Role of metapneumoviral glycoproteins in the evasion of the host cell innate immune response.

Human metapneumovirus (HMPV), an unsegmented negative-strand RNA virus, is the second most detected respiratory pathogen and one of the leading causes of respiratory illness in infants and immunodeficient individuals. HMPV infection of permissive cells in culture triggers a transient IFN response, which is efficiently suppressed later in infection. We report that two structural glycoproteins of the virus - namely G (Glycoprotein) and SH (Small Hydrophobic) - suppress the type I interferon (IFN) response in cell culture.

Comparative Effectiveness of Parent-Child Interaction Therapy for Children with and Without Autism Spectrum Disorder.

Youth with autism spectrum disorder (ASD) often display disruptive behavior and noncompliance. Disruptive behavior in youth with ASD may limit their participation in educational and therapeutic activities and impact family functioning. Several evidence-based interventions are available for typically developing children, such as Parent-Child Interaction Therapy (PCIT).

The role of mitochondrial reactive oxygen species in cartilage matrix destruction.

Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression.

An entropy-based model for basal ganglia dysfunctions in movement disorders.

During this last decade, nonlinear analyses have been used to characterize the irregularity that exists in the neuronal data stream of the basal ganglia. In comparison to linear parameters for disparity (i.e.

Three distinct motifs within the C-terminus of acid-sensing ion channel 1a regulate its surface trafficking.

Various protein motifs play a key role in regulating protein biogenesis and trafficking. Here, we discovered that three distinct motifs regulate the trafficking of acid-sensing ion channel 1a (ASIC1a), the primary neuronal proton receptor which plays critical roles in neurological diseases including stroke, multiple sclerosis and seizures. Mutating the PDZ binding motif of ASIC1a increased its surface expression and current density.

"I see my mother's face": student nurse experiences caring for cancer patients.

Purpose: With the numbers of cancer diagnoses increasing annually and the aging of the global citizenry, it is certain that more nurses with expert competencies in cancer care will be needed. Nursing students must have a broad understanding of cancer content in order to provide safe, effective care in the clinical setting as they learn to recognize their own experiences in caring for cancer patients. Experienced nursing educators are aware that student nurses bring into any clinical learning situation their unique knowledge, values, fear, uncertainty and bias.

siRNA for Influenza Therapy.

Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world's population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year.

Glucose-6-phosphate dehydrogenase: a novel therapeutic target in cardiovascular diseases.

Vascular dysfunction associated with diabetes, heart failure and pulmonary hypertension is the major cause of morbidity and mortality worldwide. Although the causes of vascular dysfunction remain unclear, altered glucose metabolism appears to be a common factor in these diseases. For example, in diabetes, increased glucose-6-phosphate dehydrogenase (G6PD) activity and elevated NADPH levels are associated with endothelial and vascular dysfunction.

An intronic microRNA silences genes that are functionally antagonistic to its host gene.

MicroRNAs (miRNAs) are short noncoding RNAs that down-regulate gene expression by silencing specific target mRNAs. While many miRNAs are transcribed from their own genes, nearly half map within introns of 'host' genes, the significance of which remains unclear. We report that transcriptional activation of apoptosis-associated tyrosine kinase (AATK), essential for neuronal differentiation, also generates miR-338 from an AATK gene intron that silences a family of mRNAs whose protein products are negative regulators of neuronal differentiation.

Mitochondrial DNA repair in aging and disease.

Mitochondria are organelles which, according to the endosymbiosis theory, evolved from purpurbacteria approximately 1.5 billion years ago. One of the unique features of mitochondria is that they have their own genome.

The effect of temperature and host species on the development of the trichomycete Smittium culisetae (Zygomycota).

We examined the growth and development of the trichomycete Smittium culisetae (Harpellales: Legeriomycetaceae) in the larval hosts Simulium vittatum Zetterstedt (Diptera: Simuliidae) and Aedes aegypti (L.) (Diptera: Culicidae) at three temperatures, 17, 22 and 30 C. Trichospore maturation of Sm.

The effect of phonological neighborhood density on eye movements during reading.

Recent research has indicated that phonological neighbors speed processing in a variety of isolated word recognition tasks. Nevertheless, as these tasks do not represent how we normally read, it is not clear if phonological neighborhood has an effect on the reading of sentences for meaning. In the research reported here, we evaluated whether phonological neighborhood density influences reading of target words embedded in sentences.

Intranasal antisense therapy: preclinical models with a clinical future?

