Stretching and contraction of extensional basins with pre-rift salt: a numerical modelling approach

We present a series of 2D thermo-mechanical numerical experiments of thick-skinned crustal extension including a pre-rift salt horizon and subsequent thin-, thick-skinned, or mixed styles of convergence accompanied by surface processes. Extension localization along steep basement faults produces half-graben structures and leads to variations in the original distribution of pre-rift salt. Thick-skinned extension rate and salt rheology control hanging wall accommodation space as well as the locus and timing of minibasin grounding. Upon shortening, extension-related basement steps hinder forward propagation of evolving shallow thrust systems; conversely, if full basin inversion takes place along every individual fault, the regional salt layer is placed back to its pre-extensional configuration, constituting a regionally continuous décollement. Continued shortening and basement involvement deform the shallow fold-thrust structures and locally breaches the shallow décollement. We aim at obtaining a series of structural, stratigraphic and kinematic templates of fold-and-thrust belts involving rift basins with an intervening pre-rift salt horizon. Numerical results are compared to natural cases of salt-related inversion tectonics to better understand their structural evolution

Absorption and cutaneous deposition of yellow pigment in male and female broilers in response to different levels of xanthophylls from Tagetes erecta

To determine the saturation point of absorption and cutaneous deposition of yellow xanthophylls (XA) in broilers, two hundred and sixteen Ross 308 chickens (108 males and 108 females) were sorted by sex and randomly assigned to 6 dietary treatments containing 6 replications of 6 birds each. Treatments consisted of increasing levels of xanthophylls from Aztec marigold flower (Tagetes erecta) (65, 92, 119, 146, 173, and 200 ppm). Weight gain, feed consumption, and feed conversion were measuredweekly. Plasma pigment levels and skin yellowness in live birds were measured twice per week. Growth performance was analysed through ANOVA for a 6X2 factorial arrangement, where the first factor was the XA adding at six levels, and the second factor was sex at two levels. Pigment plasma concentration and skin yellowness were fitted into a multiple linear regression model. Results indicated that the highest levels of plasma xanthophylls and skin yellowness were found after 28 d of feeding. Skin yellowness increased by 2.24 b* for every d of xanthophylls consumption. In the females, skin yellowness was 1.35 b* higher than in the males. Increasing dietary xanthophylls by 10 ppm was reflected in 0.83 b* of increase in skin yellowness

Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV

HIV; Immunotherapy; MetabolismVIH; Inmunoterapia; MetabolismoVIH; Immunoteràpia; MetabolismeBackground Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated. Methods We studied association of restoration of functional HIV-1-specific CD8+ T cell responses after stimulation with Gag-adjuvant-primed DC with ART duration, exhaustion, metabolic and memory cell subsets profiles. Findings HIV-1-specific CD8+ T cell responses from a larger proportion of PLWH on long-term ART (more than 10 years; LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cells in vitro. In contrast, functional improvement of CD8+ T cells from PLWH on short-term ART (less than a decade; ST-ARTp) after DC treatment was limited. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolysis induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+ PD1− cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Interpretation Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines.EMG was supported by the NIH R21 program (R21AI140930), the Ramón y Cajal Program (RYC2018-024374-I), the MINECO/FEDER RETOS program (RTI2018-097485-A-I00), by Comunidad de Madrid Talento Program (2017-T1/BMD-5396) and by Gilead becas de investigación (GLD19/00168). EMG and IDS are supported by Centro de Investigación Biomédica en Red (CIBERINF) de Enfermedades Infecciosas (CB21/13/00107). MCM was supported by NIH R21 program (R21AI140930), “La Caixa Banking Foundation (H20-00218) and Gilead becas de investigación (GLD19/00168). MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179), the MINECO/FEDER RETOS program (RTI2018-101082-B-100), and Fundació La Marató TV3 (201805-10FMTV3). EMG and MJB are both funded by “La Caixa Banking Foundation (H20-00218) and by REDINCOV grant from Fundació La Marató TV3. FSM was supported by SAF2017-82886-R and PDI-2020-120412RB-I00 grants from the Ministerio de Ciencia e Innovación, and HR17-00016 grant from “La Caixa Banking Foundation. HF was funded by PI21/01583 grant from Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III. MJC was supported by PID2019-104406RB-I00 from Ministerio de Ciencia e Innovación. ISC was funded by the CM21/00157 Rio-Hortega grant. IT was supported by grant for the promotion of research studies master-UAM 2021

Copper: Synthesis Techniques in Nanoscale and Powerful Application as an Antimicrobial Agent

