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https://www.readbyqxmd.com/read/28821097/thiolated-pectin-doxorubicin-conjugates-synthesis-characterization-and-anticancer-activity-studies
#1
Kamonrak Cheewatanakornkool, Sathit Niratisai, Somkamol Manchun, Crispin R Dass, Pornsak Sriamornsak
In this paper, pectin was cross-linked by a coupling reaction with either thioglycolic acid or cystamine dihydrochloride to form thiolated pectins. The thiolated pectins were then coupled with doxorubicin (DOX) derivative to obtain thiolated pectin-DOX conjugates by two different methods, disulfide bond formation and disulfide bond exchange. The disulfide bond exchange method provided a simple, fast, and efficient approach for synthesis of thiolated pectin-DOX conjugates, compared to the disulfide bond formation...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820907/positive-regulatory-interactions-between-yap-and-hedgehog-signalling-in-skin-homeostasis-and-bcc-development-in-mouse-skin-in-vivo
#2
Bassem Akladios, Veronica Mendoza Reinoso, Jason E Cain, Taopeng Wang, Duncan L Lambie, D Neil Watkins, Annemiek Beverdam
Skin is a highly plastic tissue that undergoes tissue turnover throughout life, but also in response to injury. YAP and Hedgehog signalling play a central role in the control of epidermal stem/progenitor cells in the skin during embryonic development, in postnatal tissue homeostasis and in skin carcinogenesis. However, the genetic contexts in which they act to control tissue homeostasis remain mostly unresolved. We provide compelling evidence that epidermal YAP and Hedgehog/GLI2 signalling undergo positive regulatory interactions in the control of normal epidermal homeostasis and in basal cell carcinoma (BCC) development, which in the large majority of cases is caused by aberrant Hedgehog signalling activity...
2017: PloS One
https://www.readbyqxmd.com/read/28820694/differential-neurovirulence-of-african-and-asian-genotype-zika-virus-isolates-in-outbred-immunocompetent-mice
#3
Nisha K Duggal, Jana M Ritter, Erin M McDonald, Hannah Romo, Farshad Guirakhoo, Brent S Davis, Gwong-Jen J Chang, Aaron C Brault
Although first isolated almost 70 years ago, Zika virus (ZIKV; Flavivirus, Flaviviridae) has only recently been associated with significant outbreaks of disease in humans. Several severe ZIKV disease manifestations have also been recently documented, including fetal malformations, such as microcephaly, and Guillain-Barré syndrome in adults. Although principally transmitted by mosquitoes, sexual transmission of ZIKV has been documented. Recent publications of several interferon receptor knockout mouse models have demonstrated ZIKV-induced disease...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28820384/chronic-wasting-disease-prion-strain-emergence-and-host-range-expansion
#4
Allen Herbst, Camilo Duque Velásquez, Elizabeth Triscott, Judd M Aiken, Debbie McKenzie
Human and mouse prion proteins share a structural motif that regulates resistance to common chronic wasting disease (CWD) prion strains. Successful transmission of an emergent strain of CWD prion, H95(+), into mice resulted in infection. Thus, emergent CWD prion strains may have higher zoonotic potential than common strains.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28819774/whole-exome-sequencing-of-wild-derived-inbred-strains-of-mice-improves-power-to-link-phenotype-and-genotype
#5
Peter L Chang, Emily Kopania, Sara Keeble, Brice A J Sarver, Erica Larson, Annie Orth, Khalid Belkhir, Pierre Boursot, François Bonhomme, Jeffrey M Good, Matthew D Dean
The house mouse is a powerful model to dissect the genetic basis of phenotypic variation, and serves as a model to study human diseases. Despite a wealth of discoveries, most classical laboratory strains have captured only a small fraction of genetic variation known to segregate in their wild progenitors, and existing strains are often related to each other in complex ways. Inbred strains of mice independently derived from natural populations have the potential to increase power in genetic studies with the addition of novel genetic variation...
August 17, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28819706/generation-of-a-functional-humanized-delta-like-ligand-4-transgenic-mouse-model
#6
John Wiseman, Pernilla Gregersson, Johan Johansson, Kerstin Magnell, Fernanda Pilataxi, Chris Morehouse, Philip Brohawn, Nicholas Holoweckyj, Patrick Strout, Song Cho
Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form...
August 17, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28819703/novel-prostate-cancer-immunotherapy-with-a-dna-encoded-anti-prostate-specific-membrane-antigen-monoclonal-antibody
#7
Kar Muthumani, Liron Marnin, Sagar B Kudchodkar, Alfredo Perales-Puchalt, Hyeree Choi, Sangya Agarwal, Veronica L Scott, Emma L Reuschel, Faraz I Zaidi, Elizabeth K Duperret, Megan C Wise, Kimberly A Kraynyak, Kenneth E Ugen, Niranjan Y Sardesai, J Joseph Kim, David B Weiner
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life...
