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https://www.readbyqxmd.com/read/28087737/a-homozygous-mutation-in-trim36-causes-autosomal-recessive-anencephaly-in-an-indian-family
#1
Nivedita Singh, Vishwanath Kumble Bhat, Ankana Tiwari, Srinivas G Kodaganur, Sagar J Tontanahal, Astha Sarda, K V Malini, Arun Kumar
Anencephaly is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to anencephaly. Anencephaly shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of anencephaly has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C>A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive anencephaly (APH) in an Indian family...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28081260/comparative-genome-sequencing-reveals-within-host-genetic-changes-in-neisseria-meningitidis-during-invasive-disease
#2
Johanna Klughammer, Marcus Dittrich, Jochen Blom, Vera Mitesser, Ulrich Vogel, Matthias Frosch, Alexander Goesmann, Tobias Müller, Christoph Schoen
Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation...
2017: PloS One
https://www.readbyqxmd.com/read/28079305/gallium-enhances-reconstructive-properties-of-a-calcium-phosphate-bone-biomaterial
#3
Ivana Strazic Geljic, Nicolas Melis, Florian Boukhechba, Sébastien Schaub, Charlotte Mellier, Pascal Janvier, Jean-Pierre Laugier, Jean-Michel Bouler, Elise Verron, Jean-Claude Scimeca
Calcium phosphate-based (CaP) biomaterials are commonly used in bone reconstructive surgery to replace the damaged tissue, and can also serve as vectors for local drug delivery. Due to its inhibitory action on osteoclasts, the semi-metallic element gallium (Ga) is used for the systemic treatment of disorders associated with accelerated bone resorption. As it was demonstrated that Ga could be incorporated in the structure of CaP biomaterials, we investigated in the present work the biological properties of Ga-loaded CaP biomaterials...
January 12, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28079006/a-new-vaccine-delivery-vehicle-and-adjuvant-candidate-bordetella-pertussis-inactivated-whole-cells-entrapped-in-alginate-microspheres
#4
Naser Mohammadpour Dounighi, Fereshteh Shahcheraghi, Mehdi Razzaghi-Abyaneh, Mojtaba Nofeli, Hossein Zolfagharian
There is no doubt about whole cell pertussis vaccine efficacy, but it is necessary to improve the vaccine quality specially to decreasing its toxicity by obtaining good immunogenicity with low bacteria number content. In this work, under optimum condition inactivated B. pertussis bacteria cells entrapped alginate microparticles were fabricated and in vivo immunogenicity and potency of new microparticle based vaccine evaluated in mice. Microspheres loaded inactive B. pertussis bacterium cells were prepared via an emulsification method and analyzed for morphology, size, polydispersity index, loading efficiency, loading capacity, release profile and in vivo potency...
January 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28076784/coupled-proliferation-and-apoptosis-maintain-the-rapid-turnover-of-microglia-in-the-adult-brain
#5
Katharine Askew, Kaizhen Li, Adrian Olmos-Alonso, Fernando Garcia-Moreno, Yajie Liang, Philippa Richardson, Tom Tipton, Mark A Chapman, Kristoffer Riecken, Sol Beccari, Amanda Sierra, Zoltán Molnár, Mark S Cragg, Olga Garaschuk, V Hugh Perry, Diego Gomez-Nicola
Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28075010/stimulatory-actions-of-a-novel-thiourea-derivative-on-large-conductance-calcium-activated-potassium-channels
#6
Sheng-Nan Wu, Jyh-Haur Chern, Santai Shen, Hwei-Hisen Chen, Ying-Ting Hsu, Chih-Chin Lee, Ming-Huan Chan, Ming-Chi Lai, Feng-Shiun Shie
AIM: In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. METHODS: The effects of compound #326 on Ca(2+) -activated K(+) channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. RESULTS: In pituitary GH3 cells, compound #326 increased the amplitude of Ca(2+) -activated K(+) currents (IK(Ca) ) with an EC50 value of 11...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28073847/identification-of-ccr2-and-cd180-as-robust-pharmacodynamic-tumor-and-blood-biomarkers-for-clinical-use-with-brd4-bet-inhibitors
#7
Tammie C Yeh, Greg O'Connor, Philip Petteruti, Austin Dulak, Maureen Hattersley, J Carl Barrett, Huawei Chen
PURPOSE: AZD5153 is a novel BRD4/BET inhibitor with a distinctive bivalent bromodomain binding mode. To support its clinical development, we identified pharmacodynamic (PD) biomarkers for use in clinical trials to establish target engagement. EXPERIMENTAL DESIGN: CCR2 and CD180 mRNAs, initially identified from whole transcriptome profiling, were further evaluated by quantitative PCR in hematologic cell lines, xenografts, and whole blood from rat, healthy volunteers, and patients with cancer...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28069010/nanoparticle-exposure-reactivates-latent-herpesvirus-and-restores-a-signature-of-acute-infection
#8
Christine Sattler, Franco Moritz, Shanze Chen, Beatrix Steer, David Kutschke, Martin Irmler, Johannes Beckers, Oliver Eickelberg, Philippe Schmitt-Kopplin, Heiko Adler, Tobias Stoeger
BACKGROUND: Inhalation of environmental (nano) particles (NP) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. We hypothesized that NP-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage...
