bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Fractalkine Administration Improves Glucose Tolerance with Improved Pancreatic Hormonal Profile in Obese Mice
Authors: Lee Yun Sok 
Published: June 2021

Previously we reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and beta cell function. In this study, we investigated whether chronic administration of a long acting form of FKN (FKN‐Fc) can exert durable effects to improve glucose tolerance in obese rodent models. Chronic FKN‐Fc administration markedly improved glucose tolerance with improved glucose‐stimulated insulin secretion and decreased beta cell apoptosis. Unexpectedly, chronic FKN‐Fc administration also decreased alpha cell glucagon secretion and decreased hepatic glucagon action. In pancreatic endocrine cells, FKN inhibited ATP‐sensitive potassium channel conductance by an ERK‐dependent mechanism, which potentiated glucose‐induced beta cell action potential (AP) firing and decreased alpha cell AP amplitude, leading to increased GSIS and decreased glucagon secretion. Beyond these islet effects, FKN‐Fc administration also enhanced hepatic insulin action and inhibited glucagon‐induced increased hepatic glucose output in obese insulin resistant mice. In hepatocytes, FKN treatment reduced glucagon‐stimulated cyclic AMP production and CREB phosphorylation in a pertussis toxin‐sensitive manner. Together, these results point to the potential use of FKN‐based therapy to improve Type 2 diabetes by increasing both insulin secretion and insulin sensitivity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
T‐Cell Protein Tyrosine Phosphatase Restricts Intestinal Epithelial Cell Expression of the Oncogene Annexin A4
Authors: Krishnan Moorthy , Aftabizadeh Maryam , Yu Hua , McCole Declan F. 
Published: June 2021

Phosphotyrosine‐based signaling is regulated by the balanced actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) to control various cellular processes including growth, differentiation, metabolism, and motility. Aberrant activation of signaling pathways by mutations and/or overexpression of PTKs and PTPs can lead to various types of cancers including colon cancer. Evolving evidence indicates that expression levels of PTPs, mainly protein tyrosine phosphatase non‐receptor type‐2 (PTPN2, protein product called T cell protein tyrosine phosphatase ‐TCPTP), PTPN22, and PTPN11 are altered in actively inflamed intestinal tissue. Loss‐of‐function single nucleotide polymorphisms (SNPs) in PTPN2 are associated with inflammatory bowel disease (IBD). The aim of this study was to determine if TCPTP functions as a tumor suppressor in intestinal epithelial cells (IEC). In this study, we used previously validated control shRNA and PTPN2 knockdown (PTPN2‐KD) HT‐29 IECs to determine if TCPTP loss affects oncogene expression. We performed proteomic analysis using mass spectrometry (MS) with Tandem Mass Tags (TMT) on PTPN2‐KD and control IECs. The most striking difference between control and PTPN2‐KD IECs was a 2.9 fold increase in the peptide count of Annexin A4 in PTPN2‐KD cells compared with control cells. Earlier studies indicated that Annexin A4 modulates membrane permeability, membrane trafficking, participates in cellular growth and apoptosis, enhances tumor invasion and promotes anti‐tumor drug resistance. To confirm the MS result, we performed RT‐PCR and Western blotting to determine if PTPN2 deficiency increased Annexin A4 mRNA and protein levels respectively. Both Annexin A4 mRNA and protein levels were significantly increased in PTPN2 KD IECs above control cells (221.5±2.4%, p<0.0001, 202±16.2 p<0.01 respectively). Immunofluorescence studies also revealed that Annexin A4 staining intensity was increased 1.5 fold in PTPN2 KD cells compared to control cells analyzed using ImageJ software. Annexin A4 expression in PTPN2‐KD IECs was further increased by IFN‐g treatment (1000 U/ml; 24 hrs). In summary, TCPTP deficiency leads to elevated expression of the tumor promoter, Annexin A4. These data suggest that loss‐of‐function mutations in the PTPN2 gene may increase pro‐tumorigenic factors that predispose to colorectal cancer.Support or Funding InformationSupported by NIH 2R01DK091281 (DFM)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Diversity of ENaC expression in different tissues and different gender
Authors: Zhai Yujia , Zou Li , Linck Valerie , Chen Guangping , Ma He‐Ping 
Published: June 2021

