bluuebunny/crossref_metadata_2025_split huggingface dataset:
Properdin mediates complement activation and is protective against infectious colitis (902.6)
Authors: Jain Umang , Thomas Nikhil , Stover Cordula , Stadnyk Andrew 
Published: June 2021

Background: Properdin amplifies complement activation and also acts as a pattern recognition receptor, facilitating the removal of microbes and apoptotic/necrotic cells in complement‐dependent and ‐independent mechanisms. C. rodentium is a natural bacterial pathogen of mice leading to colitis; we asked if properdin plays a role during C. rodentium colitis.Methods: C. rodentium was gavaged into C57BL/6 (wildtype, WT) or properdin gene knockout (P‐/‐) mice and colitis was quantified by histopathological scoring of the colon and measurements of inflammatory mediators and apoptosis. In some experiments WT or P‐/‐ serum was injected into infected mice and the effects on colitis assessed.Results: C. rodentium infected P‐/‐ mice exhibited levels of gut C3a higher than in infected WT mice but significantly less C5a than in WT mice. P‐/‐ mice suffered exacerbated colonic inflammation compared to infected WT characterized by excessive ulceration, infiltration by CD4+ T cells, neutrophils and macrophages, and increased levels of interferon‐γ. Using immunofluorescence, properdin associated with apoptotic cells and infected P‐/‐ mice had increased numbers of apoptotic cells. Lastly, properdin sufficient serum resulted in increased C5a levels and fewer apoptotic cells associated with less inflammation.Conclusion: We discovered that properdin modulates complement activation during infectious colitis, evident by a lack of C5 convertase activity associated with a paradoxical increase in inflammation. We conclude that properdin regulates colitis in a C5a‐independent mechanism possibly related to a failure to remove apoptotic cell in the mucosa.Grant Funding Source: NSERC, CCFC
The effects of enteral nutrition on gut microbiota in IL‐10‐/‐ mice (903.3)
Authors: Somero Jillian , Gulati Ajay , Uno Jennifer 
Published: June 2021

Enteral nutrition delivered by an exclusive formula‐based diet can both reduce intestinal inflammation and induce mucosal healing in individuals with Crohn’s disease (CD); however, the mechanism by which this occurs remains unclear. Recent work also indicates that individuals with CD have altered enteric bacterial composition relative to healthy individuals. Here we investigate if an exclusive formula diet alters the bacterial composition in the stool of wild‐type (WT) and IL‐10‐/‐ mice. WT and IL‐10‐/‐ mice were placed on a formula‐based (ED) or regular diet (RD) for four weeks. Histologic analysis of these mice indicated no effects of the ED on the WT group; however, unexpectedly, the IL10‐/‐ mice on the ED showed increased inflammation with 25% of the mice developing rectal prolapse. Gut cultures corresponded with histology with the ED IL10‐/‐ mice consistently exhibiting increased production of IL‐12p40 and TNF (n=3, p= 0.05). To examine the bacterial composition of the microbiota, bacterial DNA was isolated and primers were used to PCR amplify the 16S gene of specific bacterial groups. Bacterial levels were calculated as a percentage relative to total 16S bacteria. Il10‐/‐ mice on the ED showed modest, although not significant increases in total bacteria as well as decreases in genus‐specific Bifidobacterium. Furthermore, significant decreases were observed in F. prausnitzii while increases were observed in Lactobacillus (n=4, p=.05). Collectively, these data indicate a dysbiosis in bacterial communities in the genetically susceptible IL10‐/‐ mice on the enteral relative to the regular diet, which may provide insight into the underlying mechanism involved in the intestinal changes associated with enteral nutrition.Grant Funding Source: Elon University
Activation of long‐chain free fatty acid receptor FFAR1 (GPR40) and FFAR4 (GPR120) causes release of brain‐derived neurotropic factor from enteric glial cells (905.2)
Authors: Alkahtani Reem , Mahavadi Sunila , Alqudah Mohammad , Murthy Karnam , Grider John 
Published: June 2021

Recent deorphanization of several G protein‐coupled receptors (GPRs) as endogenous receptors for free fatty acids (FFARs) has increased our understanding of these nutrients as signaling molecules and the integral role of the gut microbiota in the regulation of host defense mechanisms, energy metabolism, gastrointestinal motility, and secretion. Enteric glial cells and neurotrophins such as BDNF, glial cell line‐derived neurotrophic factor (GDNF) and nerve growth factor (NGF) are essential for the development and integrity of enteric nervous system in the gut. The role of free fatty acid receptors in the regulation of BDNF release from enteric glial cells, however, is not known. Aim. To determine the expression of FFARs and the signaling pathways coupled to FFAR1 and FFAR4, receptors for long chain fatty acids, that mediate BDNF release from enteric glial cells. Results. Quantitative RT‐PCR and western blot studies showed expression of FFAR1, FFAR2, FFAR3, FFAR4 and GPR84 in enteric glial cells; expression of FFAR1, however, was more abundant than other receptors. Linolenic acid which activates FFAR1/FFAR4 caused an increase in phosphoinositide hydrolysis (measured in [3H]myo‐inositol labeled cells), intracellular Ca2+ (measured in Fura‐2 loaded cells) and BDNF release (measured by ELISA). Conclusion. Enteric glial cells express receptors for free fatty acids and activation of FFAR1 and FFAR4 causes BDNF release via stimulation of PLC‐β/IP3/Ca2+ pathway.Grant Funding Source: Supported by DK34153
Cardiac hypertrophy is associated with upregulation of alpha myosin heavy chain in Hfe‐deficient mice (907.6)
Authors: Sukumaran Abitha , Chang JuOae , Khaw Ban‐An , Kim Jonghan 
Published: June 2021

Cardiac hypertrophy is associated with up‐regulation of alpha myosin heavy chain in Hfe‐deficient mice Abitha Sukumaran, JuOae Chang, Ban‐An Khaw and Jonghan Kim Department of Pharmaceutical Sciences, Northeastern University, Massachusetts, United States of America.Cardiac damage induced by iron overload is the common cause of morbidity and mortality in patients with hereditary hemochromatosis (HH). Mutations in HFE are the major cause of hemochromatosis in humans. However, the precise molecular mechanisms involved in the pathogenesis of iron‐induced cardiotoxicity are largely unexplored. Here we investigated the effect of HFE and iron on cardiac damage using Hfe‐deficient (Hfe‐/‐) mice, a model of human HH. At the age of 5‐month, Hfe‐/‐ mice displayed elevated iron levels in the heart (p=0.0352). This was associated with increased mRNA expression of divalent metal transporter 1 (DMT1) that lacks iron‐response element (p=0.0124), which likely promotes non‐transferrin‐bound iron uptake. In addition, heart/body weight ratio was significantly increased (15% greater than controls; p=0.0004; n=6‐9/group). Cardiac hypertrophy in Hfe‐/‐ mice was consistent with increased protein levels of alpha myosin heavy chain (p=0.0381), a marker of cardiomyocytes. All these changes were not observed in 1‐month old mice, suggesting an age‐dependent effect of Hfe deficiency on the pathogenesis of cardiotoxicity. Since reduced anti‐oxidant enzyme activities are associated with hypertrophy, increased cardiac iron in Hfe deficiency could promote oxidative stress and deplete anti‐oxidant enzymes, resulting in the progression of cardiac diseases. Supported in part by NIH ES017781.Grant Funding Source: NIH ES017781
Pancreatic damage in obese mice with liver steatosis: effects of Ω 3 fatty acid (909.1)
Authors: Likhitsup Alisa , Herndon Betty , Nachnani Jagdish , Alba Laura , Quinn Tim , Torres‐Romero Luis , Molteni Agostino 
Published: June 2021

