A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres.

The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset. This interaction is mediated by binding of the 5-subunit CENP-OPQUR sub-complex of CCAN to the Scc1-SA2 sub-complex of cohesin. Mutation in the CENP-U subunit of the CENP-OPQUR complex that abolishes its binding to the composite interface between Scc1 and SA2 weakens centromeric cohesion, leading to premature separation of sister chromatids during delayed metaphase. We further show that CENP-U competes with the cohesin release factor Wapl for binding the interface of Scc1-SA2, and that the cohesion-protecting role for CENP-U can be bypassed by depleting Wapl. Taken together, this study reveals an inner kinetochore-bound pool of cohesin, which strengthens centromeric sister-chromatid cohesion to resist metaphase spindle pulling forces.

Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex.

The ring-shaped Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or its paralog SA1), topologically entraps two duplicated sister DNA molecules to establish sister chromatid cohesion in S-phase. It remains largely elusive how the Cohesin release factor Wapl binds the Cohesin complex, thereby inducing Cohesin disassociation from mitotic chromosomes to allow proper resolution and separation of sister chromatids. Here, we show that Wapl uses two structural modules containing the FGF motif and the YNARHWN motif, respectively, to simultaneously bind distinct pockets in the extensive composite interface between Scc1 and SA2. Strikingly, only when both docking modules are mutated, Wapl completely loses the ability to bind the Scc1-SA2 interface and release Cohesin, leading to erroneous chromosome segregation in mitosis. Surprisingly, Sororin, which contains a conserved FGF motif and functions as a master antagonist of Wapl in S-phase and G2-phase, does not bind the Scc1-SA2 interface. Moreover, Sgo1, the major protector of Cohesin at mitotic centromeres, can only compete with the FGF motif but not the YNARHWN motif of Wapl for binding Scc1-SA2 interface. Our data uncover the molecular mechanism by which Wapl binds Cohesin to ensure precise chromosome segregation.

Author Correction: Layered nanocomposites by shear-flow-induced alignment of nanosheets.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Layered nanocomposites by shear-flow-induced alignment of nanosheets.

Biological materials, such as bones, teeth and mollusc shells, are well known for their excellent strength, modulus and toughness1-3. Such properties are attributed to the elaborate layered microstructure of inorganic reinforcing nanofillers, especially two-dimensional nanosheets or nanoplatelets, within a ductile organic matrix4-6. Inspired by these biological structures, several assembly strategies-including layer-by-layer4,7,8, casting9,10, vacuum filtration11-13 and use of magnetic fields14,15-have been used to develop layered nanocomposites. However, how to produce ultrastrong layered nanocomposites in a universal, viable and scalable manner remains an open issue. Here we present a strategy to produce nanocomposites with highly ordered layered structures using shear-flow-induced alignment of two-dimensional nanosheets at an immiscible hydrogel/oil interface. For example, nanocomposites based on nanosheets of graphene oxide and clay exhibit a tensile strength of up to 1,215 ± 80 megapascals and a Young's modulus of 198.8 ± 6.5 gigapascals, which are 9.0 and 2.8 times higher, respectively, than those of natural nacre (mother of pearl). When nanosheets of clay are used, the toughness of the resulting nanocomposite can reach 36.7 ± 3.0 megajoules per cubic metre, which is 20.4 times higher than that of natural nacre; meanwhile, the tensile strength is 1,195 ± 60 megapascals. Quantitative analysis indicates that the well aligned nanosheets form a critical interphase, and this results in the observed mechanical properties. We consider that our strategy, which could be readily extended to align a variety of two-dimensional nanofillers, could be applied to a wide range of structural composites and lead to the development of high-performance composites.

CENP-I directly targets centromeric DNA to support CENP-A deposition and centromere maintenance.

