bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of experimental autoimmune encephalomyelitis by targeting 6-sulfo sialyl Lewis X glycans involved in lymphocyte homing
Authors: Liu Qianqian , Xiong Wei , Obara Sachiyo , Abo Hirohito , Nakatsukasa Hiroko , Kawashima Hiroto 
Published: February 2024

Abstract
Lymphocyte homing to peripheral lymph nodes (PLN) is critical for immune surveillance. However, autoimmune diseases such as multiple sclerosis (MS) can occur due to excessive immune responses in the PLN. Here we show that 6-sulfo sialyl Lewis X (6-sulfo sLex) glycans on high endothelial venules that function as ligands for l-selectin on lymphocytes play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2 double-knockout mice lacking the expression of 6-sulfo sLeX glycans, the EAE symptoms and the numbers of effector Th1 and Th17 cells in the draining lymph nodes (dLN) and spinal cords (SC) were significantly reduced. To determine whether 6-sulfo sLeX could serve as a target for MS, we also examined the effects of anti-glycan monoclonal antibody (mAb) SF1 against 6-sulfo sLeX in EAE. Administration of mAb SF1 significantly reduced EAE symptoms and the numbers of antigen-specific effector T cells in the dLN and SC in association with suppression of critical genes including Il17a and Il17f that are involved in the pathogenesis of EAE. Taken together, these results suggest that 6-sulfo sLeX glycan would serve as a novel target for MS.
Isolation of a widespread giant virus implicated in cryptophyte bloom collapse
Authors: Vieira Helena H , Bulzu Paul-Adrian , Kasalický Vojtěch , Haber Markus , Znachor Petr , Piwosz Kasia , Ghai Rohit 
Published: February 2024

Abstract
Photosynthetic cryptophytes are ubiquitous protists that are major participants in the freshwater phytoplankton bloom at the onset of spring. Mortality due to change in environmental conditions and grazing have been recognized as key factors contributing to bloom collapse. In contrast, the role of viral outbreaks as factors terminating phytoplankton blooms remains unknown from freshwaters. Here, we isolated and characterized a cryptophyte virus contributing to the annual collapse of a natural cryptophyte spring bloom population. This viral isolate is also representative for a clade of abundant giant viruses (phylum Nucleocytoviricota) found in freshwaters all over the world.
The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis
Authors: Singh Shivani , Boyd Simon , Schilling William H K , Watson James A , Mukaka Mavuto , White Nicholas J 
Published: February 2024

AbstractBackgroundEffective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear.MethodsA systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14 days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR). The VCRR is the ratio of viral clearance rates between the intervention and control arms. The relationship between the clinical and virological treatment effects was assessed by mixed-effects meta-regression.ResultsFrom 57 potentially eligible RCTs, VCRRs were derived for 44 (52 384 participants); 32 had ≥1 clinical endpoint in each arm. Overall, 9.7% (R2) of the variation in clinical benefit was explained by variation in VCRRs with an estimated linear coefficient of −0.92 (95% CI: −1.99 to 0.13; P = 0.08). However, this estimate was highly sensitive to the inclusion of the recent very large PANORAMIC trial. Omitting this outlier, half the variation in clinical benefit (R2 = 50.4%) was explained by variation in VCRRs [slope −1.47 (95% CI −2.43 to −0.51); P = 0.003], i.e. higher VCRRs were associated with an increased clinical benefit.ConclusionMethods of determining viral clearance in COVID-19 studies and the relationship to clinical outcomes vary greatly. As prohibitively large sample sizes are now required to show clinical treatment benefit in antiviral therapeutic assessments, viral clearance is a reasonable surrogate endpoint.
The synergic and addictive activity of biogenic silver nanoparticle associated with meropenem against carbapenem-resistant Acinetobacter baumannii
Authors: Allend Suzane Olachea , Oliveira Garcia Marcelle , da Cunha Kamila Furtado , de Albernaz Déborah Trota Farias , Panagio Luciano Aparecido , Nakazaro Gerson , Reis Guilherme Fonseca , Oliveira Thaís Larré , Neto Amilton Clair Pinto Seixas , Hartwig Daiane Drawanz 
Published: February 2024

Abstract

Aims
Antibiotic management of infections caused by Acinetobacter baumannii often fails due to antibiotic resistance (especially to carbapenems) and biofilm-forming strains. Thus, the objective here was to evaluate in vitro the antibacterial and antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) combined with meropenem, against multidrug-resistant isolates of A. baumannii.

