bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoupling of biomechanics of hyoid movement and bolus flow in preterm infants
Authors: Gould Francois , Catchpole Emily , Bond Laura , Stricklen Bethany , Mayerl Christopher , German Rebecca 
Published: June 2021

Determining the timing of bolus passage over the airway, and into the esophagus, is critical for biomechanical studies of swallowing. Videofluroscopy is the gold standard for determining fluid movement, but is not always possible. Hylolaryngeal movement, measured from light film or standard videography, is a reliable marker for adult human swallowing, but its validity for the biomechanics of swallowing in immature infants is unknown. We tested the relationship between hyolaryngeal movement from light camera data compared to bolus movement from video fluoroscopy in pre‐term and term infant pigs.Three term and four pre‐term pigs were fed from a bottle containing barium and a milk solution. At seven days after birth pigs were recorded feeding from the bottle using simultaneous high speed (100 fps) x‐ray and light video cameras. In the light video, the frame of most rapid elevation of the hyoid was scored as the swallow. In the x‐ray, the swallows were scored as the beginning of posterior bolus movement. The number of frames separating x‐ray and light camera swallow identifications was calculated for each swallow.Hyoid movement was found to be closely correlated to bolus movement in term pigs, but no correlation existed in pre‐term pigs. The mean frame offsets for term and pre‐term pigs were different (Wilcox test, p<0.001). The variance for the pre‐term pigs was significantly larger (Levene's test p<0.001).The light videos were found to be a good measure of swallows in term pigs, but were not a good measure of swallows in pre‐term pigs. The biomechanics of bolus movement are altered in the neurologically poorly coordinated pre‐term pigs. Specifically, hyolaryngeal elevation and bolus movement are decoupled in pre‐terms whereas they are tightly coordinated in term pigs. Prematurity leads to altered form function relationships through immature development.Support or Funding InformationNICHD grant 088561This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evolutionary Ontogeny of the Avian Adductor Musculature‐Endocranial Relationship: Evidence from the Chick
Authors: Llera Catherine J , Bever Gabriel S 
Published: June 2021

The modern avian body evolved across a stem lineage that is more than 140‐million years in length and is famously populated by a multitude of fossil forms, including all non‐avian dinosaurs. Expansion of the brain and surrounding neurocranium is an important driver of many morphological patterns, including the general reduction and ventral displacement of the adductor chamber. Nevertheless, a recent study showed that Ichthyornis — a Cretaceous stem bird that retains teeth and lies phylogenetically just outside the crown radiation — expresses both a derived braincase and a primitive adductor chamber. This unexpected co‐occurrence suggests complexity in the evolutionary trade‐off between these functionally important cranial spaces. We build on this work by examining the relationship between the developing adductor chamber and the endocranial cavity; specifically testing for temporal shifts as the adductor chamber develops and the skull grows around the precocial brain. Our sample consists of differentially stained μCT scans from a chick (Gallus) ontogenetic series that ranges from the Day 5 embryo to adult. The adductor chamber musculature and associated bones were digitally segmented. Muscle attachments at each stage and the volume for each individual muscle/undifferentiated muscle group were recorded. Results show the adductor muscle groups (adductor mandibulae posterior, externus, and internus) were clearly distinguishable by Day 15 of embryonic development. The individual muscle bellies within each group remained largely undifferentiated until postnatal week 6. Nonetheless, only in the adult stage are the muscle bellies within each group fully discernible. Analyses of muscle locations relative to skull bones show that attachment points tend to shift ventrally during development. Additionally, preliminary results indicate that the increase in muscle mass standardized by head weight is non‐linear and the relative adductor muscle mass is smaller as the chick matures. These results indicate an ontogeny‐phylogeny parallel, with the adductor muscles decreasing in relative size and shifting ventrally as the braincase expands. The timing and tempo of adductor muscle differentiation and maturation, and the morphological dynamics of the other feeding‐related structures (e.g., lower jaw) has potential implications for understanding the evolutionary trade‐off that occurred between brain expansion and reduced chewing musculature. Our data will serve as baseline trajectories for future developmental studies, including modelling how heterochronic or heterotopic alterations explain observed‐ phylogenetic patterns and predict future fossil discoveries.Support or Funding InformationNSF‐DEB‐1801224 to GSBThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Caloric Restriction Increases Parkin Recruitment in Hearts of Obese Insulin‐Resistant Rats
Authors: Cummings Chelsy Tiy , Cornejo Manuel A , Nguyen Julie , Cazaress Joshua , Escobedo Benny , Nishiyama Akira , Ortiz Rudy M 
Published: June 2021

