The learning characteristics of rats under free-choice conditions]

The ability to organize a four-link operant food-procuring habit in a multiple alternative maze using the free-choice method was studied in albino rats. Three types of animals were observed which were different in the character of learning. The learning curve of 20% of rats had of exponential character (type I). Some animals (37%) acquired the skill through "insight" and the process of learning in these cases could be described by a logistic regression function (type II). The remaining rats (43%) refused from solving the intricate task and were able to acquire only the simplest form of a response, i.e., running to feeders. It is suggested that learning differences between the I and II types of animals may be associated with different strategies of problem solving: "procedural" (algorithmic) and "conceptual" (semantic).     

The effect of the animals' emotional state on ethanol consumption under free-choice conditions

Voluntary ethanol consumption (20% solution) in mice of C57BL/6J strain with different experience in social agonistic confrontations was studied. It has been shown, that aggressive males daily winning other individuals did not change the level of ethanol consumption, while the submissive mice with daily experience of defeat in intermale encounters dramatically increased that level. Ethanol enhanced the behavioural reactivity of submissive animals to other individuals. It was supposed that emotionally positive or negative states differentiate the ethanol motivations in mice.     

The formation of a complex habit in Black Sea bottle-nosed dolphins under free-choice conditions]

In experiment situation was created of "free choice", which was characterized by the reinforcement of any succession of bottle-nosed dolphin action on the manipulators, placed in the open-air cage under the condition of pressing three definite levers in the required order independently of the number of "superfluous" reactions before and between necessary actions. In the first series of the experiments with eight above-water levers no succession of actions leading to the reinforcement was formed in the bottle-nosed dolphin [correction of aphaline]. In the second series with eight under-water manipulators--both experimental dolphins regularly reached the reinforcement. Stereotype trajectories of movements in the cage were formed, which included swimming past the levers and successive actions on them. Minimum chain of motor reactions was not formed, though some of "superfluous" levers were not pressed. At solving the task efferent generalization in dolphins in both series of experiments was manifested in two ways: the animals reacted in different ways on one and the same manipulator and pressed different levers.     

Reducing alcohol intake.

Alcohol is second in importance only to smoking as a proved cause of cancer. The risk associated with excessive alcohol consumption can be reduced by adopting national and local population based policies. The population approach is aimed at reducing the level of consumption across the whole population, which contains many modest drinkers. Underlying this approach is the fact that a larger proportion of the total morbidity and mortality attributed to alcohol in a population occurs in modest drinkers, even though individually they are at lower risk. This approach should be complemented by risk reduction initiatives in primary care, focused on high risk individuals. Several studies have shown the efficacy of brief interventions by general practitioners in patients with excessive alcohol consumption. Brief interventions, taking 5 to 10 minutes, use simple assessments to identify those at risk and provide information and advice. Evidence exists that general practitioners underuse opportunities to identify and advise patients about excessive drinking.     

Comparison of plankton intake by Indian carp fingerlings under different feeding conditions

The influence of different culture systems on the amount of plankton consumed by fingerlings of three carp species (Labeo rohita, Catla catla and Cirrhinus mrigala) was examined in outdoor culture tanks during a 90 day growing period. The fish were raised under two basically different feeding conditions: (a) fed with allochthonous live plankton; (b) fed with plankton grown autochthonously in the fish growing tanks fertilized with manures. Both feeding regimes were compared with control groups. It was found that the plankton intake for carp held in the live food system was significantly higher than with the manured and control systems. Related to maximum intake, maximum abundance of plankton in the live food system was a consequence of improved water quality expressed in terms of lower values of BOD and COD and higher values of DO and pH; this was conducive to fast reproduction of some of the zooplankton which constituted the major food items for the test carp, as well as to the regular exogenous introduction of live plankton. The ingestion of plankton was found to be related to carp body weight raised to the power b. The exponent b ranged from 0.29 to 0.93 during the 90-day growing period.     

A mouse model for monitoring calpain activity under physiological and pathological conditions

Calpains are Ca(2+)-dependent cysteine proteases known to be important for the regulation of cell functions and which aberrant activation causes cell death in a number of degenerative disorders. To provide a tool for monitoring the status of calpain activity in vivo under physiological and pathological conditions, we created a mouse model that expresses ubiquitously a fluorescent reporter consisting of eCFP and eYFP separated by a linker cleavable by the ubiquitous calpains. We named this mouse CAFI for calpain activity monitored by FRET imaging. Our validation studies demonstrated that the level of calpain activity correlates with a decrease in FRET (fluorescence resonance energy transfer) between the two fluorescent proteins. Using this model, we observed a small level of activity after denervation and fasting, a high level of activity during muscle regeneration and ischemia, and local activity in damaged myofibers after exercise. Finally, we crossed the CAFI mouse with the alpha-sarcoglycan-deficient model, demonstrating an increase of calpain activity at the steady state. Altogether, our results present evidence that CAFI mice could be a valuable tool in which to follow calpain activity at physiological levels and in disease states.     

