bluuebunny/crossref_metadata_2025 huggingface dataset:
2 The work of the British School at Athens, 2023–2024
Authors: Sweetman Rebecca
Published: December 2024

This article, based on an oral presentation in virtual format by the author at its Annual General Meeting in February 2024, summarizes the activities of the British School at Athens with a focus on the calendar year 2023. It gives us great pleasure to present the innovative and varied work of BSA sponsored field and research projects, the Fitch Laboratory, Knossos Research Centre, archive, and library as well as the inspiring work of the School students, post docs, and fellows.
Prevalence of burnout and its determinants among Indonesian nurses: a multicentre study
Authors: Juanamasta I. Gede , Aungsuroch Yupin , Gunawan Joko , Dino Michael Joseph , Polsook Rapin
Published: December 2024

Frontline health workers face a significant issue concerning mental health, particularly stress and burnout. Nurses, being among them, grapple with this problem. The study aims to investigate the prevalence and determinants of burnout among nurses. A multicenter cross-sectional study was conducted across twenty two hospitals. A total of nine hundred nurses participated through convenience sampling. Burnout was measured using a single-measurement approach. Both individual and unit-related factors were examined. Over half of the nurses experienced stress, while 7.3% had symptoms of exhaustion. One in every hundred nurses faced a high likelihood of experiencing complete burnout. Job satisfaction, basic salary, motivation, age, incentives, competence, extra responsibilities, and knowledge of quality emerged as significant predictors of burnout. Addressing burnout among nurses requires hospitals to improve job satisfaction, revisit salaries, and foster supportive environments with incentives. Tailored training and ongoing support are crucial for resilience. Prioritizing these strategies is vital for nurses' well-being and sustainable healthcare delivery.
Synthesis and performance evaluation of ZnO/CdS photoanodes with copper sulfide (Cu2S) and carbon counter electrodes
Authors: More Pooja B. , Jagtap Chaitali V. , Kadam Vishal S. , Naushad Mu. , Naik Nithesh , Hiremath Pavan , M. Pathan Habib
Published: December 2024

The present study demonstrates the synthesis of compact ZnO layers using CdS sensitized on ZnO as a photoanode with copper sulfide (Cu2S) and carbon as a counter electrode (CE). In this study, a compact ZnO layer was fabricated using the simple and low-cost successive ionic layer adsorption and reaction (SILAR) method, and Cu2S CE films were synthesized using the chemical bath deposition method. Various characterizations, such as X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), confirmed the formation of ZnO and CdS sensitizations on the ZnO . UV-visible spectroscopy revealed that the bandgaps of the ZnO and Cu2S films were 3.2 and 1.3 eV, respectively. Furthermore, the morphology of the ZnO films was optimized by varying the number of SILAR cycles. Scanning electron microscopy revealed the formation of a nanorod compact layer (CL) and the porous nature of the ZnO photoanode films. However, the porosity increased with the number of SILAR cycles. Various parameters, such as the current density, voltage, fill factor, and efficiency, were measured using the J-V characteristics. The highest 0.85% efficiency was achieved by using the ZnO compact film with 30 SILAR cycles for the Cu2S CE. Furthermore, the study revealed that the Cu2S counter electrode had a higher electrocatalytic response than the carbon CE.
Mechanisms of breast cancer treatment using Gentiana robusta: evidence from comprehensive bioinformatics investigation
Authors: Xiong Bo , Zhang Xinxin , Sangji Dongzhi , Ni Lianghong , Fan Mingjie , Fan Beibei
Published: December 2024

This study investigates the potential treatment of breast cancer utilizing Gentiana robusta King ex Hook. f. (QJ) through an integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulation. Building upon prior research on QJ’s chemical constituents, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the DAVID database. Network interactions and core genes were identified using Cytoscape 3.9.1. Key target genes, including Interleukin-6 (IL-6), tumour suppressor gene P53 (TP53), and epidermal growth factor receptor (EGFR), were selected for molecular docking with QJ’s active components, 2′-O-β-D-glucopyranosyl-gentiopicroside and macrophylloside D, employing Schrodinger Maestro 13.5. Molecular dynamics (MD) simulations were performed using the Desmond program. A total of 270 intersection targets of active ingredients and diseases were identified, with three core targets determined through network topology screening. Enrichment analysis highlighted the involvement of QJ in breast cancer treatment, primarily through the hsa05200 cancer signaling pathway and the hsa04066 HIF-1 signaling pathway. Molecular docking and dynamics simulations demonstrated the close interaction of 2′-O-β-D-glucopyranosyl-gentiopicroside (QJ17) and macrophylloside D (QJ25) with IL6, TP53, and EGFR, and other target genes, showcasing a stabilizing effect. In conclusion, this study unveils the effective components and potential mechanisms of 2′-O-β-D-glucopyranosyl-gentiopicroside and macrophylloside D in breast cancer prevention and treatment. The identified components act on target genes such as IL6, TP53, and EGFR, regulating crucial pathways including the cancer signaling and Hypoxia-inducible factor 1 (HIF-1) signaling pathways. These findings provide valuable insights into the therapeutic potential of QJ in breast cancer management. However, further experimental research are needed to validate the computational findings of QJ.
Continual deep reinforcement learning with task-agnostic policy distillation
Authors: Hafez Muhammad Burhan , Erekmen Kerim
Published: December 2024

