Distribution of Na+, K+ and Cl− between nucleus and cytoplasm inChironomus salivary gland cells

Summary Previous studies of the electrochemical activity coefficients of intracellular Na⁺ and K⁺ have suggested that the free form of these ions may be unevenly distributed within the intracellular fluids. One possible site of such subcellular compartmentalization is the cell nucleus. In order to examine this possibility, the cells ofChironomus salivary glands were studied with conventional liquid ion-exchange microelectrodes sensitive to K⁺ and Cl^–, with a new liquid ion-exchange microelectrode sensitive to Na⁺, and with open-tipped micropipets. Both the electrochemical activities for Na⁺, K⁺ and Cl^–, and the electrical potential were the same on both sides of the nuclear membrane. The possibility was considered that a difference in the junction potentials within the nucleoplasm and cytoplasm might have masked a real difference in electrical potential between these two phases. To study that possibility, changes were induced in the junction potentials by altering the composition of the fluid filling the exploring micropipets. The results have suggested that the magnitudes of the junction potentials are the same on both sides of the nuclear envelope. The simplest interpretation of the data is that the chemical activities of Na⁺, K⁺ and Cl^– are the same within the nucleus and cytoplasm. This suggests that other subcellular structures, possibly the endoplasmic reticulum and mitochondria, are responsible for subcellular compartmentalization.     

Prevalence of antibody to human T lymphotropic virus type III by risk group and area,United Kingdom 1978-84.

Antibody to human T lymphotropic virus type III (anti-HTLV-III) was sought in 2150 patients in three groups at risk with a radioimmunoassay and an immunofluorescence test. Results by the two methods were closely concordant. Anti-HTLV-III was already present in some British homosexuals in 1980 and in some British haemophiliacs in 1981, and since then its prevalence has increased. Of homosexual patients needing laboratory tests for hepatitis B virus infection in 1984, 34% of 282 in London and 5% of 955 in five centres outside London were positive for anti-HTLV-III. Of haemophiliacs sampled in 1984, 38% of 81 were anti-HTLV-III positive. Most of the seropositive haemophiliacs were regular recipients of commercial factor VIII concentrates. Few British intravenous drug abusers sampled in 1984 (2.5% of 203) were positive for anti-HTLV-III. These results show that infection with HTLV-III has rapidly become widespread among homosexuals attending sexually transmitted disease clinics and among haemophiliacs receiving pooled blood products. Thus, while many anti-HTLV-III positive individuals may remain asymptomatic, there may soon be a considerable increase in the incidence of the acquired immune deficiency syndrome and related disease in Britain.     

Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies

The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (P_LYM = 3.89×10⁻⁸, OR = 1.29) and rs948562 (P_LYM = 5.85×10⁻⁷, OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, P_NHL = 5.72×10⁻⁷) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (P_FL = 2.69×10⁻¹², OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.     

Abnormal Glycosphingolipid Mannosylation Triggers Salicylic Acid–Mediated Responses in Arabidopsis

The Arabidopsis thaliana protein GOLGI-LOCALIZED NUCLEOTIDE SUGAR TRANSPORTER (GONST1) has been previously identified as a GDP-d-mannose transporter. It has been hypothesized that GONST1 provides precursors for the synthesis of cell wall polysaccharides, such as glucomannan. Here, we show that in vitro GONST1 can transport all four plant GDP-sugars. However, gonst1 mutants have no reduction in glucomannan quantity and show no detectable alterations in other cell wall polysaccharides. By contrast, we show that a class of glycosylated sphingolipids (glycosylinositol phosphoceramides [GIPCs]) contains Man and that this mannosylation is affected in gonst1. GONST1 therefore is a Golgi GDP-sugar transporter that specifically supplies GDP-Man to the Golgi lumen for GIPC synthesis. gonst1 plants have a dwarfed phenotype and a constitutive hypersensitive response with elevated salicylic acid levels. This suggests an unexpected role for GIPC sugar decorations in sphingolipid function and plant defense signaling. Additionally, we discuss these data in the context of substrate channeling within the Golgi.