A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium.     

Growth and Sink to Source Transition in Developing Leaves of Sugarbeet

The growth and sink to source transition (cessation of assimilateimport) in light-grown leaves were compared to those of dark-grownleaves. Darkening chambers were placed over sugarbeet (Betavulgaris L.) plants so that new leaves emerged and grew in thedark. New leaves emerged at 1.8 day intervals, regardless ofthe light conditions. The dark-grown leaves were reversiblyretarded in overall growth; they were unable to photosynthesize,but attained photosyn-thetic, vein loading and export capacityafter exposure to sufficient amount and duration of light. Despitethe inability to fix carbon, dark-grown leaves showed dry weightgain. The increase in the dry weight, however, was localizedin the petiole and major veins and not in the laminar tissue.Despite metabolic differences in the two leaf types, sink tosource transition occurred in about a week in both light- anddark-grown leaves; and assimilate importing stopped at about8 days after emergence. While sink to source transition (asdetermined by assimilate import) per se did not appear to belight-regulated, the ability to accumulate sucrose in the veinsfor export out.of leaves was light dependent. This was basedon the observation that post-transitional dark-grown leaveswhich had ceased importing could not export exogenously appliedsucrose unless they were exposed to light for several days.The data indicated that transition is developmentally regulatedand not coupled to photosynthetic capacity. ¹Contribution No. D-15192-1-89 from the New Jersey AgriculturalExperiment Station. This work was funded in part by the BeetSugar Development Foundation and Rutgers Universi ty ResearchCouncil and was submitted as partial fulfillment for M.S. degreeby Lynne H. Pitcher. (Received August 22, 1990; Accepted January 9, 1991)     

Grain Yield in Pearl Millet in Relation to Source Size and Proximity to Sink

Two pearl millet [Pennisetum glaucum (L.) R. Br. emend. Stuntz] hybrids GHB-30 and MH-179 were given defoliation treatments prior to anthesis comprising zero leaf to intact control. Keeping or removing even flag leaf only significantly altered the grain yield. With increasing leaf area (leaf numbers) the grain yield also significantly increased. Test mass showed more or less a similar trend. The leaves in the upper portion (nearer to sink) showed a greater contribution to the grain yield than the lower ones (away from sink). However, the highest leaf efficiency in terms of contribution per unit leaf area and the contribution by the whole leaf to the grain yield was recorded by 4^th and 3^rd leaf, respectively. The stem (covered with petioles) contributed to the extent of around 12 %. The existing leaves compensated to some extent for the defoliated ones.     

Modulation of the Photosynthetic Source:Sink Relationship in Cultures of the Cyanobacterium Nostoc Rivulare

Nostoc rivulare was grown in batch cultures under controlled CO₂ and NO₃ ^– concentrations to modulate the photosynthetic source:sink relationship. Increasing CO₂ supply accelerated the accumulation of chlorophyll (Chl) a, i.e., supplemental CO₂ combined with double concentrations of NO₃ ^– more than doubled the amounts of Chl a relative to those of the original medium. Photosynthetic oxygen evolution and respiratory oxygen uptake were both enhanced by elevated CO₂ and NO₃ ^–. Contents of soluble sugars and starch (total non-structural saccharides) as well as insoluble saccharides (structural fraction) were affected by altering CO₂-NO₃ ^– combinations. Uptake as well as reduction of either NO₃ ^– or NO₂ ^– was inhibited by CO₂ deprivation. Expanding the sink size via increasing NO₃ ^– supply enhanced photosynthesis and thus the sink (NO₃ ^–) acted as a feed forward stimulator of the source (photosynthesis). The regulatory role of nitrate on photosynthesis was most influential in CO₂-deprived cultures since it could enhance photosynthesis to higher levels than CO₂-supplemented, nitrate-free cultures.     

