bluuebunny/crossref_metadata_2025_split huggingface dataset:
EWS/Fli1‐regulated microRNAs in Ewing Sarcoma pathogenesis
Authors: Jedlicka Paul , Parrish Janet , McKinsey Erin , Dylla Layne , Niemeyer Brian , Moore Colin 
Published: June 2021

Ewing Sarcoma is an aggressive malignancy with poor long‐term outcome. In an effort to identify more effective therapeutic approaches for Ewing Sarcoma, our laboratory has been studying the biology of microRNAs, novel regulators of gene expression with therapeutic potential. As a first approach, we have focused on microRNAs downstream of the EWS/Fli1 fusion oncoprotein, the dominant oncogenic driver in Ewing Sarcoma. Initial studies have identified growth suppressive microRNAs that target the IGF signaling pathway, an important tumor‐promoting axis in Ewing Sarcoma. Ongoing studies seek to understand: 1) how these and other microRNAs contribute to Ewing Sarcoma pathogenesis; 2) how the expression of microRNAs is regulated by the EWS/Fli1 oncoprotein; and 3) how these findings could be harnessed for novel therapies for this aggressive disease.This work has been supported by the Boettcher Foundation's Webb‐Waring Biomedical Research Program, Alex's Lemonade Stand Foundation for Childhood Cancer, Ruth L. Kirschstein National Research Service Award Institutional Training Grant, and the University of Colorado Cancer Center and School of Medicine.
Edwardsiella tarda Alter Their Protein Expression Profiles at Permissive Human Temperatures and Control the Host Cytoskeleton for their Benefit
Authors: Tenkink Byron Joel , Noort Rebecca , Siame Bupe Anthony , Guttman Julian Andrew , Leung Ka Yin 
Published: June 2021

Edwardsiella tarda is an emerging enteric pathogen that infects both warm‐water fish and humans. While it is known that E. tarda utilizes syringe‐like type III and type VI secretion systems to deliver effector proteins into fish host cells during infection, little is known about E. tarda pathogenesis in humans at the sub‐cellular level. To investigate the pathogenic strategies employed by E. tarda we tested two hypotheses; (1) E. tarda alter the expression of secreted proteins at 37°C and (2) E. tarda hijack the host cytoskeletal system in human cells as part of their pathogenesis. To test these hypotheses we grew E. tarda at 30°C and at 37°C and compared type III and type VI secretion system protein expression profiles at the two temperatures. Some strains of E. tarda produced more secreted proteins at 37°C than at 30°C, which suggests greater activity from the pathogen's secretion systems at human body temperature. When E. tarda infections in HeLa cells were examined microscopically, we found cytoskeletal and organellar alterations in infected cells as compared to uninfected controls, demonstrating effector‐driven sub‐cellular alterations. Taken together our results indicate that E. tarda hone their protein expression machinery to their environment and control crucial aspects of their host cells during their infectious processes.Grant Funding Source: Natural Science and Engineering Research Council of Canada
Magnetic resonance elastography (MRE) detects medullary renal fibrosis
Authors: Korsmo Michael James , Ebrahimi Behzad , Woollard John R. , Crane John A. , Eirin Alfonso , Krier James D. , Ehman Richard L. , Lerman Lilach O. 
Published: June 2021

