Optimisation, by response surface methodology, of degree of hydrolysis and antioxidant and ACE-inhibitory activities of whey protein hydrolysates obtained with cardoon extract

The hydrolysis of bovine whey protein concentrate (WPC), alpha-lactalbumin (alpha-La) and caseinomacropeptide (CMP), by aqueous extracts of Cynara cardunculus, was optimized using response surface methodology. Degree of hydrolysis (DH), angiotensin-converting enzyme (ACE)-inhibitory activity and antioxidant activity were used as objective functions, and hydrolysis time and enzyme/substrate ratio as manipulated parameters. The model was statistically appropriate to describe ACE-inhibitory activity of hydrolysates from WPC and alpha-La, but not from CMP. Maximum DH was 18% and 9%, for WPC and alpha-La, respectively. 50% ACE-inhibition was produced by 105.4 (total fraction) and 25.6 mu g mL(-1) (<3 kDa fraction) for WPC, and 47.6 (total fraction) and 22.5 mu g mL(-1) (<3 kDa fraction) for alpha-La. Major peptides of fractions exhibiting ACE-inhibition were sequenced. The antioxidant activities of WPC and alpha-La were 0.96 +/- 0.08 and 1.12 +/- 0.13 mmol trolox equivalent per mg hydrolysed protein, respectively.info:eu-repo/semantics/acceptedVersio

Identification of a new cholesterol-binding site within the IFN-γ receptor that is required for signal transduction.

The cytokine interferon-gamma (IFN-γ) is a master regulator of innate and adaptive immunity involved in a broad array of human diseases that range from atherosclerosis to cancer. IFN-γ exerts it signaling action by binding to a specific cell surface receptor, the IFN-γ receptor (IFN-γR), whose activation critically depends on its partition into lipid nanodomains. However, little is known about the impact of specific lipids on IFN-γR signal transduction activity. Here, a new conserved cholesterol (chol) binding motif localized within its single transmembrane domain is identified. Through direct binding, chol drives the partition of IFN-γR2 chains into plasma membrane lipid nanodomains, orchestrating IFN-γR oligomerization and transmembrane signaling. Bioinformatics studies show that the signature sequence stands for a conserved chol-binding motif presented in many mammalian membrane proteins. The discovery of chol as the molecular switch governing IFN-γR transmembrane signaling represents a significant advance for understanding the mechanism of lipid selectivity by membrane proteins, but also for figuring out the role of lipids in modulating cell surface receptor function. Finally, this study suggests that inhibition of the chol-IFNγR2 interaction may represent a potential therapeutic strategy for various IFN-γ-dependent diseases

Temperature dependence of the anomalous effective action of fermions in two and four dimensions

The temperature dependence of the anomalous sector of the effective action of fermions coupled to external gauge and pseudo-scalar fields is computed at leading order in an expansion in the number of Lorentz indices in two and four dimensions. The calculation preserves chiral symmetry and confirms that a temperature dependence is compatible with axial anomaly saturation. The result checks soft-pions theorems at zero temperature as well as recent results in the literature for the pionic decay amplitude into static photons in the chirally symmetric phase. The case of chiral fermions is also considered.Comment: RevTex, 19 pages, no figures. References adde

Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1

Combination antiretroviral therapy (cART) can effectively suppress HIV-1 replication, but the latent viral reservoir in resting memory CD4+ T cells is impervious to cART and represents a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 represents a possible strategy for elimination of this reservoir. In this study we describe the discovery of 1,2,9,10-tetramethoxy-7H-dibenzo[de,g]quinolin-7-one (57704) which reactivates latent HIV-1 in several cell-line models of latency (J89GFP, U1 and ACH-2). 57704 also increased HIV-1 expression in 3 of 4 CD8+-depleted blood mononuclear cell preparations isolated from HIV-1-infected individuals on suppressive cART. In contrast, vorinostat increased HIV-1 expression in only 1 of the 4 donors tested. Importantly, 57704 does not induce global T cell activation. Mechanistic studies revealed that 57704 reactivates latent HIV-1 via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. 57704 was found to be an agonist of PI3K with specificity to the p110a isoform, but not the p110β, δ or γ isoforms. Taken together, our work suggests that 57704 could serve as a scaffold for the development of more potent activators of latent HIV-1. Furthermore, it highlights the involvement of the PI3K/Akt pathway in the maintenance of HIV-1 latency. © 2014 Doyon et al

