Mantra 2.0: An online collaborative resource for drug mode of action and repurposing by network analysis

Elucidation of molecular targets of a compound (mode of action, MoA) and of its off-targets is a crucial step in drug development. We developed an online collaborative resource (MANTRA 2.0) that supports this process by exploiting similarities between drug-induced transcriptional profiles. Drugs are organised in a network of nodes (drugs) and edges (similarities) highlighting “communities” of drugs sharing a similar MoA. A user can upload gene expression profiles (GEPs) before and after drug treatment in one or multiple cell types. An automated processing pipeline transforms the GEPs into a unique drug ”node” embedded in the drug-network. Visual inspection of the neighbouring drugs and communities helps in revealing its MoA, and to suggest new applications of known drugs (drug repurposing). MANTRA 2.0 allows storing and sharing user-generated network nodes, thus making MANTRA 2.0 a collaborative ever-growing resource

A Vanadium(III) Complex with Blue and NIR-II Spin-Flip Luminescence in Solution

Luminescence from Earth-abundant metal ions in solution at room temperature is a very challenging objective due to the intrinsically weak ligand field splitting of first-row transition metal ions, which leads to efficient nonradiative deactivation via metal-centered states. Only a handful of 3dn metal complexes (n ≠ 10) show sizable luminescence at room temperature. Luminescence in the near-infrared spectral region is even more difficult to achieve as further nonradiative pathways come into play. No Earth-abundant first-row transition metal complexes have displayed emission >1000 nm at room temperature in solution up to now. Here, we report the vanadium(III) complex mer-[V(ddpd)2][PF6]3 yielding phosphorescence around 1100 nm in valeronitrile glass at 77 K as well as at room temperature in acetonitrile with 1.8 × 10–4% quantum yield (ddpd = N,N′-dimethyl-N,N′-dipyridine-2-ylpyridine-2,6-diamine). In addition, mer-[V(ddpd)2][PF6]3 shows very strong blue fluorescence with 2% quantum yield in acetonitrile at room temperature. Our comprehensive study demonstrates that vanadium(III) complexes with d2 electron configuration constitute a new class of blue and NIR-II luminophores, which complement the classical established complexes of expensive precious metals and rare-earth elements

An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein

Neuropathological and experimental evidence suggests that the cell-to-cell transfer of α-synuclein has an important role in the pathogenesis of Parkinson's disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of α-synuclein. A genetically encoded reporter, GFP-2A-αSynuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing α-synuclein. We find that 38 genes regulate the transfer of α-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of α-synuclein spread

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae

Femto-assisted versus conventional phacoemulsification differently impact on choroid structure after surgery

Purpose: To report potential choroidal changes in eyes undergoing femtosecond laser cataract surgery (FLACS) and phacoemulsification surgery (PCS) by OCT. Methods: The patients were images by means Spectral Domain OCT imaging with EDI technology which may obtain OCT image. We exported a single EDI-OCT scan passing through the fovea and then it was imported into ImageJ program to perform a quantitative analysis. Main outcome measures: The main outcome measures were: (i) sub foveal choroidal thickness (SFCT); (ii) the choroidal vascularity index (CVI); and (iii) central retinal thickness (CRT). Results: At postoperative 1 week, FLACS group showed an increased CRT (241.2 ± 31.6–245.5 ± 36.4 μm; p = 0.016). Likewise, CVI and SFCT exhibited a slight increase but no statistically differences were highlighted (p > 0.05). At the follow-up visit of 1 month, all OCT parameters did not display any significant difference (p > 0.05). At post-operative 1 week, the PCS group displayed a significant increase in CRT, SFCT, and CVI. On the contrary, at the follow-up visit of 1-month, all choroidal parameters were characterized by a no statistically significant reduction (p > 0.05). Conclusions: Our study exhibited a significant increase in CT and CVI in eyes that underwent conventional cataract surgery. Femtosecond laser-assisted cataract extraction did not result in macular change due to less postoperative inflammation