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Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection. Nanopore reads have been advantageous for de novo genome assembly; however these reads have high error rates. Here, the authors develop an error correction and de novo assembly tool, NECAT, which produces efficient, high quality assemblies of nanopore reads.

C( sp 3 )–Cl bonds are present in numerous biologically active molecules and can also be used as a site for diversification by substitution or cross-coupling reactions. Herein, we report a remote internal site-selective C( sp 3 )–H bond chlorination of alkenes through sequential alkene isomerization and hydrochlorination, enabling the synthesis of both benzylic and tertiary chlorides with excellent site-selectivity. This transformation offers exciting possibilities for the late-stage chlorination of derivatives of natural products and pharmaceuticals. We also demonstrate the regioconvergent synthesis of a single alkyl chloride from unrefined mixtures of isomeric alkenes, which can be extracted directly from petrochemical sources. C(sp 3 )–Cl bonds are present in numerous biologically active molecules and can also be used as a site for diversification by substitution or cross-coupling reactions. Here, the authors report a remote internal site-selective C(sp 3 )–H bond chlorination of alkenes through sequential alkene isomerization and hydrochlorination, enabling the synthesis of both benzylic and tertiary chlorides with excellent site-selectivity.

We present measurements of more than 80 magnetic Feshbach resonances in collisions of ultracold 23Na40K with 40K. We assign quantum numbers to a group of low-field resonances and show that they are probably due to long-range states of the triatomic complex in which the quantum numbers of the separated atom and molecule are approximately preserved. The resonant states are not members of chaotic bath of short-range states. Similar resonances are expected to be a common feature of alkali-metal diatom + atom systems.

Sclerotinia sclerotiorum (Ss) is one of the most devastating fungal pathogens, causing huge yield loss in multiple economically important crops including oilseed rape. Plant resistance to Ss pertains to quantitative disease resistance (QDR) controlled by multiple minor genes. Genome-wide identification of genes involved in QDR to Ss is yet to be conducted. In this study, we integrated several assays including genome-wide association study (GWAS), multi-omics co-localization, and machine learning prediction to identify, on a genome-wide scale, genes involved in the oilseed rape QDR to Ss. Employing GWAS and multi-omics co-localization, we identified seven resistance-associated loci (RALs) associated with oilseed rape resistance to Ss. Furthermore, we developed a machine learning algorithm and named it Integrative Multi-Omics Analysis and Machine Learning for Target Gene Prediction (iMAP), which integrates multi-omics data to rapidly predict disease resistance-related genes within a broad chromosomal region. Through iMAP based on the identified RALs, we revealed multiple calcium signaling genes related to the QDR to Ss. Population-level analysis of selective sweeps and haplotypes of variants confirmed the positive selection of the predicted calcium signaling genes during evolution. Overall, this study has developed an algorithm that integrates multi-omics data and machine learning methods, providing a powerful tool for predicting target genes associated with specific traits. Furthermore, it makes a basis for further understanding the role and mechanisms of calcium signaling genes in the QDR to Ss.

Guanylate cyclases (GCs) are enzymes that catalyze the reaction to produce cyclic GMP (cGMP), a key signaling molecule in eukaryotes. Nevertheless, systemic identification and functional analysis of GCs in crop plant species have not yet been conducted. In this study, we systematically identified GC genes in the economically important crop tomato ( Solanum lycopersicum L.) and analyzed function of two putative tomato GC genes in disease resistance. Ninety-nine candidate GCs containing GC catalytic center (GC-CC) motif were identified in tomato genome. Intriguingly, all of them were putative protein kinases embedding a GC-CC motif within the protein kinase domain, which was thus tentatively named as GC-kinases here. Two homologs of Arabidopsis PEPRs, SlGC17 and SlGC18 exhibited in vitro GC activity. Co-silencing of SlGC17 and SlGC18 genes significantly reduced resistance to tobacco rattle virus, fungus Sclerotinia sclerotiorum , and bacterium Pseudomonas syringae pv. tomato ( Pst ) DC3000. Moreover, co-silencing of these two genes attenuated PAMP and DAMP-triggered immunity as shown by obvious decrease of flg22, chitin and AtPep1-elicited Ca 2+ and H 2 O 2 burst in SlGC -silenced plants. Additionally, silencing of these genes altered the expression of a set of Ca 2+ signaling genes. Furthermore, co-silencing of these GC-kinase genes exhibited stronger effects on all above regulations in comparison with individual silencing. Collectively, our results suggest that GC-kinases might widely exist in tomato and the two SlPEPR-GC genes redundantly play a positive role in resistance to diverse pathogens and PAMP/DAMP-triggered immunity in tomato. Our results provide insights into composition and functions of GC-kinases in tomato.

