bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronically implantable µLED arrays for optogenetic cortical surface stimulation in mice
Authors: Greer Ryan , Verdier Antonin , Butt Emma , Cheng Yunzhou , Callas Ella , McAlinden Niall , Dawson Martin D. , Bathellier Brice , Mathieson Keith 
Published: February 2025

AbstractCortical implants are a proven clinical neurotechnology with the potential to transform our understanding of cognitive processes. These processes rely on complex neuronal networks that are difficult to selectively probe or stimulate. Optogenetics offers cell-type specificity, but achieving the density and coverage required for chronic, high-resolution modulation remains a challenge. Here we present a 100-element µLED array (200 µm pixel pitch, 2 × 2 mm2 footprint) coupled into a miniaturised, flexible system suitable for chronic implantation and optogenetic stimulation of the surface of the mouse cortex. The µLEDs can remain stable for over 300 hours continuous operation timein-vivo, allowing for months-long chronic experiments. Simultaneous electrophysiology recordings confirmed robust neuronal responses corresponding to low µLED drive currents (<5 mA), minimising thermal effects and supporting future wireless operation. The spatial resolution of neuronal responses was consistent with a simulated model of light scattering in the cortical layers, enabling device optimisation. Behavioural experiments with chronically implanted mice demonstrated robust learning during discrimination tasks using spatially distinct optogenetic stimulation patterns.
Community-level plant functional strategies explain ecosystem carbon storage across a tropical elevational gradient
Authors: Mauki Dickson , Manning Peter , Schleuning Matthias , Hemp Andreas , Costa David Schellenberger , Cornejo Natalia Sierra , Becker Joscha N. , Ensslin Andreas , Rutten Gemma , Neyret Margot 
Published: February 2025

Abstract1. Plant functional traits play an important role in shaping plant ecological responses to environmental conditions and influencing ecosystem functioning. However, how whole-plant functional strategies manifest at the community level to influence aboveground and belowground carbon storage across environmental gradients remains poorly understood.2. We measured aboveground and belowground carbon stocks and the variation in whole-plant (above- and belowground) functional strategies at the community level in twelve ecosystem types across a broad savanna-forest-alpine elevational gradient of climate and land use on Mt. Kilimanjaro, Tanzania. Using Structural Equation Models, we disentangled the direct and land use mediated influences of climate on carbon storage from indirect influences mediated by variation in plant functional strategies.3. We found strong coordination between above- and belowground functional traits at the whole community level, which corresponded with functional strategies related to two major trade-offs: aslow-conservation tofast-resource acquisition axis represented by a spectrum from high leaf dry matter content to high fine root nitrogen concentration; and a size-relatedwoodytograssycommunity axis represented by a spectrum spanning high canopy height to high specific root length. Theslow-fastandwoody-grassystrategy axes were primarily driven by precipitation and land-use intensity, respectively.4. Both functional strategies mediated the effects of climate on carbon storage. Theslow-faststrategy axis was strongly and positively associated with aboveground carbon stocks. Meanwhile, thewoody-grassystrategy axis was negatively associated with both aboveground carbon stocks and soil organic carbon stocks.5.Synthesis. We demonstrated that major plant functional strategies manifest at the community level along elevational gradients. These strategies also explain variation in carbon storage, although aboveground storage is mostly driven by trait effects, and belowground storage by direct effects of climate. Together, these results underscore the importance of incorporating functional community data into future analysis of climate change impacts on carbon storage, which would enhance our ability to predict potential shifts in ecosystem functioning.
CDKN2ALowcancer cells outcompete macrophages for microenvironmental zinc to drive immunotherapy resistance
Authors: Buj Raquel , Cole Aidan R. , Danielson Jeff , Xu Jimmy , Hurd Drew , Kishore Akash , Kedziora Katarzyna M. , Chen Jie , Yang Baixue , Barras David , Uboveja Apoorva , Amalric Amandine , Apiz Saab Juan J. , Wickramasinghe Jayamanna , Tangudu Naveen Kumar , Levasseur Evan , Wang Hui , Minasyan Aspram , Dadey Rebekah E. , Sharrow Allison C. , Vendetti Frank P. , Rivadeneira Dayana B. , Bakkenist Christopher J. , Delgoffe Greg M. , Hempel Nadine , Snyder Nathaniel W. , Bao Riyue , Soloff Adam C. , Kirkwood John M. , Dangaj Laniti Denarda , Kossenkov Andrew V. , Muir Alexander , Das Jishnu , Davar Diwakar , Mesaros Clementina , Aird Katherine M. 
Published: February 2025

