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Full-Text Articles in Life Sciences

Seasons Fall 2018 Volume 47 Number 3, Leslie Crane, Pamela Olshefski, Jason Lubar, Anthony S. Aiello, Susan Crane Oct 2018

Seasons Fall 2018 Volume 47 Number 3, Leslie Crane, Pamela Olshefski, Jason Lubar, Anthony S. Aiello, Susan Crane

Seasons Newsletter

Highlights :

  • Thompson-Morris Plot Restoration Complete
  • Botany for Beginners
  • Preserving Our Tree Canopy
  • Three Great Native Trees
  • ArbNet Accreditation


Monasteries Of The Future, Miles G. Bukiet Aug 2018

Monasteries Of The Future, Miles G. Bukiet

Master of Applied Positive Psychology (MAPP) Capstone Projects

For millennia, monasteries have been at the forefront of training virtues such as compassion, transcendence, service, gratitude, forgiveness, and grit, as well as foundational psychological capacities such as self-regulation, sustained, voluntary attention, emotional intelligence, and meta-cognitive awareness. Monasteries of the Future are modern institutions, both secular and religious, designed to provide the requisite financial, social, intellectual, and instructional support necessary to train a new generation of contemplative adepts. Forming a network of centers which collaborate and compete, Monasteries of the Future will establish and uphold the highest standards in the contemplative field. By partnering with modern science, most notably positive ...


Activities And Classroom Demonstrations In Biological Physics: A Resource Document, Philip C. Nelson, William Berner Jul 2018

Activities And Classroom Demonstrations In Biological Physics: A Resource Document, Philip C. Nelson, William Berner

Department of Physics Papers

We give detailed recipes for a number of classroom demonstrations relevant to biological physics instruction. We developed them mainly for use in 2nd-3rd year undergraduate Physics courses. But you can (and we do) use them for primary school, through high school, up to PhD candidates. You adapt the words for each audience, but a phenomenon is a phenomenon.

We also outline a 1-hour introduction to Python for undergraduate scientific computing.

Finally we document some outcomes from courses taught at U Pennsylvania using these resources and others cited here. This material was presented at a workshop at the AAPT meeting in ...


Socioeconomic Status And The Brain: Prospects For Neuroscience-Informed Policy, Martha J. Farah Jun 2018

Socioeconomic Status And The Brain: Prospects For Neuroscience-Informed Policy, Martha J. Farah

Neuroethics Publications

Socioeconomic status (SES) is associated with health (physical and mental) and cognitive ability. Understanding and ameliorating the problems of low SES have long been goals of economics and sociology; in recent years, these have also become goals of neuroscience. However, opinion varies widely on the relevance of neuroscience to SES-related policy. The present article addresses the question of whether and how neuroscience can contribute to the development of social policy concerning poverty and the social and ethical risks inherent in trying. I argue that the neuroscience approach to SES-related policy has been both prematurely celebrated and peremptorily dismissed and that ...


Comparison Between Silicon Nanopillars Prepared By Bosch Process And Metal Assisted Chemical Etching, Rimjhim Chaudhary May 2018

Comparison Between Silicon Nanopillars Prepared By Bosch Process And Metal Assisted Chemical Etching, Rimjhim Chaudhary

Protocols and Reports

Nanopillars fabricated by Metal Assisted Chemical Etching (MacEtch) wet-etch process have been compared with those by Bosch dry-etch process. The Bosch process in this study gave vertical nanopillars with smooth side walls, which was better than the typical Bosch process. However, the verticality of the nanopillars depended on the location within the wafer where they were etched. On the other hand, MacEtch process gave a very consistent feature from 100 to 1000 nm diameter using 20 nm thick Au film without an expensive etching tool. The present technical report discuss the difference between MacEtch and Bosch processes.


A Functional Near Infrared Spectroscopy (Fnirs) Replication Of The Sunscreen Persuasion Paradigm, Shannon M. Burns, Lianne N. Barnes, Perri L. Katzman, Daniel L. Ames, Emily B. Falk, Matthew D. Lieberman May 2018

A Functional Near Infrared Spectroscopy (Fnirs) Replication Of The Sunscreen Persuasion Paradigm, Shannon M. Burns, Lianne N. Barnes, Perri L. Katzman, Daniel L. Ames, Emily B. Falk, Matthew D. Lieberman

Departmental Papers (ASC)

Activity in medial prefrontal cortex (mPFC) during persuasive messages predicts future message-consistent behavior change, but there are significant limitations to the types of persuasion processes that can be invoked inside an MRI scanner. For instance, real world persuasion often involves multiple people in conversation. Functional near infrared spectroscopy (fNIRS) allows us to move out of the scanner and into more ecologically valid contexts. As a first step, the current study used fNIRS to replicate an existing fMRI persuasion paradigm (i.e. the sunscreen paradigm) to determine if mPFC shows similar predictive value with this technology. Consistent with prior fMRI work ...


