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Neuroligin3 Splice Isoforms Shape Inhibitory Synaptic Function In The Mouse Hippocampus, Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai 2020 University of Massachusetts Medical School

Neuroligin3 Splice Isoforms Shape Inhibitory Synaptic Function In The Mouse Hippocampus, Motokazu Uchigashima, Ming Leung, Takuya Watanabe, Amy Cheung, Timmy Le, Sabine Pallat, Alexandre Luis Marques Dinis, Masahiko Watanabe, Yuka Imamura Kawasawa, Kensuke Futai

Open Access Articles

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, transsynaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate Neuroligin (Nlgn) genes that ...


Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. VanDerWolde, Katelyn Hillson 2020 South Dakota State University

Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. Vanderwolde, Katelyn Hillson

The Journal of Undergraduate Research

Bone cancer is an aggressive disease and has peak occurrence during physiological stimulation of growth and aging. Astronauts who undergo long-term space missions also acquire an increased risk of bone tissue degeneration and cancer. Few in-vitro models currently exist capable of reproducing the complex microenvironment of bone tissue to support multicellular activity in a three-dimensional structure. This limits the ability to understand disease progression and develop suitable treatment strategies. Therefore, developing a bone tissue model and an associated bioreactor is critical to understand the risks associated with cancer progression and improve treatment and preventions related to those risks. The goal ...


Single Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech 2020 University of Massachusetts Medical School

Single Cell Rna Profiling Reveals Adipocyte To Macrophage Signaling Sufficient To Enhance Thermogenesis, Felipe Henriques, Alexander H. Bedard, Adilson L. Guilherme, Mark Kelly, Lawrence M. Lifshitz, Karl D. Bellve, Leslie Rowland, Batuhan Yenilmez, Shreya Kumar, Yetao Wang, Jeremy Luban, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

The “browning” of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF activity. Thus, the strong induction of thermogenic adipocytes prompted by deletion of adipocyte fatty acid synthase (iAdFASNKO mice) was unaffected by denervation or the deletion of SNF modulator Neuregulin-4 ...


Control Of Adipocyte Thermogenesis And Lipogenesis Through Beta3-Adrenergic And Thyroid Hormone Signal Integration, Adilson L. Guilherme, Batuhan Yenilmez, Alexander H. Bedard, Felipe Henriques, Dianxin Liu, Alexandra Lee, Lauren Goldstein, Mark Kelly, Sarah M. Nicoloro, Min Chen, Lee Weinstein, Sheila Collins, Michael P. Czech 2020 University of Massachusetts Medical School

Control Of Adipocyte Thermogenesis And Lipogenesis Through Beta3-Adrenergic And Thyroid Hormone Signal Integration, Adilson L. Guilherme, Batuhan Yenilmez, Alexander H. Bedard, Felipe Henriques, Dianxin Liu, Alexandra Lee, Lauren Goldstein, Mark Kelly, Sarah M. Nicoloro, Min Chen, Lee Weinstein, Sheila Collins, Michael P. Czech

Open Access Articles

Here, we show that beta adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), and both effects are blocked in mice lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsalphaKO) in adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, beta3-adrenergic agonist CL316243 readily upregulates thermogenic but not lipogenic genes in cultured adipocytes, indicating that additional regulators must operate on DNL in sWAT in vivo. We identify one such factor as thyroid hormone T3, which is elevated locally by adrenergic signaling. T3 administration to wild-type mice enhances both thermogenesis and DNL ...


Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber 2020 Liberty University

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature ...


Quantification Of Mammalian Circadian Rhythms In Response To Photopollution With A Focus On Splitting Behavior, Mehdi Khan 2020 Northeastern Illinois University

Quantification Of Mammalian Circadian Rhythms In Response To Photopollution With A Focus On Splitting Behavior, Mehdi Khan

University Honors Program Senior Projects

Circadian rhythms are generated by internal biological clocks of organisms and are responsible for the synchronization of an organism’s external and internal environment. The cells responsible for conducting and maintaining the circadian system are known to be coupled in order to maintain a harmonic rhythm. Desynchronization of the master circadian rhythm can cause the presence of two or more rhythms to emerge in a single organism, also known as splitting behavior. Photopollution and artificial light is known to disrupt this synchronization and result in a desynchronized or split rhythm. Many studies have highlighted that photopollution can disrupt the biological ...


Sensing Ribonuclease H Activity With Dna Nanoswitches, Ruju Trivedi 2020 University at Albany, State University of New York

Sensing Ribonuclease H Activity With Dna Nanoswitches, Ruju Trivedi

Biological Sciences

Ribonuclease H (RNase H) is a damage-repair protein and ribonuclease that specifically catalyzes the hydrolysis of RNA in an RNA/DNA duplex and breaks down RNA/DNA junctions. It plays an important role in a variety of biological processes including DNA replication, DNA repair, and transcription. It is also pivotal in anti-HIV drug development and the analysis of cellular processes and has been shown to be a potential therapeutic target for various neoplastic diseases. This thesis discusses a unique assay based on DNA nanoswitches to detect RNase H levels and activity. The assay is based on conformational changes of DNA ...


Glutamine Antagonist 6-Diazo-5-Oxo-L-Norleucine, A Hyaluronan Synthesis Inhibitor, Slows Triple Negative Breast Cancer Growth, Le Gia Cat Pham 2020 University at Albany, State University of New York

Glutamine Antagonist 6-Diazo-5-Oxo-L-Norleucine, A Hyaluronan Synthesis Inhibitor, Slows Triple Negative Breast Cancer Growth, Le Gia Cat Pham

Biological Sciences

Triple-negative breast cancers (TNBC) are the most aggressive subtype of breast cancer with few treatment options and poor outcomes. TNBCs are characterized by elevations in hexosamine biosynthetic pathway (HBP) enzyme expression, hyaluronan synthase 2 (HAS2) expression and hyaluronan (HA) production. Glutamine is an important substrate for HA production via the HBP. 6-diazo-5-oxo-L-norleucine (DON) is a well-known glutamine antagonist with validated antitumoral efficacy. This project examined the effects of DON on HA production and energy metabolism in TNBC cells. We examined the effect of DON treatment on Hs578T cells, which represent the mesenchymal stem-like subtype of TNBC. We specifically analyzed the ...


Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori 2020 University of Connecticut

Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori

Honors Scholar Theses

Mycoplasma pneumoniae is a high-burden pathogen which causes mild to significant infections of the respiratory system. According to the CDC, an estimated two million cases occur yearly in the United States alone, demonstrating the widespread effect of the pathogen. In addition to being the cause of respiratory infections, M. pneumoniae has also been implicated in exacerbating pre-existing asthma conditions. These morbidities make finding a vaccine candidate a vital part of easing the healthcare burden caused by the pathogen. The current mechanism of infection is unknown, but recent evidence points to the Community Acquired Respiratory Distress Syndrome (CARDS) toxin as being ...


A Putative Cystathionine Beta-Synthase Homolog Of Mycolicibacterium Smegmatis Is Involved In De Novo Cysteine Biosynthesis, Saroj Kumar Mahato 2020 University of Arkansas, Fayetteville

A Putative Cystathionine Beta-Synthase Homolog Of Mycolicibacterium Smegmatis Is Involved In De Novo Cysteine Biosynthesis, Saroj Kumar Mahato

Theses and Dissertations

Mycobacteria include serious pathogens of humans and animals. Mycolicibacterium smegmatis is a non-pathogenic model that is widely used to study core mycobacterial metabolism. This thesis explores mycobacterial pathways of cysteine biosynthesis by generating and study of genetic mutants of M. smegmatis. Published in vitro biochemical studies had revealed three independent routes to cysteine synthesis in mycobacteria involving separate homologs of cysteine synthase, namely CysK1, CysK2, and CysM. However, in vivo data were lacking. The M. smegmatis genome encodes only a CysM homolog and lacks orthologs for CysK1 or CysK2. The gene that codes for CysM is a part of an ...


Mechanisms Of Statin Effects On Muscle And Neuronal Proteostasis, Daniel Yu 2020 University of Connecticut

Mechanisms Of Statin Effects On Muscle And Neuronal Proteostasis, Daniel Yu

University Scholar Projects

Statins are widely prescribed and used chronically, but we know little about the effects on long-term protein homeostasis during stress and aging. Our aim was to quantify the effect of statins on stress-induced protein damage. We administered atorvastatin in a dose-response curve in Caenorhabditis elegans under naïve control conditions and in conditions of hypertonic and heat stress known to induce muscle damage measurable as countable puncta in a polyglutamine aggregation model of damage. We observed that there is significant polyglutamine aggregation variability among worms at baseline and thus further study requires within experiment baseline controls, per worm. Our results are ...


Investigating The Redox Sensitivity Of Mitf Splice Variants, Rachel Berryman 2020 Linfield College

Investigating The Redox Sensitivity Of Mitf Splice Variants, Rachel Berryman

Senior Theses

Within pigment-producing cells known as melanocytes, the transcription factor MITF is intimately involved in regulating genes associated with cell cycle maintenance and melanocyte differentiation. Research, however, has provided conflicting results on the relationship between the expression levels of MITF and melanocyte cell fate. To complicate matters, two splice variants of MITF exist, differing by only 18 base pairs. These variants have been observed at variable levels of expression in melanocyte and melanoma cells, raising the question as to their functional purpose. Building upon previous research by the Leachman/Cassidy lab that identified the redox sensitivity of MITF while additionally establishing ...


Surface Runoff Alters Cave Microbial Community Structure And Function, Madison Davis, Maria A. Messina, Giuseppe Nicolosi, Salvatore Petralia, Melvin D. Baker, Christiana K. S. Mayne, Chelsea M. Dinon, Christina J. Moss, Bogdan P. Onac, James R. Garey 2020 University of South Florida

Surface Runoff Alters Cave Microbial Community Structure And Function, Madison Davis, Maria A. Messina, Giuseppe Nicolosi, Salvatore Petralia, Melvin D. Baker, Christiana K. S. Mayne, Chelsea M. Dinon, Christina J. Moss, Bogdan P. Onac, James R. Garey

Cell Biology, Microbiology, and Molecular Biology Faculty Publications

Caves formed by sulfuric acid dissolution have been identified worldwide. These caves can host diverse microbial communities that are responsible for speleogenesis and speleothem formation. It is not well understood how microbial communities change in response to surface water entering caves. Illumina 16S rRNA sequencing and bioinformatic tools were used to determine the impact of surface water on the microbial community diversity and function within a spring pool found deep in the Monte Conca Cave system in Sicily, Italy. Sulfur oxidizers comprised more than 90% of the microbial community during the dry season and were replaced by potential anthropogenic contaminants ...


Motor Neuron Connections And Innervation Of Muscles In Drosophila Melanogaster, Sharon Tang 2020 City University of New York (CUNY)

Motor Neuron Connections And Innervation Of Muscles In Drosophila Melanogaster, Sharon Tang

Student Theses

Drosophila melanogaster have two sets of muscle systems: larval muscles and adult muscles. The larval somatic muscle system is established during embryogenesis and is necessary for hatching, feeding, and crawling of the larvae. Like humans, Drosophila muscles have individual characteristics, like unique sizes, shapes, orientations, attachment sites, and innervation patterns by motor neurons. These properties are encoded by a group of transcriptional regulators that are expressed in specific muscle subsets. Currently, there are over twenty known transcription factors required for the development of the 30 distinct larval somatic muscles and specification of those muscle properties. We have examined how muscle-specific ...


Nutritional Supplementation And Skeletal Muscle Health In Chronic Diseases, Hexirui Wu 2020 University of Arkansas, Fayetteville

Nutritional Supplementation And Skeletal Muscle Health In Chronic Diseases, Hexirui Wu

Theses and Dissertations

Prevalence of chronic diseases in the United States keeps increasing in recent years. There are approximately four in ten adults having chronic diseases in America. Chronic diseases include obesity, aging, heart diseases, cancer and many others. This thesis mainly focuses on obesity and aging. Skeletal muscle performance is impaired in obesity and aging conditions. One common reason causing this could be higher fat mass and lower muscle mass. However, there is no study showing what pathways are involved in the imbalance of body composition. Therefore, the first objective of the thesis is to determine gene expression of selected pathways in ...


