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https://www.readbyqxmd.com/read/29774105/pre-clinical-activity-of-targeting-the-pi3k-akt-mtor-pathway-in-burkitt-lymphoma
#1
Maria Bhatti, Thomas Ippolito, Cory Mavis, Juan Gu, Mitchell S Cairo, Megan S Lim, Francisco Hernandez-Ilizaliturri, Matthew J Barth
Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been implicated in Burkitt lymphomagenesis and increased PI3K/AKT activation has been associated with worse outcomes in adults with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Inhibitors of the PI3K/AKT pathway have been approved for the treatment of refractory indolent B-NHL and continue to be investigated for treatment of aggressive B-NHLs...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29770420/selenium-species-dependent-toxicity-bioavailability-and-metabolic-transformations-in-caenorhabditis-elegans
#2
Isabelle Rohn, Talke Anu Marschall, Nina Kroepfl, Kenneth Bendix Jensen, Michael Aschner, Simon Tuck, Doris Kuehnelt, Tanja Schwerdtle, Julia Bornhorst
The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys)...
May 17, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29761397/quantitative-phagocytosis-assays-in-primary-and-cultured-macrophages
#3
Fernando Montaño, Sergio Grinstein, Roni Levin
This chapter describes methods to induce and quantify phagocytosis in primary macrophages and in myeloid cell lines. To this end, we initially detail the isolation of primary human monocytes and their differentiation into macrophages. Because primary cells are comparatively refractory to molecular manipulation, we also describe the culture of RAW 264.7 cells-an immortalized monocyte/macrophage cell line, which is more tractable. The chapter also includes methods for preparation of phagocytic targets, specifically sheep erythrocytes opsonized with immunoglobulin G (IgG), as well as means of distinguishing bound from internalized targets, using fluorescently labeled secondary antibodies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29760681/sex-steroids-adult-neurogenesis-and-inflammation-in-cns-homeostasis-degeneration-and-repair
#4
REVIEW
Tracy A Larson
Sex steroidal hormones coordinate the development and maintenance of tissue architecture in many organs, including the central nervous systems (CNS). Within the CNS, sex steroids regulate the morphology, physiology, and behavior of a wide variety of neural cells including, but not limited to, neurons, glia, endothelial cells, and immune cells. Sex steroids spatially and temporally control distinct molecular networks, that, in turn modulate neural activity, synaptic plasticity, growth factor expression and function, nutrient exchange, cellular proliferation, and apoptosis...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29760206/alternative-oxidase-activity-reduces-stress-in-vibrio-fischeri-cells-exposed-to-nitric-oxide
#5
Anne K Dunn
Alternative oxidase (Aox) is a non-energy conserving respiratory oxidase found in certain eukaryotes and bacteria, whose role in physiology is not entirely clear. Using the genetically tractable bacterium Vibrio fischeri as a model organism, we have identified a role for Aox to reduce levels of stress in cells exposed to oxygen and nitric oxide (NO). In V. fischeri lacking the NO-detoxifying enzyme flavohemoglobin (Hmp), deletion of aox in cells grown in the presence of oxygen and NO results in alterations to the transcriptome that include increases in transcripts mapping to stress-related genes...
May 14, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29760202/survey-of-human-chromosome-21-gene-expression-effects-on-early-development-in-danio-rerio
#6
Sarah Edie, Norann A Zaghloul, Carmen C Leitch, Donna K Klinedinst, Janette Lebron, Joey F Thole, Andrew S McCallion, Nicholas Katsanis, Roger H Reeves
Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS), one of the most genetically complex conditions compatible with human survival. Assessment of the physiological consequences of dosage-driven overexpression of individual Hsa21 genes during early embryogenesis and the resulting contributions to DS pathology in mammals are not tractable in a systematic way. A recent study looked loss-of-function of C. elegans orthologues of Hsa21 genes and identified ten candidates with behavioral phenotypes, but the equivalent over-expression experiment has not been done...
