bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative splicing of Cav1.3 in the mouse
Authors: Sabzanov Samuel , Mirkovic Jovan , Wang Ruizhi , Hossain Faruk , Ruggiu Matteo 
Published: June 2021

L‐type voltage‐gated Ca2+ channel Cav1.3, which is encoded by CACNA1D, is one of four poreforming 1α‐subunits and it has been shown to undergo alternative splicing. Mutations of CACNA1D have been associated with neurological disorders such as Parkinson's Disease and Epilepsy. Previous studies have shown that a Calmodulin‐IQ domain present in some splicing isoforms of CACNA1D is critical for Cav1.3 binding affinity to the pharmaceutical inhibitor drug DHP. Our results further characterize the alternative splicing of Cav1.3 for the development of further potential clinical applications.We were able to confirm four alternatively spliced regions, E8–E11, E12–E15, E32–36, and E46–E48 in Cacna1d. By semi‐quantitative RT‐PCR analysis, we found alternatively spliced variants of Cacna1d that were expressed at higher levels in brain‐derived tissues when compared to non‐brain derived tissues. Given how previously characterized alternatively spliced exons encode protein domains that are targeted by drugs that selectively inhibit Cav1.3 activity, the alternative splicing events described could also be important for drug discovery and therapeutic intervention.Support or Funding InformationNational Institute of General Medical Sciences Grant 1R15GM119099‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel AKT Activator SC79 Protects Airway Epithelial Cells Against Cadmium‐Induced Lung Injury
Authors: Gopallawa Indiwari , Lee Robert J 
Published: June 2021

Study ObjectiveActivation of constitutively expressed nitric oxide synthase (NOS) isoforms has beneficial effects via increased ciliary beat frequency and antibacterial nitric oxide (NO) production in the airway and anti‐inflammatory effects in other tissues. It is known that activation of Ca2+/Calmodulin can activate endothelial (e) NOS and subsequent NO production. However, other signaling pathways (e.g., AKT, also known as protein kinase B) can activate e/neuronal (n) NOS. These signaling pathways have not been investigated in the airway cells. We hypothesized that activation of the AKT/eNOS pathway, which also activates nuclear factor erythroid 2–related factor 2 (NRF‐2) in many tissues, may have protective effects in lung cells during injury. We tested the responses of airway cells to SC79, a novel AKT activator. To model epithelial injury, we used cadmium (Cd2+), a highly reactive component of cigarette smoke that has been shown to disrupt epithelial barrier integrity and cause oxidative stress in some cell types.MethodsTo test if SC79 up‐regulates phospho (p)‐AKT, p‐eNOS, and/or NRF‐2 levels, A549 human type II alveolar epithelial cells were stimulated with SC79 for 2 hrs ± pre‐treatment with phosphoinositide‐3‐kinase (PI3K) inhibitor LY294002 for 1hr. Cell lysates were subjected for Western blotting. To determine the nuclear translocation of NRF‐2, cells were subjected to immunofluorescence (IF) with a specific NRF‐2 primary antibody after stimulation with SC79 for 2 hrs. To test if SC79 could protect against disruption of tight junction integrity during lung injury, 16HBE human bronchial epithelial cells were pretreated with Cd2+ for 1hr and then stimulated with SC79 for an additional 2hrs. Transepithelial electrical resistant (TEER) measurements were taken using an epithelial ohm meter.ResultsWe observed an approximately 2‐fold induction of p‐AKT, p‐eNOS and NRF‐2 with SC79 treatment that lasted >2 hrs. Pre‐incubation with LY294002 blocked p‐AKT, p‐eNOS, and NRF‐2 induction. IF revealed a 2‐fold increase in nuclear‐localized NRF‐2 upon SC79 stimulation. Additionally, exposure of 16HBE cells to Cd2+ led to an almost complete reduction in TEER, which was blocked by SC79 for up to 24 hrs.ConclusionsOur preliminary data suggest that SC79 upregulates pAKT, peNOS and NRF‐2 in lung cells through a mechanism involving PI3K. Furthermore, treatment with SC79 protects the epithelial integrity against cadmium‐induced injury. Future work will be directed toward testing the role(s) of eNOS and Nrf2 in the protective effects of SC79.Support or Funding InformationR01DC016309, R21AI137484This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Genesis of Antibiotic Resistance: XLI Herd Immunity Mitigates Waning Immunity
Authors: Martinez Thaliza , Soto Elsa , Escobedo Julio , Mendoza Jonathan , Barrientos April , Chavez Norma , Perez Ashley , Riojas Robert , Galindo Oscar , Kannan Subburaj 
Published: June 2021

