Myelin lipids in vitamin B12 deficiency in chicks

Lipid profile of the spinal cord myelin was studied in normal and vitamin B₁₂ deficient chicks. The significant findings were a reduction in the total galactolipids and an increase in the total phospholipids of myelin in vitamin B₁₂ deficiency. The altered molar ratios of these lipids suggest a relative immaturity of the myelin in this condition. These changes may initiate the degenerative changes in the central nervous system in vitamin B₁₂ deficiency.Vitamin B₁₂ is essential for normal functioning of both the hemopoietic and the nervous system. Sub-acute combined degeneration of the spinal cord is seen both in association with pernicious anemia and in megaloblastic anemia of dietary origin (1,2). Though many biochemical postulates (3, 4) have been advanced to explain the neurological changes, the role of vitamin B₁₂ in maintaining the integrity of myelin is still obscure. So far only in two animal species the monkey (5) and the chick (6) has myelin degeneration been reported in vitamin B₁₂ deficiency. However, in neither of these reports, have changes in the composition of myelin been described. The results of a study in chicks wherein the effects of vitamin B₁₂ on the lipid profile of myelin were investigated are reported here.     

A Biofloc-Based Aquaculture System Bio-augmented with Probiotic Bacteria Bacillus tequilensis AP BFT3 Improves Culture Environment,Production Performances,and Proteomic Changes in Penaeus vannamei

Probiotics and Antimicrobial Proteins - Experiments were conducted to evaluate the probiotic effect of bio-augmented Bacillus tequilensis AP BFT3 on improving production, immune response, and...     

Dasatinib Attenuates Pressure Overload Induced Cardiac Fibrosis in a Murine Transverse Aortic Constriction Model

Reactive cardiac fibrosis resulting from chronic pressure overload (PO) compromises ventricular function and contributes to congestive heart failure. We explored whether nonreceptor tyrosine kinases (NTKs) play a key role in fibrosis by activating cardiac fibroblasts (CFb), and could potentially serve as a target to reduce PO-induced cardiac fibrosis. Our studies were carried out in PO mouse myocardium induced by transverse aortic constriction (TAC). Administration of a tyrosine kinase inhibitor, dasatinib, via an intraperitoneally implanted mini-osmotic pump at 0.44 mg/kg/day reduced PO-induced accumulation of extracellular matrix (ECM) proteins and improved left ventricular geometry and function. Furthermore, dasatinib treatment inhibited NTK activation (primarily Pyk2 and Fak) and reduced the level of FSP1 positive cells in the PO myocardium. In vitro studies using cultured mouse CFb showed that dasatinib treatment at 50 nM reduced: (i) extracellular accumulation of both collagen and fibronectin, (ii) both basal and PDGF-stimulated activation of Pyk2, (iii) nuclear accumulation of Ki67, SKP2 and histone-H2B and (iv) PDGF-stimulated CFb proliferation and migration. However, dasatinib did not affect cardiomyocyte morphologies in either the ventricular tissue after in vivo administration or in isolated cells after in vitro treatment. Mass spectrometric quantification of dasatinib in cultured cells indicated that the uptake of dasatinib by CFb was greater that that taken up by cardiomyocytes. Dasatinib treatment primarily suppressed PDGF but not insulin-stimulated signaling (Erk versus Akt activation) in both CFb and cardiomyocytes. These data indicate that dasatinib treatment at lower doses than that used in chemotherapy has the capacity to reduce hypertrophy-associated fibrosis and improve ventricular function.     

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.Cancer cells favor glycolysis over oxidative phosphorylation (OXPHOS) to meet their energy demand,¹ suggesting that they have adapted to survive and proliferate in the absence of fully functional mitochondria. Research in the last two decades demonstrates that, in addition to generation of energy, mitochondria including cancer cell mitochondria regulate multiple cellular signaling pathways encompassing cell death, proliferation, cellular redox balance, and metabolism.^{2, 3} As cancer cells possess defects in these pathways that provide an opportunity to target this organelle for therapeutic purposes. Subsequently, several agents have been developed that target cancer cell mitochondria to induce apoptosis, a cell death pathway, and eradicate cancer cells.^{4, 5} Cancer cell mitochondria harbor several proapoptotic proteins including cytochrome c, which is released from mitochondria in response to anticancer agents and activates caspases to execute apoptosis.^{5, 6} Thus, anticancer agents that induce cytochrome c release from mitochondria will be beneficial for induction of apoptosis in cancer cells. Indeed, several such agents have been developed, which include inhibitors targeting prosurvival Bcl-2 family members including Bcl-2, Bcl-xL, and Mcl-1.^{7, 8, 9} Unfortunately, cancer cells have developed multiple mechanisms to resist or overcome cytochrome c release and evade apoptosis.Although underlying mechanisms of cancer cell resistance to apoptosis are still undefined, the OXPHOS defect is known to be one of the key reasons for the attenuation of apoptosis in cancer cells.^{10, 11} Multiple lines of evidence support the notion that cancer cell survival and proliferation commonly associate with an OXPHOS defect in cancer.^{1, 12} Active OXPHOS is an efficient form of respiration but also regulates apoptosis through the OXPHOS complexes. The OXPHOS system consists of five multimeric protein complexes (I, II, III, IV, and V). The components of these complexes (except complex-II) are encoded by both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA).^{12, 13} Thus mutations, deletions, and translocations in either mtDNA or nDNA can potentially result in OXPHOS deficiency. MtDNA mutations associate with inhibition of apoptosis, induction of angiogenesis, invasion and metastasis of various types of cancer.^{3, 12, 14} Thus, mtDNA could potentially be an important target to restore cell death in cancer and attenuate cancer growth. Therefore, there is an urgent need to investigate the role of OXPHOS in the molecular mechanisms underlying cancer cell death.We investigated the effects of several anticancer agents of different classes including DNA-damaging agents (etoposide and doxorubicin), protein kinase inhibitors (staurosporine and sorafenib), mitotic inhibitor (taxol), ER stressor/inhibitor of Ca²⁺-ATPases (thapsigargin), and histone deacetylase (HDAC) inhibitor (apicidin) on mtDNA. We also determined the impact of OXPHOS defects on apoptosis induction by these agents. Although most anticancer agents induced caspase activation and apoptosis, the mtDNA level was elevated maximally by etoposide and it was not modulated by a caspase inhibitor but reduced by an autophagy inhibitor. Induction of mtDNA is associated with increased reactive oxygen species (ROS) production and elevated mitochondrial mass. Pharmacologic inhibition of OXPHOS complexes reduced the etoposide-induced elevation in mtDNA, suggesting the involvement of these complexes in etoposide-induced apoptosis. Together, we define the impact of mtDNA and OXPHOS function on mitochondrial apoptosis, which has significance in restoring cancer cell apoptosis for therapeutic purposes.     

