The evolution and functional divergence of FT-related genes in controlling flowering time in Brassica rapa ssp. rapa.

KEY MESSAGE: The BrrFT paralogues exhibit distinct expression patterns and play different roles in regulating flowering time, and BrrFT4 competes with BrrFT1 and BrrFT2 to interact with BrrFD proteins. Flowering time is an important agricultural trait for Brassica crops, and early bolting strongly affects the yield and quality of Brassica rapa ssp. rapa. Flowering Locus T paralogues play an important role in regulating flowering time. In this study, we identified FT-related genes in turnip by phylogenetic classification, and four BrrFT homoeologs that shared with high identities with BraFT genes were isolated. The different gene structures, promoter binding sites, and expression patterns observed indicated that these genes may play different roles in flowering time regulation. Further genetic and biochemical experiments showed that as for FT-like paralogues, BrrFT2 acted as the key floral inducer, and BrrFT1 seems to act as a mild 'florigen' protein. However, BrrFT4 acts as a floral repressor and antagonistically regulates flowering time by competing with BrrFT1 and BrrFT2 to bind BrrFD proteins. BrrFT3 may have experienced loss of function via base shift mutation. Our results revealed the potential roles of FT-related genes in flowering time regulation in turnip.

Structural diversity in the membrane-bound hIAPP dimer correlated with distinct membrane disruption mechanisms.

Amyloid deposits of the human islet amyloid polypeptide (hIAPP) have been identified in 90% of patients with type II diabetes. Cellular membranes accelerate the hIAPP fibrillation, and the integrity of membranes is also disrupted at the same time, leading to the apoptosis of ß cells in pancreas. The molecular mechanism of hIAPP-induced membrane disruption, especially during the initial membrane disruption stage, has not been well understood yet. Herein, we carried out extensive all-atom molecular dynamics simulations investigating the hIAPP dimerization process in the anionic POPG membrane, to provide the detailed molecular mechanisms during the initial hIAPP aggregation stage in the membrane environment. Compared to the hIAPP monomer on the membrane, we observed not only an increase of α-helical structures, but also a substantial increase of ß-sheet structures upon spontaneous dimerization. Moreover, the random coiled and α-helical dimer structures insert deep into the membrane interior with a few inter-chain contacts at the C-terminal region, while the ß-sheet-rich structures reside on the membrane surface accompanied by strong inter-chain hydrophobic interactions. The coexistence of α and ß structures constitutes a diverse structural ensemble of the membrane-bound hIAPP dimer. From α-helical to ß-sheet structures, the degree of membrane disruption decreases gradually, and thus the membrane damage induced by random coiled and α-helical structures precedes that induced by ß-sheet structures. We speculate that insertion of random coiled and α-helical structures contributes to the initial stage of membrane damage, while ß-sheet structures on the membrane surface are more involved in the later stage of fibril-induced membrane disruption.

Genomic analyses provide insights into sex differentiation of tetraploid strawberry (Fragaria moupinensis).

The strawberry genus, Fragaria, exhibits a wide range of sexual systems and natural ploidy variation. Nearly, all polyploid strawberry species exhibit separate sexes (dioecy). Research has identified the sex-determining sequences as roughly conserved but with repeatedly changed genomic locations across octoploid strawberries. However, it remains unclear whether tetraploid wild strawberries evolved dioecy independently or shared a common origin with octoploid strawberries. In this study, we investigated the sex determinants of F. moupinensis, a dioecious plant with heterogametic females (ZW). Utilizing a combination of haplotype-resolved genome sequencing of the female F. moupinensis, k-mer-based and coverage-based genome-wide association studies (GWAS), and transcriptomic analysis, we discovered a non-recombining, approximately 33.6 kb W-specific region on chromosome 2a. Within this region, only one candidate sex-determining gene (FmoAFT) was identified. Furthermore, an extensive resequencing of the entire Fragaria genus indicated that the W-specific region displays conservative female specificity across all tetraploid species. This observation suggests that dioecy evolved independently in tetraploid and octoploid strawberries. Moreover, employing virus-induced gene silencing (VIGS), we knocked down the expression of the FmoAFT homologue transcript in cultivated strawberries, revealing its potential role in promoting female functions during early carpel development. We also applied DNA affinity purification sequencing (DAP-seq) and yeast one-hybrid assays to identify potential direct targets of FmoAFT. These insights shed new light on the genetic basis and evolutionary history of sex determination in strawberries, thereby facilitating the formulation of strategies to manipulate sex determination in breeding programs.