Methods and results
In this study, A. baumannii ATCC® 19606™ and four carbapenem-resistant A. baumannii (Ab) strains were used. The antibacterial activity of Bio-AgNP and meropenem was evaluated through broth microdilution. The effect of the Bio-AgNP association with meropenem was determined by the checkboard method. Also, the time-kill assay and the integrity of the bacterial cell membrane were evaluated. Furthermore, the antibiofilm activity of Bio-AgNP and meropenem alone and in combination was determined. Bio-AgNP has antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 0.46 to 1.87 μg ml−1. The combination of Bio-AgNP and meropenem showed a synergistic and additive effect against Ab strains, and Bio-AgNP was able to reduce the MIC of meropenem from 4- to 8-fold. Considering the time-kill of the cell, meropenem and Bio-AgNP when used in combination reduced bacterial load to undetectable levels within 10 min to 24 h after treatment. Protein leakage was observed in all treatments evaluated. When combined, meropenem/Bio-AgNP presents biofilm inhibition for Ab2 isolate and ATCC® 19606™, with 21% and 19%, and disrupts the biofilm from 22% to 50%, respectively. The increase in nonviable cells in the biofilm can be observed after treatment with Bio-AgNP and meropenem in carbapenem-resistant A. baumannii strains.

Conclusions
The combination of Bio-AgNP with meropenem can be a therapeutic option in the treatment of infections caused by carbapenem-resistant A. baumannii.
Production of CA125 with Tn antigens using a glycosylphosphatidylinositol anchoring system
Authors: Tang Yu-He , Leng Ji-Xiong , Yang Ganglong , Gao Xiao-Dong , Liu Yi-Shi , Fujita Morihisa 
Published: February 2024

Abstract
Cancer antigen 125 (CA125) is a serum marker associated with ovarian cancer. Despite its widespread use, CA125 levels can also be elevated in benign conditions. Recent reports suggest that detecting serum CA125 that carries the Tn antigen, a truncated O-glycan containing only N-acetylgalactosamine on serine or threonine residues, can improve the specificity of ovarian cancer diagnosis. In this study, we engineered cells to express CA125 with a Tn antigen. To achieve this, we knocked out C1GALT1 and SLC35A1, genes encoding Core1 synthase and a transporter for cytidine-5′-monophospho-sialic acid respectively, in human embryonic kidney 293 (HEK293) cells. In ClGALT1-SLC35A1-knockout (KO) cells, the expression of the Tn antigen showed a significant increase, whereas the expression of the T antigen (galactose-β1,3-N-acetylgalactosamine on serine or threonine residues) was decreased. Due to the inefficient secretion of soluble CA125, we employed a glycosylphosphatidylinositol (GPI) anchoring system. This allowed for the expression of GPI-anchored CA125 on the cell surface of ClGALT1-SLC35A1-KO cells. Cells expressing high levels of GPI-anchored CA125 were then enriched through cell sorting. By knocking out the PGAP2 gene, the GPI-anchored form of CA125 was converted to a secretory form. Through the engineering of O-glycans and the use of a GPI-anchoring system, we successfully produced CA125 with Tn antigen modification.
Morphinan Evolution: The Impact of Advances in Biochemistry and Molecular Biology
Authors: Kajino Keita , Tokuda Akihisa , Saitoh Tsuyoshi 
Published: February 2024

