bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Analysis of Global Hepatic Gene Expression in Adolescents and Adults with Non-alcoholic Fatty Liver Disease
Authors: Gawrieh Samer , Karns Rebekah , Kleiner David E. , Olivier Michael , Jenkins Todd , Inge Thomas H. , Chalasani Naga P. , Xanthakos Stavra 
Published: December 2022

AbstractIntroductionTo gain insights into the mechanisms underlying distinct nonalcoholic fatty liver disease (NAFLD) histological phenotypes between children and adults, we compared hepatic gene expression profiles associated with NAFLD phenotypes between the two age groups.MethodsHistological characteristics of intra-operative liver biopsies from adolescents and adults undergoing bariatric surgery were assessed by the same pathologist using the non-alcoholic steatohepatitis (NASH) Clinical Research Network scoring system. Hepatic gene expression was measured by microarray analysis. Transcriptomic signatures of histological phenotypes between the two groups were compared, with significance defined as p-value <0.05 and a fold change >1.5.ResultsIn 67 adolescents and 76 adults, distribution of histological phenotypes was: not-NAFLD (controls) 51% vs 39%, NAFL 39% vs 37%, and NASH 10% vs 24%, respectively. There were 279 differentially expressed genes in adolescents and 213 in adults with NAFLD vs controls. In adolescents, transcriptomes for NAFL vs controls, and borderline vs definite NASH were undifferentiable, whereas in adults, NAFL and borderline NASH demonstrated a transcriptomic gradient between controls and definite NASH. When applied to adolescents, significant adult genes discriminated borderline and definite NASH from control and NAFL, but the majority of significant pediatric genes were not portable to adults. Genes associated with NASH in adolescents and adults showed some ontological consistency but notable differences.ConclusionsThere is some similarity but major differences in the transcriptomic profiles associated with NAFLD between adolescents and adults with severe obesity. These data suggest different mechanisms contribute to the pathogenesis of NAFLD severity at different stages in life.Study HighlightsWHAT IS KNOWNNonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adultsNAFLD histological features and severity differ between children and adults but reasons for these differences are not clear.WHAT IS NEW HEREComparison of hepatic gene expression profiles between adolescents and adults with severe obesity and NAFLD showed some similarities but major differences in expressed genesThe findings suggest the mechanisms driving different NAFLD severity and phenotypes are different at different stages in life.
Effect of Zn fertilization on yield, protein content, protein yield and zinc use efficiency in pearl millet
Authors: Yadav Ganesh Narayan , Summaria Rakesh , Yadav Shankar Lal , Sharma Seema , Yadav L. R. 
Published: December 2022

AbstractTwo year field experiment was conducted at Rajasthan Agriculture Research Institute, Durgapura, during rainy seasons of 2019 and 2020 in factorial block design with three replications to study the growth, productivity and economics of pearl millet – chickpea cropping system by using three genotypes (RHB-173, MPMH-17 and RHB-177) and five treatments of zinc [0, 5, 7.5 kg Zn/ha through ZnSO4.7H2O and 5, 7.5 kg Zn/ha through Zn-EDTA) applied to pearl millet and two foliar spray treatments applied in both of crop at booting stage in pearl millet and pre-flowering stage in chickpea. Results revealed that total nitrogen and zinc contents of chickpea were increased significantly and highest with the residual effect of 7.5 kg Zn/ha through Zn-EDTA and 7.5 kg Zn/ha through ZnSO4.7H2O and phosphorus contents of chickpea was recorded depressive effect on residual zinc fertilization, while, potassium contents was not influenced significantly. However, the significant increase in uptake of nutrients nitrogen, phosphorous, potassium and zinc were obtained with 7.5 kg Zn/ha through Zn-EDTA higher per cent over control, during the years 2019-20 and 2020-21. The highest nitrogen, protein content and zinc contents and uptake values were obtained with 5, 7.5 kg Zn/ha through Zn-EDTA. The residual effect of 7.5 kg Zn/ha through Zn-EDTA was at par with 7.5 kg Zn/ha through ZnSO4.7H2O. The increased in total uptake of nitrogen, it could be ultimately increased protein yield were 16.54 and 27.48 per cent, during respective years over control. The highest nutrient use efficiency was obtain with lowest of fertilizer dose of Zn-EDTA as compare to zinc sulphate.
Identification of the riceRcgene as a main regulator of seed survival under dry storage conditions
Authors: Manjunath Prasad C.T. , Kodde Jan , Angenent Gerco C. , Hay Fiona R. , McNally Kenneth L. , Groot Steven P.C. 
Published: December 2022

