Background: Psoriasis is a chronic immune-mediated skin disease with systemic inflammation and comorbidities. Although the disease severity may vary over time, many patients suffer from mild to moderate disease. Often local treatment will be sufficient to control the symptoms, but they may have several side effects.
View Article and Find Full Text PDFThe networks of transcription factors (TFs) that control intestinal-resident memory CD8 T (T) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role of the TF Bcl11b in T cells during infection with using mice with post-activation, conditional deletion of Bcl11b in CD8 T cells. Conditional deletion of Bcl11b resulted in increased numbers of intestinal T cells and their precursors as well as decreased splenic effector and circulating memory cells and precursors.
View Article and Find Full Text PDFEquestrian sports, including racing (e.g., flat, steeple-chasing, harness or donkey derby); show-jumping; cross-country; dressage; polo; polocrosse; endurance; carriage driving; vaulting and hunting; are hugely popular in the UK, and they involve a significant number of people, both as participants and spectators, and tens of thousands of equids.
View Article and Find Full Text PDFEpigenetic landscapes can provide insight into regulation of gene expression and cellular diversity. Here, we examined the transcriptional and epigenetic profiles of seven human blood natural killer (NK) cell populations, including adaptive NK cells. The gene, encoding a transcription factor (TF) essential for T cell development and function, was the most extensively regulated, with expression increasing throughout NK cell differentiation.
View Article and Find Full Text PDFThe activation of natural killer (NK) cells depends on a change in the balance of signals from inhibitory and activating receptors. The activation threshold values of NK cells are thought to be set by engagement of inhibitory receptors during development. Here, we found that the activating receptor NKG2D specifically set the activation threshold for the activating receptor NCR1 through a process that required the adaptor DAP12.
View Article and Find Full Text PDFHeterozygous mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying mutation, NK cells persist.
View Article and Find Full Text PDFSeveral monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied 2 families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in , a tumor suppressor gene located on chromosome arm 7q.
View Article and Find Full Text PDFEmpirical work has shown that people like visual symmetry. We used a gaze-driven evolutionary algorithm technique to answer three questions about symmetry preference. First, do people automatically evaluate symmetry without explicit instruction? Second, is perfect symmetry the best stimulus, or do people prefer a degree of imperfection? Third, does initial preference for symmetry diminish after familiarity sets in? Stimuli were generated as phenotypes from an algorithmic genotype, with genes for symmetry (coded as deviation from a symmetrical template, deviation-symmetry, DS gene) and orientation (0° to 90°, orientation, ORI gene).
View Article and Find Full Text PDFImmune memory has traditionally been considered a hallmark of vertebrate T and B lymphocytes. However, given the advantage in mounting quicker and more robust responses to recurrent infection, it is unsurprising that alternative strategies of memory are found in various immune cells throughout the evolutionary tree. In this context, a variety of NK cell memory subsets have recently been identified.
View Article and Find Full Text PDFThe mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we describe the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins after human cytomegalovirus (HCMV) infection. The absence of B and myeloid cell-related signaling protein expression in these NK cell subsets correlated with promoter DNA hypermethylation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2014
Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, we have analyzed the response of human NK cells to tumor cells, and we identify a pathway by which NK-DC interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNF superfamily member 14 [TNFSF14; also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT)], a cytokine implicated in the enhancement of antitumor responses.
View Article and Find Full Text PDFStudying aesthetic preference is notoriously difficult because it targets individual experience. Eye movements provide a rich source of behavioral measures that directly reflect subjective choice. To determine individual preferences for simple composition rules we here use fixation duration as the fitness measure in a Gaze Driven Evolutionary Algorithm (GDEA), which has been demonstrated as a tool to identify aesthetic preferences (Holmes and Zanker, 2012).
View Article and Find Full Text PDFForensic Sci Int
September 2013
There is considerable value in developing tools capable of accurately and reliably determining when bruises were inflicted in humans. Previous work has focused on the visual changes observed in a bruise as the injury develops and heals. However, due to variables such as how and where on the body the bruise was inflicted, differing tissue compositions at the injured skin site between individuals and inter- and intra-observer variation; a technique sufficiently robust for use in a clinical or medicolegal setting has not yet been identified.
View Article and Find Full Text PDFEye movements are strongly influenced by the task given to an observer. The immediacy of such eye movements, which are difficult to control consciously, offers the potential to explore highly variable subjective evaluations, such as aesthetic preference, with reliable objective measures. We presented a variety of images in sets of 2, 4, or 8 items for different durations and analyzed oculomotor statistics such as cumulative fixation duration, refixations, and the sequence of fixations while participants searched for their preferred image, after which participants indicated their preference using a button press.
View Article and Find Full Text PDFNK cell activation is negatively regulated by the expression of target cell MHC class I molecules. We show that this relationship is nonlinear due to an NK cell activation/inhibition threshold. Ewing's sarcoma family tumor cell monolayers, which were highly susceptible to NK cells in vitro, developed a highly resistant phenotype when cultured as three-dimensional multicellular tumor spheroid structures.
View Article and Find Full Text PDFNK cells induce apoptosis in target cells via the perforin-mediated delivery of granzyme molecules. Cytotoxic human NK cells can be generated by IL-15-mediated differentiation of CD34(+) cells in vitro and these cultures have been used extensively to analyze the development of the NK cell surface phenotype. We have used NK cell differentiation in vitro together with protease-deficient human NK cells to analyze the acquisition of the cytotoxic phenotype.
View Article and Find Full Text PDFRecent evidence suggests a role for natural killer (NK) cells in the control of multiple myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56(dim) NK cells from myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-myeloma interactions.
View Article and Find Full Text PDFA multifaceted tomotherapy quality assurance procedure has been developed. This procedure tests most of the features inherent in the tomotherapy Hi-Art device. This includes the megavoltage imaging quality, spatial and temporal accuracy of the dynamic delivery properties, as well as more traditional beam output characteristics.
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