ABSTRACTApproximately 50% of cancers exhibit decreasedCDKN2Aexpression (CDKN2ALow), which is linked to immune checkpoint blockade (ICB) resistance. WhileCDKN2Ais traditionally recognized as a tumor suppressor and cell cycle regulator, we have previously put forth a new paradigm demonstrating its role in intracellular metabolic reprogramming. Whether the metabolic derangement due toCDKN2Aloss alters metabolites within the tumor microenvironment (TME) and how that affects the immune compartment and ICB response has never been investigated. Here we found thatCDKN2ALowcancer cells reorganize zinc compartmentalization by upregulating the zinc importer SLC39A9 in the plasma membrane, leading to intracellular zinc accumulation in cancer cells and concurrent zinc depletion in the TME. This competition for zinc results in zinc-starved macrophages, leading to reduced phagocytic activity. Remarkably, restoring zinc levels in the TME through a dietary intervention re-educates macrophages to a pro-phagocytic phenotype, sensitizingCDKN2ALowtumors to ICB. Unexpectedly, T cells are not required for this response. Clinically, macrophages fromCDKN2ALowcancer patients have decreased zinc signatures, corresponding to reduced phagocytosis signatures. Moreover, patients with low circulating zinc levels have reduced time-to-event outcomes compared to those with higher zinc levels. Our work reveals a previously unrecognized mechanism through whichCDKN2ALowcancer cells outcompete macrophages for zinc, directly disrupting their function and ICB efficacy.
The substrate changes matrix metalloprotease-1 dynamics, allostery, and ligand binding affinity
Authors: Harms Chase , Nash Anthony , Sarkar Susanta K. 
Published: February 2025

ABSTRACTUsing single-molecule experiments, ensemble assays, and Molecular Dynamics (MD) simulations, we showed that collagen actively influences MMP1 interdomain dynamics. This paper extends the previous experimental work to validate MD simulations and gain more insights into MMP1-collagen interactions. We include virtual screening with free energy calculations to uncover key insights regarding substrate-dependent dynamics, allostery, and ligand binding. Our findings reveal that MMP1 interdomain dynamics are influenced by the strain in collagen, and collagen-specific allosteric residues exhibit strong correlations with the active site. Additionally, allosteric paths connecting these residues to the active site bypass the linker region. Collagen also induces changes in the configurations of the catalytic motif. Furthermore, MD simulation and virtual screening identify molecules that bind to allosteric residues, alter MMP1 dynamics, and potentially change activity. Free energy calculations highlight the essential role of the substrate in small molecule screening against a protein. We have developed a comprehensive framework for identifying substrate-specific allosteric residues in MMP1 and screening small molecules incorporating protein dynamics in the presence of substrates. These results significantly impact our understanding of MMP1 interactions with collagen fibrils and pave the way for selectively modulating specific MMP1 functions without altering its other functions in future applications.SignificanceIn this paper, we validated all-atom simulations of free and collagen-bound MMP1 and gained insights into MMP1 function. We have found that collagen changes dynamics, allostery, and ligand binding in MMP1. Collagen strain, known to be age-dependent, also changes MMP1 dynamics and ligand binding. Interdomain allosteric paths do not go through the linker connecting the MMP1 domains. Instead, paths from the collagen-specific allosteric residue to the active site have non-bonded interactions. Screening of small molecules against collagen-specific MMP1 residue suggests that collagen alters ligand binding to MMP1. These results will significantly impact understanding MMPs and small molecule screening against proteins. Substrate-specific allosteric residues may enable controlling one function of MMPs without altering their other functions, leading to fewer side effects.
Molecular convergence analyses identify candidate genes for low susceptibility to the ash dieback pathogen
Authors: Kelly Laura J. , Coates Sarah E. R. , Lee Steve J. , Rossiter Stephen J. , Buggs Richard J. A. 
Published: February 2025

