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Michelle M Kim, Yoshie Umemura, Denise Leung
Glioblastoma (GBM) is the most common and lethal intracranial malignancy, with few advances in treatment over the last several decades. Much excitement surrounded the initial approval for bevacizumab for recurrent GBM, given the marked radiographic responses and improvement in progression-free survival observed in early studies. However, phase III studies have failed to demonstrate an overall survival advantage with the use of this agent. An overview of the mechanism of action and activity of bevacizumab in adult gliomas, a timeline of pivotal clinical trials, data on its impact on quality of life and imaging, and its role in managing the sequelae of treatment provide evidence for its current use...
July 2018: Cancer Journal
Sarmistha Talukdar, Anjan K Pradhan, Praveen Bhoopathi, Xue-Ning Shen, Laura A August, Jolene J Windle, Devanand Sarkar, Frank B Furnari, Webster K Cavenee, Swadesh K Das, Luni Emdad, Paul B Fisher
Glioblastoma multiforme (GBM) is a frequent and aggressive glial tumor, containing a small population of therapy-resistant cells, glioma stem cells (GSCs). Current dogma suggests that tumors regrow from GSCs, and these cells contribute to therapy resistance, poor prognosis, and recurrence; highlighting the importance of GSCs in glioma pathophysiology and therapeutic targeting. Macroautophagy/autophagy-based cellular homeostasis can be changed from pro-survival to pro-cell death by modulating SDCBP/MDA-9/Syntenin (syndecan binding protein)-mediated signaling...
August 17, 2018: Autophagy
Jiahua Jiang, Yanqiu Li, Shihuan Shen, Shanshan Mao
High-numerical-aperture (NA) anamorphic imaging projection objectives are the industrial choice for extreme ultraviolet lithography under the advanced technology node. The illumination system has to match the elliptical entrance pupil of the high-NA projector. In this paper, an illumination system suitable for a high-NA anamorphic projection objective is designed. The two-mirror relay system of the illumination system is designed by a two-stage process. The first-order initial configuration with spherical surfaces is calculated by a method based on matrix optics...
July 10, 2018: Applied Optics
Olga Pereira, Alexandra Teixeira, Belém Sampaio-Marques, Isabel Castro, Henrique Girão, Paula Ludovico
Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial...
August 17, 2018: Journal of Cellular and Molecular Medicine
Filippo Disanto, Noah A Rosenberg
Compact coalescent histories are combinatorial structures that describe for a given gene tree G and species tree S possibilities for the numbers of coalescences of G that take place on the various branches of S. They have been introduced as a data structure for evaluating probabilities of gene tree topologies conditioning on species trees, reducing computation time compared to standard coalescent histories. When gene trees and species trees have a matching labeled topology [Formula: see text], the compact coalescent histories of t are encoded by particular integer labelings of the branches of t, each integer specifying the number of coalescent events of G present in a branch of S...
August 16, 2018: Journal of Mathematical Biology
Koen A Marijt, Laura Blijleven, Els M E Verdegaal, Michel G Kester, Daniel J Kowalewski, Hans-Georg Rammensee, Stefan Stevanović, Mirjam H M Heemskerk, Sjoerd H van der Burg, Thorbald van Hall
Most T cell-based immunotherapies of cancer depend on intact antigen presentation by HLA class I molecules (HLA-I). However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8+ T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans...
August 16, 2018: Journal of Experimental Medicine
Marcos Malumbres
CDK4/6 inhibitors have shown a great potential in the new armamentarium against cancer. However, their effect as single agents is limited and the hopes are on new combinatory strategies. Recent data suggest that inhibiting mTOR may significantly cooperate with cell cycle arrest in a variety of cancers.
August 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hoon Lee, Inkyu Lee, Tony Q S Quek, Sang Hyun Lee
This paper develops a deep learning framework for the design of on-off keying (OOK) based binary signaling transceiver in dimmable visible light communication (VLC) systems. The dimming support for the OOK optical signal is achieved by adjusting the number of ones in a binary codeword, which boils down to a combinatorial design problem for the codebook of a constant weight code (CWC) over signal-dependent noise channels. To tackle this challenge, we employ an autoencoder (AE) approach to learn a neural network of the encoder-decoder pair that reconstructs the output identical to an input...
July 9, 2018: Optics Express
Amit N Pandya, Arshi B Baraiya, Hitesh B Jalani, Dhaivat Pandya, Jitendra C Kaila, Sonja Kachler, Veronica Salmaso, Stefano Moro, Karl-Norbert Klotz, Kamala K Vasu
A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl resin. The generated compound library was tested against all the human adenosine receptors subtypes. The 2-aminoimidazole derivatives ( 6a-6l ) showed weak to moderate affinity towards the human adenosine receptors. Further modification to 2-aminoimidazolyl-thiazole derivatives ( 12a-12l ) resulted in an improvement of affinity at adenosine A1 , A2A and A3 receptor subtypes...
April 1, 2018: MedChemComm
Nicholas Annetta, Jeffrey Friend, Andrew Schimmoeller, Vimal S Buck, David Friedenberg, Chad E Bouton, Marcia A Bockbrader, Patrick Ganzer, Sam Colachis, Mingming Zhang, W Jerry Mysiw, Ali R Rezai, Gaurav Sharma
OBJECTIVE: Paralysis resulting from spinal cord injury (SCI) can have a devastating effect on multiple arm and hand motor functions. Rotary hand movements, such as supination and pronation, are commonly impaired by upper extremity paralysis, and are essential for many activities of daily living. In this proof-of-concept study, we utilize a neural bypass system (NBS) to decode motor intention from motor cortex to control combinatorial rotary hand movements elicited through stimulation of the arm muscles, effectively bypassing the SCI of the study participant...
August 7, 2018: IEEE Transactions on Bio-medical Engineering
Zhi-Jie Han, Wei-Wei Xue, Lin Tao, Feng Zhu
AIMS: Alzheimer's disease (AD) is one of the leading causes of death in elderly people. Its pathogenesis is greatly associated with the abnormality of immune system. However, only a few immune-relevant AD drug target genes have been discovered up to now, and it is speculated that there are still many potential drug target genes of AD (at least immune-relevant genes) to be discovered. Thus, this study was designed to identify novel AD drug target genes and explore their biological properties...
August 14, 2018: CNS Neuroscience & Therapeutics
Wenlong Ma, Yanfeng Liu, Yue Wang, Xueqin Lv, Jianghua Li, Guocheng Du, Long Liu
Glucosamine-6-phosphate N-acetyltransferase (GNA1) that catalyzes acetyl transfer from acetyl-coenzyme A to glucosamine-6-phosphate (GlcN-6P), and glutamine-fructose-6- phosphate aminotransferase (GlmS) that catalyzes the formation of GlcN-6P from fructose-6-phosphate (Fru-6P), are two key enzymes in Bacillus subtilis for the bioproduction of N-acetylglucosamine (GlcNAc), a nutraceutical that has various applications in the healthcare. In this study, we fine-tuned the expression of GNA1 and GlmS by 5'-terminus fusion engineering to improve GlcNAc production...
August 14, 2018: Biotechnology Journal
Mohammed Shafi Sofi, M K Sateesh, Mohsin Bashir, Mohd Ashraf Ganie, Shabnum Nabi
The present study focuses on isolation and evaluation of the anti-cancer activity of compounds from the leaves of Abrus precatorius . The bioassay-directed strategy was adopted using chromatographic, gas chromatographic-mass spectrum analysis, nuclear magnetic resonance and X-ray crystallography techniques for purification and characterization of active cytotoxic compounds. Further, MDA-MB-231 breast cancer cell lines and 7,12-dimethylbenz (a) anthracene (DMBA) induced virgin female Sprague Dawley (SD) rats were used for in vitro and in vivo cytotoxicity evaluation...
August 2018: 3 Biotech
Rajat Vashistha, Arun Kumar Dangi, Ashwani Kumar, Deepak Chhabra, Pratyoosh Shukla
Biosensor-based devices are pioneering in the modern biomedical applications and will be the future of cardiac health care. The coupling of artificial intelligence (AI) for cardiac monitoring-based biosensors for the point of care (POC) diagnostics is prominently reviewed here. This review deciphers the most significant machine-learning algorithms for the futuristic biosensors along with the internet of things, computational techniques and microchip-based essential cardiac biomarkers for real-time health monitoring and improving patient compliance...
