Chemically Active Rheological Modifiers for the Improved Clinical Use of Cyanoacrylates

Over 100 million surgical incisions, 50 million traumatic wounds, and 20 million minor lacerations from cuts and grazes are treated globally each year. One study determined that globally internal and external wounds occur for 40% and 37% of cases respectively for a total of 111 million patients that were treated for wounds. The remaining 23% of patients were treated for minor lacerations and trauma in the emergency room. These wounds require immediate medical attention including pressure application, sutures, clips, tissue cautery, and/or topical hemostatic agents to cease hemorrhage or the exit of other bodily fluids. With blood flow ceased, wound approximation or sealant is used temporarily to close the wound until fresh tissue is formed. There are several different approaches to close a wound with each lacking in one or more properties to achieve ideal wound healing. Tissue welding and cauterization are two methods employed; however, these methods result in the formation of necrotic tissue, which is undesirable. Sutures are the wound approximation gold standard due to their flexibility and ability to resist tensile forces, but they can result in complications such as bleeding from the holes created during the suturing application required to place them. Staples and tapes are common wound approximation devices, but unlike sutures, they lack the ability to resist large tensile forces. In addition to these mechanical closure devices, fibrin and thrombin based sealants have been employed to approximate or seal tissues. These biological sealants are very biocompatibility, but they also have a low mechanical strength especially as compared to the mechanical closure devices. This low strength has resulted in re-bleeding when this type of sealant was applied externally and also in cases when it was applied internally. In comparison, BioGlue®, a non-biological sealant has a high mechanical strength, but is limited by its poor biocompatibility. Alternatively, there have been advancements based on gecko and mussel adhesions (bioadhesion) in order to fabricate synthetic materials that mimic these naturally occurring dry and wet adhesives respectively. Studies have demonstrated that these materials have a great potential, but they still require additional research in order to render them clinically relevant for wound approximation. Cyanoacrylate adhesives is another family of wound approximation and sealant devices. As a general overview, these materials are able to penetrate into tissue due to their liquid monomer form, rapidly polymerize due to their highly electrophilic nature, and then form bonds due to the interpenetrating networks formed. They have been fabricated in many varieties by differing the side chain for the adhesive monomer during its synthesis, blending additives into the adhesive, or mixing insoluble materials into the adhesive. A myriad of studies have demonstrated that these variations can control the properties of the adhesive in its monomer and polymer forms. Several of these properties include viscosity, mechanical strength and flexibility, polymerization rate and reaction temperature, degradation rate, and biocompatibility. By controlling the side chain type and materials added to it, researchers are able to tailor cyanoacrylates for specific external and internal medical and industrial uses. These adhesives are well known for their typically successful external medical uses and industrial uses; however, their internal medical use has been slow to reach global use due to the heat released during the adhesives polymerization, and the cytotoxic formaldehyde byproduct released as the polymerized adhesive degrades. In order to overcome this issue, researchers commonly synthesize cyanoacrylates for internal use by attaching long alkane side chains (e.g. 2-octyl) to them. The resulting cyanoacrylate releases a lower amount of heat during its polymerization and minimal formaldehyde as it degrades; however, several studies have demonstrated that this degradation take years, if it degrades at all, which can result in a prolonged, chronic wound healing. Nevertheless, this material has excellent clinical usefulness when the specific cyanoacrylate types are used for their specific intended uses. There is therefore great potential to modulate the adhesive to improve its clinical usefulness. The completed research presented in this dissertation focused on using this information to formulate cyanoacrylates with potentially improved clinical usefulness. The cyanoacrylates were improved through the addition of novel chemically active polyesters (rheological modifiers). Methoxypropyl cyanoacrylate was selected for this research due to its inclusion of a short alkoxy side chain resulting in a flexible, high strength bond as well as the adhesive’s proven biocompatibility. Poly(glycolide-cocaprolactone) polymers (PGCL) were synthesized as the polyesters for this research due to the fast degrading, low pH producing ability of glycolide and slow degrading, increased flexibility of ε-caprolactone. The combination of both fast and slow degrading monomers allows one specifically to control the polyester’s degradation rate and thus resulting pH level for the eluent. Based on these properties, it was hypothesized that mixing PGCL as an amorphous polymer into cyanoacrylate, polymerizing the cyanoacrylate, and then allowing the polycyanoacrylate to degrade in water or a phosphate buffered saline will allow the adhesive modifier contained within the polycyanoacrylate to also hydrolyze and self-modulate the pH of the surrounding environment to an acidic level. When a polycyanoacrylate degrades in an acidic instead of basic solution, then the formaldehyde levels released should be minimized, and the alcohol and cyanoacrylic acid released should be less toxic; thus, rendering the polycyanoacrylate potentially safer for internal use