The epithelial sodium channel (ENaC) plays an important role in different organs such as kidney, lung, and colon. We performed Western blot experiments using the tissues from these organs of mice to determine whether ENaC expression is dependent on either tissue types or gender. Our data show that the kidney expressed more α‐ENaC than the lung and the colon whereas the lung expressed more β‐ and γ‐ENaC than the kidney and more γ‐ENaC than the colon. The diversity of ENaC expression may account for the different roles of ENaC in these organs. Our data also show that a 60 kD band was consistently detected with antibody to γ‐ENaC in the male mouse kidney, but barely seen in the female mouse kidney. The expression of this band was not altered by low sodium diet. It was also observed in cultured cortical collecting duct cells which were from the male mouse kidney. Interestingly, this band was not observed in the lung of any gender, but was the only band found in the colon of both male and female mouse. To determine whether this band represents a novel cleaved γ‐ENaC, we examined the enzymes that can cleave γ‐ENaC. The data show that the expression levels of prostasin, furin, kallikrein‐2, and plasmin were not significantly different between male and female, but the levels of prostasin was significantly different between the tissues of kidney and lung. These results suggest that there is a diversity of ENaC expression in different tissues and different gender. However, it remains to be further determined whether the 60 kD band represents a novel cleaved γ‐ENaC.Support or Funding InformationNIH R01‐DK100582 to H.M.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel Loss‐of‐function Variants in the Epithelial Na+ Channel Extracellular Domain
Authors: Sheng Shaohu , Chen Jingxin , Wang Xueqi , Kleyman Thomas R. 
Published: June 2021

Mutations in epithelial Na+ channel (ENaC) subunits cause hypertensive or hypotensive human diseases. Several genetic variants in ENaC genes are associated with high blood pressure or salt sensitivity. Certain ENaC variants reportedly serve as modifiers to diseases such as cystic fibrosis. In this study, we sought to identify loss‐of‐function human ENaC variants in a heterologous expression system. A total of 48 variants in extracellular domains of α and γ ENaC subunits were selected. Mutant α subunits were co‐expressed with wild type β and γ subunits whereas mutant γ subunits were co‐expressed with wild type α and β subunits in Xenopus oocytes. Amiloride‐sensitive currents measured by two‐electrode voltage clamp in cells expressing wild type and mutant ENaCs were compared to identify functional variants. Among the tested 24 αENaC variants, four (αH255R, αT274M, αG454V and αΔF528) showed significantly less currents than wild type channels (p< 0.001, n=16~26). Four out of 24 γENaC variants (γS134F, γN282S, γE314K and γW486X) also had significantly less currents than wild type channels (p < 0.05, n=16~30). To explore the underlying mechanisms for the loss‐of function phenotype, we examined Na+ self‐inhibition responses of the mutant channels. All four α (H255R, T274M, G454V and ΔF528) and one γ (E314K) mutants displayed significantly greater Na+ self‐inhibition responses than wild type channels, corresponding to lower open probabilities. Our results identify eight novel loss‐of‐function ENaC variants in the extracellular domain and suggest that five variants are ENaC gating modifiers.Support or Funding InformationSupported by NIH DK079307, DK038470 and a DCI grantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
DISTINCT EFFECTS OF GLUTATHIONE DISULFIDE ON δ‐ AND α‐EPITHELIAL SODIUM CHANNEL SUBUNITS
Authors: Coca Camila , Downs Charles , Wu Wei , Helms My 
Published: June 2021

