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1.
Article in English | MEDLINE | ID: mdl-38724320
2.
Science ; : eadn1262, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38815088

ABSTRACT

Rivers and streams contribute to global carbon cycling by decomposing immense quantities of terrestrial plant matter. However, decomposition rates are highly variable and large-scale patterns and drivers of this process remain poorly understood. Using a cellulose-based assay to reflect the primary constituent of plant detritus, we generated a predictive model (81% variance explained) for cellulose decomposition rates across 514 globally distributed streams. A large number of variables were important for predicting decomposition, highlighting the complexity of this process at the global scale. Predicted cellulose decomposition rates, when combined with genus-level litter quality attributes, explain published leaf-litter-decomposition rates with impressive accuracy (70% variance explained). Our global map provides estimates of rates across vast understudied areas of Earth, and reveals rapid decomposition across continental-scale areas dominated by human activities.

3.
Mol Cell ; 84(7): 1321-1337.e11, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38513662

ABSTRACT

Intracellular Mg2+ (iMg2+) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg2+ transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major iMg2+ compartment refilled by a largely uncharacterized ER-localized protein, TMEM94. Conventional and AlphaFold2 predictions suggest that ERMA (TMEM94) is a multi-pass transmembrane protein with large cytosolic headpiece actuator, nucleotide, and phosphorylation domains, analogous to P-type ATPases. However, ERMA uniquely combines a P-type ATPase domain and a GMN motif for ERMg2+ uptake. Experiments reveal that a tyrosine residue is crucial for Mg2+ binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg2+ ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca2+ cycling in mouse Erma+/- cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of ERMg2+ uptake in eukaryotes.


Subject(s)
Adenosine Triphosphatases , P-type ATPases , Animals , Mice , Humans , Adenosine Triphosphatases/metabolism , Membrane Transport Proteins/metabolism , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/metabolism , Biological Transport , P-type ATPases/metabolism , Calcium/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases
4.
Data Brief ; 50: 109607, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37823067

ABSTRACT

The data presented in this article were collected in the field at an experimental station in southern France under a Mediterranean climate. Experiments were conducted under three plastic walk-in tunnels used as blocks with organic farming practices over two successive years in a completely randomized design. The aim was to compare the intercropping of sweet pepper with basil, onion, lettuce, parsley or French bean to a sole crop of sweet pepper used as a control. The dataset provides information on cultural practices with details on inputs and working times used to estimate economic costs. The data also describe the climatic conditions under tunnels as well as the dynamics of soil nitrate concentration and water tension over time through treatments. Yields, economic benefits and the rates of products with visual defects are presented. In addition, some variables applied exclusively to sweet pepper crops, namely nitrate concentration in petiole sap, growth parameters, abundance of aerial pests and beneficials, incidence of root necrosis, arbuscular mycorrhizal fungi colonization rates and diversity in roots. The field dataset is made publicly available to allow free and easy access for the scientific and professional community to enable analysis and reuse. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

