A specific decrease in collagen synthesis in acutely fasted, vitamin C-supplemented, guinea pigs

Weight loss often results from various experimental conditions including scurvy in guinea pigs, where we showed that decreased collagen synthesis was directly related to weight loss, rather than to defective proline hydroxylation (Chojkier, M., Spanheimer, R., and Peterkofsky, B. (1983) J. Clin. Invest. 72, 826-835). In the study described here, this effect was reproduced by acutely fasting normal guinea pigs receiving vitamin C, as determined by measuring collagen and non-collagen protein production after labeling tissues in vitro with [3H]proline. Collagen production (dpm/microgram of DNA) decreased soon after initiating fasting and by 96 h it had reached levels 8-12% of control values. Effects on non-collagen protein were much less severe, so that the percentage of collagen synthesis relative to total protein synthesis was 20-25% of control values after a 96-h fast. These effects were not due to changes in the specific radioactivity of free proline. Refeeding reversed the effects on non-collagen protein production within 24 h, but collagen production did not return to normal until 96 h. The effect of fasting on collagen production was independent of age, sex, ascorbate status, species of animal, and type of connective tissue and also was seen with in vivo labeling. Pulse-chase experiments and analysis of labeled and pre-existing proteins by gel electrophoresis showed no evidence of increased collagen degradation as a result of fasting. Procollagen mRNA was decreased in tissues of fasted animals as determined by cell-free translation and dot-blot hybridization with cDNA probes. In contrast, there was no decrease in translatable mRNAs for non-collagen proteins. These results suggest that loss of nutritional factors other than vitamin C lead to a rapid, specific decrease in collagen synthesis mainly through modulation of mRNA levels.     

Estimate of mean tissue O2 consumption at onset of exercise in males

A mathematical model has been developed that permitted the calculation of the flow-weighted mean tissue O2 consumption (VO2T) at the onset of a step increase in work rate. From breath-by-breath measurements of alveolar O2 consumption (VO2A) and cardiac output (Q) by impedance cardiography and assumptions about the site of depletion of O2 stores, the rate of change in O2 stores (VO2s) was determined. The sum of VO2A + VO2s = VO2T. Six very fit males performed six repetitions of each of two step increases in work rate. STlo was a transition from rest to 100-W cycling; SThi was a transition from 100- to 200-W cycling. For each work rate transition, the responses of VO2A and Q were averaged over the six repetitions of each subject and the model was solved to yield VO2T. The responses of VO2A, VO2T, and Q after the increase in work rate were fit with a monoexponential function. This function included a time constant and time delay, the sum of which gave the mean response time (MRT). In the STlo test, the MRT of VO2A (24.9 +/- 1.1 s, mean +/- SE) was longer than that of VO2T (15.3 +/- 1.3 s) and of Q (16.5 +/- 6.5 s) (P less than 0.05). The MRT of VO2T and Q did not differ significantly. Also for SThi, the MRT of VO2A (34.4 +/- 3.3 s) was significantly longer than that of VO2T (30.0 +/- 3.4 s) (P less than 0.05). The MRT of VO2T and Q (30.3 +/- 5.5 s) were not significantly different at this work rate either.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inositol 1,4,5-trisphosphate is not effective in releasing calcium from skeletal sarcoplasmic reticulum microsomes

Regulation of many cell systems has been shown to be mediated by Inositol 1,4,5-trisphosphate which causes a release of calcium from intracellular sites. We have shown that release of Ca2+ from sarcoplasmic reticulum microsomes was not stimulated by IP3. The phorbol ester, TPA, also had no effect on Ca2+ release or Ca2+ ATPase activity. Thus, it is unlikely that the breakdown of polyphosphatidylinositides serves as a second messenger to mediate release of Ca2+ in skeletal muscle.     

Neurospecific proteins in human malignant brain tumors

The content of neurospecific proteins S-100, GFA and D2 was measured in malignant cerebral tumors by electrophoresis with the use of monospecific antisera. Concomitant measurement of proteins S-100 and GFA is a more reliable diagnostic criterion as to the tumor histogenesis than study of each protein alone. D2 protein appeared to be the most stable specific marker.     

Mechanism and dynamics of conformational ordering in xanthan polysaccharide

The thermally induced order-disorder transition of xanthan (extracellular bacterial polysaccharide from Xanthomonas campestris) has been investigated by optical rotation, differential scanning calorimetry, stopped-flow reaction kinetics and low-angle laser light scattering, and the results have been analysed in terms of Zimm -Bragg helix-coil transition theory. The reciprocal of the transition midpoint temperature (Tm) varies linearly with the logarithm of cation (K+) the salt dependence of Tm, is in agreement with Manning polyelectrolyte theory the ordered structure. The associated increase in cation binding, calculated from the salt dependence of tm, is in agreement with the Manning polyelectrolyte theory for one of the candidate structures from X-ray diffraction, a 5(1) single helix stabilized by packing of side-chains along the polymer backbone, but not for the alternative double-helix structure that has also been proposed. At each salt concentration, the two fundamental parameters of the Zimm -Bragg theory, s and sigma, were calculated. The equilibrium constant for growth of the ordered structure (s) is derived directly from calorimetric measurement of transition enthalpy (delta Hcal ), and sigma, which quantifies the relative instability of the helix nucleus, is derived from the ratio of delta Hcal to the apparent transition enthalpy (delta Happ ) obtained by van't Hoff analysis of the optical rotation data. The temperature course of conformational ordering calculated theoretically is in good quantitative agreement with experimental results from both optical rotation and scanning calorimetry. The calculated average length of stable, ordered chain-sequences increases with decreasing temperature, but equals or exceeds the total chain length from light scattering only at temperatures more than approximately equal to 70 K below Tm, suggesting that ordered and disordered regions may co-exist within the same xanthan molecule. Consistent with this interpretation, the observed rate of conformational ordering increases sharply under conditions where the starting solution for dynamic measurements is partially ordered, suggesting that ordered sequences within each chain may act as helix nuclei for adjacent disordered regions, so that helix growth, rather than the slower nucleation process, becomes rate limiting.     

Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus

The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKR^kd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (C^ko) virus but had no effect on the growth of either wild-type (WT) or V knockout (V^ko) virus. Increased growth of the C^ko virus in PKR^kd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, V^ko, or especially C^ko virus caused significantly less apoptosis in PKR^kd cells than in PKR-sufficient cells. Although apoptosis induced by C^ko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of C^ko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR.     

The steroidal glycoalkaloid α-tomatine

The literature relating to chemical, biochemical and biological aspects of the steroidal glycoalkaloid, α-tomatine, is reviewed. The alkaloid, which can be used as a starting compound for the synthesis of steroidal hormones, is toxic to a wide range of living organisms. The significance of tomatine to plants which elaborate it is discussed and some possible uses of the compound are mentioned.     

Population increases of buffalo and wildebeest in the Serengeti*

Censuses of buffalo and wildebeest in the Serengeti-Mara region have been carried out by various workers at intervals since 1958. The methods of these censuses, which normally employ a total count, are described and the errors inherent in such techniques are analysed in detail. After the appropriate corrections had been made the results showed that both populations have increased considerably over the years 1961–1971.