bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial susceptibility testing ofClostridioides difficile: a dual-site study of three different media and three therapeutic antimicrobials
Authors: Freeman Jane , Sanders Ingrid M.J.G. , Harmanus Céline , Clark Emma V. , Berry Andrea M , Smits Wiep Klaas 
Published: November 2024

ABSTRACTObjectivesIncreasing resistance to antimicrobials used for the treatment ofClostridioides difficileinfections necessitates reproducible antimicrobial susceptibility testing. Current guidelines take a one-size-fits-all approach and/or offer limited guidance. We investigated how the choice of medium affects measured MIC values across two sites.MethodsWe determined MIC values for the antimicrobials fidaxomicin, metronidazole and vancomycin for a representative collection of EuropeanC. difficilestrains (n=235) using agar dilution on three different media: Brucella Blood Agar (BBA), Fastidious Anaerobe Agar supplemented with horseblood (FAA-HB) and Wilkins-Chalgren (WC) agar. The study was conducted at two sites to compare reproducibility. Useability (ease of preparation of the media as well as read-out of the assay) was assessed through a survey.ResultsWe found that all media result in highly consistent aggregated MIC data for all antibiotics, with MIC50and MIC90within 2-fold of each other across sites. For fidaxomin, MIC values on WC were lower than on the other media. Metronidazole showed the lowest MIC on BBA, and the highest on WC. For vancomycin, there was little difference between media. Though absolute values for individual isolates differed between sites, identified resistant isolates were similar. Results obtained on FAA-HB were most consistent between sites and results obtained on WC showed the most divergence. FAA-HB was positively evaluated in the usability survey.ConclusionsThis study shows medium-dependent differences inC. difficileMICs for at least two antimicrobials across two sites. We suggest the use of FAA-HB to align with general EUCAST recommendations for susceptibility testing of anaerobic bacteria and deposited reference strains for standard susceptibility testing ofC. difficileto increase interlaboratory reproducibility.
Potential for Biodiversity in Shared Residential Yards
Authors: Livne Havi , Gruntman Michal , Blumenfeld Lieberthal Efrat 
Published: November 2024

AbstractIn urban environments, attention has traditionally been paid to public open spaces. However, private open spaces constitute a significant percentage of the urban area and can thus play a significant role in enhancing biological diversity and facilitating direct interactions between humans and nature within urban settings. According to the 2018 European Union report, 46% of homeowners across Europe live in apartment buildings and yet, most studies that examine the effect of private open spaces on biodiversity focus primarily on yards of single-family housing. The objective of this study is to examine the biodiversity potential offered by shared residential yards focusing exclusively on wild plant species, with the aim of offering planning guidelines that address both the management practices of these lot spaces and their spatial arrangement and qualities. The study was conducted in the city of Givatayim, Israel, in shared residential yards. The basic units (lots and buildings on them) in the city were delineated using a novel approach through a separate characterization of lot sizes and building types, as well as their combination. This process resulted in typologies that cover all residential fabric in the city, allowing systematic sampling. In the spring of 2022, plant surveys were conducted in 56 randomly chosen yards. In these lots, potential open area was measured, and the level of non-maintenance (neglection) was also rated. 74 species of wild plants were found, representing a quarter of all wild plant species in the city. Our results show the combined positive effect of available open space and levels of non-maintenance in these yards on the richness and diversity of wild species. This study highlights the substantial area occupied by residential yards in the city and its role in maintaining biodiversity in urban environments. This study indicates the importance of considering these aspects in architectural and management policies in cities.
Inhibition of Myoglobin Oxidation by Food Grade Botanical Antioxidant Formulations
Authors: Vergara-Stange Valentina , Batista-Gonzalez Ana , Contreras Rodrigo A. 
Published: November 2024

