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Articles 1 - 12 of 12
Full-Text Articles in Life Sciences
Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar
Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar
Wayne State University Theses
Number of small RNA (sRNA) gene regulators have mounted in E. coli over the years whereas the number of validated protein partners has not changed considerably. Hfq has remained the only well studied global regulatory partner of sRNAs in E. coli. However, direct or indirect involvement of other protein partners has always been speculated. Study from Blasi lab has shown that CsdA, one of the five DEAD-box RNA helicases of E. coli, is required for the DsrA mediated upregulation of rpoS under cold stress condition. Previous study from our lab has identified two other DEAD-box RNA helicases, RhlB and RhlE, …
Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett
Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett
Wayne State University Theses
Abstract
DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS
by
KHALIN NISBETT
May 2017
Advisor: Dr. Jeremy Kodanko
Major: Chemistry
Degree: Master of Science
Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …
Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef
Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef
Wayne State University Theses
Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating …
Design And Synthesis Of Isatin-Based Caspase Inhibitors For Ruthenium Caging Applications, Kasun Chinthaka Ratnayake
Design And Synthesis Of Isatin-Based Caspase Inhibitors For Ruthenium Caging Applications, Kasun Chinthaka Ratnayake
Wayne State University Theses
ABSTRACT
DESIGN AND SYNTHESIS OF ISATIN BASED CASPASE INHIBITORS FOR RUTHENIUM CAGING APPLICATIONS
by
KASUN CHINTHAKA RATNAYAKE
August 2015
Advisor: Jeremy J. Kodanko, Ph.D.
Major: Chemistry (Organic)
Degree: Master of Science
Apoptosis is the energy dependent programmed cell death. Improper function of apoptosis could lead to diseases such as cancers, strokes, Alziemer’s disease. Caspases are the enzymes involved in the later stage of this process. Peptidyl and non-peptidyl caspase inhibitors have been synthesized recently. These non-peptidyl compound classes which consist of pyrrolidinyl-5-sulfo isatins have showed a greater potency against executioner caspases, caspase-3 and -7. According to literature and for further …
Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala
Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala
Wayne State University Theses
Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …
Effects Of Statin Drugs And Tocotrienol Rich Fraction Supplementation In Chronic Hemodialysis Patients And Metabolomic Profile, Eno Latifi
Wayne State University Theses
Chronic kidney disease (CKD) is known as a heterogeneous disorder which currently is on the rise and lately has been classified as a public health issues in the United State and worldwide. CKD is an irreversible and progressive disease which can lead to kidney failure, and this is depicted by the advanced stage of the disorder when it reaches the point, that is classified as end stage of renal disease (ESRD) (Stage 5 of CKD) (eGRF <15 mL/min/ 1.73 m2 working capacity), where both organs are in a total or permanent kidney failure. End-Stage renal disease patients, on hemodialysis have been associated to experience an accelerated form of atherosclerosis, which is induced by inflammation, impairment of antioxidant system and elevated oxidative stress. Since the problem effecting ESRD patients is multifactorial, the objective of this investigation is to explore and look at the effects of supplementing with vitamin E-tocotrienol rich fraction (TRF), a micronutrient which has anti-inflammatory, antioxidant, and lipid lower capabilities into tackling these comorbid conditions experienced by this population. Therefore the aims of this investigation will be to explore changes in lipid profiles, inflammatory markers, and oxidative status, as well as look at any changes in metabolomic profiles. It was hypothesized that by supplementing with TRF a vitamin E, for 16 weeks in ESRD patients undergoing hemodialysis, it may help reverse and/or improve, oxidative status, inflammatory markers, increase antioxidants status and improve lipid profiles.
