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Low complexity domain

Yi Lin, Eiichiro Mori, Masato Kato, Siheng Xiang, Leeju Wu, Ilmin Kwon, Steven L McKnight
Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent...
October 20, 2016: Cell
Kyung-Ha Lee, Peipei Zhang, Hong Joo Kim, Diana M Mitrea, Mohona Sarkar, Brian D Freibaum, Jaclyn Cika, Maura Coughlin, James Messing, Amandine Molliex, Brian A Maxwell, Nam Chul Kim, Jamshid Temirov, Jennifer Moore, Regina-Maria Kolaitis, Timothy I Shaw, Bing Bai, Junmin Peng, Richard W Kriwacki, J Paul Taylor
Expansion of a hexanucleotide repeat GGGGCC (G4C2) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts carrying (G4C2) expansions undergo unconventional, non-ATG-dependent translation, generating toxic dipeptide repeat (DPR) proteins thought to contribute to disease. Here, we identify the interactome of all DPRs and find that arginine-containing DPRs, polyGly-Arg (GR) and polyPro-Arg (PR), interact with RNA-binding proteins and proteins with low complexity sequence domains (LCDs) that often mediate the assembly of membrane-less organelles...
October 20, 2016: Cell
William M Jackson, Nicholas Davis, Stephen A Sands, Robert A Whittington, Lena S Sun
RESEARCH QUESTION: Is there an association between regular exercise, defined as a structured program of increased physical activity at least 1 month in duration, and improvements in measures of executive functions compared with children who engage in their normal daily activities? CONTEXT: The association between increased physical activity and changes in performance on tasks of executive functions have not been well elucidated in children. Executive functioning is important to intellectual development and academic success in children, and inexpensive, nonpharmacological methods for the treatment of executive dysfunction represent an attractive interventional target...
October 2016: Journal of Neurosurgical Anesthesiology
Brittany L Zastrow, Michelle M Martel, Thomas A Widiger
Oppositional defiant disorder (ODD) is conceptualized as a disorder of negative affect and low effortful control. Yet empirical tests of trait associations with ODD remain limited. The current study examined the relationship between temperament and personality traits and Diagnostic and Statistical Manual of Mental Disorders (5th ed.) ODD symptom domains and related impairment in a preschool-age sample. Participants were 109 children ages 3-6 (59% male), overrecruited for ODD from the community, and their primary caregivers (87% mothers)...
October 21, 2016: Journal of Clinical Child and Adolescent Psychology
C-Y Lin, T-W Chang, W-H Hsieh, M-C Hung, I-H Lin, S-C Lai, Y-J Tzeng
Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1...
2016: Cell Death Discovery
Nicola Jones, Leigh M Riby, Michael A Smith
BACKGROUND AND AIMS: Older adults with type 2 diabetes mellitus (DM2) exhibit accelerated decline in some domains of cognition including verbal episodic memory. Few studies have investigated the influence of DM2 status in older adults on recognition memory for more complex stimuli such as faces. In the present study we sought to compare recognition memory performance for words, objects and faces under conditions of relatively low and high cognitive load. METHODS: Healthy older adults with good glucoregulatory control (n = 13) and older adults with DM2 (n = 24) were administered recognition memory tasks in which stimuli (faces, objects and words) were presented under conditions of either i) low (stimulus presented without a background pattern) or ii) high (stimulus presented against a background pattern) cognitive load...
July 2016: Archives of Medical Research
Michael Hund, Dominic Böhm, Werner Sturm, Michael Sedlmair, Tobias Schreck, Torsten Ullrich, Daniel A Keim, Ljiljana Majnaric, Andreas Holzinger
Medical doctors and researchers in bio-medicine are increasingly confronted with complex patient data, posing new and difficult analysis challenges. These data are often comprising high-dimensional descriptions of patient conditions and measurements on the success of certain therapies. An important analysis question in such data is to compare and correlate patient conditions and therapy results along with combinations of dimensions. As the number of dimensions is often very large, one needs to map them to a smaller number of relevant dimensions to be more amenable for expert analysis...
