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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
Kaipeng Huang, Ruiming Li, Wentao Wei
Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-related factor 2/ anti-oxidant response element (Nrf2/ARE) pathway had remarkable renoprotective effects. However, whether Sirt1 and Nrf2/ARE pathway can regulate the pathological process of MsPGN remains unknown...
May 18, 2018: European Journal of Pharmacology
Bert Manuel Pilles, Benjamin Maerz, Jinquan Chen, Dominik B Bucher, Peter Gilch, Bern Kohler, Benjamin P Fingerhut, Wolfgang Zinth, Wolfgang J Schreier
The decay of electronically excited states of thymine (Thy) and thymidine 5'-monophosphate (TMP) was studied by time-resolved UV/vis and IR spectroscopy. In addition to the well-established ultrafast internal conversion to the ground state, a so far unidentified UV induced species is observed. In D2O this species decays with a time constant of 300 ps for thymine and of 1 ns for TMP. The species coexists with the lowest triplet state and is formed with a comparably high quantum yield of about 10 % independent of the solvent...
May 11, 2018: Journal of Physical Chemistry. A
Lauren A Maggio, Barbara J Daley, Daniel D Pratt, Dario M Torre
Increasingly health professions education (HPE) faculty are choosing or being required to transition their face-to-face teaching to online teaching. For many faculty, the online learning environment may represent a new context with unfamiliar technology, changing expectations, and unknown challenges. In this context, faculty members may find themselves teaching in ways that are dissonant with the existing assumptions, beliefs, and views that are central to their pedagogical or teaching identity. This "identity dissonance" may lead to dissatisfaction and frustration for the faculty and potentially suboptimal learning experience for students...
May 8, 2018: Academic Medicine: Journal of the Association of American Medical Colleges
Patrick M Brunner, Ariel Israel, Ning Zhang, Alexandra Leonard, Huei-Chi Wen, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Annette Wagner, Xiuzhong Zheng, Yeriel D Estrada, Hui Xu, James G Krueger, Amy S Paller, Emma Guttman-Yassky
BACKGROUND: Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. OBJECTIVE: We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects. METHODS: We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children (<5 years old) with early-onset AD (<6 months disease duration) compared with age-matched control subjects and adults with longstanding AD...
April 19, 2018: Journal of Allergy and Clinical Immunology
Liang Cheng, Jianping Ma, Guangming Li, Lishan Su
Immunodeficient mice reconstituted with human immune tissues and cells (humanized mice) are relevant and robust models for the study of HIV-1 infection, immunopathogenesis, and therapy. In this study, we performed a comprehensive comparison of human immune reconstitution and HIV-1 infection, immunopathogenesis and therapy between immunodeficient NOD/Rag2-/- /γc -/- (NRG) mice transplanted with human HSCs (NRG-hu HSC) and mice transplanted with HSCs and thymus fragments (NRG-hu Thy/HSC) from the same donors...
2018: Frontiers in Immunology
Rohit Anand, Piyush C Kothary, Monte A Del Monte
Valproic acid (VPA) has been reported to inhibit cancer cell growth and has therapeutic use in retinal diseases. However, the mechanism of this action remains unclear. In order to explore this mechanism, primary human retinal pigment epithelial (hRPE) cell cultures were established. Cell viability was assessed by the trypan blue exclusion method (T), and the cell proliferation was measured by 3 H-thymidine incorporation (3H-thy). P38 synthesis was quantitated by using 14C-methionine-labeled P38 (14C-P38) by using P38-specific antibody...
2018: Advances in Experimental Medicine and Biology
Owen Scudamore, Thomas Ciossek
Increasing evidence suggests a relationship between oxidative stress and α-synuclein aggregation, the primary pathological hallmark of Parkinson disease (PD). However, a direct causal relationship has not yet been established in vivo in mouse models of PD. Superoxide dismutase 2 (SOD2) is rate limiting in the antioxidant machinery of the mitochondria and even its partial deficiency elevates oxidative stress in mice. Therefore, in order to investigate a possible interaction between oxidative stress and α-synuclein aggregation in vivo, a transgenic model of PD with haplodeficiency for SOD2 was generated on the basis of the well-characterized murine (Thy-1)-h[A30P]-α-synuclein transgenic line...
