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Julia M Fraile, Diana Campos-Iglesias, Francisco Rodríguez, Yaiza Español, José M P Freije
Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis...
October 19, 2016: Oncotarget
Sanja Dacic, Liza C Villaruz, Shira Abberbock, Alyssa Mahaffey, Pimpin Incharoen, Marina N Nikiforova
Break-apart ALK FISH probe is the FDA approved approach for detection of ALK rearrangements in lung carcinoma patients who may benefit from ALK kinase inhibitors. The FISH assay can be technically challenging and difficult to interpret. ALK immunohistochemistry and next generation sequencing have been proposed as alternative approaches. In this study, we compared various ALK -FISH patterns to next -generation sequencing (NGS) for gene fusion detection, ALK immunohistochemistry (IHC) and tumor responses to crizotinib...
October 17, 2016: Oncotarget
Yanyan Zheng, Li Zhu, Lulu Fan, Wenna Zhao, Jianlong Wang, Xianxiao Hao, Yunhui Zhu, Xiufang Hu, Yaofeng Yuan, Jingwei Shao, Wenfeng Wang
Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been demonstrated to exhibit good anti-cancer effect. In this study, a series of novel quaternary ammonium salts of emodin, anthraquinone and anthrone were synthesized and their anticancer activities were tested in vitro. The effects of emodin quaternary ammonium salts on cell viability, apoptosis, intracellular ROS, and mitochondrial membrane potential were investigated in A375, BGC-823, HepG2 and HELF cells. The results demonstrated that compound 4a induced morphological changes and decreased cell viability...
October 7, 2016: European Journal of Medicinal Chemistry
Laura M Seske, William C Ralston, Louis J Muglia, James M Greenberg
Infant mortality rate is generally regarded as a fundamental indicator of population health and is often used to validate public health interventions. Hamilton County, Ohio, has one of the highest rates in the nation. Most deaths that do not occur in the hospital fall under the jurisdiction of a coroner/medical examiner. We reviewed all infant deaths evaluated by the Hamilton County Coroner from 2006 to 2013 in order to identify opportunities for public health interventions. We predicted that the majority of these infant deaths were unintentional, but preventable...
October 17, 2016: Journal of Forensic and Legal Medicine
T Lavender, S Wakasiaka, L McGowan, M Moraa, J Omari, W Khisa
AIM: this study aimed to gain understanding of the views of community members in relation to obstetric fistula. DESIGN AND METHOD: a qualitative, grounded theory approach was adopted. Data were collected using in-depth interviews with 45 community members. The constant comparison method enabled generation of codes and subsequent conceptualisations, from the data. SETTING: participants were from communities served by two hospitals in Kenya; Kisii and Kenyatta...
October 4, 2016: Midwifery
Jowita Marszewska, Mietek Jaroniec
Highly-porous carbon spheres were prepared by modified Stöber method combined with silica templating and CO2 activation. Silica was delivered in the form of either colloids or tetraethyl orthosilicate and used to create porosity. Subsequently, CO2 activation was used to develop microporosity. CO2 activation was done either: (1) on carbon spheres, following silica etching or (2) on silica-carbon composites, before silica removal. Both methods delivered carbon materials with well-developed structures and, importantly, preserved spherical morphology...
October 15, 2016: Journal of Colloid and Interface Science
Sanna Rönkä, Anu Katainen
BACKGROUND: The non-medical use of prescription drugs is a growing phenomenon associated with increasing health-related harms. However, little is known about the drivers of this process among illicit drug users. Our aim is to show how the qualities of pharmaceutical drugs, pharmaceutical related knowledge, online communities sharing this knowledge and medical professionals mediate and transform the consumption behaviour related to pharmaceutical drugs. METHODS: The data consist of discussion threads from an online drug use forum...
October 18, 2016: International Journal on Drug Policy
Raquel Marin, Noemí Fabelo, Virginia Martín, Paula Garcia-Esparcia, Isidre Ferrer, David Quinto-Alemany, Mario Díaz
Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes...
September 6, 2016: Neurobiology of Aging
Troy A Skwor, Stephanie Klemm, Hanyu Zhang, Brianna Schardt, Stephanie Blaszczyk, Matthew A Bork
Increasing rates of antibiotic resistance coupled with the lack of novel antibiotics threatens proper clinical treatment and jeopardizes their use in prevention. A photodynamic approach appears to be an innovative treatment option, even for multi-drug resistant strains of bacteria. Three components are utilized in photodynamic inactivation: a photosensitizer, light source, and oxygen. Variations in photosensitizers strongly influence microbial binding and bactericidal activity. In this study, four different cationic metalloporphyrins (Cu(2+), Fe(2+), Pd(2+), Zn(2+)) were compared to the free-base ligand 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin regarding their electronic properties and generation of reactive oxygen species upon subsequent 405nm violet-blue irradiation...
October 15, 2016: Journal of Photochemistry and Photobiology. B, Biology
Stacy-Anne Morgan, Dana C Nadler, Rayka Yokoo, David F Savage
Metabolic engineering offers the potential to renewably produce important classes of chemicals, particularly biofuels, at an industrial scale. DNA synthesis and editing techniques can generate large pathway libraries, yet identifying the best variants is slow and cumbersome. Traditionally, analytical methods like chromatography and mass spectrometry have been used to evaluate pathway variants, but such techniques cannot be performed with high throughput. Biosensors - genetically encoded components that actuate a cellular output in response to a change in metabolite concentration - are therefore a promising tool for rapid and high-throughput evaluation of candidate pathway variants...
