bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between the expressions of the natriuretic peptide system and morphological changes in mouse heart during prenatal development
Authors: Li Terry Yantian , Tse M. Yat , Ventura Nicole M. , Croy B. Anne , Reifel Conrad W. , Pang Stephen C. 
Published: June 2021

Natriuretic peptides, most noticeably ANP and BNP are synthesized by heart and play an important role in blood pressure regulation and fluid homeostasis. These hormones express during early fetal development and have a different expression pattern than that in adults. In addition, ANP is known to serve as a growth modulator in the adult heart. In this study we sought to determine the expression of ANP and BNP during fetal development in order to correlate them with morphological changes in the heart during this critical period of cardiac growth. The expression of ANP and BNP were studied using real‐time quantitative PCR (qPCR) at daily intervals from 12 to 19 gestational days (GD), as well as in neonatal and adult hearts. The expression of GATA4, a transcriptional factor of ANP and BNP, was also measured. In another series of mice, hearts were dissected for LM morphological analysis. Results showed that peak ANP expression was observed on 15GD; whereas expression levels of GATA4 and BNP were significantly increased after 12GD. Morphological analysis demonstrated that there was an increase in cardiomyocyte size between 14–15GD, which was coincided with the peak of ANP expression. We suggest that ANP may play a role in modulating cellular hypertrophy in the heart during prenatal development.Grant Funding Source: Garfield Kelly Foundation at Queen's University, HSFC and CFI
Radiosensitivity of Human Inducible Pluripotential Stem Cells (iPSCs)
Authors: Greenberger Joel S. , Houghton Frank D. , Zhang Xichen , Nimgaonkar Vishwajit L. , D'Aiuto Leonardo , Epperly Michael W. 
Published: June 2021

Inducible human pluripotent stem cells, derived from fibroblasts, have been purposed for repair of tissue damage in various organs. iPSCs have displayed robust potential for providing reagent stem cells for tissue repair and regeneration. We evaluated the radiobiologic properties of a parent human fibroblast cell line and the iPSC derivative from plasmid transfection with OCT4, SOX2, NONOG and LIN28. We determined the radiosensitivity of iPSC cells compared to parental fibroblasts, and derivitive neural rosettes, prepared by growth of the iPSCs in 1% N2 supplement and bFGF. Cells of each cell type were irradiated to doses ranging from 0 to 2.5 Gy and the percent of apoptotic cells determined 24 or 48 hr after irradiation. The iPSC cells and rosettes were radiosensitive compared to fibroblasts: 43.6 ± 8.0 and 35.1 ± 3.9% apoptotic cells, respectively, compared to 1.9 ± 0.5% of fibroblasts cell at 24hrs after 2.5 Gy (p = 0.0261 and 0.0146, respectively). By 48 hr after irradiation, after significant cell loss, remaining iPSCs showed 18.0 ± 4.1 apoptosis compared to 7.1 ± 3.9% for fibroblasts and 30.9 ± 1.7% for rosettes. Five days after 2.5 Gy irradiation iPSCs showed a 98.5% decrease in cell number compared to 78% for fibroblasts (p = 0.0174). Elucidation of the mechanism of radiosensitivity of iPSCs may reveal a specific role for expression of one or more of the 4 transgene products in the parental fibroblast cell line.Supported by NIAID /NIH grant U191A168021–01 from NIAID
Comparison of 3D Reconstructive Technologies used for Morphometric Research and the Translation of Knowledge using a Decision Matrix
Authors: Martin Charys M , Roach Victoria A , Nguyen Ngan , Rice Charles L , Wilson Timothy D 
Published: June 2021

The use of three‐dimensional (3D) models for education and measurement has become more prevalent, which has resulted in an increase in 3D reconstructive software programs. These programs differ in reconstruction concepts, operating system requirements, user features, cost, and no one program has emerged as the standard. The purpose of the current study was to conduct a systematic comparison of three widely available 3D reconstructive software programs, Amira, OsiriX, and Mimics, with respect to the software's ability to be used in morphometric research and education to translate morphological knowledge. Cost, system requirements, and inherent features of each program are compared. A novel concept selection tool, a decision matrix, was employed to objectify comparisons of usability of the interface, quality of the output, and efficiency of the tools. Findings indicate that Mimics was the best‐suited program for construction of 3D anatomical models and morphometric analysis, but for creating a learning tool the results were less clear. OsiriX was very user‐friendly; however, it had limited capabilities. Conversely, although Amira had endless potential and could create complex dynamic videos, it had a challenging interface. These results provide a resource for morphometric researchers and educators to assist the selection of appropriate reconstruction programs when starting a new 3D modelling project.Grant Funding Source: Departmental
Anatomical validation of diffusion tensor imaging (DTI)
Authors: Liu Robert Ming , Hageman Nathan , Yang Gloria , Cheng Nathan , Chan Kelly , Liu Erica , Ortiz Jake , Honarpisheh Helen , Wong Anita , Stark M. Elena , Dong Hongwei , Vinters Harry , Toga Arthur , Wisco Jonathan 
Published: June 2021

