Front Plant Sci. 2023 Mar 8;14:1170103. doi: 10.3389/fpls.2023.1170103. eCollection 2023.

NO ABSTRACT

PMID:36968384 | PMC:PMC10031092 | DOI:10.3389/fpls.2023.1170103

Front Plant Sci. 2023 Mar 8;14:1145510. doi: 10.3389/fpls.2023.1145510. eCollection 2023.

ABSTRACT

The ease of accepting or donating electrons is the raison d'être for the pivotal role iron (Fe) plays in a multitude of vital processes. In the presence of oxygen, however, this very property promotes the formation of immobile Fe(III) oxyhydroxides in the soil, which limits the concentration of Fe that is available for uptake by plant roots to levels well below the plant's demand. To adequately respond to a shortage (or, in the absence of oxygen, a possible surplus) in Fe supply, plants have to perceive and decode information on both external Fe levels and the internal Fe status. As a further challenge, such cues have to be translated into appropriate responses to satisfy (but not overload) the demand of sink (i.e., non-root) tissues. While this seems to be a straightforward task for evolution, the multitude of possible inputs into the Fe signaling circuitry suggests diversified sensing mechanisms that concertedly contribute to govern whole plant and cellular Fe homeostasis. Here, we review recent progress in elucidating early events in Fe sensing and signaling that steer downstream adaptive responses. The emerging picture suggests that Fe sensing is not a central event but occurs in distinct locations linked to distinct biotic and abiotic signaling networks that together tune Fe levels, Fe uptake, root growth, and immunity in an interwoven manner to orchestrate and prioritize multiple physiological readouts.

PMID:36968364 | PMC:PMC10032465 | DOI:10.3389/fpls.2023.1145510

Eng Biol. 2022 Nov 30;6(4):71-81. doi: 10.1049/enb2.12026. eCollection 2022 Dec.

ABSTRACT

The bioeconomy drives the development of life science and biotechnology as a blueprint for the future development of human society, and offers a cross-cutting perspective on the societal transformation towards long-term sustainability and the transition away from the non-renewable economy. Moreover, the sustainable bioeconomy strategies are consistent with the United Nation's (UN) Sustainable Development Goals (SDG) and are becoming the centre of the achievement for SDG. The Chinese '14th Five-Year Plan for Bioeconomy Development' (2021-2025), including the development goals of China's bioeconomy containing biomedicine, agriculture, bio-manufacturing and bio-security as a strategic priority, is discussed. The plan offers three pathways to improve bioeconomy, including technological innovation, industrialisation and policy supports. Finally, it concludes China's first bioeconomy development plan as a success, suggesting the key role of industrial biotechnology in bioeconomy.

PMID:36968339 | PMC:PMC9995158 | DOI:10.1049/enb2.12026

Front Mol Biosci. 2023 Mar 10;10:1129602. doi: 10.3389/fmolb.2023.1129602. eCollection 2023.

ABSTRACT

[This corrects the article DOI: 10.3389/fmolb.2022.1042231.].

PMID:36968282 | PMC:PMC10038211 | DOI:10.3389/fmolb.2023.1129602

Front Cell Infect Microbiol. 2023 Mar 10;12:962945. doi: 10.3389/fcimb.2022.962945. eCollection 2022.

ABSTRACT

The ability to efficiently isolate antigen-specific B cells in high throughput will greatly accelerate the discovery of therapeutic monoclonal antibodies (mAbs) and catalyze rational vaccine development. Traditional mAb discovery is a costly and labor-intensive process, although recent advances in single-cell genomics using emulsion microfluidics allow simultaneous processing of thousands of individual cells. Here we present a streamlined method for isolation and analysis of large numbers of antigen-specific B cells, including next generation antigen barcoding and an integrated computational framework for B cell multi-omics. We demonstrate the power of this approach by recovering thousands of antigen-specific mAbs, including the efficient isolation of extremely rare precursors of VRC01-class and IOMA-class broadly neutralizing HIV mAbs.

PMID:36968243 | PMC:PMC10036767 | DOI:10.3389/fcimb.2022.962945

iScience. 2023 Mar 7;26(4):106324. doi: 10.1016/j.isci.2023.106324. eCollection 2023 Apr 21.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T cells in the PDAC microenvironment to develop alternative therapeutic strategies. In this study, we performed RNA velocity-based pseudotime analysis on a scRNA-seq dataset from surgically resected human PDAC specimens to gain insight into temporal gene expression patterns that best characterize the cell fates. The tumor microenvironment was seen to encompass a range of terminal states for the T cell trajectories with suppressive and non-tumor-responsive T cells dominating them. However, the results also reveal the existence of a functional branch of the T cell population that was not transitioning to exhausted and senescent states. These findings reveal various microenvironmental signals driving T cell patterns which can be useful in identifying new therapeutic avenues.

