bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Fire Emissions to PM2.5 and Its Transport Mechanism Over the Yungui Plateau, China During 2015–2019
Authors: Zhu Jun , Yue Xu , Che Huizheng , Xia Xiangao , Lei Yadong , Wang Jun , Zhao Tianliang , Yu Xingna , Zhou Hao , Liao Hong 
Published: June 2022

AbstractAir pollution over the Yungui Plateau (YGP) in southwestern China can be caused by the transport of biomass burning aerosols from Southeast Asia; however, the magnitude and mechanisms of such long‐range transport have not been fully investigated. Here, we studied the impacts of fire emissions on vertical PM2.5 over the YGP and the transport mechanisms of PM2.5 during the fire seasons (March–April) of the neighboring Indo‐China Peninsula (ICP) region in 2015–2019 using ground‐based monitoring data, reanalysis of meteorology, and GEOS‐Chem model simulations. Average daily PM2.5 concentrations of 36.06 ± 14.86 μg m−3 were measured at 16 ground stations in the YGP with the highest value of 53.77 μg m−3 at Xishuangbanna, the nearest station to the ICP. Model simulations showed that fire emissions contributed approximately 50%–60% of the vertical PM2.5 over the YGP at a height of 3–4 km, with larger contributions in meridional than zonal cross‐sections. Four weather patterns with low pressure over the YGP were identified as favorable conditions for smoke transport. The pattern with the lowest pressure over the northern YGP and the strongest vertical wind disturbance was the most favorable for the eastward transport of fire air pollution to the YGP. Another pattern, which had the strongest southerly wind, promoted smoke aerosols to climb from eastern Myanmar and northern Laos/Vietnam to the YGP. Through these typical pathways, ICP biomass burning significantly impacted PM2.5 pollution in southwestern China.
Inhibition of BAD-Ser99 phosphorylation synergizes with PARP inhibition to ablate PTEN-deficient endometrial carcinoma
Authors: Zhang Xi , Huang Peng , Wang Liqiong , Chen Shu , Basappa Basappa , Zhu Tao , Lobie Peter E. , Pandey Vijay 
Published: June 2022

AbstractLoss of phosphatase and tensin homolog (PTEN) impairs DNA double-strand repair and confers sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPis). However, PARPis also hyperactivate the MAPK and PI3K/AKT/mTOR pathways in PTEN-deficient endometrial carcinoma (EC), which allows the emergence of PARPi resistance. BCL-2–associated death promoter (BAD), integrates the common cell survival effects of the RAS/MEK/MAPK and PI3K/AKT/mTOR pathways. Herein, it was observed that increased BADSer99 (BADS99) phosphorylation in EC cells was significantly associated with PTEN-deficient status. Forced expression of phosphorylation deficient human BADS99A in PTEN-deficient EC cells significantly increased CASPASE 3/7 activity and decreased EC cell viability. Using NPB as a pharmacological inhibitor of pBADS99 phosphorylation, it was demonstrated that NPB synergized with PARPis (Olaparib, Rucaparib and Talazoparib) to enhance PARPi IC50 up to 60-fold and decreased survival, foci formation, and growth in 3D ex vivo culture of PTEN-deficient EC cells. Combined NPB-PARPi treatment of PTEN-deficient EC cells stimulated apoptosis and promoted DNA damage by impairment of homologous recombination. Using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonuclease system it was demonstrated that deletion of PTEN in PTEN replete EC cells enhanced the efficacy of combined NPB-PARPi treatment. Furthermore, combined inhibition of BADS99 phosphorylation and PARP ablated xenograft growth of PTEN-deficient EC cells. Similarly, a combination of NPB and PARPis significantly suppressed the growth of PTEN deficient patient-derived EC organoids. Hence, combined inhibition of BADS99 phosphorylation and PARP represents a rational and efficacious strategy to improve the prognosis of recurrent EC patients.
Optimal CD8+ T cell effector function requires costimulation-induced RNA-binding proteins that reprogram the transcript isoform landscape
Authors: Karginov Timofey A. , Ménoret Antoine , Vella Anthony T. 
Published: June 2022

AbstractBoosting T cell activation through costimulation directs defense against cancer and viral infections. Despite multiple studies targeting costimulation in clinical trials, the increased potency and reprogramming of T cells endowed by costimulation is poorly understood. Canonical dogma states that transcription mediates T cell activation. Here, we show that the spliceosome, controlling post-transcriptional alternative splicing and alternative polyadenylation, is the most enriched pathway in T cells after CD134/CD137 costimulation. Costimulation of CD8+ T cells significantly increases expression of 29 RNA-binding proteins while RNA-seq uncovers over 1000 differential alternative splicing and polyadenylation events. Using in vivo mouse and in vitro human models, we demonstrate that RNA-binding protein Tardbp is required for effector cytokine production, CD8+ T cell clonal expansion, and isoform regulation after costimulation. The prospect of immune response optimization through reprogramming of mRNA isoform production offered herein opens new avenues for experimentally and therapeutically tuning the activities of T cells.
Deep brain stimulation rectifies the noisy cortex and irresponsive subthalamus to improve parkinsonian locomotor activities
Authors: Lee Lan-Hsin Nancy , Huang Chen-Syuan , Wang Ren-Wei , Lai Hsing-Jung , Chung Chih-Ching , Yang Ya-Chin , Kuo Chung-Chin 
Published: June 2022

AbstractThe success of deep brain stimulation (DBS) therapy indicates that Parkinson’s disease is a brain rhythm disorder. However, the manifestations of the erroneous rhythms corrected by DBS remain to be established. We found that augmentation of α rhythms and α coherence between the motor cortex (MC) and the subthalamic nucleus (STN) is characteristically prokinetic and is decreased in parkinsonian rats. In multi-unit recordings, movement is normally associated with increased changes in spatiotemporal activities rather than overall spike rates in MC. In parkinsonian rats, MC shows higher spike rates at rest but less spatiotemporal activity changes upon movement, and STN burst discharges are more prevalent, longer lasting, and less responsive to MC inputs. DBS at STN rectifies the foregoing pathological MC-STN oscillations and consequently locomotor deficits, yet overstimulation may cause behavioral restlessness. These results indicate that delicate electrophysiological considerations at both cortical and subcortical levels should be exercised for optimal DBS therapy.
Functional DNA-based cytoskeletons for synthetic cells
Authors: Zhan Pengfei , Jahnke Kevin , Liu Na , Göpfrich Kerstin 
Published: June 2022

AbstractThe cytoskeleton is an essential component of a cell. It controls the cell shape, establishes the internal organization, and performs vital biological functions. Building synthetic cytoskeletons that mimic key features of their natural counterparts delineates a crucial step towards synthetic cells assembled from the bottom up. To this end, DNA nanotechnology represents one of the most promising routes, given the inherent sequence specificity, addressability and programmability of DNA. Here we demonstrate functional DNA-based cytoskeletons operating in microfluidic cell-sized compartments. The synthetic cytoskeletons consist of DNA tiles self-assembled into filament networks. These filaments can be rationally designed and controlled to imitate features of natural cytoskeletons, including reversible assembly and ATP-triggered polymerization, and we also explore their potential for guided vesicle transport in cell-sized confinement. Also, they possess engineerable characteristics, including assembly and disassembly powered by DNA hybridization or aptamer–target interactions and autonomous transport of gold nanoparticles. This work underpins DNA nanotechnology as a key player in building synthetic cells.
Characterization of inositol lipid metabolism in gut-associated Bacteroidetes
Authors: Heaver Stacey L. , Le Henry H. , Tang Peijun , Baslé Arnaud , Mirretta Barone Claudia , Vu Dai Long , Waters Jillian L. , Marles-Wright Jon , Johnson Elizabeth L. , Campopiano Dominic J. , Ley Ruth E. 
Published: June 2022

AbstractInositol lipids are ubiquitous in eukaryotes and have finely tuned roles in cellular signalling and membrane homoeostasis. In Bacteria, however, inositol lipid production is relatively rare. Recently, the prominent human gut bacterium Bacteroides thetaiotaomicron (BT) was reported to produce inositol lipids and sphingolipids, but the pathways remain ambiguous and their prevalence unclear. Here, using genomic and biochemical approaches, we investigated the gene cluster for inositol lipid synthesis in BT using a previously undescribed strain with inducible control of sphingolipid synthesis. We characterized the biosynthetic pathway from myo-inositol-phosphate (MIP) synthesis to phosphoinositol dihydroceramide, determined the crystal structure of the recombinant BT MIP synthase enzyme and identified the phosphatase responsible for the conversion of bacterially-derived phosphatidylinositol phosphate (PIP-DAG) to phosphatidylinositol (PI-DAG). In vitro, loss of inositol lipid production altered BT capsule expression and antimicrobial peptide resistance. In vivo, loss of inositol lipids decreased bacterial fitness in a gnotobiotic mouse model. We identified a second putative, previously undescribed pathway for bacterial PI-DAG synthesis without a PIP-DAG intermediate, common in Prevotella. Our results indicate that inositol sphingolipid production is widespread in host-associated Bacteroidetes and has implications for symbiosis.
The diversity of quinoa morphological traits and seed metabolic composition
Authors: Tabatabaei Iman , Alseekh Saleh , Shahid Mohammad , Leniak Ewa , Wagner Mateusz , Mahmoudi Henda , Thushar Sumitha , Fernie Alisdair R. , Murphy Kevin M. , Schmöckel Sandra M. , Tester Mark , Mueller-Roeber Bernd , Skirycz Aleksandra , Balazadeh Salma 
Published: June 2022

AbstractQuinoa (Chenopodium quinoa Willd.) is an herbaceous annual crop of the amaranth family (Amaranthaceae). It is increasingly cultivated for its nutritious grains, which are rich in protein and essential amino acids, lipids, and minerals. Quinoa exhibits a high tolerance towards various abiotic stresses including drought and salinity, which supports its agricultural cultivation under climate change conditions. The use of quinoa grains is compromised by anti-nutritional saponins, a terpenoid class of secondary metabolites deposited in the seed coat; their removal before consumption requires extensive washing, an economically and environmentally unfavorable process; or their accumulation can be reduced through breeding. In this study, we analyzed the seed metabolomes, including amino acids, fatty acids, and saponins, from 471 quinoa cultivars, including two related species, by liquid chromatography – mass spectrometry. Additionally, we determined a large number of agronomic traits including biomass, flowering time, and seed yield. The results revealed considerable diversity between genotypes and provide a knowledge base for future breeding or genome editing of quinoa.
Adipose cells and tissues soften with lipid accumulation while in diabetes adipose tissue stiffens
Authors: Abuhattum Shada , Kotzbeck Petra , Schlüßler Raimund , Harger Alexandra , Ariza de Schellenberger Angela , Kim Kyoohyun , Escolano Joan-Carles , Müller Torsten , Braun Jürgen , Wabitsch Martin , Tschöp Matthias , Sack Ingolf , Brankatschk Marko , Guck Jochen , Stemmer Kerstin , Taubenberger Anna V. 
Published: June 2022

AbstractAdipose tissue expansion involves both differentiation of new precursors and size increase of mature adipocytes. While the two processes are well balanced in healthy tissues, obesity and diabetes type II are associated with abnormally enlarged adipocytes and excess lipid accumulation. Previous studies suggested a link between cell stiffness, volume and stem cell differentiation, although in the context of preadipocytes, there have been contradictory results regarding stiffness changes with differentiation. Thus, we set out to quantitatively monitor adipocyte shape and size changes with differentiation and lipid accumulation. We quantified by optical diffraction tomography that differentiating preadipocytes increased their volumes drastically. Atomic force microscopy (AFM)-indentation and -microrheology revealed that during the early phase of differentiation, human preadipocytes became more compliant and more fluid-like, concomitant with ROCK-mediated F-actin remodelling. Adipocytes that had accumulated large lipid droplets were more compliant, and further promoting lipid accumulation led to an even more compliant phenotype. In line with that, high fat diet-induced obesity was associated with more compliant adipose tissue compared to lean animals, both for drosophila fat bodies and murine gonadal adipose tissue. In contrast, adipose tissue of diabetic mice became significantly stiffer as shown not only by AFM but also magnetic resonance elastography. Altogether, we dissect relative contributions of the cytoskeleton and lipid droplets to cell and tissue mechanical changes across different functional states, such as differentiation, nutritional state and disease. Our work therefore sets the basis for future explorations on how tissue mechanical changes influence the behaviour of mechanosensitive tissue-resident cells in metabolic disorders.
Characteristics and stability of sensorimotor activity driven by isolated-muscle group activation in a human with tetraplegia
Authors: Nickl Robert W. , Anaya Manuel A. , Thomas Tessy M. , Fifer Matthew S. , Candrea Daniel N. , McMullen David P. , Thompson Margaret C. , Osborn Luke E. , Anderson William S. , Wester Brock A. , Tenore Francesco V. , Crone Nathan E. , Cantarero Gabriela L. , Celnik Pablo A. 
Published: June 2022

AbstractUnderstanding the cortical representations of movements and their stability can shed light on improved brain-machine interface (BMI) approaches to decode these representations without frequent recalibration. Here, we characterize the spatial organization (somatotopy) and stability of the bilateral sensorimotor map of forearm muscles in an incomplete-high spinal-cord injury study participant implanted bilaterally in the primary motor and sensory cortices with Utah microelectrode arrays (MEAs). We built representation maps by recording bilateral multiunit activity (MUA) and surface electromyography (EMG) as the participant executed voluntary contractions of the extensor carpi radialis (ECR), and attempted motions in the flexor carpi radialis (FCR), which was paralytic. To assess stability, we repeatedly mapped and compared left- and right-wrist-extensor-related activity throughout several sessions, comparing somatotopy of active electrodes, as well as neural signals both at the within-electrode (multiunit) and cross-electrode (network) levels. Wrist motions showed significant activation in motor and sensory cortical electrodes. Within electrodes, firing strength stability diminished as the time increased between consecutive measurements (hours within a session, or days across sessions), with higher stability observed in sensory cortex than in motor, and in the contralateral hemisphere than in the ipsilateral. However, we observed no differences at network level, and no evidence of decoding instabilities for wrist EMG, either across timespans of hours or days, or across recording area. While map stability differs between brain area and hemisphere at multiunit/electrode level, these differences are nullified at ensemble level.
Germline variants of ATG7 in familial cholangiocarcinoma alter autophagy and p62
Authors: Greer Stephanie U. , Chen Jiamin , Ogmundsdottir Margret H. , Ayala Carlos , Lau Billy T. , Delacruz Richard Glenn C. , Sandoval Imelda T. , Kristjansdottir Sigrun , Jones David A. , Haslem Derrick S. , Romero Robin , Fulde Gail , Bell John M. , Jonasson Jon G. , Steingrimsson Eirikur , Ji Hanlee P. , Nadauld Lincoln D. 
Published: June 2022

AbstractAutophagy is a housekeeping mechanism tasked with eliminating misfolded proteins and damaged organelles to maintain cellular homeostasis. Autophagy deficiency results in increased oxidative stress, DNA damage and chronic cellular injury. Among the core genes in the autophagy machinery, ATG7 is required for autophagy initiation and autophagosome formation. Based on the analysis of an extended pedigree of familial cholangiocarcinoma, we determined that all affected family members had a novel germline mutation (c.2000C>T p.Arg659* (p.R659*)) in ATG7. Somatic deletions of ATG7 were identified in the tumors of affected individuals. We applied linked-read sequencing to one tumor sample and demonstrated that the ATG7 somatic deletion and germline mutation were located on distinct alleles, resulting in two hits to ATG7. From a parallel population genetic study, we identified a germline polymorphism of ATG7 (c.1591C>G p.Asp522Glu (p.D522E)) associated with increased risk of cholangiocarcinoma. To characterize the impact of these germline ATG7 variants on autophagy activity, we developed an ATG7-null cell line derived from the human bile duct. The mutant p.R659* ATG7 protein lacked the ability to lipidate its LC3 substrate, leading to complete loss of autophagy and increased p62 levels. Our findings indicate that germline ATG7 variants have the potential to impact autophagy function with implications for cholangiocarcinoma development.
Discriminating the occurrence of inundation in tsunami early warning with one-dimensional convolutional neural networks
Authors: Núñez Jorge , Catalán Patricio A. , Valle Carlos , Zamora Natalia , Valderrama Alvaro 
Published: June 2022

AbstractTsunamis are natural phenomena that, although occasional, can have large impacts on coastal environments and settlements, especially in terms of loss of life. An accurate, detailed and timely assessment of the hazard is essential as input for mitigation strategies both in the long term and during emergencies. This goal is compounded by the high computational cost of simulating an adequate number of scenarios to make robust assessments. To reduce this handicap, alternative methods could be used. Here, an enhanced method for estimating tsunami time series using a one-dimensional convolutional neural network model (1D CNN) is considered. While the use of deep learning for this problem is not new, most of existing research has focused on assessing the capability of a network to reproduce inundation metrics extrema. However, for the context of Tsunami Early Warning, it is equally relevant to assess whether the networks can accurately predict whether inundation would occur or not, and its time series if it does. Hence, a set of 6776 scenarios with magnitudes in the range $$M_w$$

