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INTRODUCTION: MODEL‐AD (Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late‐onset Alzheimer's disease (LOAD) more accurately. METHODS: We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid‐beta (Aβ). Mice were subjected to a control diet or a high‐fat/high‐sugar diet (LOAD2+HFD). We assessed disease‐relevant outcome measures in plasma and brain including neuroinflammation, Aβ, neurodegeneration, neuroimaging, and multi‐omics. RESULTS: By 18 months, LOAD2+HFD mice exhibited sex‐specific neuron loss, elevated insoluble brain Aβ42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen‐based cognitive tasks were observed. DISCUSSION: The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles. Highlights: By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL).Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease‐relevant processes including lipid metabolism and synaptic function.In vivo imaging revealed an age‐dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT).LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen‐based cognitive tasks. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that four and a half LIM domains 2 (FHL2) plays a crucial role in the progression of various cancers. However, the biological functions and molecular mechanism of FHL2 in lung adenocarcinoma (LUAD) remain unclear. Methods: We evaluated the prognostic value of FHL2 in LUAD using public datasets and further confirmed its prognostic value with our clinical data. The biological functions of FHL2 in LUAD were evaluated by in vitro and in vivo experiments. Pathway analysis and rescue experiments were subsequently performed to explore the molecular mechanism by which FHL2 promoted the progression of LUAD. Results: FHL2 was upregulated in LUAD tissues compared to adjacent normal lung tissues, and FHL2 overexpression was correlated with unfavorable outcomes in patients with LUAD. FHL2 knockdown significantly suppressed the proliferation, migration and invasion of LUAD cells, while FHL2 overexpression had the opposite effect. Mechanistically, FHL2 upregulated the PI3K/AKT/mTOR pathway and subsequently inhibited autophagy in LUAD cells. The effects FHL2 on the proliferation, migration and invasion of LUAD cells are dependent on the inhibition of autophagy, as of induction autophagy attenuated the aggressive phenotype induced by FHL2 overexpression. Conclusions: FHL2 promotes the progression of LUAD by activating the PI3K/AKT/mTOR pathway and subsequently inhibiting autophagy, which can be exploited as a potential therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

Diffusion‐weighted imaging (DWI) is an established MRI technique that can investigate tissue microstructure at the scale of a few micrometers. Musculoskeletal tissues typically have a highly ordered structure to fulfill their functions and therefore represent an optimal application of DWI. Even more since disruption of tissue organization affects its biomechanical properties and may indicate irreversible damage. The application of DWI to the musculoskeletal system faces application‐specific challenges on data acquisition including susceptibility effects, the low T2 relaxation time of most musculoskeletal tissues (2–70 msec) and the need for sub‐millimetric resolution. Thus, musculoskeletal applications have been an area of development of new DWI methods. In this review, we provide an overview of the technical aspects of DWI acquisition including diffusion‐weighting, MRI pulse sequences and different diffusion regimes to study tissue microstructure. For each tissue type (growth plate, articular cartilage, muscle, bone marrow, intervertebral discs, ligaments, tendons, menisci, and synovium), the rationale for the use of DWI and clinical studies in support of its use as a biomarker are presented. The review describes studies showing that DTI of the growth plate has predictive value for child growth and that DTI of articular cartilage has potential to predict the radiographic progression of joint damage in early stages of osteoarthritis. DTI has been used extensively in skeletal muscle where it has shown potential to detect microstructural and functional changes in a wide range of muscle pathologies. DWI of bone marrow showed to be a valuable tool for the diagnosis of benign and malignant acute vertebral fractures and bone metastases. DTI and diffusion kurtosis have been investigated as markers of early intervertebral disc degeneration and lower back pain. Finally, promising new applications of DTI to anterior cruciate ligament grafts and synovium are presented. The review ends with an overview of the use of DWI in clinical routine. Evidence Level: 5 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Summary: Callus formation is important for numerous biological processes in plants. Previously, we revealed that the PdeWRKY75–PdeRBOHB module positively regulates hydrogen peroxide (H2O2) accumulation, thereby affecting callus formation in poplar.In this study, we identified and confirmed a transcription factor, PdeERF114, that interacts with PdeWRKY75 both in vitro and in vivo. Gene expression analysis identified both PdeRBOHB and PdeEXPB2 as downstream genes of PdeERF114 and PdeWRKY75. Overexpression (OE) and reduced‐expression (RE) transgenic poplar lines for these four genes were generated, and the observation of callus formation was also performed in all plant materials.We demonstrated that PdeERF114 and PdeWRKY75 formed a protein complex and that this complex could bind W‐Box motifs in the promoters of PdeRBOHB and PdeEXPB2, thereby positively regulating the expression of PdeRBOHB and PdeEXPB2. The OE/RE transgenic lines for these four genes also showed enhanced/reduced callus formation.Overall, we revealed a novel gene regulatory network for the regulation of callus formation in plants that involves four genes and regulates callus formation through two pathways: the accumulation of H2O2 in explants and the relaxation of cell walls. In the future, the four genes could be used to enhance transformation effectiveness in genetic engineering. [ABSTRACT FROM AUTHOR]

Purpose: To introduce a method of inducing Bloch‐Siegert shift and magnetization Transfer Simultaneously (BTS) and demonstrate its utilization for measuring binary spin‐bath model parameters free pool spin–lattice relaxation (T1F$$ {T}_1^{\mathrm{F}} $$), macromolecular fraction (f$$ f $$), magnetization exchange rate (kF$$ {k}_{\mathrm{F}} $$) and local transmit field (B1+$$ {B}_1^{+} $$). Theory and Methods: Bloch‐Siegert shift and magnetization transfer is simultaneously induced through the application of off‐resonance irradiation in between excitation and acquisition of an RF‐spoiled gradient‐echo scheme. Applying the binary spin‐bath model, an analytical signal equation is derived and verified through Bloch simulations. Monte Carlo simulations were performed to analyze the method's performance. The estimation of the binary spin‐bath parameters with B1+$$ {B}_1^{+} $$ compensation was further investigated through experiments, both ex vivo and in vivo. Results: Comparing BTS with existing methods, simulations showed that existing methods can significantly bias T1$$ {T}_1 $$ estimation when not accounting for transmit B1$$ {B}_1 $$ heterogeneity and MT effects that are present. Phantom experiments further showed that the degree of this bias increases with increasing macromolecular proton fraction. Multi‐parameter fit results from an in vivo brain study generated values in agreement with previous literature. Based on these studies, we confirmed that BTS is a robust method for estimating the binary spin‐bath parameters in macromolecule‐rich environments, even in the presence of B1+$$ {B}_1^{+} $$ inhomogeneity. Conclusion: A method of estimating Bloch‐Siegert shift and magnetization transfer effect has been developed and validated. Both simulations and experiments confirmed that BTS can estimate spin‐bath parameters (T1F$$ {T}_1^{\mathrm{F}} $$, f$$ f $$, kF$$ {k}_{\mathrm{F}} $$) that are free from B1+$$ {B}_1^{+} $$ bias. [ABSTRACT FROM AUTHOR]

To date developments of seismic attenuation models of the Earth have lagged those of velocity models. This is partly due to difficulties in isolating waveform perturbations caused by attenuation and velocity heterogeneities and partly due to different theories (e.g., ray theory, finite frequency theory) used in most previous and current studies to approximate sensitivity kernels and invert for the attenuation structure. We present in this paper a new method for computing the 3D waveform Fréchet kernels that account for full physical‐dispersion and dissipation attenuation. For solving the 3D isotropic anelastic wave equation described by the generalized Maxwell body model, we extend our previously proposed full waveform modeling method in Cartesian coordinates to that in spherical coordinates, which can provide stable numerical solutions even in the presence of strong attenuation. Then, we apply the scattering‐integral method for calculating 3D travel time and amplitude sensitivity kernels with respect to velocity and attenuation structures. We demonstrate the accuracy of our forward method and the effectiveness of the implementation of absorbing and free surface boundary conditions through numerical tests. Moreover, by choosing the Northwestern United States region as a realistic example, we verify the accuracy of the computed 3D sensitivity kernels through comparing the waveform measurements with predictions from the kernels. Finally, we discuss the importance of calculating full anelastic sensitivity kernels including both effects of physical dispersion and dissipation, where we specially explore the effect of scattering due to random velocity and attenuation heterogeneities on waveform measurements. Plain Language Summary: Anelasticity is an intrinsic property of the Earth that causes energy reduction of propagating seismic waves. Anelastic structures (including velocities and attenuation) are strongly related to temperature, partial melt, and water contents of the Earth, which provide crucial insight into the plate tectonics and geodynamic processes. To date developments of seismic attenuation models have lagged those of velocity models, because of difficulties in isolating effects of velocity heterogeneities and attenuation on waveform perturbations and large discrepancies in various theoretical methods and the resulting attenuation models. The full waveform inversion (FWI) method is promising to deal with the two difficulties and here we develop a novel anelasitc scattering‐integral‐based FWI method. We verify the effectiveness of our forward method in anelastic modeling even in the presence of strong attenuation, and we testify the accuracy of the computed 3D velocity and attenuation sensitivity kernels using the Northwestern United States region as a realistic example. We also demonstrate the importance of computing full anelastic sensitivity kernels including both effects of physical dispersion and dissipation, where we specially estimate the amount of scattering due to heterogeneous velocity and attenuation perturbations on waveform perturbations in subduction zones. Key Points: We develop a new method for computing 3D sensitivity kernels with full attenuation and verify its accuracy through numerical experimentsWe demonstrate the importance of computing full anelastic sensitivity kernels including both effects of physical dispersion and dissipationScattering due to 30% attenuation heterogeneities alone in subduction zones could contribute up to 9% of observed waveform perturbations [ABSTRACT FROM AUTHOR]