Fatty liver disease (FLD) correlates with obesity and insulin resistance. The OB/OB leptin knock out mouse is used here to evaluate FLD, effects on the pancreas and the response to Ω 3 fatty acid (Ω3FA) treatment. The receptor for Ω3FA (Ω3FA‐r) stimulates incretin which reduces inflammation, insulin resistance and type 2 diabetes. However, the Ω3FA‐r has 2 isoforms, only one with activity. Our pilot studies showed elevated blood glucose in OB/OB mice following Ω3FA. Does this suggest an inactive receptor isoform in our model? Is it related to FLD or to pancreatic changes? OB/OB mice (10/group) were fed a standard or Ω3FA supplemented diet. Liver and pancreas were evaluated. Liver: Fat replaced about 70% of the parenchyma. Many hepatocytes contained pyknotic nuclei. Portal triads and biliary ducts were inflamed. Pancreas: Acinar structure disruption, necrosis, vasculitis and ductal inflammation were seen in the exocrine pancreas and peripancreatic fat but not in the endocrine pancreas. Blood glucose was significantly elevated in the Ω3 FA group vs untreated (p=0.046). Ω3 FA decreased hepatic steatosis and inflammation, but did not reduce inflammation in the exocrine pancreas. Ω3 FA was further associated with some severe hyperglycemia in this model. The two different activities of Ω3 FA in the leptin k/o mice livers vs pancreas suggests the need for study of the Ω3FA‐r and its isoforms as they relate to the two tissues.Grant Funding Source: Funding: Saint Luke’s Hospital Foundation grant to LA
Maternal‐fetal cholesterol transport in the second half of pregnancy does not involve LRP2 (910.2)
Authors: Zwier Mathijs , Baardman Maria , Jurdzinski Angelika , Bloks Vincent , van Dijk Theo , Groen Albert , Plösch Torsten 
Published: June 2021

Cholesterol is of crucial importance during fetal development and relies on both maternal transport and fetal synthesis. During gestation, Lipoprotein related receptor protein type 2 (Megalin or LRP2) is expressed in both yolk sac and placenta, suggesting a possible role in maternal‐fetal cholesterol transport. Although lipoproteins have been identified as potential LRP2 ligands, the contributing effect of LRP2 on maternal‐fetal cholesterol transport and fetal cholesterol levels in utero have not been adequately addressed.Using stable isotope techniques we quantified maternal‐fetal cholesterol transport in Lrp2 ‐/‐ and WT fetal mice during gestation. Additionally, we administered probucol to half of the dams to reduce maternal cholesterol availability.We found no difference in maternal‐fetal cholesterol transport or synthesis between Lrp2 ‐/‐ and WT littermates, suggesting that LRP2 is not quantitatively involved in maternal‐fetal cholesterol transport.Probucol supplementation lead to a large reduction in maternal plasma cholesterol and was associated with a 50% reduction of maternally derived cholesterol in the fetus, while overall cholesterol levels were unchanged. These results support that the mouse fetus can compensate for decreased maternal cholesterol levels by increasing cholesterol synthesis in utero.
Diet‐induced obesity compromises lactation through zinc‐mediated ER stress and autophagy, promoting premature involution (910.4)
Authors: Hennigar Stephen , Velasquez Vanessa , Kelleher Shannon 
Published: June 2021

Overweight/obese mothers are less likely to initiate and maintain lactation; however, the biological mechanisms are not understood. During normal involution, the proinflammatory cytokine TNFα stimulates the redistribution of the zinc (Zn) transporter ZnT2 to lysosomes to activate autophagic cell death. Thus, we hypothesized that obesity‐associated inflammation compromises lactation by redistributing subcellular Zn pools and promoting premature involution. Female DBA/J2 mice were fed a high fat diet (HFD; 45% kcal fat) until they were >20% heavier than mice fed a control diet (CD; 10% kcal fat). Mice were mated and fed their diets until lactation day 5. 77% of HFD mice failed to nurse their pups to day 5 (CD, 39%; p<0.001). Lactating HFD mice had 55% more macrophages (p<0.001) and elevated TNFα expression (p<0.05) in the mammary gland compared with CD mice. HFD mice had greater ZnT2 abundance in lysosomes, a 41% increase in acid phosphatase activity (p<0.05) and greater LC3‐II expression. HFD mice had decreased expression of the endoplasmic reticulum (ER) Zn exporter ZIP7 and increased ER Zn (p<0.05) and BiP expression (p<0.05). Importantly, HFD mice had significantly higher pStat3 expression (p<0.05). Our results suggest inflammation compromises lactation by mediating Zn retention in the ER and lysosomes, activating ER stress and autophagy and promoting premature involution.Grant Funding Source: NIH grants
Changes in gene expression profiles in chronic kidney disease patients treated with tetrahydrobiopterin versus placebo: a randomized controlled trial (912.11)
Authors: Park Jeanie , Deveaux Don , Gibson Greg , Jefferson Melanie , Quyyumi Arshed 
Published: June 2021

