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Components of the COP9 signalosome (CSN), a key member of the conserved 26S proteasome degradation pathway, have been detected to be altered in patients of several debilitating syndromes. These findings suggest that CSN acts in neural circuits, but the exact function of CSN in brain remains unidentified. Previously, using Drosophila peripheral nervous system (PNS) as a model system, we determined that CSN is a critical regulator of dendritic morphogenesis. We found that defects in CSN led to the strikingly contrast phenotype of either reducing or stimulating dendritic branching. In particular, we have reported that CSN stimulates dendritic branching via Cullin1-mediated proteolysis. Here we describe that CSN inhibits dendritic arborization in PNS neurons acting via control of Cullin3 function: loss of Cullin3 causes excessive dendritic branching. We also identified a downstream target for Cullin3-dependent degradation in neurons – the actin-crosslinking BTB-domain protein Kelch. Inappropriate accumulation of Kelch, either due to the impaired Cullin3-dependent turnover, or ectopic expression of Kelch, leads to uncontrolled dendritic branching. These findings indicate that the CSN pathway modulates neuronal network in a multilayer manner, providing the foundation for new insight into the CSN role in human mental retardation disorders and neurodegenerative disease. 相似文献
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Christopher A. Koczor Inna N. Shokolenko Amy K. Boyd Shawn P. Balk Glenn L. Wilson Susan P. LeDoux 《The Journal of biological chemistry》2009,284(52):36191-36201
Previous work from our laboratory has focused on mitochondrial DNA (mtDNA) repair and cellular viability. However, other events occur prior to the initiation of apoptosis in cells. Because of the importance of mtDNA in ATP production and of ATP in fuel cell cycle progression, we asked whether mtDNA damage was an upstream signal leading to cell cycle arrest. Using quantitative alkaline Southern blot technology, we found that exposure to menadione produced detectable mtDNA damage in HeLa cells that correlated with an S phase cell cycle arrest. To determine whether mtDNA damage was causatively linked to the observed cell cycle arrest, experiments were performed utilizing a MTS-hOGG1-Tat fusion protein to target the hOGG1 repair enzyme to mitochondria and enhance mtDNA repair. The results revealed that the transduction of MTS-hOGG1-Tat into HeLa cells alleviated the cell cycle block following an oxidative insult. Furthermore, mechanistic studies showed that Chk2 phosphorylation was enhanced following menadione exposure. Treatment of the HeLa cells with the hOGG1 fusion protein prior to menadione exposure resulted in an increase in the rate of Chk2 dephosphorylation. These results strongly support a direct link between mtDNA damage and cell cycle arrest. 相似文献
4.
James T. Li Mark C. Swanson Roy J. Rando Patricia Wentz-Murtha Inna G. Ovsyannikova Ferran Morell Manuel Lopez Charles E. Reed 《Aerobiologia》1996,12(1):173-176
There have been reported epidemics of severe asthma in Barcelona, Spain, linked to a 10 kDa low molecular mass (LMM) allergen from soybean hulls that became airborne during unloading of ships. As a preliminary probe of the potential for dispersion of this allergen in USA cities, four automated air samplers were placed around a grain elevator in New Orleans and operated continuously from May to October 1990. The allergen was extracted from the filters and immunochemically assayed for soybean aeroallergen. On 31 separate days, the airborne allergen concentration in at least one of the samples was over 10000 U/m3 similar to those observed in Barcelona on some epidemic days. Areas North and East of the elevator were most affected. Serologie studies showed that of 50 asthmatics from New Orleans who were participants in an unrelated clinical study 4 or 8% demonstrated elevated titers of IgE antibody to LMM soybean allergen. Only 1 of 475 control sera (half of which were also asthmatic) obtained elsewhere in the US was positive for LMM soybean IgE antibody. Based on the findings in this study, there is a great possibility that on some days there is enough soybean allergen in the air and a sufficient frequency of soybean aeroallergen RAST positive asthmatics in New Orleans to warrant further investigation of the contribution of soybean aeroallergen to asthma around the port of New Orleans.Supported by NIAID # A121255. Mayo Clinic and Foundation and Minnesota Lung Association. 相似文献
