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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Role Of Sirna Pathway In Epigenetic Modifications Of The Drosophila Melanogaster X Chromosome, Nikita Deshpande Jan 2018

Role Of Sirna Pathway In Epigenetic Modifications Of The Drosophila Melanogaster X Chromosome, Nikita Deshpande

Wayne State University Dissertations

Eukaryotic genomes are organized into large domains of coordinated regulation. The role of small RNAs in formation of these domains is largely unexplored. An extraordinary example of domain-wide regulation is X chromosome compensation in Drosophila melanogaster males. This process occurs by hypertranscription of genes on the single male X chromosome. Extensive research in this field has shown that the Male Specific Lethal (MSL) complex binds X-linked genes and modifies chromatin to increase expression. The components of this complex, and their actions on chromatin, are well studied. In contrast, the mechanism that results in exclusive recruitment to the X chromosome is ...


Identification Of Oxygen Optima For Mouse Trophoblast Stem Cells And Human Embryos And The Stress Responses Upon Departing Optima, Yu Yang Jan 2017

Identification Of Oxygen Optima For Mouse Trophoblast Stem Cells And Human Embryos And The Stress Responses Upon Departing Optima, Yu Yang

Wayne State University Dissertations

Low level of oxygen (O2) occurs physiologically during in vivo embryo development. As developing embryos moving from fallopian tube to uterus, oxygen level gradually decreases to ≤ 5% at the time of blastocyst implantation. Blastocysts are made of two major cell populations, trophoblast cells and inner cell mass, from which trophoblast stem cells (TSCs) and embryonic stem cells (ESCs) are derived respectively. TSCs serve as placental stem cells that later on proliferate and differentiate into placenta. Previous study has shown that 2% O2 is the optimal O2 level for mTSC in vitro growth and potency maintenance, which agrees with their low ...


Studies Of Sumoylation In Regulating Mif Stability And Rangap1 Nucleo-Cytoplasmic Shuttling In Controlling Its Sumo Modification, Progga Sen Jan 2017

Studies Of Sumoylation In Regulating Mif Stability And Rangap1 Nucleo-Cytoplasmic Shuttling In Controlling Its Sumo Modification, Progga Sen

Wayne State University Dissertations

SUMOylation is an essential post-translational modification that regulates a variety of critical cellular pathways ranging from nuclear transport to protein stability. Accumulating lines of evidence have shown that a perturbation of the SUMOylation pathway is associated with human diseases, especially various types of cancer. Our recent proteomic studies revealed a drastic increase in levels of SUMO2/3 modification on the proinflammatory cytokine MIF in the metastatic breast cancer cell line compared to the non-metastatic control cell line. Interestingly, the increase in levels of both MIF and global SUMO-2/3 modification in the metastatic cells are positively correlated to that of ...


Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj Jan 2017

Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj

Wayne State University Dissertations

Despite converging incidence rates for breast cancers by race, disparities in mortality persist where black women suffer from poorer prognosis compared to white counterparts. To understand the clinical, demographic, and molecular characteristics underlying these disparities, we examined differences among patients with breast cancer to understand the role of human epidermal growth factor receptor 2 (HER2) status, age, and race/ethnicity among women diagnosed with hormone receptor-positive breast cancer, and disparities in surgical therapy among female patients with early stage young-onset breast cancer. Benign breast disease, another known risk factor for breast cancer, includes a histological spectrum of lesions, could contribute ...


Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki Jan 2017

Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki

Wayne State University Dissertations

The work of this project was to develop, test and characterize a potential novel mouse model of the neurodegenerative disease Multiple Sclerosis (MS). Historically, MS has been identified as a primary autoimmune disease of the central nervous system (CNS). However, treatments based on this view have met with limited success, and in most cases, fail to prevent progression of MS from mild to moderate and severe forms. Original observations regarding axonal and neuronal pathology in the white and gray matter of the CNS were rediscovered in the 1990s. These observations indicated that even in the absence of the immune system ...


