In the healthy individuum lymphocyte traffic into the central nervous system (CNS) is very low and tightly controlled by the highly specialized blood-brain barrier (BBB). In contrast, under ...inflammatory conditions of the CNS such as in multiple sclerosis or in its animal model experimental autoimmune encephalomyelitis (EAE) circulating lymphocytes and monocytes/macrophages readily cross the BBB and gain access to the CNS leading to edema, inflammation and demyelination. Interaction of circulating leukocytes with the endothelium of the blood-spinal cord and blood-brain barrier therefore is a critical step in the pathogenesis of inflammatory diseases of the CNS. Leukocyte/endothelial interactions are mediated by adhesion molecules and chemokines and their respective chemokine receptors. We have developed a novel spinal cord window preparation, which enables us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Applying this technique of intravital fluorescence videomicroscopy we could provide direct in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that alpha4-integrin mediates the G-protein independent capture and subsequently the G-protein dependent adhesion strengthening of T cell blasts to microvascular VCAM-1. LFA-1 was found to neither mediate the G-protein independent capture nor the G- protein dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessel, but was rather involved in T cell extravasation across the vascular wall into the spinal cord parenchyme. Our observation that G-protein mediated signalling is required to promote adhesion strengthening of encephalitogenic T cells on BBB endothelium in vivo suggested the involvement of chemokines in this process. We found functional expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in CNS venules surrounded by inflammatory cells in brain and spinal cord sections of mice afflicted with EAE suggesting that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing to secondary lymphoid tissue might be involved in T lymphocyte migration into the immuneprivileged CNS during immunosurveillance and chronic inflammation. Here, I summarize our current knowledge on the sequence of traffic signals involved in T lymphocyte recruitment across the healthy and inflamed blood-brain and blood-spinal cord barrier based on our in vitro and in vivo investigations.
The aim of this study is to characterize baseline regional oxygen saturations (rSO(2)) in stable preterm infants during the first weeks of life.
Cerebral, renal and abdominal rSO(2) were continuously ...monitored from the time of birth to 21 days in twelve preterm infants of 29-34 weeks gestation. Regional saturations were evaluated for trends over time, variability and differences between gestational ages (GAs) and reported pediatric values.
Both cerebral (66-83%) and renal (64-87%) rSO(2) baselines were within the range of reported neonatal values but consistently decreased over the first weeks of life (P<0.01). The baseline abdominal rSO(2) was 32-66% and increased with GA (P=0.05). The rSO(2) variability was lowest for cerebral measurements and highest at the abdomen. Abdominal rSO(2) variability decreased over time (P≤0.05).
Daily baseline rSO(2) in preterm infants changes over the first weeks of life, especially at the abdomen. Evolution in baseline rSO2 over time may indicate regional developmental maturation of physiological oxygen balance.
J. Greenwood, S. J. Heasman, J. I. Alvarez, A. Prat, R. Lyck and B. Engelhardt (2011) Neuropathology and Applied Neurobiology37, 24–39 Leucocyte–endothelial cell crosstalk at the blood–brain barrier: ...A prerequisite for successful immune cell entry to the brain
Leucocyte migration into the central nervous system is a key stage in the development of multiple sclerosis. While much has been learnt regarding the sequential steps of leucocyte capture, adhesion and migration across the vasculature, the molecular basis of leucocyte extravasation is only just being unravelled. It is now recognized that bidirectional crosstalk between the immune cell and endothelium is an essential element in mediating diapedesis during both normal immune surveillance and under inflammatory conditions. The induction of various signalling networks, through engagement of cell surface molecules such as integrins on the leucocyte and immunoglobulin superfamily cell adhesion molecules on the endothelial cell, play a major role in determining the pattern and route of leucocyte emigration. In this review we discuss the extent of our knowledge regarding leucocyte migration across the blood–brain barrier and in particular the endothelial cell signalling pathways contributing to this process.
