bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of macromolecular organic nitrogen degrading enzymes identifies potential mediators of soil organic N availability to an annual grass
Authors: Sieradzki Ella T , Nuccio Erin E , Pett-Ridge Jennifer , Firestone Mary K 
Published: April 2023

Abstract
Nitrogen (N) is frequently limiting to plant growth, in part because most soil N is present as polymeric organic compounds that are not readily taken up by plants. Microbial depolymerization of these large macromolecular N-substrates gradually releases available inorganic N. While many studies have researched and modeled controls on soil organic matter formation and bulk N mineralization, the ecological—spatial, temporal and phylogenetic—patterns underlying organic N degradation remain unclear. We analyzed 48 time-resolved metatranscriptomes and quantified N-depolymerization gene expression to resolve differential expression by soil habitat and time in specific taxonomic groups and gene-based guilds. We observed much higher expression of extracellular serine-type proteases than other extracellular N-degrading enzymes, with protease expression of predatory bacteria declining with time and other taxonomic patterns driven by the presence (Gammaproteobacteria) or absence (Thermoproteota) of live roots and root detritus (Deltaproteobacteria and Fungi). The primary chitinase chit1 gene was more highly expressed by eukaryotes near root detritus, suggesting predation of fungi. In some lineages, increased gene expression over time suggests increased competitiveness with rhizosphere age (Chloroflexi). Phylotypes from some genera had protease expression patterns that could benefit plant N nutrition, for example, we identified a Janthinobacterium phylotype and two Burkholderiales that depolymerize organic N near young roots and a Rhizobacter with elevated protease levels near mature roots. These taxon-resolved gene expression results provide an ecological read-out of microbial interactions and controls on N dynamics in specific soil microhabitats and could be used to target potential plant N bioaugmentation strategies.
CEBPD is a master transcriptional factor for hypoxia regulated proteins in glioblastoma and augments hypoxia induced invasion through extracellular matrix-integrin mediated EGFR/PI3K pathway
Authors: Mao Xing-gang , Xue Xiao-yan , Lv Rui , Ji Ang , Shi Ting-yu , Chen Xiao-yan , Jiang Xiao-fan , Zhang Xiang 
Published: April 2023

AbstractHypoxia contributes to the initiation and progression of glioblastoma by regulating a cohort of genes called hypoxia-regulated genes (HRGs) which form a complex molecular interacting network (HRG-MINW). Transcription factors (TFs) often play central roles for MINW. The key TFs for hypoxia induced reactions were explored using proteomic analysis to identify a set of hypoxia-regulated proteins (HRPs) in GBM cells. Next, systematic TF analysis identified CEBPD as a top TF that regulates the greatest number of HRPs and HRGs. Clinical sample and public database analysis revealed that CEBPD is significantly up-regulated in GBM, high levels of CEBPD predict poor prognosis. In addition, CEBPD is highly expressed in hypoxic condition both in GBM tissue and cell lines. For molecular mechanisms, HIF1α and HIF2α can activate the CEBPD promotor. In vitro and in vivo experiments demonstrated that CEBPD knockdown impaired the invasion and growth capacity of GBM cells, especially in hypoxia condition. Next, proteomic analysis identified that CEBPD target proteins are mainly involved in the EGFR/PI3K pathway and extracellular matrix (ECM) functions. WB assays revealed that CEBPD significantly positively regulated EGFR/PI3K pathway. Chromatin immunoprecipitation (ChIP) qPCR/Seq analysis and Luciferase reporter assay demonstrated that CEBPD binds and activates the promotor of a key ECM protein FN1 (fibronectin). In addition, the interactions of FN1 and its integrin receptors are necessary for CEBPD-induced EGFR/PI3K activation by promoting EGFR phosphorylation. Furthermore, GBM sample analysis in the database corroborated that CEBPD is positively correlated with the pathway activities of EGFR/PI3K and HIF1α, especially in highly hypoxic samples. At last, HRPs are also enriched in ECM proteins, indicating that ECM activities are important components of hypoxia induced responses in GBM. In conclusion, CEPBD plays important regulatory roles in the GBM HRG-MINW as a key TF, which activates the EGFR/PI3K pathway through ECM, especially FN1, mediated EGFR phosphorylation.
Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death
Authors: Woodley Keith , Dillingh Laura S. , Giotopoulos George , Madrigal Pedro , Rattigan Kevin M. , Philippe Céline , Dembitz Vilma , Magee Aoife M. S. , Asby Ryan , van de Lagemaat Louie N. , Mapperley Christopher , James Sophie C. , Prehn Jochen H. M. , Tzelepis Konstantinos , Rouault-Pierre Kevin , Vassiliou George S. , Kranc Kamil R. , Helgason G. Vignir , Huntly Brian J. P. , Gallipoli Paolo 
Published: April 2023

AbstractResistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukaemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR). This in turn leads to cellular accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. Our findings provide further support to the role of rewired metabolism in AML therapy resistance, unveil a connection between two apparently independent metabolic pathways and support further efforts to achieve eradication of therapy-resistant AML cells by sensitizing them to ferroptotic cell death.
IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart
Authors: Nanadikar Maithily S. , Vergel Leon Ana M. , Guo Jia , van Belle Gijsbert J. , Jatho Aline , Philip Elvina S. , Brandner Astrid F. , Böckmann Rainer A. , Shi Runzhu , Zieseniss Anke , Siemssen Carla M. , Dettmer Katja , Brodesser Susanne , Schmidtendorf Marlen , Lee Jingyun , Wu Hanzhi , Furdui Cristina M. , Brandenburg Sören , Burgoyne Joseph R. , Bogeski Ivan , Riemer Jan , Chowdhury Arpita , Rehling Peter , Bruegmann Tobias , Belousov Vsevolod V. , Katschinski Dörthe M. 
Published: April 2023

AbstractRedox signaling and cardiac function are tightly linked. However, it is largely unknown which protein targets are affected by hydrogen peroxide (H2O2) in cardiomyocytes that underly impaired inotropic effects during oxidative stress. Here, we combine a chemogenetic mouse model (HyPer-DAO mice) and a redox-proteomics approach to identify redox sensitive proteins. Using the HyPer-DAO mice, we demonstrate that increased endogenous production of H2O2 in cardiomyocytes leads to a reversible impairment of cardiac contractility in vivo. Notably, we identify the γ-subunit of the TCA cycle enzyme isocitrate dehydrogenase (IDH)3 as a redox switch, linking its modification to altered mitochondrial metabolism. Using microsecond molecular dynamics simulations and experiments using cysteine-gene-edited cells reveal that IDH3γ Cys148 and 284 are critically involved in the H2O2-dependent regulation of IDH3 activity. Our findings provide an unexpected mechanism by which mitochondrial metabolism can be modulated through redox signaling processes.
Unconventional correlated insulator in CrOCl-interfaced Bernal bilayer graphene
Authors: Yang Kaining , Gao Xiang , Wang Yaning , Zhang Tongyao , Gao Yuchen , Lu Xin , Zhang Shihao , Liu Jianpeng , Gu Pingfan , Luo Zhaoping , Zheng Runjie , Cao Shimin , Wang Hanwen , Sun Xingdan , Watanabe Kenji , Taniguchi Takashi , Li Xiuyan , Zhang Jing , Dai Xi , Chen Jian-Hao , Ye Yu , Han Zheng 
Published: April 2023

