Search

Maize yield is mostly determined by its grain size. Although numerous quantitative trait loci (QTL) have been identified for kernel-related traits, the application of these QTL in breeding programs has been strongly hindered because the populations used for QTL mapping are often different from breeding populations. However, the effect of genetic background on the efficiency of QTL and the accuracy of trait genomic prediction has not been fully studied. Here, we used a set of reciprocal introgression lines (ILs) derived from 417F × 517F to evaluate how genetic background affects the detection of QTLassociated with kernel shape traits. A total of 51 QTL for kernel size were identified by chromosome segment lines (CSL) and genome-wide association studies (GWAS) methods. These were subsequently clustered into 13 common QTL based on their physical position, including 7 genetic-background-independent and 6 genetic-background-dependent QTL, respectively. Additionally, different digenic epistatic marker pairs were identified in the 417F and 517F ILs. Therefore, our results demonstrated that genetic background strongly affected not only the kernel size QTL mapping via CSL and GWAS but also the genomic prediction accuracy and epistatic detection, thereby enhancing our understanding of how genetic background affects the genetic dissection of grain size-related traits.

Maize rough dwarf disease (MRDD) is caused by a virus and seriously affects maize quality and yield worldwide. MRDD can be most effectively controlled with disease-resistant hybrids of corn. Here, MRDD-resistant (Qi319) and -susceptible (Ye478) parental inbred maize lines and their 314 recombinant inbred lines (RILs) that were derived from a cross between them were evaluated across three environments. A stable resistance QTL, qMrdd2, was identified and mapped using best linear unbiased prediction (BLUP) values to a 0.55-Mb region between the markers MK807 and MK811 on chromosome 2 (B73 RefGen_v3) and was found to explain 8.6 to 11.0% of the total phenotypic variance in MRDD resistance. We validated the effect of qMrdd2 using a chromosome segment substitution line (CSSL) that was derived from a cross between maize inbred Qi319 as the MRDD resistance donor and Ye478 as the recipient. Disease severity index of the CSSL haplotype II harboring qMrdd2 was significantly lower than that of the susceptible parent Ye478. Subsequently, we fine-mapped qMrdd2 to a 315-kb region flanked by the markers RD81 and RD87, thus testing recombinant-derived progeny using selfed backcrossed families. In this study, we identified a novel QTL for MRDD resistance by combining the RIL and CSSL populations, thus providing important genetic information that can be used for breeding MRDD-resistant varieties of maize.

Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a balance between comprehensiveness and precision. Here we present a catalog of 355,667 SVs (59.34% novel) across autosomes and the X chromosome (50bp+) from 138,134 individuals in the diverse TOPMed consortium. We describe our methodologies for SV inference resulting in high variant quality and >90% allele concordance compared to long-read de-novo assemblies of well-characterized control samples. We demonstrate utility through significant associations between SVs and important various cardio-metabolic and hematologic traits. We have identified 690 SV hotspots and deserts and those that potentially impact the regulation of medically relevant genes. This catalog characterizes SVs across multiple populations and will serve as a valuable tool to understand the impact of SV on disease development and progression.

Genomic medicine holds great promise for improving health care, but integrating searchable and actionable genetic data into electronic health records (EHRs) remains a challenge. Here we describe Neptune, a system for managing the interaction between a clinical laboratory and an EHR system during the clinical reporting process. We developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis, and EHR integration. Neptune has been applied for the generation and delivery of over 15,000 clinical genomic reports. This work spans two clinical tests based on targeted gene panels that contain 68 and 153 genes respectively. These projects demanded customizable clinical reports that contained a variety of genetic data types including single-nucleotide variants (SNVs), copy-number variants (CNVs), pharmacogenomics, and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. Methods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open source and available at https://gitlab.com/bcm-hgsc/neptune .

