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https://www.readbyqxmd.com/read/29793041/-selenoproteins-in-colon-cancer
#1
REVIEW
Kristin M Peters, Bradley A Carlson, Vadim N Gladyshev, Petra A Tsuji
Selenocysteine-containing proteins (selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor-enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins...
May 21, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29792217/hypoargininemia-exacerbates-airway-hyperresponsiveness-in-a-mouse-model-of-asthma
#2
Roy H E Cloots, Matthew E Poynter, Els Terwindt, Wouter H Lamers, S Eleonore Köhler
BACKGROUND: Asthma is a chronic respiratory condition, with airway hyperresponsiveness (AHR) and inflammation as hallmarks. The hypothesis that the substantially increased expression of arginase 1 in activated macrophages limits the availability of L-arginine for nitric oxide synthesis, and thus increases AHR in lungs of mice with experimentally induced allergic asthma was recently refuted by several studies. In the present study, we tested the hypothesis that, instead, a low circulating concentration of arginine aggravates AHR in the same murine asthma model...
May 23, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29792157/long-term-health-and-germline-transmission-in-transgenic-cattle-following-transposon-mediated-gene-transfer
#3
Soo-Young Yum, Song-Jeon Lee, Sin-Gi Park, In-Gang Shin, Sang-Eun Hahn, Woo-Jae Choi, Hee-Soo Kim, Hyeong-Jong Kim, Seong-Hun Bae, Je-Hyeong Lee, Joo-Yeong Moon, Woo-Sung Lee, Ji-Hyun Lee, Choong-Il Lee, Seong-Jin Kim, Goo Jang
BACKGROUND: Transposon-mediated, non-viral gene delivery is a powerful tool for generating stable cell lines and transgenic animals. However, as multi-copy insertion is the preferred integration pattern, there is the potential for uncontrolled changes in endogenous gene expression and detrimental effects in cells or animals. Our group has previously reported on the generation of several transgenic cattle by using microinjection of the Sleeping Beauty (SB) and PiggyBac (PB) transposons and seeks to explore the long-term effects of this technology on cattle...
May 23, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29791850/the-memory-of-environmental-chemical-exposure-in-c-elegans-is-dependent-on-the-jumonji-demethylases-jmjd-2-and-jmjd-3-utx-1
#4
Jessica Camacho, Lisa Truong, Zeyneb Kurt, Yen-Wei Chen, Marco Morselli, Gerardo Gutierrez, Matteo Pellegrini, Xia Yang, Patrick Allard
How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A in C. elegans. We show that Bisphenol A (BPA) exposure causes the derepression of an epigenomically silenced transgene in the germline for 5 generations, regardless of ancestral response. Chromatin immunoprecipitation sequencing (ChIP-seq), histone modification quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3, as well as with reproductive dysfunctions, including germline apoptosis and embryonic lethality...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29790378/effect-of-hwnt10b-transgene-overexpression-on-peri-implant-osteogenesis-in-ovariectomized-rats
#5
Hanghang Liu, Nian Zhang, Yao Liu, Li Liu, Guozhu Yin, En Luo
Purpose This study aims to investigate the efficacy of human Wnt10b (hWnt10b) transgene in accelerating osseointegration around titanium implant in ovariectomized (OVX) rats, and to provide a new strategy for implant treatment of osteoporotic patients. Methods In vivo, osteoporosis rat model was constructed by bilateral ovariectomy and the expression change of Wnt pathway related genes was investigated. Then Ad-hWnt10b was locally administered to the femur defect prior to implant placement in OVX rats, surrounding femur tissues were collected 1 and 3 weeks respectively after implantation for imaging, biomechanical test, molecular and histological analysis...
May 23, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29790257/functionalized-silk-fibers-from-transgenic-silkworms-for-wound-healing-applications-surface-presentation-of-bioactive-epidermal-growth-factor
#6
Michael Wöltje, Melanie Böbel, Michaela Bienert, Sabine Neuss, Dilibaier Aibibu, Chokri Cherif
Growth factors play a crucial role in wound healing in general and are promising tools for the treatment of chronic wounds as they can restore the physiological wound healing process. In growth factor-loaded wound dressings, human epidermal growth factor (EGF) is released in a burst and washed out quickly. The developed matrix consists of recombinant EGF produced in transgenic silkworms as a fusion protein with the fibroin light chain. The covalent linkage prevents EGF from draining into the surrounding tissue while presenting the growth factor on the surface...
