The ab initio multi-dimensional interaction PES was computed using the explicitly correlated coupled cluster approach with simple, double, and perturbative triple excitation in conjunction with the augmented-correlation consistent-polarized valence triple zeta Gaussian basis set...

Intraepithelial lymphocytes (IELs) are resident cells localized within the intestinal epithelia and play an important role in regulating gut inflammations and host defense against pathogens. CD8α(+) TCRαβ(+) IELs are heterogeneous populations that are generated from T cell precursors including CD4(-) CD8α(-) double-negative (DN) cells and CD4(+) CD8α(+) double-positive (DP) cells. However, developmental pathways of TCRαβ(+) IELs remained unclear. To gain insight into the mechanisms, we generated mice (Bcl11b(ΔDN2) mice) that lack thymic precursors (DN CD5(+) TCRβ(+) cells) for CD4(-) CD8αα(+) TCRαβ(+) IELs...

OBJECTIVES: We aimed to investigate alpha beta double negative (αβ DN) T-cell percentages in juvenile systemic lupus erythematosus (JSLE) and their relation to disease activity and organ involvement. METHODS: This prospective study was carried out over a period of 12 months and included 21 JSLE patients and 20 healthy matched controls. SLE disease activity index 2000 (SLEDAI-2K) scores were recorded in addition to αβ DN T-cell percentages measurement at enrollment and after remission...

Activation of protease-activated receptor-2 (PAR2) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR2 conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR2-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR2 in thymocytes isolated from T cell-specific PAR2-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus...

Negative selection against highly self-reactive thymocytes is critical for preventing autoimmunity. Thymocyte deletion, anergy induction, and agonist selection are all forms of negative selection that can occur following a high-affinity TCR signal. Of Bim and Nur77, two TCR-induced proteins with proapoptotic function, Bim has been shown to be important for clonal deletion in several model systems, whereas Nur77 was often dispensable. However, Nur77 has been reported to influence other aspects of T cell development by mechanisms that may not be related to its proapoptotic function...

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The mismatch negativity (MMN) reflects the early detection of changes in sensory stimuli at the cortical level. The mechanisms underlying its genesis remain debated. This magnetoencephalography study investigates the spatio-temporal dynamics and the neural mechanisms of the magnetic somatosensory MMN. Somatosensory evoked magnetic fields elicited by tactile stimulation of the right fingertip (Single), tactile stimulation of the right middle phalanx and fingertip (Double) or omissions (Omitted) of tactile stimuli were studied in different paradigms: in oddballs where Double/Omitted followed a sequence of four Single, in sequences of two stimuli where Double occurred after one Single, and in random presentation of Double only...

Human mucosal-associated invariant T (MAIT) cells are an important T cell subset that are enriched in tissues and possess potent effector functions. Typically such cells are marked by their expression of Vα7.2-Jα33/Jα20/Jα12 T cell receptors, and functionally they are major histocompatibility complex class I-related protein 1 (MR1)-restricted, responding to bacterially derived riboflavin synthesis intermediates. MAIT cells are contained within the CD161++ Vα7.2+ T cell population, the majority of which express the CD8 receptor (CD8+), while a smaller fraction expresses neither CD8 or CD4 coreceptor (double negative; DN) and a further minority are CD4+...

Background and Aims: The genetic basis of increased rooting below the plough layer, post-anthesis in the field, of an elite wheat line (Triticum aestivum 'Shamrock') with recent introgression from wild emmer (T. dicoccoides), is investigated. Shamrock has a non-glaucous canopy phenotype mapped to the short arm of chromosome 2B (2BS), derived from the wild emmer. A secondary aim was to determine whether genetic effects found in the field could have been predicted by other assessment methods...

Longitudinal maternal mental health data are needed from high HIV prevalence settings. The Siyakhula Cohort (SC) is a population-based cohort of HIV-positive and negative mothers (n=1506) with HIV-negative children (n=1536) from rural South Africa. SC includes 767 HIV-negative mothers; 465 HIV-positive in pregnancy; 272 HIV-positive since pregnancy (n=2 missing HIV status). A subgroup (n=890) participated in a non-randomized breastfeeding intervention [Vertical Transmission Study (VTS)]; the remaining (n=616) were resident in the same area and received antenatal care at the time of the VTS, but were not part of the VTS, instead receiving the standard of care Prevention of Mother-to-Child Transmission (PMTCT) Programme...

Growing insight into the pathogenesis of autoimmune diseases and numerous studies in preclinical models highlights the potential of regulatory T cells to restore tolerance. By using non-obese diabetic (NOD) BDC2.5 TCR-transgenic (Tg), and IL-10 and Foxp3 double-reporter mice, we demonstrate that alteration of gut microbiota during cohousing experiments or treatment with anti-CD3 mAb significantly increase intestinal IL-10-producing type 1 regulatory T (Tr1) cells and decrease diabetes incidence. These intestinal antigen-specific Tr1 cells have the ability to migrate to the periphery via a variety of chemokine receptors such as CCR4, CCR5, and CCR7 and to suppress proliferation of Th1 cells in the pancreas...

Alternative splicing of the oncogene murine double minute 2 (MDM2) is induced in response to genotoxic stress. MDM2-ALT1, the major splice variant generated, is known to activate the p53 pathway and impede full-length MDM2's negative regulation of p53. Despite this perceptible tumor-suppressive role, MDM2-ALT1 is also associated with several cancers. Furthermore, expression of MDM2-ALT1 has been observed in aggressive metastatic disease in pediatric rhabdomyosarcoma (RMS), irrespective of histological subtype...

The crystal structure, electronic structure and magnetic properties were systematically studied in a series of Fe-doped La1.5Sr0.5CoMnO6 double perovskites. The X-ray diffraction patterns of the samples are all refined with a rhombohedral (R3[combining macron]c) structure. The parameters a and c continuously increase with increasing Fe doping concentration x. X-ray photoelectron spectroscopy (XPS) spectra of the Mn, Co, and Fe 2p core levels, consistent with the soft X-ray absorption spectroscopy (XAS) spectra of Mn, Co, and Fe L2,3 edges, indicate that their valence states are Mn(3+) and Mn(4+), Co(2+) and Co(3+), and Fe(3+), respectively...