The Magnetic Resonance Image (MRI) based Diffusion Tensor Imaging (DTI) technique reveals brain white matter architecture in vivo by measuring the direction of the diffusion of water molecules along the anisotropic fiber bundles. Validation of DTI at present is limited to qualitative comparisons of previously known connections in the common normal human brain. Anatomical validation of DTI through histological analysis ensures that each image is representative of the inherent white matter architecture, and improves algorithms that create a tractographic image from the tensor signals in each voxel of the image. Human brain samples were imaged at 3 Tesla (T) (2.5 mm voxels) followed by sectioning and histologic processing of the tissue. Results comparing the histologic data to the imaging show good correspondence in white matter areas between both fiber integrity and axonal orientation. Vector coordinates drawn from the tissue image match the principal fiber direction derived from the probability density function of the corresponding image voxel. We anticipate that this will provide a valuable resource for the validation of DTI methods.Grant Funding Source: NIH/NIA 1 R21 AG037843‐02, NIH/NCRR P41 RR013642‐12S1, Translational Research Fund (UCLA), and the McGinty Family Foundation
Effects of heroin dependence on the expression of DBH and CCK in the VTA and NAc regions of rat brain
Authors: Li Yi‐xin , Liang Wen‐mei 
Published: June 2021

To investigate the effect of the heroin addicts on rat's DβH‐, CCK‐immunoreactive cells in the ventral tegmental area(VTA) and nucleus accumbens(NAc) regions, and exploring the effect of heroin dependence on regulation of dopamine release and self‐protective mechanism in brain. Adulthood 55 male SD rats were randomly divided into normal control group(NCG), saline control group(SCG) and the heroin‐dependent group(HDG). Heroin‐dependent rat models were set up by the way of subcutaneous injection of heroin and brain tissues are excised on the 10th, 17th, 24th, 31th, and 38th days after models are set up. Immunohistochemical staining was performed to test the expression of DβH and CCK in the VTA and NAc regions. The expression of DβH and CCK was observed as brown yellow particle in the cytoplasm of neurons in the VTA and NAc regions. The expression of DβH‐ immunoreactive cells is down‐regulated, while the expression of CCK‐immunoreactive cells is up‐regulated in the VTA and NAc regions from HDG rats than that from SCG and NCG rats at different time points. The results suggest that the secretion of DβH is inhibited during heroin dependence, and it might be one reason causing dopamine increase in VTA and NAc. The increased secretion of CCK in VTA and NAc might be self‐protective mechanism in brain.Grant sponsor(s): NSFC(Natural Science Foundation of China)Grant number(s):81060110Grant Funding Source: Natural Science Foundation of China
Histological validation of iron as an imaging biomarker for amyloid beta and tau depositions in Alzheimer's Disease
Authors: Salin Ashley , Hansen Megan Salin , Barzee Brigham , Stone Megan , Bridgewater James , Kavafyan Talar , Steed Kevin , Stark Elena , Dong Hongwei , Toga Arthur , Vinters Harry , Wisco Jonathan 
Published: June 2021

At present, no one can diagnose a patient with Alzheimer's disease (AD) until postmortem examination. Analyzing spatial overlap of non‐heme iron, tau protein, and amyloid beta (Aβ) depositions in consecutive tissue slices of the hippocampus of human subjects would ultimately facilitate characterization and detection of diseases, such as AD, through MRI. Iron is readily visible in T2* MRI, and has been shown to be spatially correlated with Aβ plaques. Neurofibrillary tangles of tau protein are also associated with AD. In this study, we verified iron deposition to pathology of the hippocampus. We used Olympus OlyVIA software to capture virtual microscopic images, and Adobe Photoshop to register serial stained sections of iron, tau, and Aβ. Our initial results indicate spatial similarities between all three components. We plan to perform this entire procedure for the hippocampus in hopes of providing useful diagnostic research relative to AD. Pathological validation through these images will clarify the configuration of these probable biomarkers and their specificity to AD and other neurodegenerative diseases.Grant Funding Source: NIH/NIA 1 R21 AG037843‐02, NIH/NCRR P41 RR013642‐12S1, Translational Research Fund (UCLA), and the McGinty Family Foundation
Neurotensinergic periaqueductal gray‐rostral ventromedial medulla‐spinal dorsal horn pathway
Authors: Li Yunqing 
Published: June 2021