Background The control of schistosomiasis is particularly difficult in sub-Saharan Africa, which currently harbours 95% of this disease. The target population for preventive chemotherapy (PC) is expanded to all age group at risk of infection, thus increasing the demands of praziquantel (PZQ) tablets according to the new released guideline by World Health Organization. Due to the gap between available PZQ for PC and requirements, alternative approaches to assess endemicity of schistosomiasis in a community, are urgently needed for more quick and precise methods. We aimed to find out to which degree the infection status of snails can be used to guide chemotherapy against schistosomiasis. Methods We searched literature published from January 1991 to December 2022, that reported on the prevalence rates of Schistosoma mansoni , S. haematobium in the intermediate snails Biomphalaria spp. and Bulinus spp., respectively, and in humans. A random effect model for meta-analyses was used to calculate the pooled prevalence estimate (PPE), with heterogeneity assessed using I-squared statistic ( I 2 ), with correlation and regression analysis for the exploration of the relationship between human S. mansoni and S. haematobium infections and that in their specific intermediate hosts. Results Forty-seven publications comprising 59 field investigations were included. The pooled PPE of schistosomiasis, schistosomiasis mansoni and schistosomiasis haematobium in humans were 27.5% [95% confidence interval ( CI ): 24.0–31.1%], 25.6% (95% CI : 19.9–31.3%), and 28.8% (95% CI : 23.4–34.3%), respectively. The snails showed an overall infection rate of 8.6% (95% CI : 7.7–9.4%), with 12.1% (95% CI : 9.9–14.2%) in the Biomphalaria spp. snails and 6.9% (95% CI : 5.7–8.1%) in the Bulinus spp. snails. The correlation coefficient was 0.3 (95% CI : 0.01–0.5%, P  < 0.05) indicating that the two variables, i.e. all intermediate host snails on the one hand and the human host on the other, were positively correlated. Conclusions The prevalence rate of S. mansoni and S. haematobium is still high in endemic areas. Given the significant, positive correlation between the prevalence of schistosomes in humans and the intermediate snail hosts, more attention should be paid to programme integration of snail surveillance in future. Graphical Abstract

In the roadmap on the neglected tropical diseases (NTD) the World Health Organization (WHO) aims at attaining at least 75% coverage of preventive chemotherapy in pre-school and school-age children by 2020. A randomized controlled trial was used to compare the effectiveness of praziquantel in treating Schistosoma haematobium in Africa using two different sources for the drug, Merck Limited Partnership (KgaA), Germany and Nanjing Pharmaceutical Factory (NPF), China. More than 6,000 participants testing positive for S. haematobium infection were enrolled from three villages (shehias) situated in the northern, middle and southern part of Pemba Island, Zanzibar. Applying criteria of inclusion and exclusion, resulted in a study population of 152 people (84 males, 68 females). A randomized controlled trial was conducted assigning participants to either praziquantel from NPF or Merck KGaA. After one month, the cure rate of S. haematobium and adverse events were compared to evaluate effectiveness. The ratio of male to female, the ratio of light/high infection intensity, and the average value of age were calculated between the two drug manufacturers. Chi-squared test and T-test were used for consistency analysis. Out of the total of 73 cases receiving praziquantel from NPF, the cure rate achieved was 97.3% (73/75), while the 74 cases receiving the drug from Merck KgaA reached a similar cure rate (96.1% or 74/77). There was no significant difference between the two outcomes (χ2 = 0.003, P = 0.956). Among the 75 patients treat, only one (a 16-years old female student), who had received the drug made in China had slight adverse reactions manifested as dizziness, headache and abdominal pain. The efficacy of China-made praziquantel does not differ significantly from praziquantel made by Merck KGaA in Germany. ClinicalTrials.gov, NCT03133832.

