bluuebunny/crossref_metadata_2025 huggingface dataset:
Lauda Sion as Doxological Compendium of St. Thomas’s Eucharistic Theology
Authors: Hannon Urban
Published: February 2024

In 1264 in the town of Orvieto, St. Thomas Aquinas composed the Lauda Sion as the Mass sequence for Pope Urban IV’s new universal solemnity of the Body and Blood of our Lord Jesus Christ, the feast of Corpus Christi. The present paper will consider this text of St. Thomas’s liturgical sequence in relation to the eucharistic theology that he teaches in the Summa Theologiae. Just as, according to the Dionysian Aquinas, the Psalms contain all the doctrines revealed in the rest of scripture but transposed into the highest literary genre of praise, so the Lauda Sion contains all the essential eucharistic doctrines of the Summa Theologiae, now set in that same laudatory genre as the Psalter. The paper is divided into ten sections, corresponding to the questions in St. Thomas’s treatment of the Holy Eucharist in the Tertia Pars. Proceeding one topic at a time, this paper will show how the Lauda Sion serves as a doxological compendium of St. Thomas Aquinas’s whole eucharistic theology.
Can Deliberation Have Lasting Effects?
Authors: FISHKIN JAMES , BOLOTNYY VALENTIN , LERNER JOSHUA , SIU ALICE , BRADBURN NORMAN
Published: February 2024

Does deliberation produce any lasting effects? “America in One Room” was a national field experiment in which more than 500 randomly selected registered voters were brought from all over the country to deliberate on five major issues facing the country. A pre-post control group was also surveyed on the same questions after the weekend and about a year later. There were significant differences in voting intention and in actual voting behavior a year later among the deliberators compared to the control group. This article accounts for these differences by showing how deliberation stimulated a latent variable of political engagement. If deliberation has lasting effects on political engagement, then it provides a rationale for attempts to scale the deliberative process to much larger numbers. The article considers methods for doing so in the context of the broader debate about mini-publics, isolated spheres of deliberation situated within a largely non-deliberative society.
The effects of saturated fat intake from dairy on CVD markers: the role of food matrices
Authors: Dunne Simone , Gibney Eileen R. , McGillicuddy Fiona C. , Feeney Emma L.
Published: February 2024

CVD is the leading cause of death worldwide, and is commonly associated with modifiable risk factors. Most studies to date examining link between food intake and risk of CVD, have focused on modulation of plasma cholesterol concentrations (total cholesterol (TC), LDL-C). However, recent studies suggest LDL particle size is a more sensitive risk marker for CVD with smaller, dense LDL particles reported as more atherogenic than larger, more buoyant LDL. Although dietary guidelines recommend SFA intake of < 10 % of total energy, this does not consider food source, with recent evidence suggesting differing, sometimes beneficial, lipid responses following consumption of SFA from dairy compared to other food sources. This may be from differences in the physical food matrices, the nutrient content of the foods, and/or how these components interact with each other, described as a ‘dairy matrix effect’. Dietary fat not only raises LDL-C, but also HDL cholesterol (HDL-C), associated with reduced CVD risk. HDL particles are complex emulsions of lipids, proteins and microRNAs that exhibit atheroprotective properties. In addition, HDL particles exhibit a very heterogeneous proteomic composition, dependent on a person’s disease state – with a more pro-inflammatory proteome evident in patients with established CVD. This review will discuss the evidence to date on the importance of the food matrix in modulating response to dietary SFA and impact on CVD risk factors. A focus on potential biomarker properties of lipoprotein particles beyond cholesterol and current use of such biomarkers in human nutrition research will be considered.
Genetic and non-genetic predictors of risk for opioid dependence
Authors: Na Peter J. , Deak Joseph D. , Kranzler Henry R. , Pietrzak Robert H. , Gelernter Joel
Published: February 2024

Background

Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD).

Methods

Data from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD.

Results

A total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21–1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85–0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04–2.35).

Conclusions

Results suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.
SMOKE ON THE WATER: HES AT 50 AND THE NON-NEUTRALITY OF HISTORY
Authors: Maas Harro
Published: February 2024

Recently, I participated in the thesis defense on an eminently local subject, political economic writing in the eighteenth century in the cantons of Vaud (where I live and teach) and Berne (which at the time had occupied the Canton of Vaud) in Switzerland. I will spare you the details of this 700-pages-thick thesis, with an appendix of another 200 pages, which was not even about political economic writing in all of the Swiss Federation, but only in these two small regions in one of the most beautiful spots of Europe. But I became mesmerized by the profoundness of the political economic thinking of a group of now largely forgotten administrators and members of the Swiss socio-economic elite that grappled with questions of how to position their economic doings against a Europe that was plagued by the early eighteenth-century War of Succession, questions about the economic consequences not of population growth but of population decline, and the consequences of what David Hume has characterized so well as the “Jealousy of Trade” between the emerging European colonial empires. More in particular, these local men of politics and power were concerned with if and how they could preserve the agricultural system of common pastures—that were to figure prominently in Elinor Ostrom’s early studies of the “commons”—or whether they should copy the English model of enclosures that seemed to promise agricultural innovation and economic growth. How would this pan out for the means of existence of the local population? And, of course, what would this mean for their own economic and political interests and standing? All these concerns brought them in conversation with the work of such writers as François Forbonnais, Richard Cantillon, the Physiocrats, and Scottish philosophers such as Hume, James Steuart, and Adam Smith, with some of whom they were also in correspondence. The measures the local elites implemented on the basis of these discussions were consequential for such important issues as land use, manufacture and commerce, and poor relief. Unsurprisingly perhaps, the thesis was supervised by one of Istvan Hont’s students, Béla Kapossy, a professor in the history department of the University of Lausanne.
Period–Luminosity Relations in the Local Group of Galaxies
Authors: Soszyński Igor
Published: February 2024

Local Group galaxies, particularly the Large and Small Magellanic Clouds, have historically played and continue to play a unique role in studies of the period–luminosity (PL), period–luminosity–color (PLC), and period–Wesenheit (PW) relations, not just for pulsating stars. In recent years, significant efforts have been devoted to calibrate the PL, PLC, and PW relationships at different wavelengths, including studies of the influence of metallicity and nonlinearities on the accuracy of measured distances. However, the PL diagram has many more astrophysical applications. It serves as a vital tool for classifying different types of pulsating stars and can even facilitate the discovery of new classes of variable stars. Moreover, it aids in distinguishing among various modes of pulsation, facilitates the identification of pulsating stars that are members of binary systems, and enables studies of the three-dimensional structures of neighboring galaxies. In this contribution, I present the latest results on the PL, PLC, and PW relations obeyed by various types of variable stars in Local Group galaxies – from δ Scuti stars to Mira variabless and from close binary systems to the mysterious long secondary periods exhibited by red giant and supergiant stars.
A multi-wavelength analysis of BL Her stars: Models versus Observations
Authors: Das S. , Molnár L. , Kanbur S. M. , Joyce M. , Bhardwaj A. , Singh H. P. , Marconi M. , Ripepi V. , Smolec R.
Published: February 2024

We present new theoretical period–luminosity (PL) and period–radius (PR) relations at multiple wavelengths (Johnson–Cousins–Glass and Gaia passbands) for a fine grid of BL Herculis models computed using mesa-rsp. The non-linear models were computed for periods typical of BL Her stars, i.e. 1 ≤ P(days) ≤ 4, covering a wide range of input parameters: metallicity (−2.0 dex ≤ [Fe/H] ≤ 0.0 dex), stellar mass (0.5–0.8 ), luminosity (50–300 ) and effective temperature (full extent of the instability strip; in steps of 50K). We investigate the impact of four sets of convection parameters on multi-wavelength properties. Most empirical relations match well with theoretical relations from the BL Her models computed using the four sets of convection parameters. No significant metallicity effects are seen in the PR relations. Another important result from our grid of BL Her models is that it supports combining PL relations of RR Lyrae and Type II Cepheids together as an alternative to classical Cepheids for the extragalactic distance scale calibration.
Empirical constraints for the instability strip from the analysis of LMC Cepheids
Authors: Espinoza-Arancibia F. , Pilecki B.
Published: February 2024

The instability strip (IS) of classical Cepheids has been extensively studied theoretically. Comparison of the theoretical IS edges with those obtained empirically, using the most recent Cepheids catalogs available, can provide us with insights into the physical processes that determine the position of the IS boundaries. We investigate the empirical positions of the IS of the classical Cepheids in the Large Magellanic Cloud (LMC) using data of classical fundamental-mode and first-overtone LMC Cepheids from the OGLE-IV variable star catalog, together with a recent high-resolution reddening map from the literature. We studied their position on the Hertzsprung-Russell diagram and determined the IS borders by tracing the edges of the color distribution along the strip. We obtain the blue and red edges of the IS in V- and I-photometric bands, in addition to Teff and log L⊙. The results obtained show a break located at the Cepheids’ period of about 3 days, which was not reported before. This phenomenon is most likely explained by the depopulation of second and third crossing classical Cepheids in the faint part of the IS, since blue loops of evolutionary tracks in this mass range do not extend blueward enough to cross the IS at the LMC metallicity. Furthermore, our empirical borders show good agreement with theoretical ones published in the literature. This proves that our empirical IS is a useful tool to put constraints on theoretical models.
The Local Value of H0
Authors: Riess Adam G. , Breuval Louise
Published: February 2024

