bluuebunny/crossref_metadata_2025 huggingface dataset:
No evidence of an association of multiple sclerosis (MS) with Borna disease virus 1 (BoDV-1) infections in patients within an endemic region: a retrospective pilot study
Authors: Bauswein Markus , Knoll Gertrud , Schmidt Barbara , Gessner André , Hemmer Bernhard , Flaskamp Martina
Published: October 2023

Background

Borna disease virus 1 (BoDV-1) causes rare human infections within endemic regions in southern and eastern Germany. The infections reported to date have been linked to severe courses of encephalitis with high mortality and mostly irreversible symptoms. Whether BoDV-1 could act as a trigger for other neurological conditions, is, however, incompletely understood.

Objectives and methods

In this study, we addressed the question of whether the presentation of a clinically isolated syndrome (CIS) or of multiple sclerosis (MS) might be associated with a milder course of BoDV-1 infections. Serum samples of 100 patients with CIS or MS diagnosed at a tertiary neurological care center within an endemic region in southern Germany and of 50 control patients suffering from headache were retrospectively tested for BoDV-1 infections.

Results

In none of the tested sera, confirmed positive results of anti-BoDV-1-IgG antibodies were retrieved. Our results support the conclusion that human BoDV-1 infections primarily lead to severe encephalitis with high mortality.
Initiating Binary Metal Oxides Microcubes Electromagnetic Wave Absorber Toward Ultrabroad Absorption Bandwidth Through Interfacial and Defects Modulation
Authors: Li Fushan , Wu Nannan , Kimura Hideo , Wang Yuan , Xu Ben Bin , Wang Ding , Li Yifan , Algadi Hassan , Guo Zhanhu , Du Wei , Hou Chuanxin
Published: October 2023

Cobalt nickel bimetallic oxides (NiCo2O4) have received numerous attentions in terms of their controllable morphology, high temperature, corrosion resistance and strong electromagnetic wave (EMW) absorption capability. However, broadening the absorption bandwidth is still a huge challenge for NiCo2O4-based absorbers. Herein, the unique NiCo2O4@C core–shell microcubes with hollow structures were fabricated via a facile sacrificial template strategy. The concentration of oxygen vacancies and morphologies of the three-dimensional (3D) cubic hollow core–shell NiCo2O4@C framework were effectively optimized by adjusting the calcination temperature. The specially designed 3D framework structure facilitated the multiple reflections of incident electromagnetic waves and provided rich interfaces between multiple components, generating significant interfacial polarization losses. Dipole polarizations induced by oxygen vacancies could further enhance the attenuation ability for the incident EM waves. The optimized NiCo2O4@C hollow microcubes exhibit superior EMW absorption capability with minimum RL (RLmin) of −84.45 dB at 8.4 GHz for the thickness of 3.0 mm. Moreover, ultrabroad effective absorption bandwidth (EAB) as large as 12.48 GHz (5.52–18 GHz) is obtained. This work is believed to illuminate the path to synthesis of high-performance cobalt nickel bimetallic oxides for EMW absorbers with excellent EMW absorption capability, especially in broadening effective absorption bandwidth.

Graphic Abstract
Management of medical record data with multi-level security on Amazon Web Services
Authors: Elghoul Mohammed K. , Bahgat Sayed F. , Hussein Ashraf S. , Hamad Safwat H.
Published: October 2023

Blockchain technology has gained significant attention in the most recent years due to its potential to address related issues to privacy, transparency, and security. In the healthcare industry, it is considered a promising solution to challenges related to data management, medical data privacy, and security. This paper proposes a novel framework for managing electronic medical healthcare records that uses Amazon Web Services (AWS) to create a secure and cost-effective solution. The proposed solution uses a serverless approach to reduce costs and only pay for the compute resources when needed. The framework focuses on improving the security of access to the blockchain network by implementing a multi-level security approach, starting from protecting the Hyperledger and implementing role-based access for end-users who require access to the stored data. The effectiveness of the proposed framework is demonstrated by creating a role-based access matrix for three different user types and performing multiple experiments to validate access for each user type.
The impact of growing season and cultivation systems on the dissipation of profenofos and λ- cyhalothrin on Brassica juncea: a comparative study
Authors: Henry Michelle Crystal , Ngaini Zainab , Chai Lian-Kuet , Farooq Saba
Published: October 2023

