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1.
Phys Rev E ; 101(1-1): 013105, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32069655

ABSTRACT

In this work, we model and simulate the shape evolution of critically charged droplets, from the initial spherical shape to the charge emission and back to the spherical shape. The shape deformation is described using the viscous correction for viscous potential flow model, which is a potential flow approximation of the Navier-Stokes equation for incompressible Newtonian fluids. The simulated shapes are compared to snapshots of experimentally observed drop deformations. We highlight the influence of the dimensionless viscosity and charge carrier mobility of the liquid on the shape evolution of droplets and discuss the observed trends. We give an explanation as to why the observed deformation pathways of positively and negatively charged pure water droplets differ and give a hint as to why negatively charged water droplets emit more charge during charge breakup than positively charged ones.

2.
J Autoimmun ; 38(1): 49-58, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22264504

ABSTRACT

Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked (IPEX) syndrome is a unique example of primary immunodeficiency characterized by autoimmune manifestations due to defective regulatory T (Treg) cells, in the presence of FOXP3 mutations. However, autoimmune symptoms phenotypically resembling IPEX often occur in the absence of detectable FOXP3 mutations. The cause of this "IPEX-like" syndrome presently remains unclear. To investigate whether a defect in Treg cells sustains the immunological dysregulation in IPEX-like patients, we measured the amount of peripheral Treg cells within the CD3(+) T cells by analysing demethylation of the Treg cell-Specific-Demethylated-Region (TSDR) in the FOXP3 locus and demethylation of the T cell-Specific-Demethylated-Region (TLSDR) in the CD3 locus, highly specific markers for stable Treg cells and overall T cells, respectively. TSDR demethylation analysis, alone or normalized for the total T cells, showed that the amount of peripheral Treg cells in a cohort of IPEX-like patients was significantly reduced, as compared to both healthy subjects and unrelated disease controls. This reduction could not be displayed by flow cytometric analysis, showing highly variable percentages of FOXP3(+) and CD25(+)FOXP3(+) T cells. These data provide evidence that a quantitative defect of Treg cells could be considered a common biological hallmark of IPEX-like syndrome. Since Treg cell suppressive function was not impaired, we propose that this reduction per se could sustain autoimmunity.


Subject(s)
DNA Methylation , Forkhead Transcription Factors/genetics , Polyendocrinopathies, Autoimmune/genetics , Polyendocrinopathies, Autoimmune/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Adolescent , Adult , CD3 Complex/immunology , CD3 Complex/metabolism , Child , Child, Preschool , Cohort Studies , Female , Flow Cytometry , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Infant , Male , Syndrome , Young Adult
3.
J Virol ; 75(19): 9415-26, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11533204

ABSTRACT

Arenaviruses have a bisegmented negative-strand RNA genome whose proteomic capability is limited to only four polypeptides, namely, nucleoprotein (NP), surface glycoprotein (GP) that is proteolytically processed into GP1+GP2, polymerase (L), and a small (11-kDa) RING finger protein (Z). The role of Z during the Lymphocytic choriomeningitis virus (LCMV) life cycle is poorly understood. We investigated the function of Z in virus transcription and replication by using a reverse genetic system for the prototypic arenavirus LCMV. This system involves an LCMV minigenome and the minimal viral trans-acting factors (NP and L), expressed from separated cotransfected plasmids. Cotransfection of the Z cDNA strongly inhibited LCMV minigenome expression. The effect required synthesis of Z protein; its magnitude was dose dependent and occurred with levels of Z protein substantially lower than those observed in LCMV-infected cells. Coexpression of Z did not prevent the encapsidation of plasmid supplied minigenome, but it affected both transcription and RNA replication similarly. Mutations in Z that unfolded its RING finger domain eliminated its inhibitory activity, but RING proteins not related to Z did not affect LCMV minigenome expression. Consistent with the minigenome results, cells transiently expressing Z exhibited decreased susceptibility to infection with LCMV.


Subject(s)
Carrier Proteins/physiology , Lymphocytic choriomeningitis virus/physiology , Animals , Cell Line , Cricetinae , Genome, Viral , Intracellular Signaling Peptides and Proteins , Mutation , RNA, Viral/physiology , Virus Replication
4.
Blood ; 97(12): 3746-54, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11389012

