Association mapping and meta-analysis: two complementary approaches for the detection of reliable Septoria tritici blotch quantitative resistance in bread wheat (Triticum aestivum L.)

Septoria tritici blotch (STB), caused by the ascomycete Mycosphaerella graminicola, is one of the most ubiquitous and important diseases of bread wheat worldwide. The aim of this study was to identify markers linked to loci conferring resistance to STB from seven biparental populations. Linkage analysis, meta-analysis and association mapping were combined to identify robust quantitative trait loci (QTLs) for resistance. Linkage analysis led to the detection of 115 QTLs for resistance to STB and 66 QTLs linked to plant height and/or earliness. Meta-analysis clustered these 115 QTLs into 27 Meta-QTLs (MQTLs) of pathogen resistance, of which 14 were found to be linked to plant height and/or earliness. Both the relationship between dwarfing and susceptibility to STB and the significant negative correlation between earliness and STB symptoms were confirmed. Eleven loci were linked to STB resistance by association mapping using a general linear model and/or a mixed linear model, of which eight co-located with STB MQTLs and two co-located with individual QTLs. Associated markers located in MQTL regions enhanced the relevance of the results and validated the potential of an association mapping approach. With several biparental populations, meta-analysis is the most relevant form of genetic analysis study, but association mapping can be used as a validation method. Regions linked to resistance in both methods should be relevant for use in breeding programs for improving resistance to STB in wheat varieties. The main interest in comparing both approaches is to detect robust loci that will be functional in many genetic backgrounds rather than just in one or a few specific backgrounds.     

Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile

Epithelial mesenchymal transition (EMT) and cancer stem cells (CSC) have been associated with resistance to chemotherapy. Eighty percent of ovarian cancer patients initially respond to platinum-based combination therapy but most return with recurrence and ultimate demise. To better understand such chemoresistance we have assessed the potential role of EMT in tumor cells collected from advanced-stage ovarian cancer patients and the ovarian cancer cell line OVCA 433 in response to cisplatin in vitro. We demonstrate that cisplatin-induced transition from epithelial to mesenchymal morphology in residual cancer cells correlated with reduced E-cadherin, and increased N-cadherin and vimentin expression. The mRNA expression of Snail, Slug, Twist, and MMP-2 were significantly enhanced in response to cisplatin and correlated with increased migration. This coincided with increased cell surface expression of CSC-like markers such as CD44, α2 integrin subunit, CD117, CD133, EpCAM, and the expression of stem cell factors Nanog and Oct-4. EMT and CSC-like changes in response to cisplatin correlated with enhanced activation of extracellular signal-regulated kinase (ERK)1/2. The selective MEK inhibitor U0126 inhibited ERK2 activation and partially suppressed cisplatin-induced EMT and CSC markers. In vivo xenotransplantation of cisplatin-treated OVCA 433 cells in zebrafish embryos demonstrated significantly enhanced migration of cells compared to control untreated cells. U0126 inhibited cisplatin-induced migration of cells in vivo, suggesting that ERK2 signaling is critical to cisplatin-induced EMT and CSC phenotypes, and that targeting ERK2 in the presence of cisplatin may reduce the burden of residual tumor, the ultimate cause of recurrence in ovarian cancer patients.     

Ultrastructure and histochemistry of the subepithelial glands of the nasal septal island in dromedaries with special reference to the possible functions

The nasal septal island (NSI) is a sensory patch of neuroepithelium located within the soft tissue of the nasal septum in dromedaries. The island has unique anatomical features, including the specialized subepithelial glands. The aim of the present study was to describe the microscopic features and ultrastructure of these subepithelial glands and to speculate the possible functions. A total of 10 camel heads were used for the study. Unlike the serous and mucous airway glands, the NSI glands’ ultrastructural features were typical for cells of the (Amine Precursor Uptake and Decarboxylation, APUD) system. These features were included, membrane bound secretory vesicles of varying electron density, smooth endoplasmic reticulum in the form of vesicles; electron dense mitochondria, abundant rough endoplasmic reticulum and free ribosomes. Alcian-PAS identifiable mucus granules were not observed, except for few clusters of cells, located at the luminal surface. The probable functions were discussed on basis of cellular morphology and context. In a conclusion, the NSI subepithelial glands in dromedaries had unique anatomical structures, and as many other APUD cells, they had the machinery required for synthesis of a variable number of biologically active peptides, amines and chemical mediators.     

