Macrophage autophagy plays a protective role in advanced atherosclerosis

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Highlights? Proapoptotic oxidative stress induces autophagy in macrophages (M?s) ? Inhibition of autophagy enhances oxidative stress and apoptosis in M?s ? Atheromata of M?-Atg5^?/?Ldlr^?/? mice have increased apoptosis and plaque necrosis ? Apoptotic Atg5^?/? M?s are poorly recognized by phagocytes in vitro and in atheromata     

Wavelet threshold based ECG compression using USZZQ and Huffman coding of DSM

In this paper, a new Wavelet threshold based ECG signal compression technique using uniform scalar zero zone quantizer (USZZQ) and Huffman coding on differencing significance map (DSM) is proposed. Wavelet coefficients are selected based on the energy packing efficiency of each sub-band. Significant Wavelet coefficients are quantized with uniform scalar zero zone quantizer. Significance map is created to store the indices of the significant coefficients. This map is encoded efficiently with less number of bits by applying Huffman coding on the differences between indices in the significance map. ECG records from the MIT-BIH arrhythmia database are selected as test data. For the record 117, the proposed technique achieves a compression ratio of 18.7:1 with lower percentage root mean square difference (PRD) compared to other threshold based methods. The proposed technique is tested for MIT-BIH arrhythmia record 119 and a compression ratio of 21.81:1 is achieved with a PRD value of 3.716% which is much lower compared to the reported PRD value of 5.0 and 5.5% of set partitioning in hierarchical tress (SPIHT) and analysis by synthesis ECG compressor (ASEC), respectively. The noise eliminating capability of the proposed technique is also demonstrated in this work. The proposed technique achieves the required compression ratio with less reconstruction error for GSM-based cellular telemedicine system.     

Characterization and cloning of the cry2A gene from indigenous isolates of Bacillus thuringiensis

Molecular Biology - Discovery of novel cry genes of Bacillus thuringiensis (Bt) with higher toxicity is important for the development of transgenic Bt crops resistant to target pests. Two new...     

Iodine catalyzed three component synthesis of 1-((2-hydroxy naphthalen-1-yl)(phenyl)(methyl))pyrrolidin-2-one derivatives: Rationale as potent PI3K inhibitors and anticancer agents

A series of 1-((2-hydroxynaphthalen-1-yl)(phenyl)(methyl))pyrrolidin-2-one derivatives by an efficient iodine catalyzed domino reaction involving various aromatic aldehydes, 2-pyrrolidinone and β-naphthol was achieved and the structures were elucidated by FTIR ¹H NMR, ¹³C NMR, and HRMS. Subsequently they were evaluated for cytotoxicity against breast cancer (MCF-7), colon cancer (HCT116) cell lines. In the cytotoxicity, the relative inhibition activity was remarkably found to be high in MCF-7 cell lines as 79% (4c), 83% (4f) and the IC₅₀values were 1.03 µM (4c), 0.98 µM (4f). Compounds 4a, 4e, 4k–m, and 4q were found to be inactive and rest showed a moderate activity. In order to get more insight into the binding mode and inhibitor binding affinity, compounds (4a–q) were docked into the active site phosphoinositide 3-kinase (PI3K) (PDB ID: 4JPS) which is a crucial regulator of apoptosis or programmed cell death. Results suggested that the hydrophobic interactions in the binding pockets of PI3K exploited affinity of the most favourable binding ligands (4c and 4f: inhibitory constant (ki) = 66.22 nM and 107.39 nM). The SAR studies demonstrated that the most potent compounds are 4c and 4f and can be developed into precise PI3K inhibitors with the capability to treat various cancers.     

Wavelet threshold based TDL and TDR algorithms for real-time ECG signal compression

In this paper, two novel and simple, target distortion level (TDL) and target data rate (TDR), Wavelet threshold based ECG compression algorithms are proposed for real-time applications. The issues on the use of objective error measures, such as percentage root mean square difference (PRD) and root mean square error (RMSE) as a quality measures, in quality controlled/guranteed algorithm are investigated with different sets of experiments. For the proposed TDL and TDR algorithm, data rate variability and reconstructed signal quality is evaluated under different ECG signal test conditions. Experimental results show that the TDR algorithm achieves the required compression data rate to meet the demands of wire/wireless link while the TDL algorithm does not. The compression performance is assessed in terms of number of iterations required to achieve convergence and accuracy, reconstructed signal quality and coding delay. The reconstructed signal quality is evaluated by correct diagnosis (CD) test through visual inspection. Three sets of ECG data from three different databases, the MIT-BIH Arrhythmia (mita) (F_s=360 Hz, 11 b/sample), the Creighton University Ventricular Tachyarrhythmia (cuvt) (F_s=250 Hz, 12 b/sample) and the MIT-BIH Supraventricular Arrhythmia (mitsva) (F_s=128 Hz, 10 b/sample), are used for this work. For each set of ECG data, the compression ratio (CR) range is defined. The CD value of 100% is achieved for CR ≤12, CR ≤ 8 and CR ≤ 4 for data from mita, cuvt and mitsva databases, respectively. The experimental results demonstrate that the proposed TDR algorithm is suitable for real-time applications.     

