Digital Commons Network^™

De Novo Missense Variants In Zbtb47 Are Associated With Developmental Delays, Hypotonia, Seizures, Gait Abnormalities, And Variable Movement Abnormalities, Scott K Ward, Alexandrea Wadley, Chun-Hui Anne Tsai, Paul J Benke, Lisa Emrick, Kristen Fisher, Kimberly M Houck, Hongzheng Dai, Undiagnosed Diseases Network, Maria J Guillen Sacoto, William Craigen, Kimberly Glaser, David R Murdock, Luis Rohena, Karin E M Diderich, Hennie T Bruggenwirth, Brendan Lee, Carlos Bacino, Lindsay C Burrage, Jill A Rosenfeld

Faculty, Staff and Students Publications

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in ZBTB47, with p.(Glu680Gly) (c.2039A>G) detected …

Long-Term Efficacy And Safety Of Cardiac Genome Editing For Catecholaminergic Polymorphic Ventricular Tachycardia, Oliver M Moore, Yuriana Aguilar-Sanchez, Satadru K Lahiri, Mohit M Hulsurkar, J Alberto Navarro-Garcia, Tarah A Word, Joshua A Keefe, Dean Barazi, Elda M Munivez, Charles T Moore, Vaidya Parthasarathy, Jaysón Davidson, William R Lagor, So Hyun Park, Gang Bao, Christina Y Miyake, Xander H T Wehrens

Faculty, Staff and Students Publications

INTRODUCTION: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model.

AIM: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for

METHODS …

Β2-Glycoprotein I Promotes The Clearance Of Circulating Mitochondria, Swapan Kumar Dasgupta, Jahnavi Gollamudi, Stefanie Rivera, Ross A Poche, Rolando E Rumbaut, Perumal Thiagarajan

Faculty, Staff and Students Publications

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood. We show that β2-Gp1 binds to cell-free mitochondria (CFM) in the circulation and promotes its phagocytosis by macrophages at physiological plasma concentrations. Exogenous CFM had a short circulation time of less than 10 minutes in mice. Following infusion of CFM, β2-Gp1-deficient mice had significantly higher levels of transfused mitochondria at 5 minutes (9.9 ± 6.4 pg/ml versus 4.0 …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Cristin G Welle, Kevin B Wilkins, Helen M Bronte-Stewart, Valerie Voon, Takashi Morishita, Yuki Sakai, Amanda R Merner, Gabriel Lázaro-Muñoz, Theresa Williamson, Andreas Horn, Ro'ee Gilron, Jonathan O'Keeffe, Aryn H Gittis, Wolf-Julian Neumann, Simon Little, Nicole R Provenza, Sameer A Sheth, Alfonso Fasano, Abbey B Holt-Becker, Robert S Raike, Lisa Moore, Yagna J Pathak, David Greene, Sara Marceglia, Lothar Krinke, Huiling Tan, Hagai Bergman, Monika Pötter-Nerger, Bomin Sun, Laura Y Cabrera, Cameron C Mcintyre, Noam Harel, Helen S Mayberg, Andrew D Krystal, Nader Pouratian, Philip A Starr, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …

The Why, When, Where, How, And So What Of So-Called Rapidly Acting Antidepressants, Alan F Schatzberg, Sanjay J Mathew

Staff and Researcher Publications

Developing antidepressants that are not only more effective but are rapidly acting is the Holy Grail for psychiatry. We review multiple issues that arise in determining rapid responses in antidepressant trials. The current status of purportedly rapid acting agents is first reviewed. Then, a number of key questions/issues are addressed: Is there a unifying definition for rapid response across studies? Should rapid response criteria be based on required measurable effects on overall improvement? On specific symptoms such as psychomotor retardation, depressed mood, or anhedonia? In associated symptoms such as anxiety or insomnia? When should onset be considered rapid-by Day 3? …

Comparative Exploration Of Mammalian Deafness Gene Homologues In The Drosophila Auditory Organ Shows Genetic Correlation Between Insect And Vertebrate Hearing, Daniel C Sutton, Jonathan C Andrews, Dylan M Dolezal, Ye Jin Park, Hongjie Li, Daniel F Eberl, Shinya Yamamoto, Andrew K Groves

