Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation.

Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism, in part, through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated. Here we identified otopetrin 1 (Otop1) as a component of a counterinflammatory pathway that is induced in WAT during obesity. Otop1 expression is markedly increased in obese mouse WAT and is stimulated by tumor necrosis factor-α in cultured adipocytes. Otop1 mutant mice respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation. Otop1 attenuates interferon-γ (IFN-γ) signaling in adipocytes through selective downregulation of the transcription factor STAT1. Using a tagged vector, we found that Otop1 physically interacts with endogenous STAT1. Thus, Otop1 defines a unique target of cytokine signaling that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity

Estimation of spleen volume and surface area of the newborns’ cadaveric spleen using stereological methods

Background: The purpose of this study was to compare different techniques for the estimation of spleen volume and surface area using magnetic resonance imaging (MRI) images, ultrasonography (USG) images and cadaveric specimen, and to evaluate errors associated with volume estimation techniques based onfluid displacement.Materials and methods: Five new born cadavers, aged 39.7 ± 1.5 weeks, weighted 2.220 ± 1.056 g, were included in the present study. Three different methods were used to assess the spleen volume. The vertical section technique was applied using cycloid test probes for estimation of spleen surface area in MRI.Results: The mean ± standard deviation of spleen volumes by fluid displacement was 4.82 ± 3.85 cm3. Volumes determined by the Cavalieri’s principle using physical section and point-counting techniques were 4.45 ± 3.47 cm3 and 4.65 ± 3.75 cm3, respectively; volumes measured by USG and cadaver using ellipsoid formula were 4.70 ± 3.02 cm3 and 5.98 ± 4.58 cm3, respectively. No significant differences were found among all methods (p > 0.05). The spleen surface area was calculated as a 32.3 ± 20.6 cm2 by physical sections using cadaver and also it was determined on axial, sagittal and coronal MR planes as 24.9 ± 15.2 cm2, 18.5 ± 5.92 cm2 and 24.3 ± 12.7 cm2, respectively.Conclusions: As a result, MR images allow an easy, reliable and reproducible volume and surface area estimation of normal and abnormal spleen using Cavalieri’sprinciple. We consider that our study may serve as a reference for similar studies to be conducted in future

Hepatic Carcinoma—Associated Fibroblasts Promote an Adaptative Response in Colorectal Cancer Cells That Inhibit Proliferation and Apoptosis: Nonresistant Cells Die by Nonapoptotic Cell Death

AbstractCarcinoma-associated fibroblasts (CAFs) are important contributors of microenvironment in determining the tumor’s fate. This study aimed to compare the influence of liver microenvironment and primary tumor microenvironment on the behavior of colorectal carcinoma. Conditioned medium (CM) from normal colonic fibroblasts (NCFs), CAFs from primary tumor (CAF-PT) or liver metastasis (CAF-LM) were obtained. We performed functional assays to test the influence of each CM on colorectal cell lines. Microarray and gene set enrichment analysis (GSEA) were performed in DLD1 cells cultured in matched CM. In DLD1 cells, CAF-LM CM compared with CAF-PT CM and NCF led to a more aggressive phenotype, induced the features of an epithelial-to-mesenchymal transition more efficiently, and stimulated migration and invasion to a greater extent. Sustained stimulation with CAF-LM CM evoked a transient G2/M cell cycle arrest accompanied by a reduction of apoptosis, inhibition of proliferation, and decreased viability of SW1116, SW620, SW480, DLD1, HT-29, and Caco-2 cells and provoked nonapoptotic cell death in those cells carrying KRAS mutations. Cells resistant to CAF-LM CM completely changed their morphology in an extracellular signal-regulated protein kinase-dependent process and depicted an increased stemness capacity alongside the Wnt pathway stimulation. The transcriptomic profile of DLD1 cells treated with CAF-LM CM was associated with Wnt and mitogen-activated protein kinase pathways activation in GSEA. Therefore, the liver microenvironment induces more efficiently the aggressiveness of colorectal cancer cells than other matched microenvironments do but secondarily evokes cell death. Resistant cells displayed higher stemness capacity

The transition towards a sustainable energy system in Europe: What role can North Africa's solar resources play?

