Life Sciences Commons^™

Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams

Dartmouth Scholarship

Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in …

A Detergent-Free Strategy For The Reconstitution Of Active Enzyme Complexes From Native Biological Membranes Into Nanoscale Discs, Ashley R. Long, Catherine C. O’Brien, Ketan Malhotra, Christine T. Schwall, Arlene D. Albert, Nathan N. Alder

Open Access Author Fund Awardees' Articles

Background

The reconstitution of membrane proteins and complexes into nanoscale lipid bilayer structures has contributed significantly to biochemical and biophysical analyses. Current methods for performing such reconstitutions entail an initial detergent-mediated step to solubilize and isolate membrane proteins. Exposure to detergents, however, can destabilize many membrane proteins and result in a loss of function. Amphipathic copolymers have recently been used to stabilize membrane proteins and complexes following suitable detergent extraction. However, the ability of these copolymers to extract proteins directly from native lipid bilayers for subsequent reconstitution and characterization has not been explored.

Results

The styrene-maleic acid (SMA) copolymer effectively …

Regulation Of Succinate-Fuelled Mitochondrial Respiration In Liver And Skeletal Muscle Of Hibernating Thirteen-Lined Ground Squirrels., Jason C L Brown, Dillon J Chung, Alex N Cooper, James F Staples

Biology Publications

Hibernating ground squirrels (Ictidomys tridecemlineatus) alternate between two distinct metabolic states throughout winter: torpor, during which metabolic rate (MR) and body temperature (Tb) are considerably suppressed, and interbout euthermia (IBE), during which MR and Tb briefly return to euthermic levels. Previous studies showed suppression of succinate-fuelled respiration during torpor in liver and skeletal muscle mitochondria; however, these studies used only a single, saturating succinate concentration. Therefore, they could not address whether mitochondrial metabolic suppression occurs under physiological substrate concentrations or whether differences in the kinetics of mitochondrial responses to changing substrate concentration might also contribute to mitochondrial metabolic regulation during …

Mitochondrial Genomes Of Two Barklice, Psococerastis Albimaculata And Longivalvus Hyalospilus (Psocoptera: Psocomorpha): Contrasting Rates In Mitochondrial Gene Rearrangement Between Major Lineages Of Psocodea, Hu Li, Renfu Shao, Fan Song, Xuguo Zhou, Qianqian Yang, Zhihong Li, Wanzhi Cai

Entomology Faculty Publications

The superorder Psocodea has ∼10,000 described species in two orders: Psocoptera (barklice and booklice) and Phthiraptera (parasitic lice). One booklouse, Liposcelis bostrychophila and six species of parasitic lice have been sequenced for complete mitochondrial (mt) genomes; these seven species have the most rearranged mt genomes seen in insects. The mt genome of a barklouse, lepidopsocid sp., has also been sequenced and is much less rearranged than those of the booklouse and the parasitic lice. To further understand mt gene rearrangements in the Psocodea, we sequenced the mt genomes of two barklice, Psococerastis albimaculata and Longivalvus hyalospilus, the first representatives from …

Intrinsic Apoptotic Pathway: Effects Of Calcium On Murine Cytochrome C Release In Brain And Liver Mitochondria, Dane M. Edwards

Senior Honors Theses

A cell may use one of three main apoptotic pathways leading to programmed cell death: the extrinsic pathway, the perforin/granzyme pathway and the intrinsic pathway. The most pertinent to this discussion is the intrinsic pathway, which utilizes the mitochondria as an essential intermediary. Mitochondria’s primary function in relation to this pathway is the subsequent release of pro-apoptotic factors including cytochrome c, which activate a caspase cascade leading to the death of the cell. Cytochrome c is released partly due to an increase in cytosolic calcium levels. Two methods of the release of cytochrome c have been proposed. The first is …

Integrated Analysis Of Cytochrome P450 Gene Superfamily In The Red Flour Beetle, Tribolium Castaneum, Fang Zhu, Timothy W. Moural, Kapil Shah, Subba Reddy Palli

Entomology Faculty Publications

BACKGROUND: The functional and evolutionary diversification of insect cytochrome P450s (CYPs) shaped the success of insects. CYPs constitute one of the largest and oldest gene superfamilies that are found in virtually all aerobic organisms. Because of the availability of whole genome sequence and well functioning RNA interference (RNAi), the red flour beetle, Tribolium castaneum serves as an ideal insect model for conducting functional genomics studies. Although several T. castaneum CYPs had been functionally investigated in our previous studies, the roles of the majority of CYPs remain largely unknown. Here, we comprehensively analyzed the phylogenetic relationship of all T. castaneum CYPs …

Metabolism Of Brain Cortex And Cardiac Muscle Mitochondria In Hibernating 13-Lined Ground Squirrels Ictidomys Tridecemlineatus., Kirsten Gallagher, James F Staples

Biology Publications

During bouts of torpor, mitochondrial metabolism is known to be suppressed in the liver and skeletal muscle of hibernating mammals. This suppression is rapidly reversed during interbout euthermic (IBE) phases, when whole-animal metabolic rate and body temperature (T(b)) return spontaneously to euthermic levels. Such mitochondrial suppression may contribute significantly to energy savings, but the capacity of other tissues to suppress mitochondrial metabolism remains unclear. In this study we compared the metabolism of mitochondria from brain cortex and left ventricular cardiac muscle between animals sampled while torpid (stable T(b) near 5°C) and in IBE (stable T(b) near 37°C). Instead of isolating …

Reconstruction Of Family-Level Phylogenetic Relationships Within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes, Malcolm S. Hill, April L. Hill, Jose V. Lopez, Kevin J. Peterson, Shirley Pomponi, Maria C. Diaz, Robert W. Thacker, Maja Adamska, Nicole Boury-Esnault, Paco Cárdenas, Andia Chaves-Fonnegra, Elizabeth Danka, Bre-Onna De Laine, Dawn Formica, Eduardo Hajdu, Gisele Lobo-Hajdu, Sarah Klontz, Christine C. Morrow, Jignasa Patel, Bernard Picton, Davide Pisani, Deborah Pohlmann, Niamh E. Redmond, John Reed, Stacy Richey, Ana Riesgo, Ewelina Rubin, Zach Russell, Klaus Rützler, Erik A. Sperling, Michael Di Stefano, James E. Tarver, Allen G. Collins

Marine & Environmental Sciences Faculty Articles

Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges.

Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosa^p, …

Reconstruction Of Family-Level Phylogenetic Relationships Within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes, Malcolm Hill, April L. Hill, Et. Al.

Biology Faculty Publications

Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges.

Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosa^p, Myxospongiae …