March 21, 2016: Brain Informatics
John E Stone, William R Sherman, Klaus Schulten
Immersive molecular visualization provides the viewer with intuitive perception of complex structures and spatial relationships that are of critical interest to structural biologists. The recent availability of commodity head mounted displays (HMDs) provides a compelling opportunity for widespread adoption of immersive visualization by molecular scientists, but HMDs pose additional challenges due to the need for low-latency, high-frame-rate rendering. State-of-the-art molecular dynamics simulations produce terabytes of data that can be impractical to transfer from remote supercomputers, necessitating routine use of remote visualization...
May 2016: IEEE International Symposium on Parallel & Distributed Processing, Workshops and Phd Forum: [proceedings]
Manik Lal Saha, Xuzhou Yan, Peter J Stang
Over the past couple of decades, coordination-driven self-assembly has evolved as a broad multidisciplinary domain that not only covers the syntheses of aesthetically pleasing supramolecular architectures but also emerges as a method to form new optical materials, chemical sensors, theranostic agents, and compounds with light-harvesting and emissive properties. The majority of these applications depend upon investigations that reveal the photophysical nature and electronic structure of supramolecular coordination complexes (SCCs), including two-dimensional (2D) metallacycles and three-dimensional (3D) metallacages...
October 13, 2016: Accounts of Chemical Research
Irma Mehmedagic, Stefan Santén, Stefan Acosta
OBJECTIVE: Advanced endovascular aortic repair can be used to treat patients with extensive and complex aortic disease who are at risk of spinal cord ischaemia. The aim of this study was to compare whether life satisfaction differs between patients with and without spinal cord ischaemia at mid-term follow-up. DESIGN: Nested case-control study. PATIENTS: Among patients undergoing advanced endovascular aortic repair between 2009 and 2012, 18 patients with spinal cord ischaemia and 33 without were interviewed at home...
October 13, 2016: Journal of Rehabilitation Medicine
Shoichiro Horita, Yayoi Nomura, Yumi Sato, Tatsuro Shimamura, So Iwata, Norimichi Nomura
Pembrolizumab is an FDA-approved therapeutic antibody that targets the programmed cell death-1 (PD-1) to block the immune checkpoint pathway for the treatment of various types of cancer. It receives remarkable attention due to the high degree of efficacy. Very recently, the crystal structure of the Fab fragment of pembrolizumab (PemFab) in complex with the extracellular domain of human PD-1 (PD-1ECD) was reported at a resolution of 2.9 Å. However, this relatively low-resolution structural data fails to provide sufficient information on interfacial water molecules at the binding interface that substantially contribute to affinity and specificity between the therapeutic antibody and target...
October 13, 2016: Scientific Reports
Luigi Martino, Louise Holland, Evangelos Christodoulou, Simone Kunzelmann, Diego Esposito, Katrin Rittinger
NOD-like receptors represent an important class of germline-encoded pattern recognition receptors that play key roles in the regulation of inflammatory signalling pathways. They function as danger sensors and initiate inflammatory responses and the production of cytokines. Since NLR malfunction results in chronic inflammation and auto-immune diseases, there is a great interest in understanding how they work on a molecular level. To date, a lot of insight into the biological functions of NLRs is available but biophysical and structural studies have been hampered by the difficulty to produce soluble and stable recombinant NLR proteins...
2016: PloS One
Yue Zhang, Xueying Zhang, Jingtong Hu, Jiang Nan, Zhenyi Zheng, Zhizhong Zhang, Youguang Zhang, Nicolas Vernier, Dafine Ravelosona, Weisheng Zhao
Racetrack memory (RM) has sparked enormous interest thanks to its outstanding potential for low-power, high-density and high-speed data storage. However, since it requires bi-directional domain wall (DW) shifting process for outputting data, the mainstream stripe-shaped concept certainly suffers from the data overflow issue. This geometrical restriction leads to increasing complexity of peripheral circuits or programming as well as undesirable reliability issue. In this work, we propose and study ring-shaped RM, which is based on an alternative mechanism, spin orbit torque (SOT) driven chiral DW motions...
