bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid‐base regulation of intestinal oxalate transport (LB716)
Authors: Whittamore Jonathan , Freel Robert , Hatch Marguerite 
Published: June 2021

Primary Hyperoxaluria (PH) is a rare, inherited disease caused by an absence of specific liver enzyme(s) leading to overproduction of oxalate (Ox2‐), kidney stones and eventual renal failure. Alongside the kidney, the intestine is capable of secreting Ox2‐ and reducing the systemic Ox2‐ burden. Preserving renal function in PH is paramount therefore the notion of extra‐renal Ox2‐ elimination should not be under‐estimated. Identification of chloride/bicarbonate (Cl‐/HCO3‐) exchangers with an affinity for Ox2‐ raises the possibility of these membrane‐bound proteins serving as future therapeutic targets for promoting Ox2‐ secretion in PH. Despite this interest, understanding how these transporters are regulated is not well defined. Components of the HCO3‐‐buffering system (pH, CO2 and HCO3‐) are important, but under‐appreciated regulators of Cl‐/HCO3‐ exchange. The objective of this study was to determine whether these acid‐base variables, and associated enzyme, carbonic anhydrase (CA), are involved in Ox2‐ handling. Isolated mouse intestinal preparations were mounted in an Ussing chamber and experiments systematically examined how changes to pH, PCO2 and [HCO3‐] impacted Ox2‐ fluxes. Results showed that Ox2‐ secretion by the distal colon requires CA activity, is sensitive to changing [HCO3‐], but not pH, and can be stimulated > 70 % by increasing PCO2. In contrast, Ox2‐ transport by the ileum was impervious to these maneuvers. This sets the foundation for more detailed studies into the identity of the transporter(s) responsible, the role of CA, and the underlying signaling pathway. These findings also highlight the heterogeneity of intestinal Ox2‐ handling, being regulated by distinct stimuli in different segments that express a similar suite of Cl‐/HCO3‐ exchangers.Grant Funding Source: Supported by a Career Development Fellowship from the Rare Kidney Stone Consortium at the Mayo Clinic, Rochester, MN (NIH 5U54 DK083908‐05)
HEK‐293 cells expressing the cystic fibrosis transmembrane conductance regulator (CFTR): a model for studying bile acid (BA) regulation of Cl‐ transport. (LB720)
Authors: Domingue Jada , Ao Mei , Sarathy Jayashree , Nelson Deborah , Alrefai Waddah , Rao Mrinalini 
Published: June 2021

While human colonic T84 cells are a good model for studying Cl‐ secretion via CFTR, they respond poorly to genetic manipulations. As an alternate model, we stably transfected human embryonic kidney 293 cells (HEK), with CFTR‐EGFP (HEKCFTR) and assessed function by the I‐ efflux assay (nmol ± SEM). Forskolin (FSK; 2‐50µM) increased I‐ efflux compared to DMSO in HEKCFTR (n=3); CFTRinh‐172 (20µM) reduced FSK’s (10µM) effect by 45% (n=4). However, FSK (10µM) did not alter I‐ efflux in HEK (n=4). Disrupting microtubules with nocodazole (NOC, 33µM) did not alter FSK action in HEKCFTR (FSK: 876±103; FSK+NOC: 872±94; n=5). We had shown that the BA, chenodeoxycholic acid stimulates I‐ efflux in HEKCFTR (EB 2013). Expression studies revealed that HEK cells possess transcript and protein of the Gαs‐coupled BA receptor, TGR5. We next examined the effects of the potent TGR5 ligand, lithocholic acid (LCA) in HEKCFTR. While LCA alone had no effect on [cAMP]i it potentiated FSK’s effect (fmol/well: DMSO: 110±30; FSK: 1162±57; 50μM LCA: 146±8; FSK+ LCA: 7793±728; n=3). The functional effects of LCA on I‐ efflux were measured. Low, [10‐100μM] but not high [250‐500μM] doses of LCA increased I‐ efflux (35%, n蠅3) and pretreatment with LCA (15min, 50μM) blocked FSK’s effect (FSK: 724±66; FSK+LCA: 354±36; n=4). In summary, HEKCFTR are a good model to study CFTR because CFTR‐EGFP is functional, FSK induced efflux is CFTR specific, CFTR’s activation by FSK is not dependent on MTs and CFTR is regulated by BAs. HEKCFTR can be used to elucidate the cross talk by signals such as BAs and FSK in CFTR regulation.Grant Funding Source: NIH and VA
Altered TRPV5 Expression in Dahl Salt‐sensitive Rats (LB728)
Authors: Burns Rebecca , Wells Candace , Pointer MIldred 
Published: June 2021

