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cell replacement

Yiling Hong, Nymph Chan, Aynun N Begum
Stem cells are undifferentiated biological cells that can differentiate into all lineages under defined control condition. Stem cell neuronal differentiation can faithfully recapitulate stages of neural development and generate neuronal progenitors, mature neurons, and glial cells. Stem cell technology will largely allow for the replacement of animal studies and reduce costs, and will provide a new paradigm for in toxic genomics, bioinformatics, systems biology, and epigenetics studies. Here, we describe a nonadherent neuronal differentiation methodology developed in our laboratory, which can rapidly derive neurons and astrocytes from human embryonic stem cells (hESCs) and induced pluripotent stem cell (hiPSC) and use of this platform for nanoparticle neurotoxicity study...
2019: Methods in Molecular Biology
Youichi Kumagai, Kaiyo Takubo, Kenro Kawada, Kazuharu Aoyama, Yuma Endo, Tsuyoshi Ozawa, Toshiaki Hirasawa, Toshiyuki Yoshio, Soichiro Ishihara, Mitsuhiro Fujishiro, Jun-Ichi Tamaru, Erito Mochiki, Hideyuki Ishida, Tomohiro Tada
BACKGROUND AND AIMS: The endocytoscopic system (ECS) helps in virtual realization of histology and can aid in confirming histological diagnosis in vivo. We propose replacing biopsy-based histology for esophageal squamous cell carcinoma (ESCC) by using the ECS. We applied deep-learning artificial intelligence (AI) to analyse ECS images of the esophagus to determine whether AI can support endoscopists for the replacement of biopsy-based histology. METHODS: A convolutional neural network-based AI was constructed based on GoogLeNet and trained using 4715 ECS images of the esophagus (1141 malignant and 3574 non-malignant images)...
December 13, 2018: Esophagus: Official Journal of the Japan Esophageal Society
Tracy L Habermehl, Kate C Parkinson, Gene B Hubbard, Yuji Ikeno, Jennifer I Engelmeyer, Björn Schumacher, Jeffrey B Mason
Cardiovascular disease, rare in premenopausal women, increases sharply at menopause and is typically accompanied by chronic inflammation. Previous work in our laboratory demonstrated that replacing senescent ovaries in post-reproductive mice with young, actively cycling ovaries restored many health benefits, including decreased cardiomyopathy and restoration of immune function. Our objective here was to determine if depletion of germ cells from young transplanted ovaries would alter the ovarian-dependent extension of life and health span...
December 13, 2018: GeroScience
Shigeru Miyagawa, Keitaro Domae, Satoshi Kainuma, Ryouhei Matsuura, Daisuke Yoshioka, Hiroki Hata, Yasushi Yoshikawa, Koichi Toda, Yoshiki Sawa
BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening heart muscle disease characterized by progressive heart failure, which often requires left ventricular assist device (LVAD) implantation or heart transplantation (HTx). A tissue engineering strategy using cell sheets for end-stage heart failure has emerged in recent years. CASE PRESENTATION: Here, we describe a 50-year-old DCM patient with severe symptoms of heart failure with severe mitral regurgitation (MR) who was not a candidate for LVAD or HTx...
December 13, 2018: Surgical Case Reports
Vanida Ann Serna, Takeshi Kurita
Uterine leiomyoma (UL) or fibroid is a benign smooth muscle tumor of the myometrium with a lifetime incidence of approximately 70%. ULs often require medical intervention due to severe symptoms such as heavy menstrual bleeding and abdominal pain. Although the most common and effective management of ULs is surgical removal, the invasive surgical procedure imposes physical and psychological burdens on the patients. Moreover, the economic burden of UL on health care system is enormous due to the high cost of surgeries...
2018: Journal of Biological Methods
Huagang Peng, Yifan Rao, Wenchang Yuan, Ying Zheng, Weilong Shang, Zhen Hu, Yi Yang, Li Tan, Kun Xiong, Shu Li, Junmin Zhu, Xiaomei Hu, Qiwen Hu, Xiancai Rao
The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) has raised healthcare concerns worldwide. VISA is often associated with multiple genetic changes. However, the relative contributions of these changes to VISA phenotypes are incompletely defined. We have characterized VISA XN108 with vancomycin MIC of 12 μg/ml. Genome comparison revealed that WalK(S221P), GraS(T136I), and RpoB(H481N) mutations possibly contributed to the VISA phenotype of XN108. In this study, the above mutations were stepwise cured, and the phenotypes between XN108 and its derivates were compared...
