Optimization of media nitrogen and copper concentrations for regeneration of green plants from polyembryogenic cultures of barley (Hordeum vulgare L.). Plant Sci

Abstract In recent years particle bombardment has become the most used method for gene transfer to barley (Hordeum 6ulgare L.). Transformation efficiency depends greatly on the ability of the target material to regenerate into green plants. In this work we improved the regeneration efficiency of polyembryogenic cultures of barley (cv. Kymppi) by optimizing the nitrogen and copper concentrations in the media

Certainly Unsupervisable States

This paper proposes an abstraction method for compositional synthesis. Synthesis is a method to automatically compute a control program or supervisor that restricts the behaviour of a given system to ensure safety and liveness. Compositional synthesis uses repeated abstraction and simplification to combat the state-space explosion problem for large systems. The abstraction method proposed in this paper finds and removes the so-called certainly unsupervisable states. By removing these states at an early stage, the final state space can be reduced substantially. The paper describes an algorithm with cubic time complexity to compute the largest possible set of removable states. A practical example demonstrates the feasibility of the method to solve real-world problems

Skeletal muscle mitochondrial DNA content and aerobic metabolism in patients with antiretroviral therapy-associated lipoatrophy

Objectives To assess whether mitochondrial dysfunction in skeletal muscle characterizes antiretroviral therapy (ART)-associated lipoatrophy (LA). Methods A cross-sectional study comparing HIV-infected, antiretroviral-treated patients with LA (n = 5; LA+) and without LA (n = 5; non-LA) was conducted. Positron emission tomography was used to measure blood flow, oxygen extraction and oxygen consumption in quadriceps femoris muscle during rest and aerobic exercise. Mitochondrial DNA (mtDNA) was quantified by PCR. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. All data are given as means ± SEM. Results Compared with the non-LA group, the LA+ group had significantly less limb fat and more intra-abdominal fat, but similar leg muscle mass. The LA+ group versus the non-LA group had reduced mtDNA content per nucleus in adipose tissue (173 ± 38 versus 328 ± 62; P = 0.067), but not in skeletal muscle (2606 ± 375 versus 2842 ± 309; P = 0.64). Perfusion in resting muscle (34 ± 7 versus 28 ± 6 mL/kg/min in the LA+ group versus the non-LA group; P = 0.5), and the mean absolute (277 ± 30 versus 274 ± 43 mL/kg/min, respectively; P = 0.95) and relative (10.6 ± 2.5- versus 11.9 ± 1.5-fold change, respectively; P = 0.67) increases in perfusion during exercise were similar between the groups. Oxygen consumption at rest (2.2 ± 0.7 versus 2.1 ± 0.3 mL/kg/min in the LA+ group versus the non-LA group; P = 0.9), and the mean absolute (14.6 ± 1.7 versus 24.3 ± 8.8 mL/kg/min, respectively; P = 0.3) and relative (10.3 ± 2.8- versus 11.7 ± 2.4-fold change, respectively; P = 0.73) exercise-induced increases in oxygen consumption were similar between the groups. The oxygen extraction fraction was comparable between the groups, both at rest and during exercise. Plasma lactate concentrations remained unchanged in both groups during exercise. Conclusions HIV-infected patients with ART-associated LA have similar mtDNA content in skeletal muscle and comparable skeletal muscle aerobic exercise metabolism to antiretroviral-treated non-lipoatrophic patient

In vivo printing of growth factor-eluting adhesive scaffolds improves wound healing

Acute and chronic wounds affect millions of people around the world, imposing a growing financial burden on patients and hospitals. Despite the application of current wound management strategies, the physiological healing process is disrupted in many cases, resulting in impaired wound healing. Therefore, more efficient and easy-to-use treatment modalities are needed. In this study, we demonstrate the benefit of in vivo printed, growth factor-eluting adhesive scaffolds for the treatment of full-thickness wounds in a porcine model. A custom-made handheld printer is implemented to finely print gelatin-methacryloyl (GelMA) hydrogel containing vascular endothelial growth factor (VEGF) into the wounds. In vitro and in vivo results show that the in situ GelMA crosslinking induces a strong scaffold adhesion and enables printing on curved surfaces of wet tissues, without the need for any sutures. The scaffold is further shown to offer a sustained release of VEGF, enhancing the migration of endothelial cells in vitro. Histological analyses demonstrate that the administration of the VEGF-eluting GelMA scaffolds that remain adherent to the wound bed significantly improves the quality of healing in porcine wounds. The introduced in vivo printing strategy for wound healing applications is translational and convenient to use in any place, such as an operating room, and does not require expensive bioprinters or imaging modalities

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity

n/

Pancreatic metabolism, blood flow, and β-cell function in obese humans.

