Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Identification of reference genes for quantitative RT-PCR in ascending aortic aneurysms.

Hypertension and congenital aortic valve malformations are frequent causes of ascending aortic aneurysms. The molecular mechanisms of aneurysm formation under these circumstances are not well understood. Reference genes for gene activity studies in aortic tissue that are not influenced by aortic valve morphology and its hemodynamic consequences, aortic dilatation, hypertension, or antihypertensive medication are not available so far. This study determines genes in ascending aortic tissue that are independent of these parameters. Tissue specimens from dilated and undilated ascending aortas were obtained from 60 patients (age ≤70 years) with different morphologies of the aortic valve (tricuspid undilated n = 24, dilated n = 11; bicuspid undilated n = 6, dilated n = 15; unicuspid dilated n = 4). Of the studied individuals, 36 had hypertension, and 31 received ACE inhibitors or AT1 receptor antagonists. The specimens were obtained intraoperatively from the wall of the ascending aorta. We analyzed the expression levels of 32 candidate reference genes by quantitative RT-PCR (RT-qPCR). Differential expression levels were assessed by parametric statistics. The expression analysis of these 32 genes by RT-qPCR showed that EIF2B1, ELF1, and PPIA remained constant in their expression levels in the different specimen groups, thus being insensitive to aortic valve morphology, aortic dilatation, hypertension, and medication with ACE inhibitors or AT1 receptor antagonists. Unlike many other commonly used reference genes, the genes EIF2B1, ELF1, and PPIA are neither confounded by aortic comorbidities nor by antihypertensive medication and therefore are most suitable for gene expression analysis of ascending aortic tissue.

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta.

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.

The intrinsic mechanisms of softwood fiber damage in brown stock fiber line unit operations Lappeenranta 2010

The effects of pulp processing on softwood fiber properties strongly influence the properties of wet and dry paper webs. Pulp strength delivery studies have provided observations that much of the strength potential of long fibered pulp is lost during brown stock fiber line operations where the pulp is merely washed and transferred to the subsequent processing stages. The objective of this work was to study the intrinsic mechanisms which maycause fiber damage in the different unit operations of modern softwood brown stock processing. The work was conducted by studying the effects of industrial machinery on pulp properties with some actions of unit operations simulated in laboratory scale devices under controlled conditions. An optical imaging system was created and used to study the orientation of fibers in the internal flows during pulp fluidization in mixers and the passage of fibers through the screen openings during screening. The qualitative changes in fibers were evaluated with existing and standardized techniques. The results showed that each process stage has its characteristic effects on fiber properties: Pulp washing and mat formation in displacement washers introduced fiber deformations especially if the fibers entering the stage were intact, but it did not decrease the pulp strength properties. However, storage chests and pulp transfer after displacement washers contributed to strength deterioration. Pulp screening proved to be quite gentle, having the potential of slightly evening out fiber deformations from very deformed pulps and vice versa inflicting a marginal increase in the deformation indices if the fibers were previously intact. Pulp mixing in fluidizing industrial mixers did not have detrimental effects on pulp strength and had the potential of slightly evening out the deformations, provided that the intensity of fluidization was high enough to allow fiber orientation with the flow and that the time of mixing was short. The chemical and mechanical actions of oxygen delignification had two distinct effects on pulp properties: chemical treatment clearly reduced pulp strength with and without mechanical treatment, and the mechanical actions of process machinery introduced more conformability to pulp fibers, but did not clearly contribute to a further decrease in pulp strength. The chemical composition of fibers entering the oxygen stage was also found to affect the susceptibility of fibers to damage during oxygen delignification. Fibers with the smallest content of xylan were found to be more prone to irreversibledeformations accompanied with a lower tensile strength of the pulp. Fibers poor in glucomannan exhibited a lower fiber strength while wet after oxygen delignification as compared to the reference pulp. Pulps with the smallest lignin content on the other hand exhibited improved strength properties as compared to the references.

Corporate governance, accountability and mechanisms of accountability: an overview

Purpose – This paper aims to review traditional corporate governance and accountability research, to suggest opportunities for future research in this field. Design/methodology/approach – The first part adopts an analytical frame of reference based on theory, accountability mechanisms, methodology, business sector/context, globalisation and time horizon. The second part of the paper locates the seven papers in the special issue in a framework of analysis showing how each one contributes to the field. The paper presents a frame of reference which may be used as a “roadmap” for researchers to navigate their way through the prior literature and to position their work on the frontiers of corporate governance research. The paper is primarily discursive and conceptual. Findings – The paper encourages broader approaches to corporate governance and accountability research beyond the traditional and primarily quantitative approaches of prior research. Broader theoretical perspectives, methodological approaches, accountability mechanism, sectors/contexts, globalisation, and time horizons are identified. Research limitations/implications – Greater use of qualitative research methods are suggested, which present challenges particularly of access to the “black box” of corporate boardrooms. Originality/value – Drawing on the analytical framework, and the papers in the special issue, the paper identifies opportunities for further research of accountability and corporate governance. Keywords Corporate governance, Management accountability, Research Paper type General review

