A “parallel plate” electrostatic model for bimolecular rate constants applied to electron transfer proteins

A “parallel plate” model describing the electrostatic potential energy of protein-protein interactions is presented that provides an analytical representation of the effect of ionic strength on a bimolecular rate constant. The model takes into account the asymmetric distribution of charge on the surface of the protein and localized charges at the site of electron transfer that are modeled as elements of a parallel plate condenser. Both monopolar and dipolar interactions are included. Examples of simple (monophasic) and complex (biphasic) ionic strength dependencies obtained from experiments with several electron transfer protein systems are presented, all of which can be accommodated by the model. The simple cases do not require the use of both monopolar and dipolar terms (i.e., they can be fit well by either alone). The biphasic dependencies can be fit only by using dipolar and monopolar terms of opposite sign, which is physically unreasonable for the molecules considered. Alternatively, the high ionic strength portion of the complex dependencies can be fit using either the monopolar term alone or the complete equation; this assumes a model in which such behavior is a consequence of electron transfer mechanisms involving changes in orientation or site of reaction as the ionic strength is varied. Based on these analyses, we conclude that the principal applications of the model presented here are to provide information about the structural properties of intermediate electron transfer complexes and to quantify comparisons between related proteins or site-specific mutants. We also conclude that the relative contributions of monopolar and dipolar effects to protein electron transfer kinetics cannot be evaluated from experimental data by present approximations.     

Effects of different doses of free 𝛂-linolenic acid infused to the duodenum on the immune function of lactating dairy cows

This study investigated the effect of a duodenal infusion of a C18:3 free fatty acid on the immune function of lactating dairy cows. Four primiparous Chinese Holstein cows fitted with duodenal cannulas received 0, 100, 200, 300, and 400 g/d of α-linolenic acid (LNA) in a two-treatment crossover design. Blood was collected and serum IgA, IgG, IgM, prostaglandin E₂ (PGE₂) and Th1/Th2 cytokines were determined. Results showed that increasing the supply of LNA to the small intestine of dairy cows linearly increased serum IgG and quadratically enhanced interferon-γ (p < 0.05), whereas the concentrations of PGE₂ declined linearly (p < 0.05) and those of interleukin (IL)-4 tended to decrease (p = 0.08). No difference was observed in serum IgA, IgM or other cytokines, such as IL-2, IL-6 and IL-10. This study demonstrated that in dairy cows, a post-ruminal infusion of high doses of LNA has immunomodulatory effects, possibly associated with a predisposition to a Th1-type response.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Transfemoral catheterization of the cavernous sinus outflow with comparison of “central” and “peripheral” gonadotropin patterns in bonnet monkeys

Concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in central (C) samples obtained by transfemorally catheterizing the inferior petrosal sinus of female bonnet monkeys were compared with those in peripheral (P) samples obtained simultaneously from the saphenous veins of two intact and two oophorectomized bonnet monkeys, before, during, and after luteinizing hormone releasing hormone (LHRH) stimulation. Significant differences between central and peripheral gonadotropin concentrations were detected intermittently in the resting state, and tended to be magnified by LHRH administration. In one animal in which LHRH was fortuitously administered during the course of a spontaneous LH surge, a C/P ratio for LH of 12.71, the maximum observed, was obtained. Spectral analysis exhibited periodicity for LH and, to a lesser extent, for FSH in the oophorectomized, but not in the intact, animals.     

