bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ESCRT Membrane Scission Machine
Authors: Hurley James , Flower Thomas , Pavlin Mark Remec 
Published: April 2020

The ESCRT complexes I, II, and III and the AAA+ ATPase VPS4, catalyze reverse‐topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We previously found that VPS4 disassembles model ESCRT‐III filaments by processively unfolding entire ESCRT‐III subunits. Reverse‐topology membrane scission was reconstituted by encapsulating ESCRT‐III and VPS4 in a system allowing membrane nanotubes to be pulled from giant unilamellar vesicles using optical tweezers. In this reconstitution, ESCRT‐III subunits and VPS4 colocalize in puncta on nanotubes throughout the process of membrane scission. Another AAA+ enzyme, spastin, which is best known as a microtubule severing enzyme, is closely related in sequence and structure to VPS4. Spastin associates with the ESCRT‐III subunits CHMP1B and IST1. CHMP1B and IST1 form an unusual ESCRT‐III coat on the outside of membrane tubes and we found that these coats can carry out normal‐topology membrane scission. The roles of VPS4 and spastin in normal topology tube scission by, and disassembly of, CHMP1B‐IST1 complexes will be discussed. ESCRT‐III has long been known to form helical coats and spiral rings on membranes, but the assembly properties of the upstream ESCRTs have been little characterized. We found that ESCRT‐I can assemble into helices with a 12‐fold repeat, and that this helical assembly is important for function.Support or Funding InformationNIAID, NIH
Filament assembly by the liver phosphofructokinase‐1, the “gatekeeper” of glycolysis
Authors: Webb Bradley , Dosey Anne , Wittmann Torsten , Kollmann Justin , Barber Diane 
Published: April 2020

Despite abundant knowledge of the regulation and biochemistry of glycolytic enzymes, we have limited understanding on how they are spatially organized in the cell. Emerging evidence indicates that metabolic enzymes from diverse pathways can assemble into filaments. We show that the liver isoform of glycolytic “gatekeeper” enzyme phosphofructokinase‐1 (PFKL), which catalyzes the step committing glucose to breakdown, forms filaments in vitro and dynamic punctae in cells. Recombinant PFKL, but not platelet or muscle isoforms, assembles into filaments in a concentration‐, substrate‐, and tetramer‐dependent manner. Filaments are apolar and made of stacked tetramers oriented with exposed catalytic sites positioned along the edge of the polymer as determined by negative‐stain electron micrographs. Quantified live‐cell imaging shows PFKL‐EGFP appears as dynamic puncta that are enriched at discrete locations at the plasma membrane. These findings reveal a new behavior of a key glycolytic enzyme with insights on spatial organization and isoform‐specific glucose metabolism in cells.Support or Funding InformationWest Virginia University Start up funds
Characterization of Formate Dehydrogenase of Shewanella amazonensis
Authors: Usman Kabiru , Clarke Thomas , Bowater Richards 
Published: April 2020

BackgroundMembers of the family Shewanellacea have the ability to utilise formate as an electron donor for ATP generation under anaerobic respiration. A preliminary study conducted on different strains of Shewanella species shows that the Shewanella amazonensis formate dehydrogenase has a low catalytic activity of formate oxidation, and a high carbon dioxide reductase activity using methyl viologen as an electron acceptor or donor.ObjectivesThe aim of this research was to characterize formate dehydrogenase of Shewanella amazonensis and to investigate its possible use as a biocatalyst for the reduction of CO2 to formate. The growth phenotypes of Shewanella amazonensis was compared to Shewanella oneidensis on formate under aerobic and anaerobic conditions, and the catalytic properties of the formate dehydrogenase from Shewanella amazonensis were investigated further to better understand the preliminary data.MethodsShewanella amazonensis and Shewanella oneidensis cells were grown aerobically in LB media supplemented with formate. Minimal media supplemented with formate and fumarate was used to study the ability of the strains to utilize formate and fumarate. Methyl viologen was used to study formate oxidation and carbon dioxide reduction using minimal media under anaerobic condition.ResultsAnaerobic growth on Minimal media supplemented with formate and fumarate suggested that the Shewanella amazonensis growth rate was lower than the growth rate of Shewanella oneidensis. Kinetic assays suggest a lower Vmax was responsible for the observed kinetic differences.
OmpA Porin of Salmonella enterica serovar Enteritidis Possesses Aamyloid‐Forming Properties
Authors: Belousov Mikhail V. , Kosolapova Anastasiia O. , Antonets Kirill S. , Nizhnikov Anton A. 
Published: April 2020

The major focus of Salmonella enterica studies is the molecular determinants of the virulence and host‐specificity. Important virulence factors shared by the majority of pathogenic gram‐negative bacteria are the outer membrane proteins (OMP), many of which belong to the porins – beta barrel proteins serving as passive membrane pores. One of the most studied in terms of pathogenesis is the OmpA porin family. The proteins of the OmpA family are involved in the important virulence‐ and pathogenesis‐related processes including adhesion, penetration and damage of host tissues, as well as avoiding the immune response. Proteins of this family are highly conserved. For instance, the amino acid sequence similarity of OmpA proteins of Escherichia coli and S. enterica serovar Enteritidis is 94%. Considering ability of the E. coli OmpA porin to form amyloid‐like aggregates, we have produced recombinant OmpA protein from S. enterica serovar Enteritidis in vitro and have analyzed its amyloid properties. We have determined the typical fibrillary morphology of the obtained OmpA aggregates using transmission electron microscopy and have demonstrated that these aggregates exhibit yellow‐green birefringence being stained with amyloid‐specific dye Congo Red. We have also found that OmpA protein fused with YFP aggregates in yeast Saccharomyces cerevisiae while OmpA fibrils secreted in vivo at the surface of bacterial cells in the Curli‐Dependent Amyloid Generator system demonstrate properties typical for amyloids including unbranched morphology and birefringence upon binding with Congo Red. Taken together, these results suggest that the S. enterica serovar Enteritidis OmpA porin has amyloid‐forming properties.Support or Funding InformationThis work was supported by the Russian Science Foundation (Grant No 19‐76‐00026).
Impact of an aspartame‐containing diet soft drink on postprandial metabolism
Authors: Pearson Regis C. , Green Edward S. , Olenick Alyssa A. , Jenkins Nathan T. 
Published: April 2020

ObjectiveNon‐nutritive sweeteners (NNS) are widely used to lower daily caloric intake. However, controversy exists concerning possible metabolic effects of NNS. We hypothesized that Diet Coke, containing aspartame, differentially affects postprandial metabolism compared to a sugar‐sweetened beverage (Coke), but not water when co‐ingested with a mixed meal.MethodsSix healthy lean (26±1% body fat) males aged 20–26 yrs completed three separate tests consisting of a mixed meal (0.4g fat, 0.8g carbohydrates, and 0.3g protein/kg FFM) with the addition of 20oz of Coca‐Cola (CC: 787±49kcal), Diet Coke (NNS: 547±49kcal), or water (CON: 547±49kcal). Resting metabolic rate was measured via indirect calorimetry and blood samples were obtained immediately before, 5, 10 and 30 min, and 1, 2 and 3 hours after meal and beverage ingestion.ResultsThere was a significant main effect of treatment on fat oxidation rate, with post hoc analysis indicating differences between effect between CC and CON (P < 0.001), and CC and NNS (P = 0.012). For all measures of fat oxidation, including total fat oxidized, area under the fat oxidation curve (AUC), and total postprandial fat oxidized, NNS and CON were significantly higher compared to CC (P < 0.05). Additionally, there was a significant main effect of treatment on the rate of carbohydrate oxidation, with post hoc testing indicating differences between CC and CON (P < 0.001), and CC and NNS (P = 0.023). All measures of carbohydrate oxidation, including total carbohydrate oxidized, carbohydrate oxidation AUC, and total postprandial carbohydrate oxidized were significantly lower during NNS and CON treatments compared to CC (P < 0.05), with no differences between NNS and CON. There were no significant differences among treatments in glucose concentrations.ConclusionDiet Coke does not impact postprandial metabolism, whereas Coca‐Cola suppresses fat oxidation and increases carbohydrate oxidation compared to Diet Coke and water.Support or Funding InformationR.C.P. was support by the University of Georgia Graduate School Georgia Research Education Award Traineeship Follows Program
Age‐Dependent Decrease in PI3K p110 gamma
Authors: Askvig Jason , Ihry Victoria , Weidner Emily , Irmen Riley , Bexell Sydney 
Published: April 2020

