Remote Health Monitoring in the Workplace for Early Detection of COVID-19 Cases during the COVID-19 Pandemic Using a Mobile Health Application: COVIDApp.

Background: COVIDApp is a platform created for management of COVID-19 in the workplace. Methods: COVIDApp was designed and implemented for the follow-up of 253 workers from seven companies in Catalonia. The assessment was based on two actions: first, the early detection and management of close contacts and potential cases of COVID-19, and second, the rapid remote activation of protocols. The main objectives of this strategy were to minimize the risk of transmission of COVID-19 infection in the work area through a new real-time communication channel and to avoid unnecessary sick leave. The parameters reported daily by workers were close contact with COVID cases and signs and/or symptoms of COVID-19. Results: Data were recorded between 1 May and 30 November 2020. A total of 765 alerts were activated by 76 workers: 127 green alarms (16.6%), 301 orange alarms (39.3%), and 337 red alarms (44.1%). Of all the red alarms activated, 274 (81.3%) were activated for symptoms potentially associated with COVID-19, and 63 (18.7%) for reporting close contact with COVID-19 cases. Only eight workers (3.1%) presented symptoms associated with COVID-19 infection. All of these workers underwent RT-PCR tests, which yielded negative results for SARS-CoV2. Three workers were considered to have had a risk contact with COVID-19 cases; only 1 (0.4%) asymptomatic worker had a positive RT-PCR test result, requiring the activation of protocols, isolation, and contact tracing. Conclusions: COVIDApp contributes to the early detection and rapid activation of protocols in the workplace, thus limiting the risk of spreading the virus and reducing the economic impact caused by COVID-19 in the productive sector. The platform shows the progression of infection in real time and can help design new strategies.

What are the letters e and é in a language with vowel reduction? The case of Catalan

Although the Latin-based orthographies of most Western languages employ vowels with accent marks (e.g., é vs. e), extant models of letter and word recognition are agnostic as to whether these accented letters and their non-accented counterparts are represented by common or separate abstract units. Recent research in French with a masked priming alphabetic decision task was interpreted as favoring the idea that accented and non-accented vowels are represented by separate abstract orthographic units (orthographic account: é↛e and e↛é; Chetail & Boursain, 2019). However, a more parsimonious explanation is that salient (accented) vowels are less perceptually similar to non-salient (non-accented) vowels than vice versa (perceptual account: e→é, but é↛e; Perea et al., 2021a; Tversky, 1977). To adjudicate between the two accounts, we conducted a masked priming alphabetic decision experiment in Catalan, a language with a complex orthography-to-phonology mapping for non-accented vowels (e.g., e→/e/, /ə/, /ε/). Results showed faster responses in the identity than in the visually similar condition for accented targets (é–É < e–É), but not for non-accented targets (e–E = é–E). Neither of the above accounts can fully capture this pattern. We propose an explanation based on the rapid activation of both orthographic and phonological codes.

Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma

Loss-of-function mutations in the RB1 tumour suppressor are key drivers in cancer, including osteosarcoma. RB1 loss-of-function compromises genome-maintenance and hence could yield vulnerability to therapeutics targeting such processes. Here we demonstrate selective hypersensitivity to clinically-approved inhibitors of Poly-ADP-Polymerase1,2 inhibitors (PARPi) in RB1-defective cancer cells, including an extended panel of osteosarcoma-derived lines. PARPi treatment results in extensive cell death in RB1-defective backgrounds and prolongs survival of mice carrying human RB1-defective osteosarcoma grafts. PARPi sensitivity is not associated with canonical homologous recombination defect (HRd) signatures that predict PARPi sensitivity in cancers with BRCA1,2 loss, but is accompanied by rapid activation of DNA replication checkpoint signalling, and active DNA replication is a prerequisite for sensitivity. Importantly, sensitivity in backgrounds with natural or engineered RB1 loss surpasses that seen in BRCA-mutated backgrounds where PARPi have established clinical benefit. Our work provides evidence that PARPi sensitivity extends beyond cancers identifiable by HRd and advocates PARP1,2 inhibition as a personalised strategy for RB1-mutated osteosarcoma and other cancers.

Efficient Electrosynthesis of White Phosphorus from Molten Condensed Phosphate Salts

Elemental white phosphorus (P4) is a crucial feedstock for the entire phosphorus-derived chemicals industry, spanning everything from herbicides to food additives. Currently, industrial P4 production is gated by the infrastructurally demanding reduction of phosphate rock by carbon coke in an arc furnace at temperatures of up to 1500 °C. The electrochemical reduction of phosphate salts could enable the sustainable, point-of-use manufacture of white phosphorus; however, such P4 electrosynthesis requires the rapid activation of strong P—O bonds. Herein, we show that the intrinsic oxide-accepting character of phosphoryl anhydride linkages in molten condensed phosphate salts promotes the reduction of phosphate to white phosphorus at high electron and energy efficiencies. These findings could enable an efficient, low-carbon alternative to legacy carbothermal synthesis of P4.

Gezielte Injektion von Effektoren durch Kontrolle der Proteindynamik

The type III secretion system (T3SS) enables direct injection of bacterial effector proteins into eukaryotic cells. We found that the dynamic cytosolic interface of the system allows Yersinia enterocolitica to suppress premature secretion at low pH, ensuring rapid activation at the site of action. Exploiting this principle, we developed a light-controlled T3SS based on optogenetic interaction switches, which provides unprecedented spatiotemporal control of protein secretion and translocation.

Evolutionarily divergent mTOR remodels the translatome to drive rapid wound closure and regeneration

An outstanding mystery in biology is why some species, such as the axolotl, can scarlessly heal and regenerate tissues while most mammals cannot. Here, we demonstrate that rapid activation of protein synthesis is a unique, and previously uncharacterized, feature of the injury response critical for limb regeneration in the axolotl (A. mexicanum). By applying polysome sequencing, we identify hundreds of transcripts, including antioxidants and ribosome components, which do not change in their overall mRNA abundance but are selectively activated at the level of translation from pre-existing mRNAs in response to injury. In contrast, we show that protein synthesis is not activated in response to digit amputation in the non-regenerative mouse. We further identify the mTORC1 pathway as a key upstream signal that mediates this regenerative translation response in the axolotl. Inhibition of this pathway is sufficient to suppress translation and axolotl regeneration. Surprisingly, although mTOR is highly evolutionarily conserved, we discover unappreciated expansions in mTOR protein sequence among urodele amphibians. By engineering an axolotl mTOR in human cells, we demonstrate that this change creates a hypersensitive kinase that may allow axolotls to maintain this pathway in a highly labile state primed for rapid activation. This may underlie metabolic differences and nutrient sensing between regenerative and non-regenerative species that are key to regeneration. Together, these findings highlight the unanticipated impact of the translatome on orchestrating the early steps of wound healing in highly regenerative species and provide a missing link in our understanding of vertebrate regenerative potential.