bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Mucin Expression in the Gastric Epithelium After Injury and Regeneration May Result in Increased Helicobacter pylori‐Induced Gastric Ulcers in the Elderly
Authors: Dua‐Awereh Martha B. , Chakrabarti Jayati , Goker Sevde , Engevik Amy , Hawkins Jennifer , Helmrath Michael , Zavros Yana 
Published: June 2021

Background/HypothesisPrevalence of gastric ulcers increase in the elderly, yet the cause of the age‐associated escalation is unknown. Once Helicobacter pylori (H. pylori) enters the stomach lumen, bacterial urease not only converts water & urea to ammonia & bicarbonate to neutralize the acidic environment of the stomach, but also breaks down the protective mucous barrier by breaking down mucin. Subsequently, chronic inflammation induced by H. pylori infection results in epithelial cell death and damage to the stomach lining, also known as a gastric ulcer. We tested the hypothesis that the regenerative process of the aged gastric epithelium is impaired in response to injury, such that there is mis‐localization of mucin expression leading to a compromised protective barrier.MethodsGastric ulcers were induced in young (2–3 months old) and aged (>8 months old) C57/BL6 mice with acetic acid applied on the serosal side of the stomach. Samples were harvested from euthanized mice with ulcer durations from 3 to 60 days. Biopsies were collected from human gastric ulcer patients. Organoids were grown from young mouse gastric epithelium and transplanted at the site of acetic acid‐induced injury in aged mice. Immunofluorescence staining was used to analyze the expression of MUC5AC, MUC2, Griffonia simplicifolia II (GSII), Ulex europeus I (UEAI), H+, K+‐ATPase, intrinsic factor and chromogranin A.ResultsWithin 3 days post‐injury, there was the emergence of spasmolytic polypeptide‐expressing metaplasia (SPEM) at the ulcer margins of both young and aged gastric epithelium. Sixty days post‐injury there was complete regeneration of the gastric epithelium that exhibited the expression of parietal, chief and endocrine cells, and no evidence of SPEM in the young mice. However, the aged gastric epithelium exhibited the persistence of SPEM glands, expression of MUC2 and gastric cancer stem cell marker CD44v9. Aged mice transplanted with gastric organoids derived from young mice exhibited normal MUC5AC, GSII and UEAI expression similar to young mice 60 days post‐injury. Organoid transplantation of the aged gastric epithelium resulted in the normal expression of gastric cell lineages with an intact mucosal layer.ConclusionsFollowing injury in aged gastric tissues, the mucous layer becomes altered such that SPEM persists uncontrolled and there is loss of normal MUC5AC expression and gastric cell lineages. Ongoing experiments include studies of increased susceptibility to H. pylori‐induced metaplasia and cancer development using an in vivo acetic acid‐induced injury mouse model and human‐ and mouse‐derived gastric organoids.Support or Funding InformationNIH (NIDDK) 5R01DK083402‐08 grant (YZ)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluation of NanoString Technology for Detection and Genotyping of Human Papillomavirus (HPV)
Authors: Patel Sonya , Unger Elizabeth , Rajeevan Mangalathu 
Published: June 2021