5.
Eur J Nucl Med Mol Imaging ; 50(11): 3251-3264, 2023 09.
Article in English | MEDLINE | ID: mdl-37291448

ABSTRACT

PURPOSE: We aimed to assess the effect of concomitant medication, age, sex, body mass index and 18-kDa translocator protein (TSPO) binding affinity status on the metabolism and plasma pharmacokinetics of [18F]DPA-714 and their influence on the plasma input function in a large cohort of 201 subjects who underwent brain and whole-body PET imaging to investigate the role of neuroinflammation in neurological diseases. METHODS: The non-metabolized fraction of [18F]DPA-714 was estimated in venous plasma of 138 patients and 63 healthy controls (HCs; including additional arterial sampling in 16 subjects) during the 90 min brain PET acquisition using a direct solid-phase extraction method. The mean fraction between 70 and 90 min post-injection ([18F]DPA-71470-90) and corresponding normalized plasma concentration (SUV70-90) were correlated with all factors using a multiple linear regression model. Differences between groups (arterial vs venous measurements; HCs vs patients; high- (HAB), mixed- (MAB) and low-affinity binders (LAB); subjects with vs without co-medications, females vs males were also assessed using the non-parametric Mann-Whitney or Kruskal-Wallis ANOVA tests. Finally, the impact of co-medications on the brain uptake of [18F]DPA-714 at equilibrium was investigated. RESULTS: As no significant differences were observed between arterial and venous [18F]DPA-71470-90 and SUV70-90, venous plasma was used for correlations. [18F]DPA-71470-90 was not significantly different between patients and HCS (59.7 ± 12.3% vs 60.2 ± 12.9%) despite high interindividual variability. However, 47 subjects exhibiting a huge increase or decrease of [18F]DPA-71470-90 (up to 88% or down to 23%) and SUV70-90 values (2-threefold) were found to receive co-medications identified as inhibitors or inducers of CYP3A4, known to catalyse [18F]DPA-714 metabolism. Comparison between cortex-to-plasma ratios using individual input function (VTIND) or population-based input function derived from untreated HCs (VTPBIF) indicated that non-considering the individual metabolism rate led to a bias of about 30% in VT values. Multiple linear regression model analysis of subjects free of these co-medications suggested significant correlations between [18F]DPA-71470-90 and age, BMI and sex while TSPO polymorphism did not influence the metabolism of the radiotracer. [18F]DPA-714 metabolism fell with age and BMI and was significantly faster in females than in males. Whole-body PET/CT exhibited a high uptake of the tracer in TSPO-rich organs (heart wall, spleen, kidneys…) and those involved in metabolism and excretion pathways (liver, gallbladder) in HAB and MAB with a strong decrease in LAB (-89% and -85%) resulting in tracer accumulation in plasma (4.5 and 3.3-fold increase). CONCLUSION: Any co-medication that inhibits or induces CYP3A4 as well as TSPO genetic status, age, BMI and sex mostly contribute to interindividual variations of the radiotracer metabolism and/or concentration that may affect the input function of [18F]DPA-714 and consequently its human brain and peripheral uptake. TRIAL REGISTRATION: INFLAPARK, NCT02319382, registered December 18, 2014, retrospectively registered; IMABIO 3, NCT01775696, registered January 25, 2013, retrospectively registered; INFLASEP, NCT02305264, registered December 2, 2014, retrospectively registered; EPI-TEP, EudraCT 2017-003381-27, registered September 24, 2018.


Subject(s)
Cytochrome P-450 CYP3A , Positron Emission Tomography Computed Tomography , Male , Female , Humans , Body Mass Index , Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 CYP3A/pharmacology , Fluorine Radioisotopes , Brain/metabolism , Carrier Proteins/metabolism , Carrier Proteins/pharmacology , Positron-Emission Tomography/methods , Receptors, GABA/metabolism
7.
Heredity (Edinb) ; 130(3): 163-176, 2023 03.
Article in English | MEDLINE | ID: mdl-36585503

ABSTRACT

Low dispersal, occurrence of asexual reproduction and geographic discontinuity increase genetic differentiation between populations, which ultimately can lead to speciation. In this work, we used a multidisciplinary framework to characterize the genetic and phenotypic differentiation between and within two cryptic ant species with restricted dispersal, Cataglyphis cursor and C. piliscapa and used behavioral experiments to test for reproductive isolation. Their distribution is segregated by the Rhône River and they have been traditionally distinguished only by hair numbers, although a statistical assessment is still lacking. We found strong genetic (microsatellites, nuclear and mitochondrial sequences), morphological (number of hairs, tibia length, male genitalia) and chemical (cuticular hydrocarbons) differentiation not only between species but also among localities within species. However, inter-specific differentiation was slightly higher than intra-specific differentiation for most markers. Overall, this pattern could either reflect reproductive isolation or could result from a longer period of geographic isolation between species than among localities within species without necessarily involving reproductive isolation. Interestingly, our behavioral experiments showed an absence of mating between species associated to a higher aggressiveness of workers towards heterospecific males. This suggests that sexual selection may, at least partially, fuel reproductive isolation. We also showed that cuticular hydrocarbons, mtDNA sequences and number of hairs provide reliable criteria allowing species discrimination. Overall, this species complex offers a case study to further investigate varying stages of a speciation continuum by estimating reproductive isolation between pairs of localities varying by their level of genetic differentiation.


Subject(s)
Ants , Animals , Male , Ants/genetics , Reproduction , Reproductive Isolation , Genetic Drift , Hydrocarbons
8.
Appl Opt ; 61(19): 5749-5754, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-36255808

ABSTRACT

39K atoms have the smallest ground state (2S1/2) hyperfine splitting of all the most naturally abundant alkali isotopes and, consequently, the smallest characteristic magnetic field value B0=A2S1/2/µB≈170G, where A2S1/2 is the ground state's magnetic dipole interaction constant. In the hyperfine Paschen-Back regime (B≫B0, where B is the magnitude of the external magnetic field applied on the atoms), only eight Zeeman transitions are visible in the absorption spectrum of the D1 line of 39K, while the probabilities of the remaining 16 Zeeman transitions tend to zero. In the case of 39K, this behavior is reached already at relatively low magnetic field B>B0. For each circular polarization (σ-,σ+), four spectrally resolved atomic transitions having sub-Doppler widths are recorded using a sub-microsized vapor cell of thickness L=120-390nm. We present a method that allows to measure the magnetic field in the range of 0.1-10kG with micrometer spatial resolution, which is relevant in particular for the determination of magnetic fields with large gradients (up to 3 G/µm). The theoretical model describes well the experimental results.

9.
Nat Cardiovasc Res ; 1(2): 142-156, 2022 Feb.
Article in English | MEDLINE | ID: mdl-36051854

ABSTRACT

Some missense gain-of-function mutations in CACNA1C gene, encoding calcium channel CaV1.2, cause a life-threatening form of long QT syndrome named Timothy syndrome, with currently no clinically-effective therapeutics. Here we report that pharmacological targeting of sigma non-opioid intracellular receptor 1 (SIGMAR1) can restore electrophysiological function in iPSC-derived cardiomyocytes generated from patients with Timothy syndrome and two common forms of long QT syndrome, type 1 (LQTS1) and 2 (LQTS2), caused by missense trafficking mutations in potassium channels. Electrophysiological recordings demonstrate that an FDA-approved cough suppressant, dextromethorphan, can be used as an agonist of SIGMAR1, to shorten the prolonged action potential in Timothy syndrome cardiomyocytes and human cellular models of LQTS1 and LQTS2. When tested in vivo, dextromethorphan also normalized the prolonged QT intervals in Timothy syndrome model mice. Overall, our study demonstrates that SIGMAR1 is a potential therapeutic target for Timothy syndrome and possibly other inherited arrhythmias such as LQTS1 and LQTS2.

10.
iScience ; 25(5): 104184, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35494220

ABSTRACT

The response of vital organs to different types of nutrition or diet is a fundamental question in physiology. We examined the cardiac response to 4 weeks of high-fat diet in mice, measuring cardiac metabolites and mRNA. Metabolomics showed dramatic differences after a high-fat diet, including increases in several acyl-carnitine species. The RNA-seq data showed changes consistent with adaptations to use more fatty acid as substrate and an increase in the antioxidant protein catalase. Changes in mRNA were correlated with changes in protein level for several highly responsive genes. We also found significant sex differences in both metabolomics and RNA-seq datasets, both at baseline and after high fat diet. This work reveals the response of a vital organ to dietary intervention at both metabolomic and transcriptomic levels, which is a fundamental question in physiology. This work also reveals significant sex differences in cardiac metabolites and gene expression.

11.
Hum Reprod ; 37(6): 1334-1350, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35413094

ABSTRACT

STUDY QUESTION: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)? SUMMARY ANSWER: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA. WHAT IS KNOWN ALREADY: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE. STUDY DESIGN, SIZE, DURATION: In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein. MAIN RESULTS AND THE ROLE OF CHANCE: Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]. LARGE SCALE DATA: Data available on request. LIMITATIONS, REASONS FOR CAUTION: More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene-confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Azoospermia , Azoospermia/diagnosis , Azoospermia/genetics , Azoospermia/pathology , Cohort Studies , Comparative Genomic Hybridization , DNA Helicases , DNA-Binding Proteins/genetics , Humans , Male , Nuclear Proteins/genetics , RNA Helicases , Retrospective Studies , Sperm Retrieval , Spermatozoa/pathology , Testis/pathology , Trans-Activators , Exome Sequencing
12.
Nature ; 602(7895): 63-67, 2022 02.
Article in English | MEDLINE | ID: mdl-35110756

ABSTRACT

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

13.
Eur Heart J Open ; 2(6): oeac069, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36600882

ABSTRACT

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

14.
Trends Ecol Evol ; 37(4): 309-321, 2022 04.
Article in English | MEDLINE | ID: mdl-34955328

ABSTRACT

Wild bee populations are declining due to human activities, such as land use change, which strongly affect the composition and diversity of available plants and food sources. The chemical composition of food (i.e., nutrition) in turn determines the health, resilience, and fitness of bees. For pollinators, however, the term 'health' is recent and is subject to debate, as is the interaction between nutrition and wild bee health. We define bee health as a multidimensional concept in a novel integrative framework linking bee biological traits (physiology, stoichiometry, and disease) and environmental factors (floral diversity and nutritional landscapes). Linking information on tolerated nutritional niches and health in different bee species will allow us to better predict their distribution and responses to environmental change, and thus support wild pollinator conservation.


