bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fiber‐type specificity of cancer cachexia‐induced muscle wasting is phosphorylated p70S6K‐dependent
Authors: Tanaka Minoru , Matsumoto Tomohiro , Sugimoto Ken , Fujino Hidemi 
Published: June 2021

The purpose of the present study is to investigate the differences between slow‐ and fast‐twitch muscles in cancer cachexia‐induced muscle wasting.Twelve male Wistar rats were randomly divided into two groups; control and cancer cachexia‐induced group. The cancer cachexia‐induced rats received an intraperitoneal injection of AH‐130 ascites hepatoma cells. The serum, the soleus and plantaris muscles were collected nine days after injection. Then, the expression levels of TNF‐α, p70S6K, FoxO1, FoxO3a, IL‐6, Atrogin‐1, and MuRF‐1 were measured.The cachexia‐induced rats resulted in a loss in body weight and muscle mass, and an increase in the expression level of TNF‐α in serum. In addition, the mass in fast ‐twitch muscle decreased significantly higher than that in slow‐twitch muscle. The levels of Atrogin‐1 and MuRF‐1 expression, which are the indicators related to protein degradation, increased in the cachexia‐induced group compared with the control group. However, there were no significant differences in Atrogin‐1 and MuRF‐1expression between slow‐ and fast‐twitch muscles. The expression level of phosphorylated p70S6K, which is one of the indicators related to protein synthesis, decreased in the cachexia‐induced group. In addition, the expression level of phosphorylated p70S6K in the cachexia‐induced group was significantly lower in fast‐twitch than in slow‐twitch muscles.These results indicated that cancer cachexia‐induced both in slow‐ and fast‐twitch muscle wasting might be caused by increased protein degradation factors whereas preferential fast‐twitch muscle wasting depended on the suppression of phosphorylated p70S6K expression, which was different from slow muscle wasting.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of FADS2 Inhibition in Combination with Increased Dietary n‐3 PUFAs on Skeletal Muscle Protein Turnover in Mice Fed a High Fat Diet.
Authors: Brown Katie , Baker Ella , Hawkins William , Sharma Sunita , van der Merwe Marie , Puppa Melissa 
Published: June 2021

IntroductionPolyunsaturated fatty acids (PUFAs) are essential dietary components. They are not only used for energy, but also act as signaling molecules. The delta‐6 desaturase (D6D) enzyme, encoded by the FADS2 gene, is one of two rate limiting enzymes that convert the PUFA precursors – α‐linolenic (n‐3) and linoleic acid (n‐6) to their respective metabolites. Alterations in the D6D enzyme activity alters fatty acid profiles and are associated with metabolic and inflammatory diseases including cardiovascular disease and type 2 diabetes. Omega‐3 PUFAs, specifically its constituent fatty acids DHA and EPA, are known for their anti‐inflammatory capability and may be beneficial in the prevention of skeletal muscle wasting through maintenance of protein turnover.PurposeThe purpose of this study was to determine the role of PUFA metabolites in skeletal muscle protein turnover, in the presence or absence of FADS2 activity.MethodsTwenty C57BL6 male mice were fed a high‐fat lard (HFL, 45% fat (mostly lard), 35% carbohydrate and 20% protein, n‐6:n‐3 PUFA, 13:1) diet for 6 weeks. Mice were then divided into 2 groups (n=10 per group). One group remained on the HFL diet, while the other group was fed a diet high in n‐3 PUFAs (HFO, 45% fat (mostly Menhaden oil), 35% carbohydrate and 20% protein, n‐6:n‐3 PUFA, 1:3). Each group was further subdivided with half of the animals receiving an orally administered FADS2 inhibitor (100mg/kg/day). After 2 weeks on their respective diets and treatments, animals were sacrificed and gastrocnemius muscle harvested. Protein turnover signaling were analyzed via Western Blot.ResultsLevels of MTOR and AMPK phosphorylation were measured. There was a trend towards increased MTOR phosphorylation with FADS2 inhibition regardless of diet (p=0.07). There was no difference in phosphorylation of AMPK regardless of diet or inhibitor. We analyzed markers of mitochondrial biogenesis which is closely linked with protein synthesis through PGC1‐α and Cytochrome‐C expression, however no significant differences were associated with either marker across all groups.ConclusionWe conclude that by inhibiting the FADS2 enzyme, there is potential for increased protein synthesis via activation of the MTOR pathway.Support or Funding InformationUniversity of Memphis School of Health Studies Faculty Research GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The C‐terminus of CsgE Is Involved In Preventing Protein Aggregation
Authors: Aranda Isamar , Binmahfooz Ashwag , Kaur Kuldeep , Rabi Huda , Yeh Lisa , Jayasinghe Sajith 
Published: June 2021