Faculty, Staff and Students Publications

Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to …

Divergent Responses Of Human Intestinal Organoid Monolayers Using Commercial In Vitro Cytotoxicity Assays, Miranda A Lewis, Ketki Patil, Khalil Ettayebi, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

In vitro models, such as primary cells and continuous cell lines routinely used for evaluating drug candidates, have limitations in their translational relevance to human diseases. Organotypic cultures are increasingly being used to assess therapeutics for various cancers and infectious diseases. Monitoring drug cytotoxicity in cell cultures is crucial in drug development, and several commercially available kits for cytotoxicity assessment offer distinct advantages and limitations. Given the complexity of organoid cultures, including donor-driven variability, we investigated drug-treated, tissue stem cell-derived human intestinal organoid responses with commonly used cell cytotoxicity assay kits. Using seven different compounds, we compared the cytotoxicity assay …

Inference Of Phylogenetic Trees Directly From Raw Sequencing Reads Using Read2tree, David Dylus, Adrian Altenhoff, Sina Majidian, Fritz J Sedlazeck, Christophe Dessimoz

Faculty, Staff and Students Publications

Current methods for inference of phylogenetic trees require running complex pipelines at substantial computational and labor costs, with additional constraints in sequencing coverage, assembly and annotation quality, especially for large datasets. To overcome these challenges, we present Read2Tree, which directly processes raw sequencing reads into groups of corresponding genes and bypasses traditional steps in phylogeny inference, such as genome assembly, annotation and all-versus-all sequence comparisons, while retaining accuracy. In a benchmark encompassing a broad variety of datasets, Read2Tree is 10-100 times faster than assembly-based approaches and in most cases more accurate-the exception being when sequencing coverage is high and reference …

Neuronal Ablation Of Ghsr Mitigates Diet-Induced Depression And Memory Impairment Via Ampk-Autophagy Signaling-Mediated Inflammation, Hongying Wang, Zheng Shen, Chia-Shan Wu, Pengfei Ji, Ji Yeon Noh, Cédric G Geoffroy, Sunja Kim, David Threadgill, Jianrong Li, Yu Zhou, Xiaoqiu Xiao, Hui Zheng, Yuxiang Sun

Faculty, Staff and Students Publications

Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the …

Trpv4 Affects Visual Signals In Photoreceptors And Rod Bipolar Cells, Ye Long, Maxim Kozhemyakin, Samuel M Wu, Ji-Jie Pang

Faculty, Staff and Students Publications

INTRODUCTION: Mechanical sensitive channels expressed in mammalian retinas are effectors of elevated pressure stresses, but it is unclear how their activation affects visual function in pressure-related retinal disorders.

METHODS: This study investigated the role of the transient potential channel vanilloid TRPV4 in photoreceptors and rod bipolar cells (RBCs) with immunohistochemistry, confocal microscopy, electroretinography (ERG), and patch-clamp techniques.

RESULTS: TRPV4 immunoreactivity (IR) was found in the outer segments of photoreceptors, dendrites and somas of PKCα-positive RBCs and other BCs, plexiform layers, and retinal ganglion cells (RGCs) in wild-type mice. TRPV4-IR was largely diminished in the retinas of homozygous TRPV4 transgenic mice. …

Forum: The Russia–Ukraine War And Reactions From The Global South, Vidya Nadkarni, Paul D’Anieri, S. A. Kerr, Gulnaz Sharafutdinova, Xiaoyu Pu, Deepa M. Ollapally, Paulo Velasco, Candice Moore, Abdolrasool Divsallar

Political Science and International Relations Faculty Publications

The war between Russia and Ukraine has been a topic of interest for scholars and policymakers worldwide. Western countries have condemned and imposed sanctions on Russia, while countries in the Global South have taken varying positions. In this Forum, we will analyse the origins of the war and the responses to it of key countries in the Global South, including China, India, Brazil, South Africa, and Iran. The war has multiple causes, and identifying them has implications for understanding what is necessary to regain peace. However, reaching a consensus on its causes will not be easy. Great and middle powers …

Mechanistic Approach To Understanding Adverse Liver Outcomes Related To Pfas Exposure In Neonatal And Adult Mice, Emily Kaye

