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https://www.readbyqxmd.com/read/28228269/diverse-central-projection-patterns-of-retinal-ganglion-cells
#1
Emily M Martersteck, Karla E Hirokawa, Mariah Evarts, Amy Bernard, Xin Duan, Yang Li, Lydia Ng, Seung W Oh, Benjamin Ouellette, Joshua J Royall, Michelle Stoecklin, Quanxin Wang, Hongkui Zeng, Joshua R Sanes, Julie A Harris
Understanding how >30 types of retinal ganglion cells (RGCs) in the mouse retina each contribute to visual processing in the brain will require more tools that label and manipulate specific RGCs. We screened and analyzed retinal expression of Cre recombinase using 88 transgenic driver lines. In many lines, Cre was expressed in multiple RGC types and retinal cell classes, but several exhibited more selective expression. We comprehensively mapped central projections from RGCs labeled in 26 Cre lines using viral tracers, high-throughput imaging, and a data processing pipeline...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228267/nrf2-improves-leptin-and-insulin-resistance-provoked-by-hypothalamic-oxidative-stress
#2
Yoko Yagishita, Akira Uruno, Toshiaki Fukutomi, Ritsumi Saito, Daisuke Saigusa, Jingbo Pi, Akiyoshi Fukamizu, Fumihiro Sugiyama, Satoru Takahashi, Masayuki Yamamoto
The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout (KO) of selenocysteine-tRNA (Trsp) using rat-insulin-promoter-driven-Cre (RIP-Cre). These Trsp-KO (Trsp(RIP)KO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β cells, leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals are suppressed, and numbers of proopiomelanocortin-positive neurons in the hypothalamus are decreased...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28224990/rapid-and-tunable-method-to-temporally-control-gene-editing-based-on-conditional-cas9-stabilization
#3
Serif Senturk, Nitin H Shirole, Dawid G Nowak, Vincenzo Corbo, Debjani Pal, Alexander Vaughan, David A Tuveson, Lloyd C Trotman, Justin B Kinney, Raffaella Sordella
The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing in the presence of an FKBP12 synthetic ligand. This system can be easily adapted to co-express, from the same promoter, DD-Cas9 with any other gene of interest without co-modulation of the latter...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#4
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223138/foxc1-and-foxc2-are-necessary-to-maintain-glomerular-podocytes
#5
Masaru Motojima, Tsutomu Kume, Taiji Matsusaka
Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreER(T2)) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreER(T2) was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreER(T2); Foxc1(+/flox); Foxc2(flox/flox) mice developed microalbuminuria, while ROSA26-Cre ER(T2); Foxc1(flox/flox); Foxc2(+/flox) mice had no microalbuminuria...
February 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28223045/crystal-structures-reveal-a-new-and-novel-foxo1-binding-site-within-the-human-glucose-6-phosphatase-catalytic-subunit-1-gene-promoter
#6
Puja Singh, Eun Hee Han, James A Endrizzi, Richard M O'Brien, Young-In Chi
Human glucose-6-phosphatase plays a vital role in blood glucose homeostasis and holds promise as a therapeutic target for diabetes. Expression of its catalytic subunit gene 1 (G6PC1) is tightly regulated by metabolic-response transcription factors such as FoxO1 and CREB. Although at least three potential FoxO1 binding sites (insulin response elements, IREs) and one CREB binding site (cAMP response element, CRE) within the proximal region of the G6PC1 promoter have been identified, the interplay between FoxO1 and CREB and between FoxO1 bound at multiple IREs has not been well characterized...
February 18, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28222355/neuroimaging-of-major-depression-in-parkinson-s-disease-cortical-thickness-cortical-and-subcortical-volume-and-spectroscopy-findings
#7
Marcos Hortes N Chagas, Vitor Tumas, Márcio A Pena-Pereira, João Paulo Machado-de-Sousa, Antonio Carlos Dos Santos, Rafael Faria Sanches, Jaime E C Hallak, José Alexandre S Crippa
Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex...
February 13, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28222099/morphological-study-of-tooth-development-in-podoplanin-deficient-mice
#8
Kenyo Takara, Naoki Maruo, Kyoko Oka, Chiaki Kaji, Yuji Hatakeyama, Naruhiko Sawa, Yukinari Kato, Junro Yamashita, Hiroshi Kojima, Yoshihiko Sawa
Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28220032/pharmacologic-blockade-of-%C3%AE-v%C3%AE-1-integrin-ameliorates-renal-failure-and-fibrosis-in-vivo
#9
Yongen Chang, Wei Ling Lau, Hyunil Jo, Kazuyuki Tsujino, Leslie Gewin, Nilgun Isik Reed, Amha Atakilit, Ane Claudia Fernandes Nunes, William F DeGrado, Dean Sheppard
Activated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells in vivo is poorly understood. PDGF receptor β (PDGFRβ) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFRβ promoter-driven Cre system to delete αv integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFRβ-Cre line to isolate and study renal fibroblasts ex vivo We found that renal fibroblasts express three αv integrins, namely αvβ1, αvβ3, and αvβ5...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28219987/a-unique-angiotensin-sensitive-neuronal-population-coordinates-neuroendocrine-cardiovascular-and-behavioral-responses-to-stress
#10
Annette D de Kloet, Lei Wang, Soledad Pitra, Helmut Hiller, Justin A Smith, Yalun Tan, Dani Nguyen, Karlena M Cahill, Colin Sumners, Javier E Stern, Eric G Krause
Stress elicits neuroendocrine, autonomic and behavioral responses that mitigate homeostatic imbalance and ensure survival; however, chronic engagement of such responses promotes psychological, cardiovascular and metabolic impairments. Over recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#11
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28211872/rictor-mtorc2-deficiency-enhances-keratinocyte-stress-tolerance-via-mitohormesis
#12
Beatrice Tassone, Stefania Saoncella, Francesco Neri, Ugo Ala, Davide Brusa, Mark A Magnuson, Paolo Provero, Salvatore Oliviero, Chiara Riganti, Enzo Calautti
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28210097/epac1-agonist-decreased-inflammatory-proteins-in-retinal-endothelial-cells-and-loss-of-epac1-increased-inflammatory-proteins-in-the-retinal-vasculature-of-mice
#13
Li Liu, Youde Jiang, Adam Chahine, Elizabeth Curtiss, Jena J Steinle
PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that β-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of β-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28209809/macrophage-to-myofibroblast-transition-contributes-to-interstitial-fibrosis-in-chronic-renal-allograft-injury
#14
Ying-Ying Wang, Hong Jiang, Jun Pan, Xiao-Ru Huang, Yu-Cheng Wang, Hong-Feng Huang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan, Jiang-Hua Chen
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers...
