bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of distal regulatory regions for the human LAT gene (946.11)
Authors: Finco Timothy , Glowka Lena , Son Geurim 
Published: June 2021

The human LAT gene encodes a transmembrane adaptor protein linking receptor engagement to the activation of downstream signaling pathways. This gene, highly conserved among mammals, is critical for the development and/or function of T cells, mast cells, Natural Killer cells, and megakaryocytes/platelets. Previously, we characterized the LAT promoter region and identified members of the Ets and Runx family of transcription factors as important regulators of LAT gene expression. In the present study, we sought to identify and characterize distal control regions that also contribute to LAT gene expression. Using a variety of criteria, including DNase hypersensitivity, sequence conservation, the presence of various histone modifications, and RNA polymerase binding, we identified three regions, either within introns or downstream of the gene, that displayed features consistent with enhancer elements. One of these regions displayed significant enhancer activity in a transient transfection assays. Further characterization of this region as well as the identification and testing of additional potential LAT enhancer regions will be presented.Grant Funding Source: NIH grant #11255497
Hereditary kidney cancer models for understanding the cancer genome (95.2)
Authors: Spellman Paul 
Published: June 2021

Von Hippel‐Lindau syndrome manifests primarily as hereditary kidney cancer. The syndrome is caused by single loss of function alleles in the VHL tumor suppressor that act in an autosomal dominant pattern. Patients with the syndrome develop clear cell kidney cancers in which the wild‐type germline allele is mutated or lost. The penetrance of the phenotype is so severe that most patients develop multiple independent tumors because of the somatic mutations are distinct.My group in collaboration with Marston Linehan's group have sequenced the genomes of 43 tumors from seven individuals as well as matched normal DNA. I will present an analysis of mutation spectra in the samples and show patterns that suggest individual level biases in those spectra. Further, I will present analyses of the genomes that suggests guiding biases that have influenced the development of tumors guided by the host genome.
Filamin A is required for HIV‐1 Vpu to promote HIV‐1 release (950.2)
Authors: Dotson Dominique , Liu Ling , Sutton Jessica , Dong Xinhong 
Published: June 2021

The interferon‐induced tetherin is a restriction factor that inhibits the release of HIV‐1 and other enveloped viruses from infected cells. The unique topology of tetherin, featured with two different membrane anchors at the opposite ends, enables it to capture the mature virions at the cell surface through a direct tethering mechanism. HIV‐1 has evolved the strategy to overcome tetherin restriction by encoding an accessory protein, Vpu. HIV‐1 Vpu neutralizes tetherin through multiple mechanisms. Recently, we identified that the host cytoskeletal component, filamin A (FLNa) acts as a cofactor in HIV‐1 assembly and release. By cell‐based assays, we demonstrated that FLNa was capable of binding tetherin. FLNa depletion increased steady‐state and cell surface levels of tethrin expression, whereas FLNa overexpression reduced tetherin expression. Furthermore, FLNa depletion or overexpression redistributed tetherin subcellular localization. These findings suggest that FLNa is involved in tetherin turnover by mediating tetherin trafficking pathways. Transmission electron microscopy studies illustrated that FLNa depletion induces a defect in HIV‐1 particle release, characterized with virions tethered to each other as well as to cell surface. Finally, virus release experiments revealed that FLNa depletion abolished the activity of Vpu to enhance particle release. Taken together, our results suggest that HIV‐1 Vpu takes advantage of the FLNa‐dependent tetherin trafficking pathways to neutralize tetherin and promote virus release. These studies shed new insights into the mechanisms of Vpu‐mediated counteraction of tetherin restriction.Grant Funding Source: AI089330, GM059994
Effects of avocado oil on kidney mitochondrial membrane potential of L‐NAME‐treated rats (953.4)
Authors: Hernandez De La Paz Lucio , Ortiz‐Avila Omar , Canizal‐Garcia Melina , Calderon‐Cortes Elizabeth , Clemente‐Guerrero Monica , Saavedra‐Molina Alfredo , Cortes‐Rojo Christian 
Published: June 2021

