bluuebunny/crossref_metadata_2025_split huggingface dataset:
Provenance of the Mesozoic Succession of Franz Josef Land (North‐Eastern Barents Sea): Paleogeographic and Tectonic Implications for the High Arctic
Authors: Ershova Victoria , Prokopiev Andrei , Stockli Daniel , Kurapov Mikhail , Kosteva Natalia , Rogov Mikhail , Khudoley Andrei , Petrov Eugeny O. 
Published: November 2022

AbstractStudy of the Mesozoic succession of Franz Josef Land (FJL) has shed new insights on the stratigraphy and geological history of the neighboring portion of the Arctic. Based on the composition of pebbles and cobbles from Lower Jurassic conglomerates, we suggest that the pre‐Mesozoic stratigraphy of the NE Barents Sea comprises Cambrian metasandstones intruded by Late Paleozoic granites and overlain by Carboniferous–Permian sedimentary deposits. U‐Pb and ZHe ages of detrital zircons from Uppermost Triassic–Lower Cretaceous strata of FJL reveal Precambrian to Early Mesozoic grains. The most abundant Late Paleozoic detrital zircon population suggests the existence of the same in age magmatic events in the provenance area. ZHe ages show Late Triassic (ca. 225 Ma) exhumation of the provenance area. Moreover, the youngest grains of detrital zircons are Middle‐Late Triassic in age pointing that significant uplift of provenance coincides with magmatic activity. Based on these data, we suggest that the provenance area for Triassic–Lower Cretaceous strata of FJL was characterized by a similar geological composition, as well as magmatic and tectonic history, to the Taimyr fold‐and‐thrust belt and Kara terrane. A comparison of detrital zircon data from coeval strata elsewhere in the Arctic realm suggests that this eastern provenance area was actively sourcing sediments right across the Barents Sea Basin, and possibly as far as the Sverdrup basin, during the Latest Triassic–Jurassic. The period of Late Triassic uplift represented a significant tectonic event across the north‐eastern Barents Sea, and likely initiated an increase in sediment supply and a reorganization of pre‐existing sediment transport pathways.
Future climate conditions accelerate wheat straw decomposition alongside altered microbial community composition, assembly patterns, and interaction networks
Authors: Wahdan Sara Fareed Mohamed , Ji Li , Schädler Martin , Wu Yu-Ting , Sansupa Chakriya , Tanunchai Benjawan , Buscot François , Purahong Witoon 
Published: November 2022

AbstractAlthough microbial decomposition of plant litter plays a crucial role in nutrient cycling and soil fertility, we know less about likely links of specific microbial traits and decomposition, especially in relation to climate change. We study here wheat straw decomposition under ambient and manipulated conditions simulating a future climate scenario (next 80 years) in agroecosystems, including decay rates, macronutrient dynamics, enzyme activity, and microbial communities. We show that future climate will accelerate straw decay rates only during the early phase of the decomposition process. Additionally, the projected climate change will increase the relative abundance of saprotrophic fungi in decomposing wheat straw. Moreover, the impact of future climate on microbial community assembly and molecular ecological networks of both bacteria and fungi will strongly depend on the decomposition phase. During the early phase of straw decomposition, stochastic processes dominated microbial assembly under ambient climate conditions, whereas deterministic processes highly dominated bacterial and fungal communities under simulated future climate conditions. In the later decomposition phase, similar assembly processes shaped the microbial communities under both climate scenarios. Furthermore, over the early phases of decomposition, simulated future climate enhanced the complexity of microbial interaction networks. We concluded that the impact of future climate on straw decay rate and associated microbial traits like assembly processes and inter-community interactions is restricted to the early phase of decomposition.
RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway
Authors: Chen Shiyu , Cai Kun , Zheng Dijie , Liu Yanqing , Li Lin , He Zhiwei , Sun Chengyi , Yu Chao 
Published: November 2022

AbstractPancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.
Oxidative degradation of dihydrofolate reductase increases CD38-mediated ferroptosis susceptibility
Authors: Ma Yingying , Yi Meiqi , Wang Weixuan , Liu Xiaohui , Wang Qingtao , Liu Chongdong , Chen Yuling , Deng Haiteng 
Published: November 2022

AbstractHigh expression of CD38 in tissues is a characteristic of aging, resulting in a decline in nicotinamide adenine dinucleotide (NAD) and increasing cellular reactive oxygen species (ROS). However, whether CD38 increases susceptibility to ferroptosis remains largely unexplored. Our previous study showed that CD38 overexpression decreased dihydrofolate reductase (DHFR). In the present study, we confirmed that high expression of CD38 increased ROS levels and induced DHFR degradation, which was prevented by nicotinamide mononucleotide (NMN) replenishment. We further revealed that ROS-mediated sulfonation on Cys7 of DHFR induced its degradation via the autophagy and non-canonical proteasome pathways. Mutation of Cys7 to alanine abolished ROS-induced DHFR degradation. Moreover, oxidative degradation of DHFR was responsible for the increased ferroptosis susceptibility of cells in which CD38 was highly expressed. We also found that CD38 expression was higher in bone-marrow-derived macrophages (BMDMs) from aged mice than those from young mice, while the DHFR level was lower. Consequently, we demonstrated that BMDMs from aged mice were more susceptible to ferroptosis that can be reverted by NMN replenishment, suggesting that CD38 high expression rendered cells more susceptible to ferroptosis. Taken together, these results indicated that CD38-mediated NAD+ decline promoted DHFR oxidative degradation, thus resulting in increased cellular susceptibility to ferroptosis and suggesting that NMN replenishment may protect macrophages from ferroptosis in aged mice.
PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism
Authors: Liao Yunfei , Luo Zaili , Lin Yifeng , Chen Huiyao , Chen Tong , Xu Lingli , Orgurek Sean , Berry Kalen , Dzieciatkowska Monika , Reisz Julie A. , D’Alessandro Angelo , Zhou Wenhao , Lu Q. Richard 
Published: November 2022

AbstractGlioblastoma (GBM) is the most common and aggressive primary brain tumor, but the mechanisms underlying tumor growth and progression remain unclear. The protein arginine methyltransferases (PRMTs) regulate a variety of biological processes, however, their roles in GBM growth and progression are not fully understood. In this study, our functional analysis of gene expression networks revealed that among the PRMT family expression of PRMT3 was most significantly enriched in both GBM and low-grade gliomas. Higher PRMT3 expression predicted poorer overall survival rate in patients with gliomas. Knockdown of PRMT3 markedly reduced the proliferation and migration of GBM cell lines and patient-derived glioblastoma stem cells (GSC) in cell culture, while its over-expression increased the proliferative capacity of GSC cells by promoting cell cycle progression. Consistently, stable PRMT3 knockdown strongly inhibited tumor growth in xenograft mouse models, along with a significant decrease in cell proliferation as well as an increase in apoptosis. We further found that PRMT3 reprogrammed metabolic pathways to promote GSC growth via increasing glycolysis and its critical transcriptional regulator HIF1α. In addition, pharmacological inhibition of PRMT3 with a PRMT3-specific inhibitor SGC707 impaired the growth of GBM cells. Thus, our study demonstrates that PRMT3 promotes GBM progression by enhancing HIF1A-mediated glycolysis and metabolic rewiring, presenting a point of metabolic vulnerability for therapeutic targeting in malignant gliomas.
Micronutrient supplementation interventions in preconception and pregnant women at increased risk of developing pre-eclampsia: a systematic review and meta-analysis
Authors: Gunabalasingam Sowmiya , De Almeida Lima Slizys Daniele , Quotah Ola , Magee Laura , White Sara L. , Rigutto-Farebrother Jessica , Poston Lucilla , Dalrymple Kathryn V. , Flynn Angela C. 
Published: November 2022

