Sizing the length of complex networks

Among all characteristics exhibited by natural and man-made networks the small-world phenomenon is surely the most relevant and popular. But despite its significance, a reliable and comparable quantification of the question `how small is a small-world network and how does it compare to others' has remained a difficult challenge to answer. Here we establish a new synoptic representation that allows for a complete and accurate interpretation of the pathlength (and efficiency) of complex networks. We frame every network individually, based on how its length deviates from the shortest and the longest values it could possibly take. For that, we first had to uncover the upper and the lower limits for the pathlength and efficiency, which indeed depend on the specific number of nodes and links. These limits are given by families of singular configurations that we name as ultra-short and ultra-long networks. The representation here introduced frees network comparison from the need to rely on the choice of reference graph models (e.g., random graphs and ring lattices), a common practice that is prone to yield biased interpretations as we show. Application to empirical examples of three categories (neural, social and transportation) evidences that, while most real networks display a pathlength comparable to that of random graphs, when contrasted against the absolute boundaries, only the cortical connectomes prove to be ultra-short

Inhibiting the inflammasome with MCC950 counteracts muscle pyroptosis and improves Duchenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) is the most common inherited human myopathy. Typically, the secondary process involving severe inflammation and necrosis exacerbate disease progression. Previously, we reported that the NLRP3 inflammasome complex plays a crucial role in this disorder. Moreover, pyroptosis, a form of programmed necrotic cell death, is triggered by NLRP3 via gasdermin D (GSDMD). So far, pyroptosis has never been described either in healthy muscle or in dystrophic muscle. The aim of this study was to unravel the role of NLRP3 inflammasome in DMD and explore a potentially promising treatment with MCC950 that selectively inhibits NLRP3. Methods: Four‐week‐old mdx mice (n=6 per group) were orally treated for 2 months with MCC950 (mdx‐T), a highly potent, specific, small-molecule inhibitor of NLRP3, and compared with untreated (mdx) and wild-type (WT) mice. In vivo functional tests were carried out to measure the global force and endurance of mice. Ex vivo biochemical and molecular analyses were performed to evaluate the pathophysiology of the skeletal muscle. Finally, in vitro tests were conducted on primary cultures of DMD human myotubes. Results: After MCC950 treatment, mdx mice exhibited a significant reduction of inflammation, macrophage infiltration and oxidative stress (-20 to -65%, P<0.05 vs untreated mdx). Mdx‐T mice displayed considerably less myonecrosis (-54%, P<0.05 vs mdx) and fibrosis (-75%, P<0.01 vs mdx). Moreover, a more mature myofibre phenotype, characterized by larger-sized fibres and higher expression of mature myosin heavy chains 1 and 7 was observed. Mdx-T also exhibited enhanced force and resistance to fatigue (+20 to 60%, P<0.05 or less). These beneficial effects resulted from MCC950 inhibition of both active caspase-1 (-46%, P=0.075) and cleaved gasdermin D (N-GSDMD) (-42% in medium-sized-fibres, P<0.001). Finally, the anti-inflammatory action and the anti-pyroptotic effect of MCC950 were also recapitulated in DMD human myotubes. Conclusion: Specific inhibition of the NLRP3 inflammasome can significantly attenuate the dystrophic phenotype. A novel finding of this study is the overactivation of GSDMD, which is hampered by MCC950. This ultimately leads to less inflammation and pyroptosis and to a better muscle maturation and function. Targeting NLRP3 might lead to an effective therapeutic approach for a better management of DMD.Fund for Scientific Research de Bélgica (FNRS)-PDR/T.0026.2

Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self-and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR

Quantitative description of metal center organization and interactions in single-atom catalysts

