Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3.

CC chemokine ligand 5 (CCL5) and CCL3 are critical for immune surveillance and inflammation. Consequently, they are linked to the pathogenesis of many inflammatory conditions and are therapeutic targets. Oligomerization and glycosaminoglycan (GAG) binding of CCL5 and CCL3 are vital for the functions of these chemokines. Our structural and biophysical analyses of human CCL5 reveal that CCL5 oligomerization is a polymerization process in which CCL5 forms rod-shaped, double-helical oligomers. This CCL5 structure explains mutational data and offers a unified mechanism for CCL3, CCL4, and CCL5 assembly into high-molecular-weight, polydisperse oligomers. A conserved, positively charged BBXB motif is key for the binding of CC chemokines to GAG. However, this motif is partially buried when CCL3, CCL4, and CCL5 are oligomerized; thus, the mechanism by which GAG binds these chemokine oligomers has been elusive. Our structures of GAG-bound CCL5 and CCL3 oligomers reveal that these chemokine oligomers have distinct GAG-binding mechanisms. The CCL5 oligomer uses another positively charged and fully exposed motif, KKWVR, in GAG binding. However, residues from two partially buried BBXB motifs along with other residues combine to form a GAG-binding groove in the CCL3 oligomer. The N termini of CC chemokines are shown to be involved in receptor binding and oligomerization. We also report an alternative CCL3 oligomer structure that reveals how conformational changes in CCL3 N termini profoundly alter its surface properties and dimer-dimer interactions to affect GAG binding and oligomerization. Such complexity in oligomerization and GAG binding enables intricate, physiologically relevant regulation of CC chemokine functions

Cladistic relationships within the genus Cinnamomum (Lauraceae) in Taiwan based on analysis of leaf morphology and inter-simple sequence repeat (ISSR) and internal transcribed spacer (ITS) molecular markers

We examined leaf morphological characteristics, ISSR (inter-simple sequence repeat) genetic polymorphisms and ITS (rDNA internal transcribed spacer) molecular markers in 12 endemic species of Cinnamomum in Taiwan to determine their cladistic relationships. The leaf morphology and ISSR data support the division of the genus into sections Camphora and Cinnamomum. The genetic relationship between Cinnamomum camphora and Cinnamomum micranthum is very close; both species share a specific 11 bp deletion in their ITS sequences. A close relationship between Cinnamomum insularimontanum and Cinnamomum macrostemon was supported by leaf morphology, ISSR and ITS data and the ITS analysis indicates that Cinnamomum subavenium is closely related to these two species. The ITS analysis also indicates that Cinnamomum japonicum, Cinnamomum austrosinense and Cinnamomum reticulatum are closely related. Leaf morphology and ISSRs also support the kinship between C. japonicum and C. austrosinense. The ITS data support a close cluster consisting of C. osmophloeum, C. camphora and C. micranthum, suggesting that Cinnamomum osmophloeum might be a key species in the evolutionary transition from section Camphora to section  Cinnamomum. Our results demonstrate that ISSR and ITS markers can clearly identify the 12 endemic Cinnamomum species in Taiwan.Key words: Cinnamomum, morphology, taxonomy, ISSR (inter-simple sequence repeat), ITS (internal transcribed spacer), phylogeny

A prospective randomized, open-label trial comparing the safety and efficacy of dose sparing intradermal 2010/2011 trivalent influenza vaccine delivered by two different devices

Poster Abstract Session - Influenza Vaccines: no. 533BACKGROUND: We performed intradermal 2010/11 trivalent influenza vaccination (TIV) in adult subjects delivered by two different intradermal (ID) devices, using 20% and 60% of the standard dose and compared the immunogenicity and safety with full dose intramuscular (IM) immunization. METHODS: This is a prospective randomized trial conducted from December 2010 to March 2011, comprising chronically ill adults. Subjects were randomly assigned …postprin

Additional molecular testing of saliva specimens improves the detection of respiratory viruses

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Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

© 2016 by the authors; licensee MDPI, Basel, Switzerland.To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.published_or_final_versio

Carbyne-based Sensing Device For High Spatial Resolution In DNA Sequencing And Biomolecule Characterization And Method Of Fabricating The Same

A method of fabricating a sensing device for DNA sequencing and biomolecule characterization including the steps of fabricating a microelectrode chip having a silicon substrate and a silicon nitride diaphragm, attaching a monolayer graphene sheet to the silicon nitride diaphragm, dicing a portion of the monolayer graphene sheet to form a graphene microribbon, converting the graphene microribbon to a graphene nanoribbon, and converting the graphene nanoribbon to a carbyne. A sensing device for DNA sequencing and biomolecule characterization is also disclosed. The sensing device includes a silicon substrate, a cavity in the silicon substrate covered by a silicon nitride layer, microelectrodes attached to the silicon nitride layer, graphene covering the microelectrodes, and carbyne attached to a portion of the silicon nitride layer covering said cavity

Carbyne-based Sensing Device For High Spatial Resolution In DNA Sequencing And Biomolecule Characterization And Method Of Fabricating The Same

A method of fabricating a sensing device for DNA sequencing and biomolecule characterization including the steps of fabricating a microelectrode chip having a silicon substrate and a silicon nitride diaphragm, attaching a monolayer graphene sheet to the silicon nitride diaphragm, dicing a portion of the monolayer graphene sheet to form a graphene microribbon, converting the graphene microribbon to a graphene nanoribbon, and converting the graphene nanoribbon to a carbyne. A sensing device for DNA sequencing and biomolecule characterization is also disclosed. The sensing device includes a silicon substrate, a cavity in the silicon substrate covered by a silicon nitride layer, microelectrodes attached to the silicon nitride layer, graphene covering the microelectrodes, and carbyne attached to a portion of the silicon nitride layer covering said cavity

Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease

Exploring Temporal and Intensity Effects of Resistance Exercise on Inhibition: A Four-Arm Crossover Randomized Controlled Trial

Ting-Yu Lin, Hao-Chien Cheng, Hung-Wen Liu, Tsung-Min Hung Department of Physical Education and Sport Sciences, National Taiwan Normal University, Taipei, TaiwanCorrespondence: Tsung-Min Hung, Institute for Research Excellence in Learning Sciences, National Taiwan Normal University, 162, Section 1, Heping E. Road, Taipei City, 106, Taiwan, Tel/Fax +886-2-7749-1111, Email [email protected]: Given the recognized benefits of resistance exercise on both physical and cognitive domains, elucidating how to maximize its benefit is pivotal. This study aims to evaluate these effects in terms of their timing and intensity on cognitive performance.Methods: This was a four-arm, crossover randomized controlled trial. Healthy college-aged male adults with recreational resistance training experience participated in this study. Participants completed three separate sessions of circuit barbell resistance exercises, including back squat, press, and deadlift. Each session corresponded to a different intensity level: 65% 1RM, 72% 1RM, and 78% 1RM. Each session consisted of 5 repetitions across 3 sets, with a 3-minute rest between exercises and sets. For the control condition, participants engaged in a reading activity for the same duration. The subjective exercise intensity was measured using the rating of perceived exertion and repetitions in reserve immediately after each set. The primary outcome was the temporal effect of acute resistance exercise on inhibition, measured by the Stroop color-word task. The secondary outcome was the effect of different intensities.Results: 30 out of 31 recruited participants were randomized, with 28 completing all experiment sessions. Using repeated measures correlation (rrm), a linear temporal effect was observed on accuracy-adjusted congruent reaction time: rrm = 0.114, p = 0.045, 95% CI [0.002, 0.223]. Participants responded 19.1 ms faster than the control condition approximately 10 minutes post-intervention. This advantage, however, gradually declined at a rate of 4.3 ms every 15 minutes between 10– 55 minutes post-intervention. In contrast, no significant effects were detected for incongruent trials or the Stroop effect. When examining the linear relationship across exercise intensities, no significant correlations emerged for congruent trials.Conclusion: Resistance exercise demonstrates a temporal effect on cognitive performance, particularly in reaction speed for congruent trials, without significant changes in incongruent trials or the overall Stroop effect. The findings highlight the importance of timing in leveraging the cognitive benefits of acute resistance exercise, suggesting a window of enhanced cognitive performance following exercise. However, this study has a limitation regarding Type I error inflation, due to multiple measurements of cognitive performance being undertaken, suggesting caution in interpreting the observed temporal effects. Practically, scheduling crucial, cognitively demanding tasks within 10– 60 minutes post-exercise may maximize benefits, as positive effects diminish after this period.Keywords: executive function, physical exercise, resistance training, cognition, RC

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse