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Animal models of self-destructive behavior and suicide.

In this article we have addressed selected aspects of animal models that may have ramifications in our understanding of suicide and human self-destructive behavior. It should be kept in mind that these human behaviors have many determinants. In considering animal models, we do not propose that similar behaviors necessarily have the same causation nor that a particular experimental manipulation that produces a behavioral syndrome in one species will produce that response in another species. Even if environmental conditions or the resulting behaviors vary for different species, the biochemical intermediaries may be similar. The simplification inherent in the laboratory modeling of an aspect of human behavior should not mean that the complexity of the human syndrome be forgotten. However, if a simple explanation can account for the production of a particular behavioral syndrome in animals, it can help to structure our thoughts regarding the etiology of the behavior in humans. The ethologic observations discussed in this article may help to place human self-destructive behavior in a continuum with that of animals in the wild. Although care should be given to drawing direct parallels, the clear conclusion is that humans are not alone in exhibiting self-initiated behaviors that ultimately produce self-harm or death. Whereas laboratory models have been extensively used for modeling psychiatric illnesses or for producing specific pharmacologic manipulations of the CNS, surprisingly little attention has been given to the modeling of self-destructive behaviors themselves. Emphasis on self-destructive behaviors, as well as on their biologic and genetic underpinnings, represent an important future direction for work on animal models in psychiatry.

Altruism↗

The assessment of genetic risk of breast cancer: a set of GP guidelines.

BACKGROUND: Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to refer or not to refer for genetic counselling), giving no guidance for the GP on the management of women with a moderately increased risk of familial breast cancer. OBJECTIVES: We aimed to develop a set of simple practical guidelines for use in primary care for assessing risk and advising women with a positive family history in general practice and aimed to explore its performance. METHODS: Based on a consensus meeting of the Leiden working party of hereditary tumours, the GPs of a university-related health care centre developed a set of GP guidelines to assess risk and advise women with a family history positive for breast cancer in general practice. The GP guidelines include four therapeutic strategies (reassuring, starting surveillance, starting surveillance and contacting a family cancer clinic, referring to a family cancer clinic). Its performance was tested in 67 patients whose pedigrees were available together with the risk assessment of a clinical geneticist using Claus' tables as a gold standard. The gold standard was dichotomized regarding (i) referral to a family cancer clinic and (ii) surveillance. Two existing expert guidelines were similarly compared. RESULTS: Regarding referral to a family cancer clinic, the GP guidelines were very specific, whereas the expert guidelines were more sensitive. Regarding surveillance, the GP guidelines were very sensitive, whereas the expert guidelines were very specific. The total number of misclassified patients was lowest when using the GP guidelines, and higher when using the expert guidelines. CONCLUSIONS: The GP guidelines provide a simplification of current guidelines. Before using them on a larger scale, more testing and refining are needed to increase their sensitivity regarding a referral to a family cancer clinic and their specificity regarding surveillance. They incorporate a role for the GP in the care for women with a family history positive for breast cancer with a moderately increased risk.

Adolescent↗

Agonism and inverse agonism at dopamine D2-like receptors.

1. The processes that follow the binding of ligands to receptors are critical for their physiological functions. In the present paper I intend to review our own work and the work of other laboratories attempting to understand these processes for the dopamine D2-like receptors (D2, D3, D4) and how they contribute to the mechanisms of drug action. It is thought that the key event in agonist action for these receptors is the stabilization, by the agonist, of the agonist-receptor-G-protein ternary complex. The majority of the work I shall describe has been performed using recombinant receptors expressed in cell lines and the mechanisms of receptor action have been probed using ligand binding (competition vs [3H]-spiperone), the stimulation of [35S]-GTP gamma S binding and inhibition of adenylyl cyclase. 2. Measures of the ability of agonists to stabilize the agonist-receptor-G-protein ternary complex may be obtained in ligand-binding studies using the ratio of dissociation constants for the higher and lower affinity states (KI/KH ratio). The stimulation of [35S]-GTP gamma S binding provides a very convenient assay for agonist action and allows the determination of agonist potency and maximal response. Estimates of these quantities may also be obtained from the inhibition of adenylyl cyclase. For a range of agonists at the D2 receptor, there is a tendency for high values of KI/KH to predict high maximal activity and vice versa, but there is no general correlation. This suggests that the simple scheme of agonist action depending on the stabilization of the ternary complex is an over-simplification and further efficacy determining steps need to be included. For a number of receptors, including the D2 and D3 receptors, it has now been shown that there is activity in the absence of agonist (so-called constitutive activity). This agonist-independent activity can be inhibited by compounds previously considered to be antagonists (e.g. the antipsychotic drugs). Therefore, these compounds are inverse agonists rather than antagonists. The mechanism of this inverse agonist effect is unclear and we are examining this using a variety of biochemical approaches, including the use of constitutively active mutants. 3. The mechanisms of agonism and inverse agonism may be probed using biochemical assays and these studies are of great relevance to the understanding of drug action.

