Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Delayed Double Treatment with Adult-Sourced Adipose-Derived Mesenchymal Stem Cells Increases Striatal Medium-Spiny Neuronal Number, Decreases Striatal Microglial Number, and Has No Subventricular Proliferative Effect, after Acute Neonatal Hypoxia-Ischemia in Male Rats

Perinatal hypoxia-ischemia (HI) is a major cause of striatal injury. Delayed post-treatment with adult-sourced bone marrow-derived mesenchymal stem cells (BMSCs) increased the absolute number of striatal medium-spiny neurons (MSNs) following perinatal HI-induced brain injury. Yet extraction of BMSCs is more invasive and difficult compared to extraction of adipose-derived mesenchymal stem cells (AD-MSCs), which are easily sourced from subcutaneous tissue. Adult-sourced AD-MSCs are also superior to BMSCs in the treatment of adult ischemic stroke. Therefore, we investigated whether delayed post-treatment with adult-sourced AD-MSCs increased the absolute number of striatal MSNs following perinatal HI-induced brain injury. This included investigation of the location of injected AD-MSCs within the brain, which were widespread in the dorsolateral subventricular zone (dlSVZ) at 1 day after their injection. Cells extracted from adult rat tissue were verified to be stem cells by their adherence to tissue culture plastic and their expression of specific ‘cluster of differentiation’ (CD) markers. They were verified to be AD-MSCs by their ability to differentiate into adipocytes and osteocytes in vitro. Postnatal day (PN) 7/8, male Sprague-Dawley rats were exposed to either HI right-sided brain injury or no HI injury. The HI rats were either untreated (HI + Diluent), single stem cell-treated (HI + MSCs×1), or double stem cell-treated (HI + MSCs×2). Control rats that were matched-for-weight and litter had no HI injury and were treated with diluent (Uninjured + Diluent). Treatment with AD-MSCs or diluent occurred either 7 days, or 7 and 9 days, after HI. There was a significant increase in the absolute number of striatal dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-positive MSNs in the double stem cell-treated (HI + MSCs×2) group and the normal control group compared to the HI + Diluent group at PN21. We therefore investigated two potential mechanisms for this effect of double-treatment with AD-MSCs. Specifically, did AD-MSCs: (i) increase the proliferation of cells within the dlSVZ, and (ii) decrease the microglial response in the dlSVZ and striatum? It was found that a primary repair mechanism triggered by double treatment with AD-MSCs involved significantly decreased striatal inflammation. The results may lead to the development of clinically effective and less invasive stem cell therapies for neonatal HI brain injury

Canadian prescription drug atlas

"Canadians spent almost $23-billion on prescription drugs at retail pharmacies in 2012/13 – or over$650 per capita. That is a lot of money. However, after adjusting for general inflation, spending per capita actually fell over the past five years – despite the fact that the population was getting older. This 3rd edition of The Canadian Rx Atlas breaks down retail spending on prescription drugs Canada, providing a detailed portrait of the factors driving spending trends over time and variations across provinces. The Atlas gives a first-ever portrait of age- and sex-specific patterns of prescription drug use and costs across provinces. It also provides first-of-kind estimates of the source of financing for the prescriptions filled in every province. Unique to the Canadian Rx Atlas, these details are not provided simply for all spending on prescription drugs; it also provides these details for each of 33 clinically and economically important therapeutic categories." -CHSPR websiteNon UBCMedicine, Faculty ofPopulation and Public Health (SPPH), School ofUnreviewedFacultyResearcherPostdoctora

1200-talet: Ett århundrade för städer

Core Updates: Adds numpy backend for basic (same pattern) processing Framework restructuring to expose local and global slicing methods Allows multiple plugins to process 'raw' data Adds beamline logger for auto-processing Adds 'nprocs' option to previewing Fixes 'File write failed' error caused by ROMIO 2GB read/write limit and h5py create_dataset Replaces h5py create_dataset (with chunking) with direct hdf5 calls, to avoid initialisation of the created file. Updates configurator arg parser to allow negative values in a list Adds beginnings of a GUI for creating plugin templates Plugin Updates: Adds iterative plugin driver Adds iterative vo_centering plugin Adds edfsaver Improves vo_centering Fixes scikitimage to use values from parameters Fixes error in upper and lower bounds for darkandflatfieldcorrection Fixes distortion correction Fixes previewing and parameter tuning at the same time in reconstruction methods Improves all reconstruction wrappers: Improves astra toolbox wrappers Improves base recon and centre/outer padding Padding is now only allowed for suitable methods (e.g. yes for FBP but no for iterative methods

DiamondLightSource/Savu: Version 2.2.1

Core updates: Improves dockerfile for external use Improves HDF5 data chunking, with significant speed increases Plugin updates: Amends DistortionCorrection parameters as agreed and tested with DLS beamline staff Adds 'multiple' frames request with a maximum limit DezingFilter renamed as DezingerSimple Adds Dezinger plugin Adds updated version of Robert Atwood's C-implemented algorithm back in to Savu This is a faster more accurate implementation Updates to DezingerSimple Maximum 8 frames now requested due to memory issues Darks and flats now only processed 8 at a tim

Identification of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1,2 and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies

Pan Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2 and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model and pre-clinical profile of the potent and selective pan PIM kinase inhibitor 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor 1, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, 8 entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies

FIGURE 2 in LepNet: The Lepidoptera of North America Network

FIGURE 2. Existing (black) and expected (blue, yellow, and green) number of records to be produced by LepNet for the 3 major groups and 15 families of Lepidoptera that are most common in the collections of the partner institutions. Existing records were obtained from the SCAN and iDigBio data portals