Open Access Dissertations

Per- and polyfluoroalkyl substances (PFAS) are a unique class of over 15,000 manmade chemicals that are still widely used in manufacturing and are resistant to degradation. Accumulation in the environment and general population has been associated with an array of adverse health outcomes. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) specifically have been associated with markers of liver injury, high serum cholesterol, thyroid disease, low fetal birth weight, suppressed vaccine response, and cancer. Exposure to PFAS is commonly investigated individually, however, humans are exposed to a multitude of PFAS daily. Additionally, with the pervasive nature of these …

Effects Of Western Diet Or Exercise Exposure In A Novel Rat Model Of Late-Onset Alzheimer’S Disease, Jennifer M. Mattar

Open Access Dissertations

Sporadic, late-onset Alzheimer’s disease (LOAD) accounts for a staggering 98% of cases yet does not arise from a single genetic mutation. Rather, an extensive body of research has revealed that LOAD is likely the result of complex interactions between genetics and several lifestyle factors. There exists a substantial gap in understanding the mechanisms behind LOAD development and the impacts of lifestyle on disease progression. Enhanced rodent models may help elucidate mechanisms by which LOAD develops. This longitudinal study introduces a novel rat model of LOAD (CrAβ), created using CRISPR-Cas9 gene editing technology to express humanized Aβ. The effects of a …

Design And Application Of Ph Sensitive Peptides For Fluorescence Imaging And Therapy Of Tumors, Michael Dupont

Open Access Dissertations

The most common cancer treatments are chemotherapy and radiation therapy which include an untargeted delivery of toxic molecules, resulting in systemic effects and reduction in patient comfort. This leads to research for cancer treatments that are targeted and will reduce the severity of systemic effects on patients. Tumor resection surgery also has its own complications relating to not having real time confirmation of tumor geometry and position. pHLIP peptide targets acidity which is a characteristic of most cancer lines due to the Warburg effect, along with targeting tumor associated macrophages, cancer associated fibroblasts, and myeloid derives suppresser cells that are …

Developing Effective Physical And Chemical Adjuvants For Influenza And Tumor Vaccines, Yibo Li

Open Access Dissertations

An adjuvant is a pharmacological substance added to a vaccine to enhance the intensity, breadth and endurance of the immune responses. Traditional discovery and development of vaccine adjuvants mainly based on empirical experiences have been slow, but the situation has improved in the past two decades as more molecular mechanisms of vaccine adjuvants were revealed. Now it has been widely recognized that most adjuvants activate innate immune system by targeting pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) to enhance adaptive immune responses. PRRs are proteins expressed mainly on innate immune cells, such as dendritic cells (DCs) and macrophages, …

From Woke-Washing To Authentic Brand Activism: Essays On Its Impact On Consumer Identity, Brand Morality And Brand Responses, Priscilla Yamilet Peña

Open Access Dissertations

Brand activism, in which a brand publicly takes a political or social justice stance, has gained momentum, positioning brands as agents of societal change. However, accusations of inauthentic brand activism or "woke washing" present a significant challenge. Understanding the basis for these accusations and their effects on consumer identity, particularly among stigmatized groups, requires further exploration. This dissertation aims to shed light on consumers' perspectives of inauthentic brand activism and proposes effective brand messaging strategies. The first manuscript explores consumer accusations of woke-washing using the Zaltman Metaphor Elicitation Technique (ZMET), uncovering emerging themes, and assessing the damage to identity within …

Design, Simulation, And Rapid Prototyping Of Soft Robotic Actuators For Deep-Sea Applications, Alexander Yin

Open Access Dissertations

A new design and rapid prototyping approach for hydraulic soft actuators was developed and used to create bio-inspired underwater soft actuators that were tested and applied in the field. Underwater soft-bodied animals demonstrate complex approaches to move around the ocean and sophisticated methods of physically interacting with other organism and objects. Studying the functional design and kinematics of these animals can provide insight and solutions for complex tasks and locomotion, and soft robotics provides pathways to create complex actuators that imitate or are inspired by these animals. However, creating a complex soft actuator is currently an arduous and time-consuming process …

Mechanistic And Toxicokinetic Analysis Of Perfluoroalkyl Substances: Proteomics Approach And The Role Of Fatty Acid Binding (Fabp), Seyed Mohamad Sadegh Modaresi

Open Access Dissertations

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals used in many industries, known for their resilience and resistance to degradation. The extended half-lives of PFAS in the human body result in bioaccumulation, with serum half-lives for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) estimated at 3.4, 4.6, and 7.1 years, respectively. PFAS primarily accumulate in the liver, hypothesized due to their resemblance to fatty acids and their binding with liver fatty acid-binding proteins (LFABP), affecting lipid metabolism and leading to liver toxicity. Although extensive research has been performed on long-chain PFAS over the past decade, …

