bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interethnic Diversity and Association of STAT6 Genetic Variants With Schistosomiasis in West Africa
Authors: Liou Gialeigh , Seamans Brooke , Adedokun Samuel , Ojurongbe Olusola , Thomas Bolaji 
Published: June 2021

Published reports suggests a major role for signal transducer and activator of transcription (STAT6) polymorphisms in driving susceptibility and response to several diseases, including urinary schistosomiasis, showing an association with disease burden. We have shown previously that Th2 cytokine genes (IL‐4, IL‐10 and IL‐13) are differentially regulated in urinary schistosomiasis, with significant interethnic delineation across sub‐Saharan Africa. Therefore, we analyzed the genetic frequency of the STAT6 gene (rs3024974), located in the promoter region, in interethnic and disease groups, as well as evaluate association with urinary schistosomiasis and other disease covariates. Blood and urine samples collected from 114 urinary schistosomiasis patients, recruited from Nigeria were used for DNA extraction and egg counts respectively. Additional genomic DNA samples extracted from 225, 284 and 159 uninfected Africans, African Americans and Caucasians respectively served as uninfected controls. We genotyped these samples for comparative analysis among and between groups, utilizing a polymerase chain reaction‐restriction fragment length polymorphism assay. The prevalence of rs3024974 wild type genotype (CC) was 70.7%, 82.4% and 81.1% for Africans, African Americans and Caucasians respectively, and significantly different between groups (chi square=12.28; p=0.001). Mutant variants (rs302497TT) showed frequencies of 4.9%, 0.4% and 3.2% between groups (chi square=13.53; p=0.003), with similar results obtained for the minor allele, rs302497T (17.1% versus 8.8% versus 11.0% for Africans, African Americans and Caucasians respectively; p=1.42E‐05). Among the schistosome‐infected group, the frequencies of the rs3024974 genotypes CC and CT genotypes were 75.4% and 24.6%; none of the subjects had the TT genotype. The frequencies of the minor allele were 87.7% (rs3024974C) and 12.3% (rs3024974T), with subjects carrying the mutant genotype TT significantly protected from infection (p=0.02), while both CC and CT genotypes show an association with schistosomiasis. Despite minor differences in covariates between infected and uninfected subjects, we found no association between STAT6 (rs3024974) genetic variants with age, gender, packed cell volume, temperature or egg burden. The absence of the mutant allele among infected subjects reveal the necessity of the STAT6 promoter gene in driving susceptibility to, and association with schistosomiasis in Nigeria. Additionally, our results show that its genetic variants are insignificant for driving disease covariates.Support or Funding InformationLaboratory Support and Faculty Development Award, College of Health Sciences and Technology, Rochester Institute of TechnologyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Transcriptional Fusions of Putative G‐protein Coupled‐Receptors from Hookworm (Ancylostoma ceylanicum) Expressed in Caenorhabditis elegans
Authors: Erickson Patti T. , Ratnappan Ramesh , Bernot James , Haile Meseret , Hawdon John M. 
Published: June 2021

Many parasites, including hookworms of the genus Ancylostoma, are specialists and require host‐specific signals to resume development upon infection. Although little is known about the nature of these signaling molecules, evolutionary conservation between hookworms and the model nematode C. elegans suggests that hookworm host‐signal receptors are likely to be G‐protein coupled receptors (GPCRs) that are expressed in amphid neurons. Based on bioinformatic analysis of developmental stage‐specific RNA‐Seq data from A. caninum and A. ceylanicum, predicted hookworm GPCRs with increased expression levels during the infective larval stage 3 (iL3) were identified.Approximately 1500 bp of genomic sequence upstream of the predicted start site for the putative A. ceylanicum GPCRs were fused to green fluorescent protein (GFP) coding sequence to generate promoter‐GFP transcriptional fusion constructs, which were microinjected into C. elegans. Of nine hookworm promoter fusions tested, four drove differential GFP expression in C. elegans tissues, including the digestive tract, pharynx, and a neuron pair. Preliminary analysis identified the neurons as interneurons, potentially involved in locomotion responses to chemosensory input in C. elegans. The putative GPCR encoded by the neuronally expressed gene is upregulated in both A. ceylanicum and A. caninum, suggesting that it may play a general role in hookworm development during host infection. These experiments indicate that hookworm promoters can be expressed in C. elegans, providing a surrogate system for the study of hookworm gene expression patterns.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of Acylated Homoserine Lactone Among Predator‐Prey Interactions of Arthrobotrys oligospora and Caenorhabditis elegans
Authors: Jauregui Mario Richard , Rocha Destany , Ochoa Roxanna 
Published: June 2021

