bluuebunny/crossref_metadata_2025_split huggingface dataset:
Illuminating measuring lives: snuffing out Twisden’s candles
Authors: Pratt Simon D 
Published: June 2021

Abstract
Building upon an earlier article exploring ancient Greek, Roman, Neoplatonic and Avicennian influences upon English trusts, the discussion moves on to consider how—whether wittingly or unwittingly—the Bracton authors subsequently misapplied Roman jurisprudence in their treatise. From this, a hotchpotch of discordant ideas is argued to have laid the foundations for one of the most enthralling issues raised in modern times: Which living persons are relevant to the common law Rule Against Perpetuities and what purpose do they serve? Attorneys advising citizens in nine US states where the common law Rule still applies deserve an answer.
Knowledge Transfer Between Younger and Older Employees: A Temporal Social Comparison Model
Authors: Fasbender Ulrike , Gerpott Fabiola H 
Published: June 2021

AbstractKnowledge transfer between younger and older employees can help to prevent organizational knowledge loss and contribute to business success. However, despite its potential benefits, knowledge transfer does not occur automatically. To better understand the challenges associated with age-diverse knowledge transfer, we develop a conceptual model outlining 10 propositions. Specifically, we adopt a temporal social comparison perspective suggesting that employees compare their current and future status (i.e., the prestige, respect, and esteem provided by others). Expected future status differences are meaningful among age-diverse employees because older employees may have a higher current status than their younger colleagues, whereas younger employees may gain a higher status in the future. In our conceptual model, we propose 2 opposing pathways through which temporal social comparison impacts knowledge transfer, namely age-specific motives (i.e., generativity and development striving) and discrete emotions (i.e., fear of losing status and fear of losing face). In addition, we introduce individual and organizational boundary conditions that can modify the downstream consequences of temporal social comparison on knowledge transfer between younger and older employees.
Leptin acts as a metabolic regulator of Angptl6 expression
Authors: Kim Na Hyun , Kim Min Jeong , Kim Dae Sik , Kong In Deok 
Published: June 2021

Leptin, an adipocyte‐secreted protein, is one of the crucial regulators of food intake and energy expenditure. Circulating leptin concentration is correlated with energy intake and body fatness in rodents and humans. Recently, it has been known that some angiopoietin‐like proteins (Angptls) regulate lipid, glucose and energy metabolism. We examined the effect of leptin on the level of some Angptls using high‐fat diet and hyperleptinemia model. C57BL/6 mice were fed a HF diet or normal chow for the periods of 12 weeks.HF diet caused obesity, elevation of serum transaminase levels, and hyperlipidemia. And also HF diet induced an impaired glucose tolerance (IGT). Plasma concentration of leptin was approximately increased 4‐fold; adiponectin and RBP4 level were also increased in HF diet group. Plasma Angptl3 concentration of HF diet mice was lower than that of control mice. Angptl4 was decreased in liver, but no difference in epididyimal fat. Quantitative real‐time PCR analysis revealed that the mRNA expression level of Angptl6/AGF in liver was significantly increased in HF diet group. In leptin‐treated mice, food intake and body weight were decreased time‐dependently. Blood level of fasting glucose and triglycerides were decreased in leptin‐injected mice. Serum Angptl3 concentration of leptin‐treated mice was lower than that of control mice. Quantitative real‐time PCR analysis revealed that the mRNA expression level of Angptl3 and Angptl4 in liver were decreased, Angptl6/AGF was significantly increased in liver and epididymal fat in leptin‐treated mice.In conclusion, Angptl3, 4 were down‐regulated and Angptl6/AGF was up‐regulated by HF diet model and leptin injection mice. It could be suggested that leptin is an important regulator of Angptl6/AGF expression in hyperleptinemia.
Mechanical Stretch Stimulates Cholangiocyte Proliferation and Profibrotic Gene Expression
Authors: Munshi Md KAMRUZZAMAN , Wise Candace , Yang Fuquan , Dostal David E. , Glaser Shannon S. 
Published: June 2021