Dopamine Agonists↗

From homogeneous dispersion to micelles-a molecular dynamics simulation on the compromise of the hydrophilic and hydrophobic effects of sodium dodecyl sulfate in aqueous solution.

The structural and functional diversity of surfactant systems has attracted simulation works in atomistic, coarse grain, and mesoscopic models (Bandyopadhyay, S.; et al. Langmuir 2000, 16, 942; Senapati, S.; et al. J. Phys. Chem. B 2003, 107, 12906; Maiti, P. K.; et al. Langmuir 2002, 18, 1908; Srinivas, G.; et al. J. Phys. Chem. B 2004, 108, 8153; Groot, R. D.; et al. J. Chem. Phys. 1999, 110, 9739; Rekvig, L.; et al. Langmuir 2003, 19, 8195). However, atomistic models have suffered from their tremendous computational cost and are, so far, not able to simulate the structural behaviors in sufficient spatio-temporal scales (Shelley, J. C.; Shelley, M. Y. Curr. Opin. Colloid Interface Sci. 2000, 5, 101). The other two approaches are not microscopic enough to describe the configurations of the surfactants that determine their behaviors (Shelley and Shelley). In this study, we propose to simplify atomistic models based on the observation that the compromise of the hydrophilic and hydrophobic effects (Li, J.; Kwauk, M. Chem. Eng. Sci. 2003, 58, 521-535) and molecular structures of surfactants are the dominant factors shaping their structures in the systems. With this simplification, we are able to simulate with moderate computing cost the whole process of micelle formation from an initially uniform dispersion of sodium dodecyl sulfate (SDS) in aqueous solution. The resulting micelle structures are different from those predicted by atomistic simulations that started with a predefined micelle configuration at the same surfactant concentrations. However, if we use their initial micelle configuration, micelle structures the same as theirs are obtained. Analyses show that our results are more realistic and that the results of the atomistic simulations suffer from artificial initial conditions. Therefore, our model may serve as a reasonable simplification of atomistic models in terms of the general structure of micelles.

Journal Article↗

Membrane bio-reactor for advanced textile wastewater treatment and reuse.

Textile wastewater contains slowly- or non-biodegradable organic substances whose removal or transformation calls for advanced tertiary treatments downstream Activated Sludge Treatment Plants (ASTP). This work is focused on the treatment of textile industry wastewater using Membrane Bio-reactor (MBR) technology. An experimental activity was carried out at the Baciacavallo Wastewater Treatment Plant (WWTP) (Prato, Italy) to verify the efficiency of a pilot-scale MBR for the treatment of municipal wastewater, in which textile industry wastewater predominates. In the Baciacavallo WWTP the biological section is followed by a coagulation-flocculation treatment and ozonation. During the 5 months experimental period, the pilot-scale MBR proved to be very effective for wastewater reclamation. On average, removal efficiency of the pilot plant (93% for COD, 96% for ammonium and 99% for total suspended solids) was higher than the WWTP ones. Color was removed as in the WWTP. Anionic surf actants removal of pilot plant and WWTP were very similar (92.5 and 93.3% respectively), while the non-ionic surfactants removal was higher in the pilot plant (99.2 vs. 97.1). In conclusion the MBR technology demonstrated to be effective for textile wastewater reclamation, leading both to an improvement of pollutants removal and to a draw-plate simplification.

Bioreactors↗

Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method.

UNLABELLED: The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET.

Adolescent↗

[Current status of the female condom in Africa].

