Matching Items (77)
Description
Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution.
ContributorsLi, Dianfan (Author) / Stansfeld, Phillip J. (Author) / Sansom, Mark S. P. (Author) / Keogh, Aaron (Author) / Vogeley, Lutz (Author) / Howe, Nicole (Author) / Lyons, Joseph A. (Author) / Aragao, David (Author) / Fromme, Petra (Author) / Fromme, Raimund (Author) / Basu, Shibom (Author) / Grotjohann, Ingo (Author) / Kupitz, Christopher (Author) / Rendek, Kimberley (Author) / Weierstall, Uwe (Author) / Zatsepin, Nadia (Author) / Cherezov, Vadim (Author) / Liu, Wei (Author) / Bandaru, Sateesh (Author) / English, Niall J. (Author) / Gati, Cornelius (Author) / Barty, Anton (Author) / Yefanov, Oleksandr (Author) / Chapman, Henry N. (Author) / Diederichs, Kay (Author) / Messerschmidt, Marc (Author) / Boutet, Sebastien (Author) / Williams, Garth J. (Author) / Seibert, M. Marvin (Author) / Caffrey, Martin (Author) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / Department of Physics (Contributor)
Created2015-12-17
Description
Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 Å resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 Å resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
ContributorsEdlund, Petra (Author) / Takala, Heikki (Author) / Claesson, Elin (Author) / Henry, Leocadie (Author) / Dods, Robert (Author) / Lehtivuori, Heli (Author) / Panman, Matthijs (Author) / Pande, Kanupriya (Author) / White, Thomas (Author) / Nakane, Takanori (Author) / Berntsson, Oskar (Author) / Gustavsson, Emil (Author) / Bath, Petra (Author) / Modi, Vaibhav (Author) / Roy Chowdhury, Shatabdi (Author) / Zook, James (Author) / Berntsen, Peter (Author) / Pandey, Suraj (Author) / Poudyal, Ishwor (Author) / Tenboer, Jason (Author) / Kupitz, Christopher (Author) / Barty, Anton (Author) / Fromme, Petra (Author) / Koralek, Jake D. (Author) / Tanaka, Tomoyuki (Author) / Spence, John (Author) / Liang, Mengning (Author) / Hunter, Mark S. (Author) / Boutet, Sebastien (Author) / Nango, Eriko (Author) / Moffat, Keith (Author) / Groenhof, Gerrit (Author) / Ihalainen, Janne (Author) / Stojkovic, Emina A. (Author) / Schmidt, Marius (Author) / Westenhoff, Sebastian (Author) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / Department of Physics (Contributor)
Created2016-10-19
Description
Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 Å resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within the crystal lattice is confirmed by time-resolved visible absorption spectroscopy. This study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX.
ContributorsNogly, Przemyslaw (Author) / Panneels, Valerie (Author) / Nelson, Garrett (Author) / Gati, Cornelius (Author) / Kimura, Tetsunari (Author) / Milne, Christopher (Author) / Milathianaki, Despina (Author) / Kubo, Minoru (Author) / Wu, Wenting (Author) / Conrad, Chelsie (Author) / Coe, Jesse (Author) / Bean, Richard (Author) / Zhao, Yun (Author) / Bath, Petra (Author) / Dods, Robert (Author) / Harimoorthy, Rajiv (Author) / Beyerlein, Kenneth R. (Author) / Rheinberger, Jan (Author) / James, Daniel (Author) / Deponte, Daniel (Author) / Li, Chufeng (Author) / Sala, Leonardo (Author) / Williams, Garth J. (Author) / Hunter, Mark S. (Author) / Koglin, Jason E. (Author) / Berntsen, Peter (Author) / Nango, Eriko (Author) / Iwata, So (Author) / Chapman, Henry N. (Author) / Fromme, Petra (Author) / Frank, Matthias (Author) / Abela, Rafael (Author) / Boutet, Sebastien (Author) / Barty, Anton (Author) / White, Thomas A. (Author) / Weierstall, Uwe (Author) / Spence, John (Author) / Neutze, Richard (Author) / Schertler, Gebhard (Author) / Standfuss, Jorg (Author) / College of Liberal Arts and Sciences (Contributor) / Department of Physics (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / School of Molecular Sciences (Contributor)
Created2016-08-22
Description
The main purpose of this investigation is to determine the intensity, economic costs, and potential solutions to HIV/AIDS stigma in the United States and Tanzania. In order to accomplish this goal, a literature review was conducted, and an economic model was created to determine how HIV/AIDS treatment deterrence manifests and affects these countries. The results of the economic model suggested that Tanzania suffers greater economic loss due to HIV treatment deterrence than the United States, however, both countries lose a significant portion of GDP due to HIV treatment deterrence. Stigma materializes differently in each country based on a variety of sociocultural factors. These include the demographic groups most affected, the perception of those living with HIV, and how sexually transmitted infections are perceived within communities. The solutions to HIV stigma must be tailored to the country, culture, and context that it arises for interventions to be effective. To further prevent HIV/AIDS stigma and its economic consequences, the etiology of stigma and how it presents in different communities must be understood.
ContributorsSangha, Pooja (Co-author) / Hopewell, Sophia (Co-author) / Baldwin, Marjorie (Thesis director) / Hruschka, Daniel (Committee member) / Department of Psychology (Contributor) / Department of Economics (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This paper explores the impacts of dam-induced displacement on the health of populations. By the start of the 21st century, an estimated 40-80 million people worldwide were forced to resettle due to the construction of large dams. The process of displacement and resettlement is connected to numerous social impacts on communities such as decreases in household income, natural resources, and social connectivity, but less seems to be known about specific health impacts. Analyzing literature in a formal review allowed for increased understanding about what information already exists in published research regarding the connections between dams, displacement, and health. Some negative health impacts as a result of forced displacement were identified, including increases in infectious disease transmission, depression, and mortality rates as well as losses of food and water sources. However, the small amount of cases found in the literature review when compared to the massive scale of dam development worldwide indicates a gap in knowledge in the dam industry and research field specifically about the health of the vast majority of populations forcibly displaced by dams. Health impacts must be considered and systematically studied in dam projects involving displacement to fully understand the needs of resettled populations and move towards equitable processes in development projects worldwide.
ContributorsWalker, Erika (Author) / Hruschka, Daniel (Thesis director) / Brian, Jennifer (Committee member) / Drake, Alexandria (Committee member) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In Western medicine, the hard sciences have generally been understood as the sole guiding force in patient care and treatment. However, both history and the present day suggest another strong influence on Western medicine: folklore. The term folklore can easily be dismissed as a term representing beliefs and stories of the past, but its relevance transcends time and continues to impact people daily. It “involves values, traditions, ways of thinking and behaving. It’s about art. It’s about people and the way people learn. It helps us learn who we are and how to make meaning in the world around us” (Sims & Stephens, 2011, pp. 1-2). With its wide range of influence, folklore exists as the umbrella term encompassing several categories. Folk beliefs are one of these categories and can develop from “observation, memory, testimony or inference” (Hutton, 1942, p. 83). Given that each of these forms are subject to some sort of error, folk beliefs become “a jumble of the true and the erroneous” (p. 84). Similarly, contemporary legends are narratives that often combine the physical and supernatural world to explain nuances or uncertainty present in the relevant experiences of a people. Folk beliefs can result in the formation of contemporary legends and they can also stem from contemporary legends. These two categories are often associated with subjects that promote fear and uncertainty, and thus play an essential role in navigating folklore’s application to biomedicine. This paper explores the historical and modern effects that folklore has had on two separate maladies: Hansen’s Disease (leprosy) and Major Depressive Disorder (depression). While these conditions do not resemble each other in physical presentations, Hansen’s Disease and Major Depressive Disorder patients both have faced and continue to face discrimination. Andrea Wiley and John Allen’s three-part definition of a malady: society’s perception (sickness), the individual’s experience (illness), and medical professionals’ diagnosis and treatment (disease); was utilized as a tool for analyzing the application of folklore to modern medicine. The way that a society views a particular malady often dictates the sick role expected of a diagnosed individual. Additionally, the public’s view can directly affect medical professionals’ understanding of a malady. This then can drastically shape a patient’s diagnosis, treatment, and prognosis. This anthropological analysis acts as an interdisciplinary bridge between medicine and the humanities.
ContributorsPeake, Ashley E (Co-author) / Peake, Ashley (Co-author) / Ellis, Lawrence (Thesis director) / Hoyt, Heather (Committee member) / Hruschka, Daniel (Committee member) / School of Molecular Sciences (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Menstruation - a stigmatized topic and a social taboo- has led to a lack of menstrual hygiene awareness and improper practices impacting women’s health adversely over generations in India. Akshara aims to increase menstrual hygiene education and reduce stigma in India. A creative children’s illustrated book, and interactive workshop curriculum about menstruation were designed and published in Hindi and English. Menstrual hygiene workshops, utilizing the designed tools, were conducted in Delhi and Ghaziabad, India to over 230 students through NGO partnerships in December 2018. The response to the menstrual hygiene and stigma workshops was overwhelmingly positive, and a significant increase in the knowledge and awareness survey scores was observed after the curriculum teachings and classroom discussions. This evaluation highlights and provides a potential solution path to eradicate the root cause of the menstruation stigma in underprivileged women through education and open conversations on the topic starting at a pivotal young age. The main aim of the workshop was to help eradicate the stigma associated with menstruation and menstrual health in India through education.