2018: Frontiers in Microbiology
Sameer B Shah, David Parmiter, Christian Constantine, Paul Elizalde, Michael Naldrett, Tatiana S Karpova, John S Choy
The Dam1 complex is an essential component of the outer kinetochore that mediates attachments between spindle microtubules and chromosomes. Dam1p, a subunit of the Dam1 complex, binds to microtubules and is regulated by Aurora B/Ipl1p phosphorylation. We find that overexpression of cAMP-dependent protein kinase (PKA) catalytic subunits (i.e. TPK1 , TPK2 , TPK3 ) is lethal in DAM1 mutants and increases the rate of chromosome loss in wild-type cells. Replacing an evolutionarily conserved PKA site (S31) in Dam1p with a non-phosphorylatable alanine suppressed the high copy PKA dosage lethality in dam1-1 Consistent with Dam1p as a target of PKA we find that in vitro PKA can directly phosphorylate S31 in Dam1p and we observed phosphorylation of S31 in Dam1p purified from asynchronously growing yeast cells...
December 13, 2018: Genetics
Christian Opitz, Erik Ahrné, Kenneth N Goldie, Alexander Schmidt, Stephan Grzesiek
Substitution of protium (H) for deuterium (D) strongly affects biological systems. Whereas higher eukaryotes such as plants and mammals hardly survive a deuterium content of > 30%, many microorganisms can grow on fully deuterated media, albeit at reduced rates. Very little is known about how the H/D replacement influences life at the systems level. Here, we used MS-based analysis to follow the adaptation of a large part of the Escherichia coli proteome from growth on a protonated full medium, over a protonated minimal medium, to a completely deuterated minimal medium...
December 13, 2018: Journal of Biological Chemistry
Sandrine Delignat, Jules Russick, Bagirath Gangadharan, Julie Rayes, Mathieu Ing, Jan Voorberg, Srinivas V Kaveri, Sébastien Lacroix-Desmazes
Hemophilia A is a rare hemorrhagic disorder due to the lack of functional pro-coagulant factor VIII. Factor VIII replacement therapy in patients with severe hemophilia A results in the development of inhibitory anti-factor VIII IgG in up to 30% of the cases. To date, immune tolerance induction upon daily injection of large amounts of factor VIII is the only strategy to eradicate factor VIII inhibitors. It is however efficient in only 60-80% of the patients. Here, we investigated whether blocking B-cell receptor signaling upon inhibition of the Bruton's tyrosine kinase prevents anti-factor VIII immune responses in a mouse model of severe hemophilia A...
December 13, 2018: Haematologica
Michael J Burke, Wanda L Salzer, Meenakshi Devidas, Yunfeng Dai, Lia Gore, Joanne M Hilden, Eric Larsen, Karen R Rabin, Patrick A Zweidler-McKay, Michael J Borowitz, Brent Wood, Nyla A Heerema, Andrew J Carroll, Naomi Winick, William L Carroll, Elizabeth A Raetz, Mignon L Loh, Stephen P Hunger
With modern chemotherapy, approximately 90% of patients with pediatric acute lymphoblastic leukemia are now cured. However, subsets of patients can be identified who remain at very high risk of relapse with expected 4-year disease-free survival <80% and are appropriate candidates for intensive therapeutic strategies designed to improve survival. AALL1131 aimed to determine, in a randomized fashion, if the substitution with cyclophosphamide/etoposide (Experimental Arm 1) would improve the 4-year disease-free survival of children, adolescents, and young adults with very high-risk B-cell acute lymphoblastic leukemia compared to a modified Berlin-Frankfurt-Munster regimen (Control Arm)...
December 13, 2018: Haematologica
Janine Wörthmüller, Anne Oberson, Valérie Salicio, Walter Blum, Beat Schwaller
Calretinin (CR; CALB2 ) belonging to the family of EF-hand Ca2+ -binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca2+ buffer protein, i.e., limiting the amplitude of Ca2+ signals but also as a Ca2+ sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR's functions(s) in MM cells...
December 12, 2018: International Journal of Molecular Sciences
Marcia Bodero, Arjen Gerssen, Liza Portier, Mirjam D Klijnstra, Ron L A P Hoogenboom, Leonardo Guzmán, Peter J M Hendriksen, Toine F H Bovee
Marine biotoxins in fish and shellfish can cause several symptoms in consumers, such as diarrhea, amnesia, or even death by paralysis. Monitoring programs are in place for testing shellfish on a regular basis. In some countries testing is performed using the so-called mouse bioassay, an assay that faces ethical concerns not only because of animal distress, but also because it lacks specificity and results in high amounts of false positives. In Europe, for lipophilic marine biotoxins (LMBs), a chemical analytical method using LC-MS/MS was developed as an alternative and is now the reference method...
