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Articles 1 - 22 of 22
Full-Text Articles in Molecular Biology
Sex Determination In Beetles: Production Of All Male Progeny By Parental Rnai Knockdown Of Transformer, Jayendra Nath Shukla, Subba Reddy Palli
Sex Determination In Beetles: Production Of All Male Progeny By Parental Rnai Knockdown Of Transformer, Jayendra Nath Shukla, Subba Reddy Palli
Entomology Faculty Publications
Sex in insects is determined by a cascade of regulators ultimately controlling sex-specific splicing of a transcription factor, Doublesex (Dsx). We recently identified homolog of dsx in the red flour beetle, Tribolium castaneum (Tcdsx). Here, we report on the identification and characterization of a regulator of Tcdsx splicing in T. castaneum. Two male-specific and one female-specific isoforms of T. castaneum transformer (Tctra) were identified. RNA interference-aided knockdown of Tctra in pupa or adults caused a change in sex from females to males by diverting the splicing of Tcdsx pre-mRNA to male-specific isoform. All the pupa and adults developed from Tctra …
Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang
Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang
Faculty Publications
Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell–matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo …
Dietary Analysis And Epigenetic Comparisons Of Drosphila Melanogaster Through Multiple Generations, Xu (Kevin) F. Zheng
Dietary Analysis And Epigenetic Comparisons Of Drosphila Melanogaster Through Multiple Generations, Xu (Kevin) F. Zheng
Holster Scholar Projects
Nutrition and the lack thereof has been a demanding issue in both the undeveloped and developed country. The unbalance diet between healthy and unhealthy diet has led to many of the problems presented in society such as obesity, heart disorders, and loss of longevity. It is now known that calorie may not provide the most accurate information in terms of the lifestyle and the well-being of humans. Rather the composition of the calorie is what becomes integral in people's understanding of the effect of food physiologically. With this knowledge, we seek to use a Drosophila melanogaster as a model organism …
Host Pathogen Interactions: Is Arabidopsis Thaliana Remembered By Its Nemesis Pseudomonas Syringae?, Daniel Z. Kreiser
Host Pathogen Interactions: Is Arabidopsis Thaliana Remembered By Its Nemesis Pseudomonas Syringae?, Daniel Z. Kreiser
Lawrence University Honors Projects
Plants contain innate immune systems that deter pathogen infection. Pattern recognition receptors bind microbe-associated molecular patterns (MAMPs), triggering immunity. MAMPs are proteins exclusive to pathogens that are typically indispensable for their survival. For this reason, MAMPs cannot be mutated or removed without causing pathogen death. However, this does not necessitate constitutive expression of MAMPs. In this study, the MAMP response of Arabidopsis thaliana was utilized to determine differential detection of MAMPs expressed by Pseudomonas syringe pv. tomato DC3000 when pretreated with A. thaliana. Results demonstrated that more MAMPs are detected when P. syringae had previously encountered A. thaliana, …
Elucidating The Mechanism Of Antimigratory Activity Of Cardiac Glycosides, Joshua H. Johnson
Elucidating The Mechanism Of Antimigratory Activity Of Cardiac Glycosides, Joshua H. Johnson
Honors Scholar Theses
The focus of this research is on cell migration and how it can be better understood through the use of small molecules that modulate cell migratory activity. The results have particular relevance in the realm of cancer pharmacology. Cardiac glycosides, which are known inhibitors of the eukaryotic Na+/K+-ATPase, have been determined to have antimigratory activities through the screening of several small molecule libraries. Here we investigate the antimigratory activities of the cardiac glycoside digitoxin as well as its analogs that we synthesized. Antimigratory activity was determined by conducting a wound closure assay with MDA-MB-231 human breast …
Identifying Progenitor Cells Of Heterotopic Ossification, Eileen E. Semancik
Identifying Progenitor Cells Of Heterotopic Ossification, Eileen E. Semancik
Honors Scholar Theses
Heterotopic Ossification (HO) is the abnormal formation of bone within extraskeletal soft tissues. The condition can occur through both genetic and acquired means. Acquired cases of HO result from invasive surgery or traumatic injuries, with increasing prevalence of ectopic skeletogenesis as a result of combat-related blast injuries. HO has been characterized to some extent, including the histological features and the mutation underlying the genetic form, but the cells resident in skeletal muscle that represent the progenitors of heterotopic bone have yet to be determined. Only a few publications have attempted to definitively determine the progenitor cells in this disorder. Findings …