Summary: Vigna unguiculata is an important legume crop worldwide. The subsp. sesquipedalis and unguiculata are the two major types grown; the former is mainly grown in Asia to produce fresh pods, while the latter is mainly grown in Africa to produce seeds. Here, a chromosome‐scale genome for subsp. sesquipedalis was generated by combining high‐fidelity (HiFi) long‐read sequencing with high‐throughput chromosome conformation capture (Hi‐C) technology. The genome size for all contigs and N50 were 594 and 18.5 Mb, respectively. The Hi‐C interaction map helped cluster 91% of the contigs into 11 chromosomes. Genome comparisons between subsp. sesquipedalis and unguiculata revealed extensive genomic variations, and some variations resulted in gene loss. A germplasm panel with 315 accessions of V. unguiculata was resequenced, and a genomic variation map was constructed. Population structure and phylogenetic analyses suggested that subsp. sesquipedalis originated from subsp. unguiculata. Highly differentiated genomic regions were also identified, and a number of genes functionally enriched in adaptations were located in these regions. Two traits, pod length (PL) and pod width (PW), were observed for this germplasm, and genome‐wide association analysis of these traits was performed. The quantitative trait loci (QTLs) for these two traits were identified, and their candidate genes were uncovered. Interestingly, genomic regions of PL QTLs also showed strong signals of artificial selection. Taken together, the results of this study provide novel insights into the population differentiation and genetic basis of key agricultural traits in V. unguiculata. [ABSTRACT FROM AUTHOR]

SUMMARY: Flowering cherry is a very popular species around the world. High‐quality genome resources for different elite cultivars are needed, and the understanding of their origins and the regulation of key ornamental traits are limited for this tree. Here, a high‐quality chromosome‐scale genome of Prunus campanulata 'Plena' (PCP), which is a native and elite flowering cherry cultivar in China, was generated. The contig N50 of the genome was 18.31 Mb, and 99.98% of its contigs were anchored to eight chromosomes. Furthermore, a total of 306 accessions of flowering cherry germplasm and six lines of outgroups were collected. Resequencing of these 312 lines was performed, and 761 267 high‐quality genomic variants were obtained. The origins of flowering cherry were predicted, and these 306 accessions could be classified into three clades, A, B and C. According to phylogenetic analysis, we predicted two origins of flowering cherry. Flowering cherry in clade A originated in southern China, such as in the Himalayan Mountains, while clades B and C originated in northeastern China. Finally, a genome‐wide association study of flower colour was performed for all 312 accessions of flowering cherry germplasm. A total of seven quantitative trait loci (QTLs) were identified. One gene encoding glycosylate transferase was predicted as the candidate gene for one QTL. Taken together, our results provide a valuable genomic resource and novel insights into the origin, evolution and flower colour variations of flowering cherry. Significance Statement: Genome assembly, resequencing and genome‐wide association analyses provide novel insights into the origin, evolution and flower colour variations of flowering cherry. [ABSTRACT FROM AUTHOR]

High‐resolution magnetic resonance imaging (MRI) affords unique image contrasts to nondestructively probe the tissue microstructure; validation of MRI findings with conventional histology is essential to better understand the MRI contrasts. However, the dramatic difference in the spatial resolution and image contrast of these two techniques impedes accurate comparison between MRI metrics and traditional histology. To better validate various MRI metrics, we acquired whole mouse brain multigradient recalled‐echo and multishell diffusion MRI datasets at 25‐μm isotropic resolution. The recently developed Allen Mouse Brain Common Coordinate Framework (CCFv3) provides opportunities to integrate multimodal and multiscale datasets of the whole mouse brain in a common three‐dimensional (3D) space. The T2*, quantitative susceptibility mapping, diffusion tensor imaging, and neurite orientation dispersion and density imaging parameters were compared with both serial two‐photon tomography images and 3D Nissl staining images in the CCFv3 at the same spatial resolution. The correlation between MRI and Nissl staining strongly depends on different metrics and different regions of the brain. Integrating different imaging modalities to the same space may substantially improve our understanding of the complexity of the brain at different scales. [ABSTRACT FROM AUTHOR]

Summary: The plasma membrane (PM) functions as a physical border between the extracellular and cytoplasmic environments that contribute to the interaction between host plants and pathogenic fungi. As a specific sterol constituent in the cell membrane, ergosterol plays a significant role in fungal development.However, the role of ergosterol in the infection of the rice blast fungus Magnaporthe oryzae remains unclear. In this study, we found that a sterol reductase, MoErg4, is involved in ergosterol biosynthesis and the regulation of plasma membrane integrity in M. oryzae.We found that defects in ergosterol biosynthesis disrupt lipid raft formation in the PM and cause an abnormal distribution of the t‐soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) protein MoSso1, inhibiting its interaction with the v‐SNARE protein MoSnc1. In addition, we found that MoSso1–MoSnc1 interaction is important for biotrophic interface complex development and cytoplasmic effector protein secretion.Our findings suggested that ergosterol‐enriched lipid rafts constitute a platform for interactions among various SNARE proteins that are required for the development and pathogenicity of M. oryzae. [ABSTRACT FROM AUTHOR]

Disentangling the numerous processes that affect patterns of genome‐wide diversity in widespread tree species has important implications for taxonomy, conservation, and forestry. Here, we investigate the population genomic structure of Asian white birch (Betula platyphylla) in China and seek to explain it in terms of hybridization, demography and adaptation. We generate whole genome sequence data from 83 individuals across the species range in China. Combining this with an existing data set for 79 European and Russian white birches, we show a clear distinction between B. pendula and B. platyphylla, which have sometimes been lumped taxonomically. Genomic diversity of B. platyphylla in north‐western China and Central Russia is affected greatly by hybridization with B. pendula. Excluding these hybridized populations, B. platyphylla in China has a linear distribution from north‐eastern to south‐western China, along the edge of the inland mountainous region. Within this distribution, three genetic clusters are found, which we model as long diverged with subsequent episodes of gene flow. Patterns of covariation between allele frequencies and environmental variables in B. platyphylla suggest the role of natural selection in the distribution of diversity at 7609 SNPs of which 3767 were significantly differentiated among the genetic clusters. The putative adaptive SNPs are distributed throughout the genome and span 1633 genic regions. Of these genic regions, 87 were previously identified as candidates for selective sweeps in Eurasian B. pendula. We use the 7609 environmentally associated SNPs to estimate the risk of nonadaptedness for each sequenced B. platyphylla individual under a scenario of future climate change, highlighting areas where populations may be under future threat from rising temperatures. [ABSTRACT FROM AUTHOR]

SUMMARY: Structural variations (SVs) are critical factors affecting genome evolution and important traits. However, identification results and functional analyses of SVs in upland cotton are rare. Here, based on the genetic relationships, breeding history and cumulative planting area of upland cotton in China, nine predominant cultivars from the past 60 years (1950s–2010s) were selected for long read sequencing to uncover genic variations and breeding improvement targets for this crop. Based on the ZM24 reference genome, 0.88–1.47 × 104 SVs per cultivar were identified, and an SV set was constructed. SVs affected the expression of a large number of genes during fiber elongation, and a transposable element insertion resulted in the glandless phenotype in upland cotton. Six widespread inversions were identified based on nine draft genomes and high‐throughput chromosome conformation capture data. Multiple haplotype blocks that were always associated with aggregated SVs were demonstrated to play a pivotal role in the agronomic traits of upland cotton and drove its adaptation to the northern planting region. Exotic introgression was the source of these haplotype blocks and increased the genetic diversity of upland cotton. Our results enrich the genome resources of upland cotton, and the identified SVs will promote genetic and breeding research in cotton. Significance Statement: The present study uncovered structural variants in upland cottons, many of which affected gene expression in cotton fibers. A transposable element insertion resulting in the glandless phenotype was identified. Inversions affecting population differentiation and adaptation in upland cotton were identified. Haplotype blocks generated from interspecies introgressions associated with upland cotton agronomic traits, providing new ideas for cotton breeding. [ABSTRACT FROM AUTHOR]