AbstractThe detection of molecular convergence can be an effective approach for uncovering loci underlying adaptive traits that have evolved independently between lineages. Within the genusFraxinus(ash trees) low susceptibility to the fungal pathogenHymenoscyphus fraxineus, the causative agent of the ash dieback disease (ADB) epidemic, is observed in three independent lineages of known or plausible natural hosts. Here, we seek to identify the genetic basis of this trait, which is key to the future survival ofFraxinus excelsiorpopulations in Europe. We analysed 4,300 protein-coding loci for amino acid convergence between lineages with low susceptibility. After filtering for potential false positives, we find 62 genes that have a signal of excess convergence betweenFraxinuslineages with low ADB susceptibility. Eleven of these loci have additional evidence for a role in defence against fungal pathogens, with a further 17 linked to more general immunity or defence, or to other functions relevant to the response against ADB such as cell wall biogenesis. Two of the loci we detect have previously been identified as differentially expressed inF. excelsiorin response to infection byH. fraxineusin controlled inoculations. The set of candidate loci discovered here complements those reported by previous genomic studies ofF. excelsior, and can be targeted in efforts to mitigate the devastation caused by this deadly disease by informing breeding programmes involving hybridisation and marker-assisted back-crossing.
From Vodka to Craft Beer: The Craft Beer Revolution in the Baltic States
Authors: Fertő Imre , Viira Ants‐Hannes , Stalgiené Aldona , Bakucs Zoltán 
Published: February 2025

SummaryThe once flourishing beer sector of the Baltic states was decimated and homogenised into low‐quality mass‐produced beer during Soviet times. Against this background, the article examines the micro‐ and craft beer scenes in the Baltic States, exploring their historical growth, regulatory changes, cultural and economic factors, and the key differences across the three countries. The focus is on Estonia, Latvia, and Lithuania, where craft beer has once again gained prominence over traditional spirits like vodka.This shift reflects the broader cultural and economic changes in the region. In Lithuania, the revival of ancient farmhouse brewing techniques has been central to the craft beer movement. Latvia, with its strong German‐influenced brewing history, has seen the craft beer sector emerge as a competitive force, despite the dominance of large breweries. However, Latvian microbreweries face challenges from established players. Estonia, despite a late start, has rapidly developed a thriving craft beer industry, driven by its strong digital infrastructure and entrepreneurial spirit, particularly in urban centres like Tallinn. The shift from vodka to beer in the Baltic States reflects deeper socio‐economic changes shaped by regulatory frameworks, cultural evolution, and economic restructuring, resulting in dynamic and diverse beer markets across the region.
Conformational, physiochemical, and functional properties of quinoa protein isolate influenced by thermal treatment
Authors: Chang Jiaojiao , Zhao Yong , Xu Jingwen 
Published: February 2025

AbstractThis study investigated the effect of various thermal treatments, including atmospheric boiling (AB), high‐pressure boiling (HPB), and baking (B), on the conformational, physicochemical, and functional properties of quinoa protein isolate (QPI), as well as its in vitro digestibility. Thermal treatment resulted in QPI denaturation, unfolding, and more exposure of hydrophobic groups, which was reflected as the reduced content of α‐helix and increased contents of β‐sheet and β‐turn. The reduced content of free sulfhydryl (SH) groups and total SH groups in thermally treated QPI also indicated that thermal treatment promoted QPI denaturation and unfolding. The functionalities of QPI, such as solubility, oil‐holding capacity, emulsification index, emulsion stability, and gel strength, were improved by thermal treatment, wherein HPB‐QPI > AB‐QPI > B‐QPI > control QPI. Thermal treatment improved in vitro digestibility of QPI and the contents of essential amino acids and hydrophobic amino acids compared to those of control QPI. HPB‐QPI showed the highest digestibility in vitro up to 88.26%, and the highest content of essential amino acids and hydrophobic amino acids up to 497.17 mg/g and 344.45 mg/g, respectively. This study provided new insights into the conformational behaviors and functionalities of QPI through thermal processing for benefiting their applications in the food industry.Practical ApplicationThrough thermal treatment, the functional properties of quinoa protein were significantly enhanced, leading to improvements in plant‐based beverages, emulsified foods, and baked goods, thereby expanding its range of applications in the food industry.
The Long and the Short of It: Nanopore‐Based eDNA Metabarcoding of Marine Vertebrates Works; Sensitivity and Species‐Level Assignment Depend on Amplicon Lengths
Authors: Doorenspleet Karlijn , Jansen Lara , Oosterbroek Saskia , Kamermans Pauline , Bos Oscar , Wurz Erik , Murk Albertinka , Nijland Reindert 
Published: February 2025

