Mitochondrial dysfunction in perinatal asphyxia: role in pathogenesis and potential therapeutic interventions

Molecular and Cellular Biochemistry - Perinatal asphyxia (PA)-induced brain injury may present as hypoxic-ischemic encephalopathy in the neonatal period, and long-term sequelae such as spastic...     

Mutagenic evaluation of propranolol in somatic and germ cells of mice

The mutagenic effect of an antihypertensive drug, propranolol, was studied on somatic and germ cells of Swiss albino mice. The induction of a significant increase in the frequency of micronuclei in erythrocytes was observed at higher dose levels, whereas, in germ cells, propranolol failed to induce significant chromosomal aberrations at any dose tested.     

‘Leaf tip hooding’ — an induced mutation inN. Tabacum,var. Delcrest

A leaf tip hooded mutant was isolated in the progenies of the irradiated seeds of a commercial tobacco variety, namely Delcrest. The mutant character was determined as monogenic recessive. Along with leaf tip hooding, certain other characters such as increase in size of leaves, number and clasping arrangement of leaves on stem, and delayed flowering, were found to be closely associated and this was attributed to the pleiotropic effect of the leaf tip hooding gene.     

Trisomy 18q: 46,XX,-10,+der(10) t(10;18) (p15;q12) pat: a case report.

A 2-month-old female with intrauterine and postnatal growth retardation, multiple congenital anomalies, absent right kidney, congenital heart disease was investigated. Her karyotype revealed, 46,XX,-10,+der(10), t(10;18) (p15;q12) pat. The child died at 2 months 2 weeks. This is the third case of trisomy 18q resulting from translocation of chromosome 10 and 18.     

Segregation of Cytoplasmic Incompatibility Properties in CULEX PIPIENS FATIGANS

Maternally inherited variants, which arose within a laboratory colony of Culex pipiens fatigans, have been studied by rearing cultures from single egg rafts. Segregation, i.e, variation of cytoplasmic incompatibility properties between the male progeny of individual females, was demonstrated. Also, from the daughters of individual females, sub-lines were derived within which all the males showed the same incompatibility or compatibility properties. Among the descendants of tetracycline-treated individuals were lines which superficially simulated these phenomena, but theses lines ultimately reverted to the cytoplasmic compatibility type of the strain which was submitted to the treatment. The types of variation s in cytoplasmic incompatibility properties that have been studied are discussed.     

Crystallization of the NAD-dependent malic enzyme from the parasitic nematode Ascaris suum.

The malic enzyme from muscle mitochondria of the parasitic nematode Ascaris suum is a tetramer of 65 kDa monomers that catalyzes the oxidative decarboxylation of malate to pyruvate and CO2 with NAD cofactor as oxidant. This malic enzyme is critical to the nematode for muscle function under anaerobic conditions. Unlike mammalian versions of the enzyme such as that found in rat liver, which require NADP as cofactor, the nematode version is an NAD-dependent enzyme. We report the crystallization of samples of the nematode enzyme at room temperature from pH 7.5 solutions of polyethylene glycol 4000 containing magnesium sulfate, NAD and sodium tartronate. Immediately upon mixing of protein and precipitant solutions, a marked precipitation of the protein occurs. Out of this precipitate, crystals appear almost immediately, most commonly in a truncated cube form that can grow to 0.5 to 0.7 mm on a cube edge in two to three days. The crystals are trigonal, space group P3(1)21 or its enantiomer, with a = b = 131.2(7) A, c = 152.6(9) A, and two monomers per asymmetric unit. Fresh crystals diffract X-radiation from a synchrotron source (lambda = 0.95 A) to about 3.0 A resolution. Rotational analysis of Patterson functions indicates that the malic enzyme tetramer has 222 symmetry.     

Population Genetics of DROSOPHILA NASUTA NASUTA, DROSOPHILA NASUTA ALBOMICANA and Their Hybrids. I. Karyotypic Mosaicism in the Hybrid Populations

D. n. nasuta and D. n. albomicana constitute a pair of chromosomal races with 2n=8 and 2n=6, respectively. The F₁ of these has 2n=7 and it is fertile. There exists a state of karyotypic mosaicism as evidenced by the presence of 26 types of chromosome combinations in F₂, F₃ and F₁₀ populations. In the midst of this karyotypic noise, the karyotype similar to that of F₁ reached 51% of the population. Implications of these findings are discussed.     

Studies on hemolysis of human erythrocytes by linoleic acid

The results presented in this paper show that lysis of human erythrocytes by linoleic acid is not caused by peroxidation of the fatty acid. Peroxidase, superoxide dismutase and scavengers of O ₂ ⁻ and OH had no effect on the lysis while catalase showed only marginal inhibition suggesting that O ₂ ⁻ , OH, O ₂ ⁻ and H₂O₂ do not play any direct role in hemolysis by linoleic acid. Generators of H₂O₂ inhibited the lysis completely and methemoglobin cells were more resistant to hemolysis by linoleic acid. The fatty acid did neither bind to nor fomed complex with red cell ghosts. Membrane oxidation of sulphydryl groups was also not involved in the lysis. Β-Carotene, retinol and bile salts enhanced the lysis, while, cholesterol but not cholesterol acetate, inhibited it. Taurocholate-pretreated cells were more susceptible to linoleic acid lysis. These observations suggested-that lysis by linoleic acid may be due to its detergent property.     

Daboxin P,a Major Phospholipase A2 Enzyme from the Indian Daboia russelii russelii Venom Targets Factor X and Factor Xa for Its Anticoagulant Activity

In the present study a major protein has been purified from the venom of Indian Daboia russelii russelii using gel filtration, ion exchange and Rp-HPLC techniques. The purified protein, named daboxin P accounts for ~24% of the total protein of the crude venom and has a molecular mass of 13.597 kDa. It exhibits strong anticoagulant and phospholipase A₂ activity but is devoid of any cytotoxic effect on the tested normal or cancerous cell lines. Its primary structure was deduced by N-terminal sequencing and chemical cleavage using Edman degradation and tandem mass spectrometry. It is composed of 121 amino acids with 14 cysteine residues and catalytically active His48 -Asp49 pair. The secondary structure of daboxin P constitutes 42.73% of α-helix and 12.36% of β-sheet. It is found to be stable at acidic (pH 3.0) and neutral pH (pH 7.0) and has a Tm value of 71.59 ± 0.46°C. Daboxin P exhibits anticoagulant effect under in-vitro and in-vivo conditions. It does not inhibit the catalytic activity of the serine proteases but inhibits the activation of factor X to factor Xa by the tenase complexes both in the presence and absence of phospholipids. It also inhibits the tenase complexes when active site residue (His48) was alkylated suggesting its non-enzymatic mode of anticoagulant activity. Moreover, it also inhibits prothrombinase complex when pre-incubated with factor Xa prior to factor Va addition. Fluorescence emission spectroscopy and affinity chromatography suggest the probable interaction of daboxin P with factor X and factor Xa. Molecular docking analysis reveals the interaction of the Ca⁺² binding loop; helix C; anticoagulant region and C-terminal region of daboxin P with the heavy chain of factor Xa. This is the first report of a phospholipase A₂ enzyme from Indian viper venom which targets both factor X and factor Xa for its anticoagulant activity.