Context: Glucolipotoxicity is believed to induce pancreatic &beta;-cell dysfunction in obesity. Previously, it has not been possible to study pancreatic metabolism and blood flow in humans. Objective: The objective of the study was to investigate whether pancreatic metabolism and blood flow are altered in obesity using positron emission tomography (PET). In the preclinical part, the method was validated in animals. Design: This was a cross-sectional study. Setting: The study was conducted in a clinical research center. Participants: Human studies consisted of 52 morbidly obese and 25 healthy age-matched control subjects. Validation experiments were done with rodents and pigs. Interventions: PET and magnetic resonance imaging studies using a glucose analog ([18F]fluoro-2-deoxy-d-glucose), a palmitate analog [14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid], and radiowater ([15O]H2O) were performed. In animals, a comparison between ex vivo and in vivo data was performed. Main Outcome Measures: Pancreatic glucose/fatty acid (FA) uptake, fat accumulation, and blood flow parameters of &beta;-cell function were measured. Results: PET proved to be a feasible method to measure pancreatic metabolism. Compared with healthy participants, obese participants had elevated pancreatic FA uptake (P &lt; .0001), more fat accumulation (P = .0001), lowered glucose uptake both during fasting and euglycemic hyperinsulinemia, and blunted blood flow (P &lt; .01) in the pancreas. Blood flow, FA uptake, and fat accumulation were negatively associated with multiple markers of &beta;-cell function. Conclusions: Obesity leads to changes in pancreatic energy metabolism with a substrate shift from glucose to FAs. In morbidly obese humans, impaired pancreatic blood flow may contribute to &beta;-cell dysfunction and in the pathogenesis of type 2 diabetes. &nbsp;</div

Renal perfusion, oxygenation and metabolism: the role of imaging

Thanks to technical advances in the field of medical imaging, it is now possible to study key features of renal anatomy and physiology, but so far poorly explored due to the inherent difficulties in studying both the metabolism and vasculature of the human kidney. In this narrative review, we provide an overview of recent research findings on renal perfusion, oxygenation, and substrate uptake. Most studies evaluating renal perfusion with positron emission tomography (PET) have been performed in healthy controls, and specific target populations like obese individuals or patients with renovascular disease and chronic kidney disease (CKD) have rarely been assessed. Functional magnetic resonance (fMRI) has also been used to study renal perfusion in CKD patients, and recent studies have addressed the kidney hemodynamic effects of therapeutic agents such as glucagon-like receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) in an attempt to characterise the mechanisms leading to their nephroprotective effects. The few available studies on renal substrate uptake are discussed. In the near future, these imaging modalities will hopefully become widely available with researchers more acquainted with them, gaining insights into the complex renal pathophysiology in acute and chronic diseases

Novel effects of the gastrointestinal hormone secretin on cardiac metabolism and renal function

The cardiac benefits of gastrointestinal hormones have been of interest in recent years. The aim of this study was to explore the myocardial and renal effects of the gastrointestinal hormone secretin in the GUTBAT trial (NCT03290846). A placebo-controlled crossover study was conducted on 15 healthy males in fasting conditions, where subjects were blinded to the intervention. Myocardial glucose uptake was measured with [F-18]2-fluoro-2-deoxy-o-glucose ([F-18]FDG) positron emission tomography. Kidney function was measured with [F-18]FDG renal clearance and estimated glomerular filtration rate (eGFR). Secretin increased myocardial glucose uptake compared with placebo (secretin vs. placebo, means +/- SD, 15.5 +/- 7.4 vs. 9.7 +/- 4.9 gmol/100 g/min, 95% confidence interval (CI) [2.2, 9.4], P = 0.004). Secretin also increased [F-18]FDG renal clearance (44.5 +/- 5.4 vs. 39.5 8.5 mL/min, 95%CI [1.9, 8.1], P = 0.004), and eGFR was significantly increased from baseline after secretin, compared with placebo (17.8 +/- 9.8 vs. 6.0 +/- 5.2 Delta mL/min/1.73 m(2),( ) 95%CI [6.0, 17.6], P = 0.001). Our results implicate that secretin increases heart work and renal filtration, making it an interesting drug candidate for future studies in heart and kidney failure. NEW & NOTEWORTHY Secretin increases myocardial glucose uptake compared with placebo, supporting a previously proposed inotropic effect. Secretin also increased renal filtration rate.Peer reviewe

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

PurposeBrown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging.MethodsHealthy, lean men (n = 10) participated in PET/CT imaging with two radioligands. Perfusion of BAT, white adipose tissue (WAT) and muscle was quantified with [15O]H2O at baseline, during cold exposure and during intravenous administration of adenosine. A2AR density of the tissues was quantified with [11C]TMSX at baseline and during cold exposure.ResultsAdenosine increased the perfusion of BAT even more than cold exposure (baseline 8.3 ± 4.5, cold 19.6 ± 9.3, adenosine 28.6 ± 7.9 ml/100 g/min, p 11C]TMSX in BAT was significantly lower during cold exposure compared to baseline. In cold, low [11C]TMSX binding coincided with high concentrations of noradrenaline.ConclusionsAdenosine administration caused a maximal perfusion effect in human supraclavicular BAT, indicating increased oxidative metabolism. Cold exposure increased noradrenaline concentrations and decreased the density of A2AR available for radioligand binding in BAT, suggesting augmented release of endogenous adenosine. Our results show that adenosine and A2AR are relevant for activation of human BAT, and A2AR provides a future target for enhancing BAT metabolism.</div