Computer simulation of the effect of dDAVP with saline loading on fluid balance after 24-hour head-down tilt

Fluid loading (FL) before Shuttle reentry is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during reentry and postflight. The fluid load consists of water and salt tablets equivalent to 32 oz (946 ml) of isotonic saline. However, the effectiveness of this countermeasure has been observed to decrease with the duration of spaceflight. The countermeasure's effectiveness may be improved by enhancing fluid retention using analogs of vasopressin such as lypressin (LVP) and desmopressin (dDAVP). In a computer simulation study reported previously, we attempted to assess the improvement in fluid retention obtained by the use of LVP administered before FL. The present study is concerned with the use of dDAVP. In a recent 24-hour, 6 degree head-down tilt (HDT) study involving seven men, dDAVP was found to improve orthostatic tolerance as assessed by both lower body negative pressure (LBNP) and stand tests. The treatment restored Luft's cumulative stress index (cumulative product of magnitude and duration of LBNP) to nearly pre-bedrest level. The heart rate was lower and stroke volume was marginally higher at the same LBNP levels with administration of dDAVP compared to placebo. Lower heart rates were also observed with dDAVP during stand test, despite the lower level of cardiovascular stress. These improvements were seen with only a small but significant increase in plasma volume of approximately 3 percent. This paper presents a computer simulation analysis of some of the results of this HDT study.     

Poliovirus-induced intracellular alkalinization involves a proton ATPase and protein phosphorylation

We reported previously that poliovirus infection induces alkalinization in HeLa cells and that an alkaline intracellular pH (pHi) promoted viral replication. Additional experiments were carried out to understand the underlying mechanism. Virus-infected or control monolayer cultures were incubated with nominally bicarbonate-free Eagle's minimal essential medium (MEM) buffered with N-2-hydroxyethylpiperazine-N-3-ethanesulfonic acid (HEPES), and immediately following preincubations, changes in pHi were monitored via benzoic acid uptake around 2 h postinfection. The absence of pH increase in cells infected with ultraviolet light-inactivated virus (UV-virus) indicated that viral gene expression was required for this effect. On the other hand, lack of effect of 3 mM guanidine, an inhibitor of poliovirus-specific RNA but not protein synthesis, suggested that translation of input viral genome RNA is sufficient for the pH increase. Activation of Na⁺/H⁺ exchange, Cl^?HCO^?₃ exchange, or H⁺-ATPase was considered as possible mechanisms by which alkalinization occurs in virus-infected cells. Na⁺/H⁺ exchange was excluded because the pH effect occurred in a Na⁺/H⁺ exchange deficient HeLa cell mutant. Similarly, Cl^?/HCO^?₃ exchange was excluded because virus-specific alkalinization was evident in the presence of Cl^? or bicarbonate deficient medium and was not associated with an increase in HCO^?₃ uptake or a decrease in Cl^? uptake. Lack of dependence on Na⁺, abrogation by 10 μM 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl), and resistance to 1 mM vandate suggested that this effect was due to the activation of a vacuolar-type (V) proton ATPase. Studies using protein kinase inhibitors indicated that activation of the ATPase in virus-infected cells probably involved protein kinase C-mediated phosphorylation. © 1993 Wiley-Liss, Inc.     

Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.

Interaction with the CD4 receptor enhances the exposure on the human immunodeficiency type 1 gp120 exterior envelope glycoprotein of conserved, conformation-dependent epitopes recognized by the 17b and 48d neutralizing monoclonal antibodies. The 17b and 48d antibodies compete with anti-CD4 binding antibodies such as 15e or 21h, which recognize discontinuous gp120 sequences near the CD4 binding region. To characterize the 17b and 48d epitopes, a panel of human immunodeficiency virus type 1 gp120 mutants was tested for recognition by these antibodies in the absence or presence of soluble CD4. Single amino acid changes in five discontinuous, conserved, and generally hydrophobic regions of the gp120 glycoprotein resulted in decreased recognition and neutralization by the 17b and 48d antibodies. Some of these regions overlap those previously shown to be important for binding of the 15e and 21h antibodies or for CD4 binding. These results suggest that discontinuous, conserved epitopes proximal to the binding sites for both CD4 and anti-CD4 binding antibodies become better exposed upon CD4 binding and can serve as targets for neutralizing antibodies.     

Hand preference in capuchin monkeys varies with age

The purpose of this research was to examine the influence of age on hand preference in capuchin monkeys (Cebus apella). Twenty-two capuchins, aged 6 months to 30 years, were presented with a task that involved reaching for food and a task that involved using sponging tools to absorb juice. Adults exhibited a greater percentage of right-handed actions in each task than did immature subjects. Adults also exhibited a stronger lateral bias than did immature subjects in the sponging task. These results are consistent with hypotheses: a) adult capuchin monkeys are biased toward use of their right hand for reaching; b) adult capuchins exhibit a greater incidence of right-hand preference than do immature capuchins; and c) primates exhibit age-related differences in the strength and direction of hand preference in tasks that involve the use of tools.     

