System-wide analysis of the GATC-binding nucleoid-associated protein Gbn and its impact on Streptomyces development

Bacterial chromosome structure is, to a great extent, organized by a diverse group of proteins collectively referred to as nucleoid-associated proteins (NAPs). Many NAPs have been well studied in Streptomyces, including Lsr2, HupA, HupS, and sIHF. Here, we show that SCO1839 represents a novel family of Actinobacteria NAPs and recognizes a consensus sequence consisting of GATC followed by (A/T)T. The protein, which is expressed in particular during sporulation, was designated Gbn for GATC-binding NAP. Deletion of gbn led to alterations in development and antibiotic production in Streptomyces coelicolor. Chromatin immunoprecipitation sequencing (ChIP-Seq) detected more than 2,800 binding regions, encompassing around 3,600 GATCWT motifs. This amounts to 55% of all such sequences in the S. coelicolor genome. DNA binding of Gbn in vitro minimally changes DNA conformation, suggesting a modest role in chromosome organization only, in addition to a gene regulatory role. Transcriptomics analysis showed that Gbn binding generally leads to reduced gene expression. The DNA binding profiles were nearly identical between vegetative and aerial growth. Exceptions are SCO1311 and SCOt32, for a tRNA editing enzyme and a tRNA that recognizes the rare leucine codon CUA, respectively, which nearly exclusively bound during vegetative growth. Taken together, our data show that Gbn is a highly pleiotropic NAP that impacts growth and development in streptomycetes.IMPORTANCE A large part of the chemical space of bioactive natural products is derived from Actinobacteria. Many of the biosynthetic gene clusters for these compounds are cryptic; in others words, they are expressed in nature but not in the laboratory. Understanding the global regulatory networks that control gene expression is key to the development of approaches to activate this biosynthetic potential. Chromosome structure has a major impact on the control of gene expression in eukaryotes. In bacteria, the organization of chromosome structure is mediated by multiple factors, including macromolecular biophysics processes, biological processes, and, more importantly, a diverse group of proteins referred to collectively as nucleoid-associated proteins (NAPs). We here present the discovery of a novel and extremely pleiotropic NAP, which we refer to as Gbn. Gbn is an Actinobacteria-specific protein that binds to GATC sequences, with a subtle but broad effect on global gene expression, especially during the late developmental stage. The discovery of Gbn is a new step toward better understanding of how gene expression and chromosome structure are governed in antibiotic-producing streptomycetes.Microbial Biotechnolog

Tests of the co-integration rank in VAR models in the presence of a possible break in trend at an unknown point

In this paper we consider the problem of testing for the co-integration rank of a vector autoregressive process in the case where a trend break may potentially be present in the data. It is known that un-modelled trend breaks can result in tests which are incorrectly sized under the null hypothesis and inconsistent under the alternative hypothesis. Extant procedures in this literature have attempted to solve this inference problem but require the practitioner to either assume that the trend break date is known or to assume that any trend break cannot occur under the co-integration rank null hypothesis being tested. These procedures also assume the autoregressive lag length is known to the practitioner. All of these assumptions would seem unreasonable in practice. Moreover in each of these strands of the literature there is also a presumption in calculating the tests that a trend break is known to have happened. This can lead to a substantial loss in finite sample power in the case where a trend break does not in fact occur. Using information criteria based methods to select both the autoregressive lag order and to choose between the trend break and no trend break models, using a consistent estimate of the break fraction in the context of the former, we develop a number of procedures which deliver asymptotically correctly sized and consistent tests of the co-integration rank regardless of whether a trend break is present in the data or not. By selecting the no break model when no trend break is present, these procedures also avoid the potentially large power losses associated with the extant procedures in such cases

A global call for action to include gender in research impact assessment

Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal, and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we – a group of scholars and practitioners from Africa, America, Asia, and Europe– argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal, and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions, and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action

Genetic variants for head size share genes and pathways with cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.</p

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters

Microbial Biotechnolog

Exploring the potential of biomass-templated Nb/ZnO nanocatalysts for the sustainable synthesis of N-heterocycles

Herein, we report a Nb/ZnO nanocatalyst for the efficient conversion of levulinic acid, a platform molecule easily obtained from lignocellulosic biomass, to N-heterocycles under mild reaction conditions and the absence of solvent. Nb/ZnO nanocatalysts were synthesized by a mechanochemical-assisted and sacrificial template method, involving orange peel valorization toward nanostructured materials. Two different synthetic approaches, either one-step or two-step, as well as the amount of niobium deposited onto the ZnO support were investigated in order to obtain the nanocatalyst with the optimal catalytic properties. Results revealed the critical role of the niobium for LA conversion. The nanocatalyst containing 10 wt% of niobium and prepared following a two-step approach (10 %Nb/ZnO_2) exhibited the best catalytic performance with a 94.5% of conversion and 97.4% of selectivity towards one specific N-heterocycle compound. This work exemplifies the possibility of sustainable production of value-added compounds, in particular N-heterocycles, from biomass-derived feedstocks by playing with the design of improved catalysts. Importantly, this research area provides sustainable alternatives to the current chemical industry that is heavily dependent on fossil fuels. © 2020 Elsevier B.V

The ubiquitous catechol moiety elicits siderophore and angucycline production in Streptomyces

Microbial Biotechnolog