Predicting olfactory receptor neuron responses from odorant structure

Background Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. Their main purpose is to translate chemical space into information that can be processed by neural circuits. Assuming that these receptors have evolved to cope with this task, the analysis of their coding strategy promises to yield valuable insight in how to encode chemical information in an efficient way. Results We mimicked olfactory coding by modeling responses of primary olfactory neurons to small molecules using a large set of physicochemical molecular descriptors and artificial neural networks. We then tested these models by recording in vivo receptor neuron responses to a new set of odorants and successfully predicted the responses of five out of seven receptor neurons. Correlation coefficients ranged from 0.66 to 0.85, demonstrating the applicability of our approach for the analysis of olfactory receptor activation data. The molecular descriptors that are best-suited for response prediction vary for different receptor neurons, implying that each receptor neuron detects a different aspect of chemical space. Finally, we demonstrate that receptor responses themselves can be used as descriptors in a predictive model of neuron activation. Conclusions The chemical meaning of molecular descriptors helps understand structure-response relationships for olfactory receptors and their 'receptive fields'. Moreover, it is possible to predict receptor neuron activation from chemical structure using machine-learning techniques, although this is still complicated by a lack of training data

Unexpected removal of the most neutral cationic pharmaceutical in river waters

Contamination of surface waters by pharmaceuticals is now widespread. There are few data on their environmental behaviour, particularly for those which are cationic at typical surface water pH. As the external surfaces of bacterio-plankton cells are hydrophilic with a net negative charge, it was anticipated that bacterio-plankton in surface-waters would preferentially remove the most extensively-ionised cation at a given pH. To test this hypothesis, the persistence of four, widely-used, cationic pharmaceuticals, chloroquine, quinine, fluphenazine and levamisole, was assessed in batch microcosms, comprising water and bacterio-plankton, to which pharmaceuticals were added and incubated for 21 days. Results show that levamisole concentrations decreased by 19 % in microcosms containing bacterio-plankton, and by 13 % in a parallel microcosm containing tripeptide as a priming agent. In contrast to levamisole, concentrations of quinine, chloroquine and fluphenazine were unchanged over 21 days in microcosms containing bacterio-plankton. At the river-water pH, levamisole is 28 % cationic, while quinine is 91–98 % cationic, chloroquine 99 % cationic and fluphenazine 72–86 % cationic. Thus, the most neutral compound, levamisole, showed greatest removal, contradicting the expected bacterio-plankton preference for ionised molecules. However, levamisole was the most hydrophilic molecule, based on its octanol–water solubility coefficient (K ow). Overall, the pattern of pharmaceutical behaviour within the incubations did not reflect the relative hydrophilicity of the pharmaceuticals predicted by the octanol–water distribution coefficient, D ow, suggesting that improved predictive power, with respect to modelling bioaccumulation, may be needed to develop robust environmental risk assessments for cationic pharmaceuticals

Recull de propostes per minimitzar l'impacte negatiu de gènere del sistema de teletreball a l'Ajuntament de Barcelona

Finançat amb el projecte "Impacto de GÉnero del TEletrabajo y rutinas de COnfinamiento: más allá de lo obvio" (Ref. SUPERACOVID19_2.2.IGETECO) i a través de l'Ajuntament de Barcelona pel Servei d'Estudi sobre propostes per minimitzar l'impacte negatiu de gènere del sistema de teletreball a l'Ajuntament de Barcelona (exp.20002682)El present document recull les propostes d'actuació contingues a l'estudi Propostes per minimitzar l'impacte negatiu de gènere del sistema de teletreball a l'Ajuntament de Barcelona realitzat pel Centre d'Estudis Sociològics sobre la Vida Quotidiana i el Treball (QUIT) de la Universitat Autònoma de Barcelona. L'emergència sanitària provocada per la Covid19 i el necessari confinament de la població per combatre la pandèmia ha significat, des del punt de vista de l'organització del treball, un canvi molt important cap a l'impuls de formes de treball a distància. Però aquest impuls del teletreball ha estat una resposta fruit de l'emergència, lògica davant la situació viscuda i, com a tal, no ha pogut ser planificada amb el temps i els mitjans necessaris

Inhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells

Genetic analysis has revealed that the dual specificity protein kinase DYRK1A has multiple roles in the development of the central nervous system. Increased DYRK1A gene dosage, such as occurs in Down syndrome, is known to affect neural progenitor cell differentiation, while haploinsufficiency of DYRK1A is associated with severe microcephaly. Using a set of known and newly synthesized DYRK1A inhibitors, along with CRISPR-mediated gene activation and shRNA knockdown of DYRK1A, we show here that chemical inhibition or genetic knockdown of DYRK1A interferes with neural specification of human pluripotent stem cells, a process equating to the earliest stage of human brain development. Specifically, DYRK1A inhibition insulates the self-renewing subpopulation of human pluripotent stem cells from powerful signals that drive neural induction. Our results suggest a novel mechanism for the disruptive effects of the absence or haploinsufficiency of DYRK1A on early mammalian development, and reveal a requirement for DYRK1A in the acquisition of competence for differentiation in human pluripotent stem cells