Genetics of Hypercholesterolemia: Comparison Between Familial Hypercholesterolemia and Hypercholesterolemia Nonrelated to LDL Receptor

Severe hypercholesterolemia (HC) is defined as an elevation of total cholesterol (TC) due to the increase in LDL cholesterol (LDL-C) >95th percentile or 190 mg/dl. The high values of LDL-C, especially when it is maintained over time, is considered a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), mostly expressed as ischemic heart disease (IHD). One of the best characterized forms of severe HC, familial hypercholesterolemia (FH), is caused by the presence of a major variant in one gene (LDLR, APOB, PCSK9, or ApoE), with an autosomal codominant pattern of inheritance, causing an extreme elevation of LDL-C and early IHD. Nevertheless, an important proportion of serious HC cases, denominated polygenic hypercholesterolemia (PH), may be attributed to the small additive effect of a number of single nucleotide variants (SNVs), located along the whole genome. The diagnosis, prevalence, and cardiovascular risk associated with PH has not been fully established at the moment. Cascade screening to detect a specific genetic defect is advised in all first- and second-degree relatives of subjects with FH. Conversely, in the rest of cases of HC, it is only advised to screen high values of LDL-C in first-degree relatives since there is not a consensus for the genetic diagnosis of PH. FH is associated with the highest cardiovascular risk, followed by PH and other forms of HC. Early detection and initiation of high-intensity lipid-lowering treatment is proposed in all subjects with severe HC for the primary prevention of ASCVD, with an objective of LDL-C <100 mg/dl or a decrease of at least 50%. A more aggressive reduction in LDL-C is necessary in HC subjects who associate personal history of ASCVD or other cardiovascular risk factors

OBTENTION OF SPECIFIC MONOCLONAL ANTIBODIES AND ANTISERA AGAINST XYLELLA FASTIDIOSA AND THEIR USE FOR DETECTION AND DIAGNOSIS

Monoclonal antibodies (MAb) specific to Xylella fastidiosa were obtained by fusion of a nonsecreting myeloma cell line with spleen cells from immunized BALB/c mice by intraperitoneal injections of 0.1 ml of 108 cfu/ml of X. fastidiosa subsp. fastidiosa (LMG17159 strain) (somatic antigens O) emulsified in Freund’s incomplete adjuvant. Specific antibody-secreting hybridoma selected by indirect-ELISA was three times cloned under conditions of limiting dilution and established hybrids were grown in HT medium. Ten MAb lines producing the highest bacterial titre were selected, isotype determined and their specificity tested. Three MAbs (MAb2G1/PPD, MAb1C6/PPD and MAb9F7/PPD) were selected for their wide reaction spectrum against X. fastidiosa strains and good specificity. Furthermore six polyclonal antisera against X. fastidiosa were raised in CalifornianxNeozelander rabbits with O antigens from Conn Creek, LMG15099 and LMG17159 strains. LMG17159-O antiserum was selected for the higher titre and because it recognized all the X. fastidiosa strains challenged. Polyclonal immunoglobulins as trapping/coating antibodies and specific MAb2G1/PPD as intermediate-detecting antibodies (DASI-ELISA method) reached a sensitivity of 105 cfu/ml of Xylella fastidiosa in almond extracts and of 105-106 in olive extracts. A DAS-ELISA prototype was then developed, prior to commercial distribution, using MAb2G1/PPD conjugated with alkaline phosphatase. The sensitivity reached was 105 cfu/ml and showed excellent specificity. One hundred twelve samples of different almond tree plots from the Demarcated Zone for X. fastidiosa in Alicante (Spain) were analysed comparatively by the developed DAS-ELISA, the LOEWE kit and the protocols of real-time PCR by Harper et al. (2010) and Francis et al. (2006). The agreement between the techniques was almost perfect according to the estimated Cohen’s kappa index, even in symptomless almond trees. The production of specific MAbs to X. fastidiosa will supply a continuous source of homogenous and well characterized antibodies to increase the accuracy of diagnosis and detection methods. A direct tissue-print or DTBIA kit is being also validated in order to supply an available user-friendly system to test in a low cost, fast, discreet, sensitive, an accurate manner this harmful bacterium in samples from nurseries, gardens and wide surveys, such as is available for other plant pathogens

An [Fe^III₃₀] molecular metal oxide

Dearle AE, Cutler DJ, Coletta M, et al. An [FeIII30] molecular metal oxide. Chemical Communications. 2021.Dissolution of FeBr3 in a mixture of acetonitrile and 3,4-lutidine in the presence of an amine results in the formation of an [Fe30] molecular metal oxide containing alternating layers of tetrahedral and octahedral FeIII ions. Mass spectrometry suggests the cluster is formed quickly and remains stable in solution, while magnetic measurements and DFT calculations reveal competing antiferromagnetic exchange interactions

Daf-2 Signaling Modifies Mutant SOD1 Toxicity in C. elegans

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS

A facility to Search for Hidden Particles (SHiP) at the CERN SPS

A new general purpose fixed target facility is proposed at the CERN SPS accelerator which is aimed at exploring the domain of hidden particles and make measurements with tau neutrinos. Hidden particles are predicted by a large number of models beyond the Standard Model. The high intensity of the SPS 400~GeV beam allows probing a wide variety of models containing light long-lived exotic particles with masses below ${\cal O}$(10)~GeV/c$^2$, including very weakly interacting low-energy SUSY states. The experimental programme of the proposed facility is capable of being extended in the future, e.g. to include direct searches for Dark Matter and Lepton Flavour Violation.Comment: Technical Proposa

El proyecto CALIOPE: sistema de calidad del aire operativo para España. Objetivo y estado actual

Ponencia presentada en: XXX Jornadas Científicas de la AME y el IX Encuentro Hispano Luso de Meteorología celebrado en Zaragoza, del 5 al 7 de mayo de 2008.Este trabajo está financiado por el proyecto CALIOPE del Ministerio de Medioambiente (441/2006/3-12.1 y A357/200/2-12.1)

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum