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Masanori Tachikawa, Yuna Sumiyoshiya, Daisuke Saigusa, Kazunari Sasaki, Michitoshi Watanabe, Yasuo Uchida, Tetsuya Terasaki
The purpose of the present study was to clarify the molecular basis of zonated drug distributions in mouse liver based on the protein expression levels of transporters and metabolizing enzymes in peri-portal vein (PP) and peri-central vein (PC) regions of mouse hepatic lobules. The distributions of sulforhodamine 101 (SR-101), a substrate of organic anion transporting polypeptides (Oatps), and ribavirin, a substrate of equilibrative nucleoside transporter 1 (Ent1), were elucidated in frozen liver sections of mice to which each compound had been intravenously administered...
March 5, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Ruoxiao Xie, Peidi Xu, Yupeng Liu, Lili Li, Guoan Luo, Mingyu Ding, Qionglin Liang
Fiber materials with different structural features, which in many cases endow the fibers extraordinary functions, are drawing considerable attention from biomedical and material researchers. Here, perfusable necklace-like knotted microfibers are presented for the first time. Additionally, a novel microfluidic spinning method facilitates the production of variable knots and channels. Not only spindle-, but also hemisphere- and petal-knotted microfibers can be controllably fabricated. Generation and perfusion of both Janus channels and helical channel in the knotted microfibers are also shown...
February 27, 2018: Advanced Materials
Tainá Carneiro de Castro Monte, Brunna Vianna Braga, Maurício Carvalho de Vasconcellos, Arnon Dias Jurberg, Ester Maria Mota, Helene Santos Barbosa, Juberlan Silva Garcia, Arnaldo Maldonado Júnior
Helminth parasites have been studied as potential accumulators for different pollutants. Echinostoma paraensei is a foodborne trematode whose vertebrate host, the rodent Nectomys squamipes, is naturally exposed to environmental pesticides. However, little information exists regarding the pesticide's effects on helminths. This study investigated the morphological effects on the trematode, E. paraensei, after experimental Roundup® herbicide exposure, in concentrations below those recommended for agricultural use...
February 19, 2018: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
Tim B Fessenden, Yvonne Beckham, Mathew Perez-Neut, Guillermina Ramirez-San Juan, Aparajita H Chourasia, Kay F Macleod, Patrick W Oakes, Margaret L Gardel
Developing tissues change shape and tumors initiate spreading through collective cell motility. Conserved mechanisms by which tissues initiate motility into their surroundings are not known. We investigated cytoskeletal regulators during collective invasion by mouse tumor organoids and epithelial Madin-Darby canine kidney (MDCK) acini undergoing branching morphogenesis in collagen. Use of the broad-spectrum formin inhibitor SMIFH2 prevented the formation of migrating cell fronts in both cell types. Focusing on the role of the formin Dia1 in branching morphogenesis, we found that its depletion in MDCK cells does not alter planar cell motility either within the acinus or in two-dimensional scattering assays...
February 5, 2018: Journal of Cell Biology
Kenichiro Koshiyama, Keisuke Nishimoto, Satoshi Ii, Toshihiro Sera, Shigeo Wada
BACKGROUND: The pulmonary acinus is a dead-end microstructure that consists of ducts and alveoli. High-resolution micro-CT imaging has recently provided detailed anatomical information of a complete in vivo acinus, but relating its mechanical response with its detailed acinar structure remains challenging. This study aimed to investigate the mechanical response of acinar tissue in a whole acinus for static inflation using computational approaches. METHODS: We performed finite element analysis of a whole acinus for static inflation...
January 20, 2018: Clinical Biomechanics
Priyanka Somanath, Kelly M Bush, Paul S Knoepfler
Developmental Pluripotency-Associated-4 (DPPA4) is one of the few core pluripotency genes lacking clearly defined molecular and cellular functions. Here we used a proteomics screening approach of human embryonic stem cell (hESC) nuclear extract to determine DPPA4 molecular functions through identification of novel cofactors. Unexpectedly, the signaling molecule ERBB3-binding protein 1 (EBP1) was the strongest candidate binding partner for DPPA4 in hESC. EBP1 is a growth factor signaling mediator present in two isoforms, p48 and p42...