ABSTRACT

Derivatives of the Edmonston-B strain of measles virus (MV-Ed) are safe, live attenuated measles virus (MV) vaccines that have been used worldwide for more than 30 years. The cytoreductive potential of MV-Ed has been investigated in murine models of both aggressive and indolent B-cell lymphoma in severe combined immunodeficient (SCID) mice. The rationale for these studies was generated by experience with viral fusogenic membrane glycoproteins as cytotoxic genes and the recognition of the potential of replicating viruses in the treatment of human malignancy. Intratumoral injection of both unmodified MV-Ed and a strain of MV-Ed genetically modified by the addition of a beta-galactosidase reporter gene (MVlacZ) induced regression of large established human lymphoma xenografts, in contrast to control therapy with UV-inactivated virus, in which all tumors progressed. The antitumor effect still occurred in the presence of passively transferred anti-MV antibody. Intravenous administration of MV also resulted in considerable slowing of tumor progression. Analysis of sections of residual tumor confirmed replication of MV within the tumors. Thus, the vaccine strain of MV mediates regression of large, established human B-cell lymphoma xenografts in SCID mice, and proof of principle is established that MV is oncolytic for lymphomas in vivo. Attenuated MVs may have value as a novel replicating-virus therapy for this group of disorders. (Blood. 2001;97:3746-3754)


Subject(s)
Lymphoma/therapy , Measles virus , Vaccines, Attenuated/therapeutic use , Animals , Antibodies, Viral/pharmacology , Cytopathogenic Effect, Viral/physiology , Genes, Reporter , Humans , Immunohistochemistry , Lymphoma/pathology , Measles virus/growth & development , Mice , Mice, Inbred BALB C , Mice, SCID , Neoplasm Transplantation , Time Factors , Transplantation, Heterologous , Tumor Cells, Cultured , Vaccines, Attenuated/standards , beta-Galactosidase/genetics
5.
Vaccine ; 19(17-19): 2329-36, 2001 Mar 21.
Article in English | MEDLINE | ID: mdl-11257357

ABSTRACT

We have genetically engineered a panel of recombinant measles viruses (rMVs) that express from various positions within the MV genome either the HN or F surface glycoproteins of mumps virus (MuV) or the env, gag or pol proteins from simian immunodeficiency virus (SIV). All rMVs were rescued from the respective antigenomic plasmid constructs; progeny viruses replicated comparably to the progenitor Edmonston B MV, but showed slight propagation retardation, which was dependent on the size and nature of the expressed proteins and on the genomic position of the inserts. All transgenes except that encoding mumps F glycoprotein were faithfully maintained and expressed even after virus amplification by 10(20). Our results suggest possible applications of rMVs as live-attenuated, multivalent vaccines against retroviruses such as SIV and HIV as well as other pathogens more distantly related to MV than MuV.


Subject(s)
Antigens, Viral/genetics , Measles virus/genetics , Measles virus/immunology , Mumps virus/genetics , Mumps virus/immunology , Simian Immunodeficiency Virus/genetics , Simian Immunodeficiency Virus/immunology , Animals , Base Sequence , Chlorocebus aethiops , DNA Primers/genetics , Gene Expression , Genes, Viral , Genetic Engineering , Genetic Vectors , Measles virus/growth & development , Plasmids/genetics , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombination, Genetic , Vaccines, Attenuated/genetics , Vaccines, Attenuated/isolation & purification , Vaccines, Synthetic/genetics , Vaccines, Synthetic/isolation & purification , Vero Cells , Viral Proteins/genetics , Viral Proteins/immunology
6.
Virology ; 291(2): 215-25, 2001 Dec 20.
Article in English | MEDLINE | ID: mdl-11878891

ABSTRACT

Subacute sclerosing panencephalitis (SSPE) is a progressive degenerative disease of the brain uniformly leading to death. Although caused by measles virus (MV), the virus recovered from patients with SSPE differs from wild-type MV; biologically SSPE virus is defective and its genome displays a variety of mutations among which biased replacements of many uridine by cytidine resides primarily in the matrix (M) gene. To address the question of whether the SSPE MVs with M mutations are passive in that they are not infectious, cannot spread within the CNS, and basically represent an end-stage result of a progressive infection or alternatively SSPE viruses are infectious, and their mutations enable them to persist and thereby cause a prolonged neurodegenerative disease, we utilized reverse genetics to generate an infectious virus in which the M gene of MV was replaced with the M gene of Biken strain SSPE MV and inoculated the recombinant virus into transgenic mice bearing the MV receptor. Our results indicate that despite biased hypermutations in the M gene, the virus is infectious in vivo and produces a protracted progressive infection with death occurring as long as 30 to 50 days after that caused by MV. In primary neuron cultures, the mutated M protein is not essential for MV replication, prevents colocalization of the viral N with membrane glycoproteins, and is associated with accumulation of nucleocapsids in cells' cytoplasm and nucleus.


Subject(s)
SSPE Virus/metabolism , Subacute Sclerosing Panencephalitis/virology , Viral Matrix Proteins/physiology , Animals , Cells, Cultured , Chlorocebus aethiops , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Neurons/cytology , Neurons/virology , Nucleocapsid Proteins/metabolism , SSPE Virus/genetics , SSPE Virus/growth & development , SSPE Virus/physiology , Subacute Sclerosing Panencephalitis/mortality , Subcellular Fractions , Vero Cells , Viral Fusion Proteins/metabolism , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism
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