477 research outputs found

    Luminosities of H alpha emitting regions in a pair of interacting galaxies in the Bootes void

    Get PDF
    Luminosities of H alpha emission from a pair of interacting galaxies in the low density environment of the Bootes void are presented. CG 692 (IRAS 1519+5050) has an H alpha luminosity of 2 x 10(exp 42) ergs s(exp -1), indicating a star formation rate of 18.4 solar mass yr(exp -1). Individual extranuclear H alpha regions have luminosities of approximately 10(exp 40) ergs s(exp -1). These luminosities are similar to those found for H II regions in bright, late-type galaxies in more densely populated parts of the Universe

    Substrate-derived Sortase A inhibitors: targeting an essential virulence factor of Gram-positive pathogenic bacteria

    Get PDF
    The bacterial transpeptidase Sortase A (SrtA) is a surface enzyme of Gram-positive pathogenic bacteria. It has been shown to be an essential virulence factor for the establishment of various bacterial infections, including septic arthritis. However, the development of potent Sortase A inhibitors remains an unmet challenge. Sortase A relies on a five amino acid sorting signal (LPXTG), by which it recognizes its natural target. We report the synthesis of a series of peptidomimetic inhibitors of Sortase A based on the sorting signal, supported by computational binding analysis. By employing a FRET-compatible substrate, our inhibitors were assayed in vitro. Among our panel, we identified several promising inhibitors with IC50 values below 200 mu M, with our strongest inhibitor - LPRDSar - having an IC50 of 18.9 mu M. Furthermore, it was discovered that three of our compounds show an effect on growth and biofilm inhibition of pathogenic Staphylococcus aureus, with the inclusion of a phenyl ring seemingly key to this effect. The most promising compound in our panel, BzLPRDSar, could inhibit biofilm formation at concentrations as low as 32 mu g mL(-1), manifesting it as a potential future drug lead. This could lead to treatments for MRSA infections in clinics and diseases such as septic arthritis, which has been directly linked with SrtA

    Identification of rare earth elements in synthetic and natural monazite and xenotime by visible-to-shortwave infrared reflectance spectroscopy

    Get PDF
    To support the role of proximal and remote sensing in geological rare earth element (REE) resource exploration, we studied the reflectance spectroscopy of synthetic single- and mixed-REE phosphate phases. Synthesis yielded monazite for the elements La to Gd, and xenotime for Dy to Lu and Y. Visible-to-shortwave infrared (350–2500Β nm) reflectance spectra of synthetic single-REE monazites and xenotimes can be used to identify the ions responsible for the absorption features in natural monazites and xenotimes. Nd3+, Pr3+ and Sm3+ produce the main absorption features in monazites. In natural xenotime, Dy3+, Er3+, Ho3+ and Tb3+ ions cause the prevalent absorptions. The majority of the REE-related absorption features are due to photons exciting electrons within the 4f subshell of the trivalent lanthanide ions to elevated energy levels resulting from spin-orbit coupling. There are small (&lt; 20Β nm) shifts in the wavelengths of these absorptions depending on the nature of the ligands. The energy levels are further split by crystal field effects, manifested in the reflectance spectra as closely spaced (∼ 5–20Β nm) multiplets within the larger absorption features. Superimposed on the electronic absorptions are vibrational absorptions in the H2O molecule or within [OH]βˆ’, [CO3]2βˆ’ and [PO4]3βˆ’ functional groups, but so far only the carbonate-related spectral features seem usable as a diagnostic tool in REE-bearing minerals. Altogether, our study creates a strengthened knowledge base for detection of REE using reflectance spectroscopy and provides a starting point for the identification of REE and their host minerals in mineral resources by means of hyperspectral methods.</p

    РСгиосСлСктивный синтСз ΠΈ свойства Π°Ρ†Π΅Ρ‚ΠΈΠ»ΡŒΠ½Ρ‹Ρ… ΠΏΡ€ΠΎΠΈΠ·Π²ΠΎΠ΄Π½Ρ‹Ρ… Ρ„Π΅Π½ΠΎΠ»Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ²

    Get PDF
    РСгиосСлСктивный синтСз ΠΈ свойства Π°Ρ†Π΅Ρ‚ΠΈΠ»ΡŒΠ½Ρ‹Ρ… ΠΏΡ€ΠΎΠΈΠ·Π²ΠΎΠ΄Π½Ρ‹Ρ… Ρ„Π΅Π½ΠΎΠ»Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ². Π Π°Π±ΠΎΡ‚Π° посвящСна Π²Ρ‹ΡΠ²Π»Π΅Π½ΠΈΡŽ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΎΠ½Π½ΠΎΠΉ способности ΠΏΡ€ΠΈ кислотном Π΄Π΅Π·Π°Ρ†Π΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠΈ с использованиСм HCl / EtOH Π² CHCl3, которая ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΡ‚ ΠΊ Π΄Π΅Π·Π°Ρ†Π΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΡŽ Π½Π° O-3, O-4 ΠΈ O-6. ΠžΠΏΠΈΡΠ°Π½Π½Ρ‹ΠΉ Ρ€Π΅Π°Π³Π΅Π½Ρ‚ оказался ΠΎΠ±Ρ‰ΠΈΠΌ ΠΈ ΡƒΠ½ΠΈΠΊΠ°Π»ΡŒΠ½Ρ‹ΠΌ, ΠΈ Π±Ρ‹Π»Π° ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π° сСрия 2-О-Π°Ρ†Π΅Ρ‚ΠΈΠ»Π°Ρ€ΠΈΠ»Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ². Π’ΠΎΠΎΠ±Ρ‰Π΅, частично Π°Ρ†Π΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Π΅ Π°Ρ€ΠΈΠ»Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄Ρ‹ ΡˆΠΈΡ€ΠΎΠΊΠΎ Π²ΡΡ‚Ρ€Π΅Ρ‡Π°ΡŽΡ‚ΡΡ Π² ΠΏΡ€ΠΈΡ€ΠΎΠ΄Π΅. Π’ частности, ΠΌΠΎΠΆΠ½ΠΎ Π½Π°ΠΉΡ‚ΠΈ мноТСство ΠΏΡ€ΠΈΠΌΠ΅Ρ€ΠΎΠ² 2-O-Π°Ρ†Π΅Ρ‚ΠΈΠ»Π°Ρ€ΠΈΠ»Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ΄ΠΎΠ².Regioselective synthesis and properties of acetyl derivatives of phenol glycosides. The thesis is devoted to the detection of reactivity during acid deacetylation using HCl / EtOH in CHCl3, which leads to deacetylation at O-3, O-4 and O-6. The described reagent proved to be general and unique and the series of 2-О-acetyl aryl glycosides were prepared. Generally, partially acetylated aryl glycosides are widely found in nature. Particularly, many examples of 2-O-acetyl aryl glycosides can be found

    Moderate-Resolution Spectroscopy of the Lensed Quasar 2237+0305: A search for Ca ii Absorption Due to the Interstellar Medium in the Foreground Lensing Galaxy

    Get PDF
    The gravitational lens system 2237 + 0305 consists of a low-redshift barred spiral galaxy (z = 0.0394) centered on a more distant quasar (z = 1.695). Because the lensing galaxy is nearly face on, spectroscopy of the background quasar affords a unique opportunity to study the interstellar medium in the galaxy\u27s center and buW:. We report moderate-resolution spectroscopy of QS02237 + 0305 yielding a 3u upper limit of 72 rnA forthe rest equivalent width of Ca II K absorption d);le to gas in the intervening galaxy. Since gas in the Milky Way thick disk typically produces 220 mA Ca II lines along lines of sight at high galactic latitude, while our line of sight to QSO 2237 + 0305 is effectively the weighted mean of four lines of sight, each of which transects an entire halo diameter in the lensing galaxy rather than just a radius, our Ca II upper limit argues against the presence. of such a thick disk near the center of the lensing galaxy. Also, published studies indicate that at 8200 A, QSO 2237 + 0305 suffers roughly 0.5 mag of extinction due to the lensing galaxy. Assuming a normal gas-to-dust ratio and allowing for various sources of uncertainty, this absorption estimate combined with our Ca II Kupper limit implies that calcium is depleted with respect to hydrogen by at least 2.7-3.7 dex, compared to solar abundances. This depletion is similar to the more extreme cases seen in our own galaxy, and higher-dispersion observations may further decrease the upper limit on Ca II absorption