Strategies To Stress Less: A Meta-Analytic Review Of The Effects Of Mindfulness-Based Stress Reduction (Mbsr) On Self-Reported Stress, Gregory J. Champion

Open Access Dissertations

Introduction: Stress negatively impacts health, well-being, and productivity. Mindfulness-based stress reduction (MBSR) interventions are a promising strategy to reduce stress, but they are not covered by most health insurance policies in the United States (US). A recent Delphi process gathered feedback from key stakeholders, such as clinicians, MBSR instructors and students, policymakers, healthcare administrators, and health insurance company leaders. The results indicated synthesizing the existing evidence of the impact of MBSR interventions on stress was the 2nd highest priority out of 43 options evaluated. Past research has indicated MBSR interventions may be as effective as active controls at reducing …

Treading Carefully In The Deep Ocean: Insights Into The Effects Of Artificial Light And Sound From Robotic Platforms On Pelagic Animal Surveys Using Active Acoustics And Low-Light Imaging Techniques, Rendhy Moreno Sapiie

Open Access Dissertations

Science and technology are coupled disciplines. Breakthroughs in ocean science are often pertinent to the ability to observe physical, chemical, and biological processes at the right temporal and spatial scales, which typically involves the use of robots. Large, powerful, and extremely capable, the scientific work-class remotely operated vehicle (ROV) is the golden standard when observing fine temporal scale intricate processes in the full ocean stratum and has unraveled important discoveries in deep-sea biology and ecology. Sound, light, and hydrodynamic forces produced from these vehicles are sources of disturbances that may impact quantitative observations in the twilight zone, an environment absent …

Nanotube Spectral Fingerprinting And Machine Learning For Optimized Bioimaging/Sensing Applications, Aceer Nadeem

Open Access Dissertations

This thesis presents a multifaceted exploration of the optimization and application of single-walled carbon nanotubes (SWCNTs) in biomedical contexts, with a specific focus on enhancing their stability, functionality, and use as optical biosensors. The research spans several key areas, including the development of innovative techniques that couple machine learning with spectral fingerprinting for advanced diagnostics, the investigation of SWCNT chirality and its implications for cellular interactions, and the optimization of lyophilization processes to improve long-term stability and reproducibility.

The first section of the thesis delves into the fundamental properties of SWCNTs, emphasizing their unique electronic and optical characteristics. These properties, …

From Page To Stage: Enlightenment Common Sense & The Semiotics Of The Body, 1660–1820, Nilton X. Gomes

Open Access Dissertations

How did eighteenth-century audience members or novel readers come to see beyond the facades of literary characters and narrators? By looking into moments of bodily concealment in the eighteenth-century novel and theater, this dissertation examines how authors and playwrights in this period wrote with subtly and force to make the body as and in many instances more legible to their readers as the words on the page or the dialogues on the stage in attempts to suture the gap that lies between what a writer intends and what a reader grasps in a literary work. It also stresses the body’s …

The Distribution And Habitat Use Of Semi-Aquatic Mammals In A Changing New England Landscape, Josh Crockett

Open Access Dissertations

Semi-aquatic mammals (i.e., animals that depend on both terrestrial and aquatic environments for their daily needs) are an ecologically and economically important group, but they are often difficult to monitor because of their restricted habitat which makes them unlikely to appear in monitoring schemes designed for all mammals (e.g., camera trapping). Rhode Island is home to several semi-aquatic mammal species, including North American beavers (Castor canadensis), North American river otters (Lontra candensis), and muskrats (Ondatra zibethicus). Historically, these species were all exploited for their furs, which led to drastic declines in otter and (especially) …

Telechelic Polymers As High-Performance Rheological Modifiers In Biomimetic Polymer-Linked Emulsions, Daniel P. Keane

Open Access Dissertations

Due to the complexity of biological tissue and the numerous challenges associated with research into biological particle transport, it is of interest to scientists to develop a synthetic mimic that can replicate key attributes of multicellular tissue. The work presented in this dissertation details the design, characterization, and application of a synthetic material for use as a phantom material in research into biological particle transport. Furthermore, the designed materials introduce exciting polymer physics problems and present broad potential uses as rheological modifiers for colloidal systems and 3D printing inks. The polymer-linked emulsions which form the basis of this work are …

