bluuebunny/crossref_metadata_2025 huggingface dataset:
Disciplining the disciplined: Making sense of the gender gap that lies at the core of puritanical morals
Authors: Royzman Edward B. , Borislow Samuel H.
Published: October 2023

Because suppression of sex has been and is at the core of puritanical morals, a proper account thereof would need to explain why suppression of sex has been largely directed towards the human female. Not only do the authors not account for this pattern, but their general model would seem to predict the reverse – that is, greater suppression/control of the male libido.
Puritanism as moral advertisement helps solve the puzzle of ineffective moralization
Authors: Blancke Stefaan
Published: October 2023

The moral disciplining theory proposes that people moralize excessive innocent behavior to discipline others to behave in ways that facilitate cooperation. However, such disciplining might not always be effective. To solve this puzzle of ineffective moralization we should think of puritanism in terms of moral advertisement aimed at reputation management rather than the manipulation of others.
Signals of discipline and puritanical challenges to liberty
Authors: Celniker Jared B. , Ditto Peter H. , Piff Paul K. , Shariff Azim F.
Published: October 2023

We extend the target authors' moral disciplining theory (MDT) by discussing signaling, proscriptive and prescriptive morality, and the dynamics by which signaling may operate in tandem with proscriptive and prescriptive forms of moral disciplining. We also suggest that MDT can help explain challenges to economic and social progress by revealing fundamental tensions between puritanical intuitions and liberal ideals.
The evolution of puritanical morality has not always served to strengthen cooperation, but to reinforce male dominance and exclude women
Authors: Szocik Konrad
Published: October 2023

Puritanical morality regulates a range of seemingly insignificant behaviors, including those involving human sexuality. A sizable portion of the latter particularly burdens women, who are held responsible for the moral conduct of men. In my paper, I show that these norms have not necessarily served to evolve cooperation, but to subjugate and eliminate women from public life.
Puritanical morality and the scaffolded evolution of self-control
Authors: Veit Walter , Browning Heather
Published: October 2023

There is a puzzle in reconciling the widespread presence of puritanical norms condemning harmless pleasures with the theory that morality evolved to reap the benefits of cooperation. Here, we draw on the work of several philosophers to support the argument by Fitouchi et al. that these norms evolved to facilitate and scaffold self-control for the sake of cooperation.
As the crow flies: tracking policy diffusion through stakeholder networks
Authors: Mistur Evan M. , Matisoff Daniel C.
Published: October 2023

Policy diffusion is an important element of the policy formation process. However, understanding of the micro-level interactions governing policy spread remains limited. Much of the literature focuses on macro-level proxies for intergovernmental connectivity. These proxies outline broad diffusion patterns without specifying the micro-level mechanisms that govern how individuals facilitate that diffusion. The role of stakeholders in diffusion in the policy subsystem is also poorly understood. We construct a panel dataset covering the spread of the US ecotourism programs from 1993 to 2016 to investigate how micro-level movement within stakeholder networks explains state-level policy diffusion over time. Using fixed-effects regression, we find that stakeholder movement significantly drives diffusion, acting as a mechanism of knowledge transfer. Our findings provide a more precise theoretical understanding of how policy knowledge diffuses at the micro level, empirically explain the role of policy stakeholders in diffusion, and highlight the value of citizen-science data for policy research.
Descending aortic translocation for left aortic arch with right descending aorta and coarctation of the aorta
Authors: Lee Cheul , Lee Won Young , Shin Ju Ae , Lee Jae Young
Published: October 2023

Left aortic arch with right descending aorta associated with coarctation of the aorta is a rare congenital cardiac anomaly. Conventional aortic arch repair in this condition may cause airway compression by the abnormally coursing descending aorta. We present the case of a neonate with this anomaly who underwent successful descending aortic translocation to prevent postoperative left main bronchial stenosis.
Comparative Studies of Russian and European Welfare Polities
Authors: Titterton Mike , Iarskaia-Smirnova Elena
Published: October 2023

The authors provide a scholarly conspectus of comparative studies involving Russian, EU8 and EU15 Welfare Polities. They elaborate the notion of the ‘welfare polity’ and its potential for enhancing comparative studies of welfare institutions, policies and practices. This is accompanied by an overview of trends in comparative studies involving Russian, EU8 and EU15 countries, along with a consideration of how comparative research involving these states can be strengthened. Gaps in the literature and evidence base, including systematic cross-national and temporal data on the design and implementation of social policies and social protection, are highlighted. A shared concern was found with the growth of division and exclusion exacerbated by global economic factors and by state-level policy shifts, a trend especially notable in Russian studies. Fruitful pointers for future research and international collaboration are indicated and the need for further comparative efforts emphasised at a challenging time for geopolitical relations.
How Long Do Runoff‐Generated Debris‐Flow Hazards Persist After Wildfire?
Authors: Graber Andrew P. , Thomas Matthew A. , Kean Jason W.
Published: October 2023

