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https://www.readbyqxmd.com/read/28350984/autophagy-it-s-in-your-blood
#1
Sergei Doulatov, George Q Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28350968/induced-pluripotent-stem-cell-derived-cardiomyocytes-cardiac-applications-opportunities-and-challenges
#2
Adrien Moreau, Mohamed Boutjdir, Mohamed Chahine
Chronic diseases are the primary cause of mortality worldwide, accounting for 67% of deaths. One of the major challenges in developing new treatments is the lack of understanding of the exact underlying biological and molecular mechanisms. Chronic cardiovascular diseases are the single most common cause of death worldwide, and sudden deaths due to cardiac arrhythmias account for approximately 50% of all such cases. Traditional genetic screening for genes involved in cardiac disorders is laborious and frequently fails to detect the mutation that explains or causes the disorder...
March 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28350951/novel-osteobiologics-and-biomaterials-in-the-treatment-of-spinal-disorders
#3
Wellington K Hsu, Christina L Goldstein, Mohammed F Shamji, Sam K Cho, Paul M Arnold, Michael G Fehlings, Tom E Mroz
Spinal osteobiologics have evolved substantially in this century after the development of many product categories such as growth factors, allograft, and stem cells. The indications for the use of novel biologics within spine surgery are rapidly expanding as the mechanism of each is elucidated. While the knowledge base of bone morphogenetic protein increases with each subsequent year, the application of new nanotechnology and cell-based strategies are being reported. This review will discuss the most recent data in novel osteobiologics, and where we could use future study...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28350945/intervertebral-disk-degeneration-and-repair
#4
James Dowdell, Mark Erwin, Theodoe Choma, Alexander Vaccaro, James Iatridis, Samuel K Cho
Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28350869/in-vitro-skin-models-to-study-epithelial-regeneration-from-the-hair-follicle
#5
Nkemcho Ojeh, Baki Akgül, Marjana Tomic-Canic, Mike Philpott, Harshad Navsaria
The development of dermal equivalents (DEs) for the treatment of burns has contributed toward efficient wound closure. A collagen-glycosaminoglycan DE (C-GAG) grafted with hair follicles converted a full-thickness wound to partial-thickness resulting in complete wound closure and restored hair. In this study we compared the ability of both intact pilosebaceous units (PSU) or truncated hair follicles (THF) to regenerate a multilayered epidermis in vitro when implanted into de-epidermalized dermis (DED) or C-GAG with the epidermis generated in vivo using C-CAG...
2017: PloS One
https://www.readbyqxmd.com/read/28350815/-the-evil-virus-cell-students-knowledge-and-beliefs-about-viruses
#6
Uwe K Simon, Sonja M Enzinger, Andreas Fink
Education about virus biology at school is of pivotal interest to raise public awareness concerning means of disease transmission and, thus, methods to prevent infection, and to reduce unnecessary antibiotic treatment due to patient pressure on physicians in case of viral diseases such as influenza. This study aimed at making visible the knowledge of Austrian high school and university students with respect to virus biology, virus structure and health-education issues. The data presented here stem from comprehensive questionnaire analyses, including the task to draw a virus, from a cross-sectional study with 133 grade 7 and 199 grade 10 high school students, and 133 first-year biology and 181 first-year non-biology university students...
2017: PloS One
https://www.readbyqxmd.com/read/28350668/regeneration-of-vascularized-corticocancellous-bone-and-diploic-space-using-muscle-derived-stem-cells-a-translational-biologic-alternative-for-healing-critical-bone-defects
#7
Denver Lough, Edward Swanson, Nikolai A Sopko, Christopher Madsen, Devin Miller, Howard Wang, Qiongyu Guo, Srinivas M Sursala, Anand R Kumar
BACKGROUND: Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing...
April 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28346802/metabolome-profiling-of-partial-and-fully-reprogrammed-induced-pluripotent-stem-cells
#8
Soon-Jung Park, Sang A Lee, Nutan Prasain, Daekyeong Bae, Hyunsu Kang, Taewon Ha, Jong Soo Kim, Ki-Sung Hong, Charlie Mantel, Sung-Hwan Moon, Hal E Broxmeyer, Man Ryul Lee
Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs...
March 27, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28346796/harnessing-external-cues-development-and-evaluation-of-an-in-vitro-culture-system-for-osteochondral-tissue-engineering
#9
Deborah L Dorcemus, Eve O George, Caroline N Dealy, Syam P Nukavarapu
Over the last decade, engineered structures have been developed for osteochondral (OC) tissue regeneration. While the optimal structure design is yet to be determined, these scaffolds require in vitro evaluation before clinical use. However, the means by which complex scaffolds, such as OC scaffolds, can be tested are limited. Taking advantage of a mesenchymal stem cell's (MSC's) ability to respond to its surrounding we harness external cues, such as the cell's mechanical environment and delivered factors, to create an in vitro culture system for OC tissue engineering with a single cell source on a gradient yet integrated scaffold system...