ObjectiveTo date, CDC's HPV vaccine effectiveness studies have relied on one highly quality‐controlled commercial assay that uses consensus PCR of the HPV L1 gene followed by type‐specific hybridization. However, the reporting process is complex and additional testing is needed to resolve ambiguous results. Alternative assays with increased automation, faster turnaround and digital readout are needed.MethodsWe evaluated NanoString technology as a method for digital readout of the L1 gene for 48 HPV types in a single reaction. Unique probe pairs targeting the L1 and globin genes were designed in collaboration with NanoString. Forty residual DNA extracts from epidemiologic specimens and eight controls were tested directly (no amplification step) as well as after L1 consensus PCR. After overnight hybridization, type‐specific hybridization signals from scans were normalized and background assessed per the recommendations of NanoString. A positive result was defined as specimen‐normalized counts greater than the calculated sample specific background (average+2SD).ResultsThe NanoString assay produces a direct unambiguous readout of type‐specific results directly populating a database without manipulation. HPV detection in plasmid controls was successful only at the highest copy number tested (10,000 copies) and comparison of results of prior method and NanoString in residual extracts showed good type‐specific agreement (k=0.621) but lower sensitivity (65%) of NanoString. With PGMY primer L1 amplification, 45 cycles, hybridizing the highly diluted product gave almost‐perfect type‐specific agreement (k=0.862) between NanoString and prior method. Relative to prior results, NanoString had 82% sensitivity and 99% specificity. Initial evaluation of reduced amplification cycles suggest that sensitivity is maintained with only 15 cycles.ConclusionsThis proof‐of‐principle study demonstrates the potential of using the NanoString platform for highly multiplexed, high throughput and digital genotyping of HPV with a low number of PCR cycles. The platform improves the reliability of data management. NanoString technology is a candidate to improve the quality and reduce the cost of surveillance in studies of HPV and other infectious diseases.Support or Funding InformationSource of research support: Centers for Disease Control and PreventionThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Impact of Artificial Sweeteners on Insulin, Body Composition and Drink Choice in Mice
Authors: Provost Terri , Bortiatynski Garrett , Scalise Anthony , Smith Quinaya , Twitchell Brielynn 
Published: June 2021

The average American consumes almost 42 gallons of artificially sweetened beverages per year and about 66 pounds of sucrose. Although the USFDA supports that aspartame and stevia are safe for consumption, both nutritive and non‐nutritive sweeteners have been shown to negatively impact health. Sucrose causes addictive behaviors as well as excessive release of dopamine. Our study was designed to determine the behaviors and physiological changes in mice associated with consumption of aspartame and stevia when compared with sucrose. We exposed mice to untainted water or water containing 0.2% aspartame, 0.2% stevia, or 0.2% sucrose for 8 weeks, then provided the animals with a two‐bottle, treated and untreated, choice test for an additional week. After 9 weeks of treatment, mice were sacrificed and body composition, blood glucose, and serum insulin were determined. Stevia animals gained significantly more body weight than all other groups (p<0.05) and consumed significantly more food than controls (p<0.05). All treatment animals consumed significantly more fluid than control animals (p<0.05). When provided with the two‐bottle choice, the treated animals chose the sweetened drink significantly more than untreated water (p<0.05), while the control animals consumed water equally from both bottles. Aspartame treated animals had significantly heavier relative heart weights (p<0.05). We found no significant difference in relative liver weights, blood glucose or serum insulin concentrations in this short term test. These results are consistent with previous studies reporting addictive behavior with sucrose consumption. Current work is focused on the presence of brain lesions and dopamine release with exposure to sugar versus substitutes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nicotinate supplements slow onset and severity of symptoms in the monosodium iodoacetate (MIA) rat model for osteoarthritis (OA)
Authors: Bellamine Aouatef 
Published: June 2021

High doses of niacinamide have been used for the treatment of rheumatoid arthritis in humans. However, it is unclear if nicotinate supplementation can slow the onset of osteoarthritis. To assess this possibility, we supplemented Sprague Dawley rats with niacin (80 mg/kg) or niacinamide (400 mg/kg) then induced arthritis using a single intra‐articular injection of mono‐iodoacetate (MIA). Three MIA concentrations (0.5 mg, 1.0 mg and 2.0 mg) were used to simulate mild, moderate and severe OA disease levels. Changes in levels of pain and inflammation were assessed via dynamic weight bearing (DWB) and joint diameter, respectively. Supplementation with niacinamide, but not niacin, led to a significant decrease in knee joint diameter in both the 0.5 mg and the 1.0 mg MIA cohorts, with relatively better effects in the 0.5 mg MIA group presenting with nearly complete reversal of disease at day 14. Nicotinate treatment did not improve the DWB characteristics of these animals. Blinded histopathological examinations showed that niacinamide's favorable clinical outcomes were correlated mostly in the 0.5 mg MIA group. A second, dose‐response study, using the 1.0 mg MIA model, found that supplementation with niacinamide at 130 mg/kg, and niacin at 10 mg/kg, also yielded beneficial outcomes. These results indicate that supplementation with niacinamide may alleviate some OA symptoms in a relative short period of time.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Resistance Exercise on Bones in Calcium‐deficient Rats
Authors: Hirakawa Tomoe , Fujii Takako , Matsumoto Kinuyo , Okamura Koji 
Published: June 2021