This study was conducted to contour dissipation patterns of two pesticides (profenofos and λ-cyhalothrin) on B. juncea (green mustard) grown under green house (G.H.) and open field (O.F.) during dry and wet season. The dissipation data of studied pesticides were fitted into the first order kinetic equation. Based on the dissipation rate constant, k obtained, profenofos dissipates faster than λ-cyhalothrin regardless of growing system and season. The dissipation of both pesticides were found to be more rapid during dry season compare to wet season. Growing system however displayed a rather contradictory results for profenofos where during dry season, faster dissipation took place in O.F., while during wet season rapid dissipation took place in G.H. λ-Cyhalothrin on the other hand exhibits faster dissipation in G.H. during both seasons. The half-lives obtained for profenofos and λ-cyhalothrin in B. juncea were 0.66–1.8 days and 1.18–3.7 days, respectively. Based on this experiment, terminal residue obtained for profenofos and λ-cyhalothrin for B. juncea were lower than the stipulated MRL. This work was momentous to guide appropriate applications and establishment of accurate PHI of pesticides in B. juncea that will benefit farmers in a country with humid tropical climate.
Stress Fractures of the Distal Phalanx in Skeletally Immature Sport Climbers
Authors: Weber Andreas D. , Reissner Lisa , Schweizer Andreas
Published: October 2023

Stress fractures in the distal phalanx of skeletally immature patients are rare and previously unreported clinical occurrences. We report on 2 adolescent sport climbers with such fractures of the dorsal metaphysis of the distal phalanx at the point where parts of the extensor tendon insert. A conservative treatment approach alone was sufficient in healing this fracture type in both patients after 12 wk. Clinicians should be informed of the existence of this rare clinical phenomenon and counsel patients that a conservative treatment approach may result in complete healing without the need for an invasive procedure.
Adaptive backstepping fault-tolerant control for hypersonic aircraft with unknown control direction under actuator and sensor faults
Authors: Gou X.Y. , Liu J.K. , Zhang Q.Z.
Published: October 2023

In this paper, an adaptive backstepping controller of hypersonic flight vehicle (HFV) system is investigated in the presence of unknown actuator and sensor faults, unknown control direction and varying external disturbance, which expands traditional fault-tolerant control (FTC) approaches in HFV field. The control-oriented model is established with reasonable and comprehensive analysis of various fault types. Compared with the previous FTC research on HFV system, the time-varying and fixed fault types are simultaneously designed for actuator and sensors, and the control direction is unknown, which can more accurately simulate the real fault situations in the hypersonic flight environment. To avoid singularity problems caused by the unknown control direction, the Nussbaum gain function technique is adopted in the control algorithm, which is also capable of overcoming the influence of unknown time-varying fault parameters. The boundness and stability of system under the designed control scheme are theoretically verified. Finally, numerical simulation results demonstrate the effectiveness and superiority of the proposed control strategy.
Unlocking CEDAW's Transformative Potential: Asylum Cases Before the Committee on the Elimination of Discrimination Against Women
Authors: Gleeson Madeline
Published: October 2023

One of the most important developments in international law for the protection of displaced women and girls—the implied non-refoulement obligation in the Convention on the Elimination of Discrimination Against Women has received little scholarly or jurisprudential attention. This Article presents, for the first time, a doctrinal analysis of the full corpus of asylum complaints decided by the Committee on the Elimination of Discrimination Against Women (Committee). It analyzes the early development of a prohibition on return to real, personal, and foreseeable risks of serious forms of discrimination against women; highlights critical shortcomings in the Committee's asylum practice; identifies key areas for improvement; and reflects on the Committee's as-yet-unrealized potential to contribute to international law in this area.
From a decentralized clinical trial to a decentralized and clinical-trial-in-a-box platform: Towards patient-centric and equitable trials
Authors: Dulko Dorothy , Kwong Manlik , Palm Marisha E. , Trinquart Ludovic , Selker Harry P.
Published: October 2023

Background/Objective:

Despite the intuitive attractiveness of bringing research to participants rather than making them come to central study sites, widespread decentralized enrollment has not been common in clinical trials.

Methods:

The need for clinical research in the context of the COVID-19 pandemic, along with innovations in technology, led us to use a decentralized trial approach in our Phase 2 COVID-19 trial. We used real-time acquisition and transmission of health-related data using home-based monitoring devices and mobile applications to assess outcomes. This approach not only avoids spreading COVID-19 but it also can support inclusion of participants in more diverse socioeconomic circumstances and in rural settings.

Results:

Our team developed and deployed a decentralized trial platform to support patient engagement and adverse event reporting. Clinicians, engineers, and informaticians on our research team developed a Clinical-Trial-in-a-Box tool to optimally collect and analyze data from multiple decentralized platforms.