MRE is a noninvasive novel MRI modality that detects changes in tissue viscoelastic properties by imaging shear wave propagation. Renal artery stenosis (RAS) induces kidney fibrosis, yet we have previously shown that concomitant reductions in renal perfusion pressure mask an increase in cortical stiffness. We hypothesized that due to its lower vascular volume and turgor, change es in medullary elasticity in RAS would be detectable by MRE. MRE 3D elastograms were obtained in pigs after 10 weeks of RAS or matched controls (n=6 per group), and contrast‐enhanced computed tomography images obtained in the same pigs guided selection of MRE medullary regions of interest (Fig 1). Trichrome staining was used for computer‐aided quantification of medullary fibrosis ex‐vivo. The renal medulla was significantly more fibrotic (5.96±0.19 vs. 1.82±0.49%, p<0.001) and stiffer (10.9±0.84 vs. 7.88±0.26 kPa, p<0.05) in RAS compared to controls (Fig 1 and 2). The histological degree of medullary fibrosis directly correlated with MRE‐derived stiffness (R2=0.55, p<0.05, Fig 3). This study therefore suggests that renal medullary MRE may be useful for detection of chronic kidney fibrosis in RAS.Grant Funding Source: NIH DK73608, HL77131, HL085307, and EB001981
FOXO Transcription Factors are Critical regulators of Neonatal Cardiomyocyte Proliferation
Authors: Sengupta Arunima , Yutzey katherine E 
Published: June 2021

Cardiomyocytes (CM) are highly proliferative during embryogenesis and withdraw from the cell cycle soon after birth. Here, the role of FOXO in regulating CM proliferation in neonatal cardiomyocytes in mice is investigated. CM‐specific deficiency of FOXO1 and FOXO3 results in increased CM proliferation 1–3 days after birth. Inhibition of AMP‐activated protein kinase (AMPK), an upstream activator of FOXO, increases proliferation in cultured rat neonatal CM and this increase is attenuated with overexpression of FOXO1 supporting the requirement of an active AMPK/FOXO signaling to promote cell cycle withdrawal in neonatal CM. FOXM1 and IGF1 both promote CM proliferation, and CM‐specific loss of FOXOs results in increased expression of FOXM1 and IGF1. Furthermore, FOXO1 and FOXO3 directly bind to regulatory regions of FOXM1 in neonatal cardiomyocytes, and FOXO1 inhibits FOXM1 reporter gene expression in cotransfection assays. We identified IGF1 as a direct transcriptional target of FOXM1 by chromatin immunoprecipitation assay. These results suggest that FOXO activity inhibits FOXM1 thereby controlling IGF1 levels to promote cell cycle withdrawal in neonatal CM. Therefore, understanding the molecular mechanisms by which FOXO regulates CM proliferation could be harnessed in adults for the treatment of cardiac injury. This work is supported by an AHA Post‐Doctoral Fellowship to AS and NIH P01HL069779 to KEY.Grant Funding Source : NIH P01HL069779 to KEY and AHA postdoctoral fellowship to AS
A Comparison of Commercial Anatomy Educational Software
Authors: Attardi Stefanie M , Rogers Kem A 
Published: June 2021

An online version of an existing undergraduate, systemic human anatomy course is under development. To accommodate the laboratory component of the online section, commercially available anatomy educational software will be used to demonstrate 3D structures via application sharing within a virtual classroom. Eleven anatomy software programs were reviewed to determine their suitability, on the basis of: quality of digital models (resolution, comprehensiveness of anatomical structures and labels, inclusion of cross sectional anatomy), volumetric data used to create models, manipulation of models (virtual dissection, rotational axes, vantage points, rendering speed), program functionality (saving and sharing dissections, querying for structures, ease of use of the menu) and cost. The software we reviewed will not meet all of our online teaching needs. No program was found to have sufficient anatomical detail and visual clarity of digital models for the central nervous system (CNS). Supplementary online materials for the CNS component of the course will be developed to use in conjunction with one of the eleven existing software packages.Grant Funding Source : Departmental Funding
DNA damage‐induced NF‐kB activation promotes breast cancer metastasis via upregulation of microRNA‐21
Authors: Niu Jixiao , Tan Guangyun , Yang Chuan He , Fan Meiyun , Pfeffer Lawrence M. , Wu Zhao-Hui 
Published: June 2021

OBJECTIVETo investigate the role and mechanism of NF‐κB in cancer metastasis.METHODSDNA damage induced NF‐κB activity was determined by EMSA and microRNA‐21(miR‐21) expression was examined by Quantitative PCR separately. In addition, migration of MDA‐MB‐231 cells was investigated by Transwell invasion and wound healing assay in vitro.RESULTSWe found that chemotherapeutic drug‐induced NF‐κB activation promotes breast cancer cell migration and invasion. The increased metastatic potential is dependent on IL‐6 induction mediated by genotoxic NF‐κB activation. Moreover, genotoxic treatment also upregulates oncogenic microRNA‐21 expression through eliciting NF‐κB recruitment to miR‐21 promoter region, where it cooperates with signal transducer and activator of transcription 3 (STAT3) to activate miR‐21 transcription. Induction of miR‐21 may enable cancer cells to elude DNA damage‐induced apoptosis and enhance the metastatic potential of breast cancer cells through repressing expression of PTEN and PDCD4.CONCLUSIONSOur data support a critical role of DNA damage‐induced NF‐κB activation in promoting cancer metastasis following genotoxic treatment, and NF‐κB‐dependent miR‐21 induction may contribute to both therapeutic resistance and metastasis in breast cancer. Financial support: This work was supported by NIH grants ‐ CA149251 (to Z.W.) and CA133322 (to L.M.P)
Investigating the Control of the Actin Cytoskeleton by EF1α
Authors: Colmer Sarah , Karas Christina , Scerbo Diego , Gomez Maria , Dunaway Stephen 
Published: June 2021

Translation factor EF1α plays a critical role in protein synthesis, delivering aminoacyl tRNAs to the ribosome1. However, it has another less characterized function in regulating the actin cytoskeleton. EF1α binds actin directly or indirectly, as determined by co‐immunoprecipitation experiments2. Overexpression of EF1α in Schizosaccharomyces pombe results in aberrant cellular morphology2. EF1α homologs are potential cancer drug targets; the compound narciclasine, isolated from Amaryllidaceae, was shown to penetrate human melanoma cells, bind to eEF1A, and impede the proliferation of these cells3.Three genes encoding EF1α are present in the fission yeast genome. Previously, we determined that antibodies against Saccharomyces cerevisiae elongation factor proteins EF1α, EF2, and EF3 were effective in detecting their homologous forms in S. pombe. We found that deletions of EF1α‐a and EF1α‐c resulted in a slight decrease in total EF1α protein levels by utilizing Western blot analysis. These deletions produced no noticeable defect in cell growth on plates or in liquid culture. Continuing these studies, we plan to knock out EF1α‐b and analyze protein production. We will conduct phalloidin staining on our deletion mutants to determine if gene deletion has any visible effect on the polymerization of actin. Furthermore, we will knock out all three genes encoding EF1α in a single strain to assess its essentiality.
Role of SIRT1 in regulation of hepatic gene expression by thyroid hormone
Authors: Thakran Shalini , Sharma Pragya , Attia Ramy R , Hori Rod , Elam Marshall B , Cook George A , Park Edwards A 
Published: June 2021

Thyroid hormone induces expression of hepatic genes such as pyruvate dehydrogenase kinase 4 (PDK4) and carnitine palmitoyltransferase1a (CPT1a) through the thyroid hormone receptor. Peroxisome proliferator‐activated receptor gamma coactivator 1 (PGC‐1α) enhances the thyroid hormone (T3) induction of these genes. The NAD‐dependent sirtuin 1 (SIRT1) deacetylase plays a critical role in cellular metabolism by deacetylating and activating transcription factors including PGC‐1α. The SIRT1 activator, resveratrol, improves mitochondrial function, increases fatty acid oxidation and decreases lipogenesis. Here, we investigated the role of SIRT1 in the T3 regulation of PDK4 and CPT1a genes. Our data indicate that resveratrol increases expression of PDK4 and CPT1a genes in the liver and enhances the T3 induction of these genes. Resveratrol enhanced the T3 induction through the gene promoters. Overexpression of SIRT1 has similar effects to resveratrol whereas knockdown of SIRT 1 reduces the T3 induction of PDK4 and CPT1a. Moreover, SIRT1 interacts with the thyroid hormone receptor β. Our data indicate that SIRT1 plays an important role in the thyroid hormone induction of hepatic genes such as PDK4 and CPT1a.This work was supported by National Institute of Health and American Heart Association.
The Role of Tyk2 in Regulating Energy Expenditure and Preventing Obesity
Authors: Raje Vidisha B , Derecka Marta , Gornicka Agnieszka , Sczepanek Karol , Sisler Jennifer , Croniger Colleen M , Larner Andrew 
Published: June 2021