ProteinMAE: masked autoencoder for protein surface self-supervised learning.

SUMMARY: The biological functions of proteins are determined by the chemical and geometric properties of their surfaces. Recently, with the booming progress of deep learning, a series of learning-based surface descriptors have been proposed and achieved inspirational performance in many tasks such as protein design, protein-protein interaction prediction, etc. However, they are still limited by the problem of label scarcity, since the labels are typically obtained through wet experiments. Inspired by the great success of self-supervised learning in natural language processing and computer vision, we introduce ProteinMAE, a self-supervised framework specifically designed for protein surface representation to mitigate label scarcity. Specifically, we propose an efficient network and utilize a large number of accessible unlabeled protein data to pretrain it by self-supervised learning. Then we use the pretrained weights as initialization and fine-tune the network on downstream tasks. To demonstrate the effectiveness of our method, we conduct experiments on three different downstream tasks including binding site identification in protein surface, ligand-binding protein pocket classification, and protein-protein interaction prediction. The extensive experiments show that our method not only successfully improves the network's performance on all downstream tasks, but also achieves competitive performance with state-of-the-art methods. Moreover, our proposed network also exhibits significant advantages in terms of computational cost, which only requires less than a tenth of memory cost of previous methods. AVAILABILITY AND IMPLEMENTATION: https://github.com/phdymz/ProteinMAE.

[A Health Education Program for Home Emergency Management of Acute Complications of Diabetes in the Elderly].

Objective To establish a health education program for home emergency management of acute complications of diabetes in the elderly.Methods The program was drafted by literature review and panel discussion.The final draft was formed after two rounds of correspondence from 13 experts.Results The recovery rate of the two rounds of expert correspondence was 100%,and the expert authority coefficient was 0.98.The Kendall's harmony coefficients of the two rounds of correspondence were 0.263 and 0.212 respectively(both P<0.001).The established health education program included indicators of three categories:early stage of acute complications of diabetes at home(understanding the inducing factors),emergency warning(quick and early identification in case of emergency),and emergency treatment at home.Conclusion The contents of the health education program are systematic and reliable and meet the needs of health education for home emergency management of the elderly with diabetes.

Integrative analysis of the metabolome and transcriptome reveals the potential mechanism of fruit flavor formation in wild hawthorn (Crataegus chungtienensis).

Hawthorns are important medicinal and edible plants with a long history of health protection in China. Besides cultivated hawthorn, other wild hawthorns may also have excellent medicinal and edible value, such as Crataeguschungtienensis, an endemic species distributed in the Southwest of China. In this study, by integrating the flavor-related metabolome and transcriptome data of the ripening fruit of C. chungtienensis, we have developed an understanding of the formation of hawthorn fruit quality. The results show that a total of 849 metabolites were detected in the young and mature fruit of C. chungtienensis, of which flavonoids were the most detected metabolites. Among the differentially accumulated metabolites, stachyose, maltotetraose and cis-aconitic acid were significantly increased during fruit ripening, and these may be important metabolites affecting fruit flavor change. Moreover, several flavonoids and terpenoids were reduced after fruit ripening compared with young fruit. Therefore, using the unripe fruit of C. chungtienensis may allow us to obtain more medicinal active ingredients such as flavonoids and terpenoids. Furthermore, we screened out some differentially expressed genes (DEGs) related to fruit quality formation, which had important relationships with differentially accumulated sugars, acids, flavonoids and terpenoids. Our study provides new insights into flavor formation in wild hawthorn during fruit development and ripening, and at the same time this study lays the foundation for the improvement of hawthorn fruit flavor.

Phenoloxidases: catechol oxidase - the temporary employer and laccase - the rising star of vascular plants.

