Identification of a genetic marker associated with the resistance to Schistosoma mansoni infection using random amplified polymorphic DNA analysis

In schistosomiasis, the host/parasite interaction remains not completely understood. Many questions related to the susceptibility of snails to infection by respective trematode still remain unanswered. The control of schistosomiasis requires a good understanding of the host/parasite association. In this work, the susceptibility/resistance to Schistosoma mansoni infection within Biomphalaria alexandrina snails were studied starting one month post infection and continuing thereafter weekly up to 10 weeks after miracidia exposure. Genetic variations between susceptible and resistant strains to Schistosoma infection within B. alexandrina snails using random amplified polymorphic DNA analysis technique were also carried out. The results showed that 39.8% of the examined field snails were resistant, while 60.2% of these snails showed high infection rates.In the resistant genotype snails, OPA-02 primer produced a major low molecular weight marker 430 bp. Among the two snail strains there were interpopulational variations, while the individual specimens from the same snail strain, either susceptible or resistant, record semi-identical genetic bands. Also, the resistant character was ascendant in contrast to a decline in the susceptibility of snails from one generation to the next.     

Nanobacteria are mineralo fetuin complexes

"Nanobacteria" are nanometer-scale spherical and ovoid particles which have spurred one of the biggest controversies in modern microbiology. Their biological nature has been severely challenged by both geologists and microbiologists, with opinions ranging from considering them crystal structures to new life forms. Although the nature of these autonomously replicating particles is still under debate, their role in several calcification-related diseases has been reported. In order to gain better insights on this calciferous agent, we performed a large-scale project, including the analysis of "nanobacteria" susceptibility to physical and chemical compounds as well as the comprehensive nucleotide, biochemical, proteomic, and antigenic analysis of these particles. Our results definitively ruled out the existence of "nanobacteria" as living organisms and pointed out the paradoxical role of fetuin (an anti-mineralization protein) in the formation of these self-propagating mineral complexes which we propose to call "nanons." The presence of fetuin within renal calculi was also evidenced, suggesting its role as a hydroxyapatite nucleating factor.     

Testing alternatives: the use of adipose-derived mesenchymal stem cells to slow neurodegeneration in a rat model of Parkinson’s disease

Molecular Biology Reports - Parkinson’s disease (PD) is a chronic neurodegenerative disease. Unfortunately, the effectiveness of anti-Parkinson treatments gradually diminishes owing to the...     

Neuropathological and Cognitive Effects Induced by CuO-NPs in Rats and Trials for Prevention Using Pomegranate Juice

Copper oxide nanoparticles (CuO‐NPs) are extensively utilized in several industries and in pharmaceutical production. This excess exposure elevates the concern about its expected poisonous impacts on humans and animals. Pomegranate juice (PJ) is a natural source of polyphenols and exhibits potent antioxidant activities. Our experiment intended to explore the neurobehavioral and toxicopathological impacts of CuO-NPs and to explain the mechanistic role of PJ to reduce their toxicity. Thirty Wistar albino rats received the subsequent materials through oral gavage, every day for 28d: (1) normal saline, (2) 3 mL/kg bwt PJ, (3) 6 mL/kg bwt PJ, (4) 300 mg/kg bwt CuO-NPs, (5) CuO-NPs?+?3 mL/kg bwt PJ, (6) CuO-NPs?+?6 mL/kg bwt PJ. Continuous exposure to CuO-NPs caused a significant elevation of MDA levels and reduction of total antioxidant capacity associated with remarkable pathological alterations in all brain regions including cerebrum, hippocampus and cerebellum. Progressive decline of memory along with cognitive and psychiatric disturbances were observed in rats exposed to CuO-NPs not in PJ co-treated rats. Continuous exposure to CuO-NPs caused over expression of the immunohistochemical markers of caspase-3, iNOS and GFAP altogether with DAN fragmentation and down-regulation of HO-1 and Nrf2 gene in the whole brain tissues. Conversely, rats co-treated with PJ showed dose dependent improvements in the entire toxicological, behavioral, and pathological parameters. We showed that PJ had the ability to reduce the oxidative stress damage via up-regulation of HO-1 and Nrf2 genes in the brain. So that PJ had the ability to protect the brain and DNA from further damage.

     

Biocontrol of chickpea root rot using endophytic actinobacteria

Eleven actinobacterial strains were isolated from different plants, lentil (Lens esculentus), chickpea (Cicer arietinum L.), pea (Pisum sativum), faba bean (Vicia faba) and wheat (Triticum vulgare) from Paskerville, South Australia. Isolates were characterized and identified morphologically as well as using 16S ribosomal RNA gene sequencing. Of the actinobacteria tested, 72% produced siderophores, 33% were positive for cyanogens production, and 11% showed phosphate solubility. All isolates had antimicrobial activity against Phytophthora medicaginis, Pythium irregulare and Botrytis cinerea. In a greenhouse experiment, actinobacteria with the highest biocontrol capabilities were tested for their ability to control Phytophthora root rot on chickpea. Both Streptomyces sp. BSA25 and WRA1 successfully suppressed Phytophthora root rot when coinoculated with either Mesorhizobium ciceri WSM1666 or Kaiuroo 3. Streptomyces sp. BSA25 with either rhizobial strain enhanced vegetative growth of root (7–11 fold) and shoot dry weights (2–3 fold) compared to infected control, whereas Streptomyces sp. WRA1 increased root and shoot dry weights by 8- and 4-fold, respectively when inoculated with M. ciceri WSM1666. We suggest that careful selection of actinobacteria should be considered when coinoculated with beneficial microorganisms as plant symbionts.     