January 10, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28067253/whole-organ-and-islet-of-langerhans-dosimetry-for-calculation-of-absorbed-doses-resulting-from-imaging-with-radiolabeled-exendin
#9
Inge van der Kroon, Wietske Woliner-van der Weg, Maarten Brom, Lieke Joosten, Cathelijne Frielink, Mark W Konijnenberg, Eric P Visser, Martin Gotthardt
Radiolabeled exendin is used for non-invasive quantification of beta cells in the islets of Langerhans in vivo. High accumulation of radiolabeled exendin in the islets raised concerns about possible radiation-induced damage to these islets in man. In this work, islet absorbed doses resulting from exendin-imaging were calculated by combining whole organ dosimetry with small scale dosimetry for the islets. Our model contains the tissues with high accumulation of radiolabeled exendin: kidneys, pancreas and islets...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067100/effects-of-a-single-bout-of-strenuous-exercise-on-platelet-activation-in-female-apoe-ldlr-mice
#10
K Przyborowski, H Kassassir, M Wojewoda, K Kmiecik, B Sitek, K Siewiera, A Zakrzewska, A M Rudolf, R Kostogrys, C Watala, J A Zoladz, S Chlopicki
Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI2) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR(-)(/-) mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice...
January 9, 2017: Platelets
https://www.readbyqxmd.com/read/28065753/the-roles-of-conserved-aromatic-residues-tyr5-and-tyr42-in-interaction-of-scorpion-toxin-bmk-agp-sypu1-with-human-nav1-7
#11
Xiangxue Meng, Yijia Xu, Fangyang Wang, Mingyi Zhao, Xue Hou, Yuanyuan Ma, Yao Jin, Yanfeng Liu, Yongbo Song, Jinghai Zhang
Scorpion toxins are invaluable source of therapeutic leads and pharmacological tools which produce influence on the voltage gated sodium channels. In the previous study, our group has reported BmK AGP-SYPU1 (64 amino acids), one scorpion toxin with both potential α-type and β-type scorpion characteristics and analgesic activity in vivo, act as an activator to hNav1.4 and hNav1.5. Additionally, conserved aromatic amino acids Tyr5 and Tyr42 played important roles in bioactivity of BmK AGP-SYPU1 on hNav1.4 and hNav1...
January 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28062502/targeting-elastase-for-molecular-imaging-of-early-atherosclerotic-lesions
#12
Almut Glinzer, Xiaopeng Ma, Jaya Prakash, Melanie A Kimm, Fabian Lohöfer, Katja Kosanke, Jaroslav Pelisek, Moritz P Thon, Sandra Vorlova, Katrin G Heinze, Hans-Henning Eckstein, Michael W Gee, Vasilis Nitziachristos, Alma Zernecke, Moritz Wildgruber
OBJECTIVE: Neutrophils accumulate in early atherosclerotic lesions and promote lesion growth. In this study, we evaluated an elastase-specific near-infrared imaging agent for molecular imaging using hybrid fluorescence molecular tomography/x-ray computed tomography. APPROACH AND RESULTS: Murine neutrophils were isolated from bone marrow and incubated with the neutrophil-targeted near-infrared imaging agent Neutrophil Elastase 680 FAST for proof of principle experiments, verifying that the elastase-targeted fluorescent agent is specifically cleaved and activated by neutrophil content after lysis or cell stimulation...
December 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062357/development-qualification-validation-and-application-of-the-neutral-red-uptake-assay-in-chinese-hamster-ovary-cho-cells-using-a-vitrocell%C3%A2-vc10%C3%A2-smoke-exposure-system
#13
Wanda Fields, Kathy Fowler, Victoria Hargreaves, Lesley Reeve, Betsy Bombick
: Cytotoxicity assessment of combustible tobacco products by neutral red uptake (NRU) has historically used total particulate matter (TPM) or solvent captured gas vapor phase (GVP), rather than fresh whole smoke. Here, the development, validation and application of the NRU assay in Chinese Hamster Ovary (CHO) cells, following exposure to fresh whole smoke generated with the VITROCELL® VC10® system is described. Whole smoke exposure is particularly important as both particulate and vapor phases of tobacco smoke show cytotoxicity in vitro...
January 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28061770/viscumtt-induces-apoptosis-and-alters-iap-expression-in-osteosarcoma-in-vitro-and-has-synergistic-action-when-combined-with-different-chemotherapeutic-drugs
#14
Susann Kleinsimon, Gwenda Kauczor, Sebastian Jaeger, Angelika Eggert, Georg Seifert, Catharina Delebinski
BACKGROUND: Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids...
