Physiology Commons^™

Biological Significance Of Photoreceptor Photocycle Length: Vivid Photocycle Governs The Dynamic Vivid-White Collar Complex Pool Mediating Photo-Adaptation And Response To Changes In Light Intensity, Arko Dasgupta, Chen-Hui Chen, Changhwan Lee, Amy S. Gladfelter, Jay C. Dunlap, Jennifer J. Loros

Dartmouth Scholarship

Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths, yet the biological significance of this adduct decay length is neither understood nor has been tested. In the filamentous fungus Neurospora crassa VIVID (VVD) is a critical player in the process of photoadaptation, the attenuation of light-induced responses and the ability to maintain photosensitivity in response to changing light intensities. Detailed in vitro analysis of the photochemistry of the blue light sensing, FAD binding, LOV domain of VVD has revealed residues around the site of photo-adduct formation that influence the stability …

Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser

Physiology Faculty Publications

It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including …

Aberrant Promoter Cpg Methylation Is A Mechanism For Impaired Phd3 Expression In A Diverse Set Of Malignant Cells., Trenton L. Place, Matthew P. Fitzgerald, Sujatha Venkataraman, Sabine U. Vorrink, Adam J. Case, Melissa L.T. Teoh, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.

METHODOLOGY/PRINCIPAL FINDINGS: Using bisulfite sequencing and methylated DNA enrichment …

Genomic Profiling Of Messenger Rnas And Micrornas Reveals Potential Mechanisms Of Tweak-Induced Skeletal Muscle Wasting In Mice, Siva K. Panguluri, Shephali Bhatnagar, Akhilesh Kumar, John J. Mccarthy, Apurva K. Srivastava, Nigel G. Cooper, Robert F. Lundy, Ashok Kumar

Physiology Faculty Publications

BACKGROUND: Skeletal muscle wasting is a devastating complication of several physiological and pathophysiological conditions. Inflammatory cytokines play an important role in the loss of skeletal muscle mass in various chronic diseases. We have recently reported that proinflammatory cytokine TWEAK is a major muscle-wasting cytokine. Emerging evidence suggests that gene expression is regulated not only at transcriptional level but also at post-transcriptional level through the expression of specific non-coding microRNAs (miRs) which can affect the stability and/or translation of target mRNA. However, the role of miRs in skeletal muscle wasting is unknown.

METHODOLOGY/PRINCIPAL FINDINGS: To understand the mechanism of action of …

Systems Approach Identifies An Organic Nitrogen-Responsive Gene Network That Is Regulated By The Master Clock Control Gene Cca1, Rodrigo A. Gutierrez, Trevor L. Stokes, Karen Thum, Xiaodong Xu, Mariana Obertello, Manpreet S. Katari, Milos Tanurdzic, Alexis Dean, Damion C. Nero, C Robertson Mcclung, Gloria M. Coruzzi

Dartmouth Scholarship

Understanding how nutrients affect gene expression will help us to understand the mechanisms controlling plant growth and development as a function of nutrient availability. Nitrate has been shown to serve as a signal for the control of gene expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that downstream products of nitrogen (N) assimilation such as glutamate (Glu) or glutamine (Gln) might serve as signals of organic N status that in turn regulate gene expression. To identify genome-wide responses to such organic N signals, Arabidopsis seedlings were transiently treated with ammonium nitrate in the presence or absence of …

Following Temperature Stress, Export Of Heat Shock Mrna Occurs Efficiently In Cells With Mutations In Genes Normally Important For Mrna Export, Christiane Rollenhagen, Christine A. Hodge, Charles N. Cole

Dartmouth Scholarship

Heat shock leads to accumulation of polyadenylated RNA in nuclei of Saccharomyces cerevisiae cells, transcriptional induction of heat shock genes, and efficient export of polyadenylated heat shock mRNAs. These studies were conducted to examine the requirements for export of mRNA following heat shock. We used in situ hybridization to detect SSA4 mRNA (encoding Hsp70) and flow cytometry to measure the amount of Ssa4p-green fluorescent protein (GFP) produced following heat shock. Npl3p and Yra1p are mRNA-binding proteins recruited to nascent mRNAs and are essential for proper mRNA biogenesis and export. Heat shock mRNA was exported efficiently in temperature-sensitive npl3, yra1 …

The Relationship Between Frq-Protein Stability And Temperature Compensation In The Neurospora Circadian Clock, Peter Ruoff, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

Temperature compensation is an important property of all biological clocks. In Neurospora crassa, negative-feedback regulation on the frequency (frq) gene's transcription by the FRQ protein plays a central role in the organism's circadian pacemaker. Earlier model calculations predicted that the stability of FRQ should determine the period length of Neurospora's circadian rhythm as well as the rhythm's temperature compensation. Here, we report experimental FRQ protein stabilities in frq mutants at 20 degrees C and 25 degrees C, and estimates of overall activation energies for mutant FRQ protein degradation. The results are consistent with earlier model predictions, i.e., temperature compensation of …

Runx-Dependent Expression Of Pkc Is Critical For Cell Survival In The Sea Urchin Embryo, Carrie Dickey-Sims, Anthony J. Robertson, Dawn E. Rupp, John J. Mccarthy, James A. Coffman

Physiology Faculty Publications

BACKGROUND: Runx transcription factors play critical roles in the developmental control of cell fate and contribute variously as oncoproteins and tumor suppressors to leukemia and other cancers. To discover fundamental Runx functions in the cell biology of animal development, we have employed morpholino antisense-mediated knockdown of the sea urchin Runx protein SpRunt-1. Previously we showed that embryos depleted of SpRunt-1 arrest development at early gastrula stage and underexpress the conventional protein kinase C SpPKC1.

RESULTS: We report here that SpRunt-1 deficiency leads to ectopic cell proliferation and extensive apoptosis. Suppression of the apoptosis by pharmacological inhibition of caspase-3 prevents the …

Circadian Clock Locus Frequency: Protein Encoded By A Single Open Reading Frame Defines Period Length And Temperature Compensation., Benjamin D. Aronson, Keith A. Johnson, Jay C. Dunlap

Dartmouth Scholarship

The frequency (frq) locus encodes a key component, a state variable, in a cellular oscillator generating circadian rhythmicity. Two transcripts have been mapped to this region, and data presented here are consistent with the existence of a third transcript. Analysis of cDNA clones and clock mutants from this region focuses attention on one transcript encoding a protein. FRQ, which is a central clock component: (i) mutations in all of the semidominant frq alleles are the result of single amino acid substitutions and map to the open reading frame (ORF) encoding FRQ; (ii) deletion of this ORF, or a frameshift mutation …