Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential of spermatozoa

GLUT8 is a class 3 sugar transport facilitator which is predominantly expressed in testis and also detected in brain, heart, skeletal muscle, adipose tissue, adrenal gland, and liver. Since its physiological function in these tissues is unknown, we generated a Slc2a8 null mouse and characterized its phenotype. Slc2a8 knockout mice appeared healthy and exhibited normal growth, body weight development and glycemic control, indicating that GLUT8 does not play a significant role for maintenance of whole body glucose homeostasis. However, analysis of the offspring distribution of heterozygous mating indicated a lower number of Slc2a8 knockout offspring (30.5:47.3:22.1%, Slc2a8+/+, Slc2a8+/−, and Slc2a8−/− mice, respectively) resulting in a deviation (p = 0.0024) from the expected Mendelian distribution. This difference was associated with lower ATP levels, a reduced mitochondrial membrane potential and a significant reduction of sperm motility of the Slc2a8 knockout in comparison to wild-type spermatozoa. In contrast, number and survival rate of spermatozoa were not altered. These data indicate that GLUT8 plays an important role in the energy metabolism of sperm cells

Optical imaging of the peri-tumoral inflammatory response in breast cancer

<p>Abstract</p> <p>Purpose</p> <p>Peri-tumoral inflammation is a common tumor response that plays a central role in tumor invasion and metastasis, and inflammatory cell recruitment is essential to this process. The purpose of this study was to determine whether injected fluorescently-labeled monocytes accumulate within murine breast tumors and are visible with optical imaging.</p> <p>Materials and methods</p> <p>Murine monocytes were labeled with the fluorescent dye DiD and subsequently injected intravenously into 6 transgenic MMTV-PymT tumor-bearing mice and 6 FVB/n control mice without tumors. Optical imaging (OI) was performed before and after cell injection. Ratios of post-injection to pre-injection fluorescent signal intensity of the tumors (MMTV-PymT mice) and mammary tissue (FVB/n controls) were calculated and statistically compared.</p> <p>Results</p> <p>MMTV-PymT breast tumors had an average post/pre signal intensity ratio of 1.8+/- 0.2 (range 1.1-2.7). Control mammary tissue had an average post/pre signal intensity ratio of 1.1 +/- 0.1 (range, 0.4 to 1.4). The p-value for the difference between the ratios was less than 0.05. Confocal fluorescence microscopy confirmed the presence of DiD-labeled cells within the breast tumors.</p> <p>Conclusion</p> <p>Murine monocytes accumulate at the site of breast cancer development in this transgenic model, providing evidence that peri-tumoral inflammatory cell recruitment can be evaluated non-invasively using optical imaging.</p

Measuring Scientific Misconduct—Lessons from Criminology

This article draws on research traditions and insights from Criminology to elaborate on the problems associated with current practices of measuring scientific misconduct. Analyses of the number of retracted articles are shown to suffer from the fact that the distinct processes of misconduct, detection, punishment, and publication of a retraction notice, all contribute to the number of retractions and, hence, will result in biased estimates. Self-report measures, as well as analyses of retractions, are additionally affected by the absence of a consistent definition of misconduct. This problem of definition is addressed further as stemming from a lack of generally valid definitions both on the level of measuring misconduct and on the level of scientific practice itself. Because science is an innovative and ever-changing endeavor, the meaning of misbehavior is permanently shifting and frequently readdressed and renegotiated within the scientific community. Quantitative approaches (i.e., statistics) alone, thus, are hardly able to accurately portray this dynamic phenomenon. It is argued that more research on the different processes and definitions associated with misconduct and its detection and sanctions is needed. The existing quantitative approaches need to be supported by qualitative research better suited to address and uncover processes of negotiation and definition