October 11, 2016: Scientific Reports
Sindhu Ghanta, Michael I Jordan, Kivanc Kose, Dana H Brooks, Milind Rajadhyaksha, Jennifer G Dy
Segmenting objects of interest from 3D datasets is a common problem encountered in biological data. Small field of view and intrinsic biological variability combined with optically subtle changes of intensity, resolution and low contrast in images make the task of segmentation difficult, especially for microscopy of unstained living or freshly excised thick tissues. Incorporating shape information in addition to the appearance of the object of interest can often help improve segmentation performance. However, shapes of objects in tissue can be highly variable and design of a flexible shape model that encompasses these variations is challenging...
October 5, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
Nan Xu, Chao Ye, Xiulai Chen, Jia Liu, Liming Liu, Jian Chen
Candida glabrata CCTCC M202019 as an industrial yeast strain that is widely used to produce α-oxocarboxylic acid. Strain M202019 has been proven to have a higher pyruvate-producing capacity than the reference strain CBS138. To characterize the genotype of the M202019 strain, we generated a draft sequence of its genome, which has a size of 12.1 Mbp and a GC content of 38.47%. Evidence accumulated during genome annotation suggests that strain M202019 has strong capacities for glucose transport and pyruvate biosynthesis, defects in pyruvate catabolism, as well as variations in genes involved in nutrient and dicarboxylic acid transport, oxidative phosphorylation, and other relevant aspects of carbon metabolism, which might promote pyruvate accumulation...
October 7, 2016: Scientific Reports
Ki Seong Eom, Jin Sung Cheong, Seung Jae Lee
Zinc finger proteins are among the most extensively applied metalloproteins in the field of biotechnology due to their unique structural and functional aspects as transcriptional and translational regulators. The classical zinc fingers are the largest family of zinc proteins and they provide critical roles in physiological systems from prokaryotes to eukaryotes. Two cysteine and two histidine residues (Cys₂His₂) coordinate to the zinc ion for the structural functions to generate a ββα fold, and this secondary structure supports specific interactions with their binding partners including DNA, RNA, lipids, proteins, and small molecules...
October 6, 2016: Journal of Microbiology and Biotechnology
Yan Ma, Meijuan Yan, Hua Huang, Li Zhang, Qian Wang, Yaqi Zhao, Jianmei Zhao
Non-Hodgkin lymphoma (NHL) is a primary tumor arising in lymph nodes and lymphoid tissue. The incidence of NHL is increasing at an annual rate of 3%. The human Jun activation domain-binding protein 1/COP9 signalosome subunit 5 (Jab1/CSN5) is a negative regulator of the cell cycle inhibitor p27(Kip1) and abnormal expression of Jab1 is correlated with reduced p27 expression and associated with advanced tumor stage and poor prognosis in several human cancers. F-box protein S-phase kinase-interacting protein-2 (Skp2), the substrate recognition subunit of the Skp1-Cul1-F-box protein ubiquitin protein ligase complex, is required for the ubiquitination and consequent degradation of p27...
October 2016: Molecular and Clinical Oncology
Moran Golan, Valeria Feinshtein, Ayelet David
The key for successful gene silencing is to design a safe and efficient siRNA delivery system for the transfer of therapeutic nucleic acids into the target cells. Here, we describe the design of hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer displaying multiple copies of octaarginine (R8) and its use in promoting the effective delivery of small interfering RNA (siRNA) molecules intracellularly. Fluorescein-5-isothiocyanate (FITC)-labeled HPMA copolymer-bound R8 (P-R8-FITC) was synthesized with increasing R8 molar ratios (4 to 9...
October 1, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Guilherme L Pinheiro, Allan C de Azevedo-Martins, Rodolpho M Albano, Wanderley de Souza, Susana Frases
The giant snail Achatina fulica is considered an invasive species in most territories in which it was introduced, due to its ability to process a large amount of lignocellulose as a consequence of the presence of a cellulolytic-associated microflora. Streptomyces are well known as crucial agents in the decomposition of complex polymers in soil environments and also as cellulolytic symbionts commonly associated with herbivore insects. Here, we employed a combination of genomic and biochemical tools for a detailed evaluation of the cellulolytic potential of Streptomyces sp...
October 4, 2016: Applied Microbiology and Biotechnology
Benjamin L Timney, Barak Raveh, Roxana Mironska, Jill M Trivedi, Seung Joong Kim, Daniel Russel, Susan R Wente, Andrej Sali, Michael P Rout
Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability...
October 10, 2016: Journal of Cell Biology
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