bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphological Grouping and Body Mass Prediction Models
Authors: Lancaster Terry (Bird) Elisabeth 
Published: April 2020

Every facet of an organism’s function is affected by its body size, such as heart rate, metabolism, organ size and function, feeding ecology, and locomotion. Using body size to assess the function and size of organs in extant mammals is relatively easy. However, estimating the body size and organ function of transitional fossil species, such as the Eocene whales, is difficult. The Eocene whales are diverse in body size, structure, and habitat, therefore a single allometric model will not provide the most accurate body size estimation for each fossil whale family and therefore less accurate organ function assessment. The goal of my research is to predict the body size of the Eocene whales using morphological models of extant mammals as guides. The first stage is the morphological grouping and body mass prediction models using modern mammal skeletons.I measured the skull, vertebrae, and appendicular bones of multiple species of modern aquatic, semi‐aquatic, and terrestrial mammals. I calculated an average body mass representative of each species using recorded body weights. Using Principal Component Analysis (PCA), I determined morphological groupings for these mammals from the skeletal measurements. For each PCA analysis completed, I created a linear regression equation to predict body size from the skeletal variables used in each analysis and the calculated average body sizes. I tested these prediction models using the measurements from 12 representative skeletons that were not included in the data set used to create the model, specifically Odocoileus virginianus, Tragulus napu, Hippopotamus amphibus, Tapirus indicus, Sus scrofa, Canis lupus lycaon, Nyctereutes procyonid, Ehydra lutris, Gulo gulo, Neophoca cinerea, Lobodon carinophagus, and Ursus maritimus.From the PCA, I identified five morphological groups for the mammals selected: Aquatic, Semi‐aquatic, Semi‐terrestrial, Large Terrestrial and Small Terrestrial. For the prediction model using all skeletal variables, the standard error of the estimate (SEE) for all 12 test individuals ranged from 0.3359 – 0.7496. For the skull variables, the SEE ranged from 0.1260 – 0.3197. For the limb variables, the SEE ranged from 0.1716 – 0.3964. For the vertebral variables, the SEE ranged from 0.1511 – 0.2851. These small SEE values and the large sample size substantiate the accuracy of these predictive models and the reliability of their respective confidence intervals (CI) and prediction intervals (PI) for the models. The results confirm that these linear regression models will be appropriate to predict the body mass of the Eocene whales in the second stage of this project.Support or Funding InformationKent State University; East Tennessee State University; Sigma Xi
Role of b‐lapachone treatment mediated base excision repair protein PARylation in colorectal cancer cells.
Authors: Singh Naveen 
Published: April 2020

