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Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria and Analysis of Potential Metabolic Diversity
Get PDFThe importance of natural product discovery to society is undeniable as natural products have seemingly infinite applications, particularly in regard to pharmacological use as antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive agents. The search for new therapeutics and other new chemical commodities thus grows simultaneously with antibiotic resistance and commercial pressure on pharmaceutical research. However, the increasingly common phenomenon of natural product rediscovery continues to inhibit advancement in this field. We contend that the likelihood of rediscovery can be predicted by taxonomic distance between the bacteria in question and previously studied bacteria. That is, our data supports a correlation between chemical diversity and taxonomic distance, and we offer the hopeful perspective that less commonly explored genera have outstanding potential for unique natural product discovery. Specifically, we have examined the order Myxococcales, a reputable source of secondary metabolites. Our findings have been facilitated by the mining of bacterial genomes for biosynthetic gene clusters (BGCs), a methodology that has become a critical component to natural product discovery as it takes advantage of the increasing number of sequenced bacterial genomes available through public databases. By using the BiG-SCAPE-CORASON platform to generate sequence similarity networks that contain 994 BGCs identified by antiSMASH from 36 sequenced myxobacteria, we have observed that every predicted BGC was specific to one of three current suborders of myxobacteria. The analysis of BGCs detected within four additional, draft genomes supports the observation that myxobacterial biosynthetic diversity correlates with taxonomic distance and suggests the likelihood of rediscovery when targeting previously investigated genera. Further, 822 BGCs with no notable homology to characterized clusters within the MIBiG database are presented. This survey portrays the biosynthetic diversity of these BGCs and exemplifies the potential for natural product discovery from myxobacteria. Herein we report the likelihood for rediscovery of known metabolites from bacteria belonging to previously explored genera. The results depict significant biosynthetic potential of bacteria associated with overlooked taxa within the Myxococcales and possibly other natural product-associated bacteria orders
Effects of Mycoplasma gallisepticum on experimentally infected Eastern Bluebirds (Sialia sialis)
Get PDFThe bacterium Mycoplasma gallisepticum is an avian respiratory pathogen that causes inflammation and swelling of conjunctiva in domestic poultry and wild finches. In the past, severity of conjunctivitis symptoms has been used to quantify infection severity and host resistance. However, many songbirds function as hosts to M. gallisepticum but do not develop this symptom at all. The absence of conjunctivitis, as well as other clinical signs, hinders our understanding of M. gallisepticum infection in the songbird community because some species are responding very differently than others. One such species is the Eastern Bluebird (Sialia sialis), a common songbird of the southeastern United States. In efforts to determine if M. gallisepticum is a respiratory pathogen of Eastern Bluebirds, data and samples collected from an experimental infection of wild-caught, captive housed birds were used. We quantified relative bacterial load in the eye conjunctiva and choanal cleft palate of infected birds and found that M. gallisepticum did not localize in the conjunctiva but was present in the palate of six out of nine birds 13 days following experimental infection. At this same time point, infected birds showed no significant difference in body condition measures when compared to controls but had significantly lower levels of circulating hemoglobin than did controls. Among infected birds, individuals with the greatest number of M. gallisepticum in their palate 13 days following infection lost more mass than did those with fewer bacteria. Hemoglobin levels and other measures of condition were not significantly correlated with pathogen load. These results suggest that although Eastern Bluebirds do not develop conjunctivitis, they are suffering from physiological consequences of infection. Furthermore, this could be the case in other host species that also do not develop conjunctivitis
The Economic and Social Benefits of Gender Parity in Employment and Education
Get PDFThis thesis seeks to examine the ways in which women are disadvantaged in their participation in formal employment and participation and attainment in education relative to men across the world. Furthermore, this analysis examines the economic impacts of inequalities in education and employment at a macroeconomic level and on an individual level. Most data is compiled from various Non-Governmental Organizations that fund and orchestrate global research on gender equality. The results of this research consistently indicate that women continue to face systematic disadvantages in employment, wages, occupation, upward mobility in occupations, hours worked, entrepreneurship, burden of unpaid work, educational attainment, and types of education. Furthermore, it was found that the economic impacts of the lack of gender parity in employment are extremely large and significant. In many areas of the world regional economies could see substantial growth from women increasing their participation in the economy to the same rate as men. Similar economic returns could be seen from increased female educational attainment, both on the societal and individual level. Aside from the economic impacts from education and employment parity, there are also social benefits for women who can gain more autonomy and decision making power through access to education and employment. Overall, there are important benefits to gender parity in education and employment, but achieving these goals will require substantial commitment and efforts from governments, organizations, and the population in general. Many systemic factors impede forward progress for women and they can only be addressed through continued policy implementation and other initiatives that incentivize and normalize gender equality in education and employment