Salicylic Acid Induces Changes in Mango Fruit that Affect Oviposition Behavior and Development of the Oriental Fruit Fly,Bactrocera dorsalis

The Oriental fruit fly, Bactrocera dorsalis (Hendel) is an important quarantine pest around the globe. Although measures for its control are implemented worldwide through IPM and male annihilation, there is little effect on their population. Hence, there is a need for new strategies to control this minacious pest. A strategy that has received negligible attention is the induction of ‘natural plant defenses’ by phytohormones. In this study, we investigated the effect of salicylic acid (SA) treatment of mango fruit (cv. Totapuri) on oviposition and larval development of B. dorsalis. In oviposition choice assays, gravid females laid significantly less eggs in SA treated compared to untreated fruit. Headspace volatiles collected from SA treated fruit were less attractive to gravid females compared to volatiles from untreated fruit. GC-MS analysis of the headspace volatiles from SA treated and untreated fruit showed noticeable changes in their chemical compositions. Cis-ocimene and 3-carene (attractants to B. dorsalis) were reduced in the headspace volatiles of treated fruit. Further, reduced pupae formation and adult emergence was observed in treated fruit compared to control. Increased phenol and flavonoid content was recorded in treated fruit. We also observed differential expression of anti-oxidative enzymes namely catalase (CAT), polyphenoloxidase (PPO) and peroxidase (POD). In summary, the results indicate that SA treatment reduced oviposition, larval development and adult emergence of B. dorsalis and suggest a role of SA in enhancing mango tolerance to B. dorsalis.     

Effects of brain‐derived neurotrophic factor on dopaminergic function and motor behavior during aging

Brain‐derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In this study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing Bdnf^+/? with wildtype mice (WT) at different ages. Bdnf^+/? and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf^+/? mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf^+/? compared to WT mice, but was not influenced by age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf^+/? mice. Body weight did not correlate with any of the three behavioral measures studied. Dopamine neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase, DA transporter (DAT) or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl‐stimulated DA release were reduced in Bdnf^+/? mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age.     

Synthesis and Docking Studies of Novel Carbazole-Thiazolidinedione Hybrid Derivatives as Antibacterial Agents

Russian Journal of Bioorganic Chemistry - A series of novel carbazol-thiazolidinedione hybrid derivatives were designed, synthesised and screened for antimicrobial activity against gram-positive...     

Crystal structure and thermal characterization of cadmium oxalate [CdC2O4 · 3H2O] and barium-doped cadmium oxalate [Ba0.5Cd0.5(C2O4)2 · 5H2O] single crystals grown in silica gel

Pure cadmium oxalate trihydrate (COT) and barium added cadmium oxalate (BCO) single crystals were grown by controlled diffusion of Cd²⁺ and Ba²⁺ ions in silica gel at ambient temperature. A single test tube technique coupled with gel aging conferred maximum size crystals by controlling the nucleation rate. It was found that the pH and age of the gel greatly influenced the crystal quality, their size and transparency. Grown crystals CdC₂O₄ · 3H₂O and Ba_0.5Cd_0.5(C₂O₄)₂ · 5H₂O were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and thermal analysis. Effect of barium dopant on the growth and morphology of cadmium oxalate was studied. Pure cadmium oxalate crystallized in triclinic system and the barium-doped cadmium oxalate crystallized in hexagonal system with massive changes in their unit cell parameters. The infrared spectrum revealed the presence of oxalate ligands and water of hydration in both the pure and barium-doped crystals. Thermal analysis showed that the grown crystals were dehydrated thermally even from lower temperatures and the doped crystals were found more stable.