bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMPK: guardian of metabolism and mitochondrial homeostasis
Authors: Shaw Reuben J. 
Published: June 2021

Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP‐activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.Support or Funding InformationReuben J. Shaw holds the William R. Brody Chair. The work from the authors' laboratory described in this Review was supported by grants from the US National Institutes of Health (R01DK080425, R01CA172229, P01CA120964, P30CA014195) and The Leona M. and Harry B. Helmsley Charitable Trust (grant #2012_PGMED002).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
How telomeres solve the chromosome end‐protection problem
Authors: de Lange Titia 
Published: June 2021

Chromosome ends can activate the DNA damage response (DDR) signaling pathways and become substrates for Double‐strand Break (DSB) repair. Telomeres solve this end‐protection problem by repressing all forms of DDR signaling and DSB repair. The telomeric DNA, maintained by telomerase, binds a six‐subunit protein complex, termed shelterin, that protects chromosome ends. Shelterin binds to the double‐stranded (ds) telomeric DNA through two subunits, TRF1 and TRF2. These proteins recruit a single‐stranded (ss) telomeric DNA binding factor, POT1, which binds to the ss telomeric repeats present at all chromosome ends. POT1 is linked to TRF1 and TRF2 via interactions involving TPP1 and TIN2. A sixth component, Rap1, interacts with TRF2. Conditional knockout experiments in mouse embryonic fibroblasts (MEFs) have revealed the mechanism by which this simple protein complex prevents activation of the ATM and ATR DNA damage signaling pathways, represses 5′ end resection, and prevents non‐homologous end joining (NHEJ) and homology directed repair (HDR) at telomeres. Shelterin is compartmentalized such that TRF2 represses ATM signaling and NHEJ, whereas ATR signaling is repressed by POT1. The mechanism by which TRF2 represses ATM signaling and NHEJ involves the remodeling of telomeres into the t‐loop structure, which essentially hides the chromosome end. POT1 represses ATR signaling by preventing the ssDNA sensor in the ATR pathway, RPA, from binding to telomeres. Progress on the mechanistic aspects of shelterin mediated chromosome end protection will be presented.Support or Funding InformationDr. de Lange is funded by awards from the NIH, American Cancer Society, the Breast Cancer Research Foundation, and the STARR Cancer ConsortiumThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reading epigenetic marks
Authors: Kutateladze Tatiana G. 
Published: June 2021

Plant homeodomain (PHD) fingers, YEATS, Tudor, CW and bromodomains are found in proteins involved in a wide array of fundamental biological processes, including transcription, replication, DNA damage repair, cell differentiation and survival. These domains comprise a large family of epigenetic readers, capable of recognizing PTMs (posttranslational modifications) in histones. Here, I will detail the binding mechanisms and biological functions of the readers that select for methylated, acetylated, and unmodified histone H3 tails. I will compare specificities and discuss the significance of crosstalk between PTMs and the consequence of combinatorial readout for the recruitment of these readers to chromatin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Declining Attention Span in Medical Students: Fact or Fiction?
Authors: Ettarh Raj , Al‐Hussaini Heba , Hassan Sherif , Kilarkaje Narayana 
Published: June 2021

BackgroundDespite a lack of previous investigations, there is a common consensus that attention span among young learners is declining. The millennial generation is described as having preferences for teamwork, interactive learning experiences, and visual media but suffer from short attention spans. To address the lack of empirical data, this study examined self‐reported attention span in medical students at matriculation. Only results relating to age and self‐reported attention span are presented here.MethodsTwo groups of matriculating medical students were surveyed by questionnaire shortly after starting in medical school: 334 first‐year medical students at Tulane University (who are required to graduate with a BS degree before entry into medical school), and 108 first‐year medical students at Kuwait University (who are required to graduate high school before entry into medical school). They were asked to respond to questions relating to learning habits and preferences.ResultsThe age range for Tulane University medical students was 20–54 years with a mean of 24.3 ± 3.0 SD. The age range for Kuwait University medical students was 17–21 years with a mean of 18.8 ± 0.7 SD. Due to the wide range of ages, only data for mean age ± 1SD for both cohorts were analyzed. The average self‐reported attention span for Tulane University medical students was 69.4 ± 46.4 minutes compared to 59.3 ± 51.8 minutes for Kuwait University medical students. Median attention span was shorter in the Kuwait cohort than in the Tulane cohort. Average attention span for women in the Kuwait cohort was shorter than in the Tulane cohort, but shorter among men in the Tulane cohort than in the Kuwait cohort.ConclusionThe self‐reported attention span was lower in the younger medical students at Kuwait University. The data suggest that instructional activities, especially lectures, that last less than 60 minutes may hold the attention of older medical students, but less so for younger medical students.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sorafenib supresses TGF‐β responsiveness by promoting TGF‐β type II receptor degradation.
Authors: Wang Shi‐Weigh 
Published: June 2021

Transforming growth factor‐beta (TGF‐β) family are multifunctional and essential in growth and development. The multi‐kinase inhibitor sorafenib is the FDA approved drug for the treatment of many solid tumor. Previous studies have showed that sorafenib inhibit TGF‐β induced epithelial‐mesenchymal transition (EMT) and tissue fibrosis; but the detailed mechanism remains unknown. In this study, we found that sorafenib specific decreases TGF‐β type II receptor in liver epithelial cell through lipid raft/caveolae‐mediated endocytosis but not in hepatic stellate cell. We next find more detail mechanism to prove this different effect between epithelial and stellate cell. The degradation of TGF‐β type II receptor lead to suppression of TGF‐β signaling. Since TGF‐β have been reported that play important roles in several diseases, our study may provide a potential therapy of TGF‐β related disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synthesis of Aspirin Analogs for Anticancer and Antibacterial Testing
Authors: Sleda Melissa A. , Albasrawi Hadeel K. , Timmons Shannon C. 
Published: June 2021

Aspirin is a common over‐the‐counter drug used to treat pain, fever, and inflammation. It is one of the most widely used medications in the world with an estimated 35,000 metric tons produced and consumed annually. Recent research has shown that the regular ingestion of aspirin reduces a person's risk of developing colon cancer and even promotes colorectal tumor regression. Moreover, aspirin has a demonstrated ability to inhibit the proliferation of colorectal cancer cells in vitro. Although the mechanism of action has not yet been unequivocally established, it is clear that the synthesis of novel aspirin analogs is of medicinal interest. In this study, a library of aspirin analogs of varying degrees of hydrophobicity and steric hindrance were synthesized using salicylic acid as the molecular scaffold and a variety of acyl chlorides. These aspirin analogs will be screened against an array of cancer cell lines and will also be evaluated as antibacterial agents to determine their medicinal activity. The medicinal testing of this library of aspirin analogs will help to establish new structure‐activity relationships.Support or Funding InformationWe would like to thank the Department of Natural Sciences at Lawrence Technological University and the Howard Hughes Medical Institute Inclusive Excellence grant for support and funding.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Advancing Professional Development Strategies for Undergraduates in Chemistry and Biochemistry
Authors: Brown Christian , Fallucca Amber , Makris Thomas 
Published: June 2021

In the Department of Chemistry and Biochemistry at the University of South Carolina (the Chemistry Department), most curriculum‐driven professional development for undergraduates is reserved for third‐ and fourth‐year students. Academic instruction occurs at all levels, but the context comes late. Early exposure to career options and hands‐on training is imperative for undergraduates to obtain maximum experiential education. The purpose of this project is to advance the current professional development strategies of the Chemistry Department, specifically targeting second‐ and third‐year students. The study will survey students' current involvement in professional development activities as well as how the Chemistry Department is facilitating undergraduate involvement in professional development. We will use the data on extracurricular experience and post‐graduation interest to design a workshop series to reach students with practical tools for success, such as networking skills and synthesizing intra‐ and extracurricular experiences. The impact of each workshop will be assessed with post‐session surveys asking participants about the value and applicability of the information shared. The most beneficial topics will be incorporated into curriculum development of the Chemistry Department's one‐credit hour undergraduate seminar course. By integrating more advanced professional development into the curriculum, chemistry and biochemistry undergraduates will be encouraged to pursue experiential education in their second and third years.Support or Funding InformationThis work was supported in part by the South Carolina Honors College Senior Thesis/Project Grant (CAB) and a grant from the University of South Carolina Magellan Scholar Program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Use of Biometrics to Determine Differences in How Biochemistry Experts and Novices Read Metabolic Pathways
Authors: Cortes Kimberly Linenberger , Kammerdiener Kimberly , Randolph Adriane 
Published: June 2021

Being able to move between multiple representations is an important skill in biochemistry. Schematics are a type of representation commonly used in biochemistry instruction often combined with chemical structures to form a metabolic pathway. As little work has focused on schematics in biochemistry, this study uses the Tobii X2‐30 Compact Eye Tracker system to record biochemistry experts and students enrolled in a one semester biochemistry course and a second semester organic course as they read a familiar (glycolytic) and novel (IMP synthesis) metabolic pathway image. This presentation will focus on differences in areas of interest (AOI), fixation, and scan path analysis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sub‐Chronic Exposure to Organic Arsenic Disrupts Hepatic Energy Metabolism and Antioxidant System
Authors: Babayemi David Oluwagbemi , Adeyi Olubisi Esther , Dosumu Adebisi , Adubiagbe Hassan Taiwo , Abdulsalaam Mariam Temitope , Tijani Aliu , Olaleye Fausat Morenikeji , Akinhanmi Temilade Fola , Ugbaja Regina Ngozi , Ademuyiwa Oladipo 
Published: June 2021