May 23, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29790082/chronic-administration-of-pimozide-fails-to-attenuate-motor-and-pathological-deficits-in-two-mouse-models-of-amyotrophic-lateral-sclerosis
#7
Silvia Pozzi, Sai Sampath Thammisetty, Jean-Pierre Julien
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which presently does not have any efficient therapeutic approach. Pimozide, a Food and Drug Administration (FDA)-approved neuroepileptic drug, has been recently proposed as a promising treatment for ALS patients based on apparent stabilization of right hand muscles after a short-time administration. A new clinical trial started at the end of 2017 to recruit patients with a prolonged drug delivery schedule. Here, our aim was to investigate the effects of chronic administration of pimozide on disease progression and pathological events in two mouse models of ALS...
May 22, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29789357/reactivation-of-%C3%AE-globin-in-adult-%C3%AE-yac-mice-after-ex-vivo-and-in-vivo-hematopoietic-stem-cell-genome-editing
#8
Chang Li, Nikoletta Psatha, Pavel Sova, Sucheol Gil, Hongjie Wang, Jiho Kim, Chandana Kulkarni, Cristina Valensisi, R David Hawkins, George Stamatoyannopoulos, André Lieber
Disorders involving β-globin gene mutations, mainly β-thalassemia and sickle cell disease, represent a major target for hematopoietic stem/progenitor cell (HSPC) gene therapy. This includes CRISPR/Cas9-mediated genome editing approaches in adult CD34+ cells aimed toward the re-activation of fetal γ-globin expression in red blood cells. Because models involving erythroid differentiation of CD34+ cells have limitations in assessing γ-globin re-activation, we focused on human β-globin locus transgenic (β-YAC) mice...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29787760/in-vivo-gene-correction-with-targeted-sequence-substitution-through-microhomology-mediated-end-joining
#9
Jeong Hong Shin, Soobin Jung, Suresh Ramakrishna, Hyongbum Henry Kim, Junwon Lee
Genome editing technology using programmable nucleases has rapidly evolved in recent years. The primary mechanism to achieve precise integration of a transgene is mainly based on homology-directed repair (HDR). However, an HDR-based genome-editing approach is less efficient than non-homologous end-joining (NHEJ). Recently, a microhomology-mediated end-joining (MMEJ)-based transgene integration approach was developed, showing feasibility both in vitro and in vivo. We expanded this method to achieve targeted sequence substitution (TSS) of mutated sequences with normal sequences using double-guide RNAs (gRNAs), and a donor template flanking the microhomologies and target sequence of the gRNAs in vitro and in vivo...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29787578/mth1-driven-expression-of-htdp-43-results-in-typical-als-ftld-neuropathological-symptoms
#10
Barbara Scherz, Roland Rabl, Stefanie Flunkert, Siegfried Rohler, Joerg Neddens, Nicole Taub, Magdalena Temmel, Ute Panzenboeck, Vera Niederkofler, Robert Zimmermann, Birgit Hutter-Paier
Transgenic mouse models are indispensable tools to mimic human diseases and analyze the effectiveness of related new drugs. For a long time amyotrophic lateral sclerosis (ALS) research depended on only a few mouse models that exhibit a very strong and early phenotype, e.g. SOD1 mice, resulting in a short treatment time window. By now, several models are available that need to be characterized to highlight characteristics of each model. Here we further characterized the mThy1-hTDP-43 transgenic mouse model TAR6/6 that overexpresses wild type human TARDBP, also called TDP-43, under control of the neuronal Thy-1 promoter presented by Wils and colleagues, 2010, by using biochemical, histological and behavioral readouts...
2018: PloS One
https://www.readbyqxmd.com/read/29786785/methods-to-study-angiogenesis-in-a-mouse-model-of-prostate-cancer
#11
Ana-Rita Pedrosa, Alexandre Trindade, António Duarte
Angiogenesis is one important hallmark of cancer progression which explains the relevance of developing methods to efficiently analyze the neo-angiogenic process. In this report we make use of the transgenic adenocarcinoma of the murine prostate (TRAMP) model, considered a good model for studying clinical prostate cancer progression, to describe in detail the methods used to study angiogenesis in this type of solid tumor development. In this report we provide step-by-step procedures on the basis of previous work in our laboratory for: the mouse urogenital sinus (UGS) collection; microdissection of the prostate; preparation of the prostatic samples for immunofluorescence (to analyze vascular density, morphology, maturation, functionality, hypoxia, and others); preparation of prostatic samples to histopathological analysis and/or immunohistochemistry; and endothelial and vascular mural cell sorting and isolation by fluorescent associated cell sorting (FACS) to further analysis (mRNA, protein, or other) or to maintain in culture...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786658/melatonin-as-a-therapy-for-traumatic-brain-injury-a-review-of-published-evidence
#12
REVIEW
Nicole Osier, Emily McGreevy, Lan Pham, Ava Puccio, Dianxu Ren, Yvette P Conley, Sheila Alexander, C Edward Dixon
Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29785241/an-in-vivo-zebrafish-model-for-interrogating-ros-mediated-pancreatic-%C3%AE-cell-injury-response-and-prevention