January 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28061513/angiopoietin-2-blockade-promotes-survival-of-corneal-transplants
#15
Liwei Zhang, Guangyu Li, Roberto Sessa, Gyeong Jin Kang, Meng Shi, Shaokui Ge, Anna Jiang Gong, Ying Wen, Sudhakar Chintharlapalli, Lu Chen
Purpose: Corneal transplantation remains the last hope for vision restoration, and lymphangiogenesis (LG) is a primary mediator of transplant rejection. This study was to investigate the specific role of angiopoietin-2 (Ang-2) in transplantation-associated LG and graft rejection. Methods: Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice to assess the effects of Ang-2 blockade via neutralizing antibody...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28060755/antitumor-and-antimetastatic-activities-of-a-novel-benzothiazole-2-thiol-derivative-in-a-murine-model-of-breast-cancer
#16
XiaoLin Hu, Sen Li, Yan He, Ping Ai, Shaoyong Wu, Yonglin Su, Xiaolin Li, Lei Cai, Xingchen Peng
The prognosis of metastatic breast cancer is always very poor. Thus, it is urgent to develop novel drugs with less toxicity against metastatic breast cancer. A new drug (XC-591) derived from benzothiazole-2-thiol was designed and synthesized in our lab. In this study, we tried to assess effects of XC-591 treatment on primary breast cancer and pulmonary metastasis in 4T1 mice model. Furthermore, we tried to discover its possible molecular mechanism of action. MTT experiment showed XC-591 had significant anti-cancer activity on diverse cancer cells...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060464/rna-polymerase-ii-components-and-rrn7-form-a-pre-initiation-complex-on-the-homold-box-to-promote-ribosomal-protein-gene-expression-in-schizosaccharomyces-pombe
#17
Matías Montes, Sandra Moreira-Ramos, Diego A Rojas, Fabiola Urbina, Norbert F Käufer, Edio Maldonado
In Schizosaccharomyces pombe, ribosomal protein gene (RPG) promoters contain a TATA box analog, the HomolD box, which is bound by the Rrn7 protein. Despite the importance of ribosome biogenesis for cell survival, the mechanisms underlying RPG transcription remain unknown. In this study, we found that components of the RNA polymerase II (RNAPII) system, consisting of the initiation or general transcription factors (GTFs) TFIIA, IIB, IIE, TBP and the RNAPII holoenzyme, interacted directly with Rrn7 in vitro and were able to form a pre-initiation complex (PIC) on the HomolD box...
January 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28053068/alternative-models-of-developmental-and-reproductive-toxicity-in-pharmaceutical-risk-assessment-and-the-3rs
#18
Kimberly C Brannen, Robert E Chapin, Abigail C Jacobs, Maia L Green
In the pharmaceutical industry, preclinical developmental and reproductive toxicity studies are conducted in laboratory animals in order to predict and prevent adverse effects of drugs on human reproductive health and development. However, these studies require a relatively large number of animals and are usually conducted late in the drug development process. Early, simple, and inexpensive screening assays could facilitate smarter decisions, reductions in animal use, and development of safe drugs. The current state and future needs for alternative models of developmental and reproductive toxicity are reviewed here...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28051766/distribution-of-neurosensory-progenitor-pools-during-inner-ear-morphogenesis-unveiled-by-cell-lineage-reconstruction
#19
Sylvia Dyballa, Thierry Savy, Philipp Germann, Karol Mikula, Mariana Remesikova, Róbert Špir, Andrea Zecca, Nadine Peyriéras, Cristina Pujades
Reconstructing the lineage of cells is central to understanding how the wide diversity of cell types develops. Here, we provide the neurosensory lineage reconstruction of a complex sensory organ, the inner ear, by imaging zebrafish embryos in vivo over an extended timespan, combining cell tracing and cell fate marker expression over time. We deliver the first dynamic map of early neuronal and sensory progenitor pools in the whole otic vesicle. It highlights the remodeling of the neuronal progenitor domain upon neuroblast delamination, and reveals that the order and place of neuroblasts' delamination from the otic epithelium prefigure their position within the SAG...
January 4, 2017: ELife
https://www.readbyqxmd.com/read/28051181/the-larvicide-pyriproxyfen-blamed-during-the-zika-virus-outbreak-does-not-cause-microcephaly-in-zebrafish-embryos
#20
Stefania Dzieciolowska, Anne-Laure Larroque, Elizabeth-Ann Kranjec, Pierre Drapeau, Eric Samarut
Although the zika virus (ZIKV) has now been strongly correlated with emerging cases of microcephaly in the Americas, suspicions have been raised regarding the use of pyriproxyfen, a larvicide that prevents mosquito development, in drinking water. The effects of this compound on neurodevelopment have not yet been addressed specifically in vertebrates. As a result, we aimed at addressing the effects, if any, of pyriproxyfen on neurodevelopment in the zebrafish embryo as a vertebrate model. Using zebrafish transgenic lines expressing GFP in different cell populations (elavl3 in newborn neurons, gfap and nestin in neural stem cells), we focused on the analysis of whole embryonic brain volume after confocal 3D-reconstruction and the quantification of purified neural stem cells during early neurodevelopment by FACS-cell sorting from whole in vivo embryos...
January 4, 2017: Scientific Reports
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