Abstract
Morphinan-based opioids, derived from natural alkaloids like morphine, codeine and thebaine, have long been pivotal in managing severe pain. However, their clinical utility is marred by significant side effects and high addiction potential. This review traces the evolution of the morphinan scaffold in light of advancements in biochemistry and molecular biology, which have expanded our understanding of opioid receptor pharmacology. We explore the development of semi-synthetic and synthetic morphinans, their receptor selectivity and the emergence of biased agonism as a strategy to dissociate analgesic properties from undesirable effects. By examining the molecular intricacies of opioid receptors and their signaling pathways, we highlight how receptor-type selectivity and signaling bias have informed the design of novel analgesics. This synthesis of historical and contemporary perspectives provides an overview of the morphinan landscape, underscoring the ongoing efforts to mitigate the problems facing opioids through smarter drug design. We also highlight that most morphinan derivatives show a preference for the G protein pathway, although detailed experimental comparisons are still necessary. This fact underscores the utility of the morphinan skeleton in future opioid drug discovery.
Social media mindsets: a new approach to understanding social media use and psychological well-being
Authors: Lee Angela Y , Hancock Jeffrey T 
Published: February 2024

Abstract
Social media mindsets are the core beliefs that orient individuals’ expectations, behaviors, attributions, and goals about social media’s role in their lives. In four survey studies (N = 2,179), we show people hold distinct mindsets about the amount of agency they have over their social media use (“in control” vs. “out of control”) and the valence of its effects (“enhancing” vs. “harmful”) that are meaningfully related to psychological well-being. We develop and apply the Social Media Mindsets scale, revealing that agentic, positive mindsets are associated with better well-being and low-agency, and negative mindsets are associated with worse well-being (Studies 1, 2a, and 2b). Notably, these mindsets explained more variance in relational well-being and psychological distress than other measures (Study 3) and were related to differences in how people used social media and interpreted the time they spent on it (Studies 3 and 4). Our findings introduce a novel potential explanation for heterogeneous social media effects on well-being.
Religion, Pluralism, and the Australian State after Same-Sex Marriage
Authors: Tregenza Ian 
Published: February 2024

Abstract
Since the passing of same-sex marriage legislation in 2017, religious freedom has become a prominent feature of Australian public debate. Overwhelmingly, such debates are conducted within a human rights framework where principles such as individual autonomy and protection from discrimination are prioritized over the communal and associational elements of religious life. This in turn tends to augment the power of the state vis-à-vis religious communities and institutions. In important respects, the dominance of human rights represents a new manifestation of the kind of “liberal-statism”—a public philosophy of liberal individualism that accepts the primacy of the state in the management of cultural and religious diversity—that has been a central feature of Australian religion–state relations over time. After some historical discussion of Australian church–state practice, this article argues for a reconsideration of a largely overlooked approach deriving from the English pluralists of the early twentieth century, which promoted greater degrees of group autonomy in relation to a rapidly growing state. It is argued that this tradition has greater potential in responding to the religious diversity of our time than does the current human rights approach with its tendency to reinforce an individualistic or privatized conception of religion, diminish associational life, and thereby reinforce state power.
Bacterial resistance response and resource availability mediate viral coexistence
Authors: Butt Lisa , Meyer Justin R , Lindsay Richard J , Beardmore Robert E , Gudelj Ivana 
Published: February 2024

Abstract
Viruses that infect bacteria, known as bacteriophages or phages, are the most prevalent entities on Earth. Their genetic diversity in nature is well documented, and members of divergent lineages can be found sharing the same ecological niche. This viral diversity can be influenced by a number of factors, including productivity, spatial structuring of the environment, and host-range trade-offs. Rapid evolution is also known to promote diversity by buffering ecological systems from extinction. There is, however, little known about the impact of coevolution on the maintenance of viral diversity within a microbial community. To address this, we developed a 4 species experimental system where two bacterial hosts, a generalist and a specialist phage, coevolved in a spatially homogenous environment over time. We observed the persistence of both viruses if the resource availability was sufficiently high. This coexistence occurred in the absence of any detectable host-range trade-offs that are costly for generalists and thus known to promote viral diversity. However, the coexistence was lost if two bacteria were not permitted to evolve alongside the phages or if two phages coevolved with a single bacterial host. Our findings indicate that a host’s resistance response in mixed-species communities plays a significant role in maintaining viral diversity in the environment.
Making international trade work for sustainable development: toward a new WTO framework for subsidies
Authors: Cima Elena , Esty Daniel C 
Published: February 2024

