2,893 research outputs found
Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells
<p>Abstract</p> <p>Background</p> <p>Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells.</p> <p>Methods</p> <p>Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein.</p> <p>MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on <it>in vitro </it>motility and invasiveness, and <it>in vitro </it>and <it>in vivo </it>tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for <it>in vitro </it>tests in the presence and absence of an anti-METCAM/MUC18 antibody.</p> <p>Results</p> <p>In MCF7 cells, enforced METCAM/MUC18 expression increased <it>in vitro </it>motility, invasiveness, anchorage-independent colony formation (<it>in vitro </it>tumorigenesis), and <it>in vivo </it>tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture.</p> <p>Conclusion</p> <p>These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.</p
Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses.
Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-α response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses
Hepatitis B Virus Core Promoter Double Mutations (A1762T, G1764A) Are Associated with Lower Levels of Serum Dihydrolipoyl Dehydrogenase
Published by S. Karger AG, BaselObjectives: The aim of this study was to identify serum proteins with differential concentrations between hepatocellular carcinoma (HCC) patients and HBsAg asymptomatic carriers among individuals infected with hepatitis B virus (HBV) with basal core promoter (BCP) double mutations (A1762T, G1764A). Methods: iTRAQ and liquid chromatography-tandem mass spectrometry were used to identify differentially expressed protein, and an ELISA test was used for the validation test. Results: The total number of proteins identified was 1,125, of which 239 showed statistically significant differences in their expression. The relative concentrations of serum dihydrolipoyl dehydrogenase (DLD), which showed the most significant correlation with liver diseases and infection, were significantly lower in HCC patients than asymptomatic HBsAg carriers and individuals negative for HBsAg. However, only the difference between HCC patients with BCP double mutations and HBsAg-negative individuals could be confirmed by ELISA. Meanwhile, we found that the concentrations of serum DLD in those infected with HBV with BCP double mutations were significantly lower than in individuals with the wild-type BCP. However, the difference in the concentrations of serum DLD between individuals with wild-type BCP and those negative for HBsAg was not significant. Conclusions: HBV with BCP double mutations are associated with lower concentrations of serum DLD
Genome wide association mapping of grain arsenic, copper, molybdenum and zinc in rice (Oryza sativa L.) grown at four international field sites
Peer reviewedPublisher PD
Mechanical Metamaterials with Negative Compressibility Transitions
When tensioned, ordinary materials expand along the direction of the applied
force. Here, we explore network concepts to design metamaterials exhibiting
negative compressibility transitions, during which a material undergoes
contraction when tensioned (or expansion when pressured). Continuous
contraction of a material in the same direction of an applied tension, and in
response to this tension, is inherently unstable. The conceptually similar
effect we demonstrate can be achieved, however, through destabilisations of
(meta)stable equilibria of the constituents. These destabilisations give rise
to a stress-induced solid-solid phase transition associated with a twisted
hysteresis curve for the stress-strain relationship. The strain-driven
counterpart of negative compressibility transitions is a force amplification
phenomenon, where an increase in deformation induces a discontinuous increase
in response force. We suggest that the proposed materials could be useful for
the design of actuators, force amplifiers, micro-mechanical controls, and
protective devices.Comment: Supplementary information available at
http://www.nature.com/nmat/journal/v11/n7/abs/nmat3331.htm
Preoperative diagnosis of obscure gastrointestinal bleeding due to a GIST of the jejunum: a case report
Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms affecting the digestive tract or nearby structures within the abdomen. We present a case of a 66-year-old female patient who presented with obscure anemia due to gastrointestinal bleeding and underwent exploratory laparotomy during which a large GIST of the small intestine was discovered. Examining the preoperative results of video capsule endoscopy, computed tomography, and angiography and comparing them with the operative findings we discuss which of these investigations plays the most important role in the detection and localization of GIST. A sort review of the literature is also conducted on these rare mesenchymal tumours
