bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping PTBP2 binding in human brain identifies SYNGAP1 as a target for therapeutic splice switching
Authors: Dawicki-McKenna Jennine M. , Felix Alex J. , Waxman Elisa A. , Cheng Congsheng , Amado Defne A. , Ranum Paul T. , Bogush Alexey , Dungan Lea V. , Maguire Jean Ann , Gagne Alyssa L. , Heller Elizabeth A. , French Deborah L. , Davidson Beverly L. , Prosser Benjamin L. 
Published: May 2023

AbstractAlternative splicing of neuronal genes is controlled partly by the coordinated action of polypyrimidine tract binding proteins (PTBPs). While PTBP1 is ubiquitously expressed, PTBP2 is predominantly neuronal. Here, we define the PTBP2 footprint in the human transcriptome using brain tissue and human induced pluripotent stem cell-derived neurons (iPSC-neurons). We map PTBP2 binding sites, characterize PTBP2-dependent alternative splicing events, and identify novel PTBP2 targets including SYNGAP1, a synaptic gene whose loss-of-function leads to a complex neurodevelopmental disorder. We find that PTBP2 binding to SYNGAP1 mRNA promotes alternative splicing and nonsense-mediated decay, and that antisense oligonucleotides (ASOs) that disrupt PTBP binding redirect splicing and increase SYNGAP1 mRNA and protein expression. In SYNGAP1 haploinsufficient iPSC-neurons generated from two patients, we show that PTBP2-targeting ASOs partially restore SYNGAP1 expression. Our data comprehensively map PTBP2-dependent alternative splicing in human neurons and cerebral cortex, guiding development of novel therapeutic tools to benefit neurodevelopmental disorders.
Exploring spatial feedbacks between adaptation policies and internal migration patterns due to sea-level rise
Authors: Reimann Lena , Jones Bryan , Bieker Nora , Wolff Claudia , Aerts Jeroen C.J.H. , Vafeidis Athanasios T. 
Published: May 2023

AbstractClimate change-induced sea-level rise will lead to an increase in internal migration, whose intensity and spatial patterns will depend on the amount of sea-level rise; future socioeconomic development; and adaptation strategies pursued to reduce exposure and vulnerability to sea-level rise. To explore spatial feedbacks between these drivers, we combine sea-level rise projections, socioeconomic projections, and assumptions on adaptation policies in a spatially-explicit model (‘CONCLUDE’). Using the Mediterranean region as a case study, we find up to 20 million sea-level rise-related internal migrants by 2100 if no adaptation policies are implemented, with approximately three times higher migration in southern and eastern Mediterranean countries compared to northern Mediterranean countries. We show that adaptation policies can reduce the number of internal migrants by a factor of 1.4 to 9, depending on the type of strategies pursued; the implementation of hard protection measures may even lead to migration towards protected coastlines. Overall, spatial migration patterns are robust across all scenarios, with out-migration from a narrow coastal strip and in-migration widely spread across urban settings. However, the type of migration (e.g. proactive/reactive, managed/autonomous) depends on future socioeconomic developments that drive adaptive capacity, calling for decision-making that goes well beyond coastal issues.
Roles of adenine methylation in the physiology of Lacticaseibacillus paracasei
Authors: Zhao Jie , Zhang Meng , Hui Wenyan , Zhang Yue , Wang Jing , Wang Shaojing , Kwok Lai-Yu , Kong Jian , Zhang Heping , Zhang Wenyi 
Published: May 2023

AbstractLacticaseibacillus paracasei is an economically important bacterial species, used in the food industry and as a probiotic. Here, we investigate the roles of N6-methyladenine (6mA) modification in L. paracasei using multi-omics and high-throughput chromosome conformation capture (Hi-C) analyses. The distribution of 6mA-modified sites varies across the genomes of 28 strains, and appears to be enriched near genes involved in carbohydrate metabolism. A pglX mutant, defective in 6mA modification, shows transcriptomic alterations but only modest changes in growth and genomic spatial organization.
Large-scale control of the retroflection of the Labrador Current
Authors: Jutras Mathilde , Dufour Carolina O. , Mucci Alfonso , Talbot Lauryn C. 
Published: May 2023

