The Alternative Choice of Constitutive Exons throughout Evolution

Alternative cassette exons are known to originate from two processes exonization of intronic sequences and exon shuffling. Herein, we suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other. Examination of these exons suggests that the common ancestors were constitutively spliced. We show that relaxation of the 59 splice site during evolution is one of the molecular mechanisms by which exons shift from constitutive to alternative splicing. This shift is associated with the fixation of exonic splicing regulatory sequences (ESRs) that are essential for exon definition and control the inclusion level only after the transition to alternative splicing. The effect of each ESR on splicing and the combinatorial effects between two ESRs are conserved from fish to human. Our results uncover an evolutionary pathway that increases transcriptome diversity by shifting exons from constitutive to alternative splicin

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Understanding the role of the forecast-maker in overestimation forecasts of policy impacts: The case of Travel Demand Management policies

Forecasting the impacts of a proposed policy is an important component of the transportation planning and decision making process. Although scientific tools are often used in transportation forecasts, biases and, more specifically, overestimations of the expected impact are often observed. This study explores the correlations between forecast-maker's characteristics and forecast bias creation and reduction. The study examines two transport-related policies aiming at the reduction of car use: telecommuting and carsharing. Both are Travel Demand Management (TDM) policies, which attract much attention from transport experts. We tested the extent to which the forecast-maker's beliefs about the policy at stake affected the forecast bias. We found that attitudes and beliefs associates not only with overestimation bias but also with its reduction over time. We also tested the extent to which the forecast-maker's affiliation, the performing institute and the publication type were correlated with the biases of the forecast and with the forecaster attitudes and beliefs. These characteristics are intuitively used by the forecast user as tools to assess the 'objectivity' of the forecast, but our analysis found no association between these characteristics and the forecast bias.Optimism bias Telecommuting Carsharing Forecasting Bias

Mpox Infection in a Developed Country: A Case Report

This is the first Israeli case report of mpox (monkeypox) disease, as it is manifested in the current outbreak. This manuscript depicts two detailed patient journeys of Israeli men in their 30s who were diagnosed in recent months, depicting their symptoms, presumed exposure, and outcomes. The two cases were atypical compared to the clinical presentation prior to the current outbreak but were similar to other recent reported cases; they differed in their prodromal presentation. Importantly, both patients described that significant anxiety around the diagnosis dominated their journey while sharing that a concern is rising in the GBMSM community, a concern that should be addressed by healthcare providers