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Cong Yan, Huanhuan Huo, Cuiwei Yang, Tao Zhang, Yuanyuan Chu, Yanfen Liu
Ubiquitination modification has been shown to play a key role in autophagy. Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBs) in autophagy pathway. To systematically search how DUBs manipulate autophagy, we utilized a double fluorescence tagged LC3 stable HeLa cell line, and did a genome wide screen of 55 human DUBs which is about 60% coverage of the DUB family. We found a bunch of DUBs have impact on autophagy by either changing the LC3 puncta formation or the autophagy flux. One of them, Ubiquitin C-Terminal Hydrolase L1 (UCHL1) correlated to Parkinson's disease, strongly affects autophagy by inhibiting autophagosome formation...
February 17, 2018: Biochemical and Biophysical Research Communications
Demet Atalay, Peter Schausberger
In- and out-breeding depressions are commonly observed phenomena in sexually reproducing organisms with a patchy distribution pattern, and spatial segmentation and/or isolation of groups. At the genetic level, inbreeding depression is due to increased homozygosity, whereas outbreeding depression is due to inferior genetic compatibility of mates. Optimal outbreeding theory suggests that intermediate levels of mate relatedness should provide for the highest fitness gains. Here, we assessed the fitness consequences of genetic relatedness between mates in plant-inhabiting predatory mites Phytoseiulus persimilis, which are obligatory sexually reproducing but haplo-diploid...
February 19, 2018: Experimental & Applied Acarology
Heather Piwowar, Jason Priem, Vincent Larivière, Juan Pablo Alperin, Lisa Matthias, Bree Norlander, Ashley Farley, Jevin West, Stefanie Haustein
Despite growing interest in Open Access (OA) to scholarly literature, there is an unmet need for large-scale, up-to-date, and reproducible studies assessing the prevalence and characteristics of OA. We address this need using oaDOI, an open online service that determines OA status for 67 million articles. We use three samples, each of 100,000 articles, to investigate OA in three populations: (1) all journal articles assigned a Crossref DOI, (2) recent journal articles indexed in Web of Science, and (3) articles viewed by users of Unpaywall, an open-source browser extension that lets users find OA articles using oaDOI...
2018: PeerJ
Rajeev Raghavan, Garabed Eknoyan
Urea was identified as a urinary salt in 1662 and was the first organic bodily product to be synthesized in vitro in 1828. This heralded the end of an era that defined disease as an imbalance between vital life forces, and catalyzed the merging of organic chemical sciences into clinical medicine. The term urée (urea) was introduced in 1803, its accumulation in blood was dubbed urémie (uremia) in 1847, and the procedure for its removal from urine across semi-permeable membranes designated dialysis in 1861...
February 16, 2018: Clinical Nephrology
Jinyoung Park, Mi-Sun Kwon, Eunice EunKyeong Kim, Hyunsook Lee, Eun Joo Song
Although approximately 100 deubiquitinating enzymes (DUBs) are encoded in the human genome, very little is known about the DUBs that function in mitosis. Here, we demonstrate that DUB USP35 functions as a mitotic regulator by controlling the protein levels and downstream signaling of Aurora B and the depletion of USP35 eventually leads to several mitotic defects including cytokinesis failures. USP35 binds to and deubiquitinates Aurora B, and inhibits the APC CDH1 -mediated proteasomal degradation of Aurora B, thus maintaining its steady-state levels during mitosis...
February 15, 2018: Nature Communications
Caitlin N Suire, Sarah Nainar, Michael Fazio, Adam G Kreutzer, Tara Paymozd-Yazdi, Caitlyn L Topper, Caroline R Thompson, Malcolm A Leissring
Insulin-degrading enzyme (IDE) is an atypical zinc-metalloendopeptidase that hydrolyzes insulin and other intermediate-sized peptide hormones, many of which are implicated in skin health and wound healing. Pharmacological inhibitors of IDE administered internally have been shown to slow the breakdown of insulin and thereby potentiate insulin action. Given the importance of insulin and other IDE substrates for a variety of dermatological processes, pharmacological inhibitors of IDE suitable for topical applications would be expected to hold significant therapeutic and cosmetic potential...
2018: PloS One
Xiaofei Zhang, Arne H Smits, Gabrielle Ba van Tilburg, Huib Ovaa, Wolfgang Huber, Michiel Vermeulen
Ubiquitin-binding proteins play an important role in eukaryotes by translating differently linked polyubiquitin chains into proper cellular responses. Current knowledge about ubiquitin-binding proteins and ubiquitin linkage-selective interactions is mostly based on case-by-case studies. We have recently reported a method called ubiquitin interactor affinity enrichment-mass spectrometry (UbIA-MS), which enables comprehensive identification of ubiquitin interactors for all ubiquitin linkages from crude cell lysates...