AbstractThis study explores the antioxidant capabilities of green tea and acerola extracts in inhibiting myoglobin oxidation, a critical factor in preserving color stability in food products, mainly plant-based meat analogs. Extracts were analyzed for their antioxidant activity using DPPH and ORAC assays, followed by evaluations of their inhibitory effects on myoglobin oxidation at 25 °C and 35 °C. Acerola showed quick inhibitory effects even at lower concentrations and moderate temperatures, likely due to its high ascorbic acid levels. On the other hand, green tea’s effectiveness varied with temperature, with inhibition rates rising at 35 °C, probably because its polyphenolic compounds are sensitive to heat. The kinetics and thermodynamics analysis showed positive activation energy (Ea) for green tea, meaning it becomes more active as temperatures rise. In contrast, acerola’s negative Ea indicates heat reduces its efficacy. These results suggest that acerola and green tea could be natural alternatives to synthetic antioxidants, helping preserve the appearance and stability of different food products.
Comprehensive Evaluation of AlphaFold-Multimer, AlphaFold3 and ColabFold, and Scoring Functions in Predicting Protein-Peptide Complex Structures
Authors: Manshour Negin , Ren Jarett Zida , Esmaili Farzaneh , Bergstrom Erik , Xu Dong 
Published: November 2024

AbstractDetermining the three-dimensional structures of protein-peptide complexes is crucial for elucidating biological processes and designing peptide-based drugs. Protein-peptide docking has become essential for predicting complex structures. AlphaFold-Multimer, ColabFold and AlphaFold3 provided groundbreaking tools to enhance the protein-peptide docking accuracy. This study evaluates these three tools for predicting protein-peptide complex structures using Template-Based (TB) and Template-Free (TF) methods. AlphaFold-Multimer excels in TB predictions and performs moderately in TF scenarios in the prediction pool, but TF outperforms TB in the first-ranked models. ColabFold demonstrates versatility in both TB and TF settings. AlphaFold3 generates high-quality structures for more proteins, but the medium accuracy is not as good as AlphaFold-Multimer using a large model pool. We also assessed the performance of various scoring functions in ranking predicted protein-peptide complex structures. While the scoring function built in AlphaFold demonstrates the best performance, some other scoring functions, e.g., FoldX-Stability and HADDOCK-mdscore, provide complementary values. The findings suggest the potential for enhancing scoring functions targeting AlphaFold-based predictions by combining multiple scoring functions or using a consensus approach from many prediction models.
The Virtual Lab: AI Agents Design New SARS-CoV-2 Nanobodies with Experimental Validation
Authors: Swanson Kyle , Wu Wesley , Bulaong Nash L. , Pak John E. , Zou James 
Published: November 2024

AbstractScience frequently benefits from teams of interdisciplinary researchers. However, most scientists don’t have access to experts from multiple fields. Fortunately, large language models (LLMs) have recently shown an impressive ability to aid researchers across diverse domains by answering scientific questions. Here, we expand the capabilities of LLMs for science by introducing the Virtual Lab, an AI-human research collaboration to perform sophisticated, interdisciplinary science research. The Virtual Lab consists of an LLM principal investigator agent guiding a team of LLM agents with different scientific backgrounds (e.g., a chemist agent, a computer scientist agent, a critic agent), with a human researcher providing high-level feedback. We design the Virtual Lab to conduct scientific research through a series of team meetings, where all the agents discuss a scientific agenda, and individual meetings, where an agent accomplishes a specific task. We demonstrate the power of the Virtual Lab by applying it to design nanobody binders to recent variants of SARS-CoV-2, which is a challenging, open-ended research problem that requires reasoning across diverse fields from biology to computer science. The Virtual Lab creates a novel computational nanobody design pipeline that incorporates ESM, AlphaFold-Multimer, and Rosetta and designs 92 new nanobodies. Experimental validation of those designs reveals a range of functional nanobodies with promising binding profiles across SARS-CoV-2 variants. In particular, two new nanobodies exhibit improved binding to the recent JN.1 or KP.3 variants of SARS-CoV-2 while maintaining strong binding to the ancestral viral spike protein, suggesting exciting candidates for further investigation. This demonstrates the ability of the Virtual Lab to rapidly make impactful, real-world scientific discovery.
Phosphorylation of MdWRKY70L by MdMPK6/02G mediates reactive oxygen synthesis to regulate apple fruit senescence
Authors: Wang Hui , Zhang Shuhui , Feng Yuchen , Sun Lulong , Yan Peng , Feng Yifeng , Zhao Zhengyang 
Published: November 2024