Experimental myocardial necrosis in rats: Role of arjunolic acid on platelet aggregation,coagulation and antioxidant status

Arjunolic acid, a new triterpene and a potent principle from the bark of Terminalia arjuna, has been shown to provide significant cardiac protection in isoproterenol induced myocardial necrosis in rats. To further explore the mechanism of action of arjunolic acid, antiplatelet activity, anticoagulant assays, electrocardiographic changes, serum marker enzymes, antioxidant status, lipid peroxide and myeloperoxidase (MPO) have been measured and the results are compared with a potent cardioprotective drug, acetyl salicylic acid (ASA). Administration of isoproterenol produces electrocardiographic changes such as decreased R amplitude and increased ST segment elevation and has resulted in an increase in serum marker enzyme levels as well as a decrease in enzymatic and nonenzymatic antioxidant levels. Arjunolic acid at an effective dosage of 15 mg/kg body weight (pre and post treatment),when administered intraperitoneally (i.p.), effects a decrease in serum enzyme levels and the electrocardiographic changes get restored towards normalcy. Arjunolic acid treatment is also shown to prevent the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, -tocopherol, reduced glutathione (GSH), ascorbic acid, lipid peroxide, MPO and the cardioprotection is confirmed by the histopathological studies.This study shows that the cardioprotection of arjunolic acid pre and post treatment could possibly be due to the protective effect against the damage caused by myocardial necrosis.     

Dynamics in the Mn2+ binding site in single crystals of concanavalin A revealed by high-field EPR spectroscopy

EPR spectroscopy at 95 GHz was used to characterize the dynamics at the Mn(2+) binding site in single crystals of the saccharide-binding protein concanavalin A. The zero-field splitting (ZFS) tensor of the Mn(2+) was determined from rotation patterns in the a-c and a-b crystallographic planes, acquired at room temperature and 4.5 K. The analysis of the rotation patterns showed that while at room temperature there is only one type of Mn(2+) site, at low temperatures two types of Mn(2+) sites, not related by any symmetry, are distinguished. The sites differ in the ZFS parameters D and E and in the orientation of the ZFS tensor with respect to the crystallographic axes. Temperature-dependent EPR measurements on a crystal oriented with its crystallographic a axis parallel to the magnetic field showed that as the temperature increases, the two well-resolved Mn(2+) sextets gradually coalesce into a single sextet at room temperature. The line shape changes are characteristic of a two-site exchange. This was confirmed by simulations which gave rates in the range of 10(7)-10(8) s(-1) for the temperature range of 200-266 K and an activation energy of 23.8 kJ/mol. This dynamic process was attributed to a conformational equilibrium within the Mn(2+) binding site which freezes into two conformations at low temperatures.     

The occurrence of C--H...O hydrogen bonds in alpha-helices and helix termini in globular proteins

A comprehensive database analysis of C--H...O hydrogen bonds in 3124 alpha-helices and their corresponding helix termini has been carried out from a nonredundant data set of high-resolution globular protein structures resolved at better than 2.0 A in order to investigate their role in the helix, the important protein secondary structural element. The possible occurrence of 5 --> 1 C--H...O hydrogen bond between the ith residue CH group and (i - 4)th residue C==O with C...O < or = 3.8 A is studied, considering as potential donors the main-chain Calpha and the side-chain carbon atoms Cbeta, Cgamma, Cdelta and Cepsilon. Similar analysis has been carried out for 4 --> 1 C--H...O hydrogen bonds, since the C--H...O hydrogen bonds found in helices are predominantly of type 5 --> 1 or 4 --> 1. A total of 17,367 (9310 of type 5 --> 1 and 8057 of type 4 --> 1) C--H...O hydrogen bonds are found to satisfy the selected criteria. The average stereochemical parameters for the data set suggest that the observed C--H...O hydrogen bonds are attractive interactions. Our analysis reveals that the Cgamma and Cbeta hydrogen atom(s) are frequently involved in such hydrogen bonds. A marked preference is noticed for aliphatic beta-branched residue Ile to participate in 5 --> 1 C--H...O hydrogen bonds involving methylene Cgamma 1 atom as donor in alpha-helices. This may be an enthalpic compensation for the greater loss of side-chain conformational entropy for beta-branched amino acids due to the constraint on side-chain torsion angle, namely, chi1, when they occur in helices. The preference of amino acids for 4 --> 1 C--H...O hydrogen bonds is found to be more for Asp, Cys, and for aromatic residues Trp, Phe, and His. Interestingly, overall propensity for C--H...O hydrogen bonds shows that a majority of the helix favoring residues such as Met, Glu, Arg, Lys, Leu, and Gln, which also have large side-chains, prefer to be involved in such types of weak attractive interactions in helices. The amino acid side-chains that participate in C--H...O interactions are found to shield the acceptor carbonyl oxygen atom from the solvent. In addition, C--H...O hydrogen bonds are present along with helix stabilizing salt bridges. A novel helix terminating interaction motif, X-Gly with Gly at C(cap) position having 5 --> 1 Calpha--H...O, and a chain reversal structural motif having 1 --> 5 Calpha-H...O have been identified and discussed. Our analysis highlights that a multitude of local C--H...O hydrogen bonds formed by a variety of amino acid side-chains and Calpha hydrogen atoms occur in helices and more so at the helix termini. It may be surmised that the main-chain Calpha and the side-chain CH that participate in C--H...O hydrogen bonds collectively augment the cohesive energy and thereby contribute together with the classical N--H...O hydrogen bonds and other interactions to the overall stability of helix and therefore of proteins.     

Macroalgal susceptibility to grazing by herbivore fish Siganus spp. at Gulf of Mannar reef,Indian Ocean

Environmental Biology of Fishes - Enhancing the herbivore fish stock is envisaged as a mitigation tool to reverse the macroalgal dominance in a coral reef environment. However, identifying the key...