October 18, 2016: Current Opinion in Chemical Biology
Xiang-Xin Huang, Yun-Xuan Li, Xiang-Yu Li, Xiao-Xia Hu, Peng-Fei Tang, Guo-Xin Hu
Currently, crizotinib is the first generation drug, which has been used in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). However, more and more patients are found in crizotinib-resistance. In the last year, alectinib has been approved for treatment of patients with crizotinib-resistance. In this study, we aim to develop and validate a simple, rapid and sensitive tandem mass spectrometry (UHPLC-MS/MS) method for determination of alectinib in rat plasma. Diazepam was chosen as an internal standard (IS)...
October 14, 2016: Journal of Pharmaceutical and Biomedical Analysis
Shobini Jayaraman, Jose Luis Sánchez-Quesada, Olga Gursky
Lipids in the body are transported via lipoproteins that are nanoparticles comprised of lipids and amphipathic proteins termed apolipoproteins. This family of lipid surface-binding proteins is over-represented in human amyloid diseases. In particular, all major proteins of high-density lipoproteins (HDL), including apoA-I, apoA-II and serum amyloid A, can cause systemic amyloidoses in humans upon protein mutations, post-translational modifications or overproduction. Here, we begin to explore how the HDL lipid composition influences amyloid deposition by apoA-I and related proteins...
October 18, 2016: Biochimica et Biophysica Acta
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
Tian Hua, Kiran Vemuri, Mengchen Pu, Lu Qu, Gye Won Han, Yiran Wu, Suwen Zhao, Wenqing Shui, Shanshan Li, Anisha Korde, Robert B Laprairie, Edward L Stahl, Jo-Hao Ho, Nikolai Zvonok, Han Zhou, Irina Kufareva, Beili Wu, Qiang Zhao, Michael A Hanson, Laura M Bohn, Alexandros Makriyannis, Raymond C Stevens, Zhi-Jie Liu
Cannabinoid receptor 1 (CB1) is the principal target of Δ(9)-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study...
October 20, 2016: Cell
Iuliia Gilchuk, Pavlo Gilchuk, Gopal Sapparapu, Rebecca Lampley, Vidisha Singh, Nurgun Kose, David L Blum, Laura J Hughes, Panayampalli S Satheshkumar, Michael B Townsend, Ashley V Kondas, Zachary Reed, Zachary Weiner, Victoria A Olson, Erika Hammarlund, Hans-Peter Raue, Mark K Slifka, James C Slaughter, Barney S Graham, Kathryn M Edwards, Roselyn J Eisenberg, Gary H Cohen, Sebastian Joyce, James E Crowe
Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses...
October 20, 2016: Cell
Rebecca L Lamason, Effie Bastounis, Natasha M Kafai, Ricardo Serrano, Juan C Del Álamo, Julie A Theriot, Matthew D Welch
Spotted fever group (SFG) rickettsiae are human pathogens that infect cells in the vasculature. They disseminate through host tissues by a process of cell-to-cell spread that involves protrusion formation, engulfment, and vacuolar escape. Other bacterial pathogens rely on actin-based motility to provide a physical force for spread. Here, we show that SFG species Rickettsia parkeri typically lack actin tails during spread and instead manipulate host intercellular tension and mechanotransduction to promote spread...
October 20, 2016: Cell
Roshini Fernando, Ekaterina Placzek, Edmund A Reese, Andrew T Placzek, Samantha Schwartz, Aaron Trierweiler, Leslie M Niziol, Stephen Atkins, Thomas S Scanlan, Terry J Smith
CONTEXT: The sources and biological impact of 3,3',5,5' tetraiodothyroacetic acid (TA4) are uncertain. CD34(+) fibrocytes express several proteins involved in the production of thyroid hormones. They infiltrate the orbit in Graves' disease (GD), an autoimmune process known as thyroid-associated ophthalmopathy. It appears that the thyrotropin receptor (TSHR) plays an important role in the pathogenesis of TAO. OBJECTIVE: To quantify levels of TA4 in healthy subjects and those with Graves' disease...
October 21, 2016: Journal of Clinical Endocrinology and Metabolism
Matteo Bonomo, Danilo Dini, Andrea Giacomo Marrani
The adsorption of I(-) and I3(-) anions, i.e. the two species constituting the most common redox couple of dye-sensitized solar cells (DSCs), onto the surface of screen-printed nanoporous NiO was studied by means of X-ray photoelectron spectroscopy (XPS). Mesoporous NiO films were deposited on transparent metallic fluorine-doped tin oxide (FTO) and polarized as working electrodes in a three-electrode cell with differently concentrated I(-)/I3(-) electrolytes to simulate the different conditions experienced by the NiO cathodes during the lifecycle of a p-type DSC (p-DSC) at those atomic sites not passivated by the dye...
October 21, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Shuchi K Talati, Haibo Zhai, G Page Kyle, M Granger Morgan, Pralit Patel, Lu Liu
This research assesses climate, technological, and policy impacts on consumptive water use from electricity generation in the Southwest over a planning horizon of nearly a century. We employed an integrated modeling framework taking into account feedbacks between climate change, air temperature and humidity, and consequent power plant water requirements. These direct impacts of climate change on water consumption by 2095 differ with technology improvements, cooling systems, and policy constraints, ranging from a 3%-7% increase over scenarios that do not incorporate ambient air impacts...
October 21, 2016: Environmental Science & Technology
Harshkumar H Patel, Matthew S Sigman
In this report, we describe the generation of remote allylic quater-nary stereocenters β, γ, and δ relative to a carbonyl in high enanti-oselectivity. We utilize the redox-relay Heck reaction between alkenyl triflates and acyclic trisubstituted alkenols of varying chain lengths. A wide array of terminal (E)-alkenyl triflates are suitable for this process. The utility of this functionalization is validated further by conversion of the products, via simple organic processes to access remotely functionalized chiral tertiary acid, amine and alcohol products...
October 21, 2016: Journal of the American Chemical Society
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