The angiotensin type 1 receptor (AT1) plays a key role in pressure‐induced vascular growth. AT1 also functions as a mechanoreceptor in addition to a GPCR. Although marked cholangiocyte proliferation occurs during obstructive cholestasis, a condition associated with increased biliary pressure, the role of AT1 in this process remains unclear.METHODS/RESULTSIn vivo, administration of Ang II (50 ng/Kg/min) to normal and BDL rats resulted in a significant increase in PCNA positive cholangiocytes as compared to saline treated rats. PCNA increased 64% and 30% for normal and BDL treated with Ang II compared to controls, respectively. In vitro, Ang II increased NRIC (normal rat cholangiocyte) proliferation (maximal effect observed after 48 hrs at 10−7M Ang II (1.7‐fold)). This proliferation was mediated by AT1 as it is the only isoform expressed by rat cholangiocytes. To address the role of mechanical stress, NRIC were plated on BioFlex culture plates and static equiaxial strain was applied to the cells for 24 hrs. Mechanical strain increased NRIC growth (2‐fold) and expression of angiotensin converting enzyme (ACE) mRNA levels (19‐fold). Mechanical strain also increased CTGF, fibronectin 1, and NCAM1 profibrotic gene expression and Ang II secretion by 15%.CONCLUSIONLigand and mechanical activation of AT1 induces cholangiocyte growth and profibrotic gene expression.
Oxidative metabolism studies on thermal regulation‐Protective mechanism against free radical in zebrafish brain
Authors: TSENG YUNG‐CHE , Chen Ruo‐Dong , Hwang Pung‐Pung 
Published: June 2021

Exposure of ectothermic vertebrates to fluctuated temperatures accelerates mitochondrial respiration and has been shown to increase the formation of mitochondrial reactive oxygen species (ROS), such as O2−, H2O2, and O2−·. Excess ROS production by intensively respiring mitochondria is held responsible for cellular damage. The present study was to test whether a protective oxidative‐stress pathway would be initiated in fish central nervous system upon cold stress.Effects of acute cold exposure (from 28 °C to 18 °C) on brain oxidative stress parameters were investigated in zebrafish (Danio rerio). Concentrations of cellular protein carbonyl groups (biomarkers of oxidative stress) were significantly increased after 1‐hour cold exposure. Increased levels of anti‐oxidative stress parameters, catalase (CAT) and superoxide dismutase (SOD) were observed at 1‐ and 6‐hour cold exposure, respectively. In spite of maintained anti‐oxidant capacity, the increment status of cellular oxidized protein accumulation was still observed. A neuronal defense pathway against ROS, peroxisome proliferator‐activated receptor (PPAR), acts with genes encoding uncoupling proteins (UCPs) was further monitored. Real‐time PCR analysis indicated that ppar‐1αb increased was transcriptionally regulated the expression of zucp2 and zucp2l. Mitochondrial biogenesis activation, mild uncoupling, and reduction of free radicals may result intracellular pO2 levels drop. Moreover, these protective mechanisms in fish brain have been found to cause hypoxia‐induced factor (HIF) stabilization that facilitates an increase in energy supply.
Gender‐dependent regulation of expression of the KCNQ1 channel regulatory β‐subunit KCNE3 throughout the estrous cycle in rat distal colonic crypts
Authors: O'Mahony Fiona , Alzamora Rodrigo , Carter Derek , Thomas Warren , Harvey Brian J. 
Published: June 2021

The KCNQ1 potassium channel associates with the KCNE3 (‐subunit in the epithelium of the colon and mediates basolateral K+ recycling that is required for apical Cl− secretion. This study tested whether sexual dimorphism exists in the expression and function of the KCNQ1/KCNE3 channel complex in rat distal colonic crypts. The association of KCNE3 with KCNQ1 and the abundance of KCNE3 mRNA and protein were significantly higher in male compared to female crypts. KCNE3 protein expression in the female rat colon varied throughout the estrous cycle; expression was highest during proestrus and declined 4.8‐fold in estrus (P (0.01, n=3) and became undetectable at metaestrus. Whole‐cell K+ currents in male crypts displayed a linear current‐voltage relationship and were 10‐fold more sensitive to chromanol 293B when compared with K+ currents in female crypts which displayed outward rectification. Basolateral membrane K+ currents recorded in colonic epithelia mounted in Ussing chambers also displayed a 10‐fold higher sensitivity to chromanol 293B in male tissues compared to females. This study demonstrates gender and estrous cycle regulation of the expression of KCNE3 and the properties of the KCNQ1 channel activity required for Cl− secretion.Funded by HEA Ireland PRTLI NBIP Cycle 4.
Luminal ATP release is impaired in intestinal alkaline phosphatase knockout mice duodenum
Authors: Akiba Yasutada , Watanabe Chikako , Nakano Takanari , Narisawa Sonoko , Millan Jose Luis , Kaunitz Jonathan D 
Published: June 2021

Brush border intestinal alkaline phosphatase (IAP) pH‐dependently regulates the concentration of luminally‐released ATP, which stimulates duodenal bicarbonate secretion (DBS) via P2Y receptors. We hypothesized that lack of IAP increases luminal [ATP], enhancing DBS. We measured DBS with pH and CO2 electrodes and ATP with luciferin‐luciferase in a perfused duodenal loop in wild type (WT) or knockout (KO) mice lacking Akp3 (duodenal IAP equivalent) expression, or in SD rats. ATP degradation was impaired in KO duodenum, consistent with the role of IAP in ATP degradation. AP inhibition with glycerol phosphate (GP) increased DBS, inhibited by the P2 receptor antagonist suramin, with increased luminal [ATP] in WT mice and rat duodenum. In contrast, GP or suramin had no effect on DBS and ATP release in KO duodenum. Real‐time PCR revealed that the expression of multidrug resistant‐associate protein 2 (MRP2) was selectively downregulated with no change in the expression of other MRPs, multidrug resistance protein (MDR) 1a, ecto‐nucleoside triphosphate diphosphohydrolase isozymes or cystic fibrosis transmembrane conductance regulator. Furthermore, the MRP inhibitor MK571 inhibited GP‐induced ATP release in rat duodenum. These results suggest that lack of IAP impairs ATP release via downregulation of MRP2, which may participate in the epithelial ATP release.NIH‐NIDDK R01 DK54221
The SWI/SNF chromatin remodeling complex is required for GI smooth muscle development and differentiation
Authors: Zhang Min , Chen Meng , Zhou Jiliang , Herring B. Paul 
Published: June 2021

We have shown that myocardin related transcription factors require Brg1 or Brm containing SWI/SNF chromatin remodeling complexes to induce the transcription of smooth muscle‐specific genes in nonmuscle cells. In addition, expression of dominant negative Brg1 or knockdown of Brg1 attenuated expression of SRF dependent smooth muscle‐specific genes in primary cultures of smooth muscle cells. The goal of our current studies is to elucidate the role of SWI/SNF complexes in regulating gastrointestinal smooth muscle development in vivo. Mice harboring a smooth muscle‐specific knockout of Brg1 on a wild type or Brm null background were generated and analyzed. Both single and double KO mice exhibited a significantly shorter gut with attenuated contractility and altered smooth muscle cell organization. In Brg1/Brm double KO mice we also observed decreased expression of smooth muscle‐specific contractile proteins that contributes to the lack of GI motility and postnatal lethality of these mice. Although the Brg1 KO mice are viable they exhibit impaired GI motility and many of these mice develop megacolon. The GI phenotypes of the smooth muscle specific Brg1 KO mice, in the presence of normal levels of Brm, suggests that Brg1‐containing SWI/SNF complexes play specific roles in GI development that cannot be compensated for by Brm‐containing complexes.Supported by an AHA fellowship to MZ, DK61130 to BPH, and an AHA SDG to LZ.
Characterization of Melatonin Receptors and Signaling Pathways in Gastrointestinal Smooth Muscle
Authors: Ahmed Rashad , Mahavadi Sunila , Grider John R , Murthy Karnam S 
Published: June 2021