Brown adipose tissue(BAT) and skeletal muscle(SKM) are the two major tissues involved in energy expenditure, mediated by thermogenesis.We have observed that mice that do not express the JAK kinase‐ Tyk2 become spontaneously obese and exhibit the metabolic syndrome. Tyk2−/− mice show defects in BAT and SKM, which arise from the same lineage of Myf5+ progenitors of the mesenchymal lineage. Tyk2−/− mice exhibit decreased expression of BAT specific genes like UCP1 and PRDM16. The expression of SKM specific transcription factors is elevated in Tyk2−/− BAT. Tyk2−/− mice also have more muscle mass compared to the wild type controls. However, the skeletal muscle is functionally impaired as shown by decreased mitochondria respiration capacity, decreased expression of mRNAs involved in muscle contraction, exercise intolerence and a defect in maintaining the core‐body temperature upon cold exposure.Taken together, these findings suggest a novel role for Tyk2 kinase in regulation of energy expenditure and preventing the obese phenotype.
Determination of the Intracellular, Surface, and Extracellular Localization of Hsp70s under Different Stress Conditions
Authors: Medina Rebeca , Rashedan Manely , Nikolaidis Nikolas 
Published: June 2021

Members of the Hsp70 family are primarily localized in different subcellular compartments, including the cytosol, endoplasmic reticulum, and mitochondria. Apart from their primary localization, different Hsp70s have also been found in other places within the cell, as well as the cellular membrane and the extracellular milieu. However, it is unknown which stresses are responsible for their re‐localization, membrane translocation, and secretion. To this end we studied the localization of four members of the Hsp70 family under different stresses using sub‐cellular fractionation and confocal microscopy. These experiments revealed that under normal growth conditions all four Hsp70s were present in multiple fractions, as well as in the extracellular medium. In stressed cells, Hsp70 amounts in each fraction were significantly different from the untreated cells. These results suggest that stress causes re‐localization and differential membrane‐anchorage and secretion of the four Hsp70s. Additional experiments using pharmacological manipulation of intracellular trafficking pathways are currently being performed to identify the molecular mechanism used by Hsp70s to achieve their translocation, membrane anchorage, and subsequent secretion. This study is the first step towards elucidating the biological importance of the re‐localization and membrane occurrence of these chaperones.This project was supported by funds from CSUPERB and CSUF to NN.
Catalytic and Biological Features of Human Light Chains Suppressing of Infection of Influenza Virus A Type
Authors: Hifumi Emi , Fujimoto Naoko , Uda Taizo 
Published: June 2021

By immunizing ground‐state peptides or proteins into mice, the authors have established murine catalytic antibody light chains (antigenases) that could destroy such as HIV‐1 gp41, H. pylori urease, TNFa etc. We proposed a new concept that the antigenase posseses a catalytic‐triad structure composed Ser, His and Asp.Based on above concept, we cloned cDNAs (from a volunteer infected with influenza virus) encoding human antibody kappa light chain belonging to subgroup II of germline genes, because the group encodes a catalytic triad‐like structure with high possibility. The cDNAs were transformed into E. coli and each human light chain was expressed as the protein. The highly purified (>95%) human light chains were firstly submitted to the catalytic activity tests and to in vitro assays for examining the infectivity of influenza virus. Some clones showed the amidase and DNase activity. Surprisingly, #4 clone exhibited a strong activity to digest pBR322 plasmid. And the #4 clone suppressed the infection of influenza virus (H1N1) in vitro assay. In addition, we performed in vivo assays. The administered mice with the influenza virus treated with #4 antigenase enhanced the number of survival mice compared with non‐treated mice. Furthermore, the weigh of the antigenase‐treated mice did not decrease at all, while the antigenase‐not‐treated mice showed the marked decrease of the weigh.
Dose response effect of almond consumption on serum fatty acid profile and coronary heart disease risk: a randomized controlled crossover trial
Authors: Kendall Cyril WC , Nishi Stephanie , Yoon Ana-Maria , Esfahani Amin , Lapsley Karen G , Jenkins David JA , Bazinet Richard P 
Published: June 2021

