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https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#1
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29347996/the-apathy-in-dementia-methylphenidate-trial-2-admet-2-study-protocol-for-a-randomized-controlled-trial
#2
Roberta W Scherer, Lea Drye, Jacobo Mintzer, Krista Lanctôt, Paul Rosenberg, Nathan Herrmann, Prasad Padala, Olga Brawman-Mintzer, William Burke, Suzanne Craft, Alan J Lerner, Allan Levey, Anton Porsteinsson, Christopher H van Dyck
BACKGROUND: Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events...
January 18, 2018: Trials
https://www.readbyqxmd.com/read/29339543/genes-predisposed-to-dna-hypermethylation-during-acquired-resistance-to-chemotherapy-are-identified-in-ovarian-tumors-by-bivalent-chromatin-domains-at-initial-diagnosis
#3
Edward Curry, Constanze Zeller, Nahal Masrour, Darren Patten, John Gallon, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D L Bowtell, Robert Brown
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells aberrantly poised genes may facilitate changes in transcriptional states after exposure to anti-cancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339013/the-use-of-telemental-health-to-meet-the-mental-health-needs-of-women-using-department-of-veterans-affairs-services
#4
Jessica L Moreau, Kristina M Cordasco, Alexander S Young, Sabine M Oishi, Danielle E Rose, Ismelda Canelo, Elizabeth M Yano, Sally G Haskell, Alison B Hamilton
BACKGROUND: Women veterans are a growing segment of Department of Veterans Affairs (VA) users with distinct mental health needs and well-documented barriers to care. Telemental health holds much promise for reducing barriers to mental health care. We assessed VA stakeholders' perceptions of telemental health's appropriateness and potential to address the mental health needs of women veteran VA users. METHODS: We conducted semistructured qualitative interviews with 40 key leadership and clinical stakeholders at VA medical centers and associated outpatient clinics...
January 12, 2018: Women's Health Issues: Official Publication of the Jacobs Institute of Women's Health
https://www.readbyqxmd.com/read/29335493/biophysical-feedbacks-mediate-carbonate-chemistry-in-coastal-ecosystems-across-spatiotemporal-gradients
#5
Nyssa J Silbiger, Cascade J B Sorte
Ocean acidification (OA) projections are primarily based on open ocean environments, despite the ecological importance of coastal systems in which carbonate dynamics are fundamentally different. Using temperate tide pools as a natural laboratory, we quantified the relative contribution of community composition, ecosystem metabolism, and physical attributes to spatiotemporal variability in carbonate chemistry. We found that biological processes were the primary drivers of local pH conditions. Specifically, non-encrusting producer-dominated systems had the highest and most variable pH environments and the highest production rates, patterns that were consistent across sites spanning 11° of latitude and encompassing multiple gradients of natural variability...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328962/so-you-think-computational-approaches-to-understanding-glycosaminoglycan-protein-interactions-are-too-dry-and-too-rigid-think-again
#6
REVIEW
Nehru Viji Sankaranarayanan, Balaji Nagarajan, Umesh R Desai
Glycosaminoglycans (GAGs) play key roles in virtually all biologic responses through their interaction with proteins. A major challenge in understanding these roles is their massive structural complexity. Computational approaches are extremely useful in navigating this bottleneck and, in some cases, the only avenue to gain comprehensive insight. We discuss the state-of-the-art on computational approaches and present a flowchart to help answer most basic, and some advanced, questions on GAG-protein interactions...
January 9, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29326053/molecular-analysis-of-circulating-tumors-cells-biomarkers-beyond-enumeration
#7
William L Hwang, Haley M Pleskow, David T Miyamoto
Advances in our molecular understanding of cancer biology have paved the way to an expanding compendium of molecularly-targeted therapies, accompanied by the urgent need for biomarkers that enable the precise selection of the most appropriate therapies for individual cancer patients. Circulating biomarkers such as circulating tumor cells (CTCs) are poised to fill this need, since they are "liquid biopsies" that can be performed non-invasively and serially, and may capture the spectrum of spatial and temporal tumor heterogeneity better than conventional tissue biopsies...
January 8, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29321555/fourier-transform-infrared-microscopy-enables-guidance-of-automated-mass-spectrometry-imaging-to-predefined-tissue-morphologies
#8
Jan-Hinrich Rabe, Denis A Sammour, Sandra Schulz, Bogdan Munteanu, Martina Ott, Katharina Ochs, Peter Hohenberger, Alexander Marx, Michael Platten, Christiane A Opitz, Daniel S Ory, Carsten Hopf
Multimodal imaging combines complementary platforms for spatially resolved tissue analysis that are poised for application in life science and personalized medicine. Unlike established clinical in vivo multimodality imaging, automated workflows for in-depth multimodal molecular ex vivo tissue analysis that combine the speed and ease of spectroscopic imaging with molecular details provided by mass spectrometry imaging (MSI) are lagging behind. Here, we present an integrated approach that utilizes non-destructive Fourier transform infrared (FTIR) microscopy and matrix assisted laser desorption/ionization (MALDI) MSI for analysing single-slide tissue specimen...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320630/structural-insight-into-the-discrimination-between-8-oxoguanine-glycosidic-conformers-by-dna-repair-enzymes-a-molecular-dynamics-study-of-hogg1-and-fpg
#9
Shahin Sowlati-Hashjin, Stacey D Wetmore
hOgg1 and FPG are the primary DNA repair enzymes responsible for removing the major guanine oxidative product (G), namely 7,8-dihydro-8-oxoguanine (OG), in humans and bacteria, respectively. While natural G adopts the anti conformation and forms a Watson-Crick pair with cytosine (C), OG can also adopt the syn conformation and form a Hoogsteen pair with adenine (A). hOgg1 removes OG paired with C, but is inactive toward the OG:A pair. In contrast, FPG removes OG from OG:C pairs, and also exhibits appreciable (although diminished) activity toward OG:A pairs...
January 10, 2018: Biochemistry
https://www.readbyqxmd.com/read/29313063/using-gene-expression-data-to-direct-breast-cancer-therapy-evidence-from-a-preclinical-trial
#10
REVIEW
Shams Reaz, Deimante Tamkus, Eran R Andrechek
The heterogeneity both within and between breast cancers presents a significant clinical challenge for both diagnosis and therapy. This heterogeneity is present at all levels of analysis in breast cancer, ranging from genomic to metabolomic. A function of this heterogeneity is that numerous signaling networks are activated, and while treatment of one arm may be initially effective, this allows the tumor to be poised to evolve a resistance mechanism. Here we review the classification of breast cancers and discuss therapy of hormone positive, HER2 positive, and triple negative breast cancers...
January 8, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29311627/evolution-of-higher-torque-in-campylobacter-type-bacterial-flagellar-motors
#11
Bonnie Chaban, Izaak Coleman, Morgan Beeby
Understanding the evolution of molecular machines underpins our understanding of the development of life on earth. A well-studied case are bacterial flagellar motors that spin helical propellers for bacterial motility. Diverse motors produce different torques, but how this diversity evolved remains unknown. To gain insights into evolution of the high-torque ε-proteobacterial motor exemplified by the Campylobacter jejuni motor, we inferred ancestral states by combining phylogenetics, electron cryotomography, and motility assays to characterize motors from Wolinella succinogenes, Arcobacter butzleri and Bdellovibrio bacteriovorus...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310515/persons-with-chronic-spinal-cord-injury-have-decreased-nk-cell-and-increased-tlr-inflammatory-gene-expression
#12
Paige Herman, Adam B Stein, Katie Gibbs, Ilya Korsunsky, Peter Gregersen, Ona Bloom
Infections are the leading cause of death for individuals with traumatic spinal cord injury (SCI). Along with increased infection rates, inflammation is often also observed in persons with chronic SCI. Together, immunological changes after SCI are also poised to impede neurological recovery and to mediate common medical consequences of SCI, including atherogenesis and neuropathic pain. The molecular mechanisms contributing to increased infection susceptibility and inflammation in persons living with SCI are poorly understood...
January 8, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29302059/trithorax-dependent-changes-in-chromatin-landscape-at-enhancer-and-promoter-regions-drive-female-puberty
#13
Carlos A Toro, Hollis Wright, Carlos F Aylwin, Sergio R Ojeda, Alejandro Lomniczi
Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Here we identify two members of the Trithorax group (TrxG) of modifiers, mixed-lineage leukemia 1 (MLL1), and 3 (MLL3), as central components of an activating epigenetic machinery that dynamically counteracts PcG repression. Preceding puberty, MLL1 changes the chromatin configuration at the promoters of Kiss1 and Tac3, two genes required for puberty to occur, from repressive to permissive...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29298683/global-accumulation-of-circrnas-during-aging-in-caenorhabditis-elegans
#14
Mariela Cortés-López, Matthew R Gruner, Daphne A Cooper, Hannah N Gruner, Alexandru-Ioan Voda, Alexander M van der Linden, Pedro Miura
BACKGROUND: Circular RNAs (CircRNAs) are a newly appreciated class of RNAs that lack free 5' and 3' ends, are expressed by the thousands in diverse forms of life, and are mostly of enigmatic function. Ostensibly due to their resistance to exonucleases, circRNAs are known to be exceptionally stable. Previous work in Drosophila and mice have shown that circRNAs increase during aging in neural tissues. RESULTS: Here, we examined the global profile of circRNAs in C...
