PubMed Health⌕ Search

Biomedical subjects

B H Dietrich

Publications and source records attributed to B H Dietrich.

6 recordsLinked to original sources

Tantalus, a novel ASX-interacting protein with tissue-specific functions.

The Drosophila trithorax- and Polycomb-group (trxG and PcG) proteins maintain activated and repressed transcriptional states at specific target gene loci. The Additional sex combs (Asx) gene is of particular interest as it appears to function in both protein complexes and yet its effects on target genes are more restricted. A novel protein, Tantalus (TAN), was identified in a yeast two-hybrid screen for ASX-interacting proteins that might confer tissue-specific ASX functions. TAN contains consensus nuclear localization sites and binds DNA in vitro. However, its subcellular localization varies in a tissue-specific fashion. In salivary glands, TAN is predominantly nuclear and associates with 66 euchromatic sites on polytene chromosomes, more than half of which overlap with ASX. These loci do not include the homeotic genes of the ANT and BX complexes bound by other PcG and trxG proteins. Rather, tan mutant defects are restricted to sensory organs. We show that one of these defects, shared by Asx, is genetically enhanced by Asx. Taken together, the data suggest that TAN is a tissue-specific cofactor for ASX, and that its activity may be partially controlled by subcellular trafficking.

Amino Acid Sequence↗

Patterning of the Drosophila embryo by a homeodomain-deleted Ftz polypeptide.

Homeodomain proteins regulate diverse developmental processes in a wide range of organisms, yet bind in vitro to DNA sequences that are remarkably similar. This has raised the fundamental question of how target gene specificity is achieved in vivo. The Drosophila fushi tarazu protein (Ftz) contains a homeodomain and is required for the formation of alternate segments. We have shown previously that a homeodomain-deleted Ftz polypeptide (Ftz delta HD), incapable of binding DNA in vitro, could regulate endogenous ftz gene expression. Here we test Ftz delta HD activities in a ftz mutant background and find that, surprisingly, Ftz delta HD can directly regulate ftz-dependent segmentation, suggesting that it can control target gene expression through interactions with other proteins. A likely candidate is the pair-rule protein Paired (Prd). Ftz delta HD bound directly to Prd in vitro and required Prd to repress wingless in vivo. These results emphasize the pivotal importance of protein-protein interactions in homeodomain protein function.

Animals↗

Exercise with and without gravitational gradient: evaluation with the new random access mass spectrometer (RAMS).

Gravity adds about 40-50 mmHg perfusion pressure to the arterial supply of the quadriceps muscles in the upright posture. This could have important implications in supply of blood flow during exercise. Recently, we have shown that when subjects exercise in the supine posture the rate of increase in VO2 is considerably slower then when cycling exercise takes place in the upright posture. The most probable explanation for this slower adaptation was the altered perfusion gradient. Indeed, when the perfusion gradient from heart to legs was restored by placing the lower part of the body of supine subjects in a negative pressure chamber, the rate of increase in VO2 returned to upright values. The hypothesis advanced from these studies was that skeletal muscle blood flow was reduced at the onset of supine exercise. Exercise in the microgravity environment of space should be similar to that in the supine posture. The only experiments conducted in space to this date that have addressed the question of cardiorespiratory adaptation to changing work rates were performed on the German D2 mission using the methodology proposed by Stegemann and colleagues. To conduct these experiments, it is necessary to utilize sensitive breath-by-breath technology. Recently, NASA and the Russian space programs have commissioned a new mass spectrometer based system as part of the GASMAP project. It was the purpose of this study to evaluate the new mass spectrometer under conditions in which the gravitational effects on the cardiorespiratory response were being challenged.

Adult↗

Alignment of ventilation and gas fraction for breath-by-breath respiratory gas exchange calculations in exercise.

The effects of correct alignment of the ventilation and fractional gas concentration during breath-by-breath calculation of oxygen uptake (VO2) have been examined during exercise in four subjects, at each of 50, 100, 150, and 200 W. Data were analyzed using lagtimes in the range of 200 to 400 msec to align ventilation with gas fraction. VO2 was markedly affected by lagtime. Calculated values of VO2 at 200 W ranged from 1953 +/- 55 (mean +/- SEM), to 2583 +/- 29, to 2843 +/- 28 ml.min-1 with lagtimes of 200, 310, and 400 msec, respectively. Mean values from a mixing box system did not differ significantly from the mean of the breath-by-breath data collection with a lagtime of 310 msec. Additional computations have shown that temperature correction can markedly affect calculated ventilatory volumes and N2 balance. VO2 was not changed because of the compensation from the calculated effects of changes in lung gas stores.

Algorithms↗

Time domain analysis of oxygen uptake during pseudorandom binary sequence exercise tests.

Pseudorandom binary sequence (PRBS) exercise tests involve repeated switching between two work rates (WR) according to a computer-generated pattern. This paper presents an approach to analysis of O2 uptake (VO2) in the time domain. First, the autocorrelation function (ACF) of the input WR was recognized to be a triangular-shaped pulse that can be taken to be equivalent to a ramp increase followed by a ramp decrease in WR. Then the cross-correlation function of the input (WR) and the output (VO2) was treated as if it were the response to a triangular-shaped pulse. The cross-correlation function was analyzed by fitting a linear summation of the ramp form of a two-component exponential function to this triangular pulse. VO2 responses of eight subjects were obtained from two different PRBS tests, as well as step changes in WR. The first PRBS test consisted of 15 units, each 30 s in duration. Its ACF had a base width of 60 s. The ramp increase-ramp decrease model fit the data throughout the range of response. The second PRBS test had 63 units, each 5 s in duration; thus its ACF base width was 10 s. Again, the ramp model fit adequately. The data from the second PRBS test could be fit by the impulse form of the two-component exponential equation, although the fit in the first 30 s tended to be poorer. The time constants of VO2 dynamics estimated from step and PRBS tests were not significantly different. PRBS tests can be analyzed in the time domain, and the indicators of system dynamics reflect physiological properties similar to those investigated during step changes in WR.

Adult↗

On the estimation of pulmonary blood flow from CO2 production time series.

It may be possible to estimate a nominal pulmonary blood flow (Q) during an exercise stress test via the algorithm used to estimate breath-by-breath alveolar CO2 production. Recently it has been demonstrated that by relating breath-to-breath fluctuations in alveolar CO2 production to breath-to-breath fluctuations in end-tidal CO2, an optimizing parameter related to Q can be determined that can be used to process the CO2 production fluctuations and minimize their variation. However, the reported values of Q using this procedure appear to be biased low. Using a computer simulation of gas exchange, we demonstrate that the estimate of Q is biased low when the nominal lung volume used in the alveolar gas exchange algorithm is too large. Furthermore, alveolar CO2 transport is determined by an integral of alveolar CO2 over the breath time and, thus, is a path-dependent quantity. The use of end-tidal CO2 fluctuations to approximate fluctuations in this integral contributes to an error in the estimation of Q which yields estimates that are biased low. Alternatively, the use of mean alveolar CO2 fluctuations yield more appropriate Q estimates. These results suggest practical implications for estimating effective pulmonary blood flow during an exercise stress test by using breath-to-breath estimates of mean alveolar CO2.

Blood Flow Velocity↗