The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.

Antigen-specific memory CD4+ T cells can persist and confer rapid and efficient protection from microbial reinfection. However, the mechanisms underlying the long-term maintenance of the memory CD4+ T cell pool remain largely unknown. Here, using a mouse model of acute infection with lymphocytic choriomeningitis virus (LCMV), we found that the serine/threonine kinase complex mammalian target of rapamycin complex 2 (mTORC2) is critical for the long-term persistence of virus-specific memory CD4+ T cells. The perturbation of mTORC2 signaling at memory phase led to an enormous loss of virus-specific memory CD4+ T cells by a unique form of regulated cell death (RCD), ferroptosis. Mechanistically, mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3ß kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4+ T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4), a major scavenger of lipid peroxidation. Thus, the mTORC2-AKT-GSK3ß axis functions as a key signaling hub to promote the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.

The Kinase mTORC1 Promotes the Generation and Suppressive Function of Follicular Regulatory T Cells.

Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation. Mechanistically, mTORC1-mediated phosphorylation of the transcription factor STAT3 induced the expression of the transcription factor TCF-1 by promoting STAT3 binding to the Tcf7 5'-regulatory region. Subsequently, TCF-1 bound to the Bcl6 promoter to induce Bcl6 expression, which launched the Tfr cell differentiation program. Thus, mTORC1 initiates Tfr cell differentiation by activating the TCF-1-Bcl-6 axis during immunization or infection.

Characterization and genetic differences analysis in adventitious roots development of 38 Populus germplasm resources.

To select poplar clones with excellent adventitious roots development (ARD) and deepen the understanding of its molecular mechanism, a comprehensive evaluation was conducted on 38 Populus germplasm resources with cuttings cultured in the greenhouse. Genetic differences between poplar clones with good ARD and with poor ARD were explored from the perspectives of genomics and transcriptomics. By cluster analysis of the seven adventitious roots (AR) traits, the materials were classified into three clusters, of which cluster I indicated excellent AR developmental capability and promising breeding potential, especially P.×canadensis 'Guariento', P. 'jingtong1', P. deltoides 'Zhongcheng5', P. deltoides 'Zhongcheng2'. At the genomic level, the cross-population composite likelihood ratio (XP-CLR) analysis identified 1944 positive selection regions related to ARD, and variation detection analysis identified 3426 specific SNPs and 687 specific Indels in the clones with good ARD, 3212 specific SNPs and 583 specific Indels in the clones with poor ARD, respectively. Through XP-CLR, variation detection, and weighted gene co-expression network analysis based on transcriptome data, eight major putative genes associated with poplar ARD were primary identified, and a co-expression network of eight genes was constructed, it was discovered that CSD1 and WRKY6 may be important in the ARD. Subsequently, we confirmed that SWEET17 had a non-synonymous mutation at the site of 928,404 in the clones with poor ARD, resulting in an alteration of the amino acid. After exploring phenotypic differences and the genetic variation of adventitious roots development in different poplar clones, this study provides valuable reference information for future poplar breeding and genetic improvement.

PagJAZ5 regulates cambium activity through coordinately modulating cytokinin concentration and signaling in poplar.

Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells. Overexpression (OE) of PagJAZ5m (insensitive to JA) increased cambium activity and xylem differentiation, while jaz mutants showed opposite results. Transcriptome analyses revealed that cytokinin oxidase/dehydrogenase (CKXs) and type-A response regulators (RRs) were downregulated in PagJAZ5m OE plants. The bioactive cytokinins were significantly increased in PagJAZ5m overexpressing plants and decreased in jaz5 mutants, compared with that in 84K plants. The PagJAZ5 directly interact with PagMYC2a/b and PagWOX4b. Further, we found that the PagRR5 is regulated by PagMYC2a and PagWOX4b and involved in the regulation of xylem development. Our results showed that PagJAZ5 can increase cambium activity and promote xylem differentiation through modulating cytokinin level and type-A RR during wood formation in poplar.

MicroR-1199-5p targeting SRD5A2 promotes the biological behavior and EMT of hypospadias cells.