SummarySeed deterioration during storage results in poor germination, reduced seed vigor, and non-uniform seedling emergence. The rate of aging depends on storage conditions (RH, temperature, and oxygen) and genetic factors. This study aims to identify these genetic factors determining the longevity of rice seeds stored under experimental aging conditions mimicking long-term dry storage. Genetic variation for tolerance to aging was studied in 300Indicarice accessions and storing dry seeds under elevated partial pressure of oxygen (EPPO) condition, using a genome-wide association study. The association analysis yielded eleven unique regions across the genome for all measured germination parameters after aging. These genomic regions differed from regions previously identified in rice under humid experimental aging conditions. The significant single nucleotide polymorphism in the most prominent region was located within theRcgene, encoding a bHLH transcription factor. Storage experiments using isogenic rice lines (SD7-1D(Rc) andSD7-1d(rc)) with the same allelic variation confirmed the functional role of theRcgene, conferring a stronger tolerance to dry EPPO aging. A functionalRcgene results in the accumulation of pro-anthocyanidins in the pericarp of rice seeds, an important sub-class of flavonoids having strong antioxidant activity, which may explain why genotypes with an allelic variation for this gene show variation in seed tolerance to dry EPPO aging.
The phase separated CO2-fixing pyrenoid proteome determined by TurboID
Authors: Lau Chun Sing , Dowle Adam , Thomas Gavin H. , Girr Philipp , Mackinder Luke CM 
Published: December 2022

AbstractPhase separation underpins many biologically important processes such as RNA metabolism, signaling and CO2fixation. However, determining the composition of a phase separated organelle is often challenging due to their sensitivity to environmental conditions which limits the application of traditional proteomics techniques like organellar purification or affinity purification mass spectrometry to understand their composition. InChlamydomonas reinhardtii, Rubisco is condensed into a crucial phase separated organelle called the pyrenoid that improves photosynthetic performance by supplying Rubisco with elevated concentrations of CO2. Here, we developed a TurboID based proximity labeling technique inChlamydomonaschloroplasts, where proximal proteins are labeled by biotin radicals generated from the TurboID-tagged protein. Through the expression of two core pyrenoid components fused with the TurboID tag, we have generated a high confidence pyrenoid proxiome that contains the majority of known pyrenoid proteins plus a number of novel pyrenoid candidates. Fluorescence protein tagging of 8 previously uncharacterized TurboID-identified proteins showed 7 were localized to a range of sub-pyrenoid regions. The resulting proxiome also suggests new secondary functions for the pyrenoid in RNA-associated processes and redox sensitive iron-sulfur cluster metabolism. This developed pipeline opens the possibility of investigating a broad range of biological processes inChlamydomonasespecially at a temporally resolved sub-organellar resolution.
Ruling the unruly: Innovation in ant larval feeding led to increased caste dimorphism and social complexity
Authors: Matte Arthur , LeBoeuf Adria C. 
Published: December 2022

AbstractBuilding differences between genetically equivalent units is a fundamental challenge for every (super)organism with reproductive division of labor. In ants, reproductive or worker fate is typically determined during the larval stage. However, the methods by which adults feed their larvae, thus controlling their development, vary widely across ant species. Similarly, the body size gap between queen and worker is highly heterogeneous, ranging from species with similar-sized individuals to species with queens over 300 times larger than their smallest workers. To investigate the role of alloparental feeding control in caste dimorphism and the evolution of social complexity, we assembled data for queen:worker dimorphism, alloparental care, and larval morphology for a phylogenetically comprehensive sample of several hundred species, along with ecological and life-history traits. Using comparative phylogenetic methods, we analyzed the macroevolution of ant larvae and queen:worker dimorphism on a large scale. Our findings indicate that both extended alloparental feeding care and dimorphism are associated with the evolution of passive larval morphologies. Furthermore, greater queen:worker dimorphism co-evolved with several traits indicative of social complexity, including larger colony sizes, distinct worker subcastes, and the loss of full reproductive potential in workers. In sum, change in larval feeding habits were promoted by dietary shifts from prey to foods necessitating individualized distribution. These innovations granted adults greater capacity to manipulate larval nutrition, and consequently, caste size inequality, with significant implications for social complexity.Significance statementAnts are among the rare organisms to have extended reproductive division labor beyond the cells of a multicellular organism. However, the degree of specialization between reproductive and worker castes varies considerably between ant lineages. In this study, we demonstrate that strong caste dimorphism in ants co-evolved with complex eusociality traits, and this strong caste dimorphism was achieved by asserting adult control over larvae’ development. We conclude that this enhanced control over larval caste fate was a critical junction in the major evolutionary transition of ants toward caste specialization.Graphical abstract
Emergence and Spread of SARS-CoV-2 Variants of Concern in Canada: a Retrospective Analysis from Clinical and Wastewater Data
Authors: Champredon David , Becker Devan , Peterson Shelley W. , Mejia Edgard , Hizon Nikho , Schertzer Andrea , Djebli Mohamed , Xie Yuwei , Oloye Femi F. , Asadi Mohsen , Cantin Jenna , Brinkmann Markus , McPhedran Kerry N. , Giesy John P. , Mangat Chand 
Published: December 2022

AbstractThe spread of SARS-CoV-2 has been studied at unprecedented levels worldwide. In jurisdictions where molecular analysis was performed on large scales, the emergence and competition of numerous SARS-CoV-2 lineages has been observed in near real-time. Lineage identification, traditionally performed from clinical samples, can also be determined by sampling wastewater from sewersheds serving populations of interest. Of particular interest are variants of concern (VOCs), SARS-CoV-2 lineages that are associated with increased transmissibility and/or severity. Here, we consider clinical and wastewater data sources to retrospectively assess the emergence and spread of different VOCs in Canada. We show that, overall, wastewater-based VOC identification provides similar in-sights to the surveillance based on clinical samples. Based on clinical data, we observed a synchrony in VOC introduction as well as similar emergence speeds across most Canadian provinces despite the large geographical size of the country and differences in provincial public health measures. In particular, it took approximately four months for VOC Alpha and Delta to contribute to half of the incidence, whereas VOC Omicron achieved the same contribution in less than one month. By quantifying the timing and rapidity of SARS-CoV-2 VOCs invasion in Canada, this study provides important benchmarks to support preparedness for future VOCs, and to some extent, for future pandemics caused by other pathogens.
Identifying key residues in intrinsically disordered regions of proteins using machine learning
Authors: Ho Wen-Lin , Huang Hsuan-Cheng , Huang Jie-rong 
Published: December 2022

AbstractConserved residues in protein homolog sequence alignments are structurally or functionally important. For intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs), however, alignment often fails because they lack a steric structure to constrain evolution. Although sequences vary, the physicochemical features of IDRs may be preserved in maintaining function. Therefore, a method to retrieve common IDR features may help identify functionally important residues. We applied un-supervised contrastive learning to train a model with self-attention neuronal networks on human IDR orthologs. During training, parameters were optimized to match sequences in ortholog pairs but not in other IDRs. The trained model successfully identifies previously reported critical residues from experimental studies, especially those with an overall pattern (e.g. multiple aromatic residues or charged blocks) rather than short motifs. This predictive model can therefore be used to identify potentially important residues in other proteins.Availability and implementationThe training scripts are available on GitHub (https://github.com/allmwh/IFF). The training datasets have been deposited in an Open Science Framework repository (https://osf.io/jk29b). The trained model can be run from the Jupyter Notebook in the GitHub repository using Binder (mybinder.org). The only required input is the primary sequence.
Foldcomp: a library and format for compressing and indexing large protein structure sets
Authors: Kim Hyunbin , Mirdita Milot , Steinegger Martin 
Published: December 2022

