LRP1-Mediated AggLDL Endocytosis Promotes Cholesteryl Ester Accumulation and Impairs Insulin Response in HL-1 Cells

The cardiovascular disease (CVD) frequently developed during metabolic syndrome and type-2 diabetes mellitus is associated with increased levels of aggregation-prone small LDL particles. Aggregated LDL (aggLDL) internalization is mediated by low-density lipoprotein receptor-related protein-1 (LRP1) promoting intracellular cholesteryl ester (CE) accumulation. Additionally, LRP1 plays a key function in the regulation of insulin receptor (IR) and glucose transporter type 4 (GLUT4) activities. Nevertheless, the link between LRP1, CE accumulation, and insulin response has not been previously studied in cardiomyocytes. We aimed to identify mechanisms through which aggLDL, by its interaction with LRP1, produce CE accumulation and affects the insulin-induced intracellular signaling and GLUT4 trafficking in HL-1 cells. We demonstrated that LRP1 mediates the endocytosis of aggLDL and promotes CE accumulation in these cells. Moreover, aggLDL reduced the molecular association between IR and LRP1 and impaired insulin-induced intracellular signaling activation. Finally, aggLDL affected GLUT4 translocation to the plasma membrane and the 2-NBDG uptake in insulin-stimulated cells. We conclude that LRP1 is a key regulator of the insulin response, which can be altered by CE accumulation through LRP1-mediated aggLDL endocytosis

Aloinjertos en artrodesis vertebrales extensas

La cirugía de las deformidades, fracturas y tumores vertebrales requiere frecuentemente artrodesis amplias, lo cual conlleva la dificultad de obtener suficiente injerto óseo autólogo (particularmente en niños y en casos de deformidades paralíticas) y la necesidad de una segunda incisión, con el consiguiente aumento del tiempo quirúrgico y eventual morbilidad. Estudiamos 52 pacientes afectos de deformidades, fracturas o tumores vertebrales que fueron intervenidos mediante artrodesis vertebral extensa, en los que se utilizó aloinjerto de cabeza femoral como hueso esponjoso para aumentar la cantidad obtenida del propio lecho de artrodesis (estructuras posteriores). Además, en tres ocasiones se utilizó como injerto óseo intersomático un fragmento de cabeza femoral tallado a medida, realizándose una costotransversectomía para su colocación. El seguimiento fue entre 1 y 4 años. La única complicación observada fue la aparición de seromas de resolución espontánea en los 15 primeros casos. Posteriormente este problema se evitó con el lavado repetido del injerto, una vez triturado, con suero fisiológico caliente. En nuestra experiencia, la utilización de aloinjertos óseos permitió disminuir el tiempo quirúrgico de las intervenciones y a su vez evitar nuevas incisiones, sin reducir se las posibilidades de obtener una correcta artrodesis vertebral

RhIGF-1 treatment increases bone mineral density and trabecular bone structure in children with PAPP-A2 deficiency

KARGER: "This is the peer-reviewed but unedited manuscript version of the following article: Hormone Research in Paediatrics 89.3 (2018): 200-204 DOI: 10.1159/000486336. The final, published version is available at http://www.karger.com/. http://doi.org/10.1159/000486336]."Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25∗) resulting in a premature stop codon. Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2in patient 1 and from 0.763 to 0.829 g/cm2in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.The authors are funded by Fondos de Investigación Sanitaria and FEDER (Grants PI1302195 and PI1600485 to J.A.), Ministerio de Ciencia e Innovación (BFU2014-51836-C2-2-R to J.A.C.), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (J.A.), and Fundación Endocrinología y Nutrició

Search for the Decays Bs0→τ+τ- and B0→τ+τ-

A search for the rare decays Bs0→τ+τ- and B0→τ+τ- is performed using proton-proton collision data collected with the LHCb detector. The data sample corresponds to an integrated luminosity of 3 fb-1 collected in 2011 and 2012. The τ leptons are reconstructed through the decay τ-→π-π+π-ντ. Assuming no contribution from B0→τ+τ- decays, an upper limit is set on the branching fraction B (Bs0→τ+τ- )<6.8 ×10-3 at the 95% confidence level. If instead no contribution from Bs0→τ+τ- decays is assumed, the limit is B (B0→τ+τ- )<2.1 ×10-3 at the 95% confidence level. These results correspond to the first direct limit on B (Bs0→τ+τ- ) and the world's best limit on B (B0→τ+τ- )

Observation of Five New Narrow Ω0c States Decaying to Ξ+cK−

The Ξc+K- mass spectrum is studied with a sample of p p collision data corresponding to an integrated luminosity of 3.3 fb-1, collected by the LHCb experiment. The Ξc+ is reconstructed in the decay mode p K-π+. Five new, narrow excited Ωc0 states are observed: the Ωc(3000 )0, Ωc(3050 )0, Ωc(3066 )0, Ωc(3090 )0, and Ωc(3119 )0. Measurements of their masses and widths are reported

Study of J/ψ Production in Jets

The production of J /ψ mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J /ψ meson, z (J /ψ ) ≡pT(J /ψ )/pT(jet ) , is measured using jets with pT(jet )>20 GeV in the pseudorapidity range 2.5 <η (jet )<4.0 . The observed z (J /ψ ) distribution for J /ψ mesons produced in b -hadron decays is consistent with expectations. However, the results for prompt J /ψ production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J /ψ mesons in jets at any experiment

Measurement of the B0s→μ+μ− Branching Fraction and Effective Lifetime and Search for B0→μ+μ− Decays

A search for the rare decays Bs0→μ+μ- and B0→μ+μ- is performed at the LHCb experiment using data collected in p p collisions corresponding to a total integrated luminosity of 4.4 fb-1. An excess of Bs0→μ+μ- decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B (Bs0→μ+μ- )=(3.0 ±0. 6-0.2+0.3) ×10-9 , where the first uncertainty is statistical and the second systematic. The first measurement of the Bs0→μ+μ- effective lifetime, τ (Bs0→μ+μ- )=2.04 ±0.44 ±0.05 ps , is reported. No significant excess of B0→μ+μ- decays is found, and a 95% confidence level upper limit, B (B0 →μ+μ-) <3.4 ×10-10 , is determined. All results are in agreement with the standard model expectations

Measurement of Bs0 and Ds- meson lifetimes

We report on a measurement of the flavor-specific Bs0 lifetime and of the Ds- lifetime using proton-proton collisions at center-of-mass energies of 7 and 8 TeV, collected by the LHCb experiment and corresponding to 3.0 fb-1 of integrated luminosity. Approximately 407 000 Bs0→Ds(*)-μ+νμ decays are partially reconstructed in the K+K-π-μ+ final state. The Bs0 and Ds- natural widths are determined using, as a reference, kinematically similar B0→D(*)-μ+νμ decays reconstructed in the same final state. The resulting differences between widths of Bs0 and B0 mesons and of Ds- and D- mesons are ΔΓ(B )=-0.0115 ±0.0053 (stat ) ±0.0041 (syst ) ps-1 and ΔΓ(D )=1.0131 ±0.0117 (stat ) ±0.0065 (syst ) ps-1, respectively. Combined with the known B0 and D- lifetimes, these yield the flavor-specific Bs0 lifetime, τBs 0 fs =1.547 ±0.013 (stat ) ±0.010 (syst ) ±0.004 (τB) ps and the Ds- lifetime, τDs-=0.5064 ±0.0030 (stat ) ±0.0017 (syst ) ±0.0017 (τD) ps . The last uncertainties originate from the limited knowledge of the B0 and D- lifetimes. The results improve upon current determinations

First Observation of a Baryonic B0s Decay

We report the first observation of a baryonic Bs0 decay, Bs0→p Λ ¯K- , using proton-proton collision data recorded by the LHCb experiment at center-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3.0 fb-1. The branching fraction is measured to be B (Bs0→p Λ ¯ K- )+B (Bs0→p ¯ Λ K+ )=[5.46 ±0.61 ±0.57 ±0.50 (B )±0.32 (fs/fd)] ×10-6 , where the first uncertainty is statistical and the second systematic, the third uncertainty accounts for the experimental uncertainty on the branching fraction of the B0→p Λ ¯π- decay used for normalization, and the fourth uncertainty relates to the knowledge of the ratio of b -quark hadronization probabilities fs/fd

A Year in the Life of the EU-CardioRNA COST Action: CA17129 Catalysing Transcriptomics Research in Cardiovascular Disease

The EU-CardioRNA Cooperation in Science and Technology (COST) Action is a European-wide consortium established in 2018 with 31 European country members and four associate member countries to build bridges between translational researchers from academia and industry who conduct research on non-coding RNAs, cardiovascular diseases and similar research areas. EU-CardioRNA comprises four core working groups (WG1-4). In the first year since its launch, EU-CardioRNA met biannually to exchange and discuss recent findings in related fields of scientific research, with scientific sessions broadly divided up according to WG. These meetings are also an opportunity to establish interdisciplinary discussion groups, brainstorm ideas and make plans to apply for joint research grants and conduct other scientific activities, including knowledge transfer. Following its launch in Brussels in 2018, three WG meetings have taken place. The first of these in Lisbon, Portugal, the second in Istanbul, Turkey, and the most recent in Maastricht, The Netherlands. Each meeting includes a scientific session from each WG. This meeting report briefly describes the highlights and key take-home messages from each WG session in this first successful year of the EU-CardioRNA COST Action. © 2020 by the authors