The female condom was developed in the 1980s. It is a contraceptive device used by women that protects against both pregnancy and sexually-transmitted diseases (STDs) including HIV infection. Two studies have investigated the contraceptive effectiveness of the female condom, and it was found to be as effective as other barrier methods. It has been shown to be effective against STD and HIV transmission in vitro but there is only limited evidence of its efficacy in vivo. No serious local side effects or allergies have been reported and the female condom can be used with any type of lubricant, spermicidal cream or foam. The female condom is the only device other than the male condom that has been shown to prevent HIV transmission. The female condom has been marketed in 13 countries since the summer of 1996. Most of these countries are industrialized and the selling price in these countries is too high for developing countries. Sub-Saharan Africa has very high prevalence rates for HIV infection, at least 30% of the general population in Eastern and Central regions. The epidemic is also spreading fast in some parts of the Western region. In Ivory Coast for example, 12 to 15% of pregnant women are infected. African women are subordinate to men in many aspects of their lives, politically, educationally, socially and sexually. This sexual inequality makes them highly vulnerable to STDs, including HIV, and unwanted pregnancies. This paper reviews 10 of the 15 studies carried out in sub-Saharan African countries between 1990 and 1996 and compiled by the World Health Organization. Recruitment methods, education of subjects, methodology and assessment of acceptability differed between studies. Despite these limitations, most studies concluded that the women who participated in the trials generally found the female condom acceptable. Acceptability was established quicker among prostitutes than among other women and men found the female condom less acceptable than did women. However, the sample size is too small to draw any firm conclusions. Commercial sex workers in the studies reviewed were very interested in this new method because it gave them an additional method of safer protection during sex. However, they were occasionally faced with difficult negotiations with some clients, refusal to use the female condom and sexual violence. Reuse of the device was reported in four studies, but the term reuse is seldom defined. In cases where it was defined, the frequency of reuse, with washing of the device, accounted for no more than 1% of the total number of uses. The acceptability of the female condom among women other than prostitutes faces two obstacles, the reaction of the woman's regular partner and attitudes to the device itself (appearance, difficulties or uneasiness concerning its use). However, some women liked it because it provided dual protection against pregnancy and STDs and sexual pleasure. The moderate level of acceptability to male partners may be overestimated because women whose partners disliked the device would be more likely to discontinue its use. The studies of acceptability reviewed here show that use of the female condom in Africa is realistic and that it provides women with more independent protection. Initial negative perceptions of the device are often replaced with a more positive reaction after several uses. The experience gained with use reduces the technical problems. We need to overcome the stereotypes, simplifications and strong opinions that threaten to damage the acceptance of this new method and efforts to encourage women to adopt it. However, we still require further clinical data on the effectiveness of the female condom at preventing pregnancy and HIV transmission. Availability of the female condom is improving in Africa. Pilot marketing studies were launched in 1996 in Guinea, Zambia, South Africa, followed by Uganda and Tanzania. There are local initiatives in Ivory Coast and Zimbabwe. (ABSTRACT TRUNC

Africa↗

Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons.

We demonstrate in this work that the surface tension, water-organic solvent, transfer-free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions. We first develop a model for the curvature dependence of the hydrophobic effect and find that the macroscopic concept of interfacial free energy is applicable at the molecular level. Application of a well-known relationship involving surface tension and adhesion energies reveals that dispersion forces play little or no net role in hydrophobic interactions; rather, the standard model of disruption of water structure (entropically driven at 25 degrees C) is correct. The hydrophobic interaction is found, in agreement with the classical picture, to provide a major driving force for protein folding. Analysis of the melting behavior of hydrocarbons reveals that close packing of the protein interior makes only a small free energy contribution to folding because the enthalpic gain resulting from increased dispersion interactions (relative to the liquid) is countered by the freezing of side chain motion. The identical effect should occur in association reactions, which may provide an enormous simplification in the evaluation of binding energies. Protein binding reactions, even between nearly planar or concave/convex interfaces, are found to have effective hydrophobicities considerably smaller than the prediction based on macroscopic surface tension. This is due to the formation of a concave collar region that usually accompanies complex formation. This effect may preclude the formation of complexes between convex surfaces.

Algorithms↗

The volume conductor effects of anisotropic muscle on body surface potentials using an eccentric spheres model.

