Cytological structure of splenic white pulp in persons of different age

Spleens (27) obtained from human corpses (from 1 year up to 85 years) have been investigated. By means of morphometrical grid amount of cells in the periarterial lymphoid muffs (PLM) and in marginal zones (MZ) of the spleen have been counted. In both structures of the white pulp small lymphocytes make the greatest number. Middle lymphocytes in comparison to the small ones are 1.5-4 times less in most of the age groups investigated. Amount of plasma cells is small. The part of reticular cells is 21-46% in MZ and 20-36% in PLM from the total amount of cells. In PLM immediately around the artery tightly packed to each other small lymphocytes are situated. Among small lymphocytes reticular cells are situated. A similar arrangement of cells is kept along the whole thickness of PLM. In MZ distance between cells of the lymphoid line is a little greater than in PLM. To singularly situating reticular cells small and middle lymphocytes are immediate neighbours. Plasma cells, as a rule, occur seldom; either middle lymphocytes, or reticular cells adjoin them. Sometimes, in PLM and MZ macrophages occur; they are situated in the areas free from other cells.     

Effects of Isometric Scaling on Vertical Jumping Performance

Jump height, defined as vertical displacement in the airborne phase, depends on vertical takeoff velocity. For centuries, researchers have speculated on how jump height is affected by body size and many have adhered to what has come to be known as Borelli’s law, which states that jump height does not depend on body size per se. The underlying assumption is that the amount of work produced per kg body mass during the push-off is independent of size. However, if a big body is isometrically downscaled to a small body, the latter requires higher joint angular velocities to achieve a given takeoff velocity and work production will be more impaired by the force-velocity relationship of muscle. In the present study, the effects of pure isometric scaling on vertical jumping performance were investigated using a biologically realistic model of the human musculoskeletal system. The input of the model, muscle stimulation over time, was optimized using jump height as criterion. It was found that when the human model was miniaturized to the size of a mouse lemur, with a mass of about one-thousandth that of a human, jump height dropped from 40 cm to only 6 cm, mainly because of the force-velocity relationship. In reality, mouse lemurs achieve jump heights of about 33 cm. By implication, the unfavourable effects of the small body size of mouse lemurs on jumping performance must be counteracted by favourable effects of morphological and physiological adaptations. The same holds true for other small jumping animals. The simulations for the first time expose and explain the sheer magnitude of the isolated effects of isometric downscaling on jumping performance, to be counteracted by morphological and physiological adaptations.     

Phosphomimetic mutations enhance oligomerization of phospholemman and modulate its interaction with the Na/K-ATPase

Na/K-ATPase (NKA) activity is dynamically regulated by an inhibitory interaction with a small transmembrane protein, phospholemman (PLM). Inhibition is relieved upon PLM phosphorylation. Phosphorylation may alter how PLM interacts with NKA and/or itself, but details of these interactions are unknown. To address this, we quantified FRET between PLM and its regulatory target NKA in live cells. Phosphorylation of PLM was mimicked by mutation S63E (PKC site), S68E (PKA/PKC site), or S63E/S68E. The dependence of FRET on protein expression in live cells yielded information about the structure and binding affinity of the PLM-NKA regulatory complex. PLM phosphomimetic mutations altered the quaternary structure of the regulatory complex and reduced the apparent affinity of the PLM-NKA interaction. The latter effect was likely due to increased oligomerization of PLM phosphomimetic mutants, as suggested by PLM-PLM FRET measurements. Distance constraints obtained by FRET suggest that phosphomimetic mutations slightly alter the oligomer quaternary conformation. Photon-counting histogram measurements revealed that the major PLM oligomeric species is a tetramer. We conclude that phosphorylation of PLM increases its oligomerization into tetramers, decreases its binding to NKA, and alters the structures of both the tetramer and NKA regulatory complex.     

Characterization of the Human and Rat Phospholemman (PLM) cDNAs and Localization of the Human PLM Gene to Chromosome 19q13.1

Previous reports have demonstrated that the phospholemman (PLM), a 72-residue plasma-membrane protein enriched in skeletal muscle and heart, is a major substrate phosphorylated in response to insulin and adrenergic stimulation. Here we describe the isolation and characterization of human and rat PLM cDNA from the heart. Both PLM proteins share significant nucleotide and amino acid sequence and structural similarities with the previously published canine PLM and, to a lesser degree, with Na⁺/K⁺– ATPase γ subunit, Mat-8 protein, and CHIF protein. Despite the functional diversity, all these proteins are quite small and possess a single transmembrane domain. Human PLM appears to be a unique gene localized on chromosome 19q13.1. The PLM mRNA is widely distributed in human tissues, with the highest expression in skeletal muscle and heart, suggesting a functional role in muscle contraction. Like canine PLM, both human and rat PLM induce a hyperpolarization-activated chloride current when expressed inXenopusoocytes. The high degree of sequence and functional conservation among the mammalian PLM proteins indicates that this gene is conserved throughout evolution.     

Plasmalogens protect unsaturated lipids against UV-induced oxidation in monolayer

Oxidative stress results from the attack by free radicals of several cellular targets (proteins, DNA and lipids). The cell equilibrium is a direct consequence of the pro-/antioxidant balance. In order to understand the physiological processes involved in oxidative stress, we followed oxidation of unsaturated lipids using a biomimetic system: Langmuir monolayers. The oxidation mode chosen was UV-irradiation and the lipid model was a polyunsaturated phospholipid: 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC). The monomolecular film technique was used to measure membrane rheology before and after UV-irradiation. We showed that the UV-irradiation of a DLPC monomolecular film led to a molecular area and surface elasticity modulus decrease that attests to the apparition of new molecular species at the air-water interface. The antioxidant effect of a synthetic plasmalogen (1-O-(1'-(Z)-hexadecenyl)-2-O-oleoyl-sn-glycero-3-phosphocholine or P(PLM)OPE) was tested on the oxidation of DLPC. Indeed, for about 25% mol P(PLM)OPE in mixed DLPC/P(PLM)OPE monolayers, a complete inhibition of the molecular area and the surface elasticity modulus decreases was observed in our experimental conditions. Lower P(PLM)OPE quantities delayed but did not prevent the DLPC oxidation in mixed monolayers.     

A partial linear model in the outcome-dependent sampling setting to evaluate the effect of prenatal PCB exposure on cognitive function in children

Outcome-dependent sampling (ODS) has been widely used in biomedical studies because it is a cost-effective way to improve study efficiency. However, in the setting of a continuous outcome, the representation of the exposure variable has been limited to the framework of linear models, due to the challenge in terms of both theory and computation. Partial linear models (PLM) are a powerful inference tool to nonparametrically model the relation between an outcome and the exposure variable. In this article, we consider a case study of a PLM for data from an ODS design. We propose a semiparametric maximum likelihood method to make inferences with a PLM. We develop the asymptotic properties and conduct simulation studies to show that the proposed ODS estimator can produce a more efficient estimate than that from a traditional simple random sampling design with the same sample size. Using this newly developed method, we were able to explore an open question in epidemiology: whether in utero exposure to background levels of polychlorinated biphenyls (PCBs) is associated with children's intellectual impairment. Our model provides further insights into the relation between low-level PCB exposure and children's cognitive function. The results shed new light on a body of inconsistent epidemiologic findings.     

Effect of static load on motor behavior of the cockroach Periplaneta americana

Effect of static load on activity of motor centers controlling motor activity (walking flight) was studied in the American cockroach Periplaneta americana L. It has been established that under effect of load on the animal body the relative excitability of these centers increases. A suggestion is put forward about the presence of common neuronal elements in the generator networks providing motor acts in the American cockroach; a role of afferent systems in control of excitability of locomotor centers functioning in the regime of static load is shown.     

Two alternating motor programs drive navigation in Drosophila larva

When placed on a temperature gradient, a Drosophila larva navigates away from excessive cold or heat by regulating the size, frequency, and direction of reorientation maneuvers between successive periods of forward movement. Forward movement is driven by peristalsis waves that travel from tail to head. During each reorientation maneuver, the larva pauses and sweeps its head from side to side until it picks a new direction for forward movement. Here, we characterized the motor programs that underlie the initiation, execution, and completion of reorientation maneuvers by measuring body segment dynamics of freely moving larvae with fluorescent muscle fibers as they were exposed to temporal changes in temperature. We find that reorientation maneuvers are characterized by highly stereotyped spatiotemporal patterns of segment dynamics. Reorientation maneuvers are initiated with head sweeping movement driven by asymmetric contraction of a portion of anterior body segments. The larva attains a new direction for forward movement after head sweeping movement by using peristalsis waves that gradually push posterior body segments out of alignment with the tail (i.e., the previous direction of forward movement) into alignment with the head. Thus, reorientation maneuvers during thermotaxis are carried out by two alternating motor programs: (1) peristalsis for driving forward movement and (2) asymmetric contraction of anterior body segments for driving head sweeping movement.     

Effect of static load on motor behavior of the cockroach Periplaneta americana

Effect of static load on activity of motor centers controlling motor activity (walking, flight) was studied in the American cockroach Periplaneta americana L. It has been established that under effect of load on the animal body the relative excitability of these centers increases. A suggestion is put forward about the presence of common neuronal elements in the generator networks providing motor acts in the American cockroach; a role of afferent systems in control of excitability of loco-motor centers functioning in the regime of static load is shown.     

Characterization of the phospholemman knockout mouse heart: depressed left ventricular function with increased Na-K-ATPase activity

Phospholemman (PLM, FXYD1), abundantly expressed in the heart, is the primary cardiac sarcolemmal substrate for PKA and PKC. Evidence supports the hypothesis that PLM is part of the cardiac Na-K pump complex and provides the link between kinase activity and pump modulation. PLM has also been proposed to modulate Na/Ca exchanger activity and may be involved in cell volume regulation. This study characterized the phenotype of the PLM knockout (KO) mouse heart to further our understanding of PLM function in the heart. PLM KO mice were bred on a congenic C57/BL6 background. In vivo conductance catheter measurements exhibited a mildly depressed cardiac contractile function in PLM KO mice, which was exacerbated when hearts were isolated and Langendorff perfused. There were no significant differences in action potential morphology in paced Langendorff-perfused hearts. Depressed contractile function was associated with a mild cardiac hypertrophy in PLM KO mice. Biochemical analysis of crude ventricular homogenates showed a significant increase in Na-K-ATPase activity in PLM KO hearts compared with wild-type controls. SDS-PAGE and Western blot analysis of ventricular homogenates revealed small, nonsignificant changes in Na- K-ATPase subunit expression, with two-dimensional gel (isoelectric focusing, SDS-PAGE) analysis revealing minimal changes in ventricular protein expression, indicating that deletion of PLM was the primary reason for the observed PLM KO phenotype. These studies demonstrate that PLM plays an important role in the contractile function of the normoxic mouse heart. Data are consistent with the hypothesis that PLM modulates Na-K-ATPase activity, indirectly affecting intracellular Ca and hence contractile function.     

Extracting optimal tempo-spatial features using local discriminant bases and common spatial patterns for brain computer interfacing

Brain computer interfaces (BCI) provide a new approach to human computer communication, where the control is realised via performing mental tasks such as motor imagery (MI). In this study, we investigate a novel method to automatically segment electroencephalographic (EEG) data within a trial and extract features accordingly in order to improve the performance of MI data classification techniques. A new local discriminant bases (LDB) algorithm using common spatial patterns (CSP) projection as transform function is proposed for automatic trial segmentation. CSP is also used for feature extraction following trial segmentation. This new technique also allows to obtain a more accurate picture of the most relevant temporal–spatial points in the EEG during the MI. The results are compared with other standard temporal segmentation techniques such as sliding window and LDB based on the local cosine transform (LCT).     