Arsenic is a ubiquitous toxicant, having a wide range of toxic effects on different systems in the body. To investigate the sub‐chronic effects of exposure to low doses of cacodylic acid (organic arsenic) on some enzymes of energy metabolism and antioxidant system in the liver, rats were exposed to cacodylic acid (20 ppm and 40 ppm) in their drinking water for ten weeks. Control animals received distilled water. Activities of catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), superoxide dismutase (SOD), NAD glycohydrolase (NADase), xanthine oxidase (XO) and lactate dehydrogenase (LDH) and the levels of nitric oxide (NO), reduced glutathione (GSH) and lipid peroxidation (MDA) were determined in hepatic cytosol while malate dehydrogenase (MDH) and respiratory chain enzymes (complexes I, II and IV) activities were determined in the mitochondrial fraction. There were significant (p<0.05) decreases in the level of GSH and activities of NADase, MDH and complex IV in the exposed groups compared with the control. In the 20 ppm group, activity of hepatic SOD and level of NO increased by 419% and 142% respectively. A hormetic response was observed in the activity of GST. The activities of complexes I and II decreased as a result of exposure to cacodylic acid, these decreases were dose‐dependent. Our findings indicate that disruption of energy metabolism and antioxidant system by cacodylic acid might play a role in the pathogenesis of its hepatotoxicity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chemical Composition of the Pepper Fruit (Dennettia tripetala) Seed Flour
Authors: Oyetayo Folake L. , Ogundare Opeyemi L. 
Published: June 2021

The seed flour of the Pepper fruit (Dennettia tripetala) plant was analyzed for the amino and fatty acids, minerals and antinutrient compositions using standard methods. The total amino acid concentration of the seed flour was 83.5g/100g protein of which the total Essential amino acids concentration was 34.3g/100gprotein. Arginine (9.94g/100gprotein) was the most concentrated Essential Amino acid while Glutamic acid(16.04g/100gprotein) and Aspartic acid (15.61g/100g protein) were the most concentrated Non‐Essential Amino acids in the seeds. The lysine/arginine ratio obtained(0.13) suggests that D.tripetala seed possesses a low arteriogenic potential while the calculated P‐PER was 1.91. Linoleic acid was found to be the most abundant fatty acid in the seed oil (38.95%) while the total unsaturated fatty acid concentration (91.29%) was higher than the total saturated fatty acid concentration (8.68%). The oleic/linoleic acid ratio of the seed oil of 1.12 implies the high stability of the seed oil. Potassium (9.31±0.0.05) was the most dominant mineral element (mg/g) while manganese (0.02±0.30) was the least concentrated. Antinutrients were distributed in the seed flour in varying concentrations; phytate (1.20±0.16 mg/g), alkaloids (0.33±0.01%) and flavonoids (2.10±0.01%). The foregoing shows D. tripetala seed as a potential source of useful nutrients which have beneficial implications for human nutrition and health.Support or Funding InformationnilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exploration of a pho13 knockout growth phenotype in non‐engineered strains of Saccharomyces cerevisiae
Authors: Ulerio‐Nunez Franly , Gjestvang Mark , O'Handley Suzanne F. , Gehret Austin U. 
Published: June 2021

Pho13p from Saccharomyces cerevisiae (budding yeast) is a member of the Haloacid Dehalogenase (HAD) superfamily. Accumulating evidence indicates a loss of Pho13p function imparts an enhanced ability of engineered strains to grow on D‐xylose. Recent evidence has also indicated that Pho13p exhibits specificity towards the substrate 2‐phosphoglycolate but a growth phenotype in non‐engineered pho13 deletion strains has not been apparent. There is evidence that 2‐phosphoglycolate is generated by yeast pyruvate kinase (PYK1) as a secondary metabolic reaction and that fructose‐1,6‐bisphosphate accelerates this activity. The accumulation of 2‐phosphoglycolate under these conditions could impart a growth phenotype in pho13 deletion cells as 2‐phosphoglycolate inhibits triose phosphate isomerase (TPI1). Non‐engineered strains of yeast were subjected to the metabolic inhibitors pyrazole and 2‐thenoyltrifluoroacetone (TTA) that have been shown to increase fructose‐1,6‐bisphosphate in cells. Mutant pho13 deletion strains did not exhibit any hypersensitivity to these inhibitors under rich growth conditions. Currently, pho13 deletion strains are being examined using minimal growth media in combination with pyrazole and TTA. The yeast pyruvate kinase open reading frame is also being PCR‐amplified from genomic DNA and cloned under the control of the GAL1 promoter to assess whether overexpression could enhance a potential inhibitor effect.Support or Funding InformationThis work was supported by an internal NTID FEAD grant (A.U.G.)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification and Regulation of NRNP1, a Novel Nutritionally Regulated Gene Involved in Cell Death
Authors: Cairl Nicholas Stephen , Kalman‐Maltese Vivian , Smas Cynthia M. 
Published: June 2021

