Matching Items (202)

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The Adult Communication, Cognitive, and Reading Profile of 22q11.2 Deletion Syndrome

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22q11.2 Deletion Syndrome (22q11.2DS) is one of the most frequent chromosomal microdeletion syndromes in humans. This case study focuses on the language and reading profile of a female adult with 22q11.2 Deletion Syndrome who was undiagnosed until the age of

22q11.2 Deletion Syndrome (22q11.2DS) is one of the most frequent chromosomal microdeletion syndromes in humans. This case study focuses on the language and reading profile of a female adult with 22q11.2 Deletion Syndrome who was undiagnosed until the age of 27 years old. To comprehensively describe the participant's profile, a series of assessment measures was administered in the speech, language, cognition, reading, and motor domains. Understanding how 22q11.2DS has impacted the life of a recently diagnosed adult will provide insight into how to best facilitate long-term language and educational support for this population and inform future research.

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2018-05

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Characterization of Lipid Transport Mutants that Overcome the Iron-Transport Defect in Escherichia coli

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When limited for iron, Escherichia coli secretes a siderophore, enterobactin, to solubilize and intake extracellular Fe3+ by a TonB-dependent high-affinity pathway. Consequently, E. coli tonB mutants grow poorly on a medium limited for iron. Upon longer incubation, however, faster growing

When limited for iron, Escherichia coli secretes a siderophore, enterobactin, to solubilize and intake extracellular Fe3+ by a TonB-dependent high-affinity pathway. Consequently, E. coli tonB mutants grow poorly on a medium limited for iron. Upon longer incubation, however, faster growing colonies emerge and overcome this growth defect. The work presented in this paper reports and characterizes these faster growing colonies (revertants) in an attempt to dissect the mechanism by which they overcome the TonB deficiency. Genomic analysis revealed mutations in yejM, a putative inner-to-outer membrane cardiolipin transporter, which are responsible for the faster growth phenotype in a tonB mutant background. Further characterization of the revertants revealed that they display hypersensitivity to vancomycin, a large antibiotic that is normally precluded from entering E. coli cells, and leaked periplasmic proteins into the culture supernatant, indicating a compromised outer membrane permeability barrier. All phenotypes were reversed by supplying the wild type copy of yejM on a plasmid, suggesting that yejM mutations are solely responsible for the observed phenotypes. In the absence of wild type tonB, however, the deletion of all known of cardiolipin synthase genes (clsABC) did not produce the phenotype similar to mutations in the yejM gene, suggesting the absence of cardiolipin from the outer membrane per se is not responsible for the increased outer membrane permeability. These data show that a defect in lipid biogenesis and transport can compromise outer membrane permeability barrier to allow siderophore intake and that YejM may have additional roles other than transporting cardiolipin.

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2019-05

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In Vitro Gametogenesis (IVG): Assisted Reproductive Technology (ART) in Development

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In vitro gametogenesis (IVG) research has been growing in countries like Japan, US, and China after the development of stem cell research and other scientific advancements as well as because of the perception of infertility as a domestic and international

In vitro gametogenesis (IVG) research has been growing in countries like Japan, US, and China after the development of stem cell research and other scientific advancements as well as because of the perception of infertility as a domestic and international problem. IVG research’s progress has been deliberated internationally, with discussion of questions, challenges, and possibilities that have arisen and may arise in the future as the technology is adopted by different countries. The first section introduces the meaning of IVG, explains the importance of review by scientists and citizens for IVG, and describes a rise in infertility reported in multiple developed countries that could be addressed by IVG. The second section discusses IVG’s applications and implications using 5 ethical categories articulated by Obama’s Presidential Commission for the Study of Bioethical Issues: Public Beneficence, Responsible Stewardship, Intellectual Freedom and Responsibility, Democratic Deliberation, and Justice and Fairness. These five ethical principles were intended for analysis of emerging technologies, and IVG is an emerging technology with possible integration into clinical settings. Among the principles, it seemed that a major weak point of inquiry concerns LGBT+ and disability inclusion, especially of gender dysphoric and transgender people who may experience higher rates of infertility and have a harder time conceiving due to a mix of discrimination, gender dysphoria, and infertility due to hormone replacement therapy (HRT) treatment or gender/sex reassignment surgeries (GRSs/SRSs) that may impair or remove reproductive body parts. A number of other ethical considerations arise about this technology.