AbstractThe Labrador Current transports cold, relatively fresh, and well-oxygenated waters within the subpolar North Atlantic and towards the eastern American continental shelf. The relative contribution of these waters to either region depends on the eastward retroflection of the Labrador Current at the Grand Banks of Newfoundland. Here, we develop a retroflection index based on the pathway of virtual Lagrangian particles and show that strong retroflection generally occurs when a large-scale circulation adjustment, related to the subpolar gyre, accelerates the Labrador Current and shifts the Gulf Stream northward, partly driven by a northward shift of the wind patterns in the western North Atlantic. Starting in 2008, a particularly strong northward shift of the Gulf Stream dominates the other drivers. A mechanistic understanding of the drivers of the Labrador Current retroflection should help predict changes in the water properties in both export regions, and anticipate their impacts on marine life and deep-water formation.
Improving de novo protein binder design with deep learning
Authors: Bennett Nathaniel R. , Coventry Brian , Goreshnik Inna , Huang Buwei , Allen Aza , Vafeados Dionne , Peng Ying Po , Dauparas Justas , Baek Minkyung , Stewart Lance , DiMaio Frank , De Munck Steven , Savvides Savvas N. , Baker David 
Published: May 2023

AbstractRecently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.
Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility
Authors: Zhang Xuedi , Peng Ju , Wu Menghua , Sun Angyang , Wu Xiangyu , Zheng Jie , Shi Wangfei , Gao Guanjun 
Published: May 2023

AbstractGenetic studies elucidate a link between testis-specific serine/threonine kinases (TSSKs) and male infertility in mammals, but the underlying mechanisms are unclear. Here, we identify a TSSK homolog inDrosophila, CG14305 (termed dTSSK), whose mutation impairs the histone-to-protamine transition during spermiogenesis and causes multiple phenotypic defects in nuclear shaping, DNA condensation, and flagellar organization in spermatids. Genetic analysis demonstrates that kinase catalytic activity of dTSSK, which is functionally conserved with human TSSKs, is essential for male fertility. Phosphoproteomics identify 828 phosphopeptides/449 proteins as potential substrates of dTSSK enriched primarily in microtubule-based processes, flagellar organization and mobility, and spermatid differentiation and development, suggesting that dTSSK phosphorylates various proteins to orchestrate postmeiotic spermiogenesis. Among them, the two substrates, protamine-like protein Mst77F/Ser9and transition protein Mst33A/Ser237, are biochemically validated to be phosphorylated by dTSSK in vitro, and are genetically demonstrated to be involved in spermiogenesis in vivo. Collectively, our findings demonstrate that broad phosphorylation mediated by TSSKs plays an indispensable role in spermiogenesis.
Evaluation of multigene assays as predictors for response to neoadjuvant chemotherapy in early-stage breast cancer patients
Authors: Freeman Jincong Q. , Shubeck Sarah , Howard Frederick M. , Chen Nan , Nanda Rita , Huo Dezheng 
Published: May 2023

AbstractOncotypeDX and MammaPrint assays have not been validated to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in early-stage breast cancer patients. We analyzed the 2010–2019 National Cancer Database and found that high OncotypeDX recurrence scores or high MammaPrint scores were associated with greater odds of pCR. Our findings suggest that OncotypeDX and MammaPrint testing predict pCR after NACT and could facilitate clinical decision-making between clinicians and patients.
A dual-process model for cognitive training
Authors: Ericson Julia , Klingberg Torkel 
Published: May 2023

AbstractA key goal in cognitive training research is understanding whether cognitive training enhances general cognitive capacity or provides only task-specific improvements. Here, we developed a quantitative model for describing the temporal dynamics of these two processes. We analyzed data from 1300 children enrolled in an 8 week working memory training program that included 5 transfer test sessions. Factor analyses suggested two separate processes: an early task-specific improvement, accounting for 44% of the total increase, and a slower capacity improvement. A hidden Markov model was then applied to individual training data, revealing that the task-specific improvement plateaued on the third day of training on average. Thus, training is not only task specific or transferable but a combination of the two. The models provide methods for quantifying and separating these processes, which is crucial for studying the effects of cognitive training and relating these effects to neural correlates.
Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology
Authors: MacDonald Samual , Foley Helena , Yap Melvyn , Johnston Rebecca L. , Steven Kaiah , Koufariotis Lambros T. , Sharma Sowmya , Wood Scott , Addala Venkateswar , Pearson John V. , Roosta Fred , Waddell Nicola , Kondrashova Olga , Trzaskowski Maciej 
Published: May 2023