Hypospadias, an oft-occurring penis anomaly, ranks among neonatal's foremost birth defects. The SRD5A2 can affect male reproductive system development and is abnormally expressed in its epithelial cells. This study exploration aimed at understanding the role of SRD5A2 in the development of hypospadias from a molecular perspective. SRD5A2 levels in hypospadias primary cells were analyzed by Western blot, while targeted interaction with miR-1199-5p was ascertained by dual-luciferase gene reporter assay. In vitro biological experiments were used to confirm the biological function of SRD5A2 in hypospadias. SRD5A2 expression was significantly upregulated, and miR-1199-5p expression was significantly downregulated in hypospadias primary cells. Intervention of SRD5A2 expression can affect cell proliferation, migration, invasion, EMT, and the expression of cell cycle-related proteins. Additionally, we found that SRD5A2 is regulated by upstream miR-1199-5p and can enhance the effect of SRD5A2 on hypospadias cells. Conclusions Silencing SRD5A2 promotes cell proliferation, invasion, and migration blocks the cell cycle at the G1 phase, and simultaneously promotes EMT, cell cycle, and cell proliferation-related protein expression. The biological function of SRD5A2 in hypospadias cells is regulated by miR-1199-5p. SRD5A2 may be an effective therapeutic target for hypospadias.

Combining GS-assisted GWAS and transcriptome analysis to mine candidate genes for nitrogen utilization efficiency in Populus cathayana.

BACKGROUND: Forest trees such as poplar, shrub willow, et al. are essential natural resources for sustainable and renewable energy production, and their wood can reduce dependence on fossil fuels and reduce environmental pollution. However, the productivity of forest trees is often limited by the availability of nitrogen (N), improving nitrogen use efficiency (NUE) is an important way to address it. Currently, NUE genetic resources are scarce in forest tree research, and more genetic resources are urgently needed. RESULTS: Here, we performed genome-wide association studies (GWAS) using the mixed linear model (MLM) to identify genetic loci regulating growth traits in Populus cathayana at two N levels, and attempted to enhance the signal strength of single nucleotide polymorphism (SNP) detection by performing genome selection (GS) assistance GWAS. The results of the two GWAS analyses identified 55 and 40 SNPs that were respectively associated with plant height (PH) and ground diameter (GD), and 92 and 69 candidate genes, including 30 overlapping genes. The prediction accuracy of the GS model (rrBLUP) for phenotype exceeds 0.9. Transcriptome analysis of 13 genotypes under two N levels showed that genes related to carbon and N metabolism, amino acid metabolism, energy metabolism, and signal transduction were differentially expressed in the xylem of P. cathayana under N treatment. Furthermore, we observed strong regional patterns in gene expression levels of P. cathayana, with significant differences between different regions. Among them, P. cathayana in Longquan region exhibited the highest response to N. Finally, through weighted gene co-expression network analysis (WGCNA), we identified a module closely related to the N metabolic process and eight hub genes. CONCLUSIONS: Integrating the GWAS, RNA-seq and WGCNA data, we ultimately identified four key regulatory genes (PtrNAC123, PtrNAC025, Potri.002G233100, and Potri.006G236200) involved in the wood formation process, and they may affect P. cathayana growth and wood formation by regulating nitrogen metabolism. This study will provide strong evidence for N regulation mechanisms, and reliable genetic resources for growth and NUE genetic improvement in poplar.

Circ_0058063 regulates the development of esophageal cancer through miR-377-3p/HOXA1 axis.

