Life Sciences Commons^™

Impact Of Sleep And Circadian Disruption On Energy Balance And Diabetes: A Summary Of Workshop Discussions, Deanna M. Arble, Joseph Bass, Cecilia Diniz Behn, Matthew P. Butler, Etienne Challet, Charles Czeisler, Christopher M. Depner, Joel Elmquist, Paul Franken, Michael A. Grandner, Erin C. Hanlon, Alex C. Keene, Michael J. Joyner, Ilia Karatsoreos, Philip A. Kern, Samuel Klein, Christopher J. Morris, Allan I. Pack, Satchidananda Panda, Louis J. Ptacek, Naresh M. Punjabi, Paolo Sessone-Corsi, Frank A. Scheer, Richa Saxena, Elizabeth R. Seaquest, Matthew S. Thimgan, Eve Van Cauter, Kenneth P. Wright

Biological Sciences Faculty Research and Publications

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact …

Short And Long-Term Soil Moisture Effects Of Liana Removal In A Seasonally Moist Tropical Forest, Joseph P. Reid, Stefan A. Schnitzer, Jennifer S. Powers

Biological Sciences Faculty Research and Publications

Lianas (woody vines) are particularly abundant in tropical forests, and their abundance is increasing in the neotropics. Lianas can compete intensely with trees for above- and belowground resources, including water. As tropical forests experience longer and more intense dry seasons, competition for water is likely to intensify. However, we lack an understanding of how liana abundance affects soil moisture and hence competition with trees for water in tropical forests. To address this critical knowledge gap, we conducted a large-scale liana removal experiment in a seasonal tropical moist forest in central Panama. We monitored shallow and deep soil moisture over the …

The Reverse Transcription Signature Of N-1-Methyladenosine In Rna-Seq Is Sequence Dependent, Ralf Hauenschild, Lyudmil Tserovski, Katharina Schmid, Kathrin Thuring, Marie-Luise Winz, Sunny Sharma, Karl-Dieter Entian, Ludvine Wacheul, Denis L.J. Lafontaine, James T. Anderson, Juan Alfonzo, Andreas Hildebrandt, Andres Jaschke, Yuri Motorin, Mark Helm

Biological Sciences Faculty Research and Publications

The combination of Reverse Transcription (RT) and high-throughput sequencing has emerged as a powerful combination to detect modified nucleotides in RNA via analysis of either abortive RT-products or of the incorporation of mismatched dNTPs into cDNA. Here we simultaneously analyze both parameters in detail with respect to the occurrence of N-1-methyladenosine (m¹A) in the template RNA. This naturally occurring modification is associated with structural effects, but it is also known as a mediator of antibiotic resistance in ribosomal RNA. In structural probing experiments with dimethylsulfate, m¹A is routinely detected by RT-arrest. A specifically developed RNA-Seq protocol …

The Evolution Of Digit Form In Gonatodes (Gekkota: Sphaerodactylidae) And Its Bearing On The Transition From Frictional To Adhesive Contact In Gekkotans, Anthony P. Russell, Joelle Baskerville, Tony Gamble, Timothy E. Higham

Biological Sciences Faculty Research and Publications

Although the phenomenon of adhesion in geckos has been intensively studied for over 200 years, our understanding of how the morphological apparatus associated with this arose is less clear. Indeed, whether or not all of the intricate morphological hierarchy that is implicated in the attachment and removal of the adhesive setae originated at the same time is unknown. To explore whether setae may have arisen prior to the other parts of this structural hierarchy, we undertook morphological observations of Gonatodes, an ancestrally padless, sphaerodatyline genus known to exhibit the expression of incipient subdigital pads in some species. Focusing on …

A Cytotoxic, Co-Operative Interaction Between Energy Deprivation And Glutamate Release From System XC− Mediates Aglycemic Neuronal Cell Death, Trista L. Thorn, Yan He, Nicole A. Jackman, Doug Lobner, James A. Hewett, Sandra J. Hewett