ABSTRACTTo monitor the effect of nature restoration projects in North Sea ecosystems, accurate and intensive biodiversity assessments are vital. DNA‐based techniques and especially environmental (e)DNA metabarcoding is becoming a powerful monitoring tool. However, current approaches rely on genetic target regions under 500 bp, offering limited taxonomic resolution. We developed a method for long‐read eDNA metabarcoding, using Nanopore sequencing of a longer amplicon and present DECONA, a read processing pipeline to enable improved identification of marine vertebrate species. We designed a universal primer pair targeting a 2 kb region of fish mitochondrial DNA and compared it to the commonly used MiFish primer pair targeting a ~ 170 bp region. In silico testing showed that 2 kb fragments improved accurate identification of closely related species. Analysing eDNA from a North Sea aquarium showed that sequences from both primer pairs could be assigned to most species, and additional species level assignments could be made through the 2 kb primer pair. Interestingly, this difference was opposite in eDNA from the North Sea, where not the 2 kb but the MiFish primer pair detected more species. This study demonstrates the feasibility of using long‐read metabarcoding for eDNA vertebrate biodiversity assessments. However, our findings suggests that longer fragments are less abundant in environmental settings, but not in aquarium settings, suggesting that longer fragments may provide a more recent snapshot of the community. Thus, long‐read metabarcoding can expand the molecular toolbox for biodiversity assessments by improving species‐level identification and may be especially useful when the temporal origin of the eDNA signal is better understood.
What a relief: How do firms respond to competitors' listing delays?
Authors: Jia Ning , Qian Jiaqi , Tian Xuan , Yu Jinxin 
Published: February 2025

AbstractWe examine the effect of product market competitors' listing delays on incumbent firms' defensive strategies, including efforts in customer retention and acquisition as well as merger and acquisition (M&A) activities. To establish causality, we use four regulation‐induced IPO suspensions in China that expose firms already approved for an IPO to indeterminate listing delays. Using a difference‐in‐differences design, we find that incumbent firms reduce efforts in customer retention and acquisition, as manifested in an increase in accounts receivable turnover and a decrease in selling expenses. Incumbent firms also reduce M&A activities, including high‐premium and horizontal ones. The effects are stronger for incumbent firms that are subject to more intensive competition from the suspended firm, face larger competitive pressure from existing public firms, and are more financially constrained. Additionally, incumbent firms' managers reduce competition‐related disclosures, and the firms' financial performance improves after competitors' listing delays. Consistent with the findings based on listing delays, we find that incumbent firms increase efforts in customer retention and acquisition and M&As surrounding competitors' IPO application and approval. Our paper sheds new light on the IPO peer effect, especially on how incumbent firms respond to the product market competitor's capital market entry.
Rise of the south: How Arab‐led maritime trade transformed China, 671–1371 CE
Authors: Chen Zhiwu , Lin Zhan , Peng Kaixiang 
Published: February 2025

AbstractChina's center of socioeconomic activities was in the North prior to the Tang dynasty but is in the South today. We demonstrate that Arab and Persian Muslim traders triggered that transition when they came to China in the late seventh century, by lifting maritime trade along the South Coast and re‐creating the South. Between 742 and 1393 CE, prefectures with better access to maritime trade, or higher porcelain trade participation, experienced significantly higher population growth, but the predictive coefficient weakened substantially after the maritime trade ban of 1371 CE. These findings are robust after controlling for many confounding factors.
Exposure to potentially teratogenic medications before and during the first trimester of pregnancy compared to women of childbearing age: A retrospective analysis of Swiss claims data (2015–2021)
Authors: Marxer Carole A. , Graber Sereina M. , Surbek Daniel , Panchaud Alice , Meier Christoph R. , Spoendlin Julia 
Published: February 2025

