Digital Commons Network^™

The Enemy Within: Propagation Of Aberrant Corticostriatal Learning To Cortical Function In Parkinson’S Disease, Jeff A. Beeler, Giselle Petzinger, Michael W. Jakowec

Publications and Research

Motor dysfunction in Parkinson’s disease is believed to arise primarily from pathophysiology in the dorsal striatum and its related corticostriatal and thalamostriatal circuits during progressive dopamine denervation. One function of these circuits is to provide a filter that selectively facilitates or inhibits cortical activity to optimize cortical processing, making motor responses rapid and efficient. Corticostriatal synaptic plasticity mediates the learning that underlies this performance-optimizing filter. Under dopamine denervation, corticostriatal plasticity is altered, resulting in aberrant learning that induces inappropriate basal ganglia filtering that impedes rather than optimizes cortical processing. Human imaging suggests that increased cortical activity may compensate for striatal …

Fashion Vs. Function In Cultural Evolution: The Case Of Dog Breed Popularity, Stefano Ghirlanda, Alberto Acerbi, Harold Herzog, James A. Serpell

Publications and Research

We investigate the relationship between characteristics of dog breeds and their popularity between years 1926 and 2005. We consider breed health, longevity, and behavioral qualities such as aggressiveness, trainability, and fearfulness. We show that a breed's overall popularity, fluctuations in popularity, and rates of increase and decrease around popularity peaks show typically no correlation with these breed characteristics. One exception is the finding that more popular breeds tend to suffer from more inherited disorders. Our results support the hypothesis that dog breed popularity has been primarily determined by fashion rather than function.

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …

Myc-Dependent Genome Instability And Lifespan In Drosophila, Christina Greer, Moonsook Lee, Maaike Westerhof, Brandon Milholland, Rebecca Spokony, Jan Vijg, Julie Secombe

Publications and Research

The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs). In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence …

Chimeric Rhinoviruses Displaying Mper Epitopes Elicit Anti-Hiv Neutralizing Responses, Guohua Yi, Mauro Lapelosa, Rachel Bradley, Thomas M. Mariano, Denise Elsasser Dietz, Scott Hughes, Terri Wrin, Chris Petropoulos, Emilio Gallicchio, Ronald M. Levy, Eddy Arnold, Gail Ferstandig Arnold

Publications and Research

Background: The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.

Methodology/Principle Findings: Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV) displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic …

Lizards And Lines: Selection And Demography Affect The Fate Of L1 Retrotransposons In The Genome Of The Green Anole (Anolis Carolinensis), Marc Tollis, Stéphane Boissinot

Publications and Research

Autonomous retrotransposons lacking long terminal repeats (LTR) account for much of the variation in genome size and structure among vertebrates. Mammalian genomes contain hundreds of thousands of non-LTR retrotransposon copies, mostly resulting from the amplification of a single clade known as L1. The genomes of teleost fish and squamate reptiles contain a much more diverse array of non-LTR retrotransposon families, whereas copy number is relatively low. The majority of non-LTR retrotransposon insertions in nonmammalian vertebrates also appear to be very recent, suggesting strong purifying selection limits the accumulation of non-LTR retrotransposon copies. It is however unclear whether this turnover model, …

Magnetoelectricity In Cofe2o4 Nanocrystal-P(Vdf-Hfp) Thin Films, Xiaohua Liu, Shuangyi Liu, Myung-Geun Han, Lukas Zhao, Haiming Deng, Jackie Li, Yimei Zhu, Lia Krusin-Elbaum, Stephen O'Brien

Publications and Research

Transition metal ferrites such as CoFe2O4, possessing a large magnetostriction coefficient and high Curie temperature (Tc > 600 K), are excellent candidates for creating magnetic order at the nanoscale and provide a pathway to the fabrication of uniform particle-matrix films with optimized potential for magnetoelectric coupling. Here, a series of 0–3 type nanocomposite thin films composed of ferrimagnetic cobalt ferrite nanocrystals (8 to 18 nm) and a ferroelectric/piezoelectric polymer poly(vinylidene fluoride-co-hexafluoropropene), P(VDF-HFP), were prepared by multiple spin coating and cast coating over a thickness range of 200 nm to 1.6 μm. We describe the synthesis and structural characterization of the nanocrystals …

