Biogenic catalysis of soil formation on Mars?

The high iron abundance and the weak ferric iron spectral features of martian surface material are consistent with nanophase (nm-sized) iron oxide minerals as a major source of iron in the bright region soil on Mars. Nanophase iron oxide minerals, such as ferrihydrite and schwertmannite, and nanophase forms of hematite and goethite are formed by both biotic and abiotic processes on Earth. The presence of these minerals on Mars does not indicate biological activity on Mars, but it does raise the possibility. This work includes speculation regarding the possibility of biogenic soils on Mars based on previous observations and analyses. A remote sensing goal of upcoming missions should be to determine if nanophase iron oxide minerals, clay silicates and carbonates are present in the martian surface material. These minerals are important indicators for exobiology and their presence on Mars would invoke a need for further investigation and sample return from these sites.     

Poly(A) polymerase contains multiple functional domains

Poly(A) polymerase (PAP) contains regions of similarity with several known protein domains. Through site-directed mutagenesis, we provide evidence that PAP contains a functional ribonucleoprotein-type RNA binding domain (RBD) that is responsible for primer binding, making it the only known polymerase to contain such a domain. The RBD is adjacent to, and probably overlaps with, an apparent catalytic region responsible for polymerization. Despite the presence of sequence similarities, this catalytic domain appears to be distinct from the conserved polymerase module found in a large number of RNA-dependent polymerases. PAP contains two nuclear localization signals (NLSs) in its C terminus, each by itself similar to the consensus bipartite NLS found in many nuclear proteins. Mutagenesis experiments indicate that both signals, which are separated by nearly 140 residues, play important roles in directing PAP exclusively to the nucleus. Surprisingly, basic amino acids in the N-terminal-most NLS are also essential for AAUAAA-dependent polyadenylation but not for nonspecific poly(A) synthesis, suggesting that this region of PAP is involved in interactions both with nuclear targeting proteins and with nuclear polyadenylation factors. The serine/threonine-rich C terminus is multiply phosphorylated, including at sites affected by mutations in either NLS.     

Conformational analysis and proteolytic processing of synthetic pre-pro-GnRH/GAP protein

Homogeneous pre-pro-GnRH/GAP protein was recently synthesized in 100 mg quantities by solid-phase methods and surprisingly, the synthetic pre-pro-protein, which normally does not escape the endoplasmic reticulum, was found to inhibit the release of prolactin from cultured pituitary cells. This is the first demonstration of significant biological activity associated with a precursor protein and provides the rationale for its further study. We now report the results of our initial examination of the conformational properties of pre-pro-GnRH/GAP protein as a prelude to solving its solution phase conformation by homonuclear 1H-NMR protocols. Thermal and pH titration fluorescence and circular dichroism spectroscopies reveal that the protein is resistant to thermal-induced conformational changes but is particularly sensitive to pH-induced conformational changes; while Asp/Glu and Arg residues may contribute to structural stability, His and Lys residues predominate. Pre-pro-GnRH/GAP is about 30% helix in the range of 2-40 degrees C; however, even at 90 degrees C, the peptide retains nearly 50% of its helix character. There is no evidence for a cooperative transition; for this reason, differential scanning calorimetry failed to yield a defined transition thermogram. Pre-pro-GnRH/GAP apparently does not pass through a transition state as a function of temperature but appears to flex and retain a high percentage of helix structure, resulting in subtle changes in secondary structure. There is no discernible isodichroic point. On either side of the neutral pH range, however, there are dramatic changes in structure that result in nonreversible denaturation of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mitral valve replacement with the St. Jude Medical prosthesis: a 15-year follow-up

BACKGROUND: A retrospective study was conducted to analyze the results of St. Jude Medical mitral valve replacement. METHODS: From January 1979 to December 1989, 870 patients (54% women, 46% men; mean age, 55.8 +/- 6.2 years) underwent mitral valve replacement with the St. Jude Medical prosthesis. Of these operations 616 were isolated mitral valve replacements and 254 were double valve replacements. Coronary artery bypass grafting was performed concomitantly in 55 patients (6.3%). RESULTS: Overall, early mortality was 5.05%, with 4.2% for the isolated mitral valve procedure and 7.08% for the double valve replacement. Follow-up at 15 years was complete in 859 patients (98.74%). Mean follow-up time was 93.5 months, for a total of 6,436 years. Actuarial survival at 15 years was 59.5% +/- 5%, 60.5% +/- 6%, and 56.9% +/- 9%, for the entire group, the isolated mitral valve and double valve procedures, respectively. Multivariate analysis identified age, sex, hospital stay, and preoperative mitral regurgitation as independent prognosis factors for overall mortality. Of 606 patients alive at the latest follow-up, the New York Heart Association class improved significantly (from 67% class III/IV before the operation to 88% class I/II after the operation). All patients received warfarin to maintain an international normalized ratio between 3.5 and 4. The linearized rates (% per patient-year) of thrombosis, thromboembolism, and major hemorrhage were, respectively, 0.21, 0.75, and 0.94 for the entire group; 0.18, 0.67, and 0.88 for the isolated mitral valve operation; and 0.15, 0.92, and 1.08 for the double valve replacement. For the entire group the freedom from thrombosis and thromboembolism at 15 years was 98.1% +/- 1% and 88% +/- 4%, respectively. No case of structural dysfunction occurred. The freedom from paravalvular leak and endocarditis at 15 years was 95.3% +/- 2% and 97.3% +/- 2.4%, respectively. The probability of remaining free from reoperation at 15 years was therefore 95.6% +/- 2.5%. CONCLUSIONS: These results confirm that the St. Jude Medical valve is a reliable prosthesis with very low thrombosis and thromboembolism rates, allowing the use of a low dose of anticoagulation with an international normalized ratio of about 3.     

Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma

We investigated the consequences of Sr2+ binding to the transport sites of sarcoplasmic reticulum (SR) Ca(2+)-ATPase for two fluorescent conformational probes located in different regions of the ATPase. Using SR vesicles in which Lys-515 in the ATPase had been previously labeled with fluorescein 5'-isothiocyanate (FITC), we found that the Sr(2+)-induced a drop in the fluorescein fluorescence of this FITC-labeled ATPase shifted toward lower Sr2+ concentrations than the Sr(2+)-induced rise in Trp fluorescence for the same FITC-labeled ATPase. The curve describing the Sr(2+)-dependent rise in Trp fluorescence had a characteristic asymmetric shape, and the changes in Trp fluorescence occurred in parallel with the activation by Sr2+ of pNPP hydrolysis by the ATPase. Analysis of these results in terms of the simplest scheme describing the sequential binding of the two Sr2+ ions suggests that under the conditions of these experiments, i.e. at neutral pH in the presence of potassium, the Sr(2+)-induced rise in the Trp fluorescence mainly reflected the formation of ATPase with two ions bound to the transport sites, whereas the binding of a single Sr2+ ion was virtually sufficient to reduce the fluorescence of bound FITC to its minimal level.     

Clinical and hemodynamic performance of a totally flexible prosthetic ring for atrioventricular valve reconstruction

A new, totally flexible ring for atrioventricular annuloplasty is described. The technique for its insertion closely follows the principles of Carpentier's selective annulus reconstruction [4]. Ninety-nine such rings have been inserted (47 in the mitral and 52 in the triscuspid position); 45 valves were simultaneously replaced. There were 6 (4 hospital and 2 late) deaths. The thromboembolic incidence was 4.8%. No instances of dehiscence or late ring deterioration have been detected. Thirty-four patients have been recatheterized, 19 of them with mitral rings. The mitral gradients and angiographic findings show the correct functioning of the implanted ring. It is concluded that use of this flexible ring, which adapts to the continuous changes of the normal mitral annulus, produces a more physiological type of valve operation.