Background The prevalence of schistosomiasis japonica has decreased significantly, and the responses changing from control to elimination in Jiangsu Province, P.R. China. How to estimate the change in prevalence of schistosomiasis using only serological data will be important and useful. Methods We collected serum samples from 2011 to 2015 to build a serum bank from Dantu County of Jiangsu, China. Serum samples were detected by enzyme-linked immunosorbent assay (ELISA), the positive rate and optical density (OD) value were obtained. The Bayesian model including the prior information of sensitivity and specificity of ELISA was established, and the estimated infection rates were obtained for different years, genders and age groups. Results There was no significant difference in the mean OD between different years and genders, but there was a significant difference between the different age groups. There were statistically significant differences in the positive rate for different years and age groups, but no significant difference at different genders. The estimated infection rate for the five years was 1.288, 1.456, 1.032, 1.485 and 1.358%, respectively. There was no significant difference between different years and between genders, but a significant difference between different age groups. Conclusions The risk of schistosomiasis transmission in this area still exists, and risk monitoring of schistosomiasis should be strengthened.

Schistosomiasis remains a serious health problem in Africa. Although a strong, coordinated agenda for research on this disease has been in place for the last 50 years in Zanzibar, data storage, retrieval of survey data and management remain problem areas. We investigated the use of Google Earth (GE) in conjunction with a hand-held, global positioning system as a pilot project for managing schistosomiasis control. In this way, risk areas can be surveyed and followed up by visualizing both the distribution of human infections and that of the intermediate snail host together with environmental information. A platform with three spatial databases was created: i) Distribution of infected humans; ii) Distribution of the intermediate snail host in ponds (infected and not infected specimens); iii) Distribution of the intermediate snail host in streams (infected and non-infected specimens). The GE spatial database increased the efficiency of follow-up case treatment as well as snail control and contributed also to the discovery of previously unknown areas in need of snail control. We conclude that this platform is advantageous not only by being useful for management and visualization of spatial data, but also because it is easy to operate and available free of charge.

Ultracold assembly of diatomic molecules has enabled great advances in controlled chemistry, ultracold chemical physics and quantum simulation with molecules 1 – 3 . Extending the ultracold association to triatomic molecules will offer many new research opportunities and challenges in these fields. A possible approach is to form triatomic molecules in a mixture of ultracold atoms and diatomic molecules by using a Feshbach resonance between them 4 , 5 . Although ultracold atom–diatomic-molecule Feshbach resonances have been observed recently 6 , 7 , using these resonances to form triatomic molecules remains challenging. Here we report on evidence of the association of triatomic molecules near the Feshbach resonance between 23 Na 40 K molecules in the rovibrational ground state and 40 K atoms. We apply a radio-frequency pulse to drive the free-bound transition in ultracold mixtures of 23 Na 40 K and 40 K and monitor the loss of 23 Na 40 K molecules. The association of triatomic molecules manifests itself as an additional loss feature in the radio-frequency spectra, which can be distinguished from the atomic loss feature. The observation that the distance between the association feature and the atomic transition changes with the magnetic field provides strong evidence for the formation of triatomic molecules. The binding energy of the triatomic molecules is estimated from the measurements. Our work contributes to the understanding of the complex ultracold atom–molecule Feshbach resonances and may open up an avenue towards the preparation and control of ultracold triatomic molecules. Evidence is presented for the association of triatomic molecules near the Feshbach resonance in an ultracold gas comprising a mixture of 23 Na 40 K molecules and 40 K atoms, along with an estimation of the binding energy of the triatomic molecules.