Time-Evolving Dynamics In Brain Networks Forecast Responses To Health Messaging, Nicole Cooper, Javier O. Garcia, Steven Tompson, Matthew B. O'Donnell, Emily B. Falk, Jean M. Vettel May 2018

Time-Evolving Dynamics In Brain Networks Forecast Responses To Health Messaging, Nicole Cooper, Javier O. Garcia, Steven Tompson, Matthew B. O'Donnell, Emily B. Falk, Jean M. Vettel

Departmental Papers (ASC)

Neuroimaging measures have been used to forecast complex behaviors, including how individuals change decisions about their health in response to persuasive communications, but have rarely incorporated metrics of brain network dynamics. How do functional dynamics within and between brain networks relate to the processes of persuasion and behavior change? To address this question, we scanned forty-five adult smokers using functional magnetic resonance imaging while they viewed antismoking images. Participants reported their smoking behavior and intentions to quit smoking before the scan and one month later. We focused on regions within four atlas-defined networks and examined whether they formed consistent network ...


Surface Roughness Dependence Of Inkjet Printing Of Ag Nanoparticles, Ming Yuan Chuang Apr 2018

Surface Roughness Dependence Of Inkjet Printing Of Ag Nanoparticles, Ming Yuan Chuang

Protocols and Reports

This report describes dependence of the inkjet printing on the surface roughness of normal PI film, ultra-smooth PI film, and polished Si wafer. The printing line width and LER are discussed by the line spreading constraint due to the limited volume of the droplet, vaporization of the solvent by the substrate temperature, the contact angle of the ink, and the surface roughness of the substrate. It is also shown that the minimum line width of ~21um is achieved on the Si wafer. Furthermore, the optimization of the substrate temperature for sintering of Ag nanoparticle is discussed.


Nia-Aa Research Framework: Toward A Biological Definition Of Alzheimer's Disease, Clifford R. Jack, David A. Bennett, Kaj Blennow, Maria C. Carrillo, Billy Dunn, Samantha Budd Haeberlein, David M. Holtzman, William Jagust, Frank Jessen, Jason Karlawish, Enchi Liu, Jose Luis Molineuvo, Thomas Montine, Creighton Phelps, Katherine P. Rankin, Christopher C. Rowe, Philip Scheltens, Eric Seimers, Heather M. Snyder, Reisa Sperling Apr 2018

Nia-Aa Research Framework: Toward A Biological Definition Of Alzheimer's Disease, Clifford R. Jack, David A. Bennett, Kaj Blennow, Maria C. Carrillo, Billy Dunn, Samantha Budd Haeberlein, David M. Holtzman, William Jagust, Frank Jessen, Jason Karlawish, Enchi Liu, Jose Luis Molineuvo, Thomas Montine, Creighton Phelps, Katherine P. Rankin, Christopher C. Rowe, Philip Scheltens, Eric Seimers, Heather M. Snyder, Reisa Sperling

Neuroethics Publications

In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that ...


Associations Between Coherent Neural Activity, Nicole Cooper, Steven Tompson, Matthew B. O'Donnell, Jean M. Vettel, Danielle S. Bassett, Emily B. Falk Apr 2018

Associations Between Coherent Neural Activity, Nicole Cooper, Steven Tompson, Matthew B. O'Donnell, Jean M. Vettel, Danielle S. Bassett, Emily B. Falk

Departmental Papers (ASC)

Objective: Worldwide, tobacco use is the leading cause of preventable death and illness. One common strategy for reducing the prevalence of cigarette smoking and other health risk behaviors is the use of graphic warning labels (GWLs). This has led to widespread interest from the perspective of health psychology in understanding the mechanisms of GWL effectiveness. Here we investigated differences in how the brain responds to negative, graphic warning label-inspired antismoking ads and neutral control ads, and we probed how this response related to future behavior.

Method: A group of smokers (N = 45) viewed GWL-inspired and control antismoking ads while undergoing ...


