Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration.

Although uridine-rich small nuclear RNAs (U-snRNAs) are essential for pre-mRNA splicing, little is known regarding their function in the regulation of alternative splicing or of the biological consequences of their dysfunction in mammals. Here, we demonstrate that mutation of Rnu2-8, one of the mouse multicopy U2 snRNA genes, causes ataxia and neurodegeneration. Coincident with the observed pathology, the level of mutant U2 RNAs was highest in the cerebellum and increased after granule neuron maturation. Furthermore, neuron loss was strongly dependent on the dosage of mutant and wild-type snRNA genes. Comprehensive transcriptome analysis identified a group of alternative splicing events, including the splicing of small introns, which were disrupted in the mutant cerebellum. Our results suggest that the expression of mammalian U2 snRNA genes, previously presumed to be ubiquitous, is spatially and temporally regulated, and dysfunction of a single U2 snRNA causes neuron degeneration through distortion of pre-mRNA splicing

Loss of Clcc1 Results in ER Stress, Misfolded Protein Accumulation, and Neurodegeneration.

Folding of transmembrane and secretory proteins occurs in the lumen of the endoplasmic reticulum (ER) before transportation to the cell surface and is monitored by the unfolded protein response (UPR) signaling pathway. The accumulation of unfolded proteins in the ER activates the UPR that restores ER homeostasis by regulating gene expression that leads to an increase in the protein-folding capacity of the ER and a decrease in the ER protein-folding load. However, prolonged UPR activity has been associated with cell death in multiple pathological conditions, including neurodegeneration. Here, we report a spontaneous recessive mouse mutation that causes progressive cerebellar granule cell death and peripheral motor axon degeneration. By positional cloning, we identify the mutation in this strain as a retrotransposon insertion in the Clcc1 gene, which encodes a putative chloride channel localized to the ER. Furthermore, we demonstrate that the C3H/HeSnJ inbred strain has late onset cerebellar degeneration due to this mutation. Interestingly, acute knockdown of Clcc1 expression in cultured cells increases sensitivity to ER stress. In agreement, GRP78, the major HSP70 family chaperone in the ER, is upregulated in Clcc1-deficient granule cells in vivo, and ubiquitinated proteins accumulate in these neurons before their degeneration. These data suggest that disruption of chloride homeostasis in the ER disrupts the protein-folding capacity of the ER, leading to eventual neuron death. J Neurosci 2015 Feb 18; 35(7):3001-9

Code for Multi-Animal Mesh Model ALignment (MAMMAL)

Three-dimensional surface motion capture of multiple freely moving pigs using MAMMAL A snapshot for the code and dataset used in the paper. Liang An, Jilong Ren, Tao Yu, Tang Hai*, Yichang Jia*, and Yebin Liu

Three-dimensional surface motion capture of multiple freely moving pigs using MAMMAL

Abstract Understandings of the three-dimensional social behaviors of freely moving large-size mammals are valuable for both agriculture and life science, yet challenging due to occlusions in close interactions. Although existing animal pose estimation methods captured keypoint trajectories, they ignored deformable surfaces which contained geometric information essential for social interaction prediction and for dealing with the occlusions. In this study, we develop a Multi-Animal Mesh Model Alignment (MAMMAL) system based on an articulated surface mesh model. Our self-designed MAMMAL algorithms automatically enable us to align multi-view images into our mesh model and to capture 3D surface motions of multiple animals, which display better performance upon severe occlusions compared to traditional triangulation and allow complex social analysis. By utilizing MAMMAL, we are able to quantitatively analyze the locomotion, postures, animal-scene interactions, social interactions, as well as detailed tail motions of pigs. Furthermore, experiments on mouse and Beagle dogs demonstrate the generalizability of MAMMAL across different environments and mammal species

The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy

Abstract Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we find that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. Csg2 functions as a calcium release channel and maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase Aur1. Under starvation conditions, deletion of Csg2 causes increases in calcium levels in the ER and then disturbs Aur1 stability, leading to accumulation of the bioactive sphingolipid phytosphingosine, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the channel Csg2 translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy

DEGRADATION OF POLLUTANTS BY HYDROPHOBIC FePcCl16 UNDER ULTRAVIOLET AND VISIBLE LIGHT

Metal complex perchlorinated iron-phthalocyanine (FePcCl16) was prepared and used as a photocatalyst. The heterogeneous photocatalytic degradation of rhodamine B (RhB) and salicylic acid (SA) by FePcCl16 activated by molecular oxygen (O-2) under ultraviolet light (lambda <= 387 nm) and by hydrogen peroxide (H2O2) under visible light irradiation (lambda >= 420 nm) were studied. The experimental results indicated that organic pollutants can be effectively degraded under both ultraviolet and visible light. Under ultraviolet and visible light illumination, the removal rates of total organic carbon (TOC) for RhB reached 86.24% after 180 min and 64.73% after 300 min, respectively. The degradation process was predominated by the hydroxyl radical (center dot OH), according to the results from benzoic acid fluorescence method. The hydrophobic photocatalyst FePcCl16 was stable in aqueous solution. The photocatalytic degradation system had wide pH adaptability (3-11). The heterogeneous photocatalyst can be reused to degrade toxic organic pollutants both under ultraviolet and visible light.Metal complex perchlorinated iron-phthalocyanine (FePcCl16) was prepared and used as a photocatalyst. The heterogeneous photocatalytic degradation of rhodamine B (RhB) and salicylic acid (SA) by FePcCl16 activated by molecular oxygen (O-2) under ultraviolet light (lambda = 420 nm) were studied. The experimental results indicated that organic pollutants can be effectively degraded under both ultraviolet and visible light. Under ultraviolet and visible light illumination, the removal rates of total organic carbon (TOC) for RhB reached 86.24% after 180 min and 64.73% after 300 min, respectively. The degradation process was predominated by the hydroxyl radical (center dot OH), according to the results from benzoic acid fluorescence method. The hydrophobic photocatalyst FePcCl16 was stable in aqueous solution. The photocatalytic degradation system had wide pH adaptability (3-11). The heterogeneous photocatalyst can be reused to degrade toxic organic pollutants both under ultraviolet and visible light

Bismuth oxybromide promoted detoxification of cylindrospermopsin under UV and visible light illumination

Bismuth oxybromide (BiOBr) was prepared and characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse reflectance spectroscopy (DRS). The BiOBr promoted detoxification of cylindrospermopsin (CYN) under UV (lambda 420 nm) illumination was studied. The results revealed that the toxic uracil unit of CYN was removed, and the carboxylic group of the degraded product was also decomposed, to give the innoxious tricyclic guanidine product under the title conditions. In contrast, the traditional Fenton reagents (Fe2+ and H2O2) limited to remove the uracil moiety of CYN with the carboxylic group intact. Presumably, the decarboxylation ability of BiOBr was induced by Br 4p valence band hole (h(Br) (+)(4p)), and the degradation mechanism was also proposed based on the experimental results and theoretical calculation. (C) 2013 Elsevier B.V. All rights reserved.Bismuth oxybromide (BiOBr) was prepared and characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse reflectance spectroscopy (DRS). The BiOBr promoted detoxification of cylindrospermopsin (CYN) under UV (lambda 420 nm) illumination was studied. The results revealed that the toxic uracil unit of CYN was removed, and the carboxylic group of the degraded product was also decomposed, to give the innoxious tricyclic guanidine product under the title conditions. In contrast, the traditional Fenton reagents (Fe2+ and H2O2) limited to remove the uracil moiety of CYN with the carboxylic group intact. Presumably, the decarboxylation ability of BiOBr was induced by Br 4p valence band hole (h(Br) (+)(4p)), and the degradation mechanism was also proposed based on the experimental results and theoretical calculation. (C) 2013 Elsevier B.V. All rights reserved