Removal of the Mitochondrial Fission Factor Mff Exacerbates Neuronal Loss and Neurological Phenotypes in a Huntington’s Disease Mouse Model

Objective: Excessive mitochondrial fission has been associated with several neurodegenerative diseases, including Huntington’s disease (HD). Consequently, mitochondrial dynamics has been suggested to be a promising therapeutic target for Huntington’s disease. Mitochondrial fission depends on recruitment of Drp1 to mitochondria, and Mff (mitochondrial fission factor) is one of the key adaptor proteins for this process. Removal of Mff therefore greatly reduces mitochondrial fission. Here we investigate whether removal of Mff can mitigate HD-associated pathologies in HD transgenic mice (R6/2) expressing mutant Htt. Method: We compared the phenotype of HD mice with and without Mff. The mice were monitored for lifespan, neurological phenotypes, Htt aggregate formation, and brain histology. Results: We found that HD mice lacking Mff display more severe neurological phenotypes and have shortened lifespans. Loss of Mff does not affect mutant Htt aggregation, but it accelerates HD pathology, including neuronal loss and neuroinflammation. Conclusions: Our data indicate a protective role for mitochondrial fission in HD and suggest that more studies are needed before manipulation of mitochondrial dynamics can be applied to HD therapy

Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1

A defining feature of mitochondria is their maternal mode of inheritance. However, little is understood about the cellular mechanism through which paternal mitochondria, delivered from sperm, are eliminated from early mammalian embryos. Autophagy has been implicated in nematodes, but whether this mechanism is conserved in mammals has been disputed. Here, we show that cultured mouse fibroblasts and pre-implantation embryos use a common pathway for elimination of mitochondria. Both situations utilize mitophagy, in which mitochondria are sequestered by autophagosomes and delivered to lysosomes for degradation. The E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria. The process is associated with depolarization of paternal mitochondria and additionally requires the mitochondrial outer membrane protein FIS1, the autophagy adaptor P62, and PINK1 kinase. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process

Analyzing the video popularity characteristics of large-scale user generated content systems

Abstract—User generated content (UGC), now with millions of video producers and consumers, is re-shaping the way people watch video and TV. In particular, UGC sites are creating new viewing patterns and social interactions, empowering users to be more creative, and generating new business opportunities. Compared to traditional video-on-demand (VoD) systems, UGC services allow users to request videos from a potentially unlimited selection in an asynchronous fashion. To better understand the impact of UGC services, we have analyzed the world’s largest UGC VoD system, YouTube, and a popular similar system in Korea, Daum Videos. In this paper, we first empirically show how UGC services are fundamentally different from traditional VoD services. We then analyze the intrinsic statistical properties of UGC popularity distributions and discuss opportunities to leverage the latent demand for niche videos (or the so-called “the Long Tail ” potential), which is not reached today due to informa-tion filtering or other system scarcity distortions. Based on traces collected across multiple days, we study the popularity lifetime of UGC videos and the relationship between requests and video age. Finally, we measure the level of content aliasing and illegal content in the system and show the problems aliasing creates in ranking the video popularity accurately. The results presented in this paper are crucial to understanding UGC VoD systems and may have major commercial and technical implications for site administrators and content owners. Index Terms—Interactive TV, human factors, exponential distri-butions, log normal distributions, pareto distributions, probability, copyright protection. I

Removal of the Mitochondrial Fission Factor Mff Exacerbates Neuronal Loss and Neurological Phenotypes in a Huntington’s Disease Mouse Model

Objective: Excessive mitochondrial fission has been associated with several neurodegenerative diseases, including Huntington’s disease (HD). Consequently, mitochondrial dynamics has been suggested to be a promising therapeutic target for Huntington’s disease. Mitochondrial fission depends on recruitment of Drp1 to mitochondria, and Mff (mitochondrial fission factor) is one of the key adaptor proteins for this process. Removal of Mff therefore greatly reduces mitochondrial fission. Here we investigate whether removal of Mff can mitigate HD-associated pathologies in HD transgenic mice (R6/2) expressing mutant Htt. Method: We compared the phenotype of HD mice with and without Mff. The mice were monitored for lifespan, neurological phenotypes, Htt aggregate formation, and brain histology. Results: We found that HD mice lacking Mff display more severe neurological phenotypes and have shortened lifespans. Loss of Mff does not affect mutant Htt aggregation, but it accelerates HD pathology, including neuronal loss and neuroinflammation. Conclusions: Our data indicate a protective role for mitochondrial fission in HD and suggest that more studies are needed before manipulation of mitochondrial dynamics can be applied to HD therapy

Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1

A defining feature of mitochondria is their maternal mode of inheritance. However, little is understood about the cellular mechanism through which paternal mitochondria, delivered from sperm, are eliminated from early mammalian embryos. Autophagy has been implicated in nematodes, but whether this mechanism is conserved in mammals has been disputed. Here, we show that cultured mouse fibroblasts and pre-implantation embryos use a common pathway for elimination of mitochondria. Both situations utilize mitophagy, in which mitochondria are sequestered by autophagosomes and delivered to lysosomes for degradation. The E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria. The process is associated with depolarization of paternal mitochondria and additionally requires the mitochondrial outer membrane protein FIS1, the autophagy adaptor P62, and PINK1 kinase. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process

The Volume of Subscapularis Muscle Remains Unaffected by Supraspinatus Tendon Tears: Three-dimensionally Reconstructed Magnetic Resonance Imaging Analysis

Background This study aimed to compare the subscapularis muscle volume between the intact groups (group I) and supraspinatus tendon tear groups (group T) based on the sex and three different age groups. Methods Subjects with a group I and subjects with group T without any other lesions were retrospectively evaluated from among patients who received a magnetic resonance imaging (MRI) scan between January 2011 and December 2013. The MRI scans were studied by a consultant radiologist. The subscapularis muscle volume was compared according to the age and sex; the age groups were categorized as patients in their 40s, 50s, and 60s. The volume of subscapularis muscle was measured by three-dimensional reconstructed images acquired through the axial section of 1.5T MRI. Results No statistically significant differences were observed between subscapularis muscle volume of the group I and group T, except for male patients in their 50s (group I: 100,650 mm3 vs. group T: 106,488 mm3) and 60s (group I: 76,347 mm3 vs. group T: 99,549 mm3) (p<0.05). Males had a larger mean volume of subscapularis muscle than females, and the subscapularis muscle volume decreased in a linear manner with increasing age. Conclusions Decrease in subscapularis muscle volume was observed with increasing age, and the impact of supraspinatus tear on subscapularis muscle volume is age and sex dependent

Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer’s Disease in Mice, Observed by in Vivo Two-Photon Imaging

Monoamine oxidases (MAOs) play an important role in Alzheimer&apos;s disease (AD) pathology. We report in vivo comonitoring of MAO activity and amyloid-beta (A beta) plaques dependent on the aging of live mice with AD, using a two-photon fluorescence probe. The probe under the catalytic action of MAO produces a dipolar fluorophore that senses A beta plaques, a general AD biomarker, enabling us to comonitor the enzyme activity and the progress of AD indicated by A beta plaques. The results show that the progress of AD has a close correlation with MAO activity, which can be categorized into three stages: slow initiation stage up to three months, an aggressive stage, and a saturation stage from nine months. Histological analysis also reveals elevation of MAO activity around A beta plaques in aged mice. The close correlation between the MAO activity and AD progress observed by in vivo monitoring for the first time prompts us to investigate the enzyme as a potential biomarker of AD.1195Ysciescopu