Determining Lack of Marketability Discounts: Employing an Equity Collar

A discount for the lack of marketability is the implicit cost of quickly monetizing a non-marketable asset at its current value. These discounts are used in many venues to determine the fair market value of a non-marketable asset such as a privately-held business. There has been much written on the quantification of the discount for the lack of the marketability which is briefly summarized in this article. Marketability refers to monetizing the non-marketable asset at its cash equivalent current value. Current practice often uses the cost of a put option as a proxy for the discount. A put option insures that the investor will receive no less than the current value of the underlying asset. However, the use of a put also allows the investor to maintain the asset’s upside potential. Therefore, the cost of a put overstates the discount for the lack of marketability. We show that the cost of monetizing a non-marketable asset at its current value through a loan, secured by an at-the-money equity collar, more effectively captures the true cost of marketability. When puts and calls cannot be employed to secure the current value on the underlying asset, a portfolio consisting of the non-marketable asset and a stock index, where puts and calls can be written on the index can be constructed. The effectiveness of the portfolio in creating a risk free outcome depends upon the correlation and volatility of the stock index and the non-marketable asset. We demonstrate that, relative to current practice, the use of an equity collar with a loan greatly reduces the implied discount for the lack of marketability

United Methodist Children\u27s Center Playground Improvements

The project consists of multiple pieces that were done as a team to improve the outdoor areas of the United Methodist Children’s Center. The scope of the work consists of placing gorilla hair mulch, making a bench for the kids, removing, grading, and placing artificial turf, and replacing the canvas of a shade structure. There are a few other smaller pieces that will be completed as well but those are the main pieces of the project. The project was executed by teaming up with multiple companies and getting teams of students together to construct the pieces of the project in the timeline we were given. Being a children’s center, there was a challenge with working around their schedule and not interfering with the kids. This project began in February of 2023 and was completed on June 4, 2023. The children’s center was left with a cleaner, safer playground for their students to enjoy during their recess, and the members of the project team left with a new understanding of what goes into placing turf, mulch, building benches, and replacing a canvas shade structure