ContributorsBhalla, Jahnavi (Co-author) / Dani, Advika (Co-author) / Schuster, Roseanne (Thesis director) / Hruschka, Daniel (Thesis director) / School of Molecular Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
More than 40% of all U.S. opioid overdose deaths in 2016 involved a prescription opioid, with more than 46 people dying every day from overdoses involving prescription opioids, (CDC, 2017). Over the years, lawmakers have implemented policies and laws to address the opioid epidemic, and many of these vary from state to state. This study will lay out the basic guidelines of common pieces of legislation. It also examines relationships between 6 state-specific prescribing or preventative laws and associated changes in opioid-related deaths using a longitudinal cross-state study design (2007-2015). Specifically, it uses a linear regression to examine changes in state-specific rates of opioid-related deaths after implementation of specific policies, and whether states implementing these policies saw smaller increases than states without these policies. Initial key findings of this study show that three policies have a statistically significant association with opioid related overdose deaths are—Good Samaritan Laws, Standing Order Laws, and Naloxone Liability Laws. Paradoxically, all three policies correlated with an increase in opioid overdose deaths between 2007 and 2016. However, after correcting for the potential spurious relationship between state-specific timing of policy implementation and death rates, two policies have a statistically significant association (alpha <0.05) with opioid overdose death rates. First, the Naloxone Liability Laws were significantly associated with changes in opioid-related deaths and was correlated with a 0.33 log increase in opioid overdose death rates, or a 29% increase. This equates to about 1.39 more deaths per year per 100,000 people. Second, the legislation that allows for 3rd Party Naloxone prescriptions correlated with a 0.33 log decrease in opioid overdose death rates, or a 29% decrease. This equates to 1.39 fewer deaths per year per 100,000 people.
ContributorsDavis, Joshua Alan (Author) / Hruschka, Daniel (Thesis director) / Gaughan, Monica (Committee member) / School of Human Evolution & Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In an increasingly interconnected world, the 17 Sustainable Development Goals are the United Nations’ framework for ensuring we continue to transform our world for the better, leaving no population behind. This study examines how the terminology of Sustainable Development Goal 17 for global partnership affects its implementation, focusing on “building capacity”—a widely referenced target in the development arena—and the involvement of the private sector. Key informant interviews with experts in the fields of conflict of interest, ethics, and development revealed a wide variety of (often conflicting) notions about partnership, frameworks for capacity development, and the interactions between public and private actors. A literature review of key policy documents examined the terminology and implementation of multistakeholder partnerships, and analysis offered considerations for risks and suggestions in policy terminology. Results indicate a need for increased attention to the use of partnership terminology as a catch-all term to encompass development work, and makes several recommendations for changes to combat misuse of the partnership label. Finally, this study acknowledges that there is a continued need for research-based evidence for effectiveness of the partnership-based development approach.
ContributorsThomson, Azalea Mae (Author) / Gaughan, Monica (Thesis director) / Hruschka, Daniel (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The development of safe and effective vaccines has been one of the greatest public achievements of the 20th century. However, there is still considerable public debate about the relative health costs and benefits of vaccines, and the information and misinformation spread through these debates can have a direct impact on vaccination and whether or not herd immunity will continue in the United States for different diseases. To understand perceptions of vaccine risks and effectiveness among young adults in the U.S., this study describes Arizona State University students' perceptions of the harms and benefits of vaccines. A preliminary free list (n=30) identified what vaccines ASU college students were most likely to recall spontaneously. The six vaccines most commonly mentioned by ASU students were: influenza (flu), chickenpox, HPV, polio, MMR, and smallpox. Using these top six vaccines, we then developed a second survey about the knowledge and perceptions of each of these vaccines and vaccines as a whole. We found that students generally perceived vaccines as safe and important to their health, but they maintained an overall lack of understanding of how vaccines work and what they protect against. While this study is only a preliminary investigation into the perceptions of ASU college students on six commonly mentioned vaccines, this could lead to investigations on how to educate and promote the usage of vaccines to college students.
ContributorsGilson, Jacob (Co-author) / Sutton, Carly (Co-author) / Hruschka, Daniel (Thesis director) / Ruth, Alissa (Committee member) / W. P. Carey School of Business (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12