Hypertension is an important risk factor for the development of terminal kidney disease. Mitochondria have been proposed as a novel target for the treatment of hypertensive complications because has been demonstrated that the prevention of mitochondrial dysfunctions through the improvement of redox status by antioxidant therapy ameliorates vascular dysfunction caused by angiotensin II. Recently, we have reported that avocado oil intake has beneficial effects in kidney mitochondria of diabetic rats by improving the function of the electron transport chain (ETC) and decreasing ROS generation. Since kidney mitochondrial dysfunctions in both diabetes and hypertension shares enhanced oxidative stress features and avocado oil is a rich source of antioxidants, we aimed to test the effects of 90‐days avocado oil supplementation on kidney mitochondrial membrane potential of L‐NAME‐treated rats, a model of hypertension. No significant differences were observed in the phases of hyperpolarization and depolarization of membrane potential when succinate plus rotenone or glutamate‐malate plus succinate were used as respiratory substrates. However, when glutamate‐malate was used alone, a severe inhibition of membrane potential of control and L‐NAME rats was observed, suggesting impairment in complex I function. These effects were partially prevented by avocado oil supplementation. Interestingly, a protective effect of similar magnitude was obtained when L‐NAME rats were treated with losartan, an AT‐1 receptor antagonist. These data suggest that avocado oil may protect from mitochondrial ETC dysfunction in hypertensive kidney by decreasing pro‐oxidative effects of angiotensin II.Grant Funding Source: Supported by CONACYT (130638 to CCR) and CIC‐UMSNH (16.12 to CCR) grants
Maternal inheritance of circulating irisin in humans (954.1)
Authors: Al‐Daghri Nasser , Al‐Attas Omar , Alokail Majed , Alkharfy Khalid , Yousef Mansour , Vinodson Benjamin , Amer Osama , Alnaami Abdullah , Sabico Shaun , Tripathi Gyanendra , Piya Milan , McTernan Philip , Chrousos George 
Published: June 2021

Background The recently discovered myokine irisin has been implicated in several observational studies, suggesting a potential therapeutic target for obesity‐related diseases. However, no information is available as to the heritability of this hormone. This study aims to fill this gap.Methods A total of 120 families (N=254;121 adults and 133 children) were included in this study taken from the Biomarkers Research Program cohort. Information included anthropometrics, glycemic, lipid and adipocytokine profiles. Irisin was measured using ELISA.Results The most significant heritable traits in sons included irisin (p=1.6*10‐5), systolic blood pressure (p=3.6*10‐4), LDL‐ (p=1.2*10‐6) and total cholesterol (p=3.5*10‐7). Heritable traits between mother and daughter again included irisin (p<0.002), as well as waist (p<0.01), hips (p<0.005) and blood pressure (p<0.002); HDL‐cholesterol was the single most significant predictor for irisin in adults, explaining 17% of variance, whilst in children angiotensin II was the most significant predictor of irisin explaining 19% of variance (p=0.003).Conclusion Circulating irisin appears to be maternally inherited and is predicted by HDL‐cholesterol in adults and angiotensin II in children, both factors influenced by energy expenditure and regulation. Taken together, these findings suggest a significant role of irisin in energy‐generating processes.
Physical activity may protect against low grade systemic inflammation in young adults (954.2)
Authors: Escalante Priscilla , Vera Desiree , Weaver Kathleen , Garcia Jerome , Dunn Sarah 
Published: June 2021

Physical activity may positively impact low grade systemic inflammation by stimulating the upregulation of the multifactorial cytokine, Interluekin‐6 (IL‐6), secreted from muscle cells following chronic exercise ultimately decreasing ones risk for disease. Whether there is a significant difference in inflammatory (C‐Reactive Protein, IL‐6) markers and the gene expression molecule nuclear factor kappa B (NF‐κB) between young trained and untrained males and females is unknown. To examine the differences between C‐reactive protein (CRP), IL‐6, and NF‐κB in young (21.1 ± 2.1 yr) trained (n = 9) and untrained (n = 7) males and females. Fasting venous whole blood (40 ml) and a finger prick (triglycerides) along with body composition measurements (percent body fat, fat mass, etc…), and a medical history were obtained from young apparently healthy endurance trained (NCAA student athletes) and untrained individuals (less than three hours a week of physical activity). Enzyme‐linked immunosorbent assays were conducted to analyze fasting plasma (CRP and IL‐6) and isolated lymphocyte NF‐κB activation. Lymphocytes were isolated from whole blood samples through differential centrifugation with the use of ficoll. An Independent T‐test was used to identify differences (p<0.05) between trained and untrained groups (N = 16). Significant differences exist in body composition (p<0.05), triglycerides (p<0.05), and CRP (p<0.01). Finally, no significant difference in NF‐κB rels (p50 and p65) and IL‐6 was found between trained and untrained individuals. A significant difference exists between trained and untrained male and female participants for low grade systemic inflammation (CRP) levels despite no difference in the precursor gene expression molecule, NF‐κB or IL‐6. This suggests that physical activity has a positive protective impact on low grade systemic inflammation levels possibly through an anti‐inflammatory mediated pathway and may help minimize disease risk in a young population.Grant Funding Source: Supported by STEM
Inflammatory bowel disease is a disorder of ganglioside metabolism (959.4)
Authors: Miklavcic John , Hart Tasha , Lees Gordon , Schnabl Kareena , Thomson Alan , Mazurak Vera , Clandinin M 
Published: June 2021

