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https://www.readbyqxmd.com/read/27914058/osprey-predicts-resistance-mutations-using-positive-and-negative-computational-protein-design
#1
Adegoke Ojewole, Anna Lowegard, Pablo Gainza, Stephanie M Reeve, Ivelin Georgiev, Amy C Anderson, Bruce R Donald
Drug resistance in protein targets is an increasingly common phenomenon that reduces the efficacy of both existing and new antibiotics. However, knowledge of future resistance mutations during pre-clinical phases of drug development would enable the design of novel antibiotics that are robust against not only known resistant mutants, but also against those that have not yet been clinically observed. Computational structure-based protein design (CSPD) is a transformative field that enables the prediction of protein sequences with desired biochemical properties such as binding affinity and specificity to a target...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914018/encapsulation-of-%C3%AE-sitosterol-in-polyurethane-by-sol-gel-electrospinning
#2
Musarat Amina, Touseef Amna, Nawal Al-Musayeib, Sami A Zabin, M Shamshi Hassan, Myung-Seob Khil
Pristine β-sitosterol or in combination with other phytosterols is utilized in an array of enriched commercial foods. Considering the presence of β-sitosterol in different functional foods and its potential role in prevention and cure of neurodegenerative diseases, the aims of our investigation were to encapsulate β-sitosterol in nanofibers and to estimate influence of β-sitosterol on proliferation of fibroblasts. Electrospun nanofibers have widely been used as scaffolds to mimic natural extracellular matrix...
December 2, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27914000/from-transformation-to-metastasis-deconstructing-the-extracellular-matrix-in-breast-cancer
#3
Shelly Kaushik, Michael W Pickup, Valerie M Weaver
The extracellular matrix (ECM) is a guiding force that regulates various developmental stages of the breast. In addition to providing structural support for the cells, it mediates epithelial-stromal communication and provides cues for cell survival, proliferation, and differentiation. Perturbations in ECM architecture profoundly influence breast tumor progression and metastasis. Understanding how a dysregulated ECM can facilitate malignant transformation is crucial to designing treatments to effectively target the tumor microenvironment...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913906/synergistic-mitotoxicity-of-chloromethanes-and-fullerene-c60-nanoaggregates-in-daphnia-magna-midgut-epithelial-cells
#4
Mariana Seke, Milica Markelic, Arian Morina, Danica Jovic, Aleksandra Korac, Dragana Milicic, Aleksandar Djordjevic
Adsorption of non-polar compounds by suspended fullerene nanoaggregates (nC60) may enhance their toxicity and affect the fate, transformation, and transport of non-polar compounds in the environment. The potential of stable fullerene nanoaggregates as contaminant carriers in aqueous systems and the influence of chloromethanes (trichloromethane and dichloromethane) were studied on the midgut epithelial cells of Daphnia magna by light and electron microscopy. The size and shape of fullerene nanoaggregates were observed and measured using dynamic light scattering, transmission electron microscopy, and low vacuum scanning electron microscopy...
December 3, 2016: Protoplasma
https://www.readbyqxmd.com/read/27913891/biotransformation-of-2-4-dinitroanisole-by-a-fungal-penicillium-sp
#5
Hunter W Schroer, Kathryn L Langenfeld, Xueshu Li, Hans-Joachim Lehmler, Craig L Just
Insensitive munitions explosives are new formulations that are less prone to unintended detonation compared to traditional explosives. While these formulations have safety benefits, the individual constituents, such as 2,4-dinitroanisole (DNAN), have an unknown ecosystem fate with potentially toxic impacts to flora and fauna exposed to DNAN and/or its metabolites. Fungi may be useful in remediation and have been shown to degrade traditional nitroaromatic explosives, such as 2,4,6-trinitrotoluene and 2,4-dinitrotoluene, that are structurally similar to DNAN...
December 2, 2016: Biodegradation
https://www.readbyqxmd.com/read/27913847/patulin-transformation-products-and-last-intermediates-in-its-biosynthetic-pathway-e-and-z-ascladiol-are-not-toxic-to-human-cells
#6
Joanna Tannous, Selma P Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, André El Khoury, Ali Atoui, Ting Zhou, Roger Lteif, Isabelle P Oswald, Olivier Puel
Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913781/synchronous-microscopic-epstein-barr-virus-positive-diffuse-large-b-cell-lymphoma-of-the-adrenal-and-lymphoplasmacytic-lymphoma-de-novo-disease-or-transformation
#7
Mufaddal T Moonim, Alia Nasir, Jonathan Hubbard, Nicholas Ketley, Paul Fields
Lymphomas arising in the adrenal are rare, and to our knowledge, 2 cases of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (DLBCL) in an adrenal pseudocyst have been reported. We report an incidental EBV-positive DLBCL arising in an adrenal pseudocyst in a 58-year-old man with a 7-year history of lymphoplasmacytic lymphoma (LPL). The DLBCL was present in the fibrinous exudate, while the LPL resided in the cyst wall. The patient underwent de-roofing of the same cyst 3 years previously; review of histology revealed foci of LPL in the cyst wall, but not of DLBCL...
December 2, 2016: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27913729/qsea-modelling-of-genome-wide-dna-methylation-from-sequencing-enrichment-experiments
#8
Matthias Lienhard, Sabrina Grasse, Jana Rolff, Steffen Frese, Uwe Schirmer, Michael Becker, Stefan Börno, Bernd Timmermann, Lukas Chavez, Holger Sültmann, Gunda Leschber, Iduna Fichtner, Michal R Schweiger, Ralf Herwig
Genome-wide enrichment of methylated DNA followed by sequencing (MeDIP-seq) offers a reasonable compromise between experimental costs and genomic coverage. However, the computational analysis of these experiments is complex, and quantification of the enrichment signals in terms of absolute levels of methylation requires specific transformation. In this work, we present QSEA, Quantitative Sequence Enrichment Analysis, a comprehensive workflow for the modelling and subsequent quantification of MeDIP-seq data...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27913661/effects-of-exendin-4-on-the-intrarenal-renin-angiotensin-system-and-interstitial-fibrosis-in-unilateral-ureteral-obstruction-mice-exendin-4-and-unilateral-ureteral-obstruction
#9
Ying Le, Zongji Zheng, Junyu Xue, Mengling Cheng, Meiping Guan, Yaoming Xue
OBJECTIVE: The objective of this article is to investigate the renoprotecive effects of exendin-4 in a mouse model of unilateral ureteral obstruction (UUO) and explore the putative mechanisms. METHODS: Male Balbc mice underwent sham operation or UUO surgery, and then received intraperitoneal injection of vehicle or exendin-4, respectively. After 14 days, mice were sacrificed and the left kidneys were collected and analyzed by histology, immunohistochemistry, Western blot, quantitative real-time reverse transcription polymerase chain reaction, radioimmunoassay and enzyme-linked immunosorbent assay...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27913657/cost-benefit-analysis-of-telehealth-in-pre-hospital-care
#10
James R Langabeer, Tiffany Champagne-Langabeer, Diaa Alqusairi, Junghyun Kim, Adria Jackson, David Persse, Michael Gonzalez
OBJECTIVE: There has been very little use of telehealth in pre-hospital emergency medical services (EMS), yet the potential exists for this technology to transform the current delivery model. In this study, we explore the costs and benefits of one large telehealth EMS initiative. METHODS: Using a case-control study design and both micro- and gross-costing data from the Houston Fire Department EMS electronic patient care record system, we conducted a cost-benefit analysis (CBA) comparing costs with potential savings associated with patients treated through a telehealth-enabled intervention...
December 2, 2016: Journal of Telemedicine and Telecare
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#11
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#12
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913491/prognostic-factors-in-follicular-lymphoma-new-tools-to-personalize-risk
#13
Carla Casulo
Follicular lymphoma (FL) is the most common indolent lymphoma, and it has a long median overall survival (OS). However, the recent discovery of clinical and biological prognostic biomarkers in FL is shedding light on FL heterogeneity and the need for a precise and risk-stratified individual approach at diagnosis and relapse. Many FL patients who are asymptomatic with indolent disease can be vulnerable to the toxicity, emotional distress, and financial burden of overtreatment. Yet a subset of FL patients develop chemoresistance to standard chemoimmunotherapy, experience transformation to aggressive lymphoma and rapid progression, and represent the population most in need of novel therapies and curative approaches...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#14
Nicole Lamanna, Susan O'Brien
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913456/acute-promyelocytic-leukemia-preventing-early-complications-and-late-toxicities
#15
Sameem Abedin, Jessica K Altman
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#16
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27913366/deepr-a-convolutional-net-for-medical-records
#17
Phuoc Nguyen, Truyen Tran, Nilmini Wickramasinghe, Svetha Venkatesh
Feature engineering remains a major bottleneck when creating predictive systems from electronic medical records. At present, an important missing element is detecting predictive regular clinical motifs from irregular episodic records. We present Deepr (short for Deep record), a new end-to-end deep learning system that learns to extract features from medical records and predicts future risk automatically. Deepr transforms a record into a sequence of discrete elements separated by coded time gaps and hospital transfers...
December 1, 2016: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/27913350/guided-wavelet-shrinkage-for-edge-aware-smoothing
#18
Guang Deng
Edge-aware smoothing has been extensively studied due to its wide range of applications in computer vision and graphics.Most published works have been focused on formulating the smoothing problem in the spatial domain. In this paper, we propose a new edge-aware smoothing framework called guided wavelet shrinkage (GWS) which is formulated in the wavelet domain as a maximum a posterior estimation problem. We impose a number of desirable properties on the statistical models and the associated parameters in order to derive an effective and computationally efficient algorithm...
December 1, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/27913344/perceptual-image-fusion-using-wavelets
#19
Paul Hill, Mohammed Ebrahim Al-Mualla, David Bull
A perceptual image fusion method is proposed that employs explicit luminance and contrast masking models. These models are combined to give the perceptual importance of each coefficient produced by the Dual-Tree Complex Wavelet Transform of each input image. This combined model of perceptual importance is used to select which coefficients are retained and furthermore to determine how to present the retained information in the most effective way. This work is the first to give a principled approach to image fusion from a perceptual perspective...
December 1, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/27913336/local-spectral-analysis-of-the-cerebral-cortex-new-gyrification-indices
#20
Hamed Rabiei, Frederic Richard, Olivier Coulon, Julien Lefevre
Gyrification index (GI) is an appropriate measure to quantify the complexity of the cerebral cortex. There is, however, no universal agreement on the notion of surface complexity and there are various methods in literature that evaluate different aspects of cortical folding. In this paper, we give two intuitive interpretations on folding quantification based on the magnitude and variation of the mean curvature of the cortical surface. We then present a local spectral analysis of the mean curvature to introduce two local gyrification indices that satisfy our interpretations...
November 29, 2016: IEEE Transactions on Medical Imaging
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