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.     

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.     

The next-generation business meeting: from i-lands to flexible meeting landscapes

Meetings are an important form of interaction in business settings. However, meetings are often not held in a way that makes all participants feel engaged. Meeting support systems try to overcome this obstacle by helping meeting participants in the meeting workflow. This paper takes a complementary approach by distinguishing between different perspectives of good meetings: the peopleware perspective, the generic groupware perspective, and the roomware perspective. It is argued that all these perspectives have to be considered simultaneously when heading toward an ideal meeting system design. The paper presents excerpts of a pattern language that empowers users to improve their meeting. Besides this, the pattern language can be considered as a tool for the designer. After showing, how both groups made use of the patterns, the paper finally presents LivingAgendas, a meeting support system that can accompany the meeting participant through the meeting life cycle.     

List-based Data Structures for Efficient Management of Advance Reservations

Complex eScience and other sophisticated applications in the field of HPC imply new demands that queuing based resource management systems cannot meet. To guarantee Quality of Service and co-allocation in the Grid, planning based resource management systems implementing advance reservation are needed. These systems face new challenges as a planning based management system has to keep track of the jobs and reservations in the future. Additionally, during the negotiation process of incoming reservations, a good overview of the remaining, not-yet reserved capacity is needed—not only for the current allocation, but also for the whole book-ahead time. Therefore, the resource management problem becomes a two dimensional problem for advance reservations in this field. In this paper different data structures are investigated and discussed in order to fit to planning based resource management. As a result the benefits of using lists of resource allocation or free blocks are exposed. This general idea widely used to manage continuous resources is extended to cover not only the resource dimension but also the time dimension. The list of blocks approach is evaluated in a Grid level and a local resource management system for a computing cluster. The extensive simulations showed a better runtime and higher reservation success rate compared with the currently favored approach of a slotted time and the more sophisticated approach based on AVL trees.     

Smallholders’ Soil Fertility Management in the Central Highlands of Ethiopia: Implications for Nutrient Stocks, Balances and Sustainability of Agroecosystems

Low agricultural productivity caused by soil degradation is a serious problem in the Ethiopian Highlands. Here, we report how differences in soil fertility management between farming systems, based either on enset (Ensete ventricosum) or on teff (Eragrostis tef) as the major crops, affect the extent of nutrient stocks, balances and ecosystem sustainability. We collected information on farmers’ resources and nutrient management practices from stratified randomly selected households in two watersheds in the Central Highlands of Ethiopia. In addition, we collected soil samples from each land use and calculated nutrient stocks, partial and full nutrient balances (N, P and K) for one cropping season. Our results show that farmers in the two farming systems manage their soils differently and that nutrient inputs were positively related to farmers’ wealth status. The watershed with the enset-based system had higher soil N and K stocks than the watershed with the teff-based system, while P stocks were not different. Management related N?and K fluxes were more negative in the teff-based system (?28 kg N ha^?1 yr^?1 and ?34 kg K ha^?1 yr^?1) than in the enset-based system (?6 kg N ha^?1 yr^?1 and ?14 kg K ha^?1 yr^?1) while P fluxes were almost neutral or slightly positive. Within the enset-based system, a strong redistribution of N, P and K took place from the meadows and cereals (negative balance) to enset (positive balances). Although in the teff-based system, N, P and K were redistributed from meadows, small cereals and pulses to maize, the latter still showed a negative nutrient balance. In contrast to nutrient balances at land use level, nutrient balances at the watershed scale masked contrasting areas within the system where nutrient oversupply and deficiencies occurred.     

Light metal compound casting

‘Compound casting’simplifies joining processes by directly casting a metallic melt onto a solid metal substrate. A continuously metallurgic transition is very important for industrial applications, such as joint structures of spaceframe constructions in transport industry. In this project, ‘compound casting’ of light metals is investigated, aiming at weight-saving. The substrate used is a wrought aluminium alloy of type AA5xxx, containing magnesium as main alloying element. The melts are aluminium alloys, containing various alloying elements (Cu, Si, Zn), and magnesium. By replacing the natural oxygen layer with a zinc layer, the inherent wetting difficulties were avoided, and compounds with flawless interfaces were successfully produced (no contraction defects, cracks or oxides). Electron microscopy and EDX investigations as well as optical micrographs of the interfacial areas revealed their continu- ously metallic constitution. Diffusion of alloying elements leads to heat-treatable microstructures in the vicinity of the joining interfaces in Al-Al couples. This permits significant variability of mechanical properties. Without significantly cutting down on wettability, the formation of low-melting intermetallic phases (Al3Mg2 and Al12Mg17 IMPs) at the interface of Al-Mg couples was avoided by applying a protective coating to the substrate.