We have previously shown that urinary calcium excretion is increased in Dahl salt‐sensitive (DS) rats following a high salt diet and this higher urinary calcium excretion is associated with the elevated blood pressure observed in DS following a high salt diet. The mechanism of the calcium loss following a high salt diet is undefined. In this report we investigate whether the transient receptor potential cation channel subfamily V member 5 (TRPV5), a calcium channel protein expressed on the luminal surface of the thick ascending loop and distal tubule and involved in transcellular calcium reabsorption, expression is altered in DS rats. Dahl DS and salt‐resistant (DR) rats were placed on a high (8%) salt diet for one week. At the end of the treatment period kidneys were collected for performing western analysis for TRPV5 protein expression in renal cortical and medullary tissue. Renal medullary TRPV5 protein levels were higher in DS rats (n=3) compared to DR rats (n=3) (1.4 ± 0.3 vs. 0.03 ± 0.03 arbitrary units; p<0.05). There was no difference in renal cortical TRPV5 expression between DS and DR rats. Higher medullary TRPV5 expression in DS rats on a high salt diet suggests that there is a compensatory attempt to increase calcium reabsorption. However, the compensatory increase in TRPV5 does not appear to prevent the increased urinary calcium excretion in DS rats following a high salt diet. Further studies are needed to investigate other renal calcium transporters involved in calcium reabsorption to explain the urinary calcium loss in hypertensive DS rats.Grant Funding Source: Supported by 2P20MD000175 and APS Frontiers in Physiology
NADPH oxidase inhibitor inhibits methylglyoxal‐induced podocyte apoptosis (LB729)
Authors: Kim Young Sook , Jung Dong Ho , Pyun Bo‐Jeong , Choi So‐Jin Choi , Kim Jin Sook Kim 
Published: June 2021

Methylglyoxal (MG) is one of uremic toxins produced by glycolysis that may results in diabetic nephropathy. In this study, we investigated the effect and mechanism of MG on apoptosis in podocytes. Conditionally immortalized podocytes for differentiation were induced by culturing the cells at 37°C for 13~15 days and treated MG with various concentration (0, 50,100, 200, 400 μM). Our data show that MG induced a decrease in cell viability in a dose‐dependent manner and increased formation of dichlorofluorescein (DCF)‐sensitive intracellular reactive oxygen species (ROS). This enhanced ROS formation was significantly reduced by NADPH oxidase inhibitor (DPI, 5 μM). Furthermore, MG treatment induced apoptosis in podocyte and NADPH oxidase inhibitor inhibited MG‐induced podocytes apoptosis via cleavage inhibition of poly (ADP‐ribose) polymerase (PARP). MG treatment also induced phosphorylation of extracellular‐regulated kinase 1/2 (ERK1/2), p38 mitogen‐activated protein kinases (MAPKs), protein kinase C‐alpha and ‐ delta/zeta, and phosphoinositide‐3 kinase (PI3K). Pretreatment with these inhibitors inhibited MG‐induced phosphorylation of these molecules in podocytes. These results suggest that MG‐induced apoptosis may be mediated by signaling of ERK, MAPK, PKC and PI3K in podocyte.Grant Funding Source: KIOM13040
MicroRNA‐30 and SOX9 participate in a negative feedback loop to regulate intestinal proliferation (LB744)
Authors: Peck Bailey , Mah Amanda , Simmons Jim , Magness Scott , Lund P. Kay , Sethupathy Praveen 
Published: June 2021