Improvements To The Forensic Analysis Of Mitochondrial Dna Typing, Elizabeth Montano
Improvements To The Forensic Analysis Of Mitochondrial Dna Typing, Elizabeth Montano
Honors Scholar Theses
Sequence analysis of human mitochondrial DNA (mtDNA) is an effective and reliable tool for the genetic characterization of forensic samples. The nature of the mitochondrial genome (mtgenome), its high copy number and small size (~17kb) makes it more resistant to degradation and more stable than nuclear DNA. For this reason mitochondrial DNA is often the only feasible option for the forensic analysis of environmentally compromised samples. Currently the forensic analysis of the mtgenome is restricted to the hypervariable regions, also known as the Displacement loop (d-loop). Previous studies, confirmed in the Strausbaugh lab, have demonstrated an increased variability in the …
Metallothionein Gene Dose And The Immune Response, Meaghan Roy-O-Reilly
Metallothionein Gene Dose And The Immune Response, Meaghan Roy-O-Reilly
Honors Scholar Theses
Metallothionein (MT) is a small, cysteine-rich protein with significant immunomodulatory activity. It has been shown to play a critical role in important cellular mechanisms including heavy metal detoxification, essential metal management and the inflammatory response. MT production can be induced by a number of cellular stressors and acts to lessen the harmful effects of oxidizing agents and heavy metal exposure. Previous studies have shown that the dose of the metallothionein gene present in an individual may have significant effects on the adaptive immune response, yet the mechanism behind this phenomenon remains unknown. We hypothesize that the gene dose of metallothionein …
Mutation And Complementation Of A Cellulose Synthase (Cesa) Gene, Ahmed Y. El-Araby
Mutation And Complementation Of A Cellulose Synthase (Cesa) Gene, Ahmed Y. El-Araby
Senior Honors Projects
Cellulose is a carbohydrate polymer that is composed of repeating glucose subunits. Being the most abundant organic compound in the biosphere and comprising a large percentage of all plant biomass, cellulose is extremely plentiful and has a significant role in nature. Cellulose is present in plant cell walls, in commercial products such as those made from wood or cotton, and is of interest to the biofuel industry as a potential alternative fuel source. Although indigestible by humans, cellulose is nutritionally valuable, serving as a dietary fiber. Because of its ubiquity and importance in many areas, studying cellulose will prove to …
Characterization Of Genes In The Cftr-Mediated Innate Immune Response, Eric Peterman
Characterization Of Genes In The Cftr-Mediated Innate Immune Response, Eric Peterman
Honors College
Recently, the Kim Lab has shown that the cystic fibrosis transmembrane conductance regulator (cftr) gene is responsible for mediating resistance to Pseudomonas aeruginosa in a zebrafish infection model. Using the Gene Expression Omnibus, an NCBI functional genomics data repository, it was determined that Smad3, a transcription factor in the TGF-β signaling pathway, is upregulated in the presence of P. aeruginosa. It was found that in our zebrafish model, the Smad3 paralogs Smad3a and Smad3b are upregulated following microinjection of a cftr antisense morpholino oligomer. It was also found that microinjection of Smad3a and Smad3b morpholinos, along with …
Development And Evaluation Of A Mouse Neocortical Cells Neurodevelopment Assay To Assess The Effects Of Pyrethroids, Stephanie I. Savino
Development And Evaluation Of A Mouse Neocortical Cells Neurodevelopment Assay To Assess The Effects Of Pyrethroids, Stephanie I. Savino
Pell Scholars and Senior Theses
Pyrethroid insecticides have been used for more than 40 years and account for 25% of the global insecticide market with household, agricultural and public health applications. With increasing use of pyrethroids over recent years, human exposure to these chemicals is likely. The acute toxicity of pyrethroids to mammalian adults has been documented as moderately toxic by the U.S. Environmental Protection Agency. However, little evidence is available regarding the potential toxicological effects of pyrethroids on mammalian neurodevelopment. In this study, a neurodevelopment assay was developed for future investigation of potential pyrethroid effects on the neuronal development of Mus musculus neocortical cells.
Analysis Of The Effects And Current Treatments Of Laminin Deficiency, Joshua Mark Reynolds
Analysis Of The Effects And Current Treatments Of Laminin Deficiency, Joshua Mark Reynolds
Senior Honors Theses
Laminin (LM) is a network of proteins that functions as a connective framework of most cells in the body. It is composed of multiple different subunits and therefore has many different variations. It is a trimeric protein, meaning that it is composed primarily of ⍺, β, and γ chains. The differentiation of these subunits is what gives the different variants their functions. In addition, although LM is the primary molecule in scope, the network of other connective proteins involved in LM-associated diseases will also be covered in lesser detail because molecules like dystrophin, dystroglycan, collagen, and integrin are vital to …
Cloning And Characterization Of The Cell Wall Acting Enzyme Cd1034 From The Pathogen Clostridium Difficile, Zachary Suter
Cloning And Characterization Of The Cell Wall Acting Enzyme Cd1034 From The Pathogen Clostridium Difficile, Zachary Suter
Honors Projects in Science and Technology
The manifestation of multidrug resistance in bacteria over the past several decades has resulted in one of the foremost challenges in the management of infectious diseases. The question arises, “How do we address this growing problem?” One solution to stem the growing rise in antimicrobial resistance is to investigate new targets, while another approach is to re-examine classical antibacterial targets with a fresh perspective. The aim of this paper is to begin the process of antibacterial development for the pathogen Clostridium difficile by characterizing the cell wall acting glucosaminidase CD1034. It is inunderstanding how CD1034 functions biochemically that it can …
An Ims/Atp Assay For The Detection Of Mycobacterium Tuberculosis In Urine, Dawn M. Hunter, Daniel V. Lim
An Ims/Atp Assay For The Detection Of Mycobacterium Tuberculosis In Urine, Dawn M. Hunter, Daniel V. Lim
Molecular Biosciences Faculty Publications
Background. Although sputum smears are the gold standard for diagnosis of tuberculosis, sensitivity in HIV/TB coinfection cases is low, indicating a need for alternative methods. Urine is being increasingly evaluated. Materials and Methods. A novel method for detecting Mycobacterium tuberculosis (MTB) in synthetic urine using a combined IMS/ATP assay was evaluated. Preliminary work established standard ATP conditions and the sensitivity and specificity of the MTB antibody. Eighty-four blinded samples in four replicate assays were evaluated for the presence of MTB using labeled immunomagnetic beads for capture. Beads were separated, washed, and resuspended in broth and added to a …
Cell Wall Antibiotics Provoke Accumulation Of Anchored Mcherry In The Cross Wall Of Staphylococcus Aureus, Wenqi Yu, Friedrich Götz
Cell Wall Antibiotics Provoke Accumulation Of Anchored Mcherry In The Cross Wall Of Staphylococcus Aureus, Wenqi Yu, Friedrich Götz
Molecular Biosciences Faculty Publications
A fluorescence microscopy method to directly follow the localization of defined proteins in Staphylococcus was hampered by the unstable fluorescence of fluorescent proteins. Here, we constructed plasmid (pCX) encoded red fluorescence (RF) mCherry (mCh) hybrids, namely mCh-cyto (no signal peptide and no sorting sequence), mCh-sec (with signal peptide), and mCh-cw (with signal peptide and cell wall sorting sequence). The S. aureus clones targeted mCh-fusion proteins into the cytosol, the supernatant and the cell envelope respectively; in all cases mCherry exhibited bright fluorescence. In staphylococci two types of signal peptides (SP) can be distinguished: the +YSIRK motif SPlip and the −YSIRK …
Bacterial Host Interactions In Cystic Fibrosis, Máire Callaghan, Siobhan Mcclean
Bacterial Host Interactions In Cystic Fibrosis, Máire Callaghan, Siobhan Mcclean
Articles
Chronic infection is a hallmark of cystic fibrosis (CF) and the main contributor to morbidity. Microbial infection in CF is complex, due to the number of different species that colonise the CF lung. Their colonisation is facilitated by a host response that is impaired or compromised by highly viscous mucous, zones of hypoxia and the lack of the cystic fibrosis transmembrane regulator (CFTR). Successful dominant CF pathogens combine an effective arsenal to establish infection and counter-attack the host response, together with an ability to adapt readily to an unfavourable environment. Hypermutability is common among CF pathogens facilitating adaptation and as …
Protein Folding By 'Levels Of Separation': A Hypothesis, Lesley H. Greene, Terri M. Grant
Protein Folding By 'Levels Of Separation': A Hypothesis, Lesley H. Greene, Terri M. Grant
Chemistry & Biochemistry Faculty Publications
The protein folding process has been studied both computationally and experimentally for over 30 years. To date there is no detailed mechanism to explain the formation of long-range interactions between the transition and native states. Long-range interactions are the principle determinants of the tertiary structure. We present a theoretical model which proposes a mechanism for the acquisition of these interactions as they form in a modified version of ‘degrees of separation’, that we term ‘levels of separation’. It is based on the integration of network science and biochemistry. (C) 2012 Federation of European Biochemical Societies.
Identification Of New Cell Size Control Genes In S. Cerevisiae, Huzefa Dungrawala, Hui Hua, Jill Wright, Lesley Abraham, Thivakorn Kasemsri, Anthony Mcdowell, Jessica Stilwell, Brandt L. Schneider
Identification Of New Cell Size Control Genes In S. Cerevisiae, Huzefa Dungrawala, Hui Hua, Jill Wright, Lesley Abraham, Thivakorn Kasemsri, Anthony Mcdowell, Jessica Stilwell, Brandt L. Schneider
Molecular Biosciences Faculty Publications
Cell size homeostasis is a conserved attribute in many eukaryotic species involving a tight regulation between the processes of growth and proliferation. In budding yeast S. cerevisiae, growth to a “critical cell size” must be achieved before a cell can progress past START and commit to cell division. Numerous studies have shown that progression past START is actively regulated by cell size control genes, many of which have implications in cell cycle control and cancer. Two initial screens identified genes that strongly modulate cell size in yeast. Since a second generation yeast gene knockout collection has been generated, we screened …
The Two-Component Signal Transduction System Arlrs Regulates Staphylococcus Epidermidis Biofilm Formation In An Ica-Dependent Manner, Yang Wu, Jiaxue Wang, Tao Xu, Jingran Liu, Wenqi Yu, Qiang Lou, Tao Zhu, Nianan He, Haijing Ben, Jian Hu, Friedrich Götz, Di Qu
The Two-Component Signal Transduction System Arlrs Regulates Staphylococcus Epidermidis Biofilm Formation In An Ica-Dependent Manner, Yang Wu, Jiaxue Wang, Tao Xu, Jingran Liu, Wenqi Yu, Qiang Lou, Tao Zhu, Nianan He, Haijing Ben, Jian Hu, Friedrich Götz, Di Qu
Molecular Biosciences Faculty Publications
Due to its ability to form biofilms on medical devices, Staphylococcus epidermidis has emerged as a major pathogen of nosocomial infections. In this study, we investigated the role of the two-component signal transduction system ArlRS in regulating S. epidermidis biofilm formation. An ArlRS-deficient mutant, WW06, was constructed using S. epidermidis strain 1457 as a parental strain. Although the growth curve of WW06 was similar to that of SE1457, the mutant strain was unable to form biofilms in vitro. In a rabbit subcutaneous infection model, sterile disks made of polymeric materials were implanted subcutaneously followed with inoculation of WW06 or SE1457. …