Therapeutic Ultrasound: Osteoarthritis Symptom-Modification And Potential For Disease Modification, Daniel J. Leong, Huagang Zhang, Lin Xu, Justin Tang, David M. Hirsh, John A. Hardin, Luis Cardoso, Chandan Guha, Neil J. Cobelli, Hui B. Sun

Publications and Research

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. While joint replacement surgery is a common treatment option for end-stage disease, non-surgical management is critical for preventing disability and maintaining quality of life. Although therapeutic ultrasound, which applies mechanical and may also apply thermal energy in the form of sound waves, is widely used to treat various musculoskeletal disorders such as bone fractures, tendinopathy, and muscle contusions, its symptom- and disease-modifying effects on osteoarthritis have not been clearly demonstrated. Recent clinical evidence indicates therapeutic ultrasound is capable of relieving OAassociated pain and improving function of …

Unconscious Priming Requires Early Visual Cortex At Specific Temporal Phases Of Processing, Marjan Persuh, Tony Ro

Publications and Research

Although examples of unconscious shape priming have been well documented, whether such priming requires early visual cortex (V1/V2) has not been established. In the current study, we used TMS of V1/V2 at varying temporal intervals to suppress the visibility of preceding shape primes while the interval between primes and targets was kept constant. Our results show that, although conscious perception requires V1/V2, unconscious priming can occur without V1/V2 at an intermediate temporal interval but not at early (5–25 msec) or later (65–125 msec) stages of processing. Because the later time window of unconscious priming suppression has been proposed to interfere …

Androgen Activity And Markers Of Inflammation Among Men In Nhanes Iii, Mary Schooling

Publications and Research

Objectives
Inflammation contributes to chronic diseases. Lower serum testosterone among men is associated with less inflammation, yet immune defense is thought to trade-off against reproduction with androgens adversely affecting immune function. Anti-androgens are effective at castrate levels of serum testosterone, suggesting serum testosterone may not capture all androgen activity. The association of two androgen biomarkers with key markers of inflammation was examined.

Methods
The adjusted association of serum testosterone and androstanediol glucuronide with Creactive protein, white blood cell, granulocyte and lymphocyte count, fibrinogen and hemoglobin, as a control outcome because testosterone administration raises hemoglobin, were examined in a nationally representative …

The Variability Of Autophagy And Cell Death Susceptibility, Ben Loos, Anna-Mart Engelbrecht, Richard A. Lockshin, Daniel J. Klionsky, Zahra Zakeri

Publications and Research

Impaired autophagic machinery is implicated in a number of diseases such as heart disease, neurodegeneration and cancer. A common denominator in these pathologies is a dysregulation of autophagy that has been linked to a change in susceptibility to cell death. Although we have progressed in understanding the molecular machinery and regulation of the autophagic pathway, many unanswered questions remain. How does the metabolic contribution of autophagy connect with the cell’s history and how does its current autophagic flux affect metabolic status and susceptibility to undergo cell death? How does autophagic flux operate to switch metabolic direction and what are the …

Toward A Broader Dialectic: Joining Marxism With Mailer To Forge A Multilectics That Advances Teaching And Learning, Gene Fellner

Publications and Research

I contrast the lenses that Norman Mailer, Herbert Marcuse, and Karl Marx bring to their analyses of social life, exploring the contributions and limits of their respective approaches. I then propose what I call a “multilectical” theoretical lens that encompasses the strengths of all three and leans on the insights of post-Marxist theorists. The multilectical lens is then applied to an event that transpired in a severely underperforming middle school.

Transitions In Nirs-Type Denitrifier Diversity, Community Composition, And Biogeochemical Activity Along The Chesapeake Bay Estuary, Christopher A. Francis, Gregory D. O'Mullan, Jeffrey C. Cornwell, Bess B. Ward

Publications and Research

Chesapeake Bay, the largest estuary in North America, can be characterized as having steep and opposing gradients in salinity and dissolved inorganic nitrogen along the main axis of the Bay. In this study, the diversity of nirS gene fragments (encoding cytochrome cd1-type nitrite reductase), physical/chemical parameters, and benthic N2-fluxes were analyzed in order to determine how denitrifier communities and biogeochemical activity vary along the estuary salinity gradient. The nirS gene fragments were PCR-amplified, cloned, and sequenced from sediment cores collected at five stations. Sequence analysis of 96–123 nirS clones from each station revealed extensive overall diversity in this estuary, as …