We review the local determination of the Hubble constant, H0, focusing on recent measurements of a distance ladder constructed from geometry, Cepheid variables and Type Ia supernovae (SNe Ia). We explain in some detail the components of the ladder: (1) geometry from Milky Way parallaxes, masers in NGC 4258 and detached eclipsing binaries in the Large Magellanic Cloud; (2) measurements of Cepheids with the Hubble Space Telescope (HST) in these anchors and in the hosts of 42 SNe Ia; and (3) SNe Ia in the Hubble flow. Great attention to negating systematic uncertainties through the use of differential measurements is reviewed. A wide array of tests are discussed. The measurements provide a strong indication of a discrepancy between the local measure of H0 and its value predicted by Λ Cold Dark Matter theory, calibrated by the cosmic microwave background (Planck), a decade-long challenge known as the ‘Hubble Tension’. We present new measurements with the James Webb Space Telescope of >320 Cepheids on both rungs of the distance ladder, in a SN Ia host and the geometric calibrator NGC 4258, showing good agreement with the same as measured with HST. This provides strong evidence that systematic errors in HST Cepheid photometry do not play a significant role in the present Hubble Tension. Future measurements are expected to refine the local determination of the Hubble constant.
Theoretical Stellar Pulsation Physics
Authors: Marconi M. , De Somma G. , Molinaro R. , Musella I.
Published: February 2024

Pulsating stars play a crucial role in the calibration of the cosmic distance scale as well as in tracing the properties of the associated stellar populations. In the era of large observational surveys and precise astrometric missions, it is crucial to rely on accurate stellar pulsation models able to predict the observed behaviors for different physical assumptions. Indeed, the relations currently used in the literature to derive individual and mean distances of mainly radially pulsating stars such as Cepheids and RR Lyrae are well physically understood, but are also known to depend on a number of often unknown parameters. Recent extensive sets of stellar pulsation models developed by various authors show how variations in the physical assumptions can affect the theoretical prediction of the instability strip boundaries, the morphology and amplitude of light and radial velocity curves, and the consequent Period-Luminosity, Period-Luminosity-Color and Period-Wesenheit relations. These aspects are discussed in the framework of current open problems in the field of classical pulsating stars.
Impact of the Gaia ESA mission on the primary Period–Luminosity Calibrators in the Milky Way: Cepheids and RR Lyrae
Authors: Clementini Gisella
Published: February 2024

We discuss the impact of Gaia, the cornerstone mission of the European Space Agency (ESA), on the calibration of the period–luminosity and luminosity–metallicity relations of Cepheids and RR Lyrae stars, with specific reference to data published as part of the most recent Gaia releases: Early Data Release 3 (EDR3), on 19 December 2020, and Data Release 3 (DR3) on 13 June 2022. We provide future perspectives for the Gaia mission, including extensions approved by ESA and a tentative schedule of the data releases that will take place in the next few years. We briefly present plans for cross-Coordination Unit processing of Gaia data of Cepheids and RR Lyrae stars for DR4 and conclude by outlining the expected improvement in astrometry at the end of the extended Gaia mission, which will help to further strengthen the calibration of the first rung of the cosmic distance ladder.
The Cepheid Extragalactic Distance Scale: Past, Present and Future
Authors: Freedman Wendy L. , Madore Barry F.
Published: February 2024

Cepheids have been the cornerstone of the extragalactic distance scale for a century. With high-quality data, these luminous supergiants exhibit a small dispersion in their Leavitt (period–luminosity) relation, particularly at longer wavelengths, and few methods rival the precision possible with Cepheid distances. In these proceedings, we present an overview of major observational programs pertaining to the Cepheid extragalactic distance scale, its progress and remaining challenges. In addition, we present preliminary new results on Cepheids from the James Webb Space Telescope (JWST). The launch of JWST has opened a new chapter in the measurement of extragalactic distances and the Hubble constant. JWST offers a resolution three times that of the Hubble Space Telescope (HST) with nearly 10 times the sensitivity. It has been suggested that the discrepancy in the value of the Hubble constant based on Cepheids compared to that inferred from measurements of the cosmic microwave background requires new and additional physics beyond the standard cosmological model. JWST observations will be critical in reducing remaining systematics in the Cepheid measurements and for confirming if new physics is indeed required. Early JWST data for the galaxy, NGC 7250 show a decrease in scatter in the Cepheid Leavitt law by a factor of two relative to existing HST data and demonstrate that crowding/blending effects are a significant issue in a galaxy as close as 20 Mpc.
The distance scale of Type II Cepheids from near-infrared observations in the Magellanic Clouds
Authors: Sicignano T. , Ripepi V. , Molinaro R. , Bhardwaj A. , Marconi M. , Cioni M.-R. L.
Published: February 2024