January 3, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29290797/engineered-microenvironments-for-maturation-of-stem-cell-derived-cardiac-myocytes
#15
Rachel R Besser, Matthew Ishahak, Vera Mayo, Daniel Carbonero, Isabella Claure, Ashutosh Agarwal
Through the use of stem cell-derived cardiac myocytes, tissue-engineered human myocardial constructs are poised for modeling normal and diseased physiology of the heart, as well as discovery of novel drugs and therapeutic targets in a human relevant manner. This review highlights the recent bioengineering efforts to recapitulate microenvironmental cues to further the maturation state of newly differentiated cardiac myocytes. These techniques include long-term culture, co-culture, exposure to mechanical stimuli, 3D culture, cell-matrix interactions, and electrical stimulation...
2018: Theranostics
https://www.readbyqxmd.com/read/29288323/impact-of-holistic-review-on-student-interview-pool-diversity
#16
Christina J Grabowski
Diversity in the physician workforce lags behind the rapidly changing US population. Since the gateway to becoming a physician is medical school, diversity must be addressed in the admissions process. The Association of American Medical Colleges has implemented a Holistic Review Initiative aimed at assisting medical schools with broadening admission criteria to include relevant, mission-driven attributes and experiences in addition to academic preparation to identify applicants poised to meet the needs of a diverse patient population...
December 29, 2017: Advances in Health Sciences Education: Theory and Practice
https://www.readbyqxmd.com/read/29287474/practical-considerations-challenges-and-limitations-of-bioconjugation-via-azide-alkyne-cycloaddition
#17
Chad J Pickens, Stephanie N Johnson, Melissa M Pressnall, Martin Leon, Cory Berkland
Interrogating biological systems is often limited by access to biological probes. The emergence of "click chemistry" has revolutionized bioconjugate chemistry by providing facile reaction conditions amenable to both biologic molecules and small molecule probes such as fluorophores, toxins, or therapeutics. One particularly popular version is the copper-catalyzed azide-alkyne cycloaddition (AAC) reaction, which has spawned new alternatives such as the strain-promoted azide-alkyne cycloaddition reaction, among others...
December 29, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29286556/total-synthesis-of-%C3%A2-phomoidride-d
#18
Joyce C Leung, Aaron A Bedermann, Jón T Njardarson, David A Spiegel, Graham K Murphy, Naoto Hama, Barry M Twenter, Ping Dong, Tatsuya Shirahata, Ivar M McDonald, Munenori Inoue, Nobuaki Taniguchi, Travis C McMahon, Christopher M Schneider, Nancy Tao, Brian M Stoltz, John Wood
Described herein is a synthetic strategy for the total synthesis of phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.
December 29, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29282501/confirmatory-surface-analysis-of-equivocal-documents-with-pigment-based-gel-inks-via-laser-desorption-laser-postionization-mass-spectrometry-imaging
#19
Rong Liu, Zhibin Yin, Xiaoling Cheng, Yifan Meng, Wei Hang, Benli Huang
Laser desorption laser postionization time-of-flight mass spectrometry (L2MS) was applied for unambiguous discrimination of pigment-based inks in blue, black, and red gel pens and molecular imaging of equivocal documents in a quasi-non-destructive way. In comparison to laser desorption mass spectrometry (LD-MS), additional discriminatory information on ink components is acquired uniquely, facilitating the distinct differentiation of various pigmented gel inks. More importantly, diversified images of additional characteristic ions achieved using L2MS offer reliable support to discriminate forged documents and decipher important hidden contents...
December 28, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29277660/properties-and-mechanism-of-d-glucosaminate-6-phosphate-ammonia-lyase-an-aminotransferase-family-enzyme-with-d-amino-acid-specificity
#20
Robert S Phillips, Samuel C Ting, Ange G Tetsadjio, Kaitlin L Anderson, Kyle M Friez, Katherine A Miller, Timothy R Hoover
Salmonella enterica serovar Typhimurium utilizes a wide range of growth substrates, some of which are relatively novel. One of these unusual substrates is d-glucosaminate, which is metabolized by the enzymes encoded in the dga operon. d-Glucosaminate is transported and converted to d-glucosaminate-6-phosphate (G6P) by a phosphotransferase system, composed of DgaABCD. The protein product of dgaE, d-glucosaminate-6-phosphate ammonia lyase (DGL), converts G6P to 2-keto-3-deoxygluconate-6-phosphate, which undergoes a retroaldol reaction catalyzed by the DgaF protein to give d-glyceraldehyde-3-phosphate and pyruvate...
December 22, 2017: Biochimica et Biophysica Acta
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