Sustaining Interferon Induction by a High-Passage Atypical Porcine Reproductive and Respiratory Syndrome Virus Strain
Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Porcine reproductive and respiratory syndrome virus (PRRSV) strain A2MC2 induces type I interferons in cultured cells. The objective of this study was to attenuate this strain by serial passaging in MARC-145 cells and assess its virulence and immunogenicity in pigs. The A2MC2 serially passaged 90 times (A2MC2-P90) retains the feature of interferon induction. The A2MC2-P90 replicates faster with a higher virus yield than wild type A2MC2 virus. Infection of primary pulmonary alveolar macrophages (PAMs) also induces interferons. Sequence analysis showed that the A2MC2-P90 has genomic nucleic acid identity of 99.8% to the wild type but has a deletion of 543 nucleotides in nsp2. The deletion occurred in passage 60. The A2MC2-P90 genome has a total of 35 nucleotide variations from the wild type, leading to 26 amino acid differences. Inoculation of three-week-old piglets showed that A2MC2-P90 is avirulent and elicits immune response. Compared with Ingelvac PRRS® MLV strain, A2MC2-P90 elicits higher virus neutralizing antibodies. The attenuated IFN inducing A2MC2-P90 should be useful for development of an improved PRRSV vaccine
Star forming dwarf galaxies
Star forming dwarf galaxies (SFDGs) have a high gas content and low
metallicities, reminiscent of the basic entities in hierarchical galaxy
formation scenarios. In the young universe they probably also played a major
role in the cosmic reionization. Their abundant presence in the local volume
and their youthful character make them ideal objects for detailed studies of
the initial stellar mass function (IMF), fundamental star formation processes
and its feedback to the interstellar medium. Occasionally we witness SFDGs
involved in extreme starbursts, giving rise to strongly elevated production of
super star clusters and global superwinds, mechanisms yet to be explored in
more detail. SFDGs is the initial state of all dwarf galaxies and the relation
to the environment provides us with a key to how different types of dwarf
galaxies are emerging. In this review we will put the emphasis on the exotic
starburst phase, as it seems less important for present day galaxy evolution
but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy
Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon,
September 2010, Springer Verlag, in pres
Hospital-based, prospective, multicentre surveillance to determine the incidence of intussusception in children aged below 15 years in Germany
<p>Abstract</p> <p>Background</p> <p>A new vaccine against Rotavirus (RV) gastroenteritis was introduced in Germany in 2006. In 1997 the first RV vaccine was withdrawn due to an increased incidence in intussusception (IS). Thus, an accurate estimation of the incidence of IS is important for post-licensure surveillance.</p> <p>Methods</p> <p>IS-Data were obtained from the 'Erhebungseinheit für seltene pädiatrische Erkrankungen Deutschland' (ESPED, German surveillance unit for rare pediatric diseases) collaborations' central register where all cases of intussusception in Germany for the years 2006 and 2007 are collected (n = 1200). In order to obtain an unbiased estimate of the incidence, it is necessary to determine the population under risk out of which these cases originated, and the proportion of real cases not reported to the registry (underreporting). In order to assess underreporting, a random sample of 31 hospitals was re-assessed by an outside reviewer. The estimation of incidence was done using a single Maximum-Likelihood (ML) estimator based on data from both the registry and the sample.</p> <p>Results</p> <p>The uncorrected observed incidence was calculated to be 26.6/100,000 child-years for children below 1 year old, 23.8 for those below 2 years old, and 5.2 for those below 15 years old. The review revealed a mean reporting quota of about 41% and the ML approach yielded an incidence of 51.5/100,000 child-years (95%CI [41.7;61.1]) for children below 2 years of age.</p> <p>Conclusions</p> <p>While substantial under-reporting led to very conservative estimates of the IS incidence, the approach described here allows an accurate estimation of IS incidence including corresponding confidence bands. Therefore, ML estimation is a straightforward instrument to derive stable, unbiased estimates in epidemiological studies with incomplete data.</p
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