Viral infection induces the production of interleukin (IL)-1beta and IL-18 in macrophages through activation caspase-1, but mechanism by which host cells sense viruses to induce caspase-1 is unknown. In this report, we have identified a signaling pathway leading that induced double-stranded RNA (dsRNA) viral mediated Cryopyrin/Nalp3. Stimulation with dsRNA, RNA, or its analog poly(I:C) secretion IL-1beta cryopyrin-dependent manner. Consistently, triggered poly(I:C), was abrogated lacking...

Positive-strand RNA viruses are the largest genetic class of and include many serious human pathogens. All positive-strand replicate their genomes in association with intracellular membrane rearrangements such as single- or double-membrane vesicles. However, exact sites synthesis crucial topological relationships between relevant membranes, vesicle interiors, surrounding lumens, cytoplasm generally poorly defined. We applied electron microscope tomography complementary approaches to flock...

Rhinovirus (RV), a ssRNA virus of the picornavirus family, is major cause common cold as well asthma and chronic obstructive pulmonary disease exacerbations. Viral dsRNA produced during replication may be recognized by host pattern recognition receptors TLR-3, retinoic acid-inducible gene (RIG)-I, melanoma differentiation-associated (MDA)-5. No study has yet identified receptor required for sensing RV dsRNA. To examine this, BEAS-2B human bronchial epithelial cells were infected with intact...

ABSTRACT The identification and characterization of host cell membranes essential for positive-strand RNA virus replication should provide insight into the mechanisms viral potentially identify novel targets broadly effective antiviral agents. alphanodavirus flock house (FHV) is a with one smallest known genomes among animal viruses, it can replicate in insect, plant, mammalian, yeast cells. To investigate localization FHV replication, we generated polyclonal antisera against protein A,...

Rhinovirus (RV), a single-stranded RNA picornavirus, is the most frequent cause of asthma exacerbations. We previously demonstrated in human bronchial epithelial cells that melanoma differentiation-associated gene (MDA)-5 and adaptor protein for Toll-like receptor (TLR)-3 are each required maximal RV1B-induced interferon (IFN) responses. However, vivo, overall airway response to viral infection likely represents coordinated integrating both antiviral pro-inflammatory pathways. examined...

Natural products provide a vast array of chemical structures to explore in the discovery new medicines. Although secondary metabolites produced by microbes have been developed treat variety diseases, including bacterial and fungal infections, date there has limited investigation natural with antiviral activity. In this report, we used phenotypic cell-based replicon assay coupled an iterative biochemical fractionation process identify, purify, characterize compounds marine microbes. We...

Innate immune pathways are early defense responses important for the immediate control and eventual clearance of many pathogens, where signaling is initiated via pattern recognition receptor (PRR)-mediated events that occur in a ligand- cell-type specific manner. Within CNS neurons, innate likely crucial to pathogens target these essential yet virtually irreplaceable cells. However, relatively little known about induction regulation neuronal PRR signaling. In this report, we used human cell...

ABSTRACT The assembly of viral RNA replication complexes on intracellular membranes represents a critical step in the life cycle positive-strand viruses. We investigated role cellular chaperone heat shock protein 90 (Hsp90) complex and function using Flock House virus (FHV), an alphanodavirus whose RNA-dependent polymerase, A, is essential for mitochondrial outer membranes. Hsp90 transports proteins to membrane import receptors, thus we hypothesized that may also facilitate FHV or function....

Abstract The elucidation of B lymphocyte development has been partially achieved through genetic models such as the X‐linked immunodeficiency ( xid ) mutation. We discovered a unique developmental defect in strain A/WySnJ mice. used single‐ and two‐color flow cytometry to analyze lymphocytes from A/J Adult mice had severe cell deficiency, which was apparent spleen, lymph nodes, peritoneum peripheral blood, compared adult An ontogeny study revealed that defect, inhibiting maturation or...

We previously identified the remyelinating activity of a natural IgMκ oligodendrocyte-reactive autoantibody (SCH94.03), using virus-induced murine model multiple sclerosis. now describe second mouse monoclonal antibody (mAb) (SCH79.08) raised against normal spinal cord homogenate, which reacts with myelin basic protein and also promotes remyelination. Because these two mAbs recognize different oligodendrocyte antigens, several (O1, O4, A2B5, HNK-1), each distinct antigen specificities, were...

To determine how employment as a resident physician (resident) affects breastfeeding practices and experiences.Cross-sectional questionnaire survey.US physicians in the second half of their postgraduate year three (PGY3).1500 questionnaires were mailed at random to female 1990 graduates American medical schools. After eliminating unusable surveys, an adjusted response rate 45% produced 450 surveys; 60 delivered child during residency.None. MEASUREMENT/MAIN RESULTS: Forty-eight (80%)...

Positive-sense RNA viruses are responsible for frequent and often devastating diseases in humans, animals, plants. However, the development of effective vaccines anti-viral therapies targeted towards these pathogens has been hindered by an incomplete understanding molecular mechanisms involved viral replication. One common feature all positive-sense is manipulation host intracellular membranes assembly functional replication complexes. This review will discuss interplay between cellular...

A monoclonal antibody SCH94.03, made in syngeneic mice by injection of spinal cord homogenate, promotes central nervous system remyelination when injected into SJL/J chronically infected with Theiler's virus. To elucidate the mechanism antibody-mediated remyelination, SCH94.03 was investigated immunocytochemistry, flow cytometry, immunoelectron microscopy, Western blotting, and immuno-thin layer chromatography. All cell types vitro showed strong cytoplasmic staining a pattern resembling...

Abstract Background Cellular membranes are crucial host components utilized by positive-strand RNA viruses for replication of their genomes. Published studies have suggested that the synthesis and distribution membrane lipids particularly important assembly function virus complexes. However, impact specific lipid metabolism pathways in this process not been well defined, nor potential changes expression associated with examined detail. Results In study we used parallel complementary global...

Distal radius fractures are increasingly treated by internal fixation, but there have been relatively few studies relating to functional outcome at 12 months or more. The aim of this study was ascertain the patient reported function wrist a minimum following fixation distal fracture, time taken return work, and complication rate. We conducted retrospective review 187 consecutive patients specialist hand trauma team tertiary referral unit over 5 year period. Mean age 57.3 years (range 16–93)....

Antibodies directed against self-Ags are frequently considered detrimental, and have been shown to play a pathogenic role in certain autoimmune diseases. However, the presence of autoreactive Abs normal individuals suggests that some autoantibodies could participate physiology. Our previous studies demonstrated monoclonal SCH94.03 SCH94.32, generated from splenocytes uninfected SJL/J mice injected with homogenized spinal cord, promote central nervous system remyelination when passively...

Antigen-stimulated B lymphocytes either differentiate into IgM-secreting plasma cells or memory that secrete other immunoglobulin isotypes upon antigen restimulation. The mechanisms generate and maintain are poorly understood. Previously, we described a severe lymphocyte deficiency in adult strain A/WySnJ mice compared to subline A/J. Here show the single, autosomal co-dominant locus responsible for also diminishes IgG-secreting cell formation without interfering with differentiation....

My purpose, in this study, was to test the reflex-spasm model of chronic pain by comparing levels muscle activity lumbar paraspinal muscles subjects with and without low back (CLBP). Each group, CLBP group nonpain (NP) comprised 11 who were matched age sex. I used surface electrodes record integrated electromyographic (IEMG) from each side back. All performed three experimental tasks a reference (normalizing) task. The quiet sitting, standing, sitting during repetitive unilateral upper...