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DNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG methylation from Nanopore sequencing using individual reads, control mixtures of methylated and unmethylated reads, and bisulfite sequencing. We found that tools have a tradeoff between false positives and false negatives and present a high dispersion with respect to the expected methylation frequency values. We described various strategies to improve the accuracy of these tools, including a consensus approach, METEORE ( https://github.com/comprna/METEORE ), based on the combination of the predictions from two or more tools that shows improved accuracy over individual tools. Snakemake pipelines are also provided for reproducibility and to enable the systematic application of our analyses to other datasets. Several existing algorithms predict the methylation of DNA using Nanopore sequencing signals, but it is unclear how they compare in performance. Here, the authors benchmark the performance of several such tools, and propose METEORE, a consensus tool that improves prediction accuracy.

Biostimulation of aquifers contaminated with gasoline spills is vigorously affected by the biogeochemical environment existing there. In this study, biostimulation of benzene is simulated using a 2D coupled multispecies biogeochemical reactive transport (MBRT) model. The model is implemented at an oil spill site near a hypothetical aquifer containing natural reductants. Multiple electron acceptors are introduced to promote faster biodegradation rate. However, after reaction with natural reductants, it reduces the number of available electron acceptors, acidifies the subsurface environment, and inhibits bacterial growth. These mechanisms are assessed using seven coupled MBRT models sequentially. The finding of the present analysis reveals that biostimulation has caused a substantial drop in concentration of benzene and is efficient in reducing its penetration depth. The results also shows that the intervention of natural reductants in the biostimulation process is slightly diminished by pH adjustment of aquifers. When the pH level in aquifer changes from acidic pH 4 to neutral pH 7, it is observed that the biostimulation rate of benzene as well as microbial activity increases. Electron acceptors consumption is more at neutral pH. Overall, it can be inferred from zeroth-order spatial moment and sensitivity analyses that retardation factor, inhibition constant, pH, and dispersivity in vertical direction significantly affect benzene biostimulation in aquifers.

Background Seed germination involves progression from complete metabolic dormancy to a highly active, growing seedling. Many factors regulate germination and these interact extensively, forming a complex network of inputs that control the seed-to-seedling transition. Our understanding of the direct regulation of gene expression and the dynamic changes in the epigenome and small RNAs during germination is limited. The interactions between genome, transcriptome and epigenome must be revealed in order to identify the regulatory mechanisms that control seed germination. Results We present an integrated analysis of high-resolution RNA sequencing, small RNA sequencing and MethylC sequencing over ten developmental time points in Arabidopsis thaliana seeds, finding extensive transcriptomic and epigenomic transformations associated with seed germination. We identify previously unannotated loci from which messenger RNAs are expressed transiently during germination and find widespread alternative splicing and divergent isoform abundance of genes involved in RNA processing and splicing. We generate the first dynamic transcription factor network model of germination, identifying known and novel regulatory factors. Expression of both microRNA and short interfering RNA loci changes significantly during germination, particularly between the seed and the post-germinative seedling. These are associated with changes in gene expression and large-scale demethylation observed towards the end of germination, as the epigenome transitions from an embryo-like to a vegetative seedling state. Conclusions This study reveals the complex dynamics and interactions of the transcriptome and epigenome during seed germination, including the extensive remodelling of the seed DNA methylome from an embryo-like to vegetative-like state during the seed-to-seedling transition. Data are available for exploration in a user-friendly browser at https://jbrowse.latrobe.edu.au/germination_epigenome .