Biological Sciences Faculty Research and Publications

The astrocyte cystine/glutamate antiporter (system x_c⁻) contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system x_c⁻ expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone or with neurons—to remove glutamate from the extracellular space. Instead, we …

Rapid Liana Colonization Along A Secondary Forest Chronosequence, Kathryn E. Barry, Stefan A. Schnitzer, Michiel Van Breugel, Jefferson S. Hall

Biological Sciences Faculty Research and Publications

Lianas (woody vines) can have profound effects on tree recruitment, growth, survival, and diversity in tropical forests. However, the dynamics of liana colonization soon after land abandonment are poorly understood, and thus it is unknown whether lianas alter tree regeneration early in succession. We examined the liana community in 43 forests that ranged from 1 to 31 yr old in central Panama to determine how fast lianas colonize young forests and how the liana community changes with forest succession. We found that lianas reached high densities early in succession, commonly exceeding 1000 stems/ha within the first 5 yr of forest …

Huntington’S Disease Cerebrospinal Fluid Seeds Aggregation Of Mutant Huntingtin, Z. Tan, W. Dai, Theo G.M. Van Erp, J. Overman, A. Demuro, M. A. Digman, A. Hatami, R. Albay, Emily M. Sontag, K. T. Potkin, S. Ling, F. Macciardi, W. E. Bunney, J. D. Long, J. S. Paulsen, J. M. Ringman, I. Parker, Charles G. Glabe, L. M. Thompson, W. Chiu, Steven G. Potkin

Biological Sciences Faculty Research and Publications

Huntington’s disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. …

Viral Vector-Based Improvement Of Optic Nerve Regeneration: Characterization Of Individual Axons' Growth Patterns And Synaptogenesis In A Visual Target, Benjamin J. Yungher, Xueting Luo, Yadira Salgueiro, Murray G. Blackmore

Biological Sciences Faculty Research and Publications

Lack of axon growth ability in the central nervous system poses a major barrier to achieving functional connectivity after injury. Thus, a non-transgenic regenerative approach to reinnervating targets has important implications in clinical and research settings. Previous studies using knockout (KO) mice have demonstrated long distance axon regeneration. Using an optic nerve injury model, here we evaluate the efficacy of viral, RNAi and pharmacological approaches that target the PTEN and STAT3 pathways to improve long distance axon regeneration in wild type (WT) mice. Our data show that adeno-associated virus (AAV) expressing short hairpin RNA (shRNA) against PTEN (shPTEN) enhances retinal …

Lianas Reduce Carbon Accumulation And Storage In Tropical Forests, Geertje M. F. Van Der Heijden, Jennifer S. Powers, Stefan A. Schnitzer

Biological Sciences Faculty Research and Publications

Tropical forests store vast quantities of carbon, account for one-third of the carbon fixed by photosynthesis, and are a major sink in the global carbon cycle. Recent evidence suggests that competition between lianas (woody vines) and trees may reduce forest-wide carbon uptake; however, estimates of the impact of lianas on carbon dynamics of tropical forests are crucially lacking. Here we used a large-scale liana removal experiment and found that, at 3 y after liana removal, lianas reduced net above-ground carbon uptake (growth and recruitment minus mortality) by ∼76% per year, mostly by reducing tree growth. The loss of carbon uptake …

GabaB Receptors Couple To GαQ To Mediate Increases In Voltage-Dependent Calcium Current During Development, Andrew S. Karls, Michelle Mynlieff

Biological Sciences Faculty Research and Publications

Metabotropic GABA_B receptors are known to modulate the activity of voltage-dependent calcium channels. Previously, we have shown that GABA_B receptors couple to a non-G_i/o G-protein to enhance calcium influx through L-type calcium channels by activating protein kinase C in neonatal rat hippocampal neurons. In this study, the components of this signaling pathway were investigated further. Gα_q was knocked down using morpholino oligonucleotides prior to examining GABA_B-mediated enhancement of calcium influx. When Gα_q G-proteins were eliminated using morpholino-mediated knockdown, the enhancing effects of the GABA_B receptor agonist baclofen (10 μM) on calcium current …

