4,339 research outputs found
Adaptive immunity maintains occult cancer in an equilibrium state.
No full textThe capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes that function either independently or in sequence: elimination (cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium (expansion of transformed cells is held in check by immunity); and escape (tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected (occult) cancer from organ donor into immunosuppressed recipients. Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo. We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods
Self-compression of 4.9 µm pulses to sub-40 fs with 2 mJ energy in Zinc Sulfide
No full textNonlinear self-compression of few-cycle multi-mJ pulses at 4.9 µm in ZnS is presented. 80 fs input pulses are compressed to 37 fs with 2.1 mJ energy at a 1 kHz repetition rate. © 2024 The Author(s
A synaptic nidogen: developmental regulation and role of nidogen-2 at the neuromuscular junction
No full textBackground: The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are deposited by the muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each case, the synaptic isoform plays key roles in organizing the neuromuscular junction. Here, we analyze the fourth family, composed of nidogen-1 and -2.Results: In adult muscle, nidogen-1 is present throughout muscle fiber basal lamina, while nidogen- 2 is concentrated at synapses. Nidogen-2 is initially present throughout muscle basal lamina, but is lost from extrasynaptic regions during the first three postnatal weeks. Neuromuscular junctions in mutant mice lacking nidogen-2 appear normal at birth, but become topologically abnormal as they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans persist in the absence of nidogen-2, suggesting the phenotype is not secondary to a general defect in the integrity of synaptic basal lamina. Further genetic studies suggest that synaptic localization of each of the four families of synaptic basal lamina components is independent of the other three.Conclusion: All four core components of the basal lamina have synaptically enriched isoforms. Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction
Correction to: Chamoun et al., Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection
No full textChamoun MN, Blumenthal A, Sullivan MJ, Schembri MA, Ulett GC. 2018. Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection. Critical Reviews in Microbiology. https://doi.org/10.1080/1040841X.2018.1426556.
When the above article was first published online, the below three corrections were missed.
The author ‘Antje Blumenthal’ was wrongly affiliated to the affiliation “cSchool of Chemistry and Molecular Biosciences, and Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Australia”. Now this affiliation has been removed for this author.
The affiliation ‘bTranslational Research Institute, The University of Queensland Diamantina Institute, Woolloongabba, Australia’ of the author ‘Antje Blumenthal’ should read ‘bThe University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia’.
In Table 3, the sentence ‘Benefit of manipulating IL-17 levels to improve immunization strategies M. tuberculosis’ should read “Benefit of manipulating IL-17 levels to improve immunization strategies against M. tuberculosis”.No Full Tex
Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset
No full textAcute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations
Generation of 22-mJ, 2.0-ps Pulses from a 1-kHz Ho:YLF Regenerative Chirped Pulse Amplifier
No full textWe report a CW-pumped Ho:YLF regenerative amplifier (RA) delivering pulses with 22.5-mJ energy and 2.0-ps duration at 1 kHz. The RA emitting at 2051 nm is broadband-seeded and implemented in a chirped pulse amplification system. © 2024 The Author(s
Nonredundant roles of antibody, cytokines and perforin for the immune eradication of established Her-2/neu carcinomas
No full textSince the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185(neu)) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185(neu). Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCPI), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential
Pure-rotational 1D-CARS spatiotemporal thermometry with a single regenerative amplifier system
No full textWe report spatiotemporal pure-rotational coherent anti-Stokes Raman spectroscopy (CARS) in a one-dimensional imaging arrangement obtained with a single ultrafast regenerative amplifier system. The femtosecond pump/Stokes photon pairs, used for impulsive excitation, are delivered by an external compressor operating on a ∼35% beam split of the uncompressed amplifier output (2.5 mJ/pulse). The picosecond 1.2 mJ probe pulse is produced via the second-harmonic bandwidth compression (SHBC) of the ∼65% remainder of the amplifier output (4.5 mJ/pulse), which originates from the internal compressor. The two pump/Stokes and probe pulses are spatially, temporally, and repetition-wise correlated at the measurement, and the signal generation plane is relayed by a wide-field coherent imaging spectrometer onto the detector plane, which is refreshed at the same repetition rate as the ultrafast regenerative amplifier system. We demonstrate 1 kHz cinematographic 1D-CARS gas-phase thermometry across an unstable premixed methane/air flame-front, achieved with a single-shot precision <1% and accuracy <3%, 1.4 mm field of view, and an excellent <20 µm line-spread function.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Flight Performance and Propulsio
Multiple roles of perforin in hampering ERBB-2 (Her-2/neu) carcinogenesis in transgenic male mice.
No full textPerforin (pfp)-mediated cytotoxicity is one of the principal immunosurveillance mechanisms involved in the fight against cancer.
However, its importance in spontaneous epithelial cancer is still poorly defined. In this study, we use a realistic mouse model that
displays many features that are equivalent to human pathology to evaluate the role of pfp-dependent immunosurveillance by comparing
tumor progression in rat ERBB-2 (neu) transgenic, pfp-proficient (neu+/pfp+) or pfp-deficient (neu+/pfp2) BALB/c male
mice. Adult neu+/pfp+ males developed poorly differentiated salivary carcinomas, whereas neu+/pfp2 males displayed their
salivary carcinomas noticeably earlier and showed zones of more highly differentiated tumor, indicating that pfp-mediated
immunosurveillance is able not only to delay the growth kinetic of an aggressive epithelial tumor, but also to shape its histology.
The role of pfp-mediated immunosurveillance appeared to be of even more dramatic importance against the less aggressive male
mammary carcinomas. In neu+/pfp+ males, the incidence of mammary carcinomas was a sporadic and late event. In contrast, in
neu+/pfp2 males their incidence was four-fold higher. This higher cancer incidence was associated with a 2-fold higher occurrence
of persisting mammary remnants, a major risk factor for mammary cancer in male mice, and one that would appear to be due to
pfp’s previously unidentified involvement in male mammary gland rejection during embryogenesis. This work thus provides
further proof of the complex role that the immune system plays in the body and gives new insight into the pathogenesis of
epithelial tumors, demonstrating that the penetrance and malignancy of a tumor may be dramatically affected by pfp-dependent
mechanisms
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