bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Modified Curcumin Compounds on the Numbers and Morphology of Microglia
Authors: Gyengesi Erika , Ullah Faheem , Asgarov Rustam , Niedermayer Garry , Muench Gerald 
Published: April 2020

Chronic neuroinflammation is a promising therapeutic target in many neurodegenerative and age‐related brain disorders. In this study, we investigated two highly bioavailable curcumin preparations, Longvida (LC) and Meriva (MC) for their anti‐inflammatory properties, using the GFAP‐IL6 mouse model. We hypothesized that the highly bioavailable curcumin, as a potent cytokine‐suppressive anti‐inflammatory drug, will decrease microglial and astroglial activation measured by cell number and morphology, and consequently improve motor and cognitive functions.MethodsGFAP‐IL6 and wild type mice were fed with LC and MC for 1 and 5 months, respectively. LC fed mice were tested on the elevated walking beam, Rotarod, Barnes maze and Novel object recognition tests before all the mice were sacrificed. Immunohistological staining for microglia and astrocytes were carried out and unbiased stereological analysis was completed for all groups on microglia(labelled by Iba‐1 and TSPO) and astrocytes numbers (GFAP) as well as the morphology of the cells were analyzed using the MBF Biosciences system (StereoInvestigator and Neurolucida 360).ResultsShort term MC oral administration lead to a dose‐dependent reduction in neuroinflammatory markers. Moreover, MC decreased the number of activated microglia and astroglia, as well as changed the microglial morphology from activated to resting state. Long term LC treatment led to a significant decrease in the number of microglia in the hippocampus and cerebellum and in turn, led to significant improvement of both motor and cognitive function. Both short‐ and long‐term consumption of modified curcumin preparations significantly downregulated microglial activation GFAP‐IL6 mice. Spatial memory and recognition memory improvements were also found in mice fed with LC in comparison to control counterparts. Our results promise potential therapeutic applications of both Longvida and Meriva curcumin against brain inflammation and associated cognitive and motor decline.Support or Funding InformationThe present study was supported by a project grant (#P00023016) by Indena S.P.A, Italy to GM and EG. F.U has been supported by a postgraduate scholarship by Western Sydney University.
The Genetic Architecture of Alveolar Formation in the Lung in the Context of Bronchopulmonary Dysplasia
Authors: Minoo Parviz , Gao Fremont , Li Changgong , Chao Cho-Ming , Bellusci Saverio 
Published: April 2020

Alveologenesis is the most important and the least understood phase of lung development. Alveolar defects underlie both neonatal and adult lung diseases. Their arrested development is found in infants with BPD (BronchoPulmonary Dysplasia), while their destruction is characteristic of emphysematous lungs in adult COPD. We have developed 3 parallel, postnatal genetically‐based models to analyze the molecular basis of alveologenesis. Conditional postnatal inactivation of genes encoding receptors for TGFb, or PDGFA or IGF1 in a unique cell type we have identified as Secondary Crest Myofibroblasts, or SCMF blocks alveologenesis & produces a phenotype similar to human BPD. We reasoned that due to nearly identical phenotypes, the three BPD phenocopy models must share genetic elements whose role in alveologenesis is indispensable. To test this hypothesis, we have isolated mutant and control SCMF and identified their transcriptomic profile by RNA sequencing (RNAseq). Bioinformatic analysis of the sequencing data identified “pathway‐specific” differentially expressed genes (DEG) for TGFb, PDGFA/PDGFRa and IGF1 mutant models. Most importantly however, as predicted, we identified a cluster of “shared” genes which we propose contains conserved core alveologenesis regulatory genes. The accumulated evidence reveals a constellation of genes that makeup the genetic architecture of alveologenesis in mice with relevance to pathogenesis of BPD in human preterm neonates.Support or Funding InformationNIH/NHLBI & the Hastings Foundation
Hippo‐signaling in Heart Development and Regeneration
Authors: Martin Jim 
Published: April 2020

The mammalian heart regenerates poorly and damage commonly leads to heart failure. The Hippo pathway is an evolutionarily conserved kinase cascade that regulates heart size during development and prevents adult mammalian cardiomyocyte regeneration by inhibiting the transcription cofactor Yap. Recent work indicates that deletion of the Hippo pathway component, Salv, in cardiomyocytes can reverse ischemic heart failure in a mouse model. Further experiments have uncovered Yap target genes and provided insight into the mechanisms by which Yap regulated cardiomyocyte gene expression.I will discuss our latest findings that reveal new insights into heart size control and regeneration.
Retrieval Enhances Higher and Lower Order Thinking in Anatomy and Physiology Students
Authors: Dobson John 
Published: April 2020

