Extra-matrix Mg\u3csup\u3e2+\u3c/sup\u3e Limits Ca\u3csup\u3e2+\u3c/sup\u3e Uptake and Modulates Ca\u3csup\u3e2+\u3c/sup\u3e Uptake-independent Respiration and Redox State in Cardiac Isolated Mitochondria

Cardiac mitochondrial matrix (m) free Ca2+ ([Ca2+]m) increases primarily by Ca2+ uptake through the Ca2+ uniporter (CU). Ca2+ uptake via the CU is attenuated by extra-matrix (e) Mg2+ ([Mg2+]e). How [Ca2+]m is dynamically modulated by interacting physiological levels of [Ca2+]e and [Mg2+]e and how this interaction alters bioenergetics are not well understood. We postulated that as [Mg2+]e modulates Ca2+ uptake via the CU, it also alters bioenergetics in a matrix Ca2+–induced and matrix Ca2+–independent manner. To test this, we measured changes in [Ca2+]e, [Ca2+]m, [Mg2+]e and [Mg2+]m spectrofluorometrically in guinea pig cardiac mitochondria in response to added CaCl2 (0–0.6 mM; 1 mM EGTA buffer) with/without added MgCl2 (0–2 mM). In parallel, we assessed effects of added CaCl2 and MgCl2 on NADH, membrane potential (ΔΨm), and respiration. We found that \u3e0.125 mM MgCl2 significantly attenuated CU-mediated Ca2+ uptake and [Ca2+]m. Incremental [Mg2+]e did not reduce initial Ca2+uptake but attenuated the subsequent slower Ca2+ uptake, so that [Ca2+]m remained unaltered over time. Adding CaCl2 without MgCl2 to attain a [Ca2+]m from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15 %; up to 868 nM [Ca2+]m did not additionally enhance NADH oxidation or respiration. Adding MgCl2 did not increase [Mg2+]m but it altered bioenergetics by its direct effect to decrease Ca2+ uptake. However, at a given [Ca2+]m, state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg2+]e. Thus, [Mg2+]e without a change in [Mg2+]m can modulate bioenergetics independently of CU-mediated Ca2+ transport

Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase

<p>Abstract</p> <p>Background</p> <p>Mitochondrial 2-oxoglutarate (α-ketoglutarate) dehydrogenase complex (OGDHC), a key regulatory point of tricarboxylic acid (TCA) cycle, plays vital roles in multiple pathways of energy metabolism and biosynthesis. The catalytic mechanism and allosteric regulation of this large enzyme complex are not fully understood. Here computer simulation is used to test possible catalytic mechanisms and mechanisms of allosteric regulation of the enzyme by nucleotides (ATP, ADP), pH, and metal ion cofactors (Ca²⁺and Mg²⁺).</p> <p>Results</p> <p>A model was developed based on an ordered ter-ter enzyme kinetic mechanism combined with con-formational changes that involve rotation of one lipoic acid between three catalytic sites inside the enzyme complex. The model was parameterized using a large number of kinetic data sets on the activity of OGDHC, and validated by comparison of model predictions to independent data.</p> <p>Conclusions</p> <p>The developed model suggests a hybrid rapid-equilibrium ping-pong random mechanism for the kinetics of OGDHC, consistent with previously reported mechanisms, and accurately describes the experimentally observed regulatory effects of cofactors on the OGDHC activity. This analysis provides a single consistent theoretical explanation for a number of apparently contradictory results on the roles of phosphorylation potential, NAD (H) oxidation-reduction state ratio, as well as the regulatory effects of metal ions on ODGHC function.</p

Heuristics Techniques for Scheduling Problems with Reducing Waiting Time Variance

In real computational world, scheduling is a decision making process. This is nothing but a systematic schedule through which a large numbers of tasks are assigned to the processors. Due to the resource limitation, creation of such schedule is a real challenge. This creates the interest of developing a qualitative scheduler for the processors. These processors are either single or parallel. One of the criteria for improving the efficiency of scheduler is waiting time variance (WTV). Minimizing the WTV of a task is a NP-hard problem. Achieving the quality of service (QoS) in a single or parallel processor by minimizing the WTV is a problem of task scheduling. To enhance the performance of a single or parallel processor, it is required to develop a stable and none overlap scheduler by minimizing WTV. An automated scheduler\u27s performance is always measured by the attributes of QoS. One of the attributes of QoS is ‘Timeliness’. First, this chapter presents the importance of heuristics with five heuristic-based solutions. Then applies these heuristics on 1‖WTV minimization problem and three heuristics with a unique task distribution mechanism on Qm|prec|WTV minimization problem. The experimental result shows the performance of heuristic in the form of graph for consonant problems

A Brief Review on phytoconstituents and Ethnopharmacology of Scoparia dulcis Linn. (Scrophulariaceae)

Scoparia dulcis Linn.(S. dulcis)or sweet broom weed commonly known as Mithipatti and Bana Dhania in Western Orissa, it is also known as ‘GhodaTulsi’in Hindi. The present review attempts to narrate the chemical constituents of S.dulcis and their uses. S.dulcis is rich in flavones, terpenes and steroids. Main chemical constituents such as scoparic acid A-C, scopadulcic acid A and B, scopadulciol, scopadulin and ammelin have been shown to contribute to the observed medicinal effect of the plant. In this review we have composed the structure and functions of those active ingredients with their melting point and other physical properties individually.Some aspects of the several speculated pharmacological properties of S. dulcis have been validated by scientific research, which includes the presence of hypoglycaemic and anti-tumour promoting compound. It also has antimicrobial and antifungal effects as well as antihyperlipidemic action

