Changes in mitochondrial calcium concentration during the cardiac contraction cycle

OBJECTIVE: The aim was to examine whether mitochondrial Ca2+ fluxes are high enough to change mitochondrial and cytosolic calcium concentration during the contraction cycle. METHODS: Isolated guinea pig ventricular myocytes were stimulated with paired voltage clamp pulses until contractions were maximal (2 mM [Ca2+]o, 36 degrees C). At defined times of diastole or systole, the cells were shock frozen. Electron-probe microanalysis measured the concentration of total calcium in mitochondria (sigma Ca(mito)) and surrounding cytosol (sigma Cac). Other experiments were performed to evaluate DNP sensitive mitochondrial Ca2+ uptake from depolarisation induced [Ca2+]c transients (K5indo-1 fluorescence). RESULTS: At end of diastole, sigma Ca(mito) was 446 mumol.litre-1. During systole, sigma Ca(mito) increased with a 20 ms delay. A peak sigma Ca(mito) of 1050 mumol.litre-1 was measured 40 ms after start of systole, while 95 ms after start of systole sigma Ca(mito) had fallen to 530 mumol.litre-1. From the changes in sigma Ca(mito) the rates of net mitochondrial Ca2+ flux were estimated at 100 nmol.s-1 x mg-1 protein for Ca2+ influx and 36 nmol.s-1 x mg-1 protein for Ca2+ egress. Decay of sigma Ca(mito) was coupled to a rise in sigma Na(mito). sigma Cl(mito) and sigma K(mito) rose and fell in parallel with sigma Ca(mito), suggesting Ca2+ activation of mitochondrial anion and cation channels. Activation of the non-specific permeability can be excluded. Block of mitochondrial Ca2+ uptake with DNP (100 microM) or FCCP (10 microM) increased the amplitude of the [Ca2+]c transients for 1-3 min by about 50%; evaluation of mitochondrial Ca2+ uptake from DNP sensitive difference signals, however, was hampered by sequestration of mitochondrial Ca2+ into the sarcoplasmic reticulum. CONCLUSIONS: Mitochondrial calcium content changes during each individual contraction cycle; a substantial amount of calcium is taken up during the systole and released during later systole and diastole.     

Smoothing the electromagnetic heating pattern in polymers

In the production of polymers, particles and fibers are often added for coloring and/or improvement of mechanical, electrical, and thermal properties. Carefully choosing the electrical properties and size of these additives can allow manipulation of the electrical properties of the composite so that the material can then be heated in both the electric and magnetic fields. Heating can be induced by fields at microwave frequences, where the electric and magnetic fields tend to be concentrated in different regions, or by fields that are quasistatic. These features add a degree of freedom in smoothing the total heating pattern. Models for predicting the electrical properties with the addition of particles or fibers are developed and verified experimentally. Engineering guidelines are established in choosing the electrical properties and size of the additives. Experimentally, a rectangular cavity at 2.45 GHz is used to heat a casting resin with a 5.7 micrometer aluminum powder additive, demonstrating the dramatic smoothing in the heating, pattern made possible by using these additives. Some examples are also suggested to indicate the use of this technique in quasistatic heating configurations.     

Dual recognition of lipid A and DNA by human antibodies encoded by the VH4-21 gene: a possible link between infection and lupus

The VH4-21 (V4-34) gene segment, a member of the VH4 family, is expressed early in B-cell maturation and is utilized by approximately 6% of normal adult B lymphocytes. This prevalence indicates an importance of VH4-21 in the B-cell repertoire. The gene also encodes certain autoantibodies being mandatory for pathological IgM anti-red cell antibodies directed against the I/i antigen, and also capable of encoding anti-DNA antibodies. Recognition of I/i antigen or DNA appears to be via two distinct sites on VH, with I/i binding mediated by sequences in the framework region, and DNA binding correlating with the presence of positively charged amino acids in complementarity-determining region 3. However, these positively charged residues appear to suppress the ability of the framework region to interact with I/i, rendering a single sequence monospecific for I/i or DNA. The IgM anti-DNA antibodies also recognize bacterial lipid A, whereas the anti-I/i antibodies do not, indicating that CDR3 may be involved in binding the negatively charged lipid A. Structural similarities between the DNA backbone and lipid A provide a possible explanation for this cross-reactivity. This dual recognition of bacterial antigen and autoantigen provides a potential link between infection and autoimmunity.     

Apoptosis and antiphospholipid antibodies

This research examined the effect of peer support on breastfeeding duration and exclusivity (breastfeeding without supplements) in a population of low-income women during the first 3 months postpartum. Participants in the peer counselor group (n = 18) exhibited higher rates of exclusive breastfeeding across time than those without a counselor (n = 18), and more exclusive breastfeeding was associated with long duration overall. Mother's career plans had the greatest effect on duration of breastfeeding. Women who intended to return to work, attend school, or both breastfed 6 to 9 weeks less than participants who intended to stay home. Attendance at a breastfeeding class and knowing someone who had breastfed was significantly correlated with a longer duration of breastfeeding. Nutritionists from the Women, Infants and Children (WIC) Program were the primary source of breastfeeding information. Two main factors discouraged women from breastfeeding: returning to work, school, or both and the perception of a diminished milk supply. Greater emphasis should be placed on prenatal breastfeeding education for low-income women, and their mothers and grandmothers should be included. Peer support is one important component of social support in the area of breastfeeding that community health nurses (CHNs) can utilize. CHNs are in a unique position to assist working mothers, provide support, and develop educational programs to enhance breastfeeding success in this population.     

Development of technologies aiding large-tissue engineering

Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors.     

The State of the Art of Spatial Interfaces for 3D Visualization

We survey the state of the art of spatial interfaces for 3D visualization. Interaction techniques are crucial to data visualization processes and the visualization research community has been calling for more research on interaction for years. Yet, research papers focusing on interaction techniques, in particular for 3D visualization purposes, are not always published in visualization venues, sometimes making it challenging to synthesize the latest interaction and visualization results. We therefore introduce a taxonomy of interaction technique for 3D visualization. The taxonomy is organized along two axes: the primary source of input on the one hand and the visualization task they support on the other hand. Surveying the state of the art allows us to highlight specific challenges and missed opportunities for research in 3D visualization. In particular, we call for additional research in: (1) controlling 3D visualization widgets to help scientists better understand their data, (2) 3D interaction techniques for dissemination, which are under‐explored yet show great promise for helping museum and science centers in their mission to share recent knowledge, and (3) developing new measures that move beyond traditional time and errors metrics for evaluating visualizations that include spatial interaction.     

Co-located collaborative visual analytics around a tabletop display

Co-located collaboration can be extremely valuable during complex visual analytics tasks. We present an exploratory study of a system designed to support collaborative visual analysis tasks on a digital tabletop display. Fifteen participant pairs employed Cambiera, a visual analytics system, to solve a problem involving 240 digital documents. Our analysis, supported by observations, system logs, questionnaires, and interview data, explores how pairs approached the problem around the table. We contribute a unique, rich understanding of how users worked together around the table and identify eight types of collaboration styles that can be used to identify how closely people work together while problem solving. We show how the closeness of teams’ collaboration and communication influenced how they performed on the task overall. We further discuss the role of the tabletop for visual analytics tasks and derive design implications for future co-located collaborative tabletop problem solving systems.     

Investigating teamwork and taskwork in single- and multi-display groupware systems

Multi-display groupware (MDG) systems, which typically comprise both public and personal displays, promise to enhance collaboration, yet little is understood about how they differ in use from single-display groupware (SDG) systems. While research has established the technical feasibility of MDG systems, evaluations have not addressed the question of how users’ behave in such environments, how their interface design can impact group behavior, or what advantages they offer for collaboration. This paper presents a user study that investigates the impact of display configuration and software interface design on taskwork and teamwork. Groups of three completed a collaborative optimization task in single- and multi-display environments, under different task interface constraints. Our results suggest that MDG configurations offer advantages for performing individual task duties, whereas SDG conditions offer advantages for coordinating access to shared resources. The results also reveal the importance of ergonomic design considerations when designing co-located groupware systems.     

State of the Art of Molecular Visualization in Immersive Virtual Environments

Visualization plays a crucial role in molecular and structural biology. It has been successfully applied to a variety of tasks, including structural analysis and interactive drug design. While some of the challenges in this area can be overcome with more advanced visualization and interaction techniques, others are challenging primarily due to the limitations of the hardware devices used to interact with the visualized content. Consequently, visualization researchers are increasingly trying to take advantage of new technologies to facilitate the work of domain scientists. Some typical problems associated with classic 2D interfaces, such as regular desktop computers, are a lack of natural spatial understanding and interaction, and a limited field of view. These problems could be solved by immersive virtual environments and corresponding hardware, such as virtual reality head-mounted displays. Thus, researchers are investigating the potential of immersive virtual environments in the field of molecular visualization. There is already a body of work ranging from educational approaches to protein visualization to applications for collaborative drug design. This review focuses on molecular visualization in immersive virtual environments as a whole, aiming to cover this area comprehensively. We divide the existing papers into different groups based on their application areas, and types of tasks performed. Furthermore, we also include a list of available software tools. We conclude the report with a discussion of potential future research on molecular visualization in immersive environments.     

Microvascular transplantation in the salvage of lower extremity trauma in the elderly

In the cadaver of an 86 year old man the inferior segment of the azygos vein could not be found. Furthermore, a normally developed hemiazygos vein drained the right and left intercostal veins from T 10 to T 6. This vessel finally curved towards the right to reach the superior vena cava after having drained the right superior intercostal veins. The left superior intercostal vein ended in a short vessel draining into the left brachiocephalic vein. This condition may be represented in a standard chest radiograph by the so-called "aortic nipple". Agenesis of the azygos vein, suspected because of the presence of this radiological sign, should be confirmed in the living by means of computerized tomography. This can clarify the anatomy of the mediastinal vessels precisely. Embryological pattern of the azygos system accounting for its possible defects is discussed.