Cloning, Expression, Purification And Characterization Of Heparin-Binding Pocket Of Recombinant Fgf1, Quratulayn Ashraf 2020 University of Arkansas, Fayetteville

Cloning, Expression, Purification And Characterization Of Heparin-Binding Pocket Of Recombinant Fgf1, Quratulayn Ashraf

Theses and Dissertations

Fibroblast growth factors are polypeptide members of the FGF family, which to date comprises of at least 22 members. They belong to a group of growth factors and are involved in a variety of cellular processes including wound healing, angiogenesis, differentiation and development (organogenesis). Amongst FGF members, human acidic FGF-1 and basic FGF-2 are the most characterized. FGF-1 and FGF-2 are known to share more than 80% sequence similarity and have an identical structural fold. However, their biological roles are quite different. FGFs bind to heparin and heparan sulfate ligands through their heparin-binding pockets. The interactions are primarily electrostatic in ...


Size-Dependent Inhibitory Effects Of Antibiotic Nanocarriers On Filamentation Of E. Coli, Preeyaporn Songkiatisak, Feng Ding, Pavan Kumar Cherukuri, Xiao-Hong Nancy Xu 2020 Old Dominion University

Size-Dependent Inhibitory Effects Of Antibiotic Nanocarriers On Filamentation Of E. Coli, Preeyaporn Songkiatisak, Feng Ding, Pavan Kumar Cherukuri, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters exist in both prokaryotic and eukaryotic cells and cause multidrug resistance (MDR), which results in an urgent need for new and more effective therapeutic agents. In this study, we used three different sized antibiotic nanocarriers to study their mode of action and their size-dependent inhibitory effects against Escherichia coli (E. coli). Antibiotic nanocarriers (AgMUNH–Oflx NPs) with 8.6 × 102, 9.4 × 103 and 6.5 × 105 Oflx molecules per nanoparticle (NP) were prepared by functionalizing Ag NPs (2.4 ± 0.7, 13.0 ± 3.1 and 92.6 ± 4.4 nm) with a ...


Modeling Hybrid Novel Traits: A Case Study In Complex Petal Pigment Patterning In Hybrid Mimulus, Xingyu Zheng 2020 William & Mary

Modeling Hybrid Novel Traits: A Case Study In Complex Petal Pigment Patterning In Hybrid Mimulus, Xingyu Zheng

Undergraduate Honors Theses

Hybridization between species, by introducing dramatic trait variation into the population and creating viable, transgressive offsprings with novel phenotypes, can have huge evolutionary implications. Some hybrid traits have been studied in the classical genetics or population genetics context, but most complex traits are determined by multiple causes, e.g. the number of loci involved, the rewiring of the genetic circuitries, and the changes in gene expression pattern. Using the hybrid monkeyflower petal pigment patterning as an example, we present a case study to investigate complex hybrid traits in a systematic manner that includes empirical data analysis and quantitative mathematical modeling ...


A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham 2020 William & Mary

A Study Of Matr3 And Its Effects On The Neural Progenitor Cells Of Xenopus Laevis Tadpoles, Kendall Branham

Undergraduate Honors Theses

Understanding the genes and mechanisms that regulate the highly important process of neurogenesis in the developing nervous system is crucial to uncovering why disease arises when this system is disrupted. Neural progenitor cells and their multipotent nature allow for the growth of a large pool of stem cells in the early stages of development, but the signal that leads these cells to the irreversible fate of becoming a neuron is unclear. The gene matr3 has been implicated in having a role in the maintenance of undifferentiated neural stem cells but its role needs further investigation to fully reveal how its ...


Development Of An Auto-Bioluminescent Lung Cell Line For Evaluation Of In Vitro Effects Of E-Cigarette Compounds On Normal Cell Proliferation, Olivia Morrison 2020 University of Tennessee at Chattanooga

Development Of An Auto-Bioluminescent Lung Cell Line For Evaluation Of In Vitro Effects Of E-Cigarette Compounds On Normal Cell Proliferation, Olivia Morrison

Honors Theses

The effects of smoking have long been studied; however, with the rise of electronic cigarettes there is a growing interest in the effects of this smoking substitute. Marketed as a safer alternative to tobacco cigarettes, the popularity of electronic cigarette (e-cigarette) use has dramatically increased. This has demanded regulatory methods to be put into effect, however, scientific study is only beginning on the new fad to determine the impacts of its use on the human body. The present study aims to examine the biological effects of lung cell exposure to tobacco alkaloids found in electronic cigarette filling solutions. We hypothesize ...


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