Role Of Alström Syndrome 1 (Alms1) In Nkcc2 Endocytosis, Thick Ascending Limb Function, Blood Pressure Regulation And Metabolic Function, Ankita Bachhawat Jaykumar Jan 2017

Role Of Alström Syndrome 1 (Alms1) In Nkcc2 Endocytosis, Thick Ascending Limb Function, Blood Pressure Regulation And Metabolic Function, Ankita Bachhawat Jaykumar

Wayne State University Dissertations

NaCl absorption by the Thick Ascending Limb (TAL) is mediated by the apical Na+/K+/2Cl- co-transporter, NKCC2. Increased NKCC2 activity and apical trafficking are associated to salt sensitive hypertension in rodents and humans. NKCC2 endocytosis is important for maintaining surface NKCC2 such that blocking NKCC2 endocytosis increased NKCC2 surface abundance and NKCC2-mediated NaCl reabsorption. Despite its importance, NKCC2 endocytosis has been poorly studied and a part of the reason may be attributed to the lack of availability of methods with good time resolution. Hence, we developed a method to image apical NKCC2 to monitor its endocytosis in real-time by ...


Effect Of Endoplasmic Reticulum Stress On Vascular Smooth Muscle Cells And Its Regulation Of Sm22Α, Neeraja Priyanka Annam Jan 2017

Effect Of Endoplasmic Reticulum Stress On Vascular Smooth Muscle Cells And Its Regulation Of Sm22Α, Neeraja Priyanka Annam

Wayne State University Dissertations

Background: The vascular smooth muscle cells(VSMC) possess the ability to differentiate into a synthetic phenotype in response to stress. This phenotypic modulation may be accompanied by inflammatory or osteogenic response in chronic stress. The synthetic state is characterized by low levels of contractile markers unlike the differentiated state.

Hypothesis: Endoplasmic reticulum (ER) stress causes phenotypic modulation in VSMCs leading to apoptosis. Many transcription factors induced by ER stress contribute to the downregulation of Sm22α. Perturbation in cytoskeletal dynamics exacerbates the ER stress response.

Methods: Ex-vivo culture was used to establish importance of Sm22 in ER stress. In vitro analysis ...


Navigating Human Cytomegalovirus (Hcmv) Envelopment And Egress, William Longeway Close Jan 2017

Navigating Human Cytomegalovirus (Hcmv) Envelopment And Egress, William Longeway Close

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is a ubiquitous viral pathogen. In individuals with fully functioning and mature immune systems, HCMV is associated with mild symptoms prior to establishing latency. In individuals with naïve or compromised immune systems, HCMV is capable of causing severe organ damage. HCMV is the leading infectious cause of congenital birth defects and a major non-genetic cause of hearing loss. Unfortunately, antiviral treatment options lack diversity due to limited knowledge of virion replication. If HCMV replication were better understood, new antiviral treatments could be developed.

In this work, we describe the development and implementation of new tools to study ...


Novel Regulatory Mechanisms Of Inositol Biosynthesis In Saccharomyces Cerevisiae And Mammalian Cells, And Implications For The Mechanism Underlying Vpa-Induced Glucose 6-Phosphate Depletion, Wenxi Yu Jan 2016

Novel Regulatory Mechanisms Of Inositol Biosynthesis In Saccharomyces Cerevisiae And Mammalian Cells, And Implications For The Mechanism Underlying Vpa-Induced Glucose 6-Phosphate Depletion, Wenxi Yu

Wayne State University Dissertations

Myo-inositol is the precursor of all inositol containing molecules, including inositol phosphates, phosphoinositides and glycosylphosphatidylinositols, which are signaling molecules involved in many critical cellular functions. Perturbation of inositol metabolism has been linked to neurological disorders. Although several widely-used anticonvulsants and mood-stabilizing drugs have been shown to exert inositol depletion effects, the mechanisms of action of the drugs and the role of inositol in these diseases are not understood. Elucidation of the molecular control of inositol synthesis will shed light on the pathologies of inositol related illnesses.

In Saccharomyces cerevisiae, deletion of the four glycogen synthase kinase-3 genes, MCK1, MRK1, MDS1 ...


