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Full-Text Articles in Life Sciences
Investigating Roles Of 2 Novel Eklf Targets Involved In Erythropoiesis, Rose M. Gott
Investigating Roles Of 2 Novel Eklf Targets Involved In Erythropoiesis, Rose M. Gott
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Erythrocytes are primarily comprised of the oxygen carrying protein hemoglobin. Genetic mutations causing defects in the proper synthesis of hemoglobin result in various anemias. It is during the last phases of terminal erythroid differentiation that hemoglobin levels rise, making it a focus for therapeutic research. Fetal hemoglobin is comprised of ⍺-globin and gamma globin, then after a change in gene expression called hemoglobin switching which takes place after birth, adult hemoglobin is comprised of ⍺-globin and beta globin. We investigated hemoglobin switching and erythroid terminal differentiation by focusing on the master erythroid transcription factor Erythroid Krüppel-like Factor (EKLF). Data led …
Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques, Sudeep K. Gummadi
Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques, Sudeep K. Gummadi
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Gliomas express mutant isocitrate dehydrogenases producing excessive amounts of D 2-hydroxyglutarate (D2HG) and releasing some of it into the environment. The immune surveillance is reduced as a result, however, the mechanisms behind lymphocyte suppression by the D2HG stereoisomer remain unknown. I incubated Jurkat T cells with D2HG at concentrations present within and surrounding gliomas, or its obverse L2HG stereoisomer, and quantified 2HG isomers within washed cells by TSPC derivatization with stable isotope-labeled D2HG and L2HG internal standards, HPLC separation, and mass spectrometry. D2HG was found in quiescent cells in double the amount of L2HG. External D2HG or L2HG increased the …
A Multi-Spatial Analysis Of Land Use Effects On Freshwater Mussels In The Upper Cuyahoga River And Tinkers Creek, Tamar Atwell
A Multi-Spatial Analysis Of Land Use Effects On Freshwater Mussels In The Upper Cuyahoga River And Tinkers Creek, Tamar Atwell
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Mussels are considered one indicator of good water quality in rivers, but over the past 20 years mussel populations have continued to decline, while water quality improves. According to the Ohio Environmental Protection Agency (OEPA), water quality in the Cuyahoga River is now within safe levels for all parameters. However, what are safe levels for humans may not be safe for mussels. An analysis of freshwater mussel populations in two similarly sized watersheds, the Upper Cuyahoga River and Tinkers Creek was conducted. Correlations of mussel abundance and diversity were assessed by multivariate GIS/remote sensing tools to contrast water flow rates, …
Evaluation Of A Small Molecule Agonist Of Epha2 Receptor Tyrosine Kinase And Copalic Acid Analogs As Prostate Cancer Therapeutics, Nethrie Idippily
Evaluation Of A Small Molecule Agonist Of Epha2 Receptor Tyrosine Kinase And Copalic Acid Analogs As Prostate Cancer Therapeutics, Nethrie Idippily
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Project I: Chemotherapeutic drugs have many side effects that are undesirable and are highly toxic. Therefore, there is a growing need for the development of drugs with enhanced efficacy, specificity, and potency to provide cancer patients with a better prognosis. It was discovered that a member of the Receptor Tyrosine Kinase family, EphA2, may prove to be a viable target in developing anti-cancer agents. In the presence of its ligand, EphA2 receptor is responsible for apoptotic and anti-migratory activity. However, in the absence of ligand, EphA2 is able to stimulate cell migration and therefore tumorigenic activity. These conflicting roles of …
Biomimetic Macromolecules For Macrophage Targeting And Modulation, Joshua Whited
Biomimetic Macromolecules For Macrophage Targeting And Modulation, Joshua Whited
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Carbohydrate recognition has come to the forefront of biological aiming to uncover the mechanisms of physiological and pathological processes. Cell surface glycans are involved in processes including cellular adhesion, cell signaling, and immune response. A new approach for profiling cell surface glycans has great potential for a wide range of biomedical applications. Lectins have been conventionally used to determine the structure and function of glycoproteins, however, their numbers are still restricted compared to the number of glycan structures. Boronic acid has proven a remarkable small molecule capable of binding diols in aqueous solution. This interaction indicates boronic acid derived molecules …
A Synthesis Platform For Temperature Responsive Star Polymers, Schmitt J. Richard Jr.
A Synthesis Platform For Temperature Responsive Star Polymers, Schmitt J. Richard Jr.
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Star polymers are a class of branched polymers comprised of several polymer chains extending from a central point. Star polymers have applications in biopharmaceuticals where they have been proposed to be suitable drug delivery vehicles. Star polymers have traditionally been synthesized through chemical synthesis with added functionality provided by grafting on the arms. This complex synthesis can be simplified by using a biosynthetic approach which enables precise control of molecular weight and composition. This approach is demonstrated using star polymers with arms composed of a temperature responsive protein-based polymer termed elastin-like polypeptide (ELP). Star polymers are characterized based on the …
The Naked Mole Rat Possesses A Differently Phased Core Clock System Along With A Different Glucose Handling And Mtor Systems Compared To The Common Lab Mouse, Soumyaditya Ghosh
The Naked Mole Rat Possesses A Differently Phased Core Clock System Along With A Different Glucose Handling And Mtor Systems Compared To The Common Lab Mouse, Soumyaditya Ghosh
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INTRODUCTION The Naked Mole Rat [ Heterocephalus glaber] is a type of rodent -with the highest average lifespan-30 years-among all the rodent species. It lives underground in sealed burrow systems with little to no exposure to day-night transitions on the surface. It shows polyphasic round the clock activity within its subterranean burrow system. The activity and physiology of most animals are governed by the biological circadian clock. The biological circadian clock is a system that oscillates with a rough periodicity of 24 hours. Environmental zeitgebers regulate the entrainment of the circadian clock to the 24-hour day-night cycle and light is …
Age And Sex-Specific Effect Of Caloric Restriction On Circadian Clock And Longevity-Associated Gene Expression, Arten Andreyevich Astafev
Age And Sex-Specific Effect Of Caloric Restriction On Circadian Clock And Longevity-Associated Gene Expression, Arten Andreyevich Astafev
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The rhythms in the expression of circadian clock genes are affected by calorie restriction (CR), a dietary paradigm known to increase lifespan. In our current study, we show that circadian rhythms are influenced by sex and the effects of CR are different between males and females. In particular, we found a group of clock genes which showed a sex-dependent difference in expression, as well as in response to CR (Rev-Erb α, Ror γ and both Cryptochromes: Cry1 and Cry2 genes). Two clock genes showed no difference in expression but their response to CR showed sexual dimorphism (Ror α and Rev-Erb …
The Regulatory Role Of Interleukin-1 Receptor Associated Kinase M In Toll-Like Receptor Signaling, Hao Zhou
The Regulatory Role Of Interleukin-1 Receptor Associated Kinase M In Toll-Like Receptor Signaling, Hao Zhou
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Toll-like receptors (TLRs) are one of the major groups of pattern recognition receptors. TLRs are able to recognize the pathogen-associated molecular patterns and transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK1, 2, M and 4). IRAKM was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signaling. However, we now found that IRAKM was also able to interact with MyD88-IRAK4 to form IRAKM Myddosome to mediate TLR7-induced MEKK3-dependent second wave NF¿B activation. As a result, the IRAKM-dependent pathway only induced expression of …
Calorie Restriction Effect On Circadian Clock Gene Expression, Sonal Arvind Patel
Calorie Restriction Effect On Circadian Clock Gene Expression, Sonal Arvind Patel
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Calorie Restriction (CR) is a powerful paradigm known to delay aging and thus increase longevity in several organisms, from yeast to non-human primates. Many molecular pathways have been proposed to mediate the beneficial effects of CR, however, the mechanism is still unknown. Circadian clock which is an internal time keeping system is regulated by feeding. Thus our aim was to study the effect of CR on the circadian clock. Here we show that CR significantly affects the expression of circadian clock genes in mice at the mRNA and protein levels, suggesting that CR reprograms the clocks at the transcriptional and …
Suppression Of Pulmonary Innate Immunity By Pneumoviruses, Jayeeta Dhar
Suppression Of Pulmonary Innate Immunity By Pneumoviruses, Jayeeta Dhar
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Pneumonia Virus of Mice (PVM) and Respiratory Syncytial Virus (RSV) are negative sense, single-stranded, enveloped RNA viruses from Pneumovirus genus, Paramyxoviridae family. RSV is the leading cause of respiratory diseases in infants. PVM causes similar respiratory illness in mice. PVM is used as an animal model to study RSV pathogenesis because of its similarity with RSV infection. Viral infection induces type I interferon (IFN) response as an antiviral strategy. PVM and RSV both have two non-structural (NS) proteins that are known to be IFN antagonists. While RSV can target different signaling components of IFN pathway, the mechanism of IFN suppression …
Effects Of Hypoxic Conditions On Skeletal Myoblasts, Shuai Zhao
Effects Of Hypoxic Conditions On Skeletal Myoblasts, Shuai Zhao
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Hypoxic injury in skeletal muscle occurs in response to musculoskeletal traumas, diseases and following reconstructive and transplantation surgeries. However, the molecular mechanisms responsible for hypoxic injury in skeletal myoblasts have yet to be fully investigated. Understanding of these molecular mechanisms would identify potential therapeutic targets. Herein, we have determined that treatment with cobalt chloride (CoCl2, a hypoxia mimicking agent) first leads to an inhibition of proliferation followed by a decrease in the number of viable myoblasts over time. FACS analysis revealed a marked increase in G2/M arrest after 24 hours of treatment. We next assessed PARP cleavage, a well-known hallmark …
Ubiquitin-Proteasome System Modulates Platelet Function, Nilaksh Gupta
Ubiquitin-Proteasome System Modulates Platelet Function, Nilaksh Gupta
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Atherothrombotic diseases are responsible for more than 25 of all deaths worldwide. Anti-platelet drugs are the mainstay treatment because of the direct involvement of platelets in the initiation and propagation of thrombosis. However, the currently available anti-platelet drugs, such as antagonists of platelet receptors or of effector systems participating in platelet activation, have their own limitations. A new mode of affecting platelet reactivity may prove to offer unique advantages in a host of clinical settings. Proteasome inhibitors are in clinical use to treat hematologic cancers, but also reduce thrombosis. Whether the proteasome participates in platelet activation or function is opaque …
Acute And Chronic Rejection: Compartmentalization And Kinetics Ff Counterbalancing Signals In Cardiac Transplants, Anupurna Kaul
Acute And Chronic Rejection: Compartmentalization And Kinetics Ff Counterbalancing Signals In Cardiac Transplants, Anupurna Kaul
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Heart disease is the major cause of mortality in the United States and other parts of the world. Heart transplantation is the treatment of choice for patients with end stage heart failure. However, transplanted organs fail due to either acute or chronic rejection. This acute and chronic rejection impacts distinct compartments of cardiac allografts. Acute rejection is characterized by infiltration of mononuclear cells whereas chronic rejection is characterized by progressive narrowing of coronary arteries. In a minor histoincompatibility mismatch mouse model we found hearts transplanted from male to female C57BL/6 mice undergo an acute rejection with diffuse interstitial infiltrates at …
Trypanosoma Brucei Telomere Functions In Antigenic Variation, Unnati M. Pandya
Trypanosoma Brucei Telomere Functions In Antigenic Variation, Unnati M. Pandya
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Trypanosoma brucei is a protozoan parasite that causes sleeping sickness in humans and Nagana in cattle. They evade the host's immune defense by periodically switching their major surface antigen, variant surface glycoprotein (VSG), a phenomenon termed antigenic variation. Inside its mammalian host, bloodstream form (BF) T. brucei monoallelically expresses its major surface molecule VSG from the VSG Expression Sites (ESs) located at subtelomeric loci. Monoallelic VSG expression ensures effective antigenic variation and maximizes the efficiency of T. brucei pathogenesis. In the mid-gut of its insect host (tsetse), procyclic form (PF) T. brucei expresses procyclins as the major surface molecules and …
Study Of Role Of Ribosomal Protein L13a In Resolving Inflammation, Darshana Poddar
Study Of Role Of Ribosomal Protein L13a In Resolving Inflammation, Darshana Poddar