Runoff‐generated debris flows are a potentially destructive and deadly response to wildfire until sufficient vegetation and soil‐hydraulic recovery have reduced susceptibility to the hazard. Elevated debris‐flow susceptibility may persist for several years, but the controls on the timespan of the susceptible period are poorly understood. To evaluate the connection between vegetation recovery and debris‐flow occurrence, we calculated recovery for 25 fires in the western United States using satellite‐derived leaf area index (LAI) and compared recovery estimates to the timing of 536 debris flows from the same fires. We found that the majority (>98%) of flows occurred when LAI was less than 2/3 of typical prefire values. Our results show that total vegetation recovery is not necessary to inhibit runoff‐generated flows in a wide variety of regions in the western United States. Satellite‐derived vegetation data show promise for estimating the timespan of debris‐flow susceptibility.
Simulating Atmospheric Dust With a Global Variable‐Resolution Model: Model Description and Impacts of Mesh Refinement
Authors: Feng Jiawang , Zhao Chun , Du Qiuyan , Xu Mingyue , Gu Jun , Hu Zhiyuan , Chen Yu
Published: October 2023

In this study, a global variable‐resolution modeling framework of atmospheric dust and its radiative feedback is established and evaluated. In this model, atmospheric dust is simulated simultaneously with meteorological fields, and dust‐radiation interactions are included. Five configurations of global mesh with refinement at different resolutions and over different regions are used to explore the impacts of regional refinement on modeling dust lifecycle at regional and global scales. The model reasonably produces the overall magnitudes and spatial variabilities of global dust metrics such as surface mass concentration, deposition, aerosol optical depth, and radiative forcing compared to observations and previous modeling results. Two global variable‐resolution simulations with mesh refinement over major deserts of North Africa (V16 km‐NA) and East Asia (V16 km‐EA) simulate less dust emissions and smaller dry deposition rates inside the refined regions due to the weakened near‐surface wind speed caused by better resolved topographic complexity at higher resolution. The dust mass loadings over North Africa are close to each other between V16 km‐NA and the quasi‐uniform resolution (∼120 km) (U120 km), while over East Asia, V16 km‐EA simulates higher dust mass loading. Over the non‐refined areas with the same resolution, the difference between global variable‐resolution and uniform‐resolution experiments also exists, which is partly related to their difference in dynamic time‐step and the coefficient for horizontal diffusion. Refinement at convection‐permitting resolution around the Tibetan Plateau (TP) simulates less dust due to its more efficient wet scavenging from resolved convective precipitation around the TP against coarse resolution.
Whole-infrared-band camouflage with dual-band radiative heat dissipation
Authors: Qin Bing , Zhu Yining , Zhou Yiwei , Qiu Min , Li Qiang
Published: October 2023

Advanced multispectral detection technologies have emerged as a significant threat to objects, necessitating the use of multiband camouflage. However, achieving effective camouflage and thermal management across the entire infrared spectrum, especially the short-wave infrared (SWIR) band, remains challenging. This paper proposes a multilayer wavelength-selective emitter that achieves effective camouflage across the entire infrared spectrum, including the near-infrared (NIR), SWIR, mid-wave infrared (MWIR), and long-wave infrared (LWIR) bands, as well as the visible (VIS) band. Furthermore, the emitter enables radiative heat dissipation in two non-atmospheric windows (2.5–3 μm and 5–8 μm). The emitter’s properties are characterized by low emittance of 0.270/0.042/0.218 in the SWIR/MWIR/LWIR bands, and low reflectance of 0.129/0.281 in the VIS/NIR bands. Moreover, the high emittance of 0.742/0.473 in the two non-atmospheric windows ensures efficient radiative heat dissipation, which results in a temperature decrement of 14.4 °C compared to the Cr reference at 2000 W m−2 input power density. This work highlights the role of solar radiance in camouflage, and provides a comprehensive guideline for developing multiband camouflage compatible with radiative heat dissipation, from the visible to LWIR.
GSDMD promotes neutrophil extracellular traps via mtDNA-cGAS-STING pathway during lung ischemia/reperfusion
Authors: Zhao Chen , Liang Fangte , Ye Mengling , Wu Siyi , Qin Yi , Zhao Lu , Zhang Lu , He Jing , Cen Liming , Lin Fei
Published: October 2023

