bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discriminative histone imputation using chromatin accessibility
Authors: Wen Wen , Zhong Jiaxin , Zhang Zhaoxi , Jia Lijuan , Chu Tinyi , Wang Nating , Danko Charles G. , Wang Zhong 
Published: January 2024

AbstractHistone modifications (HMs) play a pivot role in various biological processes, including transcription, replication and DNA repair, significantly impacting chromatin structure. These modifications underpin the molecular mechanisms of cell-specific gene expression and complex diseases. However, annotating HMs across different cell types solely using experimental approaches is impractical due to cost and time constraints. Herein, we present dHICA (discriminative histone imputation using chromatin accessibility), a novel deep learning framework that integrates DNA sequences and chromatin accessibility data to predict multiple HM tracks. Employing the Transformer architecture alongside dilated convolutions, dHICA boasts an extensive receptive field and captures more cell-type-specific information. dHICA not only outperforms state-of-the-art baselines but also achieves superior performance in cell-specific loci and gene elements, aligning with biological expectations. Furthermore, dHICA’s imputations hold significant potential for downstream applications, including chromatin state segmentation and elucidating the functional implications of SNPs. In conclusion, dHICA serves as an invaluable tool for advancing the understanding of chromatin dynamics, offering enhanced predictive capabilities and interpretability.
Tviblindi algorithm identifies branching developmental trajectories of human B cell development
Authors: Bakardjieva Marina , Stuchlý Jan , Pelák Ondřej , Wentink Marjolein , Glier Hana , Novák David , Stančíková Jitka , Kužílková Daniela , Janowska Iga , Rizzi Marta , Burg Mirjam van der , Kalina Tomáš 
Published: January 2024

AbstractDetailed knowledge of the human B-cell development is crucial for proper interpretation of inborn errors of immunity and for malignant diseases. It is of interest to understand the kinetics of protein expression changes during the B cell development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human bone marrow and peripheral blood samples from healthy individuals with the aim to describe all B-cell developmental trajectories across the two tissues. We validated a 30-parameter mass cytometry panel and demonstrated the utility of “vaevictis” visualization of B-cell developmental stages. We used our recently developed trajectory inference tool “tviblindi” to exhaustively describe all trajectories leading to all developmental ends discovered in the data. Focusing on Natural Effector B cells, we demonstrated the dynamics of expression of nuclear factors (PAX-5, TdT, Ki-67, Bcl-2), cytokine and chemokine receptors (CD127, CXCR4, CXCR5) in relation to the canonical B-cell developmental stage markers (CD34, CD10, sIgM, IgD, CD20, CD27). Lastly, we performed analysis of the expression changes related to developmental branching points (Natural Effector versus Switched Memory B cells, marked by up-regulation of CD73).In conclusion, we developed, validated and presented a comprehensive set of tools for investigation of B-cell development.
TheArabidopsis thalianaTRAPPIII subunit AtTRAPPC8/AtTRS85 is involved in ER functioning and autophagy
Authors: Hoffman-Sommer Marta , Piłka Natalia , Anielska-Mazur Anna , Nowakowska Julita , Dagdas Yasin , Swiezewska Ewa 
Published: January 2024

ABSTRACTTRAPP (transport protein particle) tethering complexes are known for their function as Rab-GTPase exchange factors (GEFs). Two versions of the complex are considered functionally separate: TRAPPII, an activator of GTPases of the Rab11 family (RabA in plants) which functions in post-Golgi sorting, and TRAPPIII, activating the Rab1 family (RabD in plants) which regulates ER-to-Golgi trafficking and autophagy. InArabidopsis thaliana, the TRAPPIII complex has been identified and its subunit composition established, but little is known about its functions. Here, we found that binary subunit interactions of the plant TRAPPIII complex are analogous to those of metazoan TRAPPIII, with the two large subunits TRAPPC8 and -C11 linking the TRAPP core and the small C12-C13 dimer. To gain insight into the functions of TRAPPIII in plants, we characterized twoA. thaliana trappc8mutants. The mutants display abnormalities in plant morphology, in particular in flower and seed development. They also have autophagic defects, constitutive ER stress response, and elevated levels of the ER lipid dolichol – an indispensable cofactor of protein glycosylation. These results show that plant TRAPPC8 is involved in multiple trafficking steps in the cells and they suggest a novel link between ER membrane turnover and dolichol levels.HIGHLIGHTArabidopsis thalianaTRAPPC8 is necessary for correct functioning of the ER, in particular for its lipid homeostasis. Dysruption ofTRAPPC8leads to defects in secretion, autophagosome formation, and plant development.
Effects of point density on interpretability of lidar-derived forest structure metrics in two temperate forests
Authors: Swanson A. Christine , Merrick Trina , Abelev Andrei , Liang Robert , Vermillion Michael , Buma Willibroad , Li Rong-Rong 
Published: January 2024