Phenolics are vital for the adaptation of plants to terrestrial habitats and for species diversity. Phenoloxidases (catechol oxidases, COs, and laccases, LACs) are responsible for the oxidation and polymerization of phenolics. However, their origin, evolution, and differential roles during plant development and land colonization are unclear. We performed the phylogeny, domain, amino acids, compositional biases, and intron analyses to clarify the origin and evolution of COs and LACs, and analysed the structure, selective pressure, and chloroplast targeting to understand the species-dependent distribution of COs. We found that Streptophyta COs were not homologous to the Chlorophyta tyrosinases (TYRs), and might have been acquired by horizontal gene transfer from bacteria. COs expanded in bryophytes. Structural-functionality and selective pressure were partially responsible for the species-dependent retention of COs in embryophytes. LACs emerged in Zygnemaphyceae, having evolved from ascorbate oxidases (AAOs), and prevailed in the vascular plants and strongly expanded in seed plants. COs and LACs coevolved with the phenolic metabolism pathway genes. These results suggested that TYRs and AAOs were the first-stage phenoloxidases in Chlorophyta. COs might be the second key for the early land colonization. LACs were the third one (dominating in the vascular plants) and might be advantageous for diversified phenol substrates and the erect growth of plants. This work provided new insights into how phenoloxidases evolved and were devoted to plant evolution.

ALS-Linked A315T and A315E Mutations Enhance ß-Barrel Formation of the TDP-43307-319 Hexamer: A REST2 Simulation Study.

Pathogenic mutations of transactivation response element DNA-binding protein 43 (TDP-43) are closely linked with amyotrophic lateral sclerosis (ALS). It was recently reported that two ALS-linked familial mutants A315T and A315E of TDP-43307-319 peptides can self-assemble into oligomers including tetramers, hexamers, and octamers, among which hexamers were suggested to form the ß-barrel structure. However, due to the transient nature of oligomers, their conformational properties and the atomic mechanisms underlying the ß-barrel formation remain largely elusive. Herein, we investigated the hexameric conformational distributions of the wild-type (WT) TDP-43307-319 fragment and its A315T and A315E mutants by performing all-atom explicit-solvent replica exchange with solute tempering 2 simulations. Our simulations reveal that each peptide can self-assemble into diverse conformations including ordered ß-barrels, bilayer ß-sheets and/or monolayer ß-sheets, and disordered complexes. A315T and A315E mutants display higher propensity to form ß-barrel structures than the WT, which provides atomic explanation for their enhanced neurotoxicity reported previously. Detailed interaction analysis shows that A315T and A315E mutations increase inter-molecular interactions. Also, the ß-barrel structures formed by the three different peptides are stabilized by distinct inter-peptide side-chain hydrogen bonding, hydrophobic, and aromatic stacking interactions. This study demonstrates the enhanced ß-barrel formation of the TDP-43307-319 hexamer by the pathogenic A315T and A315E mutations and reveals the underlying molecular determinants, which may be helpful for in-depth understanding of the ALS-mutation-induced neurotoxicity of TDP-43 protein.

Integrated transcriptome and methylome analyses reveal the molecular regulation of drought stress in wild strawberry (Fragaria nilgerrensis).

BACKGROUND: Fragaria nilgerrensis, which is a diploid wild strawberry with excellent drought-resistance, would provide useful candidate genes for improving drought resistance of cultivated strawberry. So far, its molecular regulatory networks involved in drought stress are unclear. We therefore investigated the drought response regulatory networks of F. nilgerrensis based on the integrated analysis of DNA methylation, transcriptome and physiological traits during four time points under drought stress.  RESULTS: The most differentially expressed genes and the physiological changes were found at 8 days (T8) compared with 0 day (T0, control). Methylome analysis revealed slight dynamic changes in genome-wide mC levels under drought conditions, while the most hypomethylated and hypermethylated regions were identified at T4 and T8. Association analysis of the methylome and transcriptome revealed that unexpressed genes exhibited expected hypermethylation levels in mCHG and mCHH contexts, and highly expressed genes exhibited corresponding hypomethylation levels in the gene body, but mCG contexts showed the opposite trend. Then, 835 differentially methylated and expressed genes were identified and grouped into four clustering patterns to characterize their functions. The genes with either negative or positive correlation between methylation and gene expression were mainly associated with kinases, Reactive Oxygen Species (ROS) synthesis, scavenging, and the abscisic acid (ABA) signal pathway. Consistently, weighted gene co-expression network analysis (WGCNA) revealed Hub genes including NCED, CYP707A2, PP2Cs and others that play important roles in the ABA signaling pathway. CONCLUSION: F. nilgerrensis drought is dominated by ABA-dependent pathways, possibly accompanied by ABA-independent crosstalk. DNA methylation may affect gene expression, but their correlation was more subtle and multiple types of association exist. Maintaining the balance between ROS regeneration and scavenging is an important factor in drought resistance in F. nilgerrensis. These results deepen our understanding of drought resistance and its application in breeding in strawberry plants.