AbstractUncertainty estimation is crucial for understanding the reliability of deep learning (DL) predictions, and critical for deploying DL in the clinic. Differences between training and production datasets can lead to incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise and three approximate Bayesian DL models for predicting cancer of unknown primary, using three RNA-seq datasets with 10,968 samples across 57 cancer types. Our results highlight that simple and scalable Bayesian DL significantly improves the generalisation of uncertainty estimation. Moreover, we designed a prototypical metric—the area between development and production curve (ADP), which evaluates the accuracy loss when deploying models from development to production. Using ADP, we demonstrate that Bayesian DL improves accuracy under data distributional shifts when utilising ‘uncertainty thresholding’. In summary, Bayesian DL is a promising approach for generalising uncertainty, improving performance, transparency, and safety of DL models for deployment in the real world.
A water cooled, high power, dielectric barrier discharge reactor for CO2 plasma dissociation and valorization studies
Authors: Lisi Nicola , Pasqual Laverdura Umberto , Chierchia Rosa , Luisetto Igor , Stendardo Stefano 
Published: May 2023

AbstractAiming at the energy efficient use and valorization of carbon dioxide in the framework of decarbonization studies and hydrogen research, a novel dielectric barrier discharge (DBD) reactor has been designed, constructed and developed. This test rig with water cooled electrodes is capable of a plasma power tunable in a wide range from 20W to 2 kW per unit. The reactor was designed to be ready for catalysts and membrane integration aiming at a broad range plasma conditions and processes, including low to moderate high pressures (0.05–2 bar). In this paper, preliminary studies on the highly endothermic dissociation of CO2, into O2 and CO, in a pure, inert, and noble gas mixture flow are presented. These initial experiments were performed in a geometry with a 3 mm plasma gap in a chamber volume of 40cm3, where the process pressure was varied from few 200 mbar to 1 bar, using pure CO2, and diluted in N2. Initial results confirmed the well-known trade-off between conversion rate (up to 60%) and energy efficiency (up to 35%) into the dissociation products, as measured downstream of the reactor system. Improving conversion rate, energy efficiency and the trade-off curve can be further accomplished by tuning the plasma operating parameters (e.g. the gas flow and system geometry). It was found that the combination of a high-power, water-cooled plasma reactor, together with electronic and waveform diagnostic, optical emission and mass spectroscopies provides a convenient experimental framework for studies on the chemical storage of fast electric power transients and surges.
Blood spinal cord barrier disruption recovers in patients with degenerative cervical myelopathy after surgical decompression: a prospective cohort study
Authors: Schmidt Tobias Philip , Jütten Kerstin , Bertram Ulf , Brandenburg Lars Ove , Pufe Thomas , Delev Daniel , Gombert Alexander , Mueller Christian Andreas , Clusmann Hans , Blume Christian 
Published: May 2023

