The archaeology of scattered wreck-sites: formation processes and shallow water archaeology in western Lake Huron

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74939/1/j.1095-9270.2002.tb01415.x.pd

tert-Butyl 5-methoxy-3-pentylindole-1-carboxylate

he molecule of the title compound, C₁₉H₂₇NO₃, is essentially planar, with all non-H atoms within 0.2 Å of the nine-membered indole plane, except for the three tert-butyl C atoms. The C₅ pentyl chain is in an extended conformation, with three torsion angles of 179.95 (13), 179.65 (13) and -178.95 (15)° (the latter two angles include the C atoms of the C5 chain only). Three intramolecular C-H...O=C contacts are present (C...O 115°), and an intermolecular C-H...O=C contact and π-π stacking complete the intermolecular interactions

6-(4-Fluorophenyl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6-5] fused-ring system

The title compound, C₁₈H₁₃FN₂OS, is the first structural example of a [6-5] fused ring incorporating the 2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one molecular scaffold. The six-membered 2,3-dihydro-1,3-thiazin-4-one ring adopts an envelope conformation, with the S-CH₂ C atom displaced by 0.761 (2) Å from the five-atom plane (all within 0.05 Å of the mean plane). The imidazole ring is planar. The phenyl ring is twisted from coplanarity with the imidazole ring by 23.84 (5)° and the 4-fluorophenyl ring is twisted by 53.36 (6)°, due to a close C(aryl)-H...O=C contact with the thiazin-4-one carbonyl O atom. The primary intermolecular interaction involves a CH₂ group with the F atom [C...F = 3.256 (2) Å and C-H...F = 137°]

Expression of thrombospondin in the adult nervous system

Thrombospondin (TSP) is an extracellular matrix molecule that has been previously associated with neural development and neurite outgrowth in vitro. Little is known, however, about the expression of TSP in the adult nervous system. In this study, TSP localization was examined in nervous tissue from adult mouse, goldfish, newt, and adult and juvenile Xenopus. TSP was associated with neurons in the brains of all species examined. TSP was present in central nerve tracts capable of regeneration, such as the goldfish, Xenopus, and newt optic nerves, but was absent from tracts not capable of regeneration, such as the mouse optic nerve. TSP was also present in the neuropil of goldfish and newt spinal cord, but was restricted to motor neurons in mice and adult Xenopus. In addition, TSP was observed in sciatic nerves of mice, Xenopus, and newt. These results indicate a correlation between the presence of TSP and the potential for successful nerve regeneration across a wide range of animal classes. © Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50059/1/903400109_ftp.pd

Disruption of host-seeking behaviour by the salmon louse,Lepeophtheirus salmonis,using botanically derived repellents

The potential for developing botanically derived natural products as novel feed-through repellents for disrupting settlement of the salmon louse, Lepeophtheirus salmonis (Caligidae) upon farmed Atlantic salmon, Salmo salar, was investigated using an established laboratory vertical Y-tube behavioural bioassay for assessing copepodid behaviour. Responses to artificial sea water conditioned with the odour of salmon, or to the known salmon-derived kairomone component, α-isophorone, in admixture with selected botanical materials previously known to interfere with invertebrate arthropod host location were recorded. Materials included oils extracted from garlic, Allium sativum (Amaryllidaceae), rosemary, Rosmarinus officinalis (Lamiaceae), lavender, Lavandula angustifolia (Lamiaceae), and bog myrtle, Myrica gale (Myricaceae), and individual components (diallyl sulphide and diallyl disulphide from garlic; allyl, propyl, butyl, 4-pentenyl and 2-phenylethyl isothiocyanate from plants in the Brassica genus). Removal of attraction to salmon-conditioned water (SCW) or α-isophorone was observed when listed materials were presented at extremely low parts per trillion (ppt), that is picograms per litre or 10−12 level. Significant masking of attraction to SCW was observed at a level of 10 ppt for diallyl disulphide and diallyl sulphide, and allyl isothiocyanate and butyl isothiocyanate. The potential of very low concentrations of masking compounds to disrupt Le. salmonis copepodid settlement on a host fish has been demonstrated in vitro

CD4+FoxP3+ regulatory T cells confer infectious tolerance in a TGF-β–dependent manner

CD4+FoxP3+ regulatory T (T reg) cells comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. The molecular mechanism(s) by which T reg cells mediate their suppressive effects remains poorly understood. One molecule that has been extensively studied in T reg cell suppression is transforming growth factor (TGF)-β, but its importance remains controversial. We found that TGF-β complexed to latency-associated peptide (LAP) is expressed on the cell surface of activated but not resting T reg cells. T reg cell LAP–TGF-β plays an important role in the suppression of the proliferation of activated T cells, but it is not required for the suppression of naive T cell activation. More importantly, T reg cell–derived TGF-β could generate de novo CD4+FoxP3+ T cells in vitro from naive precursors in a cell contact–dependent, antigen-presenting cell–independent and αV integrin–independent manner. The newly induced CD4+FoxP3+ T cells are suppressive both in vitro and in vivo. Transfer of activated antigen-specific T reg cells with naive antigen-specific responder T cells to normal recipients, followed by immunization, also results in induction of FoxP3 expression in the responder cells. T reg cell–mediated generation of functional CD4+FoxP3+ cells via this TGF-β–dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities

Janus kinases to jakinibs : from basic insights to clinical practice

Cytokines are critical mediators of diverse immune and inflammatory diseases. Targeting cytokines and cytokine receptors with biologics has revolutionized the treatment of many of these diseases, but targeting intracellular signalling with Janus kinase (JAK) inhibitors (jakinibs) now represents a major new therapeutic advance. We are still in the first decade since these drugs were approved and there is still much to be learned about the mechanisms of action of these drugs and the practical use of these agents. Herein we will review cytokines that do, and just as importantly, do not signal by JAKs, as well as explain how this relates to both efficacy and side effects in various diseases. We will review new, next-generation selective jakinibs, as well as the prospects and challenges ahead in targeting JAKs.Peer reviewe