Real Time Spectroscopic Ellipsometry Analysis of First Stage CuIn1-xGaxSe2 Growth: Indium-Gallium Selenide Co-Evaporation

Real time spectroscopic ellipsometry (RTSE) has been applied for in-situ monitoring of the first stage of copper indium-gallium diselenide (CIGS) thin film deposition by the three-stage co-evaporation process used for fabrication of high efficiency thin film photovoltaic (PV) devices. The first stage entails the growth of indium-gallium selenide (In1-xGax)₂Se₃ (IGS) on a substrate of Mo-coated soda lime glass maintained at a temperature of 400 °C. This is a critical stage of CIGS deposition because a large fraction of the final film thickness is deposited, and as a result precise compositional control is desired in order to achieve the optimum performance of the resulting CIGS solar cell. RTSE is sensitive to monolayer level film growth processes and can provide accurate measurements of bulk and surface roughness layer thicknesses. These in turn enable accurate measurements of the bulk layer optical response in the form of the complex dielectric function ε = ε₁ - iε₂, spectra. Here, RTSE has been used to obtain the (ε₁, ε₂) spectra at the measurement temperature of 400 °C for IGS thin films of different Ga contents (x) deduced from different ranges of accumulated bulk layer thickness during the deposition process. Applying an analytical expression in common for each of the (ε₁, ε₂) spectra of these IGS films, oscillator parameters have been obtained in the best fits and these parameters in turn have been fitted with polynomials in x. From the resulting database of polynomial coefficients, the (ε₁, ε₂) spectra can be generated for any composition of IGS from the single parameter, x. The results have served as an RTSE fingerprint for IGS composition and have provided further structural information beyond simply thicknesses, for example information related to film density and grain size. The deduced IGS structural evolution and the (ε₁, ε₂) spectra have been interpreted as well in relation to observations from scanning electron microscopy, X-ray diffractometry and energy-dispersive X-ray spectroscopy profiling analyses. Overall the structural, optical and compositional analysis possible by RTSE has assisted in understanding the growth and properties of three stage CIGS absorbers for solar cells and shows future promise for enhancing cell performance through monitoring and control

Circulating indian hedgehog is a marker of the hepatocyte-TAZ pathway in experimental NASH and is elevated in humans with NASH

Background & aims: Non-alcoholic steatohepatitis (NASH)-induced liver fibrosis is emerging as the most common cause of liver disease. For evaluation of therapies, there is a pressing need to identify non-invasive, mechanism-based biomarkers. A pro-fibrotic process relevant to human NASH involves a pathway in which a transcriptional regulator called TAZ (WWTR1) in hepatocytes induces the secretion of pro-fibrotic Indian hedgehog (IHH). We therefore reasoned that circulating IHH may be a useful mechanism-based marker to assess changes in NASH fibrosis. Methods: Circulating IHH was assessed in wild-type and hepatocyte-TAZ-silenced NASH mice and in three separate cohorts of patients with mild-moderate NASH. Results: Circulating IHH was elevated in mice with diet-induced NASH compared with chow-fed mice or with NASH mice in which hepatocyte TAZ was silenced, which is an effective means to decrease NASH fibrosis. In patients with fatty liver disease with or without NASH, NASH fibrosis was associated with increased concentrations of circulating IHH. Conclusions: The results of these analyses support further investigation to determine whether circulating IHH may be useful as a mechanism-based indicator of target engagement in anticipated future clinical trials testing NASH fibrosis therapies that block the IHH pathway. Impact and implications: Non-alcoholic steatohepatitis (NASH)-induced liver fibrosis is a common cause of liver disease. Circulating biomarkers that reflect liver fibrosis in NASH would be very useful to evaluate therapies. One mechanism of NASH fibrosis with potential as a therapeutic target involves a liver-secreted protein called Indian hedgehog (IHH). We report that circulating levels of IHH in experimental and human NASH associates with NASH and NASH-associated liver fibrosis, providing the premise for further investigation into using circulating IHH to evaluate anticipated future NASH therapies that block the IHH pathway in liver

Exercise and Omega-3 Polyunsaturated Fatty Acid Supplementation for the Treatment of Hepatic Steatosis in Hyperphagic OLETF Rats

