bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole exome sequencing analysis of inter‐participant cortisol response: strategies for matching phenotype to genotype (983.1)
Authors: Murphy Patrick , Biette Kelly 
Published: June 2021

The overarching goal of this project is to identify genetic variants that are indicative of an individual’s systemic and intracellular responses to corticosteroids. We previously observed inter‐participant variability in cortisol and nuclear hsp90 concentrations following exposure to mild cardiovascular stress, which could not be attributed to demographic or lifestyle characteristics or to single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor, hsp90, or CRHR1 genes. We conducted whole exome sequencing of matched participant pairs who displayed similar demographic and lifestyle characteristics yet possessed distinct cortisol response phenotypes. Using an Agilent V4 exome enrichment platform and Illumina HiSeq2000 paired end (2 x 100 bp) sequencing, >44 million reads per sample were aligned to the hg19 reference build. This analysis resulted in average 30x coverage and combined analysis of >440,000 base pair variants. We developed a bioinformatics analysis pipeline to compare datasets of matched participant samples to one another and against the NHLBI dataset of >6,500 sequenced exomes. Filtering identified candidate causal variants associated with the phenotypic difference in cortisol response. These genes, which have the potential to impact corticosteroid‐mediated signaling and pharmacotherapy, are now being investigated for functional significance.Grant Funding Source: Supported by NIH AREA grant GM086822
Genesis of antibiotic resistance (AR) I: monitoring of microbial pathogens with AR by Texas Clean Water Program in Rio Grande Basin including Amistad Reservoir (986.1)
Authors: Kannan Subburaj , Iracheta, Alyssa , Jimenez, Brenda , Lopez, Larizza , Martinez Karenny , Amezcua Judy , Subburaj Prabavathy 
Published: June 2021

Water‐related (borne) diseases are categorized into four different classes: waterborne, water‐washed, water‐based, and water‐related insect vectors. The Pacific Institute Research Report (http://www.pacinst.org/) speculates that by 2020 a global mortality rate of 34‐76 million people will be observed due to water related diseases. One of the main sources for water in Southwest Texas is the Rio Grande River which receives its water influx from Las Vacas, Rio Conchos, Rio Rodrigo, and Rio Salado tributaries from Mexico. The Rio Grande River flows through the southwest border and is stored in the Amistad Reservoir located in Del Rio, Texas. The “Texas Clean Rivers Program” a collaborative program operated by The Amistad Reservoir ‐ International Boundary and Water Commission, US section(USIBWC) ‐ The Rio Grande Basin and The Texas Commission on Environmental Quality(TCEQ) monitor the microbial and water quality issues in Texas. As per the 2012 Basin Highlights Report for the Rio Grande Basin in Texas show that there were between 14,200 colonies/100 ml and 3,800,000 colony forming units/100ml of the fecal coli form bacteria in the water samples. High levels of Biological Oxygen Demand, and Chemical Oxygen Demand were also detected in the water samples tested in the urban areas of Del Rio, Eagle Pass and Laredo. Taken together the severity of the contamination, BOD and COD increases the mutagenic potential in the microbial pathogens (bacteria) to acquire antibiotic resistance through known and unknown mechanisms.Grant Funding Source: PROFESSIONAL DEVELOPEMENT FUNDS ‐
Genesis of antibiotic resistance IX: monitoring of antibiotics, its metabolic break down intermediates by the United States ‐ Centers for Disease Control and Prevention (986.9)
Authors: Subburaj Subburaj , Dingler Margarita , Harbison Tiffany , Carrillo Esmeralda , Subburaj Prabavathy 
Published: June 2021

CDC & P, a federal agency registry, formulating and advising the impact of the Antibiotics and Antimicrobial compounds, it’s precise role in tracking the use and its impact of the I. prescription, ii. Over the counter and iii. Non‐therapeutic use of Antibiotics is not well defined. CDC&P’s surveillance Systems in particular, The Emerging Infections Programs (EIP); Education Campaigns; and Antimicrobial Resistance, fall short of identifying, formulating, and providing specific advisory for each of the antibiotics either prescribed or antibiotics that are available over the counter (OTC) and non‐therapeutic use of the antibiotics. As per the advisory from CDC&P available on record, the CDC&P has neither role in monitoring neither antibiotics nor its metabolic breakdown products in potable water, sewage water, nor act as a registry for the harmful effects to the general public. The “Antibiotic Resistance Threats in the United States 2013” report published in April 2013 by EIP‐Active Bacterial Core Surveillance (ABCs) is based on the assumptions, expert opinions, and archived data. Though it is an update on prevailing trends in antibiotic resistance, recede of realistic advisory on the detection & preventive measure of on the antibiotics, and its metabolic breakdown products in the portable, untreated sewage, biosolids and processed clean water from raw sewage (domestic and medical/industrial sewage). Details on the dearth and desired aspect of the report will be presented in EB2014.Grant Funding Source: PROFESSIONAL DEVELOPEMENT FUNDS ‐
New immunological assays for diagnosis of Schistosoma mansoni for clinical acute and/or chronic forms (990.1)
Authors: Grenfell Queiroz Rafaella , Silva‐Moraes Vanessa , Harn Donald , Coelho Paulo Marcos 
Published: June 2021

