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

2,2-[(E)-3,3-Diphenyl­prop-2-ene-1,1-di­yl]bis­(3-hy­droxy­cyclo­hex-2-en-1-one)

In the title compound, C27H26O4, each of the cyclo­hexenone rings adopts a half-chair conformation. The dihedral angle between the two phenyl rings is 89.53 (5)°. The hy­droxy and carbonyl O atoms face each other and are orientated to allow the formation of two intra­molecular O—H⋯O hydrogen bonds, which are typical of xanthene derivatives

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

Batalin-Tyutin Quantization of the Chiral Schwinger Model

We quantize the chiral Schwinger Model by using the Batalin-Tyutin formalism. We show that one can systematically construct the first class constraints and the desired involutive Hamiltonian, which naturally generates all secondary constraints. For $a>1$, this Hamiltonian gives the gauge invariant Lagrangian including the well-known Wess-Zumino terms, while for $a=1$ the corresponding Lagrangian has the additional new type of the Wess-Zumino terms, which are irrelevant to the gauge symmetry.Comment: 15 pages, latex, no figures, to be published in Z. Phys. C (1995

Misinformation, Believability, and Vaccine Acceptance Over 40 Countries: Takeaways From the Initial Phase of The COVID-19 Infodemic

The COVID-19 pandemic has been damaging to the lives of people all around the world. Accompanied by the pandemic is an infodemic, an abundant and uncontrolled spreading of potentially harmful misinformation. The infodemic may severely change the pandemic's course by interfering with public health interventions such as wearing masks, social distancing, and vaccination. In particular, the impact of the infodemic on vaccination is critical because it holds the key to reverting to pre-pandemic normalcy. This paper presents findings from a global survey on the extent of worldwide exposure to the COVID-19 infodemic, assesses different populations' susceptibility to false claims, and analyzes its association with vaccine acceptance. Based on responses gathered from over 18,400 individuals from 40 countries, we find a strong association between perceived believability of misinformation and vaccination hesitancy. Additionally, our study shows that only half of the online users exposed to rumors might have seen the fact-checked information. Moreover, depending on the country, between 6% and 37% of individuals considered these rumors believable. Our survey also shows that poorer regions are more susceptible to encountering and believing COVID-19 misinformation. We discuss implications of our findings on public campaigns that proactively spread accurate information to countries that are more susceptible to the infodemic. We also highlight fact-checking platforms' role in better identifying and prioritizing claims that are perceived to be believable and have wide exposure. Our findings give insights into better handling of risk communication during the initial phase of a future pandemic

The Effect Of IFRS Adoption On Likelihood Of Management Earnings Forecasts: Evidence In Korea

Korean listed companies adopted International financial reporting standards (IFRS) in 2011 mandatorily. The IFRS adoption modifies corporate financial reporting structure and further it can affect managers’ incentive for disclosing their earnings forecasts. We investigate the association between IFRS adoption and likelihood of management earnings forecasts. From the empirical results, we find that mandatory IFRS adopted companies are less likely to issue their earnings forecasts after IFRS adoption. It implies that investors’ belief about management earnings forecasts as useful information is weakened after IFRS adoption compare to pre-IFRS adoption period. Therefore, managers’ incentive for providing earnings forecasts decreases. This study will contribute to academics and disclosure-related practitioners by reporting how IFRS adoption makes an influence to managers’ incentive of management earnings forecasts issuance. We also believe that the empirical evidence may shed some lights on the understanding of the spillover effect of IFRS adoption to management earnings forecasts.

943-14 Termination and Suppression of Experimental Atrial Flutter by Quinidine: Effects on Dispersion of Repolarization and Conduction

Recent studies in our canine crush-injury (CI) model of atrial flutter (AFL) suggest that elimination of dispersion of repolarization is an important antiarrhythmic effect of newer class 3 antiarrhythmic drugs. However, the effects of class 1a antiarrhythmic drugs on dispersion of repolarization and its relation to termination and suppression of AFL have not been studied. Therefore, the effects of quinidine 10) were studied in 8 dogs, using a 56-electrode plaque placed over the CI to map activation patterns during AFL and its induction and termination, and to measure effective refractory periods (ERP) at all 56 electrodes and conduction velocity (CV) parallel to the CI, before and after 0 (10mg/kg over 10 min, then 3 mg/kg/hr).ResultsInduction of AFL at baseline was due to unidirectional block below the CI. a terminated AFL in only 3 dogs, due to conduction block below the CI, occurring either abruptly or following premature eccentric activation of the reentry circuit. Sustained AFL was reinducible after a in 5 dogs, and nonsustained AFL in 3. Mean overall ERP increased 14% from 112±11msec at baseline to 128±15msec after a (p<0.001). ERP was longer below CI than above (115±10ms vs 109±10ms, p<0.001). and this difference was not eliminated by a (133±14ms vs 123±14ms, p<0.001). Overall dispersion of ERP (9.9±2.3msec) was unchanged by a (1 0.0±1.3msec, p=NS). The number of adjacent electrodes with ERP difference ≥20msec (14.4±10.4) was also not changed by a (12.5±7.9, P = NS). CV was slower below the CI than above at baseline (0.7±0.1 vs 0.9±0.1 mis,p<0.001), and this difference was unchanged by a (0.6±0.1 vs 0.8±0.1 mis,p<0.001). although CV was slowed overall(p<0.01). a prolonged AFL cycle length 57% from 123±12 to 198±37msec (p<0.01).Conclusion1) Baseline dispersion of ERP and CV is important for initiating and sustaining AFL in this model. 2) The class 1a drug quinidine is relatively ineffective in terminating and suppressing AFL in this model, because it prolongs ERP less than AFL cycle length and it does not eliminate dispersion of ERP or C

How Do Institutional Investors Interact With Sell-Side Analysts?

This paper examines how institutional investors interact with sell-side analysts (hereafter, SSAs) in Korean stock market. In particular, we examine the role of institutional investors as a more sophisticated mechanism which incorporates sell-side analysts’ stock recommendation, target price, and earnings forecast more rapidly than individual investors do. Moreover, we examine whether institutional investors differentiate the quality of sell-side analysts’ information. By using a sample of 1,421 firm-year observations in Korean stock market during 2001–2011, we find that the change of institutional investor’s ownership has a significantly positive association with the level of equity value estimates based on SSAs’ earnings forecasts relative to stock prices and their stock recommendation which are considered as SSAs’ indicator of stock market’s mispricing. In addition, we find that only when SSAs provide more accurate earnings forecasts, institutional investors incorporate SSA’s information into their stock trading. Thus, we conclude that institutional investors in Korean stock market contribute to the enhancement of stock market efficiency by incorporating SSAs’ information into their stock trading more rapidly than individual investors. Our findings add to the literature by shedding a light on the unobserved interaction among more sophisticated stock market participants, such as institutional investors and sell-side analysts