bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Spatial Ability & Anatomy Performance: It’s time for a metaanalysis
Authors: Roach Victoria A. , Mi Misa , Mussell Jason C. , Van Nuland Sonya E. , Lufler Rebecca S. , DeVeau Kathryn M. , Dunham Stacey M. , Husmann Polly R. , Herriott Hannah L. , Edwards Danielle N. , Doubleday Alison F. , Wilson Brittany M. , Wilson Adam B. 
Published: April 2020

RationaleSpatial ability has been defined theoretically as ‘the ability to make use of simulated mental imagery (often in conjunction with currently perceived images) to solve problems'. Despite being among the most investigated factors of human cognitive functioning, spatial ability has been relegated to a secondary status within human intelligence research due to inconsistent evidence supporting spatial skills as predictors for educational success. Recently, however, interest in spatial ability within the anatomical community has grown, due to correlational evidence associating spatial aptitude with educational performance in the areas of science, technology, engineering, and mathematics. As a result, a substantial volume of contemporary research has focused on further uncovering the role that spatial ability plays in anatomical knowledge acquisition and retention. As such, this current study utilized a systematic review (to be followed by a meta‐analysis) to identify the extent to which spatial ability affects performance in anatomy.MethodsRelevant studies published within the past 50 years (2019–1969) were searched for across eight databases. Predetermined eligibility criteria were applied to the screening of titles and abstracts to discern their appropriateness for study inclusion. Study outcomes were first thematically analyzed (reported herein) and will be followed by a true meta‐analysis.ResultsA total of 2,458 records were screened, 59 underwent full‐text review, and 21 studies (k) were included for final analysis. Of these studies, 57% (12 of 21) were from North America, most (15 of 21) studied graduate/professional students, and all were published in 2000 or later, except for one study from 1985. Most studies (71%; 15 of 21) evaluated the association between spatial ability and anatomy performance using the Mental Rotations Test (k=14) and some form of a practical assessment of anatomical knowledge (k=15). Of the 15 correlational studies 6, 7, and 2 reported significant, non‐significant, and inconclusive findings respectively. The prevalence of conflicting studies further necessitates the need for a meta‐analysis, which is currently underway.ConclusionsHigh spatial ability is often associated with better scores in anatomy, but some studies show no association. In the absence of a meta‐analysis, it is challenging to interpret the literature to determine the significance of practical implications, such as providing students with different study techniques or presentation modalities depending on their level of spatial ability. Only a meta‐analysis will better inform our understanding of the current literature.
PVN‐projecting NTS neurons receive both direct and indirect inputs from solitary tract afferents
Authors: Fawley Jessica , Hegarty Deborah , Aicher Sue , Doyle Mark , Beaumont Eric , Andresen Michael 
Published: April 2020

Cranial vagal afferents first synapse on second‐order neurons in the brainstem nucleus of the solitary tract (NTS). Synaptic transmission in the NTS regulates a wide diversity of homeostatic functions and NTS neurons project widely to other brain regions, including the paraventricular nucleus of the hypothalamus (PVN). The PVN itself is also highly heterogeneous and its neurons both receive and send projections to many other brain areas. Expression of the Transient Receptor Potential Vanilloid receptor (TRPV1) distinguishes solitary tract (ST) afferents as either C‐fibers (TRPV1+) or A‐fibers (TRPV1‐). Sensitivity to resiniferatoxin (RTX), an agonist to the non‐selective cation channel TRPV1, differentiates the two. It is unknown if TRPV1+ or TRPV1− afferents selectively innervate PVN‐projecting neurons or whether every contact on a single PVN neuron is from a segregated pathway to the PVN (i.e., information from A‐ and C‐fibers remains on a labelled line). To identify NTS neurons that specifically project to the PVN, we injected the fluorescent retrograde tracer rhodamine into the PVN. In rhodamine‐positive NTS neurons, responses to ST‐shocks elicited EPSCs with latencies that had either low jitters (<200 μM) that identified direct afferent connections, or high jitter (>200 μs) that identified indirect, higher order inputs. Extensive recruitment curves identified the number and synaptic order of each input. Most neurons received a mix of 2nd and higher order inputs. A minority of cells received only higher‐order contacts or only direct inputs. The amplitude variance of evoked EPSCs for higher order inputs was significantly greater and had more failures than that of second order inputs. Asynchronous release from indirect inputs was often absent. A majority of afferents were TRPV1+ and all neurons had an all‐or‐none response to RTX. These preliminary results suggest that all inputs on PVN‐projecting NTS neurons, including neurons that receive both second and higher inputs, are either all TRPV1+ or all TRPV1−.Support or Funding InformationHL133505 and HL141560
CYP3A7 drug‐hormone Interactions in the Neonate: Adrenal Insufficiency and Low Birthweight in the HIV infected Neonate caused by Inhibition of CYP3A7 DHEA‐S Oxidation by Ritonavir
Authors: Lampe Jed Noah , Kandel Sylvie Eliane 
Published: April 2020