The purpose of this paper is to determine the volume conductor effects of muscle anisotropy on body surface potentials using an eccentric spheres model with a uniform double layer source configuration. Previous eccentric spheres work assumed that cardiac muscle anisotropy was small and that skeletal muscle effects could be accounted for by boundary extension, i.e., by scaling the conductivities and dimensions. However, in this paper, anisotropy for both the myocardium and the skeletal muscle is explicitly incorporated into the eccentric spheres volume conductor model. The anisotropy is treated as having uniform orthogonal components in the radial and tangential directions for both the skeletal muscle and myocardium. The solution for Laplace's equation is written in a series expansion of appropriate basis functions for each region. In the isotropic regions spherical harmonics with integer radial dependence and Legendre polynomial azimuthal dependence are utilized. For the anisotropic regions, Legendre polynomials are still appropriate for the azimuthal dependence, but noninteger powers of radial dependence are required. The approximate representation for anisotropy, i.e., the boundary extension method for the skeletal muscle and a scaled homogeneous conductivity without boundary extension for the myocardium are compared with explicit representations for the two regions. Two basic conclusions are drawn from the results. First, the treatment of skeletal muscle anisotropy by the boundary extension method is a valid and useful simplification which yields errors of 2% for the peak body surface potential. The second conclusion drawn from this study is that myocardial anisotropy has a significant effect on the magnitude of body surface potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Conductivity↗

[Ultrasonic tissue characterisation in cardiology].

Ultrasonic tissue characterization is a relatively new non-invasive examination method the application of which in cardiology is steadily increasing. It is therefore the objective of the present work to summarize hitherto assembled knowledge on the use of this method in clinical practice. Ultrasonic tissue characterization uses scattering of ultrasonic waves which penetrate into the heart muscle. This scatter is due to particles inside the heart muscle, their size being smaller than the wave length of the incident ultrasonic undulation. Evaluation of the intensity of the backscatter makes it possible to evaluate structural and functional changes of the examined cardiac tissue. Ultrasonic tissue characterization is so far used in cardiology for evidence of myocardial ischaemia, for evaluation of structural myocardial changes with hypertrophic cardiomyopathy, to detect rejection after transplantation of the heart and in the diagnosis of myocarditis. Other possibilities for application of this method is assessment of the viability of the heart muscle, quantification of the amount of fibrous tissue in the heart muscle and differentiation of acute from chronic vegetation in patients with infectious endocarditis. Due to some limitations ultrasonic tissue characterization is in the majority of the mentioned indications rather a subsidiary method which can supplement the diagnosis and make it more accurate. Its future position will obviously depend on further technical improvement and simplification.

Echocardiography↗

Canceling buoyancy of gaseous fuel flames in a gravitational environment using an ion-driven wind.

Electric fields applied to combustion plasmas can be used to manipulate the thermofluid flow field to reduce buoyant forces and, hence, convection in locations near and within the flame. The resulting flow field is similar to that which is obtained in microgravity. Previous work has shown that buoyancy is modified in a non-premixed methane-air capillary flame when it burns in a capillary-to-plane configuration and an electric field is applied, and that regions of neutral or microbuoyancy exist, as indicated by the examined temperature and oxidizer profiles. The aim of this article is to examine in more detail this microbuoyancy condition and the coupling between the ion wind and resulting thermofluid flow field. To this end, the voltage-current characteristics (VCC) of CH4, C2H2, C2H4, C2H6, and C3H8 are measured and compared. Soot generated in the C2H(X) and propane flames lead to a hysteresis in the VCC curve whereby increased sooting leads to lower ion currents at constant flow rates and applied potentials. Buoyancy regimes for these flames in this configuration are determined. Methane can achieve the highest flow rate without sooting at the microbuoyant condition, and does not exhibit hysteresis in the VCC for the flow rates examined here. Furthermore, in this geometry, the microbuoyant condition for methane is found to coincide with ion current saturation when the capillary-to-plane distance is varied. These results allow for several simplifications to be made when modeling the flame at these conditions: the imposition of a spherical flame boundary with known ion current, and negligible recombination in the domain.

Journal Article↗

Possibilities of the method of step-by-step complication of ligand structure in studies of protein--nucleic acid interactions: mechanisms of functioning of some replication, repair, topoisomerization, and restriction enzymes.