AbstractThe realization of graphene gapped states with large on/off ratios over wide doping ranges remains challenging. Here, we investigate heterostructures based on Bernal-stacked bilayer graphene (BLG) atop few-layered CrOCl, exhibiting an over-1-GΩ-resistance insulating state in a widely accessible gate voltage range. The insulating state could be switched into a metallic state with an on/off ratio up to 107by applying an in-plane electric field, heating, or gating. We tentatively associate the observed behavior to the formation of a surface state in CrOCl under vertical electric fields, promoting electron–electron (e–e) interactions in BLG via long-range Coulomb coupling. Consequently, at the charge neutrality point, a crossover from single particle insulating behavior to an unconventional correlated insulator is enabled, below an onset temperature. We demonstrate the application of the insulating state for the realization of a logic inverter operating at low temperatures. Our findings pave the way for future engineering of quantum electronic states based on interfacial charge coupling.
Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment
Authors: Abdelnabi Rana , Jochmans Dirk , Donckers Kim , Trüeb Bettina , Ebert Nadine , Weynand Birgit , Thiel Volker , Neyts Johan 
Published: April 2023

AbstractThe SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic targets for the treatment of COVID-19. Nirmatrelvir is the first 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization. We recently reported on the in vitro selection of SARS-CoV-2 3CLpro resistant virus (L50F-E166A-L167F; 3CLprores) that is cross-resistant with nirmatrelvir and other 3CLpro inhibitors. Here, we demonstrate that the 3CLprores virus replicates efficiently in the lungs of intranasally infected female Syrian hamsters and causes lung pathology comparable to that caused by the WT virus. Moreover, hamsters infected with 3CLprores virus transmit the virus efficiently to co-housed non-infected contact hamsters. Importantly, at a dose of 200 mg/kg (BID) of nirmatrelvir, the compound was still able to reduce the lung infectious virus titers of 3CLprores-infected hamsters by 1.4 log10 with a modest improvement in the lung histopathology as compared to the vehicle control. Fortunately, resistance to Nirmatrelvir does not readily develop in clinical setting. Yet, as we demonstrate, in case drug-resistant viruses emerge, they may spread easily which may thus impact therapeutic options. Therefore, the use of 3CLpro inhibitors in combination with other drugs may be considered, especially in immunodeficient patients, to avoid the development of drug-resistant viruses.
Drivers of SARS-CoV-2 testing behaviour: a modelling study using nationwide testing data in England
Authors: Kim Younjung , Donnelly Christl A. , Nouvellet Pierre 
Published: April 2023

AbstractDuring the COVID-19 pandemic, national testing programmes were conducted worldwide on unprecedented scales. While testing behaviour is generally recognised as dynamic and complex, current literature demonstrating and quantifying such relationships is scarce, despite its importance for infectious disease surveillance and control. Here, we characterise the impacts of SARS-CoV-2 transmission, disease susceptibility/severity, risk perception, and public health measures on SARS-CoV-2 PCR testing behaviour in England over 20 months of the pandemic, by linking testing trends to underlying epidemic trends and contextual meta-data within a systematic conceptual framework. The best-fitting model describing SARS-CoV-2 PCR testing behaviour explained close to 80% of the total deviance in NHS test data. Testing behaviour showed complex associations with factors reflecting transmission level, disease susceptibility/severity (e.g. age, dominant variant, and vaccination), public health measures (e.g. testing strategies and lockdown), and associated changes in risk perception, varying throughout the pandemic and differing between infected and non-infected people.
Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development
Authors: Lismer Ariane , Kimmins Sarah 
Published: April 2023