A Meta-Analysis Of The Relationship Between Socioeconomic Status And Executive Function Performance Among Children, Gwendolyn M. Lawson, Cayce J. Hook, Martha J. Farah Mar 2018

A Meta-Analysis Of The Relationship Between Socioeconomic Status And Executive Function Performance Among Children, Gwendolyn M. Lawson, Cayce J. Hook, Martha J. Farah

Neuroethics Publications

The relation between childhood socioeconomic status (SES) and executive function (EF) has recently attracted attention within psychology, following reports of substantial SES disparities in children’s EF. Adding to the importance of this relation, EF has been proposed as a mediator of socioeconomic disparities in lifelong achievement and health. However, evidence about the relationship between childhood SES and EF is mixed, and there has been no systematic attempt to evaluate this relationship across studies. This meta-analysis systematically reviewed the literature for studies in which samples of children varying in SES were evaluated on EF, including studies with and without primary ...


Rhesus Macaques Form Preferences For Brand Logos Through Sex And Social Status Based Advertising, M. Yavus Acikalin, Karli K. Watson, Gavan J. Fitzsimons, Michael L Platt Feb 2018

Rhesus Macaques Form Preferences For Brand Logos Through Sex And Social Status Based Advertising, M. Yavus Acikalin, Karli K. Watson, Gavan J. Fitzsimons, Michael L Platt

Neuroethics Publications

Like humans, monkeys value information about sex and status, inviting the hypothesis that our susceptibility to these factors in advertising arises from shared, ancestral biological mechanisms that prioritize social information. To test this idea, we asked whether rhesus macaques (Macaca mulatta) show choice behavior that is similar to humans in response to sex and social status in advertising. Our results show that monkeys form preferences for brand logos repeatedly paired with images of macaque genitals and high status monkeys. Moreover, monkeys sustain preferences for these brand logos even though choosing them provided no tangible rewards, a finding that cannot be ...


Network Approaches To Understand Individual Differences In Brain Connectivity: Opportunities For Personality Neuroscience, Steven Tompson, Emily B. Falk, Jean M. Vettel, Danielle S. Bassett Jan 2018

Network Approaches To Understand Individual Differences In Brain Connectivity: Opportunities For Personality Neuroscience, Steven Tompson, Emily B. Falk, Jean M. Vettel, Danielle S. Bassett

Departmental Papers (ASC)

Over the past decade, advances in the interdisciplinary field of network science have provided a framework for understanding the intrinsic structure and function of human brain networks. A particularly fruitful area of this work has focused on patterns of functional connectivity derived from noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI). An important subset of these efforts has bridged the computational approaches of network science with the rich empirical data and biological hypotheses of neuroscience, and this research has begun to identify features of brain networks that explain individual differences in social, emotional, and cognitive functioning. The most ...


Time To Stop Telling Biophysics Students That Light Is Primarily A Wave, Philip C. Nelson Jan 2018

Time To Stop Telling Biophysics Students That Light Is Primarily A Wave, Philip C. Nelson

Department of Physics Papers

Standard pedagogy introduces optics as though it were a consequence of Maxwell’s equations, and only grudgingly admits, usually in a rushed aside, that light has a particulate character that can somehow be reconciled with the wave picture. Recent revolutionary advances in optical imaging, however, make this approach more and more unhelpful: How are we to describe two-photon imaging, FRET, localization microscopy, and a host of related techniques to students who think of light primarily as a wave? I was surprised to find that everything I wanted my biophysics students to know about light, including image formation, x-ray diffraction, and ...


Testing Biological Controls For Heliothrips Haemorrhoidalis (Thysanoptera: Thripidae), A Serious Pest Of The Morris Arboretum Greenhouse Complex, Amanda Quadrel Jan 2018

Testing Biological Controls For Heliothrips Haemorrhoidalis (Thysanoptera: Thripidae), A Serious Pest Of The Morris Arboretum Greenhouse Complex, Amanda Quadrel

Internship Program Reports

The greenhouse thrips (Heliothrips haemorrhoidalis) is a serious pest of fruits and ornamental plants. In the Morris Arboretum’s greenhouse complex, this thrip has been prevalent, and could cause major damage to the young plants that are being propagated. The purpose of this project was to search for a suitable biological control of the thrips since chemicals have only been marginally effective. A predatory spider mite (Amblyseius cucumeris) and minute pirate bugs (Orius insidiousus) were chosen for the study. The results suggest that the minute pirate bugs are highly effective at hunting thrips, while the spider mites had no measurable ...