X-Ray structure analysis is one of the most informative methods for investigation of enzymes. However, it does not provide quantitative estimation of the relative efficiency of formation of contacts revealed by this method, and when interpreting the data this does not allow taking into account the relative contribution of some specific and nonspecific interactions to the total affinity of nucleic acids (NA) to enzymes. This often results in unjustified overestimation of the role of specific enzyme--NA contacts in affinity and specificity of enzyme action. In recent years we have developed new approaches to analysis of the mechanisms of protein--nucleic acid interactions allowing quantitative estimation of the relative contribution of virtually every nucleotide unit (including individual structural elements) to the total affinity of enzymes to long DNA and RNA molecules. It is shown that the interaction between enzymes and NA on the molecular level can be successfully analyzed by the methods of synthesis and analysis, that is, step-by-step simplification or complication of the structure of a long NA-ligand. This approach allows the demonstration that complex formation including formation of contacts between enzymes and specific NA units can provide neither high affinity of the enzymes to NA nor the specificity of their action. Using a number of sequence-independent replication and repair enzymes specifically recognizing a modified unit in DNA and also some sequence-dependent topoisomerization and restriction enzymes as examples, it was shown that virtually all nucleotide units within the DNA binding cleft interact with the enzyme, and high affinity mainly (up to 5-7 of 7-10 orders of magnitude) is provided by many weak additive interactions between these enzymes and various structural elements of the individual NA nucleotide units. At the same time, the relative contribution of specific interactions to the total affinity of NA is rather small and does not exceed 1-2 orders of magnitude. Specificity of enzyme action is provided by the stages of the enzyme-dependent NA adaptation to the optimal conformation and directly of catalysis: kcat increases by 3-7 orders of magnitude when changing from nonspecific to specific NA. In the present work we summarized our experience in studies of enzymes by the method of step-by-step complication of the ligand structure and performed a detailed analysis of the features of this approach and its possibilities for the study of protein--nucleic acid interactions on the molecular level.

Binding Sites↗

Reactive oxygen species in the cerebral circulation: physiological roles and therapeutic implications for hypertension and stroke.

It is now clear that reactive oxygen species (ROS) can act as signalling molecules in the cerebral circulation under both physiological and pathological conditions. Some major products of superoxide (O(2)(.)(-)) metabolism, such as hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH(.)), appear to be particularly good cerebral vasodilators and may, surprisingly, represent important molecules for increasing local cerebral blood flow. A major determinant of overall ROS levels in the cerebral circulation is the rate of generation of the parent molecule, O(2)(.)(-). Although the major enzymatic source of O(2)(.)(-) in cerebral arteries is yet to be conclusively established, the two most likely candidates are cyclo-oxygenase and nicotinamide adenine dinucleotide phosphate (reduced form) [NADPH] oxidase. The activity of endogenous superoxide dismutases (SODs) play a vital role in determining levels and effects of all individual ROS derived from metabolism of O(2)(.)(-). The term 'oxidative stress' may be an over-simplification that hides the complexity and diversity of the ROS family in cerebrovascular health and disease. Although a generalised increase in ROS levels seems to occur during several vascular disease states, the consequences of this for cerebrovascular function are still unclear. Because enhanced breakdown of O(2)(.)(-) by SOD will increase the generation of the powerful cerebral vasodilator H(2)O(2), this latter molecule could conceivably act as a compensatory vasodilator mechanism in the cerebral circulation under conditions of elevated O(2)(.)(-) production. Some recent clinical data support the concept of a protective role for cerebrovascular NADPH oxidase activity. Although it is quite speculative at present, if NADPH oxidase were to emerge as a major source of beneficial vasodilator ROS in the cerebral circulation, this may represent a significant dilemma for treatment of ischaemic cerebrovascular conditions, as excessive NADPH oxidase activity is associated with the progression of several systemic vascular disease states, including hypertension and atherosclerosis. Despite data suggesting that antioxidant vitamins can have beneficial effects on vascular function and that their plasma levels are inversely correlated with risk of cardiovascular disease and stroke, the results of several recent large-scale clinical trials of antioxidant supplementation have been disappointing. Future work must establish whether or not increased ROS generation is necessarily detrimental to cerebral vascular function, as has been generally assumed, or whether localised increases in ROS in the vicinity of the arterial wall could be beneficial in disease states for the maintenance of cerebral blood flow.