AIAA Design, Build, Fly: Aerodynamics

As part of the Santa Clara University Senior Design Project, the AIAA Design, Build, Fly: Aerodynamics team was responsible for designing and testing the wings, tail, and control surfaces of an aircraft designed to participate in future AIAA Design, Build, Fly competitions. Named Evergreen in honor of professor John J. Montgomery, the unmanned aerial vehicle was designed and constructed in collaboration with the AIAA Design, Build, Fly: Structures and Controls senior design team. Aiming to construct a competitive aircraft for the competition, the team decided that a target weight of approximately 3.5 kg and a cruise speed of 25 m/s would be the starting points of the design. For the general wing configuration, three options were considered: monoplane (low-wing), cantilever (high-wing), and biplane. The cantilever configuration presented the desired wing characteristics for this aircraft, such as higher lift, stability, and ease of manufacturing. To minimize wing loading and take-off speeds, a wingspan of 1.50 m was selected considering that the maximum dimension length permitted by the competition is 1.57 m (62 in). After conducting a selection study between several high-lift airfoils, the NACA 4416 airfoil would be the most suitable, with an optimal chord length of 0.3028 m due to the previously decided weight and velocity. For the wing control surfaces, a flaperon configuration was chosen instead of separate flap and aileron structures. Through the use of flaperons, the weight and complexity of the wing is reduced while maintaining the necessary functionality from the surfaces. To avoid unpredictable behavior due to vortices created at the inward tips of the flaperons, a maximum size of 42 cm was determined, which proved sufficient at providing relatively low take-off speeds (\u3c 15 m/s). In collaboration with the Structures and Controls team, the fuselage size was used to determine the optimal dimensions of the tail, minimizing drag and guaranteeing aircraft stability in all flight modes. For the stability study, XFLR5TM was utilized as it is a powerful tool that can accurately determine the stability of the aircraft in all eight relevant flight modes given the dimension of the wing, tail assembly, and the position of the center of gravity. For complete two and three-dimensional CFD analysis, SOLIDWORKSTM Flow Simulation and ANSYSTM Fluent were exploited in parallel between the many design iterations of the Evergreen, ensuring that the theoretical design produced the desired characteristics under simulated flight conditions. Through Flow Simulation, the sizing of the aerodynamic shape of the aircraft — wing and tail — proved sufficient to sustain the anticipated weight of the aircraft, and a flap deflection study provided security on the effectiveness of the flaps for lower takeoff speeds. Additionally, the CFD analysis was useful to estimate the forces and torques experiences by the control surfaces, which was in turn used by the Structures and Controls team to select the appropriate servo motors for each control surface. Once the design was deemed aerodynamically capable, the Evergreen was constructed as a joint effort of both teams. Containing minute differences in comparison to the CAD model of the aircraft, the Evergreen performed successfully in eight separate flights, satisfying the take-off distance, control, range, and payload capacity required by the competition. With the data provided in this project, the AIAA Design, Build, Fly: Aerodynamics team is confident that future generations of students can improve and adapt the Evergreen to compete for Santa Clara University

The Bio-Psycho-Social-Cultural Domains And Their Impact On Psychopharmacological Utilization Among Latinxs

The Latinx population has become the largest minority group in the United States (U.S.).1 Compared to non-Hispanic Whites, Latinxs are younger and have less formal education. This community is also confronted with additional stressors (i.e., more likely to have problems of unemployment, poverty, lack of insurance, and language barriers).2 Although Latinxs are just as likely as non-Hispanic Whites to suffer from a mental illness, they are more likely to go untreated.3 Specifically, Latinxs experiences with psychopharmacological treatments is not well understood but can be studied through the multipath model (MPM).4 The MPM offers a way to view the variety and complexity of contributors to mental disorders. The etiology can be understood through four domains: Biological, Psychological, Social, and Sociocultural.4 To date, little attention has been given to specific domains of the MPM that contribute to psychopharmacological utilization among Latinxs. This qualitative study therefore explores the bio-psycho-social-cultural domains and its role on psychopharmacological utilization among 20 Latinx adults (50% Spanish speakers, 80% immigrant). Using thematic analysis, results indicated Latinxs underutilize psychopharmacology within three of the four domains of the MPM. Psychological factors included perceived negative outcomes, such as illness or dependency, and even fear of deportation. The role of family was the strongest social factor for underutilization. Sociocultural factors for underutilization included religion and religious fatalism. Perceived acceptance of receiving mental health treatment in the U.S. as compared to native Latin American countries was a sociocultural factor for utilizing psychopharmacology. Interestingly, participants did not highlight any biological factor as means for psychopharmacological treatments. Overall, providers can benefit from the multipath model (MPM) when working with the Latinx community in order to better understand preconceptions that may impact psychopharmacological utilization. Additional research and practical implications are therefore discussed when working with the Latinx community. References: 1. Garcia, J. A., Sanchez, G. R., Sanchez-Youngman, S., Vargas, E. D., & Ybarra, V. D. (2015). Race as lived experience: The impact of multi-dimensional measures of race/ethnicity on the self-reported health status of Latinos. Du Bois review: Social Science Research on Race, 12(2), 349-373. https://doi.org/10.1017/S1742058X15000120 2. McDonald, J. A., & Paulozzi, L. J. (2019). Parsing the paradox: Hispanic mortality in the US by detailed cause of death. Journal of Immigrant and Minority Health, 21(2), 237-245. https://doi.org/10.1007/s10903-018-0737-2 3. Moreno, O., Ortiz, M., Fuentes, L., Garcia, D., & Leon-Perez, G. (2020). Vaya con Dios: The influence of religious constructs on stressors around the migration process and U.S. lived experiences among Latina/o immigrants. International Journal of Environmental Research and Public Health,17(11), 3961. https://doi.org/10.3390/ijerph17113961 4. Neuendorf, K.A. The Content Analysis Guidebook; SAGE Publications: Thousand Oaks, CA, USA, 2017. https://dx.doi.org/10.4135/9781071802878 5. Rush, S.C. (2014) Transana: Qualitative analysis software for video and audio. Educational Psychology 30, 213–214. 6. Sue, D., Sue, D. W., Sue, S., & Sue, D. M. (2015). Understanding abnormal behavior. Cengage Learning.. doi: 01/01/2016 7. U.S. Census Bureau (2015). Quick facts: United States population estimates. Retrieved from https://www.census.gov/quickfacts/fact/table/US/PST045218. 8. Moreno, O., Nelson, T. & Cardemil. E. (2017) Religiosity and attitude toward professional mental health services: analysing religious coping as a mediator among Mexican origin Latinas/os in the southwest United States, Journal of Mental Health, Religion & Culture, 20(7), 626-637. https://doi.org/10.1080/13674676.2017.1372735 9. Moreno, O., & Cardemil, E. (2018). Religiosity and well-being among Mexican-born and U.S.-born Mexicans: A qualitative investigation. Journal of Latina/o Psychology, 6(3). 235-247. https://doi.org/10.1037/lat000009