ABSTRACTApple (Malus domestica) is a globally significant crop and a vital dietary component worldwide. During ripening, apples exhibit a longitudinal gradient, ripening first at the stalk cavity and extending toward the calyx pit. Over-ripening in the stalk cavity leads to early senescence, characterized by peel browning, which diminishes fruit quality. This study examines the natural senescence process in 6-year-old ‘Ruixue’ apples by screening transcriptome data to uncover senescence-related genes and validate their molecular functions. Our analysis of antioxidant capacity and reactive oxygen species in different peel regions revealed that malondialdehyde, hydrogen peroxide, and superoxide anion levels increased with senescence, especially in the stalk cavity. Transcriptome clustering and enrichment analyses across developmental stages revealedMdWRKY70L,MdSAG101, andMdZAT12as key regulators of peel senescence. Further invitroand invivostudies demonstrated that MdWRKY70L is phosphorylated at Ser199 by MdMPK6/02G, enhancing its stability and promoting peel senescence. These findings offer insights for developing strategies to delay fruit senescence and improve postharvest quality control.
Adaptive protein coevolution preserves telomere integrity
Authors: Lin Sung-Ya , Futeran Hannah , Levine Mia T. 
Published: November 2024

AbstractMany essential conserved functions depend, paradoxically, on proteins that evolve rapidly under positive selection. How such adaptively evolving proteins promote biological innovation while preserving conserved, essential functions remains unclear. Here, we experimentally test the hypothesis that adaptive protein-protein coevolution within an essential multi-protein complex mitigates the deleterious incidental byproducts of innovation under pressure from selfish genetic elements. We swapped a single, adaptively evolving subunit of a telomere protection complex fromDrosophila yakubainto its close relative,D. melanogaster. The heterologous subunit uncovered a catastrophic interspecies incompatibility that caused lethal telomere fusions. Restoring six adaptively evolving sites on the protein-protein interaction surface, or introducing theD. yakubainteraction partner, rescued telomere integrity and viability. Ourin vivo, evolution-guided manipulations illuminate how adaptive protein-protein coevolution preserves essential functions threatened by an evolutionary pressure to innovate.
Measuring Growth, Resistance, and Recovery after Artemisinin Treatment of Plasmodium falciparum in a single semi-high-throughput Assay
Authors: Sievert Mackenzie A.C. , Singh Puspendra P. , Shoue Douglas A. , Checkley Lisa A. , Brenneman Katelyn M. , Qahash Tarrick , Cassady Zione , Kumar Sudhir , Li Xue , Nosten François H. , Anderson Timothy J.C. , Vaughan Ashley M. , Romero-Severson Jeanne , Ferdig Michael T. 
Published: November 2024

AbstractBackgroundArtemisinin partial resistance (ART-R) has spread throughout Southeast Asia and mutations inpfKelch13, the molecular marker of resistance, are widely reported in East Africa. Effectivein vitroassays and robust phenotypes are crucial for monitoring populations for the emergence and spread of resistance. The recently developed extended Recovery Ring-stage Survival Assay used a qPCR-based readout to reduce the labor intensiveness forin vitrophenotyping of ART-R and improved correlation with the clinical phenotype of ART-R. Here, we extend and refine this assay to include measurements of parasite growth and recovery after drug exposure. Clinical isolates and progeny from two genetic crosses were used to optimize and validate the reliability of a straight-from-blood, SYBR Green-based qPCR protocol in a 96-well plate format to accurately measure phenotypes for Growth, Resistance, and Recovery.ResultsThe assay determined growth between 6 h and 96 h, resistance at 120 h, and recovery from 120 h and 192 h. Growth can be accurately captured by qPCR and is shown by reproduction of previous growth phenotypes from HB3 × Dd2. Resistance measured at 120 h continually shows the most consistent phenotype for ring stage susceptibility. Recovery identifies an additional response to drug than parasites that are determined sensitive by Fold Change at 120 h. Comparison of progeny phenotypes for Growth vs Resistance showed a minor but significant correlation, whereas Growth vs Recovery and Resistance vs Recovery showed no significant correlation. Additionally, dried blood spot (DBS) samples matched Fold Change measured from liquid samples demonstrating Resistance can be easily quantified using either storage method.ConclusionsThe qPCR-based methodology provides the throughput needed to quickly measure large numbers of parasites for multiple relevant phenotypes. Growth can reveal fitness defects and illuminate relationships between proliferation rates and drug response. Recovery serves as a complementary phenotype to resistance that quantifies the ability of sensitive parasites to tolerate drug exposure. All three phenotypes offer a comprehensive assessment of parasite-drug interaction each with independent genetic determinants of main effect and overlapping secondary effects that should be further. By adapting our method to include DBS, readouts can be easily extended toex vivosurveillance applications.
Asymmetric neuromodulation in the respiratory network contributes to rhythm and pattern generation
Authors: Dhingra Rishi R. , MacFarlane Peter M. , Thomas Peter J. , Paton Julian F.R. , Dutschmann Mathias 
Published: November 2024

