bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐2018 Caldera Collapse Re‐Inflation Uniquely Constrains Kīlauea's Magmatic System
Authors: Wang Taiyi , Zheng Yujie , Pulvirenti Fabio , Segall Paul 
Published: May 2021

AbstractFrom August 2018 to May 2019, Kīlauea’s summit exhibited unique, simultaneous, inflation and deflation, apparent in both GPS time series and cumulative InSAR displacement maps. This deformation pattern provides clear evidence that the Halema‘uma‘u (HMM) and South Caldera (SC) reservoirs are distinct. Post‐collapse inflation of the East Rift Zone (ERZ), as captured by InSAR, indicates concurrent magma transfer from the summit reservoirs to the ERZ. We present a physics‐based model that couples pressure‐driven flow between these magma reservoirs to simulate time dependent summit deformation. We take a two‐step approach to quantitatively constrain Kīlauea’s magmatic plumbing system. First, we jointly invert the InSAR displacement maps and GPS offsets for the location and geometry of the summit reservoirs, approximated as spheroidal chambers. We find that HMM reservoir has an aspect ratio of ∼1.8 (prolate) and a depth of ∼2.2 km (below surface). The SC reservoir has an aspect ratio of ∼0.14 (oblate) and a depth of ∼3.6 km. Second, we utilize the flux model to invert GPS time series from 8 summit stations. Results favor a shallow HMM‐ERZ pathway an order of magnitude more hydraulically conductive than the deep SC‐ERZ pathway. Further analysis shows that the HMM‐ERZ pathway is required to explain the deformation time series. Given high‐quality geodetic data, such an approach promises to quantify the connectivity of magmatic pathways between reservoirs in other similar volcanic systems.
Novel prostate cancer susceptibility gene SP6 predisposes patients to aggressive disease
Authors: Sipeky Csilla , Tammela Teuvo L. J. , Auvinen Anssi , Schleutker Johanna 
Published: May 2021

AbstractProstate cancer (PrCa) is one of the most common cancers in men, but little is known about factors affecting its clinical outcomes. Genome-wide association studies have identified more than 170 germline susceptibility loci, but most of them are not associated with aggressive disease. We performed a genome-wide analysis of 185,478 SNPs in Finnish samples (2738 cases, 2400 controls) from the international Collaborative Oncological Gene-Environment Study (iCOGS) to find underlying PrCa risk variants. We identified a total of 21 common, low-penetrance susceptibility loci, including 10 novel variants independently associated with PrCa risk. Novel risk loci were located in the 8q24 (CASC8 rs16902147, OR 1.86, padj = 3.53 × 10−8 and rs58809953, OR 1.71, padj = 4.00 × 10−6; intergenic rs79012498, OR 1.81, padj = 4.26 × 10−8), 17q21 (SP6 rs2074187, OR 1.66, padj = 3.75 × 10−5), 11q13 (rs12795301, OR 1.42, padj = 2.89 × 10−5) and 8p21 (rs995432, OR 1.38, padj = 3.00 × 10−11) regions. Here, we describe SP6, a transcription factor gene, as a new, potentially high-risk gene for PrCa. The intronic variant rs2074187 in SP6 was associated not only with overall susceptibility to PrCa (OR 1.66) but also with a higher odds ratio for aggressive PrCa (OR 1.89) and lower odds for non-aggressive PrCa (OR 1.43). Furthermore, the new intergenic variant rs79012498 at 8q24 conferred risk for aggressive PrCa. Our findings highlighted the power of a population-stratified approach to identify novel, clinically actionable germline PrCa risk loci and strongly suggested SP6 as a new PrCa candidate gene that may be involved in the pathogenesis of PrCa.
The prognostic power of 18F-FDG PET/CT extends to estimating systemic treatment response duration in metastatic castration-resistant prostate cancer (mCRPC) patients
Authors: Bauckneht Matteo , Bertagna Francesco , Donegani Maria Isabella , Durmo Rexhep , Miceli Alberto , De Biasi Vincenzo , Laudicella Riccardo , Fornarini Giuseppe , Berruti Alfredo , Baldari Sergio , Versari Annibale , Giubbini Raffaele , Sambuceti Gianmario , Morbelli Silvia , Albano Domenico 
Published: May 2021

Abstract
Background
We aimed to test whether the prognostic value of 18 F‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration.