The necessity for biological control agents has increased over the past decade. Many pathogens become resistant to drugs and chemicals, pesticides are harming the environment and genetically‐modified pest‐resistant crops are a problem (Mankau, 1880). It has been previously established that Acylated Homoserine Lactone (AHL) is essential for bacterial cell to cell communication known as quorum sensing. AHL is part of the Lux –R family of enzymes used to transcribe and translate bacterial pheromones (Tsai, Winans, 2011). Studies have shown that the fungal organism, Arthrobotrys oligospora, has a homologous AHL gene in its genome. The parasitic nematode, Caenorhabditis elegans, has been shown to move towards synthetic AHLs. Therefore, we hypothesize AHL acts as an attractant leading C. elegans to A. oligospora, where the fungus traps and kills the nematodes. The entrapment of C. elegans has been observed for many years; however, the mechanism is not understood. A biosensor will be used to detect AHL production in various fungus‐nematode interactions.Support or Funding InformationThe project was supported in part by grants from the Department of Education (Award #PO31S150199), Southern California Edison and through Vanguard University's SURP Program generously supported by the Office of the Provost and the Institute for Faculty Development.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Multi‐Targeted Inhibition of an Essential Bacterial Enzyme
Authors: Soares da Costa Tatiana P. , Gardi Chamodi K. , Christoff Rebecca , Sutton J. Mark , Abbott Belinda M. , Perugini Matthew A. 
Published: June 2021

The cell wall of Gram‐negative bacteria consists of peptidoglycan chains linked together by oligopeptidic sequences comprised of the amino acids L‐Ala, D‐Ala, D‐Glu and meso‐diaminopimelate (DAP). Meso‐DAP is synthesized via the DAP pathway that also yields the basic amino acid, L‐lysine. Gene knock‐out studies show that enzymes functioning in the DAP pathway are essential to bacteria, including dihydrodipicolinate synthase (DHDPS). DHDPS is an allosteric enzyme that catalyzes the first‐committed and rate‐limiting step in DAP biosynthesis. It forms a homo‐tetrameric structure that gives rise to at least two ‘druggable’ sites, namely (a) the active site and (b) the allosteric site, which binds lysine to mediate a feedback inhibition response. Given its essentiality to bacteria and absence in humans, DHDPS represents a valid but as yet unchartered target for antimicrobial development. Recently, we have developed two classes of small molecule inhibitors that target the DHDPS active site and allosteric site using a contemporary multi‐disciplinary workflow spanning biophysics, biochemistry, medicinal chemistry, microbiology and structural biology. Inhibition studies in combination with biophysical techniques have demonstrated that these compounds are broad‐spectrum inhibitors of bacterial DHDPS in vitro, representing the most potent DHDPS inhibitors discovered to date. Using viability and time‐kill assays, these inhibitors have been shown to be bactericidal against both drug‐sensitive and drug‐resistant strains of Gram‐negative bacteria (MIC = 8 – 64 μg/ml), including Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli, but were non‐toxic against cultured human cells at >1024 μg/ml. Importantly, these compounds have been shown to synergize with FDA‐approved classes of antibiotics, including β‐lactams, fluoroquinolones, rifampicin and aminoglycosides. This study illustrates the potential for DHDPS inhibitors to be developed into a new class of antimicrobials with excellent potential to be combined with current antibiotics to yield innovative multi‐targeted formulations to minimize the emergence of resistance.Support or Funding InformationAustralian National and Health Medical Research Council (NHMRC)and CASS FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Novel Functionalization of Azetidines
Authors: Gianatassio Ryan , Kadish Dora 
Published: June 2021

While azetidines have always been known to be structurally strained and difficult to synthesize, a new reaction has been invented that shortens their preparation time significantly. Out of the top 200 marketed drugs, only two have azetidine‐based functional groups. Thus, the untapped prevalence of azetidines in drug discovery was the one of the driving forces to pursue this project. The proposed synthesis allows for the regioselective preparation of functionalized azetidines. Previous syntheses of azetidines are generally 3–5 steps, while this proposed synthesis can be performed in one‐pot and is operationally simple. It is envisioned that this method will be adopted medicinal chemists to expand chemical space and improve structure‐activity relationships (SAR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigation Of Phosphoserine Aminotransferase 1 And Its Role In Breast Cancer Progression
Authors: Clem Brian , Metcalf Stephanie , Kruer Traci , Klinge Carolyn 
Published: June 2021

Metastasis and endocrine resistance are two factors that complicate therapeutic intervention in breast cancer patients and lead to poorer overall survival. Metastasis is known to be responsible for 90% of cancer related deaths, and is especially prevalent in triple negative breast cancer (TNBC); while endocrine resistance can affect up to 50% of patients diagnosed with estrogen receptor positive breast cancer (ER+BC). Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step within de novo serine biosynthesis and increased expression of enzymes in this pathway have been linked to progression of breast cancer and poor clinical outcomes. Within our preliminary retrospective analysis of human breast cancer patients, we identified an inverse association with elevated transcript levels and poorer distant metastasis free survival, which, coupled to a previously reported correlation of PSAT1 with response to endocrine therapy in patients with ER+BC, we postulate that PSAT1 contributes to breast cancer progression through promotion of metastasis and/or endocrine resistance. To initially determine relevance for PSAT1, immunohistochemistry was performed to determine PSAT1 expression in human breast cancer patients. We found that PSAT1 expression is increased through breast cancer progression, with highest levels observed within metastatic conditions. To investigate the metastatic contribution of PSAT1, we silenced PSAT1 expression within the triple negative breast cancer cell line (TNBC), MDA‐MB‐231. While suppression of PSAT1 had no effect on proliferation, there was a significant decrease in the motility and invasion of these cells. In addition, decreased PSAT1 substantially inhibited tumor nodule formation following tail‐vein injections of MDA‐MB‐231 cells in vivo. To investigate PSAT1's role in endocrine resistance, we used parental MCF‐7 cells and an endocrine‐resistant derivative cell lines and found that resistant cells exhibited higher PSAT1 expression compared to parental MCF‐7 cells. Lastly, suppression of PSAT1 trended to sensitize the resistant cells to 4‐hydroxytamoxifen treatment. Taken together, these data indicate that PSAT1 may contribute to the progression of human breast cancer via either metastasis or endocrine resistance or both and could potentially serve as a viable target for new therapies.Support or Funding InformationSupported by a Research Scholar Grant, RSG‐13‐139‐01 from the American Cancer SocietyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Selenium and Sex: Competition Between Brain and Testes for Selenium Results in Male‐ Specific Consequences in Mice and Men
Authors: Berry Marla J. , Pitts Matthew , Kremer Penny , Hashimoto Ann , Seale Lucia , Ogawa‐Wong Ashley , Torres Daniel 
Published: June 2021