Esophageal cancer is one of the deadliest cancers. Circular RNA (CircRNA) can be used as a tumor marker. Therefore, this provides an important idea for our research. Real-time quantitative PCR (RT-qPCR) was used to analyze the expression of circ_0058063, miR-377-3p and homeobox protein Hox-A1 (HOXA1), western blot was used to analyze the protein levels of HOXA1 and cyclinD1, B cell leukemia/lymphoma 2 associated X (Bax). Cell Counting Kit-8 (CCK-8) assay, colony formation assay and wound healing assay were used to analyze cell proliferation and migration; apoptosis was analyzed by flow cytometry. Dual-luciferase reporter assays were performed to analyze the luciferase activities. Transwell assay was used to analyze the cell invasion. A glycolysis metabolism assay was used to analyze cell glycolysis ability. Xenograft models were used to validate the effect of circ_0009035 in the growth of esophageal cancer in vivo . Circ_0009035 and HOXA1 were upregulated, while miR-377 was downregulated in esophageal cancer.. Circ_0058063 targeted miR-377-3p, and HOX4 was a target of miR-377-3p. Knockdown of circ_0058063 inhibited migration, invasion and proliferation and promoted apoptosis of esophageal cancer cells. MiR-377-3p inhibition or HOXA1 overexpression could restore the effect of si-circ_0058063 on esophageal cancer cells. Knockdown of circ_0058063 repressed the growth of esophageal cancer tumors in vivo. Our study found that circ_0058063 could regulate the expression of HOXA1 by targeting miR-377-3p, thereby affecting the progress of esophageal cancer.

Global Mapping of Structures and Properties of Crystal Materials.

Understanding materials' composition-structure-function relationships is of critical importance for the design and discovery of novel functional materials. While most such studies focus on individual materials, we conducted a global mapping study of all known materials deposited in the Materials Project database to investigate their distributions in the space of a set of seven compositional, structural, physical, and neural latent descriptors. These two-dimensional materials maps along with their density maps allow us to illustrate the distribution of the patterns and clusters of different shapes, which indicates the propensity of these materials and the tinkering history of existing materials. We then overlap the material properties such as composition prototypes and piezoelectric properties over the background material maps to study the relationships of how material compositions and structures affect their physical properties. We also use these maps to study the spatial distributions of properties of known inorganic materials, in particular those of local vicinities in structural space such as structural density and functional diversity. These maps provide a uniquely comprehensive overview of materials and space and thus reveal previously undescribed fundamental properties. Our methodology can be easily extended by other researchers to generate their own global material maps with different background maps and overlap properties for both distribution understanding and cluster-based new material discovery. The source code for feature generation and generated maps is available at https://github.com/usccolumbia/matglobalmapping.

Risk factors for postoperative complications following one-stage proximal hypospadias repair involving the disconnection of the urethral plate: a retrospective study.

BACKGROUND: Children with hypospadias are at risk of serious physical and mental health problems, including abnormal urination, sexual dysfunction, and infertility. The sole available treatment is the surgical restoration of genital appearance and function. Proximal hypospadias (PH) correction is more challenging and carries a higher risk of complications than does distal hypospadias correction, with a higher likelihood of postoperative complications requiring additional surgery, resulting in considerable economic and psychological strain for families. Herein, we aimed to identify factors associated with complications following one-stage PH repair with urethral plate disconnection. METHODS: We retrospectively analyzed data from 236 children who underwent PH repair at our center between December 2020 and December 2022. We collected information on age, surgical procedure, length of the reconstructed urethra (LRU), glans width (GW), ventral curvature, surgical approach, preoperative androgen use, suture type, presence of prostatic utricle, body mass index, season of surgery, anesthesia type, low birth weight, preterm birth, follow-up period, and complications. Surgical complications included urethral fistulas, urethral diverticula, anastomotic strictures, urethral strictures, glans dehiscence, and penile curvature recurrences. The study population was divided into complication and no-complication groups, and univariate and multivariate analyses were conducted. RESULTS: Of the 236 patients with PH who had a median follow-up of 10.0 (8.0, 14.0) months, 79 were included (33.5%) in the complication group and 157 were included (66.5%) in the no-complication group. In the univariate analysis, age (P < 0.001), LRU (P < 0.001), degree of penile curvature (P = 0.049), and PH with prostatic utricle (P = 0.014) were significantly associated with complications after PH repair. In the multivariate logistic regression analysis, LRU (P<0.001, odds ratio [OR] = 3.396, 95% confidence interval [CI]: 2.229-5.174) and GW (P = 0.004, OR = 0.755, 95%CI: 0.625-0.912) were independent factors influencing postoperative complications. The optimal LRU threshold was 4.45 cm (area under the curve, 0.833; sensitivity, 0.873; specificity, 0.873; P<0.001, OR = 3.396, 95% CI: 2.229-5.174). CONCLUSIONS: LRU and GW are independent factors affecting PH complications. An LRU of < 4.45 cm and an increased GW can reduce the risk of complications.