Quinol Oxidase Encoded By Cyoabcd In Rhizobium Etli Cfn42 Is Regulated By Actsr And Is Crucial For Growth At Low Ph Or Low Iron Conditions, Zachary Ryan Lunak, K. Dale Noel

Biological Sciences Faculty Research and Publications

Rhizobium etli aerobically respires with several terminal oxidases. The quinol oxidase (Cyo) encoded by cyoABCD is needed for efficient adaptation to low oxygen conditions and cyo transcription is upregulated at low oxygen. This study sought to determine how transcription of the cyo operon is regulated. The 5′ sequence upstream of cyo was analysed in silico and revealed putative binding sites for ActR of the ActSR two-component regulatory system. The expression of cyo was decreased in an actSR mutant regardless of the oxygen condition. As ActSR is known to be important for growth under low pH in another rhizobial species, the …

The Tumor Suppressor Hhex Inhibits Axon Growth When Prematurely Expressed In Developing Central Nervous System Neurons, Matthew T. Simpson, Ishwariya Venkatesh, Ben L. Callif, Laura K. Thiel, Denise M. Coley, Kristen N. Winsor, Zimei Wang, Audra A. Kramer, Jessica K. Lerch, Murray G. Blackmore

Biological Sciences Faculty Research and Publications

Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified …

Acetyl Coa Carboxylase Inactivation And Meiotic Maturation In Mouse Oocytes, Deepa S. Valsangkar, Stephen Downs

Biological Sciences Faculty Research and Publications

In mouse oocytes, meiotic induction by pharmacological activation of PRKA (adenosine monophosphate-activated protein kinase; formerly known as AMPK) or by hormones depends on stimulation of fatty acid oxidation (FAO). PRKA stimulates FAO by phosphorylating and inactivating acetyl CoA carboxylase (ACAC; formerly ACC), leading to decreased malonyl CoA levels and augmenting fatty-acid transport into mitochondria. We investigated a role for ACAC inactivation in meiotic resumption by testing the effect of two ACAC inhibitors, CP-640186 and Soraphen A, on mouse oocytes maintained in meiotic arrest in vitro. These inhibitors significantly stimulated the resumption of meiosis in arrested cumulus cell-enclosed oocytes, denuded oocytes, …

Pervasive And Strong Effects Of Plants On Soil Chemistry: A Meta-Analysis Of Individual Plant ‘Zinke’ Effects, Bonnie G. Waring, Leonor Álvarez-Cansino, Kathryn E. Barry, Kristen K. Becklund, Sarah Dale, Maria G. Gei, Adrienne B. Keller, Omar R. Lopez, Lars Markesteijn, Scott A. Mangan, Charlotte E. Riggs, Maria Elizabeth Rodríguez-Ronderos, R. Max Segnitz, Stefan A. Schnitzer, Jennifer S. Powers

Biological Sciences Faculty Research and Publications

Plant species leave a chemical signature in the soils below them, generating fine-scale spatial variation that drives ecological processes. Since the publication of a seminal paper on plant-mediated soil heterogeneity by Paul Zinke in 1962, a robust literature has developed examining effects of individual plants on their local environments (individual plant effects). Here, we synthesize this work using meta-analysis to show that plant effects are strong and pervasive across ecosystems on six continents. Overall, soil properties beneath individual plants differ from those of neighbours by an average of 41%. Although the magnitudes of individual plant effects exhibit weak relationships with …

Into The Light: Diurnality Has Evolved Multiple Times In Geckos, Tony Gamble, E. Greenbaum, Todd R. Jackman, Aaron M. Bauer

Biological Sciences Faculty Research and Publications

Geckos are the only major lizard group consisting mostly of nocturnal species. Nocturnality is presumed to have evolved early in gecko evolution and geckos possess numerous adaptations to functioning in low light and at low temperatures. However, not all gecko species are nocturnal and most diurnal geckos have their own distinct adaptations to living in warmer, sunlit environments. We reconstructed the evolution of gecko activity patterns using a newly generated time-calibrated phylogeny. Our results provide the first phylogenetic analysis of temporal activity patterns in geckos and confirm an ancient origin of nocturnality at the root of the gecko tree. We …

