Conservation of exon scrambling in human and mouse

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 21-23).Exon scrambling is a phenomenon in which the exons of an mRNA transcript are spliced in an order inconsistent with that of the genome. In this thesis, I present a computational analysis of scrambled exons in human and mouse. RNA-seq data was mapped to the genome and all unaligned reads were subsequently mapped to a database of all possible exon-exon junctions. Eight conserved genes were found to undergo scrambled splicing in both species. In several cases, not only the gene was conserved, but the particular exons involved were conserved as well. Reading frame was preserved in just over half of the events, indicating that although some transcripts may be translated into protein, some may be non-functional or may play a regulatory role. The introns flanking scrambled exons were significantly longer than average, providing clues to the mechanism for this abnormal splicing pattern. The results of this study demonstrate that presence of scrambled transcripts in the cell is infrequent, but can be conserved over tens of millions of years of evolution, suggesting it has a biological function.by Monica L. Hamilton.S.M

Computational and experimental analyses converge to reveal a coherent yet malleable aptamer structure that controls chemical reactivity

As short nucleic acids, aptamers in solution are believed to be structurally flexible. Consistent with this view, most aptamers examined for this property have been shown to bind their target molecules by mechanisms that can be described as induced fit . But, it is not known to what extent this structural flexibility affects the integrity of the target - aptamer interaction. Using the malachite green aptamer (MGA) as a model system, we show that the MGA can protect its bound target, malachite green (MG), from oxidation over several days. Protection is reversed by an oligonucleotide complementary to the MGA binding pocket. Computational cavity analysis of the MGA-MG structure predicted that MG oxidation is protected because a molecule as small as an OH- is sterically excluded from the C1 position of the bound MG. These results suggest that, while the MGA-MG interface is sufficiently coherent to prevent OH- penetration, the bases involved in the interaction are sufficiently mobile that they can exchange out of the MG binding interface to hybridize with a complementary oligonucleotide. The computational predictions were confirmed experimentally using variants of the MGA with single base changes in the binding pocket. This work demonstrates the successful application of molecular dynamics simulations and cavity analysis in determining the effects of sequence variations on the structure of a small single-stranded nucleic acid. It also shows that a nucleic acid aptamer can control access to specific chemical groups on its target, which suggests that aptamers might be applied for selectively protecting small molecules from modification

LEED and historic preservation : a study of USGBC’s LEED rating system for new construction and major renovations as it pertains to historic building renovations

textThis thesis discusses the United States Green Building Council’s proposed changes in the LEED® (Leadership in Energy and Environmental Design) Rating System for New Construction and Major Renovations from the current 2009 version to the proposed 2012 version, as they pertain to historic building renovation projects. The comparison is aimed at determining whether the proposed changes to the rating system are becoming more favorable to historic preservation, promoting the rehabilitation and reuse of historic buildings as environmentally responsible practices. The discussion is taken a step further by proposing potential modifications and metrics that could be implemented into the LEED® Rating System in order to help advance historic preservation by recognizing the many inherent sustainable qualities of historic buildings, such as regional climate-adaptive features, durable materials and skilled craftsmanship. The upcoming renovation of Battle Hall and West Mall Building, two buildings that are part of the School of Architecture complex at the University of Texas at Austin, serves as case study of historic buildings undergoing major renovations to which both the LEED 2009 and LEED 2012 Draft Rating Systems for New Construction and Major Renovations are applied. An analysis of the results informs the comparison between the two versions of the rating system. The results of the comparison indicate that changes in the LEED® rating system for New Construction and Major Renovation from the 2009 to the 2012 version are favorable for historic preservation. The USGBC is advancing in the right direction with establishing more credits for historic preservation projects. The 2012 3rd Public Comment Draft rating system introduces the notion of “historic building” and that of “historic district” for the first time, in credits that address infill within a historic district and reuse of a historic building, with work performed in accordance with The Secretary of the Interior’s Standards for the Treatment of Historic Properties. This represents a step forward toward integrating historic preservation and building reuse in the vocabulary of sustainability.Architectur

Common Secondary and Tertiary Structural Features of Aptamer–Ligand Interaction Shared by RNA Aptamers with Different Primary Sequences

