Carbapenem-Resistant Klebsiella pneumoniae Infection in Three New York City Hospitals Trended Downwards From 2006 to 2014

Background. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a rising public health threat since its first outbreaks in New York City (NYC) in the early 2000s. We investigated annual trends of CRKP infection in hospital-acquired infections (HAIs) and community-onset infections (COIs) treated in 3 NYC hospitals from 2006 to 2014. Methods. We extracted K pneumoniae infection data including carbapenem susceptibility and anatomical sites, compared clinical characteristics between CRKP and carbapenem-susceptible K pneumoniae infections, and determined CRKP infection proportions in total K pneumoniae infections in HAI and COI to identify statistically significant trends from 2006 to 2014 using the Cochran-Armitage trend test. Results. Carbapenem-resistant K pneumoniae contributed 17.3% (601 of 3477) of hospital-acquired K pneumoniae infection compared with 7.7% (149 of 1926) in COI from 2006 to 2014. Carbapenem-resistant K pneumoniae proportions in HAI and COI were positively correlated over time (r = 0.83, P < .01), and there were downward annual trends of CRKP proportions from 2006 to 2014 in both HAI and COI (25.8% to 10.5% in HAI, P < .001; 13.6% to 3.1% in COI, P < .001). By anatomical site, significant downward annual trends were present only in urinary tract infection (P < .001 for both HAI and COI) from 2006 to 2014. Conclusions. Annual trends of CRKP proportions from 2006 to 2014 were downward in both HAI and COI, and HAI and COI were positively correlated. Efforts to reduce and prevent CRKP infections in both hospital and community settings were successful and warrant continuation

Genetic Analyses of Elys Mutations in Drosophila Show Maternal-Effect Lethality and Interactions with Nucleoporin Genes

ELYS determines the subcellular localizations of Nucleoporins (Nups) during interphase and mitosis. We made loss-of-function mutations of Elys in Drosophila melanogaster and found that ELYS is dispensable for zygotic viability and male fertility but the maternal supply is necessary for embryonic development. Subsequent to fertilization, mitotic progression of the embryos produced by the mutant females is severely disrupted at the first cleavage division, accompanied by irregular behavior of mitotic centrosomes. The Nup160 introgression from D. simulans shows close resemblance to that of the Elys mutations, suggesting a common role for those proteins in the first cleavage division. Our genetic experiments indicated critical interactions between ELYS and three Nup107–160 subcomplex components; hemizygotes of either Nup37, Nup96 or Nup160 were lethal in the genetic background of the Elys mutation. Not only Nup96 and Nup160 but also Nup37 of D. simulans behave as recessive hybrid incompatibility genes with D. melanogaster. An evolutionary analysis indicated positive natural selection in the ELYS-like domain of ELYS. Here we propose that genetic incompatibility between Elys and Nups may lead to reproductive isolation between D. melanogaster and D. simulans, although direct evidence is necessary

適切な文字を求めて－最も古い英語のアルファベットの起源について－

本発表では7世紀の古英語のアルファベットの起源について考察する。まず、見本になった、あるいは、影響を与えた可能性があると思われる様々な国や地域のアルファベット、つまり、ルーン文字、フランク語、ブリトン語（ウェールズ語）、アイルランド語のアルファベットを概観する。そして、アイルランド語とそのアルファベットが古英語のアルファベットとその文字の形成に果たした役割について論じる。原著：パトリック, オニール　日本語要約：和田葉

Continuous Health Interface Event Retrieval

Knowing the state of our health at every moment in time is critical for advances in health science. Using data obtained outside an episodic clinical setting is the first step towards building a continuous health estimation system. In this paper, we explore a system that allows users to combine events and data streams from different sources to retrieve complex biological events, such as cardiovascular volume overload. These complex events, which have been explored in biomedical literature and which we call interface events, have a direct causal impact on relevant biological systems. They are the interface through which the lifestyle events influence our health. We retrieve the interface events from existing events and data streams by encoding domain knowledge using an event operator language.Comment: ACM International Conference on Multimedia Retrieval 2020 (ICMR 2020), held in Dublin, Ireland from June 8-11, 202

Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid

The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA

Short Co-occurring Polypeptide Regions Can Predict Global Protein Interaction Maps

A goal of the post-genomics era has been to elucidate a detailed global map of protein-protein interactions (PPIs) within a cell. Here, we show that the presence of co-occurring short polypeptide sequences between interacting protein partners appears to be conserved across different organisms. We present an algorithm to automatically generate PPI prediction method parameters for various organisms and illustrate that global PPIs can be predicted from previously reported PPIs within the same or a different organism using protein primary sequences. The PPI prediction code is further accelerated through the use of parallel multi-core programming, which improves its usability for large scale or proteome-wide PPI prediction. We predict and analyze hundreds of novel human PPIs, experimentally confirm protein functions and importantly predict the first genome-wide PPI maps for S. pombe (∼9,000 PPIs) and C. elegans (∼37,500 PPIs)

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Recycling Upstream Redox Enzymes Expands the Regioselectivity of Cycloaddition in Pseudo-Aspidosperma Alkaloid Biosynthesis

Nature uses cycloaddition reactions to generate complex natural product scaffolds. Dehydrosecodine is a highly reactive biosynthetic intermediate that undergoes cycloaddition to generate several alkaloid scaffolds that are the precursors to pharmacologically important compounds such as vinblastine and ibogaine. Here we report how dehydrosecodine can be subjected to redox chemistry, which in turn allows cycloaddition reactions with alternative regioselectivity. By incubating dehydrosecodine with reductase and oxidase biosynthetic enzymes that act upstream in the pathway, we can access the rare pseudoaspidosperma alkaloids pseudo-tabersonine and pseudo-vincadifformine, both in vitro and by reconstitution in the plant Nicotiana benthamiana from an upstream intermediate. We propose a stepwise mechanism to explain the formation of the pseudo-tabersonine scaffold by structurally characterizing enzyme intermediates and by monitoring the incorporation of deuterium labels. This discovery highlights how plants use redox enzymes to enantioselectively generate new scaffolds from common precursors

The variation of productivity and its allocation along a tropical elevation gradient: a whole carbon budget perspective

Why do forest productivity and biomass decline with elevation? To address this question, research to date generally has focused on correlative approaches describing changes in woody growth and biomass with elevation. We present a novel, mechanistic approach to this question by quantifying the autotrophic carbon budget in 16 forest plots along a 3300 m elevation transect in Peru. Low growth rates at high elevations appear primarily driven by low gross primary productivity (GPP), with little shift in either carbon use efficiency (CUE) or allocation of net primary productivity (NPP) between wood, fine roots and canopy. The lack of trend in CUE implies that the proportion of photosynthate allocated to autotrophic respiration is not sensitive to temperature. Rather than a gradual linear decline in productivity, there is some limited but nonconclusive evidence of a sharp transition in NPP between submontane and montane forests, which may be caused by cloud immersion effects within the cloud forest zone. Leaf-level photosynthetic parameters do not decline with elevation, implying that nutrient limitation does not restrict photosynthesis at high elevations. Our data demonstrate the potential of whole carbon budget perspectives to provide a deeper understanding of controls on ecosystem functioning and carbon cycling

Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping

Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond