A novel transgenic mouse model of lysosomal storage disorder
Knockout technology has proven useful for delineating functional roles of specific genes. Here we describe and provide an explanation for striking pathology that occurs in a subset of genetically engineered mice expressing a rat CaVβ2a transgene under control of the cardiac α-myosin heavy chain promoter. Lesions were limited to mice homozygous for transgene and independent of native Cacnb2 genomic copy number. Gross findings included an atrophied pancreas; decreased adipose tissue; thickened, orange intestines; and enlarged liver, spleen, and abdominal lymph nodes. Immune cell infiltration and cell engulfment by...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Ortiz-Miranda, S., Ji, R., Jurczyk, A., Aryee, K.-E., Mo, S., Fletcher, T., Shaffer, S. A., Greiner, D. L., Bortell, R., Gregg, R. G., Cheng, A., Hennings, L. J., Rittenhouse, A. R. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling
In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Berry, R., Miyagawa, T., Paskaranandavadivel, N., Du, P., Angeli, T. R., Trew, M. L., Windsor, J. A., Imai, Y., O'Grady, G., Cheng, L. K. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Imaging activation of peptidergic spinal afferent varicosities within visceral organs using novel CGRP{alpha}-mCherry reporter mice
In vertebrates, visceral pain from internal organs is detected by spinal afferents, whose cell bodies lie in dorsal root ganglia (DRG). Until now, all recordings from spinal afferents have been restricted to recording transmission of action potentials along axons, or from cell bodies lying outside their target organ, which is not where sensory transduction occurs. Our aim was to record directly from a major class of spinal afferent within visceral organs, where transduction of sensory stimuli into action potentials occurs. Using novel calcitonin gene-related peptide (CGRP)α reporter mice, DRG neurons expressed mCherr...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Spencer, N. J., Sorensen, J., Travis, L., Wiklendt, L., Costa, M., Hibberd, T. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Measurement of strains experienced by viscerofugal nerve cell bodies during mechanosensitive firing using digital image correlation
Mechanosensory neurons detect physical events in the local environments of the tissues that they innervate. Studies of mechanosensitivity of neurons or nerve endings in the gut have related their firing to strain, wall tension, or pressure. Digital image correlation (DIC) is a technique from materials engineering that can be adapted to measure the local physical environments of afferent neurons at high resolution. Flat-sheet preparations of guinea pig distal colon were set up with arrays of tissue markers in vitro. Firing of single viscerofugal neurons was identified in extracellular colonic nerve recordings. The locations...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Palmer, G., Hibberd, T. J., Roose, T., Brookes, S. J. H., Taylor, M. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly
In this study, we investigated the effects of aberrant glycosylation by GnT-V on high-density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants. The study also included 96 patients who underwent medical health check-ups. Total serum cholesterol levels, particularly HDL-cholesterol (HDL-C) levels, were significantly increased in Tg vs. wild-type (WT) mice. Hepatic expression of apolipoprotein AI (ApoAI) and ATP-binding cassette subfamily A member 1 (ABCA1), two important factors in HDL assembly, were higher in Tg mice compared with WT mic...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Kamada, Y., Kida, S., Hirano, K.-i., Yamaguchi, S., Suzuki, A., Hashimoto, C., Kimura, A., Sato, M., Fujii, H., Sobajima, T., Yamamoto, A., Ebisutani, Y., Takamatsu, S., Shinzaki, S., Yoshida, Y., Yamada, M., Nagasaka, H., Takehara, T., Miyoshi, E. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

TLR9 activation suppresses inflammation in response to Helicobacter pylori infection
In this study, we sought to define the role of the H. pylori cag T4SS on TLR9-mediated responses in vivo. H. pylori strain PMSS1 or its cagE– mutant, which fails to assemble a T4SS, were used to infect wild-type or Tlr9–/– C57BL/6 mice. PMSS1-infected Tlr9–/– mice developed significantly higher levels of inflammation, despite similar levels of colonization density, compared with PMSS1-infected wild-type mice. These changes were cag dependent, as both mouse genotypes infected with the cagE– mutant only developed minimal inflammation. Tlr9–/– genotypes did not alter the microbi...
Source: AJP: Gastrointestinal and Liver Physiology - November 1, 2016 Category: Gastroenterology Authors: Varga, M. G., Piazuelo, M. B., Romero-Gallo, J., Delgado, A. G., Suarez, G., Whitaker, M. E., Krishna, U. S., Patel, R. V., Skaar, E. P., Wilson, K. T., Algood, H. M. S., Peek, R. M. Tags: RAPID REPORTS Source Type: research

Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach
Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1–...
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Shaylor, L. A., Hwang, S. J., Sanders, K. M., Ward, S. M. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus
Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal, and esophageal motility was monitored using EMG, strain gauges, or manometry. The esophagus was stimulated by balloon distension or luminal fluid infusion. We found that esophageal distension increased the chance of occurrence of the EPSR, but the delay was variable. The chance of occurrence of ...
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Lang, I. M., Medda, B. K., Jadcherla, S. R., Shaker, R. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Lactobacillus acidophilus counteracts inhibition of NHE3 and DRA expression and alleviates diarrheal phenotype in mice infected with Citrobacter rodentium
In conclusion, our data provide mechanistic insights into antidiarrheal effects of LA in a model of infectious diarrhea and colitis. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Kumar, A., Anbazhagan, A. N., Coffing, H., Chatterjee, I., Priyamvada, S., Gujral, T., Saksena, S., Gill, R. K., Alrefai, W. A., Borthakur, A., Dudeja, P. K. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research

Hepatocyte ERBB3 and EGFR are required for maximal CCl4-induced liver fibrosis
Epidermal growth factor receptor (EGFR) and its ligands have been implicated in liver fibrosis. However, it has not been directly shown that hepatocellular genetic ablation of either this receptor tyrosine kinase or ERBB3, its interactive signaling partner, affects hepatic fibrosis. Carbon tetrachloride (CCl4)-induced liver fibrosis in hepatocyte-specific (HS) mouse models of EGFR and ERBB3 ablation was evaluated in both single gene knockouts and an HS-EGFR-ERBB3 double knockout (DKO). Loss of hepatocellular EGFR or ERBB3 did not impact cytochrome P450-2E1 expression, the extent of centrilobular injury, or the initial rege...
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Scheving, L. A., Zhang, X., Threadgill, D. W., Russell, W. E. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Inhibition of miR-21 rescues liver regeneration after partial hepatectomy in ethanol-fed rats
Liver regeneration is a clinically significant tissue repair process that is suppressed by chronic alcohol intake through poorly understood mechanisms. Recently, microRNA-21 (miR-21) has been suggested to serve as a crucial microRNA (miRNA) regulator driving hepatocyte proliferation after partial hepatectomy (PHx) in mice. However, we reported recently that miR-21 is significantly upregulated in ethanol-fed rats 24 h after PHx, despite inhibition of cell proliferation, suggesting a more complex role for this miRNA. Here, we investigate how inhibition of miR-21 in vivo affects the early phase of liver regeneration in ethano...
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Juskeviciute, E., Dippold, R. P., Antony, A. N., Swarup, A., Vadigepalli, R., Hoek, J. B. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Segmental differences in upregulated apical potassium channels in mammalian colon during potassium adaptation
Rat proximal and distal colon are net K+ secretory and net K+ absorptive epithelia, respectively. Chronic dietary K+ loading increases net K+ secretion in the proximal colon and transforms net K+ absorption to net K+ secretion in the distal colon, but changes in apical K+ channel expression are unclear. We evaluated expression/activity of apical K+ (BK) channels in surface colonocytes in proximal and distal colon of control and K+-loaded animals using patch-clamp recording, immunohistochemistry, and Western blot analyses. In controls, BK channels were more abundant in surface colonocytes from K+ secretory proximal colon (3...
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Perry, M. D., Rajendran, V. M., MacLennan, K. A., Sandle, G. I. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research

Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions
This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 31, 2016 Category: Gastroenterology Authors: Camilleri, M., Oduyebo, I., Halawi, H. Tags: REVIEWS Source Type: research

Corrigendum
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Tags: CORRIGENDUM Source Type: research

ClC-2 and intestinal chloride secretion
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Flores, C. A. Tags: LETTER TO THE EDITOR Source Type: research