bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pangenome of cultivated beet and crop wild relatives reveals parental relationships of a tetraploid wild beet
Authors: Sielemann Katharina , Schmidt Nicola , Guzik Jonas , Kalina Natalie , Pucker Boas , Viehöver Prisca , Breitenbach Sarah , Weisshaar Bernd , Heitkam Tony , Holtgräwe Daniela 
Published: July 2023

AbstractMost crop plants, including sugar beet (Beta vulgarissubsp.vulgaris), suffer from domestication bottlenecks and low genetic diversity caused by extensive selection for few traits. However, crop wild relatives (CWRs) harbour useful traits relevant for crop improvement, including enhanced adaptation to biotic and abiotic stresses.Especially polyploids are interesting from an evolutionary perspective as genes undergo reorganisation after the polyploidisation event. Through neo-and subfunctionalisation, novel functions emerge, which enable plants to cope with changing environments and extreme/harsh conditions. Particularly in the face of climate change, specific stress and pathogen resistances or tolerances gain importance. To introduce such traits into breeding material, CWRs have already been identified as an important source for sustainable breeding. The identification of genes underlying traits of interest is crucial for crop improvement.For beets, the sectionCorollinaecontains the tetraploid speciesBeta corolliflora(2n=4x=36) that harbours salt and frost tolerances as well as a wealth of pathogen resistances. The number of beneficial traits ofB. corolliflorais increased compared to those of the known diploids in this section (all 2n=2x=18). Nevertheless, neither the parental relationships ofB. corolliflorahave been resolved, nor are genomic resources available to steer sustainable, genomics-informed breeding.To benefit from the resources offered by polyploid beet wild relatives, we generated a comprehensive pangenome dataset includingB. corolliflora,Beta lomatogona, andBeta macrorhiza, as well as a more distant wild beetPatellifolia procumbens(2n=2x=18). Joined analyses with publicly available genome sequences of two additional wild beets allowed the identification of genomic regions absent from cultivated beet, providing a sequence database harbouring traits relevant for future breeding endeavours. In addition, we present strong evidence for the parental relationship of theB. corolliflorawild beet as an autotetraploid emerging fromB. macrorhiza.
Well-ST-seq: cost-effective spatial transcriptomics at cellular level and high RNA capture efficiency
Authors: Yu Nianzuo , Jin Zhengyang , Liang Chongyang , Zhang Junhu , Yang Bai 
Published: July 2023

AbstractSpatial transcriptomic technologies are promising tools to reveal fine anatomical profiles of tissues. As for the methodologies based on barcoded probe arrays, improving the balance among probe barcoding complexity and cost, gene capture sensitivity, and spatial resolution can accelerate the spreading of spatial transcriptomic in basic science and clinical work. Here, based on miniaturized microfluidic and microarray technologies, we constructed a spatially cellular-level RNA-capture probe arrays. Owing to the predetermined and cost-effective probe fixation characteristics of the methodology, the consumable cost and fabrication time of the probe array can be reduced to $1.21/mm2and approximately 2 hours, and the preparation process does not rely on large precision instruments. Moreover, the efficiency of the transcript captured by the probe array is even comparable to conventional single-cell RNA sequencing. Based on this technology, we achieved the spatial transcriptome expression mapping and gained insight into spatial cell heterogeneity of the mouse hippocampus.
DrugGPT: A GPT-based Strategy for Designing Potential Ligands Targeting Specific Proteins
Authors: Li Yuesen , Gao Chengyi , Song Xin , Wang Xiangyu , Xu Yungang , Han Suxia 
Published: July 2023

AbstractDrugGPT presents a ligand design strategy based on the autoregressive model, GPT, focusing on chemical space exploration and the discovery of ligands for specific proteins. Deep learning language models have shown significant potential in various domains including protein design and biomedical text analysis, providing strong support for the proposition of DrugGPT. In this study, we employ the DrugGPT model to learn a substantial amount of protein-ligand binding data, aiming to discover novel molecules that can bind with specific proteins. This strategy not only significantly improves the efficiency of ligand design but also offers a swift and effective avenue for the drug development process, bringing new possibilities to the pharmaceutical domain.In our research, we particularly optimized and trained the GPT-2 model to better adapt to the requirements of drug design. Given the characteristics of proteins and ligands, we redesigned the tokenizer using the BPE algorithm, abandoned the original tokenizer, and trained the GPT-2 model from scratch. This improvement enables DrugGPT to more accurately capture and understand the structural information and chemical rules of drug molecules. It also enhances its comprehension of binding information between proteins and ligands, thereby generating potentially active drug candidate molecules.Theoretically, DrugGPT has significant advantages. During the model training process, DrugGPT aims to maximize the conditional probability and employs the back-propagation algorithm for training, making the training process more stable and avoiding the Mode Collapse problem that may occur in Generative Adversarial Networks in drug design. Furthermore, the design philosophy of DrugGPT endows it with strong generalization capabilities, giving it the potential to adapt to different tasks.In conclusion, DrugGPT provides a forward-thinking and practical new approach to ligand design. By optimizing the tokenizer and retraining the GPT-2 model, the ligand design process becomes more direct and efficient. This not only reflects the theoretical advantages of DrugGPT but also reveals its potential applications in the drug development process, thereby opening new perspectives and possibilities in the pharmaceutical field.
Pan-cancer characterization of ncRNA synergistic competition uncovers potential carcinogenic biomarkers
Authors: Zhang Junpeng , Liu Lin , Wei Xuemei , Zhao Chunwen , Li Sijing , Li Jiuyong , Le Thuc Duy 
Published: July 2023

AbstractNon-coding RNAs (ncRNAs) act as important modulators of gene expression and they have been confirmed to play critical roles in the physiology and development of malignant tumors. Understanding the synergism of multiple ncRNAs in competing endogenous RNA (ceRNA) regulation can provide important insights into the mechanisms of malignant tumors caused by ncRNA regulation. In this work, we present a framework, SCOM, for identifying ncRNA synergistic competition. We systematically construct the landscape of ncRNA synergistic competition across 31 malignant tumors, and reveal that malignant tumors tend to share hub ncRNAs rather than the ncRNA interactions involved in the synergistic competition. In addition, the synergistic competition ncRNAs (i.e. ncRNAs involved in the synergistic competition) are likely to be involved in drug resistance, contribute to distinguishing molecular subtypes of malignant tumors, and participate in immune regulation. Furthermore, SCOM can help to infer ncRNA synergistic competition across malignant tumors and uncover potential diagnostic and prognostic biomarkers of malignant tumors. Altogether, the SCOM framework and the resulting web-based database SCOMdb (www.comblab.cn/SCOMdb/) serve as a useful resource for exploring ncRNA regulation and to accelerate the identification of carcinogenic biomarkers.Author summaryAbundant evidence reveals that ncRNAs are important modulators of gene expression, and it is important for us to understand the regulation of ncRNAs in malignant tumors. In this work, we hypothesize that ncRNAs acting as ceRNAs can crosstalk with each other in the form of synergistic competition. We name the hypothesis as thencRNA synergistic competition hypothesis. To uncover potential carcinogenic biomarkers, we present a framework, SCOM, for identifying ncRNA synergistic competition in malignant tumors. From the perspective of synergistic competition, we have shown that the synergistic competition ncRNAs are likely to involve in drug resistance, contribute to distinguishing molecular subtypes of malignant tumors, and participate in immune regulation. In addition, the synergistic competition ncRNAs are potential diagnostic and prognostic biomarkers of malignant tumors. We believe that the proposed framework SCOM and the web-based database SCOMdb can contribute to the design of reliable diagnosis and treatment biomarkers for malignant tumors.
Your place or mine? The neural dynamics of personally familiar scene recognition suggests category independent familiarity encoding
Authors: Klink Hannah , Kaiser Daniel , Stecher Rico , Ambrus Géza Gergely , Kovács Gyula 
Published: July 2023