Animals↗

Voltammetric and amperometric transduction for solvent polymeric membrane ion sensors.

This paper describes basic response features of solvent polymeric membrane ion sensors with voltammetric and amperometric transduction. The model systems used here contain no ionophore for simplicity reasons. Reasonable simplifications of the theory are introduced that allow one to understand the response mechanism in view of a practical application of these sensors. It is shown that ion-sensing membranes preferentially contain no ion-exchanger properties in order to function optimally in a voltammetric mode. As with the systems studied by Kihara, both liquid-polymer interfaces of the membrane are preferably polarizable. Specifically, they contain the highly lipophilic electrolyte tetradodecylammonium tetrakis(4-chlorophenyl)borate (ETH 500) in the membrane to improve lifetime, increase the magnitude of the potential window, and prohibit exchange reactions with sample ions. An ohmic behavior that is associated with an assisted electrolyte-transfer process is observed only above a threshold potential which can be quantitatively predicted by theory. The threshold potential depends on the nature and activity of sample anions and cations in the sample and inner filling solution of the membrane electrode. Within the experimental conditions discussed in this paper, these sensors seem to measure sample ion activities, not concentrations, since the rate-limiting step is the diffusion of extracted ions away from the interface into the membrane bulk. Similarly, no effect of sample stirring on the measured current is observed. This contrasts to work done on liquid-liquid electrolyte-transfer reactions, where large diffusion coefficients in the organic phase often lead to substantial sample depletion effects. The detection of anions and cations with the same membrane is demonstrated in a cyclic voltammetric mode. Direct continuous detection of one type of anion is accomplished by pulsed amperometry to ensure a rapid, repetitive renewal of the membrane composition between measurements.

Electrochemistry↗

Combined high pressure and temperature induced lethal and sublethal injury of Lactococcus lactis--application of multivariate statistical analysis.

It was the aim of this work to determine the combined effects of pressure, temperature, and co-solutes on Lactococcus lactis, and to detect correlations between culture-dependent and culture-independent methods for assessment of cellular viability and sublethal injury. Therefore, the pressure induced inactivation of L. lactis MG 1363 was investigated in buffer and in buffer with 1.5 M sucrose or 4 M NaCl at a pressure range of 0.1 to 500 MPa and a temperature range of 5 to 50 degrees C. The inactivation was characterised by viable cell counts, stress resistant cell counts, membrane integrity, metabolic activity, and the activity of the multi-drug-resistance transport enzyme LmrP. L. lactis was most resistant to pressure application at 20-30 degrees C. Sucrose protected towards inactivation at any temperature, NaCl provided protection at high temperatures only. By using Principal Component Analysis, correlations were detected between viable cell counts and metabolic activity as well as stress resistant cell counts and LmrP activity. In conclusion, the pressure-inactivation of L. lactis is strongly temperature dependent, baroprotection by sucrose occurs at any temperature but the baroprotective effects of NaCl is temperature dependent. Further on, a combination of two experimental methods fully describe lethal and sublethal injury of pressure treated cells. These simplification of data acquisition and model development facilitates the establishment of pressure processes in food technology.

Bacterial Proteins↗

Endopolyploidy as a morphogenetic factor of development.

This paper summarizes the works published by author and his co-workers in the Russian journal Tsitologiya concerning endopolyploidy in mollusks and appraises this phenomenon in general. Both ontogenetic and phylogenetic aspects of endopolyploidy have been studied. In the snail Succinea lauta, a complex examination of endomitosis has been performed. A regular replacement of the normal (complete) proliferative mitosis by abnormal (incomplete) restitutional mitosis, and then by Geitler's classic endomitosis has been demonstrated. We examined 29 bivalve and 82 gastropod species for the presence of polyploid cells in glandular tissues and ganglia. In the bivalve species, ordinary diploid cells form various tissues, while in the gastropods, the role of polyploidy in tissue development appears to increase in phylogenesis. The rise of endopolyploidy and cell giantism in histogeneses of a variety of animal and plant species is widely known. It is believed to be a regular event in the evolution of certain groups. To give a universal interpretation of endopolyploidy, we proposed that a single polyploid cell be better considered as an endoclone. In this case, evolutionary transformation of diploid cell clones into polyploid endoclones may be viewed as Dogel's oligomerization applied to cell-tissue level. From this viewpoint, major properties of an oligomerized system (intensification of function, functional efficiency (ergonomy), increased genomes reliability, simplification of the intra- and supersystem regulations, and acceleration of development) can be considered as principal peculiarities of polyploid growth strategy. The above peculiarities allow one to consider endopolyploidy as an additional means of integrative onto(histo)genetic regulations and correlations and as an important evolutionary factor (coordinations) acting through natural selection. Thus, in general, endopolyploidy is an adaptive morphogenetic factor, but its concrete role may differ in different tissues and organisms depending on cell specialization and histogenetic particularities.