Upregulation of Respiratory Burst of Polymorphonuclear Leukocytes By A Bleomycin Derivative, Peplomycin

The influence of peplomycin (PLM) on the respiratory burst of peripheral blood polymorphonuclear leukocytes (PMN) was investigated. Short-term (5 min) treatment of human PMN with 0.1μg/ml to 100μg/ml of PLM increased phorbol myristate acetate (PMA)-and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced luminol-dependent chemiluminescence. PMN, as well as alveolar macrophages from rabbits treated with 0.5 to 1.0 mg/kg of peplomycin per day for 5 days, generated more superoxide (O₂^-) than the cells from untreated rabbits. In both PLM-treated and untreated PMN, chemiluminescence induced by FMLP and PMA was decreased to less than 50% of the control by staurosporine, superoxide dismutase (SOD) and catalase. However, the peak intensity in PLM-untrcated PMN was decreased to about 30% of the control by genislein, while this agent induced a slight decrease in peak intensity in the PLM-treated PMN. Inositol triphosphate and diacyl glycerol levels were not clearly increased by PLM, but an increase of intracellular Ca and a shift of protein kinase C (PKC) to the membrane occurred in PMN within 1 min after PLM treatment. Western blotting revealed that the tyrosine phosphorylation of a 115 kDa protein was upregulated by 5 to 50μg/ml of PLM. While, PLM suppressed SOD activity in alveolar macrophages and PMN. These results seem to indicate that PLM increases the respiratory burst of PMN and macrophages both by way of direct PKC activation and by the upregulation of protein tyrosine phosphorylation. This increased reactive oxygen generation, together with the suppression of SOD activity seems to be tissue-impairing.     

Candida albicans phospholipomannan,a new member of the fungal mannose inositol phosphoceramide family

The pathogenic yeast Candida albicans has the ability to synthesize unique sequences of beta-1,2-oligomannosides that act as adhesins, induce cytokine production, and generate protective antibodies. Depending on the growth conditions, beta-1,2-oligomannosides are associated with different carrier molecules in the cell wall. Structural evidence has been obtained for the presence of these residues in the polysaccharide moiety of the glycolipid, phospholipomannan (PLM). In this study, the refinement of purification techniques led to large quantities of PLM being extracted from Candida albicans cells. A combination of methanolysis, gas chromatography, mass spectrometry, and nuclear magnetic resonance analyses allowed the complete structure of PLM to be deduced. The lipid moiety was shown to consist of a phytoceramide associating a C(18)/C(20) phytosphingosine and C(25), C(26), or mainly C(24) hydroxy fatty acids. The spacer linking the glycan part was identified as a unique structure: -Man-P-Man-Ins-P-. Therefore, in contrast to the major class of membranous glycosphingolipids represented by mannose diinositol phosphoceramide, which is derived from mannose inositol phosphoceramide by the addition of inositol phosphate, PLM seems to be derived from mannose inositol phosphoceramide by the addition of mannose phosphate. In relation to a previous study of the glycan part of the molecule, the assignment of the second phosphorus position leads to the definition of PLM beta-1,2-oligomannosides as unbranched linear structures that may reach up to 19 residues in length. Therefore, PLM appears to be a new type of glycosphingolipid, which is glycosylated extensively through a unique spacer. The conferred hydrophilic properties allow PLM to diffuse into the cell wall in which together with mannan it presents C. albicans beta-1,2-oligomannosides to host cells.     

Antenna modeling considerations for accurate SAR calculations in human phantoms in close proximity to GSM cellular base station antennas

International bodies such as International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the Institute for Electrical and Electronic Engineering (IEEE) make provision for human exposure assessment based on SAR calculations (or measurements) and basic restrictions. In the case of base station exposure this is mostly applicable to occupational exposure scenarios in the very near field of these antennas where the conservative reference level criteria could be unnecessarily restrictive. This study presents a variety of critical aspects that need to be considered when calculating SAR in a human body close to a mobile phone base station antenna. A hybrid FEM/MoM technique is proposed as a suitable numerical method to obtain accurate results. The verification of the FEM/MoM implementation has been presented in a previous publication; the focus of this study is an investigation into the detail that must be included in a numerical model of the antenna, to accurately represent the real-world scenario. This is accomplished by comparing numerical results to measurements for a generic GSM base station antenna and appropriate, representative canonical and human phantoms. The results show that it is critical to take the disturbance effect of the human phantom (a large conductive body) on the base station antenna into account when the antenna-phantom spacing is less than 300 mm. For these small spacings, the antenna structure must be modeled in detail. The conclusion is that it is feasible to calculate, using the proposed techniques and methodology, accurate occupational compliance zones around base station antennas based on a SAR profile and basic restriction guidelines.     