Polydnaviral Ankyrin Proteins Aid Parasitic Wasp Survival By Coordinate And Selective Inhibition Of Hematopoietic And Immune Nf-Kappa B Signaling In Insect Hosts, Gwenaelle Gueguen, Marta E. Kalamarz, Johnny Ramroop, Jeffrey Uribe, Shubha Govind

Publications and Research

Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyrins differentially impede Toll-NF-κB-dependent hematopoietic and immune signaling in a heterologous in vivo Drosophila, system. We first show that hematopoiesis and the cellular encapsulation response against parasitoid wasps are tightly-linked via NF-κB signaling. The niche, which neighbors the larval hematopoietic progenitors, responds to parasite infection. Drosophila NF-κB proteins are expressed in the niche, and non cell-autonomously …

Mood And The Market: Can Press Reports Of Investors’ Mood Predict Stock Prices?, Yochi Cohen-Charash, Charles A. Scherbaum, John D. Kammeyer-Muller, Barry M. Staw

Publications and Research

We examined whether press reports on the collective mood of investors can predict changes in stock prices. We collected data on the use of emotion words in newspaper reports on traders’ affect, coded these emotion words according to their location on an affective circumplex in terms of pleasantness and activation level, and created indices of collective mood for each trading day. Then, by using time series analyses, we examined whether these mood indices, depicting investors’ emotion on a given trading day, could predict the next day’s opening price of the stock market. The strongest findings showed that activated pleasant mood …

Signatures Of Rapid Evolution In Urban And Rural Transcriptomes Of White-Footed Mice (Peromyscus Leucopus) In The New York Metropolitan Area, Stephen Edward Harris, Jason Munshi-South, Craig Oberfell, Rachel O'Neill

Publications and Research

Urbanization is a major cause of ecological degradation around the world, and human settlement in large cities is accelerating. New York City (NYC) is one of the oldest and most urbanized cities in North America, but still maintains 20% vegetation cover and substantial populations of some native wildlife. The white-footed mouse, Peromyscus leucopus, is a common resident of NYC’s forest fragments and an emerging model system for examining the evolutionary consequences of urbanization. In this study, we developed transcriptomic resources for urban P. leucopus to examine evolutionary changes in protein-coding regions for an exemplar “urban adapter.” We used Roche 454 …

Bax And Bak Function As The Outer Membrane Component Of The Mitochondrial Permeability Pore In Regulating Necrotic Cell Death In Mice, Jason Karch, Jennifer Q. Kwong, Adam R. Burr, Michelle A. Sargent, John W. Elrod, Pablo M. Peixoto, Sonia Martinez-Caballero, Hanna Osinskka, Emily H-Y Cheng, Jeffrey Robbins, Kathleen W. Kinnally, Jeffrey D. Molkentin

Publications and Research

A critical event in ischemia-based cell death is the opening of the mitochondrial permeability transition pore (MPTP). However, the molecular identity of the components of the MPTP remains unknown. Here, we determined that the Bcl-2 family members Bax and Bak, which are central regulators of apoptotic cell death, are also required for mitochondrial pore-dependent necrotic cell death by facilitating outer membrane permeability of the MPTP. Loss of Bax/Bak reduced outer mitochondrial membrane permeability and conductance without altering inner membrane MPTP function, resulting in resistance to mitochondrial calcium overload and necrotic cell death. Reconstitution with mutants of Bax that cannot oligomerize …

Consumers' Perceptions Of Patient-Accessible Electronic Medical Records, Christina Zarcadoolas, Wendy L. Vaughon, Sara J. Czaja, Joslyn Levy, Maxine L. Rockoff

Publications and Research

Background: Electronic health information (eHealth) tools for patients, including patient-accessible electronic medical records (patient portals), are proliferating in health care delivery systems nationally. However, there has been very limited study of the perceived utility and functionality of portals, as well as limited assessment of these systems by vulnerable (low education level, racial/ethnic minority) consumers.

Objective: The objective of the study was to identify vulnerable consumers’ response to patient portals, their perceived utility and value, as well as their reactions to specific portal functions.

