bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of NDM‐X, a mononuclear zinc metallo‐β‐lactamase derived from a di‐zinc enzyme
Authors: Montgomery Jonathan , Shurina Ben , VanPelt Jamie , Page Richard 
Published: June 2021

Over the years, the continued use of antibiotics has caused an evolutionary defense mechanism in bacteria to emerge, and the resulting antibiotic resistance has become a serious issue. These antibiotic resistant bacteria employ enzymes known as β‐lactamases. These β‐lactamases are able to hydrolyze the β‐lactam ring of many antibiotics such as penicillin and carbapenems, rendering the antibiotic ineffective at killing bacteria. New Delhi metallo‐β‐lactamases (NDM), which utilize a di‐zinc catalytic center, have been observed to undergo several mutations which have led to increased thermal stability and increased Zn2+ affinity when there are low concentrations of Zn2+ present. These mutations have been suggested to enable NDM to exhibit activity in both di‐zinc and mono‐zinc states. Additionally, NDM poses a particular threat as it is able to act on a wide range of current antibiotics. One strategy for combating these β‐lactamases is the use of small molecule inhibitors that will prevent the enzyme from hydrolyzing β‐lactam containing antibiotics, allowing for their continued use. A major challenge is presented in solving the structure of NDM with an inhibitor bound prior to hydrolysis. In order to solve this problem, our lab has engineered a new version of NDM through site directed mutagenesis. We engineered a mono‐zinc version of NDM that has an approximate 10,000 fold reduction in activity while maintaining the global architecture of NDM. The structure of this new NDM variant, NDM‐X, has been solved to 1.6 Å resolution and, due to the reduced catalytic activity, could be used in crystal soaking experiments to obtain the structural information of these protein‐substrate interactions in a pre‐hydrolyzed state. These pre‐hydrolysis enzyme‐substrate complexes may allow for further development and modification of proposed inhibitors to better combat antibiotic resistance.Support or Funding InformationNIH R35 GM128595This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physiological cardiac hypertrophy activates PPARγ/PGC‐1α axis and up‐regulates perilipin family
Authors: Soñanez‐Organis José Guadalupe , Verduzco‐Avila Denisse , Padilla‐Bórquez Diana Lourdes , Del Carmen Castro‐Meza Susana , Rosas‐Rodríguez Jesús Alfredo , Godoy‐Lugo José Arquímides , Ortiz Rudy M 
Published: June 2021

Peroxisome proliferator‐activated receptor γ (PPARγ) and peroxisome proliferator‐activated receptor gamma coactivator 1‐α (PGC‐1α) are coordinately up‐regulated in hypertrophic cardiomyopathy and cooperate to mediate changes in lipid metabolism and storage that are characteristic of and contribute to common forms of heart disease. Previous results in our laboratory suggest that PPARγ regulates the shift in cardiac metabolism during physiological cardiac hypertrophy. On the other hand, the perilipin family (Plin: 1–5) is involved in the formation of lipid droplets in various tissues, and it has been demonstrated that Plin5 participates protecting the heart during myocardial ischemia and diabetic cardiomyopathy. However, the participation of PPARγ/PGC‐1α and the Plin family in physiologic hypertrophy induced by pregnancy and its reversible process (postpartum) are not well defined. We evaluated PPAR (alpha, delta, gamma) transcriptional activity, and PGC‐1α and Plin family gene expression along with triglyceride content before, during, and after pregnancy in the left ventricle of rat. The activity of PPARγ increased 1.6‐fold during pregnancy, and decreased to basal levels postpartum. Expression of mRNA for PGC‐1α increased 18‐ and 11‐fold during pregnancy and postpartum, respectively. Plin1, Plin2 y Plin5 transcript increased 9‐ to 16‐fold and 2‐ to 11‐fold during pregnancy and postpartum, respectively, while expression of Plin3 did not change and Plin4 was not detected. The results demonstrate that in, pregnancy‐induced, physiological cardiac hypertrophy activates the expression of genes involved in lipid storage suggesting that the shift in cardiac metabolism is mediated by the activation of PPARγ/PGC‐1α.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of a moderate physical training protocol on the metabolism hepatic of malnourished juvenile rats
Authors: Lima Talitta Ricarlly , Freitas Cristiane Moura , Silva‐Filho Reginaldo Correia , Braz Glauber Rudá Feitoza , Lagranha Claudia Jacques , Fernandes Mariana Pinheiro 
Published: June 2021

