bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the NCoR1 complex and its association with the molecular control of the mitochondrial biogenesis process
Authors: Silveira Leonardo R , Oliveira André G , Lima Tanes I , Guimarães Dimitrius S.P. , Favero Bianca C , Araujo Hygor N , Araujo Rafaela 
Published: June 2021

Metabolic homeostasis is regulated transcriptionally through the interaction between transcription factors, co‐regulators and proteins of the basal transcriptional complex. Nuclear co‐regulators work either as transcriptional repressors or as transcriptional activators and, therefore, are strictly regulated to synchronize metabolic pathways to environmental stimuli. Preliminary results from our laboratory have indicated that the NCoR1 co‐repressor plays an important role in the regulation of mitochondrial biogenesis and oxidative metabolism in muscle cells. During the differentiation process of C2C12 muscle cells, the expression of the NCoR1 repressor is reduced favoring the process of mitochondrial biogenesis. While, overexpression of NCoR1 negatively affects the oxidative characteristics of these cells. These observations suggest that NCoR1 plays a central role in binding the nuclear receptor to the transcriptional program of mitochondrial biogenesis. In this way, we are proposing here study to identify and characterize NCoR1 protein (s) involved in the regulation of mitochondrial biogenesis in MEF cells. Thus, we hope to identify potential therapeutic targets in the management of obesity and diabetes. The design will be performed through the following experimental steps: 1) Co‐immunoprecipitation/proteome of the NCoR1 complex; 2) In silico analysis of target candidates; 3) Identification of the target through functional/biochemical tests. Finally we intend to explore the target interface/NCoR1 as therapeutic potential in experimental models of insulin resistance/obesity. The overexpression of NCoR1 was confirmed by PCR and western blotting (Figure 1). After NCoR1 co‐imunoprecipitation (Fig. 2), cellular extract was submitted to mass spectrometry (LC‐MS/MS ) analysis and at least 15 targets were identified (Table 1). The identified proteins were listed according to (A) cellular components; (B) Molecular function; (C) Biological process (Fig. 3). Interactome analysis also demonstrated physical interaction among NcoR1 and indentified proteins including Hdac3, Tbl1xr1, GPS2 and Chd8 (Fig. 4). This analysis revealed potential candidates to control mitochondrial function/biogenesis in MEF cells.Support or Funding InformationThis work was supported by grant from Fundação de Amparo à Pesquisa do estado de São Paulo – FAPESP (2016/23008‐5), Capes and CNpq.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Suppression of NLRP3 inflammasome activation in LPS‐induced RAW264.7 cells by natural compound Lava Spirulina maxima extract
Authors: Chei Sungwoo , Song Ji‐Hyeon , Seo Young‐Jin , Lee Kippeum , Jin Heegu , Oh Hyun‐Ji , Oh Jae‐Hoon , Lee Boo‐Yong 
Published: June 2021

Spirulina is microscopic filamentous cyanobacteria. Although the Spirulina was recently reported to exert beneficial effect such as reducing cholesterol or weight loss, the correlation of Spirulina and inflammatory response has not been confirmed. The interesting about effect of functional food or nutritional value of blue‐green algae has been increased. Spirulinal maxima was recently reported to exert beneficial effect which contains high amounts of protein, lipids, essential amino acids, minerals, vitamins, photosynthetic pigments, and biologically active substance such as phycocyanin, chlorophyll, beta‐carotene. We choose RAW264.7 cell line, murine macrophages cell to evaluate the effect of Spirulina maxima. We demonstrated that Lava seawater Spirulina maxima 70% ethanol extract (LSME) effectively inhibited the Lipopolysaccharide (LPS) ‐ induced inflammatory response through antioxidant activity. It is also decrease ROS production by down regulating oxidant. LSM is the source of antioxidant which can protect against oxidative damage. Tumor necrosis factor‐alpha (TNF‐α) and interleukin 1β (IL‐1β) is decreased the LPS‐induced overproduction by LSME. We demonstrated that reducing the NLRP3(Nucleotide‐binding oligomerization domain) inflammasome through inhibit MAPK pathway by LSME.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exploring Cellular Pathways of Saturated Fatty Acid Toxicity
Authors: Nilsson Hannah , Brown Margaret , Inwards Emily , Stoeckman Angela , Listenberger Laura 
Published: June 2021