January 12, 2018: Stem Cells
Akihiro Tame, Genki Ozawa, Tadashi Maruyama, Takao Yoshida
Deep-sea vesicomyid clams harboring intracellular symbiotic sulfur-oxidizing bacteria are often dominant in chemosynthetic animal communities. Although they are known to have erythrocytes, little is known about other hemocytes. To investigate the types and roles of various hemocytes in vesicomyid clams, we performed morphological, histochemical and functional characterization of the hemocytes in two species, Phreagena okutanii, collected from 873 to 978 m depth, and Abyssogena phaseoliformis, from 5199 to 5355 m...
January 2, 2018: Fish & Shellfish Immunology
Nilay Nandi, Lauren K Tyra, Drew Stenesen, Helmut Krämer
Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels...
December 11, 2017: ELife
Azusa Nakao, Takumi Inaba, Akiko Murakami-Sekimata, Hiroyuki Nogawa
Embryonic mouse submandibular epithelia initiate branching morphogenesis within two days when embedded in Matrigel and stimulated by members of the epidermal growth factor family. However, it is unknown whether the end buds further branch over longer culture periods, and whether saliva-producing cells differentiate there. In the present study, we cultivated three major (submandibular, sublingual and parotid) salivary epithelia from 13-day embryos for 14 days in mesenchyme-free cultures. All epithelia continued to grow and branch to form numerous acinus-like structures in medium supplemented with neuregulin 1, fibroblast growth factor 1, and insulintransferrin-sodium selenite...
December 2017: Zoological Science
Fabian Garreis, Janine Jahn, Katharina Wild, Daniel B Abrar, Martin Schicht, Jens-Michael Schröder, Friedrich Paulsen
Purpose: The S100 fused-type proteins hornerin (HRNR) and filaggrin-2 (FLG2) are members of the epidermal differentiation complex, which is involved in terminal differentiation of keratinocytes via cornification as well as maintenance of the epidermal antimicrobial barrier. We investigated the expression and possible regulation of HRNR and FLG2 at the ocular surface and in the lacrimal apparatus. Methods: Tissues of the lacrimal apparatus and ocular surface were analyzed systematically by means of RT-PCR, immunohistochemistry, and immuntransmission electron microscopy (iTEM) for their ability to express and produce HRNR and FLG2...
November 1, 2017: Investigative Ophthalmology & Visual Science
Andrew G Nicholson, Kathleen Torkko, Patrizia Viola, Edwina Duhig, Kim Geisinger, Alain C Borczuk, Kenzo Hiroshima, Ming S Tsao, Arne Warth, Sylvie Lantuejoul, Prudence A Russell, Erik Thunnissen, Alberto Marchevsky, Mari Mino-Kenudson, Mary Beth Beasley, Johan Botling, Sanja Dacic, Yasushi Yatabe, Masayuki Noguchi, William D Travis, Keith Kerr, Fred R Hirsch, Lucian R Chirieac, Ignacio I Wistuba, Andre Moreira, Jin-Haeng Chung, Teh Ying Chou, Lukas Bubendorf, Gang Chen, Giuseppe Pelosi, Claudia Poleri, Frank C Detterbeck, Wilbur A Franklin
Multiple tumor nodules (MTNs) are seen with increasing frequency in clinical practice. Based on the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment (CHA) to distinguish second primary lung cancers (SPLC) from intrapulmonary metastases (IPM), looking for the most distinctive histological features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients, recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM or a combination...
November 7, 2017: Journal of Thoracic Oncology
Philipp Hofemeier, Kenishiro Koshiyama, Shigeo Wada, Josué Sznitman
Computational Fluid Dynamics (CFD) have offered an attractive gateway to investigate in silico respiratory flows and aerosol transport in the depths of the lungs. Yet, not only do existing models lack sufficient anatomical realism in capturing the heterogeneity and morphometry of the acinar environment, numerical simulations have been widely restricted to domains capturing a mere few percent of a single acinus. Here, we present to the best of our knowledge the most detailed and comprehensive in silico simulations to date on the fate of aerosols in the acinar depths...