Demographic Factors and Attitudes towards Mental Health Medication Treatments among Latinxs

Attitudes towards mental health medications vary, however negative perceptions are often born of normative cultural values, stigma, and religious fatalism,1-3 as well as overall demographic characteristics such as gender, nativity, and primary language.4,5 Further research suggests many Latinx adults fear negative outcomes from adhering to medication for mental health treatment, such as dependence and side effects and, instead, would prefer psychotherapy over psychopharmacology.1,2 Lastly, a lack of health literacy,6 culturally appropriate treatments and information,7 as well as barriers to care also have shown to impact attitudes towards mental health medication treatments among Latinxs.8 To date, little attention has been given to the attitudes towards mental health treatments that will either facilitate or impede using medication treatments for mental health. This qualitative study therefore explores the demographic factors and attitudes towards mental health medication treatment among 20 adult Latinxs (45% Puerto Rico, 20% El Salvador, 10% Guatemala, 10% Honduras, 15% other). Using thematic analysis, results indicated that Latinxs held positive, negative, and neutral attitudes toward mental health medication treatments. Participants who were neutral tended to be more open to treatment, however, still hesitant, indicating medication treatment as a last resort or would engage in it only if recommended by someone they trust (i.e., medical doctor or religious leader). Positive attitudes towards medication treatment were split between it being easier to take medication than talk to someone about one\u27s problems, or the opposite; it is easier to talk to a stranger (i.e., mental health provider) than to someone who is close and trusted (i.e., religious leader). Positive attitudes were also supported through trust in medical professionals. Negative attitudes towards receiving mental health medication treatment were more cultural such that individuals suffering from mental illness should be strong enough to get through it on their own, or that one should trust in God to heal you. The participants who held negative attitudes reported more mistrust in medical professionals, including mental health providers and psychological treatment methodology. Demographically, there were no clear trends in the data for variables such as gender, age, primary language, or educational attainment. However, there was a pattern of attitudes for those who identified with a religion (n=15). Of those who identified with either Catholicism or Christianity, 60% held negative attitudes. The participants who identified with no religion (n=4) all held positive attitudes towards medication for mental health treatment. Additional research and practical implications are therefore discussed. 1. Ailinger, R. L., Martyn, D., Lasus, H., & Lima Garcia, N. (2010). The effect of a cultural intervention on adherence to latent tuberculosis infection therapy in Latino immigrants. Public Health Nursing, 27(2), 115-120. https://doi.org/10.1111/j.1525-1446.2010.00834.x 2. Batalova, J., & Zong, J. (2016). Language diversity and English proficiency in the United States. Migration Information Source. 3. Eisenman, D. P., Meredith, L. S., Rhodes, H., Green, B. L., Kaltman, S., Cassells, A., & Tobin, J. N. (2008). PTSD in Latino patients: illness beliefs, treatment preferences, and implications for care. Journal of General Internal Medicine, 23(9), 1386–1392. https://doi.org/10.1007/s11606-008-0677-y 4. Green, B. L., Watson, M. R., Kaltman, S. I., Serrano, A., Talisman, N., Kirkpatrick, L., & Campoli, M. (2017). Knowledge and preferences regarding antidepressant medication among depressed Latino patients in primary care. The Journal of Nervous and Mental Disease, 205(12), 952–959. https://doi.org/10.1097/NMD.0000000000000754 5. Interian, A., Martinez, I. E., Guarnaccia, P. J., Vega, W. A., & Escobar, J. I. (2007). A qualitative analysis of the perception of stigma among Latinos receiving antidepressants. Psychiatric services, 58(12), 1591–1594. doi:10.1176/ps.2007.58.12.1591 6. Moreno, O., & Cardemil, E. (2018). Religiosity and well-being among Mexican-born and U.S.-born Mexicans: A qualitative investigation. Journal of Latina/o Psychology, 6(3), 235–247, https://doi.org/10.1037/lat0000099 7. Moreno, O., Nelson, T., & Cardemil, E. (2017) Religiosity and attitudes towards professional mental health services: analysing religious coping as a mediator among Mexican origin Latinas/os in the southwest United States, Mental Health, Religion & Culture, 20:7, 626-637, doi:10.1080/13674676.2017.1372735 8. Peeters, B., Van Tongelen, I., Boussery, K., Mehuys, E., Remon, J. P., & Willems, S. (2011). Factors associated with medication adherence to oral hypoglycaemic agents in different ethnic groups suffering from type 2 diabetes: a systematic literature review and suggestions for further research. Diabetic medicine: A journal of the British Diabetic Association, 28(3), 262–275. https://doi.org/10.1111/j.1464-5491.2010.03133.x 9. Shattell, M. M., Hamilton, D., Starr, S. S., Jenkins, C. J., & Hinderliter, N. A. (2008). Mental health service needs of a Latino population: A community-based participatory research project. Issues in Mental Health Nursing, 29(4), 351–370. https://doi.org/10.1080/01612840801904316 10. Zuniga J. A. (2012). Medication adherence in Hispanics to latent tuberculosis treatment: a literature review. Journal of Immigrant and Minority Health, 14(1), 23–29, https://doi.org/10.1007/s10903-010-9393-

Seasonal changes in soil organic matter after a decade of nutrient addition in a lowland tropical forest

© 2015, US Government. Soil organic matter is an important pool of carbon and nutrients in tropical forests. The majority of this pool is assumed to be relatively stable and to turn over slowly over decades to centuries, although changes in nutrient status can influence soil organic matter on shorter timescales. We measured carbon, nitrogen, and phosphorus concentrations in soil organic matter and leaf litter over an annual cycle in a long-term nutrient addition experiment in lowland tropical rain forest in the Republic of Panama. Total soil carbon was not affected by a decade of factorial combinations of nitrogen, phosphorus, or potassium. Nitrogen addition increased leaf litter nitrogen concentration by 7 % but did not affect total soil nitrogen. Phosphorus addition doubled the leaf litter phosphorus concentration and increased soil organic phosphorus by 50 %. Surprisingly, concentrations of carbon, nitrogen, and phosphorus in soil organic matter declined markedly during the four-month dry season, and then recovered rapidly during the following wet season. Between the end of the wet season and the late dry season, total soil carbon declined by 16 %, total nitrogen by 9 %, and organic phosphorus by between 19 % in control plots and 25 % in phosphorus addition plots. The decline in carbon and nitrogen was too great to be explained by changes in litter fall, bulk density, or the soil microbial biomass. However, a major proportion of the dry-season decline in soil organic phosphorus was explained by a corresponding decline in the soil microbial biomass. These results have important implications for our understanding of the stability and turnover of organic matter in tropical forest soils, because they demonstrate that a considerable fraction of the soil organic matter is seasonally transient, despite the overall pool being relatively insensitive to long-term changes in nutrient status

Amazonian White-Sand Forests Show Strong Floristic Links with Surrounding Oligotrophic Habitats and the Guiana Shield

Recognizing and understanding historical patterns and processes that have influenced the diversification of organisms on earth is one of the central goals of evolutionary biology. Within this broad area, studies within the disciplines of molecular systematics (i.e. phylogeography, phylogenetics and population genetics), allow us to address evolutionary questions from different biological, spatial and temporal scales. Phylogeography and molecular phylogenetics help us to understand aspects related to events that have given rise to patterns of genetic variation in organisms, as well as to understand the assembly of biological communities in a given area. These types of studies provide crucial information to increase knowledge about the biodiversity of little-studied ecoregions. One such ecoregion is Colombian Guyana. This ecoregion, which is located between three putative centers of speciation; Amazonia, the Andes and Guyana, is one of the least explored areas of the country. As a result of their geological composition, the western enclaves of the Guiana Shield have been described as a "heterogeneous entity", composed of savannas, catingas, lowland forests, and even white sand forests. Using bats as a biological study group, this paper presents two approaches focused on understanding how biogeographic events that have shaped the diversity of the continent have affected different lineages that inhabit Colombian Guiana. Bats are a group of vertebrates sensitive to biogeographic events that have shaped the diversity of the continent, which play different functional roles in the ecosystems they inhabit. High degrees of association with habitat have been described for numerous bat species, mainly in terms of foraging characteristics and diet types. In a first project, we comparatively analyzed the phylogeographic patterns of three widely distributed bat species, with the aim of identifying the patterns of genetic divergence of the bats that inhabit the area today. Using mitochondrial DNA sequences, we revealed the existence of bat populations established in the area, which showed different degrees of gene flow with surrounding biogeographic areas, especially with the Guiana provinces of Oriente and Pantepui and the Amazon. Additionally, we identified different demographic histories for each species, which were probably influenced to different extents by climatic changes during the Pleistocene and differential ecological characteristics. Our results highlight the influence of Colombian Guiana ecosystems on the formation and spatial configuration of bat diversity and genetic structure, and the importance of these ecosystems for bat conservation. In a second project, from a phylogenetic perspective, we evaluated the phylogenetic structure of bat communities inhabiting different eco-regions of northern South America, using mitochondrial and nuclear DNA sequences. The results of the analysis allowed us to demonstrate that the bat populations of the Western Guayana Province (which includes the Colombian portion of the Guiana Shield), are phylogenetically clustered, that is, the species that compose the communities are evolutionarily closer than expected by chance. We conclude that factors such as the high heterogeneity of habitats in the region, the high diversity of fruit bats in the sampled communities, and interspecific competition have shaped the species composition of the communities in this area. In a final chapter, a general discussion of the results obtained from the two research projects carried out is developed. Chapters one and two of this thesis will be submitted to international indexed journals, which is why they are written in English and in scientific article format.Reconocer y entender patrones y procesos históricos que han influenciado la diversificación de los organismos sobre la tierra, es uno de los objetivos centrales de la biología evolutiva. Dentro de esta gran área, estudios enmarcados en las disciplinas de la sistemática molecular (i.e. filogeografía, filogenética y genética de poblaciones), nos permiten abordar preguntas evolutivas desde diferentes escalas biológicas, espaciales y temporales. La filogeografía y la filogenética molecular nos ayudan a entender aspectos relacionados con eventos que han dado lugar a patrones de variación genética de los organismos, así como entender el ensamblaje de comunidades biológicas en un área determinada. Este tipo de estudios aportan información crucial para aumentar el conocimiento acerca de biodiversidad de eco regiones poco