Excretory nitrogen metabolism in the Chinese soft-shelled turtle, pelodiscus sinensis

Ph.DDOCTOR OF PHILOSOPH

Management by results and facets of information: focus on the Pact for Life of Pernambuco State, Brazil

The new public management (NPM) was adopted by many countries in response to the inefficiency of the public sector and economic inertia in the 1970s. The state government of Pernambuco, Brazil, adopted the NPM ideas as a broader scope of public management. This management model has several strategic objectives and their performance indicators to measure the results. The government has been using information as a strategic element and it permeates all functions of management, policy and planning. This study chose the Pacto pela Vida – PPV (Pact for Life), which is the public security policy. As object of analysis, it offers through the information management practices, based on Braman’s information policy, the theoretical and methodological examples needed to provide evidence, as informational practices reveal the use of power. It concludes that information policy demonstrated informational and symbolic powers of the actors who have been processing and gathering information in the PPV

Histone Deacetylase Expressions in Hepatocellular Carcinoma and Functional Effects of Histone Deacetylase Inhibitors on Liver Cancer Cells In Vitro

Hepatocellular carcinoma (HCC) is a leading cause for deaths worldwide. Histone deacetylase (HDAC) inhibition (HDACi) is emerging as a promising therapeutic strategy. However, most pharmacological HDACi unselectively block different HDAC classes and their molecular mechanisms of action are only incompletely understood. The aim of this study was to systematically analyze expressions of different HDAC classes in HCC cells and tissues and to functionally analyze the effect of the HDACi suberanilohydroxamic acid (SAHA) and trichostatin A (TSA) on the tumorigenicity of HCC cells. The gene expression of all HDAC classes was significantly increased in human HCC cell lines (Hep3B, HepG2, PLC, HuH7) compared to primary human hepatocytes (PHH). The analysis of HCC patient data showed the increased expression of several HDACs in HCC tissues compared to non-tumorous liver. However, there was no unified picture of regulation in three different HCC patient datasets and we observed a strong variation in the gene expression of different HDACs in tumorous as well as non-tumorous liver. Still, there was a strong correlation in the expression of HDAC class IIa (HDAC4, 5, 7, 9) as well as HDAC2 and 8 (class I) and HDAC10 (class IIb) and HDAC11 (class IV) in HCC tissues of individual patients. This might indicate a common mechanism of the regulation of these HDACs in HCC. The Cancer Genome Atlas (TCGA) dataset analysis revealed that HDAC4, HDAC7 and HDAC9 as well as HDAC class I members HDAC1 and HDAC2 is significantly correlated with patient survival. Furthermore, we observed that SAHA and TSA reduced the proliferation, clonogenicity and migratory potential of HCC cells. SAHA but not TSA induced features of senescence in HCC cells. Additionally, HDACi enhanced the efficacy of sorafenib in killing sorafenib-susceptible cells. Moreover, HDACi reestablished sorafenib sensitivity in resistant HCC cells. In summary, HDACs are significantly but differently increased in HCC, which may be exploited to develop more targeted therapeutic approaches. HDACi affect different facets of the tumorigenicity of HCC cells and appears to be a promising therapeutic approach alone or in combination with sorafenib

High throughput transcriptome analysis of lipid metabolism in Syrian hamster liver in absence of an annotated genome

Background: Whole transcriptome analyses are an essential tool for understanding disease mechanisms. Approaches based on next-generation sequencing provide fast and affordable data but rely on the availability of annotated genomes. However, there are many areas in biomedical research that require non-standard animal models for which genome information is not available. This includes the Syrian hamster Mesocricetus auratus as an important model for dyslipidaemia because it mirrors many aspects of human disease and pharmacological responses. We show that complementary use of two independent next generation sequencing technologies combined with mapping to multiple genome databases allows unambiguous transcript annotation and quantitative transcript imaging. We refer to this approach as ``triple match sequencing{''} (TMS). Results: Contigs assembled from a normalized Roche 454 hamster liver library comprising 1.2 million long reads were used to identify 10'800 unique transcripts based on homology to RefSeq database entries from human, mouse, and rat. For mRNA quantification we mapped 82 million SAGE tags (SOLiD) from the same RNA source to the annotated hamster liver transcriptome contigs. We compared the liver transcriptome of hamster with equivalent data from human, rat, minipig, and cynomolgus monkeys to highlight differential gene expression with focus on lipid metabolism. We identify a cluster of five genes functionally related to HDL metabolism that is expressed in human, cynomolgus, minipig, and hamster but lacking in rat as a non-responder species for lipid lowering drugs. Conclusions: The TMS approach is suited for fast and inexpensive transcript profiling in cells or tissues of species where a fully annotated genome is not available. The continuously growing number of well annotated reference genomes will further empower reliable transcript identification and thereby raise the utility of the method for any species of interest

Concurrent isolation of hepatic stem cells and hepatocytes from the human liver

Hepatocytes differentiated from induced pluripotent stem cells or stem cells have the potential to be representative in vitro models of the human liver for research as well as early safety assessment programs. However, up until now, there has been no definitive proof that differentiated hepatocytes recapitulate the phenotype and functional characteristics of primary hepatocytes from the same individual. Thus, a method for the concurrent isolation of hepatocytes and hepatic stem cells is presented here to provide the cells necessary for the evaluation of the required benchmarking. The method presented here generated high-quality hepatocytes with a purity of 94 ± 1% and a high percentage viability of 79 ± 2%. Furthermore, the hepatic stem cells isolated were found to be actively proliferating and have a purity of 98 ± 1%. Thus, these isolated cells can be used as a powerful tool for the validation of differentiated hepatocyte in vitro models

