Control of Intestinal Inflammation, Colitis-Associated Tumorigenesis, and Macrophage Polarization by Fibrinogen-Like Protein 2

Fibrinogen-like protein 2 (Fgl2) is critical for immune regulation in the inflammatory state. Elevated Fgl2 levels are observed in patients with inflammatory bowel disease (IBD), but little is known about its functional significance. In this study, we sought to investigate the role of Fgl2 in the development of intestinal inflammation and colitis-associated colorectal cancer (CAC). Here, we report that Fgl2 deficiency increased susceptibility to dextran sodium sulfate-induced colitis and CAC in a mouse model. During colitis development, the expression of the membrane-bound and secreted forms of Fgl2 (mFgl2 and sFgl2, respectively) in the colon were increased and predominantly expressed by colonic macrophages. In addition, using bone marrow chimeric mice, we determined that Fgl2 function in colitis is strictly related to its expression in the hematopoietic cells. Loss of Fgl2 induced the polarization of M1, but suppressed that of M2 both in vivo and in vitro, independent of intestinal inflammation. Thus, Fgl2 suppresses intestinal inflammation and CAC development through its role in macrophage polarization and may serve as a therapeutic target in inflammatory diseases, including IBD

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Real-Time Optimal States Estimation with Inertial and Delayed Visual Measurements for Unmanned Aerial Vehicles

Motion estimation is a major issue in applications of Unmanned Aerial Vehicles (UAVs). This paper proposes an entire solution to solve this issue using information from an Inertial Measurement Unit (IMU) and a monocular camera. The solution includes two steps: visual location and multisensory data fusion. In this paper, attitude information provided by the IMU is used as parameters in Kalman equations, which are different from pure visual location methods. Then, the location of the system is obtained, and it will be utilized as the observation in data fusion. Considering the multiple updating frequencies of sensors and the delay of visual observation, a multi-rate delay-compensated optimal estimator based on the Kalman filter is presented, which could fuse the information and obtain the estimation of 3D positions as well as translational speed. Additionally, the estimator was modified to minimize the computational burden, so that it could run onboard in real time. The performance of the overall solution was assessed using field experiments on a quadrotor system, compared with the estimation results of some other methods as well as the ground truth data. The results illustrate the effectiveness of the proposed method

Dry Bio-Decontamination Process in Reduced-Pressure O₂ Plasma

The main objective of this work was to fully understand the bio-decontamination process in a reduced-pressure oxygen plasma. Gram-negative Escherichia coli species was chosen as the target microorganism in this test. The comparison of decontamination efficacy between plasma total and UV radiation individually under various treatment parameters and tests of DNA agarose electrophoresis were made to evaluate the inactivation effect of UV radiation. The quantity of protein leakage and the concentration of malondialdehyde (MDA), which are markers of the end products of lipid peroxidation, in bacterial suspension after treatment were determined to estimate the contribution of both charged particles and free radicals for bacterial death. In addition, a scanning electronic microscope was used to visualize the plasma effect on microorganisms. The results showed that the essential action of the oxygen plasma on Escherichia coli is believed to be attributed to the fast and intense etching on cell membrane by electrons and ions. Attacks on polyunsaturation fatty acid (PUFA) in the cell membrane by oxygen free radicals and the destruction of the DNA in the cell by UV radiation are accessorial during an effective decontamination process

Happy but uncivil? Examining when and why positive affect leads to incivility

In this paper, we examine the interactive effects of positive affect and perspective-taking on workplace incivility and family incivility, through moral disengagement. We draw from broaden-and-build and moral disengagement theories to suggest a potential negative consequence of positive affect. Specifically, we argue that positive affect increases incivility toward coworkers and spouses through moral disengagement among employees with low, but not high perspective-taking. Data from two time-lagged field studies and one online experiment provide support for our hypotheses. These findings suggest that the beneficial effects of positive feelings are not universal, and the fostering of positive feelings at work might have unintended negative consequences, namely moral disengagement, and increased incivility at work and at home. Implications for theory and research are discussed

A Tet/Q Hybrid System for Robust and Versatile Control of Transgene Expression in C. elegans

Summary: Binary gene regulatory tools such as the Tetracycline (Tet)-controlled transcription system have revolutionized genetic research in multiple organisms, but their applications to the worm remain very limited. Here we report that the canonical Tet system is largely inactive in the worm but can be adapted for the worm by introducing multiple modifications, a crucial one being the use of the transcription activation domain from the fungal Q binary system. The resultant Tet/Q hybrid system proves more robust and flexible than either of its precursors, enabling elaborate modes of transgene manipulation previously hard to achieve in the worm, including inducible intersectional regulation and, in combination with the Q system, independent control of distinct transgenes within the same cells. Furthermore, we demonstrated, as an example of its applications, that the hybrid system can tightly and efficiently control Cre expression. This study establishes Tet/Q as a premier binary system for worm genetic research. : Genetics; Techniques in Genetics; Model Organism Subject Areas: Genetics, Techniques in Genetics, Model Organis

Antidiabetic and Neuroprotective Effect of the N-Butanol Extract of Fragaria nilgerrensis Schlecht. in STZ-Induced Diabetic Mice

Diabetes has been associated with neurodegenerative disorders that are accompanied by memory loss and cognitive impairments, but there is no effective treatment for it at present. Fragaria nilgerrensis Schlecht. (FNS), a well-known Chinese materia medica, has been traditionally used for the folkloric treatment of diabetes and other diseases. However, its effects are poorly documented. Here, we investigated the antidiabetic and neuroprotective effect of FNS in diabetic mice. Thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) evaluations of N-butanol extract of Fragaria nilgerrensis Schlecht. (N-FNS) showed the presence of flavonoid and its structure is similar to scutellarin. For the first time, we show the potential neuroprotective and antidiabetic effects of FNS. After 4 weeks of FNS intervention, a significant decrease in blood glucose, increase in body weight, and amelioration in glucose tolerance were observed in FNS treated diabetic mice. In the acute study, FNS enhanced motor activity in the open field task and significantly prevented spatial-learning deficits in Morris water maze tests. Besides, synapse ultrastructure of the hippocampus showed that the mitochondrial morphology was basically restored and all the synaptic structural parameters were gradually normalized after treatment with FNS. Importantly, we found that the activities of SOD and CAT in liver and hippocampus of diabetic mice significantly increased after FNS administration. In vitro, FNS and scutellarin showed high DPPH radical scavenging activity. The study suggests that FNS exerted significant antidiabetic and neuroprotective effects which may be attributed to its antioxidant property