bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of resistance‐induced heat on mice skin
Authors: Monte‐Alto‐Costa Andrea , dos Anjos Raquel Anacleto 
Published: June 2021

The continuous exposure to solar radiation happens to most living beings, their interaction with humans can be both positive or negative. Much of the research into its effects refers to ultraviolet (UV) and its consequences, such as skin damage and aging, with little emphasis on the effects of heat alone. The aim of this work was to investigate macroscopic, microscopic and biochemical effects of heat‐induced thermal exposure on mouse skin. Mice were divided into control (23° C – room temperature) and exposed (43° C) groups, with heat exposure induced by resistance plate in a thermal chamber for 30 minutes for 14 days on alternate days and at the end skin samples were collected for analysis. A thickness analysis of the skin layers was performed, where we observed an increase in the thickness of the dermis as well as the epidermis in the groups exposed to heat. In addition, there was an increase in the elastic and collagen fibers deposition in the 43° C group when compared to the control group. We performed a protein quantification for type I collagen, and observed a decrease in pre collagen in the 43° C group, while the mature collagen showed a slight increase in the same group, suggesting a possible renewal of this collagen, stimulated by heat. We also investigated the levels of oxidative stress in these conditions, and observed that reduction in lipid peroxidation, nitrite levels and free radicals in groups exposed to high temperature. With all these findings our results suggest that heat, without radiation, can behave as an important factor of skin anti‐aging.Support or Funding InformationSupported by: FAPERJ and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The role of sphingolipid metabolism in lifespan and healthspan extension in C. elegans
Authors: Radeny Joycelyn , Chan Jason 
Published: June 2021

Multiple advancements in research have led to a better understanding of the aging process. However, many metabolic pathways that promote healthy aging are still unknown. Here, we investigate the bioactive sphingolipid metabolism pathway and its roles in regulating lifespan and healthspan, which is the average period of one's life in good health. Sphingolipids are involved in cellular signaling and known to promote cell proliferation, secretion, stress response and survival. The sphingolipid pathway is composed of sphingomyelin, ceramide, sphingosine and sphingosine‐1‐phosphate (S1P). Ceramide synthases (CER synthases) mediate the conversion of ceramide to sphingosine while sphingosine kinase (SPHK) converts sphingosine to S1P. Using C. elegans, we previously found that mutations in sphk‐1/SPHK and hyl‐2/CER synthase result in decreased lifespan, suggesting that sphingolipids play a role in lifespan extension. However, it is unknown whether the sphingolipid genes act in known cellular pathways that mediate aging. Therefore, we tested the genetic interactions between sphingolipid enzymes and known models of aging, including the insulin like signaling (ILS) pathway that has been linked to lifespan extension. For this, lifespan analyses were performed on daf‐16/FOXO, which has a shortened lifespan phenotype, coupled with knockdown of sphingolipid metabolism genes. DAF‐16 is a downstream transcription factor target of DAF‐2/insulin‐like growth factor receptor and has important roles in mediating the gene expression of stress response. We observed that daf‐16 is epistatic to sphingolipid mutants for lifespan phenotypes, as indicated by similar short lifespan phenotypes of double knockout of daf‐16;hyl‐2 and daf‐16;sphk‐1compared to mutants with a single knockout of daf‐16. Thus, sphingolipids may act upstream of DAF‐16 to mediate stress response genes and lifespan. Future experiments will analyze transcriptional reporters for DAF‐16, and known stress response genes SOD‐3/superoxide dismutase, to determine whether cellular stress response mechanisms occurs normally in hyl‐2 and sphk‐1mutants under induced oxidative stress. An analysis of stress response will further enhance our understanding of the interaction between sphingolipids and known pathways that promote lifespan and healthspan.Support or Funding InformationResearch reported in this publication was supported by the National Institute On Aging of the National Institutes of Health under Award Number R15AG052933.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anthropometry, Energy Metabolism and Nutritional Intake of Girls with Adolescent Idiopathic Scoliosis
Authors: Normand Emilie , Franco Anita , Parent Stefan , Moreau Alain , Marcil Valerie 
Published: June 2021