Ultra-high-density single-atom catalysts (UHD-SACs) present unique opportunities for harnessing cooperative effects between neighboring metal centers. However, the lack of tools to establish correlations between the density, type, and arrangement of the isolated metal atoms with the support surface properties hinders efforts to engineer advanced material architectures. Here, we precisely describe the metal center organization in various mono- and multimetallic UHD-SACs based on nitrogen-doped carbon (NC) supports by coupling transmission electron microscopy with tailored machine-learning methods (released as a user-friendly web app) and density functional theory simulations. Our approach quantifies the non-negligible presence of multimers with increasing atom density, characterizes the size and shape of these low-nuclearity clusters, and identifies surface atom density criteria to ensure isolation. Further, it provides previously inaccessible experimental insights into coordination site arrangements in the NC host, uncovering a repulsive interaction that influences the disordered distribution of metal centers in UHD-SACs. This observation holds in multimetallic systems, where chemically-specific analysis quantifies the degree of intermixing. These fundamental insights into the materials chemistry of single-atom catalysts are crucial for designing catalytic systems with superior reactivity.This publication was created as part of NCCR Catalysis (grant number 180544), a National Centre of Competence in Research funded by the Swiss National Science Foundation. A. R.-F. acknowledges funding from the Generalitat de Catalunya and the European Union under Grant 2023 FI-3 00027. N.L. acknowledges support from the Ministerio de Ciencia e Innovación, ref. no. RTI2018-101394-B-100, and the Severo Ochoa Grant, MCIN/AEI/10.13039/501100011033-CEX2019-000925-S. The authors thank BSC-RES for generously providing computational resources.Peer ReviewedPostprint (published version

Estimation of the Mass Concentration of Volcanic Ash Using Ceilometers: Study of Fresh and Transported Plumes from La Palma Volcano

This study presents a synergistic approach to the study of the aerosol optical and microphysical properties measured in La Palma, Spain, during the 2021 eruption of the Cumbre Vieja volcano (from 19 September to 13 December 2021). This study aims to characterize the different phases of the volcanic eruption using the spatio-temporal evolution of the event together with the mass concentration quantification of four different atmospheric layers. The impact of the plume’s pathway that reached the South of France is analyzed. Here, passive and active remote sensors were used, namely CL51 and CL61 ceilometers and AERONET sunphotometers. The attenuated backscattering ranged from 0.8 to 9.1 × 10−6 (msr)−1 and the volume depolarization ratio measured nearby the volcano was up to 0.3. The ash plume remained within the first 4 km agl, with intense episodes that reached mean aerosol optical depth values of up to 0.4. Thirteen study cases were selected where coarse mode was dominant over fine mode. For the data selection, the fine and coarse lidar ratios found were 3.9 ± 0.8 and 21.0 ± 3.8 sr in the north and 6.9 ± 1.8 and 30.1 ± 10.3 sr in the south. The ash mass concentration reached moderate levels with maximum values of up to 313.7 μgm−3.This work was financially supported by ONERA within the framework of the PROMETE project 2017–2021; the Spanish Ministry of Science and Innovation (PID2019-103886RB-I00\AEI\10.13039\501100011033); and the H2020 program from the European Union (GA no. 654109, 778349, 871115, 101008004 and 101086690)

Hydrodynamics of high-redshift galaxy collisions: From gas-rich disks to dispersion-dominated mergers and compact spheroids

Disk galaxies at high redshift (z~2) are characterized by high fractions of cold gas, strong turbulence, and giant star-forming clumps. Major mergers of disk galaxies at high redshift should then generally involve such turbulent clumpy disks. Merger simulations, however, model the ISM as a stable, homogeneous, and thermally pressurized medium. We present the first merger simulations with high fractions of cold, turbulent, and clumpy gas. We discuss the major new features of these models compared to models where the gas is artificially stabilized and warmed. Gas turbulence, which is already strong in high-redshift disks, is further enhanced in mergers. Some phases are dispersion-dominated, with most of the gas kinetic energy in the form of velocity dispersion and very chaotic velocity fields, unlike merger models using a thermally stabilized gas. These mergers can reach very high star formation rates, and have multi-component gas spectra consistent with SubMillimeter Galaxies. Major mergers with high fractions of cold turbulent gas are also characterized by highly dissipative gas collapse to the center of mass, with the stellar component following in a global contraction. The final galaxies are early-type with relatively small radii and high Sersic indices, like high-redshift compact spheroids. The mass fraction in a disk component that survives or re-forms after a merger is severely reduced compared to models with stabilized gas, and the formation of a massive disk component would require significant accretion of external baryons afterwards. Mergers thus appear to destroy extended disks even when the gas fraction is high, and this lends further support to smooth infall as the main formation mechanism for massive disk galaxies.Comment: ApJ accepte