Excess long‐chain saturated fatty acids cause cell dysfunction and death, which has been linked to obesity‐related health problems like heart disease and type II diabetes. In this study, we aimed to determine if the incorporation of long‐chain saturated fatty acids into phospholipids in the endoplasmic reticulum (ER) triggers ER stress and lipotoxic cell death. We treated AML12 and NIH3T3 cells with the saturated fatty acid palmitate under conditions that reduced phospholipid synthesis. While culturing cells in the absence of choline decreased phosphatidylcholine synthesis through the Kennedy pathway, choline depletion did not prevent palmitate induction of reactive oxygen species or mitochondrial dysfunction. We also examined palmitate toxicity in the presence of tubercidin, an inhibitor of the PEMT pathway of phosphatidylcholine synthesis and ATK, a phospholipase A2 inhibitor known to decrease phospholipid recycling through the Lands Cycle. Neither inhibitor prevented the changes in mitochondrial function indicative of palmitate toxicity. Therefore, these results do not support the hypothesis that long‐chain saturated fatty acids cause lipotoxicity by changing the cellular composition of phospholipid membranes. Additional experiments are needed to identify lipotoxic pathways.Support or Funding InformationThis work was supported by the St. Olaf College Office of Collaborative Undergraduate Research and Inquiry and a Cayman Chemical undergraduate research fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Molecular mechanisms of STARD3 addiction in HER2 tumors
Authors: Voilquin Laetitia 
Published: June 2021

Human Epidermal growth factor Receptor 2 (HER2) is overexpressed and amplified in approximately 15–20% of breast cancers. HER2 is a tyrosine kinase receptor belonging to the EGFR family. HER2 amplification and overexpression play a central role in initiation, progression and metastasis of common cancers like lung, breast and gastric cancer (Hynes and MacDonald, 2009). HER2 amplification is a marker of poor prognosis, especially in breast and gastric cancer (Slamon and Clark, 1988). Although anti‐HER2‐targeted therapies have shown significant clinical benefits, de novo and acquired resistance remain a considerable issue (Garrett and Arteaga, 2011). Genomic profiling has demonstrated that HER2 positive‐tumors have additional alterations, and more importantly they co‐amplify and co‐express several genes on the 17q12 locus (Bièche et al., 1996; Kauraniemi et al., 2001; Tomasetto et al., 1995). Among these genes co‐expressed with HER2, our team identified and characterized STARD3, a gene belonging to the HER2 amplicon (Alpy and Tomasetto, 2014).STARD3 is a lipid transfer protein belonging to the START domain protein family (Alpy et al., 2001). This protein has two domains: the MENTAL domain anchors the protein in late endosomes and the cytoplasmic START domain allows cholesterol transport. Moreover, an FFAT motif present at the interface between the two domains of STARD3 interacts with VAP or MOSPD2 proteins localized in the endoplasmic reticulum (ER) (Alpy et al., 2013; Mattia et al., 2018). Thus, this interaction creates a membrane contact site between late endosomes and the ER allowing then the transfer of cholesterol towards late endosomes (Alpy et al., 2013; Wilhelm et al., 2017). Also, STARD3 has been functionally implicated in the survival of HER2‐amplified cells. Indeed, inhibition of STARD3 expression by RNA interference limits cell growth only in HER2‐amplified cells (Alpy and Tomasetto, 2014; Sahlberg et al., 2013). Thus, STARD3 belongs to the HER2 smallest region of amplification and its expression suggests that it contributes to HER2 tumor growth. We think that STARD3 cooperates with HER2 for tumor growth through an indirect molecular mechanism. Our results suggest that STARD3 acts on cancer cells by altering the normal cholesterol distribution and modifying the lipid composition of cellular membranes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differential Assessments of Blood Lipids, Lipid Peroxidation, Antioxidant Status, and Fatty Acids in Women with Uterine Tumors during Menopausal Period
Authors: Kotrikadze Nanuli , Tufinashvili Tamar , Ramishvili1 Liana , Alibegashvili Manana , Nakashidze Irina , Nemsadze Gia , Gordeziani Manana , Khazaradze Ana , Sepiashvilli Bela , Ahmad Sarfraz 
Published: June 2021