AbstractThe pathophysiology of degenerative cervical myelopathy (DCM) is characterized by chronic compression-induced damage to the spinal cord leading to secondary harm such as disruption of the blood spinal cord barrier (BSCB). It is therefore the purpose of this study to analyze BSCB disruption in pre- and postoperative DCM patients and to correlate those with the clinical status and postoperative outcome. This prospectively controlled cohort included 50 DCM patients (21 female; 29 male; mean age: 62.9 ± 11.2 years). As neurological healthy controls, 52 (17 female; 35 male; mean age 61.8 ± 17.3 years) patients with thoracic abdominal aortic aneurysm (TAAA) and indication for open surgery were included. All patients underwent a neurological examination and DCM-associated scores (Neck Disability Index, modified Japanese Orthopaedic Association Score) were assessed. To evaluate the BSCB status, blood and cerebrospinal fluid (CSF) samples (lumbar puncture or CSF drainage) were taken preoperatively and in 15 DCM patients postoperatively (4 female; 11 male; mean age: 64.7 ± 11.1 years). Regarding BSCB disruption, CSF and blood serum were examined for albumin, immunoglobulin (Ig) G, IgA and IgM. Quotients for CSF/serum were standardized and calculated according to Reiber diagnostic criteria. Significantly increased preoperative CSF/serum quotients were found in DCM patients as compared to control patients: AlbuminQ (p < .001), IgAQ (p < .001) and IgGQ (p < .001). IgMQ showed no significant difference (T = − 1.15, p = .255). After surgical decompression, neurological symptoms improved in DCM patients, as shown by a significantly higher postoperative mJOA compared to the preoperative score (p = .001). This neurological improvement was accompanied by a significant change in postoperative CSF/serum quotients for Albumin (p = .005) and IgG (p = .004) with a trend of a weak correlation between CSF markers and neurological recovery. This study further substantiates the previous findings, that a BSCB disruption in DCM patients is evident. Interestingly, surgical decompression appears to be accompanied by neurological improvement and a reduction of CSF/serum quotients, implying a BSCB recovery. We found a weak association between BSCB recovery and neurological improvement. A BSCB disruption might be a key pathomechanism in DCM patients, which could be relevant to treatment and clinical recovery.
Historic evolution of population exposure to heatwaves in Xinjiang Uygur Autonomous Region, China
Authors: Dong Diwen , Tao Hui , Zhang Zengxin 
Published: May 2023

AbstractHeatwaves have pronounced impacts on human health and the environment on a global scale. Although the characteristics of heatwaves has been well documented, there still remains a lack of dynamic studies of population exposure to heatwaves (PEH), particularly in the arid regions. In this study, we analyzed the spatio-temporal evolution characteristics of heatwaves and PEH in Xinjiang using the daily maximum temperature (Tmax), relative humidity (RH), and high-resolution gridded population datasets. The results revealed that the heatwaves in Xinjiang occur more continually and intensely from 1961 to 2020. Furthermore, there is substantial spatial heterogeneity of heatwaves with eastern part of the Tarim Basin, Turpan, and Hami been the most prone areas. The PEH in Xinjiang showed an increasing trend with high areas mainly in Kashgar, Aksu, Turpan, and Hotan. The increase in PEH is mainly contributed from population growth, climate change and their interaction. From 2001 to 2020, the climate effect contribution decreased by 8.5%, the contribution rate of population and interaction effects increased by 3.3% and 5.2%, respectively. This work provides a scientific basis for the development of policies to improve the resilience against hazards in arid regions.
Improved anticancer efficacy of methyl pyropheophorbide-a–incorporated solid lipid nanoparticles in photodynamic therapy
Authors: Yeo Sooho , Lee Tae Heon , Kim Min Je , Shim Young Key , Yoon Il , Song Young Kyu , Lee Woo Kyoung 
Published: May 2023

AbstractPhotodynamic therapy (PDT) is a promising anticancer treatment because it is patient-friendly and non-invasive. Methyl pyropheophorbide-a (MPPa), one of the chlorin class photosensitizers, is a drug with poor aqueous solubility. The purpose of this study was to synthesize MPPa and develop MPPa-loaded solid lipid nanoparticles (SLNs) with improved solubility and PDT efficacy. The synthesized MPPa was confirmed 1H nuclear magnetic resonance (1H-NMR) spectroscopy and UV–Vis spectroscopy. MPPa was encapsulated in SLN via a hot homogenization with sonication. Particle characterization was performed using particle size and zeta potential measurements. The pharmacological effect of MPPa was evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay and anti-cancer effect against HeLa and A549 cell lines. The particle size and zeta potential ranged from 231.37 to 424.07 nm and − 17.37 to − 24.20 mV, respectively. MPPa showed sustained release from MPPa-loaded SLNs. All formulations improved the photostability of MPPa. The DPBF assay showed that SLNs enhanced the 1O2 generation from MPPa. In the photocytotoxicity analysis, MPPa-loaded SLNs demonstrated cytotoxicity upon photoirradiation but not in the dark. The PDT efficacy of MPPa improved following its entrapment in SLNs. This observation suggests that MPPa-loaded SLNs are suitable for the enhanced permeability and retention effect. Together, these results demonstrate that the developed MPPa-loaded SLNs are promising candidates for cancer treatment using PDT.
Identification of sequence mutations in Phytophthora cactorum genome associated with mefenoxam resistance and development of a molecular assay for the mutant detection in strawberry (F. × ananassa)
Authors: Marin Marcus V. , Baggio Juliana S. , Oh Youngjae , Han Hyeondae , Chandra Saket , Wang Nan-Yi , Lee Seonghee , Peres Natalia A. 
Published: May 2023