We employed data from the VISTA near-infrared YJKS survey of the Magellanic System to analyse the light curves of Type II Cepheids (T2Cs) in the Large and Small Magellanic Clouds (LMC and SMC, respectively). Using the T2Cs identified by the OGLE IV survey and Gaia mission, we built up a sample of about 330 pulsators belonging to both galaxies. For all these objects we obtained accurate intensity-averaged magnitudes in the YJKS bands by means of a template-fitting technique. We complemented our near-infrared data with optical photometry from the literature to calculate period-luminosity and period-Wesenheit relations for a variety of different bands and colour combinations and separately for the different T2C subclasses (BL Herculis, W Virginis, peculiar W Virginis, RV Tauri). These relations, calibrated with the LMC distance modulus, were tested using T2Cs belonging to Galactic globular clusters. We thus calculated the distances of 22 clusters and compared them with the literature values, mainly based on RR Lyrae stars, finding good agreement within 1 σ and dispersion of the order of 0.3 – 0.5 kpc, depending on the adopted period-luminosity/period-Wesenheit relation.
Measuring It, Managing It, Fixing It? Data and Rights in Transnational and Local Climate Change Governance
Authors: Mai Laura
Published: February 2024

The Paris Agreement, related intergovernmental decisions, and transnational climate change governance initiatives mobilize data as a means of measuring, managing, and addressing changing climatic conditions. At the same time, the Paris Agreement formally acknowledges the human rights implications of the unfolding climate crisis. Given the reliance on data and rights in climate change governance, the aim of this article is twofold. Firstly, it analyzes how processes of datafication at transnational and local levels promise, yet struggle, to render the climate governable. Secondly, the article critically reflects on the capacity of human rights to complement datafied governance processes meaningfully – specifically, in what ways rights can (and cannot) alleviate local concerns regarding datafication. Methodologically, the article develops a perspective that foregrounds situated sense-making and experience in place. It is based on an empirical case study of the Global Covenant of Mayors for Climate & Energy, a transnational alliance of cities that have committed to working towards the goals of the Paris Agreement; and it engages with ethnographic literature that conceptualizes rights as lived forms of meaning-making, articulation, struggle, and resistance. Attending to place, the article confronts problematic assumptions about the universality, neutrality, and representativeness of data and rights, raising critical questions about their capacity to ‘govern’ climate change.
Entscheidungsfindung von Intensivpflegefachpersonen zur Verifikation blind applizierter Magensonden
Authors: Grebe Markus , Roos Marcelina , Höckelmann Carolin , Sadat Beyza , Eder Caroline , Dichter Martin Nikolaus , Köpke Sascha
Published: February 2024

Zusammenfassung: Hintergrund: Die Anlage und Überprüfung der korrekten Lage blind applizierter Magensonden wird in der klinischen Praxis häufig durch Pflegefachpersonen durchgeführt. Internationale Leitlinien empfehlen zur Lagebestimmung eine radiologische Überprüfung als Methode der Wahl oder wenn die pH-Wert-Messung nicht möglich ist. Für Deutschland liegen weder evidenzbasierte Empfehlungen noch aktuelle Kenntnisse vor. Fragestellung: Welche Methoden setzen Pflegefachpersonen auf deutschen Intensivstationen zur Überprüfung der korrekten Lage von blind applizierten Magensonden ein und wie wird die Zuverlässigkeit verschiedener Methoden eingeschätzt? Methoden: Multizentrisches Fragebogensurvey. Eingeschlossen wurden Überwachungs- und Intensivstationen einer Gelegenheitsstichprobe aus Krankenhäusern in und um Köln. Pro teilnehmende Station wurde eine Pflegefachperson eingeschlossen. Die Auswertung erfolgte vornehmlich deskriptiv. Ergebnisse: In 22 Krankenhäusern haben 38 Stationen ihre Teilnahme zugesagt und 32 (84%) an der Befragung teilgenommen. Die Auskultation am Oberbauch bei gleichzeitiger Luftinsufflation sowie die Aspiration von Magensekret sind wesentliche Methoden zur Lagebestimmung von Magensonden. Als zuverlässige Methoden werden die Auskultation, die Aspiration von Magensekret sowie die radiologische Kontrolle eingeschätzt. Schlussfolgerungen: Die Ergebnisse entsprechen hinsichtlich der Nutzung der Auskultationsmethode nicht internationalen Empfehlungen und belegen die Notwendigkeit evidenzbasierter Best-Practice-Empfehlungen und Schulungen. Es besteht Forschungsbedarf hinsichtlich praktikabler und valider bettseitiger Methoden.
ID4-dependent secretion of VEGFA enhances the invasion capability of breast cancer cells and activates YAP/TAZ via integrin β3-VEGFR2 interaction
Authors: Benedetti Anna , Turco Chiara , Gallo Enzo , Daralioti Theodora , Sacconi Andrea , Pulito Claudio , Donzelli Sara , Tito Claudia , Dragonetti Martina , Perracchio Letizia , Blandino Giovanni , Fazi Francesco , Fontemaggi Giulia
Published: February 2024

