cTFbase: a database for comparative genomics of transcription factors in cyanobacteria

BACKGROUND: Comprehensive identification and classification of the transcription factors (TFs) in a given genome is an important aspect in understanding transcriptional regulatory networks of a specific organism. Cyanobacteria are an ancient group of gram-negative bacteria with strong variation in genome size ranging from about 1.6 to 9.1 Mb and little is known about their TF repertoires. Therefore, we constructed the cTFbase database to classify and analyze all the putative TFs in cyanobacterial genomes, followed by genome-wide comparative analysis. DESCRIPTION: In the current release, cTFbase contains 1288 putative TFs identified from 21 fully sequenced cyanobacterial genomes. Through its user-friendly interactive interface, users can employ various criteria to retrieve all TF sequences and their detailed annotation information, including sequence features, domain architecture and sequence similarity against the linked databases. Furthermore, cTFbase provides phylogenetic trees of individual TF family, multiple sequence alignments of the DNA-binding domains and ortholog identification from any selected genomes. Comparative analysis revealed great variability of the TF sequences in cyanobacterial genomes. The high variance on the gene number and domain organization would be related to their diverse biological functions and their adaptation to various environmental conditions. CONCLUSION: cTFbase provides a centralized warehouse for comparative analysis of putative TFs in cyanobacterial genomes. The availability of such an extensive database would be of great interest for the community of researchers working on TFs or transcriptional regulatory networks in cyanobacteria. cTFbase can be freely accessible at and will be continuously updated when the newly sequenced cyanobacterial genomes are available

Cuproptosis-Related lncRNA Gene Signature Establishes a Prognostic Model of Gastric Adenocarcinoma and Evaluate the Effect of Antineoplastic Drugs

Background: One of the most frequent malignancies of the digestive system is stomach adenocarcinoma (STAD). Recent research has demonstrated how cuproptosis (copper-dependent cell death) differs from other cell death mechanisms that were previously understood. Cuproptosis regulation in tumor cells could be a brand-new treatment strategy. Our goal was to create a cuproptosis-related lncRNA signature. Additionally, in order to evaluate the possible immunotherapeutic advantages and drug sensitivity, we attempted to study the association between these lncRNAs and the tumor immune microenvironment of STAD tumors. Methods: The TCGA database was accessed to download the RNA sequencing data, genetic mutations, and clinical profiles for TCGA STAD. To locate lncRNAs related to cuproptosis and build risk-prognosis models, three techniques were used: co-expression network analysis, Cox-regression techniques, and LASSO techniques. Additionally, an integrated methodology was used to validate the models’ predictive capabilities. Then, using GO and KEGG analysis, we discovered the variations in biological functions between each group. The link between the risk score and various medications for STAD treatment was estimated using the tumor mutational load (TMB) and tumor immune dysfunction and rejection (TIDE) scores. Result: We gathered 22 genes linked to cuproptosis based on the prior literature. Six lncRNAs related to cuproptosis were used to create a prognostic marker (AC016394.2, AC023511.1, AC147067.2, AL590705.3, HAGLR, and LINC01094). After that, the patients were split into high-risk and low-risk groups. A statistically significant difference in overall survival between the two groups was visible in the survival curves. The risk score was demonstrated to be an independent factor affecting the prognosis by both univariate and multivariate Cox regression analysis. Different risk scores were substantially related to the various immunological states of STAD patients, as further evidenced by immune cell infiltration and ssGSEA analysis. The two groups had differing burdens of tumor mutations. In addition, immunotherapy was more effective for STAD patients in the high-risk group than in the low-risk group, and risk scores for STAD were substantially connected with medication sensitivity. Conclusions: We discovered a marker for six cuproptosis-associated lncRNAs linked to STAD as prognostic predictors, which may be useful biomarkers for risk stratification, evaluation of possible immunotherapy, and assessment of treatment sensitivity for STAD

Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy

Abstract HER2-positive gastric cancer (GC) makes up 15–20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients

Enantioselective Synthesis of the ABC-Tricyclic Core of Phomactin A by a γ‑Hydroxylation Strategy

An enantioselective synthesis of the ABC-tricyclic furanochroman core of phomactin A has been accomplished by a γ-hydroxylation approach. The C ring was established by γ-hydroxylation of an α-enone. The regioselectivity was optimized by using a strong base with an oxophilic cation (<i>t-</i>BuLi) and a bulky oxygen donor (Davis reagent), which afforded the γ-hydroxylation product selectively in 63% yield

Relationship between the number of TFs and the total number of ORFs in 21 cyanobacterial genomes

<p><b>Copyright information:</b></p><p>Taken from "cTFbase: a database for comparative genomics of transcription factors in cyanobacteria"</p><p>http://www.biomedcentral.com/1471-2164/8/104</p><p>BMC Genomics 2007;8():104-104.</p><p>Published online 18 Apr 2007</p><p>PMCID:PMC1858693.</p><p></p> The total number of ORFs in each genome was plotted as a function against the number of TFs. Triangle indicates marine cyanobacteria, while square indicates fresh or soil cyanobacteria

Domain architectures and classification scheme of TFs in the 21 cyanobacterial genomes

<p><b>Copyright information:</b></p><p>Taken from "cTFbase: a database for comparative genomics of transcription factors in cyanobacteria"</p><p>http://www.biomedcentral.com/1471-2164/8/104</p><p>BMC Genomics 2007;8():104-104.</p><p>Published online 18 Apr 2007</p><p>PMCID:PMC1858693.</p><p></p> The methods classifying TFs into families and identifying the domains can be referred in . Green rectangles indicate the DBD domains, while red ellipses represent associated domains. The number on the right of the domain organization represents the number of sequences in the specific family

Sequence Analysis of pKF3-70 in Klebsiella pneumoniae: Probable Origin from R100-Like Plasmid of Escherichia coli

Background: Klebsiella pneumoniae is a clinically significant species of bacterium which causes a variety of diseases. Clinical treatment of this bacterial infection is greatly hindered by the emergence of multidrug-resistant strains. The resistance is largely due to the acquisition of plasmids carrying drug-resistant as well as pathogenic genes, and its conjugal transfer facilitates the spread of resistant phenotypes. Methodology/Principal Findings: The 70,057 bp plasmid pKF3-70, commonly found in Klebsiella pneumoniae, is composed of five main functional modules, including regions involved in replication, partition, conjugation, transfer leading, and variable regions. This plasmid is more similar to several Escherichia coli plasmids than any previously reported K. pneumoniae plasmids and pKF3-70 like plasmids share a common and conserved backbone sequence. The replication system of the pKF3-70 is 100 % identical to that of RepFII plasmid R100 from E. coli. A beta-lactamase gene ctx-m-14 with its surrounding insertion elements (ISEcp1, truncated IS903 and a 20 bp inverted repeat sequence) may compose an active transposon which is directly bordered by two putative target repeats ‘‘ATTAC.’’ Conclusions/Significance: The K. pneumoniae plasmid pKF3-70 carries an extended-spectrum beta-lactamase gene, ctx-m-14. The conjugative characteristic makes it a widespread plasmid among genetically relevant genera which poses significan