Central to the development of universal learning systems is the ability to solve multiple tasks without retraining from scratch when new data arrives. This is crucial because each task requires significant training time. Addressing the problem of continual learning necessitates various methods due to the complexity of the problem space. This problem space includes: (1) addressing catastrophic forgetting to retain previously learned tasks, (2) demonstrating positive forward transfer for faster learning, (3) ensuring scalability across numerous tasks, and (4) facilitating learning without requiring task labels, even in the absence of clear task boundaries. In this paper, the Task-Agnostic Policy Distillation (TAPD) framework is introduced. This framework alleviates problems (1)–(4) by incorporating a task-agnostic phase, where an agent explores its environment without any external goal and maximizes only its intrinsic motivation. The knowledge gained during this phase is later distilled for further exploration. Therefore, the agent acts in a self-supervised manner by systematically seeking novel states. By utilizing task-agnostic distilled knowledge, the agent can solve downstream tasks more efficiently, leading to improved sample efficiency. Our code is available at the repository: https://github.com/wabbajack1/TAPD.
Globisporangium tabrizense sp. nov., Globisporangium mahabadense sp. nov., and Pythium bostanabadense sp. nov. (Oomycota), three new species from Iranian aquatic environments
Authors: Ahadi Reza , Bouket Ali Chenari , Alizadeh Alireza , Masigol Hossein , Grossart Hans-Peter
Published: December 2024

During a survey on the biodiversity of oomycetes in aquatic environments in northwest Iran (East Azarbaijan and West Azarbaijan provinces), three Pythium and four Globisporangium isolates were recovered from agricultural water pools and irrigation canals, respectively. Through a polyphasic approach combining morphology and phylogenetic analysis using the nuclear rDNA ITS1-5.8 S-ITS2 (ITS) and partial sequences of the cytochrome c oxidase subunit I and II (COX1 and COX2), three novel species were identified namely Globisporangium tabrizense sp. nov., G. mahabadense sp. nov., and Pythium bostanabadense sp. nov. Furthermore, experiments confirmed the pathogenicity of all identified species on cucumber seedlings, suggesting a pathogenic lifestyle also in aquatic systems. Our research contributes to a better understanding of the diversity, host range and distribution of oomycetes genera Globisporangium and Pythium in northwestern Iran. Detailed morphological descriptions and illustrations are provided for all species.
A sterilization method for human decellularized vaginal matrices
Authors: Sueters Jayson , de Boer Leonie , Groenman Freek , Huirne Judith A. F. , Smit Theo H. , Zaat Sebastian A. J.
Published: December 2024

Vaginal reconstruction is necessary for various congenital and acquired conditions, including vaginal aplasia, trauma, tumors, and gender incongruency. Current surgical and non-surgical treatments often result in significant complications. Decellularized vaginal matrices (DVMs) from human tissue offer a promising alternative, but require effective sterilization to ensure safety and functionality. This study aimed to develop a sterilization method for decellularized human vaginal wall scaffolds. Based on our previously implemented decellularization technique with minor modifications, we designed and examined three sterilization methods consisting of (i) chemical decellularization, (ii) decellularization with additional peracetic acid/hydrogen peroxide (PAA/H2O2); (iii) decellularization with antibiotic and antimycotic (AAE) based treatment. Sterilization efficacy was evaluated through controlled contamination with common vaginal microbes and sterility testing subsequent to each sterilization method. The extracellular matrix (ECM) structure was assessed via histological staining. Decellularization alone reduced some added bacterial contaminants but did not achieve complete sterilization. PAA/H2O2-sterilization resulted in severe ECM damage, rendering it unsuitable. The AAE-treatment demonstrated effective sterilization without compromising the ECM structure. Combined decellularization and AAE-based treatment forms a viable sterilization method for human vaginal wall tissue, maintaining ECM integrity and achieving effective micro-organism elimination. This method holds potential for clinical application in vaginal transplantation.
Pharmacokinetics of tebipenem pivoxil used in children suffering from shigellosis: a pilot study in Bangladesh
Authors: Nuzhat Sharika , Islam Md Ridwan , Bashar Syed Jayedul , Das Subhasish , Amin Rukaeya , Qadri Firdausi , Khanam Farhana , Ahmed Dilruba , Pavlinac Patricia B. , Zhang Cindy X. , Arnold Samuel L. M. , Newlands Amy , Chisti Mohammod Jobayer , Ahmed Tahmeed
Published: December 2024

