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Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic

USF Tampa Graduate Theses and Dissertations

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal …

Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic disorder affecting 1/10,000 to 1/20,000 births. This disorder arises through the genetic disruption of the maternal UBE3A allele, which when coupled with epigenetic silencing of the paternal allele UBE3A allele, gives rise to an absence of UBE3A protein in the central nervous system. Clinical manifestations of the syndrome vary in severity and include poor motor function, deficits in language and severe intellectual impairments. Previous research in the Angelman syndrome mouse model revealed abnormalities in dendritic spine density and morphology of hippocampal pyramidal cells. As seen in humans with AS, mice show abnormal behavioral …

Inflamation And Oxidative Stress : The Molecular Connectivity Between Insulin Resistance, Obesity And Alzheimer's Disease, Guiseppe Verdile, Kevin N. Keane, Vinicius F. Cruzat, Sandra Medic, Miheer Sabale, Joanne Rowles, Nadeeja Wijesekara, Ralph Martins, Paul E. Fraser, Philip Newsholme

Research outputs 2014 to 2021

Type 2 diabetes (T 2 DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T 2 DM) and decreased action of insulin are central to the development and progression of both T 2 DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance …

Ikaros Deficiency Leads To An Imbalance In Effector And Regulatory T Cell Homeostasis In Murine Pancreatic Cancer, Nadine D. Nelson

USF Tampa Graduate Theses and Dissertations

Pancreatic cancer is one of the deadliest cancers with a five-year survival rate of 6%. Pancreatic cancer is resistant to conventional chemotherapy and is usually diagnosed at late stages. Current treatment options have minimal effects in extending patients' lives beyond 10 months. One significant limitation in developing treatments to combat pancreatic cancer is its immunosuppressive microenvironment. Pancreatic cancer secretes factors that activate immunosuppressive cells, such as regulatory T cells (Tregs). These Tregs suppress effector CD4⁺ and CD8⁺ T cell anti-tumor immune responses. Therefore, novel treatment options to reduce Treg-mediated immune suppression and increase the numbers and functions of …

Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott

USF Tampa Graduate Theses and Dissertations

Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …

Utilization Of Placebo Response In Double-Blind Psychopharmacological Studies, Contextual Perspective, Margarita Olegovna Ashirova

Antioch University Dissertations & Theses

Placebo response has been an elusive phenomenon in the fields of medicine, medical research, and psychology. Even though it has been heavily utilized as a comparator treatment in double-blind psychopharmacological studies, the reliable definition and consistent understanding of placebo response are missing. In this contextual exploration, I outlined the state of current placebo response research and variable rates of placebo response reported in double-blind studies. I identified the gap in the literature—lack of consistent understanding of placebo response—that has led to a waste of resources by the psychopharmacological research industry. Further, I compared and contrasted the current inconsistent Western medical …

Functional Conservation Of An Ancestral Pellino Protein In Helminth Species, Christopher Cluxton, Brian Caffrey, Gemma Kinsella, Paul Moynagh, Mario Fares, Padraic Fallon

Articles

The immune system of H. sapiens has innate signaling pathways that arose in ancestral species. This is exemplified by the discovery of the Toll-like receptor (TLR) pathway using free-living model organisms such as Drosophila melanogaster. The TLR pathway is ubiquitous and controls sensitivity to pathogen-associated molecular patterns (PAMPs) in eukaryotes. There is, however, a marked absence of this pathway from the plathyhelminthes, with the exception of the Pellino protein family, which is present in a number of species from this phylum. Helminth Pellino proteins are conserved having high similarity, both at the sequence and predicted structural protein level, with that …

Analysis Of Vaca/Caga Genotypes/Status In Helicobacter Pylori Isolates From Iranian Children And Their Association With Clinical Outcome, Tahereh Falsafi, Afsaneh Khani, Fatemeh Mahjoub, Ezat Asgarani, Nazli Sotoudeh

Turkish Journal of Medical Sciences

More than 50% of Iranian children are infected with Helicobacter pylori; however, no data exist about the association of vacA/cagA genotype/status with disease outcomes in them. We analyzed association of vacA/cagA genotypes/status of children's isolates with gastric inflammation status as the first step in H. pylori pathogenesis. Materials and methods: Antral biopsies for culture and histopathology were taken from 328 children in 1997-2009. vacA (s, m) alleles and cagA statuses of the isolates were determined by PCR. Histopathology was performed according to the Sydney system; gastritis was scored as normal, mild, moderate, severe, and follicular. Results: A total of 159 …