Conclusion:

Applying the decentralized model in Long COVID, using digital health technology and personal devices integrated with our telehealth platform, we share the lessons learned from our work, along with challenges and future possibilities.
Proper orthogonal decomposition modal analysis in a baffled stirred tank: a base tool for the study of structures
Authors: Arosemena Arturo A. , Solsvik Jannike
Published: October 2023

Proper orthogonal decomposition (POD) is applied to three-dimensional (3-D) velocity fields collected from large-eddy simulations (LES) of a baffled stirred tank. In the LES, the tank operates with a Rushton-type impeller under turbulent conditions (at least in the near-impeller region) and the working fluid exhibits either Newtonian or shear-thinning rheology. The most energetic POD modes are analysed, and a POD reconstruction based on the higher modes is proposed to approximate the fluctuating component of the velocity field. Subsequently, the POD reconstruction is used to identify vortical structures and characterise them in terms of their shape. The structures are identified by considering a frame-invariant formulation of a popular, Eulerian, local-region-type method: the

$Q$

-criterion. Statistics of shape-related parameters are then investigated to address the morphology of the structures. It is found that: (i) regardless of the working fluid rheology, it seems feasible to decompose the 3-D field into its mean, most energetic periodic and fluctuating components using POD, allowing, for instance, reduced-order modelling of the energetic periodic motions for mixing enhancement purposes, and (ii) vortical structures related to turbulence are mostly tubular. Finding (ii) implies that, as starting point, phenomenological models for the interaction between fluid particles (drops and bubbles) and vortices should consider the latter as cylindrical structures rather than of spherical shape, as classically assumed in these models.
Stellahedral geometry of matroids
Authors: Eur Christopher , Huh June , Larson Matt
Published: October 2023

We use the geometry of the stellahedral toric variety to study matroids. We identify the valuative group of matroids with the cohomology ring of the stellahedral toric variety and show that valuative, homological and numerical equivalence relations for matroids coincide. We establish a new log-concavity result for the Tutte polynomial of a matroid, answering a question of Wagner and Shapiro–Smirnov–Vaintrob on Postnikov–Shapiro algebras, and calculate the Chern–Schwartz–MacPherson classes of matroid Schubert cells. The central construction is the ‘augmented tautological classes of matroids’, modeled after certain toric vector bundles on the stellahedral toric variety.
Legal Consciousness and Vigilantism: Seeking Justice for Witchcraft Harms in the Eastern Democratic Republic of Congo
Authors: Dunn Holly
Published: October 2023

Theories of vigilantism frequently locate its cause in the ineffectiveness of the state legal system. The state legal system does not work for some, so they take the law into their own hands. Even in communities where vigilantism is prevalent, however, only certain harms are met with vigilantism. Why are some harms met with violence while others are not? To explore this question, I draw on nine months of fieldwork in the eastern Democratic Republic of Congo, a nation with a largely ineffective state legal system and the presence of vigilantism. Yet vigilante remedies are largely reserved for harms attributed to witchcraft, and typically only particularly serious witchcraft harms. In this article I draw on the concept of legal consciousness to understand why people might turn to vigilantism in response to witchcraft. I develop two themes of legal consciousness—a disconnect in harm naming and different logics of justice—that help explain dynamics vigilantism. My research thus contributes to the scholarship on both vigilantism and legal consciousness.
The Trap of “Racial Capitalism”
Authors: Wacquant Loïc
Published: October 2023

This article weighs the meaning, potential, and pitfalls of the concept of “racial capitalism” for studying the nexus of racial division and the economy. The concept has spread like wildfire in Anglophone social science since its≠ introduction in Cedric Robinson’s revisionist account of the rise of capitalism as racializing, but it remains epistemically inchoate and analytically problematic. The critique of leading uses and common corollaries of the term shows that it stipulates that which needs to be explicated, namely, the “articulation” of capitalism “through race,” which is not a structural invariant but ranges from coevalness and synergy to parasitism and disconnection. The notion cannot accommodate the varied bases of race as a naturalizing and hierarchizing principle of vision and division as well as the historical peculiarity of the economic variant of slavery in the Atlantic world. Advocates of “racial capitalism” need to put in the hard work of epistemological elucidation, logical clarification, and historical elaboration needed if they are to make the label more than a “conceptual speculative bubble.”
FINITE BASIS PROBLEM FOR INVOLUTION MONOIDS OF ORDER FIVE
Authors: HAN BIN BIN , ZHANG WEN TING , LUO YAN FENG
Published: October 2023

An example of a nonfinitely based involution monoid of order five has recently been discovered. We confirm that this example is, up to isomorphism, the unique smallest among all involution monoids.
Automation versus openness: support for policies to address job threats
Authors: Kuo Alexander , Manzano Dulce , Gallego Aina
Published: October 2023

Does the threat of automation of workers’ employment provoke distinct policy preferences from that of globalization? We present hypotheses about how these different threats affect support for policies to prevent such shocks as well as policies to compensate via redistribution. Using vignettes and conjoint experiments embedded in survey evidence from Spain, we find that the threat of automation does not provoke any greater demand for redistribution than does openness. Nor does job loss due to automation provoke beliefs of greater deservingness of compensatory transfers, compared to job loss from openness. While the threat of offshoring and hiring foreign workers increases support for policies to prevent this process from occurring, scenarios of robot substitution do not provoke a similar reaction. These results suggest policies to prioritize automation over openness may gain less political traction.
The Labyrinths of Global Opera
Authors: Milella Francesco
Published: October 2023

In 2017, on the debut of the soprano Hui He in the role of Aida at the Hong Kong Opera, a Japanese finance and business website published a short article to introduce its readers to Verdi's monumental opera and more general issues of cultural appropriation and whitewashing related to it. What caught my attention, however, was the headline. Short and concise, it grasped an aspect that might have otherwise gone unnoticed: ‘Opera Hong Kong's new production of “Aida” in October will feature a Chinese soprano playing an African princess singing in Italian’. The headline writer was probably more intrigued by the multicultural quirkiness of this event and ignored, for the sake of the readers, its cultural and historical implications. In fact, the article itself succeeded in depicting this event as a proper, if not extreme, moment of transcultural encounters by mingling different cultures – the Ethiopian heritage of the protagonist of the opera, the musical aura of Italian operas and the Chinese nationality of the soprano Hui He, opposed to the location of the Hong Kong opera evoked by a Japanese magazine – under the unifying authority of Verdi'sAida. This article seemed to consciously invoke a multicultural dimension built around the perceived prestige ofAidaand all the debates on imperialism that, from Said to Drummond and Locke, have become attached to it. Verdi's music is safely placed at the centre of a wide transcultural discourse which, rather than undermining the cultural ‘authority’ of Italian opera, reaffirms it even more strongly as a proper vehicle of ‘global uniformity’, as Christopher A. Bayly would define it.
Indian merchants abroad: Integrating the Indian ocean world during the early first millennium CE
Authors: Cobb Matthew Adam
Published: October 2023

With the rise of post-colonialism during the latter part of the twentieth century, more focus has been given to non-western perspectives (the so-called nativist turn). In the case of Indian Ocean trade during the early first millennium CE, the view that ‘Roman’ merchants and sailors were the near-exclusive movers of goods, who were also (indirectly) responsible for commercial developments within South Asia, has largely fallen into abeyance. Rightly, the agency of those in South Asia has been acknowledged. The present article goes beyond this basic premise and considers how we can assess evidence demonstrating the role played by sailors and merchants from South Asia. In particular, it is suggested these merchants and sailors played an important role in connecting the Arabian Sea and Bay of Bengal regions.
P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-CoV-2 entry and ACE2 autophagic degradation
Authors: Liu Ming , Lu Bingtai , Li Yue , Yuan Shuofeng , Zhuang Zhen , Li Guangyu , Wang Dong , Ma Liuheyi , Zhu Jianheng , Zhao Jinglu , Chan Chris Chung-Sing , Poon Vincent Kwok-Man , Chik Kenn Ka-Heng , Zhao Zhiyao , Xian Huifang , Zhao Jingxian , Zhao Jincun , Chan Jasper Fuk-Woo , Zhang Yuxia
Published: October 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has had a significant impact on healthcare systems and economies worldwide. The continuous emergence of new viral strains presents a major challenge in the development of effective antiviral agents. Strategies that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 infection. ACE2, an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system, is the receptor for SARS-CoV-2. ACE2 interacts with the spike protein and facilitates viral attachment and entry into host cells. Yet, SARS-CoV-2 infection also promotes ACE2 degradation. Whether restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be determined. Here, we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement. In contrast, free cellular spike protein is selectively cleaved into S1 and S2 subunits in a lysosomal-dependent manner. Importantly, we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 strains. FRAX-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated hamsters. In summary, our findings have identified novel pathways regulating viral entry, as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.
Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation
Authors: Han Dandan , Wu Yujun , Lu Dongdong , Pang Jiaman , Hu Jie , Zhang Xiangyu , Wang Zhenyu , Zhang Guolong , Wang Junjun
Published: October 2023

Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.
Porphene and porphite as porphyrin analogs of graphene and graphite
Authors: Magnera Thomas F. , Dron Paul I. , Bozzone Jared P. , Jovanovic Milena , Rončević Igor , Tortorici Edward , Bu Wei , Miller Elisa M. , Rogers Charles T. , Michl Josef
Published: October 2023