Background and Aims. This study examined if exercise and omega-3 fatty acid (n3PUFA) supplementation is an effective treatment for hepatic steatosis in obese, hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods. Male OLETF rats were divided into 4 groups (n=8/group): (1) remained sedentary (SED), (2) access to running wheels; (EX) (3) a diet supplemented with 3% of energy from fish oil (n3PUFA-SED); and (4) n3PUFA supplementation plus EX (n3PUFA+EX). The 8 week treatments began at 13 weeks, when hepatic steatosis is present in OLETF-SED rats. Results. EX alone lowered hepatic triglyceride (TAG) while, in contrast, n3PUFAs failed to lower hepatic TAG and blunted the ability of EX to decrease hepatic TAG levels in n3PUFAs+EX. Insulin sensitivity was improved in EX animals, to a lesser extent in n3PUFA+EX rats, and did not differ between n3PUFA-SED and SED rats. Only the EX group displayed higher complete hepatic fatty acid oxidation (FAO) to CO2 and carnitine palmitoyl transferase-1 activity. EX also lowered hepatic fatty acid synthase protein while both EX and n3PUFA+EX decreased stearoyl CoA desaturase-1 protein. Conclusions. Exercise lowers hepatic steatosis through increased complete hepatic FAO, insulin sensitivity, and reduced expression of de novo fatty acid synthesis proteins while n3PUFAs had no effect

Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65411/1/jphysiol.2009.169060.pd

Patterns in a Low- to Middle Income Population, Zambia

Demographic features (age, gender) of pancreatic cancer using the Cancer Disease Hospital (CDH) data base in a native African population in comparison with the African-American cohort using the Surveillance, Epidemiology End Results (SEER) Program database.In 2007, the Cancer Disease Hospital (CDH) was opened as the national referral center for patients diagnosed with cancer in Zambia. Since inception of the CDH, there has been no systematic analysis of the disease burden and implication on healthcare delivery with regards to pancreatic cancer. There are limited studies describing patterns of pancreatic cancer in a native African population. Data suggest African-Americans have a higher incidence and poorer prognosis of pancreatic cancer than non-African Americans. Objective: The aim is to describe the demographic features (age, gender) of pancreatic cancer using the Cancer Disease Hospital (CDH) data base in a native African population and compare with the African-American cohort using the Surveillance, Epidemiology End Results (SEER) Program database. Methods: This was a retrospective study of patients diagnosed with pancreatic cancer at the CDH in Zambia, Southern Africa between 2007 and 2014. The term “pancreatic cancer” was entered into the CDH database, extracted patient medical records numbers, and manually located the records for review. From each chart we extracted: age, gender, geographic origin, ethnicity, clinical features at presentations, location of tumor, stage at diagnosis and treatment. Data collection tool and master code sheet created a priori were used. Data was analyzed using statistical analysis software (SAS). Descriptive statistics including means, medians as well as frequency distributions and crosstabulations were used. SEER database was used to compare subjects between Zambia and USA. Groups were compared using Chi-square tests and Wilcoxon Signed Rank test. A p-value less than 0.05 was used as the level of significance. Results: Thirty-eight charts were identified in the CDH dataset, of which 27 were included in final analysis and 11 excluded (5 non-pancreatic cancer diagnosis, 6 not manually located). The mean age of diagnosis was 55.7 years in the native African population, compared to 66.7 years for the AfricanAmericans in the SEER database, p < 0.0001. There were 63.0% males (CDH) compared to 48.1% (SEER), p=0.121. Further review of the CDH database revealed that the most common presenting symptom was abdominal pain (52.6%), mode of diagnosis surgical (83%, missing 3), histopathology adenocarcinoma (86%, missing 6), location head of pancreas (83%, missing 9) and stage 4 at diagnosis (100%, missing 3). Conclusion: Pancreatic cancer occurs at a younger age in Zambians when compared to the African American, USA population. There is no statistically significant difference in sex presentation between Zambian and USA black population.Office of Global AIDS/US Department of State

Partial Resistance to Peroxisome Proliferator–Activated Receptor-α Agonists in ZDF Rats Is Associated With Defective Hepatic Mitochondrial Metabolism

OBJECTIVE—Fluxes through mitochondrial pathways are defective in insulin-resistant skeletal muscle, but it is unclear whether similar mitochondrial defects play a role in the liver during insulin resistance and/or diabetes. The purpose of this study is to determine whether abnormal mitochondrial metabolism plays a role in the dysregulation of both hepatic fat and glucose metabolism during diabetes

Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids

Khat (Catha edulis Forsk.) is a flowering perennial shrub cultivated for its neurostimulant properties resulting mainly from the occurrence of (S)-cathinone in young leaves. The biosynthesis of (S)-cathinone and the related phenylpropylamino alkaloids (1S,2S)-cathine and (1R,2S)-norephedrine is not well characterized in plants. We prepared a cDNA library from young khat leaves and sequenced 4,896 random clones, generating an expressed sequence tag (EST) library of 3,293 unigenes. Putative functions were assigned to > 98% of the ESTs, providing a key resource for gene discovery. Candidates potentially involved at various stages of phenylpropylamino alkaloid biosynthesis from L-phenylalanine to (1S,2S)-cathine were identified