Purpose of the studyAdolescent idiopathic scoliosis (AIS) is a tridimensional spine deformation of unknown cause that affects 2–3% of children and mostly girls. Studies have suggested that girls with AIS are taller and leaner than controls, but more studies are needed to confirm these results. While differences in energy metabolism and nutritional intake could explain these discrepancies, they have been poorly studied in AIS. This study aims to thoroughly characterize the anthropometric, metabolic and nutritional profiles of girls affected by AIS and to compare them to age‐matched healthy controls.Methods20 girls with AIS and 20 healthy controls are being enrolled. Anthropometric parameters (weight, standing and sitting height, body mass index (BMI), waist circumference and arm spam) are measured. Fasting glucose, insulin and lipid profile (total cholesterol, LDL‐cholesterol, HDL‐cholesterol, triglycerides and apolipoprotein B) are assessed. Bone mineral density and body composition are determined by osteodensitometry scan and questionnaires are administered to assess food intake and physical activity level.ResultsTo this day, 17 AIS (14.9 ± 1.9 yrs, mean Cobb angle of 27.2 ± 10.0°) and 12 healthy girls (15.2 ± 1.6 yrs) have completed the study. Compared to controls, we observed in AIS girls tendencies for lower BMI (BMI‐for‐age z‐score: −0.50 ± 0.90 vs. 0.09 ± 1.20, P=0.3669), fat percentage (−15%, P=0.1213), waist circumference (−7%, P=0.0706) and bone mineral density (−8%, P=0.0217). There was no difference in fasting glucose (4.98 ± 0.27 vs. 4.84 ± 0.27 mmol/L, P=0.1852) and insulin (52.46 ± 19.87 vs. 54.12 ± 19.41 ρmol/L, P=0.8365) between groups. A tendency for a perturbed lipid profile was also found in AIS girls with higher triglycerides (18%, P=0.2866), LDL‐cholesterol (16.5 %, P=0.0306), apolipoprotein B (19%, P=0.0071) and total cholesterol (12%, P=0.0374). 47% of AIS girls had at least one abnormal lipid value. Calorie intake and physical activity levels were similar between groups. However, compared to controls, there was a tendency for higher caloric balance (consumption vs. needs) in AIS girls (+60.5 ± 417.7 vs. −223.4 ± 625.7 kcal, P=0.1706). AIS girls and controls had similar vitamin D (4.60 ± 2.30 vs. 5.40 ± 3.01 μg, P=0.4469) and calcium intake (954.78 ± 326.20 vs. 928.78 ± 385.12 mg, P=0.8509).Conclusion: Our pilot study revealed tendencies for different anthropometrical features, lipid profile and energy balance in AIS. Increasing the number of participants might confirm these results.Support or Funding InformationFondation Yves Cotrel‐Institut de FranceThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ishige okamurae Extract Reduces Obesity in High Fat Diet‐Induced Obese Mice
Authors: Seo Young‐Jin , Song Ji‐Hyeon , Chei Sungwoo , Lee Kippeum , Jin Heegu , Oh Jae‐Hoon , Oh Hyun‐Ji , Lee Boo‐Yong 
Published: June 2021

Obesity is caused by an imbalance of energy intake and physical activity. A number of pharmaceutical agents exist to reduce body weight‐related symptoms of obese patients. Ishige okamurae is brown algae and has anti‐oxidant and anti‐inflammatory activities. However, it has not been reported that Ishige okamurae has anti‐obesity property. In our study, we identified that Ishige okamurae extract (IOE) suppresses high fat diet (HFD)‐induced obesity through modulation of adipogenesis and lipolysis. IOE fed mice decreased body and WAT weight. The expression of adipogenic factors such as CCAAT/enhancer binding protein alpha (C/EBPα) and peroxisome proliferator‐activated receptor gamma (PPARγ) were decreased by IOE. Additionally, IOE up‐regulated expression of lipolysis related enzymes such as adipose triglyceride lipase (ATGL) and hormone‐sensitive lipase (HSL). Therefore, our results suggested IOE suppresses adiposity through reduction of adipogenic and enhance of lipolytic‐related factors.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A mechanism for anesthetics through membrane lipids
Authors: Pavel Mahmud Arif , Petersen E. Nicholas Arif , Lerner Richard A. , Hansen Scott 
Published: June 2021

