Genomic dissection of additive and non-additive genetic effects and genomic prediction in an open-pollinated family test of Japanese larch.

Genomic dissection of genetic effects on desirable traits and the subsequent use of genomic selection hold great promise for accelerating the rate of genetic improvement of forest tree species. In this study, a total of 661 offspring trees from 66 open-pollinated families of Japanese larch (Larix kaempferi (Lam.) Carrière) were sampled at a test site. The contributions of additive and non-additive effects (dominance, imprinting and epistasis) were evaluated for nine valuable traits related to growth, wood physical and chemical properties, and competitive ability using three pedigree-based and four Genomics-based Best Linear Unbiased Predictions (GBLUP) models and used to determine the genetic model. The predictive ability (PA) of two genomic prediction methods, GBLUP and Reproducing Kernel Hilbert Spaces (RKHS), was compared. The traits could be classified into two types based on different quantitative genetic architectures: for type I, including wood chemical properties and Pilodyn penetration, additive effect is the main source of variation (38.20-67.46%); for type II, including growth, competitive ability and acoustic velocity, epistasis plays a significant role (50.76-91.26%). Dominance and imprinting showed low to moderate contributions (< 36.26%). GBLUP was more suitable for traits of type I (PAs = 0.37-0.39 vs. 0.14-0.25), and RKHS was more suitable for traits of type II (PAs = 0.23-0.37 vs. 0.07-0.23). Non-additive effects make no meaningful contribution to the enhancement of PA of GBLUP method for all traits. These findings enhance our current understanding of the architecture of quantitative traits and lay the foundation for the development of genomic selection strategies in Japanese larch.

The complete chloroplast genome sequence of Malus × adstringens Zabel 'Hopa' (Rosaceae).

Malus × adstringens Zabel 'Hopa' is an important crabapple cultivar with significant ornamental value. Here, we assembled its complete chloroplast (cp) genome using the next-generation sequencing technology to clarify the phylogenetic relationships in Malus. The total length of the complete chloroplast genome was 160,230 base pairs (bp) with a GC content of 36.50%, consisting of a large single-copy (LSC) region with a sequence length of 88,310 bp, a small single-copy (SSC) region with a sequence length of 19,196 bp, and a pair of inverted repeat (IR) regions of 26,362 bp. The complete chloroplast genome contained 128 genes, namely 84 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. In addition, 73 SSRs were found in the M. 'Hopa' cp genome. The phylogenetic relationship of M. 'Hopa' in Malus is closely related to M. spectabilis (Aiton) Borkh. and then to M. sieversii (Lebed.) M. Roem. Our results demonstrate that it is feasible to resolve the phylogenetic relationships of crabapple cultivars and identify their putative maternal lineages using cp genomic data.

Myeloid Vamp3 deletion attenuates CFA-induced inflammation and pain in mice via ameliorating macrophage infiltration and inflammatory cytokine production.

Persistent inflammation and associated pain significantly impact individuals' quality of life, posing substantial healthcare challenges. Proinflammatory cytokines, released by activated macrophages, play crucial roles in the development of chronic inflammatory conditions such as rheumatoid arthritis. To identify and evaluate potential therapeutic interventions targeting this process for mitigating inflammation and pain, we created myeloid cell-specific knockout of Vamp3 (vesicle-associated membrane protein 3) mice (Vamp3 Δmyel) by crossing LysM-Cre mice with newly engineered Vamp3flox/flox mice. Bone marrow-derived macrophages and peritoneal resident macrophages from Vamp3 Δmyel mice exhibited a significant reduction in TNF-α and IL-6 release compared to control mice. Moreover, Vamp3 deficiency led to decreased paw edema and ankle joint swelling induced by intraplantar injection of complete Freund's adjuvant (CFA). Furthermore, Vamp3 depletion also mitigated CFA-induced mechanical allodynia and thermal hyperalgesia. Mechanistically, Vamp3 loss ameliorated the infiltration of macrophages in peripheral sites of the hind paw and resulted in reduced levels of TNF-α and IL-6 in the CFA-injected paw and serum. RT-qPCR analysis demonstrated downregulation of various inflammation-associated genes, including TNF-α, IL-6, IL-1ß, CXCL11, TIMP-1, COX-2, CD68, and CD54 in the injected paw at the test day 14 following CFA administration. These findings highlight the novel role of Vamp3 in regulating inflammatory responses and suggest it as a potential therapeutic target for the development of novel Vamp-inactivating therapeutics, with potential applications in the management of inflammatory diseases.

PH13 improves soybean shade traits and enhances yield for high-density planting at high latitudes.

Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.

Meta-analysis of the relations between gut microbiota and pathogens and Parkinson's disease.