AbstractAlthough more studies are demonstrating that a father’s environment can influence child health and disease, the molecular mechanisms underlying non-genetic inheritance remain unclear. It was previously thought that sperm exclusively contributed its genome to the egg. More recently, association studies have shown that various environmental exposures including poor diet, toxicants, and stress, perturbed epigenetic marks in sperm at important reproductive and developmental loci that were associated with offspring phenotypes. The molecular and cellular routes that underlie how epigenetic marks are transmitted at fertilization, to resist epigenetic reprogramming in the embryo, and drive phenotypic changes are only now beginning to be unraveled. Here, we provide an overview of the state of the field of intergenerational paternal epigenetic inheritance in mammals and present new insights into the relationship between embryo development and the three pillars of epigenetic inheritance: chromatin, DNA methylation, and non-coding RNAs. We evaluate compelling evidence of sperm-mediated transmission and retention of paternal epigenetic marks in the embryo. Using landmark examples, we discuss how sperm-inherited regions may escape reprogramming to impact development via mechanisms that implicate transcription factors, chromatin organization, and transposable elements. Finally, we link paternally transmitted epigenetic marks to functional changes in the pre- and post-implantation embryo. Understanding how sperm-inherited epigenetic factors influence embryo development will permit a greater understanding related to the developmental origins of health and disease.
Electrosynthesis of polymer-grade ethylene via acetylene semihydrogenation over undercoordinated Cu nanodots
Authors: Xue Weiqing , Liu Xinyan , Liu Chunxiao , Zhang Xinyan , Li Jiawei , Yang Zhengwu , Cui Peixin , Peng Hong-Jie , Jiang Qiu , Li Hongliang , Xu Pengping , Zheng Tingting , Xia Chuan , Zeng Jie 
Published: April 2023

AbstractThe removal of acetylene impurities remains important yet challenging to the ethylene downstream industry. Current thermocatalytic semihydrogenation processes require high temperature and excess hydrogen to guarantee complete acetylene conversion. For this reason, renewable electricity-based electrocatalytic semihydrogenation of acetylene over Cu-based catalysts is an attractive route compared to the energy-intensive thermocatalytic processes. However, active Cu electrocatalysts still face competition from side reactions and often require high overpotentials. Here, we present an undercoordinated Cu nanodots catalyst with an onset potential of −0.15 V versus reversible hydrogen electrode that can exclusively convert C2H2 to C2H4 with a maximum Faradaic efficiency of ~95.9% and high intrinsic activity in excess of −450 mA cm−2 under pure C2H2 flow. Subsequently, we successfully demonstrate simulated crude ethylene purification, continuously producing polymer-grade C2H4 with <1 ppm C2H2 for 130 h at a space velocity of 1.35 × 105 ml gcat−1 h−1. Theoretical calculations and in situ spectroscopies reveal a lower energy barrier for acetylene semihydrogenation over undercoordinated Cu sites than nondefective Cu surface, resulting in the excellent C2H2-to-C2H4 catalytic activity of Cu nanodots.
Biodeterioration of pre-treated polypropylene by Aspergillus terreus and Engyodontium album
Authors: Samat Amira Farzana , Carter Dee , Abbas Ali 
Published: April 2023

AbstractPolypropylene (PP) has raised severe environmental issues concerning its non-degradability, with a current recycling rate of only 1%. This current study utilisesAspergillus terreusATCC 20542 andEngyodontium albumBRIP 61534a to break down PP while focusing on pre-treatment. Polypropylene granule (GPP), film (FPP) and metallised film (MFPP) are pre-treated by either UV, heat, or Fenton’s reagent. UV and heat-treated MFPP byA. terreusexhibits notable weight loss percentage (25.29% and 22.13%, respectively). Biomass production, reduction rate, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) analyses further validate the degradation rate.A. terreusincubated with UV-treated MFPP produced a relatively high biomass yield of 1.07 mg/ml. Reduction in carbonyl index and surface morphological changes reveal consistent biodeterioration evidence. This investigation demonstrates thatA. terreusandE. albumcan grow on, change, and utilise PP as a carbon source with pre-treatments’ aid, promoting the biological pathways for plastic waste treatment.
A peptide-centric quantitative proteomics dataset for the phenotypic assessment of Alzheimer’s disease
Authors: Merrihew Gennifer E. , Park Jea , Plubell Deanna , Searle Brian C. , Keene C. Dirk , Larson Eric B. , Bateman Randall , Perrin Richard J. , Chhatwal Jasmeer P. , Farlow Martin R. , McLean Catriona A. , Ghetti Bernardino , Newell Kathy L. , Frosch Matthew P. , Montine Thomas J. , MacCoss Michael J. 
Published: April 2023