Melatonin, a close derivative of serotonin, is involved in physiological regulation of circadian rhythms. In the gastrointestinal (GI) system, melatonin exhibits endocrine, paracrine and autocrine actions and is implicated in the regulation of GI motility. Generally, melatonin actions oppose the stimulatory actions of serotonin on motility. However, it is not known whether melatonin can also act directly on GI smooth muscle cells.AIMTo determine the expression of melatonin receptors in smooth muscle and identify their signaling pathways.METHODSMuscle cells were isolated from rabbit stomach by enzymatic digestion. Expression of melatonin receptors, MT1 and MT2, was determined by RT‐PCR and Western blot. G protein activity was measured by melatonin‐induced increase in Gα binding to [35S]GTPγS. PLC‐β activity was measured by ion‐exchange chromatography. Cytosolic Ca2+ was measured in fura‐2 loaded cells and muscle contraction by scanning micrometry.RESULTSMT1 was detected by RT‐PCR and western blot. Melatonin activated Gαq, but not Gαs, Gαi1, Gαi2, or Gαi3. Consistent with activation of Gαq, melatonin stimulated PI hydrolysis, increased cytosolic Ca2+, and elicited muscle contraction.CONCLUSION. Gastric smooth muscle cells express receptors for melatonin (MT1) coupled to Gq. The receptors mediate stimulation of PLC‐β activity and increase in cytosolic Ca2+, and elicit muscle contraction.
Ghrelin enhances the regenerative potential of stem cells
Authors: Fahim Mohamed A , Karam Sherif , Al‐Ramadi Basel 
Published: June 2021

Little is known about the mechanisms involved in the regenerative potential of stem cells following damage. Ghrelin is a peptide that promotes growth hormone secretion and in the thymus, inhibits apoptosis and increase cell proliferation.Presently we examine the influence of ghrelin on the regenerative potential of stem cells in bone marrow and gut. Cell degeneration was induced in mice by 2 doses of doxorubicin (10 and 6 mg/kg, iv). Some treated mice received continuous infusion of ghrelin (1.25 μg/hr) by using an implanted osmotic pump. To label dividing stem cells, all mice received a single ip injection of BrdU two hours before sacrifice. Blood was collected for differential cell counts and the gut was processed for histology and immunohistochemistryg using anti‐BrdU antibody. The results showed that the numbers of WBCs, RBCs and platelets were substantially reduced by 3 days after administration of chemotherapy and began to recover by day 10. These findings tend to occur in parallel with the dramatic damage and recovery in mucosal gut. In ghrelin‐treated mice, a dramatic recovery in blood cell counts and gut damage was evident as early as day 3. Immunohistochemistry depicted an increase in the number of BrdU‐labeled cells in response to damage, which upon recovery were reduced, suggesting that ghrelin enhances the regenerative potential of stem cells in both the bone marrow and gut.
Activation of proteinase activated receptor‐2 (PAR‐2) inhibits spontaneous activity in rat colon
Authors: Kerr Paul M , Koshka Amanda , Plane Frances 
Published: June 2021

Proteolytic cleavage of proteinase activated receptor‐2 (PAR‐2) reveals a tethered ligand which binds to and activates the receptor. Rat colonic smooth muscle shows spontaneous contractile activity which is generated by pacemaker cells. This study investigated the effects of PAR‐2 activation on spontaneous contractile activity in the isolated rat colon.Strips of rat colon longitudinal muscle were suspended in organ baths and increasing concentrations of trypsin, or the mimetic peptide FLIGRL, were applied. In some experiments carbachol was used to increase smooth muscle tone.Trypsin and FLIGRL each induced concentration‐dependent inhibition of spontaneous contractile activity of rat colon. Trypsin‐evoked relaxations (66.6±3.3; n=8) were abolished by apamin, an inhibitor of small conductance Ca2+‐activated potassium channels (SKCa). Similar results were obtained with FLIGRL (n=5). Cyclopiazonic acid, an inhibitor of sarcoplasmic reticulum Ca2+‐ATPase, also abolished the effects of trypsin (n=7). Neither trypsin (n=4) nor FLIGRL (n=4) reduced carbachol‐induced tone.In conclusion, activation of PAR‐2 inhibits spontaneous contractile activity in the rat colon via release of Ca2+ from intracellular stores and activation of SKCa channels. PAR‐2 activation is limited to pacemaker cells since no effect was observed on carbachol stimulated smooth muscle.Supported by NSERC
Translational Regulation of CUG‐BP1 by Polyamines through the RNA‐binding Protein HuR
Authors: Cui Yuhong , Xiao Lan , Rao Jaladanki N. , Zou Tongtong , Liu Lan , Gorospe Myriam , Wang Jian‐Ying 
Published: June 2021

All mammalian cells depend on polyamines for growth and division, but the exact roles of polyamines at the molecular level remain unclear. CUG‐BP1 protein interacts with CG‐rich element of many labile mRNAs and regulates decay and translation of its target transcripts. HuR modulates mRNA turnover and translation and its activity is tightly regulated by cellular polyamines. This study tests if polyamines regulate CUG‐BP1 expression through HuR in normal intestinal epithelial cells (IEC‐6 line).MethodsPolyamine levels were depleted by inhibiting ODC (key enzyme for polyamine biosynthesis) with DFMO but increased by overexpressing ODC gene. CUG‐BP1 expression was examined by newly translated protein and reporter assay using chimeric CUG‐BP1 3′‐UTR. RNA‐binding was examined by biotin pull‐down and RNP‐IP assays.ResultsDecreased polyamines by DFMO increased CUG‐BP1 protein, whereas elevated polyamines through ODC overexpression reduced CUG‐BP1 protein, neither intervention changed CUG‐BP1 mRNA levels. Polyamine depletion also increased CUG‐BP1 translation, but it failed to alter CUG‐BP1 protein stability. HuR bound the CUG‐BP1 mRNA and this association increased following polyamine depletion. HuR silencing repressed CUG‐BP1 translation in polyamine‐deficient cells, thus reducing CUG‐BP1 expression levels.ConclusionsThese results indicate that polyamines repress CUG‐BP1 translation by reducing HuR interaction with the CUG‐BP1 mRNA.
Effect of stress on mucin‐producing cells in the intestinal tract of mice
Authors: Habiyambere Bupe Martha , Onyango Edward M 
Published: June 2021

Mucins are heavily glycosylated proteins that form part of the protective mucosal barrier of the gastrointestinal tract. This study investigated the effects of chronic stress on mouse intestinal histology especially that of mucin‐producing cells. Sixteen ICR male mice were divided into two groups of eight, a test and a control group. Test mice were restrained for 6 hours daily for 21 days. The control group had no access to feed or water during the 6‐hour restraint period of test mice. After the study period, all mice were euthanized and samples were collected. Blood was collected by retro‐orbital puncture and centrifuged to obtain serum for a corticosterone assay. Duodenal and jejunal intestinal portions were removed and fixed in Methacarn, embedded in paraffin, sectioned and stained using Alcian Blue‐Periodic acid Schiff to visualize the mucin‐producing goblet cells and measure villi length. As expected stressed mice showed higher corticosterone levels compared to control animals (P<0.05). Histology showed a decrease in the number of goblet cells in both the duodenum and jejunum of stressed mice compared to control mice (P<0.05). Villi length was lower in stressed mice compared to control animals (P<0.05). The findings suggest that stress may affect the dynamics of mucin production in the intestinal tract of mice.Research was supported by East Tennessee State University.
Taste receptor‐mediated duodenal bicarbonate secretion is associated with incretin release in rats
Authors: Wang Joonho , Akiba Yasutada , Engel Eli , Guth Paul H , Kaunitz Jonathan D 
Published: June 2021

