Szemer\'edi's theorem in the primes

Green and Tao famously proved in 2005 that any subset of the primes of fixed positive density contains arbitrarily long arithmetic progressions. Green had previously shown that in fact any subset of the primes of relative density tending to zero sufficiently slowly contains a 3-term term progression. This was followed by work of Helfgott and de Roton, and Naslund, who improved the bounds on the relative density in the case of 3-term progressions. The aim of this note is to present an analogous result for longer progressions by combining a quantified version of the relative Szemer\'edi theorem given by Conlon, Fox and Zhao with Henriot's estimates of the enveloping sieve weights.Comment: 11 page

Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy

Satellite cell-mediated myonuclear accretion is thought to be required for skeletal muscle fiber hypertrophy, and even drive hypertrophy by preceding growth. Recent studies in humans and rodents provide evidence that challenge this axiom. Specifically, Type 2 muscle fibers reliably demonstrate a substantial capacity to hypertrophy in the absence of myonuclear accretion, challenging the notion of a tightly regulated myonuclear domain (i.e., area that each myonucleus transcriptionally governs). In fact, a “myonuclear domain ceiling”, or upper limit of transcriptional output per nucleus to support hypertrophy, has yet to be identified. Satellite cells respond to muscle damage, and also play an important role in extracellular matrix remodeling during loading-induced hypertrophy. We postulate that robust satellite cell activation and proliferation in response to mechanical loading is largely for these purposes. Future work will aim to elucidate the mechanisms by which Type 2 fibers can hypertrophy without additional myonuclei, the extent to which Type 1 fibers can grow without myonuclear accretion, and whether a true myonuclear domain ceiling exists

Fusion and Beyond: Satellite Cell Contributions to Loading-Induced Skeletal Muscle Adaptation

Satellite cells support adult skeletal muscle fiber adaptations to loading in numerous ways. The fusion of satellite cells, driven by cell-autonomous and/or extrinsic factors, contributes new myonuclei to muscle fibers, associates with load-induced hypertrophy, and may support focal membrane damage repair and long-term myonuclear transcriptional output. Recent studies have also revealed that satellite cells communicate within their niche to mediate muscle remodeling in response to resistance exercise, regulating the activity of numerous cell types through various mechanisms such as secretory signaling and cell–cell contact. Muscular adaptation to resistance and endurance activity can be initiated and sustained for a period of time in the absence of satellite cells, but satellite cell participation is ultimately required to achieve full adaptive potential, be it growth, function, or proprioceptive coordination. While significant progress has been made in understanding the roles of satellite cells in adult muscle over the last few decades, many conclusions have been extrapolated from regeneration studies. This review highlights our current understanding of satellite cell behavior and contributions to adaptation outside of regeneration in adult muscle, as well as the roles of satellite cells beyond fusion and myonuclear accretion, which are gaining broader recognition

Mitonuclear discordance and patterns of reproductive isolation in a complex of simultaneously hermaphroditic species, the Allolobophora chlorotica case study

Historical events of population fragmentation, expansion and admixture over geological time may result in complex patterns of reproductive isolation and may explain why, for some taxa, the study of mitochondrial (mt) and nuclear (nu) genetic data results in discordant evolutionary patterns. Complex patterns of taxonomic diversity were recently revealed in earthworms for which distribution is largely the result of paleogeographical events. Here, we investigated reproductive isolation patterns in a complex of cryptic species of earthworms in which discordant patterns between mt and nu genetic lineages were previously revealed, the Allolobophora chlorotica aggregate. Using four nu microsatellite markers and a fragment of the cytochrome c oxidase subunit I mt gene, we carried out a parentage analysis to investigate the mating patterns (i) between individuals belonging to two divergent mt lineages that cannot be distinguished with nu markers and (ii) between individuals belonging to lineages that are differentiated both at the mt and nu levels. Amongst the 157 field-collected individuals, 66 adults were used in cross-breeding experiments to form 22 trios based on their assignment to a mt lineage, and 453 obtained juveniles were genotyped. We showed that adults that mated with both their potential mates in the trio produced significantly more juveniles. In crosses between lineages that diverged exclusively at the mt level, a sex-specific pattern of reproduction characteristic to each lineage was observed, suggesting a possible conflict of interest concerning the use of male/female function between mating partners. In crosses between lineages that diverged both at the mt and nu levels, a high production of cocoons was counterbalanced by a low hatching rate, suggesting a post-zygotic reproductive isolation. Different degrees of reproductive isolation, from differential sex allocation to post-zygotic isolation, were thus revealed. Lineages appear to be at different stages in the speciation process, which likely explain the observed opposite patterns of mitonuclear congruence

Differential Requirement for Satellite Cells During Overload-Induced Muscle Hypertrophy in Growing Versus Mature Mice

Background: Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Methods: Pax7CreER-R26RDTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6–9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Results: Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p \u3c 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p \u3c 0.05), and mature SC- mice (p \u3c 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p \u3c 0.05), and eMyHC expression was variable, specifically in mature SC+ mice. Conclusions: Reliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice

Flow and Heat Transfer Numerical Modelling in the Hainaut Limestone Geothermal Reservoir: Study at Local and Regional Scales

editorial reviewedNowadays, Europe needs to produce more sustainable energy. A possible solution includes geothermal energy. Many sites are already in activity for example in France, Germany or Italy. In Belgium, research is currently performed in the Campine Basin. In the Mons area (South-West Belgium), some wells have been exploited since the eighties. They were drilled in a deep limestone reservoir characterized by some highly permeable breccia levels. This reservoir has not been studied extensively, despite potentially important heat reserves. In this context, the MOREGEO project has been initiated by the University of Mons and the IDEA (intercommunity active in the area) with financial support from the ERDF European program. The general objective of this project is to drill a new geothermal doublet to provide heat to the largest city hospital. Hot water will be pumped from a well and cold water will be reinjected in another one. Specific objectives of the project include: (1) Modelling heat transfers at the scale of the new geothermal doublet; and (2) Modelling the whole geothermal reservoir in order to provide an efficient management tool for the future development of additional geothermal wells. The geothermal reservoir of Hainaut is mainly composed of limestone from the Carboniferous period, with breccia and evaporites levels. Three wells currently provide energy for the heat production to two hospitals, schools, station, housings and an economic area. The depth of the exploited layers is around 2000 meters and the pumping groundwater temperature is about 70°C. A first numerical model has been developed at the scale of the future new geothermal doublet. Numerical models are implemented using Hydrogeosphere and Feflow. These calculation codes simulate fluid flow, solute and heat transport in porous and fractured media. The models aim at analysing the conditions of the exploitation, the longevity of the system, and the possible interactions with surrounding geothermal wells. An important challenge lies in the representation of the complex geology. The reservoir includes layers of anhydrites, partly or totally dissolved according to the location. Another challenge is to find a good setting for the border conditions of the model. This difficulty comes from the effect of the high temperature and pressure in the reservoir, which affect the value of the hydraulic head. First simulations show that the parameters expected in the area allow the exploitation of geothermal wells to provide hot water for heating. Cold water injected at the reinjection well goes in the direction of the pumping well, located 1,400 m away. The longevity of the exploitation depends on the time taken by cold water to induce a decrease of temperature at the pumping well. The first simulations show that a decrease of temperature at the pumping well is expected to be around 2°C after 100 years. A sensitivity analysis of the model parameters has also been carried out to see which parameters have the most important impact on the exploitation and the longevity of the geothermal doublet system. The first results show the influence of the permeability of the exploited rock layer and the layers situated next to this one. The thickness of the layer and the rate of flow in the pumping and reinjected wells have also to be considered as important parameters.Modélisation dynamique du réservoir géothermique des calcaires carbonifères au droit du territoire du Coeur de Hainaut - Sources publiques européenne

Comparative Analysis of Patient Characteristics in Cardiogenic Shock Studies: Differences Between Trials and Registries

OBJECTIVES: This study sought to evaluate the differences in cardiogenic shock patient characteristics in trial patients and real-life patients. BACKGROUND: Cardiogenic shock (CS) is a leading cause of mortality in patients presenting with acute myocardial infarction (AMI). However, the enrollment of patients into clinical trials is challenging and may not be representative of real-world patients. METHODS: We performed a systematic review of studies in patients presenting with AMI-related CS and compared patient characteristics of those enrolled into randomized controlled trials (RCTs) with those in registries. RESULTS: We included 14 RCTs (n = 2,154) and 12 registries (n = 133,617). RCTs included more men (73% vs 67.7%, P \u3c 0.001) compared with registries. Patients enrolled in RCTs had fewer comorbidities, including less hypertension (61.6% vs 65.9%, P \u3c 0.001), dyslipidemia (36.4% vs 53.6%, P \u3c 0.001), a history of stroke or transient ischemic attack (7.1% vs 10.7%, P \u3c 0.001), and prior coronary artery bypass graft surgery (5.4% vs 7.5%, P \u3c 0.001). Patients enrolled in RCTs also had lower lactate levels (4.7 ± 2.3 mmol/L vs 5.9 ± 1.9 mmol/L, P \u3c 0.001) and higher mean arterial pressure (73.0 ± 8.8 mm Hg vs 62.5 ± 12.2 mm Hg, P \u3c 0.001). Percutaneous coronary intervention (97.5% vs 58.4%, P \u3c 0.001) and extracorporeal membrane oxygenation (11.6% vs 3.4%, P \u3c 0.001) were used more often in RCTs. The in-hospital mortality (23.9% vs 38.4%, P \u3c 0.001) and 30-day mortality (39.9% vs 45.9%, P \u3c 0.001) were lower in RCT patients. CONCLUSIONS: RCTs in AMI-related CS tend to enroll fewer women and lower-risk patients compared with registries. Patients enrolled in RCTs are more likely to receive aggressive treatment with percutaneous coronary intervention and extracorporeal membrane oxygenation and have lower in-hospital and 30-day mortality

The Mechanism Underlying Transient Weakness in Myotonia Congenita

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to -25 to -35 mV in the genetic and pharmacologic models of Becker disease. Both Na + and Ca 2+ currents contribute to plateau potentials. Na + persistent inward current (NaPIC) through Na V 1.4 channels is the key trigger of plateau potentials and current through Ca V 1.1 Ca 2+ channels contributes to the duration of the plateau. Inhibiting NaPIC with ranolazine prevents the development of plateau potentials and eliminates transient weakness in vivo. These data suggest that targeting NaPIC may be an effective treatment to prevent transient weakness in myotonia congenita