Xia-Gibbs syndrome is a rare mendelian disorder characterized by Development Delay (DD), intellectual disability (ID), and hypotonia. Individuals with XGS typically harbor de novo protein-truncating mutations in the AT-Hook DNA binding motif containing 1 (AHDC1) gene, although some missense mutations can also cause XGS. Large de novo heterozygous deletions that encompass the AHDC1 gene have also been ascribed as diagnostic for the disorder, without substantial evidence to support their pathogenicity. We analyzed 19 individuals with large contiguous deletions involving AHDC1, along with other genes. One individual bore the smallest known contiguous AHDC1 deletion (∼350 Kb), encompassing eight other genes within chr1p36.11 (Feline Gardner-Rasheed, IFI6, FAM76A, STX12, PPP1R8, THEMIS2, RPA2, SMPDL3B) and terminating within the first intron of AHDC1. The breakpoint junctions and phase of the deletion were identified using both short and long read sequencing (Oxford Nanopore). Quantification of RNA expression patterns in whole blood revealed that AHDC1 exhibited a mono-allelic expression pattern with no deficiency in overall AHDC1 expression levels, in contrast to the other deleted genes, which exhibited a 50% reduction in mRNA expression. These results suggest that AHDC1 expression in this individual is compensated by a novel regulatory mechanism and advances understanding of mutational and regulatory mechanisms in neurodevelopmental disorders.

KIF1A is a molecular motor for membrane-bound cargo important to the development and survival of sensory neurons. KIF1A dysfunction has been associated with several Mendelian disorders with a spectrum of overlapping phenotypes, ranging from spastic paraplegia to intellectual disability. We present a novel pathogenic in-frame deletion in the KIF1A molecular motor domain inherited by two affected siblings from an unaffected mother with apparent germline mosaicism. We identified eight additional cases with heterozygous, pathogenic KIF1A variants ascertained from a local data lake. Our data provide evidence for the expansion of KIF1A-associated phenotypes to include hip subluxation and dystonia as well as phenotypes observed in only a single case: gelastic cataplexy, coxa valga, and double collecting system. We review the literature and suggest that KIF1A dysfunction is better understood as a single neuromuscular disorder with variable involvement of other organ systems than a set of discrete disorders converging at a single locus. National Institutes of Health Revisión por pares

Maize rough dwarf disease (MRDD) is caused by viruses in the Fijivirus genus in the family Reoviridae. MRDD resistance can be improved by a combination of marker-assisted selection (MAS) and conventional breeding strategies. In our previous study, we fine-mapped a major QTL qMrdd8 and developed the functional Indel marker IDP25K. In the present study, qMrdd8 from the donor parent X178 was introgressed into elite inbred lines derived from the three corn heterotic groups using multi-generation backcrossing and MAS. Recipient lines included Huangzao4, Chang7-2, Ye478, Zheng58, Zhonghuang68, B73, and Ji846. Markers used for foreground selection included IDRQ4, IDRQ47, IDP25K, and IDP27K. Background selection was carried out in the BC3 or BC4 using 107 SSR markers to select lines with the highest rate of recovery of the particular recurrent parent genome. Plants from BC4F2 and BC3F2 that carried the shortest qMrdd8 interval from X178 and those with the highest rate of recovery of the recurrent parent genome were then selected to create converted homozygous inbred lines. In 2017, seven converted inbred lines and five hybrids exhibited enhanced resistance to MRDD, while other agronomic traits were not affected under nonpathogenic stress conditions. Thus, the MRDD resistance allele at the qMrdd8 locus, or IDP25K, should be valuable for maize breeding programs in China.

Salinity has become a crucial environmental factor seriously restricting maize (

Background The Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity. Findings Here, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gb, similar to the 2.50-Gb length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity, with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein-coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein-coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where ∼17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0, in which the number of unresolved bases is reduced to 3.00%. Conclusions Access to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models.

Summary Xia-Gibbs syndrome (XGS; MIM: 615829) is a phenotypically heterogeneous neurodevelopmental disorder (NDD) caused by newly arising mutations in the AT-Hook DNA-Binding Motif-Containing 1 (AHDC1) gene that are predicted to lead to truncated AHDC1 protein synthesis. More than 270 individuals have been diagnosed with XGS worldwide. Despite the absence of an independent assay for AHDC1 protein function to corroborate potential functional consequences of rare variant genetic findings, there are also reports of individuals with XGS-like trait manifestations who have de novo missense AHDC1 mutations and who have been provided a molecular diagnosis of the disorder. To investigate a potential contribution of missense mutations to XGS, we mapped the missense mutations from 10 such individuals to the AHDC1 conserved protein domain structure and detailed the observed phenotypes. Five newly identified individuals were ascertained from a local XGS Registry, and an additional five were taken from external reports or databases, including one publication. Where clinical data were available, individuals with missense mutations all displayed phenotypes consistent with those observed in individuals with AHDC1 truncating mutations, including delayed motor milestones, intellectual disability (ID), hypotonia, and speech delay. A subset of the 10 reported missense mutations cluster in two regions of the AHDC1 protein with known conserved domains, likely representing functional motifs. Variants outside the clustered regions score lower for computational prediction of their likely damaging effects. Overall, de novo missense variants in AHDC1 are likely diagnostic of XGS when in silico analysis of their position relative to conserved regions is considered together with disease trait manifestations.