Understanding hybridization and introgression between natural plant populations can give important insights into the origins of cultivated species. Recent studies suggest differences in ploidy might not create such strong reproductive barriers as once thought, and thus studies into cultivated origins should examine all co‐occurring taxa, including those with contrasting ploidy levels. Here, we characterized hybridization between Chrysanthemum indicum L., Chrysanthemum vestitum (Hemsley) Ling and Chrysanthemum vestitum var. latifolium (Zhou & Chen), the most important wild species involved in the origins of cultivated chrysanthemums. We analyzed the population structure of 317 Chrysanthemum accessions based on 13 microsatellite markers and sequenced chloroplast trnL‐trnF for a subset of 103 Chrysanthemum accessions. We identified three distinct genetic clusters, corresponding to the three taxa. We detected 20 hybrids between species of different ploidy levels, of which 19 were between C. indicum (4x) and C. vestitum (6x) and one was between C. indicum and C. vestitum var. latifolium (6x). Fourteen hybrids between C. indicum and C. vestitum were from one of the five study sites. Chrysanthemum vestitum and C. vestitum var. latifolium share only one chloroplast haplotype. The substantially different number of hybrids between hybridizing species was likely due to different levels of reproductive isolation coupled with environmental selection against hybrids. In addition, human activities could play a role in the different patterns of hybridization among populations. [ABSTRACT FROM AUTHOR]

SUMMARY: Phosphorus (P) is an important nutrient for plants. Here, we identify a WRKY transcription factor (TF) in poplar (Populus deltoides × Populus euramericana) (PdeWRKY65) that modulates tissue phosphate (Pi) concentrations in poplar. PdeWRKY65 overexpression (OE) transgenic lines showed reduced shoot Pi concentrations under both low and normal Pi availabilities, while PdeWRKY65 reduced expression (RE) lines showed the opposite phenotype. A gene encoding a Pi transporter (PHT), PdePHT1;9, was identified as the direct downstream target of PdeWRKY65 by RNA sequencing (RNA‐Seq). The negative regulation of PdePHT1;9 expression by PdeWRKY65 was confirmed by DNA–protein interaction assays, including yeast one‐hybrid (Y1H), electrophoretic mobility shift assay (EMSA), co‐expression of the promoters of PdePHT1;9 and PdeWRKY65 in tobacco (Nicotiana benthamiana) leaves, and chromatin immunoprecipitation–quantitative PCR. A second WRKY TF, PdeWRKY6, was subsequently identified and confirmed to positively regulate the expression of PdePHT1;9 by DNA–protein interaction assays. PdePHT1;9 and PdeWRKY6 OE and RE poplar transgenic lines were used to confirm their positive regulation of shoot Pi concentrations, under both normal and low Pi availabilities. No interaction between PdeWRKY6 and PdeWRKY65 was observed at the DNA or protein levels. Collectively, these data suggest that the low Pi‐responsive TFs PdeWRKY6 and PdeWRKY65 independently regulate the expression of PHT1;9 to modulate tissue Pi concentrations in poplar. Significance Statement: The genes PdeWRKY65 and PdeWRKY6, encoding WRKY transcription factors, and PdePHT1;9, encoding a phosphate (Pi) transporter, form a regulatory network to modulate tissue Pi concentrations in response to low Pi availability in poplar (Populus deltoides × Populus euramericana). In the regulatory network, PdeWRKY65 and PdeWRKY6 negatively and positively regulate the expression of PdePHT1;9 by binding to W‐Boxes within the PdePHT1;9 promoter, respectively. [ABSTRACT FROM AUTHOR]

Summary: Magnaporthe oryzae secretes several effectors that modulate and hijack rice processes to colonize host cells, but the underlying mechanisms remain unclear. We report on a novel cytoplasmic effector MoIug4 that targets the rice ethylene pathway as a transcription repressor to subvert host immunity.We found that MoIug4 binds to the promoter of the host OsEIN2 gene that encodes a central signal transducer in the ethylene‐signaling pathway. We also identified a MoIug4 interacting protein, OsAHL1, which acts as an AT‐hook motif‐containing protein binding to the A/T‐rich promoter regions. Our knockout and overexpression studies showed that OsAHL1 positively regulates plant immunity in response to M. oryzae infection.OsAHL1 exhibits transcriptional regulatory activities by binding the OsEIN2 promoter region, similar to MoIug4. Intriguingly, we found that MoIug4 exhibits a higher binding affinity than OsAHL1 to the OsEIN2 promoter, suggesting differential regulatory specificities.These results revealed a counter‐defense strategy by which the pathogen effector suppresses the activation of host defense genes by interfering with host transcription activator functions. [ABSTRACT FROM AUTHOR]

The cell wall provides a crucial barrier to stress imposed by the external environment. In the rice blast fungus Magnaporthe oryzae, this stress response is mediated by the cell wall integrity (CWI) pathway, consisting of a well‐characterized protein phosphorylation cascade. However, other regulators that maintain CWI phosphorylation homeostasis, such as protein phosphatases (PPases), remain unclear. Here, we identified two PPases, MoPtc1 and MoPtc2, that function as negative regulators of the CWI pathway. MoPtc1 and MoPtc2 interact with MoMkk1, one of the key components of the CWI pathway, and are crucial for the vegetative growth, conidial formation, and virulence of M. oryzae. We also demonstrate that both MoPtc1 and MoPtc2 dephosphorylate MoMkk1 in vivo and in vitro, and that CWI stress leads to enhanced interaction between MoPtc1 and MoMkk1. CWI stress abolishes the interaction between MoPtc2 and MoMkk1, providing a means of deactivation for CWI signalling. Our studies reveal that CWI signalling in M. oryzae is a highly coordinated regulatory mechanism vital for stress response and pathogenicity. [ABSTRACT FROM AUTHOR]

Single‐image dehazing is an important problem because it is a key prerequisite for most high‐level computer vision tasks. Traditional prior‐based methods adopt priors generated from clear images to restrain the atmospheric scattering model and then recover haze‐free images. However, these prior‐based methods always encounter over‐enhancement, such as halos and colour distortion. To solve this problem, many works use a convolutional neural network to retrieve original images. However, without priors as guidance, these learning‐based methods dehaze effectively in synthetic datasets but perform poorly in real scenes. Hence, in this paper, we propose a prior‐guided multiscale network for single‐image dehazing named PGMNet. Specifically, prior‐based methods are adopted to acquire dehazed images of the training dataset in advance and then send these dehazed images to a parameter‐shared encoder to form multiscale features. During the decoding process, these multiscale features are adopted to guide the prior‐guided multiscale network to recover more image details. Moreover, considering that these prior‐based dehazed images usually contain some over‐enhanced regions, a spatial attention guided feature aggregation module and squeeze‐and‐excitation module are adopted to alleviate colour distortion. The proposed PGMNet takes the advantage of prior‐based methods in real haze removal and provides superior performance compared with the state‐of‐the‐art methods on both synthetic and real‐world datasets. [ABSTRACT FROM AUTHOR]

The Huoyanshan iron meteorite shower, recently found in the Gobi Desert of Hami, Xinjiang, China, has very high Ni (21.1 wt%) content and low Au (2.0 ppm), Ir (0.02 ppm), Ge (1.7 ppm), and Ga (1.1 ppm) contents, and was classified into IAB‐sLH subgroup. The iron has a finest octahedrite structure of Widmanstätten pattern (the intergrowth of kamacite [α] and taenite [γ]) with plessite matrix, and euhedral schreibersite (Sch) crystals exclusively enclosed in kamacite bands. The textural features suggest the following formation process: γ→γ + Sch→γ + Sch + α, and then γ→α2 + γ. The metallographic cooling rate of Huoyanshan iron was determined to be 3–50°C/Myr using both the taenite Ni profile‐matching and taenite central Ni content methods, with the bandwidths corrected for crystallographic orientation by electron backscatter diffraction (EBSD). The cooling rate of Huoyanshan is consistent with other sLH irons and confirms the slow cooling history of the IAB low‐Au subgroups. These slow cooling rates require immediate re‐accretion with a thick brecciated fragments layer in the parent body after the impact melting event. The depleted but unfractionated Re, Os, Ir, Ru, and Pt and the enriched Pd and Au abundances of Huoyanshan iron and other sLH subgroup irons show complementary feature to that of refractory metal nuggets in Ca‐, Al‐rich inclusions (CAIs), which could be explained by extracting the metallic Fe‐Ni with HSE predominantly remained in CAIs from a CAI‐bearing asteroid. The very high Ni content of sLH subgroup and its Mo isotope evidence (Worsham et al., 2017, https://doi.org/10.1016/j.epsl.2017.02.044) suggest it has an oxidized parent body with non‐carbonaceous chondrite‐like precursor composition. We propose that the sLH subgroup was produced by impact melting of a LL like and CAI‐bearing asteroid, followed by fast burying of thick and porous silicate breccia. Plain Language Summary: Iron meteorites are the metal remnants of asteroids, and they were classified as magmatic and non‐magmatic. IAB complex is the major non‐magmatic irons and was divided into several subgroups. The metal‐silicate fractionation of the IAB complex was likely related with impact events in the early stage of the solar system. Here, we present the detailed petrography, trace element composition, and metallographic cooling rate of the Huoyanshan iron meteorite found recently, a new member of the IAB‐sLH subgroup, in order to reveal its petrogenesis, post‐impact thermal history and the geochemical features of its precursor parent body. Our results suggest that IAB low‐Au subgroups were buried by thick silicate breccia layers immediately after the impact events, in order to hold their slow metallographic cooling rates. The very high Ni contents, the highly siderophile element patterns, and the Mo isotopes of IAB‐sLH irons suggest a genetic relationship with an oxidized non‐carbonaceous chondritic asteroid. Key Points: Petrography and trace elements of Huoyanshan iron, a new member of the IAB‐sLH subgroup and recently found were reportedSlow metallographic cooling rates of IAB low‐Au subgroups suggest immediate re‐accretion with silicate breccia layer after impact eventsThe high‐Ni endmember parent body of IAB complex was probably contributed mainly from an oxidized (LL‐like) and Ca‐, Al‐rich inclusion (CAI)‐bearing asteroid [ABSTRACT FROM AUTHOR]