Control constraints of schistosomiasis include the lack of diagnostic methods with high sensitivity. We develop a prospective study in southeast Brazil to standardize new sensitive diagnostic methods for Schistosoma mansoni infection. Currently, we are investigating 4 endemic areas together with 84 travelers infected in a freshwater pool. Sera, urine and saliva samples from all those patients has been used for the standardization of innovative methods, including acute, chronic, post‐treatment and myeloradiculopathy schistosomiasis patients. Comparisons are performed with eggs in feces, IgG titers, encephalomyelitis by NMR and clinical symptoms. We could diagnose acute patients 10 days post‐infection and also more than 95% of positive cases from chronic and low endemicity patients. New methods for IgG detection using purified glycoprotein or recombinant protein or peptides of 10 amino acids were superior to conventional ELISA. Best results were seen for recombinant protein with 100% of sensitivity. Finally, monoclonal antibodies were produced for improvement of the new methods by promoting direct diagnosis. Data showed 100% of sensitivity of chronic patients and 98% of acute patients. Financial support: Fapemig, CNPq, Capes, Fiocruz, Fiotec, PDTIS (Brazil). Fulbright, NIH, University of Georgia (USA).Grant Funding Source: Fapemig, CNPq, Capes, Fiocruz, Fiotec, PDTIS (Brazil). Fulbright, NIH, University of Georgia (USA).
Food addiction in an urban sample of college students (LB117)
Authors: Dopler‐Nelson Mindy , Bullock Emily , Ackerson Leland 
Published: June 2021

The objectives of this investigation are to create a shortened version of a survey to assess food addiction and to determine the prevalence of food addiction in an urban population of college students. Food addiction has a web of physiological causes very similar to other addictions that trigger the reward pathway and therefore influence inter‐individual variability in response to an obesogenic environment.Methods: One question from each of the seven DSM‐IV‐TR substance dependence criteria were included in an online survey of interested college students at the beginning of the fall 2013 semester. Participants were from a convenience sample of students recruited by email invitation. Participants answered questions related to demographics and eating behavior to assess food addiction.Results: 1980 students completed the online survey. 92.5% of the students answered at least five food dependence questions and were included in the data analysis. 46.2% had at least one symptom of food dependence. 9.1% of students were identified as having higher food addiction scores (3 or more symptoms) and 1.5% had clinical impairment to be classified with the diagnosis of food addiction.Conclusions: These findings illustrate that nearly half of urban college students have symptoms of food addiction and approximately 10% meet the clinical diagnosis of food addiction. This may help to explain why certain individuals are predisposed to gain weight during their college years.No external support was used to conduct this study.
Improving DNA extraction quality by the salting‐out method to prepare blood samples for real‐time PCR. (LB124)
Authors: Araujo Natalia , Carmona Bruno , Nogueira Glaucia Regina , Minicucci Marcor Ferreira , Conde Sandro 
Published: June 2021

PCR, or “polymerase chain reaction”, is one of most useful techniques in genomics research. High quality DNA extraction is necessary to obtain satisfactory results. Some methods utilized to obtain DNA from blood include a simple salting‐out procedure for extracting DNA from human nucleated cells. This method is widely used by many laboratories because it can obtain DNA with sufficient quality to realize PCR, using materials that do not pose risk to researchers and is more cost‐efficient than other approaches. Although salting‐out has spread to many laboratories, its protocols do not highlight technical details of their steps that could affect final DNA quality and, for this reason, underwent some modifications in this work in order to obtain an efficient extraction. We used 2 to 4 mL of blood for each of 30 DNA samples. For the supernatant step in first EDTA wash, we established a subtraction pattern from 15 mL to 2.5 mL, independently of initial sample volume of blood, to avoid losing leucocytes. The number of washes required is directly proportional to loss of leukocytes in the blood sample, considering that 4 mL samples can receive five washes while 2 mL samples tolerate only four. It was noted that a “centrifuge brake” can reduce DNA extraction quality, thus indicating its inadvisability. All DNA samples were submitted to spectrophotometry, which showed the DNA/Protein ratio staying between 1.1 and 1.6. According to the literature, 93% of our samples were ready for real‐time PCR after modifications, indicating that those modifications were relevant for achieving efficient extraction. Integrity was confirmed by electrophoresis. All modifications made in the salting‐out method have improved the quality and integrity of DNA samples.Grant Funding Source: FAPESP 2013/19808‐8
Cadaveric study utilizing the ilizarov method for limb stabilization (LB17)
Authors: Summers Orianna , Welch Zachary , Lee Kelsey 
Published: June 2021

