Overexpression of ubiquitin and amino acid permease genes in association with antimony resistance in Leishmania tropica field isolates

The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime®) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance. © 2013, Korean Society for Parasitology and Tropical Medicine

Performance comparison of numerical inversion methods for Laplace and Hankel integral transforms in engineering problems

Different methods for the numerical evaluations of the inverse Laplace and inverse of joint Laplace–Hankel integral transforms are applied to solve a wide range of initial-boundary value problems often arising in engineering and applied mathematics. The aim of the paper is to present a performance comparison among different numerical methods when they are applied to transformed functions related to actual engineering problems found in the literature. Most of our selected test functions have been found in the solution of boundary value problems of applied mechanics such as those related to transient responses of isotropic and transversely isotropic half-space to concentrated impulse or those related to viscoelastic wave motion in layered media. These classes of test functions are frequently encountered in similar problems such as those in boundary element or boundary integral equations, theoretical seismology, soil–structure-interaction in time domain and so on. Therefore, their behavior with different numerical inversion algorithms could make a useful guide to a precise choice of more suitable inversion method to be used in similar problems. Some different methods are also investigated in detail and compared for the inversion of the joint Hankel–Laplace transforms, where more sophisticated integrand functions are encountered. It is shown that Durbin, Crump, D’Amore, Fixed-Talbot, Gaver–Whyn–Rho (GWR), and Direct Integration methods have excellent performance and produce good results when applied to the same problems. On the contrary, Gaver–Stehfest and Piessens methods furnish results not very reliable for almost all classes of transformed functions and they seem good only for “simple” transformed functions. Particularly the performance of GWR algorithm is very good even for transformed functions with infinite number of singularities, where the other methods fail. In addition, in case of double integral transforms, only the Fixed-Talbot, Durbin and Weeks methods are recommended

Analytical Solution of Coupled Thermoelastic Axisymmetric Transient Waves in a Transversely Isotropic Half-Space

A half-space containing transversely isotropic thermoelastic material with a depth-wise axis of material symmetry is considered to be under the effects of axisymmetric transient surface thermal and forced excitations. With the use of a new scalar potential function, the coupled equations of motion and energy equation are uncoupled, and the governing equation for the potential function, is solved with the use of Hankel and Laplace integral transforms. As a result, the displacements and temperature are represented in the form of improper double integrals. The solutions are also investigated in detail for surface traction and thermal pulses varying with time as Heaviside step function. It is also shown that the derived solutions degenerate to the results given in the literature for isotropic materials. Some numerical evaluations for displacement and temperature functions for two different transversely isotropic materials with different degree of anisotropy are presented to portray the dependency of response on the thermal properties as well as the degree of anisotropy of the medium

Detection and molecular identification of leishmania RNA virus (LRV) in Iranian Leishmania species

Leishmania RNA virus (LRV) was first detected in members of the subgenus Leishmania (Viannia), and later, the virulence and metastasis of the New World species were attributed to this virus. The data on the presence of LRV in Old World species are confined to Leishmania major and a few Leishmania aethiopica isolates. The aim of this study was to survey the presence of LRV in various Iranian Leishmania species originating from patients and animal reservoir hosts. Genomic nucleic acids were extracted from 50 cultured isolates belonging to the species Leishmania major, Leishmania tropica, and Leishmania infantum. A partial sequence of the viral RNA-dependent RNA polymerase (RdRp) gene was amplified, sequenced and compared with appropriate sequences from the GenBank database. We detected the virus in two parasite specimens: an isolate of L. infantum derived from a visceral leishmaniasis (VL) patient who was unresponsive to meglumine antimoniate treatment, and an L. major isolate originating from a great gerbil, Rhombomys opimus. The Iranian LRV sequences showed the highest similarities to an Old World L. major LRV2 and were genetically distant from LRV1 isolates detected in New World Leishmania parasites. We could not attribute treatment failure in VL patient to the presence of LRV due to the limited number of specimens analyzed. Further studies with inclusion of more clinical samples are required to elucidate the potential role of LRVs in pathogenesis or treatment failure of Old World leishmaniasis. � 2016, Springer-Verlag Wien

Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach

Pentavalent antimonial compounds have been the first line therapy for leishmaniasis; unfortunately the rate of treatment failure of anthroponotic cutaneous leishmaniasis (ACL) is increasing due to emerging of drug resistance. Elucidation of the molecular mechanisms operating in antimony resistance is critical for development of new strategies for treatment. Here, we used a cDNA-AFLP approach to identify gene(s) which are differentially expressed in resistant and sensitive Leishmania tropica field isolates. We identified five genes, aquaglyceroporin (AQP1) acts in drug uptake, ATP-binding cassette (ABC) transporter (MRPA) involved in sequestration of drug, phosphoglycerate kinase (PGK) implicated in glycolysis metabolism, mitogen activated protein kinase (MAPK) and protein tyrosine phosphatase (PTP) responsible for phosphorylation pathway. The results were confirmed using real time RT-PCR which revealed an upregulation of MRPA, PTP and PGK genes and downregulation of AQP1 and MAPK genes in resistant isolate. To our knowledge, this is the first report of identification of PTP and PGK genes potentially implicated in resistance to antimonials. Our findings support the idea that distinct biomolecules might be involved in antimony resistance in L. tropica field isolates. © 2013 Elsevier Inc

Performance Evaluation of a Class of Gravity-Compensated Gear-Spring Planar Articulated Manipulators

This paper is devoted to evaluating the gravity compensation performance of a special class of planar articulated manipulators that are gravity balanced by using a series of gear-spring modules. First, the studied manipulators with one, two, and three DOFs are revisited. Then, the gravity compensation performance of these manipulators is determined via a peak-to-peak torque reduction criterion. As the manipulators were designed via two different approaches, i.e., the ideal balancing approximation and the realistic optimization, the gravity compensation performance of these two approaches is compared. It shows that the perfect balancing approximation can achieve a satisfied performance as nearly same as that of the optimization approach, while it, on the other hand, enjoys a significant reduction of the computational effort for gravity compensation design