QTL mapping of drought-related traits in the hybrids of Populus deltoides 'Danhong'×Populus simonii 'Tongliao1'.

BACKGROUND: Poplar trees provide a large amount of wood material, but many parts of the world are arid or semi-arid areas because of insufficient annual precipitation, which seriously affects the growth of poplar trees. Populus simonii 'Tongliao1' shows strong tolerance to stress environments, and Populus deltoides 'Danhong' shows a stronger growth rate in a suitable environment. To identify drought tolerance-related QTLs and genes, an F1 population derived from the cross between the 'Danhong' and 'Tongliao 1' Populus was assessed under drought stress. RESULTS: We measured drought-related traits such as the relative height growth, relative diameter growth, leaf senescence number, specific leaf area, and leaf relative water content in the population under control and drought environments. The results showed that drought stress reduced the plant height relative growth, ground diameter relative growth, specific leaf area and leaf relative water content and increased the number of leaf drops. A total of 208 QTLs were identified by QTL mapping analysis, and they consisted of 92, 63 and 53 QTLs under control, drought stress treatment and drought index conditions, respectively. A molecular identification marker for drought tolerance, np2841, which was associated with a QTL (qDLRWC-LG10-1) for relative leaf water content, was initially developed. We mined 187 candidate genes for QTL regions of five traits under a drought environment. The reference genome annotation for Populus trichocarpa and a homologous gene analysis of Arabidopsis thaliana identified two candidate genes, Potri.003G171300 and Potri.012G123900, with significant functions in response to drought stress. We identified five key regulatory genes (Potri.006G273500, Potri.007G111500, Potri.007G111600, Potri.007G111700, and Potri.007G111800) related to drought tolerance through the poplar coexpression network. CONCLUSION: In this study, our results indicate that the QTLs can effectively enhance the drought tolerance of poplar. It is a step closer towards unravelling the genetic basis of poplar drought tolerance-related traits, and to providing validated candidate genes and molecular markers for future genetic improvement.

PagWOX11/12a positively regulates the PagSAUR36 gene that enhances adventitious root development in poplar.

Adventitious root (AR) development is an extremely complex biological process that is affected by many intrinsic factors and extrinsic stimuli. Some WUSCHEL-related homeobox (WOX) transcription factors have been reported to play important roles in AR development, but their functional relationships with auxin signaling are poorly understood, especially the developmental plasticity of roots in response to adversity stress. Here, we identified that the WOX11/12a-SMALL AUXIN UP RNA36 (SAUR36) module mediates AR development through the auxin pathway in poplar, as well as under salt stress. PagWOX11/12a displayed inducible expression during AR development, and overexpression of PagWOX11/12a significantly promoted AR development and increased salt tolerance in poplar, whereas dominant repression of PagWOX11/12a produced the opposite phenotype. PagWOX11/12a proteins directly bind to the SAUR36 promoter to regulate SAUR36 transcription, and this binding was enhanced during salt stress. Genetic modification of PagWOX11/12a-PagSAUR36 expression revealed that the PagWOX11/12a-PagSAUR36 module is crucial for controlling AR development via the auxin pathway. Overall, our results indicate that a novel WOX11-SAUR-auxin signaling regulatory module is required for AR development in poplar. These findings provide key insights and a better understanding of the involvement of WOX11 in root developmental plasticity in saline environments.

TCSP: a Template-Based Crystal Structure Prediction Algorithm for Materials Discovery.