By utilizing the Ilizarov principles as well as external fixation devices, the objective of this project is to actively demonstrate and analyze post‐fracture tibial‐fibular stabilization. This study will be conducted through the use of a cadaver supplied the University of California San Francisco’s Willed Body Program, and through the use of San Francisco State University’s Human Anatomy Laboratory. This cadaver will have stress applied to the lower limb in order to cause an accurate representation of a medically induced tibial‐fibular fracture. In order to correct this disjunction, the Ilizarov principles and external fixation device will be applied. Upon the placement of the Ilizarov external fixation device, the initial fracture will be corrected to provide stabilization of the tibia and fibula. This poster will aptly showcase the results of this study.Grant Funding Source: None
Age‐related differences in the plasma proteome in healthy adults: modulatory effect of regular aerobic exercise (LB178)
Authors: Santos‐Parker Jessica , Harrison Brooke , McQueen Matthew , Seals Douglas 
Published: June 2021

Aging causes physiological dysfunction, some of which can be prevented or reduced by habitual aerobic exercise (AE). However, the molecular mechanisms underlying these effects remain largely unknown, particularly in humans. We used a novel high‐throughput molecular assay (SOMAscan v3.0, SomaLogic Inc., Boulder, CO) to characterize the effects of age and regular AE on the plasma proteome of healthy adult humans. From 1129 analytes, the expression of 48 proteins was greater and 37 lower in older (O; 64±6 yr; n=16) vs. young (Y; 24±4 yr; n=16) healthy men (false discovery rate [FDR] < 15%, p<0.01). Expression of the non‐collagenous extracellular matrix (ECM) protein dermatopontin was greater in O vs. Y (P=0.007), but was lower in older AE‐trained men (63±7 yr; n=8; VO2max = 49.6±3.7 mL/kg⋅min) compared with their sedentary counterparts (VO2max = 27.4±2.4 mL/kg⋅min) (FDR < 1.28%, p<0.001). Within O, no other group differences in plasma protein expression associated with exercise status met our FDR threshold (>35%). These preliminary results suggest that normal human aging is associated with several changes to the plasma proteome that may serve as molecular biomarkers of physiological dysfunction or disease risk. Regular AE status influences age‐related changes in circulating dermatopontin, a possible mediator of age‐related ECM remodeling.Grant Funding Source: Supported by NIH AG013038 and RR025780
TRIM28 regulates RNA polymerase II promoter proximal pausing and pause release (LB206)
Authors: Bunch Heeyoun 
Published: June 2021

Promoter proximal pausing of RNA polymerase II (Pol II) is a major checkpoint in transcription. An unbiased search for novel human proteins that could regulate paused Pol II at the HSPA1B gene identified TRIM28. In vitro analyses indicated HSF1‐dependent attenuation of Pol II pausing upon TRIM28 depletion, whereas in vivo data revealed de novo expression of HSPA1B and other known genes regulated by paused Pol II upon TRIM28 knockdown. These results were supported by genome‐wide ChIP‐sequencing analyses of Pol II occupancy that revealed a global role for TRIM28 in regulating Pol II pausing and pause release. Furthermore, in vivo and in vitro mechanistic studies suggest that transcription‐coupled phosphorylation regulates Pol II pause release by TRIM28. Collectively, our findings identify TRIM28 as a novel factor that modulates Pol II pausing and transcriptional elongation at a large number of mammalian genes.Grant Funding Source: US National Institutes of Health (RO‐1CA047407) and The Harvard JCRT
Transforming growth factor β1 (TGF‐β1) enhances expression of pro‐fibrotic genes through a novel miRNA‐mediated cascade in renal mesangial cells (LB208)
Authors: Castro Nancy 
Published: June 2021

Increased TGF‐β1 expression in glomerular mesangial cells (MC) augments extracellular matrix accumulation, hypertrophy and pro‐fibrotic genes during the progression of diabetic nephropathy (DN), a debilitating renal complication of diabetes. microRNAs (miRNAs) play key roles in the pathogenesis of DN by modulating the actions of TGF‐β1 to enhance the expression of pro‐fibrotic genes like collagen. In this study, we found a significant decrease in the expression of key members of the miR‐130 and miR‐30 families in mouse MC (MMC) treated with TGF‐β1. In parallel there was a decrease in host genes 2610318N02RIK (RIK, miR‐130b host gene) and NF‐YC (miR‐30e* host gene), suggesting host gene‐dependent expression of these miRNAs. TGF‐β receptor1 (TGF‐βR1), was identified as a target of miR‐130b. Interestingly, the RIK promoter contains three NF‐YC binding sites and was regulated by NF‐YC, a potential target of miR‐216a which was also up‐regulated by TGF‐β1. Therefore, a novel cascade, ↑TGF‐β1>↑miR‐216a>↓NF‐YC>↓RIK (↓miR‐130b) may up‐regulate TGF‐βR1 to augment expression of TGF‐β1 target fibrotic genes. miR‐130 and miR‐30e* were down‐regulated, whereas TGF‐βR1, as well as the pro‐fibrotic genes COLIVa1, COLXIIa1, CTGF and PAI‐1 were up‐regulated by TGF‐β1 in MMC and in the glomeruli of streptozotocin injected diabetic mice, supporting in vivo relevance. Together, these results demonstrate a novel miRNA‐ and their host gene‐mediated cascade initiated by TGF‐β1 which results in the up‐regulation of pro‐fibrotic factors such as TGF‐βR1 and collagens associated with the progression of DN.Grant Funding Source: Supported by NIH R01 DK081705 and ADA 7‐10‐MI‐07
Action of fluvastatin on signal transduction pathways of an aggressive natural killer cell leukemia cell line (LB227)
Authors: Yingst Ashley , Pradhan Prajakta , Steele Timothy 
Published: June 2021

Aggressive natural killer cell leukemia is an acute neoplastic proliferation of natural killer cells, resulting in progressive disease and poor prognosis. Death ensues within months and a successful treatment plan for aggressive natural killer cell leukemia has not been established. Typically, statins are utilized to lower cholesterol by inhibiting the production of mevalonate via competitive inhibition of HMG‐CoA reductase. Statins have also been shown to exhibit anti‐cancer effects.Previous research in our lab has shown combination therapy with a chemotherapy agent and statin decreased cell proliferation and cytotoxicity. Statins alone were also shown to inhibit cytotoxicity in concentrations from 3.1uM‐5uM. Based on these previous results, we began to investigate the specific mechanism of action of statins. In this study, the effect of fluvastatin on signal transduction was examined using the aggressive natural killer cell leukemia cell line, known as YT‐INDY. YT‐INDY cells were treated with 10uM of fluvastatin every 24 hours, for a total of 72 hours. Cell lysates were prepared for both western blot analysis and human phospho‐MAP‐K analysis. Western blots demonstrated decreased phosphorylation of ERK1 and ERK2, upon statin treatment.We followed that up with human‐phospho‐ MAP‐K antibody arrays. Preliminary results indicate that 10uM fluvastatin significantly increases the phosphorylation, and activation of AKT, P38, and HSP27, suggesting an increased stress response, as expected in cancers. Significant decreases in the phosphorylation of ERK, RSK, and CREB were evident in the signal transduction pathways; thereby indicating a decrease in cell survival, proliferation, and tumorigenesis of aggressive natural killer cell leukemia cells. Current studies are investigating the use of mevalonate pathway inhibitors and pathway intermediates to more specifically identify the parts of the pathway that are responsible for the inhibition of proliferation and cytotoxicity. It is the hope that the outcome of this line of research will result in more effective treatment strategies for aggressive natural killer cell leukemia.Grant Funding Source: Iowa Osteopathic Education and Research Foundation
Pathogen‐induced lipid coalescence in the host membrane causes downstream activation of Rho GTPase (LB229)
Authors: Krachler Anne‐Marie 
Published: June 2021