A "core-complex-type structure" formed by superposed ductile and brittle extension followed by folding and high-angle normal faulting. The Santi Petri dome (western Betics, Spain)

The Santi Petri dome (western Betics, southern Spain) shows a core-complex-like structure, where migmatitic gneisses and schists outcrop below low-grade slates and phyllites, all of which form the basement of the Neogene Málaga basin. The migmatites and schists suffered a coaxial-flattening event during isothermal decompression and were later exhumed by ductile ESE non-coaxial stretching. Further exhumation was achieved by W- to SW-transport brittle low-angle normal faulting. Subsequently these extensional structures were gently folded in the core of a NE/SW-oriented antiform during the Tortonian. Finally the Santi Petri domal geometry was accentuated by the interference of orthogonal high-angle faults with ENE–WSW and NNW–SSE orientation. This core-complex-like structure, formed by superposition of extensional and compressive tectonic events, does not represent a classical, purely extensional core complex, which shows that metamorphic structure and geometry are not decisive criteria to define a core-complex

The rise and fall of the ancient northern pike master sex determining gene

The understanding of the evolution of variable sex determination mechanisms across taxa requires comparative studies among closely related species. Following the fate of a known master sex-determining gene, we traced the evolution of sex determination in an entire teleost order (Esociformes). We discovered that the northern pike (Esox lucius) master sex-determining gene originated from a 65 to 90 million-year-old gene duplication event and that it remained sex-linked on undifferentiated sex chromosomes for at least 56 million years in multiple species. We identified several independent species- or population-specific sex determination transitions, including a recent loss of a Y-chromosome. These findings highlight the diversity of evolutionary fates of master sex-determining genes and the importance of population demographic history in sex determination studies. We hypothesize that occasional sex reversals and genetic bottlenecks provide a non-adaptive explanation for sex determination transitions

Working group on ecosystem assessment of Western European shelf seas (WGEAWESS)

The ICES Working Group on Ecosystem Assessment of Western European Shelf Seas (WGEA-WESS) aims to provide high quality science in support to holistic, adaptive, evidence-based man-agement in the Celtic seas, Bay of Biscay and Iberian coast regions. The group works towards developing integrated ecosystem assessments for both the (i) Celtic Seas and (ii) Bay of Biscay and Iberian Coast which are summarized in the Ecosystem Overviews (EOs) advice products that were recently updated. Integrated Trend Analysis (ITA) were performed for multiple sub-ecoregions and used to develop an understanding of ecosystem responses to pressures at varying spatial scales. Ecosystem models (primarily Ecopath with Ecosim; EwE) were developed and identified for fisheries and spatial management advice. The updated Celtic Seas EO represents a large step forward for EOs, with the inclusion of novel sections on climate change, foodweb and productivity, the first application of the new guidelines for building the conceptual diagram, inclusion of socio-economic indicators, and progress made toward complying with the Transparent Assessment Framework (TAF). We highlight ongoing issues relevant to the development and communication of EO conceptual diagrams. A common methodology using dynamic factor analysis (DFA) was used to perform ITA in a comparable way for seven subregions. This was supported by the design and compilation of the first standardized cross-regional dataset. A comparison of the main trends evidenced among subregions over the period 1993–2020 was conducted and will be published soon. A list of available and developing EWE models for the region was also generated. Here, we re-port on the advances in temporal and spatial ecosystem modelling, such as their capacity to model the impacts of sector activities (e.g. renewables and fisheries) and quantify foodweb indi-cators. We also reflect on model quality assessment with the key run of the Irish sea EwE model. The group highlighted the hurdles and gaps in current models in support of EBM, such as the choice of a relevant functional, spatial, and temporal scales and the impacts of model structure on our capacity to draw comparisons from models of different regions. The group aims to ad-dress these issues in coming years and identify routes for ecosystem model derived information into ICES advice.info:eu-repo/semantics/publishedVersio