May 14, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29758649/framework-for-cascade-size-calculations-on-random-networks
#7
Rebekka Burkholz, Frank Schweitzer
We present a framework to calculate the cascade size evolution for a large class of cascade models on random network ensembles in the limit of infinite network size. Our method is exact and applies to network ensembles with almost arbitrary degree distribution, degree-degree correlations, and, in case of threshold models, for arbitrary threshold distribution. With our approach, we shift the perspective from the known branching process approximations to the iterative update of suitable probability distributions...
April 2018: Physical Review. E
https://www.readbyqxmd.com/read/29758626/balancing-selfishness-and-norm-conformity-can-explain-human-behavior-in-large-scale-prisoner-s-dilemma-games-and-can-poise-human-groups-near-criticality
#8
John Realpe-Gómez, Giulia Andrighetto, Luis Gustavo Nardin, Javier Antonio Montoya
Cooperation is central to the success of human societies as it is crucial for overcoming some of the most pressing social challenges of our time; still, how human cooperation is achieved and may persist is a main puzzle in the social and biological sciences. Recently, scholars have recognized the importance of social norms as solutions to major local and large-scale collective action problems, from the management of water resources to the reduction of smoking in public places to the change in fertility practices...
April 2018: Physical Review. E
https://www.readbyqxmd.com/read/29756929/anomalous-chained-turbulence-in-actively-driven-flows-on-spheres
#9
Oscar Mickelin, Jonasz Słomka, Keaton J Burns, Daniel Lecoanet, Geoffrey M Vasil, Luiz M Faria, Jörn Dunkel
Recent experiments demonstrate the importance of substrate curvature for actively forced fluid dynamics. Yet, the covariant formulation and analysis of continuum models for nonequilibrium flows on curved surfaces still poses theoretical challenges. Here, we introduce and study a generalized covariant Navier-Stokes model for fluid flows driven by active stresses in nonplanar geometries. The analytical tractability of the theory is demonstrated through exact stationary solutions for the case of a spherical bubble geometry...
April 20, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29755638/locally-adaptive-smoothing-with-markov-random-fields-and-shrinkage-priors
#10
James R Faulkner, Vladimir N Minin
We present a locally adaptive nonparametric curve fitting method that operates within a fully Bayesian framework. This method uses shrinkage priors to induce sparsity in order- k differences in the latent trend function, providing a combination of local adaptation and global control. Using a scale mixture of normals representation of shrinkage priors, we make explicit connections between our method and k th order Gaussian Markov random field smoothing. We call the resulting processes shrinkage prior Markov random fields (SPMRFs)...
March 2018: Bayesian Analysis
https://www.readbyqxmd.com/read/29752387/transfection-of-capsaspora-owczarzaki-a-close-unicellular-relative-of-animals
#11
Helena Parra-Acero, Núria Ros-Rocher, Alberto Perez-Posada, Aleksandra Kożyczkowska, Núria Sánchez-Pons, Azusa Nakata, Hiroshi Suga, Sebastián R Najle, Iñaki Ruiz-Trillo
How animals emerged from their unicellular ancestor remains a major evolutionary question. New genome data from the closest unicellular relatives of animals has provided important insights into animal origins. We know that the unicellular ancestor of animals had an unexpectedly complex genetic repertoire, including many genes key to animal development and multicellularity. Thus, assessing the function of these genes among unicellular relatives of animals is key to understand how were they co-opted at the onset of Metazoa...
May 11, 2018: Development
https://www.readbyqxmd.com/read/29752280/-drosophila-insulin-receptor-regulates-the-persistence-of-injury-induced-nociceptive-sensitization
#12
Seol Hee Im, Atit A Patel, Daniel N Cox, Michael J Galko
Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29751611/purification-and-characterization-of-recombinant-botulinum-neurotoxin-serotype-fa-also-known-as-serotype-h
#13
Gavin Hackett, Kevin Moore, David Burgin, Fraser Hornby, Bryony Gray, Mark Elliott, Imran Mir, Matthew Beard
We have purified and characterized recombinant botulinum neurotoxin serotype FA (BoNT/FA). This protein has also been named as a new serotype (serotype H), but the classification has been controversial. A lack of well-characterized, highly pure material has been a roadblock to study. Here we report purification and characterization of enzymatically active, and of inactive nontoxic, recombinant forms of BoNT/FA as tractable alternatives to purifying this neurotoxin from native Clostridium botulinum . BoNT/FA cleaves the same intracellular target proteins as BoNT/F1 and other F serotype BoNTs; the intracellular targets are vesicle associated membrane proteins (VAMP) 1, 2 and 3...