Investigating The Role Of Dna Polymerase Beta In The Aging Phenotype Of Down Syndrome, Aqila Ahmed Ahmed Jan 2016

Investigating The Role Of Dna Polymerase Beta In The Aging Phenotype Of Down Syndrome, Aqila Ahmed Ahmed

Wayne State University Dissertations

Down syndrome (DS) is a chromosomal condition characterized by accelerated aging that has yet to be directly linked to a DNA repair defect. Reduced PolB and unrepaired damage from oxidative stress observed in DS, point toward defective base excision repair (BER). In this study, we report that low PolB transcript correlates with increased markers of senescence. The gene dosage effect of Trisomy 21 is likely the source for PolB downregulation. We show that the HSA21-localized miR-155 overexpression correlates with a decrease in Creb1 and PolB, thus establishing a putative regulatory pathway. Data from the DS mouse model, Ts65Dn, reveal low ...


An Investigation Into The Molecular Basis Underlying Enhancement Of Transcription By The Intron In Budding Yeast, Neha Agarwal Agarwal Jan 2016

An Investigation Into The Molecular Basis Underlying Enhancement Of Transcription By The Intron In Budding Yeast, Neha Agarwal Agarwal

Wayne State University Dissertations

It is now quite evident that the introns, which are removed from the primary transcript by the process of splicing, are involved in a variety of important functions in eukaryotic cells. One of the evolutionarily conserved functions of introns is their role in regulating transcription of genes that harbors them. This effect of a splicing-competent intron on transcription is known as ‘Intron-Mediated Enhancement of transcription’ (IME). It has been observed that the intron-containing genes are often transcribed more efficiently than non-intronic genes. However, the molecular mechanism underlying IME in budding yeast and higher eukaryotes is not entirely clear, and that ...


The Effects Of Courtship And Pairing Behavior On The Nonapeptide And Noradrenergic Systems Of Adult Male And Female Zebra Finches, Erin Lowrey Ondercin Jan 2016

The Effects Of Courtship And Pairing Behavior On The Nonapeptide And Noradrenergic Systems Of Adult Male And Female Zebra Finches, Erin Lowrey Ondercin

Wayne State University Dissertations

Social relationships are complex and likely involve the multiple neural circuits, including those involved in learning, memory, motivation, and attention. Two neurotransmitter pathways highly involved in these neural circuits are norepinephrine (NE) and the nonapeptides, vasopressin (AVP) and oxytocin (OT). There is extensive research implicating a role for the nonapeptides in trust, sociality, parental care, and romantic relationships. There is little direct evidence for the role of nonapeptides in monogamous relationships in any species other than the prairie vole (Goodson 2013). However, there is evidence that nonapeptides are important in pair bonding for both male and female zebra finches (Lowrey ...


A Critical Role Of Cxcr2 Pdz Motif-Mediated Interactions In Endothelial Progenitor Cell Homing And Angiogenesis, Yuning Hou Jan 2016

A Critical Role Of Cxcr2 Pdz Motif-Mediated Interactions In Endothelial Progenitor Cell Homing And Angiogenesis, Yuning Hou

Wayne State University Dissertations

Bone marrow-derived endothelial progenitor cells (EPCs) participate in postnatal vascularization in response to growth factors, cytokines, and chemokines. Chemokine receptor CXCR2 and its cognate ligands are reported to mediate EPC recruitment and angiogenesis. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl terminus. The PDZ motif has been reported to regulate cellular signaling and functions. Here we investigated the potential role of the PDZ motif in CXCR2-mediated EPC motility and angiogenesis. We have found that introducing exogenous CXCR2 C-terminus significantly attenuated in vitro EPC migration and angiogenic activities in response to CXCR2 ligands, as well as in ...


Effective Drug Treatment Induces Drug Resistance Through Rapid Genome Alteration-Mediated Cancer Evolution, Steven Horne Jan 2016

Effective Drug Treatment Induces Drug Resistance Through Rapid Genome Alteration-Mediated Cancer Evolution, Steven Horne

Wayne State University Dissertations

The central paradox associated with current cancer therapeutic strategies is initially effective treatment, which eliminates a high tumor cell count, consistently results in successful drug resistance. Mathematical and evolutionary modeling have previously suggested that therapeutic intervention could provide selective pressure for the expansion of resistant variants. Drug-related stress has been associated with genome chaos, a common phenomenon in cancer characterized as rapid, stochastic genomic fragmentation and reorganization. Since cancer represents an evolutionary process, analysis within the context of genome-mediated cancer evolution can shed light on this key problem of therapeutics. We propose that genomic change is a general response to ...