Lung ischemia/reperfusion injury (LIRI) is a complex pathophysiological process, with the histopathological hallmark of neutrophils migrating into the lungs. Neutrophil extracellular traps (NETs) have been suggested to exert a critical role in the pathogenesis of inflammation and infection in humans and animals, while the exact functions and underlying mechanisms of NETs in LIRI remain insufficiently elucidated. In this study, we investigated the role of pore-forming protein gasdermin D (GSDMD) on NETs release in LIRI induced by lung ischemia/reperfusion (I/R). We found that disulfiram, a GSDMD inhibitor, dramatically reduced NETs release and pathological injury in lung I/R in vivo and in vitro. Additionally, GSDMD caused mitochondrial DNA (mtDNA) leaking into the neutrophil cytosol, and then the cytoplasmic mtDNA activated the cGAS-STING signaling pathway and stimulated NETs formation in lung I/R. Furthermore, inhibition of cGAS/STING pathway could inhibit cytosol mtDNA mediated NETs formation.
Strain control of a bandwidth-driven spin reorientation in Ca3Ru2O7
Authors: Dashwood C. D. , Walker A. H. , Kwasigroch M. P. , Veiga L. S. I. , Faure Q. , Vale J. G. , Porter D. G. , Manuel P. , Khalyavin D. D. , Orlandi F. , Colin C. V. , Fabelo O. , Krüger F. , Perry R. S. , Johnson R. D. , Green A. G. , McMorrow D. F.
Published: October 2023

The layered-ruthenate family of materials possess an intricate interplay of structural, electronic and magnetic degrees of freedom that yields a plethora of delicately balanced ground states. This is exemplified by Ca3Ru2O7, which hosts a coupled transition in which the lattice parameters jump, the Fermi surface partially gaps and the spins undergo a 90∘ in-plane reorientation. Here, we show how the transition is driven by a lattice strain that tunes the electronic bandwidth. We apply uniaxial stress to single crystals of Ca3Ru2O7, using neutron and resonant x-ray scattering to simultaneously probe the structural and magnetic responses. These measurements demonstrate that the transition can be driven by externally induced strain, stimulating the development of a theoretical model in which an internal strain is generated self-consistently to lower the electronic energy. We understand the strain to act by modifying tilts and rotations of the RuO6 octahedra, which directly influences the nearest-neighbour hopping. Our results offer a blueprint for uncovering the driving force behind coupled phase transitions, as well as a route to controlling them.
Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE
Authors: Chongsaritsinsuk Joann , Steigmeyer Alexandra D. , Mahoney Keira E. , Rosenfeld Mia A. , Lucas Taryn M. , Smith Courtney M. , Li Alice , Ince Deniz , Kearns Fiona L. , Battison Alexandria S. , Hollenhorst Marie A. , Judy Shon D. , Tiemeyer Katherine H. , Attah Victor , Kwon Catherine , Bertozzi Carolyn R. , Ferracane Michael J. , Lemmon Mark A. , Amaro Rommie E. , Malaker Stacy A.
Published: October 2023

Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of biological functions. In particular, the T cell immunoglobulin and mucin-domain containing family of proteins (TIM-1, -3, -4) decorate immune cells and act as key regulators in cellular immunity. However, their dense O-glycosylation remains enigmatic, primarily due to the challenges associated with studying mucin domains. Here, we demonstrate that the mucinase SmE has a unique ability to cleave at residues bearing very complex glycans. SmE enables improved mass spectrometric analysis of several mucins, including the entire TIM family. With this information in-hand, we perform molecular dynamics (MD) simulations of TIM-3 and -4 to understand how glycosylation affects structural features of these proteins. Finally, we use these models to investigate the functional relevance of glycosylation for TIM-3 function and ligand binding. Overall, we present a powerful workflow to better understand the detailed molecular structures and functions of the mucinome.
Genomic signatures of past and present chromosomal instability in Barrett’s esophagus and early esophageal adenocarcinoma
Authors: Bao Chunyang , Tourdot Richard W. , Brunette Gregory J. , Stewart Chip , Sun Lili , Baba Hideo , Watanabe Masayuki , Agoston Agoston T. , Jajoo Kunal , Davison Jon M. , Nason Katie S. , Getz Gad , Wang Kenneth K. , Imamura Yu , Odze Robert , Bass Adam J. , Stachler Matthew D. , Zhang Cheng-Zhong
Published: October 2023

The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we perform haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.
Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1
Authors: Xue Jing , Zeng Weizhong , Han Yan , John Scott , Ottolia Michela , Jiang Youxing
Published: October 2023

Na+/Ca2+ exchangers (NCX) transport Ca2+ in or out of cells in exchange for Na+. They are ubiquitously expressed and play an essential role in maintaining cytosolic Ca2+ homeostasis. Although extensively studied, little is known about the global structural arrangement of eukaryotic NCXs and the structural mechanisms underlying their regulation by various cellular cues including cytosolic Na+ and Ca2+. Here we present the cryo-EM structures of human cardiac NCX1 in both inactivated and activated states, elucidating key structural elements important for NCX ion exchange function and its modulation by cytosolic Ca2+ and Na+. We demonstrate that the interactions between the ion-transporting transmembrane (TM) domain and the cytosolic regulatory domain define the activity of NCX. In the inward-facing state with low cytosolic [Ca2+], a TM-associated four-stranded β-hub mediates a tight packing between the TM and cytosolic domains, resulting in the formation of a stable inactivation assembly that blocks the TM movement required for ion exchange function. Ca2+ binding to the cytosolic second Ca2+-binding domain (CBD2) disrupts this inactivation assembly which releases its constraint on the TM domain, yielding an active exchanger. Thus, the current NCX1 structures provide an essential framework for the mechanistic understanding of the ion transport and cellular regulation of NCX family proteins.
TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression
Authors: Heyes Elizabeth , Wilhelmson Anna S. , Wenzel Anne , Manhart Gabriele , Eder Thomas , Schuster Mikkel B. , Rzepa Edwin , Pundhir Sachin , D’Altri Teresa , Frank Anne-Katrine , Gentil Coline , Woessmann Jakob , Schoof Erwin M. , Meggendorfer Manja , Schwaller Jürg , Haferlach Torsten , Grebien Florian , Porse Bo T.
Published: October 2023

The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPADM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPANT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. The most frequently co-mutated genes in CEBPADM AML are GATA2 and TET2, however the molecular mechanisms underlying this co-mutational spectrum are incomplete. By combining transcriptomic and epigenomic analyses of CEBPA-TET2 co-mutated patients with models thereof, we identify GATA2 as a conserved target of the CEBPA-TET2 mutational axis, providing a rationale for the mutational spectra in CEBPADM AML. Elevated CEBPA levels, driven by CEBPANT, mediate recruitment of TET2 to the Gata2 distal hematopoietic enhancer thereby increasing Gata2 expression. Concurrent loss of TET2 in CEBPADM AML induces a competitive advantage by increasing Gata2 promoter methylation, thereby rebalancing GATA2 levels. Of clinical relevance, demethylating treatment of Cebpa-Tet2 co-mutated AML restores Gata2 levels and prolongs disease latency.
Metal to non-metal sites of metallic sulfides switching products from CO to CH4 for photocatalytic CO2 reduction
Authors: Chai Yao , Kong Yuehua , Lin Min , Lin Wei , Shen Jinni , Long Jinlin , Yuan Rusheng , Dai Wenxin , Wang Xuxu , Zhang Zizhong
Published: October 2023

The active center for the adsorption and activation of carbon dioxide plays a vital role in the conversion and product selectivity of photocatalytic CO2 reduction. Here, we find multiple metal sulfides CuInSnS4 octahedral nanocrystal with exposed (1 1 1) plane for the selectively photocatalytic CO2 reduction to methane. Still, the product is switched to carbon monoxide on the corresponding individual metal sulfides In2S3, SnS2, and Cu2S. Unlike the common metal or defects as active sites, the non-metal sulfur atom in CuInSnS4 is revealed to be the adsorption center for responding to the selectivity of CH4 products. The carbon atom of CO2 adsorbed on the electron-poor sulfur atom of CuInSnS4 is favorable for stabilizing the intermediates and thus promotes the conversion of CO2 to CH4. Both the activity and selectivity of CH4 products over the pristine CuInSnS4 nanocrystal can be further improved by the modification of with various co-catalysts to enhance the separation of the photogenerated charge carrier. This work provides a non-metal active site to determine the conversion and selectivity of photocatalytic CO2 reduction.
Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis
Authors: Li Guanqun , Liu Liwei , Lu Tianqi , Sui Yuhang , Zhang Can , Wang Yongwei , Zhang Tao , Xie Yu , Xiao Peng , Zhao Zhongjie , Cheng Chundong , Hu Jisheng , Chen Hongze , Xue Dongbo , Chen Hua , Wang Gang , Kong Rui , Tan Hongtao , Bai Xuewei , Li Zhibo , McAllister Florencia , Li Le , Sun Bei
Published: October 2023

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.
Inverse design of chiral functional films by a robotic AI-guided system
Authors: Xie Yifan , Feng Shuo , Deng Linxiao , Cai Aoran , Gan Liyu , Jiang Zifan , Yang Peng , Ye Guilin , Liu Zaiqing , Wen Li , Zhu Qing , Zhang Wanjun , Zhang Zhanpeng , Li Jiahe , Feng Zeyu , Zhang Chutian , Du Wenjie , Xu Lixin , Jiang Jun , Chen Xin , Zou Gang
Published: October 2023

Artificial chiral materials and nanostructures with strong and tuneable chiroptical activities, including sign, magnitude, and wavelength distribution, are useful owing to their potential applications in chiral sensing, enantioselective catalysis, and chiroptical devices. Thus, the inverse design and customized manufacturing of these materials is highly desirable. Here, we use an artificial intelligence (AI) guided robotic chemist to accurately predict chiroptical activities from the experimental absorption spectra and structure/process parameters, and generate chiral films with targeted chiroptical activities across the full visible spectrum. The robotic AI-chemist carries out the entire process, including chiral film construction, characterization, and testing. A machine learned reverse design model using spectrum embedded descriptors is developed to predict optimal structure/process parameters for any targeted chiroptical property. A series of chiral films with a dissymmetry factor as high as 1.9 (gabs ~ 1.9) are identified out of more than 100 million possible structures, and their feasible application in circular polarization-selective color filters for multiplex laser display and switchable circularly polarized (CP) luminescence is demonstrated. Our findings not only provide chiral films with the highest reported chiroptical activity, but also have great fundamental value for the inverse design of chiroptical materials.
Signature of spin-phonon coupling driven charge density wave in a kagome magnet
Authors: Miao H. , Zhang T. T. , Li H. X. , Fabbris G. , Said A. H. , Tartaglia R. , Yilmaz T. , Vescovo E. , Yin J.-X. , Murakami S. , Feng X. L. , Jiang K. , Wu X. L. , Wang A. F. , Okamoto S. , Wang Y. L. , Lee H. N.
Published: October 2023