AbstractPhytophthora crown rot (PhCR) caused by Phytophthora cactorum is one of the most damaging diseases of strawberry worldwide. Mefenoxam is one of the major fungicides currently used to manage PhCR. However, the emergence and spread of resistant isolates have made controlling the pathogen in the field problematic. In the present study, using whole genome sequencing analysis, mutations associated with mefenoxam-resistant isolates were identified in six different genomic regions of P. cactorum. The 95.54% reads from a sensitive isolate pool and 95.65% from a resistant isolate pool were mapped to the reference genome of P. cactorum P414. Four point mutations were in coding regions while the other two were in noncoding regions. The genes harboring mutations were functionally unknown. All mutations present in resistant isolates were confirmed by sanger sequencing of PCR products. For the rapid diagnostic assay, SNP-based high-resolution melting (HRM) markers were developed to differentiate mefenoxam-resistant P. cactorum from sensitive isolates. The HRM markers R3-1F/R3-1R and R2-1F/R2-1R were suitable to differentiate both sensitive and resistant profiles using clean and crude DNA extraction. None of the mutations associated with mefenoxam resistance found in this study were in the RNA polymerase subunit genes, the hypothesized target of this compound in oomycetes. Our findings may contribute to a better understanding of the mechanisms of resistance of mefenoxam in oomycetes since serves as a foundation to validate the candidate genes as well as contribute to the monitoring of P. cactorum populations for the sustainable use of this product.
Transfer and transformation characteristics of Zn and Cd in soil-rotation plant (Brassica napus L and Oryza sativa L) system and its influencing factors
Authors: Yan Qiuxiao , Fang Hui , Wang Daoping , Xiao Xuefeng , Deng Tingfei , Li Xiangying , Wei Fuxiao , Liu Jiming , Lin Changhu 
Published: May 2023

AbstractRice–rape rotation is a widely practiced cropping system in China. However, changes in soil properties and management could change the bioavailability of Cd, In order to explore the occurrence state, transportation and transformation characteristics of heavy metals Cd and Zn in rice-rape rotation system in Guizhou karst area with high background value of Cd. In the karst rice–rape rotation area, the physical and chemical properties of soil, chemical specifications and activities of Cd and Zn at different soil depths and during various crop growth stages, and the bioaccumulation of Cd and Zn in different tissues of rice and rape were studied by field experiment and laboratory analysis. The bioaccumulation of Cd and Zn and the effects of physical and chemical soil properties on the activities and bioavailabilities of Cd and Zn during rice–rape rotation were explored. The findings revealed that soil particle size, composition, pH, redox potential, soil organic matter, and Cd and Zn contents varied dramatically, especially in deep soils. The physical and chemical properties of the deep and surface soils were significantly related to the bioaccumulation of Cd and Zn. Cd and Zn are activated during crop rotation. Cd was easier to be enriched in rice, while Zn was easier to be enriched in rape. The correlation between Cd and Zn contents in Brassica campestris L and their enrichment abilities were not significant, but that in Oryza sativa L were significant. During rice-rape rotation, the chemical speciations and activities of Cd and Zn changed with the changes of soil properties and waterlogging environment. This study had important basic guiding significance for the evaluation, prevention and control of heavy metal pollution, and improving soil quality in different rotation systems in karst areas, and was conducive to promoting the safe production of rape and rice.