AbstractThree-dimensional forest structure plays an important role in processes such as biomass accumulation and fire spread and provides wildlife with habitat and foraging spaces. Advances in lidar mapping have improved forest structure quantification at local to global scales. However, point cloud density may have effects on estimates of forest structure variables that are not well understood and may vary by forest structural type (e.g. closed vs open canopy). In this study we investigated the effects of lidar point cloud density on forest structure parametrization in an open canopy pine-dominated forest at Assateague Island National Seashore (AINS) and a closed-canopy mixed hardwood temperate forest at the Keweenaw Research Center (KRC) using uncrewed aerial system (UAS)-based lidar. We decimated high point density (> 1000 points m-2) lidar data to between 1 and 175 points m-2and analyzed 26 forest structure metrics using Tukey’s method, reliability ratio, and correlation analyses.Effects of point density on forest structure parameters were often site-dependent, as anticipated. At AINS, maximum (zmax) and mode (zmode) height significantly differed for point densities less than 10 pts m-2and 25 points m-2, respectively, while at KRC, the thresholds were 75 points m-2forzmaxand 50 points m-2forzmode. Reliability ratio ofzmax, height skewness, height quantiles, and the coefficient of variation of mean leaf area density (LAD) also varied dependent on point density at AINS. At both sites, metrics related LAD varied significantly (p < 0.001) at all but the highest point densities, and the reliability ratio forzmode, kurtosis of height distribution and mean horizontal coefficient of variation of LAD varied across point densities without any clear pattern. Point density mainly affected correlations between LAD-derived structural metrics and other metrics (e.g., as point density increased, Shannon diversity of LAD changed from being positively to negatively correlated tozmax). This study demonstrates how point density differentially affects lidar-derived forest structure parameters in diverse forest types. Scientists must understand these effects to interpret and compare forest structure attributes derived from different lidars.
Harnessing the power of poplar tree natural genetic variation for the development of future sustainable biofuels and bioproducts: a droughted marginal-land experiment for multi-disciplinary investigations
Authors: Taylor Gail , Bailey-Bale Jack H , Klein Marie C , Milner Suzanne , Chen Jin-Gui , Muchero Wellington , Freer-Smith Peter , Tschaplinski Timothy J. , Tuskan Jerry 
Published: January 2024

AbstractThe emerging bioeconomy offers significant potential to replace fossil-fuel-based energy, manufacturing, and processing with that utilizing biomass as the raw feedstock. However, feedstock production from non-food crops such as fast-growing trees, must be delivered at scale, in a reliable and consistent manner, utilizing marginal land unsuitable for food crops and with minimum inputs. This new generation of feedstock crops has a limited history of domestication. Foundational knowledge is required to enable rapid selection and breeding for improved cultivars and varieties to enable large-scale planting of 600M ha, globally over the coming decades. Here, we describe an innovative field platform with over 1,000 unique genotypes of fast-growing poplar (Populus trichocarpa) trees, each sequenced and being subjected to a controlled drought. The 6.5 ha site provides opportunities to bring together multi-disciplinary phenotyping science linked to computational, and AI approaches, enabling the link between complex plant traits and their underlying genes to be rapidly established and translated into the development of improved climate-resilient germplasm for a future at-scale bioeconomy.
Species delimitation analysis indicates cryptic speciation forTerpios gelatinosus(Porifera, Demospongiae) from coastal regions of the northeastern Mediterranean Sea
Authors: Öztürk Esra , Temiz Berivan , Karahan Arzu 
Published: January 2024