AbstractRecognizing a stimulus as familiar is an important capacity in our everyday life. Recent investigation of visual processes has led to important insights into the nature of the neural representations of familiarity for human faces. Still, little is known about how familiarity affects the neural dynamics of non-face stimulus processing. Here we report the results of an EEG study, examining the representational dynamics of personally familiar scenes. Participants viewed highly variable images of their own apartments and unfamiliar ones, as well as personally familiar and unfamiliar faces. Multivariate pattern analyses were used to examine the time course of differential processing of familiar and unfamiliar stimuli. Time-resolved classification revealed that familiarity is decodable from the EEG data similarly for scenes and faces. The temporal dynamics showed delayed onsets and peaks for scenes as compared to faces. Familiarity information, starting at 200 ms, generalized across stimulus categories and led to a robust familiarity effect. In addition, familiarity enhanced category representations in early (250 – 300 ms) and later (>400 ms) processing stages. Our results extend previous face familiarity results to another stimulus category and suggest that familiarity as a construct can be understood as a general, stimulus-independent processing step during recognition.HighlightsWhether a face or scene is familiar can be decoded from the EEG signal with very similar temporal dynamics, starting at 200 ms and peaking around 400 ms after stimulus onset.The neural dynamics of this familiarity information generalizes across stimulus categories.Familiarity modulates stimulus category representations from 200 ms after stimulus onset, indicating deeper processing of familiar as compared to unfamiliar stimuli already during early processing stages.
Karyopherin α2 is a maternal effect gene required for early embryonic development and female fertility in mice
Authors: Rother Franziska , Depping Reinhard , Popova Elena , Huegel Stefanie , Heiler Ariane , Hartmann Enno , Bader Michael 
Published: July 2023

ABSTRACTThe nuclear transport of proteins plays an important role in mediating the transition from egg to embryo and distinct karyopherins have been implicated in this process. Here, we studied the impact of KPNA2 deficiency on preimplantation embryo development in mice. Loss of KPNA2 results in complete arrest at the 2cell stage and embryos exhibit the inability to activate their embryonic genome as well as a severely disturbed nuclear translocation of Nucleoplasmin 2. Our findings define KPNA2 as a new maternal effect gene.
Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development
Authors: Paardekooper Laurent M. , Fillié-Grijpma Yvonne E. , van der Sluijs-Gelling Alita J. , Zlei Mihaela , van Doorn Remco , Vermeer Maarten H. , Paunovic Manuela , Titulaer Maarten J. , van der Maarel Silvère M. , van Dongen Jacques J.M. , Verschuuren Jan J. , Huijbers Maartje G. 
Published: July 2023

AbstractA subset of autoimmune diseases is characterized by predominant pathogenic IgG4 autoantibodies (IgG4-AIDs). Why IgG4 predominates in these disorders is unknown. We hypothesized that dysregulated B cell maturation or aberrant class switching causes overrepresentation of IgG4+B cells and plasma cells. Therefore, we compared the B cell compartment of patients with muscle-specific kinase (MuSK) myasthenia gravis (MG), pemphigus, leucine-rich glioma inactivated (LGI1) encephalitis and contactin-associated protein-like 2 (CASPR2) encephalitis (four IgG4-AIDs) to patients with acetylcholine receptor (AChR) MG, Lambert-Eaton myasthenic syndrome (LEMS) (two IgG1-3-AIDs) and age-matched healthy donors, using flow cytometry. B cell subset relative abundance at all maturation stages was normal, except for a, possibly treatment-related, reduction in immature and naïve CD5+cells in IgG4-AIDs. IgG4+B cell and plasma cell fractions were normal in IgG4-AID patients, however they had an (sub)class-independent 8-fold increase in circulating mature CD20-CD138+plasma cells. No autoreactivity was found in this subset after sorting. In conclusion, patients with IgG4-AID do not show increased numbers of IgG4-expressing cells. These results argue against aberrant B cell development in these patients and rather suggest the autoantibody subclass predominance to be antigen-driven. The similarities between B cell subset numbers among these patients suggest that these IgG4-AIDs, despite displaying variable clinical phenotypes, share a similar underlying immune profile.Graphical abstract
Amazing structural diversity of giant virus-like particles in forest soil
Authors: Fischer Matthias G. , Mersdorf Ulrike , Blanchard Jeffrey L. 
Published: July 2023

