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Michael A. Adams

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https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#1
Adam Marc Levinson, John H McGee, Andrew G Roberts, Gardner Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered 'undruggable' due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-L- and all-D-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
April 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28448042/imaging-the-neutrophil-phagosome-and-cytoplasm-using-a-ratiometric-ph-indicator
#2
Juliet R Foote, Adam P Levine, Philippe Behe, Michael R Duchen, Anthony W Segal
Neutrophils are crucial to host innate defense and, consequently, constitute an important area of medical research. The phagosome, the intracellular compartment where the killing and digestion of engulfed particles take place, is the main arena for neutrophil pathogen killing that requires tight regulation. Phagosomal pH is one aspect that is carefully controlled, in turn regulating antimicrobial protease activity. Many fluorescent pH-sensitive dyes have been used to visualize the phagosomal environment. S-1 has several advantages over other pH-sensitive dyes, including its dual emission spectra, its resistance to photo-bleaching, and its high pKa...
April 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447278/invasiveness-is-associated-with-metastasis-and-decreased-survival-in-hemangiopericytoma-of-the-central-nervous-system
#3
Connor J Kinslow, Raj S Rajpara, Cheng-Chia Wu, Samuel S Bruce, Peter D Canoll, Shih-Hsiu Wang, Adam M Sonabend, Sameer A Sheth, Guy M McKhann, Michael B Sisti, Jeffrey N Bruce, Tony J C Wang
Meningeal hemangiopericytoma (m-HPC) is a rare tumor of the central nervous system (CNS), which is distinguished clinically from meningioma by its tendency to recur and metastasize. The histological classification and grading scheme for m-HPC is still evolving and few studies have identified tumor features that are associated with metastasis. All patients at our institution with m-HPC were assessed for patient, tumor, and treatment characteristics associated with survival, recurrence, and metastasis. New findings were validated using the SEER database...
April 26, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28446642/co-targeting-mtorc-and-egfr-signaling-as-a-therapeutic-strategy-in-hnscc
#4
Adam D Swick, Prashanth J Prabakaran, Margot C Miller, Amal M Javaid, Michael M Fisher, Emmanuel Sampene, Irene M Ong, Rong Hu, Mari Iida, Kwangok P Nickel, Justine Y Bruce, Deric L Wheeler, Randall J Kimple
Head and neck squamous cell carcinomas (HNSCCs) are frequently altered along the PI3K/AKT/mTORC signaling axis. Despite excellent preclinical data, the use of compounds targeting this pathway as monotherapy has been underwhelming in initial clinical trials and identification of predictive biomarkers remains challenging. To investigate mTORC specific inhibition we tested catalytic mTORC (AZD8055) and PI3K/mTORC (NVP-BEZ-235) inhibitors +/- cetuximab in a panel of HNSCC cell lines and patient derived xenografts (PDX)...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28445744/nmrbox-a-resource-for-biomolecular-nmr-computation
#5
Mark W Maciejewski, Adam D Schuyler, Michael R Gryk, Ion I Moraru, Pedro R Romero, Eldon L Ulrich, Hamid R Eghbalnia, Miron Livny, Frank Delaglio, Jeffrey C Hoch
Advances in computation have been enabling many recent advances in biomolecular applications of NMR. Due to the wide diversity of applications of NMR, the number and variety of software packages for processing and analyzing NMR data is quite large, with labs relying on dozens, if not hundreds of software packages. Discovery, acquisition, installation, and maintenance of all these packages is a burdensome task. Because the majority of software packages originate in academic labs, persistence of the software is compromised when developers graduate, funding ceases, or investigators turn to other projects...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28441640/lack-of-association-between-limb-hemodynamics-and-response-to-infrapopliteal-endovascular-therapy-in-patients-with-critical-limb-ischemia
#6
J A Mustapha, Larry J Diaz-Sandoval, George Adams, Michael R Jaff, Robert Beasley, Theresa McGoff, Sara Finton, Larry E Miller, Mohammad Ansari, Fadi Saab
BACKGROUND: Non-invasive limb hemodynamics may aid in diagnosis of critical limb ischemia (CLI), although the relationship with disease severity and response to endovascular therapy is unclear. METHODS AND RESULTS: This prospective, single-center study enrolled 100 CLI patients (Rutherford class 4-6) who underwent infrapopliteal endovascular revascularization (175 lesions) in the Peripheral RegIstry of Endovascular Clinical OutcoMEs (PRIME) registry. Hemodynamic measures included ankle-brachial index (ABI), toe-brachial index (TBI), and toe pressure (TP)...
May 2017: Journal of Invasive Cardiology
https://www.readbyqxmd.com/read/28440318/corrigendum-proteogenomic-integration-reveals-therapeutic-targets-in-breast-cancer-xenografts
#7
Kuan-Lin Huang, Shunqiang Li, Philipp Mertins, Song Cao, Harsha P Gunawardena, Kelly V Ruggles, D R Mani, Karl R Clauser, Maki Tanioka, Jerry Usary, Shyam M Kavuri, Ling Xie, Christopher Yoon, Jana W Qiao, John Wrobel, Matthew A Wyczalkowski, Petra Erdmann-Gilmore, Jacqueline E Snider, Jeremy Hoog, Purba Singh, Beifang Niu, Zhanfang Guo, Sam Qiancheng Sun, Souzan Sanati, Emily Kawaler, Xuya Wang, Adam Scott, Kai Ye, Michael D McLellan, Michael C Wendl, Anna Malovannaya, Jason M Held, Michael A Gillette, David Fenyö, Christopher R Kinsinger, Mehdi Mesri, Henry Rodriguez, Sherri R Davies, Charles M Perou, Cynthia Ma, R Reid Townsend, Xian Chen, Steven A Carr, Matthew J Ellis, Li Ding
No abstract text is available yet for this article.
April 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28439025/endocrine-network-essential-for-reproductive-success-in-drosophila-melanogaster
#8
Matthew Meiselman, Sang Soo Lee, Raymond-Tan Tran, Hongjiu Dai, Yike Ding, Crisalejandra Rivera-Perez, Thilini P Wijesekera, Brigitte Dauwalder, Fernando Gabriel Noriega, Michael E Adams
Ecdysis-triggering hormone (ETH) was originally discovered and characterized as a molt termination signal in insects through its regulation of the ecdysis sequence. Here we report that ETH persists in adult Drosophila melanogaster, where it functions as an obligatory allatotropin to promote juvenile hormone (JH) production and reproduction. ETH signaling deficits lead to sharply reduced JH levels and consequent reductions of ovary size, egg production, and yolk deposition in mature oocytes. Expression of ETH and ETH receptor genes is in turn dependent on ecdysone (20E)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436654/crystal-phase-transitions-and-photocatalysis-in-supramolecular-scaffolds
#9
Roman V Kazantsev, Adam J Dannenhoffer, Adam S Weingarten, Brian T Phelan, Boris Harutyunyan, Taner Aytun, Ashwin Narayanan, Daniel J Fairfield, Job Boekhoven, Hiroaki Sai, Andrew Senesi, Pascual I O'Dogherty, Liam C Palmer, Michael J Bedzyk, Michael R Wasielewski, Samuel I Stupp
The energy landscape of a supramolecular material can include different molecular packing configurations that differ in stability and function. We report here on a thermally driven crystalline order transition in the landscape of supramolecular nanostructures formed by charged chromophore amphiphiles in salt-containing aqueous solutions. An irreversible transition was observed from a metastable to a stable crystal phase within the nanostructures. In the stable crystalline phase, the molecules end up organized in a short scroll morphology at high ionic strengths and as long helical ribbons at lower salt content...
April 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28435441/comment-on-haig-et%C3%A2-al-the-conservation-genetics-juggling-act-integrating-genetics-and-ecology-science-and-policy
#10
Christian T Smith, Brice Adams, Meredith Bartron, Mary K Burnham-Curtis, Emy Monroe, Jeffrey B Olsen, Wade D Wilson, Ashantye' Williams, Michael J Millard, Molly A H Webb, John K Wenburg
No abstract text is available yet for this article.
June 2016: Evolutionary Applications
https://www.readbyqxmd.com/read/28434095/patient-reported-outcomes-in-cancer-survivors-a-population-wide-cross-sectional-study
#11
Michael Jefford, Andrew C Ward, Karolina Lisy, Karen Lacey, Jon D Emery, Adam W Glaser, Hannah Cross, Mei Krishnasamy, Sue-Anne McLachlan, Jim Bishop
PURPOSE: There is a lack of robust population-based data regarding the lived experience of cancer survivors. This study assessed the quality of life (QoL) of survivors of breast, colorectal, or prostate cancer, non-Hodgkin lymphoma or melanoma 1, 3 and 5 years post-diagnosis. Associations between various demographic and disease-related factors and QoL were assessed. METHODS: A cross-sectional postal survey was undertaken. Eligible participants were identified from a population-based cancer registry...
April 22, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28430697/abusive-head-trauma-and-mortality-an-analysis-from-an-international-comparative-effectiveness-study-of-children-with-severe-traumatic-brain-injury
#12
Nikki Miller Ferguson, Ajit Sarnaik, Darryl Miles, Nadeem Shafi, Mark J Peters, Edward Truemper, Monica S Vavilala, Michael J Bell, Stephen R Wisniewski, James F Luther, Adam L Hartman, Patrick M Kochanek
OBJECTIVES: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design...
April 20, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28429707/the-human-amygdala-parametrically-encodes-the-intensity-of-specific-facial-emotions-and-their-categorical-ambiguity
#13
Shuo Wang, Rongjun Yu, J Michael Tyszka, Shanshan Zhen, Christopher Kovach, Sai Sun, Yi Huang, Rene Hurlemann, Ian B Ross, Jeffrey M Chung, Adam N Mamelak, Ralph Adolphs, Ueli Rutishauser
The human amygdala is a key structure for processing emotional facial expressions, but it remains unclear what aspects of emotion are processed. We investigated this question with three different approaches: behavioural analysis of 3 amygdala lesion patients, neuroimaging of 19 healthy adults, and single-neuron recordings in 9 neurosurgical patients. The lesion patients showed a shift in behavioural sensitivity to fear, and amygdala BOLD responses were modulated by both fear and emotion ambiguity (the uncertainty that a facial expression is categorized as fearful or happy)...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429401/synthesis-of-l-threitol-based-crown-ethers-and-their-application-as-enantioselective-phase-transfer-catalyst-in-michael-additions
#14
Zsolt Rapi, Tamás Nemcsok, Ádám Pálvölgyi, György Keglevich, Alajos Grün, Péter Bakó
A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively)...
April 21, 2017: Chirality
https://www.readbyqxmd.com/read/28429253/modified-metformin-as-a-more-potent-anticancer-drug-mitochondrial-inhibition-redox-signaling-antiproliferative-effects-and-future-epr-studies
#15
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael B Dwinell
Metformin, one of the most widely prescribed antidiabetic drugs in the world, is being repurposed as a potential drug in cancer treatment. Epidemiological studies suggest that metformin exerts anticancer effects in diabetic patients with pancreatic cancer. However, at typical antidiabetic doses the bioavailability of metformin is presumably too low to exert antitumor effects. Thus, more potent analogs of metformin are needed in order to increase its anticancer efficacy. To this end, a new class of mitochondria-targeted metformin analogs (or mito-metformins) containing a positively-charged lipophilic triphenylphosphonium group was synthesized and tested for their antitumor efficacy in pancreatic cancer cells...
