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Joo-Hung Park, Jeong-Min Lee, Eun-Jin Lee, Won-Bhin Hwang, Da-Jeong Kim
Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of α-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent...
March 21, 2018: Molecules and Cells
Gediminas Greicius, Zahra Kabiri, Kristmundur Sigmundsson, Chao Liang, Ralph Bunte, Manvendra K Singh, David M Virshup
Wnts and R-spondins (RSPOs) support intestinal homeostasis by regulating crypt cell proliferation and differentiation. Ex vivo, Wnts secreted by Paneth cells in organoids can regulate the proliferation and differentiation of Lgr5 -expressing intestinal stem cells. However, in vivo, Paneth cell and indeed all epithelial Wnt production is completely dispensable, and the cellular source of Wnts and RSPOs that maintain the intestinal stem-cell niche is not known. Here we investigated both the source and the functional role of stromal Wnts and RSPO3 in regulation of intestinal homeostasis...
March 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yao Yao Lu, Hui Dong, Yong Jie Feng, Kai Wang, Yi Bao Jiang, Long Xian Zhang, Yu Rong Yang
Toxoplasma gondii has a complex life cycle and pathogenic mechanisms. Acute T. gondii infections in mice often result in death, whereas in chronic infections, the parasites may persist in the host tissues as intraneuronal or intramuscular cysts. However, the virulence of T. gondii strains in mice varies with its genetic background. The present study investigated the pathogenicity and pathological lesions of two T. gondii isolates from China: namely, TgCatCHn2 (ToxoDB#17) and TgCatCHn4 (ToxoDB#9). The virulent (ToxoDB#216) and avirulent (VEG) strains were employed as controls...
March 15, 2018: Veterinary Parasitology
Hee Kyoung Chung, Shelley R Wang, Lan Xiao, Navneeta Rathor, Douglas J Turner, Peixin Yang, Myriam Gorospe, Jaladanki N Rao, Jian-Ying Wang
The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and its homeostasis depends on a dynamic balance among proliferation, migration, apoptosis, and differentiation of intestinal epithelial cells (IECs). The PP2A-associated protein α4 controls the activity and specificity of serine/threonine phosphatases and is thus implicated in many cellular processes. Here we investigated the mechanisms whereby α4 controls the homeostasis of the intestinal epithelium using a genetic approach...
March 19, 2018: Molecular and Cellular Biology
Brooke L Slawinski, Nicole Talge, Brooke Ingersoll, Arianna Smith, Alicynne Glazier, Jean Kerver, Nigel Paneth, Karen Racicot
PROBLEM: Autism spectrum disorder (ASD) is one of the most commonly diagnosed neurodevelopmental disorders in the United States. While ASD can be significantly influenced by genetics, prenatal exposure to maternal infections has also been implicated in conferring risk. Despite this, the effects of several important maternal pathogens, such as cytomegalovirus (CMV) and herpes simplex virus 2 (HSV2), remain unknown. METHOD OF STUDY: We tested whether maternal CMV and/or HSV2 sero-positivity was associated with ASD symptoms in children...
March 9, 2018: American Journal of Reproductive Immunology: AJRI
B van der Hee, L M P Loonen, N Taverne, J J Taverne-Thiele, H Smidt, J M Wells
An important practical limitation of the three-dimensional geometry of stem-cell derived intestinal organoids is that it prevents easy access to the apical epithelium for testing food components, microorganisms, bioactive and toxic compounds. To this end, we here report on a new robust method for generating confluent intestinal cell monolayers from single-cell suspensions of enzymatically-dissociated porcine organoids using modified culture conditions. With this method, cell seeding densities can be standardised, overcoming problems with methods based on mechanical dissociation of organoids...
February 20, 2018: Stem Cell Research
Jonas Wizenty, Muhammad Imtiaz Ashraf, Nadine Rohwer, Martin Stockmann, Sascha Weiss, Matthias Biebl, Johann Pratschke, Felix Aigner, Tilo Wuensch
Immunofluorescence (IF) staining of paraffin-embedded tissues is a frequently used method to answer research questions or even detect the abundance of a certain protein for diagnostic use. However, the signal originating from specific antibody-staining might be distorted by autofluorescence (AF) of the assessed tissue. Although the AF phenomenon is well known, its presence is often neglected by insufficient staining controls. In this study, we describe the existence of cellular AF in paraffin-embedded healthy and inflamed human and murine colonic tissues and present ways to reduce AF...