Arabidopsis Azi1 Family Proteins Mediate Signal Mobilization For Systemic Defence Priming, Nicolas M. Cecchini, Kevin Steffes, Michael Schläppi, Andrew N. Gifford, Jean T. Greenberg

Biological Sciences Faculty Research and Publications

Priming is a major mechanism behind the immunological 'memory' observed during two key plant systemic defences: systemic acquired resistance (SAR) and induced systemic resistance (ISR). Lipid-derived azelaic acid (AZA) is a mobile priming signal. Here, we show that the lipid transfer protein (LTP)-like AZI1 and its closest paralog EARLI1 are necessary for SAR, ISR and the systemic movement and uptake of AZA in Arabidopsis. Imaging and fractionation studies indicate that AZI1 and EARLI1 localize to expected places for lipid exchange/movement to occur. These are the ER/plasmodesmata, chloroplast outer envelopes and membrane contact sites between them. Furthermore, these LTP-like proteins form …

Shell Neurons Of The Master Circadian Clock Coordinate The Phase Of Tissue Clocks Throughout The Brain And Body, Jennifer A. Evans, Ting-Chung Suen, Ben L. Callif, Andrew S. Mitchell, Oscar Castanon-Cervantes, Kimberly M. Baker, Ian Kloehn, Kenkichi Baba, Brett J.W. Teubner, J. Christopher Ehlen, Ketema N. Paul, Timothy J. Bartness, Gianluca Tosini, Tanya Leise, Alec J. Davidson

Biological Sciences Faculty Research and Publications

Background: Daily rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN). The SCN contains two main compartments (shell and core), but the role of each region in system-level coordination remains ill defined. Herein, we use a functional assay to investigate how downstream tissues interpret region-specific outputs by using in vivo exposure to long day photoperiods to temporally dissociate the SCN. We then analyze resulting changes in the rhythms of clocks located throughout the brain and body to examine whether they maintain phase synchrony with the SCN shell or core. Results: Nearly all of the 17 …

Quantitative Detection Of Syntrophic Fatty Acid-Degrading Bacterial Communities In Methanogenic Environments, Prince Peter Mathai, Daniel Zitomer, James Maki

Biological Sciences Faculty Research and Publications

In methanogenic habitats, volatile fatty acids (VFA), such as propionate and butyrate, are major intermediates in organic matter degradation. VFA are further metabolized to H2, acetate and CO2 by syntrophic fatty acid-degrading bacteria (SFAB) in association with methanogenic archaea. Despite their indispensable role in VFA degradation, little is known about SFAB abundance and their environmental distribution. To facilitate ecological studies, we developed four novel genus-specific quantitative PCR (qPCR) assays, with primer sets targeting known SFAB: Syntrophobacter, Smithella, Pelotomaculum and Syntrophomonas. Primer set specificity was confirmed using in silico and experimental (target controls, clone libraries and melt-curve analysis) …

Aversive Stimuli Drive Drug Seeking In A State Of Low Dopamine Tone, Robert C. Twining, Daniel S. Wheeler, Amanda L. Ebben, Andre J. Jacobsen, Mykel A. Robble, John R. Mantsch, Robert A. Wheeler

Biological Sciences Faculty Research and Publications

Background

Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking. Additionally, we examined the midbrain regulation of both dopamine signaling and cocaine seeking by the stress-sensitive peptide, corticotropin releasing factor (CRF).