“Patient-Like” nude mouse metastatic model of advanced human pleural cancer

Pleural Cancer in humans is a frequently occuring tumor, Recently, clinical ltrials have suggested that chemotherapy and immunotherapy administered intrapleually may elicit responses in early-stage diseases. However, atradiological and pleural endoscopic evaluation, most of the patients are found to have a visceral pleural involvement that is generally refractory to therapy and leads to a poor prognosis. The goal of this study was to construct a nude mouse model of human parietal- and visceral-pleural cancer that could reflect the clinical picture for this disease. The model could then be useful for drug discovery for pleural cancer. A well-differentiated human lung adenocarcinoma was used as intact tissue for implantation. Ten mice underwent parietal-pleural implantation and ten mice visceral-pleural implantation via a novel thoracotomy procedure we have developed. Symptoms of tumor growth were determined from weight loss, repiratory distress, or debilitation. Actual tumor growth and spread were measured at autopsy. The mouse survival curves of each group were estimated by the Kaplan-Meier Method and the difference of the median survial timje was assessed by the Log-rank test. The slopes of mean-mouse weight curves were compared using a standard two-sample t-test. 100% take rate was achieved in constructing the pleural cancer models. Tumor growth was initially assessed by symptomatology and survival: the median survival time was, repectively, 27.9 days 31 days for visceral-pleural and parietal-pleural implanted groups (P<0.05). The comparison between the slopes of the mean weight curves of corresponding groups demonstrated that visceral-pleural implanted animals lost significantly more weight than the parietal-pleural implanted animals (P <.001). Both in the visceral- and pariental-pleural implanted groups, post-mortem analysis revealed that tumor grew in all mic demonstrating local and regional spread mimicking clinical features. However, mediastinal lymph node metastases were observed only in mice with visceral pleural implantation. Patient-like models of human parietal-pleural and visceral-pleural cancer were constructed in nude mice using histologically ilntact human specimens. Tumor symptoms, growth, and spread as well as survival indicated that the parietal-pleural and visceral-pleural models represent, respectively, early-and advanced-stage disease. The “Patient-like” nude mouse models of pleural cancer now allow a rational basis for futher studies of pleural cancer biology, pathophysiology, and therapeutics.     

Light matters: testing the “Light Environment Hypothesis” under intra‐ and interspecific contexts

The “Light Environment Hypothesis” (LEH) proposes that evolution of interspecific variation in plumage color is driven by variation in light environments across habitats. If ambient light has the potential to drive interspecific variation, a similar influence should be expected for intraspecific recognition, as color signals are an adaptive response to the change in ambient light levels in different habitats. Using spectrometry, avian‐appropriate models of vision, and phylogenetic comparative methods, I quantified dichromatism and tested the LEH in both intra‐ and interspecific contexts in 33 Amazonian species from the infraorder Furnariides living in environments with different light levels. Although these birds are sexually monochromatic to humans, 81.8% of the species had at least one dichromatic patch in their plumage, mostly from dorsal areas, which provides evidence for a role for dichromatism in sex recognition. Furthermore, birds from habitats with high levels of ambient light had higher dichromatism levels, as well as brighter, more saturated, and more diverse plumages, suggesting that visual communication is less constrained in these habitats. Overall, my results provide support for the LEH and suggest that ambient light plays a major role in the evolution of color signals in this group of birds in both intra‐ and interspecific contexts. Additionally, plumage variation across light environments for these drab birds highlights the importance of considering ambient light and avian‐appropriate models of vision when studying the evolution of color signals in birds.     

A simulation test of Smith's “degrees of freedom” correction for comparative studies

Computer simulation was used to test Smith's (1994) correction for phylogenetic nonindependence in comparative studies. Smith's method finds effective N, which is computed using nested analysis of variance, and uses this value in place of observed N as the baseline degrees of freedom (df) for calculating statistical significance levels. If Smith's formula finds the correct df, distributions of computer-generated statistics from simulations with observed N nonindependent species should match theoretical distributions (from statistical tables) with the df based on effective N. The computer program developed to test Smith's method simulates character evolution down user-specified phylogenies. Parameters were systematically varied to discover their effects on Smith's method. In simulations in which the phylogeny and taxonomy were identical (tests of narrow-sense validity), Smith's method always gave conservative statistical results when the taxonomy had fewer than five levels. This conservative departure gave way to a liberal deviation in type I error rates in simulations using more than five taxonomic levels, except when species values were nearly independent. Reducing the number of taxonomic levels used in the analysis, and thereby eliminating available information regarding evolutionary relationships, also increased type I error rates (broad-sense validity), indicating that this may be inappropriate under conditions shown to have high type I error rates. However, the use of taxonomic categories over more accurate phylogenies did not create a liberal bias in all cases in the analysis performed here. The effect of correlated trait evolution was ambiguous but, relative to other parameters, negligible. © 1995 Wiley-Liss, Inc.     

