APOE4 genotype exerts greater benefit in lowering plasma cholesterol and apolipoprotein B than wild type (E3/E3), after replacement of dietary saturated fats with low glycaemic index carbohydrates

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial ('RISCK' study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC -0.28 mmol/L p = 0.03; apo B -0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates

Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection

Brouwer et al. present preclinical evidence in support of a COVID-19 vaccine candidate, designed as a self-assembling two-component protein nanoparticle displaying multiple copies of the SARS-CoV-2 spike protein, which induces strong neutralizing antibody responses and protects from high-dose SARS-CoV-2 challenge.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication i

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Azimuthal Correlations within Exclusive Dijets with Large Momentum Transfer in Photon-Lead Collisions

International audienceThe structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization. This study uses a data sample of ultraperipheral lead-lead collisions at sNN=5.02  TeV, corresponding to an integrated luminosity of 0.38  nb-1, collected with the CMS experiment at the LHC. The measured second harmonic of the correlation between the sum and difference of the two jet transverse momentum vectors is found to be positive, and rising, as the dijet transverse momentum increases. A well-tuned model that has been successful at describing a wide range of proton scattering data from the HERA experiments fails to describe the observed correlations, suggesting the presence of gluon polarization effects

Search for narrow resonances in the <math display="inline"><mi>b</mi></math>-tagged dijet mass spectrum in proton-proton collisions at <math display="inline"><msqrt><mi>s</mi></msqrt><mo>=</mo><mn>13</mn><mtext> </mtext><mtext> </mtext><mi>TeV</mi></math>

International audienceA search is performed for narrow resonances decaying to final states of two jets, with at least one jet originating from a b quark, in proton-proton collisions at s=13  TeV. The data set corresponds to an integrated luminosity of 138  fb-1 collected with the CMS detector at the LHC. Jets originating from energetic b hadrons are identified through a b-tagging algorithm that utilizes a deep neural network or the presence of a muon inside a jet. The invariant mass spectrum of jet pairs is well described by a smooth parametrization and no evidence for the production of new particles is observed. Upper limits on the production cross section are set for excited b quarks and other resonances decaying to dijet final states containing b quarks. These limits exclude at 95% confidence level models of Z′ bosons with masses from 1.8 TeV to 2.4 TeV and of excited b quarks with masses from 1.8 TeV to 4.0 TeV. This is the most stringent exclusion of excited b quarks to date

Search for Higgs boson decays to a Z boson and a photon in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceResults are presented from a search for the Higgs boson decay H → Zγ, where Z → ℓ$^{+}$ℓ$^{−}$ with ℓ = e or μ. The search is performed using a sample of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb$^{−1}$. Events are assigned to mutually exclusive categories, which exploit differences in both event topology and kinematics of distinct Higgs production mechanisms to enhance signal sensitivity. The signal strength μ, defined as the product of the cross section and the branching fraction \left[\sigma \left(\textrm{pp}\to \textrm{H}\right)\mathcal{B}\left(\textrm{H}\to \textrm{Z}\upgamma \right)\right] relative to the standard model prediction, is extracted from a simultaneous fit to the ℓ$^{+}$ℓ$^{−}$γ invariant mass distributions in all categories and is measured to be μ = 2.4 ± 0.9 for a Higgs boson mass of 125.38 GeV. The statistical significance of the observed excess of events is 2.7 standard deviations. This measurement corresponds to \left[\sigma \left(\textrm{pp}\to \textrm{H}\right)\mathcal{B}\left(\textrm{H}\to \textrm{Z}\upgamma \right)\right]=0.21\pm 0.08 pb. The observed (expected) upper limit at 95% confidence level on μ is 4.1 (1.8), where the expected limit is calculated under the background-only hypothesis. The ratio of branching fractions \mathcal{B}\left(\textrm{H}\to \textrm{Z}\upgamma \right)/\mathcal{B}\left(\textrm{H}\to \upgamma \upgamma \right) is measured to be ${1.5}_{-0.6}^{+0.7}$, which agrees with the standard model prediction of 0.69 ± 0.04 at the 1.5 standard deviation level.[graphic not available: see fulltext

Search for heavy resonances and quantum black holes in eμ\mu, eτ\tau, and μτ\mu\tau final states in proton-proton collisions at s\sqrt{s} = 13 TeV