ObjectiveTo study alterations in lipid spectrum, lipid peroxidation intensity, and fatty acid (FA) spectrum in blood of women with benign & malignant uterine tumors during menopausal period.MethodsBlood samples from benign (myoma, n=15) and malignant (n=15) cases were collected, along with healthy menopausal (control, n=15). Spectrophotometric methods assessed lipid spectrum composition, antioxidant enzymes activities & lipid peroxidation intensity. Quantitative analyses of FA were performed by gas‐liquid chromatography.ResultsSaturated FA in malignant cases: decreased myristic acid (3‐fold), palmitic acid (~1.3 fold) compared to control, but stearic acid increased (1.13‐fold). The decreased ratio between palmitic/stearic acids (C16:0/C18:0) by ~1.5‐times was noted. Unsaturated FA in malignant cases showed a percent decrease in oleic (2.9‐fold), linolenic (1.5‐fold), eicosatrienoic (3‐fold), arachidonic (1.3‐fold) acid compared to control. The increased ratio between stearic/oleic acids (C18:0/C18:1) by 3.3‐times was noted in malignant cases. Increase in lipid peroxidation intensification was associated with lipid spectrum composition (hyperlipidemia, disruption in the exchange rate of phospholipids). The negative correlation between lipid peroxidation intensity & phospholipids was r=−0.96±0.04. Total cholesterol was higher in malignant cases. Total amount & activities of superoxide dismutase (SOD), catalase (CAT) decreased in malignant cases. The negative correlation between total cholesterol & SOD, CAT activities was r=−0.99±0.014. Amine‐containing phospholipids decreased but choline‐containing phospholipids increased with the severity of the disease.ConclusionsIntensification of lipid peroxidation & alterations in lipid spectrum composition revealed hyperlipidemia, disruption of phospholipids' exchange rate and hypercholesterolemia. Thus, specific changes in these biochemical parameters can be useful in the differentiation of benign and malignant uterine tumors for menopausal women.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypolipidemic and anti‐atherogenic effect of omega‐3 enriched structured lipids from linseed oil (LSO) with refined palm olein oil (RPOO) on rats fed atherogenic diet
Authors: Dhavamani Sugasini , Thilagam Kasthuri , Prasanth Kumar PK , Shanmugam Kathiresan , Chidamabaranathan N , Kavitha B , Prabakaran K , Kanchana S 
Published: June 2021

The anti‐atherogenic effect of omega‐3 enriched structured lipids prepared by lipase catalyzed enzymatic intersterification with refined palm olein oil (RPOO) and linseed oil (LSO) was studied in rats. LSO is a good source of short chain omega‐3 fatty acid (alpha linolenic acid, ALA, omega‐3 FA) whereas an RPOO contains a higher amount of palmitic acid (SFA) and oleic acid (MUFA). But it is lacking of omega‐3 fatty acids. Based on standardization with different ratios, the ideal combination was selected based on the fatty acid composition and TAG molecular species of oils. The structured lipids (SL) of RPOO with FXO (40:60) has obtained an ideal SFA:MUFA:PUFA ratios near to 1:1:1 and enriched with omega‐3 fatty acids. This redisposition of fatty acids boost the functional properties and beneficial for cholesterol lowering properties. The feeding experiment conducted on rats fed on normal and atherogenic diet containing 10% omega‐3 SL (experimental) and RPOO(control‐native oil) indicated no adverse effects on growth and food intake. Rats fed Omega‐3 enriched structured lipids showed a decrease in cholesterol as compared to RPOO in atherogenic diets. However, the omega‐3 structured lipids potentially lowered plasma, hepatic and aortic lipids, predominantly cholesterol, LDL +VLDL cholesterol and triglycerides. Feeding of an omega‐3 enriched structured lipids resulted in the accretion of long‐chain omega‐3 PUFA and decrease in the long chain omega‐6 PUFA in plasma, hepatic and aortic lipids. The lipid accumulation observed in the aorta of rats fed atherogenic diet with Omega‐3 enriched structured lipids was considerably reduced as compared to natural oil of RPOO. However, the Omega‐3 enriched Structured lipids exhibited better incorporation of omega‐3 fatty acids and beneficial for cardiac function and reduce the risk for cardiovascular diseases.Support or Funding InformationnoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Pasteurization Types on the Content and Isomerization of Conjugated Linoleic Acid in Milk
Authors: Hurst Sarah , Bunde Terry 
Published: June 2021

The world is currently facing an epidemic of giant proportions – diet‐induced obesity (DIO) and associated co‐morbidities (type 2 diabetes, hypertension, certain cancers, etc.). While diet and exercise are the gold standards for treatment and prevention of DIO, isomers of conjugated linoleic acid (CLA) (cis‐9/trans‐11 and trans‐10/cis‐12) have been shown to reduce body fat mass and increase lean tissue mass, and more importantly, aid in the treatment of a host of co‐morbidities. Apart from supplementation, meat and dairy products from ruminants (cows, sheep, and goats) are the major source of CLA for humans. However, CLA composition ranges greatly in these products as processing i.e. cooking, pasteurization, etc. alters the content of CLA as well the isomers themselves. As the extend of these changes are unknown, the effects of time and temperature on CLA isomerization in milk through varying pasteurization types was investigated. First, raw milk samples were obtained from a local farm, and subjected to three different types of pasteurization – vat, ultra, and high temperature, short time pasteurization. Results show that the ultra‐high temperature pasteurized sample had more trans/trans isomerization than the raw sample, while the other samples were comparable to the raw. Therefore, as temperature increased, the extent of CLA isomerization also increased. Further experiments using thermochemistry and kinetics should be conducted to identify the times and temperatures at which each isomer is converted or formed. This knowledge could then be used to produce more beneficial CLA within a given sample and to decrease the undesired trans/trans CLA.Support or Funding InformationSupport for this work was provided by the Department of Chemistry, Maryville College.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Dual Specific Hemolysin‐X is a Bioactive Natural Product that Forms Pores on the Surface of Erythrocytes
Authors: Dam Tarun , Welch Christina , Edwards Jared , Kadav Priyanka , Hromada Michael , Bandyopadhyay Purnima 
Published: June 2021