Two-dimensional materials have unusual properties and promise applications in nanoelectronics, spintronics, photonics, (electro)catalysis, separations, and elsewhere. Most are inorganic and their properties are difficult to tune. Here we report the preparation of Zn porphene, a member of the previously only hypothetical organic metalloporphene family. Similar to graphene, these also are fully conjugated two-dimensional polymers, but are composed of fused metalloporphyrin rings. Zn porphene is synthesized on water surface by two-dimensional oxidative polymerization of a Langmuir layer of Zn porphyrin with K2IrCl6, reminiscent of known one-dimensional polymerization of pyrroles. It is transferable to other substrates and bridges μm-sized pits. Contrary to previous theoretical predictions of metallic conductivity, it is a p-type semiconductor due to a predicted Peierls distortion of its unit cell from square to rectangular, analogous to the appearance of bond-length alternation in antiaromatic molecules. The observed reversible insertion of various metal ions, possibly carrying a fifth or sixth ligand, promises tunability and even patterning of circuits on an atomic canvas without removing any π centers from conjugation.
Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
Authors: Rocha Ana Sofia , Collado-Solé Alejandro , Graña-Castro Osvaldo , Redondo-Pedraza Jaime , Soria-Alcaide Gonzalo , Cordero Alex , Santamaría Patricia G. , González-Suárez Eva
Published: October 2023

Rank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with lineage tracing techniques, we found that loss of luminal Rank reduces the luminal progenitor pool and leads to aberrant alveolar-like differentiation with high protein translation capacity in virgin mammary glands. These Rank-deleted luminal cells are unable to expand during the first pregnancy, leading to lactation failure and impairment of protein synthesis potential in the parous stage. The unfit parous Rank-deleted luminal cells in the alveoli are progressively replaced by Rank-proficient cells early during the second pregnancy, thereby restoring lactation. Transcriptomic analysis and functional assays point to the awakening of basal bipotency after pregnancy by the induction of Rank/NF-κB signaling in basal parous cell to restore lactation and tissue homeostasis.
Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation
Authors: Xia Lei , Komissarova Anastasia , Jacover Arielle , Shovman Yehuda , Arcila-Barrera Sebastian , Tornovsky-Babeay Sharona , Jaya Prakashan Milsee Mol , Nasereddin Abdelmajeed , Plaschkes Inbar , Nevo Yuval , Shiff Idit , Yosefov-Levi Oshri , Izhiman Tamara , Medvedev Eleonora , Eilon Elad , Wilensky Asaf , Yona Simon , Parnas Oren
Published: October 2023

Genetic engineering of immune cells has opened new avenues for improving their functionality but it remains a challenge to pinpoint which genes or combination of genes are the most beneficial to target. Here, we conduct High Multiplicity of Perturbations and Cellular Indexing of Transcriptomes and Epitopes (HMPCITE-seq) to find combinations of genes whose joint targeting improves antigen-presenting cell activity and enhances their ability to activate T cells. Specifically, we perform two genome-wide CRISPR screens in bone marrow dendritic cells and identify negative regulators of CD86, that participate in the co-stimulation programs, including Chd4, Stat5b, Egr2, Med12, and positive regulators of PD-L1, that participate in the co-inhibitory programs, including Sptlc2, Nckap1l, and Pi4kb. To identify the genetic interactions between top-ranked genes and find superior combinations to target, we perform high-order Perturb-Seq experiments and we show that targeting both Cebpb and Med12 results in a better phenotype compared to the single perturbations or other combinations of perturbations.
Reversible photoregulation of cell-cell adhesions with opto-E-cadherin
Authors: Nzigou Mombo Brice , Bijonowski Brent M. , Raab Christopher A. , Niland Stephan , Brockhaus Katrin , Müller Marc , Eble Johannes A. , Wegner Seraphine V.
Published: October 2023

E-cadherin-based cell-cell adhesions are dynamically and locally regulated in many essential processes, including embryogenesis, wound healing and tissue organization, with dysregulation manifesting as tumorigenesis and metastasis. However, the lack of tools that would provide control of the high spatiotemporal precision observed with E-cadherin adhesions hampers investigation of the underlying mechanisms. Here, we present an optogenetic tool, opto-E-cadherin, that allows reversible control of E-cadherin-mediated cell-cell adhesions with blue light. With opto-E-cadherin, functionally essential calcium binding is photoregulated such that cells expressing opto-E-cadherin at their surface adhere to each other in the dark but not upon illumination. Consequently, opto-E-cadherin provides remote control over multicellular aggregation, E-cadherin-associated intracellular signalling and F-actin organization in 2D and 3D cell cultures. Opto-E-cadherin also allows switching of multicellular behaviour between single and collective cell migration, as well as of cell invasiveness in vitro and in vivo. Overall, opto-E-cadherin is a powerful optogenetic tool capable of controlling cell-cell adhesions at the molecular, cellular and behavioural level that opens up perspectives for the study of dynamics and spatiotemporal control of E-cadherin in biological processes.
Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation
Authors: Robin Adrien , Van Ombergen Angelique , Laurens Claire , Bergouignan Audrey , Vico Laurence , Linossier Marie-Thérèse , Pavy-Le Traon Anne , Kermorgant Marc , Chopard Angèle , Py Guillaume , Green David Andrew , Tipton Michael , Choukér Alexander , Denise Pierre , Normand Hervé , Blanc Stéphane , Simon Chantal , Rosnet Elisabeth , Larcher Françoise , Fernandez Peter , de Glisezinski Isabelle , Larrouy Dominique , Harant-Farrugia Isabelle , Antunes Inês , Gauquelin-Koch Guillemette , Bareille Marie-Pierre , Billette De Villemeur Rebecca , Custaud Marc-Antoine , Navasiolava Nastassia
Published: October 2023

Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.
A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation
Authors: Valverde Juan Manuel , Dubra Geronimo , Phillips Michael , Haider Austin , Elena-Real Carlos , Fournet Aurélie , Alghoul Emile , Chahar Dhanvantri , Andrés-Sanchez Nuria , Paloni Matteo , Bernadó Pau , van Mierlo Guido , Vermeulen Michiel , van den Toorn Henk , Heck Albert J. R. , Constantinou Angelos , Barducci Alessandro , Ghosh Kingshuk , Sibille Nathalie , Knipscheer Puck , Krasinska Liliana , Fisher Daniel , Altelaar Maarten
Published: October 2023

Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation.
Electrostatic force promoted intermolecular stacking of polymer donors toward 19.4% efficiency binary organic solar cells
Authors: Gan Zirui , Wang Liang , Cai Jinlong , Guo Chuanhang , Chen Chen , Li Donghui , Fu Yiwei , Zhou Bojun , Sun Yuandong , Liu Chenhao , Zhou Jing , Liu Dan , Li Wei , Wang Tao
Published: October 2023

Conjugated polymers are generally featured with low structural order due to their aromatic and irregular structural units, which limits their light absorption and charge mobility in organic solar cells. In this work, we report a conjugated molecule INMB-F that can act as a molecular bridge via electrostatic force to enhance the intermolecular stacking of BDT-based polymer donors toward efficient and stable organic solar cells. Molecular dynamics simulations and synchrotron X-ray measurements reveal that the electronegative INMB-F adsorb on the electropositive main chain of polymer donors to increase the donor-donor interactions, leading to enhanced structural order with shortened π-π stacking distance and consequently enhanced charge transport ability. Casting the non-fullerene acceptor layer on top of the INMB-F modified donor layer to fabricate solar cells via layer-by-layer deposition evidences significant power conversion efficiency boosts in a range of photovoltaic systems. A power conversion efficiency of 19.4% (certified 18.96%) is realized in PM6/L8-BO binary devices, which is one of the highest reported efficiencies of this material system. The enhanced structural order of polymer donors by INMB-F also leads to a six-fold enhancement of the operational stability of PM6/L8-BO organic solar cells.
Mitogenomic evolutionary rates in bilateria are influenced by parasitic lifestyle and locomotory capacity
Authors: Jakovlić Ivan , Zou Hong , Ye Tong , Zhang Hong , Liu Xiang , Xiang Chuan-Yu , Wang Gui-Tang , Zhang Dong
Published: October 2023

The evidence that parasitic animals exhibit elevated mitogenomic evolutionary rates is inconsistent and limited to Arthropoda. Similarly, the evidence that mitogenomic evolution is faster in species with low locomotory capacity is limited to a handful of animal lineages. We hypothesised that these two variables are associated and that locomotory capacity is a major underlying factor driving the elevated rates in parasites. Here, we study the evolutionary rates of mitogenomes of 10,906 bilaterian species classified according to their locomotory capacity and parasitic/free-living life history. In Bilateria, evolutionary rates were by far the highest in endoparasites, much lower in ectoparasites with reduced locomotory capacity and free-living lineages with low locomotory capacity, followed by parasitoids, ectoparasites with high locomotory capacity, and finally micropredatory and free-living lineages. The life history categorisation (parasitism) explained ≈45%, locomotory capacity categorisation explained ≈39%, and together they explained ≈56% of the total variability in evolutionary rates of mitochondrial protein-coding genes in Bilateria. Our findings suggest that these two variables play major roles in calibrating the mitogenomic molecular clock in bilaterian animals.
Free riding in climate protests
Authors: Jarke-Neuert Johannes , Perino Grischa , Schwickert Henrike
Published: October 2023