Knowledge, attitude and perception on climate change and dietary choices in a predominantly Chinese university students population in Klang Valley

Climate change is a public health threat that is aggravated by the food supply chain. A dietary shift to climate-friendly foods is a feasible strategy to mitigate it. This study aimed to investigate the associations between knowledge, attitude, perception towards climate change, and barriers to climate-friendly foods with dietary choices of university students in Klang Valley. A cross-sectional study was conducted among 303 Malaysian university students (71.9% Chinese) aged 18 to 30 years in Klang Valley, by using Google form to assess knowledge, attitude, perception towards climate change, barriers to climate-friendly food, and climate-friendly dietary choices. The average climate-friendly diet score (CFDS) was 0.36±2.21, with a significantly higher CFDS among females than males (p=0.012). The majority of them were having good knowledge (76.6%), a good attitude (66.3%), and a moderate level of perception (62.0%) towards climate change. About two-thirds of them reported social media as the main (63.0%) and preferred (63.7%) sources to receive information about climate change. Through multiple linear regression, barriers to climate-friendly food choices (β=-0.084; p<0.001) significantly contributed to climate-friendly dietary choices (F=4.215; p<0.001), whereby 14.9% of the variances were climate-friendly dietary choices of university students. Findings could be incorporated into dietary education to tackle barriers to climate-friendly foods among university students

Intestinal fungi contribute to development of alcoholic liver disease

This study was supported in part by NIH grants R01 AA020703, U01 AA021856 and by Award Number I01BX002213 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (to B.S.). K.H. was supported by a DFG (Deutsche Forschungsgemeinschaft) fellowship (HO/ 5690/1-1). S.B. was supported by a grant from the Swiss National Science Foundation (P2SKP3_158649). G.G. received funding from the Yale Liver Center NIH P30 DK34989 and R.B. from NIAAA grant U01 AA021908. A.K. received support from NIH grants RC2 AA019405, R01 AA020216 and R01 AA023417. G.D.B. is supported by funds from the Wellcome Trust. We acknowledge the Human Tissue and Cell Research (HTCR) Foundation for making human tissue available for research and Hepacult GmbH (Munich, Germany) for providing primary human hepatocytes for in vitro analyses. We thank Dr. Chien-Yu Lin Department of Medicine, Fu-Jen Catholic University, Taiwan for statistical analysis.Peer reviewedPublisher PD

On the Relationship Between the Pseudo- and Superconducting Gaps: Effects of Residual Pairing Correlations Below Tc

The existence of a normal state spectral gap in underdoped cuprates raises important questions about the associated superconducting phase. For example, how does this pseudogap evolve into its below Tc counterpart? In this paper we characterize this unusual superconductor by investigating the nature of the ``residual'' pseudogap below Tc and, find that it leads to an important distinction between the superconducting excitation gap and order parameter. Our approach is based on a conserving diagrammatic BCS Bose-Einstein crossover theory which yields the precise BCS result in weak coupling at any T<Tc and reproduces Leggett's results in the T=0 limit. We explore the resulting experimental implications.Comment: REVTeX, 4 pages, 1 EPS figure (included

The pseudogap state in superconductors: Extended Hartree approach to time-dependent Ginzburg-Landau Theory

It is well known that conventional pairing fluctuation theory at the Hartree level leads to a normal state pseudogap in the fermionic spectrum. Our goal is to extend this Hartree approximated scheme to arrive at a generalized mean field theory of pseudogapped superconductors for all temperatures $T$. While an equivalent approach to the pseudogap has been derived elsewhere using a more formal Green's function decoupling scheme, in this paper we re-interpret this mean field theory and BCS theory as well, and demonstrate how they naturally relate to ideal Bose gas condensation. Here we recast the Hartree approximated Ginzburg-Landau self consistent equations in a T-matrix form. This recasting makes it possible to consider arbitrarily strong attractive coupling, where bosonic degrees of freedom appear at $T^*$ considerably above $T_c$. The implications for transport both above and below $T_c$ are discussed. Below $T_c$ we find two types of contributions. Those associated with fermionic excitations have the usual BCS functional form. That they depend on the magnitude of the excitation gap, nevertheless, leads to rather atypical transport properties in the strong coupling limit, where this gap (as distinct from the order parameter) is virtually $T$-independent. In addition, there are bosonic terms arising from non-condensed pairs whose transport properties are shown here to be reasonably well described by an effective time-dependent Ginzburg-Landau theory.Comment: 14 pages, 5 figures, REVTeX4, submitted to PRB; clarification of the diagrammatic technique added, one figure update

Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids.

The misfolding and aggregation of proteins into amyloid fibrils characterizes many neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We report here a method, termed SAVE (single aggregate visualization by enhancement) imaging, for the ultrasensitive detection of individual amyloid fibrils and oligomers using single-molecule fluorescence microscopy. We demonstrate that this method is able to detect the presence of amyloid aggregates of α-synuclein, tau, and amyloid-β. In addition, we show that aggregates can also be identified in human cerebrospinal fluid (CSF). Significantly, we see a twofold increase in the average aggregate concentration in CSF from Parkinson's disease patients compared to age-matched controls. Taken together, we conclude that this method provides an opportunity to characterize the structural nature of amyloid aggregates in a key biofluid, and therefore has the potential to study disease progression in both animal models and humans to enhance our understanding of neurodegenerative disorders.This research study was funded in part by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC) and the NIHR rare disease translational research collaboration and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. We are also grateful to the Augustus Newman and Wolfson Foundations for their support. We thank the Royal Society for the University Research Fellowship of Dr. Steven F. Lee (UF120277).This is the final version of the article. It first appeared from ACS via http://dx.doi.org/10.1021/acschemneuro.5b00324