Methods
mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration.

Results
We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy.

Conclusions
FDG-PET/CT’s prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.
Metaplasmidome-encoded functions of Siberian low-centered polygonal tundra soils
Authors: Gorecki Adrian , Holm Stine , Dziurzynski Mikolaj , Winkel Matthias , Yang Sizhong , Liebner Susanne , Wagner Dirk , Dziewit Lukasz , Horn Fabian 
Published: May 2021

Abstract
Plasmids have the potential to transfer genetic traits within bacterial communities and thereby serve as a crucial tool for the rapid adaptation of bacteria in response to changing environmental conditions. Our knowledge of the environmental pool of plasmids (the metaplasmidome) and encoded functions is still limited due to a lack of sufficient extraction methods and tools for identifying and assembling plasmids from metagenomic datasets. Here, we present the first insights into the functional potential of the metaplasmidome of permafrost-affected active-layer soil—an environment with a relatively low biomass and seasonal freeze–thaw cycles that is strongly affected by global warming. The obtained results were compared with plasmid-derived sequences extracted from polar metagenomes. Metaplasmidomes from the Siberian active layer were enriched via cultivation, which resulted in a longer contig length as compared with plasmids that had been directly retrieved from the metagenomes of polar environments. The predicted hosts of plasmids belonged to Moraxellaceae, Pseudomonadaceae, Enterobacteriaceae, Pectobacteriaceae, Burkholderiaceae, and Firmicutes. Analysis of their genetic content revealed the presence of stress-response genes, including antibiotic and metal resistance determinants, as well as genes encoding protectants against the cold.
Marine signature taxa and core microbial community stability along latitudinal and vertical gradients in sediments of the deepest freshwater lake
Authors: Reboul Guillaume , Moreira David , Annenkova Nataliia V , Bertolino Paola , Vershinin Konstantin E , López-García Purificación 
Published: May 2021

Abstract
Lake Baikal is the deepest (~1.6 km) and most voluminous freshwater reservoir on Earth. Compared to plankton, its benthos remains poorly explored. Here, we ask whether latitude and/or depth determine benthic microbial community structure and how Baikal communities compare to those of other freshwater, brackish and marine sediments. To answer, we collected sediment upper layers (0–1 cm) across a ~600 km North-South transect covering the three basins of the lake and from littoral to bathybenthic depths (0.5–1450  m). Analysis of 16S and 18S rRNA gene amplicon sequences revealed communities with high richness and evenness where rare operational taxonomic units (OTUs) collectively dominated. Archaea represented up to 25% or prokaryotic sequences. Baikal sediments harbored typically marine eukaryotic and prokaryotic OTUs recently identified in some lakes (diplonemids, Bolidophyceae, Mamiellales, SAR202, marine-like Synechococcus, Pelagibacterales) but also SAR324, Syndiniales and Radiolaria. We hypothesize that, beyond the salinity barrier, adaptation to oligotrophy explains the presence of these otherwise typically marine lineages. Baikal core benthic communities were relatively stable across sites and seemed not determined by depth or latitude. Comparative analyses with other freshwater, brackish and marine prokaryotic sediment communities confirmed the distinctness of Baikal benthos, which include elements of similarity to marine and hydrothermally influenced systems.
Alternative polyadenylation trans-factor FIP1 exacerbates UUO/IRI-induced kidney injury and contributes to AKI-CKD transition via ROS-NLRP3 axis
Authors: Zheng Tong , Tan Yuqin , Qiu Jiang , Xie Zhenwei , Hu Xiao , Zhang Jinhua , Na Ning 
Published: May 2021

