NK cells are activated and primed for skin-homing during acute dengue virus infection in humans

10.1038/s41467-019-11878-3Nature Communications101389

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Elliptic flow of muons from heavy-flavour hadron decays at forward rapidity in Pb-Pb collisions at root s(NN)=2.76TeV

The elliptic flow, v(2), of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4) is measured in Pb-Pb collisions at root s(NN)= 2.76TeVwith the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v(2) of muons from heavy-flavour hadron decays on the collision centrality, in the range 0-40%, and on transverse momentum, p(T), is studied in the interval 3 <p(T)<10 GeV/c. A positive v(2) is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10-20% and 20-40% centrality classes) for the p(T) interval from 3 to about 5GeV/c with a significance larger than 3 sigma, based on the combination of statistical and systematic uncertainties. The v(2) magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6 <p(T)<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Απομόνωση, χαρακτηρισμός και ακινητοποίηση του ενζύμου Αλλιινάση σε στοιβαγμένα διπλά υδροξείδια

Garlic (Aliium sativum) is important because of the culinary value of its flavour and odour. These characteristics are created by chemical transformation of a series of volatile sulphur compounds generated by cleavage of relatively stable, odourless, S-alk(en)yl cysteine sulphoxide flavour precursors by the enzymes alliinase and lachrymatory-factor synthase. Allicin, a cysteine sulfoxide, has been shown to possess a variety of important biological effects (anti-inflammatory, antimicrobial, antithrombotic, anticancer and antimutagenic). The garlic protein alliinase (alliin lyase) is a dimmer of two identical subunits of 51.1kDa each. The enzyme is a glycoprotein which contains about 6% of neutral sugars; it was demonstrated that alliinase binds to Con A and can form a complex with garlic lectins. The lectin-alliinase complex offers a high stability to the enzyme and its enzymatic activity. The formation of a strong lectin-alliinase complex makes the isolation of pure alliinase difficult. Alliinase catalyses the production of allicin (S-(+)-2-propenyl-L-cysteine sulfoxide) from alliin [(2-propenyl)-2-propenethiosulfinate]. Alliinase and allicin stability is considerably dependent from the storage conditions. In the crude extracts of garlic, allicin easily gives a variety of chemical compounds. Because of the instability of the enzyme and the main product, the direct clinical trials are not possible. An alternative strategy could be the use of stabilised alliinase in combination with alliin as a pill or capsule. The available pills that are found in the market do not have a significant output in alicin and this is due to the loss of activity of the enzyme during the pill preparation. Therefore, stabilisation of alliinase in biocompatible inorganic clays, as layered double hydroxides, would help in the development of clinical applications. Layered double hydroxides are a large group of compounds with the chemical formula [M(II)(1-X)M(III)X(OH)2]Y+(An-Y/n)mH2O (LDH-A), where M(II) are the cations of double-charged metals, M(III) are the cations of triple-charged metals, An- are interlayer anions. The structure of these compounds is formed by alternating charged brucite-like layers of the composition [M(II)(1-X)M(III)X(OH)2](2)Y+ and the layers containing A- anions and water molecules at the same time. The presence of two fragments of nanoscale thickness which differ sharply in composition, structure, and chemical properties makes it possible to employ these compounds as nanoreactors for chemical reactions of interlayer molecules. Layered double hydroxides have attracted interest thanks largely to their ability to exchange their anions for other negatively charged species. This property has lead to their proposed use as ion-exchange materials and hosts for biologically active molecules. The hosting of biologically active molecules inside layered double hydroxides is attractive because LDH can act as a ‘chemical flak-jacket’, protecting the host from degradation. Additionally, the hosting of a negatively charged species could provide improved ways for drugs and genetic material to be introduced into cells. If ingested, the biomolecule-LDH nano-hybrid can move across the mucous membrane of the intestine into the bloodstream. The neutral hybrid can then enter cells by moving across the negatively charged cell-membrane without the repulsive electrostatic interactions that would be experienced by the guest anion alone. Aim of the present work is the purification, characterization and subsequent immobilisation of the protein alliinase in the layers of magnesium-aluminium hydroxide - LDH. Purified alliinase was extracted from bulbs of garlic and was purified by using hydroxylapatite and concanavalin A affinity columns. The enzymatic assay demonstrated that the enzyme was very active. Antibodies anti-alliinase were prepared. In order to investigate the binding of the oligosaccharides to alliinase and their role on the properties of the enzyme, treatment of native and denatured alliinase with PNGase F was carried out. Alliinase was immobilized on LDH and analyzed by using various techniques. The immobilized enzyme demonstrated a significant stability.Η αλλιινάση (λυάση της αλλιίνης) καταλύει την σύνθεση της αλλισίνης (S-(+)-2-propenyl-L-cysteine sulfoxide) από αλλιίνη (2-propenyl)-2-propenethiosulfinate). Η αλλισίνη είναι το κύριο βιολογικά ενεργό μόριο στο αλεσμένο σκόρδο και σε αυτό οφείλονται οι περισσότερες από τις θεραπευτικές ιδιότητες του φυτού. Η σταθερότητα της αλλιινάσης και της αλλισίνης είναι σημαντικά εξαρτώμενη από τις συνθήκες αποθήκευσης. Λόγω της αστάθειας που παρουσιάζουν τόσο το ένζυμο όσο και το κύριο προϊόν δεν είναι δυνατές οι άμεσες κλινικές δοκιμές. Ως εναλλακτική στρατηγική θα μπορούσε να γίνει χρήση του σταθεροποιημένου ένζυμου σε συνδυασμό με το υπόστρωμα σε μορφή χαπιού ή κάψουλας. Τα διαθέσιμα χάπια που βρίσκονται στην αγορά δεν έχουν μεγάλη απόδοση σε αλλισίνη και αυτό οφείλεται στην απώλεια της ενεργότητας του ένζυμου κατά την διάρκεια παρασκευής του χαπιού. Σκοπός της παρούσας εργασίας είναι η απομόνωση, ο χαρακτηρισμός και η μετέπειτα ακινητοποίηση της πρωτεΐνης αλλιινάση στα στρώματα υδροξειδίων μαγνησίου-αλουμινίου. Η πιθανή σταθεροποίηση του ένζυμου αλλιινάση σε μια βιοσυμβατή ανόργανη μήτρα, όπως τις στοιβάδες διπλών υδροξειδίων, θα βοηθούσε μακροπρόθεσμα στην ανάπτυξη κλινικών εφαρμογών. Το ένζυμο απομονώθηκε από βολβούς σκόρδου χρησιμοποιώντας διάφορες τεχνικές συμπεριλαμβανομένης της χρωματογραφίας συγγένειας. Η ισχυρή αντίδραση δυο λεκτινών με την αλλιινάση οδηγεί στον σχηματισμό συμπλόκων λεκτίνης-αλλιινάση, γεγονός που δυσκόλεψε την απομόνωση καθαρής αλλιινάση. Το καθαρό ένζυμο μελετήθηκε με μια σειρά βιοχημικών και βιοφυσικών τεχνικών. Επιτεύχθηκε παραγωγή πολυκλωνικών αντισωμάτων αντι-αλλιινάσης με σκοπό την μελέτη του ενζύμου σε άλλα βιολογικά συστήματα. Στοιβάδες διπλών υδροξειδίων μαγνησίου-αλουμινίου παρασκευάστηκαν και μελετήθηκαν με φασματοσκοπικές τεχνικές. Επιτεύχθηκε η σταθεροποίηση της αλλιινάσης σε στοιβάδες διπλών υδροξειδίων. Προκαταρκτικές αναλύσεις έδειξαν ότι το ένζυμο παρέμεινε σταθερό στην βιοσυμβατή ανόργανη μήτρα για παραπάνω από τέσσερις μήνες σε θερμοκρασία 4οC