March 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28346423/mob1-yap1-taz-nkx2-1-axis-controls-bronchioalveolar-cell-differentiation-adhesion-and-tumour-formation
#10
K Otsubo, H Goto, M Nishio, K Kawamura, S Yanagi, W Nishie, T Sasaki, T Maehama, H Nishina, K Mimori, T Nakano, H Shimizu, T W Mak, K Nakao, Y Nakanishi, A Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1a(flox/flox)/Mob1b(-/-); termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#11
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346106/isolation-and-characterization-of-a-distinct-subpopulation-from-the-wm115-cell-line-that-resembles-in-vitro-properties-of-melanoma-cancer-stem-cells
#12
Sonia G Escobar, Mark H Chin, Mark L Sandberg, Han Xu
Despite key advances in cancer therapies, malignant tumors, such as melanoma, continue to be one of the leading causes of mortality. Recent debate on whether cancer can originate from a tumor-initiating subpopulation has permeated oncology and stem cell research. It has been well established that primary and immortalized tumor cells consist of heterogeneous cell populations. The profound effect of tumor heterogeneity on tumor growth and drug resistance remains elusive, but it is highly likely that subpopulations of cancer cells have different capabilities of self-renewal and drug resistance...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346100/robotic-mammosphere-assay-for-high-throughput-screening-in-triple-negative-breast-cancer
#13
P A Fitzpatrick, N Akrap, E M V Söderberg, H Harrison, G J Thomson, G Landberg
In order to identify novel treatment principles specifically affecting cancer stem cells in triple-negative breast cancer, we have developed a high-throughput screening method based on the mammosphere and anoikis resistance assays allowing us to screen compounds using a functional readout. The assay was validated against manual protocols and through the use of positive controls, such as the response to hypoxia and treatment with the known cancer stem cell-targeting compound salinomycin. Manual and robotic procedures were compared and produced similar results in cell handling, cell cultures, and counting techniques, with no statistically significant difference produced from either method...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346060/stem-cell-derived-neurons-in-the-development-of-targeted-treatment-for-schizophrenia-and-bipolar-disorder
#14
Bradley Watmuff, Bangyan Liu, Rakesh Karmacharya
The recent advent of induced pluripotent stem cells has enabled the study of patient-specific and disease-related neurons in vitro and has facilitated new directions of inquiry into disease mechanisms. With these approaches, we now have the possibility of correlating ex vivo cellular phenotypes with individual patient response to treatment and/or side effects, which makes targeted treatments for schizophrenia and bipolar disorder a distinct prospect in the coming years. Here, we briefly review the current state of stem cell-based models and explore studies that are providing new insights into the disease biology of schizophrenia and bipolar disorder, which are laying the foundations for the development of novel targeted therapies...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28345955/smoking-dependent-distal-to-proximal-repatterning-of-the-adult-human-small-airway-epithelium
#15
Jing Yang, Wu-Lin Zuo, Tomoya Fukui, IonWa Chao, Kazunori Gomi, Busub Lee, Michelle R Staudt, Robert J Kaner, Yael Strulovici-Barel, Jacqueline Salit, Ronald G Crystal, Renat Shaykhiev
RATIONALE: Small airways are the primary site of pathologic changes in chronic obstructive pulmonary disease (COPD), the major smoking-induced lung disorder. OBJECTIVES: Based on the concept of proximal-distal patterning that determines regional specialization of the airway epithelium during lung development, we hypothesized that a similar program operates in the adult human lung being altered by smoking leading to decreased regional identity of the small airway epithelium (SAE)...
March 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28345876/engineering-cellular-microenvironments-with-photo-and-enzymatically-responsive-hydrogels-toward-biomimetic-3d-cell-culture-models
#16
Roger Y Tam, Laura J Smith, Molly S Shoichet
Conventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as cell proliferation, differentiation, and cell-cell interactions. However, the physical and chemical properties of 2D culture in vitro are dramatically different than those found in the native cellular microenvironment in vivo. Cells grown on 2D substrates differ significantly from those grown in vivo, and this explains, in part, why many promising drug candidates discovered through in vitro drug screening assays fail when they are translated to in vivo animal or human models...
March 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28345658/nephronectin-plays-critical-roles-in-sox2-expression-and-proliferation-in-dental-epithelial-stem-cells-via-egf-like-repeat-domains
#17
Chieko Arai, Keigo Yoshizaki, Kanako Miyazaki, Kan Saito, Aya Yamada, Xue Han, Keita Funada, Emiko Fukumoto, Naoto Haruyama, Tsutomu Iwamoto, Ichiro Takahashi, Satoshi Fukumoto
Tooth development is initiated by epithelial-mesenchymal interactions via basement membrane (BM) and growth factors. In the present study, we found that nephronectin (Npnt), a component of the BM, is highly expressed in the developing tooth. Npnt localizes in the BM on the buccal side of the tooth germ and shows an expression pattern opposite that of the dental epithelial stem cell marker Sox2. To identify the roles of Npnt during tooth development, we performed knockdown and overexpression experiments using ex vivo organ and dental epithelial cell cultures...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345611/copy-number-variation-profile-in-the-placental-and-parental-genomes-of-recurrent-pregnancy-loss-families
#18
Laura Kasak, Kristiina Rull, Siim Sõber, Maris Laan
We have previously shown an extensive load of somatic copy number variations (CNVs) in the human placental genome with the highest fraction detected in normal term pregnancies. Hereby, we hypothesized that insufficient promotion of CNVs may impair placental development and lead to recurrent pregnancy loss (RPL). RPL affects ~3% of couples aiming at childbirth and idiopathic RPL represents ~50% of cases. We analysed placental and parental CNV profiles of idiopathic RPL trios (mother-father-placenta) and duos (mother-placenta)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345602/a-primary-human-macrophage-enteroid-co-culture-model-to-investigate-mucosal-gut-physiology-and-host-pathogen-interactions
#19
Gaelle Noel, Nicholas W Baetz, Janet F Staab, Mark Donowitz, Olga Kovbasnjuk, Marcela F Pasetti, Nicholas C Zachos
Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#20
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
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