Poly (ADP‐ribose) PAR is a protein post‐translational modification catalyzed by a family of enzymes known as PARPs. Most solid tumors overexpress NAD(P)H;Quinone Oxidoreductase 1 (NQO1), which catalyzes a futile redox cycle of b‐lapachone during exposure, resulting in the formation of high levels of reactive oxygen species (ROS). Futile cycle b‐lapachone recycling produces elevated superoxide levels, resulting in massive levels of hydrogen peroxide that lead to substantial DNA damage and endoplasmic reticulum Ca2+ release. DNA damage and Ca+2 entry into the nucleus leads to the hyperactivation of poly(ADP‐ribose) polymerase 1 (PARP1). A majority of parylation is noted when hyperactivated PARP1 self‐parylates, forming extensive Poly(ADP) ribosylated PAR‐PARP1 levels are noted within 5 mins of exposure to 4 μM β‐lap in A549 cells, as noted by Western blotting using an antibody specific for PARylated moieties. PAR‐PARP1 is a protein post‐translational modification catalyzed by a family of enzymes known as PARPs. DNA single strand breaks along with base‐damage and abasic sites together with nuclear Ca2+ levels lead to hyperactivation of PARP1, a DNA repair enzyme that utilizes NAD+ to generate PAR moieties. This is followed by dramatic NAD+/ATP losses and tumor cells die of a special programmed necrosis process, referred to as NAD+‐keresis. PAR‐PARP1 is rapidly degraded by poly(ADP‐ribose) glycohydrolase (PARG) a exo‐ and endoglycosidase.PARG‐knockdown HCT116 cells were used to gain insight into the function of PARG and whether PARG depletion would enhance b‐lapachone induced cell death by blocking PAR recycling. Proteomic screening after b‐lapachone treatment in colorectal cancer cell line revealed the PARylation landscape of base excision, mismatch and nucleotide excision repair proteins. Twenty (20) of the proteins were found to overlap with H2O2 treatments (200 μM or 2 mM), while one protein (i.e., SPSF) was unique to b‐lapachone treatment. b‐Lapachone treatment affects BER pathways and qualitative analysis of the human Asp‐ and Glu‐ADP‐ribosylated proteome after b‐lapachone treatment indicate major alterations in BER pathways. We confirmed that b‐lapachone mediated cytotoxicity was independent of PARG knockdown or TOPO I or II protein losses. In contrast, RFC1 and PCNA siRNA‐mediated protein knock downs significantly enhanced b‐lapachone lethality, whereas knockdown of Topo I or Topo IIalpha did not affect b‐lapachone lethality. Taken together, these results demonstrated that knockdown of RFC1 enhances lethality of b‐lapachone and could serve as an effective treatment strategy in cancer conditions.Support or Funding InformationThis work was funded by NIH/NCI 5 R01 CA102792‐16 to DAB.
Assessing understanding of structural relationships: early lessons in a large scale virtual reality deployment
Authors: Meyer Carolyn A. , Ivie Kenneth R. , Heise Natascha , Brown Katie , Clapp Tod R. 
Published: April 2020

The study and practice of medicine requires a comprehensive understanding of interactions and an accurate perception of spatial relationships within the body. Existing diagnostic, classroom, and patient education materials are limited by 2‐dimensional representations of these 3‐ dimensional associations. Virtual reality is an emerging technology that creates a more lifelike and intuitive learning experience by allowing users to interact with 3D data. This technology can be used to advance the efficiency of understanding the 3‐dimensional associations that constitute the human body.BananaVision is a networked, multiuser virtual reality tool that renders human anatomical structures for the creation of instructional content. It allows users to quickly explore structural relationships as well as identify and dissect in a virtual environment. Here we describe a large‐scale virtual reality deployment and examine its efficacy as a tool to engage students and aid in preparation for a human dissection course.Human gross anatomy dissection students were randomly assigned to three groups. Each group was provided different study tools; an anatomy atlas, autonomous use of BananaVision virtual reality, or autonomous use of BananaVision virtual reality along with a pre‐recorded instructional module. After the study period, students were required to complete an assessment of their knowledge of structural relationships. Students found the BananaVision to be an engaging and useful tool. Additionally, the study group given access to BananaVision along with the module were more efficient in their preparation. However, performance on assessments was similar between groups.As virtual reality technology is implemented in education, the field is in the early stages of evaluating meaningful processes and procedures that demonstrate measurable outcomes. This study begins to address some of the early challenges when integrating a virtual reality deployment in anatomy curriculum. As demands on gross anatomy classrooms continue to increase, it is important to identify technologies and strategies that improve efficiency.
Cranial Base Structures Geometric Morphometry and Description of a Clinical Relevant Anatomical Variation
Authors: Fazan Frederico Sassoli , Assis Cirino Mucio L. , Thomazini José Antônio , da Cunha Tirapelli Daniela Pretti , Tirapelli Luis Feranado , Fazan Valéria Paula Sassoli 
Published: April 2020