With increasing antibiotic resistance in gram-negative bacteria, including those causing Shigellosis, evidence of safety and pharmacokinetics data on new oral antibiotics is crucial. We aimed to investigate the safety and pharmacokinetic properties of an oral carbapenem, tebipenem pivoxil, along with it’s ability to produce desired results in childhood shigellosis. This randomized pilot clinical trial was conducted at Dhaka Hospital, icddr,b in 2022 between May and September. Thirty suspected shigellosis cases aged 24–59 months were randomized across two treatment groups equally: tebipenem pivoxil and azithromycin. Pharmacokinetics of tebipenem was assessed among fifteen children who received tebipenem pivoxil using Noncompartmental analysis (NCA). Clinical (absence of fever, abdominal pain/tenderness, diarrhoea, blood in stool, or death before Day-3) and microbiological (absence of Shigella on Day-7 culture) success after the antibiotic interventions were also evaluated. Sociodemographic and clinical characteristics were comparable between the randomization arms. Twelve children, each in the azithromycin arm and tebipenem arm, were positive for Shigella by culture on enrolment. Cmax values of 5053.3, 2546.0, and 3759.2 ng/mL were observed for plasma tebipenem on Day-0, 1, and 2 respectively. Clinical success was observed among seven participants in each arm while two in the azithromycin arm and three in the tebipenem arm failed microbiologically. The tolerability and efficaciousness of tebipenem pivoxil appear to be comparable to azithromycin in treating childhood shigellosis in Bangladesh. We recommend a larger clinical trial to determine non-inferiority of tebipenem in regards to the current treatment guidelines.
A topic modeling approach for analyzing and categorizing electronic healthcare documents in Afaan Oromo without label information
Authors: Dinsa Etana Fikadu , Das Mrinal , Abebe Teklu Urgessa
Published: December 2024

Afaan Oromo is a resource-scarce language with limited tools developed for its processing, posing significant challenges for natural language tasks. The tools designed for English do not work efficiently for Afaan Oromo due to the linguistic differences and lack of well-structured resources. To address this challenge, this work proposes a topic modeling framework for unstructured health-related documents in Afaan Oromo using latent dirichlet allocation (LDA) algorithms. All collected documents lack label information, which poses significant challenges for categorizing the documents and applying the supervised learning methods. So, we utilize the LDA model since it offers solutions to this problem by allowing discovery of the latent topics of the documents without requiring the predefined labels. The model takes a word dictionary to extract hidden topics by evaluating word patterns and distributions across the dataset. Then it extracts the most relevant document topics and generates weight values for each word in the documents per topic. Next, we classify the topics using the represented keyword as input and assign class labels based on human evaluations topic coherence. This model could be applied to classifying medical documents and used to find specialists who best suitable for patients’ requests from the obtained information. As a conclusion of our findings, the topic modeling using LDA gave the promised value of 79.17% accuracy and 79.66% F1 score for test documents of the dataset.
Adaptation portfolio – a multi-measure framework for future floods and droughts
Authors: Padiyedath Gopalan Saritha , Hanasaki Naota , Champathong Adisorn , Oki Taikan
Published: December 2024

Adaptation is critically important for coping with climate change. However, quantitative studies on which adaptation measures should be taken to maintain the present water risk level in the context of climate change have been explored little, particularly at large basin scales. Here, we devised three adaptation portfolios composed of combinations of measures to alleviate floods and drought with explicit basin-wide modelling in the Chao Phraya River basin, Thailand. Two portfolios mitigated future water scarcity to the present level but failed to eliminate extreme floods. The remaining portfolio with basin-wide reforestation substantially reduced the number of future flooding days but enhanced the number of drought months to 3–6 months a year, resulting from increased evapotranspiration by 7–11%. Overall, future flood adaptation remains challenging even in highly regulated rivers. We also observed that adaptation effects differ substantially by sub-basins. It highlights the necessity of spatio-temporal detailed impact modelling, including multiple adaptation measures.
Earthquakes yes, disasters no
Authors: Ismail-Zadeh Alik
Published: December 2024

To answer the question of why seismic hazards turn into disasters, I provide here an overview of studies on the lithosphere dynamics, seismic hazard assessments, earthquake-triggered hazards, forecasting of large earthquakes, vulnerability and resilience assessments, and risk communication. Knowledge gaps in these fields are discussed. Integrated research on risks of earthquake-triggered disasters is essential in producing useful and usable knowledge for informed decision-making to reduce disaster risks.
Multicomponent Supramolecular Hydrogels Composed of Cationic Phenylalanine Derivatives and Anionic Amino Acids
Authors: Ghosh Shruti , Distaffen Hannah E , Jones Christopher  W , Nilsson Bradley L.
Published: December 2024

Supramolecular hydrogels composed of self-assembled fluorenylmethoxycarbonyl phenylalanine (Fmoc-Phe) derivatives have been the focus of intense study as novel materials for biological applications that include drug delivery, tissue engineering, and regenerative...
Dual functional coordination interactions enable fast polysulfide conversion and robust interphase for high-loading lithium–sulfur batteries
Authors: Han Wenchang , Hou Jiyue , Wang Fei , Zhang Bao , Zhang Enfeng , Wang Yongqi , Yang Chunman , Dong Peng , Song Weili , Li Xue , Zhang Yannan , Lou Shuaifeng , Zhang Yingjie , Zhang Yiyong
Published: December 2024

DTD inhibits the shuttle effect and modulates the anode interface through coordination interactions, resulting in fast conversion kinetics and a robust SEI under high-loading conditions.
An In-Depth Examination of Phytochemicals and Medicinal Uses on Morus alba
Authors: Dubey Roshan Kumar , Shukla Satyam , Shukla Prashant
Published: December 2024

