Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.     

Quality Characteristics of Wholemeal Flour and Bread from Durum Wheat (Triticum turgidum L subsp. durum Desf.) after Field Treatment with Plant Water Extracts

The use of selected plant water extracts to control pests and weeds is gaining growing attention in organic and sustainable agriculture, but the effects that such extracts may exert on the quality aspects of durum wheat are still unexplored. In 2014, 5 plant water extracts (Artemisia arborescens, Euphorbia characias, Rhus coriaria, Thymus vulgaris, Lantana camara) were prepared and distributed on durum wheat cv Valbelice to evaluate their potential herbicidal effects. After crop harvesting, the major physicochemical and technological parameters of wholemeal flours obtained from each treatment were measured and compared with those from chemical weeding and untreated controls. A baking test was also performed to evaluate the breadmaking quality. In wholemeal flours obtained after the treatment with plant extracts protein and dry gluten content were higher than in control and chemical weeding. Wholemeal flours obtained after chemical weeding reached the highest Mixograph parameters, and that from durum wheat treated with R. coriaria extract demonstrated a very high α‐amylase activity. We concluded that the treatments with plant water extracts may influence many quality traits of durum wheat. This occurrence must be taken into account in overall decisions concerning the use of plant extracts in pest and weed management practice.     

High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

Intestinal organoids are used to analyze the differentiation of enteroendocrine cells (EECs) and to manipulate their density for treating type 2 diabetes. EEC differentiation is a continuous process tightly regulated in the gut by a complex regulatory network. However, the effect of chronic hyperglycemia, in the modulation of regulatory networks controlling identity and differentiation of EECs, has not been analyzed. This study aimed to investigate the effect of glucotoxicity on EEC differentiation in small intestinal organoid platforms. Mouse intestinal organoids were cultured in the presence/absence of high glucose concentrations (35 mM) for 48 h to mimic glucotoxicity. Chronic hyperglycemia impaired the expression of markers related to the differentiation of EEC progenitors (Ngn3) and L-cells (NeuroD1), and it also reduced the expression of Gcg and GLP-1 positive cell number. In addition, the expression of intestinal stem cell markers was reduced in organoids exposed to high glucose concentrations. Our data indicate that glucotoxicity impairs L-cell differentiation, which could be associated with decreased intestinal stem cell proliferative capacity. This study provides the identification of new targets involved in new molecular signaling mechanisms impaired by glucotoxicity that could be a useful tool for the treatment of type 2 diabetes.     

“Greening Up” Cross-Coupling Chemistry

New methodologies that enable palladium catalyzed cross-coupling reactions to be performed under environmentally benign conditions (in water and/or at room temperature) have been developed. Described approaches involve in situ activation of carbon–halogen or carbon–hydrogen bonds using zinc metal, or cationic palladium, respectively.     

CMOS Non‐tailed differential pair

A continuous‐time complementary metal–oxide–semiconductor differential pair that does not require the traditional tail current source as a way to control the direct current and common‐mode current is presented. Compared with a p‐channel long‐tailed pair, the proposed non‐tailed solution operates under a higher maximum input common‐mode voltage that includes (V_DD + V_SS)/2 even under low supply voltages. Experimental measurements on a prototype fabricated in a 0.35‐µm technology (with metal – oxide – semiconductor thresholds greater than 0.6 V) confirm this behavior for supply voltages as low as 1.2 V, whereas the long‐tailed pair with the same technology offers the same capability only for supplies higher than 1.6 V. Copyright © 2015 John Wiley & Sons, Ltd.     

A simple and effective design strategy to increase power conversion efficiency of linear charge pumps

This paper introduces a simple design strategy to increase the power efficiency of linear charge pumps. The technique exploits a voltage amplitude of the clock signal lower than the supply voltage to reduce the power conversion losses. The nominal output voltage is maintained unaltered by increasing the number of stages.     

Analytical comparison of reversed nested Miller frequency compensation techniques

In this paper, novel and previously proposed reversed nested Miller compensation (RNMC) networks are analyzed and compared, and their design equations are also presented. Hence, this paper is the natural extension of a previous paper by the authors (Int. J. Circ. Theor. Appl. 2008; 36 (1):53–80), where only the nested Miller compensation topologies were treated. In particular, a coherent and comprehensive analytical comparison of the RNMC topologies, including two new networks presented for the first time, is performed by means of the figure of merit that expresses a trade‐off among gain‐bandwidth product, load capacitance and total transconductance, for equal values of phase margin (Int. J. Circ. Theor. Appl. 2008; 36 (1):53–80). The analysis shows that there is no unique optimal solution among the RNMC topologies, as this depends on the load condition as well as on the relative transconductance magnitude of each amplifier stage. From this point of view, the proposed comparison also outlines useful design guidelines for the optimization of large‐signal and small‐signal performance. Simulations confirming the effectiveness of the proposed design methodology and analytical comparison are also included. Copyright © 2009 John Wiley & Sons, Ltd.     

Coupling of free surface and groundwater flows

In this paper we present some preliminary results about the coupling of shallow water equations for free surface flows and Darcy equation for groundwater flows. A suitable set of interface conditions is discussed: the Beavers and Joseph formula for the bottom stress is used. An iterative algorithm to solve the coupled problem is proposed and some numerical results are presented.     

Atmospheric total ozone column evaluation with a smartphone image sensor

A new method for quantifying the total ozone column (TOC) using a smartphone image sensor has been developed and validated. The TOC has been evaluated for relatively cloud free days at high air masses for solar zenith angles between 49.7° and 76.7° at a sub-tropical site. The method is based on the evaluation of the direct solar irradiances at 305 and 312 nm using the red colour pixel values of the solar disc recorded at these wavelengths by a smartphone camera. Narrow bandpass filters of 2 nm full width at half maximum at each of the two wavelengths were used in turn placed over the camera sensor to directly image the solar disc. The calibration of the pixel values of the solar disc to provide the direct solar irradiances at each of these two wavelengths allowed evaluation of the TOC calibrated to a portable sun photometer. The root mean square error (RMSE) for the smartphone-derived ozone values calibrated to corresponding values from a portable sun photometer was 4.3 Dobson Units (DU). The validation measurements for the smartphone-derived ozone values provided an average residual of 3.5% (up to a maximum of 11%) compared to the corresponding portable sun photometer values, with an RMSE of 8.4 DU during days of intermittent inclement weather conditions. The evaluation of the TOC based on a widely available device such as a smartphone has the potential to increase current citizen science initiatives valued by the general public and school-aged learners by enhancing knowledge and awareness of ozone and the resulting influences on the solar ultraviolet environment.