M
w

8.0–9.2 were used to design several 1D CNN models at two bays that have different hydrodynamic behavior, that would use as input inexpensive low-resolution numerical modeling of tsunami propagation to predict inundation time series at pinpoint locations. In addition, different configuration parameters were also analyzed to outline a methodology for model testing and design, that could be applied elsewhere. The results show that the network models are capable of reproducing inundation time series well, either for small or large flow depths, but also when no inundation was forecast, with minimal instances of false alarms or missed alarms. To further assess the performance, the model was tested with two past tsunamis and compared with actual inundation metrics. The results obtained are promising, and the proposed model could become a reliable alternative for the calculation of tsunami intensity measures in a faster than real time manner. This could complement existing early warning system, by means of an approximate and fast procedure that could allow simulating a larger number of scenarios within the always restricting time frame of tsunami emergencies.
Automated gathering of real-world data from online patient forums can complement pharmacovigilance for rare cancers
Authors: Dirkson Anne , Verberne Suzan , Kraaij Wessel , van Oortmerssen Gerard , Gelderblom Hans 
Published: June 2022

AbstractCurrent methods of pharmacovigilance result in severe under-reporting of adverse drug events (ADEs). Patient forums have the potential to complement current pharmacovigilance practices by providing real-time uncensored and unsolicited information. We are the first to explore the value of patient forums for rare cancers. To this end, we conduct a case study on a patient forum for Gastrointestinal Stromal Tumor patients. We have developed machine learning algorithms to automatically extract and aggregate side effects from messages on open online discussion forums. We show that patient forum data can provide suggestions for which ADEs impact quality of life the most: For many side effects the relative reporting rate differs decidedly from that of the registration trials, including for example cognitive impairment and alopecia as side effects of avapritinib. We also show that our methods can provide real-world data for long-term ADEs, such as osteoporosis and tremors for imatinib, and novel ADEs not found in registration trials, such as dry eyes and muscle cramping for imatinib. We thus posit that automated pharmacovigilance from patient forums can provide real-world data for ADEs and should be employed as input for medical hypotheses for rare cancers.
Metabolism and antioxidant activity of SlGSTD1 in Spodoptera litura as a detoxification enzyme to pyrethroids
Authors: Li Dongzhi , Xu Li , Liu Hongyu , Chen Xiling , Zhou Lin 
Published: June 2022

AbstractGlutathione S-transferase (GSTs) are members of multifunction enzymes in organisms and mostly known for their roles in insecticide resistance by conjugation. Spodoptera litura (Fabricius) is a voracious agricultural pest widely distributed in the world with high resistance to various insecticides. The function of GSTs in the delta group of S. litura is still lacking. Significantly up-regulation of SlGSTd1 was reported in four pyrethroids-resistant populations and a chlorpyrifos-selected population. To further explore its role in pyrethroids and organophosphates resistance, the metabolism and peroxidase activity of SlGSTD1 were studied by heterologous expression, RNAi, and disk diffusion assay. The results showed that Km and Vmax for 1-chloro-2,4-dinitrobenzene (CDNB) conjugating activity of SlGSTD1were 1.68 ± 0.11 mmol L−1 and 76.0 ± 2.7 nmol mg−1 min−1, respectively. Cyhalothrin, beta-cypermethrin, and chlorpyrifos had an obvious inhibitory effect on SlGSTD1 activity, especially for fenvalerate, when using CDNB as substrate. Fenvalerate and cyhalothrin can be metabolized by SlGSTD1 in E. coli and in vitro. Also, silencing of SlGSTd1 significantly increased the toxicity of fenvalerate and cyhalothrin, but had no significant effect on the mortality of larvae treated by beta-cypermethrin or chlorpyrifos. SlGSTD1 possesses peroxidase activity using cumene hydroperoxide as a stress inducer. The comprehensive results indicate that SlGSTD1 is involved in fenvalerate and cyhalothrin resistance of S. litura by detoxication and antioxidant capacity.