Understanding the mechanisms of breast cancer cell communication underlying cell spreading and metastasis formation is fundamental for developing new therapies. ID4 is a proto-oncogene overexpressed in the basal-like subtype of triple-negative breast cancer (TNBC), where it promotes angiogenesis, cancer stem cells, and BRACA1 misfunction. Here, we show that ID4 expression in BC cells correlates with the activation of motility pathways and promotes the production of VEGFA, which stimulates the interaction of VEGFR2 and integrin β3 in a paracrine fashion. This interaction induces the downstream focal adhesion pathway favoring migration, invasion, and stress fiber formation. Furthermore, ID4/ VEGFA/ VEGFR2/ integrin β3 signaling stimulates the nuclear translocation and activation of the Hippo pathway member’s YAP and TAZ, two critical executors for cancer initiation and progression. Our study provides new insights into the oncogenic roles of ID4 in tumor cell migration and YAP/TAZ pathway activation, suggesting VEGFA/ VEGFR2/ integrin β3 axis as a potential target for BC treatment.
Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy
Authors: Zhang Zhiqi , Xu Xiaoxuan , Du Jiawei , Chen Xin , Xue Yonger , Zhang Jianqiong , Yang Xue , Chen Xiaoyuan , Xie Jinbing , Ju Shenghong
Published: February 2024

Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.
Predicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy
Authors: Coffeng Luc E. , Stolk Wilma A. , de Vlas Sake J.
Published: February 2024

Control of soil-transmitted helminths relies heavily on regular large-scale deworming of high-risk groups (e.g., children) with benzimidazole derivatives. Although drug resistance has not yet been documented in human soil-transmitted helminths, regular deworming of cattle and sheep has led to widespread benzimidazole resistance in veterinary helminths. Here we predict the population dynamics of human soil-transmitted helminth infections and drug resistance during 20 years of regular preventive chemotherapy, using an individual-based model. With the current preventive chemotherapy strategy of mainly targeting children in schools, drug resistance may evolve in soil-transmitted helminths within a decade. More intense preventive chemotherapy strategies increase the prospects of soil-transmitted helminths elimination, but also increase the speed at which drug efficacy declines, especially when implementing community-based preventive chemotherapy (population-wide deworming). If during the last decade, preventive chemotherapy against soil-transmitted helminths has led to resistance, we may not have detected it as drug efficacy has not been structurally monitored, or incorrectly so. These findings highlight the need to develop and implement strategies to monitor and mitigate the evolution of benzimidazole resistance.
Ultra-stable and highly reactive colloidal gold nanoparticle catalysts protected using multi-dentate metal oxide nanoclusters
Authors: Xia Kang , Yatabe Takafumi , Yonesato Kentaro , Kikkawa Soichi , Yamazoe Seiji , Nakata Ayako , Ishikawa Ryo , Shibata Naoya , Ikuhara Yuichi , Yamaguchi Kazuya , Suzuki Kosuke
Published: February 2024

Owing to their remarkable properties, gold nanoparticles are applied in diverse fields, including catalysis, electronics, energy conversion and sensors. However, for catalytic applications of colloidal gold nanoparticles, the trade-off between their reactivity and stability is a significant concern. Here we report a universal approach for preparing stable and reactive colloidal small (~3 nm) gold nanoparticles by using multi-dentate polyoxometalates as protecting agents in non-polar solvents. These nanoparticles exhibit exceptional stability even under conditions of high concentration, long-term storage, heating and addition of bases. Moreover, they display excellent catalytic performance in various oxidation reactions of organic substrates using molecular oxygen as the sole oxidant. Our findings highlight the ability of inorganic multi-dentate ligands with structural stability and robust steric and electronic effects to confer stability and reactivity upon gold nanoparticles. This approach can be extended to prepare metal nanoparticles other than gold, enabling the design of novel nanomaterials with promising applications.
Synchrotron intensity gradient revealing magnetic fields in galaxy clusters
Authors: Hu Yue , Stuardi C. , Lazarian A. , Brunetti G. , Bonafede A. , Ho Ka Wai
Published: February 2024