Retrieval practice is a learning strategy that was developed by cognitive scientists and is based on the act of recalling information after exposure. Over the last two decades, many dozens of studies have found that retrieval‐based strategies can enhance learning and memory more effectively than more commonly‐used strategies such as repetitive reading. Although the advantages of retrieval practice have been demonstrated in both well‐controlled laboratories and real‐world settings such as middle school and university classrooms, the evidence also indicates that most educators and students remain unaware of the benefits of the strategy. It is especially unfortunate when such an effective learning strategy is underutilized in courses that cover anatomy and physiology information because many students find those subjects to be particularly complex, overwhelming, and difficult to learn. The purpose of this presentation is to review key studies that examined the effects of retrieval practice on lower and higher orders of thinking with anatomy, physiology, and medical information. Lower orders of thinking include the abilities to identify, define, and distinguish; whereas higher orders of thinking include the abilities to transfer, critique, and evaluate. The evidence reviewed in this presentation demonstrates that retrieval practice is a relatively effective means by which to increase both higher and lower order thinking with anatomy and physiology information.Support or Funding InformationNone
Genetic and Tissue Interactions in the Embryogenesis of the Diencephalon and Circumventricular Organs
Authors: Kiecker Clemens 
Published: April 2020

The posterior forebrain (diencephalon) is one of the vesicles that emerges in the anterior neural tube early in embryogenesis. It gives rise to the thalamus (the major relay station of the brain), the prethalamus and pretectum, the epithalamus including the habenular complex, the hypothalamus including the posterior lobe of the pituitary gland and the retinas of the eyes. It also generates a number of circumventricular organs, highly specialised sensory and secretory structures that lack a blood‐brain barrier and that allow for the exchange of substances between the brain and the circulatory system. I will give an overview of the genetic mechanisms that regulate the embryonic development of the diencephalon with a focus on (a) the role of secreted signals and transcription factors and (b) interactions between tissues. The pituitary gland proper develops through an interaction between neural (hypothalamus‐derived) and non‐neural (placode‐derived) tissues, and our recent work indicates that the pineal organ forms through a similar interaction between neural and placodal tissues, suggesting a common theme in the establishment of diencephalon‐derived neurosecretory and sensory structures.Support or Funding InformationThis work has been supported by King’s College London.
Effect of biglycan on apoptosis of neurons in acute cerebral infarction in rats
Authors: Du Yanrong , DUAN HUBIN , Qiao Xiaohong , Xue Wen , cheng junjun , Hao Chunyan , Li Youlian , Liu Wenyun , Guo Jianxun 
Published: April 2020

ObjectiveTo investigate the effect and mechanism of biglycan (BGN) on apoptosis after experimental acute cerebral infarction (CI) in rat.MethodsA total of 110 clean grade Wistar male rats were randomly divided as follow: A total of 80 clean grade Wistar male rats were randomly divided into sham group and CI group consisted of 3h, 6 h, 12h, 24h, 48h, 72h, and 7d (n=10). The expression of BGN in neuron and its time course were detected. A total of 30 clean grade Wistar male rats were randomly divided into sham group, sham + control lentivirus group, sham + BGN lentivirus group, CI + control lentivirus group, and CI + BGN lentivirus group (n=6). The silence efficiency of BGN and the effect of BGN on neuronal apoptosis and neurological score after CI were detected. CI model was induced by reforming longa method. Lentiviral vector was administered intracerebroventricularly 7 days before CI. The expression of protein and mRNA of BGN were detected by western blot and real‐time quantitative PCR (qRT‐PCR). Immunofluorescence was conducted to explore the expression of BGN on neuron. Neurological score was detected by the modified Garcia score, beam balance tests and Longa’s Five‐Point Pacification Low. The TUNEL was used to detect neuronal apoptosis.ResultsThe expression of protein and mRNA of BGN were peaked at 24h after CI (P<0.05). A majority of BGN were detected on neuron at 24 h after CI. Compared with CI + control lentivirus group, the modified Garcia score, beam balance tests and the Longa’s Five‐Point Pacification were significantly improved in CI + BGN lentivirus group (P<0.05), as well as the TUNEL‐positive neurons ratio was significantly decreased ( P<0.05).ConclusionInhibition of BGN can significantly reduce early neuronal apoptosis after CI, and attenuated neurological deficits.Support or Funding InformationThis study was supported by the National Natural Science Foundation Youth Fund (30600637), China Postdoctral Foundation (2014M561207, 2019T120195), the Shanxi Province Basic Research Program (2010021034‐4, 201601D011119), the Shanxi Scholarship Council of China (2011‐096 and Key Projects No.4), Department of Human Resources and Social Security of Shanxi province, The science and technology research projects of health department of Shanxi Province (2016D011119), The Teaching Reform Program of Shanxi Higher Education, The Education Reform Project of Postgraduate Students in Shanxi Province, Lvliang people’s hospital fund, The Education Reform Project of Shanxi Medical University.
Younger Age of First Exposure to Soccer Heading is Associated with Decreased MicroRNA‐7844‐5p
Authors: Muñoz Eric R , Caccese Jaclyn B , Wilson Brittany E , Shuler Kyle T , Santos Fernando V , Yamaguchi Felipe , Jeka John J , Hudson Matthew B 
Published: April 2020

