bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leg Bone Geometry in Human Diabetic Neuropathy
Authors: Honig Helen , Allen Matti , Allman Brian , Rice Charles 
Published: June 2021

Bone geometry is an important indicator of bone health and fracture risk, but has not been studied in individuals with diabetic neuropathy (DN). The objective was to investigate the effects of DN on tibial cortical and medullary cross‐sectional areas (CSA) using magnetic resonance imaging. Sequential images of 1mm thick slices were acquired of the right leg from the tibial plateau to the talus in 6 individuals diagnosed with DN and 8 age‐matched (32 to 79 y) controls. The CSA (cm2) was measured (average of 2 adjacent slices) at 3 sites, 20% (proximal), 50% (middle) and 80% (distal) of tibial length, by a blinded analyzer. At the proximal site only, medullary CSA in DN was significantly greater than controls (means + SD: 6.1±1.4 vs. 4.6±0.4). Also, as a percent of total CSA, DN compared with controls had significantly less cortical (~30% vs. ~38%) and greater medullary (~69% vs. ~62%) areas. At middle and distal sites there were no differences in any measures. These preliminary results indicate bone geometry is negatively affected by DN at the proximal tibia. This may be due to lower weight bearing or mechanical loading than at the middle or distal aspects. Presumed lower levels of physical activity in DN coupled with less muscle mass and strength, but heavier body weights, may be important factors influencing bone geometry to consider in future studies, including assessment of the lesser weight‐bearing fibula.Supported by NSERC.
Fungal Contamination of Plastined Specimen
Authors: Barros Mirna , Navarini Alessandra , Masuko Telma Sumie 
Published: June 2021

IntroductionPlastination is a unique technique of tissue preservation developed by Gunther von Hagens in 1978. In this process, water and lipids in biological tissues are replaced by curable polymers (silicone, epoxy) which are subsequently hardened, resulting in dry, odorless and durable specimens. The advantages of use plastinated specimens are they can be conveniently stored, the tissues are safe to handle, toxic fixatives are eliminated, they are durable, having a much longer shelf life. This study aimed to demonstrate fungal contamination of a plastined kidney.Material and methodOn the surface of a plastined kidney divided in two parts, we observe a thin layer of a white substance, which is presented into more or less dense portions. Six samples of that substance from different places were collected, inoculated in Sabouraud‐agar and incubated at room temperature. The samples were checked dailly for the presence of fungi.
ResultsWe observed the growth of fungi in one sample on the eighth day after inoculation and the fungus was identified as Penicillium sp.ConclusionThe foundation of all good tissue specimen preparations is complete fixation. The primary function of tissue fixation is to prevent putrefaction and autolysis. Probably, the fixation of the specimen was not completed and during storage, the fungal contamination occurred. We can not rule out the possibility of contamination of solutions used in the process of fixing and plastination specimen.
Effect of Cadaver Dissection on Written and Practical Gross Anatomy Test Scores
Authors: Olivieri Nina , Hurley Mary , Olivieri Marion 
Published: June 2021

Over the past five years, 325+ Italian medical students participated in D'Youville College's (DYC's) Giovanni Mazzotti Anatomy Conference (GMAC), named in honor of the late president of the Medical School of Bologna and the Italian Anatomy Society. Cadaver dissection is not common in Italy where models, drawings and computer‐generated images are utilized. Some universities select participants for anatomy competency.Before they dissect, attendees complete 50 question practical and 50 question written examinations (choice of English or Italian). After ~100 hours of available laboratory time, equivalent examinations are completed and compared. To quantify anecdotal proclamations of greater knowledge of anatomy, in this preliminary study, we examined 107 students from different populations (Group A:47, Group B:60). On average, a significant improvement was observed in test scores increasing by 5% in group A and 10% in Group B with p 蠄 0.001) in basic written and practical knowledge of anatomy. Students with the weakest practical pre‐test scores made the largest advances by conference end with as high as a 42% increase. Cadaver dissection and experience was found to be beneficial and worthwhile in increasing the practical as well as theoretical knowledge of these medical students.We expect this collaboration to continue and will include exam modifications and additional participant information to provide a more in depth analysis. We thank our friends and collaborators, Professors Zecchi, Manzoli, Nori, Papa and Sette of the Medical Universities of Florence, Bologna, Salerno, Naples, and of Rome Tor Vergata. Supported by the GMAC and approved through the IRB of DYC.
Illustrations, CT scans and Pictures of Anatomical Dissections in a 3D Atlas of the Human Hand
Authors: Burchianti Livia , Barros Mirna , Curcio Daniella 
Published: June 2021

Tridimensional anatomical atlases and apps have gained grounds in health allied educational settings and in schools for visual and fine arts. The numerous possibilities to explore different views of the studied object and observe position relations between underlying structures have helped students building more complete anatomical concepts and better understanding of neuromuscular mechanisms of the human body. We here report partial results from a project that has grown from a previous bi‐dimensional model and is now aiming at creating a 3D Atlas of the human hand. Developed by undergraduate medical students using the free 3D modeling software AutoDesk 123D Catch, the atlas is comprised by art illustrations, pictures of dissected specimens and CT scans. it allow users to enhance, hide or modify the opacity level of selected structures, so to observe anatomical features and position relations from different aspects, in superficial and deep planes. The atlas also provides essential information and quizzes involving identification and function of muscles, nerves, ligaments and bones. Art, anatomy and imaging technology are brought together to allow for a better understanding of normal function and we anticipate that the atlas may also help users to better comprehend specific conditions affecting the mechanics and/or neuromuscular control of the human hand.Grant Funding Source:Sao Paulo Research Foundation – FAPESP
Introducing cutting edge technology to the anatomy curriculum at the University of Pecs
Authors: Farkas Jozsef , Reglodi Dora , Nagy Gyorgy , Vigh Sandor 
Published: June 2021

Modern technology is a part of our life. Today, medical doctors utilize cutting edge technology in all fields for the benefit of their patients. It is essential for medical students to learn to live and work with modern technology as early as possible in their carrier.Turning towards the latest technology in education is a clear tendency now. Newly founded and dynamically developing universities, such as Ross University, School of Medicine, are in the vanguard of utilizing technology in education. This process is significantly slower and more difficult in old medical schools where there are strong traditions of teaching. The University of Pecs (UP), Hungary is one of Europe's oldest universities (founded in 1367 A.D.). In the Medical School at UP the leadership realized the necessity of introducing modern technology to the curriculum, while keeping and respecting the old traditions. The anatomy curriculum provides an excellent opportunity for this. In the anatomy department students meet their first “patient”. In the dissection rooms they meet the human body in the traditional way while dissecting cadavers, but at the same time an excellent opportunity is presented to introduce the latest technological innovations utilized both in medical education and clinical practice. With the support of the UP, School of Medicine, the Department of Anatomy started a robust modernization to help the future doctors to meet the challenges of the 21st century.
Fine‐tune Regulation of Cpn1 (Carboxypeptidase N1) to Control Vascular Patterning during Zebrafish Development
Authors: Wu Ting‐Yun , Wu Chang‐Yi 
Published: June 2021

Vascular development is important for vertebrates and regulated by regulators via complicated signaling pathways. In our previous study, transcription factor islet2 regulated vein and ISV formation mediated by notch signaling. Genome‐wide transcriptional analysis showed that cpn1 is regulated by islet2/coupTFIb, suggested its function in vasculature. However, no direct evidence shown the role of Cpn1 in vascular function so far. Thus, we hypothesize that cpn1 encode enzymatic active subunits to perform CPN activity and function in vascular developmentIn‐situ hybridization showed cpn1 is expressed in developing vessels. Overexpression of cpn1 impairs the growth of ISV (intersegmental vessel) and CVP (cardinal vein plexus), which is similar to the phenotype of isl2 morphant. Knockdown of cpn1 by morpholino injection also causes vascular defects, suggesting the role of cpn1 in controlling ISV and CVP growth. We further showed the cpn1 MO knockdown works efficiently by probing cpn1 expression products and knockdown specificity by using 2nd MO. We found that a loss of cpn1 results in a decreased expression of vascular markers flk, stabilin, ephrinb2. This indicates the regulatory role of cpn1 in controlling vascular development. Promoter analysis showed cpn1 is likely regulated by isl2/coupTFIb. To examine the interaction between cpn1 and isl2/coupTFIb, we performed luciferase assay and showed cpn1 is regulated by isl2, which is consistent with our microarray results. We also revealed cpn1 is regulated by notch and VEGF signalings. Together, we showed cpn1 plays an important role for vascular development in zebrafish. We also uncovered a fine‐tune regulation of cpn1 that controls vascular patterning mediated by isl2‐Notch signaling.
Examining microbial biodiversity in soil: A research‐based introductory biology laboratory course
Authors: Lo Stanley 
Published: June 2021