Magnetic fields and their dynamical interplay with matter in galaxy clusters contribute to the physical properties and evolution of the intracluster medium. However, the current understanding of the origin and properties of cluster magnetic fields is still limited by observational challenges. In this article, we map the magnetic fields at hundreds-kpc scales of five clusters RXC J1314.4-2515, Abell 2345, Abell 3376, MCXC J0352.4-7401, and El Gordo using the synchrotron intensity gradient technique in conjunction with high-resolution radio observations from the Jansky Very Large Array (JVLA) and the Karoo Array Telescope (MeerKAT). We demonstrate that the magnetic field orientation of radio relics derived from synchrotron intensity gradient is in agreement with that obtained with synchrotron polarization. Most importantly, the synchrotron intensity gradient is not limited by Faraday depolarization in the cluster central regions and allows us to map magnetic fields in the radio halos of RXC J1314.4-2515 and El Gordo. We find that magnetic fields in radio halos exhibit a preferential direction along the major merger axis and show turbulent structures at higher angular resolution. The results are consistent with expectations from numerical simulations, which predict turbulent magnetic fields in cluster mergers that are stirred and amplified by matter motions.
Skin muscle is the initial site of viral replication for arboviral bunyavirus infection
Authors: Schneider Christine A. , Leung Jacqueline M. , Valenzuela-Leon Paola Carolina , Golviznina Natalya A. , Toso Erik A. , Bosnakovski Darko , Kyba Michael , Calvo Eric , Peterson Karin E.
Published: February 2024

The first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families. LACV is widely myotropic, infecting distal muscle cells of the peritoneum and heart, with limited infection of draining lymph nodes. Surprisingly, muscle cells are resistant to virus-induced cell death, with long term low levels of virus release progressing through the Golgi apparatus. Thus, skin muscle may be a key cell type for the initial infection and spread of arboviral orthobunyaviruses.
Host association and intracellularity evolved multiple times independently in the Rickettsiales
Authors: Castelli Michele , Nardi Tiago , Gammuto Leandro , Bellinzona Greta , Sabaneyeva Elena , Potekhin Alexey , Serra Valentina , Petroni Giulio , Sassera Davide
Published: February 2024

The order Rickettsiales (Alphaproteobacteria) encompasses multiple diverse lineages of host-associated bacteria, including pathogens, reproductive manipulators, and mutualists. Here, in order to understand how intracellularity and host association originated in this order, and whether they are ancestral or convergently evolved characteristics, we built a large and phylogenetically-balanced dataset that includes de novo sequenced genomes and a selection of published genomic and metagenomic assemblies. We perform detailed functional reconstructions that clearly indicates “late” and parallel evolution of obligate host-association in different Rickettsiales lineages. According to the depicted scenario, multiple independent horizontal acquisitions of transporters led to the progressive loss of biosynthesis of nucleotides, amino acids and other metabolites, producing distinct conditions of host-dependence. Each clade experienced a different pattern of evolution of the ancestral arsenal of interaction apparatuses, including development of specialised effectors involved in the lineage-specific mechanisms of host cell adhesion and/or invasion.
The synthetic NLR RGA5HMA5 requires multiple interfaces within and outside the integrated domain for effector recognition
Authors: Zhang Xin , Liu Yang , Yuan Guixin , Wang Shiwei , Wang Dongli , Zhu Tongtong , Wu Xuefeng , Ma Mengqi , Guo Liwei , Guo Hailong , Bhadauria Vijai , Liu Junfeng , Peng You-Liang
Published: February 2024

Some plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). Rice RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here, we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.
Monitoring ocean currents during the passage of Typhoon Muifa using optical-fiber distributed acoustic sensing
Authors: Lin Jianmin , Fang Sunke , He Runjing , Tang Qunshu , Qu Fengzhong , Wang Baoshan , Xu Wen
Published: February 2024