Hemolysins are natural cytotoxic agents that are capable of destabilizing plasma membrane structures of erythrocytes. We recently identified a plant hemolysin named Hemolysin‐X (HelyX) that showed dual specificity for cholesterol and certain serum glycoproteins, such as asialofetuin and fibrinogen. HelyX was isolated through two different approaches: protein purification protocols as well as organic solvent extraction. Ligand binding properties of HelyX were elucidated by inhibition assays using microtiter plates as well as spectrophotometer. HelyX demonstrated significantly fast kinetics (30–180 seconds) of lysis and ligand binding. Scanning electron microscopic imaging captured distinct pores on the surface of HelyX‐treated erythrocytes. Our results indicate that HelyX disintegrates mammalian red blood cells by forming pores on their surfaces.Support or Funding InformationMichigan Technological UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A New Model for Teaching Bone Biology in a Physical Therapy Curriculum
Authors: Hogg Russell 
Published: June 2021

A holistic, up‐to‐date understanding of skeletal biology is a vital component of clinical practice in a variety of fields, including orthopedics, endocrinology, internal medicine, physical medicine and rehabilitation, physical & occupational therapy, and others. However, most entry‐level practitioners in these fields come out of their degree programs with only a cursory knowledge of skeletal biology, which does not adequately incorporate a bounty of research that has been conducted over the last several decades.One of the great difficulties in educating students in our current understanding of skeletal biology – as is the case for most physiological systems – is the overwhelming complexity and interconnectivity of the skeleton with other body systems, which we are only now fully beginning to appreciate. Since this interconnectivity is also what makes an understanding of skeletal biology so important for the clinic, it is important not to shy away from it in our curricula.Therefore, the objective of this paper is to present a skeletal homeostasis model developed to educate students in graduate clinical degree programs with a well‐rounded, current understanding of skeletal biology. This model incorporates numerous body systems and strives to adequately incorporate the last three decades of research. The model presented here emphasizes the interaction between different tissues and the skeleton, placing the diversity of humoral and nervous outputs known to affect skeletal biology within tissue‐specific contexts in an attempt to make the interconnectivity of skeletal homeostasis more digestible to students. Each interaction of the skeleton with other systems is approached piece‐by‐piece, incorporating some of the most important neuroendocrine factors sequentially to build up to a broad understanding. While not complete, this model provides the student a good basis for interpreting the influence of muscles, fat, loading, calcium homeostasis, metabolism, and the nervous system upon bone – as well as the reciprocal impact that bone has upon these factors. Is also provides a foundation for understanding how failures in these interconnected networks can lead to pathology such as osteoporosis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural Aspects of Glycosylated Protein–Glycan Interactions by NMR
Authors: Prestegard James H , Moremen Kelley W , Amster I Jon , Williams Robert V , Eletsky Alexandre , Chalmers Gordon R , Morris Laura C , Yang Jeong‐Yeh , Chapla Digantkumar 
Published: June 2021

Characterization of glycosylated proteins and their response to interaction with glycans is challenging for any method, because of the heterogeneity of glycosylation and the extensive conformational sampling by most glycans. For NMR there are extra challenges because expression in mammalian cell cultures, which can preserve near‐native glycosylation, requires expensive substrates to achieve uniform isotopic labeling with 15N or 13C, and mammalian cells do not tolerate high levels of deuteration (something required to improve spectral resolution). We have developed a sparse‐labeling approach that preserves high resolution without deuteration, proves to be economical in most applications, and returns enough structural data to define geometries of multiple domain proteins and ligand protein complexes. The approach is based on labeling proteins with a single type of amino acid isotopically labeled in methyl groups with 13C (13C‐valine or 13C alanine). NMR signals from methyl groups are special in terms of the sensitivity and resolution that they provide. The addition of paramagnetic tags to specific sites in a protein provides long range distance and angular information on the location of labeled methyl groups. In combination with a newly developed approach to assign methyl resonances to specific sites in a protein, this information proves adequate to define relative domain orientations and facilitate the identification of ligand binding sites. Application to terminal domains from a cell surface signaling molecule, ROBO1, is used to illustrate the approach. It also provides an example of how binding of a heparan sulfate oligomer alters the relative orientation of domains.Support or Funding InformationThis work was supported by grants from the National Institutes of Health, P41GM103390 and R01GM033225.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.