Recent decades have witnessed a dramatic increase of multidrug resistant (MDR) bacteria, compromising the efficacy of available antibiotics, and a continual decline in the discovery of novel antibacterials. We recently reported the first library of benzo[b]thiophen-2-ylboronic acid inhibitors sharing broad spectrum activity against β-lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of β-lactamases has been here structurally investigated. An extensive X-ray crystallographic analysis of boronic acids (BAs) binding to proteins representative of serine BLs (SBLs) and metallo β-lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recognition, especially in the interaction with MBLs. Our derivatives are the first case of noncyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.
Pseudechiniscus is the second most species-rich genus in Heterotardigrada and in the family Echiniscidae. However, previous studies have pointed out polyphyly and heterogeneity in this taxon. The recent erection of the genus Acanthechiniscus was another step in making Pseudechiniscus monophyletic, but species identification is still problematic. The present investigation aims at clarifying biodiversity and taxonomy of Pseudechiniscus taxa, with a special focus on species pertaining to the so-called ‘suillus–facettalis group’, by using an integrated approach of morphological and molecular investigations. The analysis of sequences from specimens sampled in Europe and Asia confirms the monophyly of the genus Pseudechiniscus. Inside the genus, two main evolutionary lineages are recognizable: the P. novaezeelandiae lineage and the P. suillus–facettalis group lineage. Inside the P. suillus–facettalis group, COI molecular data points out a very high variability between sampled localities, but in some cases also among specimens sampled in the same locality (up to 33.3% p-distance). The integrated approach to the study of Pseudechiniscus allows confirmation of its monophyly and highlights the relationships in the taxon, pointing to its global distribution.
Disturbances in the glutamatergic system have been increasingly documented in several neuropsychiatric disorders, including autism spectrum disorder (ASD). Glutamate-centered theories of ASD are based on evidence from patient samples and postmortem studies, as well as from studies documenting abnormalities in glutamatergic gene expression and metabolic pathways, including changes in the gut microbiota glutamate metabolism in patients with ASD. In addition, preclinical studies on animal models have demonstrated glutamatergic neurotransmission deficits and altered expression of glutamate synaptic proteins. At present, there are no approved glutamatergic drugs for ASD, but several ongoing clinical trials are currently focusing on evaluating in autistic patients glutamatergic pharmaceuticals already approved for other conditions. In this review, we provide an overview of the literature concerning the role of glutamatergic neurotransmission in the pathophysiology of ASD and as a potential target for novel treatments.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.