In the neonate and developing infant, CYP3A7 is the predominant CYP3A isoform and is responsible for the majority of metabolism of CYP3A substrates. However, its primary function is the 16α‐hydroxylation of the endogenous hormone DHEA‐S, which is important for maintenance of hormone homeostasis in the adrenal gland and production of estriol during the third trimester of pregnancy. Low maternal estriol levels have been reported to lead to low birth weight and premature birth. It has been previously reported that cohorts of HIV infected mothers and their newborns on a combined therapeutic regimen of Lopinavir and Ritonavir have increased adrenal insufficiency and low birth weight, as well as substantially elevated levels of DHEA‐S, leading to adverse outcomes in this fragile patient group. Since Ritonavir is a known potent inhibitor of CYP3A4, we hypothesized that it might also be an inhibitor of CYP3A7‐mediated DHEA‐S oxidation and that this inhibition might be responsible for the adrenal insufficiency and low birth weight associated with Lopinavir‐Ritonavir treatment. In order to test this hypothesis, we employed both recombinant CYP enzyme and neonatal human liver microsomes (nHLMs). We observed significant inhibition of CYP3A7 DHEA‐S hydroxylation activity in the presence of Ritonavir with an IC50 of 0.05 μM. Furthermore, Ritonavir displayed time‐dependent inhibition of DHEA‐S oxidation, with a Ki of 0.336 μM and a Kinact of 0.1077 min−1, suggesting that it may be a mechanism based inactivator of CYP3A7. Lopinavir was also capable of inhibiting CYP3A7, albeit to a much lesser extent than Ritonavir with an IC50 of 5.88 μM for DHEA‐S 16α‐hydroxylation, and without the associated time‐dependency. Interestingly, we observed that Lopinavir alone had a lower intrinsic clearance (Clint) rate in nHLMs compared to adult HLMs, suggesting that a pharmacokinetic enhancer adjuvant may not be necessary in this patient population in order to slow drug clearance and maintain efficacy. At a minimum, our results suggest that closer monitoring of the effective dose of the pharmacokinetic enhancer in neonatal HIV therapy may be required in order to prevent significant inhibition of CYP3A7 DHEA‐S oxidation and the associated adverse effects.Support or Funding InformationThis work was supported by the National Institutes of Health, Institute of General Medical Sciences [Grant R01 GM128508‐03] to JNL.
Identification and molecular characterization of a novel non‐inhibitory isoform of human neuroserpin gene
Authors: Kalam Sayeed ur Rehman Abul , Jairajpuri Mohamad Aman 
Published: April 2020

Neuroserpin is linked to conditions like Alzheimer’s disease, dementia, epilepsy, and FENIB. It is a member of serpin superfamily and inhibits proteases like tPA, trypsin, uPA, plasmin, and NGF‐γ. Apart from the inhibitory roles, various non‐inhibitory functions of neuroserpin are also reported.Alternative splicing leads to the generation of multiple isoforms having similar, different or opposing functions. It is a highly regulated process and is linked to various disease conditions. Alternative splicing of human neuroserpin gene may generate multiple isoforms. However, only two transcripts of neuroserpin have been reported with variations in the promoter regions.Using a combined approach of bioinformatics and molecular biology, we have identified a novel alternatively spliced transcript of the human neuroserpin gene in the brain and liver. This novel transcript codes for a truncated protein and lacks the reactive center loop which is responsible for the inhibitory action of neuroserpin. The existence of novel transcript was confirmed using RT‐PCR, DNA sequencing and qRT‐PCR. Structural and functional characterization of novel isoform was performed using recombinant protein expressed in BL21(DE3) cells. UV‐visible, fluorescence and CD spectroscopy was used to perform the structural analysis while inhibition assays using tPA and plasmin confirmed the non‐inhibitory nature of the novel isoform. The truncated isoform identified in this study is expected to be involved in crucial non‐inhibitory roles in the cell.
Connexin 43 Regulates Multiple Aspects of Chick Cranial Neural Crest Cell Development
Authors: Jourdeuil Karyn , Taneyhill Lisa A. 
Published: April 2020

Connexins are transmembrane proteins that cluster to form intercellular channels called gap junctions, which allow direct diffusion of small molecules and ions between adjacent cells. Connexin 43 (Cx43) is one of the predominant components of gap junctions and is expressed in multiple organisms and their tissues. To date, however, very little is known about the role of gap junctions, and specifically Cx43, in the neural crest. Our prior immunohistochemical analyses revealed that Cx43 is expressed in premigratory cranial neural crest cells both prior to and during their epithelial‐to‐mesenchymal transition (EMT), and in migratory neural crest cells. Given the robust expression of Cx43 in premigratory neural crest cells, we sought to elucidate the role of Cx43, and gap junctions in particular, during neural crest cell EMT. To this end, we evaluated the presence of gap junctions in the neural crest and performed perturbation experiments to alter the levels of Cx43 in both premigratory and migratory neural crest cells. Our fixed and live imaging results reveal that gap junction formation occurs within both the premigratory and migratory neural crest cell populations. Moreover, morpholino‐mediated reduction in Cx43 protein levels prevents neural crest cells from forming functional gap junctions, as assessed by live imaging of transfer of the gap junction‐specific dye Calcein in the embryo. Additionally, depletion of Cx43 from premigratory neural crest cells reduces the size of the premigratory neural crest cell domain and also delays the emergence of neural crest cells from the dorsal neural tube. This delayed neural tube exit phenotype can be rescued by introduction of full‐length rat Cx43 that is refractory to the morpholino. These data suggest that gap junctions, and Cx43 in particular, are involved in early neural crest cell specification and in the emergence of neural crest cells from the neural tube.Support or Funding InformationThe work was supported by an American Association for Anatomy Postdoctoral Fellowship to K.J. and grants to L.A.T. (NIH R01DE024217, American Cancer Society RSG‐15‐023‐01‐CSM).
Interleukin‐16 Signaling Through the CD9 Receptor Initates Rearrangement of the Actin Cytoskeleton
Authors: Charley Lindsey Allyce , McKinney Catie , Blake David , Fenster Steven D. 
Published: April 2020