The study was double-blinded, randomized, parallel, placebo-controlled design trial, of 81 adult patients undergoing chronic hemodialysis at Great Lake Dialysis Clinic, Detroit MI, where …
15>Biophysical Studies Of Mutant H69 Rna Constructs, Daya Nidhi Kharel
Biophysical Studies Of Mutant H69 Rna Constructs, Daya Nidhi Kharel
Wayne State University Theses
The importance of helix 69 (H69) of the large ribosomal subunit is emphasized by its location in the ribosome and key contacts with protein factors and tRNAs during different steps of protein synthesis. The presence of three highly conserved pseudouridine modifications in H69 has a significant impact on modulation of the ribosome conformations. Specific nucleotides of H69 may be necessary for the function of this helix-loop RNA, as some mutations are deleterious to bacterial growth. In this study, we investigated the effects of single nucleotide mutations in a 19-nucleotide H69 construct with and without pseudouridines on the RNA stability and …
Genetic And Biochemical Studies Of Human Apobec3h Enzyme, Thisari Sachithra Aluthgama Guruge
Genetic And Biochemical Studies Of Human Apobec3h Enzyme, Thisari Sachithra Aluthgama Guruge
Wayne State University Theses
The AID/APOBEC enzymes are DNA/RNA cytosine deaminases with important functions in innate and adaptive immunity. APOBEC3 enzymes play a crucial role in restricting the replication of exogenous retroviruses such HIV-1 and endogenous retrotransposition events. In particular, APOBEC3 enzymes have evolved in humans by gene duplication to compose seven members. APOBEC3H is highly diverse in its allelic sequence and the distribution is population-specific. It has evolved under strong positive selection over millions of years. To study the catalytic mechanism, structure, function and the underlying cause of its high diversity, a high resolution crystal or NMR structure is required are not yet …
Spliceosomal Prp24 Unwinds A Minimal U2/U6 Complex From Yeast, Chandani Manoja Warnasooriya
Spliceosomal Prp24 Unwinds A Minimal U2/U6 Complex From Yeast, Chandani Manoja Warnasooriya
Wayne State University Theses
Splicing plays a major role in eukaryotic gene expression by processing pre-mRNA to form mature mRNA. Pre-mRNAs undergo splicing to remove introns, non–protein coding regions, and religate exons, protein coding regions. This process is catalyzed by the spliceosome, which consists of five small nuclear ribonucleoprotein particles (snRNPs: U1, U2, U4, U5 and U6) and numerous protein factors. Proper assembly of spliceosomal components is critical for function, and thus, defects in assembly can be lethal. Several spliceosomal proteins facilitate structural rearrangements important for spliceosomal assembly and function. Prp24 is an essential factor in U6 snRNP assembly, and it has been proposed …
Investigating The Glutamine-Trna (Glutamine) Synthesis Appartus Of The Human Pathogen Helicobacter Pylori, Nilesh Joshi
Investigating The Glutamine-Trna (Glutamine) Synthesis Appartus Of The Human Pathogen Helicobacter Pylori, Nilesh Joshi
Wayne State University Theses
INVESTIGATING THE GLUTAMINE-TRNA (GLUTAMINE) SYNTHESIS APPARTUS OF THE HUMAN PATHOGEN HELICOBACTER PYLORI
by
NILESH JOSHI
August 2012
Advisor: Tamara L. Hendrickson
Major: Chemistry
Degree: Master of Science
Accurate protein biosynthesis is a vital process to all cellular life. Aminoacyl-tRNAs are at the heart of this process: A correctly formed aminoacyl-tRNA is critical for protein biosynthesis. Organisms have evolved many mechanisms to repair misacylated tRNAs before they cause errors in protein biosynthesis, thus maintaining the integrity of the genetic code. The human pathogen Helicobacter pylori (H. pylori) synthesizes Glu-tRNAGln as an intermediate to producing Gln-tRNAGln. This misacylated intermediate could cause lethal …
The Spliceosomal Protein Prp8 Stabilizes A Compact Conformation Of The U2-U6 Complex, Subasinghe Appuhamilage Lemintha Imali Subasinghe
The Spliceosomal Protein Prp8 Stabilizes A Compact Conformation Of The U2-U6 Complex, Subasinghe Appuhamilage Lemintha Imali Subasinghe
Wayne State University Theses
The spliceosome is a large, RNA-protein complex that catalyzes pre-mRNA splicing during mRNA maturation. The RNA components (small nuclear RNA; snRNAs) of the spliceosome have been well studied and are believed to be involved in the splicing catalysis. Although proteins are essential for splicing, they may not be directly involved in catalysis. Among hundreds of proteins, Prp8 is the only protein that interacts with all of the catalytically important snRNAs. Therefore, it is hypothesized that Prp8 may catalyze splicing either by directly participating in catalysis or by stabilizing the conformation of the catalytically active spliceosome. In order to test whether …
The Roles Of Rhle And Hfq In Srna-Dependent Gene Regulation, Abeykoon Jayalath Iresha Sandeepanie Rathnayake
The Roles Of Rhle And Hfq In Srna-Dependent Gene Regulation, Abeykoon Jayalath Iresha Sandeepanie Rathnayake
Wayne State University Theses
THE ROLES OF RHLE AND HFQ IN SRNA-DEPENDENT GENE REGULATION
by
ABEYKOON JAYALATH IRESHA SANDEEPANIE RATHNAYAKE
DECEMBER 2010
Advisor: Dr. Andrew Feig
Major: Chemistry
Degree: Master of Science
Bacteria are adapted to live in diverse environmental conditions. Thus, they show excellent tolerance and response to extreme environmental conditions caused by low or high temperatures, high salinity, reactive oxygen species or high nutrient concentrations. sRNAs have been identified and characterized as cis-acting or trans-acting post-transcriptional regulators in diverse cellular processes including virulence and adaptation to environmental stress (11,12,14,15). Interactions of sRNAs and target mRNAs result in translational repression, translational activation or/and …