Objectives We examined the utilisation, equity and determinants of full antenatal care (ANC), defined as 4 or more antenatal visits, at least one tetanus toxoid (TT) injection and consumption of iron folic acid (IFA) for a minimum of 100 days, in India. Methods We analysed a sample of 190,898 women from India’s National Family Health Survey 4. Concentration curves and concentration index were used to assess equity in full ANC utilisation. Multivariable logistic regression model was used to examine the factors associated with full ANC utilisation. Results In India, 21% of pregnant women utilised full ANC, ranging from 2.3–65.9% across states. Overall, 51.6% had 4 or more ANC visits, 30.8% consumed IFA for atleast 100 days, and 91.1% had one or more doses of tetanus toxoid. Full ANC utilisation was inequitable across place of residence, caste and maternal education. Registration of pregnancy, utilisation of government’s Integrated Child Development Services (ICDS) and health insurance coverage were associated with higher odds of full ANC utilisation. Lower maternal education, lower wealth quintile(s), lack of father’s participation during antenatal visits, higher birth order, teenage and unintended pregnancy were associated with lower odds of full ANC utilisation. Conclusions Full ANC utilisation in India was inadequate and inequitable. Although half of the women did not receive the minimum recommended ANC visits, the utilisation of TT immunisation was almost universal. The positive association of full ANC with ICDS utilisation and child’s father involvement may be leveraged for increasing the uptake of full ANC. Strategies to address the socio-demographic factors associated with low and inequitable utilisation of full ANC are imperative for strengthening India’s maternal health program.

Nanopore sequencing enables the efficient and unbiased measurement of transcriptomes. Current methods for transcript identification and quantification rely on mapping reads to a reference genome, which precludes the study of species with a partial or missing reference or the identification of disease-specific transcripts not readily identifiable from a reference. We present RATTLE, a tool to perform reference-free reconstruction and quantification of transcripts using only Nanopore reads. Using simulated data and experimental data from isoform spike-ins, human tissues, and cell lines, we show that RATTLE accurately determines transcript sequences and their abundances, and shows good scalability with the number of transcripts.

BackgroundAntiresorptive drugs (ARD) are associated with a known serious adverse event, known as medication-related osteonecrosis of the jaws (MRONJ). Transition from one ARD to another has become common clinical practice with the advent of more potent or safer agents; however, the influence of sequential antiresorptive therapy as a risk factor for MRONJ has not been established.ObjectivesTo investigate the prevalence of MRONJ in oncology or osteoporosis patients treated with two or more sequential ARDs as opposed to a single antiresorptive drug.Material and methodsSystematic electronic literature searches were conducted using Ovid MEDLINE, Ovid EMBASE, and Cochrane Central Register of Controlled Trials. Two review authors retrieved studies using pre-determined eligibility criteria and conducted quality assessment and data extraction. Fixed or random-effects meta-analysis models were used to summarize relative estimates for prevalence of MRONJ.ResultsA total of 483 titles and abstracts were screened, and 18 full texts were retrieved for review. Twelve studies were included in the final qualitative and quantitative synthesis. Random effects meta-analysis models revealed a weighted pooled MRONJ prevalence of 19% (95% CI 10–27%) for sequential pamidronate-zoledronate therapy, 10% (95% CI 3–22%) for sequential ibandronate-zoledronate therapy. Pooled weighted prevalence of MRONJ was 13% (95% CI 3–22%) for sequential bisphosphonate-denosumab therapy while bisphosphonates only was 5% (95% CI 0–9%) and denosumab only was 4% (95% CI 3–5%).ConclusionsThe present systematic review suggests an increased prevalence of MRONJ associated with sequential ARD therapy for pamidronate-zoledronate and bisphosphonate-denosumab administration when compared to single ARD therapy.

Molecular hybridization approach is an emerging tool in drug discovery for designing new pharmacophores with biological activity. A novel, new series of coumarin–benzimidazole hybrids were designed, synthesized and evaluated for their broad spectrum antimicrobial activity. Among all the synthesized molecules, compound ( E )-3-(2-1 H -benzo[ d ]imidazol-1-yl)-1-((4-chlorobenzyl)oxy)imino)ethyl)-2 H -chromen-2-one showed the most promising broad spectrum antibacterial activity against Pseudomonas aeruginosa , Staphylococcus aureus, Bacillus subtilis and Proteus vulgaris. In addition, it has showed no cytotoxicity and hemolysis at 10 times the MIC concentration. SAR studies indicate that position of the chlorine atom in the hybrid critically determines the antibacterial activity.

