GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability.

BACKGROUND: Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known. METHODS: Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy. RESULTS: At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type. CONCLUSION: GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp.

[Chronic rhinosinusitis with nasal polyposis : A retrospective analysis of therapeutic approaches in 463 patients]. / Chronische Rhinosinusitis mit Polyposis nasi : Retrospektive Analyse des therapeutischen Vorgehens bei 463 Patienten.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, the treatment of which has undergone significant changes in recent years. In addition to surgical approaches, topical and systemic steroids, and adaptive acetylsalicylic acid (ASA) desensitization, three specific antibodies have complemented the therapeutic portfolio since 2019. METHODS: A retrospective evaluation of all patients who presented as outpatients for the first time due to CRSwNP in 2007 and 2008 (collective A) and 2017 and 2018 (collective B) was performed, up to and including June 2023. RESULTS: The clinical courses of 463 patients (mean age 49.1 years, range 5-82 years; 65.9% male) were included in the analysis. Conservative treatment with nasal corticosteroids started before initial presentation was more frequent in collective B (collective A 43.9% vs. collective B 72.2%). In 278 of the 463 patients (60%; A: 62%, B: 58%), at least one operation on the nasal sinuses had been performed after initial presentation; in 101 of these patients (36.3%) recurrent polyposis (within mean follow-up of 2.4 years) required further treatment. The indication for ASA provocation/desensitization was applied less frequently in collective B, also due to a high discontinuation rate (at least 38%) of the maintenance therapy. Of the total cohort, 16 patients (3.5%; A: n = 8, B: n = 8) were meanwhile switched to antibody therapy at recurrence. CONCLUSION: A step-by-step guideline-orientated approach is recommended in the treatment of CRSwNP. Systemic antibodies as an add-on to nasal corticosteroids are a relatively new therapeutic option for treatment-refractory CRSwNP, which reduces the indication for ASA desensitization, which is associated with a relatively high incidence of side effects and poor compliance.

Short-term, but not acute, intake of New Zealand blackcurrant extract improves insulin sensitivity and free-living postprandial glucose excursions in individuals with overweight or obesity.

Impaired postprandial glucose handling and low-grade systemic inflammation are risk factors for developing insulin resistance in individuals with overweight or obesity. Acute ingestion of anthocyanins improves postprandial glucose responses to a single carbohydrate-rich meal under strictly controlled conditions. PURPOSE: Examine whether acute and short-term supplementation with anthocyanin-rich New Zealand blackcurrant (NZBC) extract can improve postprandial glucose responses to mixed-macronutrient meals. METHODS: Twenty-five overweight (BMI > 25 kg m2) sedentary individuals participated in one of the following double-blinded, randomised controlled trials: (1) ingestion of 600 mg NZBC extract or placebo prior to consumption of a high-carbohydrate, high-fat liquid meal (n = 12); (2) 8-days supplementation with NZBC extract (600 mg day-1) or placebo, with insulin sensitivity and markers of inflammation assessed on day-7, and free-living postprandial glucose (continuous glucose monitoring) assessed on day-8 (n = 13). RESULTS: A single dose of NZBC extract had no effect on 3 h postprandial glucose, insulin or triglyceride responses. However, in response to short-term NZBC extract supplementation insulin sensitivity was improved (+ 22%; P = 0.011), circulating C-reactive protein concentrations decreased (P = 0.008), and free-living postprandial glucose responses to both breakfast and lunch meals were reduced (- 9% and - 8%, respectively; P < 0.05), compared to placebo. CONCLUSION: These novel results indicate that repeated intake, rather than a single dose of NZBC extract, is required to induce beneficial effects on insulin sensitivity and postprandial glucose handling in individuals with overweight or obesity. Continuous glucose monitoring enabled an effect of NZBC extract to be observed under free-living conditions and highlights the potential of anthocyanin-rich supplements as a viable strategy to reduce insulin resistance.

A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle.

KEY POINTS: We have recently shown that a high-fat, high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days' HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. ABSTRACT: A high-fat, high-calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 ± 2.5 years; body mass index: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy), high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days' HFHC diet.

Double layer SiO2-TiO2 sol-gel thin films on glass for antireflection, antifogging, and UV recoverable self-cleaning.

Double layer thin films, mechanically stable and adhering to glass, were produced through the sol-gel process, using tetraethyl orthosilicate and titanium butoxide as precursors. The refractive index of the titania and silica-titania composite layers were typically 2.1 and 1.7, and their physical thicknesses were approximately 65 nm and 81 nm, respectively, as determined by ellipsometry. These optical constants allowed attainment of quarter-wave optical thicknesses at the center of the visible spectrum (550 nm) as designed, with an increase of 3.4% in transmittance. The nanometric surface roughness, measured by optical profilometry, was effective to decrease light scattering and water contact angles to below 10°. As novelty in dip-coated sol-gel films, superhydrophilicity for self-cleaning, antifogging, and antireflection in the mid-visible spectrum were simultaneously attained with durability of 9 weeks in the dark. Further application of UV light allowed regeneration of contact angles for self-cleaning.