Diversity and distribution of jellyfish along the Odisha coast - First aid measures of jellyfish stings

Diversity and distribution of jellyfish along the Odisha coast - First aid measures of jellyfish sting

UVIT study of UV bright stars in the globular cluster NGC 4147

We present far ultraviolet (FUV) observations of globular cluster NGC 4147 using three FUV filters, BaF2 (F154W), sapphire (F169M), and silica (F172M) of Ultra-Violet Imaging Telescope (UVIT) on-board the AstroSat satellite. We confirmed the cluster membership of the UVIT observed sources using proper motions from Gaia data release 2 (GAIA DR2). We identified 37 blue horizontal branch stars (BHBs), one blue straggler star (BSS) and 15 variable stars using UV-optical color magnitude diagrams (CMDs). We find that all the FUV bright BHBs are second generation population stars. Using UV-optical CMDs, we identify two sub-populations, BHB1 and BHB2, among the UV-bright BHBs in the cluster with stars count ratio of 24:13 for BHB1 and BHB2. The effective temperatures (Teff) of BHB1 and BHB2 were derived using color-temperature relation of BaSTI-IAC zero-age horizontal branch (ZAHB). We found that BHB1 stars are more centrally concentrated than BHB2 stars. We also derive physical parameters of the detected FUV bright BSS by fitting younger age BaSTI-IAC isochrones on optical and UV-optical CMDs

Globular Cluster UVIT Legacy Survey (GlobULeS) – II. Evolutionary status of hot stars in M3 and M13

We present the first comprehensive study of the most massive globular cluster, Omega Centauri, in the far-ultraviolet (FUV), extending from the center to ∼28% of the tidal radius using the Ultraviolet Imaging Telescope on board AstroSat. A comparison of the FUV-optical color–magnitude diagrams with available canonical models reveals that horizontal branch (HB) stars bluer than the knee (hHBs) and the white dwarfs (WDs) are fainter in the FUV by ∼0.5 mag than model predictions. They are also fainter than their counterparts in M13, another massive cluster. We simulated HB with at least five subpopulations, including three He-rich populations with a substantial He enrichment of Y up to 0.43 dex, to reproduce the observed FUV distribution. We find the He-rich younger subpopulations to be radially more segregated than the He-normal older ones, suggesting an in situ enrichment from older generations. The ω Cen hHBs span the same Teff range as their M13 counterparts, but some have smaller radii and lower luminosities. This may suggest that a fraction of ω Cen hHBs are less massive than those of M13, similar to the result derived from earlier spectroscopic studies of outer extreme HB stars. The WDs in ω Cen and M13 have similar luminosity–radius–Teff parameters, and 0.44–0.46 M⊙ He-core WD model tracks evolving from progenitors with Y = 0.4 dex are found to fit the majority of these. This study provides constraints on the formation models of ω Cen based on the estimated range in age, [Fe/H], and Y (in particular) for the HB stars

Characterization of Membrane Potential Dependency of Mitochondrial Ca2+ Uptake by an Improved Biophysical Model of Mitochondrial Ca2+ Uniporter

Mitochondrial Ca2+ uniporter is the primary influx pathway for Ca2+ into respiring mitochondria, and hence plays a key role in mitochondrial Ca2+ homeostasis. Though the mechanism of extra-matrix Ca2+ dependency of mitochondrial Ca2+ uptake has been well characterized both experimentally and mathematically, the mechanism of membrane potential (ΔΨ) dependency of mitochondrial Ca2+ uptake has not been completely characterized. In this paper, we perform a quantitative reevaluation of a previous biophysical model of mitochondrial Ca2+ uniporter that characterized the possible mechanism of ΔΨ dependency of mitochondrial Ca2+ uptake. Based on a model simulation analysis, we show that model predictions with a variant assumption (Case 2: external and internal Ca2+ binding constants for the uniporter are distinct), that provides the best possible description of the ΔΨ dependency, are highly sensitive to variation in matrix [Ca2+], indicating limitations in the variant assumption (Case 2) in providing physiologically plausible description of the observed ΔΨ dependency. This sensitivity is attributed to negative estimate of a biophysical parameter that characterizes binding of internal Ca2+ to the uniporter. Reparameterization of the model with additional nonnengativity constraints on the biophysical parameters showed that the two variant assumptions (Case 1 and Case 2) are indistinguishable, indicating that the external and internal Ca2+ binding constants for the uniporter may be equal (Case 1). The model predictions in this case are insensitive to variation in matrix [Ca2+] but do not match the ΔΨ dependent data in the domain ΔΨ≤120 mV. To effectively characterize this ΔΨ dependency, we reformulate the ΔΨ dependencies of the rate constants of Ca2+ translocation via the uniporter by exclusively redefining the biophysical parameters associated with the free-energy barrier of Ca2+ translocation based on a generalized, non-linear Goldman-Hodgkin-Katz formulation. This alternate uniporter model has all the characteristics of the previous uniporter model and is also able to characterize the possible mechanisms of both the extra-matrix Ca2+ and ΔΨ dependencies of mitochondrial Ca2+ uptake. In addition, the model is insensitive to variation in matrix [Ca2+], predicting relatively stable physiological operation. The model is critical in developing mechanistic, integrated models of mitochondrial bioenergetics and Ca2+ handling