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"Henderson, James W"
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ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. Recent work has raised the intriguing prospect that phase transitions in proteins and lipids can be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granules to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induces a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system serves as a potential regulatory mechanism in RNA trafficking and offers an important template to understand other examples across the cell whereby biomolecular condensates closely juxtapose organellar membranes.
Nixon-Abell et al. show that ANXA11 condensation on lysosomal membranes causes a coupled phase transition of the underlying lipids and mechanical stiffening of the overall ensemble involved in RNP granule-lysosome tethering and co-trafficking.
Journal Article
Consequences of Price Discrimination in Health Care
Too frequently, policy makers misinterpret economic principles, leading them to misguided policy, often resulting in harmful consequences. It is argued herein that such a situation exists with respect to the belief that perfect price discrimination can occur without social cost and that it should be tolerated in the nation’s healthcare system. The following explains the belief, why it is misapplied, potential signifcant nationally harmful consequences, and what can be done. According to standard economic analysis (Grinols, Microeconomics, 1994, p. 317; Henderson, Health Economics and Policy, 8e, forthcoming; Mankiw, Principles of Microeconomics, 8e, 2018, p. 302), the actions of a proft-maximizing monopolist result in dead-weight loss that represents inefciency and social cost. Higher degrees of price discrimination increase proft to the monopolist (choices are nested under frst-, second-, and third-degree price discrimination), generally with greater social cost. Katz (Review of Economic Studies, 1983) derives conditions under which the decrease in local output reduces welfare. Any number of standard microeconomics texts claim that a perfectly price-discriminating monopolist is possible without social cost (e.g., Browning and Zupan, Microeconomics, 12e, 2015, p. 308; Mankiw, Principles of Economics, 8e, 2018; Samuelson and Nordhaus, Economics, 19e, 2010, p. 209; Varian, Intermediate Microeconomics, 9e, 2020).
Journal Article
Cost-effectiveness of cervical cancer screening strategies
Despite its low incidence in the developed world, cervical cancer is the second most common cancer among women worldwide and the third most common cause of cancer-related deaths. Screening saves lives. When diagnosed and treated in the preinvasive stage, 5-year survival probabilities approach 100%. This review addresses the cost-effectiveness of the various screening strategies commonly used worldwide. The starting age of screening, interval between screens and age of women at cessation of screening are the most important variables determining cost-effectiveness. While the traditional Pap test is still the most cost-effective screening method in most settings, human papillomavirus testing can improve outcomes at reasonable costs in certain high-risk populations.
Journal Article
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. The frequent juxtaposition of proteinaceous biomolecular condensates to cellular membranes raises the intriguing prospect that phase transitions in proteins and lipids could be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granule condensates to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induce a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system offers an important template to understand the numerous other examples across the cell whereby biomolecular condensates closely juxtapose cell membranes.
Journal Article
Digitizing the Past: A New Procedure for Faded Rock Painting Photography
Faded and weathered pictographs have historically been difficult to record using standard documentary photography. Natural lighting produces inconsistent color and harsh lighting conditions that prevent color photographic films from capturing faint pigment colors. Films are also problematic, since most color films are comprised of unstable organic dyes that fade over time. The paper discusses the authors' multiplestep photographic and computer enhancement procedure to record faded, pigmented artifacts, such as pictographs, pottery, and dyed fabric. Cross-polarized lighting selectively eliminates surface reflections, but retains internal reflections from color pigments, which enhances their capture by film-based or direct-digital cameras. Selective digital enhancement substantially increases the brightness and color saturation of cross polarized photographs. This kind of specialized photography complements other, equally important recording techniques in the quest for comprehensive documentation of faded pictographs. Les pictogrammes décolorés et désagregés ont souvent été difficiles à documenter avec les méthodes photographiques traditionnelles. La lumiere naturèlle a tendance à produire des couleurs inégales et un éclairage trop intense pour capturer sur pellicule une coloration subtile. Le film photographique lui-même pose des problèmes car la pellicule couleur contient des colorants organiques qui s'affaiblissent avec le temps. Ce texte présente une méthode à étapes multiples (photographiques et numeriques) pour la documentation d'artefacts à faible coloration comme les pictogrammes, la poterie, ou les textiles teints. La lumière polarisée croisé élimine de façon selective les reflets de surface, mais retient les reflets internes des pigments, améliorant ainsi leur enregistrement numérique ou sur pellicule. Un rehaussement sélectif numérique par la suite augmente l'éclat et la saturation des couleurs de la photographie prise à la lumière polarisante. Cétte methode de photographie spécialisée est complémentaire aux autres méthodes d'enregistrement de l'information des pictogrammes estompés.
Journal Article
Predicting Turning Points in Economic Activity with Indexes of Economic Indicators: Improved Reliability Using a Logistic Model
Economists, policy makers, entrepreneurs, and many others interested in charting business activity have long desired a quick and simple way of predicting peaks and troughs in the business cycle. This study uses monthly data on the composite series of economic indicators to predict turning points in economic activity. Using a logistic regression model, we have been able to predict recessions with an average lead time of one month. More importantly, we have been able to reduce the error rate (the percentage of false signals) to less than 1 percent, representing a significant improvement over previous attempts by other researchers.
Journal Article