Climate protests are an important driver for ambitious climate policies. However, it is still unknown how individual protest participation decisions depend on each other. Exploiting the unique opportunity of the Third Global Climate Strike, we conducted multi-wave population surveys with 1,510 people in the four largest German cities. With a randomized information intervention, we changed turnout expectations of a subgroup of respondents and measured the impact on the probability to join the local protest event. Our findings provide causal evidence for strategic interdependence in protest participation decisions among members of the general public rather than among a movement’s core group of supporters. These decisions are found to be strategic substitutes: individuals who expect many other people to participate are less likely to participate themselves. This dynamic has important implications for the movement’s future communication and growth perspective.
LncTUG1 promotes hepatocellular carcinoma immune evasion via upregulating PD-L1 expression
Authors: Wu Rongshou , Liu Weiwei , Yang Qingping , Zhang Jingling , Hou Ping , Xiong Jianghui , Wu Linquan , Li Enliang
Published: October 2023

HCC is one of the most common malignant tumors worldwide. Although traditional treatment methods have been improved in recent years, the survival rate of HCC patients has not been significantly improved. Immunotherapy has shown extremely high clinical value in a variety of tumors. In this study, we found that TUG1 could regulate the expression of PD-L1 through JAK2/STAT3 to mediate immunosuppression. Here, The expression of TUG1 and PD-L1 in HCC tissues was evaluated through analysis of databases and verified in HCC tissue and HCC cancer cells by qRT-PCR. The effect of TUG1 on tumor immune escape was detected by coculture, and cell viability was detected with a CCK8 assay. The results demonstrated that TUG1 was closely associated with anticancer immunity. TUG1 and PD-L1 were highly expressed in HCC tissues and HCC cancer cells, and high expression of TUG1 and PD-L1 was related to the poor prognosis of HCC patients. In addition, knocking down TUG1 expression could reduce PD-L1 expression and enhance the cancer cell-killing capability of T cells. Downregulating TUG1 expression could also decrease the mRNA and protein expression of JAK2 and STAT3. To sum up, TUG1 and PD-L1 are overexpressed in patients with liver cancer and are related to the poor prognosis of these patients. Silencing TUG1 expression reduced the mRNA and protein expression of PD-L1 by affecting the JAK2/STAT3 pathway.
The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer
Authors: Hodgson Kirsty , Orozco-Moreno Margarita , Scott Emma , Garnham Rebecca , Livermore Karen , Thomas Huw , Zhou Yuhan , He Jiepei , Bermudez Abel , Garcia Marques Fernando Jose , Bastian Kayla , Hysenaj Gerald , Archer Goode Emily , Heer Rakesh , Pitteri Sharon , Wang Ning , Elliott David J. , Munkley Jennifer
Published: October 2023

Prostate cancer is the most common cancer in men and a major cause of cancer related deaths worldwide. Nearly all affected men develop resistance to current therapies and there is an urgent need to develop new treatments for advanced disease. Aberrant glycosylation is a common feature of cancer cells implicated in all of the hallmarks of cancer. A major driver of aberrant glycosylation in cancer is the altered expression of glycosylation enzymes. Here, we show that GCNT1, an enzyme that plays an essential role in the formation of core 2 branched O-glycans and is crucial to the final definition of O-glycan structure, is upregulated in aggressive prostate cancer. Using in vitro and in vivo models, we show GCNT1 promotes the growth of prostate tumours and can modify the glycome of prostate cancer cells, including upregulation of core 2 O-glycans and modifying the O-glycosylation of secreted glycoproteins. Furthermore, using RNA sequencing, we find upregulation of GCNT1 in prostate cancer cells can alter oncogenic gene expression pathways important in tumour growth and metastasis. Our study highlights the important role of aberrant O-glycosylation in prostate cancer progression and provides novel insights regarding the mechanisms involved.
Phytochemical analysis, antioxidant, α-glucosidase inhibitory activity, and toxicity evaluation of Orthosiphon stamineus leaf extract
Authors: Ahda Mustofa , Jaswir Irwandi , Khatib Alfi , Ahmed Qamar Uddin , Mahfudh Nurkhasanah , Ardini Yunita Dewi , Syed Mohamad Sharifah Nurul Akilah , Anwar Muslih , Hernawan Hernawan , Miyashita Kazuo , Salamatullah Ahmad Mohammad
Published: October 2023