March 2018: Nature Protocols
Ethan Tumarkin, Amila Heendeniya, Pauline Murphy, Tania Placido, Darrell H S Tan, Isaac I Bogoch
BACKGROUND: On-demand PrEP may reduce one's risk of HIV acquisition, however it is unclear if individuals with a very low frequency of HIV exposures are conferred adequate protection. We evaluated a novel approach dubbed HIV Post-Exposure Prophylaxis-in-Pocket ('PIP'), for individuals with a low frequency of high risk HIV exposures. SETTING: Two HIV clinics in Toronto, Canada, managing HIV prevention cases. METHODS: A retrospective evaluation of patients referred to HIV clinics for PrEP between January 1, 2013 and September 30, 2017, inclusive...
February 6, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Naseema Gangat, Mythri Mudireddy, Terra L Lasho, Christy M Finke, Maura Nicolosi, Natasha Szuber, Mrinal M Patnaik, Animesh Pardanani, Curtis A Hanson, Rhett P Ketterling, Ayalew Tefferi
In order to develop a genetic risk model for primary myelodysplastic syndromes (MDS), we queried the prognostic significance of next-generation sequencing (NGS)-derived mutations, in the context of the Mayo cytogenetic risk stratification, which includes high-risk (monosomal karyotype; MK), intermediate-risk (non-MK, classified as intermediate/poor/very poor, per the revised international prognostic scoring system; IPSS-R), and low-risk (classified as good/very good, per IPSS-R). Univariate analysis in 300 consecutive patients with primary MDS identified TP53, RUNX1, U2AF1, ASXL1, EZH2 and SRSF2 mutations as "unfavorable" and SF3B1 as "favorable" risk factors for survival; for the purposes of the current study, the absence of SF3B1 mutation was accordingly dubbed as an "adverse" mutation...
February 8, 2018: American Journal of Hematology
Gabriel Bidaux, Corentin Le Nézet, Mariano Gonzalez Pisfil, Mélanie Henry, Alessandro Furlan, Oliver Bensaude, Bernard Vandenbunder, Laurent Héliot
Biochemical studies have revealed that the RNA Polymerase II (RNAPII) pause release is triggered by phosphorylation of the transcription machinery by the positive transcription elongation factor b (P-TEFb). However, there are no direct report that P-TEFb and RNA polymerase II interact in single living cells and the biophysical mechanisms mediating this association are still unclear. Förster resonance energy transfer (FRET) detects molecular interactions at the subcellular level. Time domain fluorescence lifetime imaging provides an accurate quantification of FRET efficiency, EFRET, because it is fluorochrome concentration-independent and insensitive to fluorescence bleed-through...
February 6, 2018: Biophysical Journal
Megan E J Campbell, Steve Mehrkanoon, Ross Cunnington
Perception and action are inextricably linked, down to the level of single cells which have both visual and motor response properties - dubbed 'mirror neurons'. The mirror neuron system is generally associated with direct-matching or resonance between observed and executed actions (and goals). Yet in everyday interactions responding to another's movements with matching actions (or goals) is not always appropriate. Here we examine processes associated with intentionally not imitating, as separable from merely detecting an observed action as mismatching one's own...
January 30, 2018: Neuropsychologia
Di Yun, Yinghan Zhuang, Michael R Kreutz, Thomas Behnisch
Posttranslational modification and degradation of proteins by the ubiquitin-proteasome system (UPS) is crucial to synaptic transmission. It is well established that 19S proteasome associated deubiquitinases (DUBs) reverse the process of ubiquitination by removing ubiquitin from their substrates. However, their potential contribution to hippocampal synaptic plasticity has not been addressed in detail. Here, we report that inhibition of the 19S proteasome associated DUBs, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14) by b-AP15 results in an accumulation of polyubiquitinated proteins and a reduction of monomeric ubiquitin without overt effects on 26S proteasome activity...
January 30, 2018: Neuropharmacology
M A Kim, E J Kim, H K Lee
BACKGROUND: Skin elasticity is an important indicator of skin aging. The aim of this study was to demonstrate that the SkinFibrometer® is appropriate for measuring skin biomechanical properties, and to correlate it with elasticity parameters measured using the Cutometer® and with dermis structural properties measured using DUB® Skinscanner. MATERIALS AND METHODS: Twenty-one individuals participated in this study. The skin of the cheek, around the eye, and the volar forearm were evaluated...