Selenium (Se) is essential for normal neurological development and male fertility in mammals, setting the stage for competition between brain and testes when Se is limiting or its distribution is perturbed. Se supplementation studies in humans, and genetic knockout (KO) of selenium transport and recycling proteins in mice, unveiled the surprising finding that males exhibit more severe consequences than females when selenium homeostasis is altered. Se is also critical for thyroid hormone action, with implications for many downstream effects on endocrine and metabolic pathways. In one Se supplementation study in humans, an increased risk of type 2 diabetes (T2D) was reported in men with high baseline Se. However, other studies found no correlation between increased Se and T2D susceptibility, and the discrepancies in these human trials are controversial. The objective of our current studies is to elucidate the mechanisms underlying the sex specific differences in phenotype observed following disruption of the Se transport and recycling pathways in mice, the effects of varying dietary Se in combination with genetic KO, and the implications for human dietary Se requirements. Mice with KO of the Se recycling enzyme, selenocysteine lyase (Scly), exhibit metabolic syndrome that is more pronounced in males. Double KO (DKO) of Scly and the Se transport protein, Selenoprotein P (Sepp1) resulted in low viability and severe neurological deficits, including seizures. These traits are also more pronounced in males. Strikingly, while female DKO mice exhibit milder neurological deficits, they develop hallmarks of metabolic syndrome not seen in male DKO mice. Pre‐pubescent castration of male mice reversed the DKO neurological phenotype and partially attenuated the Scly KO metabolic phenotype. Assessment of brain and testes Se levels in these mice suggests that competition for available Se between these two tissues is a significant contributor to the observed phenotypes. However, preliminary data from testosterone replacement studies indicate that there are also hormone‐dependent mechanisms at play. These studies unveil novel insights into the complex mechanisms involved in Se distribution and utilization, and may be informative regarding sex specific Se requirements in humans.Support or Funding InformationSupported by grants NIH NIMHD G12MD007601, and NIH NIDDK R01DK047320 to MJB.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Role of Sphingosine Kinase 2 in Chronic Alcohol‐Induced Liver Injury and Disease
Authors: Kwong Eric K. , Li Xiaojiaoyang , Liu Runping , Wang Xuan , Hylemon Phillip B. , Zhou Huiping 
Published: June 2021

IntroductionAlcoholic liver disease (ALD) is one of the most common liver diseases worldwide. Currently, there are no effective therapeutics against ALD and liver transplantation remains the only curative option for end stage liver disease. Hepatic steatosis is a characteristic hallmark of alcohol‐induced hepatocyte injury and we have previously reported that sphingosine kinase 2 (SphK2) deficient mice on an alcohol diet develop overt fatty liver compared to wild type in the chronic and binge drinking NIAAA mouse model. In addition, there was significant downregulation of hepatic lipid genes and upregulation of pro‐inflammatory mediators in SphK2 deficient mouse livers. However, there are currently no effective mouse models that can recapitulate ALD progression and our aim is to determine whether SphK2 deficient mice on a chronic alcohol diet can produce advanced ALD pathology.MethodsMouse primary hepatocytes derived from wild type or SphK2 knockout (KO) mice were treated with different concentrations of ethanol (0–200 mM) for various time points (0–24h). For in vivo studies, C57BL/6J wild type and SphK2 KO mice (10–14‐week‐old, male and female) were fed a Lieber‐DeCarli 5% ethanol diet for 60 days. Cultured hepatocytes and liver tissue were harvested for RNA and protein using standard laboratory protocols. Quantitative RT‐PCR and western blot analysis were used to determine relative mRNA levels and protein levels, respectively. Hematoxylin and eosin (H&E) staining was performed on liver tissue for pathological analysis using standard laboratory protocols. Immunofluorescence was performed by staining frozen liver sections with anti‐CD11b antibody conjugated with FITC.ResultsEthanol increased the mRNA and protein expression levels of SphK2 in mouse primary hepatocytes (MPH). H&E staining revealed that SphK2 KO mice on an 8‐week alcohol diet produced extensive steatosis and steatohepatitis compared to wild type mice and the NIAAA binge model. In addition, liver enzyme assay levels of ALT, AST and ALP are significantly increased in SphK2 KO mice suggesting increased liver injury and inflammation. The mRNA expression levels of hepatic lipid genes and bile acid synthetic gene mediators (SIRT1, CYP7A1, CYP7B1 and FXR) are downregulated and pro‐inflammatory mediators (IL‐1β, F4/80 and TNFα) are upregulated in SphK2 KO mice compared to wild type. Immunofluorescent staining of CD11b reveals increased macrophage infiltration in SphK2 KO mouse livers.ConclusionSphK2 is involved in hepatic lipid metabolism and plays an important role in ameliorating alcohol‐induced hepatic injury. Our results suggest that SphK2 KO mice on a chronic alcohol diet exacerbate alcohol‐induced liver injury and promotes ALD progression.Support or Funding InformationNIDDK R01NIAAA F30This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Bias in Cytokines Transported by High‐Density Lipoproteins in Patients with Coronary Artery Disease
Authors: Creasy Kate Townsend , Stock Eveline , Pullinger Clive R. , Malloy Mary J. , Kane John 
Published: June 2021

