Molecular mechanisms underlying the emergence of bacterial pathogens: an ecological perspective

The rapid emergence of new bacterial diseases negatively affects both human health and agricultural productivity. Although the molecular mechanisms underlying these disease emergences are shared between human‐ and plant‐pathogenic bacteria, not much effort has been made to date to understand disease emergences caused by plant‐pathogenic bacteria. In particular, there is a paucity of information in the literature on the role of environmental habitats in which plant‐pathogenic bacteria evolve and on the stress factors to which these microbes are unceasingly exposed. In this microreview, we focus on three molecular mechanisms underlying pathogenicity in bacteria, namely mutations, genomic rearrangements and the acquisition of new DNA sequences through horizontal gene transfer (HGT). We briefly discuss the role of these mechanisms in bacterial disease emergence and elucidate how the environment can influence the occurrence and regulation of these molecular mechanisms by directly impacting disease emergence. The understanding of such molecular evolutionary mechanisms and their environmental drivers will represent an important step towards predicting bacterial disease emergence and developing sustainable management strategies for crops.     

The deubiquitinase Usp27x stabilizes the BH3‐only protein Bim and enhances apoptosis

Bim is a pro‐apoptotic Bcl‐2 family member of the BH3‐only protein subgroup. Expression levels of Bim determine apoptosis susceptibility in non‐malignant and in tumour cells. Bim protein expression is downregulated by proteasomal degradation following ERK‐dependent phosphorylation and ubiquitination. Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK‐dependent phosphorylation and can upregulate its expression levels. Overexpression of Usp27x reduces ERK‐dependent Bim ubiquitination, stabilizes phosphorylated Bim, and induces apoptosis in PMA‐stimulated cells, as well as in tumour cells with a constitutively active Raf/ERK pathway. Loss of endogenous Usp27x enhances the Bim‐degrading activity of oncogenic Raf. Overexpression of Usp27x induces low levels of apoptosis in melanoma and non‐small cell lung cancer (NSCLC) cells and substantially enhances apoptosis induced in these cells by the inhibition of ERK signalling. Finally, deletion of Usp27x reduces apoptosis in NSCLC cells treated with an EGFR inhibitor. Thus, Usp27x can trigger via its proteolytic activity the deubiquitination of Bim and enhance its levels, counteracting the anti‐apoptotic effects of ERK activity, and therefore acts as a tumour suppressor.     

Neurons acetylate their way to migration

The centrosome is crucial for neuronal migration and polarisation, processes that are disrupted in a number of neurodevelopmental disorders including schizophrenia. Mutation of DISC1, associated with increased risk of schizophrenia and psychiatric illness, has been shown to affect the centrosome, but the mechanisms involved have not been elucidated. In this issue of EMBO Reports, Fukuda and colleagues demonstrate that a DISC1‐interacting protein, CAMDI, suppresses the activity of the histone deacetylase HDAC6, thereby promoting centrosome stability and consequently neuronal migration 1 . Loss of CAMDI leads to cortical migration defects and behavioural phenotypes that model autism spectrum disorders and which can be rescued by inhibition of HDAC6. The study provides novel mechanistic insight into centrosome regulation in neurodevelopment.     

Pyrazolo[1,5-a]quinazoline scaffold as 5-deaza analogue of pyrazolo[5,1-c][1,2,4]benzotriazine system: synthesis of new derivatives,biological activity on GABAA receptor subtype and molecular dynamic study

To investigate the binding affinity of GABA_A receptor subtype, new pyrazolo [1,5-a]quinazolines were designed, synthesized, and in vitro evaluated. These compounds, 5-deaza analogues of pyrazolo[5,1-c][1,2,4]benzotriazine derivatives which were already studied in our research group, permit us to evaluate the relevance of the nitrogen or the oxygen atom at 5-position of the tricyclic scaffold. Molecular dynamic study was done on a set of the new and known ligands to rationalize and to explain the lack of affinity on the 4- or 5-substituted new derivative. In fact, from biological results, it can be found that the only 5-unsubstituted new derivative, compound 15, has receptor recognition (K_i?=?834.7?nM).     