Precise regulation of SOX9 expression is critical for normal proliferation and differentiation in the intestinal epithelium. microRNAs (miRNAs) have emerged as prominent fine‐tuners of gene expression. In silico sequence analyses revealed a putative binding site for SOX9 in the promoter of miR‐30, as well as a conserved target site for miR‐30 in the SOX9 3’ UTR. Therefore, we sought to test the hypothesis that miR‐30 mediates feedback control of SOX9 in intestinal epithelial cells. We first sorted functionally distinct cell populations from the jejunum of Sox9‐EGFP reporter mice based on different levels of Sox9‐EGFP. Real‐time PCR analysis on RNA from these sorted cells demonstrated that miR‐30 and Sox9 expression are positively correlated in the mouse intestine. Knockdown of SOX9 in a human intestinal epithelial cell line (HIECs) significantly decreased miR‐30 expression, suggesting that SOX9 positively regulates miR‐30 in the intestine. Antisense inhibition of miR‐30 in HIECs led to significantly elevated levels of SOX9 and reduced 3H‐thymidine incorporation into DNA. Collectively, these data point to a SOX9‐miR‐30 auto‐regulatory loop that controls proliferation in the intestinal epithelium.Grant Funding Source: Supported by UNC GMB T32 Training Grant GM007092‐39 (B.P., NIGMS/NIH), 5R00DK0913118 (P.S., NIDDK/NIH), R01DK091427 (S.M., NIDDK/NIH), and R01DK040247 (P.K.L., NIDDK/NIH)
Pro‐inflammatory and Anti‐adipogenic Activities of Ethanol Extracts from Water Dropwort (MINARY) in Raw 264 Macrophages and 3T3 adipocytes (LB778)
Authors: KANG Min Sook , Ahn Eun Mi , Kim Young , Lee Jin‐Young , Han Gwi‐Jung 
Published: June 2021

In Korea, the water dropwort (MINARY) is a one of the multi frequency vegetable. This study performed to investigate the effects of ethanol Extracts from MINARY (EM) of pro‐inflammatory effects on obesity‐related inflammation in Raw 264 Macrophages and anti‐adipogenic activity using 3T3‐L1 adipocytes. EM significantly suppresses the LPS‐induced production of pro‐inflammatory factors such as MCP‐1, TNFa and NO in stimulated RAW 264 Macrophages. To investigate the effects of EM on adipocyte differentiation, at 3 days post‐confluence, 3T3 preadipocytes were induced to differentiate using differentiation medium /insulin medium with EM. EM significantly inhibits lipid accumulation in 3T3 adipocytes by Oil red O‐staining. These Results suggest that EM is a valuable medical and food component for improving the inflammatory changes in obesity condition and modulation of metabolic syndrome. This Research was supported by National Academy of Agricultural Science of Korea Grant (PJ009469) * Corresponding authorGrant Funding Source: Supported by National Academy of Agricultural Science of Korea Grant (PJ009469)
Carotid denervation does not influence autoresuscitation from hypoxic‐induced apnea in newborn rat pups (LB782)
Authors: Lun Rongzhi , Zhang Chunfen , Fewell James 
Published: June 2021