BackgroundAmiloride‐sensitive epithelial sodium channel (ENaC) is a membrane bound ion channel with selective inward permeability to Na. ENaC plays a critically important role in maintaining net fluid homeostasis. To date four ENaC subunits (α‐, β‐, γ‐, and δ‐ENaC) have been cloned in mammalian species. Mice, however, only express αβγ. In humans, an additional ENaC subunit (δ1) and its slice variant (δ2) have been recently identified. Unlike αβγ‐ENaC, the physiological role and regulation of channels made up of δ1 and δ2 subunits remain unclear.HypothesisWe tested the hypothesis that sodium channels containing α and δ ENaC subunits (alongside β and γ) are differentially regulated under oxidative stress.MethodsUsing the Xenopus laevis oocyte expression system, full‐length cDNAs for human ENaC subunits, and two electrode voltage clamp measurements, we modeled antioxidant depletion (a form of oxidative stress) and compared the effects of oxidized glutathione (GSSG) on αβγ‐ENaC and δβγ‐ENaC whole cell current. High extracellular GSSG treatments (400μM) increases the redox potential, and models antioxidant depletion in an oocyte expression system. This experimental approach allows for the singular study of αβγ vs. δβγ ENaC in a cell model system capable of normal assembly of multimeric ion channels into the membrane.ResultsGSSG significantly decreased ENaC activity in oocytes expressing αβγ‐ENaC (n=10). Conversely, GSSG significantly increased whole cell current in oocytes expressing δ1βγ‐ENaC (n=12) and in δ2βγ‐ENaC expressing oocytes (n=13) immediately upon extracellular exposure. While both α and δ ENaC subunits are directly modified by GSSG at Cys thiol sites, the effect and mechanism of GSSG posttranslational modification of α vs δ expressing Na channels differed significantly in our studies. Heterologous expression of αβR566Xγ ENaC in oocytes indicate that GSSG proteolytically degrades classical αβγ ENaC. Whole cell recordings and biotinylation studies indicate that δ2 ENaC subunits increase net Na transport via insertion of new membrane protein, whereas GSSG plays no role in δ1 transport and insertion into the cell membrane.ConclusionWe found that αβγ ENaC activity is decreased by GSSG. Conversely δβγ ENaC activity is significantly increased by GSSG. This conclusion highlights the need to better understand the opposing translational effects of α vs δ ENaC subunits, as it may occur in human tissue. Additional studies are needed to better understand the molecular regulation and pathophysiological roles of α and δ ENaC subunits.Support or Funding InformationSupport for this project was made possible by the University of Utah Investigator Initiated Grant awarded to MNH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Targeted activation of excitatory hM3Dq DREADD conditionally expressed in principal cells decreases ENaC activity to promote Na excretion.
Authors: Mironova Elena , Suliman Faroug , Berman Jonathan Max , Stockand James 
Published: June 2021

The Epithelial Na+ Channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine‐tuning of electrolyte and water excretion and consequently, blood pressure. Local paracrine purinergic signaling intrinsic to the distal nephron inhibits ENaC activity via Gq‐coupled apical P2Y2 receptors. This purinergic signaling system functions in parallel with the renin‐AngII‐aldosterone system to maintain blood pressure. Loss of purinergic inhibition of ENaC causes salt‐sensitivity and elevated blood pressure. To further elaborate the cellular mechanisms and physiological consequences of local purinergic regulation of ENaC and to test whether stimulation of this inhibitory regulation of ENaC could ameliorate forced salt‐sensitivity in the DOCA‐salt mouse, we created an excitatory hM3Dq DREADD mouse with conditional expression of this synthetic receptor in principal cells. Activation of this DREADD receptor in these mice promoted renal Na+ excretion even under conditions, such as a Na+ free feeding regimen, that favored renal Na+ conservation. On‐going experiments test if this facilitation of Na+ excretion protects principal cell‐specific hM3Dq DREADD mice from elevations in blood pressure resulting from DOCA‐salt treatment.Support or Funding InformationThis research was supported by American Heart Association grants 15GRNT22930030 & 17GRNT3292002 (to JDS), and F32DK104572 (to EM).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Transpulmonary Pressure‐Dependent Regulation of Air Leaks after Peripheral Lung Injury
Authors: Servais Andrew B. , Valenzuela Cristian , Ysasi Alexandra , Wagner Willi , Kienzle Arne , Loring Stephen , Tsuda Akira , Ackermann Maximilian , Mentzer Steven 
Published: June 2021

