Structure-activity relationships of some selected beta-adrenergic blocking agents--oxidation with N-bromosuccinimide.

A relationship between in vitro rate of oxidation by N-bromosuccinimide (NBS) and the pharmacologic activity (pA2) of different beta-adrenergic blockers for different blocking agent-tissue combinations has been studied. The rates of oxidation of the alcoholic group in the drugs by NBS, as well as their molecular conformations as represented by molecular models, were studied in order to determine requirements for selectivity and potency of action of beta-adrenergic blocking agents. Using data from all 7 drugs studied--both nonselective and selective blocking agents--no significant correlation between pA2 and -log k2 (k2 is the second order rate constant for the oxidative reaction) was found. If data from only the 4 nonselective agents were used (16 drug-tissue combinations), a correlation significant at p less than 0.01 was found. Hypotheses are presented to account for the selective action of some beta-adrenergic blocking agents.     

Genetic analysis of ewe productivity traits in Moghani sheep

Genetic and environmental (co)variance components for productivity traits in Moghani sheep were estimated using data from 1344 ewes. The data were collected in the Jafarabad breeding station, north-east of Iran, during a 13-year period (1995-2008). The studied traits were litter size at birth (LSB), litter size at weaning (LSW), litter mean weight per lamb born (LMWLB), litter mean weight per lamb weaned (LMWLW), total litter weight at birth (TLWB) and total litter weight at weaning (TLWW). A model including direct additive genetic effects as well as permanent environmental effects related to repeated records of ewe was the most appropriate model for all the studied traits. Genetic parameters were estimated applying restricted maximum likelihood (REML) procedure. Direct heritability estimate for LSB, LSW, LMWLB, LMWLW, TLWB and TLWW were 0.11, 0.02, 0.15, 0.07, 0.07 and 0.06, respectively. Corresponding values for repeatability estimates were 0.16, 0.19, 0.18, 0.11, 0.13 and 0.09. Genetic correlations between the studied traits ranged from −0.99 for LSB-LMWLB and LSW-LMWLB to 0.99 for LSB-TLWB. Phenotypic and environmental correlation estimates were generally lower than those of genetic ones. Estimates of permanent environmental correlation among traits were positive and medium to high. Although low direct heritabilities were estimated for the reproductive traits, as these traits are of interest then they should be included in a breeding program.     

Possible implication of lysophosphatidylcholine in cell fusion accompanying implantation in rabbits.

Implantation in rabbits involves the cellular fusion of trophoblastic and uterine epithelial cells resulting in embryo penetration of the uterine endometrium. Since lysophospholipids, known to have fusigenic properties, could be responsible for this cell fusion, the metabolism of lysophospholipids was studied throughout gestation in blastocyst/yolk sac and extracoelic amnioallantoic fluids. Analysis of phospholipid composition revealed that lysophospholipids are present in blastocyst/yolk sac fluid. Their concentrations and haemolytic activity change during pregnancy. They increase and reach their highest values during days 7 to 9, the implantation days in rabbits. A clear correlation was observed between lysophosphatidylcholine concentrations in blastocyst/yolk sac fluid and haemolysis induced by this fluid. Phosphatidylcholine concentrations, phospholipase A2 activity, which generates lysophospholipids, and lysophospholipase A activity which hydrolyses lysophosphatidylcholine into fatty acid, were at their highest value at day 12. These data suggest that a transient accumulation of lysophospholipids could ensure local cell fusion. Moreover, we propose that the lysophospholipid concentrations in blastocyst/yolk sac fluid are dependent upon activities of phospholipase A2 and lysophospholipase.     

Limited synthesis of labile hemoglobin A1 in vivo and in vitro by the preexisting hemoglobin A1 in diabetic subjects

The synthesis of labile hemoglobin A1 in vivo was studied in subjects with non-insulin dependent diabetes mellitus, impaired and normal glucose tolerance. The labile hemoglobin A1 index defined as delta labile hemoglobin A1 divided by delta plasma glucose at 30 min after oral glucose load, representing the rate of labile hemoglobin A1 synthesis in vivo, was low in diabetic subjects and high in normal subjects, showing an inverse correlation with the amount of preexisting hemoglobin A1. The study on the synthesis of labile hemoglobin A1 in vitro showed a lower initial rate of synthesis and a smaller increase in labile hemoglobin A1 at saturation in red blood cells from diabetic subjects with a relatively large amount of preexisting hemoglobin A1, as opposed to red blood cells from normal subjects. Although the further study is necessary in which delta plasma glucose levels are kept relatively constant in each of 3 groups by glucose-clamp methods, our data suggest that the synthesis of labile hemoglobin A1 is limited in vivo and in vitro in diabetic subjects by the preexisting hemoglobin A1 due to the saturability of its synthesis.     