Luminal nutrient chemosensing during meal ingestion is mediated via intestinal endocrine cells to regulate secretion and motility. We have reported that luminal L‐glutamate (L‐Glu) with inosinate (IMP) stimulates duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers T1R1/R3. To further study this mechanism, we hypothesized the involvement of gastric inhibitory peptide (GIP) or glucagon‐like peptide (GLP) release in L‐Glu/IMP‐induced DBS. We measured DBS with a pH‐stat or with pH and CO2 electrodes through a rat duodenal loop. Rat GIP, GLP‐2, or exendin‐4 (GLP‐1 receptor agonist, Ex‐4) was continuously injected iv (0.1 – 1 nmol/kg/hr). Furthermore, L‐Glu and/or IMP was luminally perfused with or without iv injection of ProGIP (GIP receptor antagonist) or exendin‐3‐(9–39) (GLP‐1 receptor antagonist). GIP and GLP‐2 dose‐dependently increased DBS, whereas Ex‐4 decreased DBS. Perfusion of L‐Glu with IMP increased DBS, with no effect of ProGIP or exendin‐3‐(9–39). Luminal perfusion of L‐Glu with IMP increased portal venous [GLP‐1], with no effect on [GIP]. These results suggest that L‐Glu/IMP‐induced DBS is possibly mediated via GLP‐2 release.A grant from Ajinomoto Inc, NIH R01 DK54221
Prevention of Mycobacterium avium subsp. paratuberculosis (MAP) infection in BALB/c mice by feeding probiotic Lactobacillus acidophilus NP‐51®
Authors: Osman Mohamed A , Stabel Judy R , Hostetter Jesse M , Nettleton Daniel S , Beitz Donald C 
Published: June 2021

The objective of this study was to examine effects of feeding Lactobacillus acidophilus strain NP51 to mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP). Mice were randomized to ten treatment groups; sentinels, control, heat‐killed MAP, viable MAP, heat‐killed NP51, viable NP51, heat‐killed NP51 plus heat‐killed MAP, heat‐killed NP51 plus viable‐MAP, viable‐NP51 plus heat‐killed MAP, viable‐NP51 plus viable‐MAP. Mice were fed 1 × 106 CFU of NP51· mice−1· day−1. On day 45, mice were challenged with 1 × 108 CFU of MAP intraperitonealy. We hypothesized that feeding NP51would increase Th‐1 responses and decrease progression of Johne's disease in mice. Ten mice from each group were euthanized on days 45, 90, 135 and 180. Supernatante from in vitro splenocyte culture was examined for IFN‐γ production. Feeding Heat‐killed NP51 to heat‐killed MAP‐ or viable MAP‐infected mice increased interferon (IFN)‐γ by 1.4‐ and 4‐fold (44.32 and 127.14 vs. 31.69 pg/mL, respectively) over that of heat‐killed MAP‐infected control. Similarly, feeding viable‐NP51 to heat‐killed MAP‐ or viable MAP‐infected mice increased IFN‐γ by 3‐ and 4‐ fold (98.6 and 130.68 vs. 31.69, respectively) over that of heat‐killed MAP‐infected control. These data suggest that feeding NP51 can simulate IFN‐γ production and prevent progression of Johne's disease in mice.Funding source: Nutrition Physiology Company, Guymon, OK.Grant Funding Source: Nutrition Physiology Company