AbstractSponges, comprising over 9000 recorded species, represent one of the most primitive groups of metazoans. Given the importance of species distribution records and the identification of new species in scientific research, these endeavors play a crucial role in enhancing ecological insights, conserving biodiversity, facilitating a better understanding of the relationships between various groups of organisms, advancing our knowledge of evolution, and potentially expanding biomedical implications. In this study, we used basic morphological data, mitochondrial Cytochrome Oxidase I (COI) gene, and Internal Transcribed Spacer two (ITS2) regions to evaluate theTerpiossamples collected from four coastal sites along the northeastern Mediterranean Sea, covering a distance of approximately 450 km. For this purpose, 81 COI and 11 ITS2 records of the order Suberitida were mined from GenBank, and species delimitation analysis was performed using both the Automatic Barcode Gap Discovery method and the Poisson Tree Process (PTP), along with 11 samples from the present study. While we observed slight differences in spicule sizes, the overall morphology of all samples from our study was similar. Within the scope of this research, we report the first-ever presence record ofT. gelatinosusin the northeastern Mediterranean Sea. Furthermore, we document evidence pointing to the potential existence of cryptic speciation in the region.
De novo-designed minibinders expand the synthetic biology sensing repertoire
Authors: Weinberg Zara Y. , Soliman Sarah S. , Kim Matthew S. , Shah Devan H. , Chen Irene P. , Ott Melanie , Lim Wendell A. , El-Samad Hana 
Published: January 2024

AbstractSynthetic and chimeric receptors capable of recognizing and responding to user-defined antigens have enabled “smart” therapeutics based on engineered cells. These cell engineering tools depend on antigen sensors which are most often derived from antibodies. Advances in thede novodesign of proteins have enabled the design of protein binders with the potential to target epitopes with unique properties and faster production timelines compared to antibodies. Building upon our previous work combining ade novo-designed minibinder of the Spike protein of SARS-CoV-2 with the synthetic receptor synNotch (SARSNotch), we investigated whether minibinders can be readily adapted to a diversity of cell engineering tools. We show that the Spike minibinder LCB1 easily generalizes to a next-generation proteolytic receptor SNIPR that performs similarly to our previously reported SARSNotch. LCB1-SNIPR successfully enables the detection of live SARS-CoV-2, an improvement over SARSNotch which can only detect cell-expressed Spike. To test the generalizability of minibinders to diverse applications, we tested LCB1 as an antigen sensor for a chimeric antigen receptor (CAR). LCB1-CAR enabled CD8+ T cells to cytotoxically target Spike-expressing cells. We further demonstrate that two other minibinders directed against the clinically relevant epidermal growth factor receptor are able to drive CAR-dependent cytotoxicity with efficacy similar to or better than an existing antibody-based CAR. Our findings suggest that minibinders represent a novel class of antigen sensors that have the potential to dramatically expand the sensing repertoire of cell engineering tools.
Clear effects of population and sex but not rearing temperature on stress tolerance in a temperate butterfly
Authors: Verspagen Nadja , DiLeo Michelle F. , Saastamoinen Marjo 
Published: January 2024

ABSTRACTAs temperatures are rising globally, the survival of organisms depends on their tolerance of such rising temperatures as well as resistance to indirect effects such as resource shortage under these new conditions. Genetic background and phenotypic plasticity in the form of acclimation are known to affect stress resistance, but much about genetic variation in plasticity is still unknown, especially in insects other thanDrosophila. Here we aim to study the effect of population of origin, developmental temperature, and their interaction on stress tolerance (heat tolerance and starvation resistance). We test the beneficial acclimation hypothesis and how it is influenced by intraspecific differences. For this, we reared Glanville fritillary butterfly larvae originating from Finland and Spain at high and control temperatures, and measured their heat tolerance and starvation resistance. To assess potential costs of acclimation we also measured lifespan under control conditions. Neither adult heat tolerance nor starvation resistance were impacted by thermal conditions during development and thus we found no evidence for the beneficial acclimation hypothesis. Heat tolerance also did not differ between sex or population of origin. In contrast, we found interacting effects of population and sex on adult starvation resistance, with Spanish females outperforming other groups. Spanish females also had a longer lifespan under control conditions. Our study provides no evidence for the beneficial acclimation hypothesis but highlights the importance of population differences in stress tolerance.SUMMARY STATEMENTDespite their importance, the interacting effects of population of origin and developmental acclimation temperature on stress response have not often been studied together, especially in insects other thanDrosophila.
Stress Granule Protein TZF1 Enhances Salt Stress Tolerance by TargetingACA11mRNA for Degradation in Arabidopsis
Authors: He Siou-Luan , Li Bin , Zahurancik Walter J. , Arthur Henry C. , Sidharthan Vaishnavi , Gopalan Venkat , Wang Lei , Jang Jyan-Chyun 
Published: January 2024