PMID:36968070 | PMC:PMC10034436 | DOI:10.1016/j.isci.2023.106324

Comput Struct Biotechnol J. 2023 Mar 11;21:2036-2047. doi: 10.1016/j.csbj.2023.03.007. eCollection 2023.

ABSTRACT

Across biological systems, a number of genomic processes, including transcription, replication, DNA repair, and transcription factor binding, display intrinsic directionalities. These directionalities are reflected in the asymmetric distribution of nucleotides, motifs, genes, transposon integration sites, and other functional elements across the two complementary strands. Strand asymmetries, including GC skews and mutational biases, have shaped the nucleotide composition of diverse organisms. The investigation of strand asymmetries often serves as a method to understand underlying biological mechanisms, including protein binding preferences, transcription factor interactions, retrotransposition, DNA damage and repair preferences, transcription-replication collisions, and mutagenesis mechanisms. Research into this subject also enables the identification of functional genomic sites, such as replication origins and transcription start sites. Improvements in our ability to detect and quantify DNA strand asymmetries will provide insights into diverse functionalities of the genome, the contribution of different mutational mechanisms in germline and somatic mutagenesis, and our knowledge of genome instability and evolution, which all have significant clinical implications in human disease, including cancer. In this review, we describe key developments that have been made across the field of genomic strand asymmetries, as well as the discovery of associated mechanisms.

PMID:36968020 | PMC:PMC10030826 | DOI:10.1016/j.csbj.2023.03.007

Heliyon. 2023 Mar 11;9(3):e14422. doi: 10.1016/j.heliyon.2023.e14422. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Acute otitis media (AOM) may occur as a complication of viral upper respiratory infection (URI) in children. Our objective was to examine children with URI + AOM or URI alone to determine the association of infection by different common respiratory viruses with AOM.

METHODS: Nasopharyngeal swabs were collected from March 2014 to February 2015. Quantitative PCR was then used to identify the following 10 common respiratory viruses: respiratory syncytial virus (RSV); parainfluenza viruses 1-4 (PIVs); influenza virus type A (IFVA); influenza virus type B; human rhinovirus (HRV); enterovirus; human metapneumovirus; human coronavirus OC43, 229E, NL63, and HKU1; adenovirus; and human bocavirus.

RESULTS: We examined 255 children with URIs (mean age: 32.9 ± 18.7 months), and 164 (64.1%) of them tested positive for at least one respiratory virus. The most common viruses were RSV (44, 24.3%), PIVs (28, 15.5%), and IFVA (25, 13.8%). Positivity for RSV was significantly greater in the URI + AOM group than in the URI group, but these groups did not differ in infection rates for the other 9 viruses. There were also significant seasonal differences in positivity for RSV, IFVA, HRV,HBoV, PIVs and EV.

CONCLUSION: Our results indicated a relationship between infection by common respiratory viruses and AOM in children from Beijing. A URI with RSV significantly increased the risk of AOM in these children.

PMID:36967868 | PMC:PMC10036650 | DOI:10.1016/j.heliyon.2023.e14422

J Mol Biol. 2023 Mar 24:168059. doi: 10.1016/j.jmb.2023.168059. Online ahead of print.

ABSTRACT

Recent progress in cryo-EM research has ignited a revolution in biological macromolecule structure determination. Resolution is an essential parameter for quality assessment of a cryo-EM density map, and it is known that resolution varies in different regions of a map. Currently available methods for local resolution estimation require manual adjustment of parameters and in some cases necessitate acquisition or de novo generation of so-called "half maps". Here, we developed CryoRes, a deep-learning algorithm to estimate local resolution directly from a single final cryo-EM density map, specifically by learning resolution-aware patterns of density map voxels through supervised training on a large dataset comprising 1,174 experimental cryo-EM density maps. CryoRes significantly outperforms all of the state-of-the-art competing resolution estimation methods, achieving an average RMSE of 2.26Å for local resolution estimation relative to the currently most reliable FSC-based method blocres, yet requiring only the single final map as input. Further, CryoRes is able to generate a molecular mask for each map, with accuracy 12.12% higher than the masks generated by ResMap. CryoRes is ultra-fast, fully automatic, parameter-free, applicable to cryo-EM subtomogram data, and freely available at https://cryores.zhanglab.net.