Use Of Induced Pluripotent Stem Cell Models To Elucidate Retinal Disease Pathogenesis And To Develop Gene-Based Therapies, Thu Thi Duong Jan 2018

Use Of Induced Pluripotent Stem Cell Models To Elucidate Retinal Disease Pathogenesis And To Develop Gene-Based Therapies, Thu Thi Duong

Publicly Accessible Penn Dissertations

Choroideremia (CHM) is a rare monogenic, X-linked recessive inherited retinal degenerative disease caused by mutations in the Rab Escort Protein-1 (REP1) encoding CHM gene. CHM is characterized by childhood-onset night blindness (nyctalopia), progressive peripheral vision loss due to the degeneration of neural retina, RPE and choroid in a peripheral-to-central fashion. Most of CHM mutations are loss-of-function mutations leading to the complete lacking of REP1 protein. However, the primary retinal cell type leading to CHM and molecular mechanism remains unknown in addition to the fact of lacking proper disease models. In this study, we explored the utility of induced pluripotent stem ...


Reverse Micelle Encapsulation And Its Use In Examining The Interplay Between Hydration And Protein Dynamics, Bryan Stephen Marques Jan 2018

Reverse Micelle Encapsulation And Its Use In Examining The Interplay Between Hydration And Protein Dynamics, Bryan Stephen Marques

Publicly Accessible Penn Dissertations

As the universal solvent, water is unquestionably essential to most aspects of protein biophysics from protein folding to enzymatic activity. Much has been learned about the relationship between proteins and surrounding solvent waters; however, it is often difficult to experimentally examine these interactions in a site-specific manner without perturbing molecular structure. Furthermore, the effect of nearby hydration dynamics on protein dynamics (and, in effect, protein conformational entropy) is poorly understood at atomic resolution. With the use of a combination of Nuclear Magnetic Resonance (NMR) spectroscopy and protein reverse micelle (RM) encapsulation, it is possible to examine both the dynamic behavior ...


Induction Of Antibodies To Hiv-1 Envelope Using Simian Adenovirus Vaccines, Kristel Lucie Emmer Jan 2018

Induction Of Antibodies To Hiv-1 Envelope Using Simian Adenovirus Vaccines, Kristel Lucie Emmer

Publicly Accessible Penn Dissertations

Human immunodeficiency virus type 1 (HIV-1) has infected 76 million people since the beginning of the epidemic. The first evidence that an HIV-1 vaccine could prevent infection in humans was provided in the RV144 vaccine efficacy trial. RV144 demonstrated 31.2% efficacy and immune correlate analyses indicated that antibodies targeting the variable 2 (V2) region of HIV-1 envelope (Env) correlated with decreased risk of infection. However, significant improvements are needed to develop a globally effective vaccine against HIV-1.

Several approaches can be employed to improve upon vaccination strategies: heterologous prime-boost regimens, immunogen design, and alternative adjuvants. To enhance Env-specific antibodies ...


Chromatin Remodeling Dynamics During Brown Adipogenesis, Suzanne Natalie Shapira Jan 2018

Chromatin Remodeling Dynamics During Brown Adipogenesis, Suzanne Natalie Shapira

Publicly Accessible Penn Dissertations

Brown adipose tissue (BAT) is specialized to expend energy through the action of the mitochondrial uncoupling protein UCP1. Increasing brown fat mass or activity through genetic or chemical manipulation in mice suppresses obesity and its comorbidities; as such, there is great interest in developing approaches to increase the amount and/or function of brown fat to combat metabolic disorders. My thesis work aimed to dissect the molecular mechanisms by which the helix- loop-helix transcription factor Early B-Cell Factor 2 (EBF2) regulates brown adipocyte commitment and terminal differentiation. Through analysis of tissue-specific knockout mouse models, we found that EBF2 is required ...


Structural Remodeling Of Alpha-Synuclein By Small Molecules: A Novel Path To Neuroprotective Therapeutics, Malcolm James Daniels Jan 2018

Structural Remodeling Of Alpha-Synuclein By Small Molecules: A Novel Path To Neuroprotective Therapeutics, Malcolm James Daniels

Publicly Accessible Penn Dissertations

Neurodegenerative diseases share the unifying features of insoluble protein aggregates and irreversible neuron loss. Parkinson’s disease (PD) is defined by proteinaceous Lewy bodies—which contain α-synuclein—and loss of dopamine neurons leading to motor dysfunction. Growing evidence implicates α-synuclein aggregation as a causal driver of neurodegeneration in certain forms of PD. However, the precise mechanism(s) by which the process or products of α-synuclein aggregation drive neuron death remains unknown. Better understanding of this key question might further development of neuroprotective therapies for PD and related disorders. To address this gap, we reviewed how the native conformation of α-synuclein ...


