SECURITIES—DEMOCRATIZING EQUITY MARKETS WITH AND WITHOUT EXPLOITATION: ROBINHOOD, GAMESTOP, HEDGE FUNDS, GAMIFICATION, HIGH FREQUENCY TRADING, AND MORE

The stock trading frenzy of January 2021 brought a relatively new player in the securities markets into public consciousness—the platforms offering no- or low-commission trading that seek to appeal to young and less-experienced investors with a “fun” if not “delightful” user experience. Most prominent among these new brokers is Robinhood, with a slick mobile phone app, which claims that its platform will “democratize finance” by making investing cheaper and easier for the masses who have been looked down upon and locked out by the wealthy elites of Wall Street. However, Robinhood’s claims of “democratization” have all the hallmarks of manipulation and exploitation, making Robinhood’s founders multibillionaires while many of its retail customers suffer financial ruin. That is because platforms like Robinhood take arguably legal kickbacks for routing their customer orders—known as payment for order flow—to high frequency trading firms which execute those orders, almost always in dark, off-exchange venues. To maximize those kickbacks, Robinhood’s mobile trading app is gamified via predatory digital engagement practices to disarm its customers’ financial self-defense mechanisms and prompt as much frequent and risky trading as possible. Such trading behavior has been shown to be highly detrimental to retail investors, and indeed many of Robinhood’s customers have been harmed by engaging in such practices, some grievously. The result is that, unlike the legend of Robin Hood stealing from the rich and giving to the poor, the Robinhoods of the world are taking from the less experienced and enriching themselves and their fellow Wall Street billionaires. But it does not have to be this way. Finance can be genuinely democratized (easier access, lower costs, user-friendly financial tools, etc.) and trading can be demystified in ways that facilitate wealth creation rather than wealth extraction. However, for that to happen, regulators must enforce existing laws and rules against illegal conduct and impose meaningful penalties on individual corporate officers that punish and deter. Regulators must also enact new rules to prohibit, for example, predatory digital engagement practices. Once the highly profitable lawbreakers and predators are shut down, the financial industry can focus on serving Main Street investors rather than exploiting them to enrich Wall Street

The Structure of an RNAi Polymerase Links RNA Silencing and Transcription

RNA silencing refers to a group of RNA-induced gene-silencing mechanisms that developed early in the eukaryotic lineage, probably for defence against pathogens and regulation of gene expression. In plants, protozoa, fungi, and nematodes, but apparently not insects and vertebrates, it involves a cell-encoded RNA-dependent RNA polymerase (cRdRP) that produces double-stranded RNA triggers from aberrant single-stranded RNA. We report the 2.3-Å resolution crystal structure of QDE-1, a cRdRP from Neurospora crassa, and find that it forms a relatively compact dimeric molecule, each subunit of which comprises several domains with, at its core, a catalytic apparatus and protein fold strikingly similar to the catalytic core of the DNA-dependent RNA polymerases responsible for transcription. This evolutionary link between the two enzyme types suggests that aspects of RNA silencing in some organisms may recapitulate transcription/replication pathways functioning in the ancient RNA-based world

Insights into the pre-initiation events of bacteriophage phi6 RNA-dependent RNA polymerase : towards the assembly of a productive binary complex

The RNA-dependent RNA polymerase (RdRP) of double-stranded RNA (dsRNA) viruses performs both RNA replication and transcription. In order to initiate RNA polymerization, viral RdRPs must be able to interact with the incoming 3 terminus of the template and position it, so that a productive binary complex is formed. Structural studies have revealed that RdRPs of dsRNA viruses that lack helicases have electrostatically charged areas on the polymerase surface, which might facilitate such interactions. In this study, structure-based mutagenesis, enzymatic assays and molecular mapping of bacteriophage 6 RdRP and its RNA were used to elucidate the roles of the negatively charged plough area on the polymerase surface, of the rim of the template tunnel and of the template specificity pocket that is key in the formation of the productive RNA-polymerase binary complex. The positively charged rim of the template tunnel has a significant role in the engagement of highly structured ssRNA molecules, whereas specific interactions further down in the template tunnel promote ssRNA entry to the catalytic site. Hence, we show that by aiding the formation of a stable binary complex with optimized RNA templates, the overall polymerization activity of the 6 RdRP can be greatly enhanced.The RNA-dependent RNA polymerase (RdRP) of double-stranded RNA (dsRNA) viruses performs both RNA replication and transcription. In order to initiate RNA polymerization, viral RdRPs must be able to interact with the incoming 3 terminus of the template and position it, so that a productive binary complex is formed. Structural studies have revealed that RdRPs of dsRNA viruses that lack helicases have electrostatically charged areas on the polymerase surface, which might facilitate such interactions. In this study, structure-based mutagenesis, enzymatic assays and molecular mapping of bacteriophage 6 RdRP and its RNA were used to elucidate the roles of the negatively charged plough area on the polymerase surface, of the rim of the template tunnel and of the template specificity pocket that is key in the formation of the productive RNA-polymerase binary complex. The positively charged rim of the template tunnel has a significant role in the engagement of highly structured ssRNA molecules, whereas specific interactions further down in the template tunnel promote ssRNA entry to the catalytic site. Hence, we show that by aiding the formation of a stable binary complex with optimized RNA templates, the overall polymerization activity of the 6 RdRP can be greatly enhanced.The RNA-dependent RNA polymerase (RdRP) of double-stranded RNA (dsRNA) viruses performs both RNA replication and transcription. In order to initiate RNA polymerization, viral RdRPs must be able to interact with the incoming 3 terminus of the template and position it, so that a productive binary complex is formed. Structural studies have revealed that RdRPs of dsRNA viruses that lack helicases have electrostatically charged areas on the polymerase surface, which might facilitate such interactions. In this study, structure-based mutagenesis, enzymatic assays and molecular mapping of bacteriophage 6 RdRP and its RNA were used to elucidate the roles of the negatively charged plough area on the polymerase surface, of the rim of the template tunnel and of the template specificity pocket that is key in the formation of the productive RNA-polymerase binary complex. The positively charged rim of the template tunnel has a significant role in the engagement of highly structured ssRNA molecules, whereas specific interactions further down in the template tunnel promote ssRNA entry to the catalytic site. Hence, we show that by aiding the formation of a stable binary complex with optimized RNA templates, the overall polymerization activity of the 6 RdRP can be greatly enhanced.Peer reviewe

Towards in cellulo virus crystallography

Viruses are a significant threat to both human health and the economy, and there is an urgent need for novel anti-viral drugs and vaccines. High-resolution viral structures inform our understanding of the virosphere, and inspire novel therapies. Here we present a method of obtaining such structural information that avoids potentially disruptive handling, by collecting diffraction data from intact infected cells. We identify a suitable combination of cell type and virus to accumulate particles in the cells, establish a suitable time point where most cells contain virus condensates and use electron microscopy to demonstrate that these are ordered crystalline arrays of empty capsids. We then use an X-ray free electron laser to provide extremely bright illumination of sub-micron intracellular condensates of bacteriophage phiX174 inside living Escherichia coli at room temperature. We have been able to collect low resolution diffraction data. Despite the limited resolution and completeness of these initial data, due to a far from optimal experimental setup, we have used novel methodology to determine a putative space group, unit cell dimensions, particle packing and likely maturation state of the particles.Peer reviewe

Tracking in atomic detail the functional specializations in viral RecA helicases that occur during evolution

Peer reviewe

The structure of a prokaryotic viral envelope protein expands the landscape of membrane fusion proteins

Lipid membrane fusion is an essential function in many biological processes. Detailed mechanisms of membrane fusion and the protein structures involved have been mainly studied in eukaryotic systems, whereas very little is known about membrane fusion in prokaryotes. Haloarchaeal pleomorphic viruses (HRPVs) have a membrane envelope decorated with spikes that are presumed to be responsible for host attachment and membrane fusion. Here we determine atomic structures of the ectodomains of the 57-kDa spike protein VP5 from two related HRPVs revealing a previously unreported V-shaped fold. By Volta phase plate cryo-electron tomography we show that VP5 is monomeric on the viral surface, and we establish the orientation of the molecules with respect to the viral membrane. We also show that the viral membrane fuses with the host cytoplasmic membrane in a process mediated by VP5. This sheds light on protein structures involved in prokaryotic membrane fusion.Peer reviewe

Plate tectonics of virus shell assembly and reorganization in phage φ8, a distant relative of mammalian reoviruses

The hallmark of a virus is its capsid, which harbors the viral genome and is formed from protein subunits, which assemble following precise geometric rules. dsRNA viruses use an unusual protein multiplicity (120 copies) to form their closed capsids. We have determined the atomic structure of the capsid protein (P1) from the dsRNA cystovirus Φ8. In the crystal P1 forms pentamers, very similar in shape to facets of empty procapsids, suggesting an unexpected assembly pathway that proceeds via a pentameric intermediate. Unlike the elongated proteins used by dsRNA mammalian reoviruses, P1 has a compact trapezoid-like shape and a distinct arrangement in the shell, with two near-identical conformers in nonequivalent structural environments. Nevertheless, structural similarity with the analogous protein from the mammalian viruses suggests a common ancestor. The unusual shape of the molecule may facilitate dramatic capsid expansion during phage maturation, allowing P1 to switch interaction interfaces to provide capsid plasticity

The Structure of an RNAi Polymerase Links RNA Silencing and Transcription

RNA silencing refers to a group of RNA-induced gene-silencing mechanisms that developed early in the eukaryotic lineage, probably for defence against pathogens and regulation of gene expression. In plants, protozoa, fungi, and nematodes, but apparently not insects and vertebrates, it involves a cell-encoded RNA-dependent RNA polymerase (cRdRP) that produces double-stranded RNA triggers from aberrant single-stranded RNA. We report the 2.3-Å resolution crystal structure of QDE-1, a cRdRP from Neurospora crassa, and find that it forms a relatively compact dimeric molecule, each subunit of which comprises several domains with, at its core, a catalytic apparatus and protein fold strikingly similar to the catalytic core of the DNA-dependent RNA polymerases responsible for transcription. This evolutionary link between the two enzyme types suggests that aspects of RNA silencing in some organisms may recapitulate transcription/replication pathways functioning in the ancient RNA-based world

First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction

The first measurements of the transferred polarization for the exclusive ep --> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron beam was used to measure the hyperon polarization over a range of Q2 from 0.3 to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass angular range of the K+ meson. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A non-relativistic quark model interpretation of our data suggests that the s-sbar quark pair is produced with spins predominantly anti-aligned. Implications for the validity of the widely used 3P0 quark-pair creation operator are discussed.Comment: 6 pages, 4 figure