The complete genome sequence of the nitrile biocatalyst Rhodococcus rhodochrous ATCC BAA-870

BACKGROUND : Rhodococci are industrially important soil-dwelling Gram-positive bacteria that are well known for both nitrile hydrolysis and oxidative metabolism of aromatics. Rhodococcus rhodochrous ATCC BAA-870 is capable of metabolising a wide range of aliphatic and aromatic nitriles and amides. The genome of the organism was sequenced and analysed in order to better understand this whole cell biocatalyst. RESULTS : The genome of R. rhodochrous ATCC BAA-870 is the first Rhodococcus genome fully sequenced using Nanopore sequencing. The circular genome contains 5.9 megabase pairs (Mbp) and includes a 0.53 Mbp linear plasmid, that together encode 7548 predicted protein sequences according to BASys annotation, and 5535 predicted protein sequences according to RAST annotation. The genome contains numerous oxidoreductases, 15 identified antibiotic and secondary metabolite gene clusters, several terpene and nonribosomal peptide synthetase clusters, as well as 6 putative clusters of unknown type. The 0.53 Mbp plasmid encodes 677 predicted genes and contains the nitrile converting gene cluster, including a nitrilase, a low molecular weight nitrile hydratase, and an enantioselective amidase. Although there are fewer biotechnologically relevant enzymes compared to those found in rhodococci with larger genomes, such as the well-known Rhodococcus jostii RHA1, the abundance of transporters in combination with the myriad of enzymes found in strain BAA-870 might make it more suitable for use in industrially relevant processes than other rhodococci. CONCLUSIONS : The sequence and comprehensive description of the R. rhodochrous ATCC BAA-870 genome will facilitate the additional exploitation of rhodococci for biotechnological applications, as well as enable further characterisation of this model organism. The genome encodes a wide range of enzymes, many with unknown substrate specificities supporting potential applications in biotechnology, including nitrilases, nitrile hydratase, monooxygenases, cytochrome P450s, reductases, proteases, lipases, and transaminases.Additional file 1: SuppInfo Frederick et al. BAA-870 genome. Table S1. All sequenced Rhodococcus strains (353) according to the NCBI database (accessed 13/03/2019). Table S2. All complete sequenced Rhodococcus species ranked by release date according to the NCBI Genome database (accessed 11/03/2019). Table S3. Whole genome distance statistics between Rhodococcus rhodochrous ATCC BAA-870 and two closely matched strains. Table S4. Rhodococcus rhodochrous ATCC BAA-870 protein function breakdown based on BASys annotation COG classifications.The Department of Science and Technology (DST) Biocatalysis Initiative (Grant 0175/2013), South Africa, the CSIR Thematic Programme, the Welch Foundation (grant E-1264) and the European Science Foundation COST Action CM0701.https://bmcgenomics.biomedcentral.comam2020BiochemistryGeneticsMicrobiology and Plant Patholog

Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect

Open Research, and Professional and Technical Support Staff

This short report summarises some reflections of professional and technical support staff on their perspectives on open research. The reflections are based on input to, and discussions at, a community workshop and roundtable event co-convened by UKRN and Jisc on 20th February 2023. The report is intended to inform discussions within groups of staff in similar roles, across different professional and academic groupings in institutions, and with other stakeholders such as funders

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Many-analysts Approach to the Relation Between Religiosity and Well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer

PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2– advanced (locally unresectable) or metastatic disease (HR+/HER2– mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2– mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2– mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2– mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status