Mapping Of A Hybrid Insulin Peptide In The Inflamed Islet Β-Cells From Nod Mice, Janet M Wenzlau, Orion J Peterson, Anthony N Vomund, James E Dilisio, Anita Hohenstein, Kathryn Haskins, Xiaoxiao Wan

2020-Current year OA Pubs

There is accumulating evidence that pathogenic T cells in T1D recognize epitopes formed by post-translational modifications of β-cell antigens, including hybrid insulin peptides (HIPs). The ligands for several CD4 T-cell clones derived from the NOD mouse are HIPs composed of a fragment of proinsulin joined to peptides from endogenous β-cell granule proteins. The diabetogenic T-cell clone BDC-6.9 reacts to a fragment of C-peptide fused to a cleavage product of pro-islet amyloid polypeptide (6.9HIP). In this study, we used a monoclonal antibody (MAb) to the 6.9HIP to determine when and where HIP antigens are present in NOD islets during disease progression …

Increased Hif-2Α Activity In The Nucleus Pulposus Causes Intervertebral Disc Degeneration In The Aging Mouse Spine, Shira N Johnston, Maria Tsingas, Rahatul Ain, Ruteja A Barve, Makarand V Risbud

2020-Current year OA Pubs

Hypoxia-inducible factors (HIFs) are essential to the homeostasis of hypoxic tissues. Although HIF-2α, is expressed in nucleus pulposus (NP) cells, consequences of elevated HIF-2 activity on disc health remains unknown. We expressed HIF-2α with proline to alanine substitutions (P405A; P531A) in the Oxygen-dependent degradation domain (HIF-2αdPA) in the NP tissue using an inducible, nucleus pulposus-specific K19

Children With Non-Central Nervous System Tumors Treated With Platinum-Based Chemotherapy Are At Risk For Hearing Loss And Cognitive Impairments, Allison J L'Hotta, Anne Spence, Taniya E Varughese, Kara Felts, Susan S Hayashi, Megan Jones-White, Emily Lafentres, Judith E C Lieu, Robert J Hayashi, Allison A King

2020-Current year OA Pubs

BACKGROUND: Childhood cancer survivors (CCS) with chemotherapy induced sensorineural hearing loss (SNHL) are at risk for neurocognitive impairments. The purpose of this study was to determine the relationship between SNHL and cognitive function among CCS.

PROCEDURE: Inclusion: non-CNS solid tumor diagnosis; history of platinum chemotherapy (cisplatin and/or carboplatin); 8-17 years of age; off anti-cancer treatment for ≥6 months; and English speaking. Exclusion: history of intrathecal chemotherapy, cranial radiation, or baseline neurocognitive disorder. Participants completed the NIH Toolbox Cognition Battery at enrollment.

RESULTS: Fifty-seven individuals enrolled; 52 completed full cognitive testing. Participants were on average 12.2 years of age and 7.0 …

Hormonal And Circuit Mechanisms Controlling Female Sexual Behavior, Sayaka Inoue

2020-Current year OA Pubs

Sexual behavior is crucial for reproduction in many animals. In many vertebrates, females exhibit sexual behavior only during a brief period surrounding ovulation. Over the decades, studies have identified the roles of ovarian sex hormones, which peak in levels around the time of ovulation, and the critical brain regions involved in the regulation of female sexual behavior. Modern technical innovations have enabled a deeper understanding of the neural circuit mechanisms controlling this behavior. In this review, I summarize our current knowledge and discuss the neural circuit mechanisms by which female sexual behavior occurs in association with the ovulatory phase of …

Infringement Episodes, Shani Shisha

Faculty Journal Articles and Book Chapters

For decades, copyright scholars have waged a spirited campaign against statutory damages. Our remedial system, critics say, is an incoherent mess. The core problem is that copyright holders can recover a separate award of statutory damages for every infringed work. As a result, damages can rapidly add up in any case involving multiple works. Because the number of statutory awards is tethered to the number of works, even trivial claims can lead to crippling damages. Commentators, policymakers, and judges have criticized this system as arbitrary and overbroad. And yet it endures. This Article argues that copyright’s per-work scheme has obscured, …