In the current study, the effect of the EC 50 and LC 90 concentrations of pyrethroid insecticide alpha-cypermethrin to cyanobacteria Anabaena sp. NC-K1 was investigated at different time exposures (1st day, 4th day and 7th day) with reference to growth, photosynthetic pigments, oxidative damage and antioxidant defence system. Superoxide dismutase (1.38-fold), peroxidase (5.04) and proline content (2.27-fold) were enhanced compared to the control. After performing 2D gel electrophoresis at 1st day EC 50 exposure, where appropriate differences in the biochemical and physiological parameters were observed, 22 differentially accumulated proteins (20 upregulated and 2 downregulated) were selected for mass spectrometry. Out of 42 proteins identified, 20 upregulated protein spots were classified into twelve categories according to their metabolic functions. Proteins related to photosynthesis (phycobilisome rod-core linker polypeptide, rubisco), stress responses (Hsp70, Hsp40, catalase family peroxidase), translation (elongation factor Tu) and amino acid biosynthesis and metabolism (3-phosphoshikimate 1-carboxyvinyl transferase) were significantly upregulated. Additionally, proteins involved in transcription and DNA repair (Snf-2 histone linker phd ring helicase, RNA polymerase sigma factor RpoD and Holliday junction ATP-dependent DNA helicase RuvA) were considerably upregulated. Upregulation of these proteins against pesticide stress presumably maintained the photosynthesis, energy metabolism, carbohydrate metabolism, transport and signalling proteins, transcription, translation and DNA repair. Additionally, these proteins might involve in sufficient detoxification of ROS and play a crucial role in damage removal and repair of oxidized proteins, lipids and nucleic acids. Taken together, Anabaena sp. NC-K1 responded towards alpha-cypermethrin stress via modulating its proteome to maintain its cellular metabolism and homeostasis.

Background Lectin receptor-like kinases (Lec-RLKs), a subfamily of RLKs, have been demonstrated to play an important role in signal transduction from cell wall to the plasma membrane during biotic stresses. Lec-RLKs include legume lectin-like proteins (LLPs), an important group of apoplastic proteins that are expressed in regenerating cell walls and play a role in immune-related responses. However, it is unclear whether LLPs have a function in abiotic stress mitigation and related signaling pathways. Therefore, in this study, we examined the possible role of LLPs in Arabidopsis thaliana (AtLLPs) under various abiotic stresses. Results The study was initiated by analyzing the chromosomal localization, gene structure, protein motif, peptide sequence, phylogeny, evolutionary divergence, and sub-cellular localization of AtLLPs. Furthermore, the expression profiling of these AtLLPs was performed using publicly accessible microarray datasets under various abiotic stresses, which indicated that all AtLLPs were differently expressed in both root and shoot tissues in response to abiotic stresses. The cis -regulatory elements (CREs) analysis in 500 bp promoter sequences of AtLLPs suggested the presence of multiple important CREs implicated for regulating abiotic stress responses, which was further supported by expressional correlation analysis between AtLLPs and their CREs cognate transcription factors (TFs). qRT-PCR analysis of these AtLLPs after 2, 6, and 12 h of cold, high light, oxidative (MV), UV-B, wound, and ozone stress revealed that all AtLLPs displayed differential expression patterns in most of the tested stresses, supporting their roles in abiotic stress response and signaling again. Out of these AtLLPs , AT1g53070 and AT5g03350 appeared to be important players. Furthermore, the mutant line of AT5g03350 exhibited higher levels of ROS than wild type plants till 12 h of exposure to high light, MV, UV-B, and wound, whereas its overexpression line exhibited comparatively lower levels of ROS, indicating a positive role of this gene in abiotic stress response in A . thaliana . Conclusions This study provides basic insights in the involvement of two important representative AtLLPs , AT1g53070 and AT5g03350, in abiotic stress response. However, further research is needed to determine the specific molecular mechanism of these AtLLPs in abiotic stress mitigation and related signaling pathways in A . thaliana .