The enrichment of histone H3 variant CENP-A is the epigenetic mark of centromere and initiates the assembly of the kinetochore at centromere. The kinetochore is a multi-subunit complex that ensures accurate attachment of microtubule centromere and faithful segregation of sister chromatids during mitosis. As a subunit of kinetochore, CENP-I localization at centromere also depends on CENP-A. However, whether and how CENP-I regulates CENP-A deposition and centromere identity remains unclear. Here, we identified that CENP-I directly interacts with the centromeric DNA and preferentially recognizes AT-rich elements of DNA via a consecutive DNA-binding surface formed by conserved charged residues at the end of N-terminal HEAT repeats. The DNA binding-deficient mutants of CENP-I retained the interaction with CENP-H/K and CENP-M, but significantly diminished the centromeric localization of CENP-I and chromosome alignment in mitosis. Moreover, the DNA binding of CENP-I is required for the centromeric loading of newly synthesized CENP-A. CENP-I stabilizes CENP-A nucleosomes upon binding to nucleosomal DNA instead of histones. These findings unveiled the molecular mechanism of how CENP-I promotes and stabilizes CENP-A deposition and would be insightful for understanding the dynamic interplay of centromere and kinetochore during cell cycle.

Whole-genome sequence of Sclerotium delphinii, a pathogenic fungus of Dendrobium officinale southern blight.

Dendrobium officinale is a rare and precious medicinal plant. Southern blight is a destructive disease in the artificial cultivation of D. officinale, and one of its pathogens is Sclerotium delphinii. S. delphinii is a phytopathogenic fungus with a wide host range with extremely strong pathogenicity. In this study, S. delphinii was isolated from D. officinale with southern blight. Subsequently, this specific strain underwent thorough whole-genome sequencing using the PacBio Sequel II platform, which employed single-molecule real-time (SMRT) technology. Comprehensive annotations were obtained through functional annotation of protein sequences using various publicly available databases. The genome of S. delphinii measures 73.66 Mb, with an N90 contig size of 2,707,110 bp, and it contains 18,506 putative predictive genes. This study represents the first report on the genome size assembly and annotation of S. delphinii, making it the initial species within the Sclerotium genus to undergo whole-genome sequencing, which can provide solid data and a theoretical basis for further research on the pathogenesis, omics of S. delphinii.

Insights into response of seagrass (Zostera marina) to sulfide exposure at morphological, physiochemical and molecular levels in context of coastal eutrophication and warming.

Sulfide in sediment porewaters, is toxic to rooted macrophytes in both marine and freshwater environments. Current research on sulfide stress in seagrasses primarily focuses on morphological and physiological aspects, with little known about the molecular response and resistance mechanisms. This study first investigated the damage caused by sulfide to eelgrass (Zostera marina L.) using transcriptomic, metabolomic, and other physiological and biochemical indicators and explored the potential resistance of eelgrass at molecular level through laboratory simulated and in-situ sulfide stress experiments. Comprehensive results showed that sulfide stress severely inhibited the growth, photosynthesis, and antioxidant enzyme activities of eelgrass. Importantly, transcriptome analysis revealed significant activation of pathways related to carbohydrate and sulfur metabolism. This activation served a dual purpose: providing an energy source for eelgrass stress response and achieving detoxification through accelerated sulfur metabolism-a potential resistance mechanism. The toxicity of sulfide increased with rising temperature as evidenced by a decrease in EC50. Results from recovery experiments indicated that when Fv/Fm reduced to about 0 under sulfide stress, the growth and photosynthesis of eelgrass recovered to normal level after timely removal of sulfide. However, prolonged exposure to sulfide resulted in failure to recover, leading ultimately to plant death. This study not only enhances our understanding of the molecular-level impacts of sulfide on seagrasses but also provides guidance for the management and ecological restoration of seagrass meadows under sulfide stress.

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one-stage clotting and chromogenic substrate assays at clinical haemostasis laboratories.

INTRODUCTION: Structural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half-life. AIM: Evaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one-stage clotting assays (OSAs) and chromogenic substrate assays (CSAs). METHODS: Human plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full-length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N = 35) tested blinded samples using in-house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed. RESULTS: Efanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under- and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two- to three-fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations. CONCLUSION: Under- or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards.

Transferable machine learning interatomic potential for carbon hydrogen systems.

In this study, we developed a machine learning interatomic potential based on artificial neural networks (ANN) to model carbon-hydrogen (C-H) systems. The ANN potential was trained on a dataset of C-H clusters obtained through density functional theory (DFT) calculations. Through comprehensive evaluations against DFT results, including predictions of geometries and formation energies across 0D-3D systems comprising C and C-H, as well as modeling various chemical processes, the ANN potential demonstrated exceptional accuracy and transferability. Its capability to accurately predict lattice dynamics, crucial for stability assessment in crystal structure prediction, was also verified through phonon dispersion analysis. Notably, its accuracy and computational efficiency in calculating force constants facilitated the exploration of complex energy landscapes, leading to the discovery of a novel C polymorph. These results underscore the robustness and versatility of the ANN potential, highlighting its efficacy in advancing computational materials science by conducting precise atomistic simulations on a wide range of C-H materials.