AIM To demonstrate that the metabolism of ganglioside is altered in inflammatory bowel disease (IBD). METHODS Sections of intestinal mucosa from terminal ileum and/or colon were obtained from subjects with ulcerative colitis or inflammatory Crohn’s disease undergoing surgical resection for complications related to IBD. Control groups consisted of tissue samples of apparently normal intestinal mucosa from subjects with colorectal cancer and apparently normal intestinal mucosa from subjects with benign adenoma polyposis. Gangliosides of the intestinal mucosa were characterized using LC‐QQQ‐MS and compared among subject groups. Ganglioside catabolism enzymes HEXA and NEU3 were measured in the intestinal mucosa by western blot. RESULTS GM3 was significantly higher (P<0.01) by 2.1 fold in IBD intestine compared to apparently normal intestinal mucosa. IBD intestine exhibited 2.7 fold lower (P<0.001) GD1a content than control intestine. The mean relative expression of HEXA in IBD intestine was increased 1.7‐fold (P<0.08) and the mean relative expression of NEU3 in IBD intestine was increased 8.3‐fold (P< 0.001) compared to normal intestine. CONCLUSION Metabolism of gangliosides is altered in the intestinal mucosa of subjects with IBD. Investigation into utility of dietary ganglioside as a potential treatment of IBD is warranted.Grant Funding Source: Supported by Broad Foundation and CIHR
Antibacterial activities of new coumarine heteroaryl derivatives (973.6)
Authors: Govori Odai Sevdije , Haziri Arben , Spahiu Sabrie , Ibrahimi Hamide 
Published: June 2021

The antibacterial activities of new heteroarylderivatives with coumarine moieties were tested against several types of microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Aeromonas salmonicida, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Hafnia alvei and Bacillus cereus.The antibacterial activities of the synthesised derivatives were compared with the antibacterial activity of some standard antibiotics such as Novobiocine, Cephalexine and Streptomycin. Synthesized compounds show different bacteriostatic and bactericidal activities.
Elucidation of cellular signaling triggered by Francisella infection by comparative phosphoproteomic analysis (981.2)
Authors: Ansong Charles , Nakayasu Ernesto , Tempel Rebecca , Heffron Fred , Smith Richard , Adkins Joshua 
Published: June 2021

Francisella tularensis is a facultative intracellular bacterium that causes the deadly disease tularemia. Most evidence suggests that Francisella is not well recognized by the innate immune response that normally leads to protection against the infection. To elucidate the cellular signaling underlying this muted recognition of Francisella by the innate immune system, we performed a large‐scale comparative phosphoproteomic analysis of RAW 264.7 cells infected with either Francisella tularensis novicida or Salmonella Typhimurium, which is well recognized by the innate immune system. From our phosphoproteomics analysis >3000 phosphopeptides from >1200 phosphoproteins were identified, of which 368, 169, and 332 phosphopeptides were differentially abundant comparing Francisella‐ or Salmonella‐ infected and control cells at 0, 1, or 4 h post‐infection, respectively. Striking differences in phosphorylation levels on proteins from a diversity of cellular pathways were observed comparing Francisella and Salmonella infections, including key players of the innate immune response, such as AKT and MAP kinases and E3 ubiquitin ligases. In conclusion, our comparative phosphoproteomic analysis of cells infected with Francisella and Salmonella shows differences between the cellular signaling triggered by either pathogen, which may be reflective of specific mechanisms to evade the host immune response.Grant Funding Source: Supported by GM094623 and 8 P41 GM103493‐10
Targeted and multiplexed quantitation of CSF proteins by MRM and labeled peptide standards (981.5)
Authors: Percy Andrew , Chambers Andrew , Yang Juncong , Hardie Darryl , Borchers Christoph 
Published: June 2021