We report a novel introductory biology laboratory course designed as an independent, on‐going research program, with students as the primary researchers. This course aims to develop an understanding for biology through inquiry‐based laboratory experiments, and specific learning objectives are listed in Table 1. Students work in teams to collect, analyze, and present original data while learning core concepts and laboratory methods. Specifically, we examine if and how soil microbiomes are different for native vs. invasive plant species in the Southern California diversity hotspot. Students analyze soil properties such as moisture and pH and correlate them to functional and genetic biodiversity of microbiomes, assessed by carbon source utilization and 16S rDNA sequencing. Together, these elements span macroscopic to molecular scales, providing opportunities to connect student learning across biology disciplines.This presentation will focus on the design, implementation, and evaluation of the course. Laboratory experiments are designed to be completed by introductory students within a 3‐hour laboratory and 1.5‐hour lecture per week while allowing for the reliable collection of research data. We found that student‐generated data are consistent across groups: soil genomic DNA preparations and PCR clean‐up reactions have standard deviations <10% of average DNA concentrations, and >95% of PCRs result in products at appropriate sizes. Student outcomes are evaluated by pre‐ and post‐surveys and ‐tests to track changes affective domain (Science Motivation Questionnaire II), self‐efficacy in research skills (Classroom Undergraduate Research Experience survey), and ability to draw conclusions based on data (open‐ended questions that test scientific argumentation).

Learning objectives
Activities
Student assessments

Understand functional and genetic biodiversity
Discuss material in laboratory and lectures
Quizzes in lectures, laboratory reports

Develop testable hypotheses and design controlled experiments
Carry out scientific processes in the context of the course
Data collection by students, laboratory reports

Draw conclusions based on data and evidence
Analyze and discuss laboratory data using statistics
Figures and results in laboratory reports

Communicite scientific results in a publication‐style laboratory report
Write, review, and revise laboratory reports
Laboratory reports, peer review of laboratory reports
De novo Thymidylate Biosynthesis and Uracil Misincorporation in DNA as Related to Neural Tube Defect and Cancer Outcomes in Mouse Models
Authors: Field Martha , Lan Xu , Stover Patrick 
Published: June 2021

In the absence of adequate thymidylate (dTMP) synthesis, uracil is misincorporated into DNA during replication and/or repair, as DNA polymerases do not distinguish dTTP from dUTP. Current dogma holds that the dUTP/dTTP ratio determines the rate at which dU is incorporated into DNA. Here we show that the dTMP precursors uridine (U) and deoxyuridine (dU) have distinct fates in DNA. Radioactive tracer studies in HeLa and mouse embryonic fibroblast (MEF) cells demonstrate that exogenous dU is incorporated into DNA as the base dT, and not misincorporated as dU. Exogenous U is incorporated primarily as the pyrmidine base dC. In HeLa cells both exogenous U and dU modestly stimulate proliferation, but U in culture media also increase caspase 3/7 activity, a marker of apoptosis. Exogenous U and dU also have distinct and opposing effects on cytotoxicity of 5‐flourouracil (5‐FU) in HeLa cells.The ApcMin/+ and Shmt1‐/‐ mouse models were used to investigate whether supplementation of folate‐deficient diets with U, dU, or thymidine (T) affected colorectal cancer or NTD incidence, respectively. Unexpectedly, exencephaly in offspring from Shmt1‐/‐ mice was rescued by dietary dU but exacerbated by dietary U. Conversely, U supplementation reduced intestinal tumor number in ApcMin/+ mice by more than 30% relative to the unsupplemented diet, whereas dietary dU did not affect tumor number. Supplemental thymidine did not affect the phenotype of either mouse model. Taken together, these data challenge the assumption that uracil accumulation in DNA is driven simply by the dUMP/dTMP ratio.
Characterizing CDK12 and CDK13 Activity in Transcription and mRNA Biogenesis in Mouse Embryonic Stem Cells
Authors: Dubbury Sara , Sharp Phillip 
Published: June 2021