Suppression of Excited ϒ States Relative to the Ground State in Pb-Pb Collisions at sqrt[s]_{NN}=5.02 TeV.

The relative yields of ϒ mesons produced in pp and Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV and reconstructed via the dimuon decay channel are measured using data collected by the CMS experiment. Double ratios are formed by comparing the yields of the excited states, ϒ(2S) and ϒ(3S), to the ground state, ϒ(1S), in both Pb-Pb and pp collisions at the same center-of-mass energy. The double ratios, [ϒ(nS)/ϒ(1S)]_{Pb-Pb}/[ϒ(nS)/ϒ(1S)]_{pp}, are measured to be 0.308±0.055(stat)±0.019(syst) for the ϒ(2S) and less than 0.26 at 95% confidence level for the ϒ(3S). No significant ϒ(3S) signal is found in the Pb-Pb data. The double ratios are studied as a function of collision centrality, as well as ϒ transverse momentum and rapidity. No significant dependencies are observed.

Training alters the distribution of perilipin proteins in muscle following acute free fatty acid exposure.

KEY POINTS: The lipid droplet (LD)-associated perilipin (PLIN) proteins promote intramuscular triglyceride (IMTG) storage, although whether the abundance and association of the PLIN proteins with LDs is related to the diverse lipid storage in muscle between trained and sedentary individuals is unknown. We show that lipid infusion augments IMTG content in type I fibres of both trained and sedentary individuals. Most importantly, despite there being no change in PLIN protein content, lipid infusion did increase the number of LDs connected with PLIN proteins in trained individuals only. We conclude that trained individuals are able to redistribute the pre-existing pool of PLIN proteins to an expanded LD pool during lipid infusion and, via this adaptation, may support the storage of fatty acids in IMTG. ABSTRACT: Because the lipid droplet (LD)-associated perilipin (PLIN) proteins promote intramuscular triglyceride (IMTG) storage, we investigated the hypothesis that differential protein content of PLINs and their distribution with LDs may be linked to the diverse lipid storage in muscle between trained and sedentary individuals. Trained (n = 11) and sedentary (n = 10) subjects, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed using confocal immunofluorescence microscopy for fibre type-specific IMTG content and PLIN associations with LDs. In both groups, lipid infusion increased IMTG content in type I fibres (trained: +62%, sedentary: +79%; P < 0.05) but did not affect PLIN protein content. At baseline, PLIN2 (+65%), PLIN3 (+105%) and PLIN5 (+53%; all P < 0.05) protein content was higher in trained compared to sedentary individuals. In trained individuals, lipid infusion increased the number of LDs associated with PLIN2 (+27%), PLIN3 (+73%) and PLIN5 (+40%; all P < 0.05) in type I fibres. By contrast, in sedentary individuals, lipid infusion only increased the number of LDs not associated with PLIN proteins. Acute free fatty acid elevation therefore induces a redistribution of PLIN proteins to an expanded LD pool in trained individuals only and this may be part of the mechanism that enables fatty acids to be stored in IMTG.

Observation of Charge-Dependent Azimuthal Correlations in p-Pb Collisions and Its Implication for the Search for the Chiral Magnetic Effect.

Charge-dependent azimuthal particle correlations with respect to the second-order event plane in p-Pb and PbPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV have been studied with the CMS experiment at the LHC. The measurement is performed with a three-particle correlation technique, using two particles with the same or opposite charge within the pseudorapidity range |η|<2.4, and a third particle measured in the hadron forward calorimeters (4.4<|η|<5). The observed differences between the same and opposite sign correlations, as functions of multiplicity and η gap between the two charged particles, are of similar magnitude in p-Pb and PbPb collisions at the same multiplicities. These results pose a challenge for the interpretation of charge-dependent azimuthal correlations in heavy ion collisions in terms of the chiral magnetic effect.

Relative Modification of Prompt ψ(2S) and J/ψ Yields from pp to PbPb Collisions at sqrt[s_{NN}]=5.02 TeV.

The relative modification of the prompt ψ(2S) and J/ψ yields from pp to PbPb collisions, at the center-of-mass energy of 5.02 TeV per nucleon pair, is presented. The analysis is based on pp and PbPb data samples collected by the CMS experiment at the LHC in 2015, corresponding to integrated luminosities of 28.0 pb^{-1} and 464 µb^{-1}, respectively. The double ratio of measured yields of prompt charmonia reconstructed through their decays into muon pairs, (N_{ψ(2S)}/N_{J/ψ})_{PbPb}/(N_{ψ(2S)}/N_{J/ψ})_{pp}, is determined as a function of PbPb collision centrality and charmonium transverse momentum p_{T}, in two kinematic intervals: |y|<1.6 covering 6.5

Study of Jet Quenching with Z+jet Correlations in Pb-Pb and pp Collisions at sqrt[s]_{NN}=5.02 TeV.