A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli

Methionine oxidation into methionine sulfoxide is known to be involved in many pathologies and to exert regulatory effects on proteins. This oxidation can be reversed by a ubiquitous monomeric enzyme, the peptide methionine sulfoxide reductase (MsrA), whose activity in vivo requires the thioredoxin-regenerating system. The proposed chemical mechanism of Escherichia coli MsrA involves three Cys residues (positions 51, 198, and 206). A fourth Cys (position 86) is not important for catalysis. In the absence of a reducing system, 2 mol of methionine are formed per mole of enzyme for wild type and Cys-86 --> Ser mutant MsrA, whereas only 1 mol is formed for mutants in which either Cys-198 or Cys-206 is mutated. Reduction of methionine sulfoxide is shown to proceed through the formation of a sulfenic acid intermediate. This intermediate has been characterized by chemical probes and mass spectrometry analyses. Together, the results support a three-step chemical mechanism in vivo: 1) Cys-51 attacks the sulfur atom of the sulfoxide substrate leading, via a rearrangement, to the formation of a sulfenic acid intermediate on Cys-51 and release of 1 mol of methionine/mol of enzyme; 2) the sulfenic acid is then reduced via a double displacement mechanism involving formation of a disulfide bond between Cys-51 and Cys-198, followed by formation of a disulfide bond between Cys-198 and Cys-206, which liberates Cys-51, and 3) the disulfide bond between Cys-198 and Cys-206 is reduced by thioredoxin-dependent recycling system process.     

Protein implicated in nonsyndromic mental retardation regulates protein kinase A (PKA) activity

Mutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been linked to severe autosomal recessive nonsyndromic mental retardation. Using a mouse model that produces a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show that CC2D1A is important for neuronal differentiation and brain development. CC2D1A mutant neurons are hypersensitive to stress and have a reduced capacity to form dendrites and synapses in culture. At the biochemical level, CC2D1A transduces signals to the cyclic adenosine 3',5'-monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell differentiation. PKA activity is compromised, and the translocation of its catalytic subunit to the nucleus is also defective in CC2D1A mutant cells. Consistently, phosphorylation of the PKA target cAMP-responsive element-binding protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal primary cells derived from the CC2D1A KO mice. CC2D1A associates with the cAMP-PKA complex following forskolin treatment and accumulates in vesicles or on the plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the PKA complex to the membrane to facilitate signal transduction. Together, our data show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway, which may be the underlying cause for impaired mental function in nonsyndromic mental retardation patients with CC2D1A mutation.     

Fibronectin inhibits osteoclastogenesis while enhancing osteoclast activity via nitric oxide and interleukin‐1β‐mediated signaling pathways

Osteoclasts are bone‐resorbing cells formed by fusion of mononuclear precursors. The matrix proteins, fibronectin (FN), vitronectin (VN), and osteopontin (OPN) are implicated in joint destruction and interact with osteoclasts mainly through integrins. To assess the effects of these matrix proteins on osteoclast formation and activity, we used RAW 264.7 (RAW) cells and mouse splenocytes differentiated into osteoclasts on tissue culture polystyrene (TCP) or osteologic? slides pre‐coated with 0.01–20 µg/ml FN, VN, and OPN. At 96 h, osteoclast number and multinucleation were decreased on VN and FN compared to OPN and TCP in both RAW and splenocytes cell cultures. When early differentiation was assessed, VN but not FN decreased cytoplasmic tartrate‐resistant acid phosphatase activity and pre‐osteoclast number at 48 h. OPN had the opposite effect to FN on osteoclast formation. When RAW cells were differentiated on OPN and treated by FN and OPN, osteoclast number only in the FN treated group was 40–60% lower than the control, while the total number of nuclei was unchanged, suggesting that FN delays osteoclast fusion. In contrast to its inhibitory effect on osteoclastogenesis, FN increased resorption by increasing both osteoclast activity and the percentage of resorbing osteoclasts. This was accompanied by an increase in nitric oxide (NO) levels and interleukin‐1β (IL‐1β). IL‐1β production was inhibited using the NO‐synthase inhibitor only on FN indicating a FN‐specific cross‐talk between NO and IL‐1β signaling pathways. We conclude that FN upregulates osteoclast activity despite inhibiting osteoclast formation and that these effects involve NO and IL‐1β signaling. J. Cell. Biochem. 111: 1020–1034, 2010. © 2010 Wiley‐Liss, Inc.     

Non-Newtonian behaviour of yeast suspensions

Summary The rheological properties of yeast (Baker's yeast) suspensions in water and in water-methanol-electrolyte solutions have been investigated using a Fann V.G. concentric cylinder viscometer. The resulted rheograms could be described by the power law model for non-Newtonian fluids with the flow behaviour index n<1 indicating pseudo-plastic behaviour. This flow behaviour index was constant under all operating conditions while the consistancy index k increased exponentially with increasing wet yeast volume fraction. The addition of methanol and electrolytes had a negligible effect on the rheological properties. Changing the pH of the suspension acidic to lowered the apparent viscosities.     

Challenging inflammatory process at molecular,cellular and in vivo levels via some new pyrazolyl thiazolones

The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC₅₀ values of 0.09–0.14 µM) with significant 15-LOX inhibitory activities (IC₅₀s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates.