Effective stiffening of DNA due to nematic ordering causes DNA molecules packed in phage capsids to preferentially form torus knots

Observation that DNA molecules in bacteriophage capsids preferentially form torus type of knots provided a sensitive gauge to evaluate various models of DNA arrangement in phage heads. Only models resulting in a preponderance of torus knots could be considered as close to reality. Recent studies revealed that experimentally observed enrichment of torus knots can be qualitatively reproduced in numerical simulations that include a potential inducing nematic arrangement of tightly packed DNA molecules within phage capsids. Here, we investigate what aspects of the nematic arrangement are crucial for inducing formation of torus knots. Our results indicate that the effective stiffening of DNA by the nematic arrangement not only promotes knotting in general but is also the decisive factor in promoting formation of DNA torus knots in phage capsid

Die Immunantwort boviner und capriner Euterepithelzellen auf verschiedene Mastitiserreger

Infections of the bovine mammary gland are, in addition to the affliction of the animals, a great economic burden in the dairy industry. A better understanding of the innate immune response of the host could lead to a better selection of mastitis resistant cows or to better prophylactic and therapeutical treatments. The objective of the present study was to investigate the involvement of the epithelial cells into the outcome of mastitis induced by different pathogens. Primary epithelial cell cultures isolated from milk of Brown swiss cows and coloured german goats, and tissue of cows were used to test the immune response. Because the cells of the cows showed different responses to isolated bacterial endotoxins (lipopolysaccharide, lipoteichoic acid, and peptidoglycans) compared to whole bacteria, they were treated with heat inactivated (10 MOI) gram-negative Escherichia coli (E.coli), a very common pathogen causing acute and severe intra-mammary infections, with Staphylococcus aureus (S.aureus) and coagulase-negative Staphylococcus (CNS), both prevalent cause of chronic and subclinical, and, Streptococcus uberis (Str.uberis) an inducer of acute and chronic mastitis. Goat cells were treated with 10 MOI heat inactivated S.aureus causing in opposite to cows an acute, clinical mastitis and LPS. In cows E.coli induced an increased mRNA expression of interleukin-(IL) 8, IL-6, tumor necrosis factor alpha (TNF) and granulozytes, macrophage-stimulating factor (GM-CSF) within a 30 min treatment. IL-8, IL-6 and TNF mRNA levels were still elevated after 60 min, 90 min, 6 h and 24 h. After 6 h S.aureus induced an increase in mRNA expression of IL-6, IL-8, TNF and SAA. After a 24 h treatment the expression of these immunomodulators was still elevated. Interestingly, Str.uberis in the same concentration did only induce the mRNA expression of GM-CSF after 60 min and the IL-8 after a 6 h treatment but had no influence on other immunomodulator mRNA expression. CNS treated cells needed a MOI of 50 for any reaction. This MOI induced a reaction on mRNA levels of IL-6 and IL-8 but not on TNF after 6 h. In goats S.aureus induced an increase in mRNA expression of IL-8 and TNF after 1 and 6 h. After a 24 h treatment just the mRNA level of TNF was elevated. In conclusion mammary gland epithelial cells are involved in the different immune response to various mastitis pathogens. In cows, E.coli always induced an earlier immune response compared to S.aureus. This pathogen induced a later and probably for the immne system weaker reaction, not strong enough to cause an acute intramammary infection. Str.uberis in the same concentration induced only an increased GM-CSF and IL-8 mRNA expression after a 60 min or a 6 h treatment, respectively. This bacterium probably stimulates different immune relevant gene expressions not measured here or does not stimulate the mammary gland epithelial cells. The cells needed a 5-fold higher dose of KNS to respond with induced mRNA levels of IL-6 and TNF but not IL-8. KNS maybe does not stimulate the immune system enough to induce an acute mastitis and is like by the epithelial cells just recognized in very high dosis. IL-8 plays an important role as a chemotactic stimulus that is missing here. Goat mammary gland epithelial cells showed a early increase of IL-8 and TNF, that could be high enough, combined with the response of the immune cells in the milk, to induce an acute and severe intra-mammary infection

