2007). Thus, the ability for folates to methylate homocysteine to its nontoxic derivative methionine plays a large role in protecting against neurotoxicity. However, the links between these illnesses and homocysteine are still not fully understood, with many downstream biochemical pathways still needing to be discovered. Research into increased homocysteine levels and altered folate metabolism confirms a variety of cytotoxic effects in Caenorhabditis elegans (Ortbauer et al., 2016), Drosophila melanogaster (Blatch, Stabler & Harrison, 2015) and Sacchaomyces cerevisiae (Kumar et al., 2011). Thus, the need to utilize mammal models of increased levels of homocysteine is necessary to produce potential theories of illness. One such model looks at the knockout of a particular enzyme in the homocysteine cycle, known as methylenetetrahydrofolate reductase (MTHFR). Folate itself cannot directly methylate homocysteine, thus it must first be converted from the form it is ingested to its primary circulating form, 5-methyltetrahydrofolate (5-methyl-THF). The key enzyme to this process is the aforementioned MTHFR, which catalyzes the production of 5-methyl-THF from a less abundant form 5,10-methyl-THF, which then methylates homocysteine. Thus, this enzyme is essential to both the metabolism of folate and homocysteine. This cycle is highlighted in Figure 1. The occurrence of MTHFR deficiency is not uncommon in humans, with two common mutations producing reduced or lack of function. One of these deficiency-causing mutations is homozygous in approximately 18 percent of humans (Zittan et al., 2007). As many as 34 mutations in this gene, however, have been identified in individuals with homocystinuria, a genetic condition resulting in elevated levels of homocysteine that is associated with neurological and vascular problems (Leclerc, Sibani & Rozen, 2000). INTRODUCTION Folate metabolism is a key mechanism in the brain that allows the downstream alteration of a variety of proteins and plays a role in the synthesis of nucleotides (Kamen, 1997). These folatemediated effects are necessary for the production of new neural cells and thus are essential to the overall health of the brain during development, adulthood and aging (McGarel, Pentieva, Strain & McNulty, 2015). One mechanism through which folates affect protein function is through the initial methylation of homocysteine to methionine. Homocysteine is a cytotoxic molecule when in high levels that produces a variety of negative effects, including endoplasmic reticulum stress, excitatory amino acid receptor overactivation, kinase hyperactivity and DNA damage (Ho, Ortiz, Rogers & Shea, 2002). These effects have been associated with many clinical pathologies in humans, being indicated as a contributing factor to cognitive impairment (Almeida et al., 2005), neural tube defects (Felkner, Suarez, Canfield, Brender & Sun, 2009), brain atrophy (den Heijer et al., 2003), stroke (Hankey & Eikelboom, 2001) and cardiovascular
{"title":"Neurogenesis Unchanged by MTHRF Deficiency in Three-Week-Old Mice","authors":"G. Owens, Patrice D. Smith, N. Jadavji","doi":"10.22186/jyi.31.6.39-43","DOIUrl":"https://doi.org/10.22186/jyi.31.6.39-43","url":null,"abstract":"2007). Thus, the ability for folates to methylate homocysteine to its nontoxic derivative methionine plays a large role in protecting against neurotoxicity. However, the links between these illnesses and homocysteine are still not fully understood, with many downstream biochemical pathways still needing to be discovered. Research into increased homocysteine levels and altered folate metabolism confirms a variety of cytotoxic effects in Caenorhabditis elegans (Ortbauer et al., 2016), Drosophila melanogaster (Blatch, Stabler & Harrison, 2015) and Sacchaomyces cerevisiae (Kumar et al., 2011). Thus, the need to utilize mammal models of increased levels of homocysteine is necessary to produce potential theories of illness. One such model looks at the knockout of a particular enzyme in the homocysteine cycle, known as methylenetetrahydrofolate reductase (MTHFR). Folate itself cannot directly methylate homocysteine, thus it must first be converted from the form it is ingested to its primary circulating form, 5-methyltetrahydrofolate (5-methyl-THF). The key enzyme to this process is the aforementioned MTHFR, which catalyzes the production of 5-methyl-THF from a less abundant form 5,10-methyl-THF, which then methylates homocysteine. Thus, this enzyme is essential to both the metabolism of folate and homocysteine. This cycle is highlighted in Figure 1. The occurrence of MTHFR deficiency is not uncommon in humans, with two common mutations producing reduced or lack of function. One of these deficiency-causing mutations is homozygous in approximately 18 percent of humans (Zittan et al., 2007). As many as 34 mutations in this gene, however, have been identified in individuals with homocystinuria, a genetic condition resulting in elevated levels of homocysteine that is associated with neurological and vascular problems (Leclerc, Sibani & Rozen, 2000). INTRODUCTION Folate metabolism is a key mechanism in the brain that allows the downstream alteration of a variety of proteins and plays a role in the synthesis of nucleotides (Kamen, 1997). These folatemediated effects are necessary for the production of new neural cells and thus are essential to the overall health of the brain during development, adulthood and aging (McGarel, Pentieva, Strain & McNulty, 