Subject(s)
Biodiversity , Pollination , Animals , Bees , Ecosystem , Flowers/physiology , Phenotype , Plants , Pollination/physiology
15.
Sci Rep ; 11(1): 17808, 2021 09 08.
Article in English | MEDLINE | ID: mdl-34497331

ABSTRACT

Obesity and diabetes increase the risk of arrhythmia and sudden cardiac death. However, the molecular mechanisms of arrhythmia caused by metabolic abnormalities are not well understood. We hypothesized that mitochondrial dysfunction caused by high fat diet (HFD) promotes ventricular arrhythmia. Based on our previous work showing that saturated fat causes calcium handling abnormalities in cardiomyocytes, we hypothesized that mitochondrial calcium uptake contributes to HFD-induced mitochondrial dysfunction and arrhythmic events. For experiments, we used mice with conditional cardiac-specific deletion of the mitochondrial calcium uniporter (Mcu), which is required for mitochondrial calcium uptake, and littermate controls. Mice were used for in vivo heart rhythm monitoring, perfused heart experiments, and isolated cardiomyocyte experiments. MCU KO mice are protected from HFD-induced long QT, inducible ventricular tachycardia, and abnormal ventricular repolarization. Abnormal repolarization may be due, at least in part, to a reduction in protein levels of voltage gated potassium channels. Furthermore, isolated cardiomyocytes from MCU KO mice exposed to saturated fat are protected from increased reactive oxygen species (ROS), mitochondrial dysfunction, and abnormal calcium handling. Activation of calmodulin-dependent protein kinase (CaMKII) corresponds with the increase in arrhythmias in vivo. Additional experiments showed that CaMKII inhibition protects cardiomyocytes from the mitochondrial dysfunction caused by saturated fat. Hearts from transgenic CaMKII inhibitor mice were protected from inducible ventricular tachycardia after HFD. These studies identify mitochondrial dysfunction caused by calcium overload as a key mechanism of arrhythmia during HFD. This work indicates that MCU and CaMKII could be therapeutic targets for arrhythmia caused by metabolic abnormalities.


Subject(s)
Arrhythmias, Cardiac/metabolism , Calcium Channels/metabolism , Diet, High-Fat , Mitochondria/metabolism , Myocytes, Cardiac/metabolism , Animals , Calcium Channels/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Mice , Mice, Knockout , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism
16.
Phys Rev Lett ; 126(7): 071801, 2021 Feb 19.
Article in English | MEDLINE | ID: mdl-33666471

ABSTRACT

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

17.
J Clin Invest ; 131(4)2021 02 15.
Article in English | MEDLINE | ID: mdl-33586686

ABSTRACT

Different fat depots have different physiologic functions. In a provocative study published in this issue of the JCI, Petrosino et al. investigate the role of paracardial fat in whole-body metabolism and exercise physiology. Petrosino et al. show that paracardial fat samples from older mice or mice fed a Western diet had decreased levels of alcohol dehydrogenase 1 (ADH1). Paracardial fat samples from humans with obesity also had decreased levels of ADH1 mRNA, supporting the translational relevance. Additional experiments with Adh1-KO mice and surgical fat transplantation experiments provide additional mechanistic insight. Paracardial fat may regulate exercise performance by altering circulating metabolites and/or endocrine effects. ADH1 appears to regulate the mitochondrial content of paracardial fat, a mechanism mediated by retinaldehyde. When ADH1 is active, the paracardial fat has characteristics of brown fat, which is beneficial for exercise performance. Further research is warranted to determine the translational potential of these findings, such as whether removing paracardial fat at the time of open-heart surgery might improve recovery time by increasing exercise capacity.


Subject(s)
Obesity , Vitamin A , Adipose Tissue, Brown , Animals , Mice , Obesity/genetics
18.
Antioxidants (Basel) ; 9(10)2020 Oct 19.
Article in English | MEDLINE | ID: mdl-33086602

ABSTRACT

Cardiac arrhythmias are responsible for many cardiovascular disease-related deaths worldwide. While arrhythmia pathogenesis is complex, there is increasing evidence for metabolic causes. Obesity, diabetes, and chronically consuming high-fat foods significantly increase the likelihood of developing arrhythmias. Although these correlations are well established, mechanistic explanations connecting a high-fat diet (HFD) to arrhythmogenesis are incomplete, although oxidative stress appears to be critical. This review investigates the metabolic changes that occur in obesity and after HFD. Potential therapies to prevent or treat arrhythmias are discussed, including antioxidants.