Strong “bottom‐up” influences on small mammal populations: State‐space model analyses from long‐term studies

“Bottom‐up” influences, that is, masting, plus population density and climate, commonly influence woodland rodent demography. However, “top‐down” influences (predation) also intervene. Here, we assess the impacts of masting, climate, and density on rodent populations placed in the context of what is known about “top‐down” influences. To explain between‐year variations in bank vole Myodes glareolus and wood mouse Apodemus sylvaticus population demography, we applied a state‐space model to 33 years of catch‐mark‐release live‐trapping, winter temperature, and precise mast‐collection data. Experimental mast additions aided interpretation. Rodent numbers in European ash Fraxinus excelsior woodland were estimated (May/June, November/December). December–March mean minimum daily temperature represented winter severity. Total marked adult mice/voles (and juveniles in May/June) provided density indices validated against a model‐generated population estimate; this allowed estimation of the structure of a time‐series model and the demographic impacts of the climatic/biological variables. During two winters of insignificant fruit‐fall, 6.79 g/m² sterilized ash seed (as fruit) was distributed over an equivalent woodland similarly live‐trapped. September–March fruit‐fall strongly increased bank vole spring reproductive rate and winter and summer population growth rates; colder winters weakly reduced winter population growth. September–March fruit‐fall and warmer winters marginally increased wood mouse spring reproductive rate and September–December fruit‐fall weakly elevated summer population growth. Density dependence significantly reduced both species' population growth. Fruit‐fall impacts on demography still appeared after a year. Experimental ash fruit addition confirmed its positive influence on bank vole winter population growth with probable moderation by colder temperatures. The models show the strong impact of masting as a “bottom‐up” influence on rodent demography, emphasizing independent masting and weather influences; delayed effects of masting; and the importance of density dependence and its interaction with masting. We conclude that these rodents show strong “bottom‐up” and density‐dependent influences on demography moderated by winter temperature. “Top‐down” influences appear weak and need further investigation.     

“Impoverished” and “enriched” living conditions influence the proliferation and survival of neurons in crayfish brain

New neurons are added to two bilateral clusters of neurons in crayfish brain throughout their lives. These interneurons are associated with the olfactory and accessory lobes, areas of the brain that receive primary olfactory information and higher order inputs from the visual and tactile receptor systems. The rate of cell proliferation in these four clusters, revealed by BrdU labeling, is sensitive to the living conditions of the animals: individuals isolated in small spaces (impoverished condition) exhibit a lower rate of cell proliferation in comparison to their siblings living together in larger areas (enriched condition), although both groups were fed to satiation. Reduction in the rate of proliferation can be measured 1 to 2 weeks after the animals are subjected to the impoverished condition. Counts of the labeled neurons that survive after 4 weeks of subjection to the two conditions show that fewer new neurons survive in the brains of animals that have lived for 2 weeks in the impoverished condition in comparison to their siblings living in the enriched conditions. Factors such as surface area, depth of water, and social interaction can all play a role in determining both the rate of new neuron production and the incorporation of the new neurons into the brain of freshwater crayfish. The results indicate a high degree of neuronal plasticity in the crayfish brain that is highly sensitive to the conditions under which the animals are kept. © 2000 John Wiley & Sons, Inc. J Neurobiol 45: 215–226, 2000     

An evolutionary interpretation of the “motivation to oviposit”

The ovipositional behavior of parasitoids and other insects is often described by phrases such as “motivation to oviposit” or “ovipositional drive”. This paper shows how an evolutionary (i.e. functional) interpretation can be given to such phrases. A detailed model for the parasitisation of Sycamore aphids by M. pseudoplatani is developed, using experiments by Collins and Dixon (1986). Two models are developed: i) one in which egg complement is the only state variable and ii) one in which egg complement and information concerning host densities are state variables. Comparisons of the behaviour of simulated parasitoids, using the decisions associated with the models, and the experiments suggest that both egg complement and information are important for the parasitoid's decision making. Accepting previously parasitized hosts may be optimal, and not simply an error in parasitoid perception. A number of other detailed predictions are made, such as the relative fitness of first and second eggs in superparasitized hosts and the nature of the memory of the parasitoid.     

Proximate Composition and Nutrient Elements in the “Unusual” Algal “Jellies” of Lake Oguta in Southern Nigeria

The proximate composition, nutrient and trace elements of the planktonic algal “jellies” of Lake Oguta in Southern Nigeria, are provided as guides to their utilization and control, using flood (rainy) and dry season samples. These “jellies” are an unusual, macroscopic planktonic algal community in the lake, made up mostly of blue-green algae (Microcystis, Anabaena, Chroococcus) with some green algae (e. g. Spirogyra) and pennate diatoms (e.g. Navicula) rather epiphytic on the mucous jellies of the blue-green algae. Water content was high (98.2% mean, range 97.5-99.5%). Ash, protein and fat had values of 41.7 (39.0-46.2%), 16.9 (15.6-19.4%), and 2.0 (1.7-2.1%) respectively. Crude fibre and carbohydrates were high (25.8% and 12.4%). The levels of phosphorus and nitrogen were rather high, so were the major cations whose order of dominance (Ca > K > Mg > Na) differed from that of the lake water. Macronutrients increased in their concentrations during the rainy flood season while the reverse was the case with the micronutrients. Diagenesis of the endogenic minerals rather than anthropogenic factors are thought to be the reason for the seasonal changes in the ionic concentrations. Possible uses of the algal jellies are discussed as well as their control options.     

