Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon

The primary structure of human apolipoprotein (apo) B-48 has been deduced and shown by a combination of DNA excess hybridization, sequencing of tryptic peptides, cloned complementary DNAs, and intestinal messenger RNAs (mRNAs) to be the product of an intestinal mRNA with an in-frame UAA stop codon resulting from a C to U change in the codon CAA encoding Gln2153 in apoB-100 mRNA. The carboxyl-terminal Ile2152 of apoB-48 purified from chylous ascites fluid has apparently been cleaved from the initial translation product, leaving Met2151 as the new carboxyl-terminus. These data indicate that approximately 85% of the intestinal mRNAs terminate within approximately 0.1 to 1.0 kilobase downstream from the stop codon. The other approximately 15% have lengths similar to hepatic apoB-100 mRNA even though they have the same in-frame stop codon. The organ-specific introduction of a stop codon to a mRNA appears unprecedented and might have implications for cryptic polyadenylation signal recognition and RNA processing.     

Cholesterol solubility in lecithin-bile salt systems

The method of sample preparation can markedly influence the rate of dissolution and attainment of supersaturated states of cholesterol. The equilibrium solubility of cholesterol, studied as a function of its physical state in a model bile system, is almost half that of previously accepted values. Slow attainment of the equilibrium state may have acted to bias previous studies. Extrapolation of our data to the clinical situation reveals that many persons considered normal by present standards actually possess bile that is supersaturated with respect to cholesterol and are thus potential gallstone formers.     

Renin-angiotensin role in thirst: paradoxical enhancement of drinking by angiotensin converting enzyme inhibitor

A competitive angiotensin converting enzyme antagonist SQ 20, 881 (SQ), was used to examine the role of the renin-angiotensin system in putative renin-dependent thirst in the albino rat. Significant enhancement of "renin-dependent" as well as renin-independent drinking was observed in the presence of peripheral SQ. Intraventricular SQ obviated this enhancement of drinking but did not affect the water intake caused by the original stimulus itself, whereas it sharply reduced drinking evoked by peripheral renin in nephrectomized rats. Prior renin depletion likewise had no influence on so-called renin-dependent thirst.     

A protein sensor for siRNA asymmetry

To act as guides in the RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) must be unwound into their component strands, then assembled with proteins to form the RNA-induced silencing complex (RISC), which catalyzes target messenger RNA cleavage. Thermodynamic differences in the base-pairing stabilities of the 5' ends of the two approximately 21-nucleotide siRNA strands determine which siRNA strand is assembled into the RISC. We show that in Drosophila, the orientation of the Dicer-2/R2D2 protein heterodimer on the siRNA duplex determines which siRNA strand associates with the core RISC protein Argonaute 2. R2D2 binds the siRNA end with the greatest double-stranded character, thereby orienting the heterodimer on the siRNA duplex. Strong R2D2 binding requires a 5'-phosphate on the siRNA strand that is excluded from the RISC. Thus, R2D2 is both a protein sensor for siRNA thermodynamic asymmetry and a licensing factor for entry of authentic siRNAs into the RNAi pathway.     

Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans

Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.