Pattern genes are a group of genes that have a modularized expression behavior under serial physiological conditions. The identification of pattern genes will provide a path toward a global and ...dynamic understanding of gene functions and their roles in particular biological processes or events, such as development and pathogenesis. In this study, we present PaGenBase, a novel repository for the collection of tissue- and time-specific pattern genes, including specific genes, selective genes, housekeeping genes and repressed genes. The PaGenBase database is now freely accessible at http://bioinf.xmu.edu.cn/PaGenBase/. In the current version (PaGenBase 1.0), the database contains 906,599 pattern genes derived from the literature or from data mining of more than 1,145,277 gene expression profiles in 1,062 distinct samples collected from 11 model organisms. Four statistical parameters were used to quantitatively evaluate the pattern genes. Moreover, three methods (quick search, advanced search and browse) were designed for rapid and customized data retrieval. The potential applications of PaGenBase are also briefly described. In summary, PaGenBase will serve as a resource for the global and dynamic understanding of gene function and will facilitate high-level investigations in a variety of fields, including the study of development, pathogenesis and novel drug discovery.
Rates of plant cell elongation change with day-night alternation, reflecting differences in metabolism related to cell wall remodeling. Information from cell wall surveillance pathways must be ...integrated with growth regulation pathways to provide feedback regulation of cell wall modification; such feedback regulation is important to ensure sufficient strength and prevent rupture of the cell wall during growth. Several lines of evidence suggest that cell wall perturbations often influence phytohormone signaling, but the identity of the nexus between these two processes remained elusive. Here, we show that wall-associated kinase11 (OsWAK11) acts as a linker connecting cell wall pectin methyl-esterification changes and brassinosteroid (BR) signaling in rice. Our data show that OsWAK11 controls several important agronomical traits by regulating cell elongation in rice. OsWAK11 directly binds and phosphorylates the BR receptor OsBRI1 at residue Thr752, within a motif conserved across most monocot graminaceous crops, thus hindering OsBRI1 interaction with its co-receptor OsSERK1/OsBAK1 and inhibiting BR signaling. The extracellular domain of OsWAK11 shows a much stronger interaction toward methyl-esterified pectin as compared with de-methyl-esterified pectin. OsWAK11 is stabilized in light but is degraded in darkness, in a process triggered by changes in the ratio of methyl-esterified to de-methyl-esterified pectin, creating fluctuations in plant BR signaling in response to day and night alternation. We conclude that OsWAK11 is a cell wall monitor that regulates cell elongation rates to adapt to the environment from the outside in, which complements the well-established inside-out signaling pathway affecting cell elongation in plants.
•OsWAK11 regulates brassinosteroid signaling and plant growth•OsWAK11 phosphorylates OsBRI1 at a conserved motif across most monocots•OsWAK11 tends to bind methyl-esterified pectin•OsWAK11 responds to pectin methyl-esterification changes
In this study, Yue et al. show that the receptor-like kinase OsWAK11 monitors pectin methyl-esterification changes in the plant cell wall to directly phosphorylate and fine-tune the activity of the brassinosteroid phytohormone receptor OsBRI1, achieving dynamic growth in response to light changes.
Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. According to the investigation report, the 3-year survival rate of ...patients with lung cancer is less than 20%. Heredity, the environment, and long-term smoking or secondhand smoke greatly promote the development and progress of the disease. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H
S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H
S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer. H
S has the characteristics of dissolving in water and passing through the cell membrane, and is widely expressed in body tissues, which determines the possibility of its participation in the occurrence of lung cancer. Both endogenous and exogenous H
S may be involved in the inhibition of lung cancer cells by regulating mitochondrial energy metabolism, mitochondrial DNA integrity, and phosphoinositide 3-kinase/protein kinase B co-pathway hypoxia-inducible factor-1α (HIF-1α). This article reviews and discusses the molecular mechanism of H
S in the development of lung cancer, and provides novel insights for the prevention and targeted therapy of lung cancer.