September 24, 2017: European Journal of Pharmaceutical Sciences
William D Klaren, David Vine, Stefan Vogt, Larry W Robertson
Animal studies show that exposure to the environmental pollutant 3,3',4,4',5-pentachlorobiphenyl (PCB126) causes alterations in hepatic metals as measured in acid-digested volume-adjusted tissue. These studies lack the detail of the spatial distribution within the liver. Here we use X-ray fluorescence microscopy (XFM) to assess the spatial distribution of trace elements within liver tissue. Liver samples from male Sprague Dawley rats, treated either with vehicle or PCB126, were formalin fixed and paraffin embedded...
September 23, 2017: Environmental Science and Pollution Research International
P G Koullapis, P Hofemeier, J Sznitman, S C Kassinos
High-fidelity simulations of the complete airway tree are still largely beyond current computational capabilities. Towards large-scale simulations of the human lung, the current study introduces a numerical methodology to predict particle deposition in a simplified approximation of the deep lung during a full breathing cycle. The geometrical model employed consists of an idealised bronchial tree that represents generations 10 to 19 of the conducting zone and an heterogeneous acinar model created using a space-filling algorithm...
September 13, 2017: European Journal of Pharmaceutical Sciences
Christine A Mills, Aussie Suzuki, Anthony Arceci, Jin Yao Mo, Alex Duncan, Edward D Salmon, Michael J Emanuele
The mitotic spindle is composed of dynamic microtubules and associated proteins that together direct chromosome movement during mitosis. The spindle plays a vital role in accurate chromosome segregation fidelity and is a therapeutic target in cancer. Nevertheless, the molecular mechanisms by which many spindle-associated proteins function remains unknown. The nucleolar and spindle-associated protein NUSAP1 is a microtubule-binding protein implicated in spindle stability and chromosome segregation. We show here that NUSAP1 localizes to dynamic spindle microtubules in a unique chromosome-centric pattern, in the vicinity of overlapping microtubules, during metaphase and anaphase of mitosis...
October 20, 2017: Journal of Biological Chemistry
Sou Hyun Kim, Yong Lim, Ju Bin Park, Jae-Hwan Kwak, Keuk-Jun Kim, Joung-Hee Kim, HyunKeun Song, Joon Young Cho, Dae Youn Hwang, Kil Soo Kim, Young-Suk Jung
Non-alcoholic fatty liver disease (NAFLD) is believed to be the most prevalent liver disease worldwide and a major cause of chronic liver injury. It is characterized by lipid accumulation in the absence of significant alcohol consumption and frequently progresses to steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Although many studies have been conducted to better understand NAFLD since it was first recognized, there are still many gaps in knowledge of etiology, prognosis, prevention and treatment...
June 2017: Laboratory Animal Research
Bhagyashree Deka, Kusum Kumari Singh
The differential deposition of RNA-binding proteins (RBPs) on pre-mRNA mediates the processes of gene expression. One of the complexes containing RBPs that play a crucial part in RNA metabolism is the apoptosis-and splicing-associated protein (ASAP) complex. In this review, we present a summary of the structure of ASAP complex and its localization. Also, we discuss the findings by different groups on various functions of the subunits of the ASAP complex in RNA metabolism. The subunits of the ASAP complex are RNPS1, Acinus and SAP18...
2017: International Journal of Biological Sciences
Jose M Irimia, Catalina M Meyer, Dyann M Segvich, Sneha Surendran, Anna A DePaoli-Roach, Nuria Morral, Peter J Roach
Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice...
June 23, 2017: Journal of Biological Chemistry
Felipe T Lee-Montiel, Subin M George, Albert H Gough, Anup D Sharma, Juanfang Wu, Richard DeBiasio, Lawrence A Vernetti, D Lansing Taylor
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS)...
October 2017: Experimental Biology and Medicine
Maryam Rezvani, Christine Menias, Kumaresan Sandrasegaran, Jeffrey D Olpin, Khaled M Elsayes, Akram M Shaaban
Heterotopic pancreas is a congenital anomaly in which pancreatic tissue is anatomically separate from the main gland. The most common locations of this displacement include the upper gastrointestinal tract-specifically, the stomach, duodenum, and proximal jejunum. Less common sites are the esophagus, ileum, Meckel diverticulum, biliary tree, mesentery, and spleen. Uncomplicated heterotopic pancreas is typically asymptomatic, with the lesion being discovered incidentally during an unrelated surgery, during an imaging examination, or at autopsy...
March 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
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