8-Amide and 8-carbamate substitution patterns as modulators of 7-hydroxy-4-methylcoumarin's antidepressant profile: Synthesis, biological evaluation and docking studies.

Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Comparison between both scaffolds has been established, and we hypothesized that the introduction of different substituents can modulate hMAO activity and selectivity. N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide (9) and ethyl N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate (20) proved to be the most active and selective hMAO-A inhibitors (IC50 = 15.0 nM and IC50 = 22.0 nM, respectively), being compound 9 an irreversible hMAO-A inhibitor twenty-four times more active in vitro than moclobemide, a drug used in the treatment of depression and anxiety. Based on PAMPA assay results, both compounds proved to be good candidates to cross the blood-brain barrier. In addition, these compounds showed non-significant cytotoxicity on neuronal viability assays. Also, the best compound proved to have a t1/2 of 6.84 min, an intrinsic clearance of 195.63 µL min-1 mg-1 protein, and to be chemically stable at pH 3.0, 7.4 and 10.0. Docking studies were performed to better understand the binding affinities and selectivity profiles for both hMAO isoforms. Finally, theoretical drug-like properties calculations corroborate the potential of both scaffolds on the search for new therapeutic solutions for psychiatric disorders as depression.

Assessing Fuzzy Cognitive Mapping as a participatory and interdisciplinary approach to explore marine microfiber pollution.

Fuzzy Cognitive Mapping (FCM) is a participatory modelling tool used to explore complex systems by facilitating interdisciplinary cooperation and integrating a variety of knowledge systems. Here FCM was used to explore marine microfiber pollution. Through individual interviews with representatives from the research, industry, water and environmental sectors, five stakeholder FCMs were developed and used to produce an aggregated community FCM in a stakeholder workshop. Stakeholder FCMs and the revised community FCM were used to compute how the modelled system reacted to changes under two scenarios developed during the stakeholder workshop; (i) Green Shift and (ii) increased textile consumption and production. Significant differences were observed in scenario results from the stakeholder-based models and the community-based model. For societal challenges characterized by unknowns around the problem and potential solutions, inclusion of a variety of knowledge systems through FCM and deliberation processes contribute to a more holistic picture of the system and its uncertainties.

Reversible Control of DNA Binding with Cucurbit[8]uril-Induced Supramolecular 4,4'-Bipyridinium-Peptide Dimers.

Many cellular processes in living organisms are regulated by complex regulatory networks, built from noncovalent interactions between relatively few proteins that perform their functions by switching between homo- and heterooligomeric assemblies or mono- and bivalent states. Herein, we demonstrate that the conjugation of a 4,4'-bipyridinium scaffold to the basic region of the GCN4 bZip transcription factor can be exploited to control the dimerization of the conjugate by formation of a supramolecular complex with cucurbit[8]uril. Importantly, this supramolecular complex is able to specifically recognize its target dsDNA, and this binding can be reversibly switched by the application of external stimuli.

Do awareness-focussed approaches to mitigating diffuse pollution work? A case study using behavioural and water quality evidence.

Efforts to tackle diffuse water pollution from agriculture are increasingly focusing on improving farmers' awareness under the expectation that this would contribute to adoption of best management practices (BMPs) and, in turn, result in water quality improvements. To date, however, no study has explored the full awareness-behaviour-water quality pathway; with previous studies having mostly addressed the awareness-behaviour link relying on disciplinary approaches. Using an interdisciplinary approach, we investigate whether awareness-focussed approaches to mitigating diffuse water pollution from agriculture indeed result in water quality improvement, addressing the pathway in full. We worked with Dwr Cymru Welsh Water (a water and waste utility company in the UK) on a pesticide pollution intervention programme, referred to as "weed wiper trial". The main goal of the trial was to raise farmers' awareness regarding pesticide management practices and to promote uptake of BMPs to tackle the rising concentrations of the pesticide MCPA (2-methyl-4-chlorophenoxyacetic acid) in raw water in three catchments in Wales. Using factorial analysis of variance, we analysed MCPA concentrations from 2006 to 2019 in the three targeted catchments and in three control catchments. This was followed by semi-structured in-depth interviews with institutional stakeholders and farmers with varying degrees of exposure to the weed wiper trial. Results show that MCPA concentration for both targeted and control catchments had reduced after the implementation of the weed wiper trial. However, the decline was significantly larger (F(1) = 6.551, p < 0.05, n = 3077, Partial eta-squared (ηp2) = 0.002) for the targeted catchments (mean = 45.2%) compared to the control catchments (mean = 10.9%). Results from the stakeholder interviews indicate that improved awareness contributed to changes in farmers' behaviour and that these can be related to the water quality improvements reflected by the decline in MCPA concentration. Alongside awareness, other psychosocial, economic, agronomic factors, catchment and weather conditions also influenced farmer's ability to implement BMPs and thus overall water quality improvements.

Cucurbit[8]uril (CB[8])-Based Supramolecular Switches.

The use of cucurbit[8]uril as a molecular host has emerged in the chemical literature as a reliable strategy for the creation of dynamic chemical systems, owing to its ability to form homo- and heteroternary complexes in aqueous media with appropriate molecular switches as guests. In this manner, CB[8]-based supramolecular switches can be designed in a predictable and modular fashion, through the selection of appropriate guests able to condition the redox, photochemical, or pH-triggered behavior of tailored multicomponent systems. Furthermore, CB[8] allows the implementation of dual/triple and linear/orthogonal stimuli-dependent properties into these molecular devices by a careful selection of the guests. This versatility in their design gives these supramolecular switches great potential for the rational development of new materials, in which their function is not only determined by the custom-made stimuli-responsiveness, but also by the transient aggregation/disaggregation of homo- or heteromeric building blocks.

A new Brazilian species of the cricket genus Megalogryllus Chopard (Orthoptera: Gryllidae) / Nova espécie de grilo do gênero Megalogryllus Chopard (Orthoptera: Gryllidae)

Megalogryllus clamosus, uma nova espécie de grilo do estado de São Paulo, é descrita. As fotografias do holótipo (macho) e do parátipo (fêmea) são apresentadas, assim como o desenho dotégmen direito do macho e a estrutura fálica. As fotografias da pars stridens para mostrar a estrutura dos dentes e o sonograma do canto de chamado do macho são também apresentados.

Megalogryllus clamosus a new species of cricket from the São Paulo State (Brazil) is described. Photographs of the holotype (male) and of the paratype (female) are provided, as well as adrawing of the structure of the right tegmen of the male and of the phallic sclerite structure. Photographs of the pars stridens teeth and sonogram of the male calling song are also provided.

Morphological characters and karyology of Miogryllus piracicabensis Piza (Orthoptera: Gryllidae) / Caracteres morfológicos e cariologia de Miogryllus piracicabensis Piza (Orthoptera: Gryllidae)

O gênero Miogryllus inclui um número considerável de espécies, sendo que a maioria delas ainda não está descrita. A quantidade de detalhes morfológicos sobre as espécies conhecidas nemsempre é suficiente para seu reconhecimento, faltando dados sobre as estruturas fálicas e da pars stridens, bem como aqueles referentes à cariologia. O presente trabalho tem o propósito de suprir tal situação para o caso de M. piracicabensis.

The genus Miogryllus includes a considerable number of species, most of them still undescribed. From those already described, the amount of afforded details on morphology is notalways enough to recognize the species, missing information on phallic and pars stridens structures as well as karyology. The present paper aims to improve these information, on the species M.piracicabensis.