The foramen magnum is a large median oval opening in the occipital bone in the base of the skull, which leads into the posterior fossa. The foramen magnum has a forwarded shift of its anterior border in humans causing a shortening of the cranial base. The foramen is described as oval, wider posteriorly than anteriorly, and its antero‐posterior diameter exceeds the transversal one. Anteriorly, the margin of the foramen magnum is slightly covered, on each side, by an occipital condyle. These condyles, oval in shape, are located obliquely, so that their anterior end is closer to the median plane. Thirty dry skulls, from adult individuals, present in the anatomy laboratory of our institution were evaluated and a study of the dimensional anatomy of the foramen magnum and the occipital condyles was performed. With the aid of an analog caliper (precision of 0.05mm), the antero‐posterior and transverse diameters of the foramen magnum (posterior to the occipital condyles) and occipital condyles were obtained. Our results showed that the mean antero‐posterior diameter of the foramen magnum was 36.1 ± 0.5 mm and the transverse diameter was 30.0 ± 0.4 mm. The mean antero‐posterior diameter of the right occipital condyle was significantly smaller than that of the left, being 22.2 ± 0.4 mm and 23.1 ± 0.4 mm, respectively. The mean transverse diameter of the right occipital condyle was also statistically smaller than that of the left, being 12.6 ± 0.2 mm and 13.2 ± 0.2 mm, respectively. One of the skulls studied (excluded from the previous statistic) showed anatomical variation in the shape and size of the foramen magnum. This foramen was narrow, with an antero‐posterior diameter of 26.75 mm and a transverse diameter of 22.50 mm. In addition, the occipital condyles were asymmetrical, with the right condyle being practically transverse in relation to the foramen magnum, making a protrusion into its interior, contributing to the transverse narrowing of this foramen. The left condyle presented antero‐posterior (22.95 mm) and transversal (15.95 mm) diameters larger than the right (19.35 mm and 13.10 mm respectively). There were no signs of fractures or previous craniotomies in this particular skull. The present study reports the geometric morphometry of some striking structures at the base of the skull, in addition to describing an important anatomical variation of these structures. We did not find reports of significant difference between the right and left condylar diameters in the literature. The anatomy of the skull base is useful for estimating the race and sex of individuals in forensic medicine. Furthermore, geometric morphometry is an important tool in primatology and anthropology.Support or Funding InformationFAPESP, CNPq, CAPES and FAEPA
3β‐Diol Attenuates COX‐2 Levels in a Neonatal In‐Vivo and In‐Vitro Ischemic Injury Rodent and Human Model
Authors: Beer Yasmin , Shi Samuel , Rodriguez Janelle , Gonzales Rayna J. 
Published: April 2020

Studies using experimental stroke models demonstrate that neuroprotective agents which provide protection from secondary injury, including inflammation, result in improved outcome. Estrogen receptor β (ESR2) has the potential to be a novel therapeutic target in the treatment of ischemic stroke. Previous studies have shown that ESR2 activation elicits beneficial effects in the cerebrovasculature by promoting vasorelaxation and by attenuating pro‐inflammatory mediator production. We previously observed that activation of the androgen, 5α‐androstane‐3β,17β‐diol (3β‐diol), reduced pro‐inflammatory mediator production in adult human vascular smooth muscle cells and rodent cerebral arteries, and this response was ESR2 dependent. The current study was designed to determine if ERS2 is expressed in both a human pediatric brain endothelial cell model and juvenile rat stroke model and whether 3β‐diol will attenuate cyclooxygenase‐2 (COX‐2) expression following ischemic injury. Male rat pups (P10–15) underwent 15 minutes of bilateral internal carotid artery occlusion (BCAO) or sham surgery and 24‐hour reperfusion. At the onset of reperfusion, pups were injected with 3β‐diol i.p. (2.5mg/kg) or vehicle (1.2% EtOH and 98.8% PEG). Next, animals were heavily sedated and whole brain removed at 24 hours. In an in‐vitro model of ischemic stroke, male primary pediatric human microvascular endothelial cells (HBMEC; Cell Systems) were exposed to hypoxia plus glucose deprivation (HGD; 1% O2) or normoxia (21% O2) plus or minus 3β‐diol (10nM) or vehicle (0.0001% ethanol) for 3h at passage 7, using a humidified chamber (BioSpherix®) housed within a 5% CO2 incubator. Total protein was extracted from rat whole brain and human endothelial cells, assayed for protein content, and COX‐2 levels assessed using western analysis. RT‐PCR analysis was used to explore whether 3β‐diol alters expression of its target receptor, ERS2. We observed that ESR2 was basally expressed in the prepubescent brain and HBMECs, and expression was not altered following ischemic injury. Proinflammatory COX‐2 protein levels were increased in both whole brain and HBMEC homogenates from BCAO and HGD groups compared to sham and vehicle controls, and the selective ERS2 agonist, 3β‐diol, attenuated this response. In conclusion, these studies suggest that 3β‐diol may have a role in modulating ischemia‐induced COX‐2 during stroke. Since ERS2 is expressed in the whole brain and brain endothelial cells, and ERS2 levels are not decreased during ischemic injury, ERS2 may be a viable target for future stroke therapeutics in the pediatric population by attenuating inflammatory modulators during ischemic injury in the developing brain.Support or Funding InformationUniversity of Arizona Valley Research Partnership Grant VRP04 P1 (RJG), American Heart Association 19AIREA34480018 (RJG).
Transcriptome of SHR Carotid Bodies Reveals Novel Peptide Receptors Associated with Hypertension
Authors: Pauza Audrys G. , Paton Julian , Murphy David 
Published: April 2020