Morus alba, commonly known as white mulberry, is a plant renowned for its diverse range of bioactive compounds that confer numerous health benefits. This review explores the plant's antioxidant, anti-inflammatory, anticancer, cardiovascular, neuroprotective, hepatoprotective, and antimicrobial properties. The antioxidant effects, primarily attributed to flavonoids, phenolic acids, and terpenoids, help mitigate oxidative stress and protect against various diseases. The anti-inflammatory properties reduce chronic inflammation, while the anticancer compounds induce apoptosis and inhibit tumor growth. Morus alba's cardiovascular benefits include improved endothelial function and lipid metabolism. Its neuroprotective effects protect the brain from oxidative damage and neuroinflammation, supporting cognitive function. The hepatoprotective activity enhances liver health and prevents damage from toxins. Additionally, the plant's antimicrobial properties make it effective against a broad spectrum of pathogens. Overall, Morus alba holds significant potential as a natural therapeutic agent, with applications in both traditional and modern medicines.
Research on the Preparation Process of Mahuang Xixin Fuzi Decoction Granules
Authors: Cao Lingli , Wang Congying , Feng Yinman
Published: December 2024

Objective The objective of this study was to investigate the preparation process of Mahuang Xixin Fuzi decoction granules based on the clinical pharmacological effects of the classic formulas and to control the quality of the product.

Methods An orthogonal experimental design was used, with extraction yield and transfer rate of key ingredients as evaluation indicators, to optimize the extraction process of Mahuang Xixin Fuzi decoction. The granulation process was optimized based on indicators such as granule formation rate, dissolution rate, and moisture absorption rate.

Results The optimal extraction process for Mahuang Xixin Fuzi decoction was determined as the following: using 10 times the amount of water to soak for 30 minutes, extracting three times, each for 60 minutes, with a concentrated extract relative density of 1.3 g/mL. A mixture of dextrin and starch at a 1:2 ratio was used as a binder for wet granulation. The granule formation rate, dissolution time, and dilution rate of three repeated batches showed relative standard deviation (RSD) values of 1.48, 2.83, and 1.55%.

Conclusion This method is stable and feasible, providing valuable data for the industrial production of Mahuang Xixin Fuzi decoction granules and further research on this formulation.
The Effect of Semen Ziziphi Spinosae Extract on the p38MAPK/NF-κB Signaling Pathway in Insomniac Rats
Authors: Ji Mingyu , Xiong Wei , Xu Zijing , Zhang Peipei , Li Shuyu , Wang Qian , Jia Dexian
Published: December 2024

Objective The objective of the study was to explore whether Suanzaoren (Semen Ziziphi Spinosae, SZS) extract could improve insomnia by inhibiting the p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-κB (NF-κB) signaling pathway.

Methods Forty SPF-grade Sprague-Dawley (SD) rats were included in the study, with 10 randomly selected rats serving as the control group. The remaining rats were injected intraperitoneally with p-chlorophenylalanine (PCPA) for 6 days to establish an insomnia model. After successful modeling, the rats were divided into the model group, SZS extract group (3.0 g/kg), and zopiclone group (1.25 g/kg). The rats in the SZS extract and zopiclone groups were administered with the corresponding drugs via gavage for 7 days, while the rats in the control and model groups received distilled water. Sleep latency and sleep duration were recorded, and behavioral changes were observed through elevated plus-maze and open field tests. The levels of oxidative stress markers and serum inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of p38 MAPK, p-p38MAPK, p-NF-κBp65, and NF-κBp65 protein in the cerebral cortex were detected by Western blot. Neuronal structures in the cerebral cortex were observed under a transmission electron microscope.

Results Compared with the control group, the model group exhibited abnormal appearances, significant body mass loss (p < 0.001), prolonged sleep latency and shortened sleep duration (p < 0.001). The SZS extract and zopiclone groups showed significant improvements in these parameters compared with the model group. Compared with the control group, the model group showed significant reduction in total movement distance (p < 0.001), fewer entries into the central zone (p < 0.01), and significant decrease in rearing frequency (p < 0.001); the levels of glutathione peroxidase (GSH-Px) and carnitine acetyltransferase (CT) in the hippocampus were significantly reduced (p < 0.001); the serum levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the expression levels of p-p38MAPK and p-NF-κBp65 in the cerebral cortex were significantly increased (p < 0.05). Compared with the model group, the SZS extract group showed significant increase in movement distance (p < 0.01) and rearing frequency (p < 0.001), significantly increased the GSH-Px and CT levels (p < 0.001), and decreased the IL-1β and TNF-α levels (p < 0.01); furthermore, the SZS extract group showed a significantly reduced p-p38MAPK and p-NF-κBp65 levels (p < 0.05). The SZS extract group showed significant improvement in the neuronal structure compared with the model group.