AbstractNLRP3, a decisive role in inflammation regulation, is obviously upregulated by oxidative stress in kidney injury. The NLRP3 upregulation leads to unsolved inflammation and other pathological effects, contributing to aggravation of kidney injury and even transition to chronic kidney disease (CKD). However, the mechanism for NLRP3 upregulation and further aggravation of kidney injury remains largely elusive. In this study, we found NLRP3 3′UTR was shortened in response to kidney injury in vivo and oxidative stress in vitro. Functionally, such NLRP3 3′UTR shortening upregulated NLRP3 expression and amplified inflammation, fibrogenesis, ROS production and apoptosis, depending on stabilizing NLRP3 mRNA. Mechanistically, FIP1 was found to bind to pPAS of NLRP3 mRNA via its arginine-rich domain and to induce NLRP3 3′UTR shortening. In addition, FIP1 was upregulated in CKD specimens and negatively associated with renal function of CKD patients. More importantly, we found FIP1 was upregulated by oxidative stress and required for oxidative stress-induced NLRP3 upregulation, inflammation activation, cell damage and apoptosis. Finally, we proved that FIP1 silencing attenuated the inflammation activation, fibrogenesis, ROS production and apoptosis induced by UUO or IRI. Taken together, our results demonstrated that oxidative stress-upregulated FIP1 amplified inflammation, fibrogenesis, ROS production and apoptosis via inducing 3′UTR shortening of NLRP3, highlighting the importance of crosstalk between oxidative stress and alternative polyadenylation in AKI-CKD transition, as well as the therapeutic potential of FIP1 in kidney injury treatment.
MYCN mediates TFRC-dependent ferroptosis and reveals vulnerabilities in neuroblastoma
Authors: Lu Yuxiong , Yang Qing , Su Yubin , Ji Yin , Li Guobang , Yang Xianzhi , Xu Liyan , Lu Zhaoliang , Dong Jiajun , Wu Yi , Bei Jin-Xin , Pan Chaoyun , Gu Xiaoqiong , Li Bo 
Published: May 2021

AbstractMYCN amplification is tightly associated with the poor prognosis of pediatric neuroblastoma (NB). The regulation of NB cell death by MYCN represents an important aspect, as it directly contributes to tumor progression and therapeutic resistance. However, the relationship between MYCN and cell death remains elusive. Ferroptosis is a newly identified cell death mode featured by lipid peroxide accumulation that can be attenuated by GPX4, yet whether and how MYCN regulates ferroptosis are not fully understood. Here, we report that MYCN-amplified NB cells are sensitive to GPX4-targeting ferroptosis inducers. Mechanically, MYCN expression reprograms the cellular iron metabolism by upregulating the expression of TFRC, which encodes transferrin receptor 1 as a key iron transporter on the cell membrane. Further, the increased iron uptake promotes the accumulation of labile iron pool, leading to enhanced lipid peroxide production. Consistently, TFRC overexpression in NB cells also induces selective sensitivity to GPX4 inhibition and ferroptosis. Moreover, we found that MYCN fails to alter the general lipid metabolism and the amount of cystine imported by System Xc(−) for glutathione synthesis, both of which contribute to ferroptosis in alternative contexts. In conclusion, NB cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB.
SRSF1 promotes the inclusion of exon 3 of SRA1 and the invasion of hepatocellular carcinoma cells by interacting with exon 3 of SRA1pre-mRNA
Authors: Lei Sijia , Zhang Bin , Huang Luyuan , Zheng Ziyou , Xie Shaohan , Shen Lianghua , Breitzig Mason , Czachor Alexander , Liu Hongtao , Luo Huiru , Chen Yanxia , Liu Kangshou , Sun Hanxiao , Zheng Qing , Li Qiang , Wang Feng 
Published: May 2021