February 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28209087/the-effect-of-hypericum-perforatum-on-kidney-ischemia-reperfusion-damage
#15
Murat Cakir, Halil Duzova, Işil Baysal, Cemile Ceren Gül, Gülbahar Kuşcu, Fatma Kutluk, Hilal Çakin, Şifanur Şeker, Esranur İlbeği, Seda Uslu, Umut Avci, Samet Demir, Cihan Akinci, Sercan Atli
It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague-Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR + HP Group which was treated with 50 mg/kg of HP...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28207886/connective-tissue-growth-factor-is-not-necessary-for-haze-formation-in-excimer-laser-wounded-mouse-corneas
#16
Xiaodi Feng, Liya Pi, Sriniwas Sriram, Gregory S Schultz, Daniel J Gibson
We sought to determine if connective tissue growth factor (CTGF) is necessary for the formation of corneal haze after corneal injury. Mice with post-natal, tamoxifen-induced, knockout of CTGF were subjected to excimer laser phototherapeutic keratectomy (PTK) and the corneas were allowed to heal. The extent of scaring was observed in non-induced mice, heterozygotes, and full homozygous knockout mice and quantified by macrophotography. The eyes from these mice were collected after euthanization for re-genotyping to control for possible Cre-mosaicism...
2017: PloS One
https://www.readbyqxmd.com/read/28206698/fkbp10-deletion-in-osteoblasts-leads-to-qualitative-defects-in-bone
#17
Caressa D Lietman, Joohyun Lim, Ingo Grafe, Yuqing Chen, Hao Ding, Xiaohong Bi, Catherine G Ambrose, Nadja Fratzl-Zelman, Paul Roschger, Klaus Klaushofer, Wolfgang Wagermaier, Ingo Schmidt, Peter Fratzl, Jyoti Rai, MaryAnn Weis, David Eyre, Douglas R Keene, Deborah Krakow, Brendan H Lee
Osteogenesis Imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65KDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon and ligaments in postnatal tissues...
February 16, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28205531/wnt5a-is-a-crucial-regulator-of-neurogenesis-during-cerebellum-development
#18
Chandramohan Subashini, Sivadasan Bindu Dhanesh, Chih-Ming Chen, Paul Ann Riya, Vadakkath Meera, Thulasi Sheela Divya, Rejji Kuruvilla, Kerstin Buttler, Jackson James
The role of Wnt5a has been extensively explored in various aspects of development but its role in cerebellar development remains elusive. Here, for the first time we unravel the expression pattern and functional significance of Wnt5a in cerebellar development using Wnt5a(-/-) and Nestin-Cre mediated conditional knockout mouse models. We demonstrate that loss of Wnt5a results in cerebellar hypoplasia and depletion of GABAergic and glutamatergic neurons. Besides, Purkinje cells of the mutants displayed stunted, poorly branched dendritic arbors...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203140/tamoxifen-activation-of-cre-recombinase-has-no-persisting-effects-on-adult-neurogenesis-or-learning-and-anxiety
#19
Peter Rotheneichner, Pasquale Romanelli, Lara Bieler, Sebastian Pagitsch, Pia Zaunmair, Christina Kreutzer, Richard König, Julia Marschallinger, Ludwig Aigner, Sébastien Couillard-Després
Adult neurogenesis is a tightly regulated process continuously taking place in the central nervous system of most mammalian species. In neuroscience research, transgenic animals bearing the tamoxifen-inducible CreER(T2)-Lox system are widely used. In this study, we made use of a Nestin-CreER(T2)/R26R-YFP transgenic mouse model in which the CreER(T2) activates the expression of YFP in multipotent neural stem cells upon tamoxifen application. Humoral factors, such as the levels of estrogens, have been reported to affect the hippocampal neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28198109/progenitors-in-peripheral-nerves-launch-heterotopic-ossification
#20
Elizabeth A Olmsted-Davis, Elizabeth A Salisbury, Diana Hoang, Eleanor L Davis, ZaWaunyka Lazard, Corinne Sonnet, Thomas A Davis, Jonathan A Forsberg, Alan R Davis
Studies presented here, using a murine model of bone morphogenetic protein type 2 (BMP2)-induced heterotopic ossification (HO) show that the protein initiates HO by signaling through progenitors in the endoneurium of peripheral nerves. In the mouse, these cells were identified in the endoneurium one day after BMP2 induction using antibody against phosphoSMAD (PS) 1, 5, and 8. Studies conducted in a tracking mouse that contains a tamoxifen-regulated Wnt1-Cre recombinase crossed with a td Tomato red (TR) reporter (Wnt1(CreErt) :Ai9Tm) confirmed their neural origin...
February 15, 2017: Stem Cells Translational Medicine
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