Mechanisms of the negative shortwave cloud feedback in mid to high latitudes

Increases in cloud optical depth and liquid water path (LWP) are robust features of global warming model simulations in high latitudes, yielding a negative shortwave cloud feedback, but the mechanisms are still uncertain. We assess the importance of microphysical processes for the negative optical depth feedback by perturbing temperature in the microphysics schemes of two aquaplanet models, both of which have separate prognostic equations for liquid water and ice. We find that most of the LWP increase with warming is caused by a suppression of ice microphysical processes in mixed-phase clouds, resulting in reduced conversion efficiencies of liquid water to ice and precipitation. Perturbing the temperature-dependent phase partitioning of convective condensate also yields a small LWP increase. Together, the perturbations in large-scale microphysics and convective condensate partitioning explain more than two-thirds of the LWP response relative to a reference case with increased SSTs, and capture all of the vertical structure of the liquid water response. In support of these findings, we show the existence of a very robust positive relationship between monthly-mean LWP and temperature in CMIP5 models and observations in mixed-phase cloud regions only. In models, the historical LWP sensitivity to temperature is a good predictor of the forced global warming response poleward of about 45°, although models appear to overestimate the LWP response to warming compared to observations. We conclude that in climate models, the suppression of ice-phase microphysical processes that deplete cloud liquid water is a key driver of the LWP increase with warming and of the associated negative shortwave cloud feedback.

On the Deactivation Mechanisms of Adenine-Thymine Base Pair

In this contribution, the multiconfigurational second-order perturbation theory method based on a complete active space reference wave function (CASSCF/CASPT2) is applied to study all possible single and double proton/hydrogen transfers between the nucleobases in the adenine-thymine (AT) base pair, analyzing the role of excited states with different nature [localized (LE) and charge transfer (CT)] and considering concerted as well as step-wise mechanisms. According to the findings, once the lowest excited states, localized in adenine, are populated during UV irradiation of the Watson-Crick base pair, the proton transfer in the N-O bridge does not require high energy in order to populate a CT state. The latter state will immediately relax toward a crossing with the ground state, which will funnel the system to either the canonical structure or the imino-enol tautomer. The base pair is also capable of repairing itself easily since the imino-enol species is unstable to thermal conversion.

Factors affecting the durability of 5.25 inch floppy diskette media and its mechanisms of wear

This project is targeted towards establishing the durability and mechanisms of wear involved in the use of 5.25 inch magnetic floppy diskettes with particular reference to the media manufactured by the Minnesota Mining and Manufacturing Company, 3M Center, St. Paul, Minnesota, USA. In the present work most stress has been laid on the presentation of the conclusions drawn from the results obtained using samples produced specifically for this project. These samples were produced on the pilot plant at 3MTM, St. Paul, USA and are identified by the code 58759-4 with sample numbers SR1 to SR4 each with different lubrication conditions. All of the categories have been produced with four different surface roughnesses by varying the degree of burnishing. It has been found that the mechanisms of wear are related to a fatigue process. Some surprises have been noted in respect of the value of burnishing compared to the observations made elsewhere. Good reasons for these observed differences have been noted, however, and it will be shown that these are merely superficial and not concerned with wear of any real type. The present work reports the effects of the changes in the media's lubrication status and its surface topography as well as presenting evidence for the suggested wear mechanisms.

Mechanisms of drying of particulate slurries

The literature on the evaporation of pure liquid drops and the drying of drops of solutions and slurries has been reviewed with particular reference to spray drying. A 0.1-0.2 mm glass filament-thermocouple was constructed and used to study simultaneously, heat and mass transfer from a single suspended drop placed in a humidity and temperature controlled, 28 mm OD vertical wind tunnel. Heat conduction through the filament was minimised eg at 100¦C it accounted for only 9.3% of the total heat transferred to a drop. Evaporation of single water drops was also studied in a 101 mm OD vertical wind tunnel. The Nusselt number was found to be a function of the Reynolds, Prandtl and Transfer number over an air temperature range of 17¦C to 107¦C. The proposed correlation is: Nu = 2+(-12.96B+0.76)Re¦-5Pr0-33 Experimental drying studies were carried out on single suspended 1 to 2.5 mm diameter drops of aqueous sodium sulphate decahydrate, sodium chloride, potassium sulphate, copper sulphate and sodium acetate solutions and slurries at temperatures of 20¦C to 124¦C. Dried crusts were examined by Scanning Electron Microscopy. The drying history of any material depended upon the nature of the crust formed. Sodium acetate formed a non-rigid skin prior to the formation of a rigid crust. A modified receding evaporation interface model was proposed for the drying of solutions and slurries. This covered both the constant rate period prior to crust formation and the subsequent falling rate period. The model was solved numerically for the variation in core temperature, drop weight and crust thickness. Good agreement was obtained between model predictions and experimental results for materials forming rigid crusts i.e. sodium sulphate decahydrate, sodium chloride, potassium sulphate and copper sulphate. However, the drying histories of drops of 10-20% weight initial concentration sodium acetate were unpredictable since formation of a non-rigid skin deviated from the model assumption of a rigid outer surface. At higher initial concentrations (40% weight) where a rigid crust was formed for sodium acetate, good agreement was obtained between experimental results and model predictions. Single suspended drop studies are concluded to provide a valuable insight into the drying mechanisms of specific solutions and slurries.

