GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer.

BACKGROUND: Alterations in glucose metabolism and epithelial-mesenchymal transition (EMT) constitute two important characteristics of carcinoma progression toward invasive cancer. Despite an extensive characterization of each of them separately, the links between EMT and glucose metabolism of tumor cells remain elusive. Here we show that the neuronal glucose transporter GLUT3 contributes to glucose uptake and proliferation of lung tumor cells that have undergone an EMT. RESULTS: Using a panel of human non-small cell lung cancer (NSCLC) cell lines, we demonstrate that GLUT3 is strongly expressed in mesenchymal, but not epithelial cells, a finding corroborated in hepatoma cells. Furthermore, we identify that ZEB1 binds to the GLUT3 gene to activate transcription. Importantly, inhibiting GLUT3 expression reduces glucose import and the proliferation of mesenchymal lung tumor cells, whereas ectopic expression in epithelial cells sustains proliferation in low glucose. Using a large microarray data collection of human NSCLCs, we determine that GLUT3 expression correlates with EMT markers and is prognostic of poor overall survival. CONCLUSIONS: Altogether, our results reveal that GLUT3 is a transcriptional target of ZEB1 and that this glucose transporter plays an important role in lung cancer, when tumor cells loose their epithelial characteristics to become more invasive. Moreover, these findings emphasize the development of GLUT3 inhibitory drugs as a targeted therapy for the treatment of patients with poorly differentiated tumors

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Prospektive statistische Analyse der DMP zur Therapiewirksamkeit bei diabetischer Nephropathie

Zielsetzung dieser Arbeit ist es, die Effizienz der DMP anhand der HbA1c-Werte und dem Auftreten der Folgekomplikation diabetische Nephropathie zu untersuchen. In einer prospektiven, statistischen Untersuchung wurden alle Patienten mit Verdacht auf diabetische Nephropathie am Universitätsklinikums Münster im Beobachtungszeitraum 2006-2007. Von der Kohorte aus 331 Patienten nahmen 214 nicht an den DMP teil, 117 waren in den DMP eingeschrieben. Als Ergebnis wurde keine Verbesserung der HbA1c-Werte der DMP-Teilnehmer gegenüber den Nicht-DMP-Teilnehmern festgestellt. Der Anteil an Folgeschäden stellte sich in Relation zur Verteilung auf die untersuchte Kohorte in der DMP als signifikant ungünstiger dar. Durch den Stichprobencharakter der Erhebung, die fehlende Randomisierung und die nicht gegebene Repräsentativität der Kohorte sind die Ergebnisse nicht auf die Gesamtheit der Menschen mit Diabetes mellitus in Deutschland übertragbar

Captive reptile mortality rates in the home and implications for the wildlife trade

The trade in wildlife and keeping of exotic pets is subject to varying levels of national and international regulation and is a topic often attracting controversy. Reptiles are popular exotic pets and comprise a substantial component of the live animal trade. High mortality of traded animals raises welfare concerns, and also has implications for conservation if collection from the wild is required to meet demand. Mortality of reptiles can occur at any stage of the trade chain from collector to consumer. However, there is limited information on mortality rates of reptiles across trade chains, particularly amongst final consumers in the home. We investigated mortality rates of reptiles amongst consumers using a specialised technique for asking sensitive questions, additive Randomised Response Technique (aRRT), as well as direct questioning (DQ). Overall, 3.6% of snakes, chelonians and lizards died within one year of acquisition. Boas and pythons had the lowest reported mortality rates of 1.9% and chameleons had the highest at 28.2%. More than 97% of snakes, 87% of lizards and 69% of chelonians acquired by respondents over five years were reported to be captive bred and results suggest that mortality rates may be lowest for captive bred individuals. Estimates of mortality from aRRT and DQ did not differ significantly which is in line with our findings that respondents did not find questions about reptile mortality to be sensitive. This research suggests that captive reptile mortality in the home is rather low, and identifies those taxa where further effort could be made to reduce mortality rate

Short-term responses to salinity of soybean and chenopodium album grown in single and mixed-species hydroponic systems

Weeds account for losses in crop yields, and this event might be exacerbated by salinity. Therefore, we investigated the responses of Chenopodium album L. and soybean (Glycine max (L.) Merr.) to salt stress, as well as interferences between species. Ten-day old plants were grown for 1 week in a single- or mixed-species set-up, either with or without 100 mM of NaCl. C. album reduced the biomass of soybean similarly to salt stress, while its growth was unaffected under any condition. C. album decreased the crop protein content when salinity was applied. This effect was ascribed to altered protein metabolism and/or N usage to produce other N metabolites, including osmolytes. The two species did not reciprocally affect the capacity to accumulate Na+, but the weed contained two-fold more Na+ in the leaves. Elevated initial K+ concentration and high K+ delivery to the shoot likely explained the better acclimation of C. album to salinity. C. album produced more phenolics and proline and exhibited greater antioxidant activity, but low lipid peroxidation, in the mixed set-up under salinity. Thus, it is possible that the weed could become more resilient to salinity when growing in a soybean field. In the long term, this might cause significant losses in soybean productivity as expected by the dramatic decline in crop protein content

The new σ-IASI code for all sky radiative transfer calculations in the spectral range 10 to 2760 cm-1: σ-IASI/F2N

The paper describes a recently developed forward model (σ-IASI/F2N) to produce spectral radiances from the far to near-infrared spectrum (100 to 2760 cm-1). The model is a pseudo-monochromatic radiative transfer tool that exploits lookup tables to compute the optical depths of atmospheric gas and clouds. Multiple scattering effects are accurately included in both the Far IR and Thermal IR by using a scaling method for cloud and aerosol radiative properties parameterized in terms of their effective radius, which allows them to be handled adopting the same formalism used in the clear sky. In this paper we apply a novel approach to a classical scaling method in the thermal IR relying on our improved parametrization of backscattering parameter over that used by Chou (Martinazzo et al., 2021), while in the Far IR a corrective term is introduced. The code is written in Fortran and runs on Unix-based (Linux and macOS) or MS Windows operating systems. σ-IASI/F2N can be used to develop custom versions of fast-forward modules for satellite instruments working in the infrared spectral range, such as the Far-Infrared Outgoing Radiation Understanding and Monitoring (FORUM) and the Polar Radiant Energy in the Far-InfraRed Experiment (PREFIRE) missions. We discuss the σ-IASI/F2N performance in simulating a set of ECMWF analyses at the global scale. For this purpose, we compare observations from the Infrared Atmospheric Sounding Interferometer (IASI) flying on MetOp B, and C. Results show that σ-IASI/F2N can easily ingest ECMWF analyses data and accurately reproduce cloud patterns. We also show that the difference between σ-IASI/F2N simulations and corresponding IASI observations is below 1 K in the 8–12 um window region, which is mainly affected by the water vapor continuum absorption and weak lines, while for night-time clear sky, the differences are below 0.3 K. again within the same window region