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Inflammation is an obligatory attempt of the host immune system to protect the body against infection. However, unregulated synthesis of pro-inflammatory products can have detrimental effects. Though mechanisms which contribute to inflammation are well appreciated, those that resolve inflammation are poorly understood. Therefore, understanding the molecular basis of such pathways will provide an entirely novel approach to treat and prevent inflammatory diseases. Transcript-selective translational control can regulate the expression of a set of inflammatory genes. We have identified one such mechanism in a novel animal model which relies on the abrogation of ribosomal protein L13a-dependent translational silencing by creating macrophage-specific …
Role Of Mtorc1 And Autophagy In The Regulation Of Chemoresistance In Leukemic B-Cells, Arishya Sharma
Role Of Mtorc1 And Autophagy In The Regulation Of Chemoresistance In Leukemic B-Cells, Arishya Sharma
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Deregulated mTORC1 contributes to tumorigenesis and chemoresistance. However, mTORC1-specific inhibitors (rapalogs) show modest efficacy in the clinic, as they unleash the feedback inhibition on upstream, prosurvival pathways. An alternative approach is to target downstream functions of mTORC1. We investigated acquired resistance to fludarabine (Flu), a purine analog, active agent for chronic lymphocytic leukemia (CLL). Elevated phospho-p70S6k (T389), an mTORC1 activation marker, predicted Flu resistance in a panel of B-cell tumor lines, and primary CLL cells. However, the rapalogs induced moderate cell death in Flu-resistant (FluR) and primary CLL cells. Activation of oncogenic pathways, including mTORC1, induces profound metabolic reprogramming to …
Conformational Regulation Of Membrane Localization And Activation Of Talin, Pallavi Dwivedi
Conformational Regulation Of Membrane Localization And Activation Of Talin, Pallavi Dwivedi
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Talin is a cytosolic protein which is known to be one of the key players involved in integrin mediated cell adhesion dependent processes, including blood coagulation, and tissue remodeling. It connects the extracellular matrix with the actin cytoskeleton. Talin comprises of a head domain (talin-H) and a rod domain (talin-R). Talin-H is further subdivided in F0, F1, F2 and F3 domains. Talin-R contains 13 contiguous helical bundle domains (R1-R13) followed by an actin binding dimerization domain (DD). The F3 domain contains a key integrin binding site that regulates integrin activation. In our previous studies, we have shown that cytosolic talin …
Regulation Of Antigenic Variation In Trypanosoma Brucei, Imaan A. Benmerzouga
Regulation Of Antigenic Variation In Trypanosoma Brucei, Imaan A. Benmerzouga
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Trypanosoma brucei is a protozoan parasite that causes sleeping sickness in humans and nagana in cattle. When inside the mammalian host, T. brucei cells stay in extracellular spaces and regularly switch their surface antigen, Variant Surface Glycoprotein (VSG), to escape the host's immune responses. To ensure the effectiveness of VSG switching, T. brucei expresses a single type of VSG at any time exclusively from one of 20 identical VSG expression sites located next to the telomere. Monoallelic expression of VSG and VSG switching are important for T. brucei's pathogenesis. Our major goal is to understand the mechanisms of antigenic variation …
Bioinformatic Analysis And In Vitro Expression Of Malaria Parasite Translocon And Ribonuclease Binding-Like Rhoptry Genes, Moses Z. Timta
Bioinformatic Analysis And In Vitro Expression Of Malaria Parasite Translocon And Ribonuclease Binding-Like Rhoptry Genes, Moses Z. Timta
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Malaria caused by the parasite Plasmodium, still remains a significant public health problem worldwide, due to lack of a vaccine and emerging drug and insecticide resistance, among malaria parasites and mosquito vectors, respectively. Rhoptry proteins of Plasmodium enable merozoite invasion of host erythrocytes. However, only a few of these proteins have been characterized. Thirty-six P. yoelii merozoite rhoptry proteins were identified as putative rhoptry proteins by proteome analysis. Some of these proteins have been characterized while others still remain an intense area of active research. Molecular characterization and understanding of these novel proteins may assist in vaccine development, design of …