Chronic kidney disease (CKD) patients are at significantly higher risk of cardiovascular mortality. One major contributing factor is decreased nitric oxide (NO) bioavailability, which leads to endothelial dysfunction and sympathetic nervous system (SNS) overactivity. Tetrahydrobiopterin (BH4) is a cofactor for endothelial NO synthase activity that has been shown to improve NO bioavailability and endothelial function in animal models of CKD; however, BH4 treatment had never before been tested in humans with CKD. We hypothesized that BH4 treatment alters gene expression profiles in CKD; particularly, the RNA activity of genes involved in the regulation of NO and SNS activity. In a randomized, double‐masked, placebo‐controlled trial, we randomized 36 hypertensive CKD patients to 12 weeks of: a) BH4 200 mg twice daily + folic acid 1 mg daily; versus b) identical placebo twice daily + folic acid 1 mg daily. Physiologic measures and blood collected in tempus tubes were obtained before and after treatment. Total RNA will be extracted, and gene expression profiling will be performed using the Illumina HT12 BeadChip technology at the Emory Integrative Genomics Core laboratory. We anticipate that expression of candidate genes involved in NO and SNS regulation may be altered with time in CKD patients treated with BH4.Grant Funding Source: Supported by K grant HL098744
The shrinking arterial genome: role of double strand DNA breaks in age‐related DNA deletion (912.9)
Authors: Morgan Richard , Ives Stephen , Cawthon Richard , Andtbacka Robert , Noyes Dirk , Lesniewski Lisa , Richardson Russell , Donato Anthony 
Published: June 2021

Age‐related genomic instability and subsequent cellular dysfunction may be important processes underlying arterial aging. To assess the novel role of double strand DNA break (DSB)‐mediated DNA deletion in arterial aging, we compared genomic DSB load (gDSB; phosphorylated ser 139 histone H2A.X localized to ALUs: ChIP), genomic ALU content (gALU; proxy for genome size: qPCR), and tumor suppressor protein p53 (P53)/bcl‐2‐associated X protein (BAX)‐dependent apoptotic signaling (P53 bound to BAX gene promoter: ChIP) in arteries from 104 younger (<40y), middle‐aged (41‐60y), and older adults (>61y). gDSB was ~120% greater in arteries from older adults compared with younger adults (P = 0.03). gALU was ~40% lower in arteries from middle‐aged and older adults compared with younger adults (all P < 0.01), which indicates DNA deletion and reduced genome size. Subjects in the highest tertile of gDSB had ~30% lower gALU than those in the lowest tertile (P = 0.03, r = ‐0.17). There was ~260% greater P53/BAX‐dependent apoptotic signaling in arteries from older adults compared with younger adults (all P = 0.03), which could lead to transient reductions in mean genome size via apoptotic DNA fragmentation. Apoptotic signaling was correlated with gDSB (r = 0.34, P < 0.01), but not gALU (r = 0.17, P = 0.08). These findings demonstrate that age‐related reductions in arterial genome size are linked to greater genomic DSB load.Grant Funding Source: Supported by National Institute of Aging‐AG040297, AG029337, AG033196, AG033755
Tyre for congenital hip dislocation (913.12)
Authors: Karabekova R. , Lozovoy V. , Lozovaya E. , Hamitov M. 
Published: June 2021

Current data on congenital dislocation of the hip show that despite the large number of original articles and monographs dealing with this issue, the problem of early treatment of this disease continues to be one of the important in pediatric orthopedics .We have a tire that can be used for early functional treatment of congenital dislocation of the hip and prevention of avascular necrosis of the femoral head (Innovative patent number 27257). The purpose of the invention ‐ to ensure optimal fixation tires on the thigh or lower leg abduction dosed lower limb. This is achieved in that the tire for the treatment of congenital dislocation of the hip, strut designed as a sliding sleeve , and with the stopper rod is provided with a damping spring which is connected with the working ends of the sliding rods. Tires are manufactured in three sizes for lower leg. Children from 3‐4 months used tires small size, children from 4 months to 1 year ‐ mid‐size tires. Structural feature of the tire‐namely, the establishment of shock‐absorbing springs damping between two sliding rods provide good results of treatment as prevention is avascular necrosis of the femoral head through improved functionality.The tire we used in 20 patients in the conservative treatment of congenital dislocation of the hip, in 2 children with aseptic necrosis of the femoral head. No complications were observed.
Anatomic localization of nerve entry points in the gluteus maximus muscle: preliminary results (915.7)
Authors: Yendo Tatiana , Itezerote Ana , Jacomo Alfredo , Akamatsu Flavia 
Published: June 2021

The knowledge of the anatomic localization of the gluteus maximus muscle nerve entry points, where the nerve branch first pierced the muscle belly, will help understanding the physiopathology and treatments in both clinical and surgical contexts, such as myofascial pain syndrome and relation to myofascial trigger points, treatment of chronic pain and surgical approaches to the hip.We dissected fourteen gluteus maximus muscles from 7 cadavers and the nerve entry points of these muscles were determined. We divided the gluteus maximus muscle in 4 quadrants based on two reference lines: the x‐coordinated line is a transversal line passing by the coccyx, and the y‐coordinated line is perpendicular to the first line, passing by its mid‐point. The quadrant (A) is superior to the x‐coordinate and medial to the y‐coordinate; (B) is superior to the x‐coordinate and lateral to the y‐coordinate; (C) is inferior to the x‐coordinate and medial to the y‐coordinate; and (D) is inferior to the x‐coordinate and lateral to the y‐coordinate.We found 12 nerve entry points in in position (A), 11 in position (B), 14 in position (C) and 20 in position (D). The medium number of nerve entry points per gluteus maximus muscle was 4.6 (maximum 7 and minimum 2).The parameters provided in this preliminary study may contribute to avoid iatrogenic lesions in surgical approaches and to understand and improve the treatments to myofascial pain syndrome.
The opening and closing mechanism of the spiracle in the spiny dogfish shark, Squalus acanthias (918.20)
Authors: Paulk Kyle , McFerren Scott , Homberger Dominique 
Published: June 2021

Benthic sharks ventilate their gills by using a dual pump mechanism. They take water in by sequentially opening their spiracle and mouth, and expel water through their gills by closing their mouth and spiracle and compressing their oropharyngeal cavity (Hughes 1960). However, the mechanism of opening and closing the spiracle and the possible role of the pseudobranch are not fully understood. Therefore, we analyzed the functional morphology of the spiracle in a Spiny Dogfish Shark by micro‐dissection and digital imaging. The immovable edges of the spiracle are held in place by radially arranged subcutaneous collagen fibers. The spiracle is opened and closed by the spiracular flap, which is formed by the underlying spiracular muscle. In the closed spiracle, the spiracular flap and muscle are contracted, wide, and flat. When the chondrocranium is raised to open the mouth, the spiracular flap and muscle are stretched, elongated, and narrowed to open the spiracle and break the watertight seal within the oropharyngeal cavity. The spiracle closes when the mouth is closed by the contraction of the levator palatoquadrati, rostral levator hyomandibulae and spiracular muscles. The pseudobranch serves as a hydraulic cushion that ensures a watertight seal in the closed spiracle.Grant Funding Source: Supported by LSU Foundation to DGH
External ear anthropometry: the search for sexual dimorphism and correlations among Nigerians (918.6)
Authors: Taura Magaji 
Published: June 2021

External ear anthropometry; the search for sexual dimorphism and correlations among Nigerians M. G. Taura1, L. H. Adamu, M. H. Modibbo Department of Anatomy, Faculty of Medicine, Bayero Univeristy, Kano Nigeria 1Corresponding author: Dr. M.G. Taura, e‐mail: mgtaura.ana@buk.edu.ng +234 (0) 8063790273Abstract There is always need for anthropometric data for a given population especially the need for identification as well as designing products suitable for utility by the population. The aim of the study was to determine the level of sexual dimorphism in ear length, ear width and ear index for both left and right sides of the body. The correlation between the ear variables was also determined. The study population consisted of 137 males and 82 females recruited among Bayero University students participated in the study. Direct method using vanier caliper was employed in measurement of ear dimensions. The result shows that mean value of ear dimensions is higher on the right side in the all variables considered. Significant differences were also observed in ear length and ear width of the right side (P < 0.05) and the width and index show a significant difference (P < 0.05) on the left side of the body. Correlation between the variables shows a negative correlation between ear length and ear index. In conclusion, the present study has established the existence of sexual dimorphism in the ear linear dimensions among Nigerian population. Therefore, the use of ear dimension in anthropometry for characterization of the differences in sex was highlighted in the study.Key words: External ear, morphometry, Nigeria, Sexual dimorphismGrant Funding Source: Bayero University Kano