August 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28819451/a-high-affinity-repebody-for-molecular-imaging-of-egfr-expressing-malignant-tumors
#8
Misun Yun, Dong-Yeon Kim, Joong-Jae Lee, Hyeon-Sik Kim, Hyung-Seok Kim, Ayoung Pyo, Yiseul Ryu, Tae-Yoon Kim, Jin Hai Zheng, Su Woong Yoo, Hoon Hyun, Gyungseok Oh, Jaeho Jeong, Myeongju Moon, Jung-Hyun Min, Seong Young Kwon, Jung Young Kim, Euiheon Chung, Yeongjin Hong, Wansik Lee, Hak-Sung Kim, Jung-Joon Min
The accurate detection of disease-related biomarkers is crucial for the early diagnosis and management of disease in personalized medicine. Here, we present a molecular imaging of human epidermal growth factor receptor (EGFR)-expressing malignant tumors using an EGFR-specific repebody composed of leucine-rich repeat (LRR) modules. The repebody was labeled with either a fluorescent dye or radioisotope, and used for imaging of EGFR-expressing malignant tumors using an optical method and positron emission tomography...
2017: Theranostics
https://www.readbyqxmd.com/read/28819373/increased-transgenerational-intestinal-tumorigenesis-in-offspring-of-ionizing-radiation-exposed-parent-apc-1638n-mice
#9
Shubhankar Suman, Santosh Kumar, Bo-Hyun Moon, Albert J Fornace, Bhaskar V S Kallakury, Kamal Datta
The purpose of the study was to assess transgenerational intestinal tumorigenic effects of low dose ionizing radiation employing a well-characterized mouse model of human colorectal cancer. Mice (6 to 8 weeks old APC(1638N/+) mice; n=20 per study group) were exposed to whole-body 25 cGy x-rays and mated 2 days post-irradiation. Intestinal tumorigenesis in male and female F1 mice from No Parents Irradiated (NPI), Both Parents Irradiated (BPI), and Male Parent Irradiated (MPI) groups were compared 210 days after birth...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819322/nampt-enzyme-activity-regulates-catabolic-gene-expression-in-gingival-fibroblasts-during-periodontitis
#10
Ka Hyon Park, Duck-Kyu Kim, Yun Hyun Huh, Gyuseok Lee, Su-Hyeon Lee, Yunkyung Hong, Sun-Hun Kim, Min-Suk Kook, Jeong-Tae Koh, Jang-Soo Chun, Shee Eun Lee, Je-Hwang Ryu
Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues...
August 18, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28819305/cardiorespiratory-pathogenesis-of-sickle-cell-disease-in-a-mouse-model
#11
Jun Ren, Xiuqing Ding, Marie Trudel, John J Greer, Joanna E MacLean
The nature and development of cardiorespiratory impairments associated with sickle cell disease are poorly understood. Given that the mechanisms of these impairments cannot be addressed adequately in clinical studies, we characterized cardiorespiratory pathophysiology from birth to maturity in the sickle cell disease SAD mouse model. We identified two critical phases of respiratory dysfunction in SAD mice; the first prior to weaning and the second in adulthood. At postnatal day 3, 43% of SAD mice showed marked apneas, anemia, and pulmonary vascular congestion typical of acute chest syndrome; none of these mice survived to maturity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819261/modified-vaccinia-virus-ankara-preferentially-targets-antigen-presenting-cells-in-vitro-ex-vivo-and-in-vivo
#12
Arwen F Altenburg, Carolien E van de Sandt, Bobby W S Li, Ronan J MacLoughlin, Ron A M Fouchier, Geert van Amerongen, Asisa Volz, Rudi W Hendriks, Rik L de Swart, Gerd Sutter, Guus F Rimmelzwaan, Rory D de Vries
Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819138/cooperative-interaction-of-bmp-signalling-and-foxn1-gene-dosage-determines-the-size-of-the-functionally-active-thymic-epithelial-compartment
#13
Jeremy B Swann, Brigitte Krauth, Christiane Happe, Thomas Boehm
Thymopoiesis strictly depends on the function of the Foxn1 transcription factor that is expressed in the thymic epithelium. During embryonic development, initial expression of the Foxn1 gene is induced in the pharyngeal endoderm by mesenchyme-derived BMP4 signals. Here, by engineering a time-delayed feedback system of BMP inhibition in mouse embryos, we demonstrate that thymopoiesis irreversibly fails if Foxn1 gene expression does not occur during a defining time span in mid-gestation. We also reveal an epistatic interaction between the extent of BMP signalling and the gene dosage of Foxn1...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819135/ribosomal-transcription-is-regulated-by-pgc-1alpha-and-disturbed-in-huntington-s-disease
#14
