In vivo assessment of hepatic ischemia/reperfusion injury in rat using diffusion tensor imaging

Session 12: Advances in Hepatobiliary Imaging - Oral presentationHepatic ischemia/reperfusion injury (IRI) occurs during liver transplantation, tumor resection, hemorrhagic shock and veno-occlusive disease, and is a major cause of acute liver failure. IRI in liver is also responsible for early organ failure and increased incidence of both acute and chronic rejection after liver transplantation. This study aims to examine the changes of diffusion measurements by diffusion tensor imaging (DTI). The experimental results demonstrated that DTI is useful in identifying hepatic IRI by characterizing the transient changes in mean diffusivity and fractional anisotropy.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 11

The effect of an NgR1 antagonist on the neuroprotection of cortical axons after cortical infarction in rats

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Complex picture for likelihood of ENSO-driven flood hazard

El Niño and La Niña events, the extremes of ENSO climate variability, influence river flow and flooding at the global scale. Estimates of the historical probability of extreme (high or low) precipitation are used to provide vital information on the likelihood of adverse impacts during extreme ENSO events. However, the nonlinearity between precipitation and flood magnitude motivates the need for estimation of historical probabilities using analysis of hydrological datasets. Here, this analysis is undertaken using the ERA-20CM-R river flow reconstruction for the 20th Century. Our results show that the likelihood of increased or decreased flood hazard during ENSO events is much more complex than is often perceived and reported; probabilities vary greatly across the globe, with large uncertainties inherent in the data and clear differences when comparing the hydrological analysis to precipitation

Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites

© 2017 The Author(s). Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites

Temperature-sensitive sarcomeric protein post-translational modifications revealed by top-down proteomics

Despite advancements in symptom management for heart failure (HF), this devastating clinical syndrome remains the leading cause of death in the developed world. Studies using animal models have greatly advanced our understanding of the molecular mechanisms underlying HF; however, differences in cardiac physiology and the manifestation of HF between animals, particularly rodents, and humans necessitates the direct interrogation of human heart tissue samples. Nevertheless, an ever-present concern when examining human heart tissue samples is the potential for artefactual changes related to temperature changes during tissue shipment or sample processing. Herein, we examined the effects of temperature on the post-translational modifications (PTMs) of sarcomeric proteins, the proteins responsible for muscle contraction, under conditions mimicking those that might occur during tissue shipment or sample processing. Using a powerful top-down proteomics method, we found that sarcomeric protein PTMs were differentially affected by temperature. Specifically, cardiac troponin I and enigma homolog isoform 2 showed robust increases in phosphorylation when tissue was incubated at either 4 °C or 22 °C. The observed increase is likely due to increased cyclic AMP levels and activation of protein kinase A in the tissue. On the contrary, cardiac troponin T and myosin regulatory light chain phosphorylation decreased when tissue was incubated at 4 °C or 22 °C. Furthermore, significant protein degradation was also observed after incubation at 4 °C or 22 °C. Overall, these results indicate that temperature exerts various effects on sarcomeric protein PTMs and careful tissue handling is critical for studies involving human heart samples. Moreover, these findings highlight the power of top-down proteomics for examining the integrity of cardiac tissue samples

Thermodynamics of a class of non-asymptotically flat black holes in Einstein-Maxwell-Dilaton theory

We analyse in detail the thermodynamics in the canonical and grand canonical ensembles of a class of non-asymptotically flat black holes of the Einstein-(anti) Maxwell-(anti) Dilaton theory in 4D with spherical symmetry. We present the first law of thermodynamics, the thermodynamic analysis of the system through the geometrothermodynamics methods, Weinhold, Ruppeiner, Liu-Lu-Luo-Shao and the most common, that made by the specific heat. The geometric methods show a curvature scalar identically zero, which is incompatible with the results of the analysis made by the non null specific heat, which shows that the system is thermodynamically interacting, does not possess extreme case nor phase transition. We also analyse the local and global stability of the thermodynamic system, and obtain a local and global stability for the normal case for 0<\gamma<1 and for other values of \gamma, an unstable system. The solution where \gamma=0 separates the class of locally and globally stable solutions from the unstable ones.Comment: 18 pages, version accepted for publication in General Relativity and Gravitatio

Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. Conclusion: This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.published_or_final_versio