Societal Impact Statement: In rapidly changing environments species conservation can be hindered by uncertainties in distinguishing closely related species. Cryptic ongoing hybridization can add further uncertainty and could be beneficial or destructive. Here, we show that a declining birch tree species is hybridizing with a more widespread relative in the Junggar basin, NW China, and their hybrids have been previously named as rare sub‐species. Given the declining numbers of this birch tree, we suggest that conservation effort should aim to slow the rate of anthropogenic habitat loss at this hybrid zone and preserve its pure populations away from the hybrid zone. Summary: In areas where closely related species meet, the possibility that they may hybridize must be taken into account by conservationists. Hybridization may have positive or negative consequences for the long‐term future of species. If present, its dynamics need to be understood.Betula microphylla is a declining wetland tree species in NW China that forms a continuum of leaf morphology and geographic distribution with its relative Betula tianshanica. We use ecological niche models to predict the distribution of B. microphylla and B. tianshanica. We use restriction site‐associated DNA sequencing and SSRs to resolve their genetic structure and patterns of allele sharing.Ecological niche models predict an expansion of the range of B. tianshanica into that of B. microphylla since the Last Glacial Maximum and the contraction of B. microphylla's range in the future. Genetic data suggest that the two species have hybridized in the Junggar basin and in the Tianshan Mountains where the two species have co‐occurred in the recent past and in the Altay Mountains where there are no records of B. tianshanica occurrence. Rare populations previously identified as sub‐species of B. microphylla were shown to be of hybrid origin.Further research is needed on the costs and benefits of hybridization between B. microphylla and B. tianshanica in the changing environment of NW China. Our current data suggest that conservation effort should aim to slow the rate of anthropogenic habitat loss at the hybrid zone in the Junggar basin and preserve pure populations far away from the hybrid zone in the Altay Mountains. [ABSTRACT FROM AUTHOR]

Summary: Multi‐omics approach was adopted to investigate the modulation of bacterial microbiota and metabolome as well as their interactions in whole crop corn ensiling systems by inoculating homofermentative Lactobacillus plantarum or heterofermentative Lactobacillus buchneri. Inoculations of the two different inoculants resulted in substantial differences in microbial community and metabolic composition as well as their dynamics in ensiled corn. Inoculants also altered the correlations of microbiota in different manners, and various keystone species were identified in corn silages with different treatments. Many metabolites with biofunctional activities like bacteriostatic, antioxidant, central nervous system inhibitory and anti‐inflammatory were found in the present silage. A constitutive difference in microbiota dynamics was found for several pathways, which were upregulated by specific taxa in middle stage of fermentation, and widespread associations between metabolites with biofunctions and the species of lactic acid bacteria dominated in silage were observed. Multiple microbial and metabolic structures and dynamics were correlated and affected the fermentation process of the corn ensiling systems. Results of the current study improve our understanding of the complicated biological process underlying silage fermentation and provide a framework to re‐evaluate silages with biofunctions, which may contribute to target‐based regulation methods to produce functional silage for animal production. [ABSTRACT FROM AUTHOR]

Summary: Climate‐driven phenological change across local spatial gradients leads to leaf shape variation. At higher elevations, leaves of broadleaf species tend to become narrower, but the underlying molecular mechanism is largely unknown.In this study, a series of morphometric analyses and biochemical assays, combined with functional identification in apple, were performed.We show that the decrease in apple leaf width with increasing altitude is controlled by a basic/helix–loop–helix transcription factor (bHLH TF), MdbHLH3. The MdbHLH3‐overexpressing lines have a lower transcript abundance of MdPIN1 encoding an auxin efflux carrier but a higher transcript abundance of MdGH3‐2 encoding a putative auxin amido conjugate synthase, resulting in a lower free auxin concentration; feeding the transgenic leaves with exogenous auxin partially restores leaf width. MdbHLH3 transcriptionally suppresses and activates MdPIN1 and MdGH3‐2, respectively, by specifically binding to their promoters. This alters auxin homeostasis and transport, consequently leading to changes in leaf shape.These findings suggest that the bHLH TF MdbHLH3 directly modulates auxin signaling in controlling leaf shape in response to local spatial gradients in apple. [ABSTRACT FROM AUTHOR]

This study evaluates the resolution‐dependent influences of compressed sensing (CS) in MRI quantification of T2 mapping in articular cartilage with osteoarthritis (OA). T2‐weighed 2D experiments of healthy and OA cartilage were fully sampled in k‐space with five echo times at both 17.6 μm and 195.3 μm in‐plane resolutions; termed as microscopic MRI (μMRI) and macroscopic MRI (mMRI) respectively. These fully sampled k‐space data were under‐sampled at various 2D CS accelerating factors (AF = 4–32). The under‐sampled data were reconstructed individually into 2D images using nonlinear reconstruction, which were used to calculate the T2 maps. The bulk and zonal variations of T2 values in cartilage were evaluated at different AFs. The study finds that the T2 images at AFs up to 8 preserved major visual information and produced negligible artifacts for μMRI. The T2 values remained accurate for different sub‐tissue zones at various AFs. The absolute difference between the CS (AF up to 32) and the Ground Truth (i.e., using 100% of the k‐space data) of the mean T2 values through the whole tissue depth was higher in mMRI versus μMRI. For mMRI (where the resolution mimics the clinical MRI of human cartilage), the quantitative T2 mapping at AFs up to 4 showed negligible variations. This study demonstrates that both clinical MRI and μMRI can benefit from the use of CS in image acquisition, and μMRI benefits more from the use of CS by acquiring much less data, without losing significant accuracy in the quantification of T2 maps in osteoarthritic cartilage. [ABSTRACT FROM AUTHOR]

This study investigates an integrated wheel slip, yaw rate, and sideslip angle control via torque vectoring to improve both the longitudinal and lateral stability of electric vehicles (EVs) with four in‐wheel motors. The algorithm is developed based on model predictive control (MPC) and thus can optimally reach a balance among different objectives while considering actuation and state constraints. Firstly, to deal with tyre non‐linearity and variations in the lateral tyre forces due to changes in tyre slip ratios, the mechanism of using torque vectoring to improve vehicle stability is analysed. Then, a non‐linear tyre model is introduced into the predictive model to characterise the tyre force coupling relationship. Here, a linear‐parameter‐varying (LPV) model is employed, which is derived by linearising the nonlinear vehicle model online. Moreover, the stability control of EVs with in‐wheel motors is transformed into a constrained online optimisation problem and solved using the proposed LPV‐MPC method. Finally, the proposed LPV‐MPC is compared with some existing well‐established techniques from literature in different test scenarios. The obtained results demonstrate that the LPV‐MPC approach could reduce the computational burden and shows a precise longitudinal control and obviously improves the lateral stability. [ABSTRACT FROM AUTHOR]