A multifactorial study (cell kinetics, cytogenetics, DNA content) of lung tumours: basic information for prognostic evaluation

Different prognostic parameters (labeling index, chromosomal pattern, DNA content) were studied in 32 cases of lung tumour. A great variability was observed in the proliferative activity and karyotype, and there was a lack of correlation between these parameters and the histologic type. It was possible to demonstrate that a diploid DNA content does not necessarily correspond to a normal karyotype. A more precise evaluation of the prognostic significance of data obtained will be possible in correlation with an extensive follow-up of the patients studied.     

Energetics of hydration of nucleic acids with various nucleotide composition

The energetics of hydration of natural DNA of different AT/GC content and model double-helical polyribonucleotides was studied. The results obtained by a new approach, which is based on calorimetric measurements of hydration-dehydration energy of nucleic acid-water systems at different relative humidities are presented. A correlation between the dehydration energy and the nucleotide composition of native DNA was found. The energetic characteristics of systems containing deoxynucleoside monophosphates and water clusters of different dimensions were obtained by the Monte Carlo method. The results of computer simulation correlate with the experimental calorimetric data.     

Preference of oxygenation between α and β subunits of haemoglobin: Results of multidimensional spectroscopic observation

The distribution of oxygen between the subunits of haemoglobin was studied spectrophotometrically. The difficulty in discriminating the spectral changes upon oxygen binding to the α or β subunit can be surmounted by means of multidimensional spectroscopic observations and a correlation analysis of the data. M-type abnormal haemoglobins are used as a control against normal haemoglobin because only one type of its subunits can bind oxygen.A multidimensional spectroscopic measuring system, which has been developed in our laboratory, makes it possible to carry out simultaneous and continuous acquisition of a set of spectroscopic data at several wavelengths on one sample solution during the course of increasing or decreasing the partial pressure of oxygen. The data-storing function of a magnetic disk memory provides enough precision for a rigorous investigation of the correlation of oxygen equilibrium curves measured at several wavelengths. No chemical modification to enhance the spectral difference between subunits is necessary.In conclusion, by detecting slight differences between the oxygenation-sensitive bands of α and β subunits, the β subunits are found to have a higher affinity for oxygen than the α subunits.     

Rotational mobility of high-affinity epidermal growth factor receptors on the surface of living A431 cells.

The rotational diffusion of epidermal growth factor (EGF) bound to its specific receptor on the surface of human carcinoma A431 cells was studied by means of time-resolved phosphorescence anisotropy measurements. The rotational mobility was measured on the total population of EGF receptors by using a saturating concentration of EGF conjugated with a phosphorescent label, erythrosin, or on the subpopulation of high-affinity EGF receptors by using a low concentration of labeled EGF. At 4 degrees C, the rotational correlation times for both the high-affinity and total (mostly low affinity) receptor populations were in the range of 60-100 microns. Elevation of the temperature to 37 degrees C resulted in a lengthening of the rotational correlation time of the total receptor population to 200-300 microns, confirming a previous study of receptor microaggregation. The high-affinity EGF receptors were completely immobilized at 37 degrees C (rotational correlation time greater than 500 microns). The data are consistent with a model involving association of the cytoskeleton with the high-affinity receptors at 37 degrees C, but not at 4 degrees C.     

Comparative study of alanine-amino-peptidase and gamma-glutamyl-transferase activity in normal Wistar rat urine

24 h urinary alanine-amino-peptidase (AAP) and gamma-glutamyl transferase (GGT) activities were studied from the 3rd-7th month of life in male Wistar rats. A close relationship was found between AAP and GGT activity, except at the beginning and at the end of this period. At the end there appear 2 subgroups, the larger (70%) showing a strong correlation between AAP and GGT activity and the other (30%), demonstrating no correlation at all. A good correlation between AAP and GGT activities, creatinine, 24 h urine volume and 24 h creatinine output was found.     

Why do identical twins differ in personality: shared environment reconsidered.

While heritability studies show that most of the variance in adult personality can be attributed to genetic or so-called nonshared environmental influence, this does not mean that shared events lack importance for the development of later personality differences. We studied the relationship between Big Five personality differences in monozygotic (MZ) twins at age 29, and life stressors at age 6 to 15, using prospective data from 26 MZ pairs studied from birth onwards. A positive significant correlation was found between stressors in childhood and early adolescence, and intrapair personality differences in Agreeableness, Openness, Conscientiousness, and five-factor profiles. We note that the effects of shared events are labeled "nonshared" environment when the effect is to make siblings more different. Case examples illustrate the relationship between stress and personality differences, and provide hypotheses for further studies in larger samples.     