Summary
Erdheim–Chester disease (ECD) is a rare form of non‐Langerhans cell histiocytosis that typically affects many organs, including the lung and pleura. However, there are few studies concerning ...pulmonary involvement in ECD patients, as well as the difference of pulmonary involvement between ECD and Langerhans cell histiocytosis (LCH). We performed a retrospective study of 54 ECD patients, and compared the pulmonary manifestations with those of adult LCH patients in our centre. The median age of diagnosis of the 54 ECD patients was 48 years (range 9–66 years). Chest computed tomography (CT) scans revealed lung involvement in 49 (91%) patients and pleural involvement in 34 (63%). Thirty‐three (61%) patients had interstitial lung disease (ILD) with varying degrees of interlobular septal thickening, micronodules, and ground‐glass opacities. ECD and LCH patients with pulmonary involvement showed significant differences in smoking status (P < 0·001), respiratory symptoms (P = 0·001) such as cough and pneumothorax (P < 0·001), and radiological findings, including cysts (P < 0·001), opacities (P < 0·001), and pleural thickening (P < 0·001). With a median follow‐up duration of 24 months (range, 1–84 months), the estimated three‐year overall survival (OS) of this entire ECD cohort was 90·2%. Patients with ILD tended to have worse progression‐free survival (PFS) than those with no ILD (P = 0·29).
Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis ...stages has not been defined. Here we demonstrate that PTP‐MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP‐MEG2 and its substrate, a peptide containing the phosphorylated NSF‐pY83 site, specify PTP‐MEG2 substrate selectivity, and modulate the fusion of catecholamine‐containing vesicles. Unexpectedly, delineation of PTP‐MEG2 mutants along with the NSF binding interface reveals that PTP‐MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP‐MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2‐pY125 and MUNC18‐1‐pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP‐MEG2 with MUNC18‐1‐pY145 or DYNAMIN2‐pY125 through a distinct structural basis compared with that of the NSF‐pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.
SYNOPSIS
The tyrosine phosphatase PTP‐MEG2 regulates multiple steps of exocytosis through two distinct substrates: it de‐phosphorylates (1) NSF‐pY83 to modulate quantal size; (2) DYNAMIN2‐pY125 and MUNC18‐1 pY145 to regulate fusion pore opening.
Structural and biochemical analysis reveals that PTP‐MEG2 regulates exocytosis via two distinct processes.
PTP‐MEG2 regulates quantal size by de‐phosphorylating NSF‐pY83 during exocytosis of chromaffin cells.
PTP‐MEG2 regulates fusion pore opening and extension through the DYNAMIN2‐pY125 site and MUNC18‐1 pY145 site.
The tyrosine phosphatase PTP‐MEG2 regulates multiple steps of exocytosis through two distinct substrates: it de‐phosphorylates (1) NSF‐pY83 to modulate quantal size; (2) DYNAMIN2‐pY125 and MUNC18‐1 pY145 to regulate fusion pore opening.
Members of the genus Bougainvillea are rich sources of natural dyes, pigments, and traditional medicines. They are also commonly used as ornamentals in roadside landscape construction. However, the ...horticultural development of Bougainvillea flowers with extended growth periods and coloration is not always feasible. One reason is limited molecular knowledge and no genomic information for Bougainvillea. Here, we compiled an integrative transcriptome of all expressed transcripts for Bougainvillea × buttiana Miss Manila by integrating 20 Illumina-sequencing RNA transcriptomes. The integrative transcriptome consisted of 97,623 distinct transcripts. Of these, 47,006 were protein-coding, 31,109 were non-coding, and 19,508 were unannotated. In addition, we affirmed that the integrative transcriptome could serve as a surrogate reference to the genome in aiding accurate transcriptome assembly. For convenience, we curated the integrative transcriptome database for Bougainvillea, namely InTransBo, which can be freely accessed at http://www.bio-add.org/InTransBo/index.jsp . To the best of our knowledge, the present study is the most comprehensive genomic resource for Bougainvillea up-to-date. The integrative transcriptome helps fill the genomic gap and elucidate the transcriptional nature of Bougainvillea. It may also advance progress in the precise regulation of flowering in horticulture. The same strategy can be readily applied toward the systematic exploration of other plant species lacking complete genomic information.