BackgroundThe epidemic of hypertension demands novel therapeutic strategies and innovative multi‐system approach to clinical management. The carotid body (CB) is the primary site of peripheral chemoreception in the human body. CB dysfunction has been implicated in numerous cardio‐respiratory and metabolic conditions, including essential hypertension, diabetes mellitus, sleep apnoea and heart failure. Recent attempts to modulate CB activity has proven successful in alleviating symptoms despite lacking specificity at the target organ. The ribbon‐cable hypothesis suggests that the CB is composed of specialised chemosensory subunits responsive to a specific stimulus in the bloodstream
1.AimWe hypothesised that the hypertensive phenotype is associated with alterations in a subset of chemosensory subunits, identification of which would offer highly specific therapeutic opportunities for clinical intervention.MethodsWe performed a high‐throughput transcriptomic screen of the CBs in the spontaneously hypertensive (SHR) and the normotensive Wistar‐Kyoto (WKY) rats.ResultsTranscriptomic screen of the SHR CBs revealed numerous differentially expressed genes associated with the hypertensive state. Our experimental design uncovered underlying lateral differences between the CBs at the intra‐individual level. Network analysis revealed genes associated with serine metabolism, oxidoreductase activity, and G protein‐coupled receptors to be significantly enriched in the WKY‐SHR comparison. A number of previously unidentified peptide receptors were found to be differentially expressed in the SHR.ConclusionNewly identified receptors serve as candidate genes for pre‐clinical proof of concept and feasibility functional studies. This provides a unique opportunity to design novel therapies to abate carotid body tonicity and hyperreflexia in neurogenic and metabolic hypertension.Support or Funding InformationThis work has been generously supported by the British Heart Foundation (BHF)
Time Course of Astrocyte Activation in Mouse Nucleus Tractus Solitarius During Exposure to Hypoxia
Authors: Howe Jacqueline Stenger , Moya Esteban , Howe Gabrielle , Mesarwi Omar , Powell Frank 
Published: April 2020

Chronic sustained hypoxia (CH) occurs in populations living at high altitude and in patients with chronic pulmonary disease. Exposure to CH produces ventilatory acclimatization to hypoxia (VAH) and increases the hypoxic ventilatory response (HVR) by mechanisms that involve areas of the brainstem that control breathing. The nucleus tractus solitarius (NTS) is a sensory integrative center in the medulla receiving carotid body afferents and known to be crucial for VAH. Our previous results demonstrated that glia cells in the rat NTS contribute to VAH but these mechanisms have not been studied in mice exposed to CH beyond 24 hours. We hypothesized that CH produces an early transient activation of astrocytes and microglia in the mouse brainstem as observed in rats. To study the activation of glial cells with CH, we exposed mice to normobaric hypoxia (10% FiO2) for 0.5, 1 and 4 hours and 1 and 7 days. Mice were perfused with 4% paraformaldehyde and brainstem sections were obtained. We quantified astrocyte activation by measuring glial fibrillary acidic protein (GFAP) intensity with immunofluorescence, and microglial activation by measuring branch morphology using Iba‐1 marker. Exposure to CH significantly increased GFAP intensity after 30 minutes and 1day while microglia morphology did not change significantly. The results differ from those in rats (J. Neurophysiol.117: 1625–1635, 2017) and suggest that time‐dependent astrocyte activation in the NTS may contribute to VAH.Support or Funding InformationSupported by NIH RO1 HL‐081823
EFFECTS OF MODERATE ETHANOL CONSUMPTION ON EXPRESSION OF GENES RELATED TO COLONIC CELL GROWTH IN YOUNG ADULT AND OLDER RATS
Authors: Wells Nicole , Quigley Jacqueline , Pascua Jeremy , Pinkowski Natalie , Almaiman Lama , Brasser Susan M. , Hong Mee Young 
Published: April 2020