ABSTRACTTandem CCCH zinc finger (TZF) proteins play diverse roles in plant growth and stress response. Although as many as 11 TZF proteins have been identified inArabidopsis, little is known about the mechanism by which TZF proteins select and regulate the target mRNAs. Here, we report thatArabidopsisTZF1 is a bona-fide stress granule protein. Ectopic expression ofTZF1(TZF1 OE), but not an mRNA binding-defective mutant (TZF1H186YOE), enhances salt stress tolerance inArabidopsis. RNA-seq analyses of NaCl-treated plants revealed that the down-regulated genes inTZF1 OEplants are enriched for functions in salt and oxidative stress responses. Because many of these down-regulated mRNAs contain AU- and/or U-rich elements (AREs and/or UREs) in their 3’-UTRs, we hypothesized that TZF1—ARE/URE interaction might contribute to the observed gene expression changes. Results from RNA immunoprecipitation-quantitative PCR analysis, gel-shift, and mRNA half-life assays indicate that TZF1 binds and triggers degradation of theautoinhibited Ca2+-ATPase 11(ACA11) mRNA, encoding a tonoplast-localized calcium pump that extrudes calcium and dampens the signal transduction pathways necessary for salt stress tolerance. Furthermore, this salt stress-tolerance phenotype was recapitulated inaca11null mutants. Remarkably, a set of positive regulators for salt stress tolerance was upregulated inTZF1 OEplants. These includeNa+/H+Exchanger(NHX) family members known to contribute to Na+homeostasis and salinity stress tolerance. Collectively, we present a model in which TZF1 targetsACA11andACA4directly, and repressors ofNHXsand other negative regulators indirectly for mRNA degradation to enhance plant salt stress tolerance.
Genome and tissue-specific transcriptome of the tropical milkweed (Asclepias curassavica)
Authors: Feng Honglin , Zhang Jing , Powell Adrian F. , Buttelmann Gretta L. , Yang Lily , Yan Ethan , Wang Fumin , Broyles Steven B. , Jander Georg , Strickler Susan R. 
Published: January 2024

AbstractTropical milkweed (Asclepias curassavica) serves as a host plant for monarch butterflies (Danaus plexippus) and other insect herbivores that can tolerate the abundant cardiac glycosides that are characteristic of this species. Cardiac glycosides, along with additional specialized metabolites, also contribute to the ethnobotanical uses ofA. curassavica. To facilitate further research on milkweed metabolism, we assembled the 197 Mbp genome of a fifth-generation inbred line ofA. curassavicainto 619 contigs, with an N50 of 10 Mbp. Scaffolding resulted in 98% of the assembly being anchored to 11 chromosomes, which are mostly colinear with the previously assembled common milkweed (A. syriaca) genome. Assembly completeness evaluations showed that 98% of the BUSCO gene set is present in theA. curassavicagenome assembly. The transcriptomes of six tissue types (young leaves, mature leaves, stems, flowers, buds, and roots), with and without defense elicitation by methyl jasmonate treatment, showed both tissue-specific gene expression and induced expression of genes that may be involved in cardiac glycoside biosynthesis. Expression of aCYP87Agene, the predicted first gene in the cardiac glycoside biosynthesis pathway, was observed only in the stems and roots and was induced by methyl jasmonate. Together, this genome sequence and transcriptome analysis provide important resources for further investigation of the ecological and medicinal uses ofA. curassavica.
AnNoBrainer, an Automated Annotation of Mouse Brain Images using Deep Learning
Authors: Peter Roman , Hrobar Petr , Navratil Josef , Vagenknecht Martin , Soukup Jindrich , Tsuji Keiko , Barrezueta Nestor X. , Stoll Anna C. , Gentzel Renee C. , Sugam Jonathan A. , Marcus Jacob , Bitton Danny A. 
Published: January 2024