AbstractSteroid receptor RNA activator 1 (SRA1) has been described as a novel transcriptional co-activator that affects the migration of cancer cells. Through RT-PCR, we identified that skipping exon 3 of SRA1 produces two isoforms, including the truncated short isoform, SRA1-S, and the long isoform, SRA1-L. However, the effect of these two isomers on the migration of HCC cells, as well as the specific mechanism of exon 3 skipping remain unclear. In this study, we found up regulated expression of SRSF1 and SRA1-L in highly metastatic HCCLM3, as well as in HCCs with SRSF1 demonstrating the strongest correlation with SRA1-L. In contrast, we observed a constitutively low expression of SRA1-S and SRSF1 in lowly metastatic HepG2 cells. Overexpression of SRSF1 or SRA1-L promoted migration and invasion by increasing the expression of CD44, while SRA1-S reversed the effect of SRSF1 and SRA1-L in vitro. In addition, lung metastasis in mice revealed that, knockdown of SRSF1 or SRA1-L inhibited the migration of HCC cells, while SRA1-L overexpression abolished the effect of SRSF1 knockout and instead promoted HCC cells migration in vivo. More importantly, RNA immunoprecipitation and Cross-link immunoprecipitation analyses showed that SRSF1 interacts with exon 3 of SRA1 to up regulate the expression of SRA1-L in HCC cells. RNA pull-down results indicated that SRSF1 could also bind to exon 3 of SRA1 in vitro. Finally, minigene -MS2 mutation experiments showed that mutation of the SRA1 exon 3 binding site for SRSF1 prevented the binding of SRA1 pre-mRNA. In summary, our results provide experimental evidence that SRA1 exon 3 inclusion is up regulated by SRSF1 to promote tumor invasion and metastasis in hepatocellular carcinoma.
Quantitative trait locus analysis of parasitoid counteradaptation to symbiont-conferred resistance
Authors: Ulrich Gabriel F. , Zemp Niklaus , Vorburger Christoph , Boulain Hélène 
Published: May 2021

AbstractInsect hosts and parasitoids are engaged in an intense struggle of antagonistic coevolution. Infection with heritable bacterial endosymbionts can substantially increase the resistance of aphids to parasitoid wasps, which exerts selection on parasitoids to overcome this symbiont-conferred protection (counteradaptation). Experimental evolution in the laboratory has produced counteradapted populations of the parasitoid waspLysiphlebus fabarum. These populations can parasitize black bean aphids (Aphis fabae) protected by the bacterial endosymbiontHamiltonella defensa, which confers high resistance againstL. fabarum. We used two experimentally evolved parasitoid populations to study the genetic architecture of the counteradaptation to symbiont-conferred resistance by QTL analysis. With simple crossing experiments, we showed that the counteradaptation is a recessive trait depending on the maternal genotype. Based on these results, we designed a customized crossing scheme to genotype a mapping population phenotyped for the ability to parasitizeHamiltonella-protected aphids. Using 1835 SNP markers obtained by ddRAD sequencing, we constructed a high-density linkage map consisting of six linkage groups (LGs) with an overall length of 828.3 cM and an average marker spacing of 0.45 cM. We identified a single QTL associated with the counteradaptation toHamiltonellainL. fabarumon linkage group 2. Out of 120 genes located in this QTL, several genes encoding putative venoms may represent candidates for counteradaptation, as parasitoid wasps inject venoms into their hosts during oviposition.
Acceleration of lipid reproduction by emergence of microscopic motion
Authors: Babu Dhanya , Scanes Robert J. H. , Plamont Rémi , Ryabchun Alexander , Lancia Federico , Kudernac Tibor , Fletcher Stephen P. , Katsonis Nathalie 
Published: May 2021

AbstractSelf-reproducing molecules abound in nature where they support growth and motion of living systems. In artificial settings, chemical reactions can also show complex kinetics of reproduction, however integrating self-reproducing molecules into larger chemical systems remains a challenge towards achieving higher order functionality. Here, we show that self-reproducing lipids can initiate, sustain and accelerate the movement of octanol droplets in water. Reciprocally, the chemotactic movement of the octanol droplets increases the rate of lipid reproduction substantially. Reciprocal coupling between bond-forming chemistry and droplet motility is thus established as an effect of the interplay between molecular-scale events (the self-reproduction of lipid molecules) and microscopic events (the chemotactic movement of the droplets). This coupling between molecular chemistry and microscopic motility offers alternative means of performing work and catalysis in micro-heterogeneous environments.
MIF is a 3’ flap nuclease that facilitates DNA replication and promotes tumor growth
Authors: Wang Yijie , Chen Yan , Wang Chenliang , Yang Mingming , Wang Yanan , Bao Lei , Wang Jennifer E. , Kim BongWoo , Chan Kara Y. , Xu Weizhi , Capota Emanuela , Ortega Janice , Nijhawan Deepak , Li Guo-Min , Luo Weibo , Wang Yingfei 
Published: May 2021