The intertwining between spin, charge, and lattice degrees of freedom can give rise to unusual macroscopic quantum states, including high-temperature superconductivity and quantum anomalous Hall effects. Recently, a charge density wave (CDW) has been observed in the kagome antiferromagnet FeGe, indicative of possible intertwining physics. An outstanding question is that whether magnetic correlation is fundamental for the spontaneous spatial symmetry breaking orders. Here, utilizing elastic and high-resolution inelastic x-ray scattering, we observe a c-axis superlattice vector that coexists with the 2$$\times$$
×
2$$\times$$
×
1 CDW vectors in the kagome plane. Most interestingly, between the magnetic and CDW transition temperatures, the phonon dynamical structure factor shows a giant phonon-energy hardening and a substantial phonon linewidth broadening near the c-axis wavevectors, both signaling the spin-phonon coupling. By first principles and model calculations, we show that both the static spin polarization and dynamic spin excitations intertwine with the phonon to drive the spatial symmetry breaking in FeGe.
Accurate energy barriers for catalytic reaction pathways: an automatic training protocol for machine learning force fields
Authors: Schaaf Lars L. , Fako Edvin , De Sandip , Schäfer Ansgar , Csányi Gábor
Published: October 2023

We introduce a training protocol for developing machine learning force fields (MLFFs), capable of accurately determining energy barriers in catalytic reaction pathways. The protocol is validated on the extensively explored hydrogenation of carbon dioxide to methanol over indium oxide. With the help of active learning, the final force field obtains energy barriers within 0.05 eV of Density Functional Theory. Thanks to the computational speedup, not only do we reduce the cost of routine in-silico catalytic tasks, but also find an alternative path for the previously established rate-limiting step, with a 40% reduction in activation energy. Furthermore, we illustrate the importance of finite temperature effects and compute free energy barriers. The transferability of the protocol is demonstrated on the experimentally relevant, yet unexplored, top-layer reduced indium oxide surface. The ability of MLFFs to enhance our understanding of extensively studied catalysts underscores the need for fast and accurate alternatives to direct ab-initio simulations.
Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets
Authors: Cheung Michael , Chang Cheng , Rathnasinghe Raveen , Rossignol Evan , Zhang Yunfei , Ferrari Annette , Patel Harsh , Huang Yanjun , Sanchez Guillen Michelle , Scalzo Tina , Lee Changkeun , Otten Gillis R. , Settembre Ethan C. , Music Nedzad , Palladino Giuseppe , Wen Yingxia
Published: October 2023

Currently licensed influenza vaccines focus immune responses on viral hemagglutinin (HA), while the other major surface glycoprotein neuraminidase (NA) is not tightly controlled in inactivated vaccine formulations despite evidence that anti-NA antibodies reduce clinical disease. We utilized a bicistronic self-amplifying mRNA (sa-mRNA) platform encoding both HA and NA from four seasonal influenza strains, creating a quadrivalent influenza vaccine. sa-mRNA vaccines encoding an NA component induced the production of NA-inhibiting antibodies and CD4+ T-cell responses in both monovalent and quadrivalent formulations. Including NA in the vaccine enabled cross-neutralization against antigenically drifted strains and provided greater protection than HA alone upon A(H3N2) challenge in ferrets. These results demonstrate that next-generation bicistronic sa-mRNA vaccines expressing HA and NA induce potent antibodies against both viral coat proteins, as well as vaccine-specific cell-mediated immunity. When formulated as a quadrivalent seasonal influenza vaccine, the sa-mRNA platform provides an opportunity to increase the breadth of protection through cross-neutralizing anti-NA antibodies.
Plasma proteomic associations with genetics and health in the UK Biobank
Authors: Sun Benjamin B. , Chiou Joshua , Traylor Matthew , Benner Christian , Hsu Yi-Hsiang , Richardson Tom G. , Surendran Praveen , Mahajan Anubha , Robins Chloe , Vasquez-Grinnell Steven G. , Hou Liping , Kvikstad Erika M. , Burren Oliver S. , Davitte Jonathan , Ferber Kyle L. , Gillies Christopher E. , Hedman Åsa K. , Hu Sile , Lin Tinchi , Mikkilineni Rajesh , Pendergrass Rion K. , Pickering Corran , Prins Bram , Baird Denis , Chen Chia-Yen , Ward Lucas D. , Deaton Aimee M. , Welsh Samantha , Willis Carissa M. , Lehner Nick , Arnold Matthias , Wörheide Maria A. , Suhre Karsten , Kastenmüller Gabi , Sethi Anurag , Cule Madeleine , Raj Anil ,   Alnylam Human Genetics,   AstraZeneca Genomics Initiative,   Biogen Biobank Team,   Bristol Myers Squibb,   Genentech Human Genetics,   GlaxoSmithKline Genomic Sciences,   Pfizer Integrative Biology,   Population Analytics of Janssen Data Sciences,   Regeneron Genetics Center, Kang Hyun Ming , Burkitt-Gray Lucy , Melamud Eugene , Black Mary Helen , Fauman Eric B. , Howson Joanna M. M. , Kang Hyun Min , McCarthy Mark I. , Nioi Paul , Petrovski Slavé , Scott Robert A. , Smith Erin N. , Szalma Sándor , Waterworth Dawn M. , Mitnaul Lyndon J. , Szustakowski Joseph D. , Gibson Bradford W. , Miller Melissa R. , Whelan Christopher D.
Published: October 2023

The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public–private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics1.
Bridging two insect flight modes in evolution, physiology and robophysics
Authors: Gau Jeff , Lynch James , Aiello Brett , Wold Ethan , Gravish Nick , Sponberg Simon
Published: October 2023

Since taking flight, insects have undergone repeated evolutionary transitions between two seemingly distinct flight modes1–3. Some insects neurally activate their muscles synchronously with each wingstroke. However, many insects have achieved wingbeat frequencies beyond the speed limit of typical neuromuscular systems by evolving flight muscles that are asynchronous with neural activation and activate in response to mechanical stretch2–8. These modes reflect the two fundamental ways of generating rhythmic movement: time-periodic forcing versus emergent oscillations from self-excitation8–10. How repeated evolutionary transitions have occurred and what governs the switching between these distinct modes remain unknown. Here we find that, despite widespread asynchronous actuation in insects across the phylogeny3,6, asynchrony probably evolved only once at the order level, with many reversions to the ancestral, synchronous mode. A synchronous moth species, evolved from an asynchronous ancestor, still preserves the stretch-activated muscle physiology. Numerical and robophysical analyses of a unified biophysical framework reveal that rather than a dichotomy, these two modes are two regimes of the same dynamics. Insects can transition between flight modes across a bridge in physiological parameter space. Finally, we integrate these two actuation modes into an insect-scale robot11–13that enables transitions between modes and unlocks a new self-excited wingstroke strategy for engineered flight. Together, this framework accounts for repeated transitions in insect flight evolution and shows how flight modes can flip with changes in physiological parameters.
A high throughput screen for pharmacological inhibitors of the carbohydrate response element
Authors: You Shaochen , Bollong Michael J.
Published: October 2023

A central regulator of metabolism, transcription factor carbohydrate response element binding protein (ChREBP) senses and responds to dietary glucose levels by stimulating the transcription of glycolytic and lipogenic enzymes. Genetic depletion of ChREBP rescues β-cell dysfunction arising from high glucose levels, suggesting that inhibiting ChREBP might represent an attractive therapeutic approach to manage diabetes and other metabolic diseases. However, the molecular mechanisms governing ChREBP activation are poorly understood and chemical tools to probe the cellular activity of ChREBP are lacking. Here, we report a high-throughput pharmacological screen in INS-1E β-cells that identified novel inhibitors of ChREBP-driven transcription at carbohydrate response element sites, including three putative covalent inhibitors and two likely non-covalent chemical scaffolds. This work affords a pharmacological toolkit to help uncover the signaling logic controlling ChREBP activation and may ultimately reveal potential therapeutic approaches for treating metabolic disease.
Impact of decreased levels of total CO2 on in-hospital mortality in patients with COVID-19
Authors: Kim Yaerim , Kwon Soie , Kim Seong Geun , Lee Jeonghwan , Han Chung-hee , Yu Sungbong , Kim Byunggun , Paek Jin Hyuk , Park Woo Yeong , Jin Kyubok , Han Seungyeup , Kim Dong Ki , Lim Chun Soo , Kim Yon Su , Lee Jung Pyo
Published: October 2023