The purpose of this study was evaluate the effects of the moderate physical training on the hepatic metabolism of juvenile rats submitted to protein restriction during critical periods of development. Wistar rats received Normoprotein (protein17%) and Low protein (protein8%) diets throughout gestation and lactation. After weaning (21 days), pups received Labina®. The offspring was submitted to the incremental aerobic run test from the 26th, 27th and 28th days and subdivided into two additional groups according to the practice or not the physical training (Normoprotein Sedentary‐NS; Normoprotein Trained‐NT; Low protein Sedentary‐LS; Low protein Trained‐LT). The animals of NT and LT groups underwent a moderate physical training (60min day/5days/ 4 weeks). At 60 days, the male were euthanized and the liver removed to biochemistry analyzes. Our results showed a decrease on mitochondrial oxygen consumption after ADP addition (State 3, 53%, p<0.01) and respiratory control ratio (RCR, 52%, p<0.0001), additionally we observe increase on mitochondrial swelling (40%, p<0.001) and ROS production (36%, p<0.01) in LS group when compared to the NS group. The levels of lipid peroxidation (42%, p<0.0001) and protein oxidation (81%, p<0.0001) were increased and SH‐content (41%, p<0.0001) was decreased in the LS group when compared to the NS group. The antioxidant enzymes activities as SOD (33%, p<0.0001), CAT (48%, p<0.0001), GPx (49%, p<0.001) and GST (64%, p<0.01) were decreased in the LS group without altering the GSH levels. The metabolic enzymes activities showed a decrease on the CS (28%, p<0.05), no change on PFK1, decrease on G6PDH (54%, p<0.001) and increase on β‐HAD (2.1 fold, p<0.0001) in the LS group when compared to the NS group. In the LT group we observe that moderate physical training induced a significant effect on the all‐hepatic metabolism pathways. Taken together, our results suggest that the physical exercise acted as a non‐pharmacological therapeutic agent capable to minimizing the effects of a protein restriction in the early life of these animals.Support or Funding InformationThis study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES) ‐ Finance Code 001 and Fundação de Amparo a Ciência e Tecnologia do Estado de Pernambuco (FACEPE)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Thyroid hormone regulation of retinoic acid synthesis in brown adipose tissue
Authors: Olson Charles Johan Henrik , Krois Charles Robert 
Published: June 2021

In mice, alterations to vitamin A status through gene knockout or treatment with pharmacological doses of retinoic acid (RA), the active form of vitamin A, affect overall energy metabolism and body weight. Generally, increases in RA lead to increased metabolism and weight loss, and reductions in RA lead to weight gain. One specific effect is that within brown adipose tissue impaired RA synthesis impairs the tissue's ability to generate heat and thus an organism's ability to maintain normal body weight and temperature. We therefore hypothesize that in a cell model of brown adipose tissue, thyroid hormone (T3), a potent activator of brown adipose function, will also increase RA synthesis through induction of retinol and retinal dehydrogenases. Together, these enzymes synthesize RA from the precursor retinol. Overall, our work contributes to a better understanding of factors that impact both obesity and metabolic disease.Support or Funding InformationMinnesota State University, MankatoUndergraduate Research GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dietary iron restriction improvement mitochondrial dysfunction and oxidative stress, and iron supplementation increases oxidative damages in kidneys mitochondria of streptozotocin‐diabetic rats
Authors: Peña‐Montes Donovan , Huerta‐Cervantes Maribel , Trujillo Xóchitl , Huerta Miguel , Montoya‐Pérez Rocío , Cortés‐Rojo Christian , Salgado‐Garciglia Rafael , Saavedra‐Molina Alfredo 
Published: June 2021

Diabetes mellitus (DM) is a multifactorial disease, characterized by a chronic increment in blood glucose (hyperglycemia). In parallel with the growing DM pandemic, there is an increasing burden of DM complications occurring in the majority that suffering, such as diabetic kidney disease (DKD). Furthermore, the chronic hyperglycemia of diabetes results in mitochondrial dysfunctionality followed by an increase in mitochondrial reactive oxygen species (ROS) production and mitochondrial oxidative stress (OE). On the other hand, iron plays an important role in all organism for the maintaining of the physiological homeostasis. However, in diabetes has been reported a disruption of iron metabolism leading to an iron accumulation in kidney. The aim of this study was to evaluate the effect of chronic iron restriction in the diet, and iron supplementation in mitochondrial function and oxidative stress in kidneys mitochondria employing male Wistar rat with experimental diabetes. 28 rats of two‐old months were divided randomly into four groups diabetic rats were administered with a single dose of STZ, (45 mg/Kg of BW in citrate buffer, pH 4.5). Experimental diabetes mellitus with STZ, increase non‐heme iron content in whole‐kidney mitochondria and chronic iron restriction restores oxygen rate consumption (OCR) and GSH:GSSG ratio, and prevents the increment in lipid‐peroxidation and decrease mitochondrial ROS production compared with the diabetic group with a standard normal diet. Meanwhile chronic iron supplementation increases the oxidative damages. Taken together, these results suggest that experimental DM increase mitochondrial iron, and iron restriction in the diet restores mitochondrial functionality and prevents mitochondrial oxidative damage in rat kidneys.Support or Funding InformationThe authors acknowledge to CONACYT (DPM) and Coordinación de Investigación Científica. UMSNH grants (ASM‐2.16).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Expression of Iron Regulatory Proteins in Healthy and Osteoarthritic Chondrocytes
Authors: Rose Brandon J , Behrens Nathan F , Harris Shelby T , Maloy Sarah A , Nelson Tanner K , Smith Jacob F , Starr Evan G , Woolstenhulme Jonathan B , Watt Richard K , Kooyman David L 
Published: June 2021

Iron dysregulation is a known risk factor in the progression of osteoarthritis and is a feature of comorbid syndromes Alzheimer's disease, insulin resistance, and age‐related macular degeneration. Little, however, is known about iron homeostasis in healthy chondrocytes or whether iron dysregulation occurs in osteoarthritis. To gain information on this matter, we performed surgical destabilization of the medial meniscus on the right knee of 8‐week‐old mice. An untreated sham group served as the control. We found and document for the first time that chondrocytes produce hepcidin, and that both hepcidin and ferroportin expression is downregulated in osteoarthritic cartilage to a statistically significant extent. We found, however, that there was no statistically significant change in ferritin expression in osteoarthritic vs. healthy chondrocytes. We submit that this data, in conjunction with observed iron metabolism trends in other tissues, suggests a role for iron dysregulation in the pathogenesis of osteoarthritis.Support or Funding InformationOffice of Research and Creative Activities, Brigham Young UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antioxidant Potential of Artocarpusaltilis Leaf Powder in Alloxan Induced Diabetic Rat
Authors: Ajayi Olubunmi Bolanle , Arowolo Godwin Oluwaseun , Akomolafe Seun Funmilola 
Published: June 2021

The possible protective effect of Artocarpus altilis leaf powder on diabetes‐induced oxidative stress was evaluated in alloxan‐induced diabetic male rat. Albino rats each weighing about 100 ± 25g were divided into five groups (A–E) (where n=8). Group A is the control fed with normal diet, Group D was pre‐treated with supplemented 5% A. altilis leaf powder for four weeks before induction with alloxan. Thereafter, groups B, C, D, and E were induced with 75mg/kg body weight of alloxan. However, group C was treated after induction with 5% A. altilis leaf powder supplemented diet and E with metformin. Significant increase (P<0.05) in lipid peroxidation and decrease in Superoxide dismutase (SOD), Catalase (CAT) and reduced glutathione (GSH), were observed in the diabetic control compared with the control rats. However, pretreatment with A. altilis leaf powder supplemented diet (Grp. D) and treatment of diabetic rats with same diet (Grp. C) resulted in a reduced lipid peroxidation and significant increase (P<0.05) in the activity of SOD, CAT, and GSH concentration in the serum, liver, and kidney of these group of rats compared with the diabetic control. These findings indicate that A. altilis leaf powder supplemented diet has a potential to reduce free radical mediated oxidative stress to cells in experimental diabetic rats. The pretreated A. altilis leaf powder supplemented diet was found to be more effective in restoring the values of these parameters to normal values, thus lending credence to its folkloric usage in the management and/or control of diabetes mellitus and possible use as a nutraceuticalSupport or Funding InformationnilThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physico‐chemical characteristics and antioxidant capacity of chickpea and wheat flour blends
Authors: Sidhu Jiwan S. , Zafar Tasleem A. , Almusallam Abdulwahab S. , Ali Muslim , Al‐Othman Amani 
Published: June 2021

Type‐2 diabetes is becoming a serious metabolic disease in the State of Kuwait. We wanted to make use of chickpea flour which is known to offer many benefits to the diabetic person especially in maintaining their blood sugar levels in acceptable range. The chemical composition and antioxidant capacity of white flour (WF), whole wheat flour (WWF) and chickpea flour (BF), in addition to the effect of replacement of WF and WWF with BF on the Texture Profile Analysis, and objective color of these blends, in terms of L* a* b* values were also investigated. Trolox Equivalent Antioxidant Capacity (TEAC), Malondialdehyde (MDA) and Total Phenolic Content (TPC) values varied significantly among all the three flour samples. WWF had the highest TEAC (117.42/100g) value, followed by WF (73.98/100g) and BF (60.67/100g). The TPC content also followed the similar trend, as the Gallic Acid Equivalent (GAE) values were the highest (8.67 GAE/g) for WWF, followed by WF (5.65GAE/g) and BF (3.45 GAE/g). Compared with WF and WWF, the b* values for BF were the highest (16.89) indicating higher yellowness in this sample. The TPA carried on the WF, WWF and their blends with BF showed significant variations in hardness and compressibility values, dough becoming less hard and less compressible when the replacement of WF and WWF with BF was increased from 0 to 40%. To overcome the deleterious effects of adding BF to WF and WWF on the rheological properties will be an interesting challenge, when a good quality pan bread or Arabic flat bread have to be produced during the follow up study.Support or Funding Information(Study funded by Research Administration, Kuwait University, Project No. WF01/13)(No human subjects used in this study)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Interactions of Perilipin 5 with Cytoskeletal Elements
Authors: Austin Rachel L , Tansey John T 
Published: June 2021