Conclusion SZS extract can inhibit the p38MAPK/NF-KB signaling pathway to improve insomnia.
Modular DNA origami–based electrochemical detection of DNA and proteins
Authors: Jeon Byoung-jin , Guareschi Matteo M. , Stewart Jaimie Marie , Wu Emily , Gopinath Ashwin , Arroyo-Currás Netzahualcóyotl , Dauphin-Ducharme Philippe , Plaxco Kevin W. , Lukeman Philip S. , Rothemund Paul W. K.
Published: December 2024

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte. Here, we demonstrate a modular electrochemical biosensor, built from DNA origami, which is easily adapted to diverse molecules by merely replacing its analyte binding domains. Instead of relying on a unique nanometer-scale movement of a single redox reporter, all sensor variants rely on the same 100-nm scale conformational change, which brings dozens of reporters close enough to a gold electrode surface that a signal can be measured via square-wave voltammetry, a standard electrochemical technique. To validate our sensor’s mechanism, we used single-stranded DNA as an analyte, and optimized the number of redox reporters and various linker lengths. Adaptation of the sensor to streptavidin and Platelet-Derived Growth Factor-BB (PDGF-BB) analytes was achieved by simply adding biotin or anti-PDGF aptamers to appropriate DNA linkers. Geometrically optimized streptavidin sensors exhibited signal gain and limit of detection markedly better than comparable reagentless electrochemical sensors. After use, the same sensors could be regenerated under mild conditions: Performance was largely maintained over four cycles of DNA strand displacement and rehybridization. By leveraging the modularity of DNA nanostructures, our work provides a straightforward route to the single-step quantification of arbitrary nucleic acids and proteins.
A minimal vertex model explains how the amnioserosa avoids fluidization during
Drosophila
dorsal closure
Authors: Tah Indrajit , Haertter Daniel , Crawford Janice M. , Kiehart Daniel P. , Schmidt Christoph F. , Liu Andrea J.
Published: December 2024

Dorsal closure is a process that occurs during embryogenesis of
Drosophila melanogaster
. During dorsal closure, the amnioserosa (AS), a one-cell thick epithelial tissue that fills the dorsal opening, shrinks as the lateral epidermis sheets converge and eventually merge. During this process, both shape index and aspect ratio of amnioserosa cells increase markedly. The standard 2-dimensional vertex model, which successfully describes tissue sheet mechanics in multiple contexts, would in this case predict that the tissue should fluidize via cell neighbor changes. Surprisingly, however, the amnioserosa remains an elastic solid with no such events. We here present a minimal extension to the vertex model that explains how the amnioserosa can achieve this unexpected behavior. We show that continuous shrinkage of the preferred cell perimeter and cell perimeter polydispersity lead to the retention of the solid state of the amnioserosa. Our model accurately captures measured cell shape and orientation changes and predicts nonmonotonic junction tension that we confirm with laser ablation experiments.
US Corn Belt enhances regional precipitation recycling
Authors: Zhang Zhe , He Cenlin , Chen Fei , Miguez-Macho Gonzalo , Liu Changhai , Rasmussen Roy
Published: December 2024

Precipitation recycling, where evapotranspiration (ET) from the land surface contributes to precipitation within the same region, is a critical component of the water cycle. This process is especially important for the US Corn Belt, where extensive cropland expansions and irrigation activities have significantly transformed the landscape and affected the regional climate. Previous studies investigating precipitation recycling typically relied on analytical models with simplifying assumptions, overlooking the complex interactions between groundwater hydrology and agricultural management. In this study, we use high-resolution climate models coupled with an explicit water vapor tracer algorithm to quantify the impacts of shallow groundwater, dynamic crop growth, and irrigation on regional precipitation recycling in the US Corn Belt. We find that these coupled groundwater–crop–irrigation processes reduce surface temperatures and increase the growing season precipitation. The increase in precipitation is attributed to a significant enhancement of the precipitation recycling ratio from 14 to 18%. This enhanced precipitation recycling is stronger in a dry year than normal and wet years, depending on both large-scale moisture transport and local ET. Our study underscores the critical role of groundwater hydrology and agricultural management in altering the regional water cycle, with important implications for regional climate predictions and food and water security.
Integration of basal and apical embryo lineage regulators controls F-actin cable integrity and zygote asymmetry in
Arabidopsis
Authors: Xiong Feng , Zhang Zhongjuan , Gong Wen , Hermann Marita , Bak Deniz Tiambeng , Garbsch Frauke , Laux Thomas
Published: December 2024

In many plants, the asymmetric division of the zygote sets up the apical–basal body axis. In the cress
Arabidopsis
, the zygote coexpresses regulators of the apical and basal embryo lineages, the transcription factors WOX2 and WRKY2/WOX8, respectively. WRKY2/WOX8 activity promotes nuclear migration, cellular polarity, and mitotic asymmetry of the zygote, which are hallmarks of axis formation in many plant species. However, the role of WOX2 and how the antagonistic WOX2 and WRKY2/WOX8 functions are integrated in the zygote have remained a long-standing question. Here, we report that
WOX2
loss-of-function completely suppresses the reduced zygote asymmetry of
wrky2
mutants and that
WOX2
overexpression mimics the
wrky2
phenotype. At the molecular level, WRKY2 downregulates
WOX2
transcription in the zygote and the basal embryo lineage, in addition to promoting
WOX8
expression. WOX2 antagonizes WRKY2 function by repressing
WOX8
transcription. As a physiological readout, the WRKY2/WOX8-WOX2 balance regulates the integrity of F-actin cables in the zygote, providing a mechanistic framework for the role of WRKY2/WOX8-WOX2-mediated zygote asymmetry.
Salmonella
infection accelerates postnatal maturation of the intestinal epithelium
Authors: Schlößer Stefan , Ullrich Anna-Lena , Modares Nastaran Fazel , Schmitz Matthias A. , Schöneich Johannes , Zhang Kaiyi , Richter Isabel , Robrahn Laura , Schraven Sarah , Nagai James S. , Haange Sven-Bastiaan , Jennings Susan A. V. , Clavel Thomas , Rolle-Kampczyk Ulrike , Kiessling Fabian , Costa Ivan G. , Muncan Vanesa , Repnik Urska , von Bergen Martin , Dupont Aline , Hornef Mathias W.
Published: December 2024

