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Phylogenomics reveals rapid, simultaneous diversification of three major clades of Gondwanan frogs at the Cretaceous–Paleogene boundary
Frogs (Anura) are one of the most diverse groups of vertebrates and comprise nearly 90% of living amphibian species. Their worldwide distribution and diverse biology make them well-suited for assessing fundamental questions in evolution, ecology, and conservation. However, despite their scientific importance, the evolutionary history and tempo of frog diversification remain poorly understood. By using a molecular dataset of unprecedented size, including 88-kb characters from 95 nuclear genes of 156 frog species, in conjunction with 20 fossil-based calibrations, our analyses result in the most strongly supported phylogeny of all major frog lineages and provide a timescale of frog evolution that suggests much younger divergence times than suggested by earlier studies. Unexpectedly, our divergence-time analyses show that three species-rich clades (Hyloidea, Microhylidae, and Natatanura), which together comprise ∼88% of extant anuran species, simultaneously underwent rapid diversification at the Cretaceous–Paleogene (K–Pg) boundary (KPB). Moreover, anuran families and subfamilies containing arboreal species originated near or after the KPB. These results suggest that the K–Pg mass extinction may have triggered explosive radiations of frogs by creating new ecological opportunities. This phylogeny also reveals relationships such as Microhylidae being sister to all other ranoid frogs and African continental lineages of Natatanura forming a clade that is sister to a clade of Eurasian, Indian, Melanesian, and Malagasy lineages. Biogeographical analyses suggest that the ancestral area of modern frogs was Africa, and their current distribution is largely associated with the breakup of Pangaea and subsequent Gondwanan fragmentation.
Journal Article
Afghanistan : graveyard of empires : a new history of the borderlands
Veteran defense analyst and Afghanistan expert David Isby provides an insightful and meticulously researched look at the current situation in Afghanistan, its history, and what he believes must be done so that the US-NATO coalition can succeed in one of the poorest countries in the world, rife with divisions that dwarf current schisms in Iraq, led by warlords who fight over control of the drug trade as much as they do over religion. After seven years and billions of dollars, the task of implementing an effective US policy and cementing Afghani rule is hampered by what Isby sees as separate but overlapping conflicts between terrorism, narcotics, and regional rivalries, each requiring different strategies to resolve. Pulling these various threads together will be the challenge for the Obama administration, yet it is a challenge that can be met.--From publisher description.
Book
Dapagliflozin in Patients with Chronic Kidney Disease
In this trial, patients with CKD (with or without type 2 diabetes) were randomly assigned to receive dapagliflozin or placebo. The primary composite outcome — a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes — was less frequent with dapagliflozin.
Journal Article
Photoredox Activation for the Direct β-Arylation of Ketones and Aldehydes
The direct β-activation of saturated aldehydes and ketones has long been an elusive transformation. We found that photoredox catalysis in combination with organocatalysis can lead to the transient generation of 5π-electron β-enaminyl radicals from ketones and aldehydes that rapidly couple with cyano-substituted aryl rings at the carbonyl β-position. This mode of activation is suitable for a broad range of carbonyl β-functionalization reactions and is amenable to enantioselective catalysis.
Journal Article
Amor Dei in the sixteenth and seventeenth centuries
\"Amor Dei, 'love of God' raises three questions: How do we know God is love? How do we experience love of God? How free are we to love God? This book presents three kinds of love, worldly, spiritual, and divine to understand God's love. The work begins with Augustine's Confessions highlighting his Manichean and Neoplatonic periods before his conversion to Christianity. Augustine's confrontation with Pelagius anticipates the unresolved disputes concerning God's love and free will. In the sixteenth-century the Italian humanist, Gasparo Contarini introduces the notion of 'divine amplitude' to demonstrate how God's goodness is manifested in the human agent. Pierre de Bâerulle, Guillaume Gibieuf, and Nicolas Malebranche show connections with Contarini in the seventeenth-century controversies relating free will and divine love. In response to the free will dispute, the Scottish philosopher, William Chalmers, offers his solution. Cornelius Jansen relentlessly asserts his anti-Pelagian interpretation of Augustine stirring up more controversy. John Norris, Malebranche's English disciple, exchanges his views with Mary Astell and Damaris Masham. In the tradition of Cambridge Platonism, Ralph Cudworth conveys a God who 'sweetly governs.' The organization of sections represents the love of God in ascending-descending movements demonstrating that, 'human love is inseparable from divine love.'\"--Publisher's website.
Book
Organic synthesis provides opportunities to transform drug discovery
Despite decades of ground-breaking research in academia, organic synthesis is still a rate-limiting factor in drug-discovery projects. Here we present some current challenges in synthetic organic chemistry from the perspective of the pharmaceutical industry and highlight problematic steps that, if overcome, would find extensive application in the discovery of transformational medicines. Significant synthesis challenges arise from the fact that drug molecules typically contain amines and N-heterocycles, as well as unprotected polar groups. There is also a need for new reactions that enable non-traditional disconnections, more C–H bond activation and late-stage functionalization, as well as stereoselectively substituted aliphatic heterocyclic ring synthesis, C–X or C–C bond formation. We also emphasize that syntheses compatible with biomacromolecules will find increasing use, while new technologies such as machine-assisted approaches and artificial intelligence for synthesis planning have the potential to dramatically accelerate the drug-discovery process. We believe that increasing collaboration between academic and industrial chemists is crucial to address the challenges outlined here.
Journal Article
Empires of medieval West Africa : Ghana, Mali, and Songhay
Explores empires of medieval west Africa.
Book
The language of chromatin modification in human cancers
The genetic information of human cells is stored in the context of chromatin, which is subjected to DNA methylation and various histone modifications. Such a ‘language’ of chromatin modification constitutes a fundamental means of gene and (epi)genome regulation, underlying a myriad of cellular and developmental processes. In recent years, mounting evidence has demonstrated that miswriting, misreading or mis-erasing of the modification language embedded in chromatin represents a common, sometimes early and pivotal, event across a wide range of human cancers, contributing to oncogenesis through the induction of epigenetic, transcriptomic and phenotypic alterations. It is increasingly clear that cancer-related metabolic perturbations and oncohistone mutations also directly impact chromatin modification, thereby promoting cancerous transformation. Phase separation-based deregulation of chromatin modulators and chromatin structure is also emerging to be an important underpinning of tumorigenesis. Understanding the various molecular pathways that underscore a misregulated chromatin language in cancer, together with discovery and development of more effective drugs to target these chromatin-related vulnerabilities, will enhance treatment of human malignancies.Deregulation of chromatin modification underlies a myriad of oncogenic processes. This Review synthesizes the many connections between chromatin modifications and cancer, discussing recent advances and highlighting options for therapeutic targeting.
Journal Article