BACKGROUND: The motor symptoms in patients with Parkinson's disease (PD) are commonly preceded by gastrointestinal (GI) symptoms. The enteric nervous system (ENS) has also been reported to exhibit neuropathological characteristics of PD. OBJECTIVES: To evaluate the relationship between the incidence of parkinsonism and alteration in gut microbiota and pathogens. MATERIAL AND METHODS: Studies in different languages that evaluate the relationship between gut microorganisms and PD were included into this meta-analysis. The outcomes of these studies were analyzed using a random effects model; it was also used to calculate the mean difference (MD) with 95% confidence interval (95% CI) in order to quantify the impact of different rehabilitation techniques on clinical parameters. Dichotomous and continuous models were used for the analysis of extracted data. RESULTS: A total of 28 studies were included in our analysis. The analysis of small intestinal bacterial overgrowth showed a significant correlation with Parkinson's subjects compared with controls (p < 0.001). In addition, the presence of Helicobacter pylori (HP) infection was significantly related to the Parkinson's group (p < 0.001). On the other hand, there was a significantly higher abundance level of Bifidobacteriaceae (p = 0.008), Verrucomicrobiaceae (p < 0.001) and Christensenellaceae (p = 0.003) in Parkinson's subjects. In contrast, a significantly lower abundance levels in Parkinson's subjects were found in Faecalibacterium (p = 0.03), Lachnospiraceae (p = 0.005) and Prevotellaceae (p = 0.005). No significant difference was related to Ruminococcaceae. CONCLUSION: Parkinson's subjects showed a higher degree of alteration of gut microbiota and pathogens compared with normal human subjects. Future multicenter randomized trials are needed.

Glutamine-Based Metabolism Normalization and Oxidative Stress Alleviation by Self-Assembled Bilirubin/V9302 Nanoparticles for Psoriasis Treatment.

Psoriasis is an immune-mediated chronic inflammatory skin disorder characterized by epidermal hyperplasia and infiltration of inflammatory cells. Even though the pathogenesis remains unclear, T helper 17 (Th17) cells-mediated inflammation and keratinocyte-involved proliferation are considered to play key roles during the occurrence and the development of psoriasis. Therefore, suppressing the infiltration/function of Th17 and the abnormal hyperplasia of keratinocytes can be a rational strategy for ameliorating and treating psoriasis. In this study, a self-assembly nanoparticle (BVn) is developed with bilirubin (an endogenous antioxidant) and V9302 (a blocker of ASCT2, an amino acid transporter mediating glutamine influx for providing energy and activating mammalian target of rapamycin [mTOR] pathway) to intervene the local metabolism and alleviate oxidative stress for psoriasis treatment. BVn effectively suppresses inflammatory keratinocyte proliferation and scavenges excess reactive oxygen species (ROS). In the in vivo psoriasis mouse model, BVn shows increased permeation and delayed retention in the psoriatic lesion and reverses the psoriasis-related symptoms, evidenced by the normalized keratinocyte condition and decreased Th17 infiltration/activation. Mechanism study indicates that BVn not only cut off the energy supply but also suppressed cell proliferation or lymph cell expansion by deactivating mTOR pathway, besides alleviated oxidative stress. BVn-based glutamine metabolism modulation strategy offers a promising strategy for psoriasis therapy.

Time series canopy phenotyping enables the identification of genetic variants controlling dynamic phenotypes in soybean.

Advances in plant phenotyping technologies are dramatically reducing the marginal costs of collecting multiple phenotypic measurements across several time points. Yet, most current approaches and best statistical practices implemented to link genetic and phenotypic variation in plants have been developed in an era of single-time-point data. Here, we used time-series phenotypic data collected with an unmanned aircraft system for a large panel of soybean (Glycine max (L.) Merr.) varieties to identify previously uncharacterized loci. Specifically, we focused on the dissection of canopy coverage (CC) variation from this rich data set. We also inferred the speed of canopy closure, an additional dimension of CC, from the time-series data, as it may represent an important trait for weed control. Genome-wide association studies (GWASs) identified 35 loci exhibiting dynamic associations with CC across developmental stages. The time-series data enabled the identification of 10 known flowering time and plant height quantitative trait loci (QTLs) detected in previous studies of adult plants and the identification of novel QTLs influencing CC. These novel QTLs were disproportionately likely to act earlier in development, which may explain why they were missed in previous single-time-point studies. Moreover, this time-series data set contributed to the high accuracy of the GWASs, which we evaluated by permutation tests, as evidenced by the repeated identification of loci across multiple time points. Two novel loci showed evidence of adaptive selection during domestication, with different genotypes/haplotypes favored in different geographic regions. In summary, the time-series data, with soybean CC as an example, improved the accuracy and statistical power to dissect the genetic basis of traits and offered a promising opportunity for crop breeding with quantitative growth curves.

Low-condensed lignin and high-purity cellulose production from poplar by synergistic deep eutectic solvent-hydrogenolysis pretreatment.

This paper presented a green and environmentally friendly method to obtain lignin with a structure similar to milled wood lignin (MWL) and high-purity cellulose from biomass in a two-step process. The first step, maleic acid (MA), choline chloride (ChCl), and ethylene glycol (EG) ternary deep eutectic solvent (DES) pretreatment was performed to obtain lignin with less-condensed structure. The results showed that the obtained lignin had similar properties to MWL under the condition (MA/ChCl/EG = 1:5:15, 80°C, 10 h). The DES recovered still had good cycle performance. The second step, the cellulose-rich residue was hydrogenated with isopropanol-water solvent and Raney nickel to obtain high-purity cellulose. The results showed that the purity of cellulose obtained by catalytic hydrogenolysis was > 94%. The glucose yield after enzymatic hydrolysis was 243.72 mg/g, which was 14.7 times higher than the untreated poplar. Overall, this work was of great significance for the effective separation of biomass.

Spatiotemporal regulation of insulin signaling by liquid-liquid phase separation.

Insulin signals through its receptor to recruit insulin receptor substrates (IRS) and phosphatidylinositol 3-kinase (PI3K) to the plasma membrane for production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) from phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], which consequently activates protein kinase B (PKB). How insulin signals transduce from the plasma membrane into the cytoplasm is not clearly understood. Here we show that liquid-liquid phase separation (LLPS) plays a critical role in spatiotemporal control of insulin signaling through regulating multiple components including IRS1. Both protein concentration and insulin stimulation can drive the formation of intracellular IRS1 condensates through LLPS. Components including PI(4,5)P2, p85-PI3K and PDK1 are constitutively present in IRS1 condensates whereas production of PIP3 and recruitment of PKB in them are induced by insulin. Thus, IRS1 condensates function as intracellular signal hubs to mediate insulin signaling, whose formation is impaired in insulin resistant cells. Collectively, these data reveal an important function of LLPS in spatiotemporal control of insulin signaling.

The RalGAPα1-RalA signal module protects cardiac function through regulating calcium homeostasis.

Sarcoplasmic/endoplasmic reticulum calcium ATPase SERCA2 mediates calcium re-uptake from the cytosol into sarcoplasmic reticulum, and its dysfunction is a hallmark of heart failure. Multiple factors have been identified to modulate SERCA2 activity, however, its regulation is still not fully understood. Here we identify a Ral-GTPase activating protein RalGAPα1 as a critical regulator of SERCA2 in cardiomyocytes through its downstream target RalA. RalGAPα1 is induced by pressure overload, and its deficiency causes cardiac dysfunction and exacerbates pressure overload-induced heart failure. Mechanistically, RalGAPα1 regulates SERCA2 through direct interaction and its target RalA. Deletion of RalGAPα1 decreases SERCA2 activity and prolongs calcium re-uptake into sarcoplasmic reticulum. GDP-bound RalA, but not GTP-bound RalA, binds to SERCA2 and activates the pump for sarcoplasmic reticulum calcium re-uptake. Overexpression of a GDP-bound RalAS28N mutant in the heart preserves cardiac function in a mouse model of heart failure. Our findings have therapeutic implications for treatment of heart failure.

Genome-Wide Association Studies of Salt-Alkali Tolerance at Seedling and Mature Stages in Brassica napus.

Most plants are sensitive to salt-alkali stress, and the degree of tolerance to salt-alkali stress varies from different species and varieties. In order to explore the salt-alkali stress adaptability of Brassica napus, we collected the phenotypic data of 505 B. napus accessions at seedling and mature stages under control, low and high salt-alkali soil stress conditions in Inner Mongolia of China. Six resistant and 5 sensitive materials, respectively, have been identified both in Inner Mongolia and Xinjiang Uygur Autonomous Region of China. Genome-wide association studies (GWAS) for 15 absolute values and 10 tolerance coefficients (TCs) of growth and agronomic traits were applied to investigate the genetic basis of salt-alkali tolerance of B. napus. We finally mapped 9 significant QTLs related to salt-alkali stress response and predicted 20 candidate genes related to salt-alkali stress tolerance. Some important candidate genes, including BnABA4, BnBBX14, BnVTI12, BnPYL8, and BnCRR1, were identified by combining sequence variation annotation and expression differences. The identified valuable loci and germplasms could be useful for breeding salt-alkali-tolerant B.napus varieties. This study laid a foundation for understanding molecular mechanism of salt-alkali stress adaptation and provides rich genetic resources for the large-scale production of B. napus on salt-alkali land in the future.

Third Generation Genome Sequencing Reveals That Endobacteria in Nematophagous Fungi Esteya vermicola Contain Multiple Genes Encoding for Nematicidal Proteins.