Resistance exercise has been reported to enhance the reuse of iron in the body (Fujii T et al. Biol Trace Elem Res. 2014). Exercise increases the calcium absorption rate and bone mass. However, aerobic exercise reportedly does not lead to any improvements in bone strength in calcium‐deficient rats (Senge et al. J Physiol Soc Japan. 2003), although the effects of resistance exercise on bone in these animals are unclear. Therefore, we investigated the effect of resistance exercise on bones in calcium‐deficient rats. Twenty‐one male Sprague‐Dawley rats (4 weeks old) were divided into a calcium‐sufficient diet group (5 g calcium/kg diet) and a calcium‐deficient diet group (1.67 g calcium/kg diet), and half of the rats in both groups were subjected to climbing exercise training (5 minutes × 6 sets, 5 minutes of rest between sets) every other day for 3 days a week. The rats were euthanized after four weeks of the treatment. There were no significant differences in the blood calcium concentration among the four groups. The body weight and the weight of the flexor hallucis longus muscle, soleus muscle and kidneys were significantly higher in the exercise groups than in the non‐exercise groups, while no significant differences in these values were found between the calcium‐sufficient and calcium‐deficient diet groups. The weight, center width, rupture strength and stiffness of the femur were significantly higher in the calcium‐sufficient group than in the calcium‐deficient group, whereas no significant effect of exercise was observed. Resistance exercise enlarged the skeletal muscle in calcium‐deficient rats; however, this form of exercise showed no marked effect on bone parameters.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High‐Protein Diet‐Induced Changes in Body Composition and Metabolic Flexibility in Women: Feasibility of a Novel Template‐based Intervention Delivery Method
Authors: Olenick Alyssa , Niersbach Abigail , Pearson Regis C. , Green Edward S. , Jenkins Nathan T. 
Published: June 2021

Current recommended dietary allowance for protein is 0.8 g/kg/d. Recently, research has posited that this value is insufficient for resistance‐trained individuals and inadequate for the retention of lean mass while on a fat loss diet. Studies support an intake of nearly double the RDA, i.e. ~1.4–2.0 g/kg/day, but effective implementation strategies for achieving this higher protein intake have not been identified. Additionally, metabolic flexibility is the ability to adjust substrate oxidation according to nutrient availability and may be reflective of metabolic health. Whether a higher protein, caloric deficit diet improves metabolic flexibility in resistance‐trained women is not known.PURPOSETo determine the effects of a novel high protein diet template on body composition and metabolic flexibility during an 8‐wk intervention in recreationally resistance trained females.METHODSRecreationally resistance‐trained females (n=7, Age=21.7±2.1 yrs) were underwent baseline and post 8‐wk intervention dual‐energy X‐ray absorptiometry scans, anthropometrics and an acute high fat meal challenge. Baseline (T1) fasting glucose, resting energy expenditure (REE), and lipid (LO) and carbohydrate oxidation (CO) were measured. Participants then consumed a high fat meal (1127±132 kcal; 77±9 g fat) and glucose, REE, LO and CO measurements were taken at 60 (T2), 120 (T3) and 180 (T4) minutes postprandial. The meals contained 61% fat/29% carbohydrate/10% protein and were standardized to participants' body surface area (BSA). Participants were instructed how to follow a high‐protein dietary template (1.5–1.6 g/kg/day) and asked to maintain their resistance training volume and intensity throughout the study. The template was a PDF document containing specific instructions on amounts of lean proteins, vegetables, carbohydrates, and fats to be consumed at each meal throughout the day.RESULTSSignificant decreases were observed in % body fat (pre: 30.7±3.9%, post: 28.3±3.0%; p=0.010), waist circumference (pre: 77.0±4.7 cm, post: 74.4±5.2 cm; p=0.030), and waist‐to‐hip ratio (pre: 0.77±0.04, post: 0.76±0.04; p=0.050), with total body weight (pre: 67.5±6.7 kg, post: 65.5±5.3 kg; p = 0.076) and fat mass (pre: 19.7±3.7 kg, post: 18.6±3.0 kg; p=0.062) approaching significance. There were no significant changes in bone density, lean mass, fasting glucose, REE, LO, or CO.CONCLUSIONSA high protein diet leads to favorable improvements in fat mass, while preserving both lean mass and bone density in resistance trained females, without affecting metabolic flexibility. Our study also supports the feasibility of delivering a dietary intervention in a user‐friendly diet template format.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exposures to L‐felinine Suppressed Plasma Testosterone in Laboratory Rats
Authors: Voznessenskaya Vera V , Laktionova Tatiana K 
Published: June 2021