Nanosized metal particles show specific physical and chemical properties that allow the creation of new composites materials, which are important for multiple applications in biology and medicine such as infections control. Metal nanoparticles, mainly copper, exhibit excellent inhibitory effect on Gram-positive and Gram-negative bacteria; therefore the exploration about the efficient, economical, and friendly environmental technics to synthesize inorganic nanoparticles is imperative. In this work a brief overview of the several methods is made including the comparison of the methods, mainly between sonochemical, microwave, and chemical routes. It allows determining the optimal parameters and technical conditions to synthesize copper nanoparticles with physical and chemical properties suitable for the oral bacterial inhibition

Remote activation of enzyme nanohybrids for cancer prodrug therapy controlled by magnetic heating

Herein, we have developed nanohybrids (nHs) to remotely activate a therapeutic enzyme for its use in Directed Enzyme Prodrug Therapy (DEPT). The coencapsulation of magnetic nanoparticles (MNPs) with horseradish peroxidase (HRP) using biomimetic silica as an entrapment matrix was optimized to obtain nanosized hybrids (∼150 nm) for remote activation of the therapeutic enzyme. HRP converts indole-3-acetic acid (3IAA) into peroxylated radicals, whereas MNPs respond to alternating magnetic fields (AMFs) becoming local hotspots. The AMF application triggered an increase in the bioconversion rate of HRP matching the activity displayed at the optimal temperature of the nHs (Topt = 50 °C) without altering the temperature of the reaction media. This showed that enzyme nanoactuation is possible with MNPs even if they are not covalently bound. After an extensive physicochemical/magnetic characterization, the spatial location of each component of the nH was deciphered, and an insulating role of the silica matrix was suggested as critical for introducing remote control over HRP. In vitro assays, using a human pancreatic cancer cell line (MIA PaCa-2), showed that only upon exposure to AMF and in the presence of the prodrug, the enzyme-loaded nHs triggered cell death. Moreover, in vivo experiments showed higher reductions in the tumor volume growth in those animals treated with nHs in the presence of 3IAA when exposed to AMF. Thus, this work demonstrates the feasibility of developing a spatiotemporally controlled DEPT strategy to overcome unwanted off-target effects

Vitamin D treatment prevents uremia-induced reductions in aortic microRNA-145 attenuating osteogenic differentiation despite hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia

The QUIJOTE experiment: project overview and first results

QUIJOTE (Q-U-I JOint TEnerife) is a new polarimeter aimed to characterize the polarization of the Cosmic Microwave Background and other Galactic and extragalactic signals at medium and large angular scales in the frequency range 10-40 GHz. The multi-frequency (10-20~GHz) instrument, mounted on the first QUIJOTE telescope, saw first light on November 2012 from the Teide Observatory (2400~m a.s.l). During 2014 the second telescope has been installed at this observatory. A second instrument at 30~GHz will be ready for commissioning at this telescope during summer 2015, and a third additional instrument at 40~GHz is now being developed. These instruments will have nominal sensitivities to detect the B-mode polarization due to the primordial gravitational-wave component if the tensor-to-scalar ratio is larger than r=0.05.Comment: To appear in "Highlights of Spanish Astrophysics VIII", Proceedings of the XI Scientific Meeting of the Spanish Astronomical Society, Teruel, Spain (2014

Oxidized low-density lipoprotein receptor in lymphocytes prevents atherosclerosis and predicts subclinical disease

Background: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease. Methods: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122). Results: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets. Conclusions: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.Funding was provided by the Spanish Ministry of Economy and Competitiveness: Plan Nacional de Salud SAF2017-82886-R to Dr Sánchez-Madrid, SAF2015-64767-R to Dr Martínez-González; Instituto de Salud Carlos III (AES 2016): PI16/01956 to Dr Martin, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares; European Research Council, ERC- 2011-AdG294340-GENTRIS to Dr Sánchez-Madrid; Proyecto Integrado de Excelencia PIE13/041 and Fundació La Marató TV3 (20152330 31); and Comunidad Autónoma de Madrid CAM (S2017/BMD-3671) to Drs Martin and Sánchez-Madrid. Dr Tsilingiri is cofunded by the European Union Marie Curie Program. M. Relaño is supported by a Contratos Predoctorales Severo Ochoa para la formación de doctores (BES-2015–072625) from the Spanish Ministry of Economy and Competitiveness. This research has been cofinanced by Fondo Europeo de Desarrollo Regional. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The PESA study is cofunded equally by the Pro CNIC Foundation and Banco Santander, Madrid, Spai