To assess the pathophysiology of pulmonary air leaks, we studied orotracheally intubated mice on mechanical ventilation with pleural injuries produced by a 25g needle inserted 1–2 mm into the lung parenchyma. The pleural injuries were studied using a standard inflation maneuver involving a 3 second ramp to 30 cmH20 followed by a 3 second breath hold. After pleural injury, the inflation maneuver resulted in a distinctive airway pressure time history; that is, peak inflation was followed by a rapid decrease to a lower plateau phase. The decay phase of the inflation maneuver was influenced by the injury area; the rate of pressure decline with multiple injuries (28+8 cmH20/sec) was significantly greater than a single injury (12+3 cmH20/sec)(p<.05). In contrast, the plateau phase pressure was independent of injury surface area, but dependent upon transpulmonary pressure. When the standard inflation maneuver was performed in a pressure‐regulated body box, the plateau transpulmonary pressures were a mean of 18+0.7 cm H2O regardless of the absolute pressures outside of the lung. Although the pleural injury resulted in a significant increase in delivered air volume (p<.01), there was no significant difference in air leak volume between 1 and 5 injuries (p>.05). These findings are consistent with the regulation of pleural air leaks by transpulmonary pressure‐dependent airway closure.Support or Funding InformationNIH Grant HL94567, HL134229, HL007734, CA009535, ES000002 and the German Research Foundation (SFB1066)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Teaching New Words in New Ways: PhUn Week Outcomes in Elementary Students
Authors: Dickens Cameron M. , Crecelius Anne R. 
Published: June 2021

Physiology Understanding (PhUn) week is organized by the American Physiological Society with the mission of promoting interaction between scientists and nonscientists, specifically through outreach to local schools to encourage science education. Elementary school students (n=27) from a local school participated in small group activities led by two undergraduate students, two graduate (masters) students, and a faculty member. The objectives of these activities were: 1) to teach basic physiological concepts, and 2) provide students an enjoyable, fun, and engaging hands‐on experience. Three separate lessons were created centering on the cardiovascular, respiratory, and muscular systems. Each lesson contained a short introduction, an individual small activity to illustrate the concept, and a larger demonstration indicative of laboratory activity. Students were given a worksheet for each station that highlighted important words related to the corresponding body system. After the completion of all 3 stations, elementary students completed a short worksheet. All three topics were evenly identified as the most interesting and fun. Less than half of the students reported being familiar with the term physiology before the event, and approximately 55% said they learned at least 3 new words over the course of the day. Students used a self‐reported 1–5 scale to assess their enjoyment (median=5) and learning (median=4). Free response answers identified key vocabulary used at the various stations (e.g. homeostasis, diaphragm). Overall, elementary students demonstrated an interest in physiology and laboratory methods when presented with this programming. Self‐reported data indicates this outreach activity was successful in achieving the intended objectives.Support or Funding InformationSupported by the American Physiological Society and the Department of Health and Sport Science.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
‘An overview of the first year Undergraduate Medical Students Feedback on the Point of Care Ultrasound Curriculum’
Authors: Mohialdin Vian , Wainman Bruce , Shali Ari 
Published: June 2021