SummaryHighly accurate protein structure predictors have generated hundreds of millions of protein structures; these pose a challenge in terms of storage and processing. Here we present Foldcomp, a novel lossy structure compression algorithm and indexing system to address this challenge. By using a combination of internal and cartesian coordinates and a bi-directional NeRF-based strategy, Foldcomp improves the compression ratio by a factor of 3 compared to the next best method. Its reconstruction error of 0.08Å is comparable to the best lossy compressor. It is 5 times faster than the next fastest compressor and competes with the fastest decompressors. With its multi-threading implementation and a Python interface that allows for easy database downloads and efficient querying of protein structures by accession, Foldcomp is a powerful tool for managing and analyzing large collections of protein structures.AvailabilityFoldcomp is a free open-source library and command-line software available for Linux, macOS and Windows athttps://foldcomp.foldseek.com. Foldcomp provides the AlphaFold Swiss-Prot (2.9GB), TrEMBL (1.1TB) and ESMatlas HQ (114GB) database ready-for-download.
Oncolytic adenovirus serotype 35 mediated tumor growth suppressionviaefficient activation and tumor infiltration of natural killer cells
Authors: Ono Ryosuke , Sakurai Fuminori , Ishii Ken J. , Mizuguchi Hiroyuki 
Published: December 2022

ABSTRACTBackgroundOncolytic adenoviruses (OAds) mediate superior antitumor effects both by inducing direct oncolysis and activating antitumor immunity. Previously, we developed a novel OAd fully composed of human adenovirus serotype 35 (OAd35). OAd35 efficiently killed a variety of human tumor cells; however, OAd35-mediated activation of antitumor immunity remains to be evaluated. In this study, we examined whether OAd35-induced activation of immune cells contributes to the antitumor effects of OAd35.MethodsTumor infiltration and activation of immune cells following intratumoral administration of OAd35 in tumor-bearing immune-competent and nude mice were analyzed. The involvement of natural killer (NK) cells in the tumor growth-suppression effects of OAd35 was evaluated in NK cell-depleted mice. The key signals for the OAd35-mediated tumor infiltration of NK cells were examined in interferon (IFN) alpha and beta receptor subunit 1 (IFNAR1) knockout and toll-like receptor 9 (TLR9) knockout mice.ResultsOAd35 efficiently induced tumor infiltration of activated NK cells. NK cell depletion apparently hindered the OAd35-mediated tumor growth suppression. In IFNAR1 knockout mice, OAd35-induced tumor infiltration of activated NK cells was significantly attenuated. OAd35 did not induce tumor infiltration of NK cells in TLR9 knockout mice, although OAd35 significantly activated NK cells and showed tumor growth suppression in TLR9 knockout mice.ConclusionsOAd35 significantly promoted activation and tumor infiltration of NK cells, leading to OAd35-mediated efficient tumor growth suppression. The type-I IFN signal was crucial for the OAd35-mediated tumor infiltration and activation of NK cells. The TLR9 signal was highly related to tumor infiltration of NK cells, but not NK cell activation and antitumor effects of OAd35. These findings suggest that OAd35 becomes a promising cancer immunotherapy agentviaits enhancement of the antitumor activities of NK cells.
Ecological and evolutionary patterns of virus-host interactions throughout a grassland soil depth profile
Authors: Muscatt George , Cook Ryan , Millard Andrew , Bending Gary D. , Jameson Eleanor 
Published: December 2022