AbstractIntroductionExposure to potentially teratogenic medications during pregnancy is underinvestigated in Switzerland. We aimed to assess exposure to potential teratogens preconceptionally, during the first trimester, and in women of childbearing age, and specifically explore the effectiveness of the valproate pregnancy prevention program (2018).Material and MethodsRetrospective study using the Swiss Helsana claims database. In a pregnancy cohort (2015–2021) and a cohort of women of childbearing age (2021 and 2018), we defined three 90‐day time periods: (1) first trimester, (2) preconceptional period (days 180–90 before pregnancy), and (3) January 01, 2021, and March 31, 2021 (women of childbearing age). During all periods, we quantified the exposure prevalence to at least one dispensed weak, proven, and unequivocally potent teratogen overall and by age strata. We quantified the exposure prevalence to each individual teratogen, and to valproate during pregnancy by calendar year to compare its use before and after the introduction of a pregnancy prevention program (2018). We investigated the use of systemic retinoids particularly isotretinoin in women of childbearing age.ResultsOf 34 584 pregnant women, 1.4% were exposed to potential teratogens during the first trimester (weak: 1.3%, proven: 0.06%, unequivocally potent: 0.04%). During the preconceptional period, 2.9% were exposed to any teratogen compared to 4.7% of women of childbearing age (Ntotal = 95 059). Systemic glucocorticoids were the most prevalent weak teratogens during all time periods (75% of all claimed teratogens during the first trimester). In the first trimester, the antibiotic cotrimoxazole and the thyreostatic thiamazole (weak teratogens), ranked second and third, followed by the antiseizure medications carbamazepine and topiramate (proven teratogens). Among women of childbearing age, exposure to weak and proven teratogens increased with age, whereas exposure to unequivocally potent teratogens decreased with age. This was due to 2.3% of women <26 years who claimed systemic isotretinoin. Valproate use during pregnancy decreased after the introduction of a pregnancy prevention program (2.39/10 000 pregnancies [2015–2018] vs. 0.93/10 000 pregnancies [2019–2021]).ConclusionsMost medications with potential teratogenic effects dispensed to women of childbearing age and pregnant women were in the group of weak teratogenicity level, and many women discontinued treatment before pregnancy. Preliminary evidence suggests the valproate pregnancy prevention program in Switzerland may be beneficial.
Involvement of the somatosensory‐autonomic reflex and muscarinic receptors in exacerbation of allergic pulmonary inflammation by electroacupuncture
Authors: Liu Shuyan , Ge Jiayi , Liu Weili , Zhuang Zhidi , Liu Shenbin 
Published: February 2025

Background and PurposeEmerging evidence suggests that electroacupuncture (EA) could cause autonomic reflexes to modulate visceral functions. However, the efficacy and underlying mechanisms for somatic stimulation on allergic pulmonary inflammation (API) remain elusive.Experimental ApproachMice were administered intranasal Papain to induce API. Distinct current (0,0.1, 0.2 and 0.5 mA) of EA at the back BL13, hindlimb ST36 and forelimb LU5 acupoint were then carried out. The control group underwent the same procedure but without current stimulation. Changes in API was assessed using immunohistochemistry, flow cytometry and haematoxylin and eosin (H&E) staining. Pharmacological approaches were used to investigate the underlying mechanisms of EA effects on API.Key ResultsEA at the back region but not limb regions, in a current intensity‐dependent manner, exacerbated API, primarily causing a decrease in the survival rate and intensified inflammation in the lung, including the infiltration of lung type 2 innate lymphoid cells and eosinophils, and lung pathology scores. Blocking local thoracic sensory nerves with lidocaine or lung‐innervated autonomic nerves with hexamethonium eliminates the EA‐produced detrimental effects. Chemical pulmonary sympathectomy with 6‐OHDA further enhanced lung pathology scores, but inhibiting the activity of pulmonary muscarinic receptors was sufficient to prevent the exacerbation of API induced by EA.Conclusion and ImplicationsOur findings suggest that BL13 EA induces a somatic‐autonomic reflex involving the pulmonary muscarinic receptors, thereby exacerbating API. The selective and intensity‐dependency activation of body thoracic regions in driving pulmonary autonomic pathways could help optimise stimulation parameters, enhancing both efficacy and safety in modulating API.