Use of recombinant interferon-α in Human Immunodeficiency Virus (HIV)-infected individuals

Rationale and objective Interferon alpha (IFN-) has anti-retroviral activity and is a possible HIV infection-limiting factor. The aim of this work is to prevent or delay disease progression in asymptomatic Human Immunodeficiency Virus (HIV) carriers.Design and interventions Recombinant IFN alpha-2b (3×10⁶ IU 3 times weekly) was compared. to no treatment (control) in a randomized trial. Endpoints were: (i) appearance of any CDC group IV symptoms and (ii) disease progression (which excluded shifts to group IVC2 or reversible IVA, or IVB). The trial lasted from October 1987 to February 1992.Setting The trial was performed at the Santiago de las Vegas sanatorium, a specialized institution for the care of HIV-infected and AIDS patients.Population Subjects were anti-HIV-1 seropositive, Western blot-confirmed, asymptomatic (CDC group II), or with generalized lymphadenopathies (CDC group III). The groups had 79 (control) and 71 (IFN) patients.Main results Long-term IFN- treatments significantly reduced the proportion of patients who shifted to any group IV (control: 46/79; IFN: 14/71;p<0.001) or developed AIDS (control: 27/79; IFN: 12/71;p<0.05). IFN also delayed progression to AIDS (95% confidence interval for 0.5 probability of progression) from 67–83 to 116–180 months after infection. The IFN group had significantly less opportunistic infections and non-infectious complications. CD4 cell count and hemoglobin decreased in the control but not in the IFN group. Fewer IFN-treated patients developed positive serum HIV antigen detection.Conclusion IFN alpha treatment during the early stages of infection seems to be beneficial to the patients.Abbreviations CI confidence interval - AIDS Acquired Immunodeficiency syndrome - HIV Human Immunodeficiency Virus - IFN Interferon - CDC Center for Disease Control (USA) - SD standard deviation     

Characterization of the effectors required for stable inheritance of Streptococcus pyogenes pSM19035-derived plasmids in Bacillus subtilis

The low-copy-number and broad-host-range pSM19035-derived plasmid pBT233 is stably inherited in Bacillus subtilis cells. Two distinct regions, segA and segB, enhance the segregational stability of the plasmid. Both regions function in a replicon-independent manner. The maximization of random plasmid segregation is accomplished by the recombination proficiency of the host or the presence of the pBT233 segA region. The segA region contains two open reading frames (or) [ and ]. Inactivation or deletion of or results in SegA^– plasmids. Better than random segregation requires an active segB region. The segB region contains two ors (or and or). Inactivation of either of the orfs does not lead to an increase in cell death, but or^– plasmids are randomly segregated. These results suggest that pBT233 stabilization relies on a complex system involving resolution of plasmid oligomers (segA) and on the function(s) encoded by the segB region.     

Replication of the promiscuous plasmid pLSI: a region encompassing the minus origin of replication is associated with stable plasmid inheritance

Deletion of a region of the promiscuous plasmid pLS1 encompassing the initiation signals for the synthesis of the plasmid lagging strand led to plasmid instability in Streptococcus pneumoniae and Bacillus subtilis. This defect could not be alleviated by increasing the number of copies (measured as double-stranded plasmid DNA) to levels similar to those of the wild-type plasmid pLS1. Our results indicate that in the vicinity of, or associated with the single-stranded origin region of pLS1 there is a plasmid component involved in its stable inheritance. Homology was found between the DNA gyrase binding site within the par region of plasmid pSC101 and the pLS1 specific recombination site RS_R.     

Temperate rainforest lichens in New Zealand: high thallus water content can severely limit photosynthetic CO2 exchange

CO₂ exchange rate in relation to thallus water content (WC, % of dry weight) was determined for 22 species of lichens, mainly members of the genera Pseudocyphellaria and Sticta, from a temperate rainforest, Urewere National Park, New Zealand. All data were obtained in the field, either using a standard technique in which the lichens were initially wetted (soaked or sprayed, then shaken) and allowed to slowly dry, or from periodic measurements on samples that were continuously exposed in their natural habitat. A wide range of WC was found, with species varying from 357 to 3360% for maximal WC in the field, and from 86 to 1300% for optimal WC for photosynthesis. Maximal WC for lichens, wetted by the standard technique, were almost always much less than the field maxima, due to the presence of water on the thalli. The relationships between CO₂ exchange rate and WC could be divided into four response types based on the presence, and degree, of depression of photosynthesis at high WC. Type A lichens showed no depression, and Type B only a little at maximal WC. Type C had a very large depression and, at the highest WC, CO₂ release could occur even in the light. Photosynthetic depression commenced soon after optimal WC was reached. Type D lichens showed a similar depression but the response curve had an inflection so that net photosynthesis was low but almost constant, and never negative, at higher WC. There was little apparent relationship between lichen genus or photobiont type and the response type. It was shown that high WC does limit photosynthetic CO₂ uptake under natural conditions. Lichens, taken directly from the field and allowed to dry under controlled conditions, had net photosynthesis rates that were initially strongly inhibited but rose to an optimum, before declining at low WC. The limiting effects of high WC were clearly shown when, under similar light conditions, severe photosynthetic depression followed a brief, midday, rain storm. Over the whole measuring period the lichens were rarely at their optimal WC for photosynthesis, being mostly too wet or, occasionally, too dry. Photosynthetic performance by the lichens exposed in the field was similar to that expected from the relationship between the photosynthetic rate and WC established by the standard procedure.     