We previously demonstrated that the hypothalamic supraoptic nucleus (SON) undergoes a robust axonal sprouting response following unilateral transection of the hypothalamo‐neurohypophysial tract in a young, 35‐day‐old rat. However, no collateral sprouting occurs following axotomy in a 125‐day‐old rat. Our lab has in vitro evidence demonstrating the role of CNTF (ciliary neurotrophic factor) in promoting process outgrowth via PI3K signaling. Thus, we compared the protein levels of the PI3K catalytic and regulatory subunits in the SON between 35‐ and 125‐day rats. We found less protein of the catalytic domain, PI3K p110γ, in the 125‐day rat SON; however, we did not observe changes in the other three catalytic domains nor the regulatory domains that we analyzed. Dual fluorescent studies demonstrated that all PI3K catalytic and regulatory subunits analyzed are localized to astrocytes and neurons in the SON. These data suggest that the lack of PI3K p110γ found in the 125‐day rat SON may prevent the collateral sprouting response from occurring, but future studies need to be performed to confirm this hypothesis.Support or Funding InformationThis material is based upon work supported by the National Science Foundation under Grant No. 1643998
Prevalence of Neuropsychiatric Disorders in Patients With Systemic Lupus Erythematosus (SLE).
Authors: Punnam Anurag Reddy , Khan Zainab Haider , Nayakanti Abraham , lambo jonathan 
Published: April 2020

BACKGROUNDNeuropsychiatric systemic lupus erythematosus (NPSLE) is a serious and well‐known complication of systemic lupus erythematosus (SLE). There are few studies on the population‐based estimates of the prevalence of NPSLE and its manifestations. Reliable prevalence estimates are needed to quantify the burden of the disease and to direct the attention of policy makers to magnitude of suffering associated with SLE. We aimed to quantify the prevalence of NPSLE in different population settings.METHODSWe searched PubMed from January 2009 to June 2019 to identify studies relevant to this review. Databases searches combined terms from three themes: all age groups/general population, psychosis, neuropsychiatric impairment, mental disorders and delusions; and SLE, lupus, and systemic lupus erythematosus. Terms were searched as both keywords (title/abstract words) and subject headings as appropriate. We also searched original papers relevant to this review from the retrieved articles. For case classification and case ascertainment, NPSLE was classified according to the American College of Rheumatology guidelines.RESULTWe excluded 79 from the initial 105 articles from the screening of titles and abstracts. The remaining 26 full text articles were reviewed and 9 were included in the review. The major neuropsychiatric comorbidities that were observed from the studies were major depression, headaches, seizures and cerebrovascular diseases. The prevalence estimates of neuropsychiatric disorders in NPSLE patients were as follows: major depression in patients (17%–52%) headaches (38.8%–60%), seizures (26.4%–63%), and cerebrovascular diseases (26%–38.8%). The overall prevalence estimates of NPSLE varies from 11% to 60% of all SLE patients.CONCLUSIONThis study confirms that the burden of neuropsychiatric manifestations of SLE, including major depression, seizures, cerebrovascular disease is high. Further studies are needed to elucidate the pathogenesis of neurological involvement in patients with SLE and to address the risk factors for NPSLE.Support or Funding InformationAmerican Association for Anatomists
ERa suppresses liver cancer EMT and amoeboid movement by targeting Ga12
Authors: Yun Jessica , Kim Sang Geon 
Published: April 2020

Several reports demonstrate the association of certain cancer progression and estrogen receptor alpha (ERa) expression. Due to poor prognosis and high relapse, hepatocellular carcinoma (HCC) is the second most common cancer worldwide. Moreover, aggressiveness and mortality of HCC is more frequent in men than women. Ga12 gep oncogene plays a critical role in promoting epithelial‐mesenchymal transition (EMT), a well‐established mechanism for tumor invasion. We previously showed that Ga12 is overly expressed in HCC patients. Here, we report an inverse correlation of ERa and Ga12 expression in HCC, which may contribute to the cancer metastasis and patient mortality. ERa transcriptionally inhibited Ga12 expression in a cancer cell model. In addition, tumor cells can take another modes of movement, characterized as amoeboid movement. Both EMT and amoeboid movement are necessary for an efficient metastasis of cancer cell. Since ROCK is one of the main downstream molecules of the Ga12 pathway and is known to activate amoeboid motility, we hypothesized whether ERa may affect amoeboid phenotype by modulating Ga12 signaling pathway, and found that ERa activation inhibited amoeboidal cell migration/invasion in conjunction with Ga12 repression. Moreover, we found microRNA‐141 and ‐200a as functional molecules affected downstream from the ERa‐Ga12 pathway, and their targeting of PTP4A1. Together, our results show that the ERa‐Ga12 pathway may play a role in targeting EMT and amoeboid movement plasticity of liver cancer, which may account for the gender disparity in HCC incidence and malignant progression.Support or Funding InformationThis work was financially supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6074045).
Transcriptome Analysis of Mice Treated with Anti‐miR‐144
Authors: Iloabuchi Vivian , Laws Tyler , Link Jenny , Vallim Thomas , Tarling Elizabeth 
Published: April 2020