Hyaluronic acid with or without bone marrow derived-mesenchymal stem cells improves osteoarthritic knee changes in rat model: a preliminary report

Despite being a complex degenerative joint disease, studies on osteoarthritis (OA) suggest that its progression can be reduced by the use of hyaluronic acid (HA) or mesenchymal stem cells (MSC). The present study thus aims to examine the effects of MSC, HA and the combination of HA-MSC in treating OA in rat model. The histological observations using O'Driscoll score indicate that it is the use of HA and MSC independently and not their combination that delays the progression of OA. In conclusion, the preliminary study suggest that the use of either HA or MSCs effectively reduces OA progression better than their combined use.     

Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis

Background

Effective fixation of fracture requires careful selection of a suitable implant to provide stability and durability. Implant with a feature of locking plate (LP) has been used widely for treating distal fractures in femur because of its favourable clinical outcome, but its potential in fixing proximal fractures in the subtrochancteric region has yet to be explored. Therefore, this comparative study was undertaken to demonstrate the merits of the LP implant in treating the subtrochancteric fracture by comparing its performance limits against those obtained with the more traditional implants; angle blade plate (ABP) and dynamic condylar screw plate (DCSP).

Materials and Methods

Nine standard composite femurs were acquired, divided into three groups and fixed with LP (n?=?3), ABP (n?=?3) and DCSP (n?=?3). The fracture was modeled by a 20?mm gap created at the subtrochanteric region to experimentally study the biomechanical response of each implant under both static and dynamic axial loading paradigms. To confirm the experimental findings and to understand the critical interactions at the boundaries, the synthetic femur/implant systems were numerically analyzed by constructing hierarchical finite element models with nonlinear hyperelastic properties. The predictions from the analyses were then compared against the experimental measurements to demonstrate the validity of each numeric model, and to characterize the internal load distribution in the femur and load bearing properties of each implant.

Results

The average measurements indicated that the constructs with ABP, DCPS and LP respectively had overall stiffness values of 70.9, 110.2 and 131.4?N/mm, and exhibited reversible deformations of 12.4, 4.9 and 4.1?mm when the applied dynamic load was 400?N and plastic deformations of 11.3, 2.4 and 1.4?mm when the load was 1000?N. The corresponding peak cyclic loads to failure were 1100, 1167 and 1600?N. The errors between the displacements measured experimentally or predicted by the nonlinear hierarchical hyperelastic model were less than 18?%. In the implanted femur heads, the principal stresses were spatially heterogeneous for ABP and DCSP but more homogenous for LP, meaning LP had lower stress concentrations.

Conclusion

When fixed with the LP implant, the synthetic femur model of the subtrochancteric fracture consistently exceeds in the key biomechanical measures of stability and durability. These capabilities suggest increased resistance to fatigue and failure, which are highly desirable features expected of functional implants and hence make the LP implant potentially a viable alternative to the conventional ABP or DCSP in the treatment of subtrochancteric femur fractures for the betterment of clinical outcome.     

Lack of association between cyclooxygenase 2−765G/C gene polymorphism and breast cancer risk in Ahvaz, west-south Iran

Cyclooxygenases are key enzymes in conversion of arachidonic acid into prostaglandin H2. Cyclooxygenase-2 (COX-2) increases prostaglandins in neoplastic tissue. COX-2 has important roles in cell proliferation cancers, angiogenesis, and alzheimer. COX-2 is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Our main objective was to evaluated the association of polymorphism COX-2 with risk of breast cancer in khouzestan province, and the second objective of the study was to evaluate the association with biochemistry parameters. This study consisting of 150 patients with breast cancer and 120 normal DNA was extracted from the white blood cells. Polymorphism cox2 gene was detected by polymerase chain reaction according to the standard methods. The profile lipids and estrogen were measured in two groups by standard methods. Chi square analysis showed that there was no association between breast cancer risk and COX-2 ?765G>C genotype and alleles. Also, no association were observed between ?765G>C polymorphism and biochemistry parameters. A multiple logistic regression model with cox2 genotypes and LDL and HDL as covariates revealed that there is no significant association between cox2 genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.