AimTo investigate the neurotensin (NT)‐containing periaqueductal gray (PAG)‐rostral ventromedial medulla (RVM)‐spinal dorsal horn (SDH) descending pathway, which has been shown functionally antinociceptive in nature.MethodsFluoro‐gold (FG) or horseradish peroxidase (HRP) retrograde and biotinylated dextran amine (BDA) anterograde tracing methods and immunohistochemistry combined with tracing methods were used in the rat.ResultsAfter FG and BDA was injected into SDH or PAG, respectively, and combined with immunohistochemistry for NT and NT receptor 1 (NTR1), we found that NTR1‐immunoreactive (IR) neurons in the RVM received NT‐IR projections from PAG and also sent projections to the SDH. Then under electron microscope, in the RVM, we further found: (a) NT‐IR terminals made synapses on HRP‐labeled dendrites showing NTR1‐immunoreactivities; (b) BDA‐labeled terminals made synapses on HRP‐labeled dendrites exhibiting NTR1‐immunoreactivities; (c) BDA‐labeled terminals containing NT made synapses on HRP‐labeled dendrites.ConclusionsPAG projecting axon terminals contain NT and form asymmetric synapses on NTR1‐IR neurons in the RVM which sent descending fibers to the SDH. They might be involved in the NT‐induced analgesia.This project was supported by grants from the National Natural Science Foundation of China (Nos. 30771133, 30971123, 31010103909).
Ameliorative role of Alpha lipoic acid (ALA) in sodium arsenite (NaAsO2) induced neurotoxicity in developing rat cerebellum
Authors: Dhar Pushpa , Kaushal Parul , Mehra Raj D 
Published: June 2021

The present study was designed to evaluate the effects of ALA on arsenic (As) induced alterations in developing rat cerebellum. Pregnant Wistar rats, obtained from Experimental Animal Facility (EAF) after ethical clearance from Institutional Ethical Committee of AIIMS were maintained on a 12 hr light‐dark cycle with ad libitum access to food and water. The day of birth of pups was designated as postnatal day (PND) 0. Mother reared pups were divided into control (normal and sham) and experimental groups receiving NaAsO2 alone or along with ALA from PND 1 to 21. Behavioral parameters (tail hung, negative geotaxis and water maze) were carried out on PND 21. Animals were sacrificed on PND 22 and the fresh cerebella were processed for estimation of antioxidant glutathione (GSH) and Lipid peroxidation product malondialdehyde (MDA) levels. Cerebella from perfusion fixed animals were processed for paraffin embedding and Cresyl Violet stained sections were observed for morphological features. Immunohistochemical expression of synaptophysin (Syp) and Myelin basic protein (MBP) was studied in cryocut sections. The observations of present study revealed alteration in cerebellar morphology and behavioral dysfunction in rat pups exposed to NaAsO2.Co‐administration of ALA resulted in partial reversal of As induced decline in the behavioral parameters, decreased GSH levels, elevated MDA levels, disruption of cerebellar cytoarchitecture and decrease in Syp and MBP expression suggesting thereby protective role of ALA in NaAsO2 induced neurotoxicity.DST INSPIRE Fellowship, Govt. of India (110053) to Parul Kaushal is acknowledged.
Taurine Protection against Endoplasmic Reticulum Stress in an Animal Stroke Model of Cerebral Artery Occlusion and Stroke Related conditions in Primary Neuronal Cell Culture
Authors: MohammadGharibani Payam , Modi Jigar , Menzi Janet , Prentice Howard , Wu Jang Yen 
Published: June 2021

Taurine has been shown to provide protection against neurological diseases, such as Huntington's and stroke. We have shown that taurine can provide effective protection against Endoplasmic Reticulum (ER) stress induced by excitotoxicity or oxidative stress in PC12 cell line or primary neuronal cell cultures. In this study, we employed hypoxia/reoxygenation conditions for primary cortical neuronal cell cultures as well as the model of rat focal Middle Cerebral Artery Occlusion (MCAO). Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6mm from 47.42±9.86% to 26.76 ± 6.91% in the MCAO model. Furthermore levels of the ER stress protein markers GRP78, Caspase12, CHOP and p‐IRE‐1 which were markedly increased in both the in vitro and in vivo models, significantly declined after taurine administration, suggesting that taurine may exert neuroprotection functions in both models. Moreover, taurine could downregulate the ratio of cleaved ATF6 and full length ATF6 in both models. In the animal model of stroke, taurine induced an upregulation of the Bcl‐2/Bax ratio and downregulation of Caspase‐3 protein activity indicating that it attenuates apoptosis in the core of the ischemic infarct. Our results show not only taurine elicits neuroprotection through the activation of the ATF6 and the IRE1 pathways, but also it can reduce apoptosis in these modelsGrant Funding Source: 09KW‐11, Department of Health, State of Florida
Investigation of the pre‐sensor 1 hairpin in minichromosome maintenance proteins 2–7.
Authors: Lam Simon Kai Wing , Sing Tina , Brandl Christopher J. , Davey Megan J. 
Published: June 2021

The minichromosome maintenance proteins 2–7 (Mcm2–7) assemble into the replicative helicase in eukaryotes. To understand how this ring‐shaped helicase translocates along DNA to unwind the duplex nucleic acid, we have analyzed the structure/function relationships of the S. cerevisiae proteins. A pre‐sensor 1 (PS1) hairpin found in archaeal MCMs is thought to be involved in DNA translocation, with a conserved lysine residue predicted to contact the phosphate backbone. We mutated the analogous lysines to alanines in the putative PS1 hairpins of each of the yeast Mcm2–7 subunits. Mutation of the Mcm3 hairpin results in a loss of cellular viability. Its overexpression in the context of a wild‐type allele results in enlarged cells and a reduced growth rate. Purified Mcm2–7 complex containing the Mcm3 hairpin mutant does not unwind DNA in vitro, yet retains wild‐type levels of ATPase activity. Interestingly, individual mutation of the PS1 hairpins of the other subunits does not affect viability. However, these strains do have growth‐related sensitivity to genotoxic stress agents, and cold. Collectively, our data indicates the importance of the PS1 hairpin for Mcm2–7 function.Support from the CIHR
POSTMORTEM TIME AFFECTS THE INTEGRITY OF DNA EXRACTED FROM THE BRAIN AND KIDNEY OF MALE ALBINO SPRAGUE DAWLEY RATS
Authors: EBUEHI ALBERT O , BALOGUN Ayooluwa , Adenike FOWORA , EBUEHI Olufunke , AMODE Tolani , OJIEH Godwin 
Published: June 2021

When an organism dies, internal nucleases existing within the cells are expected to cause DNA to degrade into smaller fragments over time that will eventually lead to alteration in the profile of the genomic structure of the organism. This study to evaluate the effect of post‐mortem time on the integrity of DNA extracted from the brain and kidney of male Sprague Dawley albino rats.Deoxy ribonucleic acid (DNA) was extracted at different post‐mortem times (0, 24, 48 hours), from the brain and kidney of the male albino rats sacrificed via cervical dislocation. Random amplification of polymorphic DNA Polymerase chain reaction (RAPD‐PCR) was used to detect the effect of post‐mortem time on the integrity of DNA by creating the current profile of the DNA at each post‐mortem time.The post‐mortem DNA profile observed in this study reveals that DNA degradation is a sequential time dependent process.There is a relationship between degradation rate of nuclear DNA and post‐mortem time in the studied organs. The rat brain showed a slower degradation rate and is therefore considered as a valuable organ for studying DNA in longer post‐mortem time. The finding from this study is very useful in forensic science and investigation.
Disruption of de Novo Mitochondrial Thymidylate Synthesis Increases mtDNA Content
Authors: Alonzo Judith Raquel , Stover Patrick J. 
Published: June 2021

