Metabolic and Endocrine correlates of cognitive function in healthy young women

Obesity has been associated with cognitive decline in longitudinal studies of older individuals. We hypothesized that the cognitive sequelae of obesity may be detectable in the reproductive years. In addition, we explored the hypothesis that these associations may be mediated by the hormonal milieu. In this study of 49 young healthy lean and overweight women aged 20–45, we investigated the association between performance on a battery of cognitive tests, body composition parameters (BMI, total fat, abdominal (visceral, subcutaneous and total) adipose tissue, and muscle), and hormone levels (insulin, adiponectin, leptin, IGF-1, estrogen, testosterone, and vitamin D). We found a significant negative association between both visceral adiposity and muscle, and performance in the domain of verbal learning and memory, after controlling for age and education. Other body composition parameters showed similar trends (0.05<p<0.10). Additionally, the degree of insulin resistance was negatively associated with executive function domain. None of the associations between the other hormones examined (adipokines, IGF-1, gonadal hormones and vitamin D) and cognitive function were significant. These preliminary findings suggest a possible association between obesity and cognitive function in healthy young women of reproductive age. More research is warranted into the potential modulatory effect of insulin resistance on this association

Carbon Cycle Trends Recorded By Organic Carbon Stable Isotopes In Paleocene Strata, Benton County, Mississippi: Implications For Chronostratigraphy Of The Porters Creek And Naheola Formations

The paleocene-eocene thermal maximum (petm) is one of the most studied carbon isotope excursions in earth\u27s history. The petm occurred 55 million years ago when excess isotopically heavy carbon (c13) was added into earth\u27s carbon cycle, resulting in ecological and environmental changes. The petm is marked by a negative stable carbon isotope excursion (cie) in marine and continental strata around the globe. The paleocene and eocene boundary is contained in the sedimentary fill of the Mississippi embayment so there is high potential to produce new petm stable isotope datasets. The purpose of this project is to analyze the boundary for evidence of the petm and other cies at the flat rock church paleobotanical site and a nearby core from Benton County, Mississippi. Fieldwork at the flat rock church site was conducted in order to observe the stratigraphic and lateral relationships of the paleocene porters creek formation and naheola formation and the eocene meridian sand and to collect samples for preliminary stable carbon isotope analysis. Continuous, high-resolution data were produced from samples from the rollison core, which were decarbonated and analyzed for stable organic carbon isotopes (î”13ctoc), percentage of carbonate, and total organic carbon. The resulting î”13ctoc curve shows an overall increase in î”13ctoc values upsection with five superimposed high-magnitude positive cies. Two of the five are discounted as the result of procedural error and the remaining three are interpreted as representing a combination of increased organic carbon burial and Caribbean volcanism. The upsection trend in î”13ctoc enrichment likely correlates to a segment of a larger, global paleocene trend known as the paleocene carbon isotope maximum. Correlation of the î”13ctoc curves allows the establishment of a more precise chronostratigraphy, revising the previously established depositional range of the porters creek and naheola from 63.8-56 ma to 60.5-56.6 ma

The George Harris Show August 08, 2022, Part 5 Spanish to English Translation

This thesis is an attempt at a Spanish-to-English translation of part of a comedy skit by Venezuelan American comedian George Harris performed on October 11, 2022, in Miami, Florida. As an academic, I have been captivated by foreign languages since a young age and have studied German up to the collegiate level. After moving to New York and studying at Pace University, an educational institution that does not offer German, I decided to teach myself Spanish. I reached the Advanced level of the language within my second semester of officially studying it at Pace University. I believe that the future of America is within its Spanish speakers, and there is true power in communicating with someone within their native language. As immigration patterns continue to suggest a rise of Latino immigrants in the United States, Latino media has an opportunity to be appreciated, available, and translated for American audiences. Throughout my academic studies of Spanish, I was consistently drawn to the culture and history of Venezuela. Notably, I was struck by the unimaginable effect of the diaspora of its people across the world since the rule of Hugo Chavez and Nicolas Maduro, as, at one time, Venezuela was once the wealthiest country in the world. I believe that Venezuela is misunderstood in the modern day on the global stage - particularly, within the United States. When proceeding with my thesis topic, I focused on translation and weighed between various options therein; I found myself constantly returning to Venezuela and wanting to work with a piece of media from the country. With Communication Studies being one of my majors, much of my coursework covered media studies. Considering Venezuelan culture is not a widely known topic to most Americans, I decided to complete a translation of Venezuelan culture in the modern-day, and I selected George Harris, a Venezuelan comedian, as the central focus of my translation. Despite their displacement worldwide, comedians like George Harris act as a cultural anchor to many Venezuelan Americans and exemplifies Venezuelan culture’s magnitude in Miami, Florida. So, in order to translate a genuine, and comedic piece of modern Venezuelan Pop Culture, I researched translation studies, particularly within the translation of media (as today’s world continues to spread foreign media to new audiences) and was not surprised to find that it is not without its flaws

The effect of thermal dose on hyperthermia-mediated inhibition of DNA repair through homologous recombination

Hyperthermia has a number of biological effects that sensitize tumors to radiotherapy in the range between 40-44 °C. One of these effects is heat-induced degradation of BRCA2 that in turn causes reduced RAD51 focus formation, which results in an attenuation of DNA repair through homologous recombination. Prompted by this molecular insight into how hyperthermia attenuates homologous recombination, we now quantitatively explore time and temperature dynamics of hyperthermia on BRCA2 levels and RAD51 focus formation in cell culture models, and link this to their clonogenic survival capacity after irradiation (0-6 Gy). For treatment temperatures above 41 °C, we found a decrease in cell survival, an increase in sensitization towards irradiation, a decrease of BRCA2 protein levels, and altered RAD51 focus formation. When the temperatures exceeded 43 °C, we found that hyperthermia alone killed more cells directly, and that processes other than homologous recombination were affected by the heat. This study demonstrates that optimal inhibition of HR is achieved by subjecting cells to hyperthermia at 41-43 °C for 30 to 60 minutes. Our data provides a guideline for the clinical application of novel combination treatments that could exploit hyperthermia's attenuation of homologous recombination, such as the combination of hyperthermia with PARP-inhibitors for non-BRCA mutations carriers