Diamondback moth (DBM), Plutella xylostella, is an important pest of crucifers worldwide. The extensive use of diamide insecticides has led to DBM resistance in the world, and this presents a serious threat to vegetable production. In the present study, transcriptomic and proteomic analyses were combined to investigate the potential flubendiamide‐resistance mechanism in DBM. The lab‐selected (Rh) and field‐collected (Rb) flubendiamide‐resistant lines of P. xylostella with resistance ratios of 1889.92‐fold and 1250.97‐fold, respectively, were used, as well as a lab‐reared flubendiamide‐susceptible line (S). Compared with the S group, the transcriptomic analysis revealed 151 upregulated and 287 downregulated gene messengers in the Rh group and 432 upregulated and 565 downregulated gene messengers in the Rb group. The most frequently enriched pathways of differentially expressed genes (DEGs) were mainly involved in metabolic pathways. Metabolism related genes, including two P450, two ABC transporters, and three trypsins, were upregulated in the Rh line. Additionally, some P450 genes, trypsin, juvenile hormone (JH), and mucin genes were also upregulated in the Rb line. In proteomic analysis comparisons with the S group, there were 78 upregulated and 90 downregulated proteins in the Rh group and 221 upregulated and 155 downregulated proteins in the Rb group. Further analyses found that three CYP and 11 CYP proteins were over‐expressed in Rh and Rb lines, respectively. Four glutathione S‐transferase (GST) and four UGTs were over‐expressed in Rb line. So, we deduced that the detoxification metabolism may be the main mechanism of flubendiamide resistance in P. xylostella. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the complex fiber orientations and 3D collagen fiber network of knee joint connective tissues, including ligaments, muscle, articular cartilage, and meniscus using high spatial and angular resolution diffusion imaging. Methods: Two rat knee joints were scanned using a modified 3D diffusion‐weighted spin echo pulse sequence with the isotropic spatial resolution of 45 μm at 9.4T. The b values varied from 250 to 1250 s/mm2 with 31 diffusion encoding directions for 1 rat knee. The b value was fixed to 1000 s/mm2 with 147 diffusion encoding directions for the second knee. Both the diffusion tensor imaging (DTI) model and generalized Q‐sampling imaging (GQI) method were used to investigate the fiber orientation distributions and tractography with the validation of polarized light microscopy. Results: To better resolve the crossing fibers, the b value should be great than or equal to 1000 s/mm2. The tractography results were comparable between the DTI model and GQI method in ligament and muscle. However, the tractography exhibited apparent difference between DTI and GQI in connective tissues with more complex collagen fibers network, such as cartilage and meniscus. In articular cartilage, there were numerous crossing fibers found in superficial zone and transitional zone. Tractography generated with GQI also resulted in more intact tracts in articular cartilage than DTI. Conclusion: High‐resolution diffusion imaging with GQI method can trace the complex collagen fiber orientations and architectures of the knee joint at microscopic resolution. [ABSTRACT FROM AUTHOR]

'Candidatus Liberibacter' species are insect‐transmitted, phloem‐limited α‐Proteobacteria in the order of Rhizobiales. The citrus industry is facing significant challenges due to huanglongbing, associated with infection from 'Candidatus Liberibacter asiaticus' (Las). In order to gain greater insight into 'Ca. Liberibacter' biology and genetic diversity, we have performed genome sequencing and comparative analyses of diverse 'Ca. Liberibacter' species, including those that can infect citrus. Our phylogenetic analysis differentiates 'Ca. Liberibacter' species and Rhizobiales in separate clades and suggests stepwise evolution from a common ancestor splitting first into nonpathogenic Liberibacter crescens followed by diversification of pathogenic 'Ca. Liberibacter' species. Further analysis of Las genomes from different geographical locations revealed diversity among isolates from the United States. Our phylogenetic study also indicates multiple Las introduction events in California and spread of the pathogen from Florida to Texas. Texan Las isolates were closely related, while Florida and Asian isolates exhibited the most genetic variation. We have identified conserved Sec translocon (SEC)‐dependent effectors likely involved in bacterial survival and virulence of Las and analysed their expression in their plant host (citrus) and insect vector (Diaphorina citri). Individual SEC‐dependent effectors exhibited differential expression patterns between host and vector, indicating that Las uses its effector repertoire to differentially modulate diverse organisms. Collectively, this work provides insights into the evolution of 'Ca. Liberibacter' species, the introduction of Las in the United States and identifies promising Las targets for disease management. [ABSTRACT FROM AUTHOR]

The temporal duration of lunar‐evolved magmatism is still poorly constrained. In lunar meteorite Northwest Africa (NWA) 10049, a melt inclusion‐bearing zircon fragment provides a new tool to understand the composition and age of the melts from which zircon directly crystallized. The studied zircon‐hosted melt inclusions are silica rich and iron poor (e.g., ~80–90 wt% SiO2; <0.5 wt% FeO), compositionally similar with immiscible silica‐rich melts found in Apollo rocks. Nano‐SIMS U–Pb analyses of the zircon yielded a minimum crystallization age of 4,382 ± 40 Ma, older than the ages for Apollo highly evolved alkali suite lithologies (~3.8–4.33 Ga). Our study shows that the melt inclusion‐bearing zircon in NWA 10049 is the oldest microscale evidence for documenting immiscible silica‐rich melts in lunar samples, suggesting that lunar‐evolved silica‐rich melts were prevalent as early as ~4.38 Ga. This work implies that there would be a prolonged silicic magmatism occurred on the Moon. Plain Language Summary: Lunar‐evolved silica‐rich melt is thought to be related to the formation of highly silicic lithologies (e.g., granitic lithologies). These rock types have been observed in Apollo returned samples as lithic clasts and also have been detected by remote‐sensing data as silicic domes. The Apollo‐evolved lithologies give a wide range of crystallization ages from ~3.8–4.33 Ga. However, there is still unclear about the temporal duration of lunar‐evolved magmatism and volcanism. In lunar meteorite breccia NWA 10049, a melt inclusions‐bearing zircon fragment provides a new tool to understand the composition and age of the melts from which zircon directly crystallized. The studied zircon‐hosted melt inclusions are compositionally similar with immiscible silica‐rich melts found in Apollo rocks. Nano‐SIMS U–Pb analyses of the zircon yielded a minimum crystallization age of ~4.38 Ga. This age is older than the ages for Apollo‐returned granites (up to 4.33 Ga) and ancient basaltic volcanism (i.e., up to ~4.37 Ga), making the studied zircon is the oldest microscale evidence for documenting lunar silicate liquid immiscibility. Key Points: A ~200‐μm‐sized melt inclusion‐bearing zircon fragment was found in lunar feldspathic breccia meteorite NWA 10049Melt inclusions in this zircon are compositionally consistent with lunar immiscible silica‐rich meltsThe zircon is 4.38 Ga and provides microscale evidence for ancient immiscible silica‐rich melt on the Moon [ABSTRACT FROM AUTHOR]

Summary: Citrus huanglongbing (HLB) is the most devastating citrus disease worldwide. 'Candidatus Liberibacter asiaticus' (Las) is the most prevalent HLB causal agent that is yet to be cultured. Here, we analysed the flagellar genes of Las and Rhizobiaceae and observed two characteristics unique to the flagellar proteins of Las: (i) a shorter primary structure of the rod capping protein FlgJ than other Rhizobiaceae bacteria and (ii) Las contains only one flagellin‐encoding gene flaA (CLIBASIA_02090), whereas other Rhizobiaceae species carry at least three flagellin‐encoding genes. Only flgJAtu but not flgJLas restored the swimming motility of Agrobacterium tumefaciens flgJ mutant. Pull‐down assays demonstrated that FlgJLas interacts with FlgB but not with FliE. Ectopic expression of flaALas in A. tumefaciens mutants restored the swimming motility of ∆flaA mutant and ∆flaAD mutant, but not that of the null mutant ∆flaABCD. No flagellum was observed for Las in citrus and dodder. The expression of flagellar genes was higher in psyllids than in planta. In addition, western blotting using flagellin‐specific antibody indicates that Las expresses flagellin protein in psyllids, but not in planta. The flagellar features of Las in planta suggest that Las movement in the phloem is not mediated by flagella. We also characterized the movement of Las after psyllid transmission into young flush. Our data support a model that Las remains inside young flush after psyllid transmission and before the flush matures. The delayed movement of Las out of young flush after psyllid transmission provides opportunities for targeted treatment of young flush for HLB control. [ABSTRACT FROM AUTHOR]

Background: Various studies by MRI exhibit that the corpus callosum (CC) is the most vulnerable to cuprizone administration, detecting the demyelination and remyelination process using different MRI parameters are, however, lacking.Purpose: To investigate the sensitivity of multiparametric MRI both in vivo and ex vivo for demyelination and remyelination.Study Type: Prospective.Animal Model: A cuprizone mice model with an age-matched control group (n = 5), 4-week cuprizone exposure group followed by 9-week on a normal diet (n = 6), and a 13-week cuprizone exposure group (n = 6).Field Strength/sequence: 3D gradient recalled echo, T2 -weighted, and diffusion tensor imaging (DTI) at 7.0T and 9.4T.Assessment: Quantification of DTI metrics, quantitative susceptibility mapping (QSM), and T2 -weighted imaging intensity in major white matter bundles.Statistical Tests: Nonparametric permutation tests were used with a cluster-forming threshold as 3.09 (equivalent to P = 0.001), and the significant level as P = 0.05 with family-wise correction.Results: In vivo susceptibility values increased from -11.7 to -0.7 ppb (P < 0.001) in CC and from -13.7 to -5.1 ppb (P < 0.001) in the anterior commissure (AC) after the 13-week cuprizone exposure. Ex vivo susceptibility values increased from -25.4 to 7.4 ppb (P < 0.001) in CC and from -41.6 to -15.8 ppb (P < 0.001) in AC. Susceptibility values showed high variations to demyelination for in vivo studies (94.0% in CC, 62.8% in AC). Susceptibility values exhibited higher variations than radial diffusivity for ex vivo studies (129.1% vs. 28.3% in CC, 62.0% vs. 25.0% in AC). In addition to the differential susceptibility variations in different white matter tracts, intraregional demyelination variation was also present not only in CC but also in the AC area by voxel-based analysis.Data Conclusion: QSM is sensitive to the demyelination process of cuprizone exposure, which can be a complementary technique to conventional T2 -weighted images and DTI metrics.Level Of Evidence: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1852-1865. [ABSTRACT FROM AUTHOR]