CD9 is a tetraspanin membrane protein that plays critical roles in various cellular processes including cellular proliferation, activation, intracellular signaling, survival, invasion, migration, cell adhesion, and cytoskeletal rearrangement. All major subsets of leukocytes, as well as some endothelial cells, express the CD9 receptor. Activation of CD9 occurs through interactions with a variety of cell surface molecules including integrins and other adhesion molecules. Recent evidence has indicated that the cytokine, Interleukin‐16 (IL‐16), can also serve as a ligand for activation of the CD9 receptor. IL‐16 is best known as an immunomodulatory, pro‐inflammatory cytokine that aids in CD4+ cell recruitment and stimulation at sites of inflammation through signaling via the CD4 receptor. However, CD9 has been implicated as an alternative receptor in several cell types lacking the CD4 receptor. For example, recent studies have established that cells deficient in CD4 are reactive to IL‐16 including increased cytokine production, cell migration, and neural outgrowth. Recently, we showed that in a human lung cancer epithelium cell line (A549 cells), CD9 is required for cell migration specifically towards IL‐16 providing compelling evidence that CD9 is an alternate receptor for IL‐16. In this study, we used A549 cells either expressing CD9 (CD9+) or lacking CD9 (CD9−) due to genetic ablation via CRISPR/Cas technology to examine the effects on cytoskeletal rearrangement upon activation following incubation with recombinant IL‐16. Our preliminary evidence indicates that in A549 cells, IL‐16 treatment initiates robust rearrangement of both the actin cytoskeleton and associated proteins such as vinculin and talin. Further studies will examine the differences in IL‐16‐mediated cytoskeleton reorganization between CD9+ and CD9− cells.Support or Funding InformationNIH‐MARC U*STAR award number T34GM092711BLaST Undergraduate Research ExperienceCO‐WYAMP of NSF LSAMP: Mini‐grant
Targeting Doublecortin‐like Kinase 1 (DCLK1) in Colon Cancer: An In‐silico Approach
Authors: Parsai Janhvi , Crockett Cooper , Kimball Hunter , Raval Nipam 
Published: April 2020

Cancer stem cells (CSCs) are proposed to be a contributing factor in colorectal cancer (CRC) recurrence and chemo‐resistance, as a result of increased expression of ABC transporters and their innate ability to self‐renew and enter a quiescent state. Current standard therapies are ineffective at eliminating these CSC populations, hence there is a need to identify novel agents to effectively inhibit their growth. Multiple surface markers have been identified for CRC‐CSCs, though few have shown promise as a clinical target. Recently, doublecortin‐like kinase 1 (DCLK1) was established as a CSC marker in CRC and pancreatic cancers. The N‐terminal doublecortin domains(DCX) bind microtubules and regulate their polymerization, while the C‐terminal serine/threonine‐protein kinase domain is involved in cellular signaling. DCLK1 is a marker of Tuft cells in normal intestinal crypts, but in cancer is found to be highly expressed in CSC populations that play a critical role in tumor progression, based on lineage tracing experiments. Specific ablation of DCLK1+ stem cells causes marked regression of polyps without apparent damage to the normal intestine, distinguishing DCLK1 as a CSC marker. Recently, marmelin, a phytochemical from Aegle marmelos, has been shown to target DCLK1 and reduce CRC tumor growth in vivo. Hence, DCLK1 represents an attractive target for CSC‐targeted drug discovery. The present study is aimed to identify small molecule inhibitors of DCLK by using in silico molecular docking‐based screening. For this, we tested a library of FDA‐approved drugs and kinase inhibitors using Autodock Vina software. Compounds were assessed on their ability to bind within the ligand binding site of the C‐terminal kinase domain. The compounds are ranked‐based on their binding energies and hydrogen bonding patterns.Support or Funding InformationThe Olathe North MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationship in this project.
Glypican‐1 and Remodeling Cardiac Hypertrophy.
Authors: Hansen Madeline , Garcia Roxanne , Dull Randal O. , Carvalho-de-Souza Joao L. , Chignalia Andreia Z. 
Published: April 2020