Autoresuscitation (AR) failure from hypoxic‐induced apnea by gasping has been suggested to play a role in sudden infant death. Little is known, however, about the factors that influence gasping and its ability to effect AR in the newborn. The present experiments were carried out on 5 to 6 day‐old rat pups to investigate the influence of carotid denervation (CD) on gasping during a single hypoxic exposure, and on AR during repeated hypoxic exposures. CD decreased basal respiratory frequency but not heart rate as compared to sham‐operated pups and eliminated the respiratory frequency response to alveolar hypoxia. CD decreased the time to hypoxic arousal/excitement but did not significantly influence the time to primary apnea, the time to last gasp or the total number of gasps during a single unrelenting hypoxic exposure. Furthermore, CD did not alter the number of hypoxic exposures tolerated before AR failure (Sham 15±2 – CD 15±3) Our data provide evidence that although the carotid chemoreceptors mediate the respiratory and arousal/excitement responses during exposure to hypoxia they do not modulate gasping or influence the ability of gasping to effect successful AR during repeated exposure to hypoxia.Grant Funding Source: CIHR
Heat stress increases global mitochondrial protein acetylation and steady state levels of SIRT3 (LB798)
Authors: Bloomer Steven , Kregel Kevin , Haak Jodie 
Published: June 2021

Aging results in exacerbated mitochondrial damage and cellular dysfunction after exposure to physiological challenges such as heat stress. Additionally, induction of mitochondrial stress‐defense proteins is blunted after heat stress with aging. The sirtuins are deacetylase enzymes implicated in stress defense and longevity. Sirtuin‐3 (SIRT3), which has been shown to reduce oxidative injury, is a mitochondrial enzyme that deacetylates mitochondrial proteins. Since little is known about the response of hepatic SIRT3 to physiological stress, the goal of the present study was to characterize protein levels of SIRT3 in young (6 mo) and old (24 mo) Fischer 344 rats after heat stress. Animals were exposed to a two‐heat stress protocol, and liver mitochondria were isolated at 2 and 24 h after the second heat stress. Nonheated animals served as controls. SIRT3 protein expression and global protein acetylation were determined by immunoblot analysis. Aging was associated with an increase in SIRT3 protein, and a trend for a decrease in protein acetylation. In each of the two age groups, heat stress increased both SIRT3 and global protein acetylation, which suggests that the increase in protein acetylation overwhelms the deacetylase activity of SIRT3. The increase in SIRT3 suggests that it is a stress‐responsive protein and warrants further inquiry into the acetylation status of selected mitochondrial proteins.Grant Funding Source: Supported by NIH R01 AG‐12350
Miniaturized wearable sensors for wireless realtime vital sign recordings, cloud based data transfer, storage, and analysis (LB858)
Authors: Federico Niksha , Federico Tessya , Federico Francesca , Sternik Gabriel , Taghizadeh Farhad , Esmaeli‐Azad Babak 
Published: June 2021

Wireless Real‐time continuous monitoring of vital signs via readily accessible cloud‐based web portals and apps is much needed for practical implementation of wireless mobile health and connected healthcare of the future. Several preliminary versions of such capabilities have recently been developed and commercialized for hospitalized patients. Using simple applications, physicians are able to use their mobile smart phone and tablet devices to readily access and analyze vital signs of patients that are in hospitals and in many cases the data is stored in the cloud for further analysis.Full potential and implementation of this capability, however, will only become a reality if wearable sensor technologies could be used for every day healthy or diseased individuals and in home settings instead of the hospital. We describe here a wearable sensor technology designed to be used by non‐hospitalized individuals that accurately monitors ECG, Blood pressure, Respiration, Oxygen saturation and body temperature. The device is wearable as a watch or a chest band, has long battery life (up to 24 hrs), and is bluetooth enabled for wireless data transmission to the cloud.Preliminary validation studies with 80 subjects using this sensor technology vs. gold standard methodologies for measurement of vital signs will be presented. Our findings demonstrate the efficacy of using this system for continuous monitoring and detection of vital signs in people of different ages, gender groups, and weight (BMI). This system is designed for home use and has direct application for mobile health diagnostics and connected care.
The Fatal Invasion of RTA: Ricin's destructive pathway to inhibiting protein synthesis. (LB86)
Authors: Doshi Ayush , Moore Melshae , Johnson‐Anthony Chasity , Spence Kecia , Spence Keiona , Ross Khadiya , Ruhashya Ashley , Parkins Asante , Stubbs Tamica , Colton Shannon 
Published: June 2021