Treponema pallidum ssp. pallidum (T. pallidum), the causative agent of the sexually transmitted disease syphilis, is an uncultivatable human pathogen. The geographical differences in T. pallidum ...genomes leading to differences in pathogenicity are not yet understood. Presently, twelve T. pallidum genomes are available to the public, all of which are American in origin and often co-infect patients with human immunodeficiency virus (HIV). In this study, we examined the T. pallidum subsp. pallidum strain Amoy, a syphilis pathogen found in Xiamen, China. We sequenced its genome using Illumina next-generation sequencing technology and obtained a nearly (98.83%) complete genome of approximately 1.12 Mbps. The new genome shows good synteny with its five T. pallidum sibling strains (Nichols, SS14, Mexico A, DAL-1, and Chicago), among which SS14 is the strain closest to the Amoy strain. Compared with strain SS14, the Amoy strain possesses four uncharacterized strain-specific genes and is likely missing six genes, including a gene encoding the TPR domain protein, which may partially account for the comparatively low virulence and toxicity of the Amoy strain in animal infection. Notably, we did not detect the 23S rRNA A2058G/A2059G mutation in the Amoy strain, which likely explains the sensitivity of Amoy strain to macrolides. The results of this study will lead to a better understanding of the pathogenesis of syphilis and the geographical distribution of T. pallidum genotypes.
The tissue-specific genes are a group of genes whose function and expression are preferred in one or several tissues/cell types. Identification of these genes helps better understanding of ...tissue–gene relationship, etiology and discovery of novel tissue-specific drug targets. In this study, a statistical method is introduced to detect tissue-specific genes from more than 123 125 gene expression profiles over 107 human tissues, 67 mouse tissues and 30 rat tissues. As a result, a novel subject-specialized repository, namely the tissue-specific genes database (TiSGeD), is developed to represent the analyzed results. Auxiliary information of tissue-specific genes was also collected from biomedical literatures. Availability: http://bioinf.xmu.edu.cn/databases/TiSGeD/index.html Contact: appo@bioinf.xmu.edu.cn; zhiliang.ji@gmail.com
Adverse drug reactions (ADRs) are noxious and unexpected effects during normal drug therapy. They have caused significant clinical burden and been responsible for a large portion of new drug ...development failure. Molecular understanding and in silico evaluation of drug (or candidate) safety in laboratory is thus so desired, and unfortunately has been largely hindered by misuse of ADR terms. The growing impact of bioinformatics and systems biology in toxicological research also requires a specialized ADR term system that works beyond a simple glossary. Adverse Drug Reaction Classification System (ADReCS; http://bioinf.xmu.edu.cn/ADReCS) is a comprehensive ADR ontology database that provides not only ADR standardization but also hierarchical classification of ADR terms. The ADR terms were pre-assigned with unique digital IDs and at the same time were well organized into a four-level ADR hierarchy tree for building an ADR-ADR relation. Currently, the database covers 6544 standard ADR terms and 34,796 synonyms. It also incorporates information of 1355 single active ingredient drugs and 134,022 drug-ADR pairs. In summary, ADReCS offers an opportunity for direct computation on ADR terms and also provides clues to mining common features underlying ADRs.
Abstract
Genes have the ability to produce transcript variants that perform specific cellular functions. However, accurately detecting all transcript variants remains a long-standing challenge, ...especially when working with poorly annotated genomes or without a known genome. To address this issue, we have developed a new computational method, TransIntegrator, which enables transcriptome-wide detection of novel transcript variants. For this, we determined 10 Illumina sequencing transcriptomes and a PacBio full-length transcriptome for consecutive embryo development stages of amphioxus, a species of great evolutionary importance. Based on the transcriptomes, we employed TransIntegrator to create a comprehensive transcript variant library, namely iTranscriptome. The resulting iTrancriptome contained 91 915 distinct transcript variants, with an average of 2.4 variants per gene. This substantially improved current amphioxus genome annotation by expanding the number of genes from 21 954 to 38 777. Further analysis manifested that the gene expansion was largely ascribed to integration of multiple Illumina datasets instead of involving the PacBio data. Moreover, we demonstrated an example application of TransIntegrator, via generating iTrancriptome, in aiding accurate transcriptome assembly, which significantly outperformed other hybrid methods such as IDP-denovo and Trinity. For user convenience, we have deposited the source codes of TransIntegrator on GitHub as well as a conda package in Anaconda. In summary, this study proposes an affordable but efficient method for reliable transcriptomic research in most species.
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