Abstract
Government subsidies for fossil fuels, agricultural production, and fisheries amount to trillions of dollars per year. This funding harms economic efficiency, disrupts trade, and actively exacerbates the global environmental and climate crises. Moreover, the scale of these subsidies far exceeds the support provided to industries and activities that contribute to the transition towards a low-carbon and sustainable future economy. In seeking to discipline such subsidies, trade law has traditionally focused on whether the funding distorts trade without regard to the rationale or purpose of the subsidies. In this article, we argue that this approach to subsidies is at once incompatible with (i) the original vision of multilateral trade law, (ii) what is needed to manage international economic interdependence in today’s world, and (iii) the present moment’s urgent need to take seriously sustainable development as the ultimate objective of the trading system. The reform package we present in this article calls for a reframing of WTO subsidies rules on a foundation that gauges alignment with sustainable development alongside trade distortions, with sustainability becoming the first and foremost test of whether subsidies should be permitted—consistent with the sustainable development mandate in the Marrakesh Agreement that established the WTO.
A rare case of small cell carcinoma of the ovary, hypercalcemic type
Authors: Boujida Ismail , Mahdi Y , Khmou M , Ech-charif S , Horache K , El-Aoufir O , Gamra L , El-Khannoussi B 
Published: February 2024

Abstract
Small cell carcinoma of ovary, hypercalcemic type (SCCOHT) is an unusual malignant tumor that most commonly affects young women. Unfortunately, it has a very poor prognosis. We describe here an unusual case of a Moroccan young woman with a left ovarian mass and a symptomatic hypercalcemia. Morphologically, there are some malignant tumors that resemble SCCOHT; thus, it is very challenging to diagnose, and immunohistochemistry has a great contribution in it. Hopefully, molecular tools and new therapies will improve the management of these cases in the near future.
Untranslated yet indispensable—UTRs act as key regulators in the environmental control of gene expression
Authors: Hardy Emma C , Balcerowicz Martin 
Published: February 2024

Abstract
To survive and thrive in a dynamic environment, plants must continuously monitor their surroundings and adjust their development and physiology accordingly. Changes in gene expression underlie these developmental and physiological adjustments, and are traditionally attributed to widespread transcriptional reprogramming. Growing evidence, however, suggests that post-transcriptional mechanisms also play a vital role in tailoring gene expression to a plant’s environment. Untranslated regions (UTRs) act as regulatory hubs for post-transcriptional control, harbouring cis-elements that affect an mRNA’s processing, localization, translation, and stability, and thereby tune the abundance of the encoded protein. Here, we review recent advances made in understanding the critical function UTRs exert in the post-transcriptional control of gene expression in the context of a plant’s abiotic environment. We summarize the molecular mechanisms at play, present examples of UTR-controlled signalling cascades, and discuss the potential that resides within UTRs to render plants more resilient to a changing climate.
Chloroplast thiol redox dynamics through the lens of genetically encoded biosensors
Authors: Müller-Schüssele Stefanie J 
Published: February 2024

Abstract
Chloroplasts fix carbon by using light energy and have evolved a complex redox network that supports plastid functions by (i) protecting against reactive oxygen species and (ii) metabolic regulation in response to environmental conditions. In thioredoxin- and glutathione/glutaredoxin-dependent redox cascades, protein cysteinyl redox steady states are set by varying oxidation and reduction rates. The specificity and interplay of these different redox-active proteins are still under investigation, for example to understand how plants cope with adverse environmental conditions by acclimation. Genetically encoded biosensors with distinct specificity can be targeted to subcellular compartments such as the chloroplast stroma, enabling in vivo real-time measurements of physiological parameters at different scales. These data have provided unique insights into dynamic behaviours of physiological parameters and redox-responsive proteins at several levels of the known redox cascades. This review summarizes current applications of different biosensor types as well as the dynamics of distinct protein cysteinyl redox steady states, with an emphasis on light responses.
A post-merger enhancement only in star-forming Type 2 Seyfert galaxies: the deep learning view
Authors: Avirett-Mackenzie M S , Villforth C , Huertas-Company M , Wuyts S , Alexander D M , Bonoli S , Lapi A , Lopez I E , Ramos Almeida C , Shankar F 
Published: February 2024

ABSTRACT
Supermassive black holes require a reservoir of cold gas at the centre of their host galaxy in order to accrete and shine as active galactic nuclei (AGN). Major mergers have the ability to drive gas rapidly inwards, but observations trying to link mergers with AGN have found mixed results due to the difficulty of consistently identifying galaxy mergers in surveys. This study applies deep learning to this problem, using convolutional neural networks trained to identify simulated post-merger galaxies from survey-realistic imaging. This provides a fast and repeatable alternative to human visual inspection. Using this tool, we examine a sample of ∼8500 Seyfert 2 galaxies ($L[\mathrm{O\, {\small III}}] \sim 10^{38.5 - 42}$ erg s−1) at z &lt; 0.3 in the Sloan Digital Sky Survey and find a merger fraction of $2.19_{-0.17}^{+0.21}$ per cent compared with inactive control galaxies, in which we find a merger fraction of $2.96_{-0.20}^{+0.26}$ per cent, indicating an overall lack of mergers among AGN hosts compared with controls. However, matching the controls to the AGN hosts in stellar mass and star formation rate reveals that AGN hosts in the star-forming blue cloud exhibit a ∼2 × merger enhancement over controls, while those in the quiescent red sequence have significantly lower relative merger fractions, leading to the observed overall deficit due to the differing M*–SFR distributions. We conclude that while mergers are not the dominant trigger of all low-luminosity, obscured AGN activity in the nearby Universe, they are more important to AGN fuelling in galaxies with higher cold gas mass fractions as traced through star formation.
The Atacama cosmology telescope: flux upper limits from a targeted search for extragalactic transients
Authors: Hervías-Caimapo Carlos , Naess Sigurd , Hincks Adam D , Calabrese Erminia , Devlin Mark J , Dunkley Jo , Dünner Rolando , Gallardo Patricio A , Hilton Matt , Ho Anna Y Q , Huffenberger Kevin M , Ma Xiaoyi , Madhavacheril Mathew S , Niemack Michael D , Orlowski-Scherer John , Page Lyman A , Partridge Bruce , Puddu Roberto , Salatino Maria , Sifón Cristóbal , Staggs Suzanne T , Vargas Cristian , Vavagiakis Eve M , Wollack Edward J 
Published: February 2024

ABSTRACT
We have performed targeted searches of known extragalactic transient events at millimetre wavelengths using nine seasons (2013–2021) of 98, 150, and 229 GHz Atacama Cosmology Telescope (ACT) observations that mapped ∼40 per cent of the sky for most of the data volume. Our data cover 88 gamma-ray bursts (GRBs), 12 tidal disruption events (TDEs), and 203 other transients, including supernovae (SNe). We stack our ACT observations to increase the signal-to-noise ratio of the maps. In all cases but one, we do not detect these transients in the ACT data. The single candidate detection (event AT2019ppm), seen at ∼5σ significance in our data, appears to be due to active galactic nuclei activity in the host galaxy coincident with a transient alert. For each source in our search we provide flux upper limits. For example, the medians for the 95 per cent confidence upper limits at 98 GHz are 15, 18, and 16 mJy for GRBs, SNe, and TDEs, respectively, in the first month after discovery. The projected sensitivity of future wide-area cosmic microwave background surveys should be sufficient to detect many of these events using the methods described in this paper.