bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of urothelial cell function by corticotrophin peptides
Authors: Hanna‐Mitchell Ann T , Buffington Tony , Birder Lori A 
Published: June 2021

Feline interstitial cystitis (FIC), a chronic idiopathic cystitis in cats, exhibits similarities to humans diagnosed with bladder pain syndrome/IC. In both syndromes, alterations in urothelial (UT) signaling/barrier may contribute to the associated pathophysiology. Corticotrophin peptides are involved in a number of functional pain syndromes and are now known to be expressed by peripheral tissues.Using time‐lapse fluorescence microscopy, we investigated a role for corticotrophin releasing factor (CRF), urocortin3 (UCN3), and receptors CRF‐1,‐2, in UT physiology. UT cells isolated from normal and FIC cat bladders were incubated with a membrane‐impermeant fluorescent dye (FM 1‐43; 5µM) and exposed to CRF (0.01µM), which has a greater affinity for CRF1. Normal UT exhibited a substantial membrane trafficking response (approximately 3 fold increase over basal/unstimulated) compared with FIC UT (1.5 fold increase over basal) .Both groups showed a low magnitude of trafficking in response to the selective CRF2 agonist, UCN3 (0.1µM).Astressin 2‐B alone (selective CRF2 antagonist; 1µM) evoked membrane trafficking in both groups; indicating cellular release of an autocrine factor, now free to act through CRF1 only. We also report a 'dis‐inhibition' of UT cell ATP release by astressin 2‐B and CRF mRNA expression by these cells. Our findings indicate a potential for CRF to play an important role in UT cell function.Funded byNIH R01 DK57284 and P50 DK64539
Global analysis of mRNA localization reveals a prominent role in the organization of cellular architecture and function
Authors: Krause Henry 
Published: June 2021

The localization of mRNA molecules is an important regulatory mechanism for targeting proteins to specific cellular compartments, although the overall prevalence and variety of transcript localization events remains unknown. To characterize subcellular mRNA localization dynamics during early Drosophila embryogenesis, we conducted a high‐throughput Fluorescent In Situ Hybridization (FISH) screen of over 4,000 distinct mRNAs, and found that the majority of expressed mRNAs (71%) are subcellularly localized. Many novel varieties of subcellular localization patterns were identified, implicating localized mRNAs in the assembly and regulation of diverse cellular modules and processes. Analysis of the localization data, which has been organized within a publicly available database (http://fly‐fish.ccbr.utoronto.ca), reveals that transcripts with similar localization dynamics are enriched for specific gene functions and putative regulatory elements. This work establishes mRNA localization as a widespread gene regulatory mechanism and underscores the predictive value of transcript localization phenotypes in assigning gene functions. We have begun dissecting the localization mechanisms and biological functions of various classes of mRNAs and the results of these ongoing studies will be presented.Funding provided by the Canadian Institutes of Health Research
Dietary patterns are associated with overweight and obesity in Mexican adults
Authors: Flores Mario , Macias Nayeli , Rivera Marta , Lozada Ana 
Published: June 2021

The objective was to identify dietary patterns and to evaluate their association with overweight and obesity in Mexican adults.Dietary information was obtained by a single, 101‐food item FFQ in 17,893 adults (20+ y) from the 2006 Mexican National Health & Nutrition Survey. Dietary patterns were defined by k‐means cluster analysis based on the % contribution to total energy intake of 30 food groups. Overweight and obesity were defined according to WHO criteria. Three dietary patterns were identified: Rural ("R", 40%), Urban‐poor ("U", 39%), and Western ("W" 21%). The "R" pattern was characterized by low dietary diversity, with maize and maize‐based foods accounting for ~50% of energy intake. This pattern had the lowest contributions of most food groups, with the exception of beans (~4.0 %). The "U" pattern had the highest contribution of alcohol (9.4%), sodas (9.3%), white bread (7.7%), fast food, sweets and snacks. The "W" pattern had the lowest contribution of maize (15.5%), and the highest contribution of dairy (12.6%), rice & pasta, meat, poultry, eggs, fats & oils, fruits, and vegetables. After adjusting for age, gender and SES, logistic regression analysis showed that "W" and "U" diets were associated with 30% and 25% increased risk of overweight/obesity, compared to the "R" pattern, respectively (p <0.001). Dietary patterns were associated with overweight and obesity in Mexican adults.Supported by SSA, Mexico.
Proteomic, metabolomic and lipidomic approaches to unravel the roles of polyunsaturated fatty acid nutrition in the developing liver
Authors: Novak Elizabeth M , Keller Bernd O , Dyer Roger A , Innis Sheila M 
Published: June 2021