AbstractLike other brain circuits, the brainstem respiratory network is continually modulated by neurotransmitters that activate slow metabotropic receptors. In many cases, activation of these receptors only subtly modulates the respiratory motor pattern. However, activation of some receptor types evokes the arrest of the respiratory motor pattern as can occur following the activation of µ-opioid receptors. We propose that the varied effects of neuromodulation on the respiratory motor pattern depend on the pattern of neuromodulator receptor expression and their influence on the excitability of their post-synaptic targets. Because a comprehensive characterization of these cellular properties across the respiratory network remains challenging, we test our hypothesis by combining computational modelling with ensemble electrophysiologic recording in the pre-Bötzinger complex (pre-BötC) using high-density multi-electrode arrays (MEA). Our computational model encapsulates the hypothesis that neuromodulatory transmission is organized asymmetrically across the respiratory network to promote rhythm and pattern generation. To test this hypothesis, we increased the strength of neuromodulatory connections in the model and used selective agonistsin situwhile monitoring pre-BötC ensemble activities. The model predictions of increasing slow inhibition were consistent with experiments examining the effect of systemic administration of the 5HT1aR agonist 8-OH-DPAT. Similarly, the predicted effects of increasing slow excitation in the model were experimentally confirmed in pre-BötC ensemble activities before and after systemic administration of the µ-opioid receptor agonist fentanyl. We conclude that asymmetric neuromodulation can contribute to respiratory rhythm and pattern generation and accounts for its varied effects on breathing.
U1 snRNP-Specific U1C Acts as the Gatekeeper of the Survival of Motor Neurons (SMN) Complex in snRNP Biogenesis
Authors: Ngu Duc Minh , Myti Sanat , Khan Ayesha Ali , Keita Jeannine , Moore Tessa , Andega Paul , Aziz Alaa , Raj Ritu , Park Meeyeon , Johnson-Winters Kayunta , Suh Eul hyun , Yong Jeongsik , So Byung Ran 
Published: November 2024

SUMMARYThe stability and abundance of spliceosomal snRNPs are determined by the assembly of an Sm protein ring (Sm core) on each snRNA, a process facilitated by the survival of motor neuron (SMN) complex. Whereas the SMN complex’s role as a chaperone is well-established, the mechanisms that regulate its activity remain unclear. Our study identifies U1C, a U1 snRNP-specific protein, as a key regulator of the SMN complex. U1C together with U1-70K facilitates U1 snRNP formation, rendering the SMN complex accessible for other snRNAs to assemble Sm cores. Remarkably, a prevalent cancer-associated mutation in U1 snRNA near the U1C binding site not only disrupts Sm core assembly but also sequesters the SMN complex, inhibiting canonical snRNP formation. Our findings provide mechanistic insights into how snRNP-specific proteins regulate the SMN complex and suggest that U1 snRNA mutations in numerous cancers disrupt the SMN complex, leading to perturbation in various RNA metabolism pathways.HighlightsU1C facilitates the formation of Sm core not only on U1 snRNA but also on other snRNAs.U1C together with U1-70K promotes U1 snRNP formation, enabling the SMN complex to recruit Gemin5/other snRNAs complex.The divalent binding of U1C to the SMN complex is mediated by U1C’s N-terminus helix, interacting with U1-70K, and its arginine-methylated C-terminus domain, binding to the SMN protein.Multiple U1 snRNA mutations in cancer patients defect in Sm core assembly and potentially sequester the SMN complex, thereby inhibiting canonical snRNP formation.
Public opinions from Malawian and Malawi refugee camp residents of wastewater and environmental surveillance
Authors: Jeboda Dammy , Shackelford Brandie Banner , Chigwechokha Petros , Chunga Brighton A. , Ercumen Ayse , Workman Cassandra , Hart Joy L. , Smith Ted , Holm Rochelle H. 
Published: November 2024