Ocimum aristatum, commonly known as O. stamineus, has been widely studied for its potential as an herbal medicine candidate. This research aims to compare the efficacy of water and 100% ethanolic extracts of O. stamineus as α-glucosidase inhibitors and antioxidants, as well as toxicity against zebrafish embryos. Based on the study findings, water extract of O. stamineus leaves exhibited superior inhibition activity against α-glucosidase, ABTS, and DPPH, with IC50 values of approximately 43.623 ± 0.039 µg/mL, 27.556 ± 0.125 µg/mL, and 95.047 ± 1.587 µg/mL, respectively. The major active compounds identified in the extract include fatty acid groups and their derivates such as linoleic acid, α-eleostearic acid, stearic acid, oleanolic acid, and corchorifatty acid F. Phenolic groups such as caffeic acid, rosmarinic acid, 3,4-Dihydroxybenzaldehyde, norfenefrine, caftaric acid, and 2-hydroxyphenylalanine and flavonoids and their derivates including 5,7-Dihydroxychromone, 5,7-Dihydroxy-2,6-dimethyl-4H-chromen-4-one, eupatorin, and others were also identified in the extract. Carboxylic acid groups and triterpenoids such as azelaic acid and asiatic acid were also present. This study found that the water extract of O. stamineus is non-toxic to zebrafish embryos and does not affect the development of zebrafish larvae at concentrations lower than 500 µg/mL. These findings highlight the potential of the water extract of O. stamineus as a valuable herbal medicine candidate, particularly for its potent α-glucosidase inhibition and antioxidant properties, and affirm its safety in zebrafish embryos at tested concentrations.
Phylogeny and symbiotic effectiveness of indigenous rhizobial microsymbionts of common bean (Phaseolus vulgaris L.) in Malkerns, Eswatini
Authors: Gunununu Rotondwa P. , Mohammed Mustapha , Jaiswal Sanjay K. , Dakora Felix D.
Published: October 2023

In most legumes, the rhizobial symbionts exhibit diversity across different environments. Although common bean (Phaseolus vulgaris L.) is one of the important legumes in southern Africa, there is no available information on the genetic diversity and N2-fixing effectiveness of its symbionts in Malkerns, Eswatini. In this study, we assessed the phylogenetic positions of rhizobial microsymbionts of common bean from Malkerns in Eswatini. The isolates obtained showed differences in morpho-physiology and N2-fixing efficiency. A dendrogram constructed from the ERIC-PCR banding patterns, grouped a total of 88 tested isolates into 80 ERIC-PCR types if considered at a 70% similarity cut-off point. Multilocus sequence analysis using 16S rRNA, rpoB, dnaK, gyrB, and glnII and symbiotic (nifH and nodC) gene sequences closely aligned the test isolates to the type strains of Rhizobium muluonense, R. paranaense, R. pusense, R. phaseoli and R. etli. Subjecting the isolates in this study to further description can potentially reveal novel species. Most of the isolates tested were efficient in fixing nitrogen and elicited greater stomatal conductance and photosynthetic rates in the common bean. Relative effectiveness (RE) varied from 18 to 433%, with 75 (85%) out of the 88 tested isolates being more effective than the nitrate fed control plants.
The moderating role of neighborhood social cohesion in the mediation effects of the loneliness between acculturation stress and post-traumatic growth among female North Korean defectors
Authors: Kim Hokon , Kim Ocksim , Kim Kyoung-A , Chu Sang Hui , Chung Misook L.
Published: October 2023

Loneliness negatively predicts post-traumatic growth (PTG) among North Korean defectors (NKD), one of the representative groups of refugees. Additionally, evidence also suggests that females, who account for 70% of NKDs entering South Korea, are vulnerable not only to past trauma but also to the current acculturation stress and loneliness affected by neighborhood social cohesion. This study explores whether the mediating effect of loneliness on the relationship between acculturation stress and PTG was moderated by the neighborhood social cohesion among female NKDs. In this study, the data of 166 female NKDs who completed an online survey regarding acculturation stress, PTG, loneliness, and neighborhood social cohesion were used. Moderated mediation analysis was conducted using SPSS PROCESS macro program. Loneliness was associated with PTG (B = − 1.896, p < 0.001), and mediated the association between acculturation stress and PTG (indirect effect = − 0.278, 95% LLCI − 0.403, 95% ULCI − 0.166). Neighborhood social cohesion moderated the mediation effect of loneliness on the association between acculturation stress and PTG (B = − 0.016, 95% LLCI 0.001, 95% ULCI 0.035). The indirect effect of acculturation stress on PTG through loneliness was notably high for those with low neighborhood social cohesion. Therefore, increasing neighborhood social cohesion would reduce loneliness caused by acculturation stress and support the positive growth among female NKDs. This represents the most effective approach to aiding female NKDs in achieving growth, even after suffering trauma.
Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform
Authors: Ernst Alexander , Piragyte Indre , MP Ayisha Marwa , Le Ngoc Dung , Grandgirard Denis , Leib Stephen L. , Oates Andrew , Mercader Nadia
Published: October 2023

Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/CoVasc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases.