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Johansson Malin E V ME Department of Medical Biochemistry, University of Gothenburg, Gothenburg, - - 2014
: The intestinal epithelium is covered with mucus with the main structural building block being the densely O-glycosylated MUC2 mucin. The intestinal epithelium is exposed to ingested material, our digestive machinery, and large amounts of microorganisms. Mucus is the first line of defense and aids to limit exposure to all ...
Maggadottir Solrun M SM The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, - - 2014
Immune deficiency and autoimmunity have been recognized as cotravelers for decades. This clinically oriented review brings together our evolving mechanistic understanding to highlight associations of particular relevance to rheumatologists. Conceptually, all autoimmunity derives from a loss of tolerance. This distinguishes it from autoinflammation in which the innate immune system is ...
Gazendam Roel P RP Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Netherlands; - - 2014
Invasive fungal infections, accompanied by high rates of mortality, represent an increasing problem in medicine. Neutrophils are the major effector immune cells in fungal killing. Based on studies with neutrophils from patients with defined genetic defects, we provide evidence that human neutrophils use two distinct and independent phagolysosomal mechanisms to ...
Lodh Sukanya S Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, - - 2014
Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with these structures results in perturbation of the development and function of a spectrum of tissue and cell types. Here, we review the role of cilia in mediating ...
Gowda Prarthana - - 2014
A novel approach is presented for achieving an enhanced photo response in a few layer graphene (FLG) based photodetector that is achieved by introducing defect sites in the FLG. Fabrication induced wrinkle formation in graphene presented a four-fold enhancement in the photocurrent when compared to unfold FLG. However, when a ...
Lee Hae-Jin HJ Medical Corps of Sangmudae Army Service Support Group, Republic of Korea Army Training and Doctrine Command, Jangsung, - - 2014
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic ...
Yuan Li L Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210029, - - 2014
Inositol requiring enzyme-1 (IRE1) is highly conserved from yeasts to humans. Upon endoplasmic reticulum (ER) stress, IRE1 activates X-box-binding protein 1 (XBP1) by unconventional splicing of XBP1 mRNA, which activates unfolded protein response (UPR) to restore ER homeostasis. In mice, IRE1α plays an essential role in extraembryonic tissues. However, its ...
Frans Glynis G Department of Microbiology and Immunology, Experimental Laboratory Immunology , KU Leuven, Leuven , Belgium - - 2014
Abstract Toll-like receptors (TLRs) play an important role in immunity and mediate their actions via multiple signaling pathways, in particular, the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) pathway. Rare inherited defects of TLR- and NF-κB-dependent responses have recently been recognized. These primary immunodeficiencies predispose children ...
Holt Patrick G - - 2014
The relative importance of respiratory viral infections vs inhalant allergy in asthma pathogenesis is the subject of ongoing debate. Emerging data from long-term prospective birth cohorts are bringing increasing clarity to this issue, in particular through the demonstration that while both of these factors can contribute independently to asthma initiation ...
Spalinger Marianne R MR Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, - - 2014
Crohn's disease (CD) is characterized by a breakdown of the intestinal epithelial barrier function leading to an uncontrolled immune response to bacterial antigens. Available data demonstrate that appropriate response and early host defense against invading bacteria are crucial to maintain tolerance towards commensal bacteria. When the mechanisms of early removal ...
Xu Ning N Key Laboratory of Molecular Microbiology and Technology for Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 - - 2013
Iron bioavailability is crucial for mitochondrial metabolism and biosynthesis. Dysregulation of cellular iron homeostasis affects multiple aspects of mitochondrial physiology and cellular processes. However, the intracellular iron trafficking pathway in C. albicans remains unclear. In this study, we characterized the Mrs4-Ccc1-Smf3 pathway, and demonstrated its important role in maintaining cellular ...
Ifrim Daniela C DC Department of Internal Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The - - 2013
Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2(-/-)) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance ...
Verbsky James W - - 2013
To summarize recent progress in our understanding of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) and IPEX-related disorders. A number of Mendelian disorders of immune dysregulation and autoimmunity have been noted to result from defects in T regulatory cell, development and function. The best characterized of these is IPEX, resulting from ...
Moulding Dale A - - 2013
The importance of the cytoskeleton in mounting a successful immune response is evident from the wide range of defects that occur in actin-related primary immunodeficiencies (PIDs). Studies of these PIDs have revealed a pivotal role for the actin cytoskeleton in almost all stages of immune system function, from hematopoiesis and ...
Kam M K M - - 2013
Neural crest cells (NCCs) migrate from different regions along the anterior-posterior axis of the neural tube (NT) to form different structures. Defective NCC development causes congenital neurocristopathies affecting multiple NCC-derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric nervous system (ENS) defects. This study aims to further ...
Wong Tiffany - - 2013
There have been exciting recent advances in identifying new mutations that cause human primary immunodeficiencies which impact innate immune defences. In this review, we will highlight the most important and influential advances published in the last 18 months related to the defects of the innate immune system. We will also ...
Dhingra Nikhil N 1] Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA [2] Columbia University College of Physicians and Surgeons, New York, New York, - - 2013
Atopic dermatitis (AD) is a common inflammatory skin disease characterized by wet, oozing, erythematous, pruritic lesions in the acute stage and xerotic, lichenified plaques in the chronic stage. It frequently coexists with asthma and allergic rhinitis, sharing some mechanistic features with these diseases as part of the "atopic march." Controversy ...
Christova Yonka - - 2013
Loss of iRhom2, a catalytically inactive rhomboid-like protein, blocks maturation of TACE/ADAM17 in macrophages, resulting in defective shedding of the cytokine tumor necrosis factor. Apart from the resulting inflammatory defects, iRhom2-null mice appear normal: they do not show the several defects seen in TACE knockouts, suggesting that TACE maturation is ...
Stoop Esther J M - - 2013
The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, remains an important worldwide health threat. Although TB is one of the oldest infectious diseases of man, a detailed understanding of the mycobacterial mechanisms underlying pathogenesis remains elusive. Here, we studied the role of the α(1→2) mannosyltransferase MptC in mycobacterial virulence, using ...
Patenaude Cassandra - - 2013
Fungal infections are on the rise, with mortality above 30% in patients with septic Candida infections. Mutants lacking V-ATPase activity are avirulent and fail to acidify endomembrane compartments, exhibiting pleiotropic defects in secretory, endosomal and vacuolar pathways. However, the individual contribution of organellar acidification to virulence and its associated traits ...
Taher Taher E - - 2013
Lupus is a complex autoimmune rheumatic disease of unknown aetiology. The disease is associated with diverse features of immunological abnormality in which B-lymphocytes play a central role. However, the cause of atypical B-lymphocyte responses remains unclear. In this article, we provide a synopsis of current knowledge on intracellular signalling abnormalities ...
Failli Alessandra - - 2013
The behaviour of circulating dendritic cells (DCs) and DC generation from monocytes in melanoma patients during the progression of disease have not been described. We report a significant decrease in the absolute number of total DCs, which mainly affects plasmacytoid DCs in stage IV. Additionally, monocyte-DC generation is less efficient ...
Todoric Krista - - 2013
Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are ...
Shim Jung Ok JO Department of Pediatrics, Korea University College of Medicine, Seoul, - - 2013
The gut mucosal barrier plays an important role in maintaining a delicate immune homeostasis. The pathogenesis of inflammatory bowel disease (IBD) is considered to involve a defective mucosal immunity along with a genetic predisposition. Recent views have suggested an excessive response to components of the gut microbiota in IBD. A ...
Drewniak Agata A - - 2013
Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing IL-17 (Th17 cells) and important in anti-fungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis mutations in the CARD9 gene were found to result in the ...
Sun Chunxiang - - 2013
Filamin-A (FLNa) has been shown to be a key cross-linker of actin filaments in the leading edge of a motile melanoma cell line, however its role in neutrophils undergoing chemotaxis is unknown. Using a murine transgenic model in which FLNa is selectively deleted in granulocytes, we report that, while neutrophils ...
