Role of OCT4 in cisplatin treatment of testicular embryonal carcinoma

Purpose: To determine the role of embryonal transcription factor OCT4 in cisplatin treatment of testicular embryonal carcinoma.Methods: In vitro assays were employed to assess the effect of cisplatin treatment on testicular embryonal carcinoma cell lines under OCT4 silencing. Following treatment with 500 ng/μL cisplatin, MTT assay was used to examine cell proliferation of 2012-EP and 833K-E cells with or without OCT silencing, while wound healing assay was used to examine cell migration ability. Transwell assay and crystal violet staining were employed to measure cell invasive capacity, whereas the distribution pattern of cell cycle was assessed by flow cytometry. The expression levels of several critical components in tumorigenicity related pathways with or without OCT silencing were determined by Western-blot analysis.Results: Cisplatin enhanced OCT4-silenced cell viability at all concentration (p < 0.01) when compared to control cells. Upon treatment with 500 ng/μL cisplatin, OCT4-silenced cells showed 2- to 3-fold enhancement in cell proliferation (p < 0.001), 2-fold increase in cell migration capacity (p < 0.001), and about 1.5-fold enhancement in invasive capacity (p < 0.001) when compared to control cells. In addition, OCT4 silencing upregulated the expression level of the proteins involved in cell proliferation, cell mobility, cancer metastasis and cell cycle control.Conclusion: The results suggest that OCT4 may serve as a therapeutic target for testicular embryonal carcinoma treatment in combination with cisplatin by modulating OCT4 expression level. This physiological evidence indicates that OCT4 downregulation contributes to cisplatin resistance in chemotherapy and subsequent disease relapse.Keywords: OCT4, Cisplatin resistance, Testicular embryonal carcinoma, Chemotherap

Dragon, 1942

https://red.mnstate.edu/yearbooks/1026/thumbnail.jp

Orientation measurement based on magnetic inductance by the extended distributed multi-pole model

This paper presents a novel method to calculate magnetic inductance with a fast-computing magnetic field model referred to as the extended distributed multi-pole (eDMP) model. The concept of mutual inductance has been widely applied for position/orientation tracking systems and applications, yet it is still challenging due to the high demands in robust modeling and efficient computation in real-time applications. Recently, numerical methods have been utilized in design and analysis of magnetic fields, but this often requires heavy computation and its accuracy relies on geometric modeling and meshing that limit its usage. On the other hand, an analytical method provides simple and fast-computing solutions but is also flawed due to its difficulties in handling realistic and complex geometries such as complicated designs and boundary conditions, etc. In this paper, the extended distributed multi-pole model (eDMP) is developed to characterize a time-varying magnetic field based on an existing DMP model analyzing static magnetic fields. The method has been further exploited to compute the mutual inductance between coils at arbitrary locations and orientations. Simulation and experimental results of various configurations of the coils are presented. Comparison with the previously published data shows not only good performance in accuracy, but also effectiveness in computation.open0

Inland alkaline brackish water aquaculture of juvenile razor clam: survival, growth, physiology and immune responses

In this study, we investigated rearing and breeding razor clam (Sinonovacula constricta) in inland alkaline brackish water. During 45 days of the experiment in candidate target inland area brackish water (TBW), survival, growth, enzyme activity and immune responses were analysed. The results showed that shell length and weight were significantly inhibited in the TBW group (p <0.001). Although the cumulative mortality was 81.479 ± 7.028 (p < 0.001) at 15 days, it increased slowly to 92.915 ± 2.271 (p < 0.001) at 45 days. The enzyme activities of Na+/K+-ATPase, aspartate aminotransferase and superoxide dismutase peaked at 15 days, and juvenile S. constricta (JSC) may engaged in partial anaerobic metabolism or damage to gill tissue, which may explain the high mortality rate at this time. Additionally, the phagocytic ability of haemocytes was inhibited (p < 0.001), but the metabolic activity was enhanced (p < 0.001). This implies that 15 days was the peak of TBW stress, and stress gradually decreased by days 30 and 45. TBW affected metabolism, osmotic regulation, and immune responses. There was an independent ionic interaction perhaps effect on JSC, primarily through Na+/K+ rate. Approximately 7 % of animals adapted successfully to TBW after 45 days. In summary, S. constricta has a great potential in further anti-TBW conditions selective breeding research.info:eu-repo/semantics/publishedVersio

SwarmDock and the Use of Normal Modes in Protein-Protein Docking

Here is presented an investigation of the use of normal modes in protein-protein docking, both in theory and in practice. Upper limits of the ability of normal modes to capture the unbound to bound conformational change are calculated on a large test set, with particular focus on the binding interface, the subset of residues from which the binding energy is calculated. Further, the SwarmDock algorithm is presented, to demonstrate that the modelling of conformational change as a linear combination of normal modes is an effective method of modelling flexibility in protein-protein docking

CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease

Protein phosphatase 2A (PP2A) inhibition causes hyperphosphorylation of tau and APP in Alzheimer's disease (AD). However, the mechanisms underlying the downregulation of PP2A activity in AD brain remain unclear. We demonstrate that Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is overexpressed in AD brain. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP beta-cleavage and A beta production. Increase in CIP2A expression also leads to tau mislocalization to dendrites and spines and synaptic degeneration. In mice, injection of AAV-CIP2A to hippocampus induced AD-like cognitive deficits and impairments in long-term potentiation (LTP) and exacerbated AD pathologies in neurons. Indicative of disease exacerbating the feedback loop, we found that increased CIP2A expression and PP2A inhibition in AD brains result from increased A beta production. In summary, we show that CIP2A overexpression causes PP2A inhibition and AD-related cellular pathology and cognitive deficits, pointing to CIP2A as a potential target for AD therapy

Effects of cadmium and phenanthrene mixtures on aquatic fungi and microbially mediated leaf litter decomposition

This version does not correspond to the published one. To access the final version go to: http://www.springerlink.com/content/t8t302617003m078/Urbanization and industrial activities have contributed to widespread contamination by metals and polycyclic aromatic hydrocarbons, but the combined effects of these toxics on aquatic biota and processes are poorly understood. We examined the effects of cadmium (Cd) and phenanthrene on the activity and diversity of fungi associated with decomposing leaf litter in streams. Leaves of Alnus glutinosa were immersed for 10 days in an unpolluted low-order stream in northwest Portugal to allow microbial colonization. Leaves were then exposed in microcosms for 14 days to Cd (0.06–4.5 mg L−1) and phenanthrene (0.2 mg L−1) either alone or in mixture. A total of 19 aquatic hyphomycete species were found sporulating on leaves during the whole study. The dominant species was Articulospora tetracladia, followed by Alatospora pulchella, Clavatospora longibrachiata, and Tetrachaetum elegans. Exposure to Cd and phenanthrene decreased the contribution of A. tetracladia to the total conidial production, whereas it increased that of A. pulchella. Fungal diversity, assessed as denaturing gradient gel electrophoresis fingerprinting or conidial morphology, was decreased by the exposure to Cd and/or phenanthrene. Moreover, increased Cd concentrations decreased leaf decomposition and fungal reproduction but did not inhibit fungal biomass production. Exposure to phenanthrene potentiated the negative effects of Cd on fungal diversity and activity, suggesting that the co-occurrence of these stressors may pose additional risk to aquatic biodiversity and stream ecosystem functioning.The Portuguese Foundation for the Science and Technology supported this work (POCI/MAR/56964/2004) and S. Duarte (SFRH/BPD/47574/2008