Obesity and Type II diabetes are co‐morbidities that are increasing at an alarming rate in the United States. A thorough understanding of the genes expressed in white adipose tissue (WAT) and the role of these genes in energy metabolism has high relevance to development of new approaches to treat diseases of dysregulated adipose tissue function. Here, we report a novel adipocyte‐enriched gene NRNP1 (Nutritionally Regulated Nuclear Protein 1) which we discovered via in silico data‐mining of whole transcriptome profiling studies of in vitro adipogenic conversion of murine 3T3‐L1 preadipocytes to adipocytes. Ectopic expression studies of NRNP1‐eGFP fusion protein in COS7 cells revealed strong localization of NRNP1 to the cell nucleus, as well as punctate cytoplasmic localization. Western blot analysis of cell lysates from 293T cells transfected with Flag‐tagged NRNP1 indicated a mass of ~22 kDa. Interestingly, such studies revealed that ectopic expression of NRNP1 in 293T cells resulted in cell death with an ~80% reduction in cell number at 24 hrs post‐transfection. The underlying mechanism for this was investigated utilizing western blot studies for apoptotic marker proteins and with DNA fragmentation analysis. In adipogenesis NRNP1 is under strong developmental control with NRNP1 transcript induced > 500‐fold during conversion of 3T3‐L1 preadipocytes to adipocytes. A similar high degree of differentiation‐dependent induction of NRNP1 transcript was observed in an in vitro model of brown adipogenesis and in adipogenesis of primary murine preadipocytes. Strong nutritional regulation of NRNP1 was noted in vivo as NRNP1 transcript was significantly increased in subcutaneous WAT (12‐fold) and in brown adipose tissue (BAT) (3‐fold) of mice that were fasted and then refed vs. levels in fasting mice. The observation of a 12‐fold increase in NRNP1 transcript level in fatty liver of ob/ob mice vs. C57BL/6J mice suggests increased NRNP1 levels may be linked to dysregulated lipid metabolism. Assessment of a broad panel of mouse tissues by qPCR indicated selective enrichment of NRNP1 in WAT depots and BAT. Together, these data support a role for NRNP1 in normal and abnormal lipid metabolism and indicate that mis‐expression of NRNP1 in non‐adipose cells can promote cell death.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PI(3,5)P2 Regulates Vacuole Cation Transport to Mediate Cellular Osmoregulation
Authors: Wilson Zachary , Odorizzi Greg 
Published: June 2021

Lysosomes are dynamic organelles with critical roles in cellular physiology. The lysosomal signaling lipid phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P2) is a key regulator that has been implicated to control lysosome ion homeostasis, but the scope of ion transporters targeted by PI(3,5)P2 and the purpose of this regulation is not well understood. We identified loss‐of‐function mutations in the vacuolar H+‐ATPase (V‐ATPase) and in Vnx1, a vacuolar monovalent cation/proton antiporter that suppress the growth defects and osmotic swelling of vacuoles (lysosomes) in Saccharomyces cerevisiae lacking PI(3,5)P2 synthesis. The loss of PI(3,5)P2 synthesis in yeast causes a robust accumulation of multiple cations, most notably a ~3‐fold increase in cellular potassium, a primary osmolyte that regulates cellular/organellar water content. The accumulation of potassium and other cations in yeast lacking PI(3,5)P2 is relieved by Vnx1 or V‐ATPase inactivation, or by increased activation of a vacuolar cation export channel, Yvc1. Furthermore, inactivating the V‐ATPase or Vnx1 rescued several vacuole functions that are defective in PI(3,5)P2‐deficient cells. Thus, our data demonstrates that a critical function of PI(3,5)P2 signaling is to orchestrate vacuole/lysosome ion transport to maintain cellular osmoregulation and lysosome homeostasis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.