Younger age of first exposure (AFE) to American football has been associated with later‐life cognitive deficits in former National Football League players experiencing cognitive and behavioral deficits, but not in other cohorts of high school, college, amateur, or professional contact/collision sports athletes. Although several studies evaluated clinical outcomes, limited information exists among these cohorts and subclinical measures, such as blood biomarkers may serve as an early indicator of future impairments. Extracellular vesicles, including exosome‐like vesicles (ELVs), are released from cells and contain a variety of molecular cargo from the originating cell, and have emerged as reliable biomarker candidates.OBJECTIVEThe purpose of this study was to compare plasma ELV concentration, size, and microRNA (miRNA) levels between soccer players reporting AFE to soccer heading before age 10 years (AFE≤10) and soccer players reporting AFE to soccer heading after age 10 years (AFE>10).METHODSCollege‐aged soccer players self‐reported AFE to soccer heading. Participants were divided into two groups based on their responses: AFE>10 (n=9, 5 males, 12.33±0.24 years) and AFE≤10 (n=18, 11 males, 7.94±0.46 years). Plasma ELV concentration and size were assessed using nanoparticle tracking analysis. Total RNA was isolated from ELVs, followed by performing miRNA first strand cDNA synthesis and subsequently qPCR. Comparisons were made via unpaired t‐test (p<0.05).RESULTSData are presented as mean ± SE. AFE≤10 was associated with decreased miR‐7844‐5p when compared to AFE>10 (~60%, p=0.03). No changes in miRNA were observed for miR‐92b‐5p, miR‐423‐5p, miR‐24‐3p, miR‐144‐5p, miR‐221‐5p, and miR‐22‐3p. Groups did not differ in concentration (AFE≤10, 8.34 ×109 ELVs/ml plasma ±0.96 ×109 vs AFE>10, 8.39 ×109 EVs/ml plasma ±0.98 ×109) or size (AFE≤10, 117.58 nm ±7.12 vs AFE>10, 106.40 nm ±4.14) of circulating ELVs.CONCLUSIONCollectively these data demonstrate that younger AFE to soccer heading was associated with decreased circulating miR‐7844‐5p. Decreased circulating miR‐7844‐5p may be an early indicator of future pathology.Support or Funding InformationSupported by NIH‐NINDS R01 NS102157‐01, NIH P20 GM113125, NIH P20 GM103446, NIH R03 HD094594
Structural Characterization of the Chondroitin Sulfate motif binding to VAR2CSA in Placenta and Cancer
Authors: Spliid Charlotte Bredo , Toledo Alejandro Gomez , Esko Jeffrey , Clausen Thomas Mandel 
Published: April 2020

Malaria parasites have evolved to express certain proteins called VAR2CSA on the surface of infected erythrocytes. This allows them to adhere to unique chondroitin sulfate (CS) motifs, which are only found in the placenta. It was recently discovered that VAR2CSA also binds to over 95% of all types of cancer. The exact structure of the CS chains, termed oncofetal CS (ofCS), has previously been reported to be mostly non‐sulfated with low levels of 4‐O‐sulfation in the placenta. In this study, we found that ofCS was ~90% 4‐O‐sulfated with the remaining ~10% being mostly 6‐O‐sulfated and 2‐O‐sulfated. Although previously thought to be purely glucuronic acid (GlcA) we found that ~25% of the uronic acid content consisted of iduronic acid (IdoA). Additionally, we identified that the CS quantity and chain length were significantly increased in placenta and colon tumors compared to healthy organs and colon. This increased CS availability along with the unique ofCS motif is likely what causes high specificity of VAR2CSA to placenta and cancer.Support or Funding InformationVAR2 PharmaceuticalsGangstedfondenLouis‐Hansen Fonden
Membrane Phospholipid Composition Governs Pah1 Phosphatidate Phosphatase Activity
Authors: Kwiatek Joanna , Carman George 
Published: April 2020