Dynamic-Bond-Mediated Chain Reptation Enhances Energy Dissipation of Elastomers.

Vibrations with various frequencies in daily life and industry can cause health hazards and fatigue failure of critical structures, which requires the development of elastomers with high energy dissipation at desired frequencies. Current strategies relying on tuning characteristic relaxation time of polymer chains are mostly qualitative empirical methods, and it is difficult to precisely control damping performances. Here, we report a general strategy for constructing dynamic crosslinked polymer fluid gels that provide controllable ultrahigh energy dissipation. This is realized by dynamic-bond-mediated chain reptation of polymer fluids in a crosslinked network, where the characteristic time of chain reptation is dominated by the presence of well-defined dissociation time of dynamic bonds and almost independent of their molar mass. Using prototypical supramolecular polydimethylsiloxane elastomers, we demonstrate that dynamic crosslinked polymer fluid gels exhibit a controllable ultrahigh damping performance at desired frequencies (10-2~102 Hz), exceeding that of typical state-of-the-art silicone damping materials. Their shock absorption is over 300 % higher than that of commercial silicone rubber under the same impact force.

Large-Area Layered Membranes with Precisely Controlled Nano-Confined Channels.

Two-dimensional (2D) nanosheets-based membranes, which have controlled 2D nano-confined channels, are highly desirable for molecular/ionic sieving and confined reactions. However, it is still difficult to develop an efficient method to prepare large-area membranes with high stability, high orientation, and accurately adjustable interlayer spacing. Here, we present a strategy to produce metal ion cross-linked membranes with precisely controlled 2D nano-confined channels and high stability in different solutions using superspreading shear-flow-induced assembly strategy. For example, membranes based on graphene oxide (GO) exhibit interlayer spacing ranging from 8.0±0.1 Što 10.3±0.2 Å, with a precision of down to 1 Å. At the same time, the value of the orientation order parameter (f) of GO membranes is up to 0.95 and GO membranes exhibit superb stability in different solutions. The strategy we present, which can be generalized to the preparation of 2D nano-confined channels based on a variety of 2D materials, will expand the application scope and provide better performances of membranes.

Enhancement of Overall Kinetics by Se-Br Chemistry in Rechargeable Li-S Batteries.

The sluggish kinetics of lithium-sulfur (Li-S) batteries severely impedes the application in extreme conditions. Bridging the sulfur cathode and lithium anode, the electrolyte plays a crucial role in regulating kinetic behaviors of Li-S batteries. Herein, we report a multifunctional electrolyte additive of phenyl selenium bromide (PhSeBr) to simultaneously exert positive influences on both electrodes and the electrolyte. For the cathode, an ideal conversion routine with lower energy barrier can be attained by the redox mediator and homogeneous catalyst derived from PhSeBr, thus improving the reaction kinetics and utilization of sulfur. Meanwhile, the presence of Se-Br bond helps to reconstruct a loose solvation sheath of lithium ions and a robust bilayer SEI with excellent ionic conductivity, which contributes to reducing the de-solvation energy and simultaneously enhancing the interfacial kinetics. The Li-S battery with PhSeBr displays superior long cycling stability with a reversible capacity of 1164.7 mAh g-1 after 300 cycles at 0.5 C rate. And the pouch cell exhibits a maximum capacity of 845.3 mAh and a capacity retention of 94.8 % after 50 cycles. Excellent electrochemical properties are also obtained in extreme conditions of high sulfur loadings and low temperature of -20 °C. This work demonstrates the versatility and practicability of the special additive, striking out an efficient but simple method to design advanced Li-S batteries.

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer.

Aryl-ketone derivatives have been acknowledged as promising organic photocatalysts for photosynthesis. However, they are limited by their photostability and have been less explored for photoinduced electron transfer (PET) applications. Herein we demonstrate a novel strategy to cover the shortage of aryl-ketone photocatalysts and control the photoreactivity by implanting symmetric aryl ketones into the conjugated covalent organic frameworks (COFs). To prove the concept, three comparative materials with the same topology and varied electronic structures were built, adopting truxenone knot and functionalized terephthalaldehyde linkers. Spectroscopic investigation and excited carrier dynamics analysis disclosed improvements in the photostability and electronic transfer efficiency as well as the structure-performance relationships toward N-aryl tetrahydroisoquinoline oxidation. This system provides a robust rule of thumb for designing new-generation aryl-ketone photocatalysts.

Combined transcriptome and proteome analysis reveal the key physiological processes in seed germination stimulated by decreased salinity in the seagrass Zostera marina L.

BACKGROUND: Zostera marina L., or eelgrass, is the most widespread seagrass species throughout the temperate northern hemisphere. Unlike the dry seeds of terrestrial plants, eelgrass seeds must survive in water, and salinity is the key factor influencing eelgrass seed germination. In the present study, transcriptome and proteome analysis were combined to investigate the mechanisms via which eelgrass seed germination was stimulated by low salinity, in addition to the dynamics of key metabolic pathways under germination. RESULTS: According to the results, low salinity stimulated the activation of Ca2+ signaling and phosphatidylinositol signaling, and further initiated various germination-related physiological processes through the MAPK transduction cascade. Starch, lipids, and storage proteins were mobilized actively to provide the energy and material basis for germination; abscisic acid synthesis and signal transduction were inhibited whereas gibberellin synthesis and signal transduction were activated, weakening seed dormancy and preparing for germination; cell wall weakening and remodeling processes were activated to provide protection for cotyledon protrusion; in addition, multiple antioxidant systems were activated to alleviate oxidative stress generated during the germination process; ERF transcription factor has the highest number in both stages suggested an active role in eelgrass seed germination. CONCLUSION: In summary, for the first time, the present study investigated the mechanisms by which eelgrass seed germination was stimulated by low salinity and analyzed the transcriptomic and proteomic features during eelgrass seed germination comprehensively. The results of the present study enhanced our understanding of seagrass seed germination, especially the molecular ecology of seagrass seeds.

Evolutionary characterization and pathogenicity of Getah virus from pigs in Guangdong Province of China.

Getah virus (GETV) is an emerging zoonotic virus that can infect humans and many mammals through mosquitoes. In this study, a novel pathogenic GETV strain, GDQY2022, was isolated from a pig farm in Guangdong Province, China. Sequence comparisons and phylogenetic analysis showed that GDQY2022 belongs to group III (GIII) and was most closely related to strain HeN202009-2, with 99.78% nucleotide sequence identity. Histopathological examination revealed significant pathological changes, such as widened alveolar septum in the lungs with mild congestion and hemorrhage. Differences in viral load between tissues were assessed by real-time RT-PCR, and significantly higher levels of GETV were found in abdominal lymph nodes and lungs of subclinically and clinically affected pigs (P < 0.01). This study provides valuable data for understanding the risk of GETV infection in the pig industry and a reliable basis for studying the pathogenic mechanisms and diagnostic surveillance of GETV.

Structural basis for RNA recognition by the N-terminal tandem RRM domains of human RBM45.

RBM45 is an RNA-binding protein involved in neural development, whose aggregation is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). However, the mechanisms of RNA-binding and aggregation of RBM45 remain unelucidated. Here, we report the crystal structure of the N-terminal tandem RRM domains of human RBM45 in complex with single-stranded DNA (ssDNA). Our structural and biochemical results revealed that both the RRM1 and RRM2 of RBM45 recognized the GAC sequence of RNA/ssDNA. Two aromatic residues and an arginine residue in each RRM were critical for RNA-binding, and the interdomain linker was also involved in RNA-binding. Two RRMs formed a pair of antiparallel RNA-binding sites, indicating that the N-terminal tandem RRM domains of RBM45 bound separate GAC motifs in one RNA strand or GAC motifs in different RNA strands. Our findings will be helpful in the identification of physiologic targets of RBM45 and provide evidence for understanding the physiologic and pathologic functions of RBM45.

Identification and Molecular Mapping of the Gene YrFL in Wheat Cultivar Flanders with Durable Resistance to Stripe Rust.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most severe diseases of wheat (Triticum aestivum L.) worldwide. Identification and characterization of resistance genes is advantageous to cultivating wheat varieties with durable resistance, which is the most economic and effective strategy to control stripe rust. Flanders, a common wheat cultivar released in France in 1986, confers effective resistance to stripe rust both at the seedling and adult plant stages. To elucidate the genetic basis of resistance in Flanders, F1, F2, and F2:3 generations derived from the cross Mingxian169 × Flanders were evaluated with the most prevalent Chinese Pst race CYR33 at the seedling stage. Inheritance analysis showed that the stripe rust resistance of Flanders was controlled by a single dominant gene, temporarily designated as YrFL. Bulked segregant analysis (BSA) combined with a wheat 660K single-nucleotide polymorphism (SNP) array indicated that polymorphic SNP markers were mainly located in the 0 to 150 Mb on wheat chromosome 5A. One hundred and eleven kompetitive allele-specific PCR (KASP) and 39 simple sequence repeat (SSR) markers on chromosome 5A were used to locate the YrFL. Linkage analysis mapped YrFL with 19 KASP and three SSR markers on wheat chromosome 5AS, and the genetic distances of the closest flanking markers AX108925494 and Xbarc56 to YrFL were 0.6 and 2.0 cM, respectively. Chromosome location, resistance characterization, and molecular marker positions indicated that YrFL is likely a novel stripe rust resistance gene on wheat chromosome 5AS and could be pyramided with other resistance genes to improve resistance in wheat breeding programs.

Strong Anchoring of Hydrogels through Superwetting-Assisted High-Density Interfacial Grafting.

Strong adhesion of hydrogels on solids plays an important role in stable working for various practical applications. However, current hydrogel adhesion suffers from poor interfacial bonding with solid surfaces. Here, we propose a general superwetting-assisted interfacial polymerization (SAIP) strategy to robustly anchor hydrogels onto solids by forming high-density interfacial covalent bonds. The key of our strategy is to make the initiator fully contact solid surfaces via a superwetting way for enhancing the interfacial grafting efficiency. The designed anchored hydrogels show strong bulk failure with a high breaking strength of ≈1.37 MPa, different from weak interfacial failure that occurs in traditional strategies. The strong interfacial adhesion greatly enhances the stability of hydrogels against swelling destruction. This work opens up new inspirations for designing strongly anchored hydrogels from an interfacial chemistry perspective.

Organohydrogels with High-Speed Lubrication by Confining Polymer Chain Mobility by an Interpenetrated Heteronetwork.

Hydrogels with pure hydrophilic network have received much attention due to their excellent low frictional behavior. However, the lubrication performance of hydrogels is not satisfied under high-speed condition due to the energy dissipation caused by adsorbed polymer chains as well as the failure of lubricating mechanisms accompanied by the transition of lubrication regime. In this work, interpenetrating double-network organohydrogels were constructed by combining hydrophilic and oleophilic polymer networks to modify the physiochemical properties of surface polymer chains, especially the chain mobility. The oleophilic polymer network spatially restricting the mobility of the swollen hydrophilic network in water, resulted in a low coefficient of friction (ca. 0.01) compared with conventional hydrogels at high speed (0.1 m s-1 ). Meanwhile, the organohydrogels had superior wear resistance, with almost no wear observed on the sliding track after 5 k cycles of rubbing at high speed. The design concept of organohydrogels can be extended to a variety of low-wear, highly-lubricating materials.

Tough and Conductive Nacre-inspired MXene/Epoxy Layered Bulk Nanocomposites.

A long-standing quest in materials science has been the development of tough epoxy resin nanocomposites for use in numerous applications. Inspired by nacre, here we report tough and conductive MXene/epoxy layered bulk nanocomposites. The orientation of MXene lamellar scaffolds is enhanced by annealing treatment. The improved interfacial interactions between MXene lamellar scaffold and epoxy through surface chemical modification resulted in a synergistic effect. Tailoring the interlayer spacing of MXene nanosheets to a critical distance resulted in a fracture toughness about eight times higher than that of pure epoxy, surpassing other epoxy nanocomposites. Our nacre-inspired MXene/epoxy layered bulk nanocomposites also show high electrical conductivity that provides self-monitoring capability for structural integrity and exhibits an excellent electromagnetic interference shielding efficiency. Our proposed strategy provides an avenue for fabricating high-performance epoxy nanocomposites.