The production of jets in association with Z bosons, reconstructed via the µ^{+}µ^{-} and e^{+}e^{-} decay channels, is studied in pp and, for the first time, in Pb-Pb collisions. Both data samples were collected by the CMS experiment at the LHC, at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The Pb-Pb collisions were analyzed in the 0%-30% centrality range. The back-to-back azimuthal alignment was studied in both pp and Pb-Pb collisions for Z bosons with transverse momentum p_{T}^{Z}>60 GeV/c and a recoiling jet with p_{T}^{jet}>30 GeV/c. The p_{T} imbalance x_{jZ}=p_{T}^{jet}/p_{T}^{Z}, as well as the average number of jet partners per Z, R_{jZ}, was studied in intervals of p_{T}^{Z}. The R_{jZ} is found to be smaller in Pb-Pb than in pp collisions, which suggests that in Pb-Pb collisions a larger fraction of partons associated with the Z bosons fall below the 30 GeV/c p_{T}^{jet} threshold because they lose energy.

Search for Supersymmetry in pp Collisions at sqrt[s]=13 TeV in the Single-Lepton Final State Using the Sum of Masses of Large-Radius Jets.

Results are reported from a search for supersymmetric particles in proton-proton collisions in the final state with a single lepton, multiple jets, including at least one b-tagged jet, and large missing transverse momentum. The search uses a sample of proton-proton collision data at sqrt[s]=13 TeV recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9 fb^{-1}. The observed event yields in the signal regions are consistent with those expected from standard model backgrounds. The results are interpreted in the context of simplified models of supersymmetry involving gluino pair production, with gluino decay into either on- or off-mass-shell top squarks. Assuming that the top squarks decay into a top quark plus a stable, weakly interacting neutralino, scenarios with gluino masses up to about 1.9 TeV are excluded at 95% confidence level for neutralino masses up to about 1 TeV.

Search for Low Mass Vector Resonances Decaying to Quark-Antiquark Pairs in Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is reported for a narrow vector resonance decaying to quark-antiquark pairs in proton-proton collisions at sqrt[s]=13 TeV, collected with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 2.7 fb^{-1}. The vector resonance is produced at large transverse momenta, with its decay products merged into a single jet. The resulting signature is a peak over background in the distribution of the invariant mass of the jet. The results are interpreted in the framework of a leptophobic vector resonance and no evidence is found for such particles in the mass range of 100-300 GeV. Upper limits at 95% confidence level on the production cross section are presented in a region of mass-coupling phase space previously unexplored at the LHC. The region below 140 GeV has not been explored by any previous experiments.

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at sqrt[s]=8 TeV.

A first search for pair production of dark matter candidates through vector boson fusion in proton-proton collisions at sqrt[s]=8 TeV is performed with the CMS detector. The vector boson fusion topology enhances missing transverse momentum, providing a way to probe supersymmetry, even in the case of a compressed mass spectrum. The data sample corresponds to an integrated luminosity of 18.5 fb^{-1}, recorded by the CMS experiment. The observed dijet mass spectrum is consistent with the standard model expectation. In an effective field theory, dark matter masses are explored as a function of contact interaction strength. The most stringent limit on bottom squark production with mass below 315 GeV is also reported, assuming a 5 GeV mass difference with respect to the lightest neutralino.

Search for Charged Higgs Bosons Produced via Vector Boson Fusion and Decaying into a Pair of W and Z Bosons Using pp Collisions at sqrt[s]=13 TeV.

A search for charged Higgs bosons produced via vector boson fusion and decaying into W and Z bosons using proton-proton collisions at sqrt[s]=13 TeV is presented. The data sample corresponds to an integrated luminosity of 15.2 fb^{-1} collected with the CMS detector in 2015 and 2016. The event selection requires three leptons (electrons or muons), two jets with large pseudorapidity separation and high dijet mass, and missing transverse momentum. The observation agrees with the standard model prediction. Limits on the vector boson fusion production cross section times branching fraction for new charged physical states are reported as a function of mass from 200 to 2000 GeV and interpreted in the context of Higgs triplet models.

Measurement of the B

The differential production cross sections of B^{±} mesons are measured via the exclusive decay channels B^{±}→J/ψK^{±}→µ^{+}µ^{-}K^{±} as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb-Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb^{-1} (351 µb^{-1}). The measurement is performed in the B^{±} meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval |y|<2.4. In this kinematic range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. These results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.

Evolutionary diversification of the auditory organ sensilla in Neoconocephalus katydids (Orthoptera: Tettigoniidae) correlates with acoustic signal diversification over phylogenetic relatedness and life history.

Neoconocephalus Tettigoniidae are a model for the evolution of acoustic signals as male calls have diversified in temporal structure during the radiation of the genus. The call divergence and phylogeny in Neoconocephalus are established, but in tettigoniids in general, accompanying evolutionary changes in hearing organs are not studied. We investigated anatomical changes of the tympanal hearing organs during the evolutionary radiation and divergence of intraspecific acoustic signals. We compared the neuroanatomy of auditory sensilla (crista acustica) from nine Neoconocephalus species for the number of auditory sensilla and the crista acustica length. These parameters were correlated with differences in temporal call features, body size, life histories and different phylogenetic positions. By this, adaptive responses to shifting frequencies of male calls and changes in their temporal patterns can be evaluated against phylogenetic constraints and allometry. All species showed well-developed auditory sensilla, on average 32-35 between species. Crista acustica length and sensillum numbers correlated with body size, but not with phylogenetic position or life history. Statistically significant correlations existed also with specific call patterns: a higher number of auditory sensilla occurred in species with continuous calls or slow pulse rates, and a longer crista acustica occurred in species with double pulses or slow pulse rates. The auditory sensilla show significant differences between species despite their recent radiation, and morphological and ecological similarities. This indicates the responses to natural and sexual selection, including divergence of temporal and spectral signal properties. Phylogenetic constraints are unlikely to limit these changes of the auditory systems.

Search for Narrow Resonances in Dijet Final States at sqrt[s]=8 TeV with the Novel CMS Technique of Data Scouting.

A search for narrow resonances decaying into dijet final states is performed on data from proton-proton collisions at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 18.8 fb^{-1}. The data were collected with the CMS detector using a novel technique called data scouting, in which the information associated with these selected events is much reduced, permitting collection of larger data samples. This technique enables CMS to record events containing jets at a rate of 1 kHz, by collecting the data from the high-level-trigger system. In this way, the sensitivity to low-mass resonances is increased significantly, allowing previously inaccessible couplings of new resonances to quarks and gluons to be probed. The resulting dijet mass distribution yields no evidence of narrow resonances. Upper limits are presented on the resonance cross sections as a function of mass, and compared with a variety of models predicting narrow resonances. The limits are translated into upper limits on the coupling of a leptophobic resonance Z_{B}^{'} to quarks, improving on the results obtained by previous experiments for the mass range from 500 to 800 GeV.

Search for Resonant Production of High-Mass Photon Pairs in Proton-Proton Collisions at sqrt[s]=8 and 13 TeV.

A search for the resonant production of high-mass photon pairs is presented. The analysis is based on samples of proton-proton collision data collected by the CMS experiment at center-of-mass energies of 8 and 13 TeV, corresponding to integrated luminosities of 19.7 and 3.3 fb^{-1}, respectively. The interpretation of the search results focuses on spin-0 and spin-2 resonances with masses between 0.5 and 4 TeV and with widths, relative to the mass, between 1.4×10^{-4} and 5.6×10^{-2}. Limits are set on scalar resonances produced through gluon-gluon fusion, and on Randall-Sundrum gravitons. A modest excess of events compatible with a narrow resonance with a mass of about 750 GeV is observed. The local significance of the excess is approximately 3.4 standard deviations. The significance is reduced to 1.6 standard deviations once the effect of searching under multiple signal hypotheses is considered. More data are required to determine the origin of this excess.

Measurement of Long-Range Near-Side Two-Particle Angular Correlations in pp Collisions at sqrt[s]=13 TeV.

Results on two-particle angular correlations for charged particles produced in pp collisions at a center-of-mass energy of 13 TeV are presented. The data were taken with the CMS detector at the LHC and correspond to an integrated luminosity of about 270 nb^{-1}. The correlations are studied over a broad range of pseudorapidity (|η|<2.4) and over the full azimuth (ϕ) as a function of charged particle multiplicity and transverse momentum (p_{T}). In high-multiplicity events, a long-range (|Δη|>2.0), near-side (Δϕ≈0) structure emerges in the two-particle Δη-Δϕ correlation functions. The magnitude of the correlation exhibits a pronounced maximum in the range 1.0

Measurement of the Top Quark Pair Production Cross Section in Proton-Proton Collisions at √[s]=13 TeV.

The top quark pair production cross section is measured for the first time in proton-proton collisions at sqrt[s]=13 TeV by the CMS experiment at the CERN LHC, using data corresponding to an integrated luminosity of 43 pb^{-1}. The measurement is performed by analyzing events with at least one electron and one muon of opposite charge, and at least two jets. The measured cross section is 746±58(stat)±53(syst)±36(lumi) pb, in agreement with the expectation from the standard model.