Antibodies against calcium-regulating hormones in infectious-allergic forms of bronchial asthma

Antibodies to calcitonin, parathyroid hormone and cortisol are detected in acute stage of infection-caused bronchial asthma. The appearance of antibodies is paralleled by marked hypercalcaemia. The antibodies may bind excessive hormones in the blood, preventing further hormonal imbalance. Ten-day treatment with glucocorticoids decreased the amount of antibodies possibly due to normalization of hormonal secretion and restoration of their balance. As a result, calcium blood levels returned to normal.     

The systematic approach to describing conformational rearrangements in G-quadruplexes

Conformational changes in DNA G-quadruplex (GQ)-forming regions affect genome function and, thus, compose an interesting research topic. Computer modelling may yield insight into quadruplex folding and rearrangement, particularly molecular dynamics simulations. Here, we show that specific parameters, which are distinct from those commonly used in DNA conformational analyses, must be introduced for adequate interpretation and, most importantly, convenient visual representation of the quadruplex modelling results. We report a set of parameters that comprehensively and systematically describe GQ geometry in dynamics. The parameters include those related to quartet planarity, quadruplex twist, and quartet stacking; they are used to quantitatively characterise various types of quadruplexes and rearrangements, such as quartet distortion/disruption or deviation/bulging of a single nucleotide from the quartet plane. Our approach to describing conformational changes in quadruplexes using the new parameters is exemplified by telomeric quadruplex rearrangement, and the benefits of applying this approach to analyse other structures are discussed.     

Effect of trehalose on the phase properties of hydrated and lyophilized dipalmitoylphosphatidylcholine multilayers

The structure and thermal behavior of hydrated and lyophilized dipalmitoylphosphatidylcholine (DPPC) multilayers in the presence of trehalose were investigated by differential scanning calorimetry and X-ray diffraction methods. Trehalose enters the aqueous space between hydrated bilayers and increases the interbilayer separation (from 0.36 to 1.37 nm in the different DPPC phases at 1 M trehalose). It does not affect the lipid chain packing and also the slow isothermal conversion at 4 degrees C of the metastable L beta' phase into the equilibrium crystalline Lc phase. Addition of trehalose leads to a slight upward shift (about 1 degrees C at 1 M trehalose) of the three phase transitions (sub-, pre-, and main transition) in fully hydrated DPPC while their other properties (enthalpy, excess specific heat, and transition width) remain unchanged. The effect of trehalose on the thermal behavior of DPPC multilayers freeze-dried from an initially completely hydrated state is qualitatively similar to that of water. These data support the "water replacement" hypothesis about trehalose action. It is suggested that trehalose prevents the formation of direct interbilayer hydrogen bonds in states of low hydration.     

Histoenzymatic activity of the delta 5-3 beta-hydroxysteroid dehydrogenase of ovary in hibernators (Citellus citellus L)

The ovaries of 24 ground squirrels (Citellus citellus L) were studied in spring (March, April), summer (July), and winter (December). The animals hibernated in a chamber at a temperature of 6-8 degrees C. The activities of the interstitial gland, theca interna, atretic follicles with theca interna and yellow bodies were measured densitometrically and studied by a specially modified histoenzymatic technique. Measurements showed that the endocrine structures were most active in March and least active in July. The atretic follicles had the highest enzymatic activity in April. The quantitative histoenzymatic approach presents an objective base for morphofunctional studies of organs and tissues at different body temperature levels in hibernators.     

Sequence variation in the outer-surface-protein genes of Borrelia burgdorferi

Borrelia burgdorferi is a spirochete pathogen transmitted among warm- blooded hosts by ixodid ticks. Frequency-dependent selection for variant outer-surface proteins might be expected to arise in this species, since rare variants are more likely to avoid immune surveillance in previously infected hosts. We sequenced the OspA and OspB genes of nine North American strains and compared them with nine strains previously described. For each gene, the mean number of synonymous substitutions per synonymous site and the mean number of nonsynonymous substitutions per nonsynonymous site show only a twofold excess of silent mutations. Synonymous rates vary widely along the OspB protein. Some regions show a significant excess of silent substitutions, while divergence in other regions is constrained by biased base composition or selection. The presence, in antigenically important regions of the protein, of significant variation among strains, as well as evidence for recombination among strains, should be considered in attempts to develop vaccines against this disease.      

Investigation of Lactobacilli Strains during Lyophilization

The Freezing Points of three lactobacilli strains cultivated in skim milk and MRS-broth were determined. Their survival was analyzed after lyophilization. A maximal preservation of the cell number of the R1 strain was found. The fermentation activity of the laclobacilli was investigated before and after lyophilization in order to characterize their species identification. Copyright 1993, 1999 Academic Press.     

Deciphering the molecular mechanisms of anti-tubulin plant derived drugs

Even though commercialized anticancer drugs are now produced by pharmaceutical companies, most of them were originally obtained from natural sources, and more particularly from plants. Indeed, many structurally diverse compounds isolated from plants or marine flora have been purified and synthesized for their anticancer bioactivity. Among these, several molecules belong to the class of anticancer drugs which target the microtubule cytoskeleton, either by stabilizing it or destabilizing it. To characterize the activity of these drugs and to understand in which physiological context they are more likely to be used as therapeutic agents, it is necessary to fully determine their interaction with tubulin. Understanding the molecular basis of their effects on microtubule cytoskeleton is an important step in designing analogs with greater pharmacological activity and with fewer side effects. In addition, knowing the molecular mechanism of action of each drug that is already used in chemotherapy protocols will also help to find strategies to circumvent resistance. By taking examples of known anti-tubulin plant derived drugs, we show how identification of microtubule targeting agents and further characterization of their activity can be achieved combining biophysical and biochemical approaches. We also illustrate how continuing in depth study of molecules with already known primary mechanisms of action can lead to the discovery of new targets or biomarkers which can open new perspectives in anticancer strategies.     

Age attenuates the T‐type CaV3.2‐RyR axis in vascular smooth muscle

Caveolae position Ca_V3.2 (T‐type Ca²⁺ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca²⁺ influx to trigger Ca²⁺ sparks and large‐conductance Ca²⁺‐activated K⁺ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca²⁺ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Ca_v3.2 channel inhibition by Ni²⁺ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca²⁺ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Ca_v3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Ca_v1.2^?/? mice, caffeine (RyR activator) and thapsigargin (Ca²⁺ transport ATPase inhibitor), we found that sufficient SR Ca²⁺ load is a prerequisite for the Ca_V3.2‐RyR axis to generate Ca²⁺ sparks. We identified a fraction of Ca²⁺ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd³⁺ (100 µM), but insensitive to Ca_V1.2 and Ca_V3.2 channel blockade. Our data demonstrate that the VSMC Ca_V3.2‐RyR axis is down‐regulated by aging. This defective Ca_V3.2‐RyR coupling is counterbalanced by a Gd³⁺ sensitive Ca²⁺ pathway providing compensatory Ca²⁺ influx for triggering Ca²⁺ sparks in aged VSMCs.