Based on the observations from the livestock show in the Maverick County, Texas, (MCJLS) (January 2006 to January 2017), and data analysis from the Texas Department of State Health Services, Health and Human Services (TDSHS‐HHS): Pertussis Emerging and Acute Infectious Disease Infectious Disease Control Unit (IDCU) and CDC, a prototype for “Transmission Model” conferring the herd protection (Herd Immunity) in combination with WASH interventions is presented here. Pertussis, a respiratory illness commonly known as whooping cough, is a contagious disease caused by Bordetella pertussis. The respiratory infection is spread via aerosol (in bacteria‐contaminated air droplets) from an infected person's cough or sneeze. Transmission often occurs from older family members to infants or children. Five doses of the DTaP vaccine, is recommended while protection gained from pertussis vaccines decline over time referred as “waning immunity.” To counter the decrease in immunity, a TDaP vaccine, a booster vaccine for tetanus and diphtheria with limited protection for pertussis. Here we present a hypothesis that immunity acquired through “community living inclusive of herd of livestock” (Herd) by the agrarian community mitigate the waning immunity there by confer the protection from the pertussis despite the observed antibiotic resistance observed across the nation and also emerging trend across the globe. Annually the MCJLS in Eagle Pass, Texas with over 300 youth exhibitors, presenting steers, goats, lambs, Hogs, and also chickens. Our observations and information gathered during the past ten years of the stock show could be best summarized as the proximity and duration of the exposure to the livestock animals and community (model) living represent the “WASH” interventions suggested in the transmission model for “Herd Immunity” (Am J Trop Med Hyg. 2016; 95(5):1201). Based on the Texas ‐ Pertussis Incidence Rates Maps by Year, Maverick County has relatively lowest pertussis incidence. Hypothetically, the scheduled DTap/TDap vaccinations conferred immunity weakens over the period of time would make the HSR8 susceptible for the pertussis which is contrary to the incidence report of TDSHS‐HHS‐IDCU. Furthermore, community living in HSR8 exemplifies the community model conferring cross protection among the agrarian community members, in addition to the protection from the scheduled pertussis immunization in combination with WASH interventions serve as a prototype for “Transmission Model” for “Herd Immunity”Support or Funding InformationSupported by the Professional Development Funds by SWTJC to Subburaj KannanThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Whole egg consumption increases plasma choline and betaine without affecting TMAO levels and gut microbiome in overweight postmenopausal woman
Authors: Zhu Chenghao , Sawrey‐Kubicek Lisa , Bardagjy Allison S. , Houts Hannah , Zhang Ruihan , Xu Weiqing , Rhodes Chris H. , Sacchi Romina , Randolph Jody M. , Steinberg Francene M. , Zivkovic Angela M. 
Published: June 2021