A search is reported for heavy resonances and quantum black holes decaying into e$\mu$, e$\tau$, and $\mu\tau$ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016-2018 at $\sqrt{s} =$ 13 TeV, corresponding to an integrated luminosity of 138 fb$^{-1}$. The e$\mu$, e$\tau$, and $\mu\tau$ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant $\tau$ sneutrino production in $R$ parity violating supersymmetric models, heavy Z' gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant $\tau$ sneutrinos are excluded for masses up to 4.2 TeV in the e$\mu$ channel, 3.7 TeV in the e$\tau$ channel, and 3.6 TeV in the $\mu\tau$ channel. A Z' boson with lepton flavor violating couplings is excluded up to a mass of 5.0 TeV in the e$\mu$ channel, up to 4.3 TeV in the e$\tau$ channel, and up to 4.1 TeV in the $\mu\tau$ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6 TeV in the e$\mu$ channel, 5.2 TeV in the e$\tau$ channel, and 5.0 TeV in the $\mu\tau$ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays.A search is reported for heavy resonances and quantum black holes decaying into eμ, eτ, and μτ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016–2018 at $\sqrt{s}$ = 13 TeV, corresponding to an integrated luminosity of 138 fb$^{−1}$. The eμ, eτ, and μτ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant τ sneutrino production in R parity violating supersymmetric models, heavy Z′ gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant τ sneutrinos are excluded for masses up to 4.2TeV in the eμ channel, 3.7TeV in the eτ channel, and 3.6TeV in the μτ channel. A Z′ boson with lepton flavor violating couplings is excluded up to a mass of 5.0TeV in the eμ channel, up to 4.3Te V in the eτ channel, and up to 4.1TeV in the μτ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6TeV in the eμ channel, 5.2TeV in the eτ channel, and 5.0TeV in the μτ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays.[graphic not available: see fulltext]A search is reported for heavy resonances and quantum black holes decaying into e$\mu$, e$\tau$, and $\mu\tau$ final states in proton-proton collision data recorded by the CMS experiment at the CERN LHC during 2016-2018 at $\sqrt{s}$ = 13 TeV, corresponding to an integrated luminosity of 138 fb$^{-1}$. The e$\mu$, e$\tau$, and $\mu\tau$ invariant mass spectra are reconstructed, and no evidence is found for physics beyond the standard model. Upper limits are set at 95% confidence level on the product of the cross section and branching fraction for lepton flavor violating signals. Three benchmark signals are studied: resonant $\tau$ sneutrino production in $R$ parity violating supersymmetric models, heavy Z' gauge bosons with lepton flavor violating decays, and nonresonant quantum black hole production in models with extra spatial dimensions. Resonant $\tau$ sneutrinos are excluded for masses up to 4.2 TeV in the e$\mu$ channel, 3.7 TeV in the e$\tau$ channel, and 3.6 TeV in the $\mu\tau$ channel. A Z' boson with lepton flavor violating couplings is excluded up to a mass of 5.0 TeV in the e$\mu$ channel, up to 4.3 TeV in the e$\tau$ channel, and up to 4.1 TeV in the $\mu\tau$ channel. Quantum black holes in the benchmark model are excluded up to the threshold mass of 5.6 TeV in the e$\mu$ channel, 5.2 TeV in the e$\tau$ channel, and 5.0 TeV in the $\mu\tau$ channel. In addition, model-independent limits are extracted to allow comparisons with other models for the same final states and similar event selection requirements. The results of these searches provide the most stringent limits available from collider experiments for heavy particles that undergo lepton flavor violating decays

Strange hadron collectivity in pPb and PbPb collisions

International audienceThe collective behavior of ${\textrm{K}}_{\textrm{S}}^0$ and $\Lambda /\overline{\Lambda}$ strange hadrons is studied by measuring the elliptic azimuthal anisotropy (v$_{2}$) using the scalar-product and multiparticle correlation methods. Proton-lead (pPb) collisions at a nucleon-nucleon center-of-mass energy $\sqrt{s_{\textrm{NN}}}$ = 8.16 TeV and lead-lead (PbPb) collisions at $\sqrt{s_{\textrm{NN}}}$ = 5.02 TeV collected by the CMS experiment at the LHC are investigated. Nonflow effects in the pPb collisions are studied by using a subevent cumulant analysis and by excluding events where a jet with transverse momentum greater than 20 GeV is present. The strange hadron v$_{2}$ values extracted in pPb collisions via the four- and six-particle correlation method are found to be nearly identical, suggesting the collective behavior. Comparisons of the pPb and PbPb results for both strange hadrons and charged particles illustrate how event-by-event flow fluctuations depend on the system size.[graphic not available: see fulltext