Heart disease is a leading cause of death each year in the United States. In this study, we investigated the regulation of reverse cholesterol transport, a process shown to attenuate heart disease. Our lab has previously shown that mice treated with anti‐miR‐144 for 4 weeks increased ABCA1, which is involved in increased levels of high‐density lipoprotein and less fat in the heart. We hypothesized that long‐term treatment with anti‐miR‐144 would reveal other key genes in reverse cholesterol transport. Mice were placed on high fat, high cholesterol diet for 16 weeks, and treated with either saline, control anti‐miRNA, or anti‐miR‐144. Liver tissues were collected and processed for RNA sequencing. Using differential gene expression analysis, we found very few differences in gene expression among the treatment groups. When we did a comparison between the control‐treated mice and the anti‐miR‐144‐treated mice there was only one gene called MerTK that showed significant changes in gene expression. When we did a comparison between anti‐miR‐144‐treated mice and PBS‐treated mice, there were five genes that were shown to be differentially expressed which were Rgs3, Cd300lf, Fabp5, Dmac2l, and Slc1a3. Rgs3 and Slc1a3 showed higher expression in the PBS‐treated mice and the Cd300lf, Fabp5, Dmac2l showed higher expression in the anti‐miR‐144‐treated mice. As a reference, we did a comparison between the control‐treated mice and PBS‐treated mice and found that Cd300lf and the Fabp5 were also significantly expressed; this means that the changes for the two genes may not be due to anti‐miR‐144 treatment. Overall, we think that long‐term treatment of anti‐miR‐144 suppressed acute effects at the mRNA transcript level.Support or Funding InformationUCLA, Bruins‐in‐Genomics Summer Program. Fisk University
Addressing and Overcoming Difficulties for Students with Color Vision Differences or Deficits (Color Blindness) in Educational Instruction and Assessment
Authors: Henry Nancy , Stephenson Connor M. , Clough Rich , Shea Sandra 
Published: April 2020

Approximately 8% of males and 0.4% of females in the United States have color vision differences that result in inabilities to discern red or green based colors. Color Vision Difference or Deficit (CVD) is often an X‐linked genetic disorder related to absent or altered functioning of certain cones in the retina. Individuals with the most prevalent forms of CVD (deuteranomaly and protanomaly) have been classified as red‐green color blind and have difficulty distinguishing between colors of reds, greens, browns, oranges, and purples. Individuals with CVD are often challenged by commonly used teaching and testing materials that rely on descriptions and discriminations based on color. Examples of problems encountered by learners include: labeled structures in textbooks, PowerPoint© presentations, and exams wherein labels are made in colors that are indiscernible to students with CVD. Additional difficulties are often evident in histology curricula where tissue specimens are most frequently stained with Hematoxylin & Eosin. Eosinophilic structures (that stain red or pink) such as collagen, muscle, mitochondria, and blood cells are very difficult to distinguish or may seem almost imperceptible to students with CVD.Although there is a high prevalence of CVD in the United States, many educators are not aware of the challenges individuals with CVD encounter when color‐based teaching and testing materials are used. There are currently several computer‐based CVD simulator tools that allow educators and learners to upload images to simulate specific perceptual difficulties for individuals with CVD. These programs combined with extensive feedback and input from learners with CVD were used to identify problem areas in teaching and assessment of students with color vision differences. Methods were developed to help CVD individuals succeed in the histology and anatomy curricula, as well as in other academic disciplines. These inexpensive, simple, and easily applied methods include: ensuring the differentiation and descriptions of structures are not based solely on color; outlining specific tissue borders in colors with high contrast (not red or green); using textured backgrounds; and avoiding the use of red, green, or color‐coded labels. Additionally, procedures utilizing gray‐scale and modified‐color images have been employed in other curricula. These approaches have increased awareness of CVD among faculty and have fostered the development of strategies to ensure fairness, parity, and accessibility in histology, anatomy, and other programs.Support or Funding InformationThis work was supported by Southern Illinois University School of Medicine.
Epithelial‐mesenchymal transition (EMT) drives mesothelial fusion during avian chorioallantoic membrane (CAM) formation
Authors: Sheng Guojun 
Published: April 2020