Methods: This qualitative study used 4 focus groups with 28 low education level, English-speaking consumers in June …

Price, Promotion, And Availability Of Nutrition Information: A Descriptive Study Of A Popular Fast Food Chain In New York City, Corey Hannah Basch, Danna Ethan, Sonali Rajan

Publications and Research

Legislation in NYC requires chain restaurants to post calorie information on menu boards in an effort to help consumers make more informed decisions about food and beverage items they are purchasing. While this is a step in the right direction in light of the current obesity epidemic, there are other issues that warrant attention in a fast food setting, namely the pricing of healthy food options, promotional strategies, and access to comprehensive nutrition information. This study focused on a popular fast-food chain in NYC. The study’s aims were threefold: (1) to determine the cost differential between the healthiest meal item …

Genome-Wide Analyses Of Shavenbaby Target Genes Reveals Distinct Features Of Enhancer Organization, Delphine Menoret, Marc Santolini, Isabelle Fernandes, Rebecca Spokony, Jennifer Zanet, Ignacio Gonzalez, Yvan Latapie, Pierre Ferrer, Hervé Rouault, Kevin P. White, Philippe Besse, Vincent Hakim, Stein Aerts, Francois Payre, Serge Plaza

Publications and Research

Background: Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes.

Results: We defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome …

Returning Home: Understanding The Challenges Of Prisoner Reentry And Reintegration, Jeremy Travis

Publications and Research

No abstract provided.

Patterns Of Anti-Muslim Violence In Burma: A Call For Accountability And Prevention, Andrea Gittleman, Marissa Brodney, Holly G. Atkinson

Publications and Research

In this report, the authors documents how persecution of and violence against the Rohingya in Burma has spread to other Muslim communities throughout the country. Physicians for Human Rights conducted eight separate investigations in Burma and the surrounding region between 2004 and 2013. PHR’s most recent field research in early 2013 indicates a need for renewed attention to violence against minorities and impunity for such crimes. The findings presented in this report are based on investigations conducted in Burma over two separate visits for a combined 21-day period between March and May 2013.

Amino Acids And Mtor Mediate Distinct Metabolic Checkpoints In Mammalian G1 Cell Cycle, Mahesh Saqcena, Deepak Menon, Deven Patel, Suman Mukhopadhyay, Victor Chow, David A. Foster

Publications and Research

Objective In multicellular organisms, cell division is regulated by growth factors (GFs). In the absence of GFs, cells exit the cell cycle at a site in G1 referred to as the restriction point (R) and enter a state of quiescence known as G0. Additionally, nutrient availability impacts on G1 cell cycle progression. While there is a vast literature on G1 cell cycle progression, confusion remains – especially with regard to the temporal location of R relative to nutrient-mediated checkpoints. In this report, we have investigated the relationship between R and a series of metabolic cell cycle checkpoints that regulate passage …

Early Innate Immunity Determines Outcome Of Mycobacterium Tuberculosis Pulmonary Infection In Rabbits, Selvakumar Subbian, Nirmalya Bandyopadhyay, Liana Tsenova, Paul O'Brien, Viraj Khetani, Nicole L. Kushner, Blas Peixoto, Patricia Soteropoulos, Joel S. Bader, Petros C. Karakousis, Dorothy Fallows, Gilla Kaplan

Publications and Research

Background: Pulmonary infection of humans by Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), results in active disease in 5-10% of individuals, while asymptomatic latent Mtb infection (LTBI) is established in the remainder. The host immune responses that determine this differential outcome following Mtb infection are not fully understood. Using a rabbit model of pulmonary TB, we have shown that infection with the Mtb clinical isolate HN878 (a hyper-virulent W-Beijing lineage strain) leads to progressive cavitary disease similar to what is seen in humans with active TB. In contrast, infection with Mtb CDC1551 (a hyper-immunogenic clinical isolate) is efficiently …

Toward A New Professionalism In Policing, Jeremy Travis

Publications and Research

No abstract provided.