In April 2013, letters addressed to the President were laced with ricin, a deadly toxin originating from the castor bean plant. This heterodimer inhibits protein synthesis by depurinating an adenine of rRNA. Ricin A Chain (RTA) and Ricin B Chain (RTB), are connected with a disulfide bond (DB). RTB attaches to a glycoprotein located on the cell membrane, initiating endocytosis, forming a clathrin‐coated vesicle. Once inside, the protein undergoes retrograde transport through the Golgi apparatus to the endoplasmic reticulum (ER). The DB is cleaved within the ER by Human Protein Disulfide Isomerase (hPDI), which contains four domains: a, a’ b, b’. In the reduced state, two amino acids in the active site of hPDI, (C397 and C400) donate two hydrogens to the cysteines in the DB that connects RTA and RTA. This event cleaves the DB in ricin, and forms an internal DB between C397 and C400, causing additional conformational changes to hPDI as it undergoes the redox reaction. After cleavage, RTA refolds with help from hPDI,, and can then bind to the 28SrRNA. T80 and T123 of RTA’s active site bind to adenine, creating an oxycarbonium ion due to an electron flow, while G177 stabilizes the ion. Ricin is then able to render 1500 ribosomes useless per minute. The Phillip O. Berry Academy of Technology SMART Team (Students Modeling A Research Topic) modeled Ricin and hPDI using 3D printing technology. Grant Funding Source: Supported by a grant from NIH‐SEPA and NIH‐CTSA.
Deleterious deoxyguanosinekinase (dGK) destroys lives (LB99)
Authors: Alberth Julia , Bielski Nick , Clements Dylan , Holloway Jared , Kirsch Evan , Kirsch Mitchell , Lawrence Becca , Mellor Julia , Murphy Madeline , Papendick Adam , Quist Sean , Reeves Angelica , Wermeling Zack , Williams Julia , Kao Jonathan , Kowalski Jason 
Published: June 2021

Mitochondrial Deficiency Syndrome (MDS) is characterized by a deficient amount of mitochondrial DNA (mtDNA). Without sufficient copies of mtDNA, the mitochondria cannot manufacture an adequate amount of ATP, leading to failure of energy expensive tissues such as the brain, skeletal muscle, and liver, ultimately causing death in early infancy. Deoxyguanosine kinase (dGK), an enzymatic protein, plays a role in regulating the replication of mtDNA by attaching a phosphate to a sugar/nitrogen‐base nucleoside at the active site, amino acids Glu70 and Arg142. Once phosphorylated, the assembly of mtDNA proceeds. Mutations in dGK prevent the phosphorylation of mtDNA and lead to a decrease in mitochondrial function. Two point mutations have been shown to have a deleterious impact on dGK: the R142K mutation is 0.2% active when compared to the wild type, and the E227K mutation is 5.5% active when compared to the wild type. The 3D model designed by the Westosha Central SMART (Students Modeling A Research Topic) Team displays the active site, two specific mutations and additional mutations reported in MDS patients. Screening for MDS is difficult because the condition can be caused by a wide variety of dysfunctional proteins. One such protein is dGK, therefore identifying its structure can hasten an accurate diagnosis. Grant Funding Source: The SMART team program is supported by a grant from NIH‐CTSA.
Nonstigmatizing and Precise Terminology to Describe Processes and Outcomes in Addiction Medicine
Authors: Pfund Rory A. , Peter Samuel C. , Swift Joshua K. , Witkiewitz Katie 
Published: June 2021