#13
Abhishek A Kulkarni, Abass M Conteh, Cody A Sorrell, Anjali Mirmira, Sarah A Tersey, Raghavendra G Mirmira, Amelia K Linnemann, Ryan M Anderson
It is well known that a chronic state of elevated reactive oxygen species (ROS) in pancreatic β -cells impairs their ability to release insulin in response to elevated plasma glucose. Moreover, at its extreme, unmitigated ROS drives regulated cell death. This dysfunctional state of ROS buildup can result both from genetic predisposition and environmental factors such as obesity and overnutrition. Importantly, excessive ROS buildup may underlie metabolic pathologies such as type 2 diabetes mellitus. The ability to monitor ROS dynamics in β -cells in situ and to manipulate it via genetic, pharmacological, and environmental means would accelerate the development of novel therapeutics that could abate this pathology...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29784759/of-what-use-is-connectomics-a-personal-perspective-on-the-drosophila-connectome
#14
REVIEW
Ian A Meinertzhagen
The brain is a network of neurons and its biological output is behaviour. This is an exciting age, with a growing acknowledgement that the comprehensive compilation of synaptic circuits densely reconstructed in the brains of model species is now both technologically feasible and a scientifically enabling possibility in neurobiology, much as 30 years ago genomics was in molecular biology and genetics. Implemented by huge advances in electron microscope technology, especially focused ion beam-scanning electron microscope (FIB-SEM) milling (see Glossary), image capture and alignment, and computer-aided reconstruction of neuron morphologies, enormous progress has been made in the last decade in the detailed knowledge of the actual synaptic circuits formed by real neurons, in various brain regions of the fly Drosophila It is useful to distinguish synaptic pathways that are major, with 100 or more presynaptic contacts, from those that are minor, with fewer than about 10; most neurites are both presynaptic and postsynaptic, and all synaptic sites have multiple postsynaptic dendrites...
May 20, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29782905/pathology-of-nnos-expressing-gabaergic-neurons-in-mouse-model-of-alzheimer-s-disease
#15
Seungho Choi, Je-Seong Won, Steven L Carroll, Balasubramaniam Annamalai, Inderjit Singh, Avtar K Singh
Alzheimer's disease (AD) is the most common form of dementia that is often accompanied by mood and emotional disturbances and seizures. There is growing body of evidence that neurons expressing γ-aminobutyric acid (GABA) play an important role in regulation of cognition, mood, and emotion as well as seizure susceptibility, but participation of GABAergic neuronal pathology in Alzheimer's disease (AD) is not understood well at present. Here, we report that transgenic mice expressing human amyloid precursor protein Swedish-Deutch-Iowa mutant (APPSweDI ) exhibit early loss of neurons expressing GAD67, a GABA synthesizing enzyme, in advance to the loss of pyramidal neurons in hippocampal CA1 region...
May 18, 2018: Neuroscience
https://www.readbyqxmd.com/read/29782541/an-unappreciated-role-for-neutrophil-dc-hybrids-in-immunity-to-invasive-fungal-infections
#16
J Scott Fites, Michael Gui, John F Kernien, Paige Negoro, Zeina Dagher, David B Sykes, Jeniel E Nett, Michael K Mansour, Bruce S Klein
Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#17
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29782018/novel-method-of-plasmid-dna-delivery-to-mouse-bladder-urothelium-by-electroporation
#18
Chuan Yu, Ofir Stefanson, Yueli Liu, Zhu A Wang
Genetically engineered mouse models (GEMMs) are extremely valuable in revealing novel biological insights into the initiation and progression mechanisms of human diseases such as cancer. Transgenic and conditional knockout mice have been frequently used for gene overexpression or ablation in specific tissues or cell types in vivo. However, generating germline mouse models can be time-consuming and costly. Recent advancements in gene editing technologies and the feasibility of delivering DNA plasmids by viral infection have enabled rapid generation of non-germline autochthonous mouse cancer models for several organs...
May 3, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29782016/in-vivo-gene-transfer-to-the-rabbit-common-carotid-artery-endothelium
#19
Bradley K Wacker, Lianxiang Bi, David A Dichek
The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves focal endothelial-selective transgenesis, thereby allowing an investigator to determine the biological roles of endothelial-expressed transgenes and to quantify the in vivo transcriptional activity of DNA sequences in large artery endothelial cells. The method uses surgical isolation of rabbit common carotid arteries and an arteriotomy to deliver a transgene-expressing viral vector into the arterial lumen...
May 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781810/active-suppression-rather-than-ignorance-tolerance-to-abacavir-induced-hla-b-57-01-peptide-repertoire-alteration
#20
Elizabeth J Phillips, Simon A Mallal
The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation...
May 21, 2018: Journal of Clinical Investigation
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