Aptamer selection can yield many oligonucleotides with different sequences and affinities for the target molecule. Here, we have combined computational and experimental approaches to understand if aptamers with different sequences but the same molecular target share structural and dynamical features. NEO1A, with a known NMR-solved structure, displays a flexible loop that interacts differently with individual aminoglycosides, its ligand affinities and specificities are responsive to ionic strength, and it possesses an adenosine in the loop that is critical for high-affinity ligand binding. NEO2A was obtained from the same selection and, although they are only 43% identical in overall sequence, NEO1A and NEO2A share similar loop sequences. Experimental analysis by 1D NMR and 2-aminopurine reporters combined with molecular dynamics modeling revealed similar structural and dynamical characteristics in both aptamers. These results are consistent with the hypothesis that the target ligand drives aptamer structure and also selects relevant dynamical characteristics for high-affinity aptamer-ligand interaction. Furthermore, they suggest that it might be possible to “migrate” structural and dynamical features between aptamer group members with different primary sequences but with the same target ligand

Variables Associated With Overweight/Obesity Among African-American Women with Hypertension and/or Diabetes

BACKGROUND Obesity is the second leading cause of preventable death next to tobacco use. Although it is prevalent in all populations, it disproportionately affects AA women. Overweight/obesity increases AA women’s chances of developing chronic illnesses such as diabetes, hypertension, heart disease, and decreases their life expectancy. The purpose of this study was to explore variables associated with overweight/obese AA women with hypertension and/or diabetes. METHODS A secondary data analysis was conducted using a descriptive-correlational design to analyze cross-sectional data obtained from the 2013 Behavioral Risk Factor Surveillance System (BRFSS). The sample consisted of AA women (n =1823). The dependent variable was overweight/obesity. The independent variables were household income, physical activity, fruits/vegetables consumption, life satisfaction, emotional support, and sleep. Chi-square analysis was used to study the relationship variables. For all analyses, alpha was set at 0.05. RESULTS The majority of the sample of was 2(1) = 13.32, p \u3c .001. There were no statistically significant results for any of the independent variables. CONCLUSIONS Further studies are needed to identify modifiable variables that relate to overweight/obesity in AA women with chronic illnesses

David Versus Goliath: Strategic Behavior of Small Firms In Consolidated Industries

This study assesses the effect of strategy selection and firm adaptability on small firm performance,  using firm  tenure  as a moderator  variable.  The study  is based  upon interviews with sixteen small firms operating in rapidly changing and consolidating industries. All of the firms in the study pursued a differentiation strategy. Half of the firms  pursued  a  broad product strategy and more than three-quarters pursued a broad service strategy. The study found that small firms adapt by addressing community needs and forming cooperative agreements with other small firms but not larger firms. Variation among the industries studied suggests that the intensity of industry concentration affects firm adaptation decisions. For instance, while the heavily concentrated hardware anti drugstore industries  showed limited adaptation, the unconsolidated bookstore industry showed greater commitment to adaptive strategies. In addition, firm tenure was found to affect the adaptation of the small firms  studied

Action on the ground: A review of community environmental groups’ restoration objectives, activities and partnerships in New Zealand

More than 600 community environmental groups across New Zealand are engaged in restoring degraded sites and improving and protecting habitat for native species. In the face of ongoing biodiversity declines, resource management agencies are increasing their reliance on these groups to enhance conservation outcomes nationally. However, little is known about community groups and their activities beyond local or regional studies. Our aim was to develop a profile of community groups and their projects through examining group and project characteristics, objectives, activities and the support provided by project partners. A total of 296 community groups from all mainland regions of New Zealand responded to an online questionnaire. Nearly 80% of these groups were established for ≥6 years and 72% operated with ≤20 participants (e.g. staff, members, and unpaid volunteers). For over half (54%) of groups, participants were mostly aged 51–65 years. Small groupsizes, combined with ageing participants, may threaten groups’ longevity. More than 20% of groups’ projects covered areas > 501 ha. Ecosystems represented within groups’ project areas included forests (64.0%), streams (42.0%) and freshwater wetlands (33.2%). Over one-third (37.2%) of freshwater wetland restoration projects occurred on private or Maori-owned land. Nearly 70% of groups carried out weed/pest control, native tree planting and advocacy/educational activities, underscoring the combination of social and ecological dimensions shaping most groups’ projects. Over 90% of groups were supported by project partners (e.g. resource management agencies for site visits, funding and technical support), highlighting the interdependence between groups and their partners. Developing a more complete profile of New Zealand community groups and their projects will assist with improving the delivery of support to groups by project partners and developing an inclusive and cohesive sector based on meaningful partnerships. These two factors combined will ultimately enhance groups’ environmental outcomes at the local level, while contributing to national biodiversity conservation goals

The association between patient attitudes and values and the strength of consideration for contralateral prophylactic mastectomy in a population‐based sample of breast cancer patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140052/1/cncr30924_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140052/2/cncr30924.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140052/3/cncr30924-sup-0002-suppinfo.pd

Patient views and correlates of radiotherapy omission in a population‐based sample of older women with favorable‐prognosis breast cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144597/1/cncr31378_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144597/2/cncr31378.pd