Ion transport modeling for retinal rod photoreceptor cells

"July 2010.""A Thesis presented to the Faculty of the Graduate School at the University of Missouri In Partial Fulfillment of the Requirements for the Degree Master of Science."Thesis supervisor: Dr. Jinglu Tan.In this study, a mathematical model is developed to describe the ion transport activities associated with the response of rod photoreceptor to light stimulus. In the model, the cell body is modeled as two capacitors connected via the connecting cilium. Roles of different ion channels during a photoreceptor light response are analyzed, and the relations between changes in ion concentration and response currents are assessed. Methods are developed for computing the membrane potential from ion concentrations and relating the material and electrical resistances. The steady state under different conditions can be uniquely defined with only three measured values. The model can effectively describe the rod photoreceptor response to different light stimuli. Model simulation of the a-wave for progressive narrowing of the connecting cilium corresponds well with published literature on hereditary retinal degeneration of Abyssinian cats. Reductions in amplitude and changes in the a-wave waveform are observed in different stages of the disease. Changes in the receptor response amplitude may not be measurable till the conductance of the connecting cilium is reduced to a comparable magnitude of the ion channels. The model can provide quantitative information of ionic activities, changes in ion concentrations and membrane voltage in the outer segment and the inner compartment. The ionic environment is found to be different between the outer segment and the inner compartment. During receptor response, changes in the outer segment appear to be stronger and quicker than those in the inner compartment. Reductions in the connecting cilium transport can reset the dark resting state.Includes bibliographical references (pages 87-91)

High Level of CXCR4 in Triple-Negative Breast Cancer Specimens Associated with a Poor Clinical Outcome

Despite high sensitivity to chemotherapy, the prognosis for triple-negative breast cancer (TNBC) remains poor because of its high rate of metastasis and low sensitivity to endocrine therapy. CXCR4 expression has been reported in many subtypes of human breast cancers, but it remains unknown whether CXCR4 is expressed in TNBC and whether CXCR4 expression in TNBC could be a prognostic indicator. TNBCs tissues were formalin fixed, paraffin embedded and hematoxylin-eosin (H&E) stained. Immunohistochemical staining was utilized to determine the CXCR4 expression in those specimens. Statistical analyses were performed using SPSS16.0 software to reveal the correlation of CXCR4 expression in TNBC specimens and cancer recurrence and cancer-related death. Our results showed that there was a strong association between CXCR4 overexpression and both menopause and the histological cancer grade of TNBC patients (p values were separately 0.004 and 0.001). The 5-y disease-free survival (DFS) and the 5-y overall survival (OS) were 57.69% and 58.33% for the low-CXCR4 group versus 42.11% and 44.74% for the high-CXCR4 group, respectively (p＝0.031 and 0.048). CXCR4 overexpression plays an important role in triple-negative breast cancers, and may be a predictor of poor prognosis

Morinda Officinalis

Varicoceles (VCs) are the predominant cause of male infertility and are a risk factor for chronic venous disease. Morinda officinalis (M. officinalis) is a traditional Chinese medicine used to tonify the kidney and strengthen yang. In this study, we evaluated the effects of water-soluble polysaccharides extracted from M. officinalis (MOPs) on gonadotropin-release hormone (GnRH) secretion in a classic experimental left VC (ELV) rat model. Intragastric administration of MOPs at a dose ranging from 50 mg kg−1 to 100 mg kg−1 facilitated improvements in sperm parameters and seminiferous epithelial structures, modulated serum hormone profiles, and stimulated GnRH synthesis and release in the hypothalamus. MOPs also promoted spinogenesis and functional spine maturation in the arcuate nuclei (Arc), wherein they acted mainly on Kiss1 and GnRH neurons. Moreover, MOP-mediated Kisspeptin-GPR54 pathway upregulation and MAPK phosphorylation activation may have been responsible for increases in GnRH synthesis and release. Collectively, the findings of this study indicate that MOPs were effective in stimulating GnRH secretion, possibly by upregulating the Kiss1/GPR54 pathway and enhancing synaptic plasticity, and that MOPs can serve as a therapy for early VCs

Biomechanics-mediated endocytosis in atherosclerosis

Biomechanical forces, including vascular shear stress, cyclic stretching, and extracellular matrix stiffness, which influence mechanosensitive channels in the plasma membrane, determine cell function in atherosclerosis. Being highly associated with the formation of atherosclerotic plaques, endocytosis is the key point in molecule and macromolecule trafficking, which plays an important role in lipid transportation. The process of endocytosis relies on the mobility and tension of the plasma membrane, which is sensitive to biomechanical forces. Several studies have advanced the signal transduction between endocytosis and biomechanics to elaborate the developmental role of atherosclerosis. Meanwhile, increased plaque growth also results in changes in the structure, composition and morphology of the coronary artery that contribute to the alteration of arterial biomechanics. These cross-links of biomechanics and endocytosis in atherosclerotic plaques play an important role in cell function, such as cell phenotype switching, foam cell formation, and lipoprotein transportation. We propose that biomechanical force activates the endocytosis of vascular cells and plays an important role in the development of atherosclerosis

Spatiotemporal Distribution of Eutrophication in Lake Tai as Affected by Wind

One common hypothesis is that wind can affect concentrations of nutrients (i.e., nitrogen and phosphorus) and chlorophyll-a (Chl-a) in shallow lakes. However, the tests of this hypothesis have yet to be conclusive in existing literature. The objective of this study was to use long-term data to examine how wind direction and wind speed affect the spatiotemporal variations of total nitrogen (TN), total phosphorus (TP) and Chl-a in Lake Tai, a typical shallow lake located in east China. The results indicated that the concentrations of nutrients and Chl-a tended to decrease from the northwest to the southeast of Lake Tai, with the highest concentrations in the two leeward bays (namely Meiliang Bay and Zhushan Bay) in the northwestern part of the lake. In addition to possible artificial reasons (e.g., wastewater discharge), the prevalent southeastward winds in warm seasons (i.e., spring and summer) and northwestward winds in cool seasons (i.e., fall and winter) might be the major natural factor for such a northwest-southeast decreasing spatial pattern. For the lake as a whole, the concentrations of TN, TP and Chl-a were highest for a wind speed between 2.1 and 3.2 m·s-1, which can be attributed to the idea that the wind-induced drifting and mixing effects might be dominant in the bays while the wind-induced drifting and resuspension effects could be more important in the other parts of the lake. Given that the water depth of the bays was relatively larger than that of the other parts, the drifting and mixing effects were likely dominant in the bays, as indicated by the negative relationships between the ratios of wind speed to lake depth, which can be a surrogate for the vertical distribution of wind-induced shear stress and the TN, TP and Chl-a concentration. Moreover, the decreasing temporal trend of wind speed in combination with the ongoing anthropogenic activities will likely increase the challenge for dealing with the eutrophication problem of Lake Tai. © 2017 by the authors