Wipi-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus Aureus For Lysosomal Degradation, Mario Mauthe, Wenqi Yu, Oleg Krut, Martin Krönke, Friedrich Götz, Horst Robenek, Tassula Proikas-Cezanne
Wipi-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus Aureus For Lysosomal Degradation, Mario Mauthe, Wenqi Yu, Oleg Krut, Martin Krönke, Friedrich Götz, Horst Robenek, Tassula Proikas-Cezanne
Molecular Biosciences Faculty Publications
Invading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated autophagosome-like vesicles. By automated fluorescence-based high content analyses, we demonstrate that Staphylococcus aureus strains (USA300, HG001, SA113) stimulate autophagy and become entrapped in intracellular PtdIns(3)P-enriched vesicles that are decorated with human WIPI-1, an essential PtdIns(3)P effector of canonical autophagy and membrane protein of both phagophores and autophagosomes. Further, agr-positive S. aureus (USA300, HG001) strains were more efficiently …
Discovery Of Marinopyrrole A (Maritoclax) As A Selective Mcl-1 Antagonist That Overcomes Abt-737 Resistance By Binding To And Targeting Mcl-1 For Proteasomal Degradation*, Kenichiro Doi, Rongshi Li, Shen-Shu Sung, Hongwei Wu, Yan Liu, Wanda Manieri, Gowdahalli Krishnegowda, Andy Awwad, Alden Dewey, Xin Liu, Shantu Amin, Chunwei Cheng, Yong Qin, Ernst Schonbrunn, Gary W. Daughdrill, Thomas P. Loughran Jr., Said M. Sebti, Hong-Gang Wang
Discovery Of Marinopyrrole A (Maritoclax) As A Selective Mcl-1 Antagonist That Overcomes Abt-737 Resistance By Binding To And Targeting Mcl-1 For Proteasomal Degradation*, Kenichiro Doi, Rongshi Li, Shen-Shu Sung, Hongwei Wu, Yan Liu, Wanda Manieri, Gowdahalli Krishnegowda, Andy Awwad, Alden Dewey, Xin Liu, Shantu Amin, Chunwei Cheng, Yong Qin, Ernst Schonbrunn, Gary W. Daughdrill, Thomas P. Loughran Jr., Said M. Sebti, Hong-Gang Wang
Molecular Biosciences Faculty Publications
The anti-apoptotic Bcl-2 family of proteins, including Bcl-2, Bcl-XL and Mcl-1, are well-validated drug targets for cancer treatment. Several small molecules have been designed to interfere with Bcl-2 and its fellow pro-survival family members. While ABT-737 and its orally active analog ABT-263 are the most potent and specific inhibitors to date that bind Bcl-2 and Bcl-XL with high affinity but have a much lower affinity for Mcl-1, they are not very effective as single agents in certain cancer types because of elevated levels of Mcl-1. Accordingly, compounds that specifically target Mcl-1 may overcome this resistance. In this study, we identified …
Oxidative Effects Of Nanosecond Pulsed Electric Field Exposure In Cells And Cell-Free Media, Olga N. Pakhomova, Vera A. Khorokhorina, Angela M. Bowman, Raminta Rodaitė-Riševičienė, Gintautas Saulis, Shu Xiao, Andrei G. Pakhomov
Oxidative Effects Of Nanosecond Pulsed Electric Field Exposure In Cells And Cell-Free Media, Olga N. Pakhomova, Vera A. Khorokhorina, Angela M. Bowman, Raminta Rodaitė-Riševičienė, Gintautas Saulis, Shu Xiao, Andrei G. Pakhomov
Bioelectrics Publications
Nanosecond pulsed electric field (nsPEF) is a novel modality for permeabilization of membranous structures and intracellular delivery of xenobiotics. We hypothesized that oxidative effects of nsPEF could be a separate primary mechanism responsible for bioeffects. ROS production in cultured cells and media exposed to 300-ns PEF (1–13 kV/cm) was assessed by oxidation of 2′, 7′-dichlorodihydrofluoresein (H2DCF), dihidroethidium (DHE), or Amplex Red. When a suspension of H2DCF-loaded cells was subjected to nsPEF, the yield of fluorescent 2′,7′dichlorofluorescein (DCF) increased proportionally to the pulse number and cell density. DCF emission increased with time after exposure in nsPEF-sensitive Jurkat …