Structural basis for double-stranded RNA recognition by SID1.

The nucleic acid transport properties of the systemic RNAi-defective (SID) 1 family make them attractive targets for developing RNA-based therapeutics and drugs. However, the molecular basis for double-stranded (ds) RNA recognition by SID1 family remains elusive. Here, we report the cryo-EM structures of Caenorhabditis elegans (c) SID1 alone and in complex with dsRNA, both at a resolution of 2.2 Å. The dimeric cSID1 interacts with two dsRNA molecules simultaneously. The dsRNA is located at the interface between ß-strand rich domain (BRD)1 and BRD2 and nearly parallel to the membrane plane. In addition to extensive ionic interactions between basic residues and phosphate backbone, several hydrogen bonds are formed between 2'-hydroxyl group of dsRNA and the contact residues. Additionally, the electrostatic potential surface shows three basic regions are fitted perfectly into three major grooves of dsRNA. These structural characteristics enable cSID1 to bind dsRNA in a sequence-independent manner and to distinguish between DNA and RNA. The cSID1 exhibits no conformational changes upon binding dsRNA, with the exception of a few binding surfaces. Structural mapping of dozens of loss-of-function mutations allows potential interpretation of their diverse functional mechanisms. Our study marks an important step toward mechanistic understanding of the SID1 family-mediated dsRNA uptake.

PancanQTLv2.0: a comprehensive resource for expression quantitative trait loci across human cancers.

Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in cancer. We further integrated the latest GWAS Catalog and identified a total of 84 592 135 linkage associations between eQTLs and the existing GWAS loci, which represents a remarkable ∼50-fold increase compared to the previous version. Additionally, PancanQTLv2.0 uncovered 659516 associations between eQTLs and drug response and identified 146948 associations between eQTLs and immune cell abundance, providing potentially clinical utility of eQTLs in cancer therapy. PancanQTLv2.0 expanded the resources available for investigating gene expression regulation in human cancers, leading to advancements in cancer research and precision oncology.

Photonic spin Hall effect driven broadband multi-focus dielectric metalens.

The multi-focus metalens can couple the light into multiple channels in optical interconnections, which is beneficial to the development of planar, miniaturized, and integrated components. We propose broadband photonic spin Hall effect (PSHE) driven multi-focus metalenses, in which each nanobrick plays a positive role for all focal points. Three PSHE driven metalenses with four, six, and eight focal points have been designed and investigated, respectively. Under the incidences of left-/right-handed circularly polarized (LCP/RCP) light, these metalenses can generate regularly distributed two, three, and four RCP/LCP focal points, respectively. The uniformity of the focusing intensity has been investigated in detail by designing an additional four six-focus metalenses with different focus distributions. The uniqueness of these metalenses makes this design philosophy very attractive for applications in spin photonics, compact polarization detection, multi-imaging systems, and information processing systems.

Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity.

The systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. Here, we report the cryo-electron microscopy (EM) structures of human SIDT2, which forms a tightly packed dimer with extensive interactions mediated by two previously uncharacterized extracellular/luminal ß-strand-rich domains and the unique transmembrane domain (TMD). The TMD of each SIDT2 protomer contains eleven transmembrane helices (TMs), and no discernible nucleic acid conduction pathway has been identified within the TMD, suggesting that it may act as a transporter. Intriguingly, TM3-6 and TM9-11 form a large cavity with a putative catalytic zinc atom coordinated by three conserved histidine residues and one aspartate residue lying approximately 6 Å from the extracellular/luminal surface of the membrane. Notably, SIDT2 can hydrolyze C18 ceramide into sphingosine and fatty acid with a slow rate. The information presented advances the understanding of the structure-function relationships in the SID1 family proteins.

Multilayer structure covalent organic frameworks (COFs) linking by double functional groups for advanced K+ batteries.

