Digital Commons Network^™

Parasitic Diseases Of The Central Nervous System: Lessons For Clinicians And Policy Makers, Arturo Carpio, Matthew L. Romo, R.M.E. Parkhouse, Brooke Short, Tarun Dua

Publications and Research

Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, …

Predicted Molecular Signaling Guiding Photoreceptor Cell Migration Following Transplantation Into Damaged Retina, Uchenna John Unachukwu, Alice Warren, Ze Li, Shawn Mishra, Jing Zhou, Moira Sauane, Hyungsik Lim, Maribel Vazquez, Stephen Redenti

Publications and Research

To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to …

Dengue-Induced Autophagy, Virus Replication And Protection From Cell Death Require Er Stress (Perk) Pathway Activation, E. Datan, S. G. Roy, G. Germain, N. Zali, J. E. Mclean, G. Golshan, S. Harbajan, R. A. Lockshin, Z. Zakeri

Publications and Research

Avirus that reproduces in a host without killing cells can easily establish a successful infection. Previously, we showed that dengue-2, a virus that threatens 40% of the world, induces autophagy, enabling dengue to reproduce in cells without triggering cell death. Autophagy further protects the virus-laden cells from further insults. In this study, we evaluate how it does so; we show that dengue upregulates host pathways that increase autophagy, namely endoplasmic reticulum (ER) stress and ataxia telangiectasiamutated (ATM) signaling followed by production of reactive oxygen species (ROS). Inhibition of ER stress or ATM signaling abrogates the dengueconferred protection against other cell …

Characterization And Recombinant Expression Of Terebrid Venom Peptide From Terebra Guttata, John Moon, Juliette Gorson, Mary Elizabeth Wright, Laurel Yee, Samer Khawaja, Hye Young Shin, Yasmine Karma, Rajeeva Lochan Musunri, Michelle Yun, Mandë Holford

Publications and Research

Venom peptides found in terebrid snails expand the toolbox of active compounds that can be applied to investigate cellular physiology and can be further developed as future therapeutics. However, unlike other predatory organisms, such as snakes, terebrids produce very small quantities of venom, making it difficult to obtain sufficient amounts for biochemical characterization. Here, we describe the first recombinant expression and characterization of terebrid peptide, teretoxin Tgu6.1, from Terebra guttata. Tgu6.1 is a novel forty-four amino acid teretoxin peptide with a VI/VII cysteine framework (C–C–CC–C–C) similar to O, M and I conotoxin superfamilies. A ligation-independent cloning strategy with an ompT …

Genesis And Growth Of Extracellular Vesicle-Derived Microcalcification In Atherosclerotic Plaques, Joshua D. Hutcheson, Claudia Goettsch, Sergio Bertazzo, Natalia Maldonado, Jessica L. Ruiz, Wilson Goh, Katsumi Yabusaki, Tyler Faits, Carlijn Bouten, Gregory Franck, Thibaut Quillard, Peter Libby, Masanori Aikawa, Sheldon Weinbaum, Elena Aikawa

Publications and Research

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the …

Testing Create At Community Colleges: An Examination Of Faculty Perspectives And Diverse Student Gains, Kristy L. Kenyon, Morgan E. Onorato, Alan J. Gottesman, Jamila Hoque, Sally G. Hoskins

Publications and Research

CREATE (Consider, Read, Elucidate the hypotheses, Analyze and interpret the data, and Think of the next Experiment) is an innovative pedagogy for teaching science through the intensive analysis of scientific literature. Initiated at the City College of New York, a minority-serving institution, and regionally expanded in the New York/New Jersey/Pennsylvania area, this methodology has had multiple positive impacts on faculty and students in science, technology, engineering, and mathematics courses. To determine whether the CREATE strategy is effective at the community college (2-yr) level, we prepared 2-yr faculty to use CREATE methodologies and investigated CREATE implementation at community colleges in seven …

"I Bought The Book And I Didn't Need It": What Reading Looks Like At An Urban Community College, Rachel Ihara, Annie Del Principe

Publications and Research

Based on a qualitative study of students’ experiences, we offer a new typology of student reading behaviors across the disciplines at a community college.

Engineered Protein Polymer-Gold Nanoparticle Hybrid Materials For Small Molecule Delivery, Min Dai, Ja Frezzo, E Sharma, R Chen, N Singh, C Yuvienco, E Caglar, S Xiao, A Saxena, Jk Montclare

Publications and Research

We have fabricated protein polymer-gold nanoparticle (P-GNP) nanocomposites that exhibit enhanced binding and delivery properties of the small hydrophobic molecule drug, curcumin, to the model breast cancer cell line, MCF-7. These hybrid biomaterials are constructed via in situ GNP templated-synthesis with genetically engineered histidine tags. The P-GNP nanocomposites exhibit enhanced small molecule loading, sustained release and increased uptake by MCF-7 cells. When compared to the proteins polymers alone, the P-GNPs demonstrate a greater than 7-fold increase in curcumin binding, a nearly 50% slower release profile and more than 2-fold increase in cellular uptake of curcumin. These results suggest that P-GNP …

Classification Accuracy Of Mixed Format Tests: A Bi-Factor Item Response Theory Approach, Wei Wang, Fritz Drasgow, Liwen Liu

Publications and Research

Mixed format tests (e.g., a test consisting of multiple-choice [MC] items and constructed response [CR] items) have become increasingly popular. However, the latent structure of item pools consisting of the two formats is still equivocal. Moreover, the implications of this latent structure are unclear: For example, do constructed response items tap reasoning skills that cannot be assessed with multiple choice items? This study explored the dimensionality of mixed format tests by applying bi-factor models to 10 tests of various subjects from the College Board’s Advanced Placement (AP) Program and compared the accuracy of scores based on the bi-factor analysis with …

Can Colour Vision Re-Evolve? Variation In The X-Linked Opsin Locus Of Cathemeral Azara’S Owl Monkeys (Aotus Azarae Azarae), N. I. Mundy, N. C. Morningstar, Andrea L. Baden, E. Fernandez-Duque, V. M. Davalos, B. J. Bradley

Publications and Research

Background: Do evolutionary specializations lead to evolutionary constraint? This appears plausible, particularly when specialization leads to loss of complex adaptations. In the owl monkey lineage, nocturnality clearly arose from a diurnal ancestor. This behavioural shift was accompanied by morphological changes in the eye and orbit and complete loss of colour vision via missense mutations in the gene encoding the short-wave sensitive visual pigment (SWS opsin). Interestingly, at least one subspecies of owl monkey, Azara’s owl monkey (Aotus azarae azarae), has regained activity in daylight. Given that all primate species that are active in daylight, including primarily diurnal species and species …

Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso

Publications and Research

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimerlike dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization …

Drug Repurposing To Target Ebola Virus Replication And Virulence Using Structural Systems Pharmacology, Zheng Zhao, Che Martin, Raymond Fan, Philip E. Bourne, Lei Xie

Publications and Research

Background: The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation.

Results: One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence …

Sexual Behavior Varies Between Same-Race And Different-Race Partnerships: A Daily Diary Study Of Highly Sexually Active Black, Latino, And White Gay And Bisexual Men, Christian Grov, Demetria Cain, H. Jonathan Rendina, Ana Ventuneac, Jeffrey T. Parsons

Publications and Research

Background. Gay and bisexual men (GBM) are at elevated risk for gonorrhea and chlamydia trachomatis (GC/CT). Rectal GC/CT symptoms may be less obvious than urethral, increasing opportunities for undiagnosed rectal GC/CT.

Method. A U.S. national sample of 1,071 GBM completed urethral and rectal GC/CT testing and an online survey.

Results. In total, 6.2% were GC/CT positive (5.3% rectal, 1.7% urethral). We calculated adjusted (for education, race, age, relationship status, having health insurance, and income) odds ratios for factors associated with rectal and urethral GC/CT diagnoses. Age was inversely associated with urethral and rectal GC/CT. Compared to White men, Latinos had …

Cogenerative Dialogue: Developing Biology Learning Accommodations For Students With Disabilities, Edward Lehner

Publications and Research

A prominent challenge, at times under-addressed in the science education literature, is considering what types of learning accommodations science teachers should employ for students with disabilities. Outside of science education, researchers have consistently outlined how Universal Design for Learning (UDL) is one efficient means by which to engage students with disabilities in the curriculum. This paper presents the results of a research study in which teachers employed cogenerative dialogue as a learning space where UDL was used to differentiate and individualize instruction in an inclusive biology class. The data originated from a larger, ongoing, longitudinal ethnography of science learning in …

Eggshell Pigment Composition Covaries With Phylogeny, Kaat Brulez, Ivan Miksik, Christopher R. Cooney, Mark E. Hauber, Paul George Lovell, Golo Maurer, Steven J. Portugal, Douglas Russell, Silas James Reynolds, Phillip Cassey

Publications and Research

No single hypothesis is likely to explain the diversity in eggshell coloration and patterning across birds, suggesting that eggshell appearance is most likely to have evolved to fulfill many nonexclusive functions. By controlling for nonindependent phylogenetic associations between related species, we describe this diversity using museum eggshells of 71 British breeding passerine species to examine how eggshell pigment composition and concentrations vary with phylogeny and with life-history and nesting ecology traits. Across species, concentrations of biliverdin and protoporphyrin, the two main pigments found in eggshells, were strongly and positively correlated, and both pigments strongly covaried with phylogenetic relatedness. Controlling for …

Editorial: Systems Biology And Ecology Of Microbial Mat