Klag Thomas - - 2013
The pathogenesis of inflammatory bowel disease (IBD) is very complex, including a variety of genetic and environmental contributing factors. In this context, over the past few years, a picture of IBD as a primary defect of the innate immune system rather than the adaptive immune system has evolved. The intestinal ...
Domingo-Gonzalez Racquel R Graduate Program in Immunology, University of Michigan , Ann Arbor, MI , - - 2013
Infectious pulmonary complications limit the success of hematopoietic stem cell transplantation (HSCT) as a therapy for malignant and non-malignant disorders. Susceptibility to pathogens in both autologous and allogeneic HSCT recipients persists despite successful immune reconstitution. As studying the causal effects of these immune defects in the human population can be ...
Muralidharan Pooja P Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA. - - 2013
Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms ...
Lo Bernice B Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, - - 2013
Deleterious mutations in genes involved in the Fas apoptosis pathway lead to Autoimmune Lymphoproliferative Syndrome (ALPS). Demonstration of an apoptosis defect is critical for the diagnosis and study of ALPS. The traditional in vitro apoptosis assay, however, requires a week of experimental procedures. Here, we show that defects in Fas-induced ...
Montes-Berrueta Daniela - - 2012
Abstract. Chronic Granulomatous Disease (CGD) is a primary immunodeficiency characterized by defects in superoxide (O2-) production, which result from mutations in one of the four NADPH oxidase components, predisposing to bacterial and fungal infections. Besides the O2-defect, it has been described that neutrophils from CGD patients are resistant to cell ...
Gogna Rajan - - 2012
BACKGROUND AND PURPOSE A novel anti-neoplastic gallium complex GaQ(3) (KP46), earlier developed by us, is currently in phase I clinical trial. GaQ(3) induced S-phase arrest and apoptosis via caspase/PARP cleavage in a variety of cancers. However, the underlying mechanism of apoptosis is unknown. Here, we have explored the mechanism(s) of ...
Caballero B - - 2012
Oxidative stress, inflammation and the aggregation of oxidized, misfolded or aberrant proteins in the brain induces deregulations in programmed cell death: apoptosis and autophagy. Apoptosis is one of processes implicated in aging and neurodegenerative pathologies, and for the last decade, has been one of the most studied processes due to ...
Joanny Eugénie - - 2012
It is thought that the anti-inflammatory effects of glucocorticoids (GCs) are largely due to GC receptor (GR)-mediated transrepression of NF-κB and other transcription factors, whereas side effects are caused by activation of gene expression (transactivation). Selective GR modulators (SGRMs) that preferentially promote transrepression should retain anti-inflammatory properties whilst causing fewer ...
Milne Gillian R GR Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, - - 2012
Chronic inflammatory diseases, such as atherosclerosis, are a major cause of death and disability in the developed world. In this respect, although cholesterol obviously plays a predominant role in atherosclerosis, targeting inflammation at lesion sites may be just as important. Indeed, elevated IL-6 (interleukin 6) levels are as strongly associated ...
Sadagopan S S Department of Microbiology and Immunology, H.M. Bligh Cancer Research Laboratories, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, - - 2012
Angiogenin, a 14-kDa multifunctional pro-angiogenic growth factor, is upregulated in several types of cancers. Anti-angiogenin monoclonal antibodies used as antagonists inhibited the establishment, progression and metastasis of human cancer cells in athymic mice (Olson et al., 1994). Silencing angiogenin and inhibition of angiogenin's nuclear translocation blocked cell survival and induced ...
Di Giovanni Simone - - 2012
The tumor suppressor p53 is a multifunctional sensor of a number of cellular signals and pathways essential for cell biology, including DNA damage, cell cycle regulation, apoptosis, angiogenesis and cell metabolism. In the last few years, a novel role for p53 in neurobiology has emerged, which includes a role in ...
Wong See Heng - - 2012
Nuocytes are essential in innate type 2 immunity and contribute to the exacerbation of asthma responses. Here we found that nuocytes arose in the bone marrow and differentiated from common lymphoid progenitors, which indicates they are distinct, previously unknown members of the lymphoid lineage. Nuocytes required interleukin 7 (IL-7), IL-33 ...
Reinhardt H Christian HC Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, University of Cologne, 50674 Cologne, Germany. - - 2012
Genome instability contributes to cancer development and accelerates age-related pathologies as evidenced by a variety of congenital cancer susceptibility and progeroid syndromes that are caused by defects in genome maintenance mechanisms. DNA damage response (DDR) pathways that are mediated through the tumor suppressor p53 play an important role in the ...
Xia Yi - - 2012
Issued from a lead optimization process, we have identified a novel triazole nucleoside analog which elicits potent anticancer activity on drug-resistant pancreatic cancer. Most importantly, this compound targets heat shock response pathways by down-regulation of heat shock transcription factor 1 and consequential down-regulation of multiple heat shock proteins HSP27, HSP70 ...
Zeng Cheng-Wu - - 2012
Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of cancer patients. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug sensitivity. However, the interaction between camptothecin and miRNA has not been previously explored. In this study, we ...
Battista Natalia - - 2012
The functional adaptation of the immune system to the surrounding environment is also a fundamental issue in space. It has been suggested that a decreased number of lymphocytes might be a cause of immunosuppression, possibly due to the induction of apoptosis. Early activation of 5-lipoxygenase (5-LOX) might play a central ...
Rockwell Cheryl E CE Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, - - 2012
NF erythroid 2-related factor 2 (Nrf2) is a transcription factor that mediates the upregulation of a battery of cytoprotective genes in response to cell stress. Recent studies showed that Nrf2 also modulates immune responses and exhibits anti-inflammatory activity. In this article, we demonstrate that a common food preservative, tert-butylhydroquinone, can ...
Niemantsverdriet Maarten - - 2012
PURPOSE: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various ...
Ding Xiaoming - - 2012
Nuclear factor kappa B (NF-κB) pathway is known for its important role in the upregulation of various inflammatory mediators and its "switch regulator" functionality for transcription factor gene networks which control cytokine-induced β-cell dysfunction and death. In this study, the islets were divided into the control group, Ad-green fluorescent protein, ...
Mansha Muhammad - - 2012
Apoptosis is a morphologically defined form of cell death that plays a major role in cell physiology, pathology and cancer therapy. The Bcl-2 family of pro- and anti-apoptotic molecules is a key regulator of this phenomenon, with the sub-family of BH3-only molecules serving as activators and/or facilitators. Apoptosis induced by ...
Miao Hongming H Department of Biochemistry and Molecular Biology, The Third Military Medical University, Chongqing, - - 2012
Hepatic insulin resistance (IR) is associated with liver inflammatory diseases, but molecular mechanisms for the association remained elusive. IR is known to increase activity of forkhead box-containing protein O subfamily-1 (FOXO1), a transcription factor that was recently shown to enhance proinflammatory cytokine production in macrophages and adipocytes. Here we report ...
Zhu Jianjian - - 2012
Cre-mediated apoptosis has been observed in many contexts in mice expressing Cre-recombinase and can confound the analysis of genetically engineered conditional mutant or transgenic alleles. Several mechanisms have been proposed to explain this phenomenon. We find that the degree of apoptosis induced correlates roughly with the copy number of loxP ...
Agbanoma Gideon - - 2012
Previously, we demonstrated that spontaneous TNF-α production by macrophages in rheumatoid arthritis (RA) synovial tissue is largely driven by contact-dependent activation with T cells in that tissue. Whereas abundant IL-10 is present in these RA synovial cultures, it does not adequately control the production of TNF-α. In this study, we ...
Nishina Takashi - - 2012
Apoptotic cells can stimulate the compensatory proliferation of surrounding cells to maintain tissue homeostasis. Although oxidative stress is associated with apoptosis and necrosis, whether it contributes to compensatory proliferation is unknown. Here, we showed that interleukin-11 (IL-11), a member of the IL-6 family of proinflammatory cytokines, was produced by cells ...
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