Mechanisms Underlying Oxidative Stress-Induced Chromatin Association Of Cockayne Syndrome Protein B (Csb), Erica Lee Boetefuer Jan 2018

Mechanisms Underlying Oxidative Stress-Induced Chromatin Association Of Cockayne Syndrome Protein B (Csb), Erica Lee Boetefuer

Publicly Accessible Penn Dissertations

Cockayne syndrome is a devastating premature aging disorder characterized by extreme sun sensitivity and severe neurological and developmental defects. The majority of Cockayne syndrome cases are due to mutations within the ATP-dependent chromatin remodeler Cockayne syndrome protein B (CSB). CSB functions in transcription regulation and is required for transcription-coupled nucleotide excision repair (TC-NER). Importantly, CSB is also critical for the relief of oxidative stress. Studies suggest CSB may participate in the major repair pathway for oxidative DNA damage repair, base excision repair (BER), yet direct evidence supporting this hypothesis remains elusive and exactly how CSB functions in this process is ...


Platelet Factor 4 And Von Willebrand Factor Form An Immunogenic, Prothrombotic Complex In Heparin-Induced Thrombocytopenia, Ian Johnston Jan 2018

Platelet Factor 4 And Von Willebrand Factor Form An Immunogenic, Prothrombotic Complex In Heparin-Induced Thrombocytopenia, Ian Johnston

Publicly Accessible Penn Dissertations

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, thrombocytopenic disorder that occurs in patients exposed to heparin due to the development of antibodies directed against complexes of platelet factor 4 (PF4) with heparin with other polyanions . We have recently shown that the perithrombus endothelium is targeted in HIT. Using a photochemical injury model and an endothelialized microfluidic system, we now show that PF4 binds to elongated strands of von Willebrand factor (VWF) released from injured endothelium. This binding appears to be periodic along the VWF strand and to favor larger VWF strands, suggesting formation of oligomers that may cross-link individual VWF subunits ...


Exploring The Role Of Tet1 In Genomic Imprinting, Jennifer Myers Sanmiguel Jan 2018

Exploring The Role Of Tet1 In Genomic Imprinting, Jennifer Myers Sanmiguel

Publicly Accessible Penn Dissertations

DNA methylation is an essential epigenetic mark crucial for normal mammalian development. This modification controls the expression of a unique class of genes, designated as imprinted, which are expressed monoallelically and in a parent-of-origin-specific manner. Proper parental allele-specific DNA methylation at imprinting control regions (ICRs) is necessary for appropriate imprinting. Processes that deregulate DNA methylation of imprinted loci cause disease in humans. DNA methylation patterns dramatically change during mammalian development: first, the majority of the genome, with the exception of ICRs, is demethylated after fertilization, and subsequently undergoes genome-wide de novo DNA methylation. Secondly, after primordial germ cells are specified ...


Extracellular Cues In The Regulation Of Tube Shape During Organogenesis, Jeffrey Bryan Rosa Jan 2018

Extracellular Cues In The Regulation Of Tube Shape During Organogenesis, Jeffrey Bryan Rosa

Publicly Accessible Penn Dissertations

Biological tubes adopt a variety of shapes to carry out their functions. In addition to multicellular tubes, single epithelial or endothelial cells build unicellular lumens lined by an apical membrane devoid of cell junctions, or seams. Such seamless tubes are highly conserved from invertebrates to vertebrate organs, but the factors regulating their formation and maintenance remain poorly understood in any system. Using a forward genetic approach in the Drosophila tracheal (respiratory) system, we have characterized a mutant called ichor, which compromises the integrity and shape of seamless tubes in tracheal terminal cells. We demonstrate that Ichor promotes seamless tube integrity ...


Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase Activity And Promotes Melanoma Metastatic Behavior, Rochelle Shirin Sadeghi Jan 2018

Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase Activity And Promotes Melanoma Metastatic Behavior, Rochelle Shirin Sadeghi

Publicly Accessible Penn Dissertations

Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood. Wnt5a signaling results in acyl protein thioesterase 1 (APT1) mediated depalmitoylation of pro-metastatic cell adhesion molecules CD44 and MCAM, resulting in increased melanoma invasion. The mechanistic details that underlie Wnt5a-mediated regulation of APT1 activity and cellular function remains unknown. Here, we show Wnt5a signaling regulates APT1 activity through induction of APT1 phosphorylation and we further investigate the functional role of APT1 phosphorylation on its depalmitoylating activity. We found phosphorylation increased APT1 depalmitoylating activity and reduced APT1 dimerization ...