Felinine is a unique sulfur‐containing amino acid found in the urine of domestic cats and select members of the Felidae family (Rutherfurd et al. 2002). L‐felinine and its sulfur‐containing volatile derivatives excreted with urine in sex‐ and age‐dependent manner (Miyazaki et al. 2006). These cat‐specific volatile compounds may represent pheromones used as territorial markers for conspecific recognition or reproductive purposes by mature cats (Miyazaki et al. 2008). Species‐specific compounds may be used also by other species to recognize potential predators and their physiological status. In our previous studies we showed that exposures of rats from laboratory heterogenous population during gestation to the cat urine or L‐felinine significantly affected reproductive output. We observed significantly lower weight of newborn pups and skewed sex ratio in favour in males. At the behavioral level, exposed to cat urine/L‐felinine male rats showed fewer mountings and mountings with intromissions in presence of receptive females. In the current study we examined the influence of domestic cat‐specific compound L‐felinine on testosterone secretion in male rats. Intact cat urine was used as positive control; tap water was used as negative control. Test subjects were 3–4 month old Norway rats Rattus norvegicus from laboratory population. Males were placed singly two weeks prior to experiment. We used concentration of L‐felinine comparable to naturally occurring in the adult cat urine (Rutherfurd et al. 2002). Cotton balls soaked with L‐Felinine (0.05% w/v, 0.2 ml, US Biologicals), cat urine (0.2 ml) or tap water (0.2 ml) in plastic perforated containers were placed directly into home cages of rats. We renewed test solutions twice a week. Experimental animals were randomly assigned to one of treatment groups. Blood samples (50 μl) were obtained from rear foot pad (Miller et al. 1997). Plasma testosterone was assayed (in duplicate) by enzyme immunoassay method (EIA‐1559, DRG). Exposure of male rats to cat urine (0.2 ml) during two weeks significantly suppressed plasma testosterone (p=0. 0020, n=10, t‐test). Analogous exposures to L‐felinine (0.05 %, 0.2ml) produced quite similar effect (p =0.049, n=10, t‐test) in male rats. The effect was dose dependent: we did not observe suppression of plasma testosterone when lower amount of L‐felinine solution (0.05 %, 0.1ml.) was applied to home cage of male rats. It appears to be that altered sexual behavior of male rats exposed to L‐felinine/cat urine could be explained by significantly lowered testosterone secretion. The expression of the secondary defense reactions by laboratory naive rats and the failure tohabituate at the hormonal level may indicate an innate nature of the response.Support or Funding InformationSupported by Russian Foundation for Basic Research grant 19‐34‐70024 mol_a_mosThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Integrin receptor α4β7+ CD4 T cells promote mucosal and hepatic inflammation in NASH
Authors: Raeman Reben , Anania Frank A , Parkos Charles , Nusrat Asma , Kumar Pradeep , Desai Chirayu , Iyer Smita S , Liu Yunshan 
Published: June 2021