In situ observations under typhoon conditions are sparse and limited. Distributed acoustic sensing (DAS) is an emerging technology that uses submarine optical-fiber (OF) cables to monitor the sea state. Here, we present DAS-based ocean current observations when a super typhoon passed overhead. The microseismic noise induced by ocean surface gravity waves (OSGWs) during Typhoon Muifa (2022) is observed in the ~0.08–0.38 Hz frequency band, with high-frequency (>0.3 Hz) component being tidally modulated. The OSGW propagation along the entire cable is successfully revealed via frequency–wavenumber analysis. Further, a method based on the current-induced Doppler shifts of DAS-recorded OSGW dispersions is proposed to calculate both speeds and directions of horizontal ocean currents. The measured current is consistent with the tidally induced sea-level fluctuations and sea-surface winds observed at a nearby ocean buoy. These observations demonstrate the feasibility of monitoring the ocean current under typhoon conditions using DAS-instrumented cables.
Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine
Authors: Zhao Sen , Zhao Hengqiang , Zhao Lina , Cheng Xi , Zheng Zhifa , Wu Mengfan , Wen Wen , Wang Shengru , Zhou Zixiang , Xie Haibo , Ruan Dengfeng , Li Qing , Liu Xinquan , Ou Chengzhu , Li Guozhuang , Zhao Zhengye , Chen Guilin , Niu Yuchen , Yin Xiangjie , Hu Yuhong , Zhang Xiaochen ,   Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, Liu Sen , Yan Zihui , Li Xiaoxin , Liu Bowen , Huang Yingzhao , Gao Guangxi , Liu Qing , Yang Jianle , Yang Xinyu , Maheshati Aoran , Cai Jihao , Zhu Yuanpeng , Wang Jie , Yang Yang , Li Ziquan , Lin Guanfeng , Ye Xiaohan , Liu Pengfei , Qiu Guixing , Liu Wanlu , Zhao Chengtian , Wu Zhihong , Zhang Jianguo , Wu Nan
Published: February 2024

Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.
Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders
Authors: Yang Qiqi , Wang Ben , Lemey Phillipe , Dong Lu , Mu Tong , Wiebe R. Alex , Guo Fengyi , Trovão Nídia Sequeira , Park Sang Woo , Lewis Nicola , Tsui Joseph L.-H. , Bajaj Sumali , Cheng Yachang , Yang Luojun , Haba Yuki , Li Bingying , Zhang Guogang , Pybus Oliver G. , Tian Huaiyu , Grenfell Bryan
Published: February 2024

Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.
Influence of microgravity on spontaneous calcium activity of primary hippocampal neurons grown in microfluidic chips
Authors: Lecoq Pierre-Ewen , Dupuis Chloé , Mousset Xavier , Benoit-Gonnin Xavier , Peyrin Jean-Michel , Aider Jean-Luc
Published: February 2024

The influence of variations of gravity, either hypergravity or microgravity, on the brain of astronauts is a major concern for long journeys in space, to the Moon or to Mars, or simply long-duration missions on the ISS (International Space Station). Monitoring brain activity, before and after ISS missions already demonstrated important and long term effects on the brains of astronauts. In this study, we focus on the influence of gravity variations at the cellular level on primary hippocampal neurons. A dedicated setup has been designed and built to perform live calcium imaging during parabolic flights. During a CNES (Centre National d’Etudes Spatiales) parabolic flight campaign, we were able to observe and monitor the calcium activity of 2D networks of neurons inside microfluidic devices during gravity changes over different parabolas. Our preliminary results clearly indicate a modification of the calcium activity associated to variations of gravity.
Dopamine transients follow a striatal gradient of reward time horizons
Authors: Mohebi Ali , Wei Wei , Pelattini Lilian , Kim Kyoungjun , Berke Joshua D.
Published: February 2024

Animals make predictions to guide their behavior and update those predictions through experience. Transient increases in dopamine (DA) are thought to be critical signals for updating predictions. However, it is unclear how this mechanism handles a wide range of behavioral timescales—from seconds or less (for example, if singing a song) to potentially hours or more (for example, if hunting for food). Here we report that DA transients in distinct rat striatal subregions convey prediction errors based on distinct time horizons. DA dynamics systematically accelerated from ventral to dorsomedial to dorsolateral striatum, in the tempo of spontaneous fluctuations, the temporal integration of prior rewards and the discounting of future rewards. This spectrum of timescales for evaluative computations can help achieve efficient learning and adaptive motivation for a broad range of behaviors.
A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates
Authors: Rebak Alexandra S. , Hendriks Ivo A. , Elsborg Jonas D. , Buch-Larsen Sara C. , Nielsen Claus H. , Terslev Lene , Kirsch Rebecca , Damgaard Dres , Doncheva Nadezhda T. , Lennartsson Caroline , Rykær Martin , Jensen Lars J. , Christophorou Maria A. , Nielsen Michael L.
Published: February 2024