Summary: The bacterial stringent response is a response to nutrition deprivation and other stress conditions. In Gram‐negative bacteria, this process is mediated by the small signal molecules guanosine pentaphosphate pppGpp and guanosine tetraphosphate ppGpp (collectively referred to as (p)ppGpp), and the RNA polymerase‐binding transcription factor DksA. The (p)ppGpp synthetase RelA and the bifunctional (p)ppGpp synthase/hydrolase SpoT are responsible for cellular (p)ppGpp levels. Here, we investigated the roles of DksA and (p)ppGpp in the virulence traits of Xanthomonas citri subsp. citri (Xcc), the causal agent of citrus canker. ΔdksA and (p)ppGpp‐deficient ΔspoTΔrelA strains caused reduced virulence and compromised growth in host plants, indicating that DksA and (p)ppGpp are required for full virulence of Xcc. To characterize the effect of stringent response regulators on gene expression, RNA‐seq was conducted using ΔdksA and ΔspoTΔrelA mutant strains grown in hrp‐inducing XVM2 medium. Transcriptome analyses showed that DksA and (p)ppGpp repressed the expression of genes encoding tRNAs, ribosome proteins, iron acquisition and flagellum assembly, and enhanced the expression of genes for histidine metabolism, type 3 secretion system (T3SS), type 2 secretion system (T2SS) and TonB‐dependent transporters. Phenotypically, the ΔdksA and ΔspoTΔrelA strains displayed altered motility, enhanced siderophore production and were unable to cause the hypersensitive response on non‐host plants. In conclusion, stringent response regulators DksA and (p)ppGpp play an important role in virulence, nutrition uptake and host adaptation of Xcc. [ABSTRACT FROM AUTHOR]

Summary: Recently, CRISPR‐Cas12a (Cpf1) from Prevotella and Francisella was engineered to modify plant genomes. In this report, we employed CRISPR‐LbCas12a (LbCpf1), which is derived from Lachnospiraceae bacterium ND2006, to edit a citrus genome for the first time. First, LbCas12a was used to modify the CsPDS gene successfully in Duncan grapefruit via Xcc‐facilitated agroinfiltration. Next, LbCas12a driven by either the 35S or Yao promoter was used to edit the PthA4 effector binding elements in the promoter (EBEPthA4‐CsLOBP) of CsLOB1. A single crRNA was selected to target a conserved region of both Type I and Type II CsLOBPs, since the protospacer adjacent motif of LbCas12a (TTTV) allows crRNA to act on the conserved region of these two types of CsLOBP. CsLOB1 is the canker susceptibility gene, and it is induced by the corresponding pathogenicity factor PthA4 in Xanthomonas citri by binding to EBEPthA4‐CsLOBP. A total of seven 35S‐LbCas12a‐transformed Duncan plants were generated, and they were designated as #D35s1 to #D35s7, and ten Yao‐LbCas12a‐transformed Duncan plants were created and designated as #Dyao1 to #Dyao10. LbCas12a‐directed EBEPthA4‐CsLOBP modifications were observed in three 35S‐LbCas12a‐transformed Duncan plants (#D35s1, #D35s4 and #D35s7). However, no LbCas12a‐mediated indels were observed in the Yao‐LbCas12a‐transformed plants. Notably, transgenic line #D35s4, which contains the highest mutation rate, alleviates XccΔpthA4:dCsLOB1.4 infection. Finally, no potential off‐targets were observed. Therefore, CRISPR‐LbCas12a can readily be used as a powerful tool for citrus genome editing. [ABSTRACT FROM AUTHOR]

Proangiogenesis is generally regarded as an effective approach for treating ischemic heart disease. Vascular endothelial growth factor (VEGF)‐A is a strong and essential proangiogenic factor. Reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy are implicated in the process of angiogenesis. This study is designed to clarify the regulatory mechanisms underlying VEGF‐A, ROS, ER stress, autophagy, and angiogenesis in acute myocardial infarction (AMI). A mouse model of AMI was successfully established by occluding the left anterior descending coronary artery. Compared with the sham‐operated mice, the microvessel density, VEGF‐A content, ROS production, expression of vascular endothelial cadherin, positive expression of 78 kDa glucose‐regulated protein/binding immunoglobulin protein (GRP78/Bip), and LC3 puncta in CD31‐positive endothelial cells of the ischemic myocardium were overtly elevated. Moreover, VEGF‐A exposure predominantly increased the expression of beclin‐1, autophagy‐related gene (ATG) 4, ATG5, inositol‐requiring enzyme‐1 (IRE‐1), GRP78/Bip, and LC3‐II/LC3‐I as well as ROS production in the human umbilical vein endothelial cells (HUVECs) in a dose and time‐dependent manner. Both beclin‐1 small interfering RNA and 3‐methyladenine treatment predominantly mitigated VEGF‐A‐induced tube formation and migration of HUVECs, but they failed to elicit any notable effect on VEGF‐A‐increased expression of GRP78/Bip. Tauroursodeoxycholic acid not only obviously abolished VEGF‐A‐induced increase of IRE‐1, GRP78/Bip, beclin‐1 expression, and LC3‐II/LC3‐I, but also negated VEGF‐A‐induced tube formation and migration of HUVECs. Furthermore, N‐acetyl‐ l‐cysteine markedly abrogated VEGF‐A‐increased ROS production, IRE‐1, GRP78/Bip, beclin‐1 expression, and LC3‐II/LC3‐I in the HUVECs. Taken together, our data demonstrated that increased spontaneous production of VEGF‐A may induce angiogenesis after AMI through initiating ROS–ER stress‐autophagy axis in the vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Methods have been developed to allow quantitative connectivity of the whole fixed mouse brain by means of magnetic resonance imaging (MRI). We have translated what we have learned in clinical imaging to the very special domain of the mouse brain. Diffusion tensor imaging (DTI) of perfusion fixed specimens can now be performed with spatial resolution of 45 μm3, that is, voxels that are 21,000 times smaller than the human connectome protocol. Specimen preparation has been optimized through an active staining protocol using a Gd chelate. Compressed sensing has been integrated into high performance reconstruction and post processing pipelines allowing acquisition of a whole mouse brain connectome in <12 hr. The methods have been validated against retroviral tracer studies. False positive tracts, which are especially problematic in clinical studies, have been reduced substantially to ~28%. The methods have been streamlined to provide high‐fidelity, whole mouse brain connectomes as a routine study. The data package provides holistic insight into the mouse brain with anatomic definition at the meso‐scale, quantitative volumes of subfields, scalar DTI metrics, and quantitative tractography. [ABSTRACT FROM AUTHOR]

Editorial for "Inversion-Recovery-Prepared Oscillating Gradient Sequence Improves Diffusion-Time Dependency Measurements in the Human Brain" The well-designed and executed study showed that IR-prepared oscillating and pulsed gradient sequences could effectively suppress the CSF and improve the I t i SB I d i sb -dependency profiles in the human brain, especially in regions close to the CSF, including the hippocampus and cortical GM. Diffusion MRI (dMRI) is a noninvasive technique to characterize tissue microstructure owing to its sensitivity to the displacement pattern of water molecules during diffusion time ( I t i SB I d i sb ).[[1]] By varying the diffusion times, the time dependency of the microstructure can be captured to infer tissue properties. [Extracted from the article]

Summary: Recombination breaks up ancestral linkage disequilibrium, creates combinations of alleles, affects the efficiency of natural selection, and plays a major role in crop domestication and improvement. However, there is little knowledge regarding the variation in the population‐scaled recombination rate in cotton. We constructed recombination maps and characterized the difference in the genomic landscape of the population‐scaled recombination rate between Gossypium hirsutum and G. arboreum and sub‐genomes based on the 381 sequenced G. hirsutum and 215 G. arboreum accessions. Comparative genomics identified large structural variations and syntenic genes in the recombination regions, suggesting that recombination was related to structural variation and occurred preferentially in the distal chromosomal regions. Correlation analysis indicated that recombination was only slightly affected by geographical distribution and breeding period. A genome‐wide association study (GWAS) was performed with 15 agronomic traits using 267 cotton accessions and identified 163 quantitative trait loci (QTL) and an important candidate gene (Ghir_COL2) for early maturity traits. Comparative analysis of recombination and a GWAS revealed that the QTL of fibre quality traits tended to be more common in high‐recombination regions than were those of yield and early maturity traits. These results provide insights into the population‐scaled recombination landscape, suggesting that recombination contributed to the domestication and improvement of cotton, which provides a useful reference for studying recombination in other species. Significance Statement: There is little knowledge regarding the population‐scaled recombination rate variation in cotton. Genome‐wide fine‐scaled recombination maps were constructed and characterized the population‐scaled recombination rate in Gossypium hirsutum and G. arboreum in the present study; and GWAS revealed that agronomic trait QTL tended to be co‐located in high‐recombination regions, which revealed that recombination contributed to the domestication and genetic improvement of cotton. [ABSTRACT FROM AUTHOR]

