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Çötelioğlu, E., Franzoni, F., & Plazzi, A. (2020). What Constrains Liquidity Provision? Evidence from Institutional Trades*. Rev Financ, .
Abstract: The article studies liquidity provision by institutional investors using trade-level data. We find that hedge fund trades are a more important predictor of stock-level liquidity than mutual fund trades. However, hedge funds’ liquidity provision is more exposed to financial conditions than that of mutual funds. Hedge funds that are more constrained in terms of leverage, age, asset illiquidity, and past performance exhibit a stronger shift toward liquidity consumption when funding condition tighten. Stocks with more exposure to constrained liquidity providing hedge funds suffered more during the financial crisis.
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Cagliani, R., Forni, D., Clerici, M., & Sironi, M. (2020). Computational inference of selection underlying the evolution of the novel coronavirus, SARS-CoV-2. J Virol, .
Abstract: The novel coronavirus (SARS-CoV-2) recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this aim, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral ORFs evolved under strong to moderate purifying selection. The most constrained sequences corresponded to some non-structural proteins (nsps) and to the M protein. Conversely, nsp1 and accessory ORFs, particularly ORF8, had a non-negligible proportion of codons evolving under very weak purifying selection or close to selective neutrality. Overall, limited evidence of positive selection was detected. The 6 bona fide positively selected sites were located in the N protein, in ORF8, and in nsp1. A signal of positive selection was also detected in the receptor-binding motif (RBM) of the spike protein but most likely resulted from a recombination event that involved the BatCoV RaTG13 sequence. In line with previous data, we suggest that the common ancestor of SARS-CoV-2 and BatCoV RaTG13 encoded/encodes an RBM similar to that observed in SARS-CoV-2 itself and in some pangolin viruses. It is presently unknown whether the common ancestor still exists and which animals it infects. Our data however indicate that divergence of SARS-CoV-2 from BatCoV RaTG13 was accompanied by limited episodes of positive selection, suggesting that the common ancestor of the two viruses was poised for human infection.IMPORTANCE Coronaviruses are dangerous zoonotic pathogens: in the last two decades three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolve under different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spill-over, these signals should not be necessarily interpreted as evidence of an adaptation to our species.
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Cagliani, R., Forni, D., Mozzi, A., & Sironi, M. (2020). Evolution and Genetic Diversity of Primate Cytomegaloviruses. Microorganisms, 8(5).
Abstract: Cytomegaloviruses (CMVs) infect many mammals, including humans and non-human primates (NHPs). Human cytomegalovirus (HCMV) is an important opportunistic pathogen among immunocompromised patients and represents the most common infectious cause of birth defects. HCMV possesses a large genome and very high genetic diversity. NHP-infecting CMVs share with HCMV a similar genomic organization and coding content, as well as the course of viral infection. Recent technological advances have allowed the sequencing of several HCMV strains from clinical samples and provided insight into the diversity of NHP-infecting CMVs. The emerging picture indicates that, with the exclusion of core genes (genes that have orthologs in all herpesviruses), CMV genomes are relatively plastic and diverse in terms of gene content, both at the inter- and at the intra-species level. Such variability most likely underlies the strict species-specificity of these viruses, as well as their ability to persist lifelong and with relatively little damage to their hosts. However, core genes, despite their strong conservation, also represented a target of adaptive evolution and subtle changes in their coding sequence contributed to CMV adaptation to different hosts. Indubitably, important knowledge gaps remain, the most relevant of which concerns the role of viral genetics in HCMV-associated human disease.
Keywords: cytomegalovirus; genome organization; non-human primates; positive selection; species-specificity
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Forni, D., & Sironi, M. (2020). Population structure of Lassa Mammarenavirus in West Africa. Viruses, 12(4).
Abstract: Lassa mammarenavirus (LASV) is the etiologic agent of Lassa fever. In endemic regions in West Africa, LASV genetic diversity tends to cluster by geographic area. Seven LASV lineages are recognized, but the role of viral genetic determinants on disease presentation in humans is uncertain. We investigated the geographic structure and distribution of LASV in West Africa. We found strong spatial clustering of LASV populations, with two major east-west and north-south diversity gradients. Analysis of ancestry components indicated that known LASV lineages diverged from an ancestral population that most likely circulated in Nigeria, although alternative locations, such as Togo, cannot be excluded. Extant sequences carrying the largest contribution of this ancestral population include the prototype Pinneo strain, the Togo isolates, and a few viruses isolated in Nigeria. The LASV populations that experienced the strongest drift circulate in Mali and the Ivory Coast. By focusing on sequences form a single LASV sublineage (IIg), we identified an ancestry component possibly associated with protection from a fatal disease outcome. Although the same ancestry component tends to associate with lower viral loads in plasma, the small sample size requires that these results are treated with extreme caution.
Keywords: Lassa mammarenavirus; ancestry component; disease outcome; geographic distribution; population structure
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Forni, D., Cagliani, R., Clerici, M., Pozzoli, U., & Sironi, M. (2020). You Will Never Walk Alone: Codispersal of JC Polyomavirus with Human Populations. Mol Biol Evol, 37(2), 442–454.
Abstract: JC polyomavirus (JCPyV) is one of the most prevalent human viruses. Findings based on the geographic distribution of viral subtypes suggested that JCPyV codiverged with human populations. This view was however challenged by data reporting a much more recent origin and expansion of JCPyV. We collected information on approximately 1,100 worldwide strains and we show that their geographic distribution roughly corresponds to major human migratory routes. Bayesian phylogeographic analysis inferred a Subsaharan origin for JCPyV, although with low posterior probability. High confidence inference at internal nodes provided strong support for a long-standing association between the virus and human populations. In line with these data, pairwise FST values for JCPyV and human mtDNA sampled from the same areas showed a positive and significant correlation. Likewise, very strong relationships were found when node ages in the JCPyV phylogeny were correlated with human population genetic distances (nuclear-marker based FST). Reconciliation analysis detected a significant cophylogenetic signal for the human population and JCPyV trees. Notably, JCPyV also traced some relatively recent migration events such as the expansion of people from the Philippines/Taiwan area into Remote Oceania, the gene flow between North-Eastern Siberian and Ainus, and the Koryak contribution to Circum-Arctic Americans. Finally, different molecular dating approaches dated the origin of JCPyV in a time frame that precedes human out-of-Africa migration. Thus, JCPyV infected early human populations and accompanied our species during worldwide dispersal. JCPyV typing can provide reliable geographic information and the virus most likely adapted to the genetic background of human populations.
Keywords: *JC polyomavirus; *codispersal; *human populations; *molecular dating; *phylogeography
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Forni, D., Pontremoli, C., Clerici, M., Pozzoli, U., Cagliani, R., & Sironi, M. (2020). Recent Out-of-Africa Migration of Human Herpes Simplex Viruses. Mol Biol Evol, 37(5), 1259–1271.
Abstract: Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplex viruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations have limited geographic structure and the most evident clustering by geography is likely due to recent bottlenecks. For HSV-2, the only level of population structure is accounted for by the so-called “worldwide” and “African” lineages. Analysis of ancestry components and nucleotide diversity, however, did not support the view that the worldwide lineage followed early humans during out-of-Africa dispersal. Although phylogeographic analysis confirmed an African origin for both viruses, molecular dating with a method that corrects for the time-dependent rate phenomenon indicated that HSV-1 and HSV-2 migrated from Africa in relatively recent times. In particular, we estimated that the HSV-2 worldwide lineage left the continent in the 18th century, which corresponds to the height of the transatlantic slave trade, possibly explaining the high prevalence of HSV-2 in the Americas (second highest after Africa). The limited geographic clustering of HSV-1 makes it difficult to date its exit from Africa. The split between the basal clade, containing mostly African sequences, and all other strains was dated at approximately 5,000 years ago. Our data do not imply that herpes simplex viruses did not infect early humans but show that the worldwide distribution of circulating strains is the result of relatively recent events.
Keywords: Hsv-1; Hsv-2; molecular dating; phylogeography; population structure
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Gandhi, P., Lustig, H., & Plazzi, A. (2020). Equity Is Cheap for Large Financial Institutions. Rev Financ Stud, 33(9), 4231–4271.
Abstract: Across a wide panel of countries, the top-10% of financial stocks on average account for over 20% of a country’s market capitalization but earn on average significantly lower returns than do nonfinancial firms of the same size and risk exposures. In a bailout-augmented, rare disasters asset pricing model, the spread in risk-adjusted returns between large and small institutions depends on country characteristics that determine the likelihood of bailouts. Consistent with this model, we find larger spreads in countries with large and interconnected financial sectors, weaker capital regulation and corporate governance, and fiscally stronger governments. Valuation gaps increase in anticipation of financial crises.Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
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Pontremoli, C., Forni, D., Clerici, M., Cagliani, R., & Sironi, M. (2020). Possible European Origin of Circulating Varicella Zoster Virus Strains. J Infect Dis, 221(8), 1286–1294.
Abstract: Varicella zoster virus (VZV) is the causative agent of chickenpox and shingles. The geographic distribution of VZV clades was taken as evidence that VZV migrated out of Africa with human populations. We show that extant VZV strains most likely originated in Europe and not in Africa. Europe was also identified as the ancestral location for most internal nodes of the VZV phylogeny, including the ancestor of clade 5 strains. We also show that strains from clades 1, 2, 3, and 5 derived a major proportion of their ancestry from each of 4 ancestral populations. Conversely, viruses from other clades displayed variable levels of admixture. Some low-level admixture was also observed for clade 5 genomes, but only for non-African viruses. This pattern indicates that the clade 5 VZV strains do not represent recent introductions from Africa due to migratory fluxes. These data have also relevance for the definition and classification of VZV clades.
Keywords: varicella zoster virus; admixture; origin; phylogeography
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