Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host-Guest Complexes with a Bis(zinc porphyrin) Tweezer.

A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 : 10 to 1 : 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1 : 2 was found.

Effect of ring rize on photoisomerization properties of stiff stilbene macrocycles.

A series of stiff stilbene macrocycles have been studied to investigate the possible impact of the macrocycle ring size on their photodynamic properties. The results show that reducing the ring size counteracts the photoisomerization ability of the macrocycles. However, even the smallest macrocycle studied (stiff stilbene subunits linked by a six carbon chain) showed some degree of isomerization when irradiated.

Design of oxophilic metalloporphyrins: an experimental and DFT study of methanol binding.

By systematic measurements we have evaluated a series of tetraphenyl metalloporphyrins and halogenated tetraphenyl metalloporphyrin derivatives for binding to ligands with oxygen containing functional groups, using methanol, acetic acid and acetone as examples. Experimental binding constants identified three metalloporphyrins with good binding to all three ligands: MgTPFPP, MgTPPBr8 and ZnTPPBr8 as well as a range of porphyrins binding to select ligands. Based on these results the optimal porphyrins can be selected for the desired binding interactions.

Brønsted acid-catalyzed intramolecular nucleophilic substitution of the hydroxyl group in stereogenic alcohols with chirality transfer.

The hydroxyl group of enantioenriched benzyl, propargyl, allyl, and alkyl alcohols has been intramolecularly displaced by uncharged O-, N-, and S-centered nucleophiles to yield enantioenriched tetrahydrofuran, pyrrolidine, and tetrahydrothiophene derivatives with phosphinic acid catalysis. The five-membered heterocyclic products are generated in good to excellent yields, with high degree of chirality transfer, and water as the only side-product. Racemization experiments show that phosphinic acid does not promote SN1 reactivity.

Genetic variation at the BDNF locus: evidence for association with long-term outcome after ischemic stroke.

Background And Purpose: Rates and extent of recovery after stroke vary considerably between individuals and genetic factors are thought to contribute to post-stroke outcome. Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair and has been shown to be involved in stroke severity, recovery, and outcome in animal models. Few clinical studies on BDNF genotypes in relation to ischemic stroke have been performed.

Genetic variants of GSK3B are associated with biomarkers for Alzheimer's disease and cognitive function.

Background: Glycogen synthase kinase 3 beta (GSK3B) is the major kinase phosphorylating tau protein. Hyperphosphorylated tau is one of the hallmarks of Alzheimer's disease (AD). Despite extensive research, the role of GSK3B in AD pathogenesis is not fully understood.

A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case-control study.

Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other 'traditional risk factors', also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study.

Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1.

Objective: In humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.

Cardioembolic and small vessel disease stroke show differences in associations between systemic C3 levels and outcome.

Background: Activation of the complement system has been proposed to play a role in the pathophysiology of stroke. As the specific involvement of the complement proteins may be influenced by stroke etiology, we compared plasma C3 and C3a levels in patients with cardioembolic (CE) and small vessel disease (SVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at three months and two years.

Methodology/principal Findings: Plasma C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and at three months after stroke, and age- and sex-matched control subjects from The Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA.

Genetic variation within the interleukin-1 gene cluster and ischemic stroke.

Background And Purpose: Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to investigate whether genetic variation in the interleukin-1α, interleukin-1β, and interleukin-1 receptor antagonist genes (IL1A, IL1B, and IL1RN) is associated with IS and/or any etiologic subtype of IS.

Methods: Twelve tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 844 patients with IS and 668 control subjects.

A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events.

Background And Purpose: Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies.

Methods: Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors.

A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene.

Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950.

Plasma C3 and C3a levels in cryptogenic and large-vessel disease stroke: associations with outcome.

Background And Purpose: Inflammation seems to be a key player in the pathophysiology of stroke. In this study, we compared plasma C3 and C3a levels in cryptogenic and large-vessel disease (LVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at 3 months and 2 years.

Methods: C3 and C3a levels in plasma of 79 cryptogenic stroke and 73 LVD stroke patients, sampled within 10 days and at 3 months after stroke, and age- and sex-matched control subjects from the Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA.

Lack of association between genetic variations in the KALRN region and ischemic stroke.

Objectives: To investigate whether KALRN gene variation is associated with ischemic stroke (IS).

Design And Methods: Associations to overall IS and IS subtypes were investigated in SAHLSIS, which comprises 844 patients with IS and 668 controls.

Results: Associations between KALRN SNPs and overall IS and cardioembolic stroke were detected.

Genetic variant on chromosome 12p13 does not show association to ischemic stroke in 3 Swedish case-control studies.

Background And Purpose: in a genome-wide association study and subsequent case-control studies, the single-nucleotide polymorphism rs12425791 on chromosome 12p13 was reported to be associated with ischemic stroke, but this could not be validated in a recent well-powered study. We therefore investigated whether an association between ischemic stroke and rs12425791 could be detected in 3 different case-control studies from the southwest of Sweden.

Methods: we examined 3606 patients with ischemic stroke and 2528 controls from 3 independent case-controls studies.

Association between genetic variation on chromosome 9p21 and aneurysmal subarachnoid haemorrhage.

Background And Aim: Genetic factors play a role in susceptibility to subarachnoid haemorrhage, but little is known about which genes are involved. Recently, genome wide association studies have identified the 9p21 region as a risk locus for intracranial aneurysms (IA). The aim of the present study was to examine the possible association between 9p21 and ruptured IA--that is, aneurysmal subarachnoid haemorrhage (aSAH)--in a Swedish population.

The macrophage beta-glucan receptor mediates arachidonate release induced by zymosan: essential role for Src family kinases.

Yeast-derived zymosan beads are among the classical agents used to induce sterile inflammatory responses in experimental animals and macrophage activation in cell culture. In macrophages the cytosolic phospholipase A2 becomes activated, leading to mobilization of arachidonate and the generation of prostaglandins and leukotrienes. Although zymosan can interact with several receptors it has not been unequivocally demonstrated which interaction is required for induction of the eicosanoid response.

Different roles for non-receptor tyrosine kinases in arachidonate release induced by zymosan and Staphylococcus aureus in macrophages.

Background: Yeast and bacteria elicit arachidonate release in macrophages, leading to the formation of leukotrienes and prostaglandins, important mediators of inflammation. Receptors recognising various microbes have been identified, but the signalling pathways are not entirely understood. Cytosolic phospholipase A2 is a major down-stream target and this enzyme is regulated by both phosphorylation and an increase in intracellular Ca2+.

The role of lipid rafts in LPS-induced signaling in a macrophage cell line.

The significance of lipid rafts in lipopolysaccharide (LPS) signaling in macrophages was studied through isolation of them by gradient centrifugation and subsequent visualization of signal molecules using antibodies. LPS signaling is initiated by binding to Toll-like receptor-4 (TLR4) and the co-receptor CD-14, leading to activation of downstream targets, such as MAP kinases. In this study, we show that LPS causes translocation of CD-14 and MAP kinases (ERK-2 and p38) to lipid rafts in the macrophage cell line RAW 264.