AbstractAnnotation of multiple regions of interest across the whole mouse brain is an indispensable process for quantitative evaluation of a multitude of study endpoints in neuroscience digital pathology. Prior experience and domain expert knowledge are the key aspects for image annotation quality and consistency. At present, image annotation is often achieved manually by certified pathologists or trained technicians, limiting the total throughput of studies performed at neuroscience digital pathology labs. It may also mean that less rigorous, less time-consuming methods of histopathological assessment are employed by non-pathologists, especially for early discovery and preclinical studies. To address these limitations and to meet the growing demand for image analysis in a pharmaceutical setting, we developed AnNoBrainer, an open-source software tool that leverages deep learning, image registration, and standard cortical brain templates to automatically annotate individual brain regions on 2D pathology slides. Application of AnNoBrainer to a published set of pathology slides from transgenic mice models of synucleinopathy revealed comparable accuracy, increased reproducibility, and a significant reduction (∼50%) in time spent on brain annotation, quality control and labelling compared to trained scientists in pathology. Taken together, AnNoBrainer offers a rapid, accurate, and reproducible automated annotation of mouse brain images that largely meets the experts’ histopathological assessment standards (>85% of cases) and enables high-throughput image analysis workflows in digital pathology labs.
Antibiotics affect the pharmacokinetics of n-butylphthalidein vivoby altering the intestinal microbiota
Authors: Li Xiangchen , Guo Xiaoli , Liu Yixin , Ren Fefei , Li Shan , Yang Xiuling , Liu Jian , Zhang Zhiqing 
Published: January 2024

ABSTRACTObjectiveN-butylphthalide (NBP) is a monomeric compound extracted from natural plant celery seeds, whether intestinal microbiota alteration can modify its pharmacokinetics is still unclear. The purpose of this study is to investigate the effect of intestinal microbiota alteration on the pharmacokinetics of NBP and its related mechanisms.MethodsAfter treatment with antibiotics and probiotics, plasma NBP concentrations in SD rats were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The effect of intestinal microbiota changes on NBP pharmacokinetics was compared. Intestinal microbiota changes after NBP treatment were analyzed by 16S rRNA sequencing. Expressions of CYP3A1 mRNA and protein in the liver and small intestine tissues under different intestinal flora conditions were determined by qRT-PCR and Western Blot. KEGG analysis was used to analyze the effect of intestinal microbiota changes on metabolic pathways.ResultsCompared to the control group, the values of Cmax, AUC0-8, AUC0-∞, t1/2in the antibiotic group increased by 56.1% (P<0.001), 56.4% (P<0.001), 53.2% (P<0.001), and 24.4% (P<0.05), respectively. In contrast, the CL and Tmaxvalues decreased by 57.1% (P<0.001) and 28.6% (P<0.05), respectively. Treatment with antibiotics could reduce the richness and diversity of the intestinal microbiota. CYP3A1 mRNA and protein expressions in the small intestine of the antibiotic group were 61.2% and 66.1% of those of the control group, respectively. CYP3A1 mRNA and protein expressions in the liver were 44.6% and 63.9% of those in the control group, respectively. There was no significant change in the probiotic group. KEGG analysis showed that multiple metabolic pathways were significantly down-regulated in the antibiotic group. Among them, the pathways of drug metabolism, bile acid biosynthesis and decomposition, and fatty acid synthesis and decomposition were related to NBP biological metabolism.ConclusionAntibiotic treatment could affect the intestinal microbiota, decrease CYP3A1 mRNA and protein expressions and increase NBP exposurein vivoby inhibiting pathways related to NBP metabolism.