Gram‐negative bacteria, such as E.coli and Salmonella, contain proteinaceous, hair‐like, cell surface organelles known as curli. Curli serve to facilitate cell‐cell interactions and are essential for host cell colonization. Curli assembly involves six proteins, CsgA, CsgB, CsgC, CsgE, CsgF, and CsgG. CsgE and CsgF act as chaperones to prevent the premature aggregation of CsgA and CsgB which are the main protein components of Curli. CsgE and CsgF help transport CsgA and CsgB proteins to the cell surface, where CsgA and CsgB begin to assemble to form Curli. We have observed that CsgE is able to inhibit the aggregation of CsgA, as well as human islet amyloid polypeptide (hIAPP), an amyloidogenic polypeptide that is unrelated to curli. We used four different mutants of CsgE (34C, 58C, 99C and 119C) where the wild type residue at the respective position was replaced by a cysteine, and labeled with the fluorophore IASEDANS together with fluorescence quenching to determine the ability of CsgE to interact with the non‐aggregating rat Islet Amyloid Polypeptide (rIAPP). rIAPP differs from hIAPP by only three amino acids, but does not aggregate to form amyloid and was used to reduce the complicating effects of hIAPP aggregation. In the absence of rIAPP IAEDANS labeled at positions 34, 58, 99 and 119 gave Stern‐Volmer quenching constants of 9.6, 9.2, 12.1, and 7.6 respectively, while in the presence of rIAPP these values were 9.7, 8.7, 12.4, and 6.5. The significant reduction in the quenching constant for position 119 in the presence of rIAPP suggests that the fluorophore at this position becomes protected from quenching. The protection could either be due to a conformational change in CsgE driven by binding to rIAPP, or could be due to residue 119 interacting directly with rIAPP, and suggests that the C‐terminal region of CsgE is involved in its ability to prevent protein aggregation.Support or Funding Information1. This work is supported by NIH grant 1R15GM123430‐01.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Live section of the brain
Authors: Bobinac Dragica , Celic Tanja , Bobinac Mirna 
Published: June 2021

Learning the basic morphology of the brain and topographic relations between certain parts of the brain is fairly complex task in itself and moreover in the Anatomical atlases there is not enough cross‐sectional view of the brain. Therefore, for a successful study of the brain structure through images in the atlas, a great number of images and schemes of coronal, sagittal and horizontal sections are needed. Through a series of such cross‐sections, the student could reconstruct brain structures and study the mutual relationships of neighboring structures.To enable such a way of learning we have made a section of the brain and we recorded it on a CD along with an explanation of all visible structure.We have made a sections of five 10% Formalin‐fixed brains.Two brains were sectioned to show lateral ventricle located within the cerebral hemisphere, third ventricle and fourth ventricle. Then we have made serial 1 cm thick cross‐sections of one brain in coronal plane. Each side of the section was recorded along with an explanation. One brain was cut in median sagittal plane. After that one cerebral hemisphere was cut in horizontal plane in 2 cm thick serial sections while the second cerebral hemisphere was cut in sagittal plane in 2 cm thick serial sections.Live section of the brain is very well accepted by the students and is very helpful for better understanding of the brain morphology.Support or Funding InformationFunded by Faculty of Medicine University of RijekaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural characterization of human uridine monophosphate synthase (UMPS) and its spatio‐temporal localization in cells
Authors: Kim‐Holzapfel Deborah M , French Jarrod 
Published: June 2021

