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Weiguang Wang, Buer Song, Teni Anbarchian, Anna Shirazyan, Joshua E Sadik, Karen M Lyons
TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes...
October 2016: PLoS Genetics
Stephen G Swisher, Jennifer Moughan, Ritsuko U Komaki, Jaffer A Ajani, Tsung T Wu, Wayne L Hofstetter, Andre A Konski, Christopher G Willett
INTRODUCTION: The impact of selective surgical resection for esophageal cancer patients treated with definitive chemoradiation has not been clearly evaluated long-term. METHODS: NRG Oncology RTOG 0246 was a multi-institutional, single arm, open-label, non-randomized phase II study, which enrolled forty-three patients from Sept 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction (GEJ) from 19 sites...
October 8, 2016: Journal of Thoracic Oncology
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
September 30, 2016: Oncotarget
Giovanni Luchetti, Ria Sircar, Jennifer H Kong, Sigrid Nachtergaele, Andreas Sagner, Eamon Fx Byrne, Douglas F Covey, Christian Siebold, Rajat Rohatgi
Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike most GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD)...
October 5, 2016: ELife
Hyun Seon Kim, Sun Woo Lim, Long Jin, Jian Jin, Byung Ha Chung, Chul Woo Yang
BACKGROUND: The use of calcineurin inhibitors is a well-known risk factor for hyperuricemia in kidney transplant recipients. We evaluated the effect of febuxostat (Fx), a new uric acid-lowering drug, on hyperuricemia and renal injury in an experimental model of chronic tacrolimus (Tac)-induced nephropathy. METHODS: Chronic Tac nephropathy was induced by administering Tac (1.5 mg/kg/day) to rats on a low-salt diet (0.05%) with oxonic acid (OA, 2%, 0.2 g/kg/day) for 28 days...
October 5, 2016: Nephron
Sarah M Isaac, Dawei Qu, S Lee Adamson
INTRODUCTION: Placental examination is recommended when genetic mutations cause fetal lethality in mice. But how fetal death alters histomorphology of the surviving mouse placenta is not known. METHODS: Placentas were examined at E17.5 after fetectomy of 1-2 fetal mice per pregnancy at either embryonic day (E) 15.5 (N = 8; Fx-2 group) or E13.5 (N = 5; Fx-4 group), which left 12 ± 2 surviving fetuses per litter. RESULTS: Fetectomy caused no changes in placental weights and no increases in placental hypoxia (pimonidazole staining)...
October 2016: Placenta
Rhys D Brady, Brian L Grills, Jarrod E Church, Nicole C Walsh, Aaron C McDonald, Denes V Agoston, Mujun Sun, Terence J O'Brien, Sandy R Shultz, Stuart J McDonald
Concomitant traumatic brain injury (TBI) and long bone fracture are commonly observed in multitrauma and polytrauma. Despite clinical observations of enhanced bone healing in patients with TBI, the relationship between TBI and fracture healing remains poorly understood, with clinical data limited by the presence of several confounding variables. Here we developed a novel trauma model featuring closed-skull weight-drop TBI and concomitant tibial fracture in order to investigate the effect of TBI on fracture healing...
September 29, 2016: Scientific Reports
P Iyengar, K D Westover, L E Court, M K Patel, A T Shivnani, M W Saunders, Y Li, J Y Chang, A Gao, C Ahn, H Choy, R D Timmerman
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Jee Hoon Kim, Joon Woo Lee, Tae In Ahn, Jong Hwa Shin, Kyung Sub Park, Jung Eek Son
Canopy photosynthesis has typically been estimated using mathematical models that have the following assumptions: the light interception inside the canopy exponentially declines with the canopy depth, and the photosynthetic capacity is affected by light interception as a result of acclimation. However, in actual situations, light interception in the canopy is quite heterogenous depending on environmental factors such as the location, microclimate, leaf area index, and canopy architecture. It is important to apply these factors in an analysis...
2016: Frontiers in Plant Science
Salina Louie, Benjamin Haley, Brett Marshall, Amy Heidersbach, Mandy Yim, Martina Brozynski, Danming Tang, Cynthia Lam, Bronislawa Petryniak, David Shaw, Jeongsup Shim, Aaron Miller, John B Lowe, Brad Snedecor, Shahram Misaghi
During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells. ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s). Several strategies have been utilized to generate fully afucosylated antibodies. A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans. However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo...
September 26, 2016: Biotechnology and Bioengineering
Yiwei Wang, Dan Huang, Kai-Yuan Chen, Min Cui, Weihuan Wang, Xiaoran Huang, Amad Awadellah, Qing Li, Ann Friedman, William W Xin, Luca Di Martino, Fabio Cominelli, Alex Miron, Ricky Chan, James Fox, Yan Xu, Xiling Shen, Mathew F Kalady, Sanford Markowitz, Ivan Maillard, John B Lowe, Wei Xin, Lan Zhou
BACKGROUND & AIMS: De novo synthesis of GDP-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or TSTA3). GMDS deletions and mutations are found in 6%-13% of colorectal cancers; these mostly affect ascending and transverse colon. We investigated whether lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. METHODS: FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency...