The Role of Non-Governmental Organizations in Global Education: A Case Study on Sub-Saharan Africa
Get PDFThis paper will work to investigate the effectiveness of educational programs of international non-governmental organizations (NGOs) in developing countries. The purpose of this study is to examine the role of policy in the relationship between a host country and a non-governmental organization. Utilizing a comparative case study approach, this paper examines three different NGOs, operating out of three developing countries in Sub-Saharan Africa, all with the mission of aiding the realm of global education. Each case study examines the state, the NGO, the historical context of NGOs and the government chosen, the relationship of the NGO selected and the government, and finally, a presentation of findings from each case study. The results are computed and compared to create large-scale findings presented through the categorization of government, civil society, and education. Primarily, the findings that weaken the role of NGOs in education are government restraints, disregard for human rights or civil society, unqualified teachers and counterproductive education models that aren’t adherent to a nation’s curriculum or are unsustainable. These issues, in summation, could benefit from policies to address human rights, sustainability and accreditation as NGOs continue to expand on an international scale. NGOs genuinely are capable to catalyze change in the realm of education; however, it is with the regulation of clear policy that will allow this change to be positive. By regulating and monitoring the role of NGOs in government, civil society, and education, the presence of NGOs in global education can allow for collaboration on an international scale, challenging the entirety of the international community to take responsibility for providing the right to accessible, quality education for all
Investigating the Binding of Fentanyl and Fentanyl Analogs to the µ-Opioid Receptor
Get PDFIn 1960, Dr. Paul Janssen of the Janssen Company synthesized fentanyl. It is a
rapid-acting analgesic that, unlike similar analgesics around that time, did not have
negative cardiovascular effects. Fentanyl, and its derivatives, are strong μ-opioid receptor
agonists. Rates of fatal opioid overdoses involving fentanyl have increases rapidly over
the past two decades Due to these increasing concerns related to fentanyl and its
derivatives, it is important to not only study fentanyl and its known derivatives, but to
also study and understand potential new derivatives and how all these compounds interact
with the opioid receptors.
This study examined the interactions that take place between fentanyl, and its
analogs, and the opioid receptors they interact with in the body. The molecular modeling
software, Maestro, was used in order to study these specific interactions. Fentanyl and its
analogs were sketched and prepped for docking to the receptors using Maestro. The
opioid receptor chosen for this study from came from an available, active-state crystal
structure. The data from this study identified specific interactions that take place between
these drugs and the binding site of corresponding opioid receptor.
The designed derivatives used in this study were derivatives of the following
analogs: N-methyl fentanyl, fentanyl, carfentanyl, lofentanyl, remifentanil, sufentanil,
and alfentanil. Based on the resulting ligand interaction diagrams, it was determined that
many of the fentanyl ligands follow expected binding patterns within the binding pocket.
Key residue interactions included aromatic stacking interactions, hydrophobic
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interactions, polar interactions and hydrogen bonding. These interactions corresponded to
varying structural changes between fentanyl and its analogs. The interactions and
structural changes were used to help better understand the potency and toxicity of
fentanyl and fentanyl analogs. Future work will include using the results of this study to
help predict potential new analogs of fentanyl before they appear on the drug market.
Scientists and law enforcement will have advanced knowledge on various fentanyl
related substances to improve both detection and treatment of fatal overdose cases
Renewables & Refugees: A Solution for Jordan
Get PDFAs the Hashemite Kingdom of Jordan continues to host the third largest Syrian refugee population in the world, the state’s infrastructure and its people are taking a toll. Before the war in Syria began, Jordan was already suffering from a weak economy, resource scarcity, and an enormous population boom. Since accepting nearly 2.5 million refugees, these issues have compounded year after year—nearly reaching a breaking point.
I propose an unconventional solution to some aspects of the refugee crisis: renewable energy. Renewables are cheaper than fossil fuels, consume less water in electricity generation, emit fewer greenhouse gases, and promote job creation and diversification. Better yet, Jordan has enormous potential for renewable energy, especially in solar photovoltaics (PV) and wind.