As a crucial part of the symbiotic system, the gut microbiome has been shown to be a metabolic organ that presents important connections to many diseases and conditions, including cardiovascular diseases (CVD), the world wide leading cause of death. Trimethylamine N‐oxide (TMAO) is a plasma metabolite that is positively correlated with CVD. Trimethylamine (TMA) is produced by gut bacteria from dietary choline, betaine, or L‐carnitine, and is then converted in the liver to TMAO, which in turn affects hepatic and intestinal lipid and cholesterol metabolism. Because eggs are rich in choline, it has been speculated that their consumption may increase plasma TMAO. The objective of this study was to examine the effect of two eggs per day on plasma TMAO level and how it is related with gut microbiome composition in mildly hypercholesterolemic postmenopausal women. In this randomized, cross‐over study, 20 overweight human subjects were given two whole eggs and the equivalent amount of yolk‐free substitute as breakfast for four weeks, in randomized order, with a four‐week washout in between. Fasting blood draws and stool were collected at the beginning and of each treatment period. Plasma TMAO, choline, betaine and other metabolites were analyzed using LC/MS, while gut microbiome composition was analyzed using 16S amplicon sequencing. Plasma choline and betaine were significantly increased after whole egg but not yolk‐free substitute, however TMAO level was not significantly affected by treatments. Gut microbiome composition showed large inter‐individual variability at baseline and in response to the treatments. Parabacteroides, Ruminococcus, and Faecalibacterium were slightly increased after whole egg but not yolk‐free substitute for the majority of the subjects, while Bilophila slightly increased after yolk‐free substitute but not whole egg. The consumption of two eggs per day in overweight, postmenopausal mildly hypercholesterolemic women significantly increased plasma choline and betaine, but not TMAO, with a subtle effect on gut microbiome composition.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Gut Microbiome on Induction of Obesity
Authors: Hanafi Ihab Sheikh , Gupta Akash , Ayar Mirat , Doke Saloni 
Published: June 2021

Obesity is considered as a multifactorial disease which depends on the complex interaction of host genetics, diet and other environmental factors. Specific alterations in gut microbiota can lead to obesity. There are a few organisms in the gut which have a great influence by the diet we eat. Organisms such as Actinobacteria, Firmicutes and Bacteriodetes are some of the common ones. The role of the gut microbiota in understanding the onset and development of obesity is gaining importance. This review covers the latest available data regarding the influence of different factors on gut microbiota in relation to obesity. Potential Therapeutic Targets and Probiotic Treatment –The gut bacteria model attributes obesity to the variable makeup of gut microbiota and its ability to modulate host energy homeostasis, adiposity and inflammation. To counteract these Student effects, strains of probiotics have been developed to manipulate gut microbiomes and improve health. This highlights recent human study data assessing the effects of probiotic supplementation on the prevention and treatment of obesity.Support or Funding InformationDr. Rajeev Pandey ‐ Department of Biochemistry, Spartan Health Sciences University, St. Lucia, West IndiesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Designer Biosynthetic Pathways for Photosynthetic Biofuels and Bioproducts: Opportunities and Challenges
Authors: Lee James Weifu 
Published: June 2021

With synthetic biology, genetically engineered (GE) cyanobacteria are now a potential photosynthetic platform for bioproducts, in that genetic transformation with a series of transgenes can encode for biosynthetic pathways to enable the conversion of CO2, water and sunlight to biofuels (e.g. butanol). This presentation will disclose designer biosynthetic pathways for photosynthetic production of bioproducts such as butanol and/or related higher alcohols from carbon dioxide and water. The designer photosynthetic organisms are created such that the endogenous photobiological regulation mechanism is tamed, and the reducing power (NADPH) and energy (ATP) acquired from the photosynthetic process are used for synthesis of butanol and/or related higher alcohols from carbon dioxide and water. This photosynthetic biofuels‐production method eliminates the problem of recalcitrant lignocellulosics by bypassing it. Furthermore, this approach enables the use of seawater and/or groundwater for photobiological production of higher alcohols (such as 1‐butanol) without requiring freshwater or agricultural soil, since the designer photosynthetic organisms can be created from certain marine algae and/or cyanobacteria that can use seawater and/or certain groundwater. However, there are still significant challenges. For example, it is also important to understand the bio‐risk of such organisms before the synthetic biology approach could be used for commercial application. Recently, using plasmid‐transformed cyanobacteria, we experimentally demonstrated that the horizontal gene transfer from GE cyanobacteria to E. coli could occur as soon as 1–3 days of liquid co‐cultures. On the other hand, there was no detectable transfer event for the integrated transgenes so far. These results suggested that even though GE cyanobacteria carrying integrated transgenes possess a more permanent change in the genomic DNA, the bio‐risk of these GE organisms in the context of gene sharing is less severe than plasmids‐carrying GE cyanobacteria. In any case, biosafety is still a potential challenge that must also be addressed.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does Urbanization Drive Adaptive Evolution in White Clover (Trifolium repens)?
Authors: Akinwole Philips , Sanders Anya , Golde Spencer 
Published: June 2021