In humans, uridine monophosphate synthase (UMPS) catalyzes the last two reactions in the pyrimidine de novo biosynthetic pathway, with N‐terminal OPRT domain and C‐terminal OMPDC domain. OMPDC has been reported to dimerize in its active state, whereas the oligomerization and structural characterization of OPRT and UMPS are not known. To understand the regulation of proteins in this pathway, we are investigating the structure of UMPS and its spatio‐temporal localization in the cell. Wild type and mutant UMPS were expressed in BL21 E.coli and purified with affinity chromatography and size exclusion chromatography for structural and biochemical studies. Our results indicate that wild type UMPS equilibrates in two different oligomeric states. In cells, UMPS is known to be a cytosolic protein, however, its localization has not been observed when the pyrimidine nucleotide demand increases. We predict that UMPS gather around the mitochondria to increase flux of intermediates under nucleotide depleted conditions. We transiently transfected FLAG‐tagged UMPS into HeLa cells and observed its localization with the mitochondria, which will be further confirmed with super resolution microscopy. UMPS has become an attractive drug target for cancer, autoimmune disease and antiviral therapeutics among others, therefore, structural characterization and cellular localization of UMPS is crucial to determine the regulatory mechanism of the pathway.Support or Funding InformationSUNY at Stony BrookThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural Plasticity Analysis of Drosophila Sleep Circuit After Thermogenetic Sleep Deprivation
Authors: Velazquez Yoheilly , Dubowy Christine , Sehgal Amita 
Published: June 2021

Sleep rebound is a homeostatic process characterized by an increase in sleep drive after sleep deprivation. Previous studies have identified neural circuits in Drosophila implicated in sleep regulation, but whether or not there are structural plasticity changes in these circuits after sleep deprivation, and if there is synaptic connectivity between them is unknown. To answer these questions, we used fluorescent markers to identify neural structural changes following thermogenetic sleep deprivation and further characterize the anatomy of two populations of neurons localized in sleep control regions, ExFl2 neurons and c584‐expressing neurons. Immunostaining of ExFl2 neurons produced strong signals in the fan‐shaped body (FSB) and superior medial protocerebrum, while immunostaining of c584‐expressing neurons produced diffused signals throughout the brain. Total fluorescence of ExFl2 neurons in the FSB showed no difference between the sleep‐deprived group and control. In addition, after developing a protocol for sophisticated analysis of 3D structures of interest, results showed no difference between the groups. Altogether, these results suggest that thermogenetic sleep deprivation does not induce plasticity changes in ExFl2 neurons or c584‐expressing neurons. For future directions, using the same approach in other populations of cells that have been related to sleep, and studying the mechanisms underlying any observed structural plasticity will help to better understand sleep control.Support or Funding InformationNational Heart, Lung, and Blood Institute (NHLBI) NIH (Grant #5R25HL084665), Biomedical Graduate Studies (BGS), PRISE Program (Grant #R25GM096955)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Therapeutic Effects and Mechanisms of Baicalein on Rotenone Induced Parkinson's disease in rats
Authors: Lyu Yang , Zhang Xue , Du Lida , Yang Yulin , WANG JINHUA , Du Guanhua 
Published: June 2021

Parkinson's disease (PD) is characterized by motor dysfunction, such as bradykinesia, resting tremors, rigidity, and difficulty with voluntary movement etc. The anti‐PD drugs currently used clinically can only relieve symptoms. Up to now, there is still lack of anti‐PD drugs or pathology to alleviate PD. Baicalein is a flavonoid isolated from Chinese medical herb, Huangqin, which has been found in recent years with significant anti‐PD activity. In this study, we investigated the therapeutic effects and mechanisms of baicalein on rotenone‐induced PD rats. We found that baicalein induced rat PD model due to significantly increase the spontaneous activity; prolongation of the rotarod latency and the retention time of the inclined plate, increased the suspension score, and shorted the latency of the rat model in grid experiment. Further research shows the baicalein neuroprotection is closely relate to that baicalein inhibited rotenone induced oxidative stress in the brain, improved the function of mitochondria of rotenone injury, increased α‐synuclein degradation by enhancing rotenone inhibited autophagy and inhibition of NF‐KB and MAPK pathway activation to prevent brain inflammation. In an addition, we also evaluate the neuroprotective effect of baicalein in the rotenone induced SH‐SY5Y and midbrain primary neuronal cell PD model. Our results show that baicalein enhanced mitochondrial biogenesis, improved fusion and fission of rotenone inhibited mitochondrial, alleviated mitochondrial autophagy dynamics process, and increased the number of mitochondria decreased by rotenone through the CREB and GSK‐3β pathway. Baicalein can significantly inhibited the activation of NF‐KB pathway, inhibition of production and release of its downstream inflammatory protein and exert anti nerve inflammation.Support or Funding InformationCAMS Innovation Fund for Medical Sciences (CIFMS)(2016‐I2M‐3‐007)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Varicella meningitis : An atypical presentation in an immunocompetent individual with seizures managed with acyclovir
Authors: SENTHILKUMAR UMA , Cheta Jordana 
Published: June 2021

Viral meningitis, also known as aseptic meningitis, is the most common cause of meningitis and is responsible for between 26,000 and 42,000 hospitalizations yearly in the United States. Bacterial meningitis affects about 4,000 people each year, while viral meningitis affects about 10 people in every 100,000. The most commonly identified pathogens are enterovirus, herpes simplex virus and human immunodeficiency virus. Varicella, rabies and influenza are other viruses that are rarely responsible for viral meningitis. Varicella Zoster is a relatively common disorder in immunocompromised patients characterized by radicular pain and grouped vesicular eruptions. The typical findings in reported cases of VZV meningitis involve skin manifestations and classical signs of meningitis such as neck stiffness. However, only a few cases of meningitis caused by Varicella Zoster Virus (VZV) have been reported. The incidence of VZV meningitis in immunocompetent patients has been reported to be as low as 0.5%. We report an atypical presentation of VZV meningitis in an immunocompetent patient with headache, dizziness, sequalae of seizures without fever and skin manifestations.Our patient is a 59‐year‐ old African American male who presented with worsening dizziness, confusion, ataxia, lethargy and left‐sided frontal headache. Magnetic resonance imaging revealed mild to moderate burden of white matter abnormality, nonspecific but most likely due to chronic microvascular ischemic disease. No acute stroke. The next day sedation was weaned off and patient remained seizure free on continuous EEG and was extubated 3 days later the CSF came back positive for an elevated Varicella PCR of 42016. Patient was seen by infectious diseases consultant and was advised a course of acyclovir 10mg/kg intravenous every 8 hours for 14 days. All other antibiotics were stopped. Upon discharge, the patient had fully recovered from his symptoms with no neurologic sequalae.This unique case illustrates an atypical presentation of VZV meningoencephalitis in an immunocompetent patient that lacks many of the obvious features that usually distinguish the disease. Our patient lacked the vesicular rash, as well as other typical features of aseptic meningitis including nuchal rigidity, headache, photophobia, etc. Additionally, the patient's course was complicated by seizure, another relatively uncommon feature of VZV meningoencephalitis. VZV infection or reactivation is, rightfully, most commonly associated with the vesicular rash and prodromal pain that usually accompanies it.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
In‐silico Design of Safe and Effective Topoisomerase IB Inhibitors from Parent Compounds Isolated from Annona muricata
Authors: Adeyemi Emmanuel Tofunmi , James Ayorinde Babatunde , Odeyemi Oluwatimilehin Ademilolani , Magbagbeola Olubunmi Abiola 
Published: June 2021

Rational drug design using in‐silico tools have helped improve the time and possibilities of the development of safer drugs in recent times. This study was designed to develop safer DNA topoisomerase 1B inhibitors from two parent compounds isolated.The adsorption, distribution, excretion and toxicity (ADMET) properties of selected isoquinoline compounds were predicted using swiss ADME online tool. Analogues of these compounds were also created using ChemDraw professional Suite 16.0 by adding and removing functional groups based on the pharmacophoric structure of topotecan. 3D in‐silico docking was carried out between the designed compounds and the DNA topoisomerase 1B using AutoDock Vina software. Search space for ligand binding was defined and the program returned the binding affinities between the designed compounds and DNA topoisomerase 1B.Five analogues were designed for each compound. Out of the analogues designed, parent compound 1‐analogue 3 proved likely to be effective and safe in cancer treatment by having a binding affinity of −9.9 kcal/mol for DNA topoisomerase 1B and good ADMET prediction. The other compound (parent‐2) analogues had very high binding affinities for DNA topoisomerase 1B but they generally had ADMET problems. They were either predicted to be P‐glycoprotein substrates or blood‐brain barrier permeants.Rational drug design for anticancer agents from selected isoquinolines in Annona muricata predicted study compounds to be safe and effective in inhibiting DNA topoisomerase 1B.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Selecting Pharmacogenomic Variables that influence Propofol Pharmacokinetic Mean Residence Times in Surgical Patients using Machine Learning
Authors: Eugene Andy Roger , Eugene Beata 
Published: June 2021