April 21, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28426940/prospective-assessment-of-virtual-screening-heuristics-derived-using-a-novel-fusion-score
#16
Dante A Pertusi, Gregory O'Donnell, Michelle F Homsher, Kelli Solly, Amita Patel, Shannon L Stahler, Daniel Riley, Michael F Finley, Eleftheria N Finger, Gregory C Adam, Juncai Meng, David J Bell, Paul D Zuck, Edward M Hudak, Michael J Weber, Jennifer E Nothstein, Louis Locco, Carissa Quinn, Adam Amoss, Brian Squadroni, Michelle Hartnett, Mee Ra Heo, Tara White, S Alex May, Evelyn Boots, Kenneth Roberts, Patrick Cocchiarella, Alex Wolicki, Anthony Kreamer, Peter S Kutchukian, Anne Mai Wassermann, Victor N Uebele, Meir Glick, Andrew Rusinko, J Christopher Culberson
High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28425714/prehydrated-one-electron-attachment-to-azido-modified-pentafuranoses-aminyl-radical-formation-rapid-h-atom-transfer-and-subsequent-ring-opening
#17
Mukesh Mudgal, Sunny Rishi, Daniel A Lumpuy, Keaton A Curran, Kathryn Lynn Verley, Adam J Sobczak, Thao P Dang, Natasha Sulimoff, Anil Kumar, Michael D Sevilla, Stanislaw F Wnuk, Amitava Adhikary
Methyl 2-azido-2-deoxy-α-D-lyxofuranoside (1a) and methyl 2-azido-2-deoxy-β-D-ribofuranoside (2) were prepared from D-xylose or D-arabinose, respectively. Employing ESR and DFT/B3LYP/6-31G* calculations, we investigated (i) aminyl radical (RNH•) formation and (ii) reaction pathways of RNH•. Prehydrated electron attachment to 1a and 2 at 77 K produced transient azide anion radical (RN3•¯) which reacts via rapid N2 loss at 77 K, forming nitrene anion radical (RN•¯). Rapid protonation of RN•¯ at 77 K formed RNH• and ¯OH...
April 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28423041/modeling-the-shape-and-composition-of-the-human-body-using-dual-energy-x-ray-absorptiometry-images
#18
John A Shepherd, Bennett K Ng, Bo Fan, Ann V Schwartz, Peggy Cawthon, Steven R Cummings, Stephen Kritchevsky, Michael Nevitt, Adam Santanasto, Timothy F Cootes
There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study...
2017: PloS One
https://www.readbyqxmd.com/read/28422537/morbidity-and-mortality-associated-with-prehospital-lift-assist-calls
#19
Lauren Leggatt, Kristine Van Aarsen, Melanie Columbus, Adam Dukelow, Michael Lewell, Matthew Davis, Shelley McLeod
INTRODUCTION: When an individual requires assistance with mobilization, emergency medical services (EMS) may be called. If a patient does not receive treatment on scene and is not transported to hospital, these are referred to as "Lift Assist" (LA) calls. It is possible this need for assistance represents a subtle onset of a disease process or decline in function. Without recognition or treatment, the patient may be at risk for recurrent falls, repeat EMS visits or worsening illness. OBJECTIVE: To examine the 14-day morbidity and mortality associated with LA calls and determine factors that are associated with increased risk of these outcomes...
April 19, 2017: Prehospital Emergency Care
https://www.readbyqxmd.com/read/28422278/decipher-test-impacts-decision-making-among-patients-considering-adjuvant-and-salvage-treatment-after-radical-prostatectomy-interim-results-from-the-multicenter-prospective-pro-impact-study
#20
John L Gore, Marguerite du Plessis, María Santiago-Jiménez, Kasra Yousefi, Darby J S Thompson, Lawrence Karsh, Brian R Lane, Michael Franks, David Y T Chen, Mark Bandyk, Fernando J Bianco, Gordon Brown, William Clark, Adam S Kibel, Hyung L Kim, William Lowrance, Murugesan Manoharan, Paul Maroni, Scott Perrapato, Paul Sieber, Edouard J Trabulsi, Robert Waterhouse, Elai Davicioni, Yair Lotan, Daniel W Lin
BACKGROUND: Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS: A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results...
April 19, 2017: Cancer
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