Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

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A long-range restriction map of the interleukin-4 and interleukin-5 linkage group on chromosome 5

The genes for two of the hematopoietic growth factors, interleukin-4 and interleukin-5, are located on a small segment of chromosome 5 (q23-31), which is frequently deleted in myeloid disorders. Using pulsed-field gel electrophoresis, we demonstrate physical linkage of these two genes and present a long-range restriction map of the locus. The two genes are closely linked (maximum separation, 310 kb) and appear to be separated by an HTF island. We were unable to physically link these genes to two other closely related hematopoietic growth factor genes, interleukin-3 and granulocyte/macrophage colony-stimulating factor, which also map to this region of the genome. The clustering of these and other growth-related genes suggests that a higher order of genetic organization exists in this region of the chromosome.     

Potentially Infectious Agents Associated with Shearling Bedpads: Effect of Laundering with Detergent-Disinfectant Combinations on Staphylococcus aureus and Pseudomonas aeruginosa

Glutaraldehyde-tanned woolskins which are used as bedpads to prevent decubitus ulcers were contaminated with Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 15442). Two methods of exposure, direct contact and aerosol, were used in separate experiments. Attempts were made to decrease the bacterial population placed on the woolskins by laundering them in a quaternary ammonium disinfectant, a phenolic disinfectant, or alkalinized glutaraldehyde, in combination with an anionic or nonionic detergent. The effect of a commercial detergent-sanitizer was also studied. Bacterial populations were significantly reduced in all experiments, but only laundering in glutaraldehyde in combination with either detergent resulted in maximum removal of bacteria. Viable bacteria were usually not detected in the rinse water (<1 viable organism/5 ml of rinse water).     

Enzymatic function in crystals of delta 5-3-ketosteroid isomerase. Catalytic activity and binding of competitive inhibitors

Crystals of the steroid-metabolizing enzyme, delta 5-3-ketosteroid isomerase (EC 5.3.3.1) from Pseudomonas testosteroni, exhibit many enzymatic properties. Each enzyme subunit in the lattice binds a competitive inhibitor, progesterone, with the same stoichiometry (1:1) and affinity (KD = 6 X 10(-6) M) as the enzyme in solution. Another competitive inhibitor, 19-nortestosterone, competes with progesterone for the same binding sites in the crystal. The enzyme crystals catalyze the conversion of delta 5- to delta 4-ketosteroids, but because the enzyme is so efficient, and substrate diffusion into the crystal is so slow, substrate cannot penetrate deeply into the crystal before being converted to product. A general theoretical formulation is presented to account for the effects of substrate diffusion into enzyme crystals of different shapes and sizes. The dependence of apparent mean enzyme activity in steroid isomerase crystals as a function of crystal size is shown to be consistent with this theoretical formulation. These inhibitor binding and catalytic properties suggest that the enzyme is in an active conformation within these crystals.     

Lecithotrophic development and metamorphosis in the Indo-West Pacific brittle star Ophiomastix venosa (Echinodermata: Ophiuroidea)

Summary

The larval development of the ophiocomid ophiuroid Ophiomastix venosais described using SEM. The gastrula transforms into a uniformly ciliated early larva which progressively changes into a lecithotrophic late premetamorphic larva with a continuous bilateral ciliated band. This stage is short-lived and equivalent to a highly reduced ophiopluteus. Comparisons between O. venosa and other ophiuroid species whose development has been investigated suggest that, whatever the developmental mode (lecithotrophic or planktotrophic), a pluteus stage always occurs in ophiuroids with planktonic development. Two metamorphic stages were identified, the late metamorphic larva differing from the early one by the closure of the larval mouth. The appearance of the permanent mouth marks the end of the metamorphosis. The postlarva still possesses remnants of larval features. The transformation of the reduced ophiopluteus into a barrel-shaped metamorphic larva with transverse ciliated bands, a vitellaria larva, is followed. The possible occurrence of a unique type of metamorphic larva in non-brooding ophiuroids is discussed. Verification of this, however, needs further SEM investigations on metamorphic larva from species having “regular” planktotrophic development.     

The Protein Data Bank: unifying the archive

The Protein Data Bank (PDB; http://www.pdb.org/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the progress that has been made in validating all data in the PDB archive and in releasing a uniform archive for the community. We have now produced a collection of mmCIF data files for the PDB archive (ftp://beta.rcsb.org/pub/pdb/uniformity/data/mmCIF/). A utility application that converts the mmCIF data files to the PDB format (called CIFTr) has also been released to provide support for existing software.     

WSR-88D doppler radar detection of corn earworm moth migration

Corn earworm (Lepidoptera: Noctuidae) (CEW) populations infesting one crop production area may rapidly migrate and infest distant crop production areas. Although entomological radars have detected corn earworm moth migrations, the spatial extent of the radar coverage has been limited to a small horizontal view above crop production areas. The Weather Service Radar (version 88D) (WSR-88D) continuously monitors the radar-transmitted energy reflected by, and radial speed of, biota as well as by precipitation over areas that may encompass crop production areas. We analyzed data from the WSR-88D radar (S-band) at Brownsville, Texas, and related these data to aerial concentrations of CEW estimated by a scanning entomological radar (X-band) and wind velocity measurements from rawinsonde and pilot balloon ascents. The WSR-88D radar reflectivity was positively correlated (r ²?=?0.21) with the aerial concentration of corn earworm-size insects measured by a scanning X-band radar. WSR-88D radar constant altitude plan position indicator estimates of wind velocity were positively correlated with wind speed (r ²?=?0.56) and wind direction (r ²?=?0.63) measured by pilot balloons and rawinsondes. The results reveal that WSR-88D radar measurements of insect concentration and displacement speed and direction can be used to estimate the migratory flux of corn earworms and other nocturnal insects, information that could benefit areawide pest management programs. In turn, identification of the effects of spatiotemporal patterns of migratory flights of corn earworm-size insects on WSR-88D radar measurements may lead to the development of algorithms that increase the accuracy of WSR-88D radar measurements of reflectivity and wind velocity for operational meteorology.     

RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ～40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ～90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins).     

Persistence of Salmonella typhimurium on Fabrics

The objective of this study was to determine the feasibility of using airborne T3 coliphage as a viral tracer in microbial aerosols. Although T3 coliphage was relatively stable when stored either at temperatures ranging from 21 to 37 C or in the frozen state at -20 C, there was a 2-log loss in infectivity when stored for 72 days at 4 C. Either agitation of stored coliphage suspensions held at 31 C or wide fluctuations in storage temperature produced an increased loss of infectivity. In the airborne state, freshly prepared coliphage and stored coliphage behaved similarly, with survival diminishing as the relative humidity (RH) was lowered. The greatest loss occurred during the first five min following aerosolization. The results showed that only under certain conditions of temperature and relative humidity can T3 coliphage be used as a satisfactory aerosol tracer.