The use of deuterium exchange for the study of the distortion of α-helices in proteins

The geometrical distortion of the α-helical structure of the globular proteins sperm-whale myoglobin, bacteriophage T4 lysozyme and hen egg-white lysozyme have been studied by means of deuterium exchange in solution. It was examined with the use of infrared spectroscopy in the region of the amide A band. The parameters of this band are known to be dependent on the length and geometry of the peptide hydrogen bond. In this way an estimation of the structural heterogeneity of the polypeptide backbone of the protein molecule has been achieved by studying the half-width of the amide A band during successive deuteration of the protein in heavy water solution. For all the proteins studied the peptide groups with broad amide A bands were exchanged at the first stage. These groups have been assigned as belonging to the unordered form of the molecule. The α-helical fragments were assigned to have smaller values of half-widths of the amide A band, and these were exchanged at the second stage. From these data α-helical fragments were shown to be characterized by a set of geometrical distortions. The results obtained also disclose a correlation between the degree of geometrical distortion of α-helical structure in the protein molecule and the dynamic accessibility of their peptide groups to a water molecule.     

The role of endoglucanase and endoxylanase in liquefaction of hydrothermally pretreated wheat straw

The role of endocellulases and endoxylanase during liquefaction and saccharification of hydrothermally pretreated wheat straw was studied. The use of a flow‐loop setup with in‐line magnetic resonance imaging enabled frequent measurements of viscosity at 55°C during saccharification at 6% total solids content. Viscosity data were complemented with off‐line measurements of fiber lengths and release of soluble sugars. A clear correlation between fiber attrition and a decrease in viscosity was found. Fiber lengths and viscosity dropped quickly within the first hour and then stagnated, while sugar yields increased substantially thereafter, illustrating that liquefaction and saccharification are separate mechanisms. Both endoglucanase and endoxylanase were shown to have a significant effect on viscosity during liquefaction while the addition of endoxylanase also increased sugar yield. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:923–931, 2014     

Resistance of mammalian red blood cells of different size to hypertonic milieu

1. The resistance of different mammalian red blood cells (RBCs) to hyperosmotic environments was studied. RBCs of six mammalian species were exposed to 10 increasingly hyperosmotic NaCl solutions for 24 hr at 5 degrees C. 2. The osmolality at which the amount of liberated haemoglobin reached a preset level (e.g. 3-4% of the total haemoglobin) showed a linear correlation with negative slope with RBC volume. This indicates that small RBCs are more resistant to hyperosmotic milieu than large ones. 3. A similar relation can be found from literature data when maximal urinary tonicities are plotted as a function of RBC volume, i.e. animals with the ability to produce highly concentrated urine have small RBCs. 4. RBC volume and maximal urinary tonicity in mammals are therefore tightly linked. Future research will have to show whether this correlation is fortuitous or not and whether, as can be speculated, RBC size is directly or indirectly regulated by the kidney.     

13C NMR relaxation times of hepatic glycogen in vitro and in vivo

The field dependence of relaxation times of the C-1 carbon of glycogen was studied in vitro by natural-abundance 13C NMR. T1 is strongly field dependent, while T2 does not change significantly with magnetic field. T1 and T2 were also measured for rat hepatic glycogen enriched with [1-13C]glucose in vivo at 4.7 T, and similar relaxation times were observed as those obtained in vitro at the same field. The in vitro values of T1 were 65 +/- 5 ms at 2.1 T, 142 +/- 10 ms at 4.7 T, and 300 +/- 10 ms at 8.4 T, while T2 values were 6.7 +/- 1 ms at 2.1 T, 9.4 +/- 1 ms at 4.7 T, and 9.5 +/- 1 ms at 8.4 T. Calculations based on the rigid-rotor nearest-neighbor model give qualitatively good agreement with the T1 field dependence with a best-fit correlation time of 6.4 X 10(-9) s, which is significantly smaller than tau M, the estimated overall correlation time for the glycogen molecule (ca. 10(-5) s). A more accurate fit of T1 data using a modified Lipari and Szabo approach indicates that internal fast motions dominate the T1 relaxation in glycogen. On the other hand, the T2 relaxation is dominated by the overall correlation time tau M while the internal motions are almost but not completely unrestricted.     

ADP-ribosylation of nuclear proteins in the rat brain

The distribution of (ADP-ribose)n synthesized from [14C]NAD labeled at the adenyl ring in several protein fractions of isolated rat brain nuclei was studied. Preferential ADP-ribosylation of nonhistone nuclear proteins was shown to occur. It was demonstrated that pol (ADP-ribose)polymerase and DNA-topoisomerase II are located spatially close to each other. A correlation between ADP-ribosylation and the activity of nuclear matrix DNA-topoisomerase II was established.     