Our previous research showed that moderate ethanol consumption reduced colonic cell proliferation regardless of age. To examine the underlying mechanism, this study examined gene expression related to colonic cell growth. Twenty‐four nondeprived young adult (109 days old) Wistar rats and twenty‐four nondeprived middle‐aged (420 days old) Wistar rats were randomly assigned to an ethanol‐exposed or a non ethanol‐exposed (water control) group (n = 12 per group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks (45 ethanol drinking sessions total), a paradigm which results in mean blood alcohol levels of ~30–50 mg/dl (0.03–0.05 mg%) in the outbred Wistar strain when measured 30–120 min into a standard drinking session. The control group was provided with standard drinking water during the same period. Gene expression of cyclin D1, cyclin dependent kinase 2 (CDK2), cyclin dependent kinase 4 (CDK4), p21, E‐cadherin and p53 were determined by real time polymerase chain reaction in colonic scraped mucosa. CDK2 was downregulated in ethanol‐fed rats compared to the control group (P = 0.017). Cyclin D1 trended toward lower expression (P = 0.095), and p21 trended toward higher expression (P = 0.095) in ethanol‐fed rats compared to controls, with no observed effect of age for either gene. Older rats showed significant decreases in CDK4 (P = 0.001), E cadherin (P = 0.013), and p53 (P = 0.005), with no observed effect of ethanol exposure. These results indicate that moderate ethanol consumption may improve expression of some genes related to important parameters of colonic cell growth and tumorigenesis.Support or Funding InformationNIH AA023291
MICRORNA‐21 EXPRESSION IN DIAGNOSIS OF PANCREATIC ADENOCARCINOMA.
Authors: DE ASSIS CIRINO MUCIO LUIZ , FADEL PATRICIA CICCILIATO , NOVAIS PAULO CEZAR , DA CUNHA TIRAPELLI DANIELA PRETTI , KEMP RAFAEL , DOS SANTOS JOSE SEBASTIAO , PERIA FERNANDA MARIS 
Published: April 2020

IntroductionThe differential diagnosis between pancreatic adenocarcinoma (PA) and chronic pancreatitis is still a challenge and the use of biomarkers association can mitigate these difficulties.ObjectivesTo evaluate the effect of combining miRNA‐21 and serum CA 19‐9 in the diagnosis of PA.Patients and MethodsWe studied 23 PA samples and 20 samples as controls: 13 from normal pancreatic tissue adjacent to the tumor (TPR) collected during pancreatic resections and 7 from normal pancreas (NP) from cadaveric donors or patients undergoing pancreatectomy for trauma. Serum CA 19‐9 was measured and miRNA‐21 expression were verified in PA, NP and TPR by quantitative real‐time polymerase chain reaction (PCR) amplification. The usefulness of miR‐21 in the diagnosis of PA, isolated or associated with CA 19‐9 were analyzed by constructing ROC curves.ResultsThere was a significant difference in miR‐21 expression in the comparison between NP and PA groups (p <0.05). However, there was no significant difference in miRNA‐21 expression between NP and TPR groups. The combination of miRNA‐21 with CA 19‐9 was more effective in discriminating PA from NP (AUC‐ROC: = 0.94; sensitivity: 78%; specificity: 99%) when compared with isolated evaluations.ConclusionThe expression of miRNA‐21 was effective in discriminating between PA and NP and its association with serum CA 19‐9 increased the sensitivity and accuracy in diagnosing PA in the sample studied.Support or Funding InformationThis study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES) ‐ Finance Code 001.