Purpose:The COVID-19 death-rate in Italy continues to climb, surpassing that in every other country. We implement one of the first nationally representative surveys about this unprecedented public health crisis and use it to evaluate the Italian government' public health efforts and citizen responses. Findings: (1) Public health messaging is being heard. Except for slightly lower compliance among young adults, all subgroups we studied understand how to keep themselves and others safe from the SARS-Cov-2 virus. Remarkably, even those who do not trust the government , or think the government has been untruthful about the crisis believe the messaging and claim to be acting in accordance. (2) The quarantine is beginning to have serious negative effects on the population's mental health. Policy Recommendations: Communications should move from explaining to citizens that they should stay at home to what they can do there. We need interventions that make staying following public health protocols more desirable, such as virtual social interactions, online social reading activities, classes, exercise routines, etc. -all designed to reduce the boredom of long term social isolation and to increase the attractiveness of following public health recommendations. Interventions like these will grow in importance as the crisis wears on around the world, and staying inside wears on people. 1 Roma Capitale (Municipality of Rome) convened our "COVID-19 International Behavioral Science Working Group" to (i) strengthen its public health policies and guidance, (ii) suggest new policies and guidance based on rigorous behavioral science, and (iii) develop empirical evidence about behavioral change. We report here empirical results and policy interventions aimed at achieving the objectives of the national Italian Government concerning the containment of the pandemic. Thanks to TIM S.p.A., Fastweb S.p.A., and Indra Italia S.p.A. for financial support. The current version of this paper is at GaryKing.org/covid-italy .

The timing of SARS-CoV-2 transmission is a critical factor to understand the epidemic trajectory and the impact of isolation, contact tracing and other non- pharmaceutical interventions on the spread of COVID-19 epidemics. We examined the distribution of transmission events with respect to exposure and onset of symptoms. We show that for symptomatic individuals, the timing of transmission of SARS-CoV-2 is more strongly linked to the onset of clinical symptoms of COVID-19 than to the time since infection. We found that it was approximately centered and symmetric around the onset of symptoms, with three quarters of events occurring in the window from 2-3 days before to 2-3 days after. However, we caution against overinterpretation of the right tail of the distribution, due to its dependence on behavioural factors and interventions. We also found that the pre-symptomatic infectious period extended further back in time for individuals with longer incubation periods. This strongly suggests that information about when a case was infected should be collected where possible, in order to assess how far into the past their contacts should be traced. Overall, the fraction of transmission from strictly pre-symptomatic infections was high (41%; 95%CI 31-50%), which limits the efficacy of symptom-based interventions, and the large fraction of transmissions (35%; 95%CI 26-45%) that occur on the same day or the day after onset of symptoms underlines the critical importance of individuals distancing themselves from others as soon as they notice any symptoms, even if they are mild. Rapid or at-home testing and contextual risk information would greatly facilitate efficient early isolation.

Single amino acid repeats are prevalent in eukaryote organisms, although the role of many such sequences is still poorly understood. We have performed a comprehensive analysis of the proteins containing homopolymeric histidine tracts in the human genome and identified 86 human proteins that contain stretches of five or more histidines. Most of them are endowed with DNA- and RNA-related functions, and, in addition, there is an overrepresentation of proteins expressed in the brain and/or nervous system development. An analysis of their subcellular localization shows that 15 of the 22 nuclear proteins identified accumulate in the nuclear subcompartment known as nuclear speckles. This localization is lost when the histidine repeat is deleted, and significantly, closely related paralogous proteins without histidine repeats also fail to localize to nuclear speckles. Hence, the histidine tract appears to be directly involved in targeting proteins to this compartment. The removal of DNA-binding domains or treatment with RNA polymerase II inhibitors induces the re-localization of several polyhistidine-containing proteins from the nucleoplasm to nuclear speckles. These findings highlight the dynamic relationship between sites of transcription and nuclear speckles. Therefore, we define the histidine repeats as a novel targeting signal for nuclear speckles, and we suggest that these repeats are a way of generating evolutionary diversification in gene duplicates. These data contribute to our better understanding of the physiological role of single amino acid repeats in proteins.

Amino acid tandem repeats are found in a large number of eukaryotic proteins. They are often encoded by trinucleotide repeats and exhibit high intra-and interspecies size variability due to the high mutation rate associated with replication slippage. The extent to which natural selection is important in shaping amino acid repeat evolution is a matter of debate. On one hand, their high frequency may simply reflect their high probability of expansion by slippage, and they could essentially evolve in a neutral manner. On the other hand, there is experimental evidence that changes in repeat size can influence protein-protein interactions, transcriptional activity, or protein subcellular localization, indicating that repeats could be functionally relevant and thus shaped by selection. To gauge the relative contribution of neutral and selective forces in amino acid repeat evolution, we have performed a comparative analysis of amino acid repeat conservation in a large set of orthologous proteins from 12 vertebrate species. As a neutral model of repeat evolution we have used sequences with the same DNA triplet composition as the coding sequences-and thus expected to be subject to the same mutational forces-but located in syntenic noncoding genomic regions. The results strongly indicate that selection has played a more important role than previously suspected in amino acid tandem repeat evolution, by increasing the repeat retention rate and by modulating repeat size. The data obtained in this study have allowed us to identify a set of 92 repeats that are postulated to play important functional roles due to their strong selective signature, including five cases with direct experimental evidence.