AbstractBackgroundPre-eclampsia can lead to maternal and neonatal complications and is a common cause of maternal mortality worldwide. This review has examined the effect of micronutrient supplementation interventions in women identified as having a greater risk of developing pre-eclampsia.MethodsA systematic review was performed using the PRISMA guidelines. The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials were searched for relevant literature and eligible studies identified according to a pre-specified criteria. A meta-analysis of randomised controlled trials (RCTs) was conducted to examine the effect of micronutrient supplementation on pre-eclampsia in high-risk women.ResultsTwenty RCTs were identified and supplementation included vitamin C and E (n = 7), calcium (n = 5), vitamin D (n = 3), folic acid (n = 2), magnesium (n = 1) and multiple micronutrients (n = 2). Sample size and recruitment time point varied across studies and a variety of predictive factors were used to identify participants, with a previous history of pre-eclampsia being the most common. No studies utilised a validated prediction model. There was a reduction in pre-eclampsia with calcium (risk difference, −0.15 (−0.27, −0.03, I2 = 83.4%)), and vitamin D (risk difference, −0.09 (−0.17, −0.02, I2 = 0.0%)) supplementation.ConclusionOur findings show a lower rate of pre-eclampsia with calcium and vitamin D, however, conclusions were limited by small sample sizes, methodological variability and heterogeneity between studies. Further higher quality, large-scale RCTs of calcium and vitamin D are warranted. Exploration of interventions at different time points before and during pregnancy as well as those which utilise prediction modelling methodology, would provide greater insight into the efficacy of micronutrient supplementation intervention in the prevention of pre-eclampsia in high-risk women.
Alkaloid binding to opium poppy major latex proteins triggers structural modification and functional aggregation
Authors: Ozber Natali , Carr Samuel C. , Morris Jeremy S. , Liang Siyu , Watkins Jacinta L. , Caldo Kristian M. , Hagel Jillian M. , Ng Kenneth K. S. , Facchini Peter J. 
Published: November 2022

AbstractOpium poppy accumulates copious amounts of several benzylisoquinoline alkaloids including morphine, noscapine, and papaverine, in the specialized cytoplasm of laticifers, which compose an internal secretory system associated with phloem throughout the plant. The contiguous latex includes an abundance of related proteins belonging to the pathogenesis-related (PR)10 family known collectively as major latex proteins (MLPs) and representing at least 35% of the total cellular protein content. Two latex MLP/PR10 proteins, thebaine synthase and neopione isomerase, have recently been shown to catalyze late steps in morphine biosynthesis previously assigned as spontaneous reactions. Using a combination of sucrose density-gradient fractionation-coupled proteomics, differential scanning fluorimetry, isothermal titration calorimetry, and X-ray crystallography, we show that the major latex proteins are a family of alkaloid-binding proteins that display altered conformation in the presence of certain ligands. Addition of MLP/PR10 proteins to yeast strains engineered with morphine biosynthetic genes from the plant significantly enhanced the conversion of salutaridine to morphinan alkaloids.
Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk
Authors: Wang Xuehai , Nissen Michael , Gracias Deanne , Kusakabe Manabu , Simkin Guillermo , Jiang Aixiang , Duns Gerben , Sarkozy Clementine , Hilton Laura , Chavez Elizabeth A. , Segat Gabriela C. , Wong Rachel , Kim Jubin , Aoki Tomohiro , Islam Rashedul , May Christina , Hung Stacy , Tyshchenko Kate , Brinkman Ryan R. , Hirst Martin , Karsan Aly , Freeman Ciara , Sehn Laurie H. , Morin Ryan D. , Roth Andrew J. , Savage Kerry J. , Craig Jeffrey W. , Shah Sohrab P. , Steidl Christian , Scott David W. , Weng Andrew P. 
Published: November 2022

AbstractFollicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling of both tumor and immune compartments in 155 diagnostic FL biopsies at single-cell resolution by mass cytometry. This revealed a diversity of phenotypes but included two recurrent patterns, one which closely resembles germinal center B-cells (GCB) and another which appears more related to memory B-cells (MB). GCB-type tumors are enriched forEZH2,TNFRSF14, andMEF2Bmutations, while MB-type tumors contain increased follicular helper T-cells. MB-type and intratumoral phenotypic diversity are independently associated with increased risk of transformation, supporting biological relevance of these features. Notably, a reduced 26-marker panel retains sufficient information to allow phenotypic profiling of future cohorts by conventional flow cytometry.
CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever
Authors: Shu Bo , Ooi Justin S. G. , Tan Aaron W. K. , Ng Thiam-Seng , Dejnirattisai Wanwisa , Mongkolsapaya Juthathip , Fibriansah Guntur , Shi Jian , Kostyuchenko Victor A. , Screaton Gavin R. , Lok Shee-Mei 
Published: November 2022

AbstractDengue virus infection can cause dengue hemorrhagic fever (DHF). Dengue NS1 is multifunctional. The intracellular dimeric NS1 (iNS1) forms part of the viral replication complex. Previous studies suggest the extracellular secreted NS1 (sNS1), which is a major factor contributing to DHF, exists as hexamers. The structure of the iNS1 is well-characterised but not that of sNS1. Here we show by cryoEM that the recombinant sNS1 exists in multiple oligomeric states: the tetrameric (stable and loose conformation) and hexameric structures. Stability of the stable and loose tetramers is determined by the conformation of their N-terminal domain – elongated β-sheet or β-roll. Binding of an anti-NS1 Fab breaks the loose tetrameric and hexameric sNS1 into dimers, whereas the stable tetramer remains largely unbound. Our results show detailed quaternary organization of different oligomeric states of sNS1 and will contribute towards the design of dengue therapeutics.
CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site
Authors: Gong Lihu , Liu Xiuli , Jiao Lianying , Yang Xin , Lemoff Andrew , Liu Xin 
Published: November 2022

AbstractPolycomb repressive complex 2 (PRC2) plays a key role in maintaining cell identity during differentiation. Methyltransferase activity of PRC2 on histone H3 lysine 27 is regulated by diverse cellular mechanisms, including posttranslational modification. Here, we report a unique phosphorylation-dependent mechanism stimulating PRC2 enzymatic activity. Residue S583 of SUZ12 is phosphorylated by casein kinase 2 (CK2) in cells. A crystal structure captures phosphorylation in action: the flexible phosphorylation-dependent stimulation loop harboring S583 becomes engaged with the catalytic SET domain through a phosphoserine-centered interaction network, stabilizing the enzyme active site and in particular S-adenosyl-methionine (SAM)-binding pocket. CK2-mediated S583 phosphorylation promotes catalysis by enhancing PRC2 binding to SAM and nucleosomal substrates and facilitates reporter gene repression. Loss of S583 phosphorylation impedes PRC2 recruitment and H3K27me3 deposition in pluripotent mESCs and compromises the ability of PRC2 to maintain differentiated cell identity.
METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury
Authors: Wang Lijun , Wang Jiaqi , Yu Pujiao , Feng Jingyi , Xu Gui-e , Zhao Xuan , Wang Tianhui , Lehmann H. Immo , Li Guoping , Sluijter Joost P. G. , Xiao Junjie 
Published: November 2022