April 27, 2018: Journal of Neuropathology and Experimental Neurology
Ngoc Thy Nguyen, Romain R Vivès, Magali Torres, Vincent Delauzun, Els Saesen, Véronique Roig-Zamboni, Hugues Lortat-Jacob, Pascal Rihet, Yves Bourne
The HS3ST3A1/B1 genes encode two homologous 3-O-sulfotransferases involved in the late modification step during heparan sulfate (HS) biosynthesis. In addition to the SNPs rs28470223 (C > T) in the promoter region of both HS3ST3A1 and rs62636623 (Gly/Arg) in the stem region of HS3ST3B1, three missense mutations (rs62056073, rs61729712 and rs9906590) located within the catalytic sulfotransferase domain of 3-OST-B1 are linked and associated to P. falciparum parasitaemia. To ascertain the functional effects of these SNP associations, we investigated the regulatory effect of rs28470223 and characterized the enzymatic activity of the missense SNP rs61729712 (Ser279Asn) localized at proximity of the substrate binding cleft...
April 28, 2018: Glycobiology
Karthik Hullahalli, Marinelle Rodrigues, Uyen Thy Nguyen, Kelli Palmer
Antibiotic-resistant bacteria are critical public health concerns. Among the prime causative factors for the spread of antibiotic resistance is horizontal gene transfer (HGT). A useful model organism for investigating the relationship between HGT and antibiotic resistance is the opportunistic pathogen Enterococcus faecalis , since the species possesses highly conjugative plasmids that readily disseminate antibiotic resistance genes and virulence factors in nature. Unlike many commensal E. faecalis strains, the genomes of multidrug-resistant (MDR) E...
May 1, 2018: MBio
Sonia Kaniuka-Jakubowska, Anna Lewczuk, Mikołaj Majkowicz, Maciej Piskunowicz, Krystyna Mizan-Gross, Adam Zapaśnik, Mariusz Kaszubowski, Piotr Lass, Krzysztof Sworczak
Objective: Despite numerous publications regarding nontoxic goiter (NTG) treatment and an increasing interest in patients' quality of life, few studies present the outcome of 131-I treatment from the patients' perspective. Our study's main aim was to verify whether there is any improvement in life quality following 131-I treatment. Materials and methods: Thirty-five patients with NTG qualified to participate in the study. All patients completed a Thyroid-Related Health-Related Quality of Life (Thy-R-HRQoL) questionnaire created by us and the Medical Outcomes Study 36-item Short Form (SF-36), right before and 1 year after 131-I...
2018: Frontiers in Endocrinology
Heena Tabassum, Asad Ahmad, Iffat Zareen Ahmad
BACKGROUND: The pharmacological properties of Nigella sativa L. are well attributed to the presence of bioactive compounds, mainly, thymoquinone (TQ), thymol (THY) and α hederin and their antioxidant effects. TQ,THY and alpha-hederin (α-hederin) provide protection to liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and (GSH) level, radical scavenging, increasing the activity of quinone reductase, catalase, superoxide dismutase(SOD) and glutathione transferase (GST), inhibition of NF-κB activity and inhibition of both (COX) and (LOX) protects liver from injuries...
April 26, 2018: Current Pharmaceutical Biotechnology
Somphouthone Phimmachak, Niane Sivongxay, Sengvilay Seateun, Siriporn Yodthong, Attapol Rujirawan, Thy Neang, Anchalee Aowphol, Bryan L Stuart
A new species of "fanged frog" in the genus Limnonectes resembling L. kohchangae (Smith, 1922) from southeastern Thailand and southwestern Cambodia is described from upper elevations of the Bolaven Plateau, southern Laos. However, the new species, L. coffeatus sp. nov., is not resolved to be the closest relative of L. kohchangae, and is further distinguished from this taxon by differences in skin texture and coloration. The new species is potentially threatened from extensive conversion of forest into coffee plantations on the Bolaven Plateau...