AbstractBackgroundSoil microbes play pivotal roles in global carbon cycling, however the fundamental interactions between microbes and their infecting viruses remain unclear. This is exacerbated with soil depth, where the patterns of viral dispersal, ecology, and evolution are markedly underexplored. To investigate viral communities across soil depth, we leveraged a publicly available metagenomic data set sampled from grassland soil in northern California.Results10,196 non-redundant vOTUs were recovered from soil sampled from 20 cm to 120 cm below the surface. Viral prevalence was high throughout the soil depth profile, with viruses infecting dominant soil phyla, includingActinomycetota. Contrary to leading hypotheses, lysogeny did not dominate in the soil viral communities. Viral diversity was investigated at both the population-level (i.e., macro diversity) and strain-level (i.e., micro diversity) to reveal diverse ecological and evolutionary patterns of virus-host interactions in surface and subsurface soil.ConclusionsBy investigating viral micro diversity in soil for the first time, we have uncovered patterns of antagonistic co-evolution across both surface and subsurface soils. Furthermore, we have provided evidence of soil viruses augmenting the remineralisation of soil carbon. While we continue to yield a more comprehensive understanding of soil viral ecology, our work appeals to future researchers to continue to investigate subsurface viral communities.
Nanobody CDR3 mimetics enhance SOS1-catalyzed nucleotide exchange on RAS
Authors: Van holsbeeck Kevin , Fischer Baptiste , Gonzalez Simon , Gadais Charlène , Versées Wim , Martins José C. , Martin Charlotte , Wohlkönig Alexandre , Steyaert Jan , Ballet Steven 
Published: December 2022

ABSTRACTRAS proteins control various intracellular signaling networks. Mutations at specific locations were shown to stabilize their active GTP-bound state, which is associated with the development of multiple cancers. An attractive approach to modulate RAS signaling is through its regulatory guanine nucleotide exchange factor (GEF) son of sevenless 1 (SOS1). With the recent discovery of Nanobody14, which potently enhances SOS1-catalyzed nucleotide exchange on RAS, we explored the feasibility of developing peptide mimetics by structurally mimicking the complementarity-determining region 3 (CDR3). Guided by a biochemical GEF assay and X-ray co-crystal structures, successive rounds of optimization and gradual conformational rigidification led to CDR3 mimetics showing half of the maximal activation potential of the native nanobody. Altogether, this study provides the first proof-of-concept that peptides able to functionally modulate a protein-protein interaction can be obtained by structural mimicry of a nanobody paratope.
The discrete update epidemics: demography, vaccination and transmission with a tensorized update approach
Authors: Guo Xiaohao , Zhao Zeyu , Yang Shiting , Guo Yichao , Chen Tianmu 
Published: December 2022

AbstractAn ordinary differential dynamical model is developed to describe the transmission of infectious diseases, considering heterogeneities of region, age, vaccination, and immigration and real-time vaccination simultaneously using a tenderized formulation. Numerical experiments are performed in Xiamen city, China, with the whole population partitioned into 6 regions × 4 age groups × 4 vaccination status groups, showing the numerical stability of the developed model. The heterogeneity consideration makes our model adequate to evaluate specific interventions accurately within specific sub-populations and carry them out.Author summaryNot applicable.
A compartmental model forXylella fastidiosadiseases with explicit vector seasonal dynamics
Authors: Giménez-Romero Àlex , Moralejo Eduardo , Matías Manuel A. 
Published: December 2022

AbstractThe bacteriumXylella fastidiosa(Xf) is mainly transmitted by the spittlebug,Philaenus spumarius, in Europe, where it has caused significant economic damage to olive and almond trees. Understanding the factors that determine disease dynamics in pathosystems that share similarities can help design control strategies focused on minimizing transmission chains. Here we introduce a compartmental model for Xf-caused diseases in Europe that accounts for the main relevant epidemiological processes, including the seasonal dynamics ofP. spumarius. The model was confronted with epidemiological data from the two major outbreaks of Xf in Europe, the olive quick disease syndrome (OQDS) in Apulia, Italy, caused by the subspeciespauca, and the almond leaf scorch disease (ALSD) in Majorca, Spain, caused by subspeciesmultiplexandfastidiosa. Using a Bayesian inference framework, we show how the model successfully reproduces the general field data in both diseases. In a global sensitivity analysis, the vector-plant and plant-vector transmission rates, together with the vector removal rate, were the most influential parameters in determining the time of the infected host population peak, the incidence peak and the final number of dead hosts. We also used our model to check different vector-based control strategies, showing that a joint strategy focused on increasing the rate of vector removal while lowering the number of annual newborn vectors is optimal for disease control.