Polyunsaturated fatty acids (PUFA) regulate metabolism in adult liver; PUFA accumulation in fetal and infant liver depends on diet. We used combined proteomics, metabolomics and lipidomics to address whether PUFA nutrition impacts metabolic development in neonatal rat liver. Rats were fed as % energy, 3.9% 18:2n‐6 and 1.5% 18:3n‐3 (high PUFA), or 1 % 18:2n‐6 and <0.1% 18:3n‐3 (low PUFA) in gestation and lactation. On day 3 postnatal, lipidomics using HPLC and GLC showed lower n‐3/n‐6 PUFA, but no difference in lipid classes in low compared to high PUFA offspring. Liver proteins were resolved on 2D gels, resolving over 800 proteins. PDQuest analysis showed 24 proteins up‐regulated and 1 down‐regulated over 3 fold in the high compared to low PUFA group, and these were identified by MALDI‐TOF MS. Up‐regulated proteins included F‐1,6‐biphosphatase 1, G‐3‐P dehydrogenase, galactokinase 1, catalase and 60 kDa heat shock protein, with argininosuccinate synthase down‐regulated. GC‐MS profiling of small molecules in liver extracts, with principal component analysis to address changes in flux through metabolic pathways showed higher gluconeogenic amino acids in the high PUFA group. Finally, integration of results from the proteomic and metabolomic analyses into metabolic pathways shows that maternal lipid nutrition impacts pathways of gluconeogenesis and oxidative stress in developing liver. Funded by CIHRGrant Funding SourceMichael Smith Fdn Health Research Studentship
Interaction design of a mobile phone food record for adolescents
Authors: Six Bethany L. , Mariappan Anand , Schap TusaRebecca E. , Kerr Deborah A. , Delp Edward J. , Ebert David S. , Boushey Carol J. 
Published: June 2021

Mobile telephones with an integrated camera can provide a unique mechanism for collecting dietary information that reduces burden on record keepers. The purpose of this study was to receive feedback from users during the interaction design of a mobile phone food record (mpFR) for adolescents that will eventually translate to an accurate account of daily food and nutrient intakes. A total of 78 adolescents (26 males, 51 females) ages 11‐18 y were recruited to participate in breakfast and lunch meal sessions and provide feedback about the mpFR. Prior to their first meal, all participants received instruction for using the mpFR. Volunteers captured an image of their meals (or snacks) before and after eating using the mpFR. After using the mpFR, the majority of participants (79%) agreed that the software was easy to use. Also, the students participated in a training activity where they received additional instruction on capturing images in various snacking situations. As a result of the additional training, significantly more participants agreed that taking images before snacking would be easy (10% vs 28%, p=0.01), as well as, after snacking (19% vs 38%, p<0.001). Though adolescents readily adopt new technologies, formative evaluation is needed to tailor technology. Further, these results suggest that additional training in using a new technology may improve the accuracy among users.Grant Funding SourceNIH‐NIDDK
Higher Leucine Content in an Essential Amino Acid Solution Enhances Human Skeletal Muscle mTOR Signaling
Authors: Glynn Erin Leigh , Fry Christopher S , Timmerman Kyle L , Dhanani Shaheen , Drummond Micah J , Volpi Elena , Rasmussen Blake B 
Published: June 2021

Essential amino acid (EAA) ingestion stimulates mammalian target of rapamycin (mTOR) signaling in humans. This effect appears to be largely due to the branched‐chain amino acid leucine. We hypothesized that increasing the leucine content of an EAA solution would enhance mTOR signaling to a greater extent as compared to an EAA solution with leucine content typical of high‐quality proteins. Subjects were randomized into two groups, each ingesting 10 grams of EAA but with differing amounts of leucine (18% or 1.8g in EAA group, n=6; 35% or 3.5g in LEU group, n=6). Muscle biopsies were taken at baseline, 1‐, 2‐ and 3‐hr post‐ingestion, and blood was sampled throughout. mTOR signaling was assessed by immunoblotting of biopsies. Phosphorylation of mTOR was increased 1‐hr following nutrient ingestion in both groups, however, the increase tended to be higher in the LEU group. mTOR signaling to downstream effectors S6K1 and 4E‐BP1 was also increased in both groups, though the time course differed between groups. Phosphorylation of eEF2 tended to decrease more at 1‐hr post‐ingestion in the LEU group, and remained dephosporylated 2‐ and 3‐hr post, indicating enhancement of translation elongation. We conclude that increasing leucine content in an EAA solution appears to alter the time course and enhance skeletal muscle mTOR signaling in young human subjects.Supported by NIH/NIAMS grant RO1 AR049877 & NIH/NIA P30 AG024832
Grape‐Enriched Diets Alter Cardiac Pathology and Cardiac Glutathione Dynamics in Hypertensive Rats
Authors: Seymour Mitchell , Lewis Sarah K , Bolling Steven F , Bennink Maurice R 
Published: June 2021