AbstractAlzheimer’s disease (AD) is a looming public health disaster with limited interventions. Alzheimer’s is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain tissue was preserved postmortem by rapid autopsy. Samples from four brain regions were processed and analyzed by data-independent acquisition LC-MS/MS. Here we present a high-quality quantitative dataset at the peptide and protein level for each brain region. Multiple internal and external control strategies were included in this experiment to ensure data quality. All data are deposited in the ProteomeXchange repositories and available from each step of our processing.
Open science and data sharing in cognitive neuroscience with MouseBytes and MouseBytes+
Authors: Memar Sara , Jiang Eric , Prado Vania F. , Saksida Lisa M. , Bussey Timothy J. , Prado Marco A. M. 
Published: April 2023

AbstractOpen access to rodent cognitive data has lagged behind the rapid generation of large open-access datasets in other areas of neuroscience, such as neuroimaging and genomics. One contributing factor has been the absence of uniform standardization in experiments and data output, an issue that has particularly plagued studies in animal models. Touchscreen-automated cognitive testing of animal models allows standardized outputs that are compatible with open-access sharing. Touchscreen datasets can be combined with different neuro-technologies such as fiber photometry, miniscopes, optogenetics, and MRI to evaluate the relationship between neural activity and behavior. Here we describe a platform that allows deposition of these data into an open-access repository. This platform, called MouseBytes, is a web-based repository that enables researchers to store, share, visualize, and analyze cognitive data. Here we present the architecture, structure, and the essential infrastructure behind MouseBytes. In addition, we describe MouseBytes+, a database that allows data from complementary neuro-technologies such as imaging and photometry to be easily integrated with behavioral data in MouseBytes to support multi-modal behavioral analysis.
Quantitative analysis of lacewing larvae over more than 100 million years reveals a complex pattern of loss of morphological diversity
Authors: Haug Carolin , Braig Florian , Haug Joachim T. 
Published: April 2023

AbstractLoss of biodiversity and especially insect decline are widely recognised in modern ecosystems. This decline has an enormous impact due to the crucial ecological roles of insects as well as their economic relevance. For comparison, the fossil record can provide important insights on past biodiversity losses. One group of insects, for which a significant decline over the last 100 million years has often been postulated, but not demonstrated quantitatively, is Neuroptera (lacewings). Many adult lacewings are pollinators, while the larvae are mostly predators, which becomes very obvious from their prominent stylet-like mouthparts. We investigated the fossil record of larvae of all neuropteran lineages as well as a large share of extant neuropteran larvae. Based on these, we performed an outline analysis of the head with stylets. This analysis provides a quantitative frame for recognising the decline of lacewings since the Cretaceous, indicating also a severe loss of ecological roles.
Design and validation of Dolosigranulum pigrum specific PCR primers using the bacterial core genome
Authors: Aziz Maliha , Palmer Amber , Iversen Søren , Salazar Juan E. , Pham Tony , Roach Kelsey , Becker Karsten , Kaspar Ursula , Price Lance B. , Baig Sharmin , Stegger Marc , Andersen Paal Skytt , Liu Cindy M. 
Published: April 2023

AbstractDolosigranulum pigrum—a lactic acid bacterium that is increasingly recognized as an important member of the nasal microbiome. Currently, there are limited rapid and low-cost options for confirming D. pigrum isolates and detecting D. pigrum in clinical specimens. Here we describe the design and validation of a novel PCR assay targeting D. pigrum that is both sensitive and specific. We designed a PCR assay targeting murJ, a single-copy core species gene identified through the analysis of 21 D. pigrum whole genome sequences. The assay achieved 100% sensitivity and 100% specificity against D. pigrum and diverse bacterial isolates and an overall 91.1% sensitivity and 100% specificity using nasal swabs, detecting D. pigrum at a threshold of 1.0 × 104D. pigrum 16S rRNA gene copies per swab. This assay adds a reliable and rapid D. pigrum detection tool to the microbiome researcher toolkit investigating the role of generalist and specialist bacteria in the nasal environment.