Postnatal establishment of enteric metabolic, host–microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen
Salmonella
Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators. Cytokine stimulation of neonatal intestinal epithelial stem cell organoids suggests a network of synergistic and antagonistic cytokine effects with a significant contribution of IL-22, IL-4/IL-13, TNF, and IL-6 to infection-induced enterocyte reprogramming. Our findings demonstrate that the infection-associated immune cell activation disrupts physiological postnatal tissue maturation and may thereby worsen clinical outcomes and alter the neonatal-adult transition.
Oncogenic IDH1
mut
drives robust loss of histone acetylation and increases chromatin heterogeneity
Authors: Furth Noa , Cohen Niv , Spitzer Avishay , Salame Tomer-Meir , Dassa Bareket , Mehlman Tevie , Brandis Alexander , Moussaieff Arieh , Friedmann-Morvinski Dinorah , Castro Maria G. , Fortin Jerome , Suvà Mario L. , Tirosh Itay , Erez Ayelet , Ron Guy , Shema Efrat
Published: December 2024

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2
mut
) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype. Yet, the complete depiction of the epigenetic alterations in IDH
mut
cells has not been thoroughly explored. Here, we applied an unbiased approach, leveraging epigenetic-focused cytometry by time-of-flight (CyTOF) analysis, to systematically profile the effect of mutant-IDH1 expression on a broad panel of histone modifications at single-cell resolution. This analysis revealed extensive remodeling of chromatin patterns by mutant-IDH1, with the most prominent being deregulation of histone acetylation marks. The loss of histone acetylation occurs rapidly following mutant-IDH1 induction and affects acetylation patterns over enhancers and intergenic regions. Notably, the changes in acetylation are not predominantly driven by 2-HG, can be rescued by pharmacological inhibition of mutant-IDH1, and reversed by acetate supplementations. Furthermore, cells expressing mutant-IDH1 show higher epigenetic and transcriptional heterogeneity and upregulation of oncogenes such as KRAS and MYC, highlighting its tumorigenic potential. Our study underscores the tight interaction between chromatin and metabolism dysregulation in glioma and highlights epigenetic and oncogenic pathways affected by mutant-IDH1-driven metabolic rewiring.
Unveiling hidden reaction kinetics of carbon dioxide in supercritical aqueous solutions
Authors: Li Chu , Yao Yuan , Pan Ding
Published: December 2024

Dissolution of CO
2
in water followed by the subsequent hydrolysis reactions is of great importance to the global carbon cycle, and carbon capture and storage. Despite numerous previous studies, the reactions are still not fully understood at the atomistic scale. Here, we combined ab initio molecular dynamics (AIMD) simulations with Markov state models to elucidate the reaction mechanisms and kinetics of CO
2
in supercritical water both in the bulk and nanoconfined states. The integration of unsupervised learning with first-principles data allows us to identify complex reaction coordinates and pathways automatically instead of a priori human speculation. Interestingly, our unbiased modeling found an unknown pathway of dissolving CO
2
(aq) under graphene nanoconfinement, involving the pyrocarbonate anion [C
2
O

5

2
−

(aq)] as an intermediate state. The pyrocarbonate anion was previously hypothesized to have a fleeting existence in water; however, our study reveals that it is a crucial reaction intermediate and stable carbon species in the nanoconfined solutions. We even observed the formation of pyrocarbonic acid [H
2
C
2
O
5
(aq)], which was unknown in water, in our AIMD simulations. The unexpected appearance of pyrocarbonates is related to the superionic behavior of the confined solutions. We also found that carbonation reactions involve collective proton transfer along transient water wires, which exhibits concerted behavior in the bulk solution but proceeds stepwise under nanoconfinement. The first-principles Markov state models show substantial promise for elucidating complex reaction kinetics in aqueous solutions. Our study highlights the importance of large oxocarbons in aqueous carbon reactions, with great implications for the deep carbon cycle and the sequestration of CO
2
.
Energy–poverty–inequality SDGs: A large-scale household analysis and forecasting in China
Authors: Li Cong , Li Minglai , Zhang Lin , Li Qiang , Zheng Hua , Feldman Marcus W.
Published: December 2024