A model for the kinetics of homotypic cellular aggregation under static conditions.

We present the formulation and testing of a mathematical model for the kinetics of homotypic cellular aggregation. The model considers cellular aggregation under no-flow conditions as a two-step process. Individual cells and cell aggregates 1) move on the tissue culture surface and 2) collide with other cells (or aggregates). These collisions lead to the formation of intercellular bonds. The aggregation kinetics are described by a system of coupled, nonlinear ordinary differential equations, and the collision frequency kernel is derived by extending Smoluchowski's colloidal flocculation theory to cell migration and aggregation on a two-dimensional surface. Our results indicate that aggregation rates strongly depend upon the motility of cells and cell aggregates, the frequency of cell-cell collisions, and the strength of intercellular bonds. Model predictions agree well with data from homotypic lymphocyte aggregation experiments using Jurkat cells activated by 33B6, an antibody to the beta 1 integrin. Since cell migration speeds and all the other model parameters can be independently measured, the aggregation model provides a quantitative methodology by which we can accurately evaluate the adhesivity and aggregation behavior of cells.     

A semi-empirical glycosylation model of a camelid monoclonal antibody under hypothermia cell culture conditions

The impact of cell culture environment on the glycan distribution of a monoclonal antibody (mAb) has been investigated through a combination of experiments and modeling. A newly developed CHO DUXB cell line was cultivated at two levels of initial Glutamine (Gln) concentrations (0, 4 mM) and incubation temperatures of (33 and 37 °C) in batch operation mode. Hypothermia was applied either through the entire culture duration or only during the post-exponential phase. Beyond reducing cell growth and increasing productivity, hypothermia significantly altered the galactosylation index profiles as compared to control conditions. A novel semi-empirical dynamic model was proposed for elucidating the connections between the extracellular cell culture conditions to galactosylation index. The developed model is based on a simplified balance of nucleotides sugars and on the correlation between sugars’ levels to the galactosylation index (GI). The model predictions were found to be in a good agreement with the experimental data. The proposed empirical model is expected to be useful for controlling the glycoprofiles by manipulating culture conditions.     

Tomato alcohol dehydrogenase. Expression during fruit ripening and under hypoxic conditions.

We have isolated and sequenced a partial tomato alcohol dehydrogenase (Adh) cDNA clone. Expression of tomato Adh was studied at the messenger RNA level in seedlings, roots, and fruit. High induction was observed under hypoxic conditions, both in tomato seedlings and in roots. In addition, the Adh mRNA was present at the mature green and pink stage of the tomato fruit, and was highly induced in late ripening. Moreover, an artificial ripening treatment resulted in at least 50-fold induction compared to the mature green mRNA level. Genomic DNA gel blotting suggested the presence of a multigene family for Adh in tomato.     

A two-state cell damage model under hyperthermic conditions: theory and in vitro experiments

The ultimate goal of cancer treatment utilizing thermotherapy is to eradicate tumors and minimize damage to surrounding host tissues. To achieve this goal, it is important to develop an accurate cell damage model to characterize the population of cell death under various thermal conditions. The traditional Arrhenius model is often used to characterize the damaged cell population under the assumption that the rate of cell damage is proportional to exp(-EaRT), where Ea is the activation energy, R is the universal gas constant, and T is the absolute temperature. However, this model is unable to capture transition phenomena over the entire hyperthermia and ablation temperature range, particularly during the initial stage of heating. Inspired by classical statistical thermodynamic principles, we propose a general two-state model to characterize the entire cell population with two distinct and measurable subpopulations of cells, in which each cell is in one of the two microstates, viable (live) and damaged (dead), respectively. The resulting cell viability can be expressed as C(tau,T)=exp(-Phi(tau,T)kT)(1+exp(-Phi(tau,T)kT)), where k is a constant. The in vitro cell viability experiments revealed that the function Phi(tau,T) can be defined as a function that is linear in exposure time tau when the temperature T is fixed, and linear as well in terms of the reciprocal of temperature T when the variable tau is held as constant. To determine parameters in the function Phi(tau,T), we use in vitro cell viability data from the experiments conducted with human prostate cancerous (PC3) and normal (RWPE-1) cells exposed to thermotherapeutic protocols to correlate with the proposed cell damage model. Very good agreement between experimental data and the derived damage model is obtained. In addition, the new two-state model has the advantage that is less sensitive and more robust due to its well behaved model parameters.     

