How enzyme-centered approaches are advancing research on cyclic oligo-nucleotides.

Cyclic nucleotides are the most diversified category of second messengers and are found in all organisms modulating diverse pathways. While cAMP and cGMP have been studied over 50 years, cyclic di-nucleotide signaling in eukaryotes emerged only recently with the anti-viral molecule 2´3´cGAMP. Recent breakthrough discoveries have revealed not only the astonishing chemical diversity of cyclic nucleotides but also surprisingly deep-rooted evolutionary origins of cyclic oligo-nucleotide signaling pathways and structural conservation of the proteins involved in their synthesis and signaling.

Structural basis for TBP displacement from TATA box DNA by the Swi2/Snf2 ATPase Mot1.

The Swi2/Snf2 family transcription regulator Modifier of Transcription 1 (Mot1) uses adenosine triphosphate (ATP) to dissociate and reallocate the TATA box-binding protein (TBP) from and between promoters. To reveal how Mot1 removes TBP from TATA box DNA, we determined cryogenic electron microscopy structures that capture different states of the remodeling reaction. The resulting molecular video reveals how Mot1 dissociates TBP in a process that, intriguingly, does not require DNA groove tracking.

Mechanistic understanding of human SLFN11.

Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to replication stress and inhibits replication of certain viruses such as the human immunodeficiency virus 1 (HIV-1) by modulating the tRNA pool. SLFN11 has been identified as a predictive biomarker in cancer, as its expression correlates with a beneficial response to DNA damage inducing anticancer drugs.

The Diamond Project: A Quality Improvement Model for Adopting Shared Service Delivery in the Washington Vaccines for Children Program.

Increasing federal requirements with no change in the Centers for Disease Control and Prevention budget creates an unsustainable delivery model between states and their local counterparts for programs like Vaccines for Children (VFC). The Washington State Department of Health collaborated with the Washington Association of Local Public Health Officials to identify how best to improve the quality of the VFC program. Utilizing Quality improvement and Lean Six Sigma methods, the project team was able to adopt a new shared-service delivery model to improve the quality of the VFC program in Washington State.

Accountable Communities of Health, Health and Social Service Systems Alignment, and Population Health: Eastern Washington State, 2017-2019.

To assess health system transformation and alignment in the Better Health Together (BHT) accountable community of health (ACH) region of Eastern Washington. This trend study leveraged cross-sectional data collected in 2017 and 2019 in Eastern Washington. A total of 165 responses from individuals representing 112 organizations were collected in 2017, and 211 responses from individuals representing 92 organizations were collected in 2019.

Gene silencing pathways found in the green alga Volvox carteri reveal insights into evolution and origins of small RNA systems in plants.

Background: Volvox carteri (V. carteri) is a multicellular green alga used as model system for the evolution of multicellularity. So far, the contribution of small RNA pathways to these phenomena is not understood.

Evidence for autocatalytic cross-linking of hydroxyproline-rich glycoproteins during extracellular matrix assembly in Volvox.

The alga Volvox carteri is one of the simplest multicellular organisms, yet it has a surprisingly complex extracellular matrix (ECM), making Volvox suitable as a model system in which to study ECM self-assembly. Here, we analyze the primary structures and post-translational modifications of two main ECM components synthesized in response to sexual induction as well as wounding. These proteins are members of the pherophorin family with as yet unknown properties.

Self-assembly and cross-linking of Volvox extracellular matrix glycoproteins are specifically inhibited by Ellman's reagent.

A major impediment to the biochemical characterization of extracellular matrices from algae (as well as higher plants) is the extensive covalent cross-linking that exists in the matrix, rendering most components insoluble and resistant to conventional extraction procedures. In the multicellular green alga Volvox, biogenesis of the extracellular matrix (ECM) is initiated immediately after the process of embryonic inversion. At this stage of development, the sulfhydryl reagent 5, 5'-dithio-bis(2-nitrobenzoic acid), known as Ellman's reagent, interferes in a highly specific manner with ECM biogenesis.

The highly efficient sex-inducing pheromone system of Volvox.

The green alga Volvox is one of the simplest multicellular organisms and is capable of both asexual and sexual reproduction. Sexual development is initiated by a glycoprotein pheromone that acts at a concentration below 10(-16) M. The extracellular matrix (ECM) appears to play a key role in signal amplification: several ECM proteins contain a domain with homology to the sex-inducing pheromone.

Differential targeting of closely related ECM glycoproteins: the pherophorin family from Volvox.

The alga Volvox carteri represents one of the simplest multicellular organisms. Its extracellular matrix (ECM) is modified under developmental control, e.g.

Intraperitoneal cholelithiasis after laparoscopic cholecystectomy--behavior of 'lost' concrements and their role in abscess formation.

Unlabelled: In two experimental studies we sought preliminary information about the behavior of concrements lost in the peritoneal cavity during laparoscopic cholecystectomy.

Materials And Methods: In study 1, human gallstones were analyzed using X-ray diffraction, classified in three groups and examined with an ultramicroscope; then they were implanted in the peritoneal cavity of rats. After 8 weeks or 6 months, the animals were sacrificed and the concrements analyzed again as before.

How a sex pheromone might act at a concentration below 10(-16) M.

The sex-inducing pheromone of Volvox carteri is a glycoprotein that triggers development of males and females at a concentration below 10(-16) M. Evidence is presented for the existence of a novel mechanism of signal amplification operating within the extracellular matrix of this multicellular organism. A family of 70 kDa matrix glycoproteins denoted pherophorins bear a C-terminal domain being homologous to the sex-inducing pheromone.

A novel extensin that may organize extracellular matrix biogenesis in Volvox carteri.

ISG is a sulphated, extracellular glycoprotein synthesized for only a few minutes in inverting Volvox embryos and inverting sperm cell packets. This control operates at the level of transcription. ISG has been characterized by studies of protein chemistry and electron microscopy.

[The cystic duct stump after laparoscopic cholecystectomy].

The aim of this study was to evaluate the length of cystic-duct stumps after laparoscopic cholecystectomy. 113 patients underwent intravenous cholangiography 2 to 3 months postoperatively, whereby a cystic-duct remnant of up to 1 cm was found in 34.5% (n = 39) and between 1 and 2 cm in 36.

The extracellular matrix of Volvox carteri: molecular structure of the cellular compartment.

The extracellular matrix (ECM) of Volvox contains insoluble fibrous layers that surround individual cells at a distance to form contiguous cellular compartments. Using immunological techniques, we identified a sulfated surface glycoprotein (SSG 185) as the monomeric precursor of this substructure within the ECM. The primary structure of the SSG 185 poly-peptide chain has been derived from cDNA and genomic DNA.

A novel glycosphingolipid that may participate in embryo inversion in Volvox carteri.

Mouse monoclonal antibody 4-I-244 detects a developmentally regulated antigen in embryos of Volvox carteri and inhibits specifically the morphogenetic process of inversion (the process by which the embryo turns inside out). Antigen 4-I-244 was chemically characterized as a complex phytosphingolipid containing the neutral sugars xylose, galactose, and glucose as well as inositol and phosphate.

Development-dependent modification of the extracellular matrix by a sulphated glycoprotein in Volvox carteri.

We report the chemical characterization of the highly sulphated glycoprotein SSG 185 from Volvox carteri. SSG 185 is a hydroxyproline-containing, extracellular glycoprotein. The sulphate residues are clustered within the parent saccharide structure of SSG 185, since on mercaptolysis all the sulphate residues are recovered in a small saccharide fragment containing mannose, arabinose and sulphate (in a molar ratio of 112).

Sulfation of a cell surface glycoprotein correlates with the developmental program during embryogenesis of Volvox carteri.

A sulfated cell surface glycoprotein with an apparent molecular weight of 185,000 is synthesized in the multicellular organism Volvox only during the limited period of embryogenesis. The lifetime of sulfate residues on this glycoprotein is very short (half-life about 20 min). Production of this sulfated glycoprotein sharply decreases to a minimum shortly before the onset of the differentiating cell cleavage--e.