Rapid Assessment of Tablet Film Coating Quality by Multispectral UV Imaging

Chemical imaging techniques are beneficial for control of tablet coating layer quality as they provide spectral and spatial information and allow characterization of various types of coating defects. The purpose of this study was to assess the applicability of multispectral UV imaging for assessment of the coating layer quality of tablets. UV images were used to detect, characterize, and localize coating layer defects such as chipped parts, inhomogeneities, and cracks, as well as to evaluate the coating surface texture. Acetylsalicylic acid tablets were prepared on a rotary tablet press and coated with a polyvinyl alcohol-polyethylene glycol graft copolymer using a pan coater. It was demonstrated that the coating intactness can be assessed accurately and fast by UV imaging. The different types of coating defects could be differentiated and localized based on multivariate image analysis and Soft Independent Modeling by Class Analogy applied to the UV images. Tablets with inhomogeneous texture of the coating could be identified and distinguished from those with a homogeneous surface texture. Consequently, UV imaging was shown to be well-suited for monitoring of the tablet coating layer quality. UV imaging is a promising technique for fast quality control of the tablet coating because of the high data acquisition speed and its nondestructive analytical nature.     

Problems with supertrees based on the subtree prune‐and‐regraft distance,with comments on majority rule supertrees

This paper examines a recent proposal to calculate supertrees by minimizing the sum of subtree prune‐and‐regraft distances to the input trees. The supertrees thus calculated may display groups present in a minority of the input trees but contradicted by the majority, or groups that are not supported by any input tree or combination of input trees. The proponents of the method themselves stated that these are serious problems of “matrix representation with parsimony”, but they can in fact occur in their own method. The majority rule supertrees, being explicitly clade‐based, cannot have these problems, and seem much more suited to retrieving common clades from a set of trees with different taxon sets. However, it is dubious that so‐called majority rule supertrees can always be interpreted as displaying those clades present (or compatible with) with a majority of the trees. The majority rule consensus is always a median tree, in terms of the Robinson–Foulds distances (i.e. it minimizes the sum of Robinson–Foulds distances to the input trees). In contrast, majority rule supertrees may not be median—different, contradictory trees may minimize Robinson–Foulds distances, while their strict consensus does not. If being “majority” results from being median in Robinson–Foulds distances, this means that in the supertree setting a “majority” is ambiguously defined, sometimes achievable only by mutually contradictory trees.     

Secondary metabolites,secretory structures and biological activity of water celery (Apium nodiflorum (L.) Lag.) growing in central Italy

Apium nodiflorum (L.) Lag. (water celery) is an hydrophytic plant forming dense submerged populations occurring along streams and rivers of Europe. In the present work we provided new insights into the phytochemistry and biology of A. nodiflorum. In particular, we studied the chemical profile of essential oil and polar extracts obtained from the flowering aerial parts of water celery growing in central Italy, together with the essential oil biological activities, namely antimicrobial, antioxidant and cytotoxicity on tumour cells. In addition, we correlated the productivity in secondary metabolites to the secreting structures through a detailed micromorphological study. The essential oil was dominated by two main chemotypes, characterized by myristicin and limonene, respectively. The oils showed significant toxicity on tumour cells, as evidenced by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, with IC₅₀ values in the range 3.8–15.9 μg mL^?1, together with inhibitory effects on Candida albicans (inhibition zones of 10–11 mm). HPLC-MS analysis showed the caffeoylquinic acids and quercetin-3-O-glucoside as the most abundant phenolic compounds. Ducts and vittae were the principal secretory structures of vegetative (leaves and stems) and reproductive (fruits) parts, respectively, storing mainly essential oil. Results of this work provide scientific evidences for the possible valorization and exploitation of water celery.