Sarah Jesse, Hanna Bayer, Marius C Alupei, Martina Zügel, Medhanie Mulaw, Francesca Tuorto, Silke Malmsheimer, Karmveer Singh, Jürgen Steinacker, Uwe Schumann, Albert C Ludolph, Karin Scharffetter-Kochanek, Anke Witting, Patrick Weydt, Sebastian Iben
PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1α localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I. Upon activation PGC-1α associates with the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819076/-molecularly-targeted-therapy-of-spinocerebellar-ataxia-type-1-by-hmgb1
#15
Kyota Fujita, Hitoshi Okazawa
Spinocerebellar ataxia type 1 (SCA1) is an untreatable neurodegenerative disease. We reported a decrease in HMGB1 levels in the nucleus of cerebellar neurons in mouse SCA 1. The decrease in this DNA architectural protein leads to the impairment of DNA repair and transcription, the two essential nuclear functions, and eventually causes neurodegeneration. We have designed a gene therapy using AAV-HMGB1 and tested it using the mouse model. Based on the results of these proof of concept (POC) studies, we are now preparing GMP-level AAV vector and designing human clinical trials...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28818972/fertile-offspring-from-sterile-sex-chromosome-trisomic-mice
#16
Takayuki Hirota, Hiroshi Ohta, Benjamin E Powell, Shantha K Mahadevaiah, Obah A Ojarikre, Mitinori Saitou, James M A Turner
Having the correct number of chromosomes is vital for normal development and health. Sex chromosome trisomy (SCT) affects 0.1% of the human population and is associated with infertility. We show that during reprogramming to induced pluripotent stem cells (iPSC), fibroblasts from sterile trisomic XXY and XYY mice lose the extra sex chromosome, by a phenomenon we term trisomy-biased chromosome loss (TCL). Resulting euploid XY iPSCs can be differentiated into the male germ cell lineage and functional sperm that can be used in intracytoplasmic sperm injection to produce chromosomally normal, fertile offspring...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818841/distinct-intestinal-adaptation-for-vitamin-b12-and-bile-acid-absorption-revealed-in-a-new-mouse-model-of-massive-ileocecal-resection
#17
Yuka Matsumoto, Wakana Mochizuki, Shintaro Akiyama, Taichi Matsumoto, Kengo Nozaki, Mamoru Watanabe, Tetsuya Nakamura
Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum...
August 17, 2017: Biology Open
https://www.readbyqxmd.com/read/28818832/b-cell-ox40l-supports-t-follicular-helper-cell-development-and-contributes-to-sle-pathogenesis
#18
Andrea Cortini, Ursula Ellinghaus, Talat H Malik, Deborah S Cunningham Grahman, Marina Botto, Timothy James Vyse
OBJECTIVES: TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus. METHODS: We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity...
August 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28818516/autoimmune-potential-of-perchloroethylene-role-of-lipid-derived-aldehydes
#19
Gangduo Wang, Jianling Wang, G A Shakeel Ansari, M Firoze Khan
Tetrachloroethene (perchloroethylene, PCE), an ubiquitous environmental contaminant, has been implicated in inducing autoimmunity/autoimmune diseases (ADs), including systemic lupus erythematosus (SLE) and scleroderma in humans. However, experimental evidence suggesting the potential of PCE in mediating autoimmunity is lacking. This study was, therefore, undertaken to explore PCE's potential in inducing/exacerbating an autoimmune response. Six-week old female MRL+/+ mice, in groups of 6 each, were treated with PCE (0...
August 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28818098/sex-chromosomes-drive-gene-expression-and-regulatory-dimorphisms-in-mouse-embryonic-stem-cells
#20
Rachael J Werner, Bryant M Schultz, Jacklyn M Huhn, Jaroslav Jelinek, Jozef Madzo, Nora Engel
BACKGROUND: Pre-implantation embryos exhibit sexual dimorphisms in both primates and rodents. To determine whether these differences reflected sex-biased expression patterns, we generated transcriptome profiles for six 40,XX, six 40,XY, and two 39,X mouse embryonic stem (ES) cells by RNA sequencing. RESULTS: We found hundreds of coding and non-coding RNAs that were differentially expressed between male and female cells. Surprisingly, the majority of these were autosomal and included RNA encoding transcription and epigenetic and chromatin remodeling factors...
August 17, 2017: Biology of Sex Differences
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