We recently discovered a family of bacterial adhesins (Multivalent Adhesion Molecules, MAMs) which mediate initial contact between pathogen and host cells during infection. MAMs are composed of tandem arrays of six to seven mammalian cell entry (mce) domains, each recognizing a phosphatidic acid lipid ligand in the host cell membrane. We utilized bacteriomimetic tools to reconstruct the process of pathogen adhesion to host cells independent of other bacterial components and virulence factors. This revealed that MAMs, through binding to phosphatidic acid ligands with high affinity, induce lipid coalescence in the host cell membrane. Clustering of phosphatidic acid ligands triggers downstream activation of the small GTPase RhoA and actin rearrangements. In vivo infection studies with Vibrio parahaemolyticus demonstrated that MAM‐triggered RhoA activation facilitates breaching of a polarized epithelial cell layer by the pathogen. This is an unprecedented mechanism utilized by a bacterial pathogen to manipulate host cells and facilitate infection.Grant Funding Source: This work was supported by an EMBO fellowship (ALTF 938‐2011).
The identification of small molecules that alter the activity of the LINE1 endonuclease (LB253)
Authors: Maurice‐Walker Lindsey , Ahmad Idrees , Reddix Sherry , Russell Brittany , Mottamal Madhu , Huang Tien , DeFreece Cecily 
Published: June 2021

Long interspersed element‐1 (LINE1) is the only currently active autonomous retroelement within the human genome. LINE1 replicates itself through a process known as retrotransposition that requires the endonuclease and reverse transcriptase activities of the LINE1 protein ORF2. During retrotransposition, the LINE1 endonuclease recognizes an AT‐rich target sequence loosely defined as 5'TTTT/AA3' (“/” denotes site of cleavage). After nicking of DNA by LINE1 endonuclease and reverse transcription of LINE1 RNA, a new copy of LINE1 is inserted into the genome. The complete details of LINE1 insertion are undefined, however, a double strand break (DSB) must occur during this process prior to integration of novel LINE1 elements. Further studies characterizing LINE1 endonuclease function demonstrated that LINE1 endonuclease induces formation of DSBs. While LINE1 mutagenic insertion events have been associated with diseases such as breast and colon cancer as well as muscular dystrophy, the full effect of LINE1 endonuclease upon stability of the genome is undetermined. Only a small fraction of LINE1‐induced DSBs results in a retrotransposition event suggesting that the damage from the LINE1 endonuclease activity may be greater than previously considered. Thus, an inhibitor of LINE1 endonuclease would be beneficial for estimating LINE1‐associated damage and to potentially minimize LINE1‐related genetic instability. Methodology: We have performed in vitro and in silico screens of small molecule libraries. The small molecules identified will be confirmed for their ability to inhibit the LINE1 endonuclease using in vitro biochemical assays. Results: We have thus far identified a subset of small molecules that inhibit the LINE1 endonuclease.Grant Funding Source: Supported by funding from the Louisiana Cancer Research Consortium and the NIH‐RCMI grant #8G12MD007595‐05 from the National Institute on Minority Health and Health Disparities, and an Institutional Development Award (IDeA) from the National Institut
Molecular identification of Trypanosoma cruzi in Anasa tristis (LB268)
Authors: Cooks‐Fagbodun Sheritta , McHugh Mark , Graham Martha , Scott Maya , Sleets Halston , Quarcoo Franklin , Witola William , Alexander A. 
Published: June 2021

Chagas’ disease is a parasitic disease caused by Trypanosoma cruzi (T. cruzi). It is a major health concern for the USA, although, mainly endemic to rural, poverty‐stricken areas, of Latin America. It is estimated 300,000 people in the USA and 8 to 14 million in Latin America are infected. The parasites are transmitted by the reduviid “kissing” bug. The kissing bug takes a blood meal and defecates on the host, which allows feces infected with T. cruzi to enter the wound. Currently, the source of T. cruzi transmission in the USA is unknown. Therefore, the objective of this study was to determine if squash bugs, common relatives of the kissing bug, can act as vectors for T. cruzi and potentially transmit the parasites to mammalian hosts. Hence, 400 squash bugs were collected from a variety of curcubit plants, identified and separated by genus/species. PCR analysis was performed on DNA isolated from bug midgut contents to determine if T. cruzi was present. Morphological examination confirmed that all samples were Anasa tristis (A. tristis). Additionally, 5‐10% of bugs were positive for T. cruzi. Putative T. cruzi parasites were also found in cell cultures inoculated with midgut contents. Thus, we concluded that A. tristis can harbor T. cruzi parasites. However, the potential for the parasite to be transmitted to mammalian hosts via squash bugs, although unlikely due to the arthropod’s host preference, is still being investigated.Grant Funding Source: Supported by Howard Hughes Medical Institute MICROBE Project# 52007563, RCMI Core Grant number#G12MD007585‐23, Center for Biomedical Research, Tuskegee University, George Washington Carver Agricultural Experiment Station