We analyze the role of retail investors in stock pricing using a database uniquely suited for this purpose. The data allow us to address selection bias concerns and to separately examine aggressive ...(market) and passive (limit) orders. Both aggressive and passive net buying positively predict firms' monthly stock returns with no evidence of return reversal. Only aggressive orders correctly predict firm news, including earnings surprises, suggesting they convey novel cash flow information. Only passive net buying follows negative returns, consistent with traders providing liquidity and benefiting from the reversal of transitory price movements. These actions contribute to market efficiency.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
Using a broad panel of NYSE-listed stocks between 1983 and 2004, we study the relation between institutional shareholdings and the relative informational efficiency of prices, measured as deviations ...from a random walk. Stocks with greater institutional ownership are priced more efficiently, and we show that variation in liquidity does not drive this result. One mechanism through which prices become more efficient is institutional trading activity, even when institutions trade passively. But efficiency is also directly related to institutional holdings, even after controlling for institutional trading, analyst coverage, short selling, variation in liquidity, and firm characteristics.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
Mitochondria are energy-producing organelles with essential functions in cell biology, and mitochondrial dysfunction is linked to a wide range of human diseases. Efforts to better understand ...mitochondrial biology have been limited by the lack of tools for manipulating and detecting processes occurring within the organelle. Here, we highlight recent significant advances in mitochondrial chemical biology that have produced new tools and techniques for studying mitochondria. Specifically, we focus on the development of chemical tools to perturb mitochondrial biochemistry, probes allowing precise measurement of mitochondrial function, and new techniques for high-throughput characterization of the mitochondrial proteome. Taken together, these advances in chemical biology will enable exciting new directions in mitochondrial research.
Mitochondria are complex organelles in the crux of many critical cellular processes, yet their biology remains incompletely understood. Wisnovsky et al. review how chemical biology is enabling studies of mitochondria and taking mitochondrial research in new directions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Retail Short Selling and Stock Prices Kelley, Eric K.; Tetlock, Paul C.
The Review of financial studies,
03/2017, Volume:
30, Issue:
3
Journal Article
Peer reviewed
Using proprietary data on millions of trades by retail investors, we provide the first large-scale evidence that retail short selling predicts negative stock returns. A portfolio that mimics weekly ...retail shorting earns an annualized risk-adjusted return of 9%. The predictive ability of retail short selling lasts for one year and is not subsumed by institutional short selling. In contrast to institutional shorting, retail shorting best predicts returns in small stocks and those that are heavily bought by other retail investors. Our findings are consistent with retail short sellers having unique insights into the retail investor community and small firms' fundamentals.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
Mitochondria are organelles with critical roles in key processes within eukaryotic cells, and their dysfunction is linked with numerous diseases including neurodegenerative disorders and cancer. ...Pharmacological manipulation of mitochondrial function is therefore important both for basic science research and eventually, clinical medicine. However, in comparison to other organelles, mitochondria are difficult to access due to their hydrophobic and dense double membrane system as well as their negative membrane potential. To tackle the challenge of targeting these important subcellular compartments, significant effort has been put forward to develop mitochondria-targeted systems capable of transporting bioactive cargo into the mitochondrial interior. Systems now exist that utilize small molecule, peptide, liposome, and nanoparticle-based transport. The vectors available vary in size and structure and can facilitate transport of a variety of compounds for mitochondrial delivery. Notably, peptide-based delivery scaffolds offer attractive features such as ease of synthesis, tunability, biocompatibility, and high uptake both in cellulo and in vivo. Owing to their simple and modular synthesis, these peptides are highly adaptable for delivering chemically diverse cargo. Key design features of mitochondria-targeted peptides include cationic charge, which allows them to harness the negative membrane potential of mitochondria, and lipophilicity, which permits favorable interaction with hydrophobic membranes of mitochondria. These peptides have been covalently tethered to target therapeutic agents, including anticancer drugs, to enhance their drug properties, and to provide probes for mitochondrial biology. Interestingly, mitochondria-targeted DNA damaging agents demonstrate high potency and the ability to evade resistance mechanisms and off-target effects. Moreover, a combination of mitochondria-targeted DNA damaging agents was applied to an siRNA screen for the elucidation of poorly understood mitochondrial DNA repair and replication pathways. In this work, a variety of novel proteins were identified that are essential for the maintenance of mitochondrial nucleic acids. Mitochondria-targeted peptides have also been used to increase the therapeutic window of antibacterial drugs with significant mammalian toxicity. Given the evolutionary similarity of mitochondria and bacteria, peptides are effective transporters that can target both of these entities. These antimicrobial peptides are highly effective even in difficult to target intracellular bacteria which reside within host cells. This peptide-based approach to targeting mitochondria has provided a variety of insights into the “druggability” of mitochondria and new biological processes that could be future drug targets. Nevertheless, the mitochondrial-targeting field is quite nascent and many exciting applications of organelle-specific conjugates remain to be explored. In this Account, we highlight the development and optimization of the mitochondria-penetrating peptides that our laboratory has developed, the unique applications of mitochondria-targeted bioactive cargo, and offer a perspective on important directions for the field.