There is mounting evidence that impairment of the intestinal epithelial barrier underlies the pathogenesis of non‐alcoholic steatohepatitis (NASH); but, the specific mechanisms by which this occurs are unknown. Using F11r−/− mice, a murine model which exhibits altered intestinal permeability, we investigated the role of gut‐homing integrin receptor α4β7 expressing CD4 T cells in diet‐induced loss of intestinal epithelial barrier. Fed a WD for eight weeks, F11r−/− mice develop features of severe NASH, the result of damage to the integrity of the intestinal epithelium induced by the WD. WD‐fedmice demonstrated a systemic increase in IFNγ and TNFaproducing α4β7+ CD4 T cells, with greater recruitment of α4β7+ CD4 T cells in the intestine of F11r−/− mice relative to controls. This correlated with a markedly higher expression of integrin receptor α4β7 ligand, mucosal addressin cell adhesion molecule 1 (MAdCAM‐1), in the colonic mucosa of F11r−/− mice fed the WD. Elevated colonic expression of MAdCAM‐1 correlated with increased mucosa‐associated Proteobacteria in F11r−/− mice, but not in control mice. Depletion of microbiota reduced colonic MAdCAM‐1 expression and attenuated mucosal inflammation suggesting microbiota promote MAdCAM‐1 expression in the colon. Abolishing α4β7/MAdCAM‐1 interaction using an α4β7 monoclonal antibody significantly decreased α4β7+ CD4 T cell recruitment to the intestine and reduced colonic inflammation. This intervention also attenuated hepatic inflammation and fibrosis, and improved indices of the metabolic syndrome by reducing hepatic α4β7+ CD4 T cell recruitment driven by diet‐induced, microbiota‐dependent hepatic MAdCAM‐1 expression. Together, these data provide the first direct evidence that α4β7+CD4 T cells regulate intestinal barrier and hepatic inflammation in NASH.Support or Funding InformationResearch reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number K01DK110264 to RR. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the US Food and Drug Administration, the US Department of Health and Human Services, or the US Government.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of Single Nucleotide Polymorphisms on HPA‐Axis Functionality
Authors: Caruso Alexa P , Sharma Tanuj , Martino Audrey , Zhou Helen , Cohen Justin R. , Lukowitsky Mark , Cohen Brian D 
Published: June 2021

The hypothalamic‐pituitary‐adrenal (HPA) axis is responsible for regulating the secretion of the glucocorticoid hormone cortisol in response to stress. Diseases of cortisol dysregulation, such as Cushing's syndrome (hypercortisolism) and Addison's disease (hypocortisolism), share a common symptom of depression. Based on this we, and others, have hypothesized that single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and other genes associated with cortisol regulation may contribute to depression. Our study investigated the genotypic frequency of several SNPs that affect GR and MR sensitivity to cortisol in a clinical population. DNA samples were acquired via buccal swab from patients suspected of suffering from depression. Extracted DNA was analyzed using a novel multiplex allele‐specific polymerase chain reaction assay to determine the allelic frequency of SNPs associated with hypersensitivity or resistance to cortisol. Saliva samples were also collected from these patients and analyzed by ELISA to measure cortisol levels. In addition, patients completed multiple measures of depression and anxiety.Preliminary results showed that mutant haplotypes of three specific alleles in the GR, BclI (rs41423247), N363S (rs56149945), and TthlllI (rs10052957), were seen more frequently in the patient population compared to the general population. Although depression (as measured by the Beck Depression Inventory) and salivary cortisol did not change significantly between clinic visits, there was a significant decrease in state anxiety (as measured by the State‐Trait Anxiety Inventory) between visits for patients with the wild type or heterozygous BclI haplotypes while patients with the homozygous mutant haplotype did not show an improvement in state anxiety. This is the first demonstration that genotypic variation in cortisol sensitivity is associated with changes in state anxiety. This could lead to more specific and successful treatments for depression and anxiety.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.