Abstract
Scholarly journals and professional organizations in addiction medicine have recently discussed the importance of adopting nonstigmatizing and precise terminology. The present commentary expands that ongoing discussion to terms related to treatment processes and outcomes. Four implicit assumptions of stigmatizing and imprecise terms related to treatment processes and outcomes are overviewed, and research evidence against these assumptions is presented. The commentary ends with recommendations for the use of positive behavioral indicators of processes and outcomes and, more importantly, accompanying them with nonevaluative, objective descriptors of patients’ behaviors.
The Effect of Changing Arterial Transducer Position on Stroke Volume Measurements Using FloTrac System Version 4.0: A Pilot Experimental Study
Authors: Ito Jiro , Kawakami Daisuke , Morimoto Takeshi , Ueta Hiroshi , Shimozono Takahiro , Mima Hiroyuki 
Published: June 2021

Objectives:
We conducted a pilot study using an experimental study protocol to evaluate the measurement error of arterial pulse contour analysis-derived stroke volume due to improper transducer leveling during the passive leg raising test and the impact of such error on the determination of fluid responsiveness.

Design:
Prospective observational study.

Setting:
A medical-surgical ICU at a tertiary referral center in Kobe, Japan.

Patients:
Consecutive critically ill adult patients using the FloTrac system Version 4.0 (Edwards Lifesciences, Irvine, CA) for hemodynamic monitoring between September 1, 2018, and November 31, 2018.

Interventions:
None.

Measurements and Main Results:
Using 20 patients, we estimated the change in the zero-reference level of an arterial transducer during head-down tilting as the vertical distance between the zero-reference levels of the transducer in the 45° semi-recumbent and supine positions. Using the FloTrac system Version 4.0, we recorded the hemodynamic variables every 20 seconds for 180 seconds at each of the following three points: 1) baseline, 2) after the transducer was elevated by the predetermined distance, and 3) after the transducer had returned to baseline. With respect to the predetermined change in the transducer level, a mean value of 18 ± 3 cm resulted in an increase in stroke volume measurement (mean value, 11 mL/beat; 95% CI, 10–13). This value corresponded to 20% (95% CI, 18–23%) of the baseline value 20 seconds after changing the transducer level. A significant correlation was observed between the predetermined change in the transducer level and the increase in the measured stroke volume (r
2 = 0.58; p < 0.001).

CONCLUSIONS:
When using the FloTrac system Version 4.0, a rapid increase in stroke volume was observed after elevating the arterial transducer. Clinicians and researchers are advised that proper leveling of the arterial transducer is necessary in order to accurately assess the change in arterial pulse contour analysis-derived stroke volume during the passive leg raising test.
Nutrition in acute pancreatitis
Authors: Arvanitakis Marianna , Gkolfakis Paraskevas , Fernandez Y. Viesca Michael 
Published: June 2021

Purpose of review
This review aims to discuss recent developments in different topics regarding nutrition and acute pancreatitis (AP), including oral refeeding, nutritional therapy, and implications of gut microbiota.

Recent findings
Obesity increases the risk for severe AP and mortality. Considering the worldwide obesity rates, this finding could have major implications in the global outcomes of patients admitted with AP. Recent research confirms that early oral feeding leads to shorter length of stay, fewer complications, and lower costs. In case of intolerance to oral feeding or severe disease, nutritional therapy should be offered within 24–72 h, whereas enteral nutrition (EN) has been shown superior to parenteral nutrition. EN can be administered through gastric or jejunal feeding, depending on digestive tolerance and the presence of ileus. Nevertheless, modalities of EN in patients undergoing endoscopic drainage of pancreatitis-related collections are still undetermined. Weight-loss after discharge occurs frequently and could reflect post-AP pancreatic exocrine failure. Finally, novel research regarding gut microbiota could open new therapeutic opportunities to prevent bacterial translocation and pancreatic necrosis’ infection.

Summary
Despite available evidence many questions regarding nutritional management in patients with AP remain open. Modulation of gut microbiota could play an important role in further therapeutic management.