Increased fruit and vegetable intake can reduce hypertension, but its effect upon hypertensive cardiac pathology is unknown. This relationship was tested in the Dahl‐Salt Sensitive rat fed a high‐salt diet. Provision of 3% (w:w) whole table grape powder for 18 weeks reduced blood pressure, reduced cardiac hypertrophy, improved cardiac function, and increased cardiac glutathione, a key endogenous antioxidant. Provision of vasodilator hydralazine matched the blood pressure reduction of grape but failed to similarly reduce cardiac pathology. In vitro, phytochemicals found in grapes can alter genes related to Phase I/II metabolism, impacting glutathione dynamics. However, cardiac effects with a whole food are unknown. RT‐PCR analysis indicated that grape provision altered genes for oxidoreductases, transferases, sulfotransferases and peroxidases which affect glutathione dynamics, which on balance, would favor elevated glutathione. Key expression changes are confirmed by immunoblot. Importantly, these changes were conserved in grape‐fed, healthy (low‐salt fed) rats, further supporting the nutrigenomic effects of grape intake. In conclusion, physiologically relevant phytochemical intake reduced hypertensive cardiac pathology and altered cardiac transcripts related to glutathione dynamics, which may be vital to its cardioprotective effects. California Table Grape Commission, NIH‐NHLBI.Grant Funding SourceNIH‐NHLBI, California Table Grape Commission
Inflammation, Collagen Deposition, and Healing in a Goldfish (Carassius auratus) Model of Heart Injury
Authors: Lafontant Pascal J , Golden Benjamin , Grivas Jamie , Cobb Adrienne , Frounfelter Tyler 
Published: June 2021

Heart disease remains the number one cause of death in the United States. Mammalian and non‐mammalian models are used to study heart healing and regeneration following injury. In the teleost zebrafish, the removal of ventricular tissue by resection is fully replaced by thirty days with little to no scarring. We hypothesized that the goldfish (Carassius auratus) is able to regenerate its heart in a manner analogous to the zebrafish. We have performed cautery injury of 25% of the ventricle of goldfish that resulted in significant destruction of the ventricular wall and ventricular myocytes. We found an intense inflammatory response in the area of injury, followed the recruitment or proliferation of cells 3 days post injury. We also found a marked increased in collagen deposition at 3 days and 7 days that is resolved by 21 days. This observation is in contrast to the lack of collagen deposition reported in other models. Our data suggests that following cautery injury the goldfish ventricular wall is rebuilt by one week and a quasi complete healing is observed by 21 days. This is the first study showing healing following cautery injury in a fish heart.FundingDePauw University
Taking a Bite out of the Lab Book: Stereoscopic Laboratory Models in Student's Hands
Authors: Hopkins Robin Marie , Wilson Timothy D 
Published: June 2021

Decreasing time for anatomical teaching, coupled with a new generation of techno‐savvy students, has encouraged educators to explore new pedagogical approaches and instructional tools. An evolving tool is a stereoscopic 3D anatomical computer model of the head and neck. The objective of this study was to explore its effectiveness as an instructional and laboratory aid. Third year student volunteers (N=74) were randomly assigned to one of three lab groups. All groups studied the muscles of mastication and completed identical learning objectives during a 45‐minute lab. Each group utilized a different laboratory model: Group I‐gross prosections; Group II‐3D stereoscopic computer model; and Group III‐a hybrid model utilizing both resources. Model efficacy was measured with a pre‐post multiple‐choice quiz. We hypothesized that students using the 3D stereoscopic model or gross prosections would yield similar change scores (post‐test minus pre‐test), while students experiencing the hybrid model would have higher change scores. One week following the initial lab session, participants completed a second post‐test and a qualitative questionnaire to gain insights of knowledge retention and participant preferences respectively. Information gathered may help form new curricula direction.Grant Funding SourceTSC‐Small Grant on Teaching
Interactive pathways of the central nervous system: a web based didactic multimedia
Authors: Brabec Jiri , Hromadka Rastislav , Nanka Ondrej , Kacvinsky Jan , Hoyt Brian , Rulseh Aaron , Petrovicky Pavel 
Published: June 2021

