Solving the riddle of codon usage preferences: a test for translational selection

Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model

Human African trypanosomiasis: pharmacological re-engagement with a neglected disease

This review discusses the challenges of chemotherapy for human African trypanosomiasis (HAT). The few drugs registered for use against the disease are unsatisfactory for a number of reasons. HAT has two stages. In stage 1 the parasites proliferate in the haemolymphatic system. In stage 2 they invade the central nervous system and brain provoking progressive neurological dysfunction leading to symptoms that include the disrupted sleep wake patterns that give HAT its more common name of sleeping sickness. Targeting drugs to the central nervous system offers many challenges. However, it is the cost of drug development for diseases like HAT, that afflict exclusively people of the world's poorest populations, that has been the principal barrier to new drug development and has led to them becoming neglected. Here we review drugs currently registered for HAT, and also discuss the few compounds progressing through clinical trials. Finally we report on new initiatives that might allow progress to be made in developing new and satisfactory drugs for this terrible disease

Dynamic Carboniferous tropical forests: new views of plant function and potential for physiological forcing of climate

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/1/nph14700_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/2/nph14700.pd

Generation of a wave packet tailored to efficient free space excitation of a single atom

We demonstrate the generation of an optical dipole wave suitable for the process of efficiently coupling single quanta of light and matter in free space. We employ a parabolic mirror for the conversion of a transverse beam mode to a focused dipole wave and show the required spatial and temporal shaping of the mode incident onto the mirror. The results include a proof of principle correction of the parabolic mirror's aberrations. For the application of exciting an atom with a single photon pulse we demonstrate the creation of a suitable temporal pulse envelope. We infer coupling strengths of 89% and success probabilities of up to 87% for the application of exciting a single atom for the current experimental parameters.Comment: to be published in Europ. Phys. J.

Hip joint articular soft tissues of non-dinosaurian Dinosauromorpha and early Dinosauria: evolutionary and biomechanical implications for Saurischia

Dinosauromorphs evolved a wide diversity of hind limb skeletal morphologies, suggesting highly divergent articular soft tissue anatomies. However, poor preservation of articular soft tissues in fossils has hampered any follow-on functional inferences. We reconstruct the hip joint soft tissue anatomy of non-dinosaurian dinosauromorphs and early dinosaurs using osteological correlates derived from extant sauropsids and infer trends in character transitions along the theropod and sauropodomorph lineagues. Femora and pelves of 107 dinosauromorphs and outgroup taxa were digitized using 3D imaging techniques. Key transitions were estimated using maximum likelihood ancestral state reconstruction. The hips of dinosauromorphs possessed wide a disparity of soft tissue morphologies beyond the types and combinations exhibited by extant archosaurs. Early evolution of the dinosauriform hip joint was characterized by the retention of a prominent femoral hyaline cartilage cone in post-neonatal individuals, with the cartilage cone independently reduced within theropods and sauropodomorphs. The femur of Dinosauriformes possessed a fibrocartilage sleeve on the metaphysis, which surrounded a hyaline core. The acetabulum of Dinosauriformes possessed distinct labrum and antitrochanter structures. In sauropodomorphs, hip congruence was maintained by thick hyaline cartilage on the femoral head, whereas theropods relied on acetabular tissues such as ligaments and articular pads. In particular, the craniolaterally ossified hip capsule of non- Avetheropoda neotheropods permitted mostly parasagittal femoral movements. These data indicate that the dinosauromorph hip underwent mosaic evolution within the saurischian lineage and that sauropodomorphs and theropods underwent both convergence and divergence in articular soft tissues, correlated with transitions in body size, locomotor posture, and joint loading

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis

Pyrethroid Resistance Reduces the Efficacy of Space Sprays for Dengue Control on the Island of Martinique (Caribbean)

The mosquito Aedes aegypti is the major vector of the Dengue virus in human populations and is responsible of serious outbreaks worldwide. In most countries, vector control is implemented by the use of insecticides to reduce mosquito populations. During epidemics, insecticides of the pyrethroid family (blocking the voltage gated sodium channel protein in the nerve sheath) are used by space spraying with vehicle mounted thermal foggers to kill adult mosquitoes. Unfortunately some populations of Ae. aegypti have become resistant to these insecticides, leading to operational challenges for public health services. In Martinique (French West Indies), resistance to pyrethroids was detected in the 1990s. The present study assessed the impact of this resistance on the efficacy of vector control operations in 9 localities of Martinique. Here we showed that the resistance strongly reduces the efficacy of pyrethroid-based treatments, thus emphasizing the urgent need for alternative insecticides or tools to reduce dengue transmission