Precise and accurate protein quantitation is essential for screening biomarkers for risk stratification, disease prognostication, and therapeutic monitoring. The most promising analytical strategy for quantitating unverified biomarkers in pre‐clinical biofluids relies on targeted MRM/MS with isotopically labeled standards. Through this approach, considerable effort has been extended toward verifying protein biomarkers of non‐communicable disease in the systematic circulation, but little in the way of accelerating the discovered markers of central nervous system‐related diseases in cerebrospinal fluid (CSF). We herein aimed to develop a rapid and robust, antibody‐free method to quantify a large panel of proteins in human CSF for disease biomarker verification and validation studies. Using pooled CSF and a complex isotopically coded peptide mixture, various denaturation/digestion approaches were evaluated within a bottom‐up proteomic workflow. For enhanced reproducibility and multiplexing, peptides were separated at standard‐flow rates and detected by dynamic MRM in a triple quadrupole mass spectrometer. The final method demonstrated excellent reproducibility (average retention times of 0.06% and signal of 5.8% CV) and enabled the quantitation of 155 protein biomarker candidates (inferred from 337 interference‐free peptides) in a 43 min run. The quantitative analyses of >100 CSF samples from spinal cord injury patients is currently being performed and will additionally be presented.Grant Funding Source: Supported by Genome BC, Genome Canada, and the Western Economic Diversification of Canada.
Aerospace medical factor gene expression patterns in live subjects persist in aviation accident victims within muscle, blood, and brain (981.6)
Authors: Burian Dennis , Williams Daniel , Budd Austin , White Vicky , Hutchings David 
Published: June 2021

In support of our efforts to validate gene expression markers for aerospace medical factors such as mild hypoxia, sleep deprivation, and alcohol use, we compared gene expression patterns between aviation accident victim samples and live subject samples. RTqPCR was performed against a panel of markers and 15 potential normalizers. Microarray data was taken from a publically available dataset of fresh post‐mortem tissue samples or our own marker discovery efforts in blood.RNA integrity from tissues was poor, ranging from RINs of 0 in most brain samples to 5 in some muscle samples. RINs in blood ranged from 2 to 6. In both tissues and blood, purity was high: A260/A280 ratios between 1.9 and 2.1. Post‐mortem interval did not correlate with quality measures or yield.Expression patterns of the gene panel within tissues between the microarray (live subjects) and RTqPCR (accident victims) data were compared by Spearman correlation coefficient. Because in qPCR data, higher Ct values reflect lower gene expression, negative coefficients were expected. Skeletal muscle (‐0.50), blood (‐0.48), brain (‐0.48), cardiac muscle (‐0.47), and lung (‐0.44) had the best correlations. Expression patterns within accident victim blood samples were highly correlated (r>0.80) suggesting that degradation was irrespective of accident conditions or post‐mortem interval.In the future, it is expected that accident investigators will utilize gene expression data to determine aviation accident causality. However, to translate tests developed in live subject studies to the field, it must be demonstrated that assays are robust to RNA degradation. These results demonstrate that in some tissues, relative gene expression patterns remain stable post‐mortem and assay development can remain focused on discovering the most accurate markers without regard for potential differential stability between mRNAs.
Protein quantification in dried blood spots by MRM mass spectrometry (981.8)
Authors: Chambers Andrew , Percy Andrew , Yang Juncong , Borchers Christoph 
Published: June 2021

Dried blood spot (DBS) sampling offers proven advantages over intravenous blood collection for clinical diagnostics targeting a wide array of biomarkers. The simplicity of this approach enables minimally‐trained staff to collect less than 100 microliters of blood from patients. Furthermore, many analytes are stable in the DBS format at room temperature reducing the challenges of sample storage and transportation. The most common clinical application of DBS sampling is the screening newborns for metabolism disorders by targeting small molecules by multiple reaction monitoring mass spectrometry (MRM‐MS). In addition, DBS‐MRM is increasingly employed for pre‐clinical toxicology and pharmacokinetics studies supporting small molecule drug development. The goal of our work is to integrate DBS methodology with multiplexed MRM assays for the quantification of endogenous proteins in human blood. Highly reproducible methods were developed for extracting dried proteins from collection cards (coefficient of variation <15% for full process technical replicates). These samples were then digested with trypsin and spiked with stable isotope‐labeled standard peptides to improve the precision of the assay. Finally, peptides were separated by reversed‐phase liquid chromatography and detected by an Agilent 6490 triple quadrupole mass spectrometer. Robust MRM assays were generated for over 30 proteins and most were stable in DBS samples over a wide range of storage temperatures. This work demonstrates considerable promise for clinical MRM assays targeting endogenous proteins in DBS samples.Grant Funding Source: Supported by Genome Canada, Genome BC, and the Western Economic Diversification of Canada
Integrative analysis of microbiome and metabolome in mouse model simulating features of post‐traumatic stress disorder (982.1)
Authors: Gautam Aarti , Sowe Bintu , Donohue Duncan , Kumar Raina , Muhie Seid , Chakraborty Nabarun , Hoke Allison , Hammamieh Rasha , Jett Marti 
Published: June 2021

The gastrointestinal tract is colonized by an enormous array of microbial symbiotes and pathogens. The symbiote influence of gut microbiota on the nervous system and behavior has been receiving profound interest. Rodent studies have provided suggestive evidence that probiotics (e.g. Lactobacillus and Bifidobacterium) can influence behavior. Using “cage‐within‐cage resident‐intruder” model, subject C57BL/6J mice were exposed to aggressors for 6 h daily for 5 or 10 days. After one day of recovery inflammatory cardiac histopathologies were prevalent. Here we report metagenomics and metabolomics approaches to understanding the microbiome activity in our social stress model of mice. Plasma samples were compared between aggressor‐exposed and control mice using various Mass Spec‐based techniques. Large effects of microbiome composition on plasma biochemistry were observed, and several microbiome‐affected molecules such as hippurate, phenylpropionylglycine, and 3‐phenylpropionic were identified in plasma. We also sequenced the 16S rRNA gene V4 variable region on DNA from duodenum tissue using an ion torrent Personal Genome Machine platform. A significant increase of Lactobacillus in the socially stressed mice compared to the control group was observed. Together, these data demonstrate that prolonged stress can significantly change the composition of the intestinal microbiome. We are in the process of analyzing possible correlations between host microbiome population structure and accumulation of metabolites in plasma.DISCLAIMER “Research was conducted in compliance with the Animal Welfare Act and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.”
Genesis of antibiotic resistance VII: implementation of unused prescription antibiotics/antimicrobial recycling and incidence of antibiotic resistant bacterial infections in Texas (986.7)
Authors: Kannan Subburaj , Amezcua Judy , Harbison Tiffany , Hernandez Lizeth , Subburaj Prabavathy 
Published: June 2021

An effort has been made to explore the implementation of a prescription medicine (Antibiotics) recycling program in Texas. According to The Office of the Regional Medical Director, Texas Department of State Health Services (TDSHS) Region 8 at present there are no programs for recycling the unused prescription medications, Antibiotics in particular in existence in the State of Texas. http://www.dshs.state.tx.us/contact.shtm. Pertaining to the infectious diseases and antibiotic resistance as per the information available and Region 8 Medical director, VISA/VRSA Vancomycin‐Intermediate/Resistant Stapylococcus aureus are the only diseases that are reportable to the TDSHS. Of the 609 infections related to Staphylococcus aureus isolated reports through TxHSN in 2012, 55% tested sensitive to oxacillin/methicillin. NDM‐1, which stands for New Delhi metallo‐beta‐lactamase 1 has been considered to become a global public health problem, but is not detected in Texas. Though 4% of US hospitals had at least one patient with a CRE (carbapenem‐resistant Enterobacteriaceae) infection during the first half of 2012, none were reported in Texas. In 2011, 1,325 cases of tuberculosis (TB) were reported in Texas however, the total number of the antibiotic resistant form of TB among this population is not known. The implications of the discrepancy in the Annual Federal Prescription Drug retake program and lack of recycling of the prescription medicines (Antibiotics) in the evolution of antibiotic resistance shall be presented in the EB2014.Grant Funding Source: Professional Development Funds from SWTJC, Eagle Pass, Texas