Neuroanatomy is difficult, but successful and innovative use of interactive multimedia presentations can serve as another source for students of medicine to truly understand relationships of structures involved in the pathways. Using Adobe Flash CS3 to create images, videos, and simple animations allows interactive multimedia to be both integrated into lectures, and made available to students on the web. Our website, www.anatonomina.org, illustrates our work in such interactive media. In the photography section, students can look at familiar images, having been also published in a neuroanatomical atlas (Petrovicky P, Brabec J, 2007). By clicking on 'Video', students are presented with a list of main sensory and motor pathways. Choosing one of these, students find a brief overview of the pathway and the option to view sections of the appropriate levels of each pathway. Students can click on the diagram of gross sections and obtain histological as well as schematic views of the section with relevant structures highlighted, and even follow one pathway through MRI. Additionally, clicking on the 'Quiz' link, students are able to assess their knowledge through simple tests. To expect students to truly understand complex neuroanatomical relationships, we feel that the continued development of such interactive media are promising pedagogical techniques.Supported by grants IGA MZ 2006 NR8931‐4 and FRVS 809 2007Grant Funding SourceIGA MZ CR NR8931‐4
Calpain 2 functions upstream of MT1‐MMP activation to regulate endothelial cell invasion in 3D collagen matrices
Authors: Kwak Hyeongil , Bayless Kayla J 
Published: June 2021

Pro‐angiogenic factors initiate endothelial sprout formation and coordinate intracellular signals to regulate these events. Here, we investigated whether calpain regulates sprout outgrowth in 3D collagen matrices. Global calpain inhibition significantly limited invasion responses. Pharmacological blockade of calpain 2 dose‐dependently reduced invasion, while blocking calpain 1 had no effect. Consistent with these data, calpain 2 knockdown using shRNA reduced invasion, while calpain 1 knockdown had no effect. Maximal invasion responses were stimulated by combining sphingosine‐1‐phosphate (S1P) and angiogenic growth factors (GFs). Quantification of calpain activation revealed control«S1P«GF «S1P+GF. Further, calpain 2 localized to areas of cell‐cell contact and lamellipodia following S1P, but not GF treatment, indicating that while GF treatment increased calpain activity, S1P induced intracellular calpain mobilization. To begin deciphering the mechanism through which calpain 2 mediates invasion, we investigated MT1‐MMP activation and localization. The activation and localization pattern of MT1‐MMP were same as calpain 2. Finally, calpain 2 blockade reduced MT1‐MMP activity, indicating that calpain acts as an intracellular upstream switch for MT1‐MMP.Grant Funding SourceAmerican Heart Association
Characterization of Transforming growth factor (TGF‐β) in human milk among US and Mexican mothers
Authors: Rosales Francisco Jose , McMahon Robert J , Ferguson Paul W , Morrow Ardythe L , Jouni Zeina E 
Published: June 2021

Human milk TGF‐β plays an important role in maintaining appropriate immune function in infants. We assessed its morphology and ontogeny during lactation in milks from geographically different populations.Milk samples from three cohorts, each of 20 clinically healthy mothers delivering term babies: donors from the Cincinnati, OH, donated during 2005 ‐07 while donors from Mexico City donated during 2006‐07. The entire content of one breast was collected between 9‐12 am over the first 26 weeks postpartum. TGF‐β1 and β2 were determined using a commercially available ELISA kit (Qunatikine®) validated for its use in human milk, and total protein concentration (PROT) by Commassie Plus.Most TGF‐β (>90%) was in a latent form and ‐b2 was 5 to10‐fold higher than ‐b1, irrespective of lactation period and sampled region. TGF‐β (‐β1 + ‐β2) concentrations were positively skewed with high variability within and between mothers (figure), which was not explained by clinical status, PROT, lactation period or sampled region. A geometric‐mean and variance were calculated for each of the 13 times and locations, from which a grand geometric‐mean was calculated, 2,700 pg/ml. These results suggest that if an infant consumes 750 ml of milk daily his/her total TGF‐β intake would range from 0.4 to 9.8μg/day.TGFb concentrations in human milk* C= Cincinnati 2005‐06; M= Mexico City 2006‐07, & U= Cincinnati 2006‐07.
Linkage to the actin cytoskeleton is critical for α4β1‐mediated leukocyte rolling and chemokine‐induced arrest, but not prolonged adhesion
Authors: Rullo Jacob , Hyduk Sharon J , Digby Genevieve , Lee Leslie , Cybulsky Myron I 
Published: June 2021