Implementing Agile Data Workflows to Unlock Climate-Resilient Urban Planning

Cities around the world are facing the implications of a changing climate as an increasingly pressing issue. The negative effects of climate change are already being felt today. Therefore, adaptation to these changes is a mission that every city must master. Leading practices worldwide demonstrate various urban efforts on climate change adaptation (CCA) which are already underway. Above all, the integration of climate data, remote sensing, and in situ data is key to a successful and measurable adaptation strategy. Furthermore, these data can act as a timely decision support tool for municipalities to develop an adaptation strategy, decide which actions to prioritize, and gain the necessary buy-in from local policymakers. The implementation of agile data workflows can facilitate the integration of climate data into climate-resilient urban planning. Due to local specificities, (supra)national, regional, and municipal policies and (by) laws, as well as geographic and related climatic differences worldwide, there is no single path to climate-resilient urban planning. Agile data workflows can support interdepartmental collaboration and, therefore, need to be integrated into existing management processes and government structures. Agile management, which has its origins in software development, can be a way to break down traditional management practices, such as static waterfall models and sluggish stage-gate processes, and enable an increased level of flexibility and agility required when urgent. This paper presents the findings of an empirical case study conducted in cooperation with the City of Constance in southern Germany, which is pursuing a transdisciplinary and trans-sectoral co-development approach to make management processes more agile in the context of climate change adaptation. The aim is to present a possible way of integrating climate data into CCA planning by changing the management approach and implementing a toolbox for low-threshold access to climate data. The city administration, in collaboration with the University of Applied Sciences Constance, the Climate Service Center Germany (GERICS), and the University of Stuttgart, developed a co-creative and participatory project, CoKLIMAx, with the objective of integrating climate data into administrative processes in the form of a toolbox. One key element of CoKLIMAx is the involvement of the population, the city administration, and political decision-makers through targeted communication and regular feedback loops among all involved departments and stakeholder groups. Based on the results of a survey of 72 administrative staff members and a literature review on agile management in municipalities and city administrations, recommendations on a workflow and communication structure for cross-departmental strategies for resilient urban planning in the City of Constance were developed

Hypereosinophilia driven by GM-CSF in large-cell carcinoma of the lung

In contrast to leukocytosis, paraneoplastic hypereosinophilia is uncommon in lung cancer. We present a patient with large-cell carcinoma of the lung, in which cancer cells generate large amounts of GM-CSF leading to a leukemoid reaction with prominent hypereosinophilia and potentially involved in autocrine tumor stimulation

Optical Imaging of Cellular Immunotherapy against Prostate Cancer

The purpose of this study was to track fluorophore-labeled, tumor-targeted natural killer (NK) cells to human prostate cancer xenografts with optical imaging (OI). NK-92-scFv(MOC31)-zeta cells targeted to the epithelial cell adhesion molecule (EpCAM) antigen on prostate cancer cells and nontargeted NK-92 parental cells were labeled with the near-infrared dye DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). The fluorescence, viability, and cytotoxicity of the labeled cells were evaluated. Subsequently, 12 athymic rats with prostate cancer xenografts underwent OI scans before and up to 24 hours postinjection of DiD-labeled parental NK-92 cells or NK-92-scFv(MOC31)-zeta cells. The tumor fluorescence intensity was measured and compared between pre- and postinjection scans and between both groups using t -tests. OI data were confirmed with fluorescence microscopy. In vitro studies demonstrated a significant increase in the fluorescence of labeled cells compared with unlabeled controls, which persisted over a period of 24 hours without any significant change in the viability. In vivo studies demonstrated a significant increase in tumor fluorescence at 24 hours postinjection of tumor-targeted NK-92-scFv(MOC31)-zeta cells but not parental NK cells. Ex vivo OI scans and fluorescence microscopy confirmed a specific accumulation of NK-92-scFv(MOC31)-zeta cells but not parental NK cells in the tumors. Tumor-targeted NK-92-scFv(MOC31)-zeta cells could be tracked to prostate cancer xenografts with OI

Neuronal functions, feeding behavior, and energy balance in Slc2a3+/– mice

Homozygous deletion of the gene of the neuronal glucose transporter GLUT3 (Slc2a3) in mice results in embryonic lethality, whereas heterozygotes (Slc2a3+/–) are viable. Here, we describe the characterization of heterozygous mice with regard to neuronal function, glucose homeostasis, and, since GLUT3 might be a component of the neuronal glucose-sensing mechanism, food intake and energy balance. Levels of GLUT3 mRNA and protein in brain were reduced by 50% in Slc2a3+/– mice. Electrographic features examined by electroencephalographic recordings give evidence for slightly but significantly enhanced cerebrocortical activity in Slc2a3+/– mice. In addition, Slc2a3+/– mice were slightly more sensitive to an acoustic startle stimulus (elevated startle amplitude and reduced prepulse inhibition). However, systemic behavioral testing revealed no other functional abnormalities, e.g., in coordination, reflexes, motor abilities, anxiety, learning, and memory. Furthermore, no differences in body weight, blood glucose, and insulin levels were detected between wild-type and Slc2a3+/– littermates. Food intake as monitored randomly or after intracerebroventricular administration of 2-deoxyglucose or D-glucose, or food choice for carbohydrates/fat was not affected in Slc2a3+/– mice. Taken together, our data indicate that, in contrast to Slc2a1, a single allele of Slc2a3 is sufficient for maintenance of neuronal energy supply, motor abilities, learning and memory, and feeding behavior