2015). One mechanism through which folates affect protein function is through the initial methylation of homocysteine to methionine. Homocysteine is a cytotoxic molecule when in high levels that produces a variety of negative effects, including endoplasmic reticulum stress, excitatory amino acid receptor overactivation, kinase hyperactivity and DNA damage (Ho, Ortiz, Rogers & Shea, 2002). These effects have been associated with many clinical pathologies in humans, being indicated as a contributing factor to cognitive impairment (Almeida et al., 2005), neural tube defects (Felkner, Suarez, Canfield, Brender & Sun, 2009), brain atrophy (den Heijer et al., 2003), stroke (Hankey & Eikelboom, 2001) and cardiovascular ","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural Dynamics of Amyloid-β Aggregation in Alzheimer’s Disease: Computational and Experimental Approaches","authors":"Cecily Wing Hei Cheng, M. Chung, J. C. F. Ng","doi":"10.22186/JYI.31.6.44-50","DOIUrl":"https://doi.org/10.22186/JYI.31.6.44-50","url":null,"abstract":"| Introduction | Methods | Results | Discussion | Conclusions |Acknowledgements | References | PDF","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EMT-Mediated Metastasis After EMT has transpired, the newly formed mesenchymal cells enter the bloodstream through the process of intravasation (invasion of cancer cells through the basement membrane) and disseminate throughout the body, eventually invading a distant organ site, through the process of extravasation (cancer cells exit the capillaries and invade an organ; Fig 1). At this distant organ site, the cancer cells undergo a Mesenchymal-Epithelial Transition (MET), the reverse process of EMT, in order to colonize and form a secondary epithelial tumor. By reverting to their original epithelial phenotype, the cells regain the ability to proliferate rapidly and form cellcell junctions, two characteristics that are necessary for successful colonization. These characteristics were lost during the original EMT, when the cells acquired the ability to metastasize (Kalluri & Weinberg, 2009). After MET has occurred and a second epithelial tumor is established, the process of metastasis is complete. Thus, EMT is considered an important process during the early stages of metastasis, while MET is considered an important process during the later stages of metastasis (Brabletz, 2012). EMT induction primarily occurs through the activation of phosphorylation cascades by various cytokines and growth factors present within the tumor microenvironment, including TransINTRODUCTION Lung cancer is currently the most prevalent form of cancer in the United States, causing over 158,000 deaths each year (American Lung Association, 2016). More than 90% of these deaths and other cancer-associated mortality can be attributed to metastasis (Ray & Jablons, 2009). An immense clinical need exists for novel treatments either targeting or preventing metastasis, especially in early stage cancer patients. In order for distant metastasis to occur, primary tumor cells must disseminate through the blood vessels and invade a distant organ site (Brabletz, 2012). A biological phenomenon known as the Epithelial-Mesenchymal Transition (EMT) is a key facilitator of this process. EMT involves a series of changes which allow a cancer cell to transition from a stationary epithelial phenotype to a migratory, drug resistant mesenchymal phenotype. This process includes the disassembly of epithelial cell-junctions and a loss of epithelial polarity in exchange for mesenchymal characteristics, such as a fibroblast-like morOpportunity for Pharmaceutical Intervention in Lung Cancer: Selective Inhibition of JAK1/2 to Eliminate EMT-Derived Mesenchymal Cells
{"title":"Opportunity for Pharmaceutical Intervention in Lung Cancer: Selective Inhibition of JAK1/2 to Eliminate EMT-Derived Mesenchymal Cells","authors":"M. Lai","doi":"10.22186/jyi.31.5.17-24","DOIUrl":"https://doi.org/10.22186/jyi.31.5.17-24","url":null,"abstract":"EMT-Mediated Metastasis After EMT has transpired, the newly formed mesenchymal cells enter the bloodstream through the process of intravasation (invasion of cancer cells through the basement membrane) and disseminate throughout the body, eventually invading a distant organ site, through the process of extravasation (cancer cells exit the capillaries and invade an organ; Fig 1). At this distant organ site, the cancer cells undergo a Mesenchymal-Epithelial Transition (MET), the reverse process of EMT, in order to colonize and form a secondary epithelial tumor. By reverting to their original epithelial phenotype, the cells regain the ability to proliferate rapidly and form cellcell junctions, two characteristics that are necessary for successful colonization. These characteristics were lost during the original EMT, when the cells acquired the ability to metastasize (Kalluri & Weinberg, 2009). After MET has occurred and a second epithelial tumor is established, the process of metastasis is complete. Thus, EMT is considered an important process during the early stages of metastasis, while MET is considered an important process during the later stages of metastasis (Brabletz, 2012). EMT induction primarily occurs through the activation of phosphorylation cascades by various cytokines and growth factors present within the tumor microenvironment, including TransINTRODUCTION Lung cancer is currently the most prevalent form of cancer in the United States, causing over 158,000 deaths