Application of the “-Omic-” technologies in phytomedicine

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. They increase substantially the number of proteins/genes that can be detected simultaneously and have the potential to relate complex mixtures to complex effects in the form of gene/protein expression profiles. Provided that phytopreparation-specific signatures in the form of gene/protein expression profiles can be developed, these technologies will be useful for the chemical and pharmacological standardization and the proof of the toxicological potential of a plant extract. Over a long-term perspective they may economize the proof of efficacy, the determination of the mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of this genomics revealed already that gene expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the information of the mode of action of isolated "active principles/lead substances" of phytopreparations questionable. The application of the "-omic-" technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new field of phytogenomics, -proteomics and -metabolomics.     

A Simple Testing Procedure “Control versus k Treatments” for One-sided Ordered Alternatives,with Application in Toxicology

A simple testing procedure “control versus k treatments” for one-sided ordered alternatives for univariate, continuous variables is given. With a simulation study both the first kind risk a and the power behaviour under several distributions, expected value profiles, sample sizes and a levels are shown.     

Genes and structural patterns in ciliates: Vance tartar and the “cellular architects”

The one form of cytoplasmic inheritance that has not been assimilated into the Central Dogma is the inheritance of surface structural patterns, a phenomenon most clearly expressed in cilates. Vance Tartar, although he worked with a genetically undomesticated organism (Stentor coeruleus), provided early evidence for the crucial role of clonally propagated features of the cell cortex. He showed that the capacity for development of cortical organelle systems is associated with a particular relational feature, the “locus of stripe contrast” (LSC), and that clonally inherited cortical variants (homopolar doublets) could be created at will by microsurgical operations that duplicated the LSC. Tartar also hoped to demonstrate the existence of what David Nanney called “cellular architects” by provoking stentors to carry out entirely novel types of morphogenetic performances. He eventually acknowledged failure, although the bizarre juxtapositions by which he attempted to elicit such novel performances did bring about specific and illuminating defects in cortical development. Subsequent analyses of similar defects in other ciliates revealed not the unitary “pattern factor” postulated by Tartar, but rather a hierarchy of distinct patterning mechanisms. Nonetheless, by pursuing an embryological approach toward morphogenesis in a highly regulative ciliate, Tartar uncovered relational aspects of pattern-determination; this, in my view, delineates the major problem that we must solve to gain understanding of intracellular patterning. © 1992 Wiley-Liss, Inc.     

Investigation of an “alternate water supply system” in enzymatic hydrolysis in the processive endocellulase Cel7A from Rasamsonia emersonii by molecular dynamics simulation

Cel7A from Rasamsonia emersonii is one of the processive endocellulases classified under family 7 glycoside hydrolase. Molecular dynamics simulations were carried out to obtain the optimized sliding and hydrolyzing conformations, in which the reducing ends of sugar chains are located on different sites. Hydrogen bonds are investigated to clarify the interactions between protein and substrate in either conformation. Nine hydrogen bonding interactions are identified in the sliding conformation, and six similar interactions are also found correspondingly in the hydrolyzing conformation. In addition, four strong hydrophobic interactions are also determined. The domain cross‐correlation map analysis shows movement correlation of protein including autocorrelation between residues. The root mean square fluctuations analysis represents the various flexibilities of different fragment in the two conformations. Comparing the two conformations reveals the water‐supply mechanism of selective hydrolysis of cellulose in Cel7A. The mechanism can be described as follow. When the reducing end of substrate slides from the unhydrolyzing site (sliding conformation) to the hydrolyzing site (hydrolyzing conformation), His225 is pushed down and rotated, the rotation leads to the movement of Glu209 with the interstrand hydrogen bonding in β‐sheet. It further makes Asp211 close to the hydrolysis center and provides a water molecule bounding on its carboxyl in the previous unhydrolyzing site. After the hydrolysis takes place and the product is excluded from the enzyme, the Asp211 comes back to its initial position. In summary, Asp211 acts as an elevator to transport outer water molecules into the hydrolysis site for every other glycosidic bond.