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2019-05

The Perception of Genetic Risk: What Do We Know About Biological and Psychological Diseases and Where Did We Learn It

Description

As a biology major, many of my classes have included studying the fundamentals of genetics or investigating the way genetics influence heritability of certain diseases. When I began taking upper-division psychology courses, the genetic factors of psychological disorders became an

As a biology major, many of my classes have included studying the fundamentals of genetics or investigating the way genetics influence heritability of certain diseases. When I began taking upper-division psychology courses, the genetic factors of psychological disorders became an important part of the material. I was exposed to a new idea: that genes were equally important in studying somatic diseases as they were to psychological disorders. As important as genetics are to psychology, they are not part of the required courses for the major; I found many of my peers in psychology courses did not have a grasp on genetic fundamentals in the same way biology majors did. This was a disconnect that I also found in my own life outside the classroom. Growing up, my mother consistently reminded me to limit my carbs and watch my sugars. Diabetes was very prevalent in my family and I was also at risk. I was repeatedly reminded of my own genes and the risk I faced in having this biological disorder. However, my friend whose father was an alcoholic did not warn her in the same way. While she did know of her father's history, she was not warned of the potential for her to become an alcoholic. While my behavior was altered due to my mother's warning and my own knowledge of the genetic risk of diabetes, I wondered if other people at genetic risk of psychological disorders also altered their behavior. Through my thesis, I hope to answer if students have the same perceived genetic knowledge of psychological diseases as they do for biological ones. In my experience, it is not as well known that psychological disorders have genetic factors. For example, alcohol is commonly used by college students. Alcohol use disorder is present in 16.2% of college aged students and "40-60% of the variance of risk explained by genetic influences." (DSM V, 2013) Compare this to diabetes that has "several common genetic variants that account for about 10% of the total genetic effects," but is much more openly discussed even though it is less genetically linked. (McVay, 2015)This stems from the stigma/taboo surrounding many psychological disorders. If students do know that psychological disorder are genetically influenced, I expect their knowledge to be skewed or inaccurate. As part of a survey, I hope to see how strong they believe the genetic risk of certain diseases are as well as where they gained this knowledge. I hypothesize that only students with a background in psychology will be able to correctly assign the genetic risk of the four presented diseases. Completing this thesis will require in-depth study of the genetic factors, an understanding of the way each disease is perceived and understood by the general population, and a statistical analysis of the survey responses. If the survey data turns out as I expect where students do not have a strong grasp of diseases that could potentially influence their own health, I hope to find a way to educate students on biological and psychological diseases, their genetic risk, and how to speak openly about them.

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2018-05

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A protocol for Resolving Indeterminate Blood Phenotypes in Rhesus (Macaca mulatta) and Cynomolgus Macaques (M. fascicularis)

Description

Rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques are the most commonly used nonhuman primate models in biomedical research. It is therefore critical to correctly infer each study animal's ABO blood group phenotype to prevent fatal transfusion- and transplantation-induced immune

Rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques are the most commonly used nonhuman primate models in biomedical research. It is therefore critical to correctly infer each study animal's ABO blood group phenotype to prevent fatal transfusion- and transplantation-induced immune responses. While most macaques can be efficiently and accurately phenotyped using a DNA-based assay, we have identified some animals that are unable to be classified as type A, B, or AB and therefore exhibit an indeterminate phenotype. The purpose of this study was to develop a protocol for resolving indeterminate blood group phenotypes and consequently determine if these animals do indeed belong to an O blood phenotype. We attempted both direct and cloning-based sequencing of 21 animals phenotyped as A, B, AB, or indeterminate in order to assess variation at the functional mutation site in exon 7 of the macaque ABO gene. Although direct-from-PCR Sanger sequencing was unable to generate reliable sequence results, our cloned plasmid protocol yielded high quality sequences consistent with known blood group-specific alleles and as such can be used to identify informative polymorphisms at this locus.