Securing energy supply and speeding up the transition towards a reliable, sustainable, low-carbon energy system are among the major current and future challenges facing Europe. Importing dispatchable solar electricity from North Africa is considered as a potential and attractive option. Nevertheless, as things currently stand, the European Commission focuses mainly on the exploitation of the existing wind power potential in the North Sea, largely ignoring the solar power potential in the Sahara region of North Africa. After discussing the major challenges and issues facing Europe to achieve the assigned ambitious objectives, the paper emphasises the importance of North Africa's solar resources in helping Europe to successfully address the challenge of decarbonising its electricity system, in particular with regards to the security of supply and sustainability. Within these two major challenges, the paper explores the issues of access, barriers and opportunities. The paper highlights why the EU’s energy and climate goals will not be achievable without adequate grid expansion and grid-scale energy storage facilities, as well as other innovative measures to manage demand and ensure a secure energy supply. In this respect, the paper shows how the import of dispatchable electricity from North Africa via specific HVDC links could play a key role in helping the EU achieve its energy targets in a cost effective way without recourse to significant investments in transmission infrastructure and storage facilities. The paper then attempts to identify and analyze the main barriers that continue to inhibit the export of solar electricity from North Africa to Europe. Finally, to make the project more attractive and achievable in the near future, the paper proposes a systematic approach for setting up energy import scenarios. A promising import scenario is presented where energy import via Italy is shown to be a more viable and effective solution than via Spain.Peer reviewe

Hepatic carcinoma-associated fibroblasts promote an adaptative response in colorectal cancer cells that inhibit proliferation and apoptosis: nonresistant cells die by nonapoptotic cell death

Carcinoma-associated fibroblasts (CAFs) are important contributors of microenvironment in determining the tumor's fate. This study aimed to compare the influence of liver microenvironment and primary tumor microenvironment on the behavior of colorectal carcinoma. Conditioned medium (CM) from normal colonic fibroblasts (NCFs), CAFs from primary tumor (CAF-PT) or liver metastasis (CAF-LM) were obtained. We performed functional assays to test the influence of each CM on colorectal cell lines. Microarray and gene set enrichment analysis (GSEA) were performed in DLD1 cells cultured in matched CM. In DLD1 cells, CAF-LM CM compared with CAF-PT CM and NCF led to a more aggressive phenotype, induced the features of an epithelial-to-mesenchymal transition more efficiently, and stimulated migration and invasion to a greater extent. Sustained stimulation with CAF-LM CM evoked a transient G(2)/M cell cycle arrest accompanied by a reduction of apoptosis, inhibition of proliferation, and decreased viability of SW1116, SW620, SW480, DLD1, HT-29, and Caco-2 cells and provoked nonapoptotic cell death in those cells carrying KRAS mutations. Cells resistant to CAF-LM CM completely changed their morphology in an extracellular signal-regulated protein kinase-dependent process and depicted an increased stemness capacity alongside the Wnt pathway stimulation. The transcriptomic profile of DLD1 cells treated with CAF-LM CM was associated with Wnt and mitogen-activated protein kinase pathways activation in GSEA. Therefore, the liver micro-environment induces more efficiently the aggressiveness of colorectal cancer cells than other matched micro-environments do but secondarily evokes cell death. Resistant cells displayed higher stemness capacity

A Soft+Rigid Hybrid Exoskeleton Concept in Scissors-Pendulum Mode: A Suit for Human State Sensing and an Exoskeleton for Assistance

In this paper, we present a novel concept that can enable the human aware control of exoskeletons through the integration of a soft suit and a robotic exoskeleton. Unlike the state-of-the-art exoskeleton controllers which mostly rely on lumped human-robot models, the proposed concept makes use of the independent state measurements concerning the human user and the robot. The ability to observe the human state independently is the key factor in this approach. In order to realize such a system from the hardware point of view, we propose a system integration frame that combines a soft suit for human state measurement and a rigid exoskeleton for human assistance. We identify the technological requirements that are necessary for the realization of such a system with a particular emphasis on soft suit integration. We also propose a template model, named scissor pendulum, that may encapsulate the dominant dynamics of the human-robot combined model to synthesize a controller for human state regulation. A series of simulation experiments were conducted to check the controller performance. As a result, satisfactory human state regulation was attained, adequately confirming that the proposed system could potentially improve exoskeleton-aided applications

A generalist–specialist trade-off between switchgrass cytotypes impacts climate adaptation and geographic range

Polyploidy results from whole-genome duplication and is a unique form of heritable variation with pronounced evolutionary implications. Different ploidy levels, or cytotypes, can exist within a single species, and such systems provide an opportunity to assess how ploidy variation alters phenotypic novelty, adaptability, and fitness, which can, in turn, drive the development of unique ecological niches that promote the coexistence of multiple cytotypes. Switchgrass, Panicum virgatum, is a widespread, perennial C4 grass in North America with multiple naturally occurring cytotypes, primarily tetraploids (4×) and octoploids (8×). Using a combination of genomic, quantitative genetic, landscape, and niche modeling approaches, we detect divergent levels of genetic admixture, evidence of niche differentiation, and differential environmental sensitivity between switchgrass cytotypes. Taken together, these findings support a generalist (8×)–specialist (4×) trade-off. Our results indicate that the 8× represent a unique combination of genetic variation that has allowed the expansion of switchgrass’ ecological niche and thus putatively represents a valuable breeding resource