The C. elegans Lifespan Machine

The measurement of lifespan pervades aging research. Because lifespan results from complex interactions between genetic, environmental and stochastic factors, it varies widely even among isogenic individuals. The action of molecular mechanisms on lifespan is therefore visible only through their statistical effects on populations. Survival assays in C. elegans provided critical insights into evolutionarily conserved determinants of aging. To enable the rapid acquisition of survival curves at arbitrary statistical resolution, we developed a scalable imaging and analysis platform to observe nematodes over multiple weeks across square meters of agar surface at 8 μm resolution. The method generates a permanent visual record of individual deaths from which survival curves are constructed and validated, producing data consistent with the manual method for several mutants in both standard and stressful environments. Our approach allows rapid, detailed reverse-genetic and chemical screens for effects on survival and enables quantitative investigations into the statistical structure of aging

Train Hard, Win Easy: Running on the Periphery in Rural Kenya: The Last Shall Be First

Past years have proven Kenyans dominant in the sport of athletics. Today, runners from the Rift Valley win more major middle- and long-distance running events than those from any other nation in the world. Although athletics is not the most lucrative of sports, modern marketing has resulted in creating a sport with various financial incentives. These include prize money, sponsorships, and the opportunity for a new life. However, runners from rural agricultural backgrounds find it very difficult to translate their athletic talent into dollars at the finish line. This study examines the economic prospects for young male runners from Kapsabet and the surrounding areas. It asks the question: how effectively is Kenya’s athletic resource being extracted? In turn, how can this famous comparative advantage be directed in order to most effectively benefit a runner, his family, and his community? The entire paper constantly revisits the background of these runners that is centered in a subsistence-based socioeconomy, with a huge emphasis on communalism. In the section entitled “Discussion, Findings, and Analysis”, I make it clear that the economic forecast for the Kenyan running project looks bleak, both in the short-term and the long-term, even if some individual athletes see tremendous rewards. However, I offer some substantial, basic, and concrete solutions that might enhance the financial prospects for athletics in the Rift Valley, and specifically in Kapsabet. This paper stands as a resource both for people genuinely interested in finding out what is behind these runners featured on television AND for people traveling to Kenya who need a basic “road map” on runners or for places like Kapsabet. Finally, this long essay is a perfect starting point for more in-depth study into either athletics in Kenya OR rural agronomics in the Rift Valley. Hope you enjoy

Lifespan-on-a-Chip: Microfluidic Chambers for Performing Lifelong Observation of C. elegans

This article describes the fabrication of a microfluidic device for the liquid culture of many individual nematode worms (Caenorhabditis elegans) in separate chambers. Each chamber houses a single worm from the fourth larval stage until death, and enables examination of a population of individual worms for their entire adult lifespans. Adjacent to the chambers, the device includes microfluidic worm clamps, which enable periodic, temporary immobilization of each worm. The device made it possible to track changes in body size and locomotion in individual worms throughout their lifespans. This ability to perform longitudinal measurements within the device enabled the identification of age-related phenotypic changes that correlate with lifespan in C. elegans.Chemistry and Chemical Biolog

Global Democracy for Europeans: A Demographic Story

Insofar as democracy is a product of long-term diffusion, scholars generally focus on colonialism (especially English) or religion (especially Protestant). Here, we focus on a third pathway from Europe – Europeans. We show that there is a persistent relationship between the share of Europeans in a society and its regime type. We conjecture that this is because Europeans viewed democracy as a basic right – for themselves. It was a club that produced club goods (excludable goods such as property rights and civil liberties). Hence, where Europeans were in the majority they were democrats. Where they were the minority they were indifferent or hostile, or they embraced a restricted form of democracy that excluded non-Europeans. And where Europeans were entirely absent there was no one – at least initially – to carry the democratic torch. To test this argument we assemble an original dataset measuring the diffusion of Europeans across the world from 1600 to the present. This is employed to predict democracy in a series of analyses that focus on various indicators of democracy and a variety of samples, specifications, time-periods, and estimators, including fixed effects and instrumental variables. The evidence offers strong support for the thesis.This research project was supported by Riksbankens Jubileumsfond, Grant M13-0559:1, PI: Staffan I. Lindberg, V-Dem Institute, University of Gothenburg, Sweden; by Knut and Alice Wallenberg Foundation to Wallenberg Academy Fellow Staffan I. Lindberg, Grant 2013.0166, V-Dem Institute, University of Gothenburg, Sweden; as well as by internal grants from the Vice-Chancellor’s office, the Dean of the College of Social Sciences, and the Department of Political Science at University of Gothenburg. We performed simulations and other computational tasks using resources provided by the Notre Dame Center for Research Computing (CRC) through the High Performance Computing section and the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Centre in Sweden, SNIC 2017/1-407 and 2017/1-68. We specifically acknowledge the assistance of In-Saeng Suh at CRC and Johan Raber at SNIC in facilitating our use of their respective systems