May 11, 2018: Toxins
https://www.readbyqxmd.com/read/29749693/modeling-the-complex-etiology-of-holoprosencephaly-in-mice
#14
Mingi Hong, Robert S Krauss
Holoprosencephaly (HPE) is a common developmental defect caused by failure to define the midline of the forebrain and/or midface. HPE is associated with heterozygous mutations in Nodal and Sonic hedgehog (SHH) pathway components, but clinical presentation is highly variable, and many mutation carriers are unaffected. It is therefore thought that such mutations interact with more common modifiers, genetic and/or environmental, to produce severe patterning defects. Modifiers are difficult to identify, as their effects are context-dependent and occur within the complex genetic and environmental landscapes that characterize human populations...
May 11, 2018: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/29748990/annual-temperature-variation-as-a-time-machine-to-understand-the-effects-of-long-term-climate-change-on-a-poleward-range-shift
#15
Sam Crickenberger, David S Wethey
Range shifts due to annual variation in temperature are more tractable than range shifts linked to decadal to century long temperature changes due to climate change, providing natural experiments to determine the mechanisms responsible for driving long-term distributional shifts. In this study we couple physiologically grounded mechanistic models with biogeographic surveys in two years with high levels of annual temperature variation to disentangle the drivers of a historical range shift driven by climate change...
May 10, 2018: Global Change Biology
https://www.readbyqxmd.com/read/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#16
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29748129/the-sarco-endo-plasmic-reticulum-calcium-atpase-sca-1-regulates-the-caenorhabditis-elegans-nicotinic-acetylcholine-receptor-acr-16
#17
Ashley A Martin, Janet E Richmond
Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances...
February 24, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29747866/understanding-taurine-cns-activity-using-alternative-zebrafish-models
#18
Nathana J Mezzomo, Barbara D Fontana, Allan V Kalueff, Leonardo J G Barcellos, Denis B Rosemberg
Taurine is a highly abundant "amino acid" in the brain. Although the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action...
May 7, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29747161/a-3d-human-renal-cell-carcinoma-on-a-chip-for-the-study-of-tumor-angiogenesis
#19
Chris P Miller, Connor Tsuchida, Ying Zheng, Jonathan Himmelfarb, Shreeram Akilesh
Tractable human tissue-engineered 3D models of cancer that enable fine control of tumor growth, metabolism, and reciprocal interactions between different cell types in the tumor microenvironment promise to accelerate cancer research and pharmacologic testing. Progress to date mostly reflects the use of immortalized cancer cell lines, and progression to primary patient-derived tumor cells is needed to realize the full potential of these platforms. For the first time, we report endothelial sprouting induced by primary patient tumor cells in a 3D microfluidic system...
May 7, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29746717/can-we-build-it-yes-we-can-but-should-we-use-it-assessing-the-quality-and-value-of-a-very-large-phylogeny-of-campanulid-angiosperms
#20
Jeremy M Beaulieu, Brian C O'Meara
PREMISE OF THE STUDY: The study of very large and very old clades holds the promise of greater insights into evolution across the tree of life. However, there has been a fair amount of criticism regarding the interpretations and quality of studies to date, with some suggesting that detailed studies carried out on smaller, tractable scales should be preferred over the increasingly grand syntheses of these data. METHODS: We provided in detail our trials and tribulations of compiling a large, sparsely sampled matrix from GenBank data and inferring a well-supported, time-calibrated phylogeny of Campanulidae...
March 2018: American Journal of Botany
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