Trophic flexibility of Eurasian otter (Lutra lutra) in Anzali Wetland,Iran, assessed by fecal and stable isotope analysis

Aquatic Ecology - Information on the feeding habits of species is essential to develop appropriate conservation actions. This study aimed to assess spatial and temporal variation in the diet of the...     

In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane

Charcot‐Marie‐Tooth (CMT) diseases are a heterogeneous group of genetic peripheral neuropathies caused by mutations in a variety of genes, which are involved in the development and maintenance of peripheral nerves. Myelin protein zero (MPZ) is expressed by Schwann cells, and MPZ mutations can lead to primarily demyelinating polyneuropathies including CMT type 1B. Different mutations demonstrate various forms of disease pathomechanisms, which may be beneficial in understanding the disease cellular pathology. Our molecular dynamics simulation study on the possible impacts of I30T mutation on the MPZ protein structure suggested a higher hydrophobicity and thus lower stability in the membranous structures. A study was also conducted to predict native/mutant MPZ interactions. To validate the results of the simulation study, the native and mutant forms of the MPZ protein were separately expressed in a cellular model, and the protein trafficking was chased down in a time course pattern. In vitro studies provided more evidence on the instability of the MPZ protein due to the mutation. In this study, qualitative and quantitative approaches were adopted to confirm the instability of mutant MPZ in cellular membranes.     

Protein modeling of cathepsin C mutations found in Papillon–Lefèvre syndrome

Background

Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by hyperkeratosis involving the palms, soles, elbows, and knees followed by periodontitis, destruction of alveolar bone, and loss of primary and permanent teeth. Mutations of the lysosomal protease cathepsin C gene (CTSC) have been shown to be the genetic cause of PLS. This study analyzed CTSC mutations in five Iranian families with PLS and modeled the protein for mutations found in two of them.

Methods

DNA analysis was performed by direct automated sequencing of genomic DNA amplified from exonic regions and associated splice intron site junctions of CTSC. RFLP analyses were performed to investigate the presence of previously unidentified mutation(s) in control groups. Protein homology modeling of the deduced novel mutations (P35 delL and R272P) was performed using the online Swiss-Prot server for automated modeling and analyzed and tested with special bioinformatics tools to better understand the structural effects caused by mutations in cathepsin C protein (CTSC).

Results

Six Iranian patients with PLS experienced premature tooth loss and palm plantar hyperkeratosis. Sequence analysis of CTSC revealed a novel mutation (P35delL) in exon 1 of Patient 1, and four previously reported mutations; R210X in Patient 2, R272P in Patient 3, Q312R in two siblings of family 4 (Patients 4 and 5), and CS043636 in Patient 6. RFLP analyses revealed different restriction fragment patterns between 50 healthy controls and patients for the P35delL mutation. Modeling of the mutations found in CTSC, P35delL in Patient 1 and R272P in Patient 3 revealed structural effects, which caused the functional abnormalities of the mutated proteins.

Conclusions

The presence of this mutation in these patients provides evidence for founder CTSC mutations in PLS. This newly identified P35delL mutation leads to the loss of a leucine residue in the protein. The result of this study indicates that the phenotypes observed in these two patients are likely due to CTSC mutations. Also, structural analyses of the altered proteins identified changes in energy and stereochemistry that likely alter protein function.     

Effect of Fiber Geometry on Pulsatile Pumping and Energy Expenditure

Myocardial fiber orientation is a topic that has recently received much attention in connection with cardiac pumping function. The twisting motion of the cardiac base to apex can be a direct result of this geometric orientation of these fibers. One important question that has not been addressed yet is whether there is any relationship between the contractile energy expenditure and the geometric orientation of myocardial fibers. In the present work, we study the effect of contractile fiber orientation on pumping function. We particularly compare the effect of fiber geometry on ejection fraction, and on the energy required for contraction in both cylindrical and half-ellipsoid shell models. The analytical models we used signify the importance of twisting motion in minimizing the energy required to generate certain ejection fraction. Indeed, we quantified that if the angle of contractile fibers is appropriate for the shape and the size of the pump, twisting scheme can tremendously reduce the energy requirement for pumping.     

DARPin Ec1-LMWP protein scaffold in targeted delivery of siRNA molecules through EpCAM cancer stem cell marker

Molecular Biology Reports - This study is to investigate the binding ability of Designed Ankyrin Repeat Proteins type Ec1that was fused to Low Molecular Weight Protamine (DARPin Ec1-LMWP) protein...