Decreased total CO2 (tCO2) is significantly associated with all-cause mortality in critically ill patients. Because of a lack of data to evaluate the impact of tCO2 in patients with COVID-19, we assessed the impact of tCO2 on all-cause mortality in this study. We retrospectively reviewed the data of hospitalized patients with COVID-19 in two Korean referral hospitals between February 2020 and September 2021. The primary outcome was in-hospital mortality. We assessed the impact of tCO2 as a continuous variable on mortality using the Cox-proportional hazard model. In addition, we evaluated the relative factors associated with tCO2 ≤ 22 mmol/L using logistic regression analysis. In 4,423 patients included, the mean tCO2 was 24.8 ± 3.0 mmol/L, and 17.9% of patients with tCO2 ≤ 22 mmol/L. An increase in mmol/L of tCO2 decreased the risk of all-cause mortality by 4.8% after adjustment for age, sex, comorbidities, and laboratory values. Based on 22 mmol/L of tCO2, the risk of mortality was 1.7 times higher than that in patients with lower tCO2. This result was maintained in the analysis using a cutoff value of tCO2 24 mmol/L. Higher white blood cell count; lower hemoglobin, serum calcium, and eGFR; and higher uric acid, and aspartate aminotransferase were significantly associated with a tCO2 value ≤ 22 mmol/L. Decreased tCO2 significantly increased the risk of all-cause mortality in patients with COVID-19. Monitoring of tCO2 could be a good indicator to predict prognosis and it needs to be appropriately managed in patients with specific conditions.
Human scent as a first-line defense against disease
Authors: Gordon Amy R. , Lundström Johan N. , Kimball Bruce A. , Karshikoff Bianka , Sorjonen Kimmo , Axelsson John , Lekander Mats , Olsson Mats J.
Published: October 2023

Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals’ body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from “sick” individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.
Behavioral responses of wild chimpanzees toward a juvenile that suddenly lost its animacy due to a fall accident
Authors: Shimada Masaki , Yano Wataru
Published: October 2023

Detailed observations of animal reactions to a collapsed individual in wild are rare but essential to debates about the perception of death by nonhuman animals, including chimpanzees. A male juvenile chimpanzee named Volta, a member of the M group in the Mahale Mountains National Park, fell from a tall tree and was temporarily incapacitated, suffering a severe concussion and nasal bone fracture. However, Volta showed signs of gradual recovery. We compared the behavior of other chimpanzees towards Volta with the previous reports on the behavior towards collapsed or recently dead group members. We found that behaviors towards Volta were similar to those observed towards collapsed or dead members. These included other-regarding behaviors and aggressive behaviors, and notably, licking of Volta’s blood, which has not been previously reported. Adult males tended to be in close proximity to Volta for longer periods than adult females. The social situation with adult males including alpha male, surrounding Volta likely influenced the behavior of other individuals. Exploring the state of recovery of the injured individual, by closely approaching, directing various behaviors, and observing the reactions of the victim, and demonstrate tolerance and consideration towards the victim.
Following the footsteps of Burmeister's leaf frog (Phyllomedusa burmeisteri) in the Atlantic forest of Brazil
Authors: Pareja-Mejía Daniela , Benevides Júlia , Gomes Lidiane , Moreira Da Silva Neto Edvaldo , Queiroz Menezes Vinícius , Silva Roseno Rafaella , Sabino Martins Amanda , Solé Mirco
Published: October 2023

Amphibians are organisms which mainly have a biphasic life cycle. When at the larval stage, their habitat is generally aquatic, and when adults, they become terrestrial. Pond-breeding amphibians are sensitive to some disturbances in their environment which lead to the decline of a population. The interactions between the species and their environment are performed through movement. Movement ecology combines and explains the movement data of organisms with biotic and abiotic factors and because of this, knowing the movement of these creatures is of great ecological importance. We used the spool-and-line methodology in individuals of the treefrog Phyllomedusa burmeisteri, at the Reserva Ecologica Michelin, located in the southern region of Bahia in Brazil to study their movement patterns in different environments inside and outside of the forest. We monitored 19 P. burmeisteri individuals that presented a mean total movement distance of 2160.76 cm (S.D. 1152.42). We found no significant difference in the trajectories of individuals in forested and open areas, as well as a positive relationship between the distances individuals moved and their weight only in forested areas. no relationship between distance and weight of these individuals. We observed that individuals followed non-linear paths and the number of steps from one place to another varied among individuals. Our movement ecology data allows us to answer questions about short-term movement patterns of Phyllomedusa burmeisteri. This is the first step to start understanding the spatial cognition of treefrogs from the Atlantic Forest and to fill gaps about life habits of these frogs. Information on the movement patterns of a species, as well as its home range can help to create conservation strategies, regarding the creation or delimitation of protected areas, for example.
Circulatory extracellular vesicle derived miR-195-5p promotes cellular apoptosis and suppresses cell proliferation in the buffalo endometrial primary cell culture
Authors: Pal Ankit , Karanwal Seema , Chera Jatinder Singh , Batra Vipul , Kumaresan Arumugam , Sarwalia Parul , Datta Tirtha K. , Kumar Rakesh
Published: October 2023

In pregnant animals, communication between the mother and conceptus occurs via extracellular vesicles (EVs) that carry several biomolecules such as nucleic acids (miRNAs, mRNAs), proteins, and lipids. At the time of implantation, the endometrium undergoes several morphological and physiological changes, such as angiogenesis, apoptosis, and cell proliferation regulation at the implantation site, to attain a receptive state. This study was conducted to detect pregnancy-specific miRNAs derived from extracellular vesicles in the systemic circulation of Bubalus bubalis (water buffalo) and to assess their functional significance in the modulation of endometrial primary cells. The extracellular vesicles were isolated from the blood plasma using a precipitation-based method and further characterized by various methods such as Differential light scattering, Nanoparticle tracking assay, Western blot, and transmission electron microscopy. The relative expression of the selected extracellular vesicles associated miRNAs (EV-miRNA) at different intervals (days 15, 19, 25, and 30) post artificial insemination (AI) was analyzed using RT-qPCR, and expression of miR-195-5p was found to be significantly higher (P < 0.01) in pregnant animals on day 19 post AI (implantation window) as compared to day 15 post AI. The elevated expression might indicate the involvement of this miRNA in the maternal-conceptus cross-talk occurring during the implantation period. The KEGG pathway enrichment and Gene Ontology analyses of the miR-195-5p target genes revealed that these were mostly involved in the PI3-Akt, MAPK, cell cycle, ubiquitin-mediated proteolysis, and mTOR signaling pathways, which are related to the regulation of cell proliferation. Transfecting the in vitro cultured cells with miR-195-5p mimic significantly suppressed (P < 0.05) the expression of its target genes such as YWHAQ, CDC27, AKT-3, FGF-7, MAPK8, SGK1, VEGFA, CACAND1, CUL2, MKNK1, and CACAN2D1. Furthermore, the downregulation of the miR-195-5p target genes was positively correlated with a significant increase in the apoptotic rate and a decrease in the proliferation. In conclusion, the current findings provide vital information on the presence of EV miR-195-5p in maternal circulation during the implantation window indicating its important role in the modulation of buffalo endometrium epithelial cells via promoting cell death. Altogether, the milieu of miR-195-5p may serve as a novel and potential molecular factor facilitating the implantation of the early embryo during the establishment of pregnancy in buffaloes. Thus, miR-195-5p may be identified as a unique circulatory EV biomarker related to establishing pregnancy in buffaloes as early as day 19 post-AI.
Pinostilbene inhibits full-length and splice variant of androgen receptor in prostate cancer
Authors: Shin Won Sik , Han Seung Hyun , Jo Kyung Won , Cho Yunje , Kim Kyong-Tai
Published: October 2023

Prostate cancer is the most prevalent cancer in men worldwide and is promoted by the sex hormone androgen. Expression of androgen from the testis can be significantly reduced through castration. However, as most prostate cancer patients acquire castration resistance, additional therapeutic solutions are necessary. Although anti-androgens, such as enzalutamide, have been used to treat castration-resistant prostate cancer (CRPC), enzalutamide-resistant CRPC (Enz-resistant CRPC) has emerged. Therefore, development of novel treatments for Enz-resistant CRPC is urgent. In this study, we found a novel anti-androgen called pinostilbene through screening with a GAL4-transactivation assay. We confirmed that pinostilbene directly binds to androgen receptor (AR) and inhibits its activation and translocalization. Pinostilbene treatment also reduced the protein level and downstream gene expression of AR. Furthermore, pinostilbene reduced the protein level of AR variant 7 in the Enz-resistant prostate cancer cell line 22Rv1 and inhibited cell viability and proliferation. Our results suggest that pinostilbene has the potential to treat Enz-resistant CRPC.
Superconductivity in a breathing kagome metals ROs2 (R = Sc, Y, Lu)
Authors: Górnicka Karolina , Winiarski Michał J. , Walicka Dorota I. , Klimczuk Tomasz
Published: October 2023

We have successfully synthesized three osmium-based hexagonal Laves compounds ROs2 (R = Sc, Y, Lu), and discussed their physical properties. LeBail refinement of pXRD data confirms that all compounds crystallize in the hexagonal centrosymmetric MgZn2-type structure (P63/mmc, No. 194). The refined lattice parameters are a = b = 5.1791(1) Å and c = 8.4841(2) Å for ScOs2, a = b = 5.2571(3) Å and c = 8.6613(2) Å for LuOs2 and a = b = 5.3067(6) Å and c = 8.7904(1) Å for YOs2. ROs2 Laves phases can be viewed as a stacking of kagome nets interleaved with triangular layers. Temperature-dependent magnetic susceptibility, resistivity and heat capacity measurements confirm bulk superconductivity at critical temperatures, Tc, of 5.36, 4.55, and 3.47 K for ScOs2, YOs2, and LuOs2, respectively. We have shown that all investigated Laves compounds are weakly-coupled type-II superconductors. DFT calculations revealed that the band structure of ROs2 is intricate due to multiple interacting d orbitals of Os and R. Nonetheless, the kagome-derived bands maintain their overall shape, and the Fermi level crosses a number of bands that originate from the kagome flat bands, broadened by interlayer interaction. As a result, ROs2 can be classified as (breathing) kagome metal superconductors.