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Translation initiation factors eIF4A and eIF4G form, together with the cap-binding factor eIF4E, the eIF4F complex, which is crucial for recruiting the small ribosomal subunit to the mRNA 5' end and for subsequent scanning and searching for the start codon. eIF4A is an ATP-dependent RNA helicase whose activity is stimulated by binding to eIF4G. We report here the structure of the complex formed by yeast eIF4G's middle domain and full-length eIF4A at 2.6-Å resolution. eIF4A shows an extended conformation where eIF4G holds its crucial DEAD-box sequence motifs in a productive conformation, thus explaining the stimulation of eIF4A's activity. A hitherto undescribed interaction involves the amino acid Trp-579 of eIF4G. Mutation to alanine results in decreased binding to eIF4A and a temperature-sensitive phenotype of yeast cells that carry a Trp579Ala mutation as its sole source for eIF4G. Conformational changes between eIF4A's closed and open state provide a model for its RNA-helicase activity.

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members.

Translation initiation factors eIF4A and eIF4G form, together with the cap-binding factor eIF4E, the eIF4F complex, which is crucial for recruiting the small ribosomal subunit to the mRNA 5′ end and for subsequent scanning and searching for the start codon. eIF4A is an ATP-dependent RNA helicase whose activity is stimulated by binding to eIF4G. We report here the structure of the complex formed by yeast eIF4G's middle domain and full-length eIF4A at 2.6-Å resolution. eIF4A shows an extended conformation where eIF4G holds its crucial DEAD-box sequence motifs in a productive conformation, thus explaining the stimulation of eIF4A's activity. A hitherto undescribed interaction involves the amino acid Trp-579 of eIF4G. Mutation to alanine results in decreased binding to eIF4A and a temperature-sensitive phenotype of yeast cells that carry a Trp579Ala mutation as its sole source for eIF4G. Conformational changes between eIF4A's closed and open state provide a model for its RNA-helicase activity.

This thesis explores mitochondrial dynamics in the AC16 cardiomyocytes. Mitochondria are capable of fission and fusion, controlled by specific proteins that respond to cell stress. The transmembrane potential(∆ψm) of the mitochondria is responsible for both bioenergetic functions and regulating the activation of the OMA-1 protein, which regulates the cutting of OPA-1. OPA- 1 has two isoforms: a long (active) and short (inactive) isoforms. Our research is exploring the impact of the levels of OPA1 expression on the observed ∆ψm threshold of mitochondrial fusion. Our laboratory has demonstrated that 143B cells lose L-OPA1 isoforms at [CCCP]> 4.75 µM and AC16 between 2-4µM of CCCP. We have also discovered that endogenous levels of OPA1 are higher in 143B in comparison to the AC16, which may confer heightened sensitivity to loss of ∆ψm. To test this, transfection of exogenous OMA1 and OPA1 will be done to monitor the resistance to CCCP treatment.

First-generation and rural college students are considered by many retention theorists and practitioners to be an at-risk population. This study examined the details of the first semester in postsecondary education from the perspective of a group of students who met the demographic criteria of being first-generation to go to college, from rural geographical areas, and from agricultural backgrounds. It focused on the first semester experience, during its occurrence, and how six students of this specific population viewed that phenomenon. A secondary objective was to determine if the understandings that issued from the research could form a foundation from which first semester retention strategies for this particular population could be configured. Information about the essence of the first semester emerged from the responses of the participants to four primary research questions in a structured interview format. A qualitative, phenomenological methodology provided the empirical approach used to gain an understanding of this multi-faceted experience for this group. Within-case and cross-case analyses were performed on the data produced by the interview transcripts. The study verified that first-generation and rural college students face difficulties in the transition to college that can be related to these demographic characteristics, such as lack of knowledge of campus culture, class size, academic expectations, and academic rigor. The analysis produced a unique set of findings regarding the status of agricultural background. These findings suggest that an agricultural background may compound the sense of different-ness encountered by first-generation and rural freshman when that heritage is added to the other two. Additionally, positive aspects of an agricultural background (i.e. self-esteem, courage, a history of hard work) may serve to mitigate some of the contrary factors. Recommendations include potential retention programs for institutions and suggestions for further research.

Capture and relocation is commonly used to reintroduce Rio Grande wild turkeys (Meleagris gallopavo intermedia) to areas of low numbers. However, isotonic muscle contraction during the capture and restraint process reduces blood flow to muscles and may induce the stress related disease, capture myopathy. The goal of this study was to determine if intramuscular injections of vitamin E and selenium could be an effective treatment for capture myopathy. Survival rates and enzyme levels did not differ between the control and treatment group. Results suggest that vitamin E and selenium injections do not significantly improve survival of wild turkeys when trapped and relocated under conditions experienced in this study.

All sensors have a threshold, defined by the smallest signal amplitude that can be detected. The detection of sub-threshold signals, however, is possible by using the principle of stochastic resonance, where noise is added to the input signal so that it randomly exceeds the sensor threshold. The choice of an optimal noise level that maximizes the mutual information between sensor input and output, however, requires knowledge of the input signal, which is not available in most practical applications. Here we demonstrate that the autocorrelation of the sensor output alone is sufficient to find this optimal noise level. Furthermore, we demonstrate numerically and analytically the equivalence of the traditional mutual information approach and our autocorrelation approach for a range of model systems. We furthermore show how the level of added noise can be continuously adapted even to highly variable, unknown input signals via a feedback loop. Finally, we present evidence that adaptive stochastic resonance based on the autocorrelation of the sensor output may be a fundamental principle in neuronal systems.