Chorioallantoic membrane (CAM) is formed through fusion of the chorion and allantois in amniote early development. The CAM mediates oxygen and calcium uptake in birds and gives rise to fetal part of the placenta in mammals. Molecular mechanism regulating CAM fusion is poorly understood. We carried out cellular and molecular analyses of CAM fusion between E3.5 and E4.5 of chicken development. we show that CAM fusion is preceded by a brief period of contact between chorionic and allantoic mesothelia (two mesoderm‐derived epithelial structures) followed by their EMT and subsequent integration. We identified molecular (EMT‐related and non‐EMT‐related) markers specific to each tissue layer during CAM fusion. We will also discuss our data on canonical (SNAI1 and ZEB2) and non‐canonical (WT1) EMT‐associated transcription factors in driving mesothelial EMT. We propose that avain CAM fusion is a new model for studying mesothelial cell EMT, which is known to play important physiological (e.g., placenta formation) and pathological (e.g., mesothelioma and ovarian cancer) roles in the human.Support or Funding InformationIRCMS, Takeda Science Foundation, JSPS
Therapeutic Extracellular Vesicles from Mesenchymal Stromal Cells: Can they help us restore lung development and evade BPD?
Authors: Kourembanas Stella 
Published: April 2020

There is currently no single effective therapy for either the prevention or treatment of bronchopulmonary dysplasia (BPD), whose incidence is on the rise. Therefore, the need for new tools to treat and reduce risks of further complications associated with extreme preterm birth is urgent. Therapies based on transplantation of mesenchymal stromal cells (MSCs) have shown effectiveness in preclinical models, and promise in recent Phase 1 clinical trials of preterm infants at high risk for BPD. Our studies over the past decade have established that the main therapeutic vector of MSCs is present in their secretome, and is comprised by Extracellular Vesicles (EV), including exosomes. These vectors are small (less than 150nm), lipid bilayer‐enclosed structures secreted by almost all cells. Their varied origin, biogenesis and molecular composition implicate them in diverse and pivotal physiological roles, the most intriguing of which is an effective method of cell‐to‐cell communication dubbed the ‘New Endocrinology’. Consequently, MSC exosomes/small EVs (termed MEx) represent promising novel reagents for therapeutic applications. Work from our group has shown that MEx can restore lung function in rodent experimental models of BPD. MEx treatment suppresses lung inflammation and lung emphysema and restores normal lung development when administered either prenatally to a high risk pregnancy (i.e., preeclampsia or chorioamnionitis), or postnatally, to neonatal mice exposed to hyperoxia‐induced lung injury. Importantly, MEx modulate both innate and adaptive immunity through their effect on lung monocyte/macrophage phenotypes and thymic T cell development as well as promoting bone marrow ‐ derived myeloid cells to adopt a non‐classical signature. Our observations support the hypothesis that reprogrammed monocytes, of bone marrow origin, mediate the protective effects of MEx therapy on the lung and other organs. MEx thus provide a novel platform for therapeutic intervention in the perinatal period to treat tissue injury associated with inflammatory insults and to restore lung development to a physiologic path.Support or Funding InformationSupported in part by NIH grants R01HL146128; United Therapeutics Research Grant; and Charles H. Hood Foundation Major Grants Initiative
Exploiting Cell‐Instructive Nanocomposites for Tissue Engineering, Bio‐printing and Therapeutics Applications
Authors: Paul Arghya 
Published: April 2020

Considerable effort has recently been directed towards the development of hydrogels for tissue engineering and printing complex tissues in 3D, as they can mimic the physical, chemical, and biological properties of most biological tissues. Dr. Paul, in his talk, will highlight the immense potential various bioactive nanomaterials (e.g. mineral based nanoparticles), biopolymers (e.g. DNA, gelatin) and their nanocomposites to develop advanced multifunctional hydrogels for additive manufacturing and therapeutic delivery applications, as well as to effectively control stem cell fate in a 3D microenvironment.Support or Funding InformationAP acknowledges the funding and support from Canada Research Chairs Program of the Natural Sciences and Engineering Research Council (NSERC) of Canada.