Genetic basis of sodium exclusion and sodium tolerance in yeast. A model for plants

A yeast strain carrying disruptions in TRK1 and ENA genes was very sensitive to Na⁺ because uptake discriminated poorly between K⁺ and Na⁺, and Na⁺ efflux was insignificant. Transformation with TRK1 and ENA1 restored discrimination, Na⁺ efflux and Na⁺ tolerance. Increasing external Ca²⁺ increased Na⁺ tolerance almost in the same proportion in TRK1 enal cells and in trkl ENAI cells, suggesting an unspecific effect of this cation. By using a vacuolar ATPase mutant, the role of the vacuole in Na⁺ tolerance was also demonstrated. The yeast model of Na⁺ exclusion and Na⁺ tolerance may be extended to plants.     

Communal Roosting of Wintering Red Kites Milvus milvus (Aves,Accipitridae): Social Feeding Strategies for the Exploitation of Food Resources

Social feeding strategies of wintering red kites are analyzed in relation to age, food, roost-sites and differences from kite residents. Whereas young and adult wintering kites gathered at roost sites almost daily, adult residents did not, and immature residents only occasionally. Kites using roost sites feed more often on prey prelocated by others, while lone roosters also forage and discover food alone. After finding food, kites tend to shift to a new roost site and foraging area. Two details of the ‘information centre’ hypothesis are confirmed in our study: carcasses are unpredictably found patches, divisible between several individuals. But carcasses disappeared fast in the study area, and no increase with time in the number of birds consuming a carcass was observed, so that information transmission was unconfirmed. When kites leave the roost in groups no leader is detectable. It seems that other types of social foraging are operating, and the model best matching our results is network foraging.     

Cyanobacteria of Rocks and Soils of the Orinoco Lowlands and the Guayana Uplands,Venezuela

The occurrence of 23 cyanobacterial species, belonging to 9 different genera and 5 cyanobacterial lichen species of 5 different genera on exposed, open rock surfaces of inselbergs and on soil in savannas of the Orinoco lowlands and the Guayana uplands is described. Their distribution patterns and frequency within the different habitats are given. The filamentous procaryotic blue-green algae/cyanobacteria Stigonema ocellatum and Scytonema crassum, together with the unicellular cyanobacterium Gloeocapsa sanguinea were the most frequent species on rocks, whereas the filamentous cyanobacterium, Schizothrix telephoroides, dominated in cyanobacterial mats on the savanna soil. All species showed intensively coloured sheaths, either brown or yellow in the case of Stigonema ocellatum and Scytonema crassum, or red in Gloeocapsa sanguinea and Schizothrix telephoroides. In addition, a number of cyanobacterial lichens occurred.     

Chromosome 14 and late-onset familial Alzheimer disease (FAD)

Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score ≤ –2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset ≥60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds.     

Dark induction of nitrate reductase in the halophilic alga Dunaliella salina

The effect of nitrogen starvation on the NO₃-dependent induction of nitrate reductase (NR) and nitrite reductases (NIR) has been investigated in the halophilic alga Dunaliella salina. When D. salina cells previously grown in a medium with NH ₄ ⁺ as the only nitrogen source (NH ₄ ⁺ -cells) were transferred into NO ₃ ^? medium, NR was induced in the light. In contrast, when cells previously grown in N-free medium were transferred into a medium containing NO ₃ ^? , NR was induced in light or in darkness. Nitrate-dependent NR induction, in darkness, in D. salina cells previously grown at a photon flux density of 500 umol · m^?2 s^?1 was observed after 4 h preculture in N-free medium, whilst in cells grown at 100 umol · m^?2 s^?1 NR induction was observed after 7–8 h. An inhibitor of mRNA synthesis (6-methylpurine) did not inhibit NO ₃ ^? -induced NR synthesis when the cells, previously grown in NH ₄ ⁺ medium, were transferred into NO ₃ ^? medium (at time 0 h) after 4-h-N starvation. However, when 6-methylpurine was added simultaneously with the transfer of the cells from NH ₄ ⁺ to NO ₃ ^? medium (at time 0 h), NO ₃ ^? induced NR synthesis was completely inhibited. The activity of NIR decreased in N-starved cells and the addition of NO ₃ ^? to those cells greatly stimulated NIR activity in the light. The ability to induce NR in darkness was observed when glutamine synthetase activity reached its maximal level during N starvation. Although cells grown in NO ₃ ^? medium exhibited high NR activity, only 0.33% of the total NR was found in intact chloroplasts. We suggest that the ability, to induce NR in darkness is dependent on the level of N starvation, and that NR in D. salina is located in the cytosol. Light seems to play an indirect regulatory role on NO ₃ ^? uptake and NR induction due to the expression of NR and NO ₃ ^? -transporter mRNAs.     

Expression of conformationally constrained adhesion peptide in an antibody CDR loop and inhibition of natural killer cell cytotoxic activity by an antibody antigenized with the RGD motif.

We report that an antibody engineered to express three Arg-Gly-Asp (RGD) repeats in the third complementarity-determining region of the heavy chain (antigenized antibody) efficiently inhibits the lysis of human erythroleukemia K-562 cells by natural killer (NK) cells. Synthetic peptides containing RGD did not inhibit. Inhibition was specific for the (RGD)3-containing loop and required simultaneous occupancy of the Fc receptor (CD16) on effector cells. The antigenized antibody inhibited other forms of cytotoxicity mediated by NK cells but not cytotoxicity mediated by major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL). A three-dimensional model of the engineered antibody loop shows the structure and physicochemical characteristics probably required for the ligand activity. The results indicate that an RGD motif is involved in the productive interaction between NK and target cells. Moreover, they show that peptide expression in the hypervariable loops of an antibody molecule is an efficient procedure for stabilizing oligopeptides within a limited spectrum of tertiary structures. This is a new approach towards imparting ligand properties to antibody molecules and can be used to study the biological function and specificity of short peptide motifs, including those involved in cell adhesion.