SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.     

The growth of tumour allografts as a measure of the immunosuppressive potency of antilymphocyte sera

Zusammenfassung Die Wirkung von Kaninchen-anti-Maus-Lymphozytenserum auf das Wachstum von Tumorallotransplantaten kann in kleineren Tiergruppen leicht bestimmt werden, indem man das immunosuppressive Potential verschiedener Serumsätze prüft. Ein gutes Verhältnis zwischen dem durchschnittlichen Durchmesser von Tumortransplantaten am 14. Tag nach dem Implantat und die entsprechende, durchschnittliche, prozentuale Zunahme der Überlebenszeit der Hauttransplantate wird demonstriert.     

Surface morphological study of ehrlich ascites tumor cells exposed to microware irradiation and heat

Summary Microwave irradiation of EAT cells caused an increase in length and number of surface microvilli. The tumor cells tend to form large aggregates by means of extensive interdigitation of surface microvilli. On the other hand, heat hyperthermia caused a decrease of surface microvilli but an increase of surface blebs. Hence the surface morphology of EAT cells after in vitro exposure to microwave irradiation differs markedly from that after heat hyperthermia.Part of the results was presented a the Fifth meeting of the European Co-operative Hyperthermia Group, Essen, July 1983.     

Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy

The assembly of retroviruses such as HIV-1 is driven by oligomerization of their major structural protein, Gag. Gag is a multidomain polyprotein including three conserved folded domains: MA (matrix), CA (capsid) and NC (nucleocapsid). Assembly of an infectious virion proceeds in two stages. In the first stage, Gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to release an enveloped immature virus particle. In the second stage, cleavage of Gag by the viral protease leads to rearrangement of the particle interior, converting the non-infectious immature virus particle into a mature infectious virion. The immature Gag shell acts as the pivotal intermediate in assembly and is a potential target for anti-retroviral drugs both in inhibiting virus assembly and in disrupting virus maturation. However, detailed structural information on the immature Gag shell has not previously been available. For this reason it is unclear what protein conformations and interfaces mediate the interactions between domains and therefore the assembly of retrovirus particles, and what structural transitions are associated with retrovirus maturation. Here we solve the structure of the immature retroviral Gag shell from Mason-Pfizer monkey virus by combining cryo-electron microscopy and tomography. The 8-? resolution structure permits the derivation of a pseudo-atomic model of CA in the immature retrovirus, which defines the protein interfaces mediating retrovirus assembly. We show that transition of an immature retrovirus into its mature infectious form involves marked rotations and translations of CA domains, that the roles of the amino-terminal and carboxy-terminal domains of CA in assembling the immature and mature hexameric lattices are exchanged, and that the CA interactions that stabilize the immature and mature viruses are almost completely distinct.