The chemical compound 'Heatin' stimulates hypocotyl elongation and interferes with the Arabidopsis NIT1-subfamily of nitrilases

Temperature passively affects biological processes involved in plant growth. Therefore, it is challenging to study the dedicated temperature signalling pathways that orchestrate thermomorphogenesis, a suite of elongation growth-based adaptations that enhance leaf-cooling capacity. We screened a chemical library for compounds that restored hypocotyl elongation in the pif4-2-deficient mutant background at warm temperature conditions in Arabidopsis thaliana to identify modulators of thermomorphogenesis. The small aromatic compound 'Heatin', containing 1-iminomethyl-2-naphthol as a pharmacophore, was selected as an enhancer of elongation growth. We show that ARABIDOPSIS ALDEHYDE OXIDASES redundantly contribute to Heatin-mediated hypocotyl elongation. Following a chemical proteomics approach, the members of the NITRILASE1-subfamily of auxin biosynthesis enzymes were identified among the molecular targets of Heatin. Our data reveal that nitrilases are involved in promotion of hypocotyl elongation in response to high temperature and Heatin-mediated hypocotyl elongation requires the NITRILASE1-subfamily members, NIT1 and NIT2. Heatin inhibits NIT1-subfamily enzymatic activity in vitro and the application of Heatin accordingly results in the accumulation of NIT1-subfamily substrate indole-3-acetonitrile in vivo. However, levels of the NIT1-subfamily product, bioactive auxin (indole-3-acetic acid), were also significantly increased. It is likely that the stimulation of hypocotyl elongation by Heatin might be independent of its observed interaction with NITRILASE1-subfamily members. However, nitrilases may contribute to the Heatin response by stimulating indole-3-acetic acid biosynthesis in an indirect way. Heatin and its functional analogues present novel chemical entities for studying auxin biology

Differing Endoplasmic Reticulum Stress Response to Excess Lipogenesis versus Lipid Oversupply in Relation to Hepatic Steatosis and Insulin Resistance

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been implicated in hepatic steatosis and insulin resistance. The present study investigated their roles in the development of hepatic steatosis and insulin resistance during de novo lipogenesis (DNL) compared to extrahepatic lipid oversupply. Male C57BL/6J mice were fed either a high fructose (HFru) or high fat (HFat) diet to induce DNL or lipid oversupply in/to the liver. Both HFru and HFat feeding increased hepatic triglyceride within 3 days (by 3.5 and 2.4 fold) and the steatosis remained persistent from 1 week onwards (p<0.01 vs Con). Glucose intolerance (iAUC increased by ∼60%) and blunted insulin-stimulated hepatic Akt and GSK3β phosphorylation (∼40–60%) were found in both feeding conditions (p<0.01 vs Con, assessed after 1 week). No impairment of mitochondrial function was found (oxidation capacity, expression of PGC1α, CPT1, respiratory complexes, enzymatic activity of citrate synthase & β-HAD). As expected, DNL was increased (∼60%) in HFru-fed mice and decreased (32%) in HFat-fed mice (all p<0.05). Interestingly, associated with the upregulated lipogenic enzymes (ACC, FAS and SCD1), two (PERK/eIF2α and IRE1/XBP1) of three ER stress pathways were significantly activated in HFru-fed mice. However, no significant ER stress was observed in HFat-fed mice during the development of hepatic steatosis. Our findings indicate that HFru and HFat diets can result in hepatic steatosis and insulin resistance without obvious mitochondrial defects via different lipid metabolic pathways. The fact that ER stress is apparent only with HFru feeding suggests that ER stress is involved in DNL per se rather than resulting from hepatic steatosis or insulin resistance

A Phospholipidomic Analysis of All Defined Human Plasma Lipoproteins

Since plasma lipoproteins contain both protein and phospholipid components, either may be involved in processes such as atherosclerosis. In this study the identification of plasma lipoprotein-associated phospholipids, which is essential for understanding these processes at the molecular level, are performed. LC-ESI/MS, LC-ESI-MS/MS and High Performance Thin Layer Chromatography (HPTLC) analysis of different lipoprotein fractions collected from pooled plasma revealed the presence of phosphatidylethanolamine (PE), phosphatidylinositol (PI), and sphingomyeline (SM) only on lipoproteins and phosphatidylcholine (PC), Lyso-PC on both lipoproteins and plasma lipoprotein free fraction (PLFF). Cardiolipin, phosphatidylglycerol (PG) and Phosphatidylserine (PS) were observed neither in the lipoprotein fractions nor in PLFF. All three approaches led to the same results regarding phospholipids occurrence in plasma lipoproteins and PLFF. A high abundancy of PE and SM was observed in VLDL and LDL fractions respectively. This study provides for the first time the knowledge about the phospholipid composition of all defined plasma lipoproteins