Light Curves of the Neutron Star Merger GW170817/SSS17a: Implications for R-Process Nucleosynthesis

On 2017 August 17, gravitational waves were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical and infrared light curves of SSS17a extending from 10.9 hours to 18 days post-merger. We constrain the radioactively-powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in r-process nucleosynthesis in the Universe.Comment: Accepted to Scienc

Nonlinear dispersive waves in repulsive lattices

[EN] The propagation of nonlinear waves in a lattice of repelling particles is studied theoretically and experimentally. A simple experimental setup is proposed, consisting of an array of coupled magnetic dipoles. By driving harmonically the lattice at one boundary, we excite propagating waves and demonstrate different regimes of mode conversion into higher harmonics, strongly influenced by dispersion and discreteness. The phenomenon of acoustic dilatation of the chain is also predicted and discussed. The results are compared with the theoretical predictions of $\alpha$-FPU equation, describing a chain of masses connected by nonlinear quadratic springs and numerical simulations. The results can be extrapolated to other systems described by this equation.The work was supported by Spanish Ministry of Economy and Innovation (MINECO) and European Union FEDER through Project No. FIS2015- 65998-C2-2 and by Project No. AICO/2016/060 by Conselleria de Educacion, Investigacion, Cultura y Deporte de la Generalitat Valenciana. L.J.S.-C. gratefully acknowledge the support of PAID-01-14 at Universitat Politscnica de Valsncia. A. M. gratefully acknowledge to Generalitat Valenciana (Santiago Grisolia program).Mehrem, A.; Jimenez, N.; Salmerón-Contreras, LJ.; García-Andrés, FX.; García-Raffi, LM.; Picó Vila, R.; Sánchez Morcillo, VJ. (2017). Nonlinear dispersive waves in repulsive lattices. Physical Review E. 96(1). https://doi.org/10.1103/PhysRevE.96.012208S00220096

Working Group Report: Heavy-Ion Physics and Quark-Gluon Plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of Quark-Gluon Plasma believed to have created in heavy-ion collisions and in early universe are reported.Comment: 20 pages, 6 eps figures, Heavy-ion physics and QGP activity report in "IX Workshop on High Energy Physics Phenomenology (WHEPP-09)" held in Institute of Physics, Bhubaneswar, India, during January 3-14, 2006. To be published in PRAMANA - Journal of Physics (Indian Academy of Science

A Possible Detection of Occultation by a Proto-planetary Clump in GM Cephei

GM Cep in the young (~4 Myr) open cluster Trumpler 37 has been known to be an abrupt variable and to have a circumstellar disk with very active accretion. Our monitoring observations in 2009-2011 revealed the star to show sporadic flare events, each with brightening of < 0.5 mag lasting for days. These brightening events, associated with a color change toward the blue, should originate from an increased accretion activity. Moreover, the star also underwent a brightness drop of ~1 mag lasting for about a month, during which the star became bluer when fainter. Such brightness drops seem to have a recurrence time scale of a year, as evidenced in our data and the photometric behavior of GM Cep over a century. Between consecutive drops, the star brightened gradually by about 1 mag and became blue at peak luminosity. We propose that the drop is caused by obscuration of the central star by an orbiting dust concentration. The UX Orionis type of activity in GM Cep therefore exemplifies the disk inhomogeneity process in transition between grain coagulation and planetesimal formation in a young circumstellar disk.Comment: In submission to the Astrophysical Journal, 4 figure

Properties of Light Flavour Baryons in Hypercentral quark model

The light flavour baryons are studied within the quark model using the hyper central description of the three-body system. The confinement potential is assumed as hypercentral coulomb plus power potential ($hCPP_\nu$) with power index $\nu$. The masses and magnetic moments of light flavour baryons are computed for different power index, $\nu$ starting from 0.5 to 1.5. The predicted masses and magnetic moments are found to attain a saturated value with respect to variation in $\nu$ beyond the power index $\nu>$ 1.0. Further we computed transition magnetic moments and radiative decay width of light flavour baryons. The results are in good agreement with known experimental as well as other theoretical models.Comment: Accepted in Pramana J. of Physic

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al