Esteya vermicola is the first recorded endoparasitic nematophagous fungus with high infectivity capacity, attacking the pinewood nematode Bursaphelenchus xylophilus which causes pine wilt disease. Endosymbionts are found in the cytoplasm of E. vermicola from various geographical areas. We sequenced the genome of endobacteria residing in E. vermicola to discover possible biological functions of these widespread endobacteria. Multilocus phylogenetic analyses showed that the endobacteria form a previously unidentified lineage sister to Phyllobacterium myrsinacearum species. The number of genes in the endobacterium was 4542, with 87.8% of the proteins having a known function. It contained a high proportion of repetitive sequences, as well as more Acyl-CoA synthetase genes and genes encoding the electron transport chain, compared with compared with plant-associated P. zundukense Tri 48 and P. myrsinacearum DSM 5893. Thus, this symbiotic bacterium is likely to be more efficient in regulating gene expression and energy release. Furthermore, the endobacteria in nematophagous fungi Esteya vermicola contained multiple nematicidal subtilase/subtilisin encoding genes, so it is likely that endobacteria cooperate with the host to kill nematodes.

Detection and Identification of Novel Intracellular Bacteria Hosted in Strains CBS 648.67 and CFCC 80795 of Biocontrol Fungi Metarhizium.

"Endosymbiosis" is a cohesive form of a symbiotic association. Endobacteria exist in many fungi and play important roles in fungal host biology. Metarhizium spp. are important entomopathogenic fungi for insect pest control. In the present study, we performed comprehensive ana-lyses of strains of Metarhizium bibionidarum and M. anisopliae using PCR, phylogenetics, and fluorescent electron microscopy to identify endobacteria within hyphae and conidia. The results of the phylogenetic ana-lysis based on 16S rRNA gene sequences indicated that these endobacteria were the most closely related to Pelomonas puraquae and affiliated with Betaproteobacteria. Ultrastructural observations indicated that endobacteria were coccoid and less than 500| |nm in diameter. The basic characteristics of endobacteria in M. bibionidarum and M. anisopliae were elucidated, and biological questions were raised regarding their biological functions in the Metarhizium hosts.

IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin disease, which is associated with intense itch, skin barrier dysfunction and eczematous lesions. Aberrant IL-20 expression has been implicated in numerous inflammatory diseases, including psoriasis. However, the role of IL-20 in AD remains unknown. Here, RNA-seq, Q-PCR, and immunocytochemistry were utilized to examine disease-driven changes of IL-20 and its cognate receptor subunits in skin from healthy human subjects, AD patients and murine AD-models. Calcium imaging, knockdown and cytokine array were used to investigate IL-20-evoked responses in keratinocytes and sensory neurons. The murine cheek model and behavioral scoring were employed to evaluate IL-20-elicited sensations in vivo. We found that transcripts and protein of IL-20 were upregulated in skin from human AD and murine AD-like models. Topical MC903 treatment in mice ear enhanced IL-20R1 expression in the trigeminal sensory ganglia, suggesting a lesion-associated and epidermal-driven mechanism for sensitization of sensory IL-20 signaling. IL-20 triggered calcium influx in both keratinocytes and sensory neurons, and promoted their AD-related molecule release and transcription of itch-related genes. In sensory neurons, IL-20 application increased TLR2 transcripts, implicating a link between innate immune response and IL-20. In a murine cheek model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings provide novel insights into IL-20 function in peripheral (skin-derived) itch and clinically relevant intercellular neuron-epidermal communication, highlighting a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.

Estimation of soybean yield parameters under lodging conditions using RGB information from unmanned aerial vehicles.

The estimation of yield parameters based on early data is helpful for agricultural policymakers and food security. Developments in unmanned aerial vehicle (UAV) platforms and sensor technology help to estimate yields efficiency. Previous studies have been based on less cultivars (<10) and ideal experimental environments, it is not available in practical production. Therefore, the objective of this study was to estimate the yield parameters of soybean (Glycine max (L.) Merr.) under lodging conditions using RGB information. In this study, 17 time point data throughout the soybean growing season in Nanchang, Jiangxi Province, China, were collected, and the vegetation index, texture information, canopy cover, and crop height were obtained by UAV-image processing. After that, partial least squares regression (PLSR), logistic regression (Logistic), random forest regression (RFR), support vector machine regression (SVM), and deep learning neural network (DNN) were used to estimate the yield parameters. The results can be summarized as follows: (1) The most suitable time point to estimate the yield was flowering stage (48 days), which was when most of the soybean cultivars flowered. (2) The multiple data fusion improved the accuracy of estimating the yield parameters, and the texture information has a high potential to contribute to the estimation of yields, and (3) The DNN model showed the best accuracy of training (R2=0.66 rRMSE=32.62%) and validation (R2=0.50, rRMSE=43.71%) datasets. In conclusion, these results provide insights into both best estimate period selection and early yield estimation under lodging condition when using remote sensing.