Exercise-induced cardiac performance in autoimmune (Type 1) diabetes is associated with a decrease in myocardial diacylglycerol

One of the fundamental biochemical defects underlying the complications of diabetic cardiovascular system is elevation of diacylglycerol (DAG) and its effects on protein kinase C (PKC) signaling. It has been noted that exercise training attenuates poor cardiac performance in Type 1 diabetes. However, the role of PKC signaling in exercise-induced alleviation of cardiac abnormalities in diabetes is not clear. We investigated the possibility that exercise training modulates PKC-βII signaling to elicit its beneficial effects on the diabetic heart. bio-breeding diabetic resistant rats, a model reminiscent of Type 1 diabetes in humans, were randomly assigned to four groups: 1) nonexercised nondiabetic (NN); 2) nonexercised diabetic (ND); 3) exercised nondiabetic; and 4) exercised diabetic. Treadmill training was initiated upon the onset of diabetes. At the end of 8 wk, left ventricular (LV) hemodynamic assessment revealed compromised function in ND compared with the NN group. LV myocardial histology revealed increased collagen deposition in ND compared with the NN group, while electron microscopy showed a reduction in the viable mitochondrial fraction. Although the PKC-βII levels and activity were unchanged in the diabetic heart, the DAG levels were increased. With exercise training, the deterioration of LV structure and function in diabetes was attenuated. Notably, improved cardiac performance in training was associated with a decrease in myocardial DAG levels in diabetes. Exercise-induced benefits on cardiac performance in diabetes may be mediated by prevention of an increase in myocardial DAG levels.     

Wild-type and feedback-resistant phosphoribosyl pyrophosphate synthetases from <Emphasis Type="Italic">Bacillus amyloliquefaciens</Emphasis>: purification,characterization, and application to increase purine nucleoside production

Bacillus strains are used for the industrial production of the purine nucleosides inosine and guanosine, which are raw materials for the synthesis of the flavor enhancers disodium inosinate and disodium guanylate. An important precursor of purine nucleosides is 5-phospho-α-d-ribosyl-1-pyrophosphate, which is synthesized by phosphoribosyl pyrophosphate synthetase (PRS, EC 2.7.6.1). Class I PRSs are widespread in bacteria and mammals, are highly conserved among different organisms, and are negatively regulated by two end products of purine biosynthesis, adenosine 5′-diphosphate (ADP) and guanosine 5′-diphosphate (GDP). The D52H, N114S, and L129I mutations in the human PRS isozyme I (PRS1) have been reported to cause uric acid overproduction and gout due to allosteric deregulation and enzyme superactivity. In this study, to find feedback-resistant Bacillus amyloliquefaciens PRS, the influence of the D58H, N120S, and L135I mutations (corresponding to the D52H, N114S, and L129I mutations in PRS1, respectively) on PRS enzymatic properties has been studied. Recombinant histidine-tagged wild-type PRS and three mutant PRSs were expressed in Escherichia coli, purified, and characterized. The N120S and L135I mutations were found to release the enzyme from ADP and GDP inhibition and significantly increase its sensitivity to inorganic phosphate (P_i) activation. In contrast, PRS with the D58H mutation exhibited nearly identical sensitivity to ADP and GDP as the wild-type protein and had a notably greater P_i requirement for activation. The N120S and L135I mutations improved B. amyloliquefaciens and Bacillus subtilis purine nucleoside-producing strains.     

Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats

Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the microglial reaction was significantly attenuated. The results indicate a therapeutic potential for NAC and ALC in the early treatment of traumatic spinal cord injury.     

Superfamily of plant monomeric GTP-binding proteins: 2. Rab proteins are the regulators of vesicles trafficking and plant responses to stresses

In plants, Rab proteins represent the largest family of monomeric GTP-binding proteins (mG-proteins). As distinct from animal cells comprising 40 subfamilies of Rab proteins, which are the key regulators of intracellular vesicular transport, numerous Rab proteins in Arabidopsis and other plant species could be grouped in only eight subfamilies on the basis of their functional properties. The available data concerning the involvement of these mG-proteins in the control of vesicle trafficking agree generally with the paradigms accepted for other eukaryotes. On the other hand, these proteins play an important role in plant responses to abiotic and biotic factors, indicating specific for plants functions of Rab proteins.     

Novel clades of chromodomain-containing Gypsy LTR retrotransposons from mosses (Bryophyta)

Retrotransposons are the major component of plant genomes. Chromodomain-containing Gypsy long terminal repeat (LTR) retrotransposons are widely distributed in eukaryotes. Four distinct clades of chromodomain-containing Gypsy retroelements are known from the vascular plants: Reina, CRM, Galadriel and Tekay. At the same time, almost nothing is known about the repertoire of LTR retrotransposons in bryophyte genomes. We have combined a search of chromodomain-containing Gypsy retroelements in Physcomitrella genomic sequences and an experimental investigation of diverse moss species. The computer-based mining of the chromodomain-containing LTR retrotransposons allowed us to describe four different elements from Physcomitrella. Four novel clades were identified that are evolutionarily distinct from the chromodomain-containing Gypsy LTR retrotransposons of other plants.     

Penicillium expansum, a Resident Fungal Strain of the Orbital Complex Mir, Producing Xanthocyllin X and Questiomycin A

It was demonstrated that the fungus Penicillium expansum 2-7, a resident strain of the orbital complex Mir, which became dominant at the end of a long-term space flight, formed biologically active secondary metabolites (antibiotics). Using physicochemical methods these metabolites were identified as xanthocyllin X and questiomycin A. The time courses of their biosyntheses during the growth and development of the producer culture were studied. The addition of zinc to the culture medium affected both the growth of the culture and the biosyntheses of the antibiotics. The concentrations of zinc in the medium, optimum for xanthocyllin X and questiomycin A production, were 0.3 and 3.0 mg/l, respectively.     

Effects of prolonged hyperbarism on lipid peroxidation and structural-functional state of erythrocytes]

Prolonged helium-oxygen hyperbaric (pressure 3,6 MPa) increased diene conjugate and Schiff's base level in plasma and erythrocyte membranes of mice. In those conditions SOD and glucose 6-phosphate dehydrogenase activities were inhibited in erythrocytes. Lipid bilayer microviscosity and cholesterol content of erythrocyte membranes were increased.