A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi Jan 2016

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly ...


Modeling The Mechanism Underlying Environmental And Genetic Determinants Of Gene Expression And Complex Traits, Gregory Alan Moyerbrailean Jan 2016

Modeling The Mechanism Underlying Environmental And Genetic Determinants Of Gene Expression And Complex Traits, Gregory Alan Moyerbrailean

Wayne State University Dissertations

Advances in next-generation sequencing technologies and functional genomics strategies have allowed researchers to identify both common and rare genetic variation, to deeply profile gene expression, and even to determine regions of active gene transcription.

While these technologies and strategies have contributed greatly to our understanding of complex traits and diseases, there are many biological questions and analytical issues to be addressed.

Genome-wide association studies (GWAS) have successfully identified large numbers of genetic variants associated with complex traits and diseases. However, in many cases the mechanistic link between the phenotype and associated variant remains unclear. This may be because most variants ...


An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu Jan 2016

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone ...


Genome Wide Analysis Identifies Sphingolipid Metabolism As A New Target Of Valproic Acid, Shyamalagauri Jadhav Jadhav Jan 2016

Genome Wide Analysis Identifies Sphingolipid Metabolism As A New Target Of Valproic Acid, Shyamalagauri Jadhav Jadhav

Wayne State University Dissertations

Bipolar disorder (BD), which is characterized by depression and mania, affects about 1% of the total world population. Current treatments are effective in only 40-60% of cases and cause severe side effects. Valproic acid (VPA), a branched short-chain fatty acid, is one of the most widely used drugs for the treatment of BD. Although many hypotheses have been postulated to explain the molecular mechanism of action of this drug in BD, the therapeutic mechanism is not understood. This knowledge gap has hampered the development of new drugs to treat this disorder. To identify candidate pathways affected by VPA, I performed ...


Investigation Of Mutations In Nuclear Genes That Affect The Atp Synthase, Russell Dsouza Jan 2016

Investigation Of Mutations In Nuclear Genes That Affect The Atp Synthase, Russell Dsouza

Wayne State University Dissertations

The F1 domain is the catalytic subunit of the mitochondrial ATP synthase. Studies with respiratory-deficient yeast identified ATP1 and ATP2 as nuclear genes encoding the alpha and beta subunits, respectively, of the mitochondrial F1-ATPase. The mutations in the atp1 and atp2 genes were cloned and sequenced, and they appear to affect the ATP synthase. Most yeast strains with mutations in the or the subunit primarily show an F1 assembly defective phenotype. This feature is similar to the assembly-defective mutants missing the chaperones required for assembly of the F1 oligomer or either the alpha/beta subunits.

Some of the atp2 and ...


Insights Into De Novo Fes-Cluster Biogenesis Via The Eukaryotic Fes-Cluster (Isc) Pathway In Vitro, Stephen Paul Dzul Jan 2016

Insights Into De Novo Fes-Cluster Biogenesis Via The Eukaryotic Fes-Cluster (Isc) Pathway In Vitro, Stephen Paul Dzul

Wayne State University Dissertations

Fe-S clusters are iron-containing cofactors utilized by numerous proteins within several biological pathways essential to life. In eukaryotes, the primary pathway for Fe-S cluster production is the iron-sulfur cluster (ISC) pathway. The eukaryotic ISC pathway, localized primarily within the mitochondria, has been best characterized within Saccharomyces cerevisiae. In yeast, de novo Fe-S cluster formation is accomplished through coordinated assembly of the substrates iron and sulfur on the primary scaffold assembly protein “Isu1”. The sulfur used for cluster assembly is provided by the cysteine desulfurase “Nfs1”, a protein that works in union with its accessory protein “Isd11”. Frataxin “Yfh1” helps direct ...


