Genome-wide identification of the MADS-box gene family in and its role in photoperiod-insensitive oat.

Background: Traditional spring-summer sown oat is a typical long-day crop that cannot head under short-day conditions. The creation of photoperiod-insensitive oats overcomes this limitation. MADS-box genes are a class of transcription factors involved in plant flowering signal transduction regulation.

Genome resequencing reveals independent domestication and breeding improvement of naked oat.

As an important cereal crop, common oat, has attracted more and more attention due to its healthy nutritional components and bioactive compounds. Here, high-depth resequencing of 115 oat accessions and closely related hexaploid species worldwide was performed. Based on genetic diversity and linkage disequilibrium analysis, it was found that hulled oat (Avena sativa) experienced a more severe bottleneck than naked oat (Avena sativa var.

Exceptional response to combination ipilimumab and nivolumab in metastatic uveal melanoma: Insights from genomic analysis.

Uveal melanoma is the most common intraocular malignancy and has a poor prognosis compared to other melanoma subtypes with a median overall survival of 6-10 months. With immune checkpoint inhibitor therapy, either PD-1 inhibitor alone or combination ipilimumab/nivolumab (anti-CTLA-4/anti-PD-1), responses are rare and often not durable. We present a case report of a now 66-year-old woman with diffuse metastatic uveal melanoma previously treated with a combination of ipilimumab/nivolumab, followed by maintenance nivolumab.

Clinical characteristics of recovered COVID-19 patients with re-detectable positive RNA test.

Background: The characteristics, significance and potential cause of positive SARS-CoV-2 diagnoses in recovered coronavirus disease 2019 (COVID-19) patients post discharge (re-detectable positive, RP) remained elusive.

Methods: A total of 262 COVID-19 patients discharged from January 23 to February 25, 2020 were enrolled into this study. RP and non-RP (NRP) patients were grouped according to disease severity, and the characterization at re-admission was analyzed.

Tocilizumab exerts anti-inflammatory activity in six critically ill COVID-19 patients: a retrospective analysis.

Background: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic, affecting countries across the globe. With no current vaccine, treatment is still a critical intervention for minimizing morbidity and preventing disease-specific mortality. This study aimed to assess the clinical outcomes of critically ill COVID-19 patients using Tocilizumab treatment to provide recommendations for the treatment of COVID-19 patients with severe disease.

-associated neurodevelopmental disorder.

Background: Dysfunction of histone methyltransferases and chromatin modifiers has been implicated in complex neurodevelopmental syndromes and cancers. encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. Previous reports of patients with rare variants in describe a distinctive phenotype that includes seizures, global developmental delay and intellectual disability.

Combined transcriptome sequencing reveals the photoperiod insensitivity mechanism of oats.

Avena sativa L. is the most important cultivated oat species worldwide. Although photoperiod-insensitive oat varieties exist, the molecular mechanisms underlying their photoperiod sensitivity are poorly understood.

Rare SUZ12 variants commonly cause an overgrowth phenotype.

The Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2-related overgrowth) and Cohen-Gibson syndrome (EED-related overgrowth). Imagawa et al.

Salicylates are interference compounds in TR-FRET assays.

Given the importance of high-throughput screening in drug discovery, the identification of compounds that interfere with assay readouts is crucial. The pursuit of false positives wastes time and money, while distracting development teams from more promising leads. In the context of TR-FRET assays, most interfering compounds are dyes or aggregators.

A pan-cancer analysis of alternative splicing events reveals novel tumor-associated splice variants of matriptase.

High-throughput transcriptome sequencing allows identification of cancer-related changes that occur at the stages of transcription, pre-messenger RNA (mRNA), and splicing. In the current study, we devised a pipeline to predict novel alternative splicing (AS) variants from high-throughput transcriptome sequencing data and applied it to large sets of tumor transcriptomes from The Cancer Genome Atlas (TCGA). We identified two novel tumor-associated splice variants of matriptase, a known cancer-associated gene, in the transcriptome data from epithelial-derived tumors but not normal tissue.

Chitosan combined with molecular beacon for mir-155 detection and imaging in lung cancer.

Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR) have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer diagnosis and treatment. Molecular beacon (MB) technology is a universal technology to detect DNA/RNA expression in living cells.

Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based assays.

Mutations of DNA repair pathways contribute to tumorigenesis and provide a therapeutic target for synthetic lethal interactions in tumor cells. Given that tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs stalled topoisomerase-I DNA complexes, we hypothesized that inhibition of Tdp1 has synthetic lethal effects in some cancers. To test this, we screened tumor arrays for Tdp1 expression and observed that Tdp1 is expressed in many tumors, including more than 90% of human breast tumors.

Mutation of the salt bridge-forming residues in the ETV6-SAM domain interface blocks ETV6-NTRK3-induced cellular transformation.

The ETV6-NTRK3 (EN) chimeric oncogene is expressed in diverse tumor types. EN is generated by a t(12;15) translocation, which fuses the N-terminal SAM (sterile α-motif) domain of the ETV6 (or TEL) transcription factor to the C-terminal PTK (protein-tyrosine kinase) domain of the neurotrophin-3 receptor NTRK3. SAM domain-mediated polymerization of EN leads to constitutive activation of the PTK domain and constitutive signaling of the Ras-MAPK and PI3K-Akt pathways, which are essential for EN oncogenesis.

Analysis of FOXO1 mutations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of newly diagnosed lymphomas and has an overall cure rate of approximately 60%. Previously, we observed FOXO1 mutations in non-Hodgkin lymphoma patient samples. To explore the effects of FOXO1 mutations, we assessed FOXO1 status in 279 DLBCL patient samples and 22 DLBCL-derived cell lines.

Molecular and structural characterization of the SH3 domain of AHI-1 in regulation of cellular resistance of BCR-ABL(+) chronic myeloid leukemia cells to tyrosine kinase inhibitors.

ABL tyrosine kinase inhibitor (TKI) therapy induces clinical remission in chronic myeloid leukemia (CML) patients but early relapses and later emergence of TKI-resistant disease remain problematic. We recently demonstrated that the AHI-1 oncogene physically interacts with BCR-ABL and JAK2 and mediates cellular resistance to TKI in CML stem/progenitor cells. We now show that deletion of the SH3 domain of AHI-1 significantly enhances apoptotic response of BCR-ABL(+) cells to TKIs compared to cells expressing full-length AHI-1.

Mutations in EZH2 cause Weaver syndrome.

We used trio-based whole-exome sequencing to analyze two families affected by Weaver syndrome, including one of the original families reported in 1974. Filtering of rare variants in the affected probands against the parental variants identified two different de novo mutations in the enhancer of zeste homolog 2 (EZH2). Sanger sequencing of EZH2 in a third classically-affected proband identified a third de novo mutation in this gene.

Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers.

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution.

A computational approach to finding novel targets for existing drugs.

Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction docking, consensus scoring, and specificity.

Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome.

CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.

Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors.

Background: Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.

Results: In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain.

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.

Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells. Targeted resequencing studies have revealed mutations in various genes encoding proteins in the NF-kappaB pathway that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified. Here we report recurrent somatic mutations affecting the polycomb-group oncogene EZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27).

A novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase.

Computational molecular docking provides an efficient and innovative approach to examine small molecule and protein interactions. We have utilized this method to identify potential inhibitors of the H5N1 neuraminidase protein. Of the 20 compounds tested, 4-(4-((3-(2-amino-4-hydroxy-6-methyl-5-pyrimidinyl)propyl)amino)phenyl)-1-chloro-3-buten-2-one (1) (NSC89853) demonstrated the ability to inhibit viral replication at a level comparable to the known neuraminidase inhibitor oseltamivir.

MicroRNA expression profile of bronchioalveolar stem cells from mouse lung.

Increasing evidence has suggested that bronchioalveolar stem cell (BASC) is the progenitor cells of lung cancer stem cells. However, the mechanisms by which self-renewal of BSACs is controlled and how BASCs turn into cancer stem cells still remains to be unknown. In the present study, we successfully isolated bronchioalveolar stem cells (BASCs) from mouse lung using FACS.

Down-regulation of layilin, a novel hyaluronan receptor, via RNA interference, inhibits invasion and lymphatic metastasis of human lung A549 cells.

Human lung carcinoma is a highly metastatic tumour that leads to a high death rate and in which lymphatic metastasis is an important early event. HYA (hyaluronan) is involved in the invasion of a variety of tumour cells. Layilin, a specific and novel HYA receptor, was detected in the human lung cell line A549 in our preliminary research, and was hypothesized to play an essential role in cell motility and tumour lymphatic metastasis.