BackgroundConsumption of almonds, has been associated with decreased risk of coronary heart disease (CHD), which may be related to their fatty acid (FA) composition.Methods27 hyperlipidemic subjects consumed three iso‐energetic (mean 423 kcal/d) supplements in 1‐month phases: 1. full‐dose almonds (50â€“100g/d); 2. half‐dose almonds with half‐dose muffins; and 3. full‐dose muffins. Fasting blood was obtained at weeks 0 and 4 of each treatment and FA concentrations analyzed by TLC and GC.ResultsOn both the half‐ and full‐dose almond supplements, the % oleic acid (OA) and monounsaturated FA (MUFA) increased in the triacylglycerol (TG) fraction (OA: P=0.003, P<0.001; MUFA: P=0.004, P<0.001, respectively) and in the free fatty acid (FFA) fraction (OA: P=0.01, P=0.12; MUFA: P=0.04, P=0.06). In both the TG and FFA fractions, MUFAs were positively associated with HDL‐C (P=0.03, P=0.003), OA and MUFA were inversely associated with ten year risk of CHD (OA: P=0.059, P=0.03; MUFA: P=0.048, P=0.01), while saturated FA were inversely associated with HDL‐C (P<0.05) and positively associated with 10 year CHD risk (P<0.05).ConclusionAlmond consumption increased the OA and MUFA content in the serum TG and FFA fractions, which were inversely associated with CHD lipid risk factors and overall 10 year CHD risk.Supported by the Almond Board of California, Modesto, CA
Dietary n‐3 fish oil protects young mice against mortality during pneumonia
Authors: Fernandes Gabriel , Hinojosa Cecilia , Williams Paul , Orihuela Carlos 
Published: June 2021

BackgroundPneumonia is a common cause of infections in the elderly, particularly during winter seasons. In recent years, use of n‐3 fatty acids is rising, as a nutritional supplement in order to reduce serum triglyceride levels or to protect against cardiovascular disease. We formed a hypothesis that consumption of fish oil may reduce mortality in fish oil fed mice following a challenge with streptococcus pneumonia.MethodsWe fed 5% corn oil (AIN‐93 diet) or 4% fish oil/1% corn oil (AIN‐93 diet) to 2 month old female C57BL/6 mice. Fish oils included: regular fish oil 18/12, and 30/20, 55/5 or 5/60 (EPA/DHA) enriched diets. After 2 months on diets, mice were challenged intra‐nasally with a lethal dose of streptococcus (s) pneumonia serotype 4, strain TIGR4 (1.0 × 107 CFU). Survival was assessed over 10 days.ResultsMice on 18/12, 30/20, 55/5 and 5/60 fish oil regimens had dramatically lower mortality than in n‐6 corn oil controls, 75% survival versus 12% survival in controls. Bacterial burden within the lungs 24 hours post infection revealed reduced levels in most of fish oil groups, except in 5/60 fed mice. All mice receiving dietary fish oil had >100‐fold less bacteria within the bloodstream than the controls.ConclusionThis data supports our hypothesis that n‐3 fish oil protects against s. pneumonia mortality by decreasing bacteria burden in young mice, however it needs to be tested in older mice.
A Rural Community Engaged in a Cancer Prevention Program
Authors: Dawkins Norma L , Carter Vivian L , Howard Barbara 
Published: June 2021

Bullock Count, Alabama is one of 17 Black Belt Counties characterized by rural socioeconomic decline, acute problem of poverty and poor health. It has one of the highest cancer rates in the state and the nation. Mortality rate for this county is 229.9 compared to the state (216.9) and the nation (188.6). The purpose was to assess health knowledge, status, and behaviors of participants engaged in a cancer prevention program.Two instruments were designed 1) fact finding questionnaire and 2) a health behavior questionnaire which consisted of four sections: demographic information, health knowledge, health behaviors and health status. Both instruments revealed reliability of 0.80 and 0.83. Results indicated that 86% of respondents were female, 33% were college graduates, and 80 % earned an average annual income of $11,000 to $35,000. Participants (95%) were willing to take part in a community‐based cancer prevention program. Responses to health questions indicated that 71% associated moderate exercise and healthy diet with disease prevention, only 69 % believed that consuming five servings of vegetables a day can lower blood pressure. Approximately 50% rated their health as good while 71% indicated that their mental health was either fair or good. Community‐based intervention is paramount to the prevention of cancer and other chronic diseases. This research is supported by the U54 Cancer Research Partnerships
Prevalence of osteoarthritis and dietary pattern in older people above 60 in southern area of Korea
Authors: Shin Dongsoon , Oh Ha-Jung 
Published: June 2021

This study was conducted by personal interview. The total number of subjects was 201(female 137, male 64), and all of them were above 60 years old. They lived in or around Changwon city and 51.7% of them resided in rural areas. The 38.8% of the subjects were suffered from joint disturbance of knee, leg or back pain. Compared to non‐symptomic group, the height and weight of symptomic group were lower(p<.05), but the body fat was higher(p<.05). Interestingly the educational status was lower in symptomic group than in non‐symptomic group(p<.001). Especially in women, the menopausal age of joint symptom group was earlier than that of non‐symptom group(p<.001). Meat, fish intake frequency were higher in joint symptomic group than in non‐symptomic group, in contrast seaweed and fruit intake were lower(p<.05). Therefore zinc and Vit C intake was significantly different according to osteoarthritic symptoms in older population(p<.05)Grant Funding Source : Kyungnam University
Automated Extraction and Analysis of Salmonella enterica From Ground Turkey and Kitchen Surfaces
Authors: Williams Patrick E , Parrish Torrey , Duggan Megan , Chapman Jessica 
Published: June 2021

Salmonella enterica is a gram negative bacterium commonly associated with raw poultry and food borne illness. Evogen has developed a fully Automated Sample Preparation (ASP) instrument which was used to extract and purify DNA from ground turkey meat cultures and kitchen surface swabs. DNA purified on the ASP was then amplified using loop‐mediated isothermal amplification (LAMP). Five gram samples of fresh ground turkey were placed in 50 mL of culture media in sterile culture flasks, inoculated with S. enterica at 3800 cfu/mL and placed in a 37°C incubator for 24 hours. Kitchen surfaces which had been in contact with the fresh turkey were inoculated at 3800 cfu/mL and allowed to dry for 30 minutes. Swabs were used to sample surfaces and placed in 1 mL of culture media and cultured at 37°C for 24 hours. Following incubation, a 200 μl aliquot from each sample was placed in an ASP cartridge for DNA extraction and purification. DNA concentration was measured after extraction. 5.0μl of extracted DNA was then used for LAMP. The LAMP reactions were held at 65ºC for 30 minutes and an annealing curve was performed at 98–75ºC. All culture and swab samples extracted on the ASP provided positive results via LAMP within 12 minutes. The mean concentration of DNA recovered from the samples was 21.0 ng/μl ± 2.8 ng/μl. This new sample preparation system provides high quality DNA that was rapidly detectable by LAMP.Private Funding