each year (American Lung Association, 2016). More than 90% of these deaths and other cancer-associated mortality can be attributed to metastasis (Ray & Jablons, 2009). An immense clinical need exists for novel treatments either targeting or preventing metastasis, especially in early stage cancer patients. In order for distant metastasis to occur, primary tumor cells must disseminate through the blood vessels and invade a distant organ site (Brabletz, 2012). A biological phenomenon known as the Epithelial-Mesenchymal Transition (EMT) is a key facilitator of this process. EMT involves a series of changes which allow a cancer cell to transition from a stationary epithelial phenotype to a migratory, drug resistant mesenchymal phenotype. This process includes the disassembly of epithelial cell-junctions and a loss of epithelial polarity in exchange for mesenchymal characteristics, such as a fibroblast-like morOpportunity for Pharmaceutical Intervention in Lung Cancer: Selective Inhibition of JAK1/2 to Eliminate EMT-Derived Mesenchymal Cells","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ular method (Herricks, Chen & Xia, 2004; Ouyang & Cho, 2011; Skrabalak, Wiley, Kim, Formo, & Xia, 2008). The chemical reduction method uses a reducing agent, such as NaBH4 and LiBEt3H, to reduce metal precursors to their pure metallic form (Gonsalvesa, Rangarajan & Wang, 2000). By controlling the experimental conditions, like the pH and precursor concentration, the shape, size and composition of NMA are well-controlled, making this method the most popular (Ouyang & Cho, 2011). Most studies employ complex chemical reduction methods to produce NMA with high catalytic capabilities. They include heating at high temperatures over 300°C (Ganesan, Freemantle, & Obare, 2007; Jana, Dutta, Bera, & Koner, 2008) or using complicated postnanoparticle immobilisation processes like layer-bylayer deposition (Ouyang & Cho, 2011). A convenient chemical reduction method by Ouyang & Cho (2011) is the low heat, solvent-free polyol reduction. The reducing agent used is ethylene glycol (EG), which is vaporized under low heat (below 200°C) so that the vapour will reduce metal precursors. EG is then oxidized to aldehydes and carboxylic acids. Gaseous products from this reaction will escape into the air, leaving the NMA end-product free of any liquid organic compounds. The formed NMA will have well-defined shapes and good adhesion to glass substrates. Thus, no additional steps of mixing metal precursors with surfactants and additives, which control the shapes, are required. Here we investigate the deposition of Pt–Au NMA of varying Pt:Au mass loading ratios on fluorine-doped tin oxide (FTO) glass substrates using the low heat, solvent-free polyol reduction by Ouyang & Cho (2011). We evaluate the hypothesis that the low heat, solvent-free polyol reduction method is able to produce the Pt–Au NMA that has better catalytic ability than that of pure Pt. We also investigate the role that the Pt:Au ratio plays in determining the catalytic capability of Pt–Au NMA. INTRODUCTION Platinum (Pt) nanoparticles act as catalysts in proton exchange membrane (PEM) fuel cells powering machinery (Bing, Liu, Zhang, Ghosh, & Zhang, 2010; Ouyang & Cho, 2011). Using H2 or liquid fuels like CH3OH, PEM fuel cells, made up of acid-soaked PEM placed in between the anode and cathode catalyst, oxidize the fuel at the cathode and reduce the oxygen entering the cell. This creates a potential difference, V, that drives an electric current. Said electric current can be used to power a variety of applications. The fuel cell could use a Pt plate or Pt coated substrate as either the anode or cathode catalysts. It has been reported in studies that by combining Pt with other metals to form nanostructured metal alloys (NMA), the adsorption of carbonaceous poisoning species like CO is suppressed (Ren et al., 2010). Such poisoning species tend to permanently bind themselves to the catalyst, leaving less sites for the oxidation and reduction of chemical species responsible for driving the electric current. Less ad
{"title":"Chemical Reduction and Deposition of Nanostructured Pt–Au Alloy","authors":"M. X. C. Seow","doi":"10.22186/jyi.31.4.7-11","DOIUrl":"https://doi.org/10.22186/jyi.31.4.7-11","url":null,"abstract":"ular method (Herricks, Chen & Xia, 2004; Ouyang & Cho, 2011; Skrabalak, Wiley, Kim, Formo, & Xia, 2008). The chemical reduction method uses a reducing agent, such as NaBH4 and LiBEt3H, to reduce metal precursors to their pure metallic form (Gonsalvesa, Rangarajan & Wang, 2000). By controlling the experimental conditions, like the pH and precursor concentration, the shape, size and composition of NMA are well-controlled, making this method the most popular (Ouyang & Cho, 2011). Most studies employ complex chemical reduction methods to produce NMA with high catalytic capabilities. They include heating at high temperatures over 300°C (Ganesan, Freemantle, & Obare, 2007; Jana, Dutta, Bera, & Koner, 2008) or using complicated postnanoparticle immobilisation processes like layer-bylayer deposition (Ouyang & Cho, 2011). A convenient chemical reduction method by Ouyang & Cho (2011) is the low heat, solvent-free polyol reduction. The reducing agent used is ethylene glycol (EG), which is vaporized under low heat (below 200°C) so that the vapour will reduce metal precursors. EG is then oxidized to aldehydes and carboxylic acids. Gaseous products from this reaction will escape into the air, leaving the NMA end-product free of any liquid organic compounds. The formed NMA will have well-defined shapes and good adhesion to glass substrates. Thus, no additional steps of mixing metal precursors with surfactants and additives, which control the shapes, are required. Here we investigate the deposition of Pt–Au NMA of varying Pt:Au mass loading ratios on fluorine-doped tin oxide (FTO) glass substrates using the low heat, solvent-free polyol reduction by Ouyang & Cho (2011). We evaluate the hypothesis that the low heat, solvent-free polyol reduction method is able to produce the Pt–Au NMA that has better catalytic ability than that of pure Pt. We also investigate the role that the Pt:Au ratio plays in determining the catalytic capability of Pt–Au NMA. INTRODUCTION Platinum (Pt) nanoparticles act as catalysts in proton exchange membrane (PEM) fuel cells powering machinery (Bing, Liu, Zhang, Ghosh, & Zhang, 2010; Ouyang & Cho, 2011). Using H2 or liquid fuels like CH3OH, PEM fuel cells, made up of acid-soaked PEM placed in between the anode and cathode catalyst, oxidize the fuel at the cathode and reduce the oxygen entering the cell. This creates a potential difference, V, that drives an electric current. Said electric current can be used to power a variety of applications. The fuel cell could use a Pt plate or Pt coated substrate as either the anode or cathode catalysts. It has been reported in studies that by combining Pt with other metals to form nanostructured metal alloys (NMA), the adsorption of carbonaceous poisoning species like CO is suppressed (Ren et al., 2010). Such poisoning species tend to permanently bind themselves to the catalyst, leaving less sites for the oxidation and reduction of chemical species responsible for driving the electric current. Less ad","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felix Tellander, J. Ulander, I. Yakimenko, K. Berggren
realization of quantum structures since they are easier to handle. Optical and laser cavities have recently been used for studying the concept of space-time reflection symmetry (Brandstetter et al., 2013; Liertzer et al., 2012) developed by Bender, Boettcher and Meisinger (Bender & Boettcher, 1998; Bender, Boettcher, & Meisinger, 1999) as an extension of Hermitian quantum mechanics. Acoustic and microwave cavities have been used to study exceptional points (Dembowski, et al., 2001; Ding, Ma, Xiao, Zhang, & Chan, 2016) which are points where the eigenvalues of two states are equal and their corresponding eigenvectors just differ by a phase (Rotter, 2009). Microwave cavities have also been important in the development of quantum chaos (Sadreev & Berggren, 2005; Stöckmann, 1999); the study of quantum systems that in the classical limit is chaotic i.e. a change in the initial conditions leads to exponential divergence of the trajectories in phase space. Earlier studies, especially of quantum structures, have focused on two-dimensional fields because they are easier to study experimentally. However, a more realistic theoretical model would need to take all three dimensions into account (Ferry, Goodnick, & Bird, 2009). In this paper, we model three-dimensional quantum billiards with different boundary conditions and study the structure of the probability current for states of different excitations. Because different boundary conditions in the modeling were employed, the results are also applicable to the other wave analogues. The probability current is a three-dimensional vector field, which is difficult to visualize. Therefore, we also study the nodal surfaces and nodal lines. Nodal surfaces are surfaces where either the real or the imaginary part of the wave function is zero and the nodal lines are the intersection between the nodal surfaces (i.e., where both the real and imaginary parts are zero). The current will create vortices around these lines (Dirac, 1931; Wyatt, 2005). If the distribution of vortices is known, the overall structure of the current is known. The appearance and location of vortices have been directly connected to minima in the conductance i.e. the transmission through INTRODUCTION Mapping and understanding the structure of wave fields and currents is relevant to a variety of structures such as quantum structures, optical and acoustic cavities, microwave billiards and water waves in a tank (Berggren & Ljung, 2009; Berggren, Yakimenko, & Hakanen, 2010; Blümel, Davidson, Reinhardt, Lin, & Sharnoff, 1992; Stöckmann , 1999; Chen, Liu, Su, Lu, Chen, & Huang, 2007; Ohlin & Berggren, 2016; Panda & Hazra, 2014). Here, cavities and billiards stand for systems with hard walls such that a particle or a wave only scatter from the walls and there is no scattering within the system. Acoustic cavities are metal enclosed cavities where a microphone is used to emit the waves. The underlying physics of all these systems is seemingly different. For
{"title":"Probability Current and a Simulation of Particle Separation","authors":"Felix Tellander, J. Ulander, I. Yakimenko, K. Berggren","doi":"10.22186/jyi.31.4.1-6","DOIUrl":"https://doi.org/10.22186/jyi.31.4.1-6","url":null,"abstract":"realization of quantum structures since they are easier to handle. Optical and laser cavities have recently been used for studying the concept of space-time reflection symmetry (Brandstetter et al., 2013; Liertzer et al., 2012) developed by Bender, Boettcher and Meisinger (Bender & Boettcher, 1998; Bender, Boettcher, & Meisinger, 1999) as an extension of Hermitian quantum mechanics. Acoustic and microwave cavities have been used to study exceptional points (Dembowski, et al., 2001; Ding, Ma, Xiao, Zhang, & Chan, 2016) which are points where the eigenvalues of two states are equal and their corresponding eigenvectors just differ by a phase (Rotter, 2009). Microwave cavities have also been important in the development of quantum chaos (Sadreev & Berggren, 2005; Stöckmann, 1999); the study of quantum systems that in the classical limit is chaotic i.e. a change in the initial conditions leads to exponential divergence of the trajectories in phase space. Earlier studies, especially of quantum structures, have focused on two-dimensional fields because they are easier to study experimentally. However, a more realistic theoretical model would need to take all three dimensions into account (Ferry, Goodnick, & Bird, 2009). In this paper, we model three-dimensional quantum billiards with different boundary conditions and study the structure of the probability current for states of different excitations. Because different boundary conditions in the modeling were employed, the results are also applicable to the other wave analogues. The probability current is a three-dimensional vector field, which is difficult to visualize. Therefore, we also study the nodal surfaces and nodal lines. Nodal surfaces are surfaces where either the real or the imaginary part of the wave function is zero and the nodal lines are the intersection between the nodal surfaces (i.e., where both the real and imaginary parts are zero). The current will create vortices around these lines (Dirac, 1931; Wyatt, 2005). If the distribution of vortices is known, the overall structure of the current is known. The appearance and location of vortices have been directly connected to minima in the conductance i.e. the transmission through INTRODUCTION Mapping and understanding the structure of wave fields and currents is relevant to a variety of structures such as quantum structures, optical and acoustic cavities, microwave billiards and water waves in a tank (Berggren & Ljung, 2009; Berggren, Yakimenko, & Hakanen, 2010; Blümel, Davidson, Reinhardt, Lin, & Sharnoff, 1992; Stöckmann , 1999; Chen, Liu, Su, Lu, Chen, & Huang, 2007; Ohlin & Berggren, 2016; Panda & Hazra, 2014). Here, cavities and billiards stand for systems with hard walls such that a particle or a wave only scatter from the walls and there is no scattering within the system. Acoustic cavities are metal enclosed cavities where a microphone is used to emit the waves. The underlying physics of all these systems is seemingly different. For","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
cial expressions or words. During the modified dot-probe task, two stimuli appear on the screen for less than 1000 milliseconds, after which a target (letter or symbol) replaces one of the stimuli. The participant is asked to respond to the target as quickly and accurately as possible. The trial is named for the type of stimulus being replaced by the target (i.e., if a threat stimulus is replaced, the trial is a threat trial). In the literature, three ABM conditions have been tested: attend positive (positive stimulus is more often replaced by a target), attend threat (negative stimulus is more often replaced by a target), and a no-training control (stimulus types are replaced by a target with equal probability; Frewen, Dozois, Joanisse, & Neufeld, 2008; Klumpp & Amir, 2010). An attention bias, the tendency to attend to a certain type of information over other types of information, can be determined by calculating the difference in reaction times between threat trials and positive trials (Amir et al., 2009; Izetelny, 2006). This calculation is most commonly carried out using data from an assessment task, which is often a dot-probe task similar to the control training (Boettcher et al., 2013; White, Suway, Pine, Bar-Haim, & Fox, 2011). Individuals with SAD often demonstrate an attention bias to threat in these tasks (Bogels & Mansell, 2004). ABM has been developed in an effort to reduce this attention bias. In the dot-probe paradigm, attention bias manifests itself in reaction times. For example, if a SAD subject has an attention bias towards threat, the subject is, on average, quicker to respond to threat trials than to positive trials. This occurs because the subject’s attention is immediately drawn to the threatening stimuli. When the stimulus is replaced with an arrow, the subject will then respond more quickly. However, previous findings on the subject are mixed, with some studies reporting no bias among SAD subjects (Boettcher et al., 2013; Bradley et al., 1997) or even a bias away from threat INTRODUCTION Social Anxiety Disorder (SAD) is characterized by excessive worry and self-consciousness surrounding social situations due to significant discomfort, negative internal evaluations, or anticipated embarrassment (American Psychological Association, 2013). SAD is a debilitating disorder which leads to significant impairment in work and social situations. Annually, about 7% of the population meets DSM-V criteria for SAD and it accounts for 10% to 20% of people with anxiety disorders in outpatient settings (American Psychological Association, 2013; Ruscio et al., 2008). Not surprisingly, treatment for this disorder is in high demand. In an effort to reduce anxiety symptoms, attention bias modification (ABM) has been explored as a potential computer-based treatment for SAD designed to alter how people process and pay attention to social information (Amir et al., 2008; Heeren, Lievens, & Philippot, 2011; Klumpp & Amir, 2010). ABM is a modified do