Development and disease of the photoreceptor cilium

Primary cilia are microtubule-rich hair-like extensions protruding from the surface of most post-mitotic cells. They act as sensory organelles that help interpret various environmental cues. Mutations in genes encoding proteins involved in ciliogenesis or protein transport to the primary cilia lead to a wide variety of diseases commonly referred to as ciliopathies,which include primary ciliary dyskinesia, situs invertus, hydrocephalus, kidney diseases, respiratory diseases, and retinal degenerations. In the retina, the photoreceptor cells have a highly specialized primary cilium called the outer segment (OS), which is essential for photosensation. Development of the photoreceptor OS shares key regulatory mechanisms with ciliogenesis in other cell types. Accumulating evidence indicates that mutations that affect OS development and/or protein transport to the OS generally lead to photoreceptor degeneration, which can be accompanied by a range of other clinical manifestations due to the dysfunction of primary cilia in different cell types. Here, we review the general mechanisms regulating ciliogenesis, and present different examples of mutations affecting OS ciliogenesis and protein transport that lead to photoreceptor degeneration. Overall, we conclude that the genetic and molecular evidence accumulated in recent years suggest a clear link between the development and function of the primary cilium and various clinical conditions. Future studies aimed at uncovering the cellular and molecular mechanisms implicated in ciliogenesis in a wide variety of animal models should greatly increase our understanding of the pathophysiology of many human diseases, including retinal degenerations.V. R. is supported by a studentship from the Foundation Fighting Blindness – Canada (FFB-C). Work in M.C.’s lab is funded by the Canadian Institutes of Health Research (CIHR) and the FFB-C. M.C. is a CIHR New Investigator and a W.K. Stell Scholar of the FFBC

Compensatory ingestion upon dietary restriction in Drosophila melanogaster

Dietary restriction extends the lifespan of numerous, evolutionarily diverse species. In D. melanogaster, a prominent model for research on the interaction between nutrition and longevity, dietary restriction is typically based on medium dilution, with possible compensatory ingestion commonly being neglected. Possible problems with this approach are revealed by using a method for direct monitoring of D. melanogaster feeding behavior. This demonstrates that dietary restriction elicits robust compensatory changes in food consumption. As a result, the effect of medium dilution is overestimated and, in certain cases, even fully compensated for. Our results strongly indicate that feeding behavior and nutritional composition act concertedly to determine fly lifespan. Feeding behavior thus emerges as a central element in D. melanogaster aging

Harbors and Democracy

Although geography is widely viewed as an important factor in long-term development, little attention has been paid to its role in democratization. This study focuses on the possible impact of a feature of littoral geography: natural harbors with access to the sea. By virtue of enhancing connections to the wider world, we argue that harbors foster (a) development, (b) mobility, (c) naval-based defense forces, and (d) diffusion. Through these pathways, operative over secular-historical time, areas blessed by natural harbors are more likely to develop democratic forms of government. This argument is tested with a unique database measuring distance to natural harbors throughout the world. We show that there is a robust negative association between this measure and democracy in country and grid-cell analyses, and in instrumental variable models where harbor distance is instrumented by ocean distance

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals

Do left and right differ on education in Latin America? : explaining unexpected convergence

What effect does partisan ideology have on education outputs (spending) and outcomes (access and quality) in Latin American democracies? Political left and right are defined based on divergent beliefs about inequality. Given that education has been touted as being essential for poverty reduction and equity enhancement, does the left devote greater resources to this sector? Previous work in the OECD has found that the left outperforms the right in this way. Do Latin American countries follow the same pattern? Within the education budget, the left may also be expected to devote greater resources to primary and secondary education (because these levels are more progressive than tertiary) and to staff expenditures (because of the left's historical connection with the teachers' unions). Is this expectation borne out in reality? Further, do left and right produce systematically different education outcomes? Are students more likely to enroll and complete their education and are they more likely to learn more under either end of the political spectrum? This project attempts to answer these questions. I find that contrary to expectations, there are no systematic differences between left and right on either education outputs or outcomes. I argue that this surprising result is due to three political factors: policy legacies, stakeholder pressures, and expert advice. These forces push left and right toward similar education policies, which in turn result in convergence on observed outputs and outcomes. Policy legacies limit the scope of potential policy reforms through bureaucratic inertia, short-term political and capital costs, and practical constraints. Powerful vested interests, namely the teachers' unions, place pressures on both left (their traditional allies) and right that cannot be ignored. Other organized actors, including business elites and parents, also have the ability to pressure politicians, but are secondary actors in this area. Finally, technocratic experts recommend policy strategies that remain consistent regardless of the ideology of the party in power. An increasing tendency by both left and right to rely on these experts further contributes to convergence. I explore this alternative theory of convergence in Chile, tracing education policy since the return to democracy in 1990. I find that the center-left and left were severely limited by the policy legacies of the military regime as well as electoral pressures from the teachers' unions and students. A willingness to rely on technocratic expertise also encouraged the left to converge on many education policies with the right. The left was only able to address equity through small, targeted programs. After 24 years of democracy, policy legacies had weakened and electoral pressures changed sufficiently that a more strongly left government was able to ignore expert advice and push through policies in line with ideological preferences. These new policies have already left legacies of their own that have constrained the governments of the right. This project seeks to contribute to an understanding of partisan politics in Latin America and an emerging literature on the politics of education.Governmen