BACKGROUNDPropofol is the most widely used intravenous anesthetic agent for surgery and outpatient procedures. We sought to test the hypothesis that CYP2B6, CYP2C9, and UGT1A9 pharmacogenes predicts prolonged Propofol Mean Residence Times (MRT), a pharmacokinetic parameter, or normal Propofol MRTs. The importance of this study will help further understanding of the pharmacogenomics of Propofol anesthesia to clinically selectively identify patients who would be at risk of delayed emergence or complications from Propofol.METHODSPropofol pharmacokinetic data was obtained from the Mikstacki et al 2017 study that genotyped patients for the following pharmacogenes: CYP2C9 1075 A>C, UGT1A9 98T>C, and CYP2B6 516G>T that included 85 Polish patients (53 males and 32 females) who were rated as a I or II according to the American Society of Anesthesiologists physical status classification system (1). The Random Forest and Adaptive Boost Machine Learning algorithms were used to classify patients as being either having a prolonged MRT or a normal MRT, relative to the population mean. All analyses were conducted using the R statistical programming language (R Foundation for Statistical Computing, Vienna, Austria).RESULTSAfter assigning the patients into the two dichotomous groups, the final machine learning model included CYP2B6, CYP2C9, UGT1A9, gender, and age (in decades) from a total of 43 patients, from the original 85. Propofol MRTs ranged from 8‐minutes to 504‐minutes, among the two groups. The Random Forest classifier resulted in best predictive performance with an ROC AUC of 0.98 with a variable importance (descending): CYP2B6, gender, CYP2C9, age (in decades), and UGT1A9.CONCLUSIONAmong the pharmacogenomics and demographic variables tested, the CYP2B6 gene and gender were identified as the most important variables predicting the Propofol pharmacokinetic parameter of Mean Residence Times in surgical patients.Support or Funding InformationNone.
Therapeutic effect of MC‐4 in combination with everolimus against progressive renal cell carcinoma by double‐targeting of PTEN/AKT/PKM2 and mTOR1 signaling pathways
Authors: Jiyeong Kim 
Published: June 2021

The purpose of this study was to assess the antitumor effects of MC‐4, a novel compound extracted from Artemisia annua L., as a monotherapy or combined with everolimus against Caki‐1 (Von Hippel‐Lindau (VHL)+/+) and 786‐O (VHL−/−) human RCC cells in vitro and in vivo. RCC cells were treated with MC‐4 alone or combined with everolimus and were analyzed for viability, apoptosis, and autophagy to evaluate synergistic antitumor effects in vitro and in xenograft in vivo models. MC‐4 inhibited Akt and pyruvate kinase M2 (PKM2), and significantly increased growth inhibition and autophagic cell death in RCC cells. However, everolimus led to compensatory Akt activation by inhibiting only the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. In contrast to everolimus, MC‐4 enhanced phosphatase and tensin homolog (PTEN) expression and reduced its downstream effector, PKM2, leading to decreased expression of glucose transporter 1 (GLUT1) associated with cancer cell metabolism. Collectively, the synergistic cytotoxic effects induced by co‐administration of MC‐4 and everolimus involve cell growth inhibition and autophagic cell death via dual targeting of Akt/PKM2 and mTOR. This suggests that MC‐4 is a novel Akt/PKM2 inhibitor that could overcome the limitation of existing mTOR inhibitors used for mRCC therapy. The data herein encourage further clinical studies combining MC‐4 with established chemotherapeutics as a strategy to treat patients with rapidly progressing RCC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.