Affordable and clean energy, eliminating poverty, and reducing inequality are important goals of the United Nations Sustainable Development Goals (SDGs). This paper examines the role of access to clean cooking fuels in promoting income growth and reducing income inequality. Using data from Chinese households, we show that a 10% increase in the adoption of clean cooking fuels would result in an increase in total annual household income of US$37 billion nationwide. Income growth from access to clean cooking fuels is greater for lower-income groups due to a shift to higher household income and reduced downward household income mobility, which contributes to a reduction in income inequality. The effect of access to clean cooking fuels on household income growth is primarily driven by improved health and increased labor supply. The use of clean cooking fuels also saves fuel collection time and cooking time, reducing time spent on household chores by about 0.4 h per day, thereby increasing labor supply in the job market and improving wage income. Improvements in income due to clean cooking fuels are influenced by external conditions, urbanization, education, employment opportunities, and good market conditions. With further promotion of clean cooking fuels, household income and inequality in China are expected to improve further by 2030 and contribute more widely to human well-being and achievement of the SDGs.
Structural basis of nearest-neighbor cooperativity in the ring-shaped gene regulatory protein TRAP from protein engineering and cryo-EM
Authors: Li Weicheng , Yang Haoyun , Stachowski Kye , Norris Andrew S. , Lichtenthal Katie , Kelly Skyler , Gollnick Paul , Wysocki Vicki H. , Foster Mark P.
Published: December 2024

The homo-dodecameric ring-shaped
trp
RNA binding attenuation protein (TRAP) from
Alkalihalobacillus halodurans (Aha)
binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5’ leader region of the
trp
operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity. To establish a solid basis for describing nearest-neighbor cooperativity in TRAP, we engineered variants constructed with two subunits connected by a flexible linker (dTRAP). We mutated the binding sites of alternating protomers such that only every other site was competent for Trp binding (WT-Mut dTRAP). Ligand binding monitored by NMR, calorimetry, and native mass spectrometry revealed strong cooperativity in dTRAP containing adjacent binding-competent sites, but a severe binding defect when the wild-type sites were separated by mutated sites. Cryo-EM experiments of dTRAP in its ligand-free apo state, and both dTRAP and WT-Mut dTRAP in the presence of Trp, revealed progressive stabilization of loops that gate the Trp binding site and participate in RNA binding. These studies provide important insights into the thermodynamic and structural basis for the observed ligand binding cooperativity in TRAP. Such insights can be useful for understanding allosteric control networks and for the development of those with defined ligand sensitivity and regulatory control.
Unlocking the catalytic precision of ligand-controlled enzymatic halogenation
Authors: Phintha Aisaraphon , Lukowski April L. , Chaiyen Pimchai
Published: December 2024

A single-component flavin-dependent halogenase, AetF, has emerged as an attractive biocatalyst for catalyzing halogenation. However, its flavin chemistry remains unexplored and cannot be predicted due to its uniqueness in sequence and structure compared to other flavin-dependent monooxygenases. Here, we investigated the flavin reactions of AetF using transient kinetics. Our data revealed that NADP
+
binding is required for formation of C4a-hydroperoxy flavin adenine dinucleotide (FAD) (FAD
C4aOOH
), a key flavin-oxygen adduct required for generating a halogenating species. In the presence of NaBr without L-tryptophan, the flavin oxygen adduct intermediates [possibly FAD
C4aOOH
and C4a-hydroxy FAD (FAD
C4aOH
)] are highly stabilized (>4,000 s) before returning to the oxidized FAD state. In the presence of L-tryptophan, the rate of FAD
C4aOH
dehydration to form oxidized FAD increased by ~825-fold. These data suggest that the presence of all substrates is required for speeding up AetF’s catalytic cycle. Our findings underscore the adeptness of AetF in managing its reactivity through ligand control. Structural and tunnel analyses revealed that the binding of NADP
+
and L-tryptophan induces changes in protein tunnels which may potentially link to the ligand-controlled mechanisms. Leveraging these catalytic insights, we employed light-induced flavin reduction and NADP
+
stimulation to enable AetF halogenation of various compounds. Our findings demonstrate the mechanisms of precise control over flavin chemistry by AetF. These mechanistic insights may be useful for the biocatalytic development of single-component flavin-dependent halogenases.
A detailed spatiotemporal atlas of the white matter tracts for the fetal brain
Authors: Calixto Camilo , Dorigatti Soldatelli Matheus , Jaimes Camilo , Pierotich Lana , Warfield Simon K. , Gholipour Ali , Karimi Davood
Published: December 2024

This study presents the construction of a comprehensive spatiotemporal atlas of white matter tracts in the fetal brain for every gestational week between 23 and 36 wk using diffusion MRI (dMRI). Our research leverages data collected from fetal MRI scans, capturing the dynamic changes in the brain’s architecture and microstructure during this critical period. The atlas includes 60 distinct white matter tracts, including commissural, projection, and association fibers. We employed advanced fetal dMRI processing techniques and tractography to map and characterize the developmental trajectories of these tracts. Our findings reveal that the development of these tracts is characterized by complex patterns of fractional anisotropy (FA) and mean diffusivity (MD), coinciding with the intensity of histogenic processes such as axonal growth, involution of the radial-glial scaffolding, and synaptic pruning. This atlas can serve as a useful resource for neuroscience research and clinical practice, improving our understanding of the fetal brain and potentially aiding in the early diagnosis of neurodevelopmental disorders. By detailing the normal progression of white matter tract development, the atlas can be used as a benchmark for identifying deviations that may indicate neurological anomalies or predispositions to disorders.
Integrating climate and physical constraints into assessments of net capture from direct air capture facilities
Authors: Shorey Patrick , Abdulla Ahmed
Published: December 2024