Despite the importance of citrullination in physiology and disease, global identification of citrullinated proteins, and the precise targeted sites, has remained challenging. Here we employed quantitative-mass-spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites within the HL60 leukemia cell line following differentiation into neutrophil-like cells. We identified 14,056 citrullination sites within 4,008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4. With this resource, we provide quantitative and site-specific information on thousands of PADI4 substrates, including signature histone marks and transcriptional regulators. Additionally, using peptide microarrays, we demonstrate the potential clinical relevance of certain identified sites, through distinct reactivities of antibodies contained in synovial fluid from anti-CCP-positive and anti-CCP-negative people with rheumatoid arthritis. Collectively, we describe the human citrullinome at a systems-wide level, provide a resource for understanding citrullination at the mechanistic level and link the identified targeted sites to rheumatoid arthritis.
Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules
Authors: Abramenko Nikita , Vellieux Fréderic , Veselá Kateřina , Kejík Zdeněk , Hajduch Jan , Masařík Michal , Babula Petr , Hoskovec David , Pacák Karel , Martásek Pavel , Smetana Karel , Jakubek Milan
Published: February 2024

Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.
Transgenic Tg(Kcnj10-ZsGreen) fluorescent reporter mice allow visualization of intermediate cells in the stria vascularis
Authors: Strepay Dillon , Olszewski Rafal T. , Nixon Sydney , Korrapati Soumya , Adadey Samuel , Griffith Andrew J. , Su Yijun , Liu Jiamin , Vishwasrao Harshad , Gu Shoujun , Saunders Thomas , Roux Isabelle , Hoa Michael
Published: February 2024

The stria vascularis (SV) is a stratified epithelium in the lateral wall of the mammalian cochlea, responsible for both endolymphatic ion homeostasis and generation of the endocochlear potential (EP) critical for normal hearing. The SV has three layers consisting predominantly of basal, intermediate, and marginal cells. Intermediate and marginal cells form an intricate interdigitated network of cell projections making discrimination of the cells challenging. To enable intermediate cell visualization, we engineered by BAC transgenesis, reporter mouse lines expressing ZsGreen fluorescent protein under the control of Kcnj10 promoter and regulatory sequences. Kcnj10 encodes KCNJ10 protein (also known as Kir4.1 or Kir1.2), an ATP-sensitive inwardly-rectifying potassium channel critical to EP generation, highly expressed in SV intermediate cells. In these transgenic mice, ZsGreen fluorescence mimics Kcnj10 endogenous expression in the cochlea and was detected in the intermediate cells of the SV, in the inner phalangeal cells, Hensen’s, Deiters’ and pillar cells, in a subset of spiral ganglion neurons, and in glial cells. We show that expression of the transgene in hemizygous mice does not alter auditory function, nor EP. These transgenic Tg(Kcnj10-ZsGreen) mice allow live and fixed tissue visualization of ZsGreen-expressing intermediate cells and will facilitate future studies of stria vascularis cell function.
Metabolite profiling and in-silico studies show multiple effects of insecticidal actinobacterium on Spodoptera littoralis
Authors: Diab Mohamed Khaled , Mead Hala Mohamed , Khedr Mohamad Ahmad , Nafie Mohamed S. , Abu-Elsaoud Abdelghafar Mohamed , El-Shatoury Sahar Ahmed
Published: February 2024

The polyphagous pest, Spodoptera littoralis (Boisduval), poses a significant global economic threat by gregariously feeding on over a hundred plant species, causing substantial agricultural losses. Addressing this challenge requires ongoing research to identify environmentally safe control agents. This study aimed to elucidate the insecticidal activity of the metabolite (ES2) from a promising endophytic actinobacterium strain, Streptomyces sp. ES2 EMCC2291. We assessed the activity of ES2 against the eggs and fourth-instar larvae of S. littoralis through spectrophotometric measurements of total soluble protein, α- and β-esterases, polyphenol oxidase (PPO), and catalase enzyme (CAT). The assessments were compared to commercial Biosad® 22.8% SC. Untargeted metabolomics using LC-QTOF-MS/MS identified 83 metabolic compounds as chemical constituents of ES2. The median lethal concentration (LC50) of ES2 (165 mg/mL) for treated Spodoptera littoralis eggs showed significant differences in polyphenol oxidase and catalase enzymatic activities, while the LC50 of ES2 (695 mg/mL) for treated S. littoralis fourth instar larvae showed lower significance in α- and β-esterase activities. Molecular docking of ES2 identified seven potent biocidal compounds, showing strong affinity to PPO and catalase CAT proteins in S. littoralis eggs while displaying limited binding to alpha and beta esterase proteins in the larvae. The results contribute to the understanding of ES2 as a promising alternative biopesticide, providing insights for future research and innovative applications in sustainable pest management strategies.