AbstractAcross low- and middle-income countries, there have been calls to expand wastewater and environmental surveillance to include non-sewered sanitation systems. Considering public opinion, understanding, and acceptance, as well as any related privacy and personal health information concerns, in this context is important. This study used an in-person survey to learn more about Malawian and Malawi refugee camp residents’ perceptions of wastewater and environmental surveillance as public health tools, and their perceptions of privacy and personal health information. A 15-question survey was conducted from May to July 2024 at three locations in northern, central, and southern Malawi, including a refugee camp (n= 536). Some respondents (n= 30) also completed a board game and a post-board game survey. The results indicated high public support for surveilling communicable diseases, deadly diseases, environmental toxicants, healthy eating, illegal drugs, mental illnesses, and prescription drugs. Respondents were less supportive of surveillance that may expose their lifestyle behaviors and alcohol use. Regarding sampling locations, the surveillance of an entire city or of camp and schools had the highest acceptance. Some opposition to surveillance in business and religious organizations was found. If their sanitation waste was to be monitored, the respondents wanted the results of the data analysis to be communicated. Our findings suggested that Malawian and Malawi camp residents supported, with little concern, ongoing wastewater and environmental surveillance for public health. Considering privacy thresholds and participant autonomy regarding public health surveillance tools among cultural relevancies is important for future policy development and investment.
Single-photon large-momentum-transfer atom interferometry scheme for Sr or Yb atoms with application to determining the fine-structure constant
Authors: Schelfhout Jesse S. , Hird Thomas M. , Hughes Kenneth M. , Foot Christopher J. 
Published: November 2024

The leading experimental determinations of the fine-structure constant α currently rely on atomic photon-recoil measurements from Ramsey-Bordé atom interferometry with large-momentum transfer to provide an absolute mass measurement. We propose an experimental scheme for an intermediate-scale differential atom interferometer to measure the photon recoil of neutral atomic species with a single-photon optical clock transition. We calculate trajectories for our scheme that optimize the recoil phase while nullifying the undesired gravity-gradient phase by considering independently launching two clouds of ultracold atoms with the appropriate initial conditions. For Sr and Yb, we find an atom interferometer of height 3 m to be sufficient for an absolute mass measurement precision of Δm/m∼1×10−11 with current technology. Such a precise measurement would halve the current uncertainty in α, an uncertainty that would no longer be limited by an absolute mass measurement. The removal of this limitation would allow the current uncertainty in α to be reduced by a factor of 10 by corresponding improvements in relative mass measurements, thus paving the way for higher-precision tests of the standard model of particle physics.

Published by the American Physical Society
2024
Experimental Demonstration of Mode-Coupled and High-Brightness Self-Amplified Spontaneous Emission in an X-Ray Free-Electron Laser
Authors: Prat Eduard , Hu Wenxiang , Arrell Christopher , Calvi Marco , Dijkstal Philipp , Follath Rolf , Reiche Sven 
Published: November 2024

X-ray free-electron lasers (FELs) are modern research tools with applications in multiple scientific fields. Standard x-ray FEL pulses are produced by the self-amplified spontaneous emission (SASE) mechanism. SASE-FEL pulses have high power, short duration, and excellent transverse coherence but exhibit poor temporal coherence with power and spectral profiles consisting of multiple randomly distributed spikes. Here, we present the demonstration of two modes that enhance the temporal coherence of SASE-FEL radiation: mode-coupled and high-brightness SASE. Both schemes are based on delaying the electron beam with magnetic chicanes placed between the undulator modules of the FEL facility. First, we show the generation of frequency combs with tunable peak separation via the mode-coupled SASE scheme. Second, we present a proof-of-principle demonstration of the high-brightness SASE mechanism, producing FEL pulses with a bandwidth reduction up to a factor of 3 with respect to standard SASE pulses. The demonstration was done at Athos, the soft x-ray beamline of SwissFEL, for photon energies between 500 and 600 eV. Our work will benefit current applications and may open up new research areas requiring frequency combs or narrow bandwidths.

Published by the American Physical Society
2024