Maintenance requirements of L-thyroxine in the treatment of hypothyroidism

By analyzing data from 68 hypothyroid patients ranging in age from 15 to 75 years who had been maintained in a euthyroid state for at least a year with oral levothyroxine sodium therapy, we attempted to determine whether there was a correlation between L-thyroxine dose and body weight or patient age. The mean replacement dose of L-thyroxine was 186 mug a day +/-69.6 or 2.76 mug per kg of body weight a day +/-0.82. There was a significant correlation between L-thyroxine dose and body weight (P<.001), but due to the small number of patients studied who were older than 65 years of age, no correlation was noted between L-thyroxine dose and age.     

The problem of using correlation methods in brain function]

In a series of publications, the author used the correlation hypothesis to explain the main mechanisms of functioning of bat and dolphin echo locators. A good fit of calculated parameters to experimental data was shown. In this work, by the example of generalization of the recognition problem, the use by the brain of correlation methods for solving more general problems independently on the modality of sensor signals was analyzed. In favor of the hypothesis that correlation methods are widely used in brain functioning are the data presented in the paper, which prove that an associative neuron is a suitable analog computer. It is suited for rapid "computation" of the intercorrelation function of discrete input and reference signals. The set of weighting coefficients of neuron synaptic inputs serve as such signals. The pool of associative neurons determines the values on the correlation function in the required range by changing the "numbers" of inputs from neuron to neuron at which discrete signals arrive.     

Quasielastic light scattering from migrating chemotactic bands of Escherichia coli. II. Analysis of anisotropic bacterial motions.

Chemotactic effects of dissolved oxygen on motions of Escherichia coli in a motility buffer solution have been studied by measurements of quasielastic light scattering. Under conditions where the bacteria form a sharp band in an oxygen concentrations gradient created by their metabolism, components of motions along the direction of the gradient and perpendicular to it were studied separately at each point within the band profile. A theoretical model for bacterial self correlation function based on two-state motions has been developed to extract the mean square speed of run motion and the relative probability of twiddle vs. run at each point of the band profile. A combined novel experimental set-up and new data analysis method allowed us to extract also the mean square displacements at short times along and perpendicular to the direction of the gradient. Parameters extracted from the measured correlation functions have been discussed in the framework of the established picture of bacterial motions under chemotaxis.     

Regulation of palmitoylcarnitine oxidation in isolated rat liver mitochondria. Role of the redox state of NAD(H)

The redox-mediated regulation of palmitoylcarnitine oxidation was studied in isolated rat liver mitochondria in which the mitochondrial free NADH/NAD⁺ ratio was controlled by graded concentrations of acetoacetate and ketomalonate in a rotenone and malonate-inhibited system in the presence of ADP. The NADH/ NAD⁺ ratio was buffered kinetically by adjusting the concentrations of the hydrogen acceptor substances and determined by calibrated NAD(P)H fluorometry of the mitochondrial suspension. A two-fold variation in the β-oxidation rate and a five-fold variation in the free NADH/NAD⁺ ratio was obtained in the presence of rotenone. A non-linear negative correlation was found between the acetyl-CoA concentration and the β-oxidation rate and a negative correlation between the long-chain acyl-CoA concentration and the β-oxidation rate. The data indicate that the redox state is a partial controller of the β-oxidation rate in liver mitochondria. The contribution of acetyl-CoA, a putative regulator of β-oxidation at the acyl-CoA thiolase step is small under the conditions used.     

Thermal properties of water in myoglobin crystals and solutions at subzero temperatures.

The water of hydration in myoglobin crystals and solutions was studied at subzero temperatures by calorimetry and infrared spectroscopy (ir). For comparison we also investigated glycine, DL-alanine and DL-valine solutions. The hydration water remains amorphous at low temperatures. We find a broad glass transition between 180 and 270 K depending on the degree of hydration. The ice component shows a noncolligative melting point depression that is attributed to a finite conformational flexibility. The ir spectrum and the specific heat of water in myoglobin crystals was determined for the first time between 180 and 290 K. The glass transition in crystals is qualitatively similar to what is found in amorphous samples at the same water content. These data are compared with M?ssbauer experiments and dielectric relaxation of water in myoglobin crystals. The similar temperature dependencies suggest a cross correlation between structural fluctuations and the thermal motion of crystal water. A hydrogen bond network model is proposed to explain these features. The essential ingredients are cooperativity and a distribution of hydrogen-bonded clusters.