Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment.

Synphilin-1 is a protein encoded by the human SNCAIP gene whose function has yet to be fully understood. However, it has been linked to familial Parkinson's disease (PD). Synphilin-1 is a major component of the Lewy bodies found in neurons in the substantia nigra pars compacta of PD patients. Synphilin-1 expression in serotonergic and/or dopaminergic neurons of Drosophila melanogaster induces neurodegeneration, as well as motor and non-motor PD like symptoms. In this work, we examined the contribution of the serotonergic and dopaminergic circuits in the development of PD-like phenotypes. We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.

Assessing the inequalities in access to online delivery services and the way COVID-19 pandemic affects marginalization.

This paper discusses the importance of incorporating online home delivery services (OHDS) into the concept of accessibility and marginalization. The authors propose a method to quantify access to OHDS and assess levels of inequalities in access to OHDS using data from OHDS providers in the pharmaceutical and food sectors, as well as from transport operators delivering parcels. The Västra Götaland Region in the West coast of Sweden is used as a case study. The results show significant inequalities in access to OHDS. Moreover, there are segments of population under a compound marginalization during the COVID-19 pandemic due to (i) limited accessibility to OHDS services, (ii) high incidence of COVID-19 cases in their area that makes physical visits to a store a risk activity, and (iii) high vulnerability (e.g., high share of individuals older than 65). These results reveal a need for the public sector to prioritize innovations in services that target specific clusters of the population that are vulnerable and marginalized, but also shows the imminent risk for some of these segments during the pandemic.

Rpt2 proteasome subunit reduction causes Parkinson's disease like symptoms in Drosophila.

The dysfunction of the proteasome-ubiquitin system is commonly reported in several neurodegenerative diseases. Post mortem samples of brains of patients with Parkinson´s disease present cytoplasmic inclusions that are rich in proteins such as ubiquitin, Tau, and α-synuclein. In Parkinson´s disease, a specific reduction of some of the proteasome subunits has also been reported. However, the specific role of the different proteasome subunits in dopaminergic neuron degeneration has not been thoroughly explored. In this work, we used the Gal4/UAS system to test fourteen Drosophila melanogaster RNAi lines from the Bloomington Drosophila Stock Center. Each of these lines targets a different proteasome subunit. To identify the strains that were able to induce neurodegeneration, we drove the expression of these lines to the eye and cataloged them as a function of the extent of neurodegeneration that they induced. The targeted proteasomal subunits are conserved in mammals and therefore may be relevant to study proteasome related diseases. The RNAi line among the regulatory subunits with the most penetrant phenotype targeted the proteasomal subunit Rpt2 and we decided to further characterize its phenotypes. Rpt2 knockdown in the Drosophila central nervous system reduced the activity of the proteasome, augmented the amount of insoluble ubiquitinated protein, and elicited motor and non-motor phenotypes that were similar to the ones found in Drosophila and other models for Parkinson's disease. When Rpt2 is silenced pan-neurally, third instar larvae have locomotion dysfunctions and die during pupation. Larval lethality was avoided using the Gal80-Gal4 system to induce the expression of the Rpt2 RNAi to dopaminergic neurons only after pupation. The reduction of Rpt2 in adult dopaminergic neurons causes reduced survival, hyperactivity, neurodegeneration, and sleep loss; probably recapitulating some of the sleep disorders that Parkinson's disease patients have before the appearance of locomotion disorders.

The Esg Gene Is Involved in Nicotine Sensitivity in Drosophila melanogaster.

In humans, there is a strong correlation between sensitivity to substances of abuse and addiction risk. This differential tolerance to drugs has a strong genetic component. The identification of human genetic factors that alter drug tolerance has been a difficult task. For this reason and taking advantage of the fact that Drosophila responds similarly to humans to many drugs, and that genetically it has a high degree of homology (sharing at least 70% of genes known to be involved in human genetic diseases), we looked for genes in Drosophila that altered their nicotine sensitivity. We developed an instantaneous nicotine vaporization technique that exposed flies in a reproducible way. The amount of nicotine sufficient to "knock out" half of control flies for 30 minutes was determined and this parameter was defined as Half Recovery Time (HRT). Two fly lines, L4 and L70, whose HRT was significantly longer than control´s were identified. The L4 insertion is a loss of function allele of the transcriptional factor escargot (esg), whereas L70 insertion causes miss-expression of the microRNA cluster miR-310-311-312-313 (miR-310c). In this work, we demonstrate that esg loss of function induces nicotine sensitivity possibly by altering development of sensory organs and neurons in the medial section of the thoracoabdominal ganglion. The ectopic expression of the miR-310c also induces nicotine sensitivity by lowering Esg levels thus disrupting sensory organs and possibly to the modulation of other miR-310c targets.