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2018-05

Data Analytics to Identify the Genetic Basis for Resilience to Temperature Stress in Soybeans

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This paper explores the ability to predict yields of soybeans based on genetics and environmental factors. Based on the biology of soybeans, it has been shown that yields are best when soybeans grow within a certain temperature range. The event

This paper explores the ability to predict yields of soybeans based on genetics and environmental factors. Based on the biology of soybeans, it has been shown that yields are best when soybeans grow within a certain temperature range. The event a soybean is exposed to temperature outside their accepted range is labeled as an instance of stress. Currently, there are few models that use genetic information to predict how crops may respond to stress. Using data provided by an agricultural business, a model was developed that can categorically label soybean varieties by their yield response to stress using genetic data. The model clusters varieties based on their yield production in response to stress. The clustering criteria is based on variance distribution and correlation. A logistic regression is then fitted to identify significant gene markers in varieties with minimal yield variance. Such characteristics provide a probabilistic outlook of how certain varieties will perform when planted in different regions. Given changing global climate conditions, this model demonstrates the potential of using data to efficiently develop and grow crops adjusted to climate changes.

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2018-05

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Role of Egr3 in Regulation of DNA Repair

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Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been

Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been shown to play a crucial role in. Additionally, high levels of DNA damage are found in the brains of schizophrenia patients. A recent study has shown that DNA damage occurs as a result of normal physiological activity in neurons and is required for induction of gene expression of a subset of early response genes. Also, failure to repair this damage can lead to gene expression in a constitutive switched on state. Egr3 knockout (Egr3-/-) mice show deficits in hippocampal synaptic plasticity and memory. We were interested in characterizing downstream targets of EGR3 in the hippocampus. To determine these targets, electroconvulsive seizure (ECS) was carried out in Egr3 -/- versus wild type (WT) mice, and a microarray study was first done in our lab. ECS maximally stimulates Egr3 expression and we hypothesized that there would be gene targets that are differentially expressed between Egr3 -/- and WT mice that had been subjected to ECS. Two separate analyses of the microarray yielded 65 common genes that were determined as being differentially expressed between WT and Egr3 -/- mice after ECS. Further Ingenuity Pathway Analysis of these 65 genes indicated the Gadd45 signaling pathway to be the top canonical pathway, with the top four pathways all being associated with DNA damage or DNA repair. A literature survey was conducted for these 65 genes and their associated pathways, and 12 of the 65 genes were found to be involved in DNA damage response and/or DNA repair. Validation of differential expression was then conducted for each of the 12 genes, in both the original male cohort used for microarray studies and an additional female cohort of mice. 7 of these genes validated through quantitative real time PCR (qRT-PCR) in the original male cohort used for the microarray study, and 4 validated in both the original male cohort and an independent female cohort. Bioinformatics analysis yielded predicted EGR3 binding sites in promoters of these 12 genes, validating their role as potential transcription targets of EGR3. These data reveal EGR3 to be a novel regulator of DNA repair. Further studies will be needed to characterize the role of Egr3 in repairing DNA damage.

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2018-05

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Characterizing the Mechanism of Action of a Potential Targeted Therapy, Triptolide, in Small Cell Carcinoma of the Ovary

Description

Small cell carcinoma of the ovary (SCCOHT) is a rare ovarian cancer affecting young women and characterized by mutation in SMARCA4 and silencing of SMARCA2, two tumor suppressors that function as ATPases in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex.