Mitochondrial DNA (mtDNA) synthesis is necessary for the replication and repair of damaged DNA; maintaining the proper balance of nucleotides is required to avoid mtDNA depletion and mutation. Mitochondrial deoxynucleotide triphosphates (dNTPs) are obtained from either salvage pathways or de novo biosynthesis within the mitochondria. In the mitochondria, de novo dTMP biosynthesis requires the enzymes serine hydroxymethyltransferase 2 (SHMT2), thymidylate synthase (TYMS), and dihydrofolate reductase‐like 1 (DHFRL1). In the nucleus, depletion of dTMP synthesis leads to misincorporation of deoxyuridine into nuclear DNA (nuDNA) resulting in genomic instability. SHMT2 in the mitochondria is responsible for transferring a one‐carbon unit from serine to tetrahydrofolate (THF), producing 5,10‐methyleneTHF and glycine in a reversible reaction; 5–10‐methyleneTHF is utilized by TYMS to create dTMP from dUMP.Our goal is to determine how mtDNA content is affected by disruptions of de novo mitochondrial dTMP synthesis, using two different approaches to decrease SHMT2 activity. First, SHMT2 expression in mammalian HeLa cells was decreased using siRNA technology. Second, HeLa cells were cultured in glycine concentrations ranging from 0mM to 10mM, which inhibits the SHMT2‐catalyzed synthesis of 5,10‐methyleneTHF. The mtDNA and nuDNA copy numbers were determined by qPCR using primers specific for the mitochondrial tRNALeu(UUR) gene and a single copy nuclear gene, β2‐microglobulin. Effects of SHMT2 inhibition on deoxyuridine misincorporation into mtDNA are being assessed.Our preliminary results suggest that mitochondrial de novo dTMP synthesis is affected by SHMT2 expression and glycine concentration. Knockdown of SHMT2 results in an increase (2.8 fold) in mtDNA copy number. Similarly, mtDNA copy number increases with increasing glycine concentration in culture media (4 fold). Supported by NIH R37DK58144.
Bortezomib Inhibits Expression of Immunosuppressive Cytokines IL‐10 and TGFβ in Cutaneous T Cell Lymphoma
Authors: Chang Tzu‐Pei , Sanacora Shannon , Manna Subrata , Singha Bipradeb , Vancurova Ivana 
Published: June 2021

Cutaneous T Cell Lymphoma (CTCL) is characterized by a clonal expansion of helper T cells that release the immunosuppressive cytokines IL‐10 and TGFβ, thus suppressing the immune responses. Proteasome inhibition by bortezomib (BZ) is a promising therapeutic strategy in a number of hematological malignancies, including CTCL. Previous studies have shown that in CTCL, BZ induces apoptosis by inhibiting the constitutive activity of NFκB and expression of NFκB‐dependent anti‐apoptotic genes. In addition to the anti‐apoptotic genes, NFκB regulates transcription of immunosuppressive genes, such as IL‐10 and TGFβ. However, their regulation by NFκB is much less understood. In this study, we investigated the regulation of IL‐10 and TGFβ expression by BZ in the CTCL Hut‐78 cells. We show that BZ inhibits both IL‐10 and TGFβ expression in Hut‐78 cells. Chromatin immunoprecipitation analysis revealed that BZ inhibits NFκB p65/p50 recruitment to the promoter regions of IL‐10 and TGFβ genes. Since a variety of human malignancies utilize IL‐10 and TGFβ to evade the immune surveillance and facilitate tumor growth, a better understanding of the mechanisms how NFκB and BZ regulate transcription of these immunosuppressive genes may lead to more effective cancer therapies.Funded by:NIH grants GM079581 and AI085497 to I.V.
Characterization of the interaction between Rrn3 and rpa43:Identification of a peptide that inhibits rDNA transcription and cell growth
Authors: Rothblum Lawrence , Penrod Yvonne , Rothblum Katrina 
Published: June 2021

Rrn3 functions to bridge core RNA polymerase I with the preinitiation complex assembled on the rDNA promoter. One of the polymerase subunits involved in this interaction is rpa43. We have studied the interaction between rpa43 and Rrn3. We identified a 22 amino acid long domain within rpa43 is both necessary and sufficient to mediate the interaction between rpa43 and Rrn3.We hypothesized that the addition of excess rpa43 or the 22 amino acid peptide would inhibit rDNA transcription in vitro. We added purified wild‐type or mutated (randomized 22mer) rpa43 to in vitro transcription reactions. The presence of excess rpa43 but not rpa43/random inhibited rDNA transcription. Similar results were obtained when we added either the 22mer or the randomized 22mer. The peptides were coupled to TAT peptide for transduction into cells. The random peptide had no effect on cell growth or rDNA transcription. When the wild type peptide was transduced into normal diploid human cells, it arrested cell growth. However, when introduced into cultured cancer cells, it induced cell death. In some instances we have observed 90% cell death within 8 hr. The 22mer is a small molecule inhibitor of rDNA transcription that is based on our understanding of the mechanism of rDNA transcription and appears to be specific for the rDNA transcription apparatus. We believe that it demonstrates a novel pharmaceutical target for the treatment of cancer cells.