A unique EF-hand motif in mnemiopsin photoprotein from Mnemiopsis leidyi: implication for its low calcium sensitivity

Up to now, all reported Ca²⁺-regulated photoproteins, except for mnemiopsin, have been cloned and expressed in Escherichia coli. In this study, the cDNA for an isotype of mnemiopsin, from the ctenophore Mnemiopsis leidyi, has been cloned, sequenced, and functionally expressed. The full length cDNA encoding mnemiopsin of M. leidyi was 624 bp open reading frame encoding a protein of 207 amino acid residues with calculated molecular mass of ∼24 kDa. The deduced amino acid sequence showed 90% and 84% identity to berovine (from ctenophore Beroe abyssicola) and bolinopsin 2 (from the ctenophore Bolinopsis infundibulum) respectively. In contrast to all known EF-hand in photoproteins, a unique EF-hand motif was found in mnemiopsin, in which a conserved glycine is substituted with glutamic acid. According to the results, the optimum pH was 9.0, time course of regeneration was 15 h and its Ca²⁺ sensitivity was lower than aequorin. Results of pK_a calculation for ionizable residues, motif scan and hydrophobic interactions of cavity aromatic residues of mnemiopsin in comparison with aequorin showed different patterns in these two photoproteins. In addition, experimental results are confirmed with the theoretical studies.     

Bioaccumulation of Trace Elements in Trophic Levels of Wetland Plants and Waterfowl Birds

Present study investigates relationships between total and bioaccessibility of trace elements (Cd, Co, Cr, Cu, Mn, NI, Pb, V, and Zn) concentrations in sediment and their bioaccumulation in species in Shadegan wetland in southwest of Iran. Bioavailability factor (BAF) and translocation factor (TF) were calculated in plants and trophic transfer factor (TTF) was determined in bird species. For this purpose, sampling of sediments, aquatic plants including Phragmites australis, Typha australis, Scripus maritimus and two bird species encircling Porphyrio porphyrio and globally threatened Marmaronetta angustirostris were carried out during winter 2009. Result of chemical analysis show that bioaccessibility concentrations of Mn (8.31 mg/kg), V (1.33 mg/kg), and Pb (1.03 mg/kg) are higher than other metals. The uptake trend of trace elements in plant decreases as root > stem > leaf. Accumulation levels of trace elements in different tissues of P. porphyrio and M. angustirostris are almost identical and considerable. Accumulation and toxicity of Cd in birds is more than plants. In addition, BAF of V, Pb, and Cr indicates high accumulation by plants and great pollution rate in the area of study. In S. maritimus TF for Mn, Cu, Pb, and V are high whereas in T. australis, Cu and Pb posses the highest TF. Also Cr, Co, Mn, Ni, and Zn have higher TF from stem to leaf than root to stem in P. australis. Finally, TTFs were compared in various bird species.     

Suppurative thyroiditis caused by Salmonella enteritidis

Bacterial thyroiditis is a rare disease, and one of which the clinical symptoms and signs are frequently misleading. On the other hand, prompt diagnosis is crucial for successful treatment. We report the case of an 82 year-old man with diabetes mellitus type 2 and a history of steroid treatment who presented with severe odynophagia and dysphagia associated with fever, chills, sore throat and right ear pain. Based on the clinical picture, radiological studies, thyroid cytology, blood and thyroid aspirate culture, suppurative thyroiditis caused by Salmonella enteritidis was diagnosed. The patient was successfully treated with antibiotics and surgical drainage.     

Unique pattern of convergent envelope evolution in simian immunodeficiency virus-infected rapid progressor macaques: association with CD4-independent usage of CCR5

The rate of disease development in simian immunodeficiency virus (SIV) infection of macaques varies considerably among individual macaques. While the majority of macaques inoculated with pathogenic SIV develop AIDS within a period of 1 to 2 years, a minority exhibit a rapid disease course characterized by absence or transience of humoral and cellular immune responses and high levels of virus replication with widespread dissemination of SIV in macrophages and multinucleated giant cells. The goal of this study was to examine viral evolution in three SIVsmE543-3-inoculated rapid progressors to determine the contribution of viral evolution to the development of rapid disease and the effect of the absence of immune pressure upon viral evolution. PCR was used to amplify and clone the entire SIV genome from tissues collected at necropsy, and the course of viral evolution was assessed by env sequences cloned from sequential plasma samples of one rapid progressor (RP) macaque. The majority of sequence changes in RP macaques occurred in the envelope gene. Substitutions were observed in all three animals at specific conserved residues in envelope, including loss of a glycosylation site in V1/V2, a D-to-N/V substitution in a highly conserved GDPE motif, and a P-to-V/H/T substitution in the V3 loop analog. A cell-cell fusion assay revealed that representative env clones utilized CCR5 as a coreceptor, independent of CD4. The selection of specific substitutions in envelope in RP macaques suggests novel selection pressures on virus in such animals and suggests that viral variants that evolve in these animals may play a role in disease progression.     

Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

ABSTRACT: BACKGROUND: Alpha 1- antitrypsin (alpha1AT) belongs to the superfamily of serpins and inhibits different proteases. alpha1AT protects the lung from cellular inflammatory enzymes. In the absence of alpha1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized alpha1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. RESULTS: Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1mu. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that alpha1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of alpha1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8, but the polymer with a ratio of 75:25 had a continuous and longer release profile. Cytotoxicity studies showed that nanoparticles do not affect cell growth and were not toxic to cells. CONCLUSION: In summary, alpha1AT-loaded nanoparticles may be considered as a novel formulation for efficient treatment of many pulmonary diseases.     

An evolutionary Wolff's law for trabecular architecture.

A continuum model is proposed to describe the temporal evolution of both the density changes and the reorientation of the trabecular architecture given the applied stress state in the bone and certain material parameters of the bone. The data upon which the proposed model is to be based consist of experimentally determined remodeling rate coefficients and quantitative stereological and anisotropic elastic constant measurements of cancellous bone. The model shows that the system of differential equations governing the temporal changes in architecture is necessarily nonlinear. This nonlinearity is fundamental in that it stems from the fact that, during remodeling, the relationship between stress and strain is changing as the stress and strain variables themselves are changing. In order to preserve the remodeling property of the model, terms that are of the order strain times the changes in density and/or microstructural properties must be retained. If these terms were dropped, there would be no feedback mechanism for architectural adaptation and no adaptation of the trabecular architecture. There is, therefore, no linearized version of the model of the temporal evolution of trabecular architecture. An application of the model is illustrated by an example problem in which the temporal evolution of homogeneous trabecular architecture is predicted. A limitation of the proposed continuum model is the length scale below which it cannot be applied. The model cannot be applied in regions of cancellous bone where the trabecular bone architecture is relatively inhomogeneous or at a bone-implant interface.