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https://www.readbyqxmd.com/read/28535269/increased-retinal-oxygen-metabolism-precedes-microvascular-alterations-in-type-1-diabetic-mice
#1
Wenzhong Liu, Shoujian Wang, Brian Soetikno, Ji Yi, Kevin Zhang, Siyu Chen, Robert A Linsenmeier, Christine M Sorenson, Nader Sheibani, Hao F Zhang
Purpose: To investigate inner retinal oxygen metabolic rate (IRMRO2) during early stages of type 1 diabetes in a transgenic mouse model. Methods: In current study, we involved seven diabetic mice (Akita/+, TSP1-/-) and seven control mice (TSP1-/-), and applied visible-light optical coherence tomography (vis-OCT) to image functional parameters including retinal blood flow rate, oxygen saturation (sO2) and the IRMRO2 value longitudinally from 5 weeks of age to 13 weeks of age...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28534274/exploring-the-validity-of-proposed-transgenic-animal-models-of-attention-deficit-hyperactivity-disorder-adhd
#2
REVIEW
June Bryan de la Peña, Irene Joy Dela Peña, Raly James Custodio, Chrislean Jun Botanas, Hee Jin Kim, Jae Hoon Cheong
Attention-deficit/hyperactivity disorder (ADHD) is a common, behavioral, and heterogeneous neurodevelopmental condition characterized by hyperactivity, impulsivity, and inattention. Symptoms of this disorder are managed by treatment with methylphenidate, amphetamine, and/or atomoxetine. The cause of ADHD is unknown, but substantial evidence indicates that this disorder has a significant genetic component. Transgenic animals have become an essential tool in uncovering the genetic factors underlying ADHD. Although they cannot accurately reflect the human condition, they can provide insights into the disorder that cannot be obtained from human studies due to various limitations...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28534229/production-of-a-gonadotropin-releasing-hormone-2-receptor-knockdown-gnrhr2-kd-swine-line
#3
A T Desaulniers, R A Cederberg, G A Mills, C A Lents, B R White
Swine are the only livestock species that produce both the second mammalian isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone secretion from porcine testes. To further explore this ligand-receptor complex, a pig model with reduced GNRHR2 expression was developed. Small hairpin RNA sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, lentiviral particles were generated and microinjected into the perivitelline space of zygotes, and embryos were transferred into a recipient...
May 22, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28534088/the-ppar-gamma-binding-sequence-pal3-is-necessary-for-basal-but-dispensable-for-high-fat-diet-regulated-human-renin-expression-in-the-kidney
#4
Peter Lachmann, Jenny Selbmann, Linda Hickmann, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of accompanying arterial hypertension. We used bacterial artificial chromosome construct and co-placement strategy to generate two transgenic mouse lines expressing the human renin gene from identical genomic locus without affecting the intrinsic mouse renin expression...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28533439/gene-introgression-in-weeds-depends-on-initial-gene-location-in-the-crop-brassica-napus-raphanus-raphanistrum-model
#5
Katarzyna Adamczyk-Chauvat, Sabrina Delaunay, Anne Vannier, Caroline François, Gwenaëlle Thomas, Frédérique Eber, Maryse Lodé, Marie Gilet, Virginie Huteau, Jérôme Morice, Sylvie Nègre, Cyril Falentin, Olivier Coriton, Henri Darmency, Bachar Alrustom, Eric Jenczewski, Mathieu Rousseau-Gueutin, Anne-Marie Chèvre
The effect of gene location within a crop genome on its transfer to a weed genome remains an open question for gene flow assessment. To elucidate this question, we analyzed advanced generations of intergeneric hybrids, derived from an initial pollination of known oilseed rape varieties (Brassica napus, AACC, 2n=38) by a local population of wild radish (Raphanus raphanistrum, RrRr, 2n=18). After five generations of recurrent pollination, 307 G5 plants with a chromosome number similar to wild radish were genotyped using 105 B...
