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Yuandong Li, Woo June Choi, Wan Qin, Utku Baran, Lauren M Habenicht, Ruikang K Wang
BACKGROUND: Arteriogenesis describes the active growth of the pre-existing collateral arterioles, which is a crucial tissue-saving process in occlusive vascular diseases. NEW METHOD: We propose to use optical coherence tomography (OCT)-based microangiography (OMAG) to monitor arteriogenesis following artery transection in mouse ear and focal stroke in mouse brain. RESULTS: Our longitudinal mouse ear study shows that the growth phase of arteriogenesis, indicated by changes in collateral vessel diameter and velocity, occurs between 12-24hours after vessel occlusion...
October 14, 2016: Journal of Neuroscience Methods
Sergio Ruiz de Galarreta, Raúl Antón, Aitor Cazon, Gorka S Larraona, Ender A Finol
An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of other biomechanical factors. Numerical studies, however, must be validated experimentally before they can be clinically implemented. We have developed a methodology for manufacturing anisotropic AAA replicas with non-uniform wall thickness. Different composites were fabricated and tested, and one was selected in order to manufacture a phantom with the same properties...
October 10, 2016: Medical Engineering & Physics
Sirui Zhou, Amirthagowri Ambalavanan, Daniel Rochefort, Pingxing Xie, Cynthia V Bourassa, Pascale Hince, Alexandre Dionne-Laporte, Dan Spiegelman, Ziv Gan-Or, Cathy Mirarchi, Vessela Zaharieva, Nicolas Dupré, Hatasu Kobayashi, Toshiaki Hitomi, Kouji Harada, Akio Koizumi, Lan Xiong, Patrick A Dion, Guy A Rouleau
Intracranial aneurysms (IAs) are the result of focal weakness in the artery wall and have a complex genetic makeup. To date, genome-wide association and sequencing studies have had limited success in identifying IA risk factors. Distinct populations, such as the French-Canadian (FC) population, have increased IA prevalence. In our study, we used exome sequencing to prioritize risk variants in a discovery cohort of six FC families affected by IA, and the analysis revealed an increased variation burden for ring finger protein 213 (RNF213)...
September 30, 2016: American Journal of Human Genetics
Anahita Dua, Steven Koprowski, Gilbert Upchurch, Cheong J Lee, Sapan S Desai
BACKGROUND: In 2014, we published a series of articles in the Journal of Vascular Surgery that detailed the decrease in volume of open aneurysm repair (OAR) completed for abdominal aortic aneurysm (AAA) by vascular surgery trainees. At that time, only data points from 2000 through 2011 were available, and reliable predictions could only be made through 2015. Lack of data on endovascular aneurysm repair (EVAR) using fenestrated (FEVAR) and branched (BrEVAR) endografts also affected our findings...
October 12, 2016: Journal of Vascular Surgery
Gergely N Nagy, Reynier Suardiaz, Anna Lopata, Olivér Ozohanics, Károly Vékey, Bernard R Brooks, Ibolya Leveles, Judit Toth, Beata G Vertessy, Edina Rosta
Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all the above properties, all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers...
October 14, 2016: Journal of the American Chemical Society
Tomomi Nakajima, Masataka Sato, Akito Imai, Yasunori Watanabe
A 79-year-old man underwent endovascular repair for abdominal aortic aneurysm (AAA), and both internal iliac arteries (IIAs) were preserved. Postoperatively, loss of appetite developed. On the fifth day, computerized tomography (CT) showed inferior mesenteric artery thrombus formation, necrosis of the descending colon and rectum, and generalized peritonitis. The endovascular devices had not migrated. A colonic resection was performed. Histological analysis confirmed intestinal necrosis associated with mesenteric thrombus...
2016: Annals of Vascular Diseases
Timothy Wai, Shotaro Saita, Hendrik Nolte, Sebastian Müller, Tim König, Ricarda Richter-Dennerlein, Hans-Georg Sprenger, Joaquin Madrenas, Mareike Mühlmeister, Ulrich Brandt, Marcus Krüger, Thomas Langer
The SPFH (stomatin, prohibitin, flotillin, HflC/K) superfamily is composed of scaffold proteins that form ring-like structures and locally specify the protein-lipid composition in a variety of cellular membranes. Stomatin-like protein 2 (SLP2) is a member of this superfamily that localizes to the mitochondrial inner membrane (IM) where it acts as a membrane organizer. Here, we report that SLP2 anchors a large protease complex composed of the rhomboid protease PARL and the i-AAA protease YME1L, which we term the SPY complex (for SLP2-PARL-YME1L)...
October 13, 2016: EMBO Reports
Sam Taylor, Ian Thomson, Jo Krysa
AIM: A ruptured abdominal aortic aneurysm (rAAA) remains a significant threat to life, with a 30-50% in-hospital mortality rate. The recent introduction of emergency endovascular aneurysm repair (rEVAR) in New Zealand presents an alternative to open repair for rAAAs. The aim of this paper is to review the current experience in New Zealand in the repair of rAAAs. METHODS: Data from the Australasian Vascular Audit (AVA) was reviewed, with data pertaining to rAAAs collected for the five-year period from January 2010 to December 2014...
October 14, 2016: New Zealand Medical Journal
Prasad Kottayil Padmanabhan, Ouafa Zghidi-Abouzid, Mukesh Samant, Carole Dumas, Bruno Guedes Aguiar, Jerome Estaquier, Barbara Papadopoulou
DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death...