19.
Nat Commun ; 11(1): 3527, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32669538

ABSTRACT

Ca2+ signaling in pulmonary arterial smooth muscle cells (PASMCs) plays an important role in pulmonary hypertension (PH). However, the underlying specific ion channel mechanisms remain largely unknown. Here, we report ryanodine receptor (RyR) channel activity and Ca2+ release both are increased, and association of RyR2 by FK506 binding protein 12.6 (FKBP12.6) is decreased in PASMCs from mice with chronic hypoxia (CH)-induced PH. Smooth muscle cell (SMC)-specific RyR2 knockout (KO) or Rieske iron-sulfur protein (RISP) knockdown inhibits the altered Ca2+ signaling, increased nuclear factor (NF)-κB/cyclin D1 activation and cell proliferation, and CH-induced PH in mice. FKBP12.6 KO or FK506 treatment enhances CH-induced PH, while S107 (a specific stabilizer of RyR2/FKBP12.6 complex) produces an opposite effect. In conclusion, CH causes RISP-dependent ROS generation and FKBP12.6/RyR2 dissociation, leading to PH. RISP inhibition, RyR2/FKBP12.6 complex stabilization and Ca2+ release blockade may be potentially beneficial for the treatment of PH.


Subject(s)
Cyclin D1/metabolism , Electron Transport Complex III/metabolism , Hypertension, Pulmonary/metabolism , NF-kappa B/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Tacrolimus Binding Proteins/metabolism , Animals , Calcium Signaling , Cell Proliferation , Cytosol/metabolism , Humans , Hypoxia/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Myocytes, Smooth Muscle/metabolism , Oxygen/metabolism , Pulmonary Artery/pathology , Reactive Oxygen Species/metabolism , Respiration Disorders/metabolism , Signal Transduction
20.
Basic Clin Androl ; 30: 10, 2020.
Article in English | MEDLINE | ID: mdl-32685170

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) metamorphosed our medical practice. In early June 2020, more than 6,400,000 COVID-19 (coronavirus-19 disease) cases were diagnosed across the world and more than 380,000 deaths were linked to COVID-19. Many medical symptoms of COVID-19 were reported. We will focus, here, on potential impacts of COVID-19 on men's andrological health. Our society (French-speaking society of andrology, SALF) also emitted some recommendations in the andrological management of men infected by SARS-CoV-2. First, considering the fever and the potential presence of SARS-CoV2 in semen, SALF recommends waiting for 3 months (duration of one spermatogenesis cycle and epididymal transit) before re-starting ART in the case of men diagnosed COVID-19 positive. Whatever the nature of testosterone and COVID-19 relationships, we recommend an andrological examination, sperm parameters, and hormonal evaluation at the time of the COVID-19 is diagnosed, and several months later. Furthermore, we are concerned by the potential morbid-mortality of the COVID-19, which mainly affects men. This "andrological bias", if proven, must be reduced by specific andrological diagnosis, therapeutic and prophylactic measures. Research in this direction must be substantiated and financially supported over the next few months (years).


Le SRAS-CoV-2 (nouveau coronavirus ou coronavirus numéro 2 responsable du syndrome respiratoire aigu sévère) a métamorphosé notre pratique médicale. Début juin 2020, plus de 6,400,000 cas de COVID-19 (maladie à coronavirus 2019) ont été diagnostiqués dans le monde et plus de 380,000 décès ont été reliés à cette maladie. De nombreux symptômes médicaux de cette infection virale ont été signalés. Nous nous concentrerons, ici, sur les impacts potentiels de COVID-19 sur la santé andrologique des hommes. Notre société (Société d'andrologie de langue Française, SALF) émet ici quelques recommandations dans la prise en charge andrologique des hommes infectés par le SRAS-CoV-2. Tout d'abord, compte tenu de la fièvre et de la présence potentielle du SRAS-CoV2 dans le sperme, la SALF recommande d'attendre 3 mois (durée d'un cycle de spermatogenèse et transit épididymaire) avant de recommencer les techniques d'assistance médicale à la procréation pour les hommes diagnostiqués COVID-19 positifs. Quelle que soit la nature des relations entre la testostérone et l'infection à SARS-CoV-2, nous recommandons un examen andrologique, un examen des paramètres du sperme et une évaluation hormonale au moment du diagnostic de l'infection, ainsi qu'à distance (3­6 mois plus tard). De plus, nous sommes préoccupés par la morbidité et la mortalité potentielles de l'infection COVID-19, qui touche principalement les hommes. Ce "biais andrologique", s'il est. prouvé, doit être réduit par un diagnostic andrologique spécifique et des mesures thérapeutiques et prophylactiques. La recherche dans ce sens doit être étayée et soutenue financièrement au cours des prochains mois (années).

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