{"title":"Exploring Carry-Over Effects to Elucidate Attention Bias Modification’s Mixed Results","authors":"Mackenna Hill, E. Duval","doi":"10.22186/jyi.31.3.9-14","DOIUrl":"https://doi.org/10.22186/jyi.31.3.9-14","url":null,"abstract":"cial expressions or words. During the modified dot-probe task, two stimuli appear on the screen for less than 1000 milliseconds, after which a target (letter or symbol) replaces one of the stimuli. The participant is asked to respond to the target as quickly and accurately as possible. The trial is named for the type of stimulus being replaced by the target (i.e., if a threat stimulus is replaced, the trial is a threat trial). In the literature, three ABM conditions have been tested: attend positive (positive stimulus is more often replaced by a target), attend threat (negative stimulus is more often replaced by a target), and a no-training control (stimulus types are replaced by a target with equal probability; Frewen, Dozois, Joanisse, & Neufeld, 2008; Klumpp & Amir, 2010). An attention bias, the tendency to attend to a certain type of information over other types of information, can be determined by calculating the difference in reaction times between threat trials and positive trials (Amir et al., 2009; Izetelny, 2006). This calculation is most commonly carried out using data from an assessment task, which is often a dot-probe task similar to the control training (Boettcher et al., 2013; White, Suway, Pine, Bar-Haim, & Fox, 2011). Individuals with SAD often demonstrate an attention bias to threat in these tasks (Bogels & Mansell, 2004). ABM has been developed in an effort to reduce this attention bias. In the dot-probe paradigm, attention bias manifests itself in reaction times. For example, if a SAD subject has an attention bias towards threat, the subject is, on average, quicker to respond to threat trials than to positive trials. This occurs because the subject’s attention is immediately drawn to the threatening stimuli. When the stimulus is replaced with an arrow, the subject will then respond more quickly. However, previous findings on the subject are mixed, with some studies reporting no bias among SAD subjects (Boettcher et al., 2013; Bradley et al., 1997) or even a bias away from threat INTRODUCTION Social Anxiety Disorder (SAD) is characterized by excessive worry and self-consciousness surrounding social situations due to significant discomfort, negative internal evaluations, or anticipated embarrassment (American Psychological Association, 2013). SAD is a debilitating disorder which leads to significant impairment in work and social situations. Annually, about 7% of the population meets DSM-V criteria for SAD and it accounts for 10% to 20% of people with anxiety disorders in outpatient settings (American Psychological Association, 2013; Ruscio et al., 2008). Not surprisingly, treatment for this disorder is in high demand. In an effort to reduce anxiety symptoms, attention bias modification (ABM) has been explored as a potential computer-based treatment for SAD designed to alter how people process and pay attention to social information (Amir et al., 2008; Heeren, Lievens, & Philippot, 2011; Klumpp & Amir, 2010). ABM is a modified do","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
pharmaceuticals, attack cancer cells, neutralize environmental pollutants, and synthesize biofuels (Khalil & Collins, 2010). Gene expression begins with transcription, the process by which DNA information, in the form of the base sequence of a gene, is converted into RNA base sequence information. For genes that encode proteins, the RNA product of transcription is used during translation to encode the sequence of amino acids in a protein. As the first step in gene expression, transcription is an important control point for gene regulation. Initiation of transcription in bacteria involves binding of an enzyme called RNA polymerase to a sequence of DNA called a transcriptional promoter. As illustrated in Figure 1, a common form of bacterial promoters includes two conserved sequence elements, a -35 region that is recognized during transcriptional initiation by RNA polymerase and its associated Sigma factor, and a -10 region that is involved in DNA melting (Ross, Aiyar, Salomon, & Gourse, 1998). The consensus sequence for the -35 region of E. coli promoters has been widely reported to be TTGACA (Harley & Reynolds, 1987; Lisser & Margalit, 1993). The consensus sequence of the -10 region is TATAAT (Waterman, Arratia, & Galas, 1984). The RNA polymerase attaches itself to one of the two DNA strands referred to as the template strand and begins to use it to make RNA. The RNA polymerase proceeds to slide along the template strand for the entire length of the gene, reading it in a 3’ to 5’ direction. Transcription ceases when the RNA polymerase encounters a transcriptional terminator. In bacteria, the resulting RNA transcript is used for translation as soon as it is available. Mutational analysis of the -35 region of naturally occurring promoters showed that the -35 region is involved in the initial binding of the RNA polymerase to the promoter, and that it is an important contributor to the overall strength of a bacterial promoter. An in vitro study of the effect of mutations in the -35 region on the INTRODUCTION Gene expression is the process by which gene information is used to direct the function of cells. It is regulated in all cells because not all genes are required all the time or under all circumstances. For example, human brain cells need to express certain genes that are not needed in muscle cells, and vice versa (Gurdon & Melton, 2008). In a similar sense, bacteria must express different genes depending on temperature, pH, osmotic pressure, or the availability of food (Beales, 2004). Knowledge of gene regulation is important for understanding the differentiation and function of eukaryotic cells, the development of tissues in multicellular organisms, and the relationships of bacteria to their environments throughout the biosphere. It helps us to understand genetic diseases, diseases impacted by genetics, and cellular disorders such as cancer (LópezBigas & Ouzounis, 2004). Gene regulation research can also be used to explore the contribution of ba
{"title":"Mutational Analysis of Transcriptional Initiation in Bacteria","authors":"Anthony J. Eckdahl, Todd J. Eckdahl","doi":"10.22186/jyi.31.3.1-8","DOIUrl":"https://doi.org/10.22186/jyi.31.3.1-8","url":null,"abstract":"pharmaceuticals, attack cancer cells, neutralize environmental pollutants, and synthesize biofuels (Khalil & Collins, 2010). Gene expression begins with transcription, the process by which DNA information, in the form of the base sequence of a gene, is converted into RNA base sequence information. For genes that encode proteins, the RNA product of transcription is used during translation to encode the sequence of amino acids in a protein. As the first step in gene expression, transcription is an important control point for gene regulation. Initiation of transcription in bacteria involves binding of an enzyme called RNA polymerase to a sequence of DNA called a transcriptional promoter. As illustrated in Figure 1, a common form of bacterial promoters includes two conserved sequence elements, a -35 region that is recognized during transcriptional initiation by RNA polymerase and its associated Sigma factor, and a -10 region that is involved in DNA melting (Ross, Aiyar, Salomon, & Gourse, 1998). The consensus sequence for the -35 region of E. coli promoters has been widely reported to be TTGACA (Harley & Reynolds, 1987; Lisser & Margalit, 1993). The consensus sequence of the -10 region is TATAAT (Waterman, Arratia, & Galas, 1984). The RNA polymerase attaches itself to one of the two DNA strands referred to as the template strand and begins to use it to make RNA. The RNA polymerase proceeds to slide along the template strand for the entire length of the gene, reading it in a 3’ to 5’ direction. Transcription ceases when the RNA polymerase encounters a transcriptional terminator. In bacteria, the resulting RNA transcript is used for translation as soon as it is available. Mutational analysis of the -35 region of naturally occurring promoters showed that the -35 region is involved in the initial binding of the RNA polymerase to the promoter, and that it is an important contributor to the overall strength of a bacterial promoter. An in vitro study of the effect of mutations in the -35 region on the INTRODUCTION Gene expression is the process by which gene information is used to direct the function of cells. It is regulated in all cells because not all genes are required all the time or under all circumstances. For example, human brain cells need to express certain genes that are not needed in muscle cells, and vice versa (Gurdon & Melton, 2008). In a similar sense, bacteria must express different genes depending on temperature, pH, osmotic pressure, or the availability of food (Beales, 2004). Knowledge of gene regulation is important for understanding the differentiation and function of eukaryotic cells, the development of tissues in multicellular organisms, and the relationships of bacteria to their environments throughout the biosphere. It helps us to understand genetic diseases, diseases impacted by genetics, and cellular disorders such as cancer (LópezBigas & Ouzounis, 2004). Gene regulation research can also be used to explore the contribution of ba","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
show strong affinity for these self-peptide/MHC complexes are deleted by activation-induced apoptosis. The deletion of autoreactive T cell clones through thymic-expressed TSAs is known as central tolerance. The discrepancy between antigens expressed and presented by cortical thymic epithelial cells (cTECs) versus mTECs has been termed the alternate peptide hypothesis. This hypothesis can partially explain how autoreactive T cells survive positive selection in the cortex but fail to pass negative selection in the medulla (Marrack, McCormack, & Kappler, 1989). In order to express TSAs, mTECs must transactivate genes that are not normally expressed in the thymus through a process called promiscuous gene expression (PGE; De Martino et al., 2013; Kyewski & Derbinski, 2004; Laan & Peterson, 2013; Metzger & Anderson, 2011; Tykocinski, Sinemus, & Kyewski, 2008). PGE is dependent upon the transcription of DNA in chromatin states often associated with inhibited expression (Abramson, Giraud, Benoist, & Mathis, 2010; Tykocinski et al., 2010; Ucar & Rattay, 2015; Žumer, Saksela, & Peterlin, 2013). The autoimmune regulator (AIRE) protein expressed in mTECs is a transcription factor that facilitates this process. Loss of AIRE function limits TSA tolerance, leading to organspecific autoimmunity and autoantibody production (Kisand & Peterson, 2015; Laan & Peterson, 2013; Metzger & Anderson, 2011). Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is the monogenic disorder caused by mutations at the AIRE locus. However, APECED may be considered a syndrome because symptoms can also stem from indirect disruptions of AIRE function (De Martino et al., 2013). While APECED cases may feature some similar symptoms such as mucocutaneous canIntroduction T cells provide capable, targeted defense against foreign antigens through their receptor specificity. The vast repertoire of T cell receptors allows the immune system to mount a response against most foreign invaders. Generation of receptor diversity is accomplished mainly through gene rearrangement at the alpha and beta chain loci. Positive selection in the thymic cortex is able to expand T cell clones with receptors that bind major histocompatibility complex (MHC)/self-peptide complexes with at least moderate affinity (De Martino et al., 2013). However, cells that pass positive selection may still have a strong affinity for self-peptides presented on MHC molecules. In order to eliminate these autoreactive T cells from escaping from the thymus into the periphery, T cell clones positively selected for in the thymic cortex undergo negative selection in the thymic medulla. During the negative selection process, T cells are presented with medullary thymic epithelial cell (mTEC)-expressed tissue-specific antigens (TSAs) in the medulla (Derbinski, Schulte, Kyewski, & Klein, 2001; Kyewski & Derbinski, 2004). T cells that AIRE Deficiency Exposes Inefficiencies of Peripheral Tolerance Leading to Variable APECE
{"title":"AIRE Deficiency Exposes Inefficiencies of Peripheral Tolerance Leading to Variable APECED Phenotypes","authors":"Jake E. Batchelder","doi":"10.22186/jyi.31.3.15-20","DOIUrl":"https://doi.org/10.22186/jyi.31.3.15-20","url":null,"abstract":"show strong affinity for these self-peptide/MHC complexes are deleted by activation-induced apoptosis. The deletion of autoreactive T cell clones through thymic-expressed TSAs is known as central tolerance. The discrepancy between antigens expressed and presented by cortical thymic epithelial cells (cTECs) versus mTECs has been termed the alternate peptide hypothesis. This hypothesis can partially explain how autoreactive T cells survive positive selection in the cortex but fail to pass negative selection in the medulla (Marrack, McCormack, & Kappler, 1989). In order to express TSAs, mTECs must transactivate genes that are not normally expressed in the thymus through a process called promiscuous gene expression (PGE; De Martino et al., 2013; Kyewski & Derbinski, 2004; Laan & Peterson, 2013; Metzger & Anderson, 2011; Tykocinski, Sinemus, & Kyewski, 2008). PGE is dependent upon the transcription of DNA in chromatin states often associated with inhibited expression (Abramson, Giraud, Benoist, & Mathis, 2010; Tykocinski et al., 2010; Ucar & Rattay, 2015; Žumer, Saksela, & Peterlin, 2013). The autoimmune regulator (AIRE) protein expressed in mTECs is a transcription factor that facilitates this process. Loss of AIRE function limits TSA tolerance, leading to organspecific autoimmunity and autoantibody production (Kisand & Peterson, 2015; Laan & Peterson, 2013; Metzger & Anderson, 2011). Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is the monogenic disorder caused by mutations at the AIRE locus. However, APECED may be considered a syndrome because symptoms can also stem from indirect disruptions of AIRE function (De Martino et al., 2013). While APECED cases may feature some similar symptoms such as mucocutaneous canIntroduction T cells provide capable, targeted defense against foreign antigens through their receptor specificity. The vast repertoire of T cell receptors allows the immune system to mount a response against most foreign invaders. Generation of receptor diversity is accomplished mainly through gene rearrangement at the alpha and beta chain loci. Positive selection in the thymic cortex is able to expand T cell clones with receptors that bind major histocompatibility complex (MHC)/self-peptide complexes with at least moderate affinity (De Martino et al., 2013). However, cells that pass positive selection may still have a strong affinity for self-peptides presented on MHC molecules. In order to eliminate these autoreactive T cells from escaping from the thymus into the periphery, T cell clones positively selected for in the thymic cortex undergo negative selection in the thymic medulla. During the negative selection process, T cells are presented with medullary thymic epithelial cell (mTEC)-expressed tissue-specific antigens (TSAs) in the medulla (Derbinski, Schulte, Kyewski, & Klein, 2001; Kyewski & Derbinski, 2004). T cells that AIRE Deficiency Exposes Inefficiencies of Peripheral Tolerance Leading to Variable APECE","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Wear Evaluation of Ultra High Molecular Weight Polyethylene (UHMWPE) against Nanostructured Diamond-Coated Ti-6Al-4V Alloy","authors":"D. Yamaleyeva, P. A. Baker, Aaron A. Cateldge","doi":"10.22186/jyi.31.3.21-26","DOIUrl":"https://doi.org/10.22186/jyi.31.3.21-26","url":null,"abstract":"","PeriodicalId":74021,"journal":{"name":"Journal of young investigators","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68279541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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