Distinct binding interactions trigger opposite conformational modulations on pathogenic and wildtype Huntingtin exon 1 proteins.

Abnormal elongation of the polyglutamine tract transforms exon 1 of the Huntingtin protein (Htt-exon-1) from wildtype to pathogenic form, and causes Huntington's disease. As an intrinsically disordered protein, the structural ensemble of Htt-exon-1 is highly heterogeneous and the detailed conformation of toxic species is still under debate. Ispinesib, a potential small-molecule drug, has been identified to selectively link the pathogenic Htt-exon-1 into the autophagosome to degrade, thus opening an innovative therapeutic direction. However, the molecular mechanisms behind this selectivity remain largely elusive. Herein, we carry out extensive molecular dynamics simulations with an enhanced sampling method to investigate the ispinesib inducing conformational changes of pathogenic and wildtype Htt-exon-1 and the corresponding binding mechanisms. Our simulations reveal that the ispinesib binding induces opposite conformational changes in pathogenic and wildtype Htt-exon-1, i.e., the 'entropy collapse' with significant reduction of ß-sheets versus the 'entropy expansion' with a slight increase of α-helices. Network analyses further reveal that there are two stable binding sites in the pathogenic Htt-exon-1, while the binding on the wildtype Htt-exon-1 is highly dynamic and non-specific. These dramatic differences originate from the underlying distinct binding interactions. More specifically, stronger hydrogen bonds serve as the specific binding anchors in pathogenic Htt-exon-1, while stronger hydrophobic interactions dominate in the dynamic binding with wildtype Htt-exon-1. Our simulations provide an atomistic mechanism for the ispinesib selective binding on the pathogenic Htt-exon-1, and further shed light on the general mechanisms of small molecule modulation on intrinsically disordered proteins.

Transcriptional memory of gene expression across generations participates in transgenerational plasticity of field pennycress in response to cadmium stress.

Transgenerational plasticity (TGP) occurs when maternal environments influence the expression of traits in offspring, and in some cases may increase fitness of offspring and have evolutionary significance. However, little is known about the extent of maternal environment influence on gene expression of offspring, and its relationship with trait variations across generations. In this study, we examined TGP in the traits and gene expression of field pennycress (Thlaspi arvense) in response to cadmium (Cd) stress. In the first generation, along with the increase of soil Cd concentration, the total biomass, individual height, and number of seeds significantly decreased, whereas time to flowering, superoxide dismutase (SOD) activity, and content of reduced glutathione significantly increased. Among these traits, only SOD activity showed a significant effect of TGP; the offspring of Cd-treated individuals maintained high SOD activity in the absence of Cd stress. According to the results of RNA sequencing and bioinformatic analysis, 10,028 transcripts were identified as Cd-responsive genes. Among them, only 401 were identified as transcriptional memory genes (TMGs) that maintained the same expression pattern under normal conditions in the second generation as in Cd-treated parents in the first generation. These genes mainly participated in Cd tolerance-related processes such as response to oxidative stress, cell wall biogenesis, and the abscisic acid signaling pathways. The results of weighted correlation network analysis showed that modules correlated with SOD activity recruited more TMGs than modules correlated with other traits. The SOD-coding gene CSD2 was found in one of the modules correlated with SOD activity. Furthermore, several TMGs co-expressed with CSD2 were hub genes that were highly connected to other nodes and critical to the network's topology; therefore, recruitment of TMGs in offspring was potentially related to TGP. These findings indicated that, across generations, transcriptional memory of gene expression played an important role in TGP. Moreover, these results provided new insights into the trait evolution processes mediated by phenotypic plasticity.

Self-reported practices, competence and difficulties towards palliative care among nurses: A cross-sectional study.

OBJECTIVE: Nurses' palliative care practice ability is the key to evaluating the quality of palliative care. This study aimed to identify the current situation of palliative care practices, competence and difficulties among nurses and determine whether difficulties play a mediating role between practices and competence. METHODS: A cross-sectional study was conducted. The online survey comprised demographics, the Palliative Care Self-Reported Practices Scale, the Palliative Care Nursing Self-competence Scale and the Palliative Care Difficulties Scale. Data were analysed by using descriptive statistics, univariate analysis, linear regression and mediation analysis. RESULTS: A total of 284 questionnaires were included for statistical analysis. The mean scores for practices, competence and difficulties were 67.81 (SD = 13.60), 124.28 (41.21) and 44.32 (12.68), respectively. There was a correlation between practices, competence and difficulties (p < 0.01). Competence and difficulties were independent predictors of practices (R2 adj  = 0.384, p < 0.001). Furthermore, difficulties mediated the relationship between practices and competence (b = 0.052, 95% confidence interval: 0.008-0.155). CONCLUSIONS: Continuous efforts should be made to enhance nurses' practices, competence and problem-solving abilities in palliative care. This study suggested further targeted education programmes, especially in special symptom management, interagency and multidisciplinary communication.

Cultivated hawthorn (Crataegus pinnatifida var. major) genome sheds light on the evolution of Maleae (apple tribe).

Cultivated hawthorn (Crataegus pinnatifida var. major) is an important medicinal and edible plant with a long history of use for health protection in China. Herein, we provide a de novo chromosome-level genome sequence of the hawthorn cultivar "Qiu Jinxing." We assembled an 823.41 Mb genome encoding 40 571 genes and further anchored the 779.24 Mb sequence into 17 pseudo-chromosomes, which account for 94.64% of the assembled genome. Phylogenomic analyses revealed that cultivated hawthorn diverged from other species within the Maleae (apple tribe) at approximately 35.4 Mya. Notably, genes involved in the flavonoid and triterpenoid biosynthetic pathways have been significantly amplified in the hawthorn genome. In addition, our results indicated that the Maleae share a unique ancient tetraploidization event; however, no recent independent whole-genome duplication event was specifically detected in hawthorn. The amplification of non-specific long terminal repeat retrotransposons contributed the most to the expansion of the hawthorn genome. Furthermore, we identified two paleo-sub-genomes in extant species of Maleae and found that these two sub-genomes showed different rearrangement mechanisms. We also reconstructed the ancestral chromosomes of Rosaceae and discussed two possible paleo-polyploid origin patterns (autopolyploidization or allopolyploidization) of Maleae. Overall, our study provides an improved context for understanding the evolution of Maleae species, and this new high-quality reference genome provides a useful resource for the horticultural improvement of hawthorn.

Biomineralized Zeolitic Imidazolate Framework-8 Nanoparticles Enable Polymerase-Driven DNA Biocomputing for Reliable Cell Identification.

Investigating multiple miRNA expression patterns in living cells by DNA logic biocomputing is a valuable strategy for diagnosis and biomedical studies. The introduction of protein enzymes in DNA logic biocomputing circuits not only expands the toolbox of nucleic acid assembly techniques, but also further improves the specificity of recognizing and processing of DNA input. Herein, a polymerase-driven primer exchange reaction, acting as the sensing module, is introduced into the biocomputing system and transduces the multiple miRNAs sensing event into the intermediate triggers for activating the subsequent processing module, which further performs signal readout through DNAzyme catalytic substrate cleavage reaction. By using biomineralized zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to deliver all the components of the biocomputing system, including polymerase and DNA probes, we realized polymerase-driven DNA biocomputing operations in living cells, including AND and OR gates. The results exhibited that biomineralized ZIF-8 NPs can protect the loaded cargoes against the external environment and deliver them efficiently to the cytoplasm. The polymerase-driven DNA biocomputing system based on multiple miRNAs sensing can be used for reliable cell identification and may provide a promising platform for more accurate diagnosis and programmable therapeutics.

Electrocardiographic localization of peripherally inserted central catheter tip position in critically ill patients with advanced cancer: An application study.

BACKGROUND: We compared the methods of electrocardiogram (ECG) and X-ray localization of the peripherally inserted central catheter (PICC) tip position, in order to find a more convenient, practical, and safe method. OBJECTIVE: To investigate the value of applying electrocardiographic localization of the PICC tip position in critically ill patients with advanced cancer in Hebei Province, China. METHOD: Enrolled 137 advanced cancers requiring PICC placement. The position of the catheter tip was localized with the bedside electrocardiogram in real time. Then, the localization was performed using a chest X-ray (the gold standard). The accuracy of electrocardiographic location was checked. RESULTS: Specific P waves were observed in 130 patients. No change in the P waves was observed for the remaining seven patients. The age of the latter group of patients was more advanced (87.29 [5.15] years), a significant difference to that of the 130 patients with specific P waves (71.58 [14.84] years) (t = -6.704, p < .001). Specific P waves not only involve ascendance in P waves but also ascendance in QRS waves. CONCLUSIONS: The use of an ECG to localize the PICC tip in critically ill patients with advanced cancer may replace the unnecessary use of chest X-rays. Specific P waves not only involve an increase in P waves but also an increase in QRS waves. If there is no change in the P wave, a chest X-ray film must be obtained. In elderly patients, because there is a possibility of catheter tip malposition, a comprehensive evaluation should be performed before surgery.

Dynamic Changes of DNA Methylation During Wild Strawberry (Fragaria nilgerrensis) Tissue Culture.

Tissue culture is an important tool for asexual propagation and genetic transformation of strawberry plants. In plant tissue culture, variation of DNA methylation is a potential source of phenotypic variation in regenerated plants. However, the genome wide dynamic methylation patterns of strawberry tissue culture remain unclear. In this study, we used whole-genome bisulfite sequencing (WGBS) to study genomic DNA methylation changes of a wild strawberry Fragaria nilgerrensis at six stages: from explants of shoot tips to outplanting and acclimation. Global methylation levels showed that CG sites exhibited the highest methylation level in all stages with an average of 49.5%, followed by CHG (33.2%) and CHH (12.4%). Although CHH accounted for the lowest proportion of total cytosine methylation, it showed the most obvious methylation change and the most of these changes occurred in the transposable element regions. The overall methylation levels alternately decreased and increased during the entire tissue culture process and the distribution of DNA methylation was non-uniform among different genetic regions. Furthermore, much more differentially methylated regions (DMRs) were detected in dedifferentiation and redifferentiation stages and most of them were transposable elements, suggesting these processes involved activating or silencing of amounts of transposons. The functional enrichment of the DMR-related genes indicated that genes involved in hormone metabolic processes, plant development and the stress response changed methylation throughout the tissue culture process. Finally, the quantitative real-time PCR (qRT-PCR) was conducted to examine the association of methylation and gene expression of a set of different methylated genes. Our findings give deeper insight into the epigenetic regulation of gene expression during the plant tissue cultures process, which will be useful in the efficient control of somaclonal variations and in crop improvement.

Evolutionary history and pan-genome dynamics of strawberry (Fragaria spp.).

Strawberry (Fragaria spp.) has emerged as a model system for various fundamental and applied research in recent years. In total, the genomes of five different species have been sequenced over the past 10 y. Here, we report chromosome-scale reference genomes for five strawberry species, including three newly sequenced species' genomes, and genome resequencing data for 128 additional accessions to estimate the genetic diversity, structure, and demographic history of key Fragaria species. Our analyses obtained fully resolved and strongly supported phylogenies and divergence times for most diploid strawberry species. These analyses also uncovered a new diploid species (Fragaria emeiensis Jia J. Lei). Finally, we constructed a pan-genome for Fragaria and examined the evolutionary dynamics of gene families. Notably, we identified multiple independent single base mutations of the MYB10 gene associated with white pigmented fruit shared by different strawberry species. These reference genomes and datasets, combined with our phylogenetic estimates, should serve as a powerful comparative genomic platform and resource for future studies in strawberry.

Heparin remodels the microtubule-binding repeat R3 of Tau protein towards fibril-prone conformations.

Abnormal aggregation of proteins into pathological amyloid fibrils is implicated in a wide range of devastating human neurodegenerative diseases. Intracellular fibrillary inclusions formed by Tau protein are characterized as the hallmark of tauopathies, including Alzheimer's disease and frontotemporal dementia. Heparin has been often used to trigger Tau aggregation in in vitro studies. However, the conformational changes induced by heparin and the underlying mechanism of promotion of Tau aggregation by heparin are not well understood. Structural characterization of Tau oligomers in the early stage of fibrillation is of great importance but remains challenging due to their dynamic and heterogeneous nature. R3, the third microtubule-binding repeat of Tau, contains the fibril-nucleating core (PHF6) and is crucial for Tau aggregation. In this study, utilizing extensive all-atom replica-exchange molecular dynamic simulations, we explored the conformational ensembles of R3 monomer/dimer in the absence and presence of heparin. Our results show that without heparin, both monomeric and dimeric R3 preferentially adopt collapsed ß-sheet-containing conformations and PHF6 plays an important role in the formation of interchain ß-sheet structures, while in the presence of heparin, R3 can populate relatively extended disordered states where chain dimension is similar to that of R3 in Tau filaments. Through electrostatic, hydrogen-bonding and hydrophobic interactions, heparin has a preference for interacting with residues V306/Q307/K317/K321/H329/H330/K331 which distribute throughout the entire sequence of R3, in turn acting as a template to extend R3 conformations. More importantly, heparin alters intramolecular/intermolecular interaction patterns of R3 and increases the intermolecular contact regions. Our results suggest that heparin remodels the conformations of R3 towards fibril-prone structures by increasing chain dimension and intermolecular contact regions, which may shed light on the atomic mechanism of heparin-induced amyloid fibrillization of Tau protein.

Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation.

BACKGROUND: Understanding how organisms evolve and adapt to extreme habitats is of crucial importance in evolutionary ecology. Altitude gradients are an important determinant of the distribution pattern and range of organisms due to distinct climate conditions at different altitudes. High-altitude regions often provide extreme environments including low temperature and oxygen concentration, poor soil, and strong levels of ultraviolet radiation, leading to very few plant species being able to populate elevation ranges greater than 4000 m. Field pennycress (Thlaspi arvense) is a valuable oilseed crop and emerging model plant distributed across an elevation range of nearly 4500 m. Here, we generate an improved genome assembly to understand how this species adapts to such different environments. RESULTS: We sequenced and assembled de novo the chromosome-level pennycress genome of 527.3 Mb encoding 31,596 genes. Phylogenomic analyses based on 2495 single-copy genes revealed that pennycress is closely related to Eutrema salsugineum (estimated divergence 14.32-18.58 Mya), and both species form a sister clade to Schrenkiella parvula and genus Brassica. Field pennycress contains the highest percentage (70.19%) of transposable elements in all reported genomes of Brassicaceae, with the retrotransposon proliferation in the Middle Pleistocene being likely responsible for the expansion of genome size. Moreover, our analysis of 40 field pennycress samples in two high- and two low-elevation populations detected 1,256,971 high-quality single nucleotide polymorphisms. Using three complementary selection tests, we detected 130 candidate naturally selected genes in the Qinghai-Tibet Plateau (QTP) populations, some of which are involved in DNA repair and the ubiquitin system and potential candidates involved in high-altitude adaptation. Notably, we detected a single base mutation causing loss-of-function of the FLOWERING LOCUS C protein, responsible for the transition to early flowering in high-elevation populations. CONCLUSIONS: Our results provide a genome-wide perspective of how plants adapt to distinct environmental conditions across extreme elevation differences and the potential for further follow-up research with extensive data from additional populations and species.

Evaluation of genetic diversity and population structure of Fragaria nilgerrensis using EST-SSR markers.

Fragaria nilgerrensis is a diploid wild strawberry widely distributed in Southwest China. Its white color and "peach-like" fragrance of fruits are valuable characters for the genetic improvement of cultivated strawberry plants. Its strong biotic and abiotic resistance and tolerance also enable it to survive in different habitats in the field. In this study, we evaluated the level of genetic variation within and between 16 populations with 169 individuals of F. nilgerrensis using 16 newly developed EST-SSR (expressed sequence tag-simple sequence repeats) markers. The results show that the genetic diversity of this species was high, based on Nei's genetic diversity (0.26) and polymorphic loci (0.41), although it is self-compatible and has clonal propagation. Significant genetic differentiation among populations was also detected by AMOVA analysis (Fst = 0.34), which could be indicative of little gene flow (Nm = 0.43) in F. nilgerrensis. The phylogenetic tree indicates that most of individuals from the same population have clustered together. These populations were not grouped based on the geographical distance, consistent with the Mantel test result (R2 = 0.0063, P > 0.05). All the populations were assigned into two ancestral groups, with some individuals admixed, suggesting ancestral gene flow had occurred between these two groups. Our developed EST-SSR markers as well as the genetic diversity and population structure analysis of F. nilgerrensis are important for genetic improvement in the breeding process. Moreover, the populations that contain high genetic diversity would be a priority for collection and conservation.