Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity

Quantitative EEG Markers of Entropy and Auto Mutual Information in Relation to MMSE Scores of Probable Alzheimer’s Disease Patients

Analysis of nonlinear quantitative EEG (qEEG) markers describing complexity of signal in relation to severity of Alzheimer’s disease (AD) was the focal point of this study. In this study, 79 patients diagnosed with probable AD were recruited from the multi-centric Prospective Dementia Database Austria (PRODEM). EEG recordings were done with the subjects seated in an upright position in a resting state with their eyes closed. Models of linear regressions explaining disease severity, expressed in Mini Mental State Examination (MMSE) scores, were analyzed by the nonlinear qEEG markers of auto mutual information (AMI), Shannon entropy (ShE), Tsallis entropy (TsE), multiscale entropy (MsE), or spectral entropy (SpE), with age, duration of illness, and years of education as co-predictors. Linear regression models with AMI were significant for all electrode sites and clusters, where R 2 is 0.46 at the electrode site C3, 0.43 at Cz, F3, and central region, and 0.42 at the left region. MsE also had significant models at C3 with R 2 > 0.40 at scales τ = 5 and τ = 6 . ShE and TsE also have significant models at T7 and F7 with R 2 > 0.30 . Reductions in complexity, calculated by AMI, SpE, and MsE, were observed as the MMSE score decreased

Active Packaging Technologies with an Emphasis on Antimicrobial Packaging and its Applications

In response to the dynamic changes in current consumer demand and market trends, the area of Active Packaging (AP) is becoming increasingly significant. Principal AP systems include those that involve oxygen scavenging, moisture absorption and control, carbon dioxide and ethanol generation, and antimicrobial (AM) migrating and nonmigrating systems. Of these active packaging systems, the AM version is of great importance. This article reviews: (1) the different categories of AP concepts with particular regard to the activity of AM packaging and its effects on food products, (2) the development of AM and AP materials, and (3) the current and future applications of AM packaging

Driving cessation and dementia: results of the prospective registry on dementia in Austria (PRODEM).

OBJECTIVE: To assess the influence of cognitive, functional and behavioral factors, co-morbidities as well as caregiver characteristics on driving cessation in dementia patients. METHODS: The study cohort consists of those 240 dementia cases of the ongoing prospective registry on dementia in Austria (PRODEM) who were former or current car-drivers (mean age 74.2 (±8.8) years, 39.6% females, 80.8% Alzheimer's disease). Reasons for driving cessation were assessed with the patients' caregivers. Standardized questionnaires were used to evaluate patient- and caregiver characteristics. Cognitive functioning was determined by Mini-Mental State Examination (MMSE), the CERAD neuropsychological test battery and Clinical Dementia Rating (CDR), activities of daily living (ADL) by the Disability Assessment for Dementia, behavior by the Neuropsychiatric Inventory (NPI) and caregiver burden by the Zarit burden scale. RESULTS: Among subjects who had ceased driving, 136 (93.8%) did so because of "Unacceptable risk" according to caregiver's judgment. Car accidents and revocation of the driving license were responsible in 8 (5.5%) and 1(0.7%) participant, respectively. Female gender (OR 5.057; 95%CI 1.803-14.180; p = 0.002), constructional abilities (OR 0.611; 95%CI 0.445-0.839; p = 0.002) and impairment in Activities of Daily Living (OR 0.941; 95%CI 0.911-0.973; p<0.001) were the only significant and independent associates of driving cessation. In multivariate analysis none of the currently proposed screening tools for assessment of fitness to drive in elderly subjects including the MMSE and CDR were significantly associated with driving cessation. CONCLUSION: The risk-estimate of caregivers, but not car accidents or revocation of the driving license determines if dementia patients cease driving. Female gender and increasing impairment in constructional abilities and ADL raise the probability for driving cessation. If any of these factors also relates to undesired traffic situations needs to be determined before recommendations for their inclusion into practice parameters for the assessment of driving abilities in the elderly can be derived from our data

A review of propulsive mechanisms in rowing

This paper reviews the fluid dynamic mechanisms that are fundamental to the rowing stroke. Complex interactions occur between the oar blade and water, and over the last 30 years our understanding of the mechanisms that govern rowing propulsion has developed significantly. The oar blade was once believed to rip through the water, generating a drag force acting normal to the blade. Current research indicates that the oar blade acts as an aerofoil making use of lift forces to propel the boat through the water early and late in the stroke, with drag being the dominant propulsive force when the oar is perpendicular to the boat. Early on-water research showed variations in the fluid dynamic behaviour of different oar blades. Recently, more controlled laboratory tests have isolated the oar blade from the rower–boat–water system to obtain blade characteristics. The isolated nature of recent oar blade studies and the complex nature of the oar blade–water interaction have led to suggestions that computational fluid dynamics (CFD) may be used to advance understanding of oar blade behaviour as a precursor to a more informed design process. By integrating a dynamic CFD model with a mathematical model of rowing mechanics, a full optimization of rower technique, boat rigging, and equipment design could be performed