February 6, 2018: Skin Research and Technology
Qingyuan Yang, Wanrun Lin, Zhiwei Liu, Jiabei Zhu, Nan Huang, Zhongqi Cui, Zeping Han, Qiuhui Pan, Ajay Goel, Fenyong Sun
Esophageal squamous cell carcinoma (ESCC) is the most popular pathology of esophageal cancer (EC) in China, especially in Henan province, mid-east of China. Presently, targeting DNA damage repair (DDR) factors is a promising approach for cancer therapy. Our group has been focusing on exploring the DDR factors overexpressed in ESCC tissues to provide potential targets for therapies for many years. RAP80/UIMC1 (ubiquitin interaction motif containing 1), one of those DDR factors we tested, was highly overexpressed in ESCC tissues compared with adjacent normal tissues...
February 2, 2018: Cell Death & Disease
Pu Wang, Jianhua Li, Pengtao Gong, Weirong Wang, Yongxing Ai, Xichen Zhang
BACKGROUND: Chicken coccidiosis, a disease caused by seven species of Eimeria (Apicomplexa: Coccidia), inflicts severe economic losses on the poultry industry. Eimeria tenella is the one of the most virulent species pathogenic to chickens. Many parasitic protozoans are parasitised by double-stranded (ds) RNA viruses, and the influence of protozoan viruses on parasitic protozoans has been extensively reported. E. tenella RNA virus 1 (Etv) was identified in E. tenella, and the complete genome sequence of Etv was analysed...
January 31, 2018: Parasites & Vectors
Gayatree Patra, Priyam Das, S Chakraborty, B C Meikap
Excessive fluoride concentration in wastewater is a major health concern worldwide. The main objective of wastewater treatment is to allow industrial effluents to be disposed of without danger to the human health and the natural environment. In this current study, experiments have been conducted to remove fluoride from aqueous solution using alumina and HCl (Hydrochloric acid) treated activated alumina in a continuous mode. A spiral rib was introduced in the cylindrical part of the conventional hydrocyclone to increase the performance, and the new hydrocyclone is dubbed as ribbed hydrocyclone...
January 30, 2018: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
Jiafeng Ge, Weiwei Hu, Hui Zhou, Juan Yu, Chongran Sun, Weilin Chen
Ubiquitin C-terminal Hydrolase-L5 (UCH-L5/UCH37), a member of the deubiquitinases (DUBs), suppresses protein degeneration via removing ubiquitin from the distal subunit of the polyubiquitin chain. The activity of UCH-L5 is enhanced when UCH-L5 combines with proteasome 19S regulatory subunit by Rpn13/Admr1 receptor and inhibited when UCH-L5 interacts with NFRKB. But the role of UCH-L5 in gliomas remains unknown. In this study, analysis of 19 frozen and 51 paraffin-embedded clinic pathological cases showed that UCH-L5 expression in glioma tissues was lower than normal brain tissues...
December 26, 2017: Oncotarget
Decebal Constantin Mocanu, Georgios Exarchakos, Antonio Liotta
Almost all the natural or human made systems can be understood and controlled using complex networks. This is a difficult problem due to the very large number of elements in such networks, on the order of billions and higher, which makes it impossible to use conventional network analysis methods. Herein, we employ artificial intelligence (specifically swarm computing), to compute centrality metrics in a completely decentralized fashion. More exactly, we show that by overlaying a homogeneous artificial system (inspired by swarm intelligence) over a complex network (which is a heterogeneous system), and playing a game in the fused system, the changes in the homogeneous system will reflect perfectly the complex network properties...
January 25, 2018: Scientific Reports
Alessandro Arrigo, Eleonora Corbelli, Emanuela Aragona, Maria Pia Manitto, Elisabetta Martina, Francesco Bandello, Maurizio Battaglia Parodi
PURPOSE: To study multimodal imaging features of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). METHODS: Six patients (3 males, mean age 11 years) and a healthy age-matched control group made up of 15 healthy subjects (8 males, mean age 12.6 years) were included in the analysis. Complete ophthalmologic examination was performed, including best-corrected visual acuity, anterior and posterior segment slit-lamp evaluation, and tonometry. The multimodal imaging protocol included fundus images, structural optical coherence tomography (OCT), and swept-source OCT angiography (OCTA)...
January 23, 2018: Retina
Raisa Yu Kiseleva, C F Greineder, C H Villa, O A Marcos-Contreras, E D Hood, V V Shuvaev, H M DeLisser, V R Muzykantov
Targeting drugs to endothelial cells has shown the ability to improve outcomes in animal models of inflammatory, ischemic and thrombotic diseases. Previous studies have revealed that certain pairs of ligands (antibodies and antibody fragments) specific for adjacent, but distinct, epitopes on PECAM-1 enhance each other's binding, a phenomenon dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL. This discovery has been leveraged to enable simultaneous delivery of multiple therapeutics to the vascular endothelium...
January 24, 2018: Scientific Reports
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