Inflammation plays an important role in the induction of Coronary Artery Disease (CAD) and the progression to deadly coronary syndromes. Cytokines are key mediators of inflammation, both in pro‐ and anti‐inflammatory capacities. We have recently discovered that cytokines are transported by high‐density lipoproteins (HDL), suggesting a novel mechanism contributing to the anti‐inflammatory effects of HDL. We examined the HDL‐associated cytokine profiles of male and female patients with CAD to better understand the differences in coronary disease presentation and therapeutic response between men and women.MethodsPatients with confirmed CAD, defined by history of myocardial infarction, coronary artery bypass surgery, or angiography, with controlled serum lipid levels were included in the study. Native HDL species were isolated from plasma samples by selected‐affinity immunosorption. Plasma and isolated HDL samples were assayed for cytokine content by a multiplex array detecting the quantity of 35 cytokines.ResultsThe majority of cytokines assayed were measurable in HDL samples. The distribution of HDL‐associated cytokines varied significantly between males and females. Female HDL samples indicate a much greater degree of remodeling of cytokine cargo than males. Cluster analysis of cytokine expression patterns suggests a difference in inflammatory pathway activation and response in females with CAD.ConclusionsThe cytokines transported by HDL in CAD patients differs greatly between men and women. The pattern of HDL‐associated cytokines provide new insights into the inflammatory processes contributing to CAD in a sex‐dependent manner. The amount of cytokine‐HDL remodeling is exhibited to a greater degree in females; the physiological relevance of this phenomenon is unknown. We aim to elucidate the mechanism of HDL transport of these cytokines and the clinical implications of sex differences in inflammatory response in CAD in future studies.Support or Funding InformationThis work is supported by the Read Family Foundation and the Campini Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulation Of Cellulase Activity Of Fungi Isolates For Bioethanol Production By Using Cassava Bagasse
Authors: Igwo‐Ezikpe Miriam Nwanna , Okunowo Wahab Oluwanisola , Ayanshina Oluwamuyiwa 
Published: June 2021

The continual energy demand worldwide and the progressive demising of oil reserves motivate the search for alternative energy resources especially from renewable sources such as agrowaste biomass. This study investigated the optimization of cellulase activity for bioethanol production through modulation of the cellulase activity of three fungi isolated from cassava bagasse. Fungi were isolated from cassava bagasse and genetically identified using 16S rDNA. The isolates were screened for cellulase enzyme production by filter paper and carboxymethylcellulase (CMC) assay. Physiochemical factors (Temperature, moisture content, nitrogen source, pH, substrate and inoculum concentration) which affect the cellulase activity were evaluated. Three fungi isolates were identified as Trichoderma Spp, Aspergillus spp and Rhizopus spp. The exoglucanase and endoglucanase had optimum activity at 25°C and 35°C, moisture content effect at 40 ml, pH 7, inoculum concentration of 10 – 20 ml and substrate concentration of 10–15g. Peptone greatly enhanced enzyme production better than urea and ammonium sulfate at day 3 incubation for both the exoglucanase and endoglucanase. Present study established the potential of these fungi isolates from agrowaste as good cellulolytic enzyme for potential use in bioethanol production.Support or Funding InformationTETFUND Research Grant Award, 2015This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.