Background Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies. Findings Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from different assembly methods based on 2 main approaches that can be applied to other Cryptosporidium species. The assembly encompasses 8 chromosomes and includes 13 telomeres that were resolved. Overall, the assembly shows a high completion rate with 98.4% single-copy BUSCO genes. Conclusions This high-quality reference genome of a zoonotic IIaA17G2R1 C. parvum subtype isolate provides the basis for subsequent comparative genomic studies across the Cryptosporidium clade. This will enable improved understanding of diversity, functional, and association studies.

Objective Commercial gene panels identify pathogenic variants in as low as 27% of patients suspected to have MODY, suggesting the role of yet unidentified pathogenic variants. We sought to identify novel gene variants associated with MODY. Research design and methods We recruited 10 children with a clinical suspicion of MODY but non-diagnostic commercial MODY gene panels. We performed exome sequencing (ES) in them and their parents. Results Mean age at diabetes diagnosis was 10 (± 3.8) years. Six were females; 4 were non-Hispanic white, 5 Hispanic, and 1 Asian. Our variant prioritization analysis identified a pathogenic, de novo variant in INS (c.94G > A, p.Gly32Ser), confirmed by Sanger sequencing, in a proband who was previously diagnosed with "autoantibody-negative type 1 diabetes (T1D)" at 3 y/o. This rare variant, absent in the general population (gnomAD database), has been reported previously in neonatal diabetes. We also identified a frameshift deletion (c.2650delC, p.Gln884AsnfsTer57) in RFX6 in a child with a previous diagnosis of "autoantibody-negative T1D" at 12 y/o. The variant was inherited from the mother, who was diagnosed with "thin type 2 diabetes" at 25 y/o. Heterozygous protein-truncating variants in RFX6 gene have been recently reported in individuals with MODY. Conclusions We diagnosed two patients with MODY using ES in children initially classified as "T1D". One has a likely pathogenic novel gene variant not previously associated with MODY. We demonstrate the clinical utility of ES in patients with clinical suspicion of MODY.

ImportanceVaccine breakthrough by an emergent SARS-CoV-2 variant poses a great risk to global public health.ObjectiveTo determine the SARS-CoV-2 variant responsible for 6 cases of vaccine breakthrough.DesignNasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 by qPCR for Wuhan-Hu1 and Alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant.SettingTransmission event occurred at events surrounding a wedding outside of Houston, TX. Two patients from India, likely transmitted the Delta variant to other guests.ParticipantsFollowing a positive SARS-CoV-2 qPCR test at a third-party site, six fully vaccinated patients were investigated. Three males and three females ranged from 53 to 69 years old. One patient suffered from diabetes while three others were classified as overweight. No significant other comorbidities were identified. None of the patients had a history of failed vaccination.Key PointsQuestionWhich SARS-CoV-2 variant is responsible for 6 cases of vaccine breakthrough, one interventional monoclonal antibody treatment, and one death?FindingsViral sequencing revealed 6 vaccinated patients were infected with the Delta SARS-CoV-2 variant. With no histories of vaccine breakthrough, this suggests Delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152.MeaningDelta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with increased transmissibility over Alpha variant and possible vaccine breakthrough.

Dense TiC-ZrC-Cr3C2 composites with various TiC content from 19.6 mol% to 78.4 mol% have been fabricated by hot-pressing sintering at 1950 °C using 2.0 mol% Cr3C2 as sintering aid. The effect of TiC content on the microstructure, mechanical and thermal properties of TiC-ZrC-Cr3C2 composites are investigated systematically. The single (Zr, Ti, Cr)C solid solution is obtained when TiC content is 19.6 mol%, while with increasing TiC content, the composites begin to consist of Zr-rich (Zr, Ti)C solid solution and Ti-rich (Ti, Zr, Cr)C solid solution phase. SEM and EDS analysis confirm that Cr element is not favorable to diffuse into ZrC lattice to form (Zr, Cr)C solid solution. Flexural strength and Vickers hardness increase gradually with increasing TiC content, but fracture toughness does not improve significantly. Fracture toughness are in the range of 3.34–4.01 MPa∙m1/2 for all composites, and the optimum value reaches 4.01 MPa·m1/2 with 49.0 mol% TiC. Experimental results of the thermal expansion coefficient reveal that the addition of TiC raises the thermal expansivity of TiC-ZrC-Cr3C2 composites. Noticeably, the thermal conductivities of TiC-ZrC-Cr3C2 composites show a decrement trend with increasing TiC content, not as theoretical predicting by the rule of mixtures. For instance, the thermal conductivity at 25 °C ranges from 18.0 W/m∙K for 8Z2T2C composite down to 10.6 W/m∙K for 2Z8T2C composite.

Maize rough dwarf disease (MRDD) is caused by a virus and seriously affects maize quality and yield worldwide. MRDD can be most effectively controlled with disease-resistant hybrids of corn. Here, MRDD-resistant (Qi319) and -susceptible (Ye478) parental inbred maize lines and their 314 recombinant inbred lines (RILs) that were derived from a cross between them were evaluated across three environments. A stable resistance QTL

Purpose Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. Methods We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. Results Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. Conclusion Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.

Xia-Gibbs syndrome (XGS) is a rare Mendelian disease typically caused by de novo stop-gain or frameshift mutations in the AT-hook DNA binding motif containing 1 (AHDC1) gene. Patients usually present in early infancy with hypotonia and developmental delay and later exhibit intellectual disability (ID). The overall presentation is variable, however, and the emerging clinical picture is still evolving. A detailed phenotypic analysis of 34 XGS individuals revealed five core phenotypes (delayed motor milestones, speech delay, low muscle tone, ID, and hypotonia) in more than 80% of individuals and an additional 12 features that occurred more variably. Seizures and scoliosis were more frequently associated with truncations that arise before the midpoint of the protein although the occurrence of most features could not be predicted by the mutation position. Transient expression of wild type and different patient truncated AHDC1 protein forms in human cell lines revealed abnormal patterns of nuclear localization including a diffuse distribution of a short truncated form and nucleolar aggregation in mid-protein truncated forms. Overall, both the occurrence of variable phenotypes and the different distribution of the expressed protein reflect the heterogeneity of this syndrome.

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.

Background: Maize rough dwarf disease (MRDD) is a disease caused by a virus that seriously affects maize yield and quality worldwide. Rice black streaked dwarf virus (RBSDV) in the Fijivirus genus in the Reoviridae family causes MRDD in maize. Typical MRDD symptoms of include severe dwarfing of plants, shortening of internodes. MRDD resistance is a complex trait that is quantitatively inherited and is controlled by several quantitative trait loci (QTL). MRDD is most efficiently controlled by the cultivation of disease-resistant corn hybrids. Results: Disease resistance in the MRDD-resistant Qi319 and -susceptible Ye478 parental inbred lines and the 314 recombinant inbred lines (RILs) that were derived from a cross between them was evaluated across three environments. A stable resistance QTL, qMrdd2 , which explained 8.64 to 11.02% of the total phenotypic variance in MRDD resistance, was identified repeatedly and was mapped using BLUP values to a 0.55-Mb region between the markers MK807 and MK811 on chromosome 2. We validated the effect of qMrdd2 using a chromosome segment substitution line population that were derived from a cross between maize inbred Qi319 as the resistance donor and Ye478 as the recipient. The disease-severity index (DSI) of CSSL haplotype II harboring qMrdd2 was significantly lower than the DSI of susceptible parent Ye478 ( P < 0.05). Mapping results using CSSLs were consistent with localization interval determined using RILs. The qMrdd2 locus acted with an additive effect but no significant dominant gene action in conferring MRDD resistance. We fine-mapped qMrdd2 locus into a 315-kb region flanked by the markers RD81 and RD87 by testing recombinant-derived progeny using selfed backcrossed families. Conclusions: qMrdd2 is a recently discovered QTL from Qi319 for resistance to MRDD with an additive effect but no significant dominant gene action for MRDD resistance. qMrdd2 was fine-mapped to a 315-kb interval on maize chromosome 2. Introgression of the MRDD resistance allele at the qMrdd2 locus of CSSL haplotype 2 using linked markers umc1824 and bnlg125 will be useful for maize breeding to reduce yield losses caused by MRDD. Keywords: Maize, Maize rough dwarf disease, QTL, Fine-mapping, RIL；CSSL.

The establishment of female inflorescence morphology is of great significance to the formation of final maize yield. defective ear1 (dea1) is a novel maize mutant with developmental defect of female inflorescence caused by natural variation. Morphological analysis revealed that the mutant dea1 was characterized as a “scar-like” crack on the adaxial side of the top of the ear, accounting for 28.6-100.0% of the ear length, with an average of 32.4%. The results of scanning electron microscope showed that there was collapse in the formation of paired spikelet primordium at the base of the axillary meristem. Most of investigated botanical and agronomical traits of dea1 were lower than those of wild type, except for ear length and hundred grain weight. The grain yield per ear of mutant dea1 was 35.93% lower than that of wild type, and the width of mutation crack contributed the most to the yield loss per ear. The identification of the mutant dea1 and the characteristically phenotypic analysis provide a theoretical basis for the study of the molecular regulation mechanism of ear development and the application of high-yield breeding in maize.The establishment of female inflorescence morphology is of great significance to the formation of final maize yield. defective ear1 (dea1) is a novel maize mutant with developmental defect of female inflorescence caused by natural variation. Morphological analysis revealed that the mutant dea1 was characterized as a “scar-like” crack on the adaxial side of the top of the ear, accounting for 28.6-100.0% of the ear length, with an average of 32.4%. The results of scanning electron microscope showed that there was collapse in the formation of paired spikelet primordium at the base of the axillary meristem. Most of investigated botanical and agronomical traits of dea1 were lower than those of wild type, except for ear length and hundred grain weight. The grain yield per ear of mutant dea1 was 35.93% lower than that of wild type, and the width of mutation crack contributed the most to the yield loss per ear. The identification of the mutant dea1 and the characteristically phenotypic analysis provide a theoretical basis for the study of the molecular regulation mechanism of ear development and the application of high-yield breeding in maize.

According to potential flow theory and considering the dispersive effect, a shallow-water wave equation that satisfies the Laplace equation and free surface and seabed boundary conditions is established in this study. On the basis of the slender ship assumption and continuous matched conditions on the interface of a dredged channel, the mathematical problems of super-supercritical mixed flow are solved by adopting the Fourier integral transform method and the finite difference method, respectively. Meanwhile, the analytical models of super-supercritical ship hydrodynamic pressure field (SHPF) are derived, and those of the open water or rectangular canal can also be deduced by further simplification. The characteristics of super-supercritical SHPF with the dispersive effect are analyzed, and the influences of transverse distance, inner or outer depth, width, and depth Froude number on SHPF are studied. Comparisons between the calculated and experimental results show that the proposed analytical models of SHPF in this research are reasonable, effective, and accurate.

This study uses DNA sequencing to trace a donor organ transplant–mediated cancer transmission and illustrates how precise molecular pathology profiles might reduce future risk for transplant recipients., Four organ transplant recipients from an organ donor diagnosed with anaplastic pleomorphic xanthoastrocytoma developed fatal malignancies for which the origin could not be confirmed by standard methods. We identified the somatic mutational profiles of the neoplasms using next-generation sequencing technologies and tracked the relationship between the different samples. The data were consistent with the presence of an aggressive clonal entity in the donor and the subsequent proliferation of descendent tumors in each recipient. Deleterious mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients’ lesions. In addition to demonstrating that DNA sequencing tracked a donor/recipient cancer transmission, this study established that the genetic profile of a donor tumor and its potential aggressive phenotype could have been determined before transplantation was considered. As the genetic correlates of tumor invasion and metastases become better known, adding genetic profiling by DNA sequencing to the data considered for transplant safety should be considered.

Water immersion treatment of potato slices with various time periods (0–30 min) was studied to find out the effect on the browning of fresh‐cut potato slices during long‐term storage (1–12 days) at 5°C. The results show that water immersion for 15 min significantly inhibit browning compared to other time periods of immersion treatment. Further studies show that the levels of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutamic acid, and proline were increased by the 15‐min water immersion treatment, while hydrogen peroxide (H₂O₂) and superoxide anion (O₂ˉ) were lowered; and all these compounds alleviated the oxidation pressure of potato slices. Chlorogenic acid, tyrosine, and tyrosinase activities were lower than those of the controls, which helped decrease the enzymatic browning levels of treated slices. Nevertheless, the browning inhibition has no observable correlation with either total phenols or the peroxidase (POD) activity. PRACTICAL APPLICATIONS: The research provides a simple anti‐browning method for fresh‐cut potatoes during long‐term storage thus maintaining quality and extending shelf life; and it reports new experimental results detailing the physiological reactions induced by the short‐time water immersion of fresh‐cut potatoes. The physiological studies may promote the understanding of the browning mechanism of fresh‐cut potatoes and provide clues to further efforts in seeking novel strategies for browning inhibition of fresh‐cut potatoes.

Maize rough dwarf disease (MRDD) is caused by viruses in the Fijivirus genus in the family Reoviridae. MRDD resistance can be improved by a combination of marker-assisted selection (MAS) and conventional breeding strategies. In our previous study, we fine-mapped a major QTL qMrdd8 and developed the functional Indel marker IDP25K. In the present study, qMrdd8 from the donor parent X178 was introgressed into elite inbred lines derived from the three corn heterotic groups using multi-generation backcrossing and MAS. Recipient lines included Huangzao4, Chang7-2, Ye478, Zheng58, Zhonghuang68, B73, and Ji846. Markers used for foreground selection included IDRQ4, IDRQ47, IDP25K, and IDP27K. Background selection was carried out in the BC3 or BC4 using 107 SSR markers to select lines with the highest rate of recovery of the particular recurrent parent genome. Plants from BC4F2 and BC3F2 that carried the shortest qMrdd8 interval from X178 and those with the highest rate of recovery of the recurrent parent genome were then selected to create converted homozygous inbred lines. In 2017, seven converted inbred lines and five hybrids exhibited enhanced resistance to MRDD, while other agronomic traits were not affected under nonpathogenic stress conditions. Thus, the MRDD resistance allele at the qMrdd8 locus, or IDP25K, should be valuable for maize breeding programs in China.

Summary: De novo germline variation in POLR2A was recently reported to associate with a neurodevelopmental disorder. We report twelve individuals harboring putatively pathogenic de novo or inherited variants in POLR2A, detail their phenotypes, and map all known variants to the domain structure of POLR2A and crystal structure of RNA polymerase II. Affected individuals were ascertained from a local data lake, pediatric genetics clinic, and an online community of families of affected individuals. These include six affected by de novo missense variants (including one previously reported individual), four clinical laboratory samples affected by missense variation with unknown inheritance—with yeast functional assays further supporting altered function—one affected by a de novo in-frame deletion, and one affected by a C-terminal frameshift variant inherited from a largely asymptomatic mother. Recurrently observed phenotypes include ataxia, joint hypermobility, short stature, skin abnormalities, congenital cardiac abnormalities, immune system abnormalities, hip dysplasia, and short Achilles tendons. We report a significantly higher occurrence of epilepsy (8/12, 66.7%) than previously reported (3/15, 20%) (p value = 0.014196; chi-square test) and a lower occurrence of hypotonia (8/12, 66.7%) than previously reported (14/15, 93.3%) (p value = 0.076309). POLR2A-related developmental disorders likely represent a spectrum of related, multi-systemic developmental disorders, driven by distinct mechanisms, converging at a single locus.

Xia-Gibbs syndrome (XGS: OMIM # 615829) results from de novo truncating mutations within the AT-Hook DNA Binding Motif Containing 1 gene (AHDC1). To further define the phenotypic and molecular spectrum of this disorder, we established an XGS Registry and recruited patients from a worldwide pool of approximately 60 probands. Additional de novo truncating mutations were observed among 25 individuals, extending both the known number of mutation sites and the range of positions within the coding region that were sensitive to alteration. Detailed phenotypic examination of 20 of these patients via clinical records review and data collection from additional surveys showed a wider age range than previously described. Data from developmental milestones showed evidence for delayed speech and that males were more severely affected. Neuroimaging from six available patients showed an associated thinning of the corpus callosum and posterior fossa cysts. An increased risk of both scoliosis and seizures relative to the population burden was also observed. Data from a modified autism screening tool revealed that XGS shares significant overlap with autism spectrum disorders. These details of the phenotypic heterogeneity of XGS implicate specific genotype/phenotype correlations and suggest potential clinical management guidelines.

Based on slender body theory (SBT), Tait׳s state equation and Riabouchinsky closure scheme, this paper has established a theoretical model and computational method including the effect of compressibility for supercavitating flow past a high speed slender conical body, derived the integer-differential equations (IDE) according to different characteristics of subsonic and supersonic flows, and presented the numerical discrete scheme and iteration method to solve the IDE. Supercavity shapes and the hydrodynamic coefficients are acquired for a slender conical body at different cone semi-angles, cavitation number and Mach number. The theoretical model and calculated results are verified by the comparison with the results of other literatures. Finally we have analyzed the influences of fluid compressibility on the supercavity shapes, pressure distribution over the cone surface and base drag coefficient. The above results show that the predicted accuracy of the supercavity shape, maximal radius, aspect ratio, drag coefficient is very good for small cone semi-angle till 15° both in incompressible and compressible flow.

To deal with the effect of compressible fluids on the supercavitating flow over the subsonic disk cavitator of a projectile, a finite volume method is formulated based on the ideal compressible potential theory. By using the continuity equation and Tait state equation as well as Riabouchinsky closure model, an “inverse problem” solution is presented for the supercavitating flow. According to the impenetrable condition on the surface of supercavity, a new iterative method for the supercavity shape is designed to deal with the effect of compressibility on the supercavity shape, pressure drag coefficient and density field. By this method, the very low cavitation number can be computed. The calculated results agree well with the experimental data and empirical formula. At the subsonic condition, the fluid compressibility will make supercavity length and radius increase. The supercavity expands, but remains spheroid. The effect on the first 1/3 part of supercavity is not obvious. The drag coefficient of projectile increases as the cavitation number or Mach number increases. With Mach number increasing, the compressibility is more and more significant. The compressibility must be considered as far as the accurate calculation of supercavitating flow is concerned.

The mitochondrial calcium uniporter (MCU), located in the organelle’s inner membrane of eukaryotic organisms, is a highly selective ion channel which plays a unique role in the calcium signaling. Six MCU-like genes (assigned as ZmMCU1≈ZmMCU6) were identified in the maize genome. Genomic analysis revealed that these six genes were located on chromosome 1, 3, 8 and 9. Sequence identity percent between ZmMCU1 and ZmMCU2, or between ZmMCU4 and ZmMCU5 was relatively high at both the nucleic acid and amino acid levels. Sequence alignment of ZmMCU indicated that for plants, there was “DVME” motif in the deduced protein sequences. Digital expression analysis showed the ZmMCU6 was strongly expressed in all of the studied organs in maize, while the other five ZmMCU genes had unique expression patterns. In the developing seeds of maize, the six ZmMCU genes had three divergent expression patterns. Finally, the phylogenetic analysis demonstrated that MCU homologs in plants could be grouped into two types and each type could be further classified into two subtypes along the monocot and dicot division. Moreover, MCU homologs in both the dicot and monocot had been independently duplicated and then those in maize had undergone an extra duplication for two subclades. Based on genomic structure, sequence similarity, digital expression profile, and phylogenetic analysis, our results clearly suggested that ZmMCU1 and ZmMCU2 as well as ZmMCU4 and ZmMCU5 are functionally redundant in maize genome.