August 2018: 3 Biotech
Han Yao, Huanbin Wang, Chushu Li, Jing-Yuan Fang, Jie Xu
Programmed death 1 (PD-1) and its two natural ligands PD-L1 and PD-L2 are responsible for delivering inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. In previous studies, PD-1 was found only expressed on the surface of immune cells, such as T cells and B cells while PD-1's ligands PD-L1 and PD-L2 were found expressed in some tumor cells. However, recent studies revealed intrinsic expression of PD-1 in melanoma and some other cancers. In melanoma cells, PD-1 can be activated by its ligand PD-L1 expressed by tumor cells, modulating downstream mammalian target of rapamycin signaling and promoting tumor growth independent of adaptive immunity...
2018: Frontiers in Immunology
Anna M Wirth, Andrei Khomenko, Dobri Baldaranov, Ines Kobor, Ohnmar Hsam, Thomas Grimm, Siw Johannesen, Tim-Henrik Bruun, Wilhelm Schulte-Mattler, Mark W Greenlee, Ulrich Bogdahn
Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative process affecting upper and lower motor neurons as well as non-motor systems. In this study, precentral and postcentral cortical thinning detected by structural magnetic resonance imaging (MRI) were combined with clinical (ALS-specific functional rating scale revised, ALSFRS-R) and neurophysiological (motor unit number index, MUNIX) biomarkers in both cross-sectional and longitudinal analyses. Methods: The unicenter sample included 20 limb-onset classical ALS patients compared to 30 age-related healthy controls...
2018: Frontiers in Neurology
Jean-Francois Poulin, Giuliana Caronia, Caitlyn Hofer, Qiaoling Cui, Brandon Helm, Charu Ramakrishnan, C Savio Chan, Daniel A Dombeck, Karl Deisseroth, Rajeshwar Awatramani
Midbrain dopamine (DA) neurons have diverse functions that can in part be explained by their heterogeneity. Although molecularly distinct subtypes of DA neurons have been identified by single-cell gene expression profiling, fundamental features such as their projection patterns have not been elucidated. Progress in this regard has been hindered by the lack of genetic tools for studying DA neuron subtypes. Here we develop intersectional genetic labeling strategies, based on combinatorial gene expression, to map the projections of molecularly defined DA neuron subtypes...
August 13, 2018: Nature Neuroscience
Bei-Bei He, Xu-Liang Bu, Ting Zhou, Shu-Ming Li, Minjuan Xu, Jun Xu
Prenylated aromatic compounds are important intermediates in the biosynthesis of bioactive molecules such as secondary metabolites from plants, ubiquinone from prokaryotes and meroterpenoids from sponges. Biosynthesis of prenylated aromatic compounds using prokaryotic microorganisms has attracted increasing attention in the field of synthetic biology. In this study, we demonstrated that the production of 3-geranyl-4-hydroxybenzoic acid (GBA) and a variety of GBA analogs was feasible in a metabolically engineered E...
August 13, 2018: ACS Synthetic Biology
Jördis-Ann Schüler, Steffen Neumann, Matthias Müller-Hannemann, Wolfgang Brandt
Identification and structural determination of small molecules by mass spectrometry is an important step in chemistry and biochemistry. However, the chemically realistic annotation of a fragment ion spectrum can be a difficult challenge. We developed ChemFrag, for the detection of fragmentation pathways and the annotation of fragment ions with chemically reasonable structures. ChemFrag combines a quantum chemical with a rule-based approach. For different doping substances as test instances, ChemFrag correctly annotates fragment ions...
August 13, 2018: Journal of Mass Spectrometry: JMS
Swati Kumari, Ramona Gutkowski, Joao Junqueira, Aleksander Kostka, Katharina Hengge, Christina Scheu, Wolfgang Schuhmann, Alfred Ludwig
The search for suitable materials for solar water splitting is addressed with combinatorial material science methods. Thin film Fe-V-O materials libraries were synthesized using combinatorial reactive magnetron co-sputtering and subsequent annealing in air. The design of the libraries comprises a combination of large compositional gradients (from Fe10V90Ox to Fe79V21Ox) and thickness gradients (from 140 nm to 425 nm). These material libraries were investigated by high throughput characterization techniques in terms of composition, structure, optical and photoelectrochemical properties in order to establish correlations between composition, thickness, crystallinity, microstructure, and photocurrent density...
August 13, 2018: ACS Combinatorial Science
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