White matter alterations in neurodegenerative and vascular dementia

Die Zuordnung einer Demenzerkrankung zu einem neurodegenerativen Pathomechanismus, wie der Demenz vom Alzheimer-Typ (DAT), oder einem vaskulären Pathomechanismus, kann trotz der Verfügbarkeit bildgebender Verfahren Probleme bereiten. Überlappungen neurodegenerativer und vaskulärer Mechanismen sind häufig. Mikroangiopathische Veränderungen des Marklagers finden sich bei einem hohen Anteil von Patienten mit der klinischen Verlaufsform einer Demenz vom Alzheimer-Typ. Es ist unklar, ob es sich um eine Koinzidenz zweier Pathomechanismen handelt oder ob eine wechselseitige Beeinflussung stattfindet. Die hohe Sensitivität der Magnet-Resonanz-Tomographie bei der Erfassung von mikroangiopathischen Veränderungen des Marklagers könnte dazu führen, dass zu häufig vaskuläre Demenzerkrankungen diagnostiziert werden. Der Einfluss mikroangiopathischer Veränderungen des Marklagers auf den Demenzverlauf wird kontrovers diskutiert. Die vorgelegte Arbeit gibt eine Übersicht über die aktuellen Konzepte zum Stellenwert von Marklagerveränderungen bei Demenzerkrankungen.Due to a significant overlap of the two syndromes, differentiation of degenerative dementia of the Alzheimer-Type from vascular dementia may be difficult even when imaging studies are available. White matter changes occur in many patients suffering from Alzheimer\u27s disease. Little is known about the impact of white matter changes on the course and clinical presentation of Alzheimer\u27s disease. High sensitivity of MRI in the detection of white matter alterations may account for over-diagnosing vascular dementia. The clinical significance of white matter alterations in dementia is still a matter of debate. The article reviews current concepts about the role of white matter alterations in dementia

Implementation and performance analysis of bridging Monte Carlo moves for off-lattice single chain polymers in globular states

Bridging algorithms are global Monte Carlo moves which allow for an efficient sampling of single polymer chains. In this manuscript we discuss the adaptation of three bridging algorithms from lattice to continuum models, and give details on the corrections to the acceptance rules which are required to fulfill detailed balance. For the first time we are able to compare the efficiency of the moves by analyzing the occurrence of knots in globular states. For a flexible homopolymer chain of length N=1000, independent configurations can be generated up to two orders of magnitude faster than with slithering snake moves.Comment: 12 pages, 5 figures, preprint submitted to computer physics communication

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location

Aims Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. Methods and results A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. Conclusion Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severit

Identification of CIITA Regulated Genetic Module Dedicated for Antigen Presentation

The class II trans-activator CIITA is a transcriptional co-activator required for the expression of Major Histocompatibility Complex (MHC) genes. Although the latter function is well established, the global target-gene specificity of CIITA had not been defined. We therefore generated a comprehensive list of its target genes by performing genome-wide scans employing four different approaches designed to identify promoters that are occupied by CIITA in two key antigen presenting cells, B cells and dendritic cells. Surprisingly, in addition to MHC genes, only nine new targets were identified and validated by extensive functional and expression analysis. Seven of these genes are known or likely to function in processes contributing to MHC-mediated antigen presentation. The remaining two are of unknown function. CIITA is thus uniquely dedicated for genes implicated in antigen presentation. The finding that CIITA regulates such a highly focused gene expression module sets it apart from all other transcription factors, for which large-scale binding-site mapping has indicated that they exert pleiotropic functions and regulate large numbers of genes

An early rise in body temperature is related to unfavorable outcome after stroke: Data from the PAIS study

Subfebrile temperature or fever is present in about a third of patients on the first day after stroke onset and is associated with poor outcome. However, the temporal profile of this association is not well established. We aimed to assess the relationship between body temperature on admission as well as the change in body temperature from admission to 24 h thereafter and functional outcome and death. We analyzed data of 1,332 patients admitted within 12 h of stroke onset. The relation between body temperature on admission or the change in body temperature from admission to 24 h thereafter (adjusted for body temperature on admission) on the one hand and unfavorable outcome (death, or a modified Rankin Scale score >2) at 3 months on the other were expressed as odds ratio per 1.0°C increase in body temperature. Adjustments for potential confounders were made with a multiple logistic regression model. No relation was found between admission body temperature and poor outcome (aOR 1.06; 95% CI 0.85-1.32) and death (aOR 1.23; 95% CI 0.95-1.60). In contrast, increased body temperature in the first 24 h after stroke onset was associated with poor outcome (aOR 1.30; 95% CI 1.05-1.63) and death (aOR 1.51; 95% CI 1.15-1.98). An early rise in body temperature rather than high body temperature on admission is a risk factor for unfavorable outcome in patients with acute stroke