In yeast and higher eukaryotes, all membrane phospholipids and the storage lipid triacylglycerol, are derived from phosphatidate (PA), which is also implicated as an activator of cell growth and proliferation, vesicular trafficking, secretion, and endocytosis. PA also regulates expression of lipid synthesis genes via the Henry (Opi1/Ino2‐Ino4) regulatory circuit, where the key step is the PA‐mediated translocation of the Opi1 repressor between the nuclear/ER membrane and the nucleus. Data indicate that several enzymes play important roles in the PA‐mediated regulation of lipid synthesis that occurs at the nuclear/ER membrane. Of the enzymes that metabolize PA, the PA phosphatase enzyme, which is encoded by the PAH1 gene, has emerged as key regulator of PA homeostasis. Indeed, cells lacking this enzyme exhibit several phenotypes that include elevated levels of PA, derepression of phospholipid synthesis genes, increased synthesis of membrane phospholipids, and the abnormal expansion of the nuclear/ER membrane. These mutant cells also exhibit a drastic reduction in TAG and lipid droplets. The PA phosphatase, which catalyzes the conversion of PA to diacylglycerol, must translocate from the cytoplasm to the ER membrane where its substrate PA resides to function in lipid synthesis. Thus, studies to examine mechanisms for the enzyme reaction at the membrane surface are warranted. In this work, we implemented defined unilamellar vesicles with a diameter of 100 nm composed of the major phospholipids within the ER membrane. Vesicles composed of phosphatidylcholine (PC) and 10 mol% PA supported PA phosphatase activity. The addition of phosphatidylethanolamine (PE) or phosphatidylinositol (PI) stimulated the activity, but phosphatidylserine (PS) had little effect. In more complex vesicle compositions, the maximum activity was observed with vesicles containing PC/PE/PS/PA or PC/PE/PI/PA. Yet, the activity was reduced when vesicles contained PC/PE/PI/PS/PA. The PA phosphatase activity was dependent on vesicle number as well as the surface concentration of PA within the vesicles. This vesicle system is being used to assess the roles of phosphorylation/dephosphorylation of Pah1 on membrane interaction and PA phosphatase activity.Support or Funding InformationSupported by NIH grant GM028140
Engineered High‐Specificity Affinity Reagents for the Detection of Glycan Sialylation
Authors: Yang Loretta , Wu Sheng-Cheng , Meng Lu , Gerner-Smidt Christian , Woods Robert J. 
Published: April 2020

As alternatives to established carbohydrate‐detection reagents (antibodies and lectins), Lectenz Bio is developing engineered proteins (known as Lectenz®), that target glycan sequences for with existing reagents either do not exist or are sub‐optimal. Lectenz® are engineered proteins derived from catalytically inactivated glycan‐processing enzymes that have been optimized for high affinity towards specific glycan sequences. The conversion of such enzymes into affinity reagents is facilitated by computationally‐guided directed evolution. Lectenz® are being developed for a variety of glycan detection and enrichment applications including affinity chromatography, Western blot, and immunohistochemistry. Here we demonstrate the performance and specificity of two novel sialic acid recognizing Lectenz® engineered from a sialidase enzyme.Support or Funding InformationNIH R44GM113351, R44OD024964
Oxidative stress‐induced germ cell apoptosis: The NOX‐ER stress connection.
Authors: Al-Saleh Farah , Al-Maghrebi May Abdulsamad , Khashab Farah Ahmed , Fadel Fatemah Mohammed , Al-Kandari Nora Yaqoub 
Published: April 2020

Testicular torsion and detorsion (DTT) can seriously damage the testes and cause infertility issues if left untreated. In animal models, it is represented as a testicular ischemia reperfusion injury (tIRI). During tIRI, excessive generation of reactive oxygen species (ROS) induces oxidative DNA damage (ODD) leading to germ cell apoptosis (GCA). The study objectives include investigating the role of NADPH oxidase (NOX), a source of cellular ROS, in instigation of ODD and subsequent GCA during tIRI and finding out NOX’s role in inducting endoplasmic reticulum (ER) stress. Male Sprague‐Dawley rats (n=36) were divided into three groups: sham, tIRI only and tIRI + apocynin (50 mg/kg), a NOX inhibitor. The tIRI rats underwent ischemia for 1 hour followed by 4 hours of reperfusion prior to rat sacrifice. Apocynin was administered 30 minutes post ischemia. Harvested testes were evaluated for spermatogenic damage by histological analysis, while biochemical and molecular modulations were assessed using biochemical assays, ELISA, immunofluorescence staining and real time PCR. Spermatogenic arrest was associated with increased lipid and protein peroxidation and decreased superoxide dismutase activity as a result of tIRI. The tIRI‐induced ODD was indicated by a significant increase in the levels of DNA strand breaks, 8‐OHdG formation, ph‐H2AX and ph‐ATM. The ASK1/JNK/survivin apoptosis pathway was significantly activated in response to tIRI. Finally, a significant increase in the immunoexpression of the unfolded protein response (UPR) pathway components like CHOP, GRP78, caspase 12 and ph‐eIF2‐alpha1 supported the occurrence of ER stress during tIRI. NOX inhibition by apocynin protected against ODD, GCA and ER stress. Our results indicate that NOX‐mediated ROS generation directly contributes to the tIRI‐induced ODD and GCA. In addition, NOX inhibition suggested its direct influence on inducing ER stress during tIRI.Support or Funding InformationThis study was supported by Kuwait University Grants YM 16/17 (College of Graduate Studies ) and SRU02/13 (Research Administration).
Improved Hepatogenic Differentiation of Human Adipose Tissue‐derived MSCs Using a Silicone‐based Cell Culture System
Authors: Stock Peggy , Hildebrand Janis , Böttcher Gunter , Christ Bruno 
Published: April 2020

Conventional two‐dimensional as well as established three‐dimensional cell culture systems exhibit a high modulus of elasticity, yet, without representing the stiffness of human organs. Previously, we established a protocol for the culture of primary rat hepatocytes on a silicone of low stiffness, which sustained their physiological functions. In terms of the development of human‐based tests to evaluate the potential risk of novel drugs, the method was adjusted for use of human adipose tissue‐derived mesenchymal stromal cells (hAT‐MSC). Aim of the study was to improve hepatogenic differentiation of hAT‐MSC on fibronectin‐coated 3D silicone scaffolds with low stiffness (E‐modulus approx. 250 kPA) mimicking the stiffness of human liver including surface modifications to increase hydrophilic properties.hAT‐MSCs were cultured on 3D silicone scaffolds. Hepatogenic differentiation was initiated by the 2 step protocol. The capability of the hepatocyte‐like cells to store glycogen, to synthesize urea and albumin as well as the enzyme activities of CYP1A1 and Cyp2B1/2 were analysed and compared to the conventional 2D cell culture and hepatogenic differentiation on polystyrene (E‐modulus 103 MPa).hAT‐MSC attached to the 3D silicone scaffolds and formed cell clusters. 10 days after starting the hepatogenic differentiation until the end of the culture on day 24, the cells on 3D silicone scaffolds displayed more intensive PAS staining for glycogen as compared to the cells on 2D cultures indicating improved glycogen storage. The urea synthesis rate [nmol/10.000 cells/24h] of these cells was significant higher as compared to cells on 2D culture throughout the culture period, though declining with ongoing culture; 10 d: 2D vs 3D 0.05±0.01 vs 1.68±0.05 and 24 d: 0.03±0.007 vs 0.4±0.04, respectively. The albumin synthesis rate [pg/10.000 cells/24h] was significant higher in cells differentiated for 24 d as compared to undifferentiated cells: 48.5±11 vs 7.4±1.9. Enzyme activity of CYP1A1 after 24 d was 3‐fold higher in cells differentiated on 3D silicone scaffolds as compared to cells cultivated on 2D and the enzyme activity of CYP2B1/2 was 12‐fold higher.With these results, medically approved silicone treated with plasma was identified to improve hepatogenic differentiation of hAT‐MSC, likely by providing the appropriate three‐dimensional growth conditions. Thus, the silicone scaffolds represent an important tool for the development of cell cultures featuring organ‐like stiffness and improving physiological functions of hepatogenic differentiated MSC.Support or Funding InformationThe study was supported by the European Regional Development Fund and the Free State of Saxony (SAB) 100282466 to J.H. and P.S.