Methods

Combining fast-scan cyclic voltammetry with behavioral pharmacology, we examined the effect of …

Inactivation Of Mandelate Racemase By 3-Hydroxypyruvate Reveals A Potential Mechanistic Link Between Enzyme Superfamilies, Mitesh Nagar, Brittney N. Wyatt, Martin St. Maurice, Stephen L. Bearne

Biological Sciences Faculty Research and Publications

Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the Mg²⁺-dependent interconversion of the enantiomers of mandelate. Several α-keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (K_i = 1.8 ± 0.3 mM) and 3-fluoropyruvate (K_i = 1.3 ± 0.1 mM)], but, surprisingly, 3-hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (k_inact/K_I = 83 ± 8 M^–1 s^–1). Protection from inactivation by the competitive inhibitor benzohydroxamate, trypsinolysis and electrospray ionization tandem mass spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP undergoes Schiff-base formation with …

Daily Environmental Conditions Determine The Competition–Facilitation Balance For Plant Water Status, Alexandra Wright, Stefan A. Schnitzer, Peter B. Reich

Biological Sciences Faculty Research and Publications

1. Plants compete with their neighbours for a finite set of limiting resources, and this decreases individual plant performance, growth and survival. However, neighbouring plants also affect each other in positive ways.
2. Positive facilitative effects can occur when neighbouring plants ameliorate harsh abiotic conditions (temperature, wind and high irradiation). Thus, when environmental conditions are severe, the importance of facilitation may increase. The co‐occurrence and masking effects of competition and facilitation among neighbouring plants have made it difficult to tease them apart in the past.
3. We planted bur oak acorns (Quercus macrocarpa) into an experimental diversity gradient in a central …

The Melanocortin-4 Receptor Integrates Circadian Light Cues And Metabolism, Deanna M. Arble, Jenna Holland, Nickki Ottaway, Joyce Sorrell, Joshua W. Pressler, Rachel Morano, Stephen C. Woods, Randy J. Seeley, James P. Herman, Darleen A. Sandoval, Diego Perez-Tilve

Biological Sciences Faculty Research and Publications

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. …

Restriction Site-Associated Dna Sequencing (Rad-Seq) Reveals An Extraordinary Number Of Transitions Among Gecko Sex-Determining Systems, Tony Gamble, Jessi Coryell, Tariq Ezaz, Joshua Lynch

Biological Sciences Faculty Research and Publications

Sex chromosomes have evolved many times in animals and studying these replicate evolutionary “experiments” can help broaden our understanding of the general forces driving the origin and evolution of sex chromosomes. However this plan of study has been hindered by the inability to identify the sex chromosome systems in the large number of species with cryptic, homomorphic sex chromosomes. Restriction site-associated DNA sequencing (RAD-seq) is a critical enabling technology that can identify the sex chromosome systems in many species where traditional cytogenetic methods have failed. Using newly generated RAD-seq data from 12 gecko species, along with data from the literature, …

Metabolic Effects Of Bariatric Surgery In Mouse Models Of Circadian Disruption, Deanna M. Arble, Darleen A. Sandoval, Fred W. Turek, Stephen C. Woods, Randy J. Seeley

Biological Sciences Faculty Research and Publications

Background/Objectives:

Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity.

Subjects/Methods:

Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption.

Results:

VSG led to a reduction in body weight and fat mass in …

Gene Mdpc Plays A Regulatory Role In The Methyl-Tert-Butyl Ether Degradation Pathway Of Methylibium Petroleiphilum Strain Pm1, Geetika Joshi, Radomir Schmidt, Kate M. Scow, Michael S. Denison, Krassimira R. Hristova

Biological Sciences Faculty Research and Publications

Among the few bacteria known to utilize methyl tert-butyl ether (MTBE) as a sole carbon source, Methylibium petroleiphilum PM1 is a well-characterized organism with a sequenced genome; however, knowledge of the genetic regulation of its MTBE degradation pathway is limited. We investigated the role of a putative transcriptional activator gene, mdpC, in the induction of MTBE-degradation genes mdpA (encoding MTBE monooxygenase) and mdpJ (encoding tert-butyl alcohol hydroxylase) of strain PM1 in a gene-knockout mutant mdpC⁻. We also utilized quantitative reverse transcriptase PCR assays targeting genes mdpA, mdpJ and mdpC to determine the effects of …

Detection Of Multi-Drug Resistant Escherichia Coli In The Urban Waterways Of Milwaukee, Wi, Anthony D. Kappell, Maxwell S. Denies, Neha H. Ahuja, Nathan A. Ledeboer, Ryan J. Newton, Krassimira R. Hristova