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Mitochondria-penetrating peptides (MPPs) are specific targeting vectors for the localization of small molecules to the mitochondrial matrix. Mitochondrial targeting of small molecules has enabled the ...development of a number of potential therapeutics and chemical probes. However, the need for covalent conjugation of small molecules to MPPs can negatively affect the activity of the appended cargo against its cellular target. Here, we describe cleavable linkers designed for the traceless release of chemical cargo from MPPs following mitochondrial transit. The cleavage kinetics of a number of disulfides were investigated using a fluorescent reporter system in order to optimize linker stability for mitochondrial release. The stability of mono- and disubstituted disulfides was determined to be sufficient during transit through the cytosol while still allowing for release of the cargo within 24 h. This linker system successfully released the compound Luminespib, an HSP90 inhibitor, which was deactivated by direct MPP conjugation. The releasable conjugate regenerated Luminespib activity and induced mitochondrial phenotypes of HSP90 inhibition. This linker may prove useful in expanding the repertoire of small molecules that can be used with mitochondrial targeting vectors.
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We examine the economics that underlie retail trading costs around discount brokers’ widespread adoption of zero commission trading in October 2019. Our analysis of participating brokers’ Rule 606 ...filings and financial statements reveals little change in payment for order flow, which suggests brokers absorbed the cost of eliminating commissions in a competitive environment. We then perform a difference-in-differences analysis of effective spreads and report economically trivial changes in retail execution costs around the commission change. Finally, we assess the total trading costs of an aggregate retail portfolio compared to a host of counterfactuals. We find that following the zero-commission change, total retail transaction costs dropped substantially even under the extreme counterfactual that these traders pay exchange quoted spreads and receive zero price improvement. Our findings support the brokerage industry's claim that dropping commissions helped retail investors and should ease regulators’ concerns to the contrary.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
We present evidence that short sellers alternate between stock picking during expansions and market timing during recessions. First, firm-level short interest is a much stronger negative ...predictor of the cross-section of stock returns during expansions than it is during recessions. High short interest also only predicts negative future earnings announcement returns during expansions. We attribute these findings to short sellers’ emphasis on collecting firm-specific signals. Second, short sellers appear to make factor bets more so during recessions than during expansions. These bets tend to pay off as we observe a strong negative relation between the betas of highly shorted stocks and future stock market returns, a result that disappears during expansions. Together, these findings are consistent with theories of information acquisition under attention constraints, endogenous information production, as well as theories of time variation in aggregate overconfidence amongst traders.
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CEKLJ, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
In a standard stock loan, the borrower reimburses the lender any dividends paid while the loan is outstanding. Since these substitute dividends may be taxed differently than dividend payments ...themselves, some investors have incentives to either remove their shares from lendable supply–if they pay high taxes on substitute dividends–or lend out their shares to arbitrageurs–if they pay high taxes on dividends. Consistent with these incentives, we find a significant tightening of the equity lending market on dividend record days driven by both a contraction of supply and an expansion of demand–although the demand effect appears to dominate. We then exploit the plausibly exogenous nature of these shifts to causally link tightness in the lending market to wider effective spreads in the stock market.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The mitochondria within human cells play a major role in a variety of critical processes involved in cell survival and death. An understanding of mitochondrial involvement in various human diseases ...has generated an appreciable amount of interest in exploring this organelle as a potential drug target. As a result, a number of strategies to probe and combat mitochondria-associated diseases have emerged. Access to mitochondria-specific delivery vectors has allowed the study of biological processes within this intracellular compartment with a heightened level of specificity. In this review, we summarize the features of existing delivery vectors developed for targeting probes and therapeutics to this highly impermeable organelle. We also discuss the major applications of mitochondrial targeting of bioactive molecules, which include the detection and treatment of oxidative damage, combating bacterial infections, and the development of new therapeutic approaches for cancer. Future directions include the assessment of the therapeutic benefit achieved by mitochondrial targeting for treatment of disease in vivo. In addition, the availability of mitochondria-specific chemical probes will allow the elucidation of the details of biological processes that occur within this cellular compartment.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
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