AbstractHow cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3’ flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3’ nuclease, excises flaps at the immediate 3’ end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.
Ecological and biogeographic drivers of biodiversity cannot be resolved using clade age-richness data
Authors: Rabosky Daniel L. , Benson Roger B. J. 
Published: May 2021

AbstractEstimates of evolutionary diversification rates – speciation and extinction – have been used extensively to explain global biodiversity patterns. Many studies have analyzed diversification rates derived from just two pieces of information: a clade’s age and its extant species richness. This “age-richness rate” (ARR) estimator provides a convenient shortcut for comparative studies, but makes strong assumptions about the dynamics of species richness through time. Here we demonstrate that use of the ARR estimator in comparative studies is problematic on both theoretical and empirical grounds. We prove mathematically that ARR estimates are non-identifiable: there is no information in the data for a single clade that can distinguish a process with positive net diversification from one where net diversification is zero. Using paleontological time series, we demonstrate that the ARR estimator has no predictive ability for real datasets. These pathologies arise because the ARR inference procedure yields “point estimates” that have been computed under a saturated statistical model with zero degrees of freedom. Although ARR estimates remain useful in some contexts, they should be avoided for comparative studies of diversification and species richness.
INDEEDopt: a deep learning-based ReaxFF parameterization framework
Authors: Sengul Mert Y. , Song Yao , Nayir Nadire , Gao Yawei , Hung Ying , Dasgupta Tirthankar , van Duin Adri C. T. 
Published: May 2021

AbstractEmpirical interatomic potentials require optimization of force field parameters to tune interatomic interactions to mimic ones obtained by quantum chemistry-based methods. The optimization of the parameters is complex and requires the development of new techniques. Here, we propose an INitial-DEsign Enhanced Deep learning-based OPTimization (INDEEDopt) framework to accelerate and improve the quality of the ReaxFF parameterization. The procedure starts with a Latin Hypercube Design (LHD) algorithm that is used to explore the parameter landscape extensively. The LHD passes the information about explored regions to a deep learning model, which finds the minimum discrepancy regions and eliminates unfeasible regions, and constructs a more comprehensive understanding of physically meaningful parameter space. We demonstrate the procedure here for the parameterization of a nickel–chromium binary force field and a tungsten–sulfide–carbon–oxygen–hydrogen quinary force field. We show that INDEEDopt produces improved accuracies in shorter development time compared to the conventional optimization method.
The nutritional quality of cereals varies geospatially in Ethiopia and Malawi
Authors: Gashu D. , Nalivata P. C. , Amede T. , Ander E. L. , Bailey E. H. , Botoman L. , Chagumaira C. , Gameda S. , Haefele S. M. , Hailu K. , Joy E. J. M. , Kalimbira A. A. , Kumssa D. B. , Lark R. M. , Ligowe I. S. , McGrath S. P. , Milne A. E. , Mossa A. W. , Munthali M. , Towett E. K. , Walsh M. G. , Wilson L. , Young S. D. , Broadley M. R. 
Published: May 2021

AbstractMicronutrient deficiencies (MNDs) remain widespread among people in sub-Saharan Africa1–5, where access to sufficient food from plant and animal sources that is rich in micronutrients (vitamins and minerals) is limited due to socioeconomic and geographical reasons4–6. Here we report the micronutrient composition (calcium, iron, selenium and zinc) of staple cereal grains for most of the cereal production areas in Ethiopia and Malawi. We show that there is geospatial variation in the composition of micronutrients that is nutritionally important at subnational scales. Soil and environmental covariates of grain micronutrient concentrations included soil pH, soil organic matter, temperature, rainfall and topography, which were specific to micronutrient and crop type. For rural households consuming locally sourced food—including many smallholder farming communities—the location of residence can be the largest influencing factor in determining the dietary intake of micronutrients from cereals. Positive relationships between the concentration of selenium in grain and biomarkers of selenium dietary status occur in both countries. Surveillance of MNDs on the basis of biomarkers of status and dietary intakes from national- and regional-scale food-composition data1–7 could be improved using subnational data on the composition of grain micronutrients. Beyond dietary diversification, interventions to alleviate MNDs, such as food fortification8,9 and biofortification to increase the micronutrient concentrations in crops10,11, should account for geographical effects that can be larger in magnitude than intervention outcomes.