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Background Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear. Methods Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables. Results Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa ( p  < 0.0001; n  = 74). Tumoral LINE-1 methylation range was 11.6–97.5 on a 0–100 scale ( n  = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p  = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09–3.99, p  = 0.023; stage-matched HR 1.88, 95 % CI 1.02–3.74, p  = 0.041; multivariate HR 1.98, 95 % CI 1.04–4.04, p  = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25). Conclusions LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.

A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems. To imagine the abiotic assembly of such an overall system, however, places great demands on hypothetical prebiotic chemistry. The perceived differences and incompatibilities between these subsystems have led to the widely held assumption that one or other subsystem must have preceded the others. Here we experimentally investigate the validity of this assumption by examining the assembly of various biomolecular building blocks from prebiotically plausible intermediates and one-carbon feedstock molecules. We show that precursors of ribonucleotides, amino acids and lipids can all be derived by the reductive homologation of hydrogen cyanide and some of its derivatives, and thus that all the cellular subsystems could have arisen simultaneously through common chemistry. The key reaction steps are driven by ultraviolet light, use hydrogen sulfide as the reductant and can be accelerated by Cu( I )–Cu (II) photoredox cycling. A minimal cell — one that has all the minimum requirements for life — is still a complex entity comprising informational, compartment-forming and metabolic subsystems. Here it is shown that, contrary to previous assumptions, a common prebiotically plausible chemistry can give rise to building blocks for all the subsystems.

Background DNA methylation has been linked to many important biological phenomena. Researchers have recently begun to sequence bisulfite treated DNA to determine its pattern of methylation. However, sequencing reads from bisulfite-converted DNA can vary significantly from the reference genome because of incomplete bisulfite conversion, genome variation, sequencing errors, and poor quality bases. Therefore, it is often difficult to align reads to the correct locations in the reference genome. Furthermore, bisulfite sequencing experiments have the additional complexity of having to estimate the DNA methylation levels within the sample. Results Here, we present a highly accurate probabilistic algorithm, which is an extension of the Genomic Next-generation Universal MAPper to accommodate bisulfite sequencing data ( GNUMAP-bs ), that addresses the computational problems associated with aligning bisulfite sequencing data to a reference genome. GNUMAP-bs integrates uncertainty from read and mapping qualities to help resolve the difference between poor quality bases and the ambiguity inherent in bisulfite conversion. We tested GNUMAP-bs and other commonly-used bisulfite alignment methods using both simulated and real bisulfite reads and found that GNUMAP-bs and other dynamic programming methods were more accurate than the more heuristic methods. Conclusions The GNUMAP-bs aligner is a highly accurate alignment approach for processing the data from bisulfite sequencing experiments. The GNUMAP-bs algorithm is freely available for download at: http://dna.cs.byu.edu/gnumap . The software runs on multiple threads and multiple processors to increase the alignment speed.

Numerical modeling has been used extensively to simulate gas-liquid transfer of sulfur dioxide, assessing how operational parameters affect absorption efficiency in packed or spray columns. Despite individual studies on these contactors, comparative analyses on the same flue gas have been rare. This study uses a numerical model for both packed and spray columns to examine how parameters influence SO absorption by sodium sulfite, describing packed and spray columns, is used to investigate the influence of operational parameters on SO absorption by sodium sulfite. The model's predictions are validated against experimental data from an industrial pilot plant. Across varying conditions ( / ratio, temperature, initial SO content or initial S(IV) concentration), the packed column achieves higher absorption efficiencies compared to the spray column, with lower assumed energy costs due to a reduced / ratio. Temperature proves to be a significant factor, decreasing absorption efficiency by approximately 40% between 40 and 70 °C. SO absorption efficiency declines with increasing concentrations of bisulfite and sulfite ions in the absorption solution, dropping to 50% at an S(IV) concentration of 2 kmol m in the liquid phase. Considering the objective of producing a concentrated bisulfite solution and a clean gas, a two-column system is recommended: one for bisulfite solution concentration at acidic pH and the other for gas purification enhancement at basic pH.

Enzymatic reduction of oxyanions such as sulfite (SO 3 2− ) requires the delivery of multiple electrons and protons, a feat accomplished by cofactors tailored for catalysis and electron transport. Replicating this strategy in protein scaffolds may expand the range of enzymes that can be designed de novo. Mirts et al. selected a scaffold protein containing a natural heme cofactor and then engineered a cavity suitable for binding a second cofactor—an iron-sulfur cluster (see the Perspective by Lancaster). The resulting designed enzyme was optimized through rational mutation into a catalyst with spectral characteristics and activity similar to that of natural sulfite reductases. Science , this issue p. 1098 ; see also p. 1071 Two metal cofactors in a protein scaffold reduce sulfite through multiple electron and proton transfer steps. Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. We report a designed heteronuclear heme-[4Fe-4S] cofactor in cytochrome c peroxidase as a structural and functional model of the enzyme sulfite reductase. The initial model exhibits spectroscopic and ligand-binding properties of the native enzyme, and sulfite reduction activity was improved—through rational tuning of the secondary sphere interactions around the [4Fe-4S] and the substrate-binding sites—to be close to that of the native enzyme. By offering insight into the requirements for a demanding six-electron, seven-proton reaction that has so far eluded synthetic catalysts, this study provides strategies for designing highly functional multicofactor artificial enzymes.