Effect of long-term restriction of protein intake,from gestation onward,on free-choice consumption of ethanol by rats

Long-term (including gestational and lactational) restriction of protein (8% of diet) significantly lowered the absolute and relative consumption of 6% ethanol (EtOH) in a two-bottle, free-choice (H₂O vs EtOH) situation during a 76-day test period. This difference in response between rats fed the low protein diet and those fed an isocaloric normal protein (24%) diet became non-significant in two subsequent 100-day test periods. Statistical analysis of observations on individual performance indicated that regularity, cyclicity, and duration of drinking in each animal was random over all three time intervals for both groups. The early, significantly lower EtOH consumption by the protein-restricted group may be due to a paucity of EtOH-metabolizing enzymes in brain and liver, thereby prolonging the CNS effects of lower doses of EtOH consumed. The disappearance of this difference in subsequent test periods may reflect either a behavioral or metabolic adaptation in the developing protein-deficient rat.     

Properties of a general model of DNA evolution under no-strand-bias conditions

Under the hypothesis of no-strand-bias conditions, the Watson and Crick base-pairing rule decreases the complexity of models of DNA evolution by reducing to six the maximum number of substitution rates. It was shown that intrastrand equimolarity between A and T (A ^* T ^*) and between G and C (G ^* C ^*) is a general asymptotic property of this class of models. This statistical prediction was observed on 60 long genomic fragments (>50 kbp) from various kingdoms, even when the effect of the two opposite orientations for coding sequences is removed. The practical consequence of the model for estimating the expected number of substitutions per site between two homologous DNA sequences is discussed.Abbreviations BPR Watson and Crick base pairing rule (A:T, G:C) - PRI Intrastrand type-1 parity rule (i j, m(i,j)m( )) - PRII Intra strand type-2 parity rule (A ^* T ^*, G ^* C ^*)     

Liver autofluorescence properties in animal model under altered nutritional conditions

Autofluorescence spectroscopy is a promising and powerful approach for an in vivo, real time characterization of liver functional properties. In this work, preliminary results on the dependence of liver autofluorescence parameters on the nutritional status are reported, with particular attention to vitamin A and lipid accumulation in liver tissue. Normally fed and 24 h starving rats were used as animal models. Histochemical and autofluorescence analysis showed that lipids and vitamin A colocalize in the liver parenchyma. Fasting condition results in a parallel increase in both lipids and vitamin A. Autofluorescence imaging and microspectrofluorometric analysis carried out on unfixed, unstained tissue sections under 366 nm excitation, evidenced differences in both spectral shape and response to continuous irradiation between liver biopsies from fed and starving rats. As to photobleaching, in particular, fitting analysis evidenced a reduction of about 85% of the signal attributable solely to vitamin A during the first 10 s of irradiation. The tissue whole emission measured in fed and starving rat livers exhibited reductions of about 35% and 52%, respectively, that are closely related to vitamin A contents. The findings open interesting perspectives for the set up of an in situ, real time diagnostic procedure for the assessment of liver lipid accumulation, exploiting the photophysical properties of vitamin A.     

Spontaneous unit activity of the monkey caudate nucleus under chronic experimental conditions

Spontaneous unit activity and changes in its statistical parameters during electrical stimulation of the palms at 25 or 50/min were studied in four monkeys under chronic experimental conditions. Altogether 337 recordings of the activity of 64 neurons for durations of 2 and 3 min were studied. The mean firing rate was relatively low (5.7 spikes/sec). As a rule the unit activity remained stable for several tens of minutes. It could change spontaneously to new patterns and again remain stationary. These transitions took place during recording of spontaneous activity and also during stimulation of the animal, but they were independent of it. Interspike interval histograms were varied and most were polymodal. Their pattern changed with changes in the firing rate of the neurons. The position of the modes along the time axis and the type of distribution were the most conservative characteristics of the histograms. The probability of appearance of intervals was highest at 30, 60, 90, and 210–240 msec. The presence of stable intervals with increased probability of appearance may be the result of the existence of chains of neurons in the caudate nucleus with fixed temporal parameters.