Covalent organic frameworks (COFs) are regarded as the potential and promising anode materials for potassium ion batteries (PIBs) on account of their robust and porous crystalline structure. In this work, multilayer structural COF connected by double functional groups, including imine and amidogent through a simple solvothermalprocess, have been successfully synthesized. The multilayer structure of COF can provide fast charge transfer and combine the merits of imine (the restraint of irreversible dissolution) and amidogent (the supply of more active sites). It presents superior potassium storage performance, including the high reversible capacity of 229.5 mAh g-1 at 0.2 A g-1 and outstanding cycling stability of 106.1 mAh g-1 at the high current density of 5.0 A g-1 after 2000 cycles, which is superior to the individual COF. The structural advantages of the covalent organic framework linking by double functional groups (d-COF) can develop a new road for that COF anode material for PIBs in further research.

Structural characterization of the novel stress response facilitator (SrfA) from Pseudomonas aeruginosa.

Chronic pulmonary infections in those living with cystic fibrosis or chronic obstructive pulmonary disease are promoted by production of alginate by the opportunistic pathogen Pseudomonas aeruginosa. Alginate biosynthesis enzymes in P. aeruginosa are regulated by the extracytoplasmic function alternative sigma factor σ22 either by mutation in mucA or in response to envelope stress. An intergenic region between ORFs PA2559 and PA2560 in P. aeruginosa is σ22-dependent and its transcription is activated by cell wall stress. This stress-responsive transcript encodes a novel stress response facilitator, SrfA, that is exclusively conserved only in P. aeruginosa species. Here we report the first three-dimensional structure of SrfA determined by molecular replacement using fold prediction to generate a search model. The SrfA structure adopts a helix-loop-helix fold that shares some similarity with structures of anti-activator or effector proteins. A ΔsrfA mutant strain of P. aeruginosa PAO1 exhibited significantly reduced biofilm formation, which was restored to wild-type levels when ΔsrfA was complemented with srfA. The ΔsrfA strain also exhibited increased sensitivity to macrolide antibiotics. We further show using MicroScale Thermophoresis that SrfA interacts with both PA2559 and PA2560 with high affinity. This work provides a starting point for further investigation into the role of SrfA in response to cell wall stress.

Co-substitution in a Prussian blue analog with a hollow heterostructure for ultrahigh capacity and rate capability aqueous Zn2+ batteries.

Nickel and manganese co-substitution into hollow Prussian blue nanocubes (H-PBMN) has been successfully carried out via utilizing a high-concentration polymer template to grow manganese-Prussian blue (PBM) and nickel-Prussian blue (PBN) through a slow nucleation process. Due to the hollow structure and double metal co-substitution, the properties of the electrode material have been optimized, and it presents an ultrahigh capacity of 138.4 mA h g-1 at 0.05 A g-1.

Structural characterization of an L-fuculose-1-phosphate aldolase from Klebsiella pneumoniae.

Fuculose phosphate aldolases play an important role in glycolysis and gluconeogenesis pathways. L-fuculose 1-phosphate aldolase catalyzes the reversible cleavage of L-fuculose 1-phosphate to DHAP and L-lactaldehyde. Class II aldolases found in bacteria are linked to pathogenesis of human pathogens, and have potential applications in the biosynthesis of carbohydrates and other chiral compounds. Here we report the structure of a putative L-fuculose 1-phosphate aldolase (KpFucA) from the nosocomial pathogen Klebsiella pneumoniae to 1.85 Å resolution. The enzyme crystallizes in space group P422 with one monomer per asymmetric unit. Analytical ultracentrifugation analysis confirms that KpFucA is a tetramer in solution. A magnesium ion cofactor and sulfate ion were identified in the active pocket. Enzyme activity assays confirmed that KpFcuA has a strong preference for L-fuculose 1-phosphate as a substrate, but can also catalyze the cleavage of fructose-1,6-bisphosphate and glucose-6-phosphate. This work should provide a starting point for further investigation of the role of KpFucA in K. pneumoniae pathogenesis or in industrial applications.

Meta-QTL analysis of tan spot resistance in wheat.

KEY MESSAGE: A total of 19 meta-QTL conferring resistance to tan spot were identified from 104 initial QTL detected in 15 previous QTL mapping studies. Tan spot, caused by the fungal pathogen Pyrenophora tritici-repentis (Ptr), is a major foliar disease worldwide in both bread wheat and durum wheat and can reduce grain yield due to reduction in photosynthetic area of leaves. Developing and growing resistant cultivars is a cost-effective and environmentally friendly approach to mitigate negative effects of the disease. Understanding the genetic basis of tan spot resistance can enhance the development of resistant cultivars. With that goal, over 100 QTL associated with resistance to tan spot induced by a variety of Ptr races and isolates have been identified from previous QTL mapping studies. Meta-QTL analysis can identify redundant QTL among various studies and reveal major QTL for targeting in marker-assisted selection applications. In this study, we performed a meta-QTL analysis of tan spot resistance using the reported QTL from 15 previous QTL mapping studies. An integrated linkage map with a total length of 4080.5 cM containing 47,309 markers was assembled from 21 individual linkage maps and three previously published consensus maps. Nineteen meta-QTL were clustered from 104 initial QTL projected on the integrated map. Three of the 19 meta-QTL located on chromosomes 2A, 3B, and 5A show large genetic effects and confer resistance to multiple races in multiple bread wheat and durum wheat mapping populations. The integration of those race-nonspecific QTL is a promising strategy to provide high and stable resistance to tan spot in wheat.

Structural characterization of an isopenicillin N synthase family oxygenase from Pseudomonas aeruginosa PAO1.

Isopenicillin N synthase (IPNS) is a nonheme-Fe2+-dependent enzyme that mediates a key step in penicillin biosynthesis. It catalyses the conversion of the tripeptide δ-(l-α-aminoadipoyl)-l-cysteine-d-valine (ACV) to isopenicillin N, which is a key precursor to ß-lactam antibiotics. The pa4191 gene in Pseudomonas aeruginosa PAO1 has provisionally been annotated as a member of the IPNS family. In this work, we report the crystal structure of PA4191 from P. aeruginosa (PaIPNS hereafter). The 1.65 Šresolution PaIPNS structure forms a jelly roll fold and is confirmed to be a member of the IPNS family based on structural homology. A metal centre within the jelly roll consists of the strictly conserved His201, Asp203 and His257 residues. MicroScale Thermophoresis binding analysis confirms that PaIPNS is a metal-binding protein with a strong preference for iron, but that it does not bind the tripeptide ACV. Structural comparison of PaIPNS with a previously reported IPNS-ACV complex structure reveals a restricted binding pocket that is unable to accommodate ACV.

Molecular Characterization and Expression Profile Analysis of Heat Shock Transcription Factors in Mungbean.

Heat shock transcription factors (Hsfs) are essential elements in plant signal transduction pathways that mediate gene expression in response to various abiotic stresses. Mungbean (Vigna radiata) is an important crop worldwide. The emergence of a genome database now allows for functional analysis of mungbean genes. In this study, we dissect the mungbean Hsfs using genome-wide identification and expression profiles. We characterized a total of 24 VrHsf genes and classified them into three groups (A, B, and C) based on their phylogeny and conserved domain structures. All VrHsf genes exhibit highly conserved exon-intron organization, with two exons and one intron. In addition, all VrHsf proteins contain 16 distinct motifs. Chromosome location analysis revealed that VrHsf genes are located on 8 of the 11 mungbean chromosomes, and that seven duplicated gene pairs had formed among them. Moreover, transcription patterns of VrHsf genes varied in different tissues, indicating their different roles in plant growth and development. We identified multiple stress related cis-elements in VrHsf promoter regions 2 kb upstream of the translation initiation codons, and the expression of most VrHsf genes was altered under different stress conditions, suggesting their potential functions in stress resistance pathways. These molecular characterization and expression profile analyses of VrHsf genes provide essential information for further function investigation.