Heart failure impacts about 5.7 million people in the U.S. alone and the clinical signs often arise from changes in heart function. Cardiac hypertrophy is a known contributor to impaired cardiac contractility and ejection fraction. The heart deals with a working relationship with volume and pressure and thus mechanosensitive proteins may play a role on heart function. This study investigates the role of heparan sulfate proteoglycans, specifically syndecan1 (Sdc1) and glypican1 (Gpc1) on heart function and hypertrophy. We investigated if global deletion of Gpc1 and Sdc1 in mice alters heart histological features and thus cardiac function. Global male knockout mice for Sdc1 (Sdc1KO) and Gpc1 (Gpc1KO) were used and compared to its respective controls C57B6 and CD1 (7 weeks old). Left ventricular posterior wall thickness at end diastole (LVPWd), interventricular septal thickness at end of diastole (IVSTd) and left ventricular internal diameter in diastole (LVIDd) and myocyte cross‐sectional area in the left ventricle were assessed by transmission microscopy using hematoxylin & eosin (H&E) staining. Collagen deposition was assessed by Masson’s Trichrome staining. No differences in heart dimensions (LVPWd, IVSTd, LVIDd) were found between C57B6 and Sdc1KO. IVSTd and LVPWd was increased in Gpc1KO compared to CD1 (IVSTd: 1.15 mm for Gpc1KO and 1.03 mm for CD1; LVPWd: 0.75 mm for Gpc1KO and 0.64 mm for CD1). Both knock out lines showed decreased myocyte cross‐sectional area in the left ventricle size compared to its control (203.86 μm2 for Gpc1KO, 248.43 μm2 for CD1, 194.64 μm2 for Sdc1KO, and 239.02 μm2 for C57B6). Blind scoring of collagen staining showed that there was not a significant difference in collagen deposition between Gpc1KO and CD1 (1.14 for Gpc1KO and 0.99 for CD1). Taking together, these findings indicate that Sdc1KO and Gpc1KO show alterations in cardiac histological features. Our data raises the possibility of heparan sulfate proteoglycans being involved in cardiomyocyte proliferation or development. Particularly, Gpc1KO show the unique characteristic of having a hypertrophic heart without collagen deposition. Heparan sulfate proteoglycans may play a key role in cardiac function and we speculate that they may be involved in heart disease progression.Support or Funding InformationDepartment of Anesthesiology, College of Medicine, University of Arizona, Tucson
Proteomics Analysis of a Phage‐Bacterium Interaction Reveals Both Hijacking and Suppression of Host Metabolic Processes
Authors: Okekeogbu Ikenna Ochiagha , Aryal Uma , Clase Kari 
Published: April 2020

The potential for phages to serve as both therapeutic agents and in broad applications ranging from food bio‐preservation, wastewater treatment, and disease diagnosis, has led to renewed interest in the study of phage‐bacteria interactions. Phages attack their hosts by hijacking its molecular machinery and using it for its own replication, subsequently shutting off the host macromolecular synthesis. Not much is known about how this mechanism occurs, however, especially at the translational level. In this study, label‐free tandem mass spectrometry based quantitative proteomics and qPCR assay of phage Ochi17‐infected Mycobacterium smegmatis suggested that shutoff of the host macromolecular synthesis also involves suppression of its resistance mechanisms. A total of 2,188 proteins were identified in the analysis, with 299 significantly up‐regulated proteins and 135 down‐regulated proteins. The results indicated phage Ochi17 DNA integration into the host’s genome, and a consequent hijack and suppression of the host’s energy metabolic processes and antibiotic resistance mechanisms as seen in the significant enrichment of proteins involved in homologous recombination, transcriptional factors, ribosomal proteins, amino acid (arginine, proline, and histidine) metabolism, and oxidoreductase activities. Majority of the proteins were found to be part of the host’s energy metabolic processes. With these results, we propose that phages counter their host defensive response by suppressing these responses in addition to evolving new attack strategies. We also reported the expression of 59 phage proteins (54%) expressed during the interaction. This study provides the first global proteome investigation and characterization of any phage‐infected bacteria with respect to the host bacterium response. These Results would serve as a rich source for further molecular studies of phage‐bacteria interactions in elucidating contributions of individual proteins, and in engineering phages that can overcome various defense strategies employed by host bacteria.Support or Funding InformationThis work was supported by the Biotechnology Innovation and Regulatory Science (BIRS) Center, Purdue University.