PMID:36967040 | DOI:10.1016/j.jmb.2023.168059

Environ Res. 2023 Mar 24:115773. doi: 10.1016/j.envres.2023.115773. Online ahead of print.

ABSTRACT

Coal mining activities are considered harmful to living organisms. These activities release compounds to the environment, such as polycyclic aromatic hydrocarbons (PAHs), metals, and oxides, which can cause oxidative damage to DNA. In this study, we compared the DNA damage and the chemical composition of peripherical blood of 150 individuals exposed to coal mining residues and 120 non-exposed individuals. Analysis of coal particles revealed the presence of elements such as copper (Cu), aluminum (Al), chrome (Cr), silicon (Si) and iron (Fe). The exposed individuals in our study had significant concentrations of Al, sulfur (S), Cr, Fe, and Cu in their blood, as well as hypokalemia. Results from the enzyme-modified comet assay (FPG enzyme) suggest that exposure to coal mining residues caused oxidative DNA damage, particularly purine damage. Furthermore, particles with a diameter of <2.5 μm indicate that direct inhalation could promote these physiological alterations. Finally, a systems biology analysis was performed to investigate the effects of these elements on DNA damage and oxidative stress pathways. Interestingly, Cu, Cr, Fe, and K are key nodes that intensely modulate these pathways. Our results suggest that understanding the imbalance of inorganic elements caused by exposure to coal mining residues is crucial to understanding their effect on human health.

PMID:36966995 | DOI:10.1016/j.envres.2023.115773

Gene. 2023 Mar 24:147393. doi: 10.1016/j.gene.2023.147393. Online ahead of print.

ABSTRACT

In angiosperms, the mitochondrial cox2 gene harbors up to two introns, commonly referred to as cox2i373 and cox2i691. We studied the cox2 from 222 fully-sequenced mitogenomes from 30 angiosperm orders and analyzed the evolution of its introns. Unlike cox2i373, cox2i691 shows a distribution among plants that is shaped by frequent intron loss events driven by localized retroprocessing. In addition, cox2i691 exhibits sporadic elongations, presumably in domain IV of the intron. Such elongations are poorly related to repeat content and two of them showed the presence of LINE transposons, suggesting that increasing intron size is very likely due to nuclear intracelular DNA transfer followed by incorporation into the mitochondrial DNA. Surprisingly, we found that cox2i691 is erroneously annotated as absent in 30 mitogenomes deposited in public databases. Although each of the cox2 introns is ∼1.5 kb in length, a cox2i691 of 4.2 kb has been reported in Acacia ligulata (Fabaceae). It is still unclear whether its unusual length is due to a trans-splicing arrangement or the loss of functionality of the interrupted cox2. Through analyzing short-read RNA sequencing of Acacia with a multi-step computational strategy, we found that the Acacia cox2 is functional and its long intron is spliced in cis in a very efficient manner despite its length.

PMID:36966978 | DOI:10.1016/j.gene.2023.147393

J Proteomics. 2023 Mar 24:104890. doi: 10.1016/j.jprot.2023.104890. Online ahead of print.

ABSTRACT

This study employed systems biology and high-throughput technologies to analyze complex molecular components of MS pathophysiology, combining data from multiple omics sources to identify potential biomarkers and propose therapeutic targets and repurposed drugs for MS treatment. This study analyzed GEO microarray datasets and MS proteomics data using geWorkbench, CTD, and CORMINE to identify differentially expressed genes associated with MS disease. Protein-protein interaction networks were constructed using Cytoscape and its plugins, and functional enrichment analysis was performed to identify crucial molecules. A drug-gene interaction network was also created using DGIdb to propose medications. This study identified 592 differentially expressed genes (DEGs) associated with MS disease using GEO, proteomics, and text-mining datasets. 37 DEGs were found to be important by topographical network studies, and 6 were identified as the most significant for MS pathophysiology. Additionally, we proposed six drugs that target these key genes. Crucial molecules identified in this study were dysregulated in MS and likely play a key role in the disease mechanism, warranting further research. Additionally, we proposed repurposing certain FDA-approved drugs for MS treatment. Our in silico results were supported by previous experimental research on some of the target genes and drugs. SIGNIFICANCE: As the long-lasting investigations continue to discover new pathological territories in neurodegeneration, here we apply a systems biology approach to determine multiple sclerosis's molecular and pathophysiological origin and identify multiple sclerosis crucial genes that contribute to candidating new biomarkers and proposing new medications.