December 12, 2018: Marine Drugs
Verena Petzer, Igor Theurl, Günter Weiss
Inflammation, being a hallmark of many chronic diseases, including cancer, inflammatory bowel disease, rheumatoid arthritis, and chronic kidney disease, negatively affects iron homeostasis, leading to iron retention in macrophages of the mononuclear phagocyte system. Functional iron deficiency is the consequence, leading to anemia of inflammation (AI). Iron deficiency, regardless of anemia, has a detrimental impact on quality of life so that treatment is warranted. Therapeutic strategies include (1) resolution of the underlying disease, (2) iron supplementation, and (3) iron redistribution strategies...
December 11, 2018: Pharmaceuticals
Sergey A Sinenko, Elena V Skvortsova, Mikhail A Liskovykh, Sergey V Ponomartsev, Andrey A Kuzmin, Aleksandr A Khudiakov, Anna B Malashicheva, Natalia Alenina, Vladimir Larionov, Natalay Kouprina, Alexey N Tomilin
AlphoidtetO -type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic diseases caused by the loss of a particular gene function. The alphoidtetO -HAC vector has been successfully transferred into murine embryonic stem cells (ESCs) and maintained stably as an independent chromosome during the proliferation and differentiation of these cells...
December 8, 2018: Cells
Pan Wu, Lingling Zhang, Tao Feng, Wenying Lu, Huayan Zhao, Jianzhong Li, Shiyou Lü
High amounts of polyunsaturated fatty acids (PUFAs) in vegetable oil are not desirable for biodiesel or food oil due to their lower oxidative stability. The oil from Idesia polycarpa fruit contains 65⁻80% (mol%) linoleic acid (C18:2). Therefore, development of Idesia polycarpa cultivars with low PUFAs is highly desirable for Idesia polycarpa oil quality. Fatty acid desaturase 2 (FAD2) is the key enzyme converting oleic acid (C18:1) to C18:2. We isolated four FAD2 homologs from the fruit of Idesia polycarpa ...
December 7, 2018: International Journal of Molecular Sciences
Ricardo Trindade, Tomas Albrektsson, Silvia Galli, Zdenka Prgomet, Pentti Tengvall, Ann Wennerberg
Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control...
December 7, 2018: Journal of Clinical Medicine
Zhengyan Feng, Zhengjing Zhang, Kai Hua, Xifeng Gao, Yanfei Mao, Jose Ramon Botella, Jian-Kang Zhu
The CRISPR/Cas9 system has been widely used for targeted genome editing in numerous plant species. In Arabidopsis , constitutive promoters usually result in a low efficiency of heritable mutation in the T1 generation. In this work, CRISPR/Cas9 gene editing efficiencies using different promoters to drive Cas9 expression were evaluated. Expression of Cas9 under the constitutive CaMV 35S promoter resulted in a 2.3% mutation rate in T1 plants and failed to produce homozygous mutations in the T1 and T2 generations...
December 7, 2018: International Journal of Molecular Sciences
John Szendrey, Shawn M Lamothe, Stephanie Vanner, Jun Guo, Tonghua Yang, Wentao Li, Jordan Davis, Mala Joneja, Adrian Baranchuk, Shetuan Zhang
Aims: The human ether-a-go-go-related gene (hERG) encodes the rapidly activating delayed rectifier potassium channel (IKr). Malfunction of hERG/IKr is the primary cause of acquired long QT syndrome (LQTS), an electrical disorder of the heart that can cause arrhythmias and sudden death. Patients with autoimmune diseases display a high incidence of LQTS. While dysfunction of hERG channels induced by autoantibodies such as anti-Ro52 may play a role in this pathology, the underlying mechanisms are not well understood...
December 13, 2018: Cardiovascular Research
Takanori Konishi, Rebecca M Schuster, Alex B Lentsch
Liver recovery after hepatic ischemia/reperfusion (I/R) injury is characterized by clearance of dead tissue and its replacement with functional liver parenchyma. Previous reports have observed fibrosis after liver I/R. In order to determine if liver fibrosis after I/R was a pathologic consequence of the injury response, we assessed the development of liver fibrosis after I/R and its impact on subsequent insult. A murine model of partial I/R was used to induce liver injury and study the reparative response. During liver remodeling after I/R, expression of the pro-fibrotic genes increased in the ischemic liver...
December 13, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Zhao Chen, Li di, Ning Xu, Jinzhang Fang, Yan Yu, Wei Hou, Haoqiang Ruan, Panpan Zhu, Renchao Ma, Shiying Lu, Danhui Cao, Rui Wu, Mowei Ni, Wei Zhang, Weike Su, Benfang Helen Ruan
Kidney-type glutaminase (KGA/isoenzyme glutaminase C [GAC]) is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, we explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol ethyl sulfide (BPTES) and CB-839 analogs with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles...
December 13, 2018: Journal of Medicinal Chemistry
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