Mitochondria provide energy to the cells, making the task of mitochondrial recycling highly important. Impairments in mitochondrial number and function can lead to dysregulation of cellular metabolism and disrupted capacity to maintain homeostasis. The Parkin gene codes for the protein, Parkin, which is a component of the Parkin/PINK1 pathway that helps regulate mitophagy. An impairment in the Parkin gene may also results in nonfunctional mitochondria, potentially leading to many diseases such as type two diabetes mellitus and cardiovascular disease. Recent studies suggest that Parkin expression is downregulated during insulin resistance. To address the hypothesis that insulin resistance downregulates Parkin in the heart, a piece of the left ventricle of the hearts of 4 groups of rats were extracted: (1) Long Evans Tokushima Otsuka (LETO), (2) Otsuka Long‐Evans Tokushima Fatty (OLETF), (3) LETO with caloric restriction, and (4) OLETF with caloric restriction. Extracted Parkin from the hearts of each group was measured by Western blot. Because Parkin expression is downregulated with insulin resistance, we anticipated lower levels of express in the insulin resistant, OLETF rats compared to LETO, and that caloric restriction would restore Parkin expression in the OLETF rats. Parkin protein expression was 71% lower in OLETF than LETO. While the 16% increase in expression in caloric restricted LETO group was not statistically significant, the expression increased nearly 7.5‐fold with caloric restriction in OLETF group compared to the ad lib OLETF group. The data suggest that the benefits of CR on CV function and health go beyond the potential benefits of mass loss (usually adiposity) but include cellular energetics and metabolism in the heart of insulin resistant rats.Support or Funding InformationThe STRIDE Fellowship is supported by the American Physiological Society and a grant from the National Heart, Lung and Blood Institute (NHLBI; 1 R25 HL115473‐01).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assessing Post‐Stroke Cardiac Dysfunction in the Insular Ischemic Stroke Rat Model
Authors: Jaremek Victoria , Iankov Stella , Milazzo Thomas , Wang Lynn , Whitehead Shawn N. , Sposato Luciano A. 
Published: June 2021

Patients who have suffered an ischemic stroke with damage to the right insular cortex (IC) often develop post‐stroke cardiac complications. However, the pathophysiology and time course of these post‐stroke myocardial changes require further investigation which is complicated by a lack of pre‐clinical models. The purpose of this work is to assess the time course of post‐stroke cardiac fibrosis and inflammation in a rat model of selective insular ischemic stroke. IC ischemic stroke was induced in six‐month‐old Wistar rats via unilateral stereotaxic injection of endothelin‐1 into the right IC (n=6/surgical group). Control rats received a phosphate‐buffered saline (PBS) injection into the right IC (n=6/surgical group). To establish a time course of cardiac dysfunction, hearts were histologically examined at 6, 24 hours, 7, 14 and 28 days post‐stroke for fibrosis (Masson's Trichrome stain), inflammation (CD45+, myeloperoxidase, CD3+, CD45R, CD68+ immunostaining) and endothelial dysfunction (phosphorylated endothelial nitric oxide synthase (eNOS)). Areas of interest included the 4 heart chambers and pulmonary vein/left atrium border (PV‐LA border). Results from this study showed that focal IC ischemic stroke led to neutrophil infiltration at 6 hours, followed by T lymphocyte infiltration at 7 days at the PV‐LA border. Left atrial tissue experienced long‐term fibrosis at 28 days following focal IC stroke. Further, B lymphocyte infiltration was seen at 28 days post‐stroke in left ventricular tissue. These findings provide insight into the progression of post‐stroke cardiac changes and suggest that inflammation is a treatable target to prevent post‐stroke myocardial injury.Support or Funding InformationThis study is funded by the Kathleen & Dr Henry Barnett Research Chair in Stroke Research (Western University, London, Ontario, Canada), the Western University Medical and Health Sciences Research Board Seed Research Grant, and the Edward and Alma Saraydar Neurosciences Fund (London Health Sciences Foundation).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Silent Treatment: miR199 Family Silences Shh during Craniofacial Development
Authors: Richbourg Heather Ashley , Hu Diane , Marcucio Ralph 
Published: June 2021