Identification Of Lipolysis-Derived Lipid Mediators And The Activation Of A Pro-Inflammatory Cyclooxygenase Pathway, Via Cyclooxygenase-2, In Adipose Tissue, Allison Christine Gartung Jan 2016

Identification Of Lipolysis-Derived Lipid Mediators And The Activation Of A Pro-Inflammatory Cyclooxygenase Pathway, Via Cyclooxygenase-2, In Adipose Tissue, Allison Christine Gartung

Wayne State University Dissertations

Adipose lipolysis triggers pro-inflammatory responses that play critical roles in insulin resistance and associated metabolic syndrome. However, pro-inflammatory mediators generated by adipose lipolysis, particularly in the context of lipid mediators, are poorly defined. In this study, the activation of the beta-3 adrenergic receptor (ADRB3)/hormone sensitive lipase (HSL) pathway, a well-employed model system, was utilized to characterize the pro-inflammatory lipid mediators generated by adipose lipolysis. Cultured adipocytes were treated with an ADRB3 agonist and the media was analyzed for eicosanoids using the LC-MS/MS lipidomic method. Among the characterized eicosanoids, I found that approximately 43 metabolites generated by cyclooxygenase (COX ...


Characterization Of The Yeast Cysteine Desulfurase Complex Within The Mitochondrial Fe-S Cluster Biogenesis, Dulmini Pabasara Barupala Jan 2016

Characterization Of The Yeast Cysteine Desulfurase Complex Within The Mitochondrial Fe-S Cluster Biogenesis, Dulmini Pabasara Barupala

Wayne State University Dissertations

Disrupted iron homeostasis within the human body materializes as various disorders. Pathophysiology of many of them relates to iron induced oxidative damage to key cellular components caused by iron accumulation within the tissues. Pertaining to the growing occurrence, cost of patient care and devastating burden associated with these diseases, the call for understanding the role of iron homeostasis within these disorders becomes inevitable. Being an abundant iron containing cofactor, the role of Fe-S clusters in cellular iron homeostasis is indisputable in the case of Friedreich’s ataxia, a disease caused by a deficiency in the protein frataxin that is indispensable ...


Cardiolipin Is Required For Optimal Acetyl-Coa Metabolism, Vaishnavi Raja Jan 2016

Cardiolipin Is Required For Optimal Acetyl-Coa Metabolism, Vaishnavi Raja

Wayne State University Dissertations

The phospholipid cardiolipin (CL) is crucial for many cellular functions and signaling pathways, both inside and outside of mitochondria. My thesis focuses on the role of CL in energy metabolism. Many reactions of electron transport and oxidative phosphorylation, the transport of metabolites needed for these processes, and the stabilization of electron transport chain supercomplexes, require CL. Recent studies indicate that CL is required for the synthesis of iron-sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways. Activation of carnitine-acetylcarnitine translocase, which transports acetyl-CoA into the mitochondria, is CL dependent. The presence of substantial amounts of CL in the peroxisomal ...


Development Of A Novel Class Of Chemicals For Labeling Abasic Sites In Cellular Dna And Killing Cancer Cells, Shanqiao Wei Jan 2016

Development Of A Novel Class Of Chemicals For Labeling Abasic Sites In Cellular Dna And Killing Cancer Cells, Shanqiao Wei

Wayne State University Dissertations

Abasic (AP) sites are the most common type of lesions in DNA. Numerous endogenous and exogenous agents and cellular processes can induce the formation of AP sites in DNA. If left unrepaired, the deleterious AP sites cause mutagenesis and cytotoxicity. Methoxyamine is known to react with AP sites and block base excision repair. Another alkoxyamine, aldehyde-reactive probe (ARP) tags AP sites with a biotin and has been widely used to quantify these sites. In this study, I have combined both these abilities into one alkoxyamine, AA3, which reacts toward AP sites with better reactivity than ARP at physiological pH. Additionally ...


Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal Jan 2015

Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal

Wayne State University Dissertations

Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for

treatment of several indications including endobronchial and esophageal cancers that are

accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)

are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal

lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients

have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is

underexplored for breast cancers but has been proposed for treatment of subtypes for which a

targeted therapy is unavailable ...


Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh Jan 2015

Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh

Wayne State University Dissertations

AMPK activation and Ubiquitin Proteasome System (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. Although the crosstalk between them is suggested, the relationship between these two important pathways is not very clear. We observed that proteasome inhibition leads to AMPK activation in human breast cancer cells. We report that a variety of proteasome inhibitors activate AMPK in all of the tested cancer cell lines. Our data using Liver Kinase B1 (LKB1)-deficient cancer cells suggests that proteasome ...


Drosophila Cyclin J And The Somatic Pirna Pathway Cooperate To Regulate Germline Stem Cells, Paul Michael Albosta Jan 2015

Drosophila Cyclin J And The Somatic Pirna Pathway Cooperate To Regulate Germline Stem Cells, Paul Michael Albosta

Wayne State University Dissertations

Cyclin J (CycJ) is a highly conserved cyclin that is uniquely expressed specifically in ovaries in Drosophila. Deletion of the genomic region containing CycJ and adjacent genes resulted in a genetic interaction with neighboring piRNA pathway gene, armitage (armi). Here I assessed oogenesis in CycJ null in the presence or absence of mutations in armi or other piRNA pathway genes. Although CycJ null flies had decreased egg laying and hatching rates, ovaries appeared normal indicating that CycJ is dispensable for oogenesis under normal conditions. Further double mutant analysis of CycJ and neighbor armi, as well as two other piRNA pathway ...


Analyzing The Interactions Of Kdm5/Lid And Sin3 In Drosophila Melanogaster, Ambikai Gajan Jan 2015

Analyzing The Interactions Of Kdm5/Lid And Sin3 In Drosophila Melanogaster, Ambikai Gajan

Wayne State University Dissertations

SIN3, the scaffold protein of a histone modifying complex is conserved from yeast to mammals. Drosophila SIN3 associates with both a histone deactylase RPD3 and a histone demethylase dKDM5/LID. Immunopurification of dKDM5/LID verifies a previously observed interaction with SIN3 and RPD3. Furthermore, deficiency of dKDM5/LID phenocopies deficiency of SIN3 in many cellular and developmental processes. Knockdown of both Sin3A and lid hinder cell proliferation in Drosophila cultured cells and developing flies. Knockdown of these genes also results in a curved wing phenotype implicating a role in wing development. Analysis of underlying gene expression changes upon decreased expression ...


Crebh, A Novel Liver Clock Keeper For Energy Metabolism, Ze Zheng Jan 2015

Crebh, A Novel Liver Clock Keeper For Energy Metabolism, Ze Zheng

Wayne State University Dissertations

Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Cyclic AMP responsive element binding protein 3-like 3 (CREB3L3, also known as CREBH) is a liver-enriched, endoplasmic reticulum (ER)-tethered transcription factor known to regulate hepatic acute-phase response and energy homeostasis under stress conditions. Here, we demonstrate that CREBH is regulated by the circadian clock and functions as a diurnal regulator of hepatic lipid and glucose metabolism. CREBH is required to maintain circadian profiles of blood triglycerides, fatty acids, and glucose as well as hepatic glycogen storage. CREBH rhythmically regulates expression levels and ...


Hrd1 Partners In Endoplasmic Reticulum-Associated Degradation, Aaron Alexander Burr Jan 2015

Hrd1 Partners In Endoplasmic Reticulum-Associated Degradation, Aaron Alexander Burr

Wayne State University Dissertations

Protein Quality Control (PQC) comprises cellular pathways that regulate the turnover of short-lived, misfolded proteins. A main component of PQC is Endoplasmic Reticulum (ER)-Associated Degradation (ERAD), which controls the degradation of proteins synthesized in the ER. Aberrations in ERAD have been linked to malignancies such as sarcomas, breast, and pancreatic carcinomas, as well as neurodegenerative disease. The machinery in this system is complex and while significant progress has been made to understand ERAD, it is not clear how the different components come together, or how they are regulated. HRD1 is a resident ubiquitin ligase that has been proposed as ...