Since their discovery more than 150 years ago, anesthetics were speculated to target the cellular membranes. Hitherto, there is no plausible mechanism that explains how anesthetics perturbation on membrane could to lead to an effect. Here we show that the volatile anesthetics chloroform and isoflurane activate TREK‐1 channels through disruption of ordered lipid domains (rafts). Employing super resolution microscopy, we found that raft disruption by anesthetics cause the raft‐localized enzyme phospholipase D2 (PLD2) to translocate and activate TREK‐1. A catalytically dead PLD2 significantly decrease the anesthetic‐specific TREK‐1 currents. Additionally, transfer of the PLD2 binding‐site to an anesthetic‐insensitive channel, TRAAK, results in anesthetic‐sensitive currents. The general anesthetics chloroform, isoflurane, diethyl ether, xenon, and propofol were all found to activate PLD2 in cellular membranes indicating a broadly applicable mechanism. We propose a two‐step model of anesthetic TREK‐1 activation. First, inhaled anesthetics disrupt lipid rafts. Second, translocation and PLD2‐dependent production of anionic lipid activate associated channels. This model suggests anesthetics could indirectly activate ion channel in contrast to direct binding models.Support or Funding InformationThis work was supported by a Director's New Innovator Award (1DP2NS087943‐01 to S.B.H.) from the NIH, a graduate fellowship from the Joseph B. Scheller & Rita P. Scheller Charitable Foundation to E.N.P. We are grateful to the Iris and Junming Le Foundation for funds to purchasea super‐resolution microscope, making this study possible.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 biological function of PIP2 clustering in enzyme activation and ion channel regulation
Authors: Hansen Scott B. , Pavel Mahmud Arif , Petersen E. Nicholas 
Published: June 2021

The signaling lipid phosphatidylcholine 4,5 bisphosphate (PIP2) clusters with proteins in the plasma membrane away from saturated domains formed by GM1 lipids and cholesterol (GM1 domains or ‘lipid rafts’). The lipid metabolizing enzyme phospholipase D2 (PLD2) localizes to both lipid raft and PIP2 clusters creating a competition for localization. We show that disruption of GM1 domains by mechanical force or inhaled anesthetics causes PLD2 to translocate to PIP2 clusters where it activates twik related potassium (TREK‐1) channels giving rise to the channel's mechano and anesthetic sensitivity. We conclude cells have evolved to (i.) sense and respond to disruption of lipid order and (ii.) utilize lipid order to dynamically regulate enzymes and ion channels through substrate presentation.Support or Funding InformationThis work was supported by a Director's New Innovator Award (1DP2NS087943‐01 to S.B.H.) from the NIH, a graduate fellowship from the Joseph B. Scheller & Rita P. Scheller Charitable Foundation to E.N.P. We are grateful to the Iris and Junming Le Foundation for funds to purchase a super‐resolution microscope, making this study possible.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycosaminoglycan Recognition of Neutrophil‐Activating Chemokines
Authors: Nagarajan Balaji , Sepuru Krishna Mohan , Rajarathnam Krishna , Desai Umesh R 
Published: June 2021

Neutrophil‐activating chemokines are known for their fundamental and diverse role in recruiting immune cells to the site of inflammation/infection. Extracellular glycosaminoglycans (GAGs), especially heparan sulfate, sequester chemokines and engineer a concentration gradient to regulate the immune cell trafficking. Not much is known about the structural and dynamical aspects of chemokine – GAG interactions. We have studied the interaction of several human and mouse chemokines, including CXCL1, CXCL2, and CXCL5 with heparin/heparan sulfate oligosaccharides using computational (modeling and dynamics) and biophysical (NMR & ITC) techniques. These studies have led to fine atomistic level understanding of GAG recognition of chemokines. First, our studies show that even though these chemokines are structurally homologous, they exhibit striking differences in their recognition of GAGs. Diverse binding geometries have been observed in which a GAG chain may bind each monomer present in a chemokine dimer or a GAG chain may bind two non‐overlapping sites by spanning across the dimer interface. Second, molecular dynamics simulations show large concerted motions of the Lys/Arg side chains bound to sulfate/carboxylates of GAGs, which imply translational motion of a GAG chain over the binding interface leading to considerable plasticity in binding. At the same time, a GAG chain may have restricted motion arising from specific interactions with a group of core amino acid residues. Third, a large number of hydrogen bond contributing residues occur in chemokines, e.g., in N‐loop, 40s turn, β3 strand and C‐helix, which provide strong/weak interactions to stabilize the complex. Interestingly, GAG recognition of chemokines is also brought about by water‐mediated interactions between amino acid side chains and sulfates/carboxylates, which introduce additional stability to GAG's dynamical motion. Fourth, relative importance of individual amino acid residues correlate well with experimental observations, thus implying that computational trajectories can be reliably used to understand GAG–chemokine systems. In addition, the computational trajectories can lead to identification of preferred chain length, mode of binding, and dynamical motions of GAGs in recognition of neutrophil‐activating chemokines. Our work contributes fundamental understanding on the structural biology of GAG–chemokine interactions.Support or Funding InformationThis work was supported in part by grants from the NIH including HL107152, HL090586 and HL128639This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Furin Inhibition as a Mechanism to Reduce Aberrant ENaC‐Mediated Sodium Transport and Rehydrate the Airways in Cystic Fibrosis Lung Disease
Authors: Douglas Lisa E.J. , Reihill James A. , Ho Melisa W.‐Y. , Axten Jeffrey M. , Martin S. Lorraine 
Published: June 2021

The epithelial sodium channel (ENaC) is found in a number of tissues including lung epithelia and is activated through proteolytic cleavage of its α and γ subunits. Dysregulation of ENaC, secondary to the loss of functional CFTR in cystic fibrosis (CF), leads to increased Na+ absorption which contributes to airways dehydration, thickened mucus and impaired mucociliary clearance (MCC). Pro‐protein convertases such as furin are implicated in the activation of a distinct pool of ENaC as it passes through the biosynthetic pathway (1). Furin cleaves α‐ENaC at two sites releasing a small inhibitory peptide from the extracellular loop, partially activating the channel, and subsequently cleaves γ‐ENaC. These actions ‘prime’ the channel for cleavage at a secondary site on the γ subunit by cell‐surface channel activating proteases such as prostasin, trypsin and neutrophil elastase (2–4). Furin, therefore plays a key role in the proteolytic regulation of ENaC‐mediated sodium absorption and presents a promising therapeutic target for CF lung disease.The aim of this first‐in‐kind study was to determine the effect of two chemically different, highly selective furin inhibitors (BOS‐981 and BOS‐318) on ENaC signaling and airway surface liquid (ASL) height, using primary human CF bronchial epithelial cells (HBEs).Fully differentiated HBEs homozygous for F508‐del, grown at air‐liquid interface, were used to determine ENaC activity via equivalent current (Ieq) readings obtained using a 24‐well Transepithelial Current Clamp (TECC‐24) system. ASL height was measured using confocal microscopy.We report BOS‐981 and BOS‐318 to be potent inhibitors of furin. Both compounds, applied basolaterally, significantly reduced ENaC‐mediated Na+ absorption as measured by an acute reduction in amiloride‐sensitive Ieq after immediate treatment, which was sustained after longer (48 hr) exposure. The compounds also protected ENaC against cell surface activation by neutrophil elastase and CF sputum supernatant. Furthermore, the reduction in ENaC activity after a 48 hr treatment correlated with an increase in ASL height.These ground‐breaking results demonstrate that highly selective inhibition of furin by the novel inhibitors BOS‐981 and BOS‐318 presents a promising mechanism for the reduction of aberrant ENaC‐mediated Na+ absorption. This strategy has the potential to rehydrate the airways, restore effective MCC and reduce the devastating pulmonary decline observed in CF.Support or Funding InformationThis work was supported by funding from the MRC Proximity to Discovery: Industry Engagement FundThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The selective BCL‐2 inhibitor ABT‐199 induces cell death via the intrinsic apoptotic pathway in canine B‐cell and T‐cell lymphoma cell lines
Authors: Meichner Kristina , Gogal Robert M. 
Published: June 2021