Selection And Validation Of Reference Genes For Functional Studies In The Calliphoridae Family.

The genera Cochliomyia and Chrysomya contain both obligate and saprophagous flies, which allows the comparison of different feeding habits between closely related species. Among the different strategies for comparing these habits is the use of qPCR to investigate the expression levels of candidate genes involved in feeding behavior. To ensure an accurate measure of the levels of gene expression, it is necessary to normalize the amount of the target gene with the amount of a reference gene having a stable expression across the compared species. Since there is no universal gene that can be used as a reference in functional studies, candidate genes for qPCR data normalization were selected and validated in three Calliphoridae (Diptera) species, Cochliomyia hominivorax Coquerel, Cochliomyia macellaria Fabricius, and Chrysomya albiceps Wiedemann . The expression stability of six genes ( Actin, Gapdh, Rp49, Rps17, α -tubulin, and GstD1) was evaluated among species within the same life stage and between life stages within each species. The expression levels of Actin, Gapdh, and Rp49 were the most stable among the selected genes. These genes can be used as reliable reference genes for functional studies in Calliphoridae using similar experimental settings.

Mechanisms Of Insulin Resistance In The Amygdala: Influences On Food Intake.

Obesity is increasing worldwide and is triggered, at least in part, by enhanced caloric intake. Food intake is regulated by a complex mechanism involving the hypothalamus and hindbrain circuitries. However, evidences have showing that reward systems are also important in regulating feeding behavior. In this context, amygdala is considered a key extra-hypothalamic area regulating feeding behavior in human beings and rodents. This review focuses on the regulation of food intake by amygdala and the mechanisms of insulin resistance in this brain area. Similar to the hypothalamus the anorexigenic effect of insulin is mediated via PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) pathway in the amygdala. Insulin decreases NPY (neuropeptide Y) and increases oxytocin mRNA levels in the amygdala. High fat diet and saturated fatty acids induce inflammation, ER (endoplasmic reticulum) stress and the activation of serine kinases such as PKCθ (protein kinase C theta), JNK (c-Jun N-terminal kinase) and IKKβ (inhibitor of nuclear factor kappa-B kinase beta) in the amygdala, which have an important role in insulin resistance in this brain region. Overexpressed PKCθ in the CeA (central nucleus of amygdala) of rats increases weight gain, food intake, insulin resistance and hepatic triglycerides content. The inhibition of ER stress ameliorates insulin action/signaling, increases oxytocin and decreases NPY gene expression in the amygdala of high fat feeding rodents. Those data suggest that PKCθ and ER stress are main mechanisms of insulin resistance in the amygdala of obese rats and play an important role regulating feeding behavior.

Mechanisms of pigmentation loss in subterranean fishes

Troglobitic (exclusively subterranean) organisms usually present, among their apomorphies related to the subterranean life (troglomorphisms), the regression of eyes and melanic pigmentation. The degree of regression varies among species, from a slight reduction to the complete loss of eyes and dark pigmentation, without a taxonomic correlation. While mechanisms of eye reduction have been intensively investigated in some troglobites such as the Mexican blind tetra characins, genus Astyanax, and the European salamander, Proteus anguinus, few studies have focused on pigmentation. The Brazilian subterranean ichthyofauna distinguishes not only by the species richness (23 troglobitic fishes so far known) but also by the variation in the degree of reduction of eyes and pigmentation. This study focused on Brazilian fishes completely devoid of melanic pigmentation: the characiform Stygichthys typhlops (Characidae) and the siluriforms Ancistrus formoso (Loricariidae), Rhamdiopsis sp.1 (Heptapteridae; from caves in the Chapada Diamantina, Bahia) and Rhamdiopsis sp. 2 (cave in Campo Formoso, Bahia). In order to investigate if such depigmentation is the result of blockage in some step in the melanogenesis, in vitro tests of administration of L-DOPA were done, using caudal-fin fragments extracted from living fish. Except for Rhamdiopsis sp. 2, all the studied species were DOPA(+), i.e., melanin was synthesized after L-DOPA administration. This indicates these fish do have melanophores but they are unable to convert L-tyrosine to L-DOPA. On the other hand, Rhamdiopsis sp. 2, like the albino specimens of Trichomycterus itacarambiensis previously studied (which correspond to one third of the population), are DOPA(-), either because the block of melanin synthesis occurs downstream in melanogenesis, which is probably the case with T. itacarambiensis (monogenic system in view of the phenotypic discontinuity), or because the so-called albinos do no possess melanophores. The physiological loss in the ability to synthesize melanin, apparently caused by different genetic processes in DOPA(+) and in DOPA(-) fishes, may co-exist in subterranean populations with a decrease in the density of melanophores, as observed in the pigmented two thirds of T. itacarambiensis population, a morphological reduction apparently controlled by polygenic systems producing a continuous phenotypic variation.