Recent progress in the development of two antisense strategies--DNA oligonucleotides and RNA interference for the treatment of respiratory diseases are discussed in this review. Appropriate formulations and chemical modifications for improved stability should foster the clinical application of antisense drugs, but the delivery of antisense drugs to their intended target tissue remains the biggest challenge for most therapeutic applications of these compounds. The nose provides a particularly attractive route for antisense drug delivery to the respiratory system; however, significant hurdles remain.

Mitochondrial DNA repair: a critical player in the response of cells of the CNS to genotoxic insults.

Cells of the CNS are constantly exposed to agents which damage DNA. Although much attention has been paid to the effects of this damage on nuclear DNA, the nucleus is not the only organelle containing DNA. Within each cell, there are hundreds to thousands of mitochondria.

Effects of specific versus variable practice on the retention and transfer of a continuous motor skill.

The effects of specific versus variable practice on retention and transfer was investigated. 30 participants were randomly assigned to one of three practice conditions. The variable speed group practiced on a pursuit rotor task at three different speeds (60, 45, 30 rpm) which were randomly distributed but equal in number for 30 10-sec.

Synthesis of alpha-chemokines IP-10, I-TAC, and MIG are differentially regulated in human corneal keratocytes.

Purpose: Chemokines responsible for recruiting lymphocytes such as activated T cells into the cornea have not been clearly defined. IP-10, I-TAC, and MIG are chemoattractants for these lymphocytes. The goal of this study was to determine whether human corneal keratocyte (HCKs) in culture synthesize these chemokines in response to proinflammatory mediators.

Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporin A and synergism with geldanamycin.

Geldanamycin (GA), an antibiotic of the ansamycin family and an inhibitor of heat shock protein 90 (Hsp90), was previously shown to inhibit the malarial parasite, Plasmodium falciparum. Here we report that cyclosporin A (CsA), an inhibitor of parasitic cyclophilin (Cyp) and protein phosphatase 2B (calcineurin, CN), acted synergistically with GA to inhibit the erythrocytic growth of the parasite. Parasitic calcineurin associated with Hsp90 in vivo, and GA inhibited the association, but CsA had no effect.

Inhibition of respiratory viruses by nasally administered siRNA.

Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are two respiratory pathogens of paramount medical significance that exert high mortality. At present, there is no reliable vaccine or antiviral drug against either virus. Using an RNA interference (RNAi) approach, we show that individual as well as joint infection by RSV and PIV can be specifically prevented and inhibited by short interfering RNAs (siRNAs), instilled intranasally in the mouse, with or without transfection reagents.

A zinc-binding dual-specificity YVH1 phosphatase in the malaria parasite, Plasmodium falciparum, and its interaction with the nuclear protein, pescadillo.

Biochemical evidence revealed protein tyrosine kinase and phosphatase activities in the human malarial parasite Plasmodium falciparum, a member of the Apicomplexa. A novel cDNA sequence of a dual-specificity phosphatase was identified in both sexual and asexual stages of P. falciparum, and named PfYVH1, since the predicted primary structure of the 278-amino acid polypeptide showed significant similarity to the human and yeast YVH1 phosphatases.

Characterization of a unique aspartate-rich protein of the SET/TAF-family in the human malaria parasite, Plasmodium falciparum, which inhibits protein phosphatase 2A.

A search for physiological inhibitors of protein phosphatases led to the identification of a Plasmodium falciparum (Pf) cDNA that had the potential to code for an aspartate-rich protein and hence named ARP. The PfARP was virtually identical to its Plasmodium berghei counterpart in gene structure and protein sequence. The PfARP coding sequence contained two introns, and the predicted protein contained 269 amino acid residues.

Detection and determination of oligonucleotide triplex formation-mediated transcription-coupled DNA repair in HeLa nuclear extracts.

Transcription-coupled repair (TCR) plays an important role in removing DNA damage from actively transcribed genes. It has been speculated that TCR is the most important mechanism for repairing DNA damage in non-dividing cells such as neurons. Therefore, abnormal TCR may contribute to the development of many age-related and neurodegenerative diseases.

Partial trisomy 7p defined by analysis of a complex chromosome rearrangement using a BAC clone panel.

Purpose: To illustrate the use of bacterial artificial chromosome (BAC) clone panels for molecular cytogenetic analysis of complex chromosome rearrangements (CCRs).

Methods: High resolution cytogenetics followed by fluorescence in situ hybridization (FISH) analysis using chromosome band-specific BAC probes, in addition to commercially available probes.

Results: High resolution cytogenetics in conjunction with FISH using commercially available probes proved inadequate to resolve problems in characterizing a balanced CCR in the mother of a patient who had inherited an unbalanced form of the CCR.