In this study, I evaluate Jordan’s readiness to implement renewable energy, analyze a case study of the Za’atari refugee camp (which recently transitioned to running entirely on solar energy), and make basic projections on potential job creation and water conservation by switching from coal and natural gas to PV and wind. I find that Jordan has successfully paved the way for jumpstarting its renewable sector, Za’atari has benefitted from solar energy, and the outlook for job creation is good, and water conservation even better. There are also some smaller, indirect positive impacts that renewable energy can have on combating the Syrian refugee crisis in Jordan
The Protective Role of Estrogen on HIV-1 Mediated Neurotoxicity
Get PDFThe prevalence of HIV among men have been in a steady inclination over the last several decades, yet the accelerated infection rate among older women is considerably concerning. Not only does the HIV virus affect the immune system but it also affects the central nervous system. One of its viral proteins, Tat, acts as an excitotoxin and disrupts the cell’s membrane potential by increasing the concentration of Ca2+ inside the cell. This influx of calcium ions leads to apoptosis and secretion of the cell’s contents into the surrounding area. Macrophages, along with other innate immune components, gather and induce the release of cytokines or chemokines. However, it has been discovered that estrogens can be used to attenuate these harmful neurotoxic effects. Acknowledging that women over the age of 50 are undergoing menopause, the body’s natural levels of estrogen begin to decline. We hypothesized that estradiol (acting at estrogen receptor α or β) would attenuate Tat-mediated formation of reactive oxygen species (ROS), neurotoxicity, and cytokine production in differentiated SH-SY5Y human neuroblastoma cells and primary murine mixed glial cultures. Our findings suggest that any concentration of estradiol (0.01-10 nM) could attenuate Tat-mediated ROS, but cell death involving was not influenced. Estrogen receptor α agonism appeared more effective than β. Tat was also observed to increase cytokine expression. This information may be particularly important for medical treatments concerning aged HIV-infected women. Restoring estrogens post-menopausally may improve the prevalence of HIV-related neurocognitive impairments that occur with age
Al-Qaida, Boko Haram, and ISIS: Tracking the Shift in Women’s Involvement
Get PDFThis paper discusses the shift in women’s roles in Islamic extremist groups over the last two decades. Focusing on three violent Sunni groups, al-Qaida, Boko Haram, and ISIS, the research aims to fill gaps in United States and global counterterrorism and reintegration efforts by providing a comprehensive, accurate, and timely assessment of the recent change in women’s roles in terrorist organizations, shifting from foundational to limited operational to fully operational. The shift occurred and continues to unfold as several moving parts have fallen into place to create this situation. Women’s desire to participate at a more operational level, the need on behalf of the organization(s) to employ female combatants, and the willingness of Muslim religious scholars and leaders to permit female involvement in jihadist operations. While many disarmament, demobilization, and reintegration (DDR) programs consider gender, there is need for a more nuanced gender-based approach which utilizes the knowledge of why this shift is occurring and how it affects women’s place within these groups and their societies
The Holy See and the Syrian Refugee Crisis: A Study of the Catholic Church's Soft Power
Get PDFThe Syrian Migrant and Refugee Crisis has created 5.6 million refugees who have fled outside of Syria and 6.1 million internally displaced peoples within Syria. Undoubtedly, it is one of the largest humanitarian crises of the modern day. The Catholic Church joins governments and NGOs in responding to the conflict, but modern scholarship has not focused heavily on its role. This paper seeks to investigate how the Catholic Church interacts in the secular field of international relations by looking at its response to the Syrian Migrant and Refugee Crisis. In order to analyze the Church’s response, this paper looks at the statements of the Holy See’s mission to the United Nations as well as statements and actions of local churches that address the conflict on the ground in Lebanon, Jordan, and Syria. Joseph Nye’s definition of soft power provided a useful framework to analyze the Church’s actions. The research indicates that the Catholic Church uses soft power methods through its actions at the UN and its local churches to pursue its goals in responding to the crisis
“The Water Changed Me as a Person” How Childhood Experiences With Water Affect Behavior and Attitudes Towards Water as an Adult.
Get PDFThis research serves to identify how childhood experiences with water
impact a person’s attitudes and behaviors towards water issues later in life. Current research looks at more one-dimensional studies, such as only attitudes and behaviors from childhood, or not exploring multiple variables such as gender and community type and childhood experiences. By interviewing two distinct groups of students in terms of typical environmental attitudes and behaviors expressed by members of each group or political party, the College Republicans and the Office of Sustainability, we can see how the individual respondents from each group may have had childhood experiences that shaped these beliefs. By exploring the connections between relation to water, community type and region, and gender all in relation to childhood experiences, we can learn how to shape a child’s experiences with water to develop pro-environmental attitudes and behaviors as adults