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Inna Székács Nóra Kaszás Pál Gróf Katalin Erdélyi István Szendr? Balázs Mihalik ágnes Pataki Ferenc A. Antoni Emilia Madarász 《PloS one》2013,8(12)
Optical waveguide lightmode spectroscopic (OWLS) techniques were probed for monitoring ion permeation through channels incorporated into artificial lipid environment. A novel sensor set-up was developed by depositing liposomes or cell-derived membrane fragments onto hydrophilic polytetrafluoroethylene (PTFE) membrane. The fibrous material of PTFE membrane could entrap lipoid vesicles and the water-filled pores provided environment for the hydrophilic domains of lipid-embedded proteins. The sensor surface was kept clean from the lipid holder PTFE membrane by a water- and ion-permeable polyethylene terephthalate (PET) mesh. The sensor set-up was tested with egg yolk lecithin liposomes containing gramicidin ion channels and with cell-derived membrane fragments enriched in GABA-gated anion channels. The method allowed monitoring the move of Na+ and organic cations through gramicidin channels and detecting the Cl–-channel functions of the (α5β2γ2) GABAA receptor in the presence or absence of GABA and the competitive GABA-blocker bicuculline. 相似文献
6.
Inna Leykin 《The journal of the Royal Anthropological Institute》2020,26(1):86-104
The article explores a series of professional development seminars for state bureaucrats in the context of the moral panic over Russia's ‘demographic crisis’. It follows the vernacularization of social knowledge for state bureaucrats – a central practice that marks these pedagogical engagements. The article explores this practice's potentialities and limitations for effectively communicating social knowledge to administrative audiences. It grounds itself in the theoretical discussions of expertise and demonstrates how vernacularizing social knowledge for post-Soviet statecraft shapes the social and political meanings of Russia's demographic crisis, investing state policies and discourses with authority. 相似文献
7.
Zeynep Eroglu Sheri L. Holmen Qing Chen Nikhil I. Khushalani Ravi Amaravadi Reena Thomas Kamran A. Ahmed Hussein Tawbi Sunandana Chandra Joseph Markowitz Inna Smalley James K. C. Liu Yian Ann Chen Yana G. Najjar Florian A. Karreth Daniel Abate‐Daga Isabella C. Glitza Jeffrey A. Sosman Vernon K. Sondak Marcus Bosenberg Meenhard Herlyn Michael B. Atkins Harriet Kluger Kim Margolin Peter A. Forsyth Michael A. Davies Keiran S. M. Smalley 《Pigment cell & melanoma research》2019,32(3):458-469
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area. 相似文献
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Indrikis Krams Sanita Kecko Katariina Kangassalo Fhionna R. Moore Eriks Jankevics Inna Inashkina Tatjana Krama Vilnis Lietuvietis Laila Meija Markus J. Rantala 《Insect Science》2015,22(3):431-439
The resources available to an individual in any given environment are finite, and variation in life history traits reflect differential allocation of these resources to competing life functions. Nutritional quality of food is of particular importance in these life history decisions. In this study, we tested trade‐offs among growth, immunity and survival in 3 groups of greater wax moth (Galleria mellonella) larvae fed on diets of high and average nutritional quality. We found rapid growth and weak immunity (as measured by encapsulation response) in the larvae of the high‐energy food group. It took longer to develop on food of average nutritional quality. However, encapsulation response was stronger in this group. The larvae grew longer in the low‐energy food group, and had the strongest encapsulation response. We observed the highest survival rates in larvae of the low‐energy food group, while the highest mortality rates were observed in the high‐energy food group. A significant negative correlation between body mass and the strength of encapsulation response was found only in the high‐energy food group revealing significant competition between growth and immunity only at the highest rates of growth. The results of this study help to establish relationships between types of food, its nutritional value and life history traits of G. mellonella larvae. 相似文献
10.
Iana H. Haralambieva Scott D. Painter Richard B. Kennedy Inna G. Ovsyannikova Nathaniel D. Lambert Krista M. Goergen Ann L. Oberg Gregory A. Poland 《PloS one》2015,10(3)