AbstractLarge DNA viruses of the phylumNucleocytoviricotainfect diverse eukaryotic hosts from protists to humans, with profound consequences for aquatic and terrestrial ecosystems. While nucleocytoviruses are known to be highly diverse in metagenomes, knowledge of their capsid structures is restricted to a few characterized representatives. Here, we visualize giant virus-like particles (VLPs, diameter >0.2 µm) directly from the environment using transmission electron microscopy. We found that Harvard Forest soils contain a higher diversity of giant VLP morphotypes than all hitherto isolated giant viruses combined. These included VLPs with icosahedral capsid symmetry, ovoid shapes similar to pandoraviruses, and bacilliform shapes that may represent novel viruses. We discovered giant icosahedral capsids with structural modifications that had not been described before including tubular appendages, modified vertices, tails, and capsids consisting of multiple layers or internal channels. Many giant VLPs were covered with fibers of varying lengths, thicknesses, densities, and terminal structures. These findings imply that giant viruses employ a much wider array of capsid structures and mechanisms to interact with their host cells than is currently known. We also found diverse tailed bacteriophages and filamentous VLPs, as well as ultra-small cells. Our study offers a first glimpse of the vast diversity of unexplored viral structures in soil and reinforces the potential of transmission electron microscopy for fundamental discoveries in environmental microbiology.
Non-covalent Linking Antibody to Yeast Using the Cell Surface Display of Staphylococcal Protein A
Authors: Shi Yi-Feng 
Published: July 2023

AbstractYeast surface display represents a commonly used platform suitable for the generation and screening of antibodies as well as the selection of high-producer clones. The methods of yeast display rely on the genetic fusion of recombinant antibodies to an abundant cell wall protein of yeast. Here, the study of proof of concept showed that the conventional strategy of expression of fusion antibodies was replaced by non-covalent binding to antibodies for yeast surface display. The use of cell surface display of an epitope tag will endow the cells with new arms for immobilizing, absorbing or targeting the proteins.Staphylococcalprotein A, which is characterized by its ability to bind selectively to the Fc region of IgG, was examined to be expressed on the surface ofSaccharomyces cerevisiaeusing a secretion signal ofRhizopus oryzaeglucoamylase and C-terminal half of α−agglutinin including glycosylphosphatidylinositol (GPI) anchor attachment signal under the control of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) promoter. On the other hand, an Fc-fused enzyme was created to construct a molecular fusion ofRhizopus oryzaeLipase with the spacer and the Fc region of IgG heavy chain. The secretion of fusion protein was carried out using pre-α-factor leader region as secretion signal under the control of the 5’-upstream region of theCandida tropicalisisocitrate lyase gene (UPR-ICL) inS. cerevisiae. The Fc-fused lipase was captured by Staphylococcal protein A as an adaptor protein displayed on the surface of yeast cells. The method of this switchable yeast display takes advantage of the “secretion-and-capture” strategy and can be applied to improve the efficiency of yeast display of full-length IgG.graphical abstractStaphylococcal protein A, which has the ability to binding to the Fc region of IgG and leaving the antigen combing site free, has been assembled on the surface of yeast cells to target antibodies or enzymes with Fc fusion.
Degradation of sulphonated mono and di-azo dye as the sole carbon source inSerratia marcescens: Insights from combined wet and dry lab analysis
Authors: Basharat Zarrin , Yasmin Azra 
Published: July 2023

AbstractThe high production volume of azo dyes for manufacturing and treating various consumer products leads to deleterious environmental consequences. Bacterial agents present in the environment can degrade these dyes. We, hereby, report the isolation, decolourization and degradation of a mono (Methyl orange) and di-azoic (Congo red) compound of this class of dyes by a versatile bacteriumSerratia marcescens. Our isolate showed the capability of sulphonated azo dye utilization/degradation i.e. Methyl orange and Congo red usage, with no inhibitory effects on its growth in minimal medium. The calorimetric analysis showed 80.83% decolourization of Methyl orange and 92.7% decolourization of Congo red after 7 days of incubation in a shaking incubator at pH: 7 and temperature: 37 °C. An azoreductase enzyme of ∼25 KDa was detected after SDS-PAGE analysis. Quantitative and qualitative testing of the degradation phenomenon was followed byin silicoanalysis. Structural modeling followed by molecular docking in Molecular Operating Environment revealed numerous residues involved in binding and assisting degradation. Changes in the apo, holo, and dye-bound enzyme energy profiles were also observed. This is the first study reporting the capability ofSerratia marcescensto use azo dyes/sulphonated azo dyes as the sole carbon source and the detailed computational analysis of the degradation phenomenon. We hope that these findings will be of use to environmental scientists, aid in better dye-degrading mutant creation to help craft future remediation strategies for sulphonated azo dyes.
Immunologically mediated trade-offs shaping transmission of sylvatic dengue and Zika viruses in native and novel non-human primate hosts
Authors: Hanley Kathryn A. , Cecilia Hélène , Azar Sasha R. , Moehn Brett , Yu Wanqin , Yun Ruimei , Althouse Benjamin M. , Vasilakis Nikos , Rossi Shannan L. 
Published: July 2023

AbstractMosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic cycles involving monkey hosts, spilled over into human transmission, and were translocated to the Americas, creating potential for spillback into neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We exposed native (cynomolgus macaque) or novel (squirrel monkey) hosts to mosquitoes infected with either sylvatic DENV or ZIKV and monitored viremia, natural killer cells, transmission to mosquitoes, cytokines, and neutralizing antibody titers. Unexpectedly, DENV transmission from both host species occurred only when serum viremia was undetectable or near the limit of detection. ZIKV replicated in squirrel monkeys to much higher titers than DENV and was transmitted more efficiently but stimulated lower neutralizing antibody titers. Increasing ZIKV viremia led to greater instantaneous transmission and shorter duration of infection, consistent with a replication-clearance trade-off.
Discovery of Eremiobacterota withnifHhomologs in tundra soil
Authors: Pessi Igor S. , Delmont Tom O. , Zehr Jonathan P. , Hultman Jenni 
Published: July 2023

AbstractWe describe the genome of an Eremiobacterota population from tundra soil that contains the minimal set ofnifgenes needed to fix atmospheric N2. This putative diazotroph population, which we nameCandidatusLamibacter sapmiensis, links for the first time Eremiobacterota and N2fixation. The integrity of the genome and itsnifgenes are well supported by both environmental and taxonomic signals.Ca. Lamibacter sapmiensis contains threenifHhomologs and the complementary set ofnifDKENBgenes that are needed to assemble a functional nitrogenase. The putative diazotrophic role ofCa. Lamibacter sapmiensis is supported by the presence of genes that regulate N2fixation and other genes involved in downstream processes such as ammonia assimilation. Similar to other Eremiobacterota,Ca. Lamibacter sapmiensis encodes the potential for atmospheric chemosynthesis via CO2fixation coupled with H2and CO oxidation. Interestingly, the presence of a N2O reductase indicates that this population could play a role as a N2O sink in tundra soils. Due to the lack of activity data, it remains uncertain ifCa. Lamibacter sapmiensis is able to assemble a functional nitrogenase and participate in N2fixation. Confirmation of this ability would be a testament to the great metabolic versatility of Eremiobacterota, which appears to underlie their ecological success in cold and oligotrophic environments.
Cross-species transmission and PB2 mammalian adaptations of highly pathogenic avian influenza A/H5N1 viruses in Chile
Authors: Pardo-Roa Catalina , Nelson Martha I. , Ariyama Naomi , Aguayo Carolina , Almonacid Leonardo I. , Munoz Gabriela , Navarro Carlos , Avila Claudia , Ulloa Mauricio , Reyes Rodolfo , Luppichini Eugenia Fuentes , Mathieu Christian , Vergara Ricardo , González Álvaro , González Carmen Gloria , Araya Hugo , Fernández Jorge , Fasce Rodrigo , Johow Magdalena , Medina Rafael A. , Neira Victor 
Published: July 2023

AbstractH5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human. Between December 9, 2022 – March 14, 2023, a coordinated government/academic response detected HPAIV by real-time RT-PCR in 8.5% (412/4735) of samples from 23 avian and 3 mammal orders. Whole-genome sequences obtained from 77 birds and 8 marine mammals revealed that all Chilean H5N1 viruses belong to lineage 2.3.4.4b and cluster monophyletically with viruses from Peru, indicating a single introduction from North America into Peru/Chile. Mammalian adaptations were identified in the PB2 segment: D701N in two sea lions, one human, and one shorebird, and Q591K in the human and one sea lion. Minor variant analysis revealed that D701N was present in 52.9 – 70.9% of sequence reads, indicating the presence of both genotypes within hosts. Further surveillance of spillover events is warranted to assess the emergence and potential onward transmission of mammalian adapted H5N1 HPAIV in South America.