Central chemoreceptors and neural mechanisms of cardiorespiratory control

The arterial partial pressure (P CO2) of carbon dioxide is virtually constant because of the close match between the metabolic production of this gas and its excretion via breathing. Blood gas homeostasis does not rely solely on changes in lung ventilation, but also to a considerable extent on circulatory adjustments that regulate the transport of CO2 from its sites of production to the lungs. The neural mechanisms that coordinate circulatory and ventilatory changes to achieve blood gas homeostasis are the subject of this review. Emphasis will be placed on the control of sympathetic outflow by central chemoreceptors. High levels of CO2 exert an excitatory effect on sympathetic outflow that is mediated by specialized chemoreceptors such as the neurons located in the retrotrapezoid region. In addition, high CO2 causes an aversive awareness in conscious animals, activating wake-promoting pathways such as the noradrenergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have projections that contribute to the CO2-induced rise in breathing and sympathetic outflow. However, since the level of activity of the retrotrapezoid nucleus is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive, the main focus of the present manuscript is to review the contribution of central chemoreceptors to the control of autonomic and respiratory mechanisms.

Protector mechanisms of the association between gastroesophageal reflux disease and asthma: experimental study in rats

BACKGROUND: It is well known the association between gastroesophageal reflux disease and asthma. The hyperreactivity of the airways is a characteristic of an asthmatic. Many studies associate the increase of the airways reactivity with gastroesophageal reflux disease. AIM: In this study we have evaluated the effect of the intraluminal exposition to gastric juice of trachea on the reactivity to methacholine from rats submitted to a pulmonary allergic inflammation. METHODS: Group of rats were sensitized and challenged with ovalbumin. After 24 hours the animals were sacrificed, and their tracheae were removed to be cultured with gastric juice. The gastric juice was obtained from a donor rat. Subsequently the segments were placed into plastic plates with RPMI-1640 for incubation, under suitable atmosphere and time. After the period of incubation the segments were put into chambers for the analysis of the contractile response to methacholine. RESULTS: We observed reduction in the contractile response of trachea cultured with gastric juice from allergic rats. This result was confirmed by the pharmacological treatments with compound 48/80 and dissodium cromoglicate (mast cells blockade), L-NAME (nitric oxide inhibitor, NO), capsaicin (neuropeptides depletion) and indomethacin (ciclooxigenase inhibitor). CONCLUSIONS: Our results highlight to the existence of a complex interaction between pulmonary allergy and gastric juice in the airways. The involvement of the non-adrenergic non-cholinergic system, NO, prostanoids and mast cells are directly related to this interaction. We suggest that the reduced contractile response observed in vitro may represent a protector mechanism of the airways. Despite its presence in the human body it can not be observed due to the predominant effects of excitatory the non-adrenergic non-cholinergic system.

Validation of reference genes for gene expression studies in the honey bee, Apis mellifera, by quantitative real-time RT-PCR

For obtaining accurate and reliable gene expression results it is essential that quantitative real-time RT-PCR (qRT-PCR) data are normalized with appropriate reference genes. The current exponential increase in postgenomic studies on the honey bee, Apis mellifera, makes the standardization of qRT-PCR results an important task for ongoing community efforts. For this aim we selected four candidate reference genes (actin, ribosomal protein 49, elongation factor 1-alpha, tbp-association factor) and used three software-based approaches (geNorm, BestKeeper and NormFinder) to evaluate the suitability of these genes as endogenous controls. Their expression was examined during honey bee development, in different tissues, and after juvenile hormone exposure. Furthermore, the importance of choosing an appropriate reference gene was investigated for two developmentally regulated target genes. The results led us to consider all four candidate genes as suitable genes for normalization in A. mellifera. However, each condition evaluated in this study revealed a specific set of genes as the most appropriated ones.