Animals↗

The gestalt of occlusion--A clinical appraisal.

1. Occlusion, with its many ramifications, cannot be over simplified. It should not be considered so varied that a sequential and subtle analysis of its ramifications defies simplification. 2. The same mechanisms produce the correct or incorrect physiologic position of the dental units. A faulty mechanism must be recognized and all efforts made to return it to efficiency as soon as possible for the benefit of the entire system. 3. The correct physiologic terminal position of the mandibular condyles is the ideal relationship in the TMJ and activates the posterior component forces of the neurologic system. This forms the dentition into its most harmonious relationship. 4. Any teminal position of the condyle in the mandibular fossa, other than the physiologic terminal position, compromises the potential of a harmonious interdental forming process. The results range from simple deflective occlusal contacts to severe malocclusions. 5. The constancy of the occlusal plane relationship, easily determined from a cephalometric tracing offers a clinical guide as to its best functioning position. 6. A TMJ radiographic technique that ensures repeatable, reproducible, and traceable radiograms is an essential diagnostic aid. It is necessary to know the position of the condyle in the fossa before, during, and after procedures that alter the interocclusal relationship. 7. Not all TMJ problems are necessarily symptomatic. Occlusal adjustment procedures should be utilized to ensure a harmonious interocclusal relationship manifest by the muscles of mastication functioning in a nonsymptomatic, optimal, and physiologic manner, in all working jaw relations. The ideal physiologic terminal position must be established as closely as possible during saliva swallowing. 8. Only occlusal adjustment techniques utilizing the natural forces of the neuromuscular system to reestablish the ideal physiologic terminal position within the TMJ should be used. A technique such as that developed by Long satisfies this requirement. 9. Although there are many imperfections in knowledge, there are no imperfections in truth.

Cephalometry↗

Allosteric gating of a large conductance Ca-activated K+ channel.

Large-conductance Ca-activated potassium channels (BK channels) are uniquely sensitive to both membrane potential and intracellular Ca2+. Recent work has demonstrated that in the gating of these channels there are voltage-sensitive steps that are separate from Ca2+ binding steps. Based on this result and the macroscopic steady state and kinetic properties of the cloned BK channel mslo, we have recently proposed a general kinetic scheme to describe the interaction between voltage and Ca2+ in the gating of the mslo channel (Cui, J., D.H. Cox, and R.W. Aldrich. 1997. J. Gen. Physiol. In press.). This scheme supposes that the channel exists in two main conformations, closed and open. The conformational change between closed and open is voltage dependent. Ca2+ binds to both the closed and open conformations, but on average binds more tightly to the open conformation and thereby promotes channel opening. Here we describe the basic properties of models of this form and test their ability to mimic mslo macroscopic steady state and kinetic behavior. The simplest form of this scheme corresponds to a voltage-dependent version of the Monod-Wyman-Changeux (MWC) model of allosteric proteins. The success of voltage-dependent MWC models in describing many aspects of mslo gating suggests that these channels may share a common molecular mechanism with other allosteric proteins whose behaviors have been modeled using the MWC formalism. We also demonstrate how this scheme can arise as a simplification of a more complex scheme that is based on the premise that the channel is a homotetramer with a single Ca2+ binding site and a single voltage sensor in each subunit. Aspects of the mslo data not well fitted by the simplified scheme will likely be better accounted for by this more general scheme. The kinetic schemes discussed in this paper may be useful in interpreting the effects of BK channel modifications or mutations.

Animals↗