AbstractRNA m6A modification is the most widely distributed RNA methylation and is closely related to various pathophysiological processes. Although the benefit of regular exercise on the heart has been well recognized, the role of RNA m6A in exercise training and exercise-induced physiological cardiac hypertrophy remains largely unknown. Here, we show that endurance exercise training leads to reduced cardiac mRNA m6A levels. METTL14 is downregulated by exercise, both at the level of RNA m6A and at the protein level. In vivo, wild-type METTL14 overexpression, but not MTase inactive mutant METTL14, blocks exercise-induced physiological cardiac hypertrophy. Cardiac-specific METTL14 knockdown attenuates acute ischemia-reperfusion injury as well as cardiac dysfunction in ischemia-reperfusion remodeling. Mechanistically, silencing METTL14 suppresses Phlpp2 mRNA m6A modifications and activates Akt-S473, in turn regulating cardiomyocyte growth and apoptosis. Our data indicates that METTL14 plays an important role in maintaining cardiac homeostasis. METTL14 downregulation represents a promising therapeutic strategy to attenuate cardiac remodeling.
Nicking mechanism underlying the DNA phosphorothioate-sensing antiphage defense by SspE
Authors: Gao Haiyan , Gong Xinqi , Zhou Jinchuan , Zhang Yubing , Duan Jinsong , Wei Yue , Chen Liuqing , Deng Zixin , Wang Jiawei , Chen Shi , Wu Geng , Wang Lianrong 
Published: November 2022

AbstractDNA phosphorothioate (PT) modification, with a nonbridging phosphate oxygen substituted by sulfur, represents a widespread epigenetic marker in prokaryotes and provides protection against genetic parasites. In the PT-based defense system Ssp, SspABCD confers a single-stranded PT modification of host DNA in the 5′-CPSCA-3′ motif and SspE impedes phage propagation. SspE relies on PT modification in host DNA to exert antiphage activity. Here, structural and biochemical analyses reveal that SspE is preferentially recruited to PT sites mediated by the joint action of its N-terminal domain (NTD) hydrophobic cavity and C-terminal domain (CTD) DNA binding region. PT recognition enlarges the GTP-binding pocket, thereby increasing GTP hydrolysis activity, which subsequently triggers a conformational switch of SspE from a closed to an open state. The closed-to-open transition promotes the dissociation of SspE from self PT-DNA and turns on the DNA nicking nuclease activity of CTD, enabling SspE to accomplish self-nonself discrimination and limit phage predation, even when only a small fraction of modifiable consensus sequences is PT-protected in a bacterial genome.
Comparing research recruitment strategies to prospectively identify patients presenting with breathlessness in primary care
Authors: Doe Gillian , Wathall Simon , Clanchy Jill , Edwards Sarah , Evans Helen , Steiner Michael C. , Evans Rachael A. 
Published: November 2022

AbstractTwo recruitment strategies for research were compared to prospectively identify patients with breathlessness who are awaiting a diagnosis in primary care. The first method utilised searches of the electronic patient record (EPR), the second method involved an electronic template triggered during a consultation. Using an electronic template triggered at the point of consultation increased recruitment to prospective research approximately nine-fold compared with searching for symptom codes and study mailouts.
The African Development Corridors Database: a new tool to assess the impacts of infrastructure investments
Authors: Thorn Jessica P. R. , Bignoli Diego Juffe , Mwangi Ben , Marchant Robert A. 
Published: November 2022

AbstractThe large-scale expansion of built infrastructure is profoundly reshaping the geographies of Africa, generating lock-in patterns of development for future generations. Understanding the impact of these massive investments can allow development opportunities to be maximised and therefore be critical for attaining the United Nations’ Sustainable Development Goals and African Union’s Agenda 2063 aims. However, until now information on the types, scope, and timing of investments, their evolution and spatial-temporal impact was dispersed amongst various agencies. We developed a database of 79 development corridors across Africa, synthesizing data from multiple sources covering 184 projects on railways, wet and dry ports, pipelines, airports, techno-cities, and industrial parks. The georeferenced interlinked tabular and spatial database includes 22 attributes. We expect this database will improve coordination, efficiency, monitoring, oversight, strategic planning, transparency, and risk assessments, among other uses for investment banks, governments, impact assessment practitioners, communities, conservationists, economists, and regional economic bodies.