Early craniofacial development requires precise timing and spatial regulation of key signaling pathways in order for proper facial structures to form. Perturbations, particularly in the sonic hedgehog (Shh) signaling pathway, can result in craniofacial birth defects that cause significant harm and financial costs. microRNAs (miRNA) play many roles in developing systems by repressing gene expression, but despite the enormous number of miRNAs that have been identified, few have been related to biological processes through direct targets. Here we identified the miR199 family as Shh‐regulated miRNAs during development of the upper jaw in a chick model.We performed a miRNA microarray analysis on chick embryonic ectoderm before (stage HH18) and after (stage HH22) formation of the Frontonasal Ectodermal Zone (FEZ) and after activating or blocking SHH signaling in the brain. We identified a family of miRNAs (miR199b, mir199* and miR199) that appeared to be regulated by SHH signaling in the brain. These are increased between stages HH18 and HH22, and increase upon activation of Shh signaling and decrease upon blockade of Shh signaling, and these data were confirmed by qPCR. To assess the function of this family of miRNAs during facial development, we performed miR199 knock‐down and overexpression experiments and examined the phenotypic and molecular changes. Up‐regulation of each miRNA led to decreased Shh expression in the FEZ and facial malformations that are consistent with decreased Shh signaling in the face. Using antagomirs to knockdown each miRNA, we observed that Shh expression was expanded and the faces were wider, reminiscent of SHH gain‐of‐function experiments. Hence, it appears that expression of these miRNAs in the FEZ are regulated by SHH signaling from the brain, and these miRNAs appear to regulate SHH signaling from the FEZ. We then identified Smurf2, Map3k4, Hif1alpha, and Dyrk1a as targets of the miR‐199 family of miRNAs via mir‐base. We confirmed that each of these genes behaved like targets in miR‐gain and loss‐of‐function experiments described above. Using pmirGLO luciferase, we identified MAP3K4 and HIF as direct targets of miR199. Finally, we generated a miRNA knockdown cassette to reduce expression of Hif1α and Map3k4. Blocking HIF1α resulted in a large reduction of Shh expression in the FEZ, and resulted in severe craniofacial malformations, while blocking Map3k4 altered facial morphology, resulting in altered mediolateral beak development at later stages. Overall, our results demonstrate that Shh signaling within the brain contributes to facial development by regulating a family of miRNAs that then regulate the expression of Shh in the FEZ via targeting the transcription factor Hif1α.Support or Funding InformationThis work was supported by the National Institutes of Health (R01 DE018234‐A1)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Craniofacial Bone Mineral Density in Mice with Osteogenesis Imperfecta (OI)
Authors: McBride Alexandra H , Ladd Summer H , Organ Jason M , Menegaz Rachel A 
Published: June 2021

Osteogenesis Imperfecta (OI) is a rare genetic disorder characterized by a point mutation in COL1A1 or COL1A2 genes that leads to the abnormal synthesis and assembly of type I collagen, a major organic component of bone. Clinical manifestations of the severe OI Type III include small body size, limb deformities, and low bone mineral density (BMD) within the post‐cranial skeleton. OI type III often co‐occurs with dentinogenesis imperfecta (DI), especially in juveniles. The goals of this study are: (1) to investigate the relationship between the organic and inorganic components of bone in the craniofacial skeleton; and (2) to examine whether an abnormality in type I collagen, as seen in OI, affects BMD within the craniofacial skeleton.The homozygous recessive murine mouse (OIM−/−) is a model for OI Type III. Similar to human OI patients, OIM−/− mice exhibit low BMD within post‐cranial elements such as the femur, smaller body size, and DI. OIM−/− mice and WT littermates were weaned at 21 days and CT scans were performed longitudinally at 4 weeks, 10 weeks, and 16 weeks of age. BMD at three regions of interest (ROIs) within the mandible were measured using Bruker CT Analyzer software. ROIs were selected on the basis of high vs. low loading during mastication, and included the temporomandibular joint (TMJ), buccal side of the mandibular corpus at the level of the second molar (M2), and the mandibular symphysis. Kruskal‐Wallis ANOVAs were used to statistically compare BMD between genotypes (α = 0.05). Adult OIM−/− mice (n=6) have significantly lower BMD within the mandibular corpus near M2 as compared to WT mice (n=6). Differences in BMD means between OIM−/− and WT mice were not significant at the TMJ or the mandibular symphysis. Future studies will quantify BMD at additional ROIs within the craniofacial skeleton, and following the ontogenetic trajectory of BMD in the craniofacial skeleton from weaning to adulthood.Support or Funding InformationThis research was supported by an Indiana University Collaborative Research Grant and the Ralph W. and Grace Showalter Trust.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The homeodomain protein Cux1 is regulated by the Notch signaling pathway in the developing kidney
Authors: Holthaus Conner , Kumar Emmanuel , Carlton Carol , Heuvel Greg Vanden 
Published: June 2021