In plants, various proteins are regulated by the ubiquitin-mediated system in response to different environmental stresses, such as drought, cold and heat. The Skp1-Cullin-F-box (SCF) complex, one of the multisubunit E3 ligases, has been shown to be involved in abiotic response pathways. In this study, Glycine max SKP1-like 1 (GmSK1), which had the typical characteristics of an SKP1 protein, with an alpha/beta structure, targeted to the cytoplasm and nucleus, was isolated from soybean [Glycine max (L.)]. GmSK1 was constitutively expressed in all the tested tissues, especially in the roots. Furthermore, the expression of GmSK1 was simultaneously induced by abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), NaCl, low temperatures and drought, which suggests important roles for GmSK1 in plant responses to hormone treatments and abiotic stress. GmSK1-overexpressing transgenic tobacco (Nicotiana tobacum cv. Samsun) plants showed enhanced tolerance to high salinity and drought stress; exhibited significantly reduced inhibition of growth, greenness and water loss; and exhibited increased MDA accumulation compared with wild-type controls. Our results suggest that GmSK1 might play a role in the crosstalk between ubiquitination and abiotic stress responses in plants.

The accumulation of sequenced Francisella strains has made it increasingly apparent that the 16S rRNA gene alone is not enough to stratify the Francisella genus into precise and clinically useful classifications. Continued whole-genome sequencing of isolates will provide a larger base of knowledge for targeted approaches with broad applicability. Additionally, examination of genomic information on a case-by-case basis will help resolve outstanding questions regarding strain stratification. We report the complete genome sequence of a clinical isolate, designated here as F. novicida-like strain TCH2015, acquired from the lymph node of a 6-year-old male. Two features were atypical for F. novicida: exhibition of functional oxidase activity and additional gene content, including proposed virulence determinants. These differences, which could potentially impact virulence and clinical diagnosis, emphasize the need for more comprehensive methods to profile Francisella isolates. This study highlights the value of whole-genome sequencing, which will lead to a more robust database of environmental and clinical genomes and inform strategies to improve detection and classification of Francisella strains.

Zirconium carbide (ZrC) reinforced tungsten (W) composite was hot-pressed at 2200 °C for 1 h in vacuum, which was subsequently heat treated in the temperature range of 2200 to 2500 °C for 1.5 or 2 h. The relative ratios of ZrC phase were 21.0, 23.3 and 25.9 mol.% for the mixture of starting powders, composites sintered for 1 h and solid-solution treated at 2500 °C for 1.5 h, respectively. The solid solubility of W in ZrC increased with the increment in heat-treating temperature and time to a maximum value of 18.9 mol.% at 2500 °C for 1.5 h. The lattice parameter of cubic ZrC phase diminished from 0.4682 nm in the starting powder to 0.4642 nm in the solid-solution composite treated at 2500 °C for 1.5 h. This work demonstrated that the relationship between the solid solubility of W in ZrC and the lattice parameter of ZrC is linear, with a slope of −1.93 × 10−4 nm/at.%. Overall, more W atoms diffused into ZrC lattice after heat treatment, meanwhile, the previous precipitated nano-sized W dissolved in the supersaturated (Zr,W)C solid-solution, as detected by SEM and TEM.

Maize rough dwarf disease (MRDD), caused by the Maize rough dwarf virus (MRDV) is highly prevalent across summer at maize-growing areas in China. To investigate the genetic architecture underlying this viral disease, a set of 236 Chinese maize inbred lines was evaluated for resistance to MRDD in 2010 and 2011. Based on 41,101 single-nucleotide polymorphism (SNP) markers with minor allele frequencies (MAF) greater than 5 %, a genome-wide association study (GWAS) was employed to identify genomic loci for resistance to MRDD. A total of 73 SNPs were found to be associated with resistance to MRDD at a significance threshold of -log10 (P) > 4 controlling the false discovery rate (FDR) at α = 0.1. Fourteen of these SNPs were detected in both of the two environments tested. A total of 48 SNPs were identified in linkage disequilibrium (LD) blocks containing candidate resistance genes, including protein kinase genes. Using the pedigree information and whole-genome SNP analysis of five highly resistant inbred lines derived from the hybrid ‘P78599’, nine derivative fragments harbouring SNPs associated with MRDD resistance were detected. One 81.57 Mb fragment in particular located in bin 8.03, which contained six SNPs associated with MRDD resistance, and included the major quantitative trait loci (QTL) that had been identified in the previous study. These results suggest that the SNPs and fragments associated with MRDD resistance, especially those in bin 8.03, could be used for fine mapping of resistance genes and developing resistant varieties in maize.