    The impact of monosomies, trisomies and segmental aneuploidies on chromosomal stability

    Get PDF
    Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal instability leads to karyotype heterogeneity in tumors and is associated with therapy resistance, metastasis and poor prognosis. It has been hypothesized that aneuploidy per se is sufficient to drive CIN, however due to limited models and heterogenous results, it has remained controversial which aspects of aneuploidy can drive CIN. In this study we systematically tested the impact of different types of aneuploidies on the induction of CIN. We generated a plethora of isogenic aneuploid clones harboring whole chromosome or segmental aneuploidies in human p53-deficient RPE-1 cells. We observed increased segregation errors in cells harboring trisomies that strongly correlated to the number of gained genes. Strikingly, we found that clones harboring only monosomies do not induce a CIN phenotype. Finally, we found that an initial chromosome breakage event and subsequent fusion can instigate breakage-fusion-bridge cycles. By investigating the impact of monosomies, trisomies and segmental aneuploidies on chromosomal instability we further deciphered the complex relationship between aneuploidy and CIN

    Oncostatin M-induced and constitutive activation of the JAK2/STAT5/CIS pathway suppresses CCL1, but not CCL7 and CCL8, chemokine expression

    Get PDF
    The recruitment of leukocytes to injured tissue is crucial for the initiation of inflammatory responses as well as for immune surveillance to fight tumor progression. In this study, we show that oncostatin M, a member of the IL-6-type cytokine family and potent proinflammatory cytokine stimulates the expression of the chemokines CCL1, CCL7, and CCL8 in primary human dermal fibroblasts at a faster kinetic than IL-1beta or TNF-alpha. The production of CCL1 and CCL8 is important for migration of monocytes, while specific Abs against CCL1 additionally inhibit the migration of T lymphocytes. We identify the mitogen-activated protein kinases ERK1/2 and p38 as crucial factors for the enhanced expression of CCL1 and CCL8. Depletion of the ERK1/2 target genes c-Jun or c-Fos strongly decrease CCL1 and CCL8 expression, while p38 MAPK prolongs the half-life of CCL1, CCL7, and CCL8 mRNA through inhibition of tristetraprolin. None of the STAT transcription factors STAT1, STAT3, or STAT5 stimulate transcription of CCL1 or CCL8. However, we identify a negative regulatory function of activated STAT5 for the gene expression of CCL1. Importantly, not STAT5 itself, but its target gene cytokine inducible SH2-domain containing protein is required for the STAT5 inhibitory effect on CCL1 expression. Finally, we show that constitutive activation of STAT5 through a mutated form of JAK2 (JAK2 V617F) occurring in patients with myeloproliferative disorders similarly suppresses CCL1 expression. Taken together, we identify novel important inflammatory target genes of OSM which are independent of STAT signaling per se, but depend on MAPK activation and are partly repressed through STAT5-dependent expression of cytokine inducible SH2-domain containing protein

    B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

    Get PDF
    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and experience affinity maturation. Paired tissues were used to determine whether the B cells that populate the CNS mature in the draining cervical lymph nodes (CLNs). High-throughput sequencing of the antibody repertoire demonstrated that clonally expanded B cells were present in both compartments. Founding members of clones were more often found in the draining CLNs. More mature clonal members derived from these founders were observed in the draining CLNs and also in the CNS, including lesions. These data provide new evidence that B cells traffic freely across the tissue barrier, with the majority of B cell maturation occurring outside of the CNS in the secondary lymphoid tissue. Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS
    • …
    corecore