Evidence for extra-mitochondrial localization of the VDAC/porin channel in eucaryotic cells

The expression of bacterial porin in outer membranes of gram-negative bacteria and of mitochondrial porin or voltage-dependent anion channel (VDAC) in outer mitochondrial membranes (OMM) of eucaryotic cells was demonstrated about 15 years ago. However, the expression of VDAC in the plasmalemma (PLM) of transformed human B lymphoblasts has recently been indicated by cytotoxicity and indirect immunofluorescence studies. New data suggest that the expression of VDAC may be even more widespread. Different cell types express porin channels in their PLM and in intracellular membranes other than OMM. The functional expression of these channels may differ in the various compartments since recent experiments have demonstrated that the voltage dependence and ion selectivity of mitochondrial VDAC may be altered by their interaction with modulators. The present paper proposes a unifying concept for the ion-selective channels of cell membranes, in particular, those whose regulation is affected in cystic fibrosis.     

An Allometric Modelling Approach to Identify the Optimal Body Shape Associated with,and Differences between Brazilian and Peruvian Youth Motor Performance

Children from developed and developing countries differ in their body size and shape due to marked differences across their life history caused by social, economic and cultural differences which are also linked to their motor performance (MP). We used allometric models to identify size/shape characteristics associated with MP tests between Brazilian and Peruvian schoolchildren. A total of 4,560 subjects, 2,385 girls and 2,175 boys aged 9–15 years were studied. Height and weight were measured; biological maturation was estimated with the maturity offset technique; MP measures included the 12 minute run (12MR), handgrip strength (HG), standing long jump (SLJ) and the shuttle run speed (SR) tests; physical activity (PA) was assessed using the Baecke questionnaire. A multiplicative allometric model was adopted to adjust for body size differences across countries. Reciprocal ponderal index (RPI) was found to be the most suitable body shape indicator associated with the 12MR, SLJ, HG and SR performance. A positive maturation offset parameter was also associated with a better performance in SLJ, HG and SR tests. Sex differences were found in all motor tests. Brazilian youth showed better scores in MP than their Peruvian peers, even when controlling for their body size differences The current study identified the key body size associated with four body mass-dependent MP tests. Biological maturation and PA were associated with strength and motor performance. Sex differences were found in all motor tests, as well as across countries favoring Brazilian children even when accounting for their body size/shape differences.     

Analysis of the Changes In the Proportion of Clustered Labelled Cells In Epidermis

Abstract. A new cell kinetic approach is presented from which the duration of the S and G₂+ M phases can be estimated. the technique involves an analysis of the spatial distribution of labelled cells in sections or sheets of epithelium (i.e. an analysis of clustered labelled cells). the technique is largely independent of the absolute number of labelled cells and hence is not influenced by factors which affect the absolute number of labelled cells. the technique is described and experimental data from dorsal murine skin are presented. the technique has also been simulated mathematically so that the phase durations and their variances could be estimated. the advantages of the technique are: (1) it is technically simple; (2) it provides at least two independent estimates of the phase durations; (3) unlabelled cells need not be counted (compare with LI or PLM analysis); (4) it is independent of variations in the absolute yield of labelled cells, and (5) it is applicable if the LI is low and the S phase is short (where the PLM technique tends to fail).     

Performance limitations from delay in human and mechanical motor control

We discuss natural limitations on motor performance caused by the time delay required for feedback signals to propagate within the human body or mechanical control systems. By considering a very simple delayed linear servomechanism model, we show there exists a best possible speed-accuracy trade-off similar to Fitts' law that cannot be exceeded when delay is present. This is strictly a delay effect and does not occur for the ideal case of instantaneous feedback. We then examine the performance of the vector integration to endpoint (VITE) circuit as a model of human movement and show that when this circuit is generalized to include delayed feedback the performance may not exceed that of the servomechanism with an equal delay. We suggest the existence of such a limitation may be a ubiquitous consequence of delay in motor control with the implication that the index of performance in Fitts' law cannot arbitrarily large.