May 22, 2017: Genetics
https://www.readbyqxmd.com/read/28533388/selective-lowering-of-synapsins-induced-by-oligomeric-%C3%AE-synuclein-exacerbates-memory-deficits
#6
Megan E Larson, Susan J Greimel, Fatou Amar, Michael LaCroix, Gabriel Boyle, Mathew A Sherman, Hallie Schley, Camille Miel, Julie A Schneider, Rakez Kayed, Fabio Benfenati, Michael K Lee, David A Bennett, Sylvain E Lesné
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532825/growth-performance-reproductive-traits-and-offspring-survivability-of-genetically-modified-rams-overexpressing-toll-like-receptor-4
#7
Yu-Chang Yao, Hong-Bing Han, Xu-Ting Song, Shou-Long Deng, Yu-Feng Liu, Ming-Hai Lu, Yun-Hai Zhang, Mei-Yu Qi, Hai-Juan He, Su-Mei Wang, Guo-Shi Liu, Wu Li, Zheng-Xing Lian
Genetic modification provides a means to enhancing disease resistance in animals. Toll-like receptor 4 (TLR4), a member of the TLR family, is critical for the recognition of lipopolysaccharide (LPS)/endotoxin from Gram-negative bacteria by host immune cells, which initiates cell activation and subsequently triggers a proinflammatory response to the invading pathogens. In this study, the first generation of genetically modified (GM) sheep overexpressing TLR4 was produced by microinjection for better disease resistance...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28531191/exogenous-expression-of-drp1-plays-neuroprotective-roles-in-the-alzheimer-s-disease-in-the-a%C3%AE-42-transgenic-drosophila-model
#8
Fengshou Lv, Xiaopeng Yang, Chuanju Cui, Chunhe Su
BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila. METHODS: Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28531186/parvovirus-b19-induced-vascular-damage-in-the-heart-is-associated-with-elevated-circulating-endothelial-microparticles
#9
Katrin Bachelier, Susanne Biehl, Viktoria Schwarz, Ingrid Kindermann, Reinhard Kandolf, Martina Sauter, Christian Ukena, Ali Yilmaz, Karen Sliwa, Claus-Thomas Bock, Karin Klingel, Michael Böhm
BACKGROUND: Diagnosis of viral myocarditis is difficult by clinical criteria but facilitated by detection of inflammation and viral genomes in endomyocardial biopsies. Parvovirus B19 (B19V) targets endothelial cells where viral nucleic acid is exclusively detected in the heart. Microparticles (MPs) are released after cell damage or activation of specific cells. We aimed to investigate whether circulating endothelial MPs (EMPs) in human and experimental models of myocarditis are associated with B19V myocarditis...
2017: PloS One
https://www.readbyqxmd.com/read/28530328/-the-israeli-rat-genome-center
#10
REVIEW
Yoram Yagil, Chana Yagil
The Israeli Rat Genome Center, which is located at the Barzilai Medical Center Campus of the Faculty of Health Sciences of the Ben-Gurion University of the Negev in Ashkelon, was established to provide a repository of unique genetic strains of rats that were created in Israel and that simulate complex diseases. The Center incorporates models of: salt-sensitive hypertension (SBN/y and SBH/y rats), type 2 diabetes (CDr and CDs rats), combined hypertension and diabetes (CRDH) and additional genetic strains (transgenics, consomics, congenics)...
August 2016: Harefuah
https://www.readbyqxmd.com/read/28529630/spectroscopic-photoacoustic-molecular-imaging-of-breast-cancer-using-a-b7-h3-targeted-icg-contrast-agent
#11
Katheryne E Wilson, Sunitha V Bachawal, Lotfi Abou-Elkacem, Kristen Jensen, Steven Machtaler, Lu Tian, Jürgen K Willmann
Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed. The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular endocytosis and degradation, and spectroscopic photoacoustic (sPA) imaging to differentiate normal breast tissue from breast cancer by imaging B7-H3, a novel breast cancer associated molecular target...
2017: Theranostics
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#12
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28529323/an-immunogenic-phenotype-in-paternal-antigen-specific-cd8-t-cells-at-embryo-implantation-elicits-later-fetal-loss-in-mice
#13
Lachlan M Moldenhauer, Kerrilyn R Diener, John D Hayball, Sarah A Robertson
Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8(+) T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8(+) T cell priming in early pregnancy. Transgenic Act-mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen...