Urban areas are functioning ecosystems with profound effects on the ecology and evolution of organisms. In fact, urban ecosystems with myriad deviations from natural systems provides potent evolutionary stimuli, however, the mechanisms through which urbanization drives natural selection on populations are poorly understood. To facilitate our understanding of the selective factors driving adaptation in cities, we examined adaptive phenotypic changes by quantifying the relative frequency of cyanogenesis (hydrogen cyanide production after tissue damage) in 110 white clover (Trifolium repens) populations along urbanization gradients in three Midwest (USA) cities. White clover is naturally polymorphic for cyanogenesis; a chemical defense against herbivores. We found that the frequency of cyanogenic plants within populations increased towards the urban center in two of three cities, but no consistent pattern in genetic diversity in one city. The area of a city strongly predicted the average cyanogenesis frequency within a city. Population density did not account for significant variations in the clines along urbanization gradient. Our study suggests that plant populations are adapting to urbanization gradients, but more studies are needed to assess whether the capacity of this species to adapt to urban ecosystems is a general phenomenon.Support or Funding InformationWe thank Biology Department, DePauw University, Greencastle, IN for funding.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Functional characterization of microsomal fatty acid desaturation pathway genes in Buglossoides arvensis: A stearidonic acid rich oilseed plant
Authors: Prasad P , Sreedhar RV 
Published: June 2021

Buglossoides arvensis seed oil contains a significant amount of stearidonic acid (SDA, 18:4 n−3), an unusual omega‐3‐fatty acid with nutraceutical potential superior to α‐linoleic acid (18:3 n−3). Stearidonic acid biosynthesis occurs by sequential desaturation of oleic acid, linoleic acid and α‐linolenic acid by Delta‐12‐desaturase (FAD2), Delta‐15‐desaturase (FAD3) and Delta‐6‐desaturase (D6D), respectively. Molecular characterization of these enzymes was essential to exploit them as potential target genes for transgenic production of SDA in traditional oilseed crops. In the present study, putative full‐length coding sequence of BaFAD2, BaFAD3 and BaD6D genes were identified from B. arvensis developing seed transcriptome data (NCBI SRA ID: SRX2191688). Absolute quantification of gene expression levels by quantitative RT‐PCR showed that BaFAD2, BaFAD3 and BaD6D genes were ubiquitously expressed in both vegetative and reproductive tissues but with different levels of transcript abundance. BaFAD2, BaFAD3 and BaD6D were cloned in yeast expression vector pYES/NTC and were functionally characterized by heterologous expression in Saccharomyces cerevisiae strain INVSC1. Overexpression followed fatty acid feeding studies in INVSC1 strain revealed that the encoded enzyme activities of BaFAD2 and BaFAD3 efficiently converted oleic acid and linoleic acid into linoleic acid and α‐linolenic acid, respectively. BaD6D efficiently converted both linolenic and α‐linolenic acid substrates in to γ‐linolenic acid and stearidonic acid, respectively. In conclusion, the identification and characterization of these new fatty acid desaturase genes not only provide an insight into the biosynthesis of SDA in B. arvensis but also expand the repository of fatty acid desaturase targets available for genetic engineering of omega‐3 fatty acid traits in traditional oilseed crops.Support or Funding InformationThis research is financially supported by the Council of Scientific and Industrial Research (CSIR), New Delhi, under the 12th five‐year plan project LIPIC (BSC0401). Prasad P is grateful to UGC, New Delhi, India for providing senior research fellowship and United States‐India Educational Foundation, India for providing Fulbright Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Topical Application of Wogonin Provides a Novel Treatment of Knee Osteoarthritis
Authors: Smith Jacob F , Starr Evan G , Goodman Michael A , Hanson Romney B , Palmer Trent A , Woolstenhulme Jonathan B , Weyand Jeffery A , Sterling Matthew T , Marchant Andrew D , Rose Brandon J , Porter James P , Eggett Dennis L , Kooyman David L 
Published: June 2021

Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain, decreased functional mobility, and deformation of articular cartilage and consequentially diminishing quality of life. Wogonin (WG), a compound extracted from the Skullcap Baicalensis plant, has been shown to have anti‐inflammatory effects on the Toll‐like Receptor 4 (TLR‐4) inflammatory pathway and antioxidant properties via Nrf2. We have shown that TLR‐4 is a major receptor for pain in OA. In our study, we examined the pain reducing, anti‐inflammatory, and chondroprotective effects of WG when applied as a topical cream (TC). After destabilizing the menisci of mice to induce OA, we examined the severity and progression of OA with and without the topical application of WG. Using a running wheel to track mice activity, we found that mice with WG treatment were statistically more active than mice without WG treatment. OA progression analyzed using Modified Mankin and OARSI scoring showed a significant attenuation of OA severity among mice treated with WG. Immunohistochemistry revealed a significant decrease in protein expression of TGF‐β1, but no significant differences were found among the biomarkers HTRA1, MMP‐13, or BMP‐2, suggesting an alternative pathway of cartilage rescue.Support or Funding InformationBYU Office of Research and Creative WorksThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prospective Changes in Fasting Glucose Inversely Affects Spexin Levels in Females with Prediabetes
Authors: Al‐Daghri Nasser , Wani Kaiser , Yakout Sobhy , Al‐Hazmi Hazim , Amer Osama , Hussain Syed Danish , Sabico Shaun , Almusharaf Sara , Alenad Amal , Alokail Majed , Clerici Mario 
Published: June 2021

BackgroundSpexin (SPX) is a novel peptide thought to have a role in various metabolic regulations. Given its presumed body‐weight regulatory function, we aimed to determine whether lifestyle intervention programs focusing on weight loss and improvement in fasting glucose (FG) among people with impaired glucose regulation also induces changes in circulating levels of SPX.Materials and MethodsA total of 160 Saudi males and females with prediabetes were randomly selected from a larger cohort of 294 who underwent a 6‐month lifestyle modification and/or metformin treatment to improve their glycemic status. Participants were split in two groups based on differences in glucose levels post‐intervention, with the first 50% (improved group) having the most significant reduction in FG. SPX was measured in both time‐points.ResultsChanges in SPX was significant only in this group [baseline median (Q1–Q3) 164pg/ml (136–227) vs follow‐up 176pg/ml (146–285); p<0.01]. When stratified by sex, the significant increase was observed only in females [159pg/ml (127–252) vs 182.5 (152,369.1); p<0.01], not in males. Furthermore, SPX levels showed a significant inverse association with FG (β=−0.22, p=0.003) only in females after adjustment for age and BMI.ConclusionsThe study demonstrated that prospective changes in FG inversely modulates SPX levels in a sexually dimorphic manner.Support or Funding InformationDeanship of Scientific Research, KSU and the Chair for Biomarkers of Chronic Diseases (CBCD), Biochemistry Department, College of Science, King Saud University
Association of spexin with glycemic indexes. Fasting glucose (3A), insulin (3B) and HOMA‐IR (3C) on X‐axis and spexin on Y‐axis. Significant inverse correlations between SPX and glycemic indices were seen only in females. “r” depicts pearson correlation coefficient and “p” is the associated p‐value. P‐value <0.05 is considered significantimageAssociation of spexin with glycemic indexes. Fasting glucose (3A), insulin (3B) and HOMA‐IR (3C) on X‐axis and spexin on Y‐axis. Significant inverse correlations between SPX and glycemic indices were seen only in females. “r” depicts pearson correlation coefficient and “p” is the associated p‐value. P‐value <0.05 is considered significantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.