The B cell lymphoma 2 (BCL‐2) family of proteins are critical regulators of apoptosis, acting as either activators or inhibitors of the intrinsic apoptotic pathway. Evasion of apoptosis by shifting the balance toward anti‐apoptotic proteins including BCL‐2 is an established mechanism of cancer cells. Lymphoma is a leading cause of cancer‐related deaths in dogs and there is evidence that BCL2 is overexpressed and can contribute to a therapy‐resistant phenotype. A selective BCL2 inhibitor, ABT‐199, shows clinical activity in human lymphoid malignancies but the effect in canine lymphoma is unknown. This study evaluated the effects of ABT‐199 on cell growth and different stages of apoptosis in two canine B‐cell lymphoma (CLBL‐1, 17–71) and three canine T‐cell lymphoma (OSW, Ema, Nody) cell lines. Cells were cultured for 72h in the presence of ABT‐199 at increasing concentrations to establish half maximal inhibitory concentrations (IC50). Nody (IC50: 0.49 μM), CLBL‐1 (2.72 μM), Ema (3.53 μM), and OSW (3.6 μM) were more sensitive to anti‐proliferative effects of ABT‐199 than 17–71 (12.93 μM). ABT‐199 rapidly induced key features of apoptosis including loss of mitochondrial membrane potential, increased caspase−3/−7 activity, and externalization of phosphatidylser‐ine. This effect was abrogated in cells co‐cultured with the pan‐caspase inhibitor Z‐VAD(OMe)‐FMK. The responses to ABT‐199 treatment are currently correlated with expression levels of BCL‐2 family members. These findings support that ABT‐199 induces cytotoxicity via induction of the intrinsic apoptotic pathway in canine lymphoma cell lines and that ABT‐199 shows promise to overcome drug resistance and to improve outcome in dogs with lymphoma.Support or Funding InformationThis study was supported by the University of Georgia VMES Research Grant 2926GR207002.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 Effects of Gossypol on Apoptosis‐Related Gene Expression in Racially Different Triple‐Negative Breast Cancer Cells
Authors: Messeha Samia , Mendonca Patricia , Soliman Karam F.A. 
Published: June 2021

Apoptosis is a gene‐directed mechanism that regulates cell proliferation and maintains homeostasis. However, the uncontrolled apoptotic process can lead to several pathological conditions such as tumorigenesis, and cancer metastasis. In the current study, the apoptotic effect of the natural polyphenol compound gossypol (GOSS) was investigated in the triple negative breast cancer (TNBC) cells. The effect of GOSS was evaluated in two cell lines representing Caucasian Americans and African Americans: MDA‐MB‐231 (MM‐231) and MDA‐MB‐468 (MM‐468), respectively. In both cell lines, a similar response was noticed in both cytotoxicity and proliferation studies. However, MM‐468 cells were 3‐fold more sensitive to the apoptotic effect of the compound that was accompanied by a longer delay in the colony formation. Furthermore, GOSS was found to alter the expression of many apoptosis‐related genes in our mRNA expression investigation. The compound significantly upregulated GADD45A, TNFRSF9, and BNIP3 in MM‐231 cells. Similarly, GADD45A and BNIP3 were upregulated in MM‐468. A significant finding observed in this study is the profound 159‐fold increase in the TNF gene expression that was found in MM‐468 cells. Moreover, the apoptosis‐suppressor gene, BIRC5 was significantly repressed by more than 90% in both cell lines as well as DAPK1 in MM‐231 and TP73 in MM‐468 cells. In conclusion, the data obtained in this study can provide a more understanding of the GOSS‐induced apoptosis effect and enhance the importance of this polyphenol compound as targeted towards BC treatment, particularly in African American women.Support or Funding InformationThis research was supported by NIH NIMHD Grants G12 MD007582 and P20 MD 006738This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
"Incidence of Intracranial Pathologies in Acute Ocular Motor Mononeuropathies Suggests Preferred Practice Pattern"
Authors: DelGiodice Michael John 
Published: June 2021

Imaging of the brain by magnetic resonance enables visualization of intracranial structures involved in the pathogenesis of acute, isolated ocular motor nerve palsies. However, a preferred practice pattern has yet to be determined. Meta‐analysis of prospective data, involving acute ocular motor mononeuropathy, identifies brain pathology with an incidence of 8.8%. Neuroimaging studies were associated with neoplasm, infarction, hemorrhage, aneurysm and demyelination. The recommendation is to obtain magnetic resonance imaging for acute ocular motor mononeuropathies, irrespective of neurologic isolation, diabetes and cardiovascular disease. These findings will be of value for clinicians seeking to adopt a preferred practice pattern.Support or Funding InformationUSAT College of MedicineAssociated Eye PhysiciansThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.