Cardiovascular diseases, obesity, and diabetes are disease that are affecting the American population at alarming rates. Central to these diseases is lipid metabolism and lipid storage. Perilipin 5 is a protein found on the surface of lipid droplets within cells, but has also been found within the cytoplasm, mitochondria, and nucleus, and is implicated in the mobilization of lipid droplets. This mobilization is required to associate triglycerides with mitochondria, where beta oxidation occurs. Cellular trafficking of lipids is also aided by cytoskeletal elements – like actin filaments. These filaments provide a mode for transportation for molecules within the cell. We hypothesize perilipin 5 will interact with cytoskeletal elements. To test this, we are conducting immmunofluorescence on cultured cells expressing perilipin 5 and stained with antibodies against perilipin 5 and fluorescent actin filaments. Evidence of this interactions will add more information about the role of Perilipin 5 in fatty acid oxidation, the dysfunction of lipolysis, and its associated diseases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Crystal Structure of Poly(Aspartic Acid) Hydrolase‐1
Authors: Bolay Austin L , Salvo Henry F , Wallen Jamie R , Weiland Mitch H 
Published: June 2021

Poly(aspartic acid) (PAA) is a biodegradable synthetic polymer that is easily produced through heating aspartic acid followed by the subsequent addition of sodium hydroxide. Polymer applications range from drug delivery and biomimetics to hygiene products. Partial biodegradation of PAA is accomplished using poly(aspartic acid) hydrolase‐1 (PAAH‐1) which selectively cleaves a specific cross‐link. E. coli expressions of recombinant PAAH‐1 showed the production of significant amounts of protein which could be purified using a single Ni‐NTA column. Analysis of the PAAH‐1 sequence using the Phyre2 Protein Fold Recognition Server resulted in a 33% similarity to a “putative” poly(3‐hydroxybutyrate) depolymerase belonging to a family of enzymes that hydrolyze carboxylic ester bonds; however, no known structure of PAAH‐1 has been reported. Protein crystallization screening at the Hauptman‐Woodward Research Institute resulted in numerous protein crystallization hits being identified. Crystallization experiments were optimized in‐house and the structure was determined at 2.45Å using molecular replacement. The progress of PAAH‐1 characterization and its structure will be discussed.Support or Funding InformationNSF‐IUSE Grant: DUE 1611988This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dystrophin Promotes Colorectal Carcinoma Metastasis and Exosome Secretion via Protein‐Protein Interaction with Rab GTPase 3C
Authors: Chen Chi‐Long , Chang Yu‐Chan , Hsiao Michael 
Published: June 2021

RAB GTPases is involved in membrane trafficking (vesicle formation) and cell motility. Recently, exocytotic RABs has been noted that the exocytosis by RABs is correlated with drug resistance and immune response in tumorigenesis. However, the molecular mechanisms of exocytotic RABs in colorectal tumorigenicity remain unknown. RAB GTPase 3C (RAB3C) has been identified as the key component for exosome formation and exocytosis. In clinical colorectal carcinoma patient cohort, high RAB3C expression maintained its independent prognostic significance for both overall survival and disease‐free survival. We further established RAB3C‐based proteomics datasets and mass spectrometry analyses and found dystrophin (DMD) is upregulated in RAB3C ectopically overexpressed colon cancer cell lines. High DMD expression levels were found correlated with poor survival in colorectal cancer patient cohorts. Moreover, Dystrophin‐complex components including dystrobrevin (DTNA) and syntrophin (SNTA1/SNTB1) also showed the same prognosis trends in colorectal cancer patients. We further found that DMD is a rare mutant event in colorectal clinical cohort by next generation sequencing analysis. Our results showed that DMD could be stabilized by RAB3C through protein‐protein interaction. Besides, our results revealed RAB3C co‐localized with dystrophin complex by immunohistochemistry staining analysis. Merged DMD with RAB3C serves as a significant independent prognostic factor in colorectal cancer and is associated with several clinical parameters. In addition, dystrophin complex decreased cell membrane integrity and altered calcium channel activity for exocytosis. In summary, our results identified DMD is a new functional binding protein for RAB3C that affected colorectal carcinogenesis. These findings suggest a new therapeutic strategy for targeting cancer‐specific protein‐protein interactions in the treatment patients with colorectal cancer.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.