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Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
This study pushes our understanding of research reliability by reproducing and replicating claims from 110 papers in leading economic and political science journals. The analysis involves computational reproducibility checks and robustness assessments. It reveals several patterns. First, we uncover a high rate of fully computationally reproducible results (over 85%). Second, excluding minor issues like missing packages or broken pathways, we uncover coding errors for about 25% of studies, with some studies containing multiple errors. Third, we test the robustness of the results to 5,511 re-analyses. We find a robustness reproducibility of about 70%. Robustness reproducibility rates are relatively higher for re-analyses that introduce new data and lower for re-analyses that change the sample or the definition of the dependent variable. Fourth, 52% of re-analysis effect size estimates are smaller than the original published estimates and the average statistical significance of a re-analysis is 77% of the original. Lastly, we rely on six teams of researchers working independently to answer eight additional research questions on the determinants of robustness reproducibility. Most teams find a negative relationship between replicators' experience and reproducibility, while finding no relationship between reproducibility and the provision of intermediate or even raw data combined with the necessary cleaning codes.
Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
X-ray free-electron lasers (XFELs) and table-top sources of x-rays based upon high harmonic generation (HHG) have revolutionized the field of ultrafast x-ray atomic and molecular physics, largely due to an explosive growth in capabilities in the past decade. XFELs now provide unprecedented intensity (10(20) W cm(-2)) of x-rays at wavelengths down to similar to 1 Angstrom, and HHG provides unprecedented time resolution (similar to 50 attoseconds) and a correspondingly large coherent bandwidth at longer wavelengths. For context, timescales can be referenced to the Bohr orbital period in hydrogen atom of 150 attoseconds and the hydrogen-molecule vibrational period of 8 femtoseconds; wavelength scales can be referenced to the chemically significant carbon K-edge at a photon energy of similar to 280 eV (44 Angstroms) and the bond length in methane of similar to 1 Angstrom. With these modern x-ray sources one now has the ability to focus on individual atoms, even when embedded in a complex molecule, and view electronic and nuclear motion on their intrinsic scales (attoseconds and Angstroms). These sources have enabled coherent diffractive imaging, where one can image non-crystalline objects in three dimensions on ultrafast timescales, potentially with atomic resolution. The unprecedented intensity available with XFELs has opened new fields of multiphoton and nonlinear x-ray physics where behavior of matter under extreme conditions can be explored. The unprecedented time resolution and pulse synchronization provided by HHG sources has kindled fundamental investigations of time delays in photoionization, charge migration in molecules, and dynamics near conical intersections that are foundational to AMO physics and chemistry. This roadmap coincides with the year when three new XFEL facilities, operating at Angstrom wavelengths, opened for users (European XFEL, Swiss-FEL and PAL-FEL in Korea) almost doubling the present worldwide number of XFELs, and documents the remarkable progress in HHG capabilities since its discovery roughly 30 years ago, showcasing experiments in AMO physics and other applications. Here we capture the perspectives of 17 leading groups and organize the contributions into four categories: ultrafast molecular dynamics, multidimensional x-ray spectroscopies; high-intensity x-ray phenomena; attosecond x-ray science.
Aus dem Inhalt dieser Ausgabe: Artikel und Miszellen: Karl E. Grözinger: Manfred Voigts zum Sechzigsten - 2.5.2006 Caspar Battegay: Wie nicht erinnern? - Die Frage nach der Jüdischkeit in Heinrich Heines autobiographischen Texten Edith Lutz: Heinrich Heine im "Verein für Cultur und Wissenschaft der Juden" Jakob Hessing: Wahrheit und Dichtung - Die Damaskusaffäre und Heines Der Rabbi von Bacharach Elvira Grözinger: Im Venusberg. Zu Gesundheit und Krankheit bei Heinrich Heine zwischen Eros und Thanatos Sabine Bierwirth: Meilenstein der Zeitgeschichtsschreibung: Heinrich Heines Berichte über die Judenverfolgung in Damaskus 1840 Hans Otto Horch: Die unheilbar große Brüderkrankheit - Zum programmatischen Zeitgedicht Das neue Israelitische Hospital zu Hamburg von H. Heine Hendrik Madsen: Vom Überleben der toten Schrift - Eine medientheoretisch orientierte Lektüre des Jeremiabuches Manfred Voigts: Moses Mendelssohn und Franz Kafka: Die Heilige Schrift Olivia Franz-Klauser: Samaritanerforschung im 19. Jahrhundert: Die Anfänge der historischen Kritik im Schatten religiöser Vorurteile, gezeigt an der Rezeption Moritz Heidenheims (1824-1898) Rezensionen: Mark R. Cohen: Unter Kreuz und Halbmond. Die Juden im Mittelalter (Daniel Jütte) Erika Timm: Historische jiddische Semantik. (Karl E. Grözinger) David B. Ruderman, Giuseppe Veltri (Hrsg.): Cultural Intermediaries. Jewish Intellectuals in Early Modern Italy (Daniel Jütte) Gian Maria Varanini, Reinhold C. Mueller (Hrsg.): Ebrei nella Terraferma veneta del Quattrocento (Daniel Jütte) Stefanie B. Siegmund: The Medici State and the Ghetto of Florence (Daniel Jütte) Johannes Mordstein: Selbstbewußte Untertänigkeit (Robert Jütte) Werner Heegewaldt, Oliver Sander (Hrsg.): Salomo Sachs (Elvira Grözinger) Philipp Theisohn: Die Urbarkeit der Zeichen. Zionismus und Literatur - eine andere Poetik der Moderne (Joachim Schlör) Jascha Nemtsov: Die Neue Jüdische Schule in der Musik (Susanne Hudak-Laziç) Ines Sonder: Gartenstädte in Eretz Israel. (Robert Jütte) Cilly Kugelmann (Hrsg.): Weihnukka. Geschichten von Weihnachten und Chanukka. (Daniel Jütte) Moshe Zimmermann, Yotam Hotam (Hrsg.): Zweimal Heimat. Die Jeckes zwischen Mitteleuropa und Nahost. (Anat Feinberg) Birgit Schlachter: Schreibweisen der Abwesenheit. (Elvira Grözinger) Jüdische Studien in aller Welt: Juden und Judentum im Iran - Einige zufällige und weniger zufällige Reiseeindrücke (Hans-Michael Haußig) Nachrichten Rückblicke
Economists argue that land rent taxation is an ideal form of taxation as it causes no deadweight losses. Nevertheless, pure land rent taxation is rarely applied. This paper revisits the case of land taxation for developing countries. We first provide an up-to-date review on land taxation in development countries, including feasibility and implementation challenges. We then simulate land tax reforms for Rwanda, Peru, Nicaragua and Indonesia, based on household surveys. We find that (i) land taxes provide a substantial untapped potential for tax revenues at minimal deadweight losses; that (ii) linear land value taxes tend to put a high relative burden on poor households as land ownership is pervasive; (iii) non-linear tax schemes could avoid adverse effects on the poor; and that (iv) with technological advances, administrative costs of land taxes have reduced substantially and are outweighed by tax revenues and co-benefits of formalized land tenure. Enforcement and compliance remain, however, a key challenge.
Background/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 mu M CORM-2. Results: CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)(2)D-3 plasma levels, renal Cyp27b1 gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased Fgf23 transcript levels. Conclusion: CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)(2)D-3 synthesis.
The terrestrial biosphere is a key component of the global carbon cycle and its carbon balance is strongly influenced by climate. Continuing environmental changes are thought to increase global terrestrial carbon uptake. But evidence is mounting that climate extremes such as droughts or storms can lead to a decrease in regional ecosystem carbon stocks and therefore have the potential to negate an expected increase in terrestrial carbon uptake. Here we explore the mechanisms and impacts of climate extremes on the terrestrial carbon cycle, and propose a pathway to improve our understanding of present and future impacts of climate extremes on the terrestrial carbon budget.