The RNA Polymerase II (RNAPII) C‐terminal domain (CTD) heptapeptide repeat (YSPTSPS) is dynamically phosphorylated during transcription. Serine 2 phosphorylation of the RNAPII CTD (Ser2P) occurs upon the transition to productively elongating RNAPII and extends through the gene body. Ser2P recruits mRNA processing machinery, histone modifying enzymes, chromatin remodelers, and transcription elongation factors directly to the transcription machinery consequently coupling transcription and mRNA processing. Recently, two paralogous kinases in mammals, CDK12 and CDK13, were identified as members of the family of cyclin‐dependent kinases responsible for Ser2P. Additionally, CDK12 has been identified as a tumor suppressor in several tumor types. However, the function of each kinase in regulating transcription and mRNA biogenesis remains unclear.Here, we report the establishment of a genetic system to interrogate CDK12 and CDK13 activity. CDK12 or CDK13 knockouts were generated in mouse embryonic stem cells using CRISPR/Cas9 genome editing. The rescue of knockout cells with an inducible CDK12 or CDK13 epitope‐tagged expression system permits high‐confidence genomic characterization. Currently RNA sequencing (RNA‐seq) and Chromatin Immunoprecipitation Sequencing (ChIP‐seq) with antibodies specific for phosphorylated and total RNAPII, CDK12, and CDK13 are being performed in knockout and rescued cells. The derivation of this cell system and progress in CDK12 and CDK13 characterization will be presented.NIH RO1‐CA133404 to P.A. Sharp, NIH Pre‐Doctoral Training Grant T32GM007287 to MIT Biology Dept., and MIT School of Science Fellowship in Cancer Research Award to S. Dubbury supported this work.
Molecular Basis for Substrate and Inhibitor Interactions with the Glycine Transporter, GlyT2
Authors: Vandenberg Robert , Carland Jane , Edington Ashleigh , Ryan Renae 
Published: June 2021

The glycine transporter GlyT2 regulates synaptic glycine concentrations to control inhibitory neurotransmission. We aim to understand how glycine and GlyT2 inhibitors interact with the transporter. We have used the crystal structure of the leucine transporter, LeuT, to better understand the structural basis for GlyT2 function. Mutations of residues in GlyT2, that correspond to the leucine binding site of LeuT, change substrate selectivity of the transporter. For example, W482F changes GlyT2 from being selective for glycine to a promiscuous transporter that allows transport of Alanine, Valine, Leucine, Cysteine, Serine, Tyrosine and Phenylalanine. These results suggest that this site forms the primary substrate binding site and other secondary sites are not required for determining substrate selectivity.ALX1393 is a GlyT2 inhibitor that in analgesic in animal models of pain. Inhibition of GlyT2 by ALX1393 causes a reduction in maximal rate of glycine transport and also increases the K0.5 for glycine demonstrating that it has characteristics of both a competitive and non‐competitive inhibitor. 7 mutations, that alter substrate selectivity of GlyT2, cause 4‐20 fold reductions in potency of ALX1393 inhibition confirming the overlap in substrate and inhibitor binding sites. The outward facing conformation of LeuT contains an aqueous accessible vestibule, which has been proposed to form a low affinity binding site for non‐competitive inhibitors. We introduced a variety of mutations in this vestibule that may have the capacity to interact with ligands, but none of the 10 mutations caused any change in the potency or selectivity for glycine or ALX1393 inhibition. We conclude that the external vestibule does not contribute to the inhibitor or substrate binding sites.
Effect of oxidized linoleic acid on plasma apoC 3 levels in C57BL mice
Authors: Ainsworth Gregory , Mahini Halleh , Alaimo Hope , Jamil Naseeha , Garelnabi Mahdi 
Published: June 2021

