As administrated clinically, erythropoietin has a polypeptide backbone with complex

dishomogeneity in its carbohydrate domains. Here we describe the total synthesis of homogeneous erythropoietin with consensus carbohydrate domains incorporated at all of the native glycosylation sites. The oligosaccharide sectors were built by total synthesis and attached stereospecifically to peptidyl fragments of the wild-type primary sequence, themselves obtained by solid-phase peptide synthesis. The glycopeptidyl constructs were joined by chemical ligation, followed by metal-free dethiylation, and subsequently folded. This homogeneous erythropoietin glycosylated at the three wild-type aspartates with N-linked high-mannose sialic acid-containing Selinexor oligosaccharides and O-linked glycophorin exhibits Procrit-level in vivo activity in mice.”
“Trends in streamflow timing and volume in the Pacific Northwest United States have been attributed to increased temperatures, because trends in precipitation at lower-elevation stations were negligible. We demonstrate that observed streamflow declines are probably associated with declines in mountain precipitation, revealing previously unexplored differential trends. Lower-troposphere winter (November to March) westerlies are strongly correlated with high-elevation precipitation but weakly correlated with low-elevation precipitation. Decreases in lower-tropospheric

winter westerlies across the region from 1950 to 2012 are hypothesized to have reduced orographic

precipitation Gemcitabine nmr enhancement, yielding differential trends in precipitation across elevations and contributing to the decline in annual streamflow. Climate projections show weakened lower-troposphere zonal flow across the region under enhanced greenhouse forcing, highlighting an additional stressor that is relevant for climate change impacts on hydrology.”
“Experimental studies of evolution have increased greatly in number in recent years, stimulated by the growing power of genomic tools. However, organismal fitness remains the ultimate metric for interpreting these experiments, and the dynamics of fitness remain poorly understood over Selleck Ganetespib long time scales. Here, we examine fitness trajectories for 12 Escherichia coli populations during 50,000 generations. Mean fitness appears to increase without bound, consistent with a power law. We also derive this power-law relation theoretically by incorporating clonal interference and diminishing-returns epistasis into a dynamical model of changes in mean fitness over time.”
“Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. We used genomic deoxyribonuclease I footprinting to map nucleotide resolution TF occupancy across the human exome in 81 diverse cell types.