February 16, 2018: Journal of Immunological Methods
Zhi-Jian Sun, Yi-Zhe Zhang, Fan Liu, Juan-Juan Chen, Dong-Xue Chen, Hong-Bao Liu, Liang Liang, Hua Han
Intestine is vulnerable to irradiation injury, which induces cell death and compromises regeneration of intestinal crypts. It is well accepted that cryptic stem cells, which are responsible for cryptic regeneration under physiological and pathological conditions, are controlled by multiple cell-intrinsic and environmental signals such as Notch signaling. Therefore in this study, we tested whether a soluble Notch ligand tethered to endothelial cells -- mD1R -- ¬¬¬the DSL domain of mouse Notch ligand Delta-like1 fused with a RGD motif, could protect cryptic cells from irradiation-induced intestinal injury...
February 14, 2018: Bioscience Reports
B Sayyaf Dezfuli, M Manera, G Bosi, P Merella, J A DePasquale, L Giari
This investigation aims to fill gaps in our understanding of the intestinal immune cells of elasmobranchs. Whole digestive tracts of fifteen thornback ray Raja clavata were provided by a trawl fleet from the Gulf of Asinara (Sardinia, western Mediterranean Sea). Histochemical, immunohistochemical and ultrastructural observations were conducted on the spiral intestine. Three types of granular cells were identified; type I in epithelium, types II and III in lamina propria-submucosa, with each of them containing cytoplasmic granules with different ultrastructural characteristics...
February 9, 2018: Fish & Shellfish Immunology
Sara H Rouhanifard, Aime Lopez Aguilar, Lu Meng, Kelley W Moremen, Peng Wu
At the base of the intestinal crypt, long-lived Lgr5+ stem cells are intercalated by Paneth cells that provide essential niche signals for stem cell maintenance. This unique epithelial anatomy makes the intestinal crypt one of the most accessible models for the study of adult stem cell biology. The glycosylation patterns of this compartment are poorly characterized, and the impact of glycans on stem cell differentiation remains largely unexplored. We find that Paneth cells, but not Lgr5+ stem cells, express abundant terminal N-acetyllactosamine (LacNAc)...
February 1, 2018: Cell Chemical Biology
Sarah C Pearce, Arwa Al-Jawadi, Kunihiro Kishida, Shiyan Yu, Madeleine Hu, Luke F Fritzky, Karen L Edelblum, Nan Gao, Ronaldo P Ferraris
BACKGROUND: Mammalian small intestinal tight junctions (TJ) link epithelial cells to one another and function as a permselective barrier, strictly modulating the passage of ions and macromolecules through the pore and leak pathways, respectively, thereby preventing the absorption of harmful compounds and microbes while allowing regulated transport of nutrients and electrolytes. Small intestinal epithelial permeability is ascribed primarily to the properties of TJs between adjoining enterocytes (ENTs), because there is almost no information on TJ composition and the paracellular permeability of nonenterocyte cell types that constitute a small but significant fraction of the intestinal epithelia...
February 1, 2018: BMC Biology
Shai Bel, Lora V Hooper
Secretion of antimicrobial proteins is an important host defense mechanism against bacteria, yet how secretory cells maintain function during bacterial invasion has been unclear. We discovered that Paneth cells, specialized secretory cells in the small intestine, react to bacterial invasion by rerouting a critical secreted antibacterial protein through a macroautophagy/autophagy-based secretion system termed secretory autophagy. Mice harboring a mutation in an essential autophagy gene, a mutation which is common in Crohn disease patients, cannot reroute their antimicrobial cargo during bacterial invasion and thus have compromised innate immunity...
February 1, 2018: Autophagy
Hirosato Mashima, Noboru Watanabe, Masanari Sekine, Satohiro Matsumoto, Takeharu Asano, Kazuhito Yuhashi, Noriyoshi Sagihara, Shunsuke Urayoshi, Takeshi Uehara, Junichi Fujiwara, Takehiro Ishii, Rumiko Tsuboi, Hiroyuki Miyatani, Hirohide Ohnishi
Intestinal homeostasis and the coordinated actions of digestion, absorption and excretion are tightly regulated by a number of gastrointestinal hormones. Most of them exert their actions through G-protein-coupled receptors. Recently, we showed that the absence of Gαq/Gα11 signaling impaired the maturation of Paneth cells, induced their differentiation toward goblet cells, and affected the regeneration of the colonic mucosa in an experimental model of colitis. Although an immunohistochemical study showed that Gαq/Gα11 were highly expressed in enterocytes, it seemed that enterocytes were not affected in Int-Gq/G11 double knock-out intestine...