This protocol describes how to prepare a sequencing library for MethylC-seq analysis, enabling the methylation status of cytosines in genomic DNA to be determined at nucleotide resolution on a genome-wide scale. Current high-throughput DNA sequencing technologies enable acquisition of billions of data points through which myriad biological processes can be interrogated, including genetic variation, chromatin structure, gene expression patterns, small RNAs and protein–DNA interactions. Here we describe the MethylC-sequencing (MethylC-seq) library preparation method, a 2-d protocol that enables the genome-wide identification of cytosine DNA methylation states at single-base resolution. The technique involves fragmentation of genomic DNA followed by adapter ligation, bisulfite conversion and limited amplification using adapter-specific PCR primers in preparation for sequencing. To date, this protocol has been successfully applied to genomic DNA isolated from primary cell culture, sorted cells and fresh tissue from over a thousand plant and animal samples.

Single-cell bisulfite sequencing (scBS-seq) allows robust DNA methylation analysis in rare cells and heterogeneous populations. We report a single-cell bisulfite sequencing (scBS-seq) method that can be used to accurately measure DNA methylation at up to 48.4% of CpG sites. Embryonic stem cells grown in serum or in 2i medium displayed epigenetic heterogeneity, with '2i-like' cells present in serum culture. Integration of 12 individual mouse oocyte datasets largely recapitulated the whole DNA methylome, which makes scBS-seq a versatile tool to explore DNA methylation in rare cells and heterogeneous populations.

Sulfur dioxide (SO2) is commonly employed as an antioxidant and preservative in food processing, but excessive intake of SO2 can pose significant health risks. Therefore, accurate detection of sulfite content in food is crucial for ensuring food quality and safety. A novel fluorescent probe, BODIPY-Y, composed of a BODIPY derivative and an ethyl cyanoacetate group linked by a carbon–carbon double bond, was synthesized for detecting sulfur dioxide derivatives. When the BODIPY-Y probe interacts with SO32−, the probe exhibits enhanced fluorescence at 514 nm. Spectrometric experiments show that the probe exhibits high sensitivity (LOD: 0.263 μmol/L), a fast response time (50 s) and excellent selectivity for SO32−. Mechanistic studies confirm that the BODIPY-Y probe operates via an intramolecular charge transfer (ICT) mechanism. The carbon–carbon double bond in BODIPY-Y undergoes nucleophilic addition with SO32−, blocking the ICT process and resulting in a blue shift in the fluorescence spectrum. In addition, the probe was applied to quantify SO32− levels in real food samples. The measured concentrations of SO2 in the white sugar and red wine were 15.93 μmol/L and 7.30 μmol/L, respectively, with recovery rates of 77.9–98.1%. This work presents a prospective chemical tool for monitoring sulfur dioxide derivatives in food products.

RnBeads facilitates user-friendly analysis of large-scale DNA methylation data and fosters reproducibility and data sharing. RnBeads is a software tool for large-scale analysis and interpretation of DNA methylation data, providing a user-friendly analysis workflow that yields detailed hypertext reports ( http://rnbeads.mpi-inf.mpg.de/ ). Supported assays include whole-genome bisulfite sequencing, reduced representation bisulfite sequencing, Infinium microarrays and any other protocol that produces high-resolution DNA methylation data. Notable applications of RnBeads include the analysis of epigenome-wide association studies and epigenetic biomarker discovery in cancer cohorts.

The acaricide propargite has been widely used for over 50 years without significant resistance issues. Addressing to the propargite defects of poor crop safety, thirty-six novel halogenated propargite analogues were designed, synthesized, and characterized using 1 H NMR, 13 C NMR spectroscopy, and HRMS. All target compounds were screened for activity against adult Tetranychus cinnabarinus (spider mites) and Myzus persicae (aphids). Two compounds exhibiting higher insecticidal activity were further evaluated for crop safety on cowpea seedlings. Structural modifications, such as replacing the tert -butyl group on the propargite benzene ring with chlorine or trifluoromethoxy, and substituting the propargyl group with fluorinated alkyl groups (e.g., 2-fluoroethyl or 3,3,3-trifluoropropyl), significantly enhanced both acaricidal and aphicidal activity. Compound 5.16 demonstrated superior acaricidal activity (LC 50 : 14.85 mg L -1 ) on Tetranychus cinnabarinus and excellent crop safety on cowpea seedlings. Additionally, Compound 5.32 exhibited both acaricidal (LC 50 : 14.32 mg L -1 ) and aphicidal activity, which is unusual in this chemical class. The compounds 5.16 and 5.32 could be used as promising leads for the discovery of novel acaricides or insecticides.