PMID:36966969 | DOI:10.1016/j.jprot.2023.104890

Curr Opin Chem Biol. 2023 Mar 24;74:102288. doi: 10.1016/j.cbpa.2023.102288. Online ahead of print.

ABSTRACT

The computational metabolomics field brings together computer scientists, bioinformaticians, chemists, clinicians, and biologists to maximize the impact of metabolomics across a wide array of scientific and medical disciplines. The field continues to expand as modern instrumentation produces datasets with increasing complexity, resolution, and sensitivity. These datasets must be processed, annotated, modeled, and interpreted to enable biological insight. Techniques for visualization, integration (within or between omics), and interpretation of metabolomics data have evolved along with innovation in the databases and knowledge resources required to aid understanding. In this review, we highlight recent advances in the field and reflect on opportunities and innovations in response to the most pressing challenges. This review was compiled from discussions from the 2022 Dagstuhl seminar entitled "Computational Metabolomics: From Spectra to Knowledge".

PMID:36966702 | DOI:10.1016/j.cbpa.2023.102288

G3 (Bethesda). 2023 Mar 26:jkad067. doi: 10.1093/g3journal/jkad067. Online ahead of print.

ABSTRACT

The genome sequence of the diploid and highly homozygous V. vinifera genotype PN40024 serves as the reference for many grapevine studies. Despite several improvements to the PN40024 genome assembly, its current version PN12X.v2 is quite fragmented and only represents the haploid state of the genome with mixed haplotypes. In fact, being nearly homozygous, this genome contains several heterozygous regions that are yet to be resolved. Taking the opportunity of improvements that long-read sequencing technologies offer to fully discriminate haplotype sequences, an improved version of the reference, called PN40024.v4, was generated. Through incorporating long genomic sequencing reads to the assembly, the continuity of the 12X.v2 scaffolds was highly increased with a total number decreasing from 2,059 to 640 and a reduction in N bases of 88%. Additionally, the full alternative haplotype sequence was built for the first time, the chromosome anchoring was improved and the number of unplaced scaffolds was reduced by half. To obtain a high-quality gene annotation that outperforms previous versions, a liftover approach was complemented with an optimized annotation workflow for Vitis. Integration of the gene reference catalogue and its manual curation have also assisted in improving the annotation, while defining the most reliable estimation of 35,230 genes to date. Finally, we demonstrated that PN40024 resulted from nine selfings of cv. 'Helfensteiner' (cross of cv. 'Pinot noir' and 'Schiava grossa') instead of a single 'Pinot noir'. These advances will help maintain the PN40024 genome as a gold-standard reference, also contributing towards the eventual elaboration of the grapevine pangenome.

PMID:36966465 | DOI:10.1093/g3journal/jkad067

Nat Commun. 2023 Mar 25;14(1):1662. doi: 10.1038/s41467-023-37349-4.

ABSTRACT

A long-term objective of network medicine is to replace our current, mainly phenotype-based disease definitions by subtypes of health conditions corresponding to distinct pathomechanisms. For this, molecular and health data are modeled as networks and are mined for pathomechanisms. However, many such studies rely on large-scale disease association data where diseases are annotated using the very phenotype-based disease definitions the network medicine field aims to overcome. This raises the question to which extent the biases mechanistically inadequate disease annotations introduce in disease association data distort the results of studies which use such data for pathomechanism mining. We address this question using global- and local-scale analyses of networks constructed from disease association data of various types. Our results indicate that large-scale disease association data should be used with care for pathomechanism mining and that analyses of such data should be accompanied by close-up analyses of molecular data for well-characterized patient cohorts.

PMID:36966134 | DOI:10.1038/s41467-023-37349-4

Plant Sci. 2023 Mar 23:111689. doi: 10.1016/j.plantsci.2023.111689. Online ahead of print.

ABSTRACT

Saussurea lappa (S. lappa) has been known to synthesize medicinally important, costunolide. Due to its immense therapeutic importance, understanding of regulatory mechanism associated with its biosynthesis is crucial. MicroRNAs (miRNAs) have been well established in the regulation of secondary metabolites synthesis. The identification of genes and transcription factors (TFs) in S. lappa, created a clear picture of costunolide biosynthesis pathways. Further to understand the regulation of costunolide biosynthesis, an integrated study of transcriptome, miRNAs, and degradome was performed. Identified candidate miRNAs and associated feed-forward loops (FFLs) illustrates their regulatory role in secondary metabolite biosynthesis. Small RNA and degradome sequencing were performed for leaf and root tissues to determine miRNAs-targets pairs. A total of 711 and 525 such targets were obtained for novel and known miRNAs. This data was used to generate costunolide-specific miRNA-TF-gene interactome to perform systematic analyses through graph theoretical approach. Interestingly, miR171c.1 and sla-miR121 were identified as key regulators to connect and co-regulate both mevalonate and sesquiterpenoid pathways to bio-synthesize costunolide. Tissue-specific FFLs were identified to be involved in costunolide biosynthesis which further suggests the evolutionary co-relation of root-specific networks in synthesis of secondary metabolites in addition to leaf-specific networks. This integrative approach allowed us to determine candidate miRNAs and associated tissue-specific motifs involved in the diversification of secondary metabolites. MiRNAs identified in present study can provide alternatives for bioengineering tool to enhance the synthesis of costunolide and other secondary metabolites in S. lappa.

PMID:36965630 | DOI:10.1016/j.plantsci.2023.111689

STAR Protoc. 2023 Mar 24;4(2):102193. doi: 10.1016/j.xpro.2023.102193. Online ahead of print.

ABSTRACT

Variance of gene expression is intrinsic to any given natural population. Here, we present a protocol to analyze this variance using a conditional quasi loss- and gain-of-function approach. The huva (human variation) package takes advantage of population-scale multi-omics data to infer gene function and the relationship between phenotype and gene expression. We describe the steps for setting up the huva workspace, formatting datasets, performing huva experiments, and exporting data. For complete details on the use and execution of this protocol, please refer to Bonaguro et al. (2022).1.

PMID:36964906 | DOI:10.1016/j.xpro.2023.102193

BMC Bioinformatics. 2023 Mar 24;24(1):114. doi: 10.1186/s12859-023-05231-1.

ABSTRACT

This study evaluates both a variety of existing base causal inference methods and a variety of ensemble methods. We show that: (i) base network inference methods vary in their performance across different datasets, so a method that works poorly on one dataset may work well on another; (ii) a non-homogeneous ensemble method in the form of a Naive Bayes classifier leads overall to as good or better results than using the best single base method or any other ensemble method; (iii) for the best results, the ensemble method should integrate all methods that satisfy a statistical test of normality on training data. The resulting ensemble model EnsInfer easily integrates all kinds of RNA-seq data as well as new and existing inference methods. The paper categorizes and reviews state-of-the-art underlying methods, describes the EnsInfer ensemble approach in detail, and presents experimental results. The source code and data used will be made available to the community upon publication.

PMID:36964499 | DOI:10.1186/s12859-023-05231-1

Arch Pharm Res. 2023 Mar 24. doi: 10.1007/s12272-023-01445-2. Online ahead of print.

ABSTRACT

Metformin has been used clinically for more than 60 years. As time goes by, more and more miraculous effects of metformin beyond the clinic have been discovered and discussed. In addition to the clinically approved hypoglycemic effect, it also has a positive metabolic regulation effect on the human body that cannot be ignored. Such as anti-cancer, anti-aging, brain repair, cardiovascular protection, gastrointestinal regulation, hair growth and inhibition of thyroid nodules, and other nonclinical effects. Metformin affects almost the entire body in the situation taking it over a long period, and the preventive effects of metformin in addition to treating diabetes are also beginning to be recommended in some guidelines. This review is mainly composed of four parts: the development history of metformin, the progress of clinical efficacy, the nonclinical efficacy of metformin, and the consideration and prospect of its application.

PMID:36964307 | DOI:10.1007/s12272-023-01445-2

Nat Commun. 2023 Mar 24;14(1):1650. doi: 10.1038/s41467-023-36845-x.

ABSTRACT

Sea ice is a key factor for the functioning and services provided by polar marine ecosystems. However, ecosystem responses to sea-ice loss are largely unknown because time-series data are lacking. Here, we use shotgun metagenomics of marine sedimentary ancient DNA off Kamchatka (Western Bering Sea) covering the last ~20,000 years. We traced shifts from a sea ice-adapted late-glacial ecosystem, characterized by diatoms, copepods, and codfish to an ice-free Holocene characterized by cyanobacteria, salmon, and herring. By providing information about marine ecosystem dynamics across a broad taxonomic spectrum, our data show that ancient DNA will be an important new tool in identifying long-term ecosystem responses to climate transitions for improvements of ocean and cryosphere risk assessments. We conclude that continuing sea-ice decline on the northern Bering Sea shelf might impact on carbon export and disrupt benthic food supply and could allow for a northward expansion of salmon and Pacific herring.

PMID:36964154 | DOI:10.1038/s41467-023-36845-x