The avidity or strength of integrin‐mediated cell adhesion is attributed to affinity (strength of individual bonds) and valency (number of bonds formed). We investigated the role of the actin cytoskeleton in α4β1 integrin mediated adhesion to VCAM‐1 in assays that model distinct steps of leukocyte emigration.In U937 cells stably transfected with the formyl peptide receptor, α4β1 integrin affinity up‐regulation induced by GPCR signaling remained intact following disruption of the actin cytoskeleton by cytochalasin D (cytoD) or latrunculin B (latB) (2 µM, 30 min incubation). Parallel plate flow chamber adhesion assays revealed that U937 cells pretreated with cytoD or latB failed to roll on surfaces coated with VCAM‐1 and arrest on surfaces co‐coated with VCAM‐1 and SDF‐1α. High affinity α4β1 induced by Mn2+ independent of GPCR signaling mediated spontaneous U937 arrest, which was blocked by cytoD or latB pretreatment. In contrast, U937 cell adhesion in 15 min assays was not inhibited by cytoD or latB. Fluorescence recovery after photobleaching demonstrated increased diffusion of α4β1 integrins in cells pretreated with cytoD, consistent with a disruption of integrin linkage to the actin cytoskeleton.These studies suggest that constitutive linkage of α4β1 integrins to the actin cytoskeleton is critical for mediating α4β1‐dependent rolling and arrest, but not prolonged leukocyte adhesion.Funded by CIHR.
A high fat diet reduces blood pressure, but not cardiac hypertrophy in spontaneously hypertensive rats
Authors: Lin Han‐yi , Soesanto Will S. , Symons J. David , Jalili Thunder 
Published: June 2021

High fat diets can attenuate cardiac hypertrophy in Dahl Salt Sensitive rats (DSS), a model of severe hypertension, cardiac hypertrophy & dysfunction, independent of changes in blood pressure. We hypothesized that a high fat diet can prevent hypertrophy in spontaneously hypertensive rats (SHR), a model of gradually increasing hypertension. Five‐week old SHR and Wistar Kyoto (WKY; normotensive control) rats were fed either a low fat (LF) or high fat (HF) diet with 10% and 60% of Calories from lard, respectively, for 10 weeks. In contrast to our hypothesis, cardiac hypertrophy was unchanged in SHR HF vs. SHR LF but, surprisingly, blood pressure was lower in SHR HF. Pooled statistical analysis also indicated lower plasma glucose (2 h fast) in HF vs. LF rats. These data indicate a markedly different response to high fat diets in the SHR vs. those previously reported in the DSS rats.(Different letters denote significant differences at p<0.05)
Stem cells homing and vascular differentiation in lung, heart and skeletal muscle in an experimental model of heart failure
Authors: Castellani Chiara , Ravara Barbara , Gobbo Valerio , Piccoli Martina , Franzin Chiara , Pozzobon Michela , Vettor Roberto , Thiene Gaetano , Dalla Libera Luciano , Vescovo Giorgio , Angelini Annalisa 
Published: June 2021

PurposeAim of our study was to investigate the homing and differentiation of human amniotic stem cell (hAFC) and rat vascular stromal adipocite GFP positive cells (rGFP) in a rat model of heart failure.Methods and MaterialsMale Sprague‐Dowley rats were injected with monocrotaline to develop right heart failure. hAFC or rat GFP cells were injected via tail vein three weeks after MCT injection. Stem cells differentiation were studied by double immunofluorescence technique.ResultsPlasma brain natriuretic peptide (BNP), was elevated in HF compared to controls (2.01±0.12 HF rats;0.56±0.37 ng/ml controls, p< 0.0001),while was similar to controls in HF animals injected with stem cells (0.75±0.06 ng/ml,p<0.001).HF stem cells animals showed a RVM/Vol value lower than HF and similar to controls (0.34±0.02 treated animals;0.49±0.29 in controls, p<0.001). Both rGFP and hAFC were detected in the lung (1.01±0.6% hAFC and 0.44±0.4% rGFP) and few of them (0.11±0.1% of hAFC) were differentiated into vascular cells. In the heart stem cells were 0.36±0.3% for hAFC and 0.55±0.2 for rGFP positive cells and hAFC showed a 0.01±0.01 % and rGFP 0.16±0.1% of SMA differentiation. In skeletal muscle stem cells were hAFC 0,31±0,09% and rGFP 0,36±0,2%.ConclusionsThese results suggest that hAFC and rGFP cells are both engrafted with a topographical recruitment gradient in the lung, heart and skeletal muscle and seems to reduce heart remodelling and failure.