Limiting climate change to targets enshrined in the Paris Agreement will require both deep decarbonization of the energy system and the deployment of carbon dioxide removal at potentially large scale (gigatons of annual removal). Nations are pursuing direct air capture to compensate for inertia in the expansion of low-carbon energy systems, decarbonize hard-to-abate sectors, and address legacy emissions. Global assessments of this technology have failed to integrate factors that affect net capture and removal cost, including ambient conditions like temperature and humidity, as well as emission factors of electricity and natural gas systems. We present an integrated assessment of the global deployment potential of this technology. Employing a chemical process model, climate data, grid emission factors, and fugitive methane emission factors, we predict critical performance metrics, including carbon dioxide capture rates, and water-, energy-, and emissions-intensity of capture. Our results support investors and policy makers as they site facilities and develop credible policy instruments to support expansion.
Electron transfer in polysaccharide monooxygenase catalysis
Authors: Sayler Richard I. , Thomas William C. , Rose Alexander J. , Marletta Michael A.
Published: December 2024

Polysaccharide monooxygenase (PMO) catalysis involves the chemically difficult hydroxylation of unactivated C–H bonds in carbohydrates. The reaction requires reducing equivalents and will utilize either oxygen or hydrogen peroxide as a cosubstrate. Two key mechanistic questions are addressed here: 1) How does the enzyme regulate the timely and tightly controlled electron delivery to the mononuclear copper active site, especially when bound substrate occludes the active site? and 2) How does this electron delivery differ when utilizing oxygen or hydrogen peroxide as a cosubstrate? Using a computational approach, potential paths of electron transfer (ET) to the active site copper ion were identified in a representative AA9 family PMO from
Myceliophthora thermophila
(
Mt
PMO9E). When Y62, a buried residue 12 Å from the active site, is mutated to F, lower activity is observed with O
2
. However, a WT-level activity is observed with H
2
O
2
as a cosubstrate indicating an important role in ET for O
2
activation. To better understand the structural effects of mutations to Y62 and axial copper ligand Y168, crystal structures were solved of the wild type
Mt
PMO9E and the variants Y62W, Y62F, and Y168F. A bioinformatic analysis revealed that position 62 is conserved as either Y or W in the AA9 family. The
Mt
PMO9E Y62W variant has restored activity with O
2
. Overall, the use of redox-active residues to supply electrons for the reaction with O
2
appears to be widespread in the AA9 family. Furthermore, the results provide a molecular framework to understand catalysis with O
2
versus H
2
O
2
.
Collaborative management partnerships strongly decreased deforestation in the most at-risk protected areas in Africa since 2000
Authors: Desbureaux Sébastien , Kabore Ibrahim , Vaglietti Giulia , Baghai Mujon , Lindsey Peter , Robson Ashley , Delacote Philippe , Leblois Antoine
Published: December 2024

Collaborative management partnerships (CMPs) between state wildlife authorities and nonprofit conservation organizations to manage protected areas (PAs) have been used increasingly across Sub-Saharan Africa since the 2000s. They aim to attract funding, build capacity, and increase the environmental effectiveness of PAs. Our study documents the rise of CMPs, examines their current extent, and measures their effectiveness in protecting habitats. We combine statistical matching and Before-After-Control-Intervention regressions to quantify the impact of CMPs, using tree cover loss as a proxy. We identify 127 CMPs located in 16 countries. CMPs are more often located in remote PAs, with habitats that are least threatened by human activity. Our results indicate that, on average, each year in a CMP results in an annual decrease in tree cover loss of about 55% compared to PAs without CMPs. Where initial anthropogenic pressure was low, we measure no effect. Where it was high, we see a 66% decrease in tree cover loss. This highly heterogeneous effect illustrates the importance of moving beyond average effect size when assessing conservation interventions, as well as the need for policy makers to invest public funds to protect the areas the most at risk.
The changing relationship between racial identity and skin color in Brazil
Authors: Freeman Nicholas C. , Telles Edward E. , Goldberg Rachel E.
Published: December 2024

In recent years, Brazil’s non-White (Brown and Black) population became a numerical majority for the first time since the 19th century. Although we know this change was mostly due to racial reclassification, we do not know how such changes are related to skin color, the primary marker of race in Brazil. Using data from six Latin American Public Opinion Project (LAPOP), or America’s Barometer, surveys from 2010 to 2023, we examine how changes in racial self-identification (White, Brown, or Black) are related to respondent skin color (light, medium, or dark). We ask how the association between self-identified race and skin color changed over the 13-y period and to what extent these trends varied by educational level. We found a “darkening” of racial identification over time, especially among those with medium and dark skin, who increasingly identified as Black. Brazilians with light skin increasingly identified as Brown, but this was partly explained by changes in interviewer reporting of skin color in the same period. We found only minor evidence that education level was related to changing racial classification over time. Our findings further understanding of recent trends in racial reclassification, which may reflect growing Black consciousness and the extension of racial quotas to both Brown and Black Brazilians in federal universities and public sector jobs.