Fast and accurate crystal structure prediction (CSP) algorithms and web servers are highly desirable for the exploration and discovery of new materials out of the infinite chemical design space. However, currently, the computationally expensive first-principles calculation-based CSP algorithms are applicable to relatively small systems and are out of reach of most materials researchers. Several teams have used an element substitution approach for generating or predicting new structures, but usually in an ad hoc way. Here we develop a template-based crystal structure prediction (TCSP) algorithm and its companion web server, which makes this tool accessible to all materials researchers. Our algorithm uses elemental/chemical similarity and oxidation states to guide the selection of template structures and then rank them based on the substitution compatibility and can return multiple predictions with ranking scores in a few minutes. A benchmark study on the 98290 formulas of the Materials Project database using leave-one-out evaluation shows that our algorithm can achieve high accuracy (for 13145 target structures, TCSP predicted their structures with root-mean-square deviation < 0.1) for a large portion of the formulas. We have also used TCSP to discover new materials of the Ga-B-N system, showing its potential for high-throughput materials discovery. Our user-friendly web app TCSP can be accessed freely at www.materialsatlas.org/crystalstructure on our MaterialsAtlas.org web app platform.

Studying patterns and predictors of HIV viral suppression using A Big Data approach: a research protocol.

BACKGROUND: Given the importance of viral suppression in ending the HIV epidemic in the US and elsewhere, an optimal predictive model of viral status can help clinicians identify those at risk of poor viral control and inform clinical improvements in HIV treatment and care. With an increasing availability of electronic health record (EHR) data and social environmental information, there is a unique opportunity to improve our understanding of the dynamic pattern of viral suppression. Using a statewide cohort of people living with HIV (PLWH) in South Carolina (SC), the overall goal of the proposed research is to examine the dynamic patterns of viral suppression, develop optimal predictive models of various viral suppression indicators, and translate the models to a beta version of service-ready tools for clinical decision support. METHODS: The PLWH cohort will be identified through the SC Enhanced HIV/AIDS Reporting System (eHARS). The SC Office of Revenue and Fiscal Affairs (RFA) will extract longitudinal EHR clinical data of all PLWH in SC from multiple health systems, obtain data from other state agencies, and link the patient-level data with county-level data from multiple publicly available data sources. Using the deidentified data, the proposed study will consist of three operational phases: Phase 1: "Pattern Analysis" to identify the longitudinal dynamics of viral suppression using multiple viral load indicators; Phase 2: "Model Development" to determine the critical predictors of multiple viral load indicators through artificial intelligence (AI)-based modeling accounting for multilevel factors; and Phase 3: "Translational Research" to develop a multifactorial clinical decision system based on a risk prediction model to assist with the identification of the risk of viral failure or viral rebound when patients present at clinical visits. DISCUSSION: With both extensive data integration and data analytics, the proposed research will: (1) improve the understanding of the complex inter-related effects of longitudinal trajectories of HIV viral suppressions and HIV treatment history while taking into consideration multilevel factors; and (2) develop empirical public health approaches to achieve ending the HIV epidemic through translating the risk prediction model to a multifactorial decision system that enables the feasibility of AI-assisted clinical decisions.

Crystal Structure Prediction Using an Age-Fitness Multiobjective Genetic Algorithm and Coordination Number Constraints.

Crystal structure prediction (CSP) has emerged as one of the most important approaches for discovering new materials. CSP algorithms based on evolutionary algorithms and particle swarm optimization have discovered a great number of new materials. However, these algorithms based on ab initio calculation of free energy are inefficient. Moreover, they have severe limitations in terms of scalability. We recently proposed a promising crystal structure prediction method based on atomic contact maps, using global optimization algorithms to search for the Wyckoff positions by maximizing the match between the contact map of the predicted structure and the contact map of the true crystal structure. However, our previous contact-map-based CSP algorithms have two major limitations: (1) the loss of search capability due to getting trapped in local optima; (2) it only uses the connection of atoms in the unit cell to predict the crystal structure, ignoring the chemical environment outside the unit cell, which may lead to unreasonable coordination environments. Herein, we propose a novel multiobjective genetic algorithm for contact-map-based crystal structure prediction by optimizing three objectives, including contact map match accuracy, individual age, and coordination number match. Furthermore, we assign the age values to all the individuals of the GA and try to minimize the age, aiming to avoid the premature convergence problem. Our experimental results show that compared to our previous CMCrystal algorithm, our multiobjective crystal structure prediction algorithm (CMCrystalMOO) can reconstruct the crystal structure with higher quality and alleviate the problem of premature convergence. The source code is open sourced and can be accessed at https://github.com/usccolumbia/MOOCSP.

Transcriptome Analysis of Populus euphratica under Salt Treatment and PeERF1 Gene Enhances Salt Tolerance in Transgenic Populus alba × Populus glandulosa.

Populus euphratica is mainly distributed in desert environments with dry and hot climate in summer and cold in winter. Compared with other poplars, P. euphratica is more resistant to salt stress. It is critical to investigate the transcriptome and molecular basis of salt tolerance in order to uncover stress-related genes. In this study, salt-tolerant treatment of P. euphratica resulted in an increase in osmo-regulatory substances and recovery of antioxidant enzymes. To improve the mining efficiency of candidate genes, the analysis combining both the transcriptome WGCNA and the former GWAS results was selected, and a range of key regulatory factors with salt resistance were found. The PeERF1 gene was highly connected in the turquoise modules with significant differences in salt stress traits, and the expression levels were significantly different in each treatment. For further functional verification of PeERF1, we obtained stable overexpression and dominant suppression transgenic lines by transforming into Populus alba × Populusglandulosa. The growth and physiological characteristics of the PeERF1 overexpressed plants were better than that of the wild type under salt stress. Transcriptome analysis of leaves of transgenic lines and WT revealed that highly enriched GO terms in DEGs were associated with stress responses, including abiotic stimuli responses, chemical responses, and oxidative stress responses. The result is helpful for in-depth analysis of the salt tolerance mechanism of poplar. This work provides important genes for poplar breeding with salt tolerance.

Genome-Wide Analysis of the AAAP Gene Family in Populus and Functional Analysis of PsAAAP21 in Root Growth and Amino Acid Transport.

The adventitious root (AR) is the basis for successful propagation by plant cuttings and tissue culture and is essential for maintaining the positive traits of a variety. Members of the amino acid/auxin permease (AAAP) gene family play indispensable roles in various plant metabolisms and have few studies on root growth and amino acid transport. In this study, with a systematic bioinformatics analysis of the Populus AAAP family, 83 PtrAAAPs were identified from Populus trichocarpa and grouped into 8 subfamilies. Subsequently, chromosomal distribution, genetic structure, cis-elements analysis, and expression pattern analysis of the AAAP family were performed and the potential gene AAAP21 regulating root development was screened by combining the results of RNA-Seq and QTL mapping. PsAAAP21 was proven as promoting root development by enhancing AR formation. Differentially expressed genes (DEGs) from RNA-seq results of overexpressing lines were enriched to multiple amino acid-related pathways, and the amino acid treatment to transgenic lines indicated that PsAAAP21 regulated amino acid transport, including tyrosine, methionine, and arginine. Analysis of the AAAP gene family provided a theoretical basis for uncovering the functions of AAAP genes. The identification of PsAAAP21 on root promotion and amino acid transport in Populus will help with breeding new woody plant species with strong rooting ability.

Deep learning pan-specific model for interpretable MHC-I peptide binding prediction with improved attention mechanism.

Accurate prediction of peptide binding affinity to the major histocompatibility complex (MHC) proteins has the potential to design better therapeutic vaccines. Previous work has shown that pan-specific prediction algorithms can achieve better prediction performance than other approaches. However, most of the top algorithms are neural networks based black box models. Here, we propose DeepAttentionPan, an improved pan-specific model, based on convolutional neural networks and attention mechanisms for more flexible, stable and interpretable MHC-I binding prediction. With the attention mechanism, our ensemble model consisting of 20 trained networks achieves high and more stabilized prediction performance. Extensive tests on IEDB's weekly benchmark dataset show that our method achieves state-of-the-art prediction performance on 21 test allele datasets. Analysis of the peptide positional attention weights learned by our model demonstrates its capability to capture critical binding positions of the peptides, which leads to mechanistic understanding of MHC-peptide binding with high alignment with experimentally verified results. Furthermore, we show that with transfer learning, our pan model can be fine-tuned for alleles with few samples to achieve additional performance improvement. DeepAttentionPan is freely available as an open-source software at https://github.com/jjin49/DeepAttentionPan.