Relationship Among Mif, Mcp-1, Viral Loads, And Hbs Ag Levelsin Chronic Hepatitis B Patients, Hayati̇ Güneş, Rafet Mete, Murat Aydin, Bi̇rol Topçu, Mustafa Oran, Mustafa Doğan, Oğuzhan Yildirim, İlknur Erdem, Aynur Eren Topkaya, Ahmet Gürel

Turkish Journal of Medical Sciences

Background/aim: To determine whether macrophage migration inhibitory factor (MIF) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with hepatitis B (HB) are different than in normal individuals and whether the HB surface antigen (HBs Ag) level and viral load are correlated with each other and with the two aforementioned parameters. Materials and methods: Sera were obtained from 52 chronic active HB (CAHB) patients and 33 healthy controls, and their MIF and MCP-1 levels were measured. Statistical analyses were performed. A value of P < 0.05 was considered statistically significant. Results: The MIF and MCP-1 values of the control group were increased compared to those of the CAHB group. The MIF and MCP-1 levels were negatively correlated with HBs Ag levels and viral loads. The MIF and MCP-1 levels were positively correlated. The HBs Ag levels and the log10 of the viral loads were positively correlated. Conclusion: We conclude that the negative correlation of MIF and MCP-1 with viral load and HBs Ag levels may be due to T-cell deficiency, antinuclear antibody seropositivity, and/or inhibition of chemokine ligand 2 receptors by viral antigens. More studies with a greater number of subjects are needed to evaluate the potential role of MIF and MCP in CAHB.

Prevalence Of Helicobacter Pylori Caga, Baba2, And Dupa Genotypes Andcorrelation With Clinical Outcome In Malaysian Patients With Dyspepsia, Hussein Ali Osman, Habsah Hasan, Rapeah Suppian, Syed Hassan, Dzulkarnaen Zakaria Andee, Noorizan Abdul Majid, Bin Alwi Zilfalil

Turkish Journal of Medical Sciences

Background/aim: The severity of disease outcome in dyspepsia has been attributed to Helicobacter pylori virulence genes. The aim of this study was to determine the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to determine whether or not there arises a significant correlation with clinical dyspepsia outcomes. Materials and methods: H. pylori genotypes cagA, babA2, and dupA were identified by polymerase chain reactions from gastric biopsy samples in 105 H. pylori-positive patients. Results: The positive rates for cagA, babA2, and dupA genes in H. pylori dyspeptic patients were 69.5%, 41.0%, and 22.9%, respectively. cagA was more prevalent …

A Quantum Theory Of Consciousness May Require A Paradigm Shift In Biology, Maurice Goodman

Articles

It is often assumed that the known physical laws form a closed system and are complete. It is also assumed that biological theories require no additional principles that are fundamental other than those we already know. Assumptions such as these are acting as a barrier to progress in biological theories and an understanding of consciousness. This paper examines the unexplained inconsistencies among fundamental particles and forces and the fundamental gaps in our knowledge of biology and the cell in particular that may impact on such progress. Also, the laws of quantum mechanics are examined and found to be grossly incomplete. …

Validation Of Simple Sequence Length Polymorphism Regions Of Commonly Used Mouse Strains For Marker Assisted Speed Congenics Screening., Channabasavaiah B. Gurumurthy, Poonam S. Joshi, Scott G. Kurz, Masato Ohtsuka, Rolen M. Quadros, Donald W. Harms, K.C. Kent Lloyd

Journal Articles: Genetics, Cell Biology & Anatomy

Marker assisted speed congenics technique is commonly used to facilitate backcrossing of mouse strains in nearly half the time it normally takes otherwise. Traditionally, the technique is performed by analyzing PCR amplified regions of simple sequence length polymorphism (SSLP) markers between the recipient and donor strains: offspring with the highest number of markers showing the recipient genome across all chromosomes is chosen for the next generation. Although there are well-defined panels of SSLP makers established between certain pairs of mice strains, they are incomplete for most strains. The availability of well-established marker sets for speed congenic screens would enable the …

De Novo Assembly Of The Chimpanzee Transcriptome From Nextgen Mrna Sequences, Mnirnal D. Maudhoo, Jacob D. Madison, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the species most closely related to humans. For this reason, it is especially important to have complete and accurate chimpanzee nucleotide and protein sequences to understand how humans evolved their unique capabilities. We provide transcriptome data from four untransformed cell types derived from the reference Pan troglodytes, "Clint", to better annotate the chimpanzee genome and provide empirical validation for proposed gene models of this important species.

FINDINGS: RNA was extracted from primary cells cultured from four tissues: skin, adipose stroma, vascular smooth muscle and skeletal muscle. These four RNA samples …

The Metabolism Of Alcohol: Risk And Protective Factors, Sydney E. Levan, Amy Adkins, Danielle Dick, Karen G. Chartier

UROP Posters

Purpose: Abstract for poster submission to VCU Poster Symposium for

Undergraduate Research and Creativity

Title: The Metabolism of Alcohol: Risk and Protective Factors

Background: In 2002, it was reported by the National Institutes of Health that

60.3% of college aged students (18-22) drank alcohol in the past month of being

asked, as compared to 51.9% of those not in college. They also found that 20% of

college students met the criteria for at least one alcohol use disorder (AUDs)1.

Many genes have been linked to an increased risk for AUDs and how individuals

with various ethnic backgrounds respond to alcohol. …

Use Of Oxytocin As A Preventative Treatment For Ptsd, Laurel V. Kovalchick

UROP Posters

Posttraumatic stress disorder (PTSD) is a mental health disorder triggered by experiencing a traumatic event. PTSD causes recurrent flashbacks of traumatic memories that lead to over-consolidation. Memory over-consolidation prevents extinction of emotional and physiological responses to the memory. Because individuals can respond differently to stress and frightening experiences, no measures are currently practiced to prevent PTSD. By studying the changes in the brain during PTSD and after stress, it can be hypothesized that treatments that regulated HPA axis activity may prevent PTSD symptoms if applied soon after stress. Risk of developing PTSD is associated with abnormal cortisol and norepinephrine levels …

Preparing The Periphery For A Subsequent Behavior: Motor Neuronal Activity During Biting Generates Little Force But Prepares A Retractor Muscle To Generate Larger Forces During Swallowing In Aplysia, Hui Lu, Jeffrey M. Mcmanus, Miranda J. Cullins, Hillel J. Chiel

Faculty Scholarship

Some behaviors occur in obligatory sequence, such as reaching before grasping an object. Can the earlier behavior serve to prepare the musculature for the later behavior? If it does, what is the underlying neural mechanism of the preparation? To address this question, we examined two feeding behaviors in the marine mollusk Aplysia californica, one of which must precede the second: biting and swallowing. Biting is an attempt to grasp food. When that attempt is successful, the animal immediately switches to swallowing to ingest food. The main muscle responsible for pulling food into the buccal cavity during swallowing is the I3 …

Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance In High Fat-Fed Mice, Michelle B. Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V. Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai

Mathematics & Statistics Faculty Publications

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, …

The Effect Of Δ9-Tetrahydrocannabinol, Cannabidiol, Menthol And Propofol On 5-Hydroxytryptamine Yype 3 Receptors--A Computational Approach, Andreas C. Schilbach, Tatiana Prytkova, Keun-Hang Susan Yang

Mathematics, Physics, and Computer Science Faculty Articles and Research

This study investigates the function of 5-HT type 3 (5- HT3) receptors using a computational approach.

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Pharmaceutical Science and Research

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. …

Cd151-Α3Β1 Integrin Complexes Suppress Ovarian Tumor Growth By Repressing Slug-Mediated Emt And Canonical Wnt Signaling, Lauren A. Baldwin, John T. Hoff, Jason Lefringhouse, Michael Zhang, Changhe Jia, Zeyi Liu, Sonia Erfani, Hongyan Jin, Mei Xu, Qing-Bai She, John R. Van Nagell Jr., Chi Wang, Li Chen, Rina Plattner, David M. Kaetzel, Jia Luo, Michael Lu, Dava West, Chunming Liu, Fred R. Ueland, Ronny Drapkin, Binhua P. Zhou, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by …

Marine Population Connectivity: Range Boundaries And Climate Change, Rhiannon Leigh Rognstad