May 22, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28528452/tumor-suppressor-protein-p53-exerts-negative-transcriptional-regulation-on-human-sodium-iodide-symporter-gene-expression-in-breast-cancer
#14
Madhura G Kelkar, Bhushan Thakur, Abhishek Derle, Sushmita Chatterjee, Pritha Ray, Abhijit De
PURPOSE: Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate their regulatory role. METHODS: The differences in transcription and translation were measured by real-time PCR, luciferase reporter assay, site-directed mutagenesis, in vivo optical imaging, and chromatin immunoprecipitation...
May 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#15
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28526353/stretch-activated-two-pore-domain-k2p-potassium-channels-in-the-heart-focus-on-atrial-fibrillation-and-heart-failure
#16
REVIEW
Constanze Schmidt, Felix Wiedmann, Stefan M Kallenberger, Antonius Ratte, Jan S Schulte, Beatrix Scholz, Frank Ulrich Müller, Niels Voigt, Maria-Patapia Zafeiriou, Joachim R Ehrlich, Ursula Tochtermann, Gábor Veres, Arjang Ruhparwar, Matthias Karck, Hugo A Katus, Dierk Thomas
Two-pore-domain potassium (K2P) channels modulate cellular excitability. The significance of stretch-activated cardiac K2P channels (K2P2.1, TREK-1, KCNK2; K2P4.1, TRAAK, KCNK4; K2P10.1, TREK-2, KCNK10) in heart disease has not been elucidated in detail. The aim of this work was to assess expression and remodeling of mechanosensitive K2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models. Cardiac K2P channel levels were quantified in atrial (A) and ventricular (V) tissue obtained from patients undergoing open heart surgery...
May 16, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28526302/an-important-role-of-vegf-c-in-promoting-lymphedema-development
#17
Epameinondas Gousopoulos, Steven T Proulx, Samia B Bachmann, Lothar C Dieterich, Jeannette Scholl, Sinem Karaman, Roberta Bianchi, Michael Detmar
Secondary lymphedema is a common post-cancer treatment complication but the pathomechanisms underlying the disease remain unclear. Using a mouse-tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor VEGF-C, and identified CD68+ macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage in comparison to wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGFR3 reduced edema development, diminishing inflammation and blood vascular leakage...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28525963/the-use-of-transgenic-parasites-in-malaria-vaccine-research
#18
Ahmad Syibli Othman, Catherin Marin-Mogollon, Ahmed M Salman, Blandine M Franke-Fayard, Chris J Janse, Shahid M Khan
Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas Covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection...
May 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28524166/homology-mediated-end-joining-based-targeted-integration-using-crispr-cas9
#19
Xuan Yao, Xing Wang, Xinde Hu, Zhen Liu, Junlai Liu, Haibo Zhou, Xiaowen Shen, Yu Wei, Zijian Huang, Wenqin Ying, Yan Wang, Yan-Hong Nie, Chen-Chen Zhang, Sanlan Li, Leping Cheng, Qifang Wang, Yan Wu, Pengyu Huang, Qiang Sun, Linyu Shi, Hui Yang
Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome...
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28523532/progressive-pathological-changes-in-neurochemical-profile-of-the-hippocampus-and-early-changes-in-the-olfactory-bulbs-of-tau-transgenic-mice-rtg4510
#20
Jieun Kim, In-Young Choi, Karen E Duff, Phil Lee
Tauopathies such as Alzheimer's disease and frontotemporal lobe degeneration (FTLD-tau) dementia, characterized by pathologic aggregation of the microtubule-associated tau protein and formation of neurofibrillary tangles, have been linked to neurodegeneration and cognitive decline. The early detection of cerebral abnormalities and the identification of biological contributors to the continuous pathologic processes of neurodegeneration in tauopathies critically hinge on sensitive and reliable measures of biomarkers in the living brain...
May 18, 2017: Neurochemical Research
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