Accurate and robust source location is fundamental in seismology. Previously, we proposed a new full waveform location method using waves scattered by topography near the source, and we demonstrated its potential in obtaining accurate source location using synthetic data. In the work presented here, we validate this method with observed seismic data from the 1993 Non‐Proliferation Experiment, a chemical explosion with a precisely known location in a region with moderate topography at the Nevada Test Site. We select the first arrivals (Pn/Pg) and their immediate codas to determine the source location and compare our solution with the known location. We use a collocated‐grid finite‐difference method to calculate the strain Green's tensor in a grid‐search volume containing the source and obtain three‐component synthetic waveforms at 12 broadband seismic stations at regional distances using source‐receiver reciprocity. We assess the solution using a least squares misfit between the observed and synthetic waveforms. When scattered coda waves are incorporated, the best solution is within a few hundreds of meters of the exact source location, and the estimated uncertainty of the solution is reduced compared to the waveform‐based solution using only the P waves. The solution is robust to the choice of the frequency content and to the addition of random velocity heterogeneity. We conclude that the full waveform source location method is effective for real seismic data, though more validation tests like this one are needed to further understand its efficacy for source‐station geometry, roughness of topography, signal quality, and other factors. Key Points: We explore the power and limitation of a new full‐waveform location method incorporating scattering by topography with real seismic dataThis location method uses scattering waves to achieve accurate absolute source locations with robust determinations of the source depthThe solution is robust with overlapping finite frequency bands and unmodeled random velocity heterogeneities [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whole knee joint tractography, including articular cartilage, ligaments, meniscus, and growth plate using diffusion tensor imaging (DTI) at microscopic resolution. Methods: Three rat knee joints were scanned using a modified 3D diffusion‐weighted spin echo pulse sequence with 90‐ and 45‐μm isotropic spatial resolution at 9.4T. The b values varied from 250 to 1250 s/mm2 with 4 times undersampling in phase directions. Fractional anisotropy (FA) and mean diffusivity (MD) were compared at different spatial resolution and b values. Tractography was evaluated at multiple b values and angular resolutions in different connective tissues, and compared with conventional histology. The mean tract length and tract volume in various types of tissues were also quantified. Results: DTI metrics (FA and MD) showed consistent quantitative results at 90‐ and 45‐μm isotropic spatial resolutions. Tractography of various connective tissues was found to be sensitive to the spatial resolution, angular resolution, and diffusion weightings. Higher spatial resolution (45 μm) supported tracking the cartilage collagen fiber tracts from the superficial zone to the deep zone, in a continuous and smooth progression in the transitional zone. Fiber length and fiber volume in the growth plate were strongly dependent on angular resolution and b values, whereas tractography in ligaments was found to be less dependent on spatial resolution. Conclusion: High spatial and angular resolution DTI and diffusion tractography can be valuable for knee joint research because of its visualization capacity for collagen fiber orientations and quantitative evaluation of tissue's microscopic properties. [ABSTRACT FROM AUTHOR]

Summary: The type III secretion system (T3SS) is required for Xanthomonas citri subsp. citri (Xcc) virulence by translocating effectors into host cytoplasm to promote disease development. The T3SS is controlled by the master transcriptional regulators HrpG and HrpX. While the function of HrpG and HrpX are well characterized, their upstream regulation remains elusive. By using transposon mutagenesis, we identified XAC3052, a TetR‐family transcriptional regulator, which regulates T3SS gene expression. Deletion of XAC3052 caused significant reduction in the expression of T3SS and effector genes in vitro and in planta; as well as reduction of virulence in sweet orange (Citrus sinensis). Overexpression of hrpG restored the virulence of ∆XAC3052, suggesting that the loss of virulence is caused by reduction of T3SS gene expression. XAC3052 directly binds to the promoter region and represses the transcription of fadE, mhpC and fadH genes. FadE, MhpC and FadH are not involved in T3SS regulation, but involved in fatty acid catabolism. ∆XAC3052 displays altered fatty acid composition and retarded growth in environments limited in fatty acids. Exogenously supplemented long‐chain fatty acids activate the fadE/mhpC promoter and suppress T3SS promoters in wild‐type Xac but not in ∆XAC3052. Moreover, the binding of XAC3052 to its target promoter was disrupted by long‐chain fatty acids in vitro. Herein, XAC3052 is designated as TfmR (T3SS and Fatty acid Mechanism Regulator). This study identifies a novel regulator of fatty acid metabolism and suggests that fatty acids play an important role in the metabolic control of virulence in Xcc. [ABSTRACT FROM AUTHOR]

Accurate and efficient forward modeling methods are important for simulation of seismic wave propagation in 3D realistic Earth models and crucial for high‐resolution full waveform inversion. In the presence of attenuation, wavefield simulation could be inaccurate or unstable over time if not well treated, indicating the importance of the implementation of a strong stability preserving time discretization scheme. In this study, to solve the anelastic wave equation, we choose the optimal strong stability preserving Runge‐Kutta (SSPRK) method for the temporal discretization and apply the fourth‐order MacCormack scheme for the spatial discretization. We approximate the rheological behaviors of the Earth by using the generalized Maxwell body model and use an optimization procedure to calculate the anelastic coefficients determined by the Q(ω) law. This optimization constrains positivity of the anelastic coefficients and ensures the decay of total energy with time, resulting in a stable viscoelastic system even in the presence of strong attenuation. Moreover, we perform theoretical and numerical analyses of the SSPRK method, including the stability criteria and the numerical dispersion. Compared with the traditional fourth‐order Runge‐Kutta method, the SSPRK has a larger stability condition number and can better suppress numerical dispersion. We use the complex‐frequency‐shifted perfectly matched layer for the absorbing boundary conditions based on the auxiliary difference equation and employ the traction image method for the free‐surface boundary condition on curvilinear grids representing the surface topography. Finally, we perform several numerical experiments to demonstrate the accuracy of our anelastic modeling in the presence of surface topography. Key Points: We develop a new optimal strong stability preserving Runge‐Kutta (SSPRK) method for solving the anelastic wave equationWe perform theoretical and numerical analyses of the SSPRK methodWe demonstrate the accuracy and efficiency of the SSPRK method in anelastic wavefield modeling in the presence of surface topography [ABSTRACT FROM AUTHOR]

Summary: Taxonomic status: Bacteria; Phylum Proteobacteria; Class Gammaproteobacteria; Order Xanthomonadales; Family Xanthomonadaceae; Genus Xanthomonas; Species Xanthomonas citri ssp. citri (Xcc). Host range: Compatible hosts vary in their susceptibility to citrus canker (CC), with grapefruit, lime and lemon being the most susceptible, sweet orange being moderately susceptible, and kumquat and calamondin being amongst the least susceptible. Microbiological properties: Xcc is a rod‐shaped (1.5–2.0 × 0.5–0.75 µm), Gram‐negative, aerobic bacterium with a single polar flagellum. The bacterium forms yellow colonies on culture media as a result of the production of xanthomonadin. Distribution: Present in South America, the British Virgin Islands, Africa, the Middle East, India, Asia and the South Pacific islands. Localized incidence in the USA, Argentina, Brazil, Bolivia, Uruguay, Senegal, Mali, Burkina Faso, Tanzania, Iran, Saudi Arabia, Yemen and Bangladesh. Widespread throughout Paraguay, Comoros, China, Japan, Malaysia and Vietnam. Eradicated from South Africa, Australia and New Zealand. Absent from Europe. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potentials of compressed sensing (CS) in MRI quantification of glycosaminoglycan (GAG) concentration in articular cartilage at microscopic resolution. Methods: T1‐weighted 2D experiments of cartilage were fully sampled in k‐space with five inversion times at 17.6 μm resolution. These fully sampled k‐space data were re‐processed, by undersampling at various 1D and 2D CS undersampling factors (UFs). The undersampled data were reconstructed individually into 2D images using nonlinear reconstruction, which were used to calculate 2D maps of T1 and GAG concentration. The values of T1 and GAG in cartilage were evaluated at different UFs (up to 16, which used 6.25% of the data). K‐space sampling pattern and zonal variations were also investigated. Results: Using 2D variable density sampling pattern, the T1 images at UFs up to eight preserved major visual information and produced negligible artifacts. The GAG concentration remained accurate for different sub‐tissue zones at various UFs. The variation of the mean GAG concentration through the whole tissue depth was 1.20%, compared to the fully sampled results. The maximum variation was 2.24% in the deep zone of cartilage. Using 1D variable density sampling pattern, the quantitative T1 mapping and GAG concentration at UFs up to 4 showed negligible variations. Conclusion: This study demonstrates that CS could be beneficial in microscopic MRI (µMRI) studies of cartilage by acquiring less data, without losing significant accuracy in the quantification of GAG concentration. Magn Reson Med 79:3163–3171, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Abstract: Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro‐angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro‐angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks. It was found that HSYA significantly improved ischaemia‐induced cardiac haemodynamics, enhanced the survival rate, alleviated the myocardial injury and increased the expressions of CD31, vascular endothelial growth factor‐A (VEGF‐A) and nucleolin in the ischaemic myocardium. In addition, HSYA promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs), enhanced the expressions of nucleolin, VEGF‐A and matrix metalloproteinase‐9 (MMP‐9) in a dose‐ and time‐dependent manner. However, down‐regulation of nucleolin expression sharply abrogated the effect mentioned above of HSYA. Further protein‐RNA coimmunoprecipitation and immunoprecipitation‐RT‐PCR assay showed that nucleolin binded to VEGF‐A and MMP‐9 mRNA and overexpression of nucleolin up‐regulated the mRNA expressions of VEGF‐A and MMP‐9 in the HUVECs through enhancing the stability of VEGF‐A and MMP‐9 mRNA. Furthermore, HSYA increased the mRNA expressions of VEGF‐A and MMP‐9 in the extract of antinucleolin antibody‐precipitated protein from the heart of AMI mice. Our data revealed that nucleolin mediated the pro‐angiogenic effect of HSYA through post‐transcriptional regulation of VEGF‐A and MMP‐9 expression, which contributed to the protective effect of HSYA on ischaemic cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Summary: Introgression of genomic variation between and within related crop species is a significant evolutionary approach for population differentiation, genome reorganization and trait improvement. Using the Illumina Infinium Brassica 60K SNP array, we investigated genomic changes in a panel of advanced generation new‐type Brassica napus breeding lines developed from hundreds of interspecific crosses between 122 Brassica rapa and 74 Brassica carinata accessions, and compared them with representative accessions of their three parental species. The new‐type B. napus population presented rich genetic diversity and abundant novel genomic alterations, consisting of introgressions from B. rapa and B. carinata, novel allelic combinations, reconstructed linkage disequilibrium patterns and haplotype blocks, and frequent deletions and duplications (nonrandomly distributed), particularly in the C subgenome. After a much shorter, but very intensive, selection history compared to traditional B. napus, a total of 15 genomic regions with strong selective sweeps and 112 genomic regions with putative signals of selective sweeps were identified. Some of these regions were associated with important agronomic traits that were selected for during the breeding process, while others were potentially associated with restoration of genome stability and fertility after interspecific hybridization. Our results demonstrate how a novel method for population‐based crop genetic improvement can lead to rapid adaptation, restoration of genome stability and positive responses to artificial selection. [ABSTRACT FROM AUTHOR]