Einfluss von professioneller Zahnreinigung und Scaling and Root Planing auf Viridans-Streptokokken im subgingivalen Biofilm

Die von mir vorgelegte Monografie thematisiert den Einfluss von professioneller Zahnreinigung und Scaling and Root Planing auf bestimmte Viridans-Streptokokkenspezies. Die Zusammensetzung des Biofilms ist von großem klinischen Interesse, da Parodontalerkrankungen in der Praxis sehr häufig auftreten. Die vorgelegte Arbeit nimmt sich der Frage an, inwieweit die parodontale Initialtherapie den Biofilm, im Speziellen die Streptokokken, beeinflusst. Die Ergebnisse dieser Studie bestätigen Streptokokken als frühe Rekolonisierer. Durch die unterschiedliche Reihenfolge in der Rekolonisation der einzelnen Streptokokkenspezies kann möglicherweise durch Applikation dieser Frühkolonisierer die Zusammensetzung des Biofilms dahingehend geändert werden, dass parodontopathogene Keime besser kontrolliert werden können auf Basis einer kompetetiven Hemmung.:1. Einleitung 2. Ziele der Arbeit 3. Material und Methoden 4. Ergebnisse 5. Diskussion 6. Zusammenfassung der Arbeit 7. Literaturverzeichnis 8. Anlage

HaploBlocks : Efficient Detection of Positive Selection in Large Population Genomic Datasets

Genomic regions under positive selection harbor variation linked for example to adaptation. Most tools for detecting positively selected variants have computational resource requirements rendering them impractical on population genomic datasets with hundreds of thousands of individuals or more. We have developed and implemented an efficient haplotype-based approach able to scan large datasets and accurately detect positive selection. We achieve this by combining a pattern matching approach based on the positional Burrows-Wheeler transform with model-based inference which only requires the evaluation of closed-form expressions. We evaluate our approach with simulations, and find it to be both sensitive and specific. The computational resource requirements quantified using UK Biobank data indicate that our implementation is scalable to population genomic datasets with millions of individuals. Our approach may serve as an algorithmic blueprint for the era of "big data" genomics: a combinatorial core coupled with statistical inference in closed form.Peer reviewe

Regulation of DNA Damage Response by Estrogen Receptor β-Mediated Inhibition of Breast Cancer Associated Gene 2

Accumulating evidence suggests that ubiquitin E3 ligases are involved in cancer development as their mutations correlate with genomic instability and genetic susceptibility to cancer. Despite significant findings of cancer-driving mutations in the BRCA1 gene, estrogen receptor (ER)-positive breast cancers progress upon treatment with DNA damaging-cytotoxic therapies. In order to understand the underlying mechanism by which ER-positive breast cancer cells develop resistance to DNA damaging agents, we employed an estrogen receptor agonist, Erb-041, to increase the activity of ERβ and negatively regulate the expression and function of the estrogen receptor α (ERα) in MCF-7 breast cancer cells. Upon Erb-041-mediated ERα down-regulation, the transcription of an ERα downstream effector, BCA2 (Breast Cancer Associated gene 2), correspondingly decreased. The ubiquitination of chromatin-bound BCA2 was induced by ultraviolet C (UVC) irradiation but suppressed by Erb-041 pretreatment, resulting in a blunted DNA damage response. Upon BCA2 silencing, DNA double-stranded breaks increased with Rad51 up-regulation and ataxia telangiectasia mutated (ATM) activation. Mechanistically, UV-induced BCA2 ubiquitination and chromatin binding were found to promote DNA damage response and repair via the interaction of BCA2 with ATM, γH2AX and Rad51. Taken together, this study suggests that Erb-041 potentiates BCA2 dissociation from chromatin and co-localization with Rad51, resulting in inhibition of homologous recombination repair

Toward an Ising Model of Cancer and Beyond

Theoretical and computational tools that can be used in the clinic to predict neoplastic progression and propose individualized optimal treatment strategies to control cancer growth is desired. To develop such a predictive model, one must account for the complex mechanisms involved in tumor growth. Here we review resarch work that we have done toward the development of an "Ising model" of cancer. The review begins with a description of a minimalist four-dimensional (three in space and one in time) cellular automaton (CA) model of cancer in which healthy cells transition between states (proliferative, hypoxic, and necrotic) according to simple local rules and their present states, which can viewed as a stripped-down Ising model of cancer. This model is applied to model the growth of glioblastoma multiforme, the most malignant of brain cancers. This is followed by a discussion of the extension of the model to study the effect on the tumor dynamics and geometry of a mutated subpopulation. A discussion of how tumor growth is affected by chemotherapeutic treatment is then described. How angiogenesis as well as the heterogeneous and confined environment in which a tumor grows is incorporated in the CA model is discussed. The characterization of the level of organization of the invasive network around a solid tumor using spanning trees is subsequently described. Then, we describe open problems and future promising avenues for future research, including the need to develop better molecular-based models that incorporate the true heterogeneous environment over wide range of length and time scales (via imaging data), cell motility, oncogenes, tumor suppressor genes and cell-cell communication. The need to bring to bear the powerful machinery of the theory of heterogeneous media to better understand the behavior of cancer in its microenvironment is presented.Comment: 55 pages, 21 figures and 3 tables. To appear in Physical Biology. Added reference