High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). Up to now 14 different mutations have been described. In an effort to investigate the molecular epidemiology of AIP we have undertaken a systematic study of different exons of the PBGD gene from a large number of unrelated patients. Here, exon 8 from 82 unrelated Dutch and French AIP patients was examined using single strand confirmation polymorphism analysis (SSCP) after polymerase chain reaction (PCR) amplification. A single base mutation, C to T, at position 346 of the sequence coding for PBGD was observed in 15 Dutch families but in only 1 French family. A simple PCR assay is described to facilitate the diagnosis of this common mutation at the DNA level.     

Pan-Arctic soil moisture control on tundra carbon sequestration and plant productivity

Long-term atmospheric CO₂ concentration records have suggested a reduction in the positive effect of warming on high-latitude carbon uptake since the 1990s. A variety of mechanisms have been proposed to explain the reduced net carbon sink of northern ecosystems with increased air temperature, including water stress on vegetation and increased respiration over recent decades. However, the lack of consistent long-term carbon flux and in situ soil moisture data has severely limited our ability to identify the mechanisms responsible for the recent reduced carbon sink strength. In this study, we used a record of nearly 100 site-years of eddy covariance data from 11 continuous permafrost tundra sites distributed across the circumpolar Arctic to test the temperature (expressed as growing degree days, GDD) responses of gross primary production (GPP), net ecosystem exchange (NEE), and ecosystem respiration (ER) at different periods of the summer (early, peak, and late summer) including dominant tundra vegetation classes (graminoids and mosses, and shrubs). We further tested GPP, NEE, and ER relationships with soil moisture and vapor pressure deficit to identify potential moisture limitations on plant productivity and net carbon exchange. Our results show a decrease in GPP with rising GDD during the peak summer (July) for both vegetation classes, and a significant relationship between the peak summer GPP and soil moisture after statistically controlling for GDD in a partial correlation analysis. These results suggest that tundra ecosystems might not benefit from increased temperature as much as suggested by several terrestrial biosphere models, if decreased soil moisture limits the peak summer plant productivity, reducing the ability of these ecosystems to sequester carbon during the summer.     

Carbon uptake in Eurasian boreal forests dominates the high-latitude net ecosystem carbon budget

Arctic-boreal landscapes are experiencing profound warming, along with changes in ecosystem moisture status and disturbance from fire. This region is of global importance in terms of carbon feedbacks to climate, yet the sign (sink or source) and magnitude of the Arctic-boreal carbon budget within recent years remains highly uncertain. Here, we provide new estimates of recent (2003–2015) vegetation gross primary productivity (GPP), ecosystem respiration (R_eco), net ecosystem CO₂ exchange (NEE; R_eco − GPP), and terrestrial methane (CH₄) emissions for the Arctic-boreal zone using a satellite data-driven process-model for northern ecosystems (TCFM-Arctic), calibrated and evaluated using measurements from >60 tower eddy covariance (EC) sites. We used TCFM-Arctic to obtain daily 1-km² flux estimates and annual carbon budgets for the pan-Arctic-boreal region. Across the domain, the model indicated an overall average NEE sink of −850 Tg CO₂-C year⁻¹. Eurasian boreal zones, especially those in Siberia, contributed to a majority of the net sink. In contrast, the tundra biome was relatively carbon neutral (ranging from small sink to source). Regional CH₄ emissions from tundra and boreal wetlands (not accounting for aquatic CH₄) were estimated at 35 Tg CH₄-C year⁻¹. Accounting for additional emissions from open water aquatic bodies and from fire, using available estimates from the literature, reduced the total regional NEE sink by 21% and shifted many far northern tundra landscapes, and some boreal forests, to a net carbon source. This assessment, based on in situ observations and models, improves our understanding of the high-latitude carbon status and also indicates a continued need for integrated site-to-regional assessments to monitor the vulnerability of these ecosystems to climate change.     

Hydrolysis of Butteroil by Immobilized Lipase Using a Hollow-Fiber Reactor: Part VI. Multiresponse Analyses of Temperature and pH Effects

A lipase from Aspergillus niger, immobilized by physical adsorption on hydrophobic hollow fibers made of microporous polypropylene, was used to effect the hydrolysis of the glycerides of melted butterfat at 40, 50, 55, and 60°C (pH 7.0), and at pH 3.0, 4.0, 5.0, 7.0, 8.0, and 9.0 (40°C). McIlvane buffer and melted butterfat were pumped cocurrently through the hollow fiber reactor. The concentrations of ten different free fatty acids in the effluent oil stream were measured by HPLC. Multiresponse nonlinear regression methods were employed to fit the data to multisubstrate rate expressions derived from a Ping Pong Bi Bi mechanism in which the rate controlling step is deacylation of the enzyme. Thermal deactivation of the immobilized lipase was also included in the mathematical model of reactor performance. A postulated normal distribution of v_max with respect to the number of carbon atoms of the fatty acid residue (with an additive correction for the number of double bonds) was found to provide the best statistical fit of the data. The models developed can be used to independently predict the effects of either the pH or the temperature, as well as the reactor space time and the time elapsed after immobilization, on the free fatty acid profile of the lipolyzed butteroil product.