Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK

Hypoxia-Targeting Carbonic Anhydrase IX Inhibitors by a New Series of Nitroimidazole-Sulfonamides/Sulfamides/Sulfamates

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ARMC4 Mutations Cause Primary Ciliary Dyskinesia with Randomization of Left/Right Body Asymmetry

The motive forces for ciliary movement are generated by large multiprotein complexes referred to as outer dynein arms (ODAs), which are preassembled in the cytoplasm prior to transport to the ciliary axonemal compartment. In humans, defects in structural components, docking complexes, or cytoplasmic assembly factors can cause primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease and defects in laterality. By using combined high resolution copy-number variant and mutation analysis, we identified ARMC4 mutations in twelve PCD individuals whose cells showed reduced numbers of ODAs and severely impaired ciliary beating. Transient suppression in zebrafish and analysis of an ENU mouse mutant confirmed in both model organisms that ARMC4 is critical for left-right patterning. We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs

DYX1C1 is required for axonemal dynein assembly and ciliary motility

DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2–4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start-codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary motility defects. In humans, we identified recessive loss-of-function DYX1C1 mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4)

The use of emulsion, water induction and EGR for controlling diesel engine emissions.

This paper was initially presented at an SAE Fuel & Lubricant Conference. It was selected for inclusion in the Transactions. SAE Transactions represent only the best papers from many thousands published during the year. The technique was applied to biodiesel resulting in a paper presented at the clean air conference, Portugal, July 07 and resulted in invitation to produce a follow on journal paper

Modelling and experimental studies on a mixed-mode natural convection solar crop dryer.

An output from collaboration with Kwame Nkrumah University in Ghana. The mathematical model developed at DMU was used to build a full-scale dryer in Ghana, which in turn helped to further validate the model. This research is relevant to developing countries where use of conventional energy in food drying is too expensive. The Ghanian government is sponsoring follow on research at DMU (Dr F. Forson, Dep. of Mech. Eng., Kwame Nkrumah University of Science and Technology, Kumasi, Ghana)

Experimental and simulation studies on a single pass, double duct solar air-heater.

A mathematical model of a single pass, double duct solar air heater (SPDDSAH) is described. The model provides a design tool capable of predicting: incident solar radiation, heat transfer coefficients, mean air flow rates, mean air temperature and relative humidity at the exit. Results from the simulation are presented and compared with experimental ones obtained on a full scale air heater and a small scale laboratory one. Reasonable agreement between the predicted and measured values is demonstrated. Predicted results from a parametric study are also presented. It is shown that significant improvement in the SPDDSAH performance can be obtained with an appropriate choice of the collector parameters and the top to bottom channel depth ratio of the two ducts. The air mass flow rate is shown to be the dominant factor in determining the overall efficiency of the heater