The Neural Mechanisms Underlying Invariant Object Search In V4 And Inferotemporal Cortex, Noam Roth Jan 2018

The Neural Mechanisms Underlying Invariant Object Search In V4 And Inferotemporal Cortex, Noam Roth

Publicly Accessible Penn Dissertations

Finding a specific visual target, such as your car keys, requires the brain to combine visual information about objects in the currently viewed scene with working memory information about your target to determine whether your target is in view. This combination of context-specific signals with visual information is thought to happen via feedback of target information from higher brain areas to the ventral visual pathway. However, exactly where and how these signals are combined remains unknown. To investigate, we recorded neural responses in V4 and inferotemporal cortex (IT) while monkeys performed an invariant object search task, where targets could appear ...


Enhancement Of Ebola Virus Infection By Seminal Amyloid Fibrils, Stephen Michael Bart Jan 2018

Enhancement Of Ebola Virus Infection By Seminal Amyloid Fibrils, Stephen Michael Bart

Publicly Accessible Penn Dissertations

The 2014-2016 West Africa epidemic was the worst Ebola virus outbreak on record, with the infected numbering over 28,000 and the dead more than 11,000. Among those who survived the disease, Ebola virus was found to persist in numerous anatomical locations and be shed in semen. During the West Africa outbreak, numerous occurrences of Ebola sexual transmission were documented. While sexual transmission has the potential to compromise public health eradication efforts and reignite outbreaks, no molecular details of host factors influencing this phenomenon are known. Amyloid fibrils present in healthy individuals’ semen have been suggested to be a ...


A Synthetic Circuit For Control Of The Bacterial Dna Damage Response Without Dna Damage, Jeffrey Kubiak Jan 2018

A Synthetic Circuit For Control Of The Bacterial Dna Damage Response Without Dna Damage, Jeffrey Kubiak

Publicly Accessible Penn Dissertations

Prokaryotes possess a remarkable ability to respond to environmental stressors

using simple genetic circuits that detect signals of stress and mount an appropriate

response. The SOS pathway is an example of such a genetic circuit mediating error-prone

DNA repair in response to DNA damage. Native control over the SOS pathway is

orchestrated by the repressor-protease, LexA. Following a DNA damaging event, the

damage sensor RecA activates LexA to undergo a self-cleavage reaction that results in

LexA dissociation from SOS promoters and subsequent pathway activation. However, the

inability to decouple upstream events – DNA damage and RecA activation – from LexA

cleavage by ...


The Molecular Pathogenesis Of Cerebral Cavernous Malformations, Alan Tien Tang Jan 2018

The Molecular Pathogenesis Of Cerebral Cavernous Malformations, Alan Tien Tang

Publicly Accessible Penn Dissertations

Cerebral cavernous malformation (CCM) is a human genetic, cerebrovascular disease that is caused by loss of function mutations in three non-homologous protein coding genes: KRIT1, CCM2, and PDCD10. These proteins form a heterotrimeric CCM adaptor complex that is required in endothelial cells to prevent disease. How loss of this complex causes disease remains unknown. Here, utilizing a neonatal mouse model of disease, we demonstrate that the CCM complex negatively regulates Mitogen-Activated Protein Kinase Kinase Kinase 3 (MAP3K3 aka MEKK3) signaling in endothelial cells. During disease, loss of the CCM complex results in gain of MEKK3 signaling and pathologic overexpression of ...


Nonclassical Sex Hormone Signaling In Melanocytes And Melanoma, Christopher Anthony Natale Jan 2018

Nonclassical Sex Hormone Signaling In Melanocytes And Melanoma, Christopher Anthony Natale

Publicly Accessible Penn Dissertations

The primary pigment in mammalian skin and hair is melanin, which is synthesized locally by differentiated melanocytes and transferred into surrounding epidermal keratinocytes and hair shafts. Because pigmentation differences are often readily visible clinically, melanocyte function is known to correlate with changes in environment, as well as physiologic and pathologic changes in other organ systems. We utilized these clinical associations to inspire the hypothesis that sex hormones influence melanocyte biology. For over 2,000 years, it has been appreciated that pregnancy is associated with changes in skin pigmentation, but the specific processes, hormones, receptors, and downstream signaling cascades responsible have ...