October 13, 2016: Cell Death & Disease
Alexander R Siegel, David E Wemmer
Bacterial sigma factors are subunits of RNA polymerase that direct the holoenzyme to specific sets of promoters in the genome, and are a central element of regulating transcription. Most polymerase holoenzymes open the promoter and initiate transcription rapidly after binding. However, polymerase containing members of the σ(54) family must be acted on by a transcriptional activator before DNA opening and initiation occur. A key domain in these transcriptional activators forms a hexameric AAA+ ATPase that acts through conformational changes brought on by ATP hydrolysis...
October 9, 2016: Journal of Molecular Biology
Prabhakar Bastola, Lisa Neums, Frank J Schoenen, Jeremy Chien
Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum-associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline-based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap-dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis...
September 28, 2016: Molecular Oncology
Smita S Kale, Krishnacharya G Akamanchi
Protein aggregation is a major problem of therapeutic proteins because aggregation decreases their therapeutic activity, shelf life and induces immunogenicity. Stabilization against aggregation is commonly attained by addition of different excipients like sugars, surfactants, buffers, salts, amino acids, polymers etc. Generally these excipients are required in combination for stabilization. Sugars are required at a higher concentration and commonly used surfactants like polysorbates have shortcomings due to oxidative degradation...
October 11, 2016: Molecular Pharmaceutics
Ewa Waclawek, Ewa Joachimiak, Malgorzata Hanna Hall, Hanna Fabczak, Dorota Wloga
Katanin is a microtubule severing protein that functions as a heterodimer composed of an AAA domain catalytic subunit, p60, and a regulatory subunit, a WD40 repeat protein, p80. Katanin-dependent severing of microtubules is important for proper execution of key cellular activities including cell division, migration, and differentiation. Published data obtained in C. elegans, Xenopus and mammals indicate that katanin is regulated at multiple levels including transcription, posttranslational modifications (of both katanin and microtubules) and degradation...
October 11, 2016: Molecular Microbiology
Simon Ho, Bo Liu, Raul Loya, Ibrahim Koury
Aortoenteric fistulas (AEFs) are deadly, abnormal connections between the aorta and gastrointestinal (GI) tract. While secondary aortoenteric fistulas (SAEFs) are more common and arise after aortic reconstruction, primary aortoenteric fistulas (PAEFs) are generally caused by abdominal aortic aneurysms (AAAs). PAEFs may present with self-limited GI bleeds called "herald bleeds," and the fistula often goes undiagnosed until patients undergo laparotomy for a massive GI bleed. We describe a case of a PAEF in a 79-year-old man with known AAA...
September 1, 2016: Curēus
Xiao-Shuai Yuan, Zhi-Tian Wang, Ye-Ji Hu, Fei-Chao Bao, Ping Yuan, Chong Zhang, Jin-Lin Cao, Wang Lv, Jian Hu
Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5'-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Mohammad H Eslami, Denis V Rybin, Gheorghe Doros, Alik Farber
OBJECTIVE: Despite vast improvement in the field of vascular surgery, elective abdominal aortic aneurysm (AAA) repair still leads to perioperative death. Patients with asymptomatic AAAs, therefore, would benefit from an individual risk assessment to help with decisions regarding operative intervention. The purpose of this study was to describe such a 30-day postoperative (POD) risk prediction model using American College of Surgeons National Surgical Quality Improvement Project (NSQIP) data...
October 5, 2016: Journal of Vascular Surgery
Albert Busch, Elena Hartmann, Caroline Grimm, Süleyman Ergün, Ralph Kickuth, Christoph Otto, Richard Kellersmann, Udo Lorenz
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease...
October 5, 2016: Journal of Vascular Surgery
Hervé Bègue, Sylvain Jeandroz, Cécile Blanchard, David Wendehenne, Claire Rosnoblet
BACKGROUND: The chaperone-like p97 is a member of the AAA+ ATPase enzyme family that contributes to numerous cellular activities. P97 has been broadly studied in mammals (VCP/p97) and yeasts (CDC48: Cell Division Cycle 48/p97) and numerous investigations highlighted that this protein is post-translationally regulated, is structured in homohexamer and interacts with partners and cofactors that direct it to distinct cellular signalization pathway including protein quality control and degradation, cell cycle regulation, genome stability, vesicular trafficking, autophagy and immunity...
October 4, 2016: Biochimica et Biophysica Acta
Johannes van den Boom, Markus Wolf, Lena Weimann, Nina Schulze, Fanghua Li, Farnusch Kaschani, Anne Riemer, Christian Zierhut, Markus Kaiser, George Iliakis, Hironori Funabiki, Hemmo Meyer
During DNA double-strand break (DSB) repair, the ring-shaped Ku70/80 complex becomes trapped on DNA and needs to be actively extracted, but it has remained unclear what provides the required energy. By means of reconstitution of DSB repair on beads, we demonstrate here that DNA-locked Ku rings are released by the AAA-ATPase p97. To achieve this, p97 requires ATP hydrolysis, cooperates with the Ufd1-Npl4 ubiquitin-adaptor complex, and specifically targets Ku80 that is modified by K48-linked ubiquitin chains...
October 6, 2016: Molecular Cell
Séverine Massenet, Edouard Bertrand, Céline Verheggen
Box C/D and box H/ACA snoRNAs are abundant non-coding RNAs that localize in the nucleolus and mostly function as guides for nucleotide modifications. While a large pool of snoRNAs modifies ribosomal RNAs, an increasing number of snoRNAs could also potentially target mRNAs. ScaRNAs belong to a family of specific RNAs that localize in Cajal bodies and that are structurally similar to snoRNAs. Most scaRNAs are involved in snRNA modification, while telomerase RNA, which contains H/ACA motifs, functions in telomeric DNA synthesis...
October 7, 2016: RNA Biology
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