estudiadas. Una de estas eco regiones es la Guyana colombiana. Esta eco región, la cual se encuentra ubicada entre tres centros putativos de especiación; Amazonía, Andes y Guayana, es una de las zonas menos exploradas del país. Como resultado de su composición geológica, los enclaves occidentales del escudo Guayanés han sido descritos como una "entidad heterogénea", compuesta de sabanas, catingas, bosques bajos, e inclusive bosques de arena blanca. Usando como grupo biológico de estudio los murciélagos, este trabajo de grado presentan dos aproximaciones enfocadas a entender como eventos biogeográficos que han moldeado la diversidad del continente, han afectado diferentes linajes que habitan la Guayana colombiana. Los murciélagos son un grupo de vertebrados sensibles a los eventos biogeográficos que han moldeado la diversidad del continente, el cuál cumple diferentes roles funcionales en los ecosistemas que habitan. Altos grados de asociación con el hábitat han sido descritos para numerosas especies de murciélagos, principalmente en cuanto a características de forrajeo y tipos de dieta. En un primer proyecto, analizamos comparativamente los patrones filogeográficos de tres especies de murciélagos de amplia distribución, con el objetivo de identificar los patrones de divergencia genética de los murciélagos que habitan el área en la actualidad. Utilizando secuencias de ADN mitocondrial, revelamos la existencia de poblaciones de murciélagos establecidas en el área, las cuales mostraron diferentes grados de flujo genético con áreas biogeográficas circundantes, en especial con las provincias guayanesas del Oriente y Pantepui y el Amazonas. Adicionalmente identificamos diferentes historias demográficas para cada especie, las cuales probablemente fueron influenciadas en diferente medida por cambios climáticos durante el pleistoceno y características ecológicas diferenciales. Nuestros resultados destacan la influencia de los ecosistemas guayaneses colombianos en la formación y configuración espacial de la diversidad y estructura genética en murciélagos, y la importancia de estos ecosistemas para la conservación dicha diversidad. En un segundo proyecto, desde una perspectiva filogenética, evaluamos la estructura filogenética de la comunidad de murciélagos de diferentes eco-regiones del norte de sur américa, usando secuencia de ADN mitocondrial. Los resultados de los análisis nos permitieron demostrar que las poblaciones de murciélagos de la Provincia Guayanesa del Occidente (la cual incluye la porción colombiana del escudo guayanés), se encuentran filogenéticamente agregadas, es decir, las especies que componen las comunidades son más cercanas evolutivamente de lo esperado por el azar. Concluimos que factores como la alta heterogeneidad de hábitats en la región, la alta diversidad de murciélagos frugívoros en las comunidades muestreadas, y la competencia interespecífica han moldeado la composición de especies de las comunidades en esta zona. En un capítulo final, se desarrolla una discusión general de los resultados obtenidos de los dos proyectos de investigación realizados. Los capítulos uno y dos de esta tesis serán sometidos a revistas indexadas internacionales, razón por la cual están escritos en idioma inglés y en formato de artículo científico.Línea de Investigación: Biología EvolutivaMaestrí

Satb1 overexpression drives tumor-promoting activities in cancer-associated dendritic cells

Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.Fil: Tesone, Amelia J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Rutkowski, Melanie R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Brencicova, Eva. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Svoronos, Nikolaos. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Perales Puchal, Alfredo. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Stephen, Tom L.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Allegrezza, Michael J.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Payne, Kyle K.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Nguyen, Jenny M.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados UnidosFil: Wickramasinghe, Jayamanna. The Wistar Institute. Center for Systems and Computational Biology; Estados UnidosFil: Tchou, Julia. University of Pennsylvania; Estados UnidosFil: Borowsky, Mark E.. Christiana Care Health System. Helen F. Graham Cancer Center; Estados UnidosFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kossenkov, Andrew V.. The Wistar Institute. Center for Systems and Computational Biology; Estados UnidosFil: Conejo Garcia, José R.. The Wistar Institute. Tumor Microenvironment and Metastasis Program; Estados Unido