Small cell carcinoma of the ovary (SCCOHT) is a rare ovarian cancer affecting young women and characterized by mutation in SMARCA4 and silencing of SMARCA2, two tumor suppressors that function as ATPases in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. SCCOHT patients face a 5-year survival rate of only 26%, but recently we have identified sensitivity of SCCOHT models to a natural product, triptolide. This study aims to ascertain the mechanism of action of triptolide. Previous SCCOHT epigenetic drug research has shown that some drugs reverse SMARCA2 epigenetic silencing to inhibit tumor growth, therefore it is hypothesized that triptolide acts the same and restores SWI/SNF function. Cells treated with triptolide have no change in SMARCA2 expression, suggesting that re-expression of epigenetically silenced tumor suppressor gene does not underlie its mechanism of action. Growth rates following triptolide treatment were observed in the presence and absence of SMARCA4, but no difference in sensitivity was observed. Thus, it is not likely that triptolide acts by restoring SWI/SNF. Others have observed that triptolide acts on xeroderma pigmentosa type B protein (XPB), a component of super-enhancers, which are DNA regions with high levels of transcription that regulate genes responsible for cell identity and oncogenes driving tumorigenesis. Both SCCOHT-1 and BIN67 cell lines treated with triptolide displayed lower expression of the super-enhancer associated MYC oncogene compared to untreated cells, supporting the theory that triptolide could be inhibiting super-enhancers regulating oncogenes.. A western blot confirmed reduced protein levels of RNA polymerase II and bromodomain 4 (BRD4), two essential components found at high levels at super-enhancers, in BIN67 cells treated with triptolide. ChIP-sequencing of Histone H3 Lysine-27 Acetylation (H3K27ac) marks in BIN67 and SCCOHT-1 cell lines identified super-enhancers in SCCOHT using tools CREAM and ROSE, which were mapped to neighboring genes associated genes and compared with the COSMIC database to identify oncogenes, of which the top 11 were examined by qRT-PCR to ascertain whether triptolide reduces their expression. It has been found that 6 out of 11 of the oncogenes examined (SALL4, MYC, SGK1, HIST1H3B, HMGA2, and CALR) decreased in expression when treated with triptolide. Thus, there is reason to believe that triptolide’s mechanism of action is via inhibition of super-enhancers that regulate oncogene expression.

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2020-05

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Genetics of Athletic Performance

Description

Abstract
Purpose—Use a framework of genetic knowledge to investigate the association between the genotypes of various genes with phenotypes, specifically the traits of elite athletes, in order to establish a personal opinion on their relevance to athletic performance.

Abstract
Purpose—Use a framework of genetic knowledge to investigate the association between the genotypes of various genes with phenotypes, specifically the traits of elite athletes, in order to establish a personal opinion on their relevance to athletic performance.
Methods—Assemble and analyze selected published scientific studies on genotype and athletic performance and lastly to formulate a personal opinion on the value of genetic testing of athletes. ACTN3, ACE, MSTN, and apoE were the genes selected for analyses.
Results—Two genes, ACTN3 and ACE, showed a significant relationship of genotype to phenotypic traits related to athletic performance. ApoE did not demonstrate a phenotypic association with athletic performance, however it showed a correlation with injury susceptibility leading to traumatic brain injury (TBI). MSTN did not show a phenotypic association with athletic performance.
Conclusion—When considering the multifactorial nature of athletics, each sport must be investigated individually due to the different individual requirements. ACTN3 and ACE are the most widely studied genes, therefore, considerable data on their relevance to athletic performance was easily obtained and supported a relationship between genotype and athletic performance.

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2017-05

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An Analysis of the Benchmark Test lzbench for Open-Source Compressors

Description

With the rising data output and falling costs of Next Generation Sequencing technologies, research into data compression is crucial to maintaining storage efficiency and costs. High throughput sequencers such as the HiSeqX Ten can produce up to 1.8 terabases of

With the rising data output and falling costs of Next Generation Sequencing technologies, research into data compression is crucial to maintaining storage efficiency and costs. High throughput sequencers such as the HiSeqX Ten can produce up to 1.8 terabases of data per run, and such large storage demands are even more important to consider for institutions that rely on their own servers rather than large data centers (cloud storage)1. Compression algorithms aim to reduce the amount of space taken up by large genomic datasets by encoding the most frequently occurring symbols with the shortest bit codewords and by changing the order of the data to make it easier to encode. Depending on the probability distribution of the symbols in the dataset or the structure of the data, choosing the wrong algorithm could result in a compressed file larger than the original or a poorly compressed file that results in a waste of time and space2. To test efficiency among compression algorithms for each file type, 37 open-source compression algorithms were used to compress six types of genomic datasets (FASTA, VCF, BCF, GFF, GTF, and SAM) and evaluated on compression speed, decompression speed, compression ratio, and file size using the benchmark test lzbench. Compressors that outpreformed the popular bioinformatics compressor Gzip (zlib -6) were evaluated against one another by ratio and speed for each file type and across the geometric means of all file types. Compressors that exhibited fast compression and decompression speeds were also evaluated by transmission time through variable speed internet pipes in scenarios where the file was compressed only once or compressed multiple times.

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2017-05