March 2018: Biochemistry and Biophysics Reports
Nigel Paneth, Catherine Monk
PURPOSE OF REVIEW: The current review addresses the importance of the prospective cohort design in large, unselected populations starting early in life for understanding the origins of childhood health disorders. RECENT FINDINGS: Cohort studies originating in healthy populations have contributed to great advances in health, especially in cardiovascular diseases, but have only recently been applied systematically to study the origins of childhood disorders. Several large population-based pregnancy and/or birth cohorts have been developed in different parts of the world, and these are beginning to contribute to better understanding of the underlying causes of rare but important childhood disorders, such as autism...
January 25, 2018: Current Opinion in Pediatrics
Carlos Tejeda-Guzmán, Abraham Rosas-Arellano, Thomas Kroll, Samuel M Webb, Martha Barajas-Aceves, Beatriz Osorio, Fanis Missirlis
Membrane transporters and sequestration mechanisms concentrate metal ions differentially into discrete subcellular microenvironments for usage in protein cofactors, signaling, storage, or excretion. Here we identify zinc storage granules as the insect's major zinc reservoir in principle Malpighian tubule epithelial cells of Drosophila melanogaster The concerted action of Adaptor Protein-3, Rab32, HOPS and BLOC complexes as well as of the white-scarlet (ABCG2-like) and ZnT35C (ZnT2/ZnT3/ZnT8-like) transporters is required for zinc storage granule biogenesis...
January 24, 2018: Journal of Experimental Biology
Mary Jo Cooley Hidecker, Jaime Slaughter, Purni Abeysekara, Nhan T Ho, Nancy Dodge, Edward A Hurvitz, Marilyn Seif Workinger, Ray D Kent, Peter Rosenbaum, Madeleine Lenski, Suzette Báez Vanderbeek, Steven DeRoos, Nigel Paneth
Birth characteristics and developmental milestones were evaluated as early predictors/correlates of communication in children with cerebral palsy. The hypothesis was that maternal report of child's age for vocal play and first words would predict current functional communication. A case series of 215 children, 2 to 17 years (mean age = 8.2 years, SD = 3.9) with cerebral palsy was recruited from medical practices in 3 Michigan cities. Early developmental data were collected by maternal interview. The child's Communication Function Classification System (CFCS) level was obtained from parent...
January 1, 2018: Journal of Child Neurology
Allison R Rogala, Alexi A Schoenborn, Brian E Fee, Viviana A Cantillana, Maria J Joyce, Raad Z Gharaibeh, Sayanty Roy, Anthony A Fodor, R Balfour Sartor, Gregory A Taylor, Ajay S Gulati
Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-Related GTPase M (IRGM) is an established CD risk allele. We have shown previously that conventionally-raised (CV) mice lacking the IRGM ortholog, Irgm1, exhibit abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD...
December 22, 2017: Disease Models & Mechanisms
Elise Burger, Alessandra Araujo, Américo López-Yglesias, Michael W Rajala, Linda Geng, Beth Levine, Lora V Hooper, Ezra Burstein, Felix Yarovinsky
The protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by IFN-γ- and intestinal microbiota-mediated inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a prominent secretory epithelial cell type that resides at the base of intestinal crypts and releases antimicrobial peptides. We demonstrate that the microbiota triggers basal Paneth cell-specific autophagy via induction of IFN-γ, a known trigger of autophagy, to maintain intestinal homeostasis...
January 17, 2018: Cell Host & Microbe
Dominik Filipp, Tomáš Brabec, Matouš Vobořil, Jan Dobeš
The gut is the biggest immune organ in the body that encloses commensal microbiota which aids in food digestion. Paneth cells, positioned at the frontline of host-microbiota interphase, can modulate the composition of microbiota. Paneth cells achieve this via the delivery of microbicidal substances, among which enteric α-defensins play the primary role. If microbiota is dysregulated, it can impact the function and fitness of the local mucosal immune system. Importantly, this system is also exposed to an enormous number of antigens which are derived from the gut-resident microbiota and processed food, and may potentially trigger undesirable local inflammatory responses...
January 16, 2018: Seminars in Cell & Developmental Biology
Nigel Paneth
No abstract text is available yet for this article.
February 2018: Developmental Medicine and Child Neurology
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