September 14, 2016: Gastroenterology
Svetlana Atasheva, Dmitry M Shayakhmetov
The host immune system developed multiple ways for recognition of viral pathogens. Upon disseminated adenovirus infection, the immune system senses adenovirus invasion from the moment it enters the bloodstream. The soluble blood factors, FX, antibodies, and complement, can bind and activate plethora of host-protective immune responses. Adenovirus binding to the cellular β3 integrin and endosomal membrane rupture trigger activation of IL-1α/IL-1R1 proinflammatory cascade leading to attraction of cytotoxic immune cells to the site of infection...
September 14, 2016: Current Opinion in Virology
Jessica A Liu, Randi J Hagerman, Robert M Miller, Lisa T Craft, Brenda Finucane, Nicole Tartaglia, Elizabeth M Berry-Kravis, Stephanie L Sherman, Sharon A Kidd, Jeffrey Cohen
The objectives of the study were to assess the attitudes and experiences of clinicians involved in a consortium of clinics serving people with fragile X-associated disorders to gauge satisfaction with the consortium and its efforts to improve quality of life for patients and the community. An internet survey was sent to 26 fragile X (FX) clinic directors participating in the Fragile X Clinical and Research Consortium (FXCRC). Respondents were asked to complete 19 questions on consortium performance and outcomes relevant for their own clinic...
September 8, 2016: American Journal of Medical Genetics. Part A
Oliver Schnell, Jun Thorsteinsdottir, Daniel Felix Fleischmann, Markus Lenski, Wolfgang Abenhardt, Armin Giese, Jörg-Christian Tonn, Claus Belka, Friedrich Wilhelm Kreth, Maximilian Niyazi
The place of bevacizumab (BEV) in salvage re-irradiation (Re-RT) settings of malignant glioma is poorly defined. In the current study risk/benefit profiles of two BEV-based Re-RT protocols were analyzed and compared with that of salvage BEV plus irinotecan (BEV/IRI). According to interdisciplinary tumor board recommendations, patients were assigned to one of three BEV-based treatment protocols: (1) BEV/IRI, (2) Re-RT (36 Gy/18 fx) with concomitant BEV (Re-RT/BEV), and (3) Re-RT with concomitant/maintenance BEV (Re-RT/BEV→BEV)...
September 6, 2016: Journal of Neuro-oncology
Mio Matsui, Kosuke Tanaka, Naoki Higashiguchi, Hisato Okawa, Yoichi Yamada, Ken Tanaka, Soichiro Taira, Tomoko Aoyama, Misaki Takanishi, Chika Natsume, Yuuki Takakura, Norihisa Fujita, Takeshi Hashimoto, Takashi Fujita
Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity...
September 2016: Journal of Pharmacological Sciences
Stephanie M Beeman, Andrew R Kemper, Stefan M Duma
OBJECTIVE: The objective of this study was to quantify the effects of active muscles (e.g. conscious bracing, resting tone, and reflex response) and acceleration severity on the neck forces and moments generated during low-speed frontal sled tests with adult male human volunteers and post mortem human surrogates (PMHSs). METHODS: A total of 24 frontal sled tests were analyzed including male volunteers of approximately 50th percentile height and weight (n = 5) and PMHSs (n = 2)...
September 2016: Traffic Injury Prevention
N Kaku, T Tabata, H Tsumura
PURPOSE: To compare the past and present bipolar hip arthroplasty (BHA) models in terms of balance between pull-out strength and oscillation angle (OA). METHODS: The pull-out strength and OA of 8 BHA models were compared: UPF-II, IBC, and Tandem XLPE (Smith & Nephew); Ringloc x (Biomet); J-FX (DePuy); Bipolar (Nakashima Medical); Multipolar (Zimmer); and Centrax (Stryker). RESULTS: Respectively for the UPF-II, IBC, Tandem, Ringloc, J-FX, Nakashima Bipolar, Multipolar, and Centrax, the mean pull-out strength was 2219 N, 3303 N, 1503 N, 951 N, 1453 N, 1856 N, 1536 N, and 753 N, whereas the mean OA was 54...
August 2016: Journal of Orthopaedic Surgery
Y Lei, S F Li, Y L Yu, J Tan
OBJECTIVE: To explore the clinical effects of ultra pulse mode of ultra pulse carbon dioxide fractional laser combined with Deep FX mode or Scaar FX mode on the treatment of patients with hypertrophic scars on face and neck. METHODS: One hundred and fifty-eight patients with hypertrophic scars on face and neck who met the inclusion criteria were admitted to Hunan Provincial People's Hospital from January 2012 to January 2015. Firstly, the scar areas were cleaned and given compound lidocaine cream for surface anesthesia...
August 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Vallerinteavide Mavelli Girish, R Manjunatha Kini
Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin...
2016: Scientific Reports
Waldo G Nuez-Ortín, Chris G Carter, Richard Wilson, Ira Cooke, Peter D Nichols
Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon...
2016: PloS One
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