Lattice Thermal Conductivity Prediction Using Symbolic Regression and Machine Learning.

Prediction models of lattice thermal conductivity (κL) have wide applications in the discovery of thermoelectrics, thermal barrier coatings, and thermal management of semiconductors. However, κL is notoriously difficult to predict. Although classic models such as the Debye-Callaway model and the Slack model have been used to approximate the κL of inorganic compounds, their accuracy is far from being satisfactory. Herein we propose a genetic programming-based symbolic regression (SR) approach for finding analytical κL models and compare them with multilayer perceptron neural networks and random forest regression models using a hybrid cross-validation (CV) approach including both K-fold CV and holdout validation. Four formulae have been discovered by our SR approach that outperform the Slack formula as evaluated on our dataset. Through the analysis of our models' performance and the formulae generated, we found that the trained formulae successfully reproduce the correct physical law that governs the lattice thermal conductivity of materials. We also systematically show that currently extrapolative prediction over datasets with different distributions as the training set remains to be a big challenge for both SR and machine learning-based prediction models.

PagGRF12a interacts with PagGIF1b to regulate secondary xylem development through modulating PagXND1a expression in Populus alba × P. glandulosa.

Growth-regulating factors (GRFs) are important regulators of plant development and growth, but their possible roles in xylem development in woody plants remain unclear. Here, we report that Populus alba × Papulus glandulosa PagGRF12a negatively regulates xylem development in poplar. PagGRF12a is expressed in vascular tissues. Compared to non-transgenic control plants, transgenic poplar plants overexpressing PagGRF12a exhibited reduced xylem width and plants with repressed expression of PagGRF12a exhibited increased xylem width. Xylem NAC domain 1 (XND1) encodes a NAC domain transcription factor that regulates xylem development and transcriptional analyses revealed that PagXND1a is highly upregulated in PagGRF12a-overexpressing plants and downregulated in PagGRF12a-suppressed plants, indicating that PagGRF12a may regulate xylem development through PagXND1a. Transient transcriptional assays and chromatin immunoprecipitation-polymerase chain reaction assays confirmed that PagGRF12a directly upregulates PagXND1a. In addition, PagGRF12a interacts with the GRF-Interacting Factor (GIF) PagGIF1b, and this interaction enhances the effects of PagGRF12a on PagXND1a. Our results indicate that PagGRF12a inhibits xylem development by upregulating the expression of PagXND1a.

Genome resequencing reveals demographic history and genetic architecture of seed salinity tolerance in Populus euphratica.

Populus euphratica is a dominant tree species in desert riparian forests and possesses extraordinary adaptation to salinity stress. Exploration of its genomic variation and molecular underpinning of salinity tolerance is important for elucidating population evolution and identifying stress-related genes. Here, we identify approximately 3.15 million single nucleotide polymorphisms using whole-genome resequencing. The natural populations of P. euphratica in northwest China are divided into four distinct clades that exhibit strong geographical distribution patterns. Pleistocene climatic fluctuations and tectonic deformation jointly shaped the extant genetic patterns. A seed germination rate-based salinity tolerance index was used to evaluate seed salinity tolerance of P. euphratica and a genome-wide association study was implemented. A total of 38 single nucleotide polymorphisms were associated with seed salinity tolerance and were located within or near 82 genes. Expression profiles showed that most of these genes were regulated under salt stress, revealing the genetic complexity of seed salinity tolerance. Furthermore, DEAD-box ATP-dependent RNA helicase 57 and one undescribed gene (CCG029559) were demonstrated to improve the seed salinity tolerance in transgenic Arabidopsis. These results provide new insights into the demographic history and genetic architecture of seed salinity tolerance in desert poplar.