We studied 172 patients for development of ocular graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) from 2002 to 2009. Ocular GVHD was diagnosed in 60 patients ...(38%), with 27 (16%) being diagnosed at days 100 and 33 (23%) beyond day 100 for a 2-year cumulative incidence of 35% (95% confidence interval (CI), 28-43). The positive and negative predictive values of a Schirmer I test score (using 5 mm as a cutoff) in predicting ocular GVHD (day 100) were 41 and 82%, respectively. In patients with ocular GVHD beyond day 100, extraocular manifestations of GVHD preceded the development of ocular GVHD in most patients (27 of 33, 81%). Prior acute skin GVHD (odds ratio 2.57, 95% CI 1.17-5.64, P=0.019) and male recipients of female donors (odds ratio 2.57, 95% CI 1.09-6.06, P=0.03) were independent risk factors for ocular GVHD. We recommend comprehensive ocular evaluation rather than a screening Schirmer's test to establish the diagnosis of ocular GVHD. Early diagnosis and preventive strategies in high-risk populations need to be studied in clinical trials to prevent devastating impact on quality of life in patients with prolonged ocular GVHD.
The application of the highly efficient ruthenium catalyst Ru(CO)2{P(p‐CF3–C6H4)3}2(O2CPh)2 (1) in the selective syn‐addition of carboxylic acids to internal alkynes, yielding valuable trisubstituted ...enol esters with (E)‐configuration, is described. All reactions feature excellent stereoselectivities and good regioselectivities. The regioselectivity is dictated by electronic and steric aspects of the alkyne substituents and the acidity of the carboxylic acid. The catalytic activity can be significantly increased by the addition of catalytic amounts of B(C6F5)3. Relative to known catalysts for the synthesis of (E)‐enol esters, this methodology offers improved selectivity and requires lower catalyst loadings. Moreover, a broad range of alkynes and carboxylic acids can be successfully converted to their corresponding (E)‐enol esters in high yields.
The metal complex Ru(CO)2{P(p‐CF3–C6H4)3}2(O2CPh)2 is demonstrated to be a highly efficient catalyst in the challenging hydrocarboxylation of internal alkynes. Using this catalyst, a diverse array of substrates were selectively converted to their trisubstituted (E)‐enol esters.
The rising pollution of surface water by endocrine disruptive chemicals (EDCS) could lead to the persistent harm of aquatic wildlife. Addressing this concern, advanced waste water treatment ...techniques should be established in addition to the present sewage treatment. Therefore, the promising advanced oxidation process of photocatalysis is discussed. With the aim of establishing a novel high throughput screening approach for photocatalysts, a workflow resting upon the use of a self-constructed 60-fold parallel stirring UV-A LED photoreactor, followed by parallel sample extraction by SPE and sequential automated analysis by GC-MS, was developed, and is presented in this article. With the described system, TiO2-based photocatalysts, doped with different amounts of zinc, and synthesised by a sol-gel-route, were tested regarding their activity in the photocatalytic degradation of the synthetic estrogen 17α-ethinylestradiol. Thereby, the functional behavior of the photoreactor system and its applicability in a high throughput process could be evaluated. As a result of the catalyst screening, TiO2 catalysts with low amounts of zinc were found with a significantly higher activity, compared to undoped TiO2. In conclusion, the presented system provides an easily accessible high throughput method for a variety of photocatalytic experiments.
The mountain pine beetle, Dendroctonus ponderosae, is an irruptive bark beetle that causes extensive mortality to many pine species within the forests of western North America. Driven by climate ...change and wildfire suppression, a recent mountain pine beetle (MPB) outbreak has spread across more than 18 million hectares, including areas to the east of the Rocky Mountains that comprise populations and species of pines not previously affected. Despite its impacts, there are few tactics available to control MPB populations. Beauveria bassiana is an entomopathogenic fungus used as a biological agent in agriculture and forestry and has potential as a management tactic for the mountain pine beetle population. This work investigates the phenotypic and genomic variation between B. bassiana strains to identify optimal strains against a specific insect.
Using comparative genome and transcriptome analyses of eight B. bassiana isolates, we have identified the genetic basis of virulence, which includes oosporein production. Genes unique to the more virulent strains included functions in biosynthesis of mycotoxins, membrane transporters, and transcription factors. Significant differential expression of genes related to virulence, transmembrane transport, and stress response was identified between the different strains, as well as up to nine-fold upregulation of genes involved in the biosynthesis of oosporein. Differential correlation analysis revealed transcription factors that may be involved in regulating oosporein production.
This study provides a foundation for the selection and/or engineering of the most effective strain of B. bassiana for the biological control of mountain pine beetle and other insect pests populations.
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