January 25, 2018: Zootaxa
Thy Neang, Somaly Chan, Nikolay A Poyarkov
Based on morphological and genetic evidence we evaluated the taxonomic status of a newly discovered forest-dwelling population of skink (genus Scincella) from the Keo Seima Wildlife Sanctuary, Mondulkiri Province, Cambodia. From phylogenetic analysis of a 668-bp fragment of the mtDNA COI and diagnostic morphological characters we allocate the newly discovered population to the Scincella reevesii-S. rufocaudata species complex and describe it as Scincella nigrofasciata sp. nov. The new skink species can be distinguished from all other Southeast Asian congeners by the following combination of morphological characters: snout-vent length (SVL) 40...
April 20, 2018: Zoological Research
Mostafa Ebraheem Morra, Le Van Thanh, Mohamed Gomaa Kamel, Ahmed Abdelmotaleb Ghazy, Ahmed M A Altibi, Lu Minh Dat, Tran Ngoc Xuan Thy, Nguyen Lam Vuong, Mostafa Reda Mostafa, Sarah Ibrahim Ahmed, Sahar Samy Elabd, Samreen Fathima, Tran Le Huy Vu, Ali S Omrani, Ziad A Memish, Kenji Hirayama, Nguyen Tien Huy
Middle East respiratory syndrome (MERS) is a respiratory disease caused by MERS coronavirus. Because of lack of vaccination, various studies investigated the therapeutic efficacy of antiviral drugs and supportive remedies. A systematic literature search from 10 databases was conducted and screened for relevant articles. Studies reporting information about the treatment of MERS coronavirus infection were extracted and analyzed. Despite receiving treatment with ribavirin plus IFN, the case fatality rate was as high as 71% in the IFN-treatment group and exactly the same in patients who received supportive treatment only...
April 17, 2018: Reviews in Medical Virology
Gholam Hassan Danaei, Bahram Memar, Ramin Ataee, Mohammad Karami
Several studies have shown that oxidative stress and cell damage can occur at very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin), against DZN cardio-toxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages (10 mg/kg/day) and Thy + DVN gavages (2...
April 12, 2018: Drug and Chemical Toxicology
Ying Gao, Shisi Hu, Qiqin Li, Muran Wang, Zhina Zhi, Xiuli Kuang, Yaoyao Li, Sergii Vakal, Yun Wang
Perinatal inflammatory insult in preterm babies is associated with vision impairment, but the underlying cellular mechanism is still unknown. In this study, we set out to explore whether systemic inflammatory stress affects the development of retinal ganglion cells (RGCs). Neonatal inflammation was induced by single and systemic injection of lipopolysaccharide (LPS, 1 mg/kg) at postnatal day 4 (P4). Morphological changes of RGCs were investigated by using 3D neuron reconstruction technique in Thy-1 YFPH transgenic mice at P21, of which a fraction of RGCs selectively expresses the yellow fluorescent protein (YFP)...
April 5, 2018: Neuroscience Letters
Leire Almandoz-Gil, Emma Persson, Veronica Lindström, Martin Ingelsson, Anna Erlandsson, Joakim Bergström
The aggregation of alpha-synuclein (αSyn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of αSyn is to promote the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between αSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA)...
2018: Frontiers in Neurology
Andrea Popelová, Veronika Pražienková, Barbora Neprašová, Barbora Judita Kasperová, Lucie Hrubá, Martina Holubová, Jana Zemenová, David Blum, Blanka Železná, Marie-Christine Galas, Jaroslav Kuneš, Lenka Maletínská
Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology...
2018: Journal of Alzheimer's Disease: JAD
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