Purpose To investigate the B0 orientation-dependent magnetic susceptibility of collagen fibrils within the articular cartilage and to determine whether susceptibility tensor imaging (STI) can detect the 3D collagen network within cartilage. Methods Multiecho gradient echo datasets (100-μm isotropic resolution) were acquired from fixed porcine articular cartilage specimens at 9.4 T. The susceptibility tensor was calculated using phase images acquired at 12 or 15 different orientations relative to B0. The susceptibility anisotropy of the collagen fibril was quantified and diffusion tensor imaging (DTI) was compared against STI. 3D tractography was performed to visualize and track the collagen fibrils with DTI and STI. Results STI experiments showed the distinct and significant anisotropic magnetic susceptibility of collagen fibrils within the articular cartilage. STI can be used to measure and quantify susceptibility anisotropy maps. Furthermore, STI provides orientation information of the underlying collagen network via 3D tractography. Conclusion The findings of this study demonstrate that STI can characterize the orientation variation of collagen fibrils where diffusion anisotropy fails. We believe that STI could serve as a sensitive and noninvasive marker to study the collagen fibrils microstructure. Magn Reson Med 78:1683-1690, 2017. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the magnetic susceptibility properties of different anatomical structures within the knee joint using quantitative susceptibility mapping (QSM). Methods A collagen tissue model was simulated and ex vivo animal cartilage experiments were conducted at 9.4 Tesla (T) to evaluate the B0 orientation-dependent magnetic susceptibility contrast observed in cartilage. Furthermore, nine volunteers (six healthy subjects without knee pain history and three patients with known knee injury, between 29 and 58 years old) were scanned using gradient-echo acquisitions on a high-field 7T MR scanner. Susceptibility values of different tissues were quantified and diseased cartilage and meniscus were compared against that of healthy volunteers. Results Simulation and ex vivo animal cartilage experiments demonstrated that collagen fibrils exhibit an anisotropic susceptibility. A gradual change of magnetic susceptibility was observed in the articular cartilage from the superficial zone to the deep zone, forming a multilayer ultrastructure consistent with anisotropy of collagen fibrils. Meniscal tears caused a clear reduction of susceptibility contrast between the injured meniscus and surrounding cartilage illustrated by a loss of the sharp boundaries between the two. Moreover, QSM showed more dramatic contrast in the focal degenerated articular cartilage than [ABSTRACT FROM AUTHOR]

The lateral organ boundary domain (LBD) genes encode a group of plant-specific proteins that function as transcription factors in the regulation of plant growth and development. Citrus sinensis lateral organ boundary 1 ( CsLOB1) is a member of the LBD family and functions as a disease susceptibility gene in citrus bacterial canker (CBC). Thirty-four LBD members have been identified from the Citrus sinensis genome. We assessed the potential for additional members of LBD genes in citrus to function as surrogates for CsLOB1 in CBC, and compared host gene expression on induction of different LBD genes. Using custom-designed transcription activator-like (TAL) effectors, two members of the same clade as CsLOB1, named CsLOB2 and CsLOB3, were found to be capable of functioning similarly to CsLOB1 in CBC. RNA sequencing and quantitative reverse transcription-polymerase chain reaction analyses revealed a set of cell wall metabolic genes that are associated with CsLOB1, CsLOB2 and CsLOB3 expression and may represent downstream genes involved in CBC. [ABSTRACT FROM AUTHOR]

Citrus is a highly valued tree crop worldwide, while, at the same time, citrus production faces many biotic challenges, including bacterial canker and Huanglongbing ( HLB). Breeding for disease-resistant varieties is the most efficient and sustainable approach to control plant diseases. Traditional breeding of citrus varieties is challenging due to multiple limitations, including polyploidy, polyembryony, extended juvenility and long crossing cycles. Targeted genome editing technology has the potential to shorten varietal development for some traits, including disease resistance. Here, we used CRISPR/Cas9/sg RNA technology to modify the canker susceptibility gene Cs LOB1 in Duncan grapefruit. Six independent lines, DLOB2, DLOB3, DLOB9, DLOB10, DLOB11 and DLOB12, were generated. Targeted next-generation sequencing of the six lines showed the mutation rate was 31.58%, 23.80%, 89.36%, 88.79%, 46.91% and 51.12% for DLOB2, DLOB3, DLOB9, DLOB10, DLOB11 and DLOB12, respectively, of the cells in each line. DLOB2 and DLOB3 showed canker symptoms similar to wild-type grapefruit, when inoculated with the pathogen Xanthomonas citri subsp. citri (Xcc). No canker symptoms were observed on DLOB9, DLOB10, DLOB11 and DLOB12 at 4 days postinoculation ( DPI) with Xcc. Pustules caused by Xcc were observed on DLOB9, DLOB10, DLOB11 and DLOB12 in later stages, which were much reduced compared to that on wild-type grapefruit. The pustules on DLOB9 and DLOB10 did not develop into typical canker symptoms. No side effects and off-target mutations were detected in the mutated plants. This study indicates that genome editing using CRISPR technology will provide a promising pathway to generate disease-resistant citrus varieties. [ABSTRACT FROM AUTHOR]

Purpose: Because the roles of striatal-thalamo-cortical and cerebello-thalamo-cortical circuits in the heterogeneous motor impairments of Parkinson's disease (PD) are becoming recognized, this study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei in these circuits and the different motor impairments.Materials and Methods: Sixty-two PD patients and 40 normal subjects were included and accepted for Enhanced T2 -Star Weighted Angiography Scanning (3.0T). According to the Unified Parkinson's Disease Rating Scale, patients were divided into tremor-dominant (PD-TD) and akinetic/rigid-dominant groups (PD-AR). The intergroup differences of magnetic susceptibility in those cardinal nuclei were measured. Correlation analyses between magnetic susceptibility and motor impairments were performed in all patients.Results: Nigral magnetic susceptibility significantly increased for each PD group compared with controls (P < 0.001 for PD-TD; P = 0.001 for PD-AR). Magnetic susceptibility in the dentate nucleus (DN) and red nucleus (RN) for the PD-TD patients were significantly increased compared with controls (P < 0.001 and P = 0.004, respectively). Magnetic susceptibility in these regions was also significantly correlated with tremor severity (r = 0.444, P = 0.001 for DN; r = 0.418, P = 0.001 for RN). Significant correlation between caudate magnetic susceptibility and akinetic/rigid severity were observed (r = -0.322, P = 0.015).Conclusion: This study provides evidence that nigral iron accumulation is a common characteristic in PD, while iron accumulation in the DN and RN is correlated with tremor symptoms. Our data also indicate that caudate iron content may be a potential marker for akinetic/rigid progression.Level Of Evidence: 3 J. MAGN. RESON. IMAGING 2017;45:1335-1342. [ABSTRACT FROM AUTHOR]