BackgroundWe have previously shown that oxidized linoleic acid significantly lower plasma triglyceride (TG) levels as compared to animals fed oleic acid, the changes was associated with increased APOA5 and acetyl‐CoA oxidase genes expression in the mice. The focus of the current study is to determine the mechanisms and plasma and tissue metabolites associated with the plasma triglycerides decreased levels.Study DesignWe fed C57BL6 normal male mice 4 groups (N=10 each) 4 different types of mouse diet formulations as follows: normal mouse chow (P), normal chow supplemented with 18 mg/day linoleic acid (C), oxidized linoleic acid 9 mg (A) or 18 mg /animal/day) for 2 months. Mice were sacrificed; blood and tissues (liver, adipose, kidney, and heart) were collected. We measured the plasma lipids, performed Western Blot for the Apo5, ApoC3 and related proteins expression.Results and ConclusionThis is a going study, we currently completed the plasma APoC3 measurements; as anticipated our data have shown a significant dose dependent decreases in plasma ApC3 on mice fed low (P<0.01) and high (P<0.003) dose oxidized linoleic acid compared to the control group on linoleic acid. These finding indicate for the first time that intake of oxidized linoleic acid decreases plasma ApoC3 levels and modulatesplasma TG..
The Interplay between Cholesterol and Vitamin D Biosynthesis
Authors: Prabhu Anika , Luu Winnie , Sharpe Laura , Brown Andrew 
Published: June 2021

Cholesterol is dangerous to human health in excess, but is also essential for normal embryogenesis. Hence, enzymes involved in its synthesis possess many layers of regulation to balance cholesterol levels. 7‐dehydrocholesterol reductase (DHCR7) is the terminal enzyme of cholesterol synthesis, acting on 7‐dehydrocholesterol (7DHC) to produce cholesterol. In the absence of DHCR7, a lack of cholesterol production leads to the devastating developmental disorder, Smith‐Lemli‐Opitz Syndrome (SLOS).We examined human DHCR7 at the transcriptional level to characterize its promoter and identified two sterol regulatory elements (SREs) that work cooperatively to activate DHCR7 expression [Prabhu et al. BBA Lipids 1841 (2014) 1431‐9]. This method of cooperativity ensures that there is high demand for cholesterol before resources are committed to the energetically expensive process of cholesterol synthesis. Although this is similar to other cholesterol synthetic enzymes we have studied, DHCR7 differs at the post‐translational level.We found that unlike other enzymes involved in the final stages of cholesterol synthesis (e.g. DHCR24), DHCR7 is rapidly turned over. This degradation is induced by the cholesterol product itself, resulting in decreased DHCR7 protein levels and activity, resulting in 7DHC accumulation. As 7DHC is a precursor to both cholesterol and Vitamin D, we have also shown that in conditions of high cholesterol, DHCR7 degradation is associated with increased Vitamin D production. Investigating these unique modes of regulation of DHCR7 is important for further understanding SLOS etiology, and the interplay between cholesterol and Vitamin D biosynthesis.This work is supported by funding from the National Health and Medical Research Council (NHMRC).
Acrolein Exacerbates HAART–Induced Apoptotic Death in Hepatocytes by Enhancing Transcriptionally Permissive Epigenetic Modifications at FasL Promoter
Authors: Ghare Smita , Donde Hridgandh , Joshi‐Barve Swati , McClain Craig , Barve Shirish 
Published: June 2021

Highly active antiretroviral therapy (HAART) ‐ associated hepatotoxicity is becoming a major clinical problem leading to morbidity, mortality and treatment discontinuation in HIV patient. Environmental/dietary factors are known to significantly impact general health as well as therapeutic outcomes. Acrolein is one such common dietary and environmental pollutant and is also generated endogenously by cellular metabolism. The present study examines the hepatotoxic interactions of acrolein with HAART drug, azidothymidine (AZT).Human hepatoma cells (HepG2) as well as rat primary hepatocytes were used to examine the cytotoxic effects of acrolein (ACR) and AZT treatment either individually or in combination (AZT+ACR). Data showed that acrolein enhances expression of FasL gene, leading to increased apoptosis in AZT treated cells. Chromatin immunoprecipitation (ChIP) analysis revealed that ACR+AZT induced enhanced FasL transcription was mediated by increased in promoter histone H3K9 acetylation allowing recruitment of NFkB and RNA Polymerase II at the FasL promoter. Notably, acrolein scavenger, hydralazine significantly attenuated acrolein induced transcriptionally permissive modifications at the FasL promoter preventing FasL expression and hepatocyte cell death. Overall, the data suggest that environmental and/or dietary exposure to acrolein can induce chromatin modifications and further exacerbate the hepatotoxic effects of HAART medication affecting treatment options for HIV patients. This work was supported by NIH grants.