Biological Sciences Faculty Research and Publications

Urban waterways represent a natural reservoir of antibiotic resistance which may provide a source of transferable genetic elements to human commensal bacteria and pathogens. The objective of this study was to evaluate antibiotic resistance of Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics covering 10 different families were utilized to determine the phenotypic antibiotic resistance for all 259 E. coli isolates. All obtained isolates were determined to be multi-drug resistant. The E. coli isolates were also screened for the presence of the genetic determinants of …

Genetic And Molecular Analysis Of Dec-11 In C. Elegans' Intestinal Pacemaker Activity, Adele Joan Gordon

Master's Theses (2009 -)

Rhythmic behaviors are ubiquitous phenomena in plant and animal phyla. Ultradian rhythmic behaviors occur with a period of less than 24 hours and include such rhythmic behaviors as the beating of the heart and peristalsis in the gut. The nematode C. elegans exhibits three well-characterized ultradian rhythmic behaviors: ovulation, pharyngeal pumping, and the defecation motor program (DMP). The DMP occurs every ~45 seconds in wild-type worms and comprises three distinct muscle contractions: a posterior body contraction (pBoc), an anterior body contraction (aBoc), and an enteric muscle contraction (Emc), which is coupled to expulsion (Exp). The rhythmicity of the DMP is …

Intrinsically Disordered C-Terminal Tails Of E. Coli Single-Stranded Dna Binding Protein Regulate Cooperative Binding To Single-Stranded Dna, Alexander G. Kozlov, Elizabeth A. Weiland, Anuradha Mittal, Vince Waldman, Edwin Antony, Nicole Fazio, Rohit V. Pappu, Timothy M. Lohman

Biological Sciences Faculty Research and Publications

The homotetrameric Escherichia coli single-stranded DNA binding protein (SSB) plays a central role in DNA replication, repair and recombination. E. coli SSB can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all four subunits [(SSB)₆₅ mode] or only two subunits [(SSB)₃₅ binding mode], with the binding mode preference regulated by salt concentration and SSB binding density. These binding modes display very different ssDNA binding properties with the (SSB)₃₅ mode displaying highly cooperative binding to ssDNA. SSB tetramers also bind an array of partner proteins, recruiting them to their sites of action. This is …

Weekly Versus Monthly Testosterone Administration On Fast And Slow Skeletal Muscle Fibers In Older Adult Males, Robert Fitts, James R. Peters, E. Lichar Dillon, William J. Durham, Melinda Sheffield-Moore, Randall J. Urban

Biological Sciences Faculty Research and Publications

Context: In older adults, loss of mobility due to sarcopenia is exacerbated in men with low serum T. T replacement therapy is known to increase muscle mass and strength, but the effect of weekly (WK) vs monthly (MO) administration on specific fiber types is unknown.

Objective: To determine the efficacy of WK vs MO T replacement on the size and functional capacity of individual fast and slow skeletal muscle fiber types.

Design, Setting, and Patients:

Subjects were randomized into a 5-month, double-blind, placebo-controlled trial. All subjects (ages, 61–71 y) were community-dwelling men who had T levels < 500 ng/dL.

Intervention: Subjects were dosed …

Mechanisms Underlying Weight Loss And Metabolic Improvements In Rodent Models Of Bariatric Surgery, Deanna M. Arble, Darleen A. Sandoval, Randy J. Seeley

Biological Sciences Faculty Research and Publications

Obesity is a growing health risk with few successful treatment options and fewer still that target both obesity and obesity-associated comorbidities. Despite ongoing scientific efforts, the most effective treatment option to date was not developed from basic research but by surgeons observing outcomes in the clinic. Bariatric surgery is the most successful treatment for significant weight loss, resolution of type 2 diabetes and the prevention of future weight gain. Recent work with animal models has shed considerable light on the molecular underpinnings of the potent effects of these ‘metabolic’ surgical procedures. Here we review data from animal models and how …