Cux1 is the murine homologue of the Drosophila gene Cut. In Drosophila, multiple genetic interactions between Cut and the Notch and Wingless signaling pathways occur during development. Cux1 is upregulated in rat kidney epithelial cells expressing a constitutively active Notch1 (Notch1ic), and interacts with the groucho homologue Grg4 to regulate p27 expression in the developing kidney. Moreover, Cux1 co‐localizes with several components of the Notch signaling pathway during kidney development. To further evaluate whether Cux1 is an effector of the Notch signaling pathway we used the γ‐secretase inhibitor DAPT to block all Notch signaling in kidney organ cultures. DAPT treatment significantly inhibited growth of wild‐type metanephroi. In contrast, Cux1 transgenic kidney cultures treated with DAPT were not growth inhibited, but showed high levels of cell proliferation in the nephrogenic zone, and ureteric bud branching was similar to vehicle treated kidney cultures. Notch1ic cells showed an increase in cell proliferation compared to wild type RKE cells, however, antisense knockdown of Cux1 in the Notch1ic cells reduced cell proliferation to the same level as wild type cells. Finally, the targeted deletion of RBPJ/k, a transcription factor required for canonical Notch signaling, in the developing ureteric bud and collecting duct, resulted in the complete absence of Cux1 protein specifically in the ureteric bud and collecting duct cells. Taken together, these results suggest that Notch signaling regulates the expression of Cux1 in the developing kidney, and that this pathway is conserved across species.Support or Funding InformationNIH DK58377, WMED Research FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In Utero Exposure to Nicotine Causes Post‐natal Anemia
Authors: Durham Emily L , Howie R Nicole , Grey Zachary , Hall SarahRose , Larson Nicholas , Patterson Kimberly , Warren Graham , LaRue Amanda C , Cray James 
Published: June 2021

Almost ¼ of the world population suffers from anemia, a condition characterized by an insufficient number of red blood cells or oxygen‐carrying capacity within the blood. Anemia is associated with fatigue, weakness, and dizziness, and when it occurs early in life it may alter the course of behavioral and cognitive development in human and murine populations causing decreased physical activity and responsiveness. Pregnant women and children are particularly vulnerable to anemia as are individuals who use nicotine. Despite the link between adverse birth outcomes of pre‐ and perinatal nicotine exposure, 11% of US women continue smoking or using alternative nicotine products throughout pregnancy. We hypothesize that in utero exposure to nicotine will result in post‐natal anemia precipitating a characteristic abnormal bone phenotype. To test this hypothesis, wild type C57BL6 males and females were utilized to produce in utero nicotine exposed litters. Drinking water for pregnant dams was supplemented with nicotine. Pups were grown to 15 days postnatal then sacrificed. Blood and whole skulls were collected for complete blood count, micro‐computed tomography (μCT), and histological analyses. Complete blood count data comparing nicotine exposed pups to unexposed controls indicated increased mean corpuscular volume indicative of macrocytic anemia in nicotine exposed mice. Additionally, nicotine exposed pups presented with low platelet counts also associated with anemia. μCT analysis of bone surface compared to bone volume indicated a greater ratio in individuals exposed to nicotine, which suggests weaker pitted bone also associated with anemia. Histological investigation of osteoclast activity indicated greater osteoclast activity in individuals exposed to nicotine. Together, these data indicate that exposure to nicotine in utero precipitates a negative bone phenotype associated with nutritional deficiency and anemia.Support or Funding InformationThis research was supported by the National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research (NIDCR) [R03DE026192, 5T32DE017551 F31DE026684], National Center for Advancing Translational Sciences [UL1TR000062], and Plastic Surgery Foundation [Pilot Award 512114]. This study utilized the facilities and resources of the Medical University of South Carolina Center for Oral Health Research supported by the NIH/NIGM [P30GM103331].This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing the Expression Pattern and Requirement of Sf3b4 During Mouse Embryonic Development
Authors: Kumar Shruti , Alam Sabrina , Chan Wesley , Beauchamp Marie‐Claude , Jerome‐Majewska Lodyie 
Published: June 2021

Nager Syndrome (NS) is a rare disorder that affects the face as well as the limb including both hands and feet. Patients with NS typically have malar and mandibular hypoplasia, cleft palate, as well as hearing problems. Limb defects include radial hypoplasia as well as thumb abnormalities. Using exome sequencing, NS was attributed to haploinsufficiency of the SF3B4 gene, an important component of the U2 subunit of the spliceosome complex. We hypothesized that Sf3b4 will show tissue‐specific expression during development and that mice with heterozygous mutation in this gene will model NS. To create heterozygous Sf3b4 mutant mice, we used CRISPR/Cas9 to target loxP sequences in intronic regions flanking exon 2 and 3 of the Sf3b4 gene. We will breed loxP founders with Wnt‐1 Cre transgenic mice, and report the resulting phenotypes. Additionally, whole mount in situ hybridization was used to examine expression of Sf3b4 during embryonic development of wild type mouse. We found that Sf3b4 shows ubiquitous expression at early stages of development. In midgestation embryos, although still globally expressed, Sf3b4 expression becomes stronger in the maxillomandibular region, limbs and tail bud. Our research will elucidate the expression of Sf3b4 in embryonic tissues affected in NS patients and generate a mouse model that will be used to further characterize the molecular basis of this syndrome. As there are currently no mouse models or therapy available for NS our work will help to identify some of the targets of Sf3b4 and pave the path for the creation of new therapies for spliceosomal disorders.Support or Funding InformationCanadian Institutes of Health ResearchThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.