Early coronary sinus reroofing using the left atrial baffle

Surgical correction of unroofed coronary sinus, left superior vena cava, dextrocardia, and situs solitus in a 4-month-old infant consisted of reroofing the coronary sinus by means of a left atrial flap while redirecting the left superior vena cava to the right atrium. Excellent access to the left side of the left atrium was afforded by the associated dextrocardia.     

Insulin therapy could prevent salt-induced high blood pressure in diabetes mellitus

The effectiveness of insulin replacement therapy in the prevention of salt-induced hypertension in diabetes mellitus was examined using Alloxan diabetic rats. Early daily (eight units/day) treatment with insulin prevented the development of high blood pressure after six weeks of high-salt feeding. The mean arterial pressure (MAP) for the early insulin-treated and salt-fed group (DET-SF) was 123.37 +/- 6.37 mmHg which was close to the value for normal (control) rats 128.17 +/- 4.84 mmHg, but significantly (p < 0.001) less than that of the untreated diabetic salt-fed group (DSF) which was 164.58 +/- 8.33 mmHg. The nondiabetic salt-fed (NDSF) group had MAP of 150.27 +/- 4.24 mmHg. Late commencement of insulin therapy did not significantly affect the sensitivity of the diabetic rats to high-salt diet. The results suggest that early commencement of insulin therapy could prevent the development of high blood pressure in diabetic rats.     

Impact of barrier deposition process on electrical and reliability performance of Cu/CVD low k SiOCH metallization

Integration of Cu with low k dielectrics provided solution to reduce both resistance-capacitance time delay and parasitic capacitance of BEOL interconnections for 130 nm and beyond technology node. The motivation of this work is to study and improve electrical and reliability performance of two-level Cu/CVD low k SiOCH metallization from the results of diffusion barrier deposition schemes. Barrier deposition schemes are (a) high-density-plasma 250 Å Ta; (b) surface treatment of forming gas followed by high-density-plasma 250 Å Ta and (c) bi-layer of 100 Å Ta(N)/150 Å Ta. In this work, we demonstrated the superior and competency of high-density-plasma Ta deposition for Cu/CVD low k metallization and achieved excellent electrical and reliability results. Wafers fabricated with high-density-plasma Ta barrier scheme resulted in the best electrical yields, >90% for testing vehicles of dense via chains (via size=200 nm) and interspersed comb structures (width/space=200 nm/200 nm). Dielectric breakdown strength of the interspersed comb structures obtained at electric field of 0.3 MV/cm was ∼4 MV/cm.     

Recombinant scrapie-like prion protein of 106 amino acids is soluble

The N terminus of the scrapie isoform of prion protein (PrPSc) can be truncated without loss of scrapie infectivity and, correspondingly, the truncation of the N terminus of the cellular isoform, PrPC, still permits conversion into PrPSc. To assess whether additional segments of the PrP molecule can be deleted, we previously removed regions of putative secondary structure in PrPC; in the present study we found that deletion of each of the four predicted helices prevented PrPSc formation, as did deletion of the stop transfer effector region and the C178A mutation. Removal of a 36-residue loop between helices 2 and 3 did not prevent formation of protease-resistant PrP; the resulting scrapie-like protein, designated PrPSc106, contained 106 residues after cleavage of an N-terminal signal peptide and a C-terminal sequence for glycolipid anchor addition. Addition of the detergent Sarkosyl to cell lysates solubilized PrPSc106, which retained resistance to digestion by proteinase K. These results suggest that all the regions of proposed secondary structure in PrP are required for PrPSc formation, as is the disulfide bond stabilizing helices 3 and 4. The discovery of PrPSc106 should facilitate structural studies of PrPSc, investigations of the mechanism of PrPSc formation, and the production of PrPSc-specific antibodies.     

Pharmacological characterization of human m1 muscarinic acetylcholine receptors with double mutations at the junction of TM VI and the third extracellular domain

A mutant human m5 receptor containing the mutations of Ser465 to Tyr and Thr466 to Pro showed constitutive activity. By replacing the equivalent Ser388 with Tyr and Thr389 with Pro, we created a mutant human m1 (Hm1) receptor with comparable double mutations. The mutant receptor, Hm1(Ser388Tyr, Thr389Pro), was stably expressed in A9 L cells and displayed enhanced responses to classical muscarinic agonists with significantly increased potencies. Choline, a normal component of growth media, showed an efficacy comparable to acetylcholine and carbachol at Hm1(Ser388Tyr, Thr389Pro) receptors. Methylcarbachol, a selective nicotinic agonist, exhibited partial agonist activity at human m1 wild-type receptors and full agonist activity at Hm1(Ser388Tyr, Thr389Pro) receptors. l-Hyoscyamine inhibited the activities of choline and methylcarbachol. Muscarinic antagonists displayed small reductions in binding affinities, although muscarinic agonists showed greatly increased binding affinities for Hm1(Ser388Tyr, Thr389Pro) receptors. All agonists, including choline and methylcarbachol, showed multiple affinity states at Hm1(Ser388Tyr, Thr389Pro) receptors in the absence of GppNHp. The high affinity binding sites for acetylcholine, arecoline and choline were shifted in the presence of GppNHp. These results suggest that Hm1(Ser388Tyr, Thr389Pro) is conformationally favorable for agonist binding and receptor activation.     

An import signal in the cytosolic domain of the Neurospora mitochondrial outer membrane protein TOM22

TOM22 is an integral component of the preprotein translocase of the mitochondrial outer membrane (TOM complex). The protein is anchored to the lipid bilayer by a central trans-membrane segment, thereby exposing the amino-terminal domain to the cytosol and the carboxyl-terminal portion to the intermembrane space. Here, we describe the sequence requirements for the targeting and correct insertion of Neurospora TOM22 into the outer membrane. The orientation of the protein is not influenced by the charges flanking its trans-membrane segment, in contrast to observations regarding proteins of other membranes. In vitro import studies utilizing TOM22 preproteins harboring deletions or mutations in the cytosolic domain revealed that the combination of the trans-membrane segment and intermembrane space domain of TOM22 is not sufficient to direct import into the outer membrane. In contrast, a short segment of the cytosolic domain was found to be essential for the import and assembly of TOM22. This sequence, a novel internal import signal for the outer membrane, carries a net positive charge. A mutant TOM22 in which the charge of the import signal was altered to -1 was imported less efficiently than the wild-type protein. Our data indicate that TOM22 contains physically separate import and membrane anchor sequences.