Immunotherapy using algal‐produced Ara h 1 core domain suppresses peanut allergy in mice

Peanut allergy is an IgE‐mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen‐specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal‐produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut‐allergic patients. We further found that immunotherapy using algal‐produced Ara h 1 core domain confers protection from peanut‐induced anaphylaxis in a murine model of peanut allergy.     

Gastrointestinal nematodes of wild sheep (Ovis orientalis) from Iran.

A total of 250 wild sheep (Ovis orientalis) from different national parks and protected regions of Iran were examined for gastrointestinal nematodes at necropsy. Twenty five species of nematodes were found. Marshallagia marshalli, Ostertagia spp; Nematodirus spp; and Skrjabinema ovis were the most prevalent. Although all the species found are recorded from wild sheep for the first time in Iran, 88% were reported previously from domestic sheep. New host and distribution records for Nematodirus davtiani, N. gazellae and Nematodirella longissimespiculata were established during the present study.     

Generation of mouse–human hybridomas secreting antibodies against peanut allergen Ara h1

Two clones of mouse–human hybridomas, secreting human monoclonal antibodies to a peanut allergen Ara h1, were generated from human peripheral blood lymphocytes transformed with Epstein--Barr virus, followed by cell fusion with mouse myeloma cells. Epitope analysis with overlapping peptides synthesized on a multi-pin apparatus revealed antibody-binding sequences of Ara h1 protein.     

Antiviral protein Ski8 is a direct partner of Spo11 in meiotic DNA break formation, independent of its cytoplasmic role in RNA metabolism

Meiotic recombination initiates with double-strand breaks (DSBs) catalyzed by Spo11 in conjunction with accessory proteins whose roles are not understood. Two-hybrid analysis reveals a network of interactions connecting the yeast DSB proteins to one another. Of these proteins, Ski8 was known to function in cytoplasmic RNA metabolism, suggesting that its role in recombination might be indirect. However, obligate partners of Ski8 in RNA metabolism are dispensable for recombination and Ski8 relocalizes to the nucleus and associates with chromosomes specifically during meiosis. Interaction of Ski8 with Spo11 is essential for DSB formation and Ski8 relocalization. Thus, Ski8 plays distinct roles in RNA metabolism and, as a direct partner of Spo11, in DSB formation. Ski8 works with Spo11 to recruit other DSB proteins to meiotic chromosomes, implicating Ski8 as a scaffold protein mediating assembly of a multiprotein complex essential for DSB formation.     

Theoretical study of chemisorption of cyanuric fluoride and S-triazine on the surface of Al-doped graphene

We studied the adsorption of cyanuric fluoride (CF) and s-triazine (ST) molecules on the surface of pristine as well as Al-doped graphenes using density functional theory calculations. Our results reveal low adsorption on the surface of pristine graphene; but by modification of surface using aluminium, resulted Al-doped graphene becomes more reactive towards both CF and ST molecules. We aimed to focus on the adsorption energy, electronic structure, charge analysis, density of state and global indices of each system upon adsorption of CF and ST molecules on the above-mentioned surfaces. Our calculated adsorption energies for the most stable position configurations of CF and ST on Al-doped graphene were ?76.53 kJ mol^?1 (?57.45 kJ mol^?1 BSSE corrected energy) and ?115.55 kJ mol^?1 (?86.87 kJ mol^?1 BSSE corrected energy), respectively, which point to the chemisorption process. For each CF and ST molecule, upon adsorption on the surface of Al-doped graphene, the band gap of HOMO-LUMO was reduced considerably and it becomes a p-type semiconductor, whereas there is no hybridisation between the above-mentioned molecules and pristine graphene.     

Hepatoprotective and antioxidant effects of Hedera helix extract on acetaminophen induced oxidative stress and hepatotoxicity in mice

ABSTRACT

Exposure to high doses of acetaminophen is the most common cause of drug induced liver injury. We investigated the protective effects of Hedera helix extract against acetaminophen induced oxidative stress and hepatotoxicity using a mouse model. We used two control groups: group A was given 0.9% NaCl, group B was an acetaminophen control that was given a single injection of 600 mg/kg acetaminophen. T1?T4 groups were pretreated orally with different doses of H. helix extract. The mice were sacrificed and blood samples were collected to estimate the levels of glutathione peroxidase (GPx), malondialdehyde (MDA), superoxide dismutase (SOD) and total bilirubin. Liver samples also were used for histopathological studies. We found that acetaminophen significantly increased the levels of serum ALP, ALT, AST and MDA, and also significantly reduced the antioxidant factors, CAT, GPX and SOD. H. helix extract treatment produced a significant reduction in the levels of ALP, ALT, AST and MDA in serum and restored the levels of CAT, GPX and SOD to control levels. The histopathological findings were consistent with the biochemical findings. H. helix extract exhibited antioxidant and hepatoprotective effects against acetaminophen induced liver damage.     

Interval aerobic training improves bioenergetics state and mitochondrial dynamics of different brain regions in restraint stressed rats

Molecular Biology Reports - Evidence has validated the prophylactic effects of exercising on different aspects of health. On the opposite side, immobilization may lead to various destructive...     

Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study

Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (<4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.