Doubling the CO2 Concentration Enhanced the Activity of Carbohydrate-Metabolism Enzymes,Source Carbohydrate Production,Photoassimilate Transport,and Sink Strength for Opuntia ficus-indica

After exposure to a doubled CO2 concentration of 750 [mu]mol mol-1 air for about 3 months glucose and starch in the chlorenchyma of basal cladodes of Opuntia ficus-indica increased 175 and 57%, respectively, compared with the current CO2 concentration of 370 [mu]mol mol-1, but sucrose content was virtually unaffected. Doubling the CO2 concentration increased the nocturnal malate production in basal cladodes by 75%, inorganic phosphate (Pi) by 32%, soluble starch synthase activity by 30%, and sucrose-Pi synthase activity by 146%, but did not affect the activity of hexokinase. Doubling CO2 accelerated phloem transport of sucrose out of the basal cladodes, resulting in a 73% higher dry weight for the daughter cladodes. Doubling CO2 increased the glucose content in 14-d-old daughter cladodes by 167%, increased nocturnal malate production by 22%, decreased total amino acid content by 61%, and increased soluble starch synthase activity by 30% and sucrose synthase activity by 62%. No downward acclimation of photosynthesis during long-term exposure to elevated CO2 concentrations occurs for O. ficus-indica (M. Cui, P.M. Miller, P.S. Nobel [1993] Plant Physiol 103: 519-524; P.S. Nobel, A.A. Israel [1994] J Exp Bot 45: 295-303), consistent with its higher source capacity and sink strength than under current CO2. These changes apparently do not result in Pi limitation of photosynthesis or suppression of genes governing photosynthesis for this perennial Crassulacean acid metabolism species, as occur for some annual crops.     

New Source for Positive Controls Used for the Identification of Spirochaetes in Tissue Sections

Lyophilized T. pallidum is reconstituted or purchased as a suspension, evenly dispersed, made into smears using alcohol-cleaned slides and a bacteriological platinum wire loop. Smears are air dried for 15 minutes and fixed in concentrated formaldehyde fumes for 30 minutes and stored at room temperature. These preparations are used as positive controls for conventional silver impregnation techniques recommended for spirochaete detection in tissue sections.     

Mycorrhizae in Prairie Restoration: Response of Three Little Bluestem (Schizachyrium scoparium) Populations to Mycorrhizal Inoculum from a Single Source

In prairie restoration, use of seeds from nonlocal sources has been of concern to restorationists. We examined the specificity between vesicular-arbuscular mycorrhizal fungi obtained from a single location and little bluestem obtained from three localities. Seed was obtained from three sources: (1) a commercial seed supplier in Nebraska, (2) Sand Ridge State Forest (SRSF), Mason County, Illinois, the site from which the experimental soil containing the mycorrhizal inoculum was obtained, and (3) Sand Prairie Scrub Oak Nature Preserve (SPSO), 32 km southwest of SRSF. Plants were grown in three substrates: (1) autoclaved soil, (2) autoclaved soil to which a mycorrhizal fungal-free sieving of nonautoclaved soil was added, and (3) nonautoclaved soil. All plants grown in nonautoclaved soil were colonized by mycorrhizal fungi, whereas none of those grown in other substrates were colonized. Plants grown from SRSF seeds produced significantly (p < 0.05) more biomass than those grown from Nebraska seeds (X?± SE, SRSF = 0.54 ± 0.04 g, SPSO = 0.49 ± 0.03 g, Nebraska = 0.37 ± 0.03 g). Plants grown in nonautoclaved soil, regardless of seed source, produced less biomass (0.27 ± 0.02 g) than plants grown in autoclaved soil (0.58 ± 0.03 g) or autoclaved soil plus sievings (0.59 ± 0.03 g). The results provide no clear indication of a host-endophyte specificity. However, the data suggest that the local genotypes of S. scoparium are better adapted to their native soil environment than are genotypes from other localities.     

So, you want to look for biomarkers (introduction to the special biomarkers issue)

The burgeoning field of proteomics plays a powerful and relevant role in the discovery of biomarkers, which are biometric measurements that convey information about the biological condition of the subject being tested. Biomarkers have changed the manner in which we diagnose disease, monitor the effect of therapy, classify disease, detect toxicity, and develop new drugs. The central part that proteins command in both disease etiology and treatment make them prime biomarker candidates. Indeed, the majority of clinical tests in use today measure proteins. This perspective introduces the Journal of Proteome Research Special Issue on Proteomics and Biomarkers. It outlines the major applications of biomarkers, discusses the basics of statistically assessing them and considers the crucial choice of sample type. Central considerations of biomarker discovery and validation, particularly with respect to their intended clinical and research applications, are highlighted.     

Regulation of beta-Glucan Synthetase Activity by Auxin in Pea Stem Tissue: II. Metabolic Requirements

The 2- to 4-fold rise in particle-bound β-glucan synthetase (uridine diphosphate-glucose: β-1, 4-glucan glucosyltransferase) activity that can be induced by indoleacetic acid in pea stem tissue is not prevented by concentrations of actinomycin D or cycloheximide that inhibit growth and macromolecule synthesis. The rise is concluded to be a hormonally induced activation of previously existing, reversibly deactivated enzyme. The activation is not a direct allosteric effect of indoleacetic acid or sugars. It is blocked by inhibitors of energy metabolism, by 2-deoxyglucose, and by high osmolarity, but not by Ca²⁺ at concentrations that inhibit auxin-induced elongation and prevent promotion of sugar uptake by indoleacetic acid, and not by α, α′-dipyridyl at concentrations that inhibit formation of hydroxyproline. Regulation of the system could be due either to an ATP-dependent activating reaction affecting this enzyme, or to changes in levels of a primer or a lipid cofactor.     

Regulation of Ribulose-l,5-bisphosphate Carboxylase Activity in Response to Changes in the Source/Sink Balance in Single-Rooted Soybean Leaves: The Role of Inorganic Orthophosphate in Activation of the Enzyme

The results of our previous study [Sawada et al. (1989) PlantCell Physiol. 30: 691] implied that, under sink-limited conditions,a decrease in the activity of ribulose-l,5-bisphosphate carboxylase(EC 4.1.1.39 [EC] ) caused a reduction in the rate of photosyntheticfixation of CO₂ in single-rooted leaves of soybean (Glycinemax L. Merr. cv. Tsurunoko). This reduction in the rate of photosynthesisin source leaves seemed to correspond to a decrease in the demandby sink tissues for photoassimilates. In the present study,the activity of RuBPcase in vivo was estimated by measuringthe "initial" activity immediately after extraction from standardleaves (grown under a regime of 10 h of light and 14 h of darkness)and from sink-limited leaves (exposed for 6 or 7 d to continuouslight to alter the source/sink balance). The rate of photosynthesisin the sink-limited leaves decreased to 47% of that in the standardleaves. The "initial" activity of RuBPcase was 4.3 in the standardleaves but only 1.6 µmole CO₂.(mg Chl)^–1.min^–1in the sink-limited leaves. These results appear to indicatethat the reduction in photosynthetic activity under sink-limitedconditions was mostly due to a deactivation of RuBPcase. Theactivity of deactivated RuBPcase in the sink-limited leaveswas restored to 4.1 µmole CO₂.(mg Chl)^–1.min^–1by incubation of the enzyme in a medium that contained onlyNa₂HPO₄. This result suggests that free P_i in chloro-plastsplays an important role in the activation of the enzyme. Thelevel of P_i in the sink-limited leaves was 62% of that in thestandard leaves. On the basis of these various results, it appearsthat the deactivation of RuBPcase in the sink-limited leavesis the result of a decrease in the level of P_i. The role offree P_i in the activation of RuBPcase, in particular at atmosphericconcentrations of CO₂, was also investigated. (Received November 30, 1989; Accepted May 11, 1990)     

Force to Divide: Structural and Mechanical Requirements for Actomyosin Ring Contraction

One of the unresolved questions in the field of cell division is how the actomyosin cytoskeleton remains structurally organized while generating the contractile force to divide one cell into two. In analogy to the actomyosin-based force production mechanism in striated muscle, it was originally proposed that contractile stress in the actomyosin ring is generated via a sliding filament mechanism within an organized sarcomere-like array. However, over the last 30 years, ultrastructural and functional studies have noted important distinctions between cytokinetic structures in dividing cells and muscle sarcomeres. Myosin-II motor activity is not always required, and there is evidence that actin depolymerization contributes to contraction. In this Review, the architecture and contractile dynamics of the actomyosin ring at the cell division plane will be discussed. We will report the interdisciplinary advances in the field as well as their integration into a mechanistic understanding of contraction in cell division and in other biological processes that rely on an actomyosin-based force-generating system.     

Force to Divide: Structural and Mechanical Requirements for Actomyosin Ring Contraction

One of the unresolved questions in the field of cell division is how the actomyosin cytoskeleton remains structurally organized while generating the contractile force to divide one cell into two. In analogy to the actomyosin-based force production mechanism in striated muscle, it was originally proposed that contractile stress in the actomyosin ring is generated via a sliding filament mechanism within an organized sarcomere-like array. However, over the last 30 years, ultrastructural and functional studies have noted important distinctions between cytokinetic structures in dividing cells and muscle sarcomeres. Myosin-II motor activity is not always required, and there is evidence that actin depolymerization contributes to contraction. In this Review, the architecture and contractile dynamics of the actomyosin ring at the cell division plane will be discussed. We will report the interdisciplinary advances in the field as well as their integration into a mechanistic understanding of contraction in cell division and in other biological processes that rely on an actomyosin-based force-generating system.     

Good Fat, Essential Cellular Requirements for Triacylglycerol Synthesis to Maintain Membrane Homeostasis in Yeast

Storage triacylglycerols (TAG) and membrane phospholipids share common precursors, i.e. phosphatidic acid and diacylglycerol, in the endoplasmic reticulum. In addition to providing a biophysically rather inert storage pool for fatty acids, TAG synthesis plays an important role to buffer excess fatty acids (FA). The inability to incorporate exogenous oleic acid into TAG in a yeast mutant lacking the acyltransferases Lro1p, Dga1p, Are1p, and Are2p contributing to TAG synthesis results in dysregulation of lipid synthesis, massive proliferation of intracellular membranes, and ultimately cell death. Carboxypeptidase Y trafficking from the endoplasmic reticulum to the vacuole is severely impaired, but the unfolded protein response is only moderately up-regulated, and dispensable for membrane proliferation, upon exposure to oleic acid. FA-induced toxicity is specific to oleic acid and much less pronounced with palmitoleic acid and is not detectable with the saturated fatty acids, palmitic and stearic acid. Palmitic acid supplementation partially suppresses oleic acid-induced lipotoxicity and restores carboxypeptidase Y trafficking to the vacuole. These data show the following: (i) FA uptake is not regulated by the cellular lipid requirements; (ii) TAG synthesis functions as a crucial intracellular buffer for detoxifying excess unsaturated fatty acids; (iii) membrane lipid synthesis and proliferation are responsive to and controlled by a balanced fatty acid composition.     

Assessment of the Soil Organic Carbon Sink in a Project for the Conversion of Farmland to Forestland: A Case Study in Zichang County,Shaanxi, China

The conversion of farmland to forestland not only changes the ecological environment but also enriches the soil with organic matter and affects the global carbon cycle. This paper reviews the influence of land use changes on the soil organic carbon sink to determine whether the Chinese “Grain-for-Green” (conversion of farmland to forestland) project increased the rate of SOC content during its implementation between 1999 and 2010 in the hilly and gully areas of the Loess Plateau in north-central China. The carbon sink was quantified, and the effects of the main species were assessed. The carbon sink increased from 2.26×10⁶ kg in 1999 to 8.32×10⁶ kg in 2010 with the sustainable growth of the converted areas. The black locust (Robinia pseudoacacia L.) and alfalfa (Medicago sativa L.) soil increased SOC content in the top soil (0–100 cm) in the initial 7-yr period, while the sequestration occurred later (>7 yr) in the 100–120 cm layer after the “Grain-for-Green” project was implemented. The carbon sink function measured for the afforested land provides evidence that the Grain-for-Green project has successfully excavated the carbon sink potential of the Shaanxi province and served as an important milestone for establishing an effective organic carbon management program.