Theses and Dissertations

Population connectivity, particularly in open systems, is an important metric for understanding population-level processes on both ecological and evolutionary timescales. In coastal marine systems, adults are typically sedentary and dispersal occurs primarily during a larval stage when individuals are transported in ocean currents. Because coastal marine populations exist as networks of interconnected subpopulations, variation in the magnitude and extent of population connectivity can have profound effects on population dynamics and species distribution limits. Connectivity is a complex process, affected by a multitude of factors, including adult inputs and physical dispersal, which operate at multiple scales and may interact. This dissertation …

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Oligomerization, Conformational Stability And Thermal Unfolding Of Harpin, Hrpzpss And Its Hypersensitive Response-Inducing C-Terminal Fragment, C-214-Hrpzpss., Pradip K Tarafdar, Lakshmi Vasudev Vedantam, Rajeshwer S Sankhala, Pallinti Purushotham, Appa Rao Podile, Musti J Swamy

Department of Biochemistry and Molecular Biology Faculty Papers

HrpZ-a harpin from Pseudomonas syringae-is a highly thermostable protein that exhibits multifunctional abilities e.g., it elicits hypersensitive response (HR), enhances plant growth, acts as a virulence factor, and forms pores in plant plasma membranes as well as artificial membranes. However, the molecular mechanism of its biological activity and high thermal stability remained poorly understood. HR inducing abilities of non-overlapping short deletion mutants of harpins put further constraints on the ability to establish structure-activity relationships. We characterized HrpZPss from Pseudomonas syringae pv. syringae and its HR inducing C-terminal fragment with 214 amino acids (C-214-HrpZPss) using calorimetric, spectroscopic and microscopic approaches. Both …

P53 And Cancer-Associated Sialylated Glygans Are Surrogate Markers Of Cancerization Of The Bladder Associated With Schistosoma Haematobium Infection, Julio Santos, Elisabete Fernandes, Jose Alexandre Ferreira, Luis Lima, Ana Tavares, Andreia Peixoto, Beatriz Parreira, Jose Manuel Correia Da Costa, Paul J. Brindley, Carlos Lopes, Lucio L. Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.

Methodology/Principal Findings

Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder …

Ifn-Γ Causes Aplastic Anemia By Altering Hematopoietic Stem/Progenitor Cell Composition And Disrupting Lineage Differentiation, Fan Ching Lin, Megan Karwan, Bahara Saleh, Deborah L. Hodge, Tim Chan, Kimberly C. Boelte, Jonathan R. Keller, Howard A. Young

United States Public Health Resources

Aplastic anemia (AA) is characterized by hypocellular marrow and peripheral pancytopenia. Because interferon gamma (IFN-γ) can be detected in peripheral blood mononuclear cells of AA patients, it has been hypothesized that autoreactive T lymphocytes may be involved in destroying the hematopoietic stem cells. We have observed AA-like symptoms in our IFN-γ adenylate-uridylate-rich element (ARE)-deleted (del) mice, which constitutively express a low level of IFN-γ under normal physiologic conditions. Because no T-cell autoimmunity was observed, we hypothesized that IFN-γ may be directly involved in the pathophysiology of AA. In these mice, we did not detect infiltration of T cells in bone …

A Critical Analysis Of Infant Mortality In Kalamazoo County, Audrey Jensen

Honors Theses

The following is a review of the state of infant and fetal health in Kalamazoo County in the 21st century. Since infant health is a marker for the effectiveness of health care, this review will analyze the leading causes of infant mortality in Kalamazoo County. Statistical indicators show that Kalamazoo County falls below both state and national IMR averages. The leading causes of infant mortality in Kalamazoo are considered preventable infant deaths. Therefore, this review will make recommendations for the reduction of IMR through the improvement of preventative prenatal healthcare practices.

Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta

Student Scholar Symposium Abstracts and Posters

Small interfering RNAs have been an emerging medical treatment for molecular based diseases as they are capable of gene-specific knockdown. Appropriate and efficient delivery remains one of the biggest challenges in the development of siRNA as an anti-cancer treatment. Nanoparticles containing siRNA were characterized and the efficacy of various peptides in the transfection of the nanoparticles were tested. A gene silencing assay was developed in order to determine the effect of siRNA therapeutics on gene functionality in breast cancer cells.

Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky

Department of Chemistry: Dissertations, Theses, and Student Research

High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.

The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such …

E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung

Dartmouth Scholarship

Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score …

Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe

Dartmouth Scholarship

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation-based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset …