Genomic structure and cloning of two transcript isoforms of human Sp8

BACKGROUND: The Specificity proteins (Sp) are a family of transcription factors that have three highly conserved zinc-fingers located towards the carboxy-terminal that bind GC-boxes and assist in the initiation of gene transcription. Human Sp1-7 genes have been characterized. Recently, the phenotype of Sp8 null mice has been described, being tailless and having severe truncation of both fore and hind limbs. They also have malformed brains with defective closure of the anterior and posterior neuropore during brain development. RESULTS: The human Sp8 gene is a three-exon gene that maps to 7p21.3, close to the related Sp4 gene. From an osteosarcoma cell line we cloned two transcript variants that use two different first exons and have a common second exon. One clone encodes a 508-residue protein, Sp8L (isoform 1) and the other a shorter 490-residue protein, Sp8S (isoform 2). These two isoforms are conserved being found also in mice and zebrafish. Analysis of the Sp8L protein sequence reveals an amino-terminal hydrophobic Sp-motif that is disrupted in Sp8S, a buttonhead box and three C(2)H(2 )zinc-fingers. Sp8 mRNA expression was detected in a wide range of tissues at a low level, with the highest levels being found in brain. Treatment of the murine pluripotent cell line C3H10T1/2 with 100 ng/mL BMP-2 induced Sp8 mRNA after 24 hours. CONCLUSIONS: There is conservation of the two Sp8 protein isoforms between primates, rodents and fish, suggesting that the isoforms have differing roles in gene regulation. Sp8 may play a role in chondrogenic/osteoblastic differentiation in addition to its role in brain and limb development

Expression of alternatively spliced isoforms of human Sp7 in osteoblast-like cells

BACKGROUND: Osteogenic and chondrocytic differentiation involves a cascade of coordinated transcription factor gene expression that regulates proliferation and matrix protein formation in a defined temporo-spatial manner. Bone morphogenetic protein-2 induces expression of the murine Osterix/Specificity protein-7 (Sp7) transcription factor that is required for osteoblast differentiation and bone formation. Regulation of its expression may prove useful for mediating skeletal repair. RESULTS: Sp7, the human homologue of the mouse Osterix gene, maps to 12q13.13, close to Sp1 and homeobox gene cluster-C. The first two exons of the 3-exon gene are alternatively spliced, encoding a 431-residue long protein isoform and an amino-terminus truncated 413-residue short protein isoform. The human Sp7 protein is a member of the Sp family having 78% identity with Sp1 in the three, Cys2-His2 type, DNA-binding zinc-fingers, but there is little homology elsewhere. The Sp7 mRNA was expressed in human foetal osteoblasts and craniofacial osteoblasts, chondrocytes and the osteosarcoma cell lines HOS and MG63, but was not detected in adult femoral osteoblasts. Generally, the expression of the short (or beta) protein isoform of Sp7 was much higher than the long (or alpha) protein isoform. No expression of either isoform was found in a panel of other cell types. However, in tissues, low levels of Sp7 were detected in testis, heart, brain, placenta, lung, pancreas, ovary and spleen. CONCLUSIONS: Sp7 expression in humans is largely confined to osteoblasts and chondrocytes, both of which differentiate from the mesenchymal lineage. Of the two protein isoforms, the short isoform is most abundant

Data base management system analysis and performance testing with respect to NASA requirements

Several candidate Data Base Management Systems (DBM's) that could support the NASA End-to-End Data System's Integrated Data Base Management System (IDBMS) Project, later rescoped and renamed the Packet Management System (PMS) were evaluated. The candidate DBMS systems which had to run on the Digital Equipment Corporation VAX 11/780 computer system were ORACLE, SEED and RIM. Oracle and RIM are both based on the relational data base model while SEED employs a CODASYL network approach. A single data base application which managed stratospheric temperature profiles was studied. The primary reasons for using this application were an insufficient volume of available PMS-like data, a mandate to use actual rather than simulated data, and the abundance of available temperature profile data

Emergency escape system uses self-braking mechanism on fixed cable

Slide-wire system with a twist level slide device incorporates automatic descent and braking for the safe and rapid evacuation of personnel from tall structures. This device is used on any tall structure that might require emergency evacuation. It is also used to transfer materials and equipment

Parameter space exploration of an ocean general circulation model using an isopycnal mixing parameterization

In this study we have employed statistical methods to efficiently design experiments and analyze output of an ocean general circulation model that uses an isopycnal mixing parameterization. Full ranges of seven inputs are explored using 51 numerical experiments. Fifteen of the cases fail to reach satisfactory equilibria. These are attributable to numerical limitations specific to the isopycnal model. Statistical approximating functions are evaluated using the remaining cases to determine the dependency of each of the six scalar outputs on the inputs. With the exception of one output, the approximating functions perform well. Known sensitivities, particularly the importance of diapycnal (vertical) eddy diffusivity and wind stress, are reproduced. The sensitivities of the model to two numerical constraints specific to the isopycnal parameterization, maximum allowable isopycnal slope and horizontal background eddy diffusivity, are explored. Isopycnal modelling issues, convection reduction and the Veronis effect, are examined and found to depend crucially on the isopycnal modelling constraints

Prospects for Measuring Differential Rotation in White Dwarfs Through Asteroseismology

We examine the potential of asteroseismology for exploring the internal rotation of white dwarf stars. Data from global observing campaigns have revealed a wealth of frequencies, some of which show the signature of rotational splitting. Tools developed for helioseismology to use many solar p-mode frequencies for inversion of the rotation rate with depth are adapted to the case of more limited numbers of modes of low degree. We find that the small number of available modes in white dwarfs, coupled with the similarity between the rotational-splitting kernels of the modes, renders direct inversion unstable. Accordingly, we adopt what we consider to be plausible functional forms for the differential rotation profile; this is sufficiently restrictive to enable us to carry out a useful calibration. We show examples of this technique for PG 1159 stars and pulsating DB white dwarfs. Published frequency splittings for white dwarfs are currently not accurate enough for meaningful inversions; reanalysis of existing data can provide splittings of sufficient accuracy when the frequencies of individual peaks are extracted via least-squares fitting or multipeak decompositions. We find that when mode trapping is evident in the period spacing of g modes, the measured splittings can constrain dOmega/dr.Comment: 26 pages, 20 postscript figures. Accepted for publication in The Astrophysical Journa

Wave chaos in rapidly rotating stars

Effects of rapid stellar rotation on acoustic oscillation modes are poorly understood. We study the dynamics of acoustic rays in rotating polytropic stars and show using quantum chaos concepts that the eigenfrequency spectrum is a superposition of regular frequency patterns and an irregular frequency subset respectively associated with near-integrable and chaotic phase space regions. This opens new perspectives for rapidly rotating star seismology and also provides a new and potentially observable manifestation of wave chaos in a large scale natural system.Comment: 5 pages, 3 figures; accepted for publication in Phys. Rev.

Clinical impact of double protease inhibitor boosting with Lopinavir/Ritonavir and Amprenavir as part of salvage antiretroviral therapy

Purpose: Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone. Method: Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician. Results: Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p = .12) or with time to virologic rebound (adjusted HR = 1.46, p = .34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p = .03). In a subset of 27 patients, the median LPV Ctrough was significantly lower in patients receiving APV (p = .04), and the median APV Ctrough was reduced compared to reported controls. Conclusion: Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings

The effects of sodium bicarbonate ingestion on swimming interval performance in trained competitive swimmers

The use of sodium bicarbonate (NaHCO) supplementation to improve repeated high-intensity performance is recommended; however, most swimming performance studies examine time trial efforts rather than repeated swims with interspersed recovery that are more indicative of training sessions. The aim of this study, therefore, was to investigate the effects of 0.3 g.kg BM NaHCO supplementation on sprint interval swimming (8 × 50 m) in regionally trained swimmers. Fourteen regionally competitive male swimmers (body mass (BM): 73 ± 8 kg) volunteered for this double-blind, randomised, crossover designed study. Each participant was asked to swim 8 × 50 m (front crawl) at a maximum intensity from a diving block, interspersed with 50 m active recovery swimming. After one familiarisation trial, this was repeated on two separate occasions whereby participants ingested either 0.3 g.kg BM NaHCO or 0.05 g.kg BM sodium chloride (placebo) in solution 60 min prior to exercise. Whilst there were no differences in time to complete between sprints 1-4 (p > 0.05), improvements were observed in sprint 5 (p = 0.011; ES = 0.26), 6 (p = 0.014; ES = 0.39), 7 (p = 0.005; ES = 0.60), and 8 (p = 0.004; ES = 0.79). Following NaHCO supplementation, pH was greater at 60 min (p < 0.001; ES = 3.09), whilst HCO was greater at 60 min (p < 0.001; ES = 3.23) and post-exercise (p = 0.016; ES = 0.53) compared to placebo. These findings suggest NaHCO supplementation can improve the latter stages of sprint interval swimming performance, which is likely due to the augmentation of pH and HCO prior to exercise and the subsequent increase in buffering capacity during exercise