Modeling human arthritic diseases in nonhuman primates

Models of rheumatoid arthritis (RA) in laboratory animals are important tools for research into pathogenic mechanisms and the development of effective, safe therapies. Rodent models (rats and mice) have provided important information about the pathogenic mechanisms. However, the evolutionary distance between rodents and humans hampers the translation of scientific principles into effective therapies. The impact of the genetic distance between the species is especially seen with treatments based on biological molecules, which are usually species-specific. The outbred nature and the closer anatomical, genetic, microbiological, physiological, and immunological similarity of nonhuman primates to humans may help to bridge the wide gap between inbred rodent strain models and the heterogeneous RA patient population. Here we review clinical, immunological and pathological aspects of the rhesus monkey model of collagen-induced arthritis, which has emerged as a reproducible model of human RA in nonhuman primates.     

Partitioning of the serotonin transporter into lipid microdomains modulates transport of serotonin

The serotonin transporter (SERT) is an integral membrane protein responsible for the clearance of serotonin from the synaptic cleft following the release of the neurotransmitter. SERT plays a prominent role in the regulation of serotoninergic neurotransmission and is a molecular target for multiple antidepressants as well as substances of abuse. Here we show that SERT associates with lipid rafts in both heterologous expression systems and rat brain and that the inclusion of the transporter into lipid microdomains is critical for serotonin uptake activity. SERT is present in a subpopulation of lipid rafts, which is soluble in Triton X-100 but insoluble in other non-ionic detergents such as Brij 58. Disaggregation of lipid rafts upon depletion of cellular cholesterol results in a decrease of serotonin transport capacity (V(max)), due to the reduction of turnover number of serotonin transport. Our data suggest that the association of SERT with lipid rafts may represent a mechanism for regulating the transporter activity and, consequently, serotoninergic signaling in the central nervous system, through the modulation of the cholesterol content in the cell membrane. Furthermore, SERT-containing rafts are detected in both intracellular and cell surface fractions, suggesting that raft association may be important for trafficking and targeting of SERT.     

The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 microM) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure-activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90.     

Mechanism of the Selective Action of Eosin-Methylene-Blue Agar on the Enteric Group

The actual mechanism of the differentiation of lactose-fermenting and non-lactose-fermenting organisms on eosin-methylene-blue medium is not reported in the literature. The present study is an attempt to elucidate this problem.

The color of colon forms on E.M.B. agar was found to depend on two factors: (1) the reaction of eosin with methylene blue to form a dye compound of either acidic or neutral nature, and (2) the production, by lactose-fermenting colonies, of a sufficiently low pH so that this dye compound is taken up by individual cells of the colony. Non-lactose-fermenting organisms are not colored because the compound is not taken up in alkaline reaction.

An explanation is offered to account for the occasional blue colonies found on E.M.B. medium. It is suggested that these colonies form a relatively high pH and thus cause slight dissociation of the compound. This dissociation would allow independent staining of the colonies by methylene blue.     

Reactivity of cationic carbonyl/phosphine ruthenium(II) compounds

Cis(or trans)-[RuCl₂(CO)₂(PPh₃)₂] react with two and one equivalents of AgBF₄ to give the recently reported [Ru(CO)₂(PPh₃)₂][BF₄]₂·CH₂Cl₂ (1) and novel [RuCl(CO)₂(PPh₃)₂][BF₄] · 1/2 CH₂Cl₂ (2), respectively. Cis-[RuCl₂(CO)₂(PPh₃)₂] also reacts with two equivalents of AgBF₄ in the presence of CO to give [Ru(CO)₃(PPh₃)₂][BF₄]₂ (3). Reactions of 1 and 2 with NaOMe and CO at 1 atm produce the carbomethoxy species [Ru(COOMe)₂(CO)₂(PPh₃)₂] (4) and [RuCl(COOMe)(CO)₂(PPh₃)₂] (5), respectively. Complex 4 can also be formed from the reaction of 3 with NaOMe and CO. Alternatively, 4 is formed from cis-[RuCl₂(CO)₂(PPh₃)₂] with NaOMe and CO at elevated pressure (10 atm); if these reactants are refluxed under 1 atm of CO, [Ru(CO)₃(PPh₃)₂] is the product. The reaction of [RuCl(CO)₃(PPh₃)₂][AlCl₄] with NaOMe provides an alternative route to the preparation of 5, but the product is contaminated with [RuCl₂(CO)₂(PPh₃)₂]. Compounds 1. 2, 4 and 5 have been characterised by IR, ¹H NMR and analysis, whilst the formulation of 3 is proposed from spectroscopic data only. This account also examines the reactivity of [Ru(CO)₂(PPh₃)₂][BF₄]₂ · CH₂Cl₂ with NaBH₄, conc. HCl, KI and, finally, MeCOONa in the presence of CO. The products of these reactions, namely cis-[RuH₂(CO)₂(PPh₃)₂], cis-[RuCl₂(CO)₂(PPh₃)₂], cis-[RuI₂(CO)₂(PPh₃)₂] and [Ru(OOCMe)₂(CO)₂(PPh₃)₂], have been identified by comparison of their spectra with previous literature.     

TWO NEW SPECIES OF TAYLORIELLA (RHODOMELACEAE,RHODOPHYTA) FROM THE NORTHEASTERN NORTH PACIFIC1

Two new species are recognized in the rhodomelacean genus Tayloriella Kylin: T. divaricata sp. nov. and T. abyssalis sp. nov. These two taxa are distributed in the northeastern North Pacific, the former ranging from Amchitka Island in the Aleutians through southcentral Alaska to northern British Columbia, and the latter ranging also from Amchitka Island through southcentral Alaska and British Columbia into northern Washington. A characteristic of these two species shared with the type of Tayloriella is that the abaxial lateral always overtops the monopodially developed axes in every order of branching. The laterals have little congenital fusion with the parent axes. A common feature in these two species is that the laterals are terminated in a relatively long monosiphonous portion (usually 6 or 7 cells). The relationship of Tayloriella to Pterosiphonia and Pterosiphoniella is discussed.     

Chrysymenia tigillis sp. nov. (Rhodymeniales, Rhodophyta) from the Sultanate of Oman, with a census of currently recognized species in the genus Chrysymenia

Chrysymenia tigillis sp. nov. is described on the basis of a few specimens collected from Dhofar, Sultanate of Oman. The new species is known only from southern Oman, a region of the northern Arabian Sea that is strongly impacted by the upwelling from the summertime monsoon. It is distinguished from other species of the genus by the simple nature of the blades, their dimensions (to 75 cm in length and to 21 cm in width), the rough, bumpy surface of the blades, and the presence of internal struts connecting the inner sides of the blades. A census of the currently recognized species in the genus Chrysymenia is provided.     

THE GENUS HYPOGLOSSUM KÜTZING (DELESSERIACEAE,RHODOPHYTA) IN THE TROPICAL WESTERN ATLANTIC,INCLUDING H. ANOMALUM SP. NOV.1

Observations are made on the occurrence and distribution of the red algal genus Hypoglossum Kützing (Delesseriaceae, Ceramiales) in the tropical western Atlantic. In addition to the type of the genus, H. hypoglossoides (Stackh.) Coll. & Herv., three other species are reported: H. anomalum sp. nov., H. involvens (Harv.) J. Ag., and H. tenuifolium (Harv.) J. Ag. A key is presented to distinguish these four species. The newly described species, H. anomalum, is like other species in the genus in that its branches arise endogenously from the primary axial row but it is unique in that the branches emerge from the parent blade at some point between the midline and the margin of the blade. The new species is reported from Puerto Rico and Florida.