With the technological progress of different types of portable Ultrasound machines, there is a growing demand by all health care providers to perform bedside Ultrasonography, also known as Point of Care Ultrasound (POCUS). This technique is becoming extremely useful as part of the Clinical Skills/Anatomy teaching in the undergraduate Medical School Curriculum.Teaching/training health care providers how to use these portable Ultrasound machines can complement their physical examination findings and help in a more accurate diagnosis, which leads to a faster and better improvement in patient outcomes. In addition, using portable Ultrasound machines can add more safety measurements to every therapeutic/diagnostic procedure when it is done under an Ultrasound guide. It is also considered as an extra tool in teaching Clinical Anatomy to Medical students. Using an Ultrasound is one of the different imaging modalities that health care providers depend on to reach their diagnosis, while also being the least invasive method.We thought investing in training the undergraduate Medical students on the basic Ultrasound scanning skills as part of their first year curriculum will help build up the foundation for their future career.The research we report in this manuscript is a preliminary qualitative study. And provides the template for future model for teaching a hand on Ultrasound for all health care providers in different learning institutions.A questionnaire was handed to the first year medical students to evaluate their hands on ultrasound session experience. Answers were collected and data was analyzed into multiple graphs.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Trabecular Bone Morphology in Hunter/Gatherer and Agricultural Populations
Authors: Palmer Jenna Elizabeth , Chirchir Habiba 
Published: June 2021

According to the Law of Functional Adaptation, trabecular bone will adapt to loading placed on it by increasing in bone volume and changing its directionally. Previous studies show that there are differences that can be identified in trabecular bone morphology across populations with varied subsistence strategies. As the bone responds to mechanical loading, that relationship has been shown to be complex. Consequently, it is necessary to consider diverse populations with varied subsistence strategies in order to have a complete understanding of changes in trabecular bone morphology. Therefore, this study's goal is to identify differences in trabecular bone volume in two hunter‐gatherer populations and one farming population derived from South Africa, Egypt, and Australia. The South African populations were (n=6) in populations from Khoisan, Korana, and Morolong. Populations from Australia were (n=6) who are indigenous Aboriginals. The sedentary farming population sample size was (n=8) from El‐Hesa in Egypt.This study predicts that because hunter‐gatherers engage in greater activity levels due to greater travel distances, they will exhibit greater trabecular bone volume. The agricultural group with a more sedentary lifestyle will have a lower bone volume due to presumed lower levels of activity among later agricultural societies. To test this prediction, trabecular bone volume in two limb elements (the femoral and humeral heads) was estimated using micro‐CT scanning. The Quant3D program is used to quantify trabecular bone volume fraction (BV/TV – bone volume/total volume) and we used Mann‐Whitney‐Wilcoxon test to identify the differences in BV/TV in the two populations.Interestingly, preliminary results show BV/TV is not significantly different in two populations in both upper (humerus) and lower (femur) limb elements. Although these results derive from a pilot study, they suggest caution in interpretation of the effect of mechanical loading on trabecular bone. We intend to expand and increase the sample sizes to include more limb elements to further explore variation in trabecular bone volume within these and more populations.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
N‐3 fatty acids prevent trabecular bone loss
Authors: Sanchez Diego , Mendez Daisy , Fernandes Gabriel , Banu Jameela 
Published: June 2021

N‐3 fatty acids have been implicated in preventing bone loss. Whether n‐3 fatty acids can restore bone loss is not established. We conducted a study using the ovariectomized mouse model to determine if n‐3 fatty acids can restore bone.Ten months old, C57BL/6, retired breeder mice were either sham operated or ovariectomized and left for 3 months. The different groups were: Group 1. LC S; Group 2. LC O; Group 3. 18/12 S; Group 4. 18/12 O Group 5. 30/20 S Group 6. 30/20 O. Mice were fed either LC or FO (10%). The LC and FO fed groups were kept in the respective diet regimens for the next 3 months, at the end of which they were sacrificed and long bones were subjected to pQCT analyses.In the distal femoral metaphysis, trabecular bone mineral content (Tb BMC) was decreased significantly in the LC O mice while it was increased in the 18/12 O group. Similarly in the proximal tibial metaphysis, the Tb CNT and cortical bone mineral content were significantly higher in the 18/12 O and 30/20 O groups.In summary, the 18/12 n‐3 fatty acids increased trabecular content in both the femur and tibia and the cortical BMC was increased only in the tibia, suggesting that 18/12 is more beneficial.Support or Funding InformationFunding: Engaged Scholarship for Undergraduate Research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.