Evaluating Satellite Products For Precipitation Estimation In Mountain Regions: A Case Study For Nepal, Nir Y. Krakauer, Soni M. Pradhanang, Tarendra Lakhankar, Ajay K. Jha

Publications and Research

Precipitation in mountain regions is often highly variable and poorly observed, limiting abilities to manage water resource challenges. Here, we evaluate remote sensing and ground station-based gridded precipitation products over Nepal against weather station precipitation observations on a monthly timescale. We find that the Tropical Rainfall Measuring Mission (TRMM) 3B-43 precipitation product exhibits little mean bias and reasonable skill in giving precipitation over Nepal. Compared to station observations, the TRMM precipitation product showed an overall Nash-Sutcliffe efficiency of 0.49, which is similar to the skill of the gridded station-based product Asian Precipitation-Highly Resolved Observational Data Integration Towards Evaluation of Water …

Pkc Activation In Niemann Pick C1 Cells Restores Subcellular Cholesterol Transport, Farshad Tamari, Fannie W. Chen, Chunlei Li, Jagrutiben Chaudhari, Yiannis A. Ioannou

Publications and Research

Activation of protein kinase C (PKC) has previously been shown to ameliorate the cholesterol transport defect in Niemann Pick Type C1 (NPC1) cells, presumably by increasing the soluble levels of one of its substrates, vimentin. This activity would then restore the vimentin cycle in these cells and allow vimentin-dependent retrograde transport to proceed. Here, we further investigate the effects of PKC activation in NPC1 cells by evaluating different isoforms for their ability to solubilize vimentin and correct the NPC1 cholesterol storage phenotype. We also examine the effects of PKC activators, including free fatty acids and the PKC-specific activator diazoxide, on …

Taxonomic Revision Of The Olingos (Bassaricyon), With Description Of A New Species, The Olinguito, Kristofer M. Helgen, C. Miguel Pinto, Roland Kays, Laura E. Helgen, Mirian T. N. Tsuchiya, Aleta Quinn, Don E. Wilson, Jesús E. Maldonado

Publications and Research

We present the first comprehensive taxonomic revision and review the biology of the olingos, the endemic Neotropical procyonid genus Bassaricyon, based on most specimens available in museums, and with data derived from anatomy, morphometrics, mitochondrial and nuclear DNA, field observations, and geographic range modeling. Species of Bassaricyon are primarily forest-living, arboreal, nocturnal, frugivorous, and solitary, and have one young at a time. We demonstrate that four olingo species can be recognized, including a Central American species (B. gabbii), lowland species with eastern, cis-Andean (B. alleni) and western, trans- Andean (B. medius) distributions, and a species endemic to cloud forests in …

Explorations Of Object And Location Memory Using Fmri, Andrew D. Passaro, L. Caitlin Elmore, Timothy M. Ellmore, Kenneth J. Leising, Andrew C. Papanicolaou, Anthony A. Wright

Publications and Research

Content-specific sub-systems of visual working memory (VWM) have been explored in many neuroimaging studies with inconsistent findings and procedures across experiments. The present study employed functional magnetic resonance imaging (fMRI) and a change detection task using a high number of trials and matched stimulus displays across object and location change (what vs. where) conditions. Furthermore, individual task periods were studied independently across conditions to identify differences corresponding to each task period. Importantly, this combination of task controls has not previously been described in the fMRI literature. Composite results revealed differential frontoparietal activation during each task period. A separation of object …

Β-Catenin-Independent Activation Of Tcf1/Lef1 In Human Hematopoietic Tumor Cells Through Interaction With Atf2 Transcription Factors, Luca Grumolato, Guizhong Liu, Tomomi Haremaki, Sathish Kumar Mungamuri, Phyllus Mong, Gal Akiri, Pablo Lopez-Bergami, Adriana Arita, Youssef Anouar, Marek Mlodzik, Ze'ev A. Ronai, Joshua Brody, Daniel C. Weinstein, Stuart A. Aaronson

Publications and Research

The role of Wnt signaling in embryonic development and stem cell maintenance is well established and aberrations leading to the constitutive up-regulation of this pathway are frequent in several types of human cancers. Upon ligand-mediated activation, Wnt receptors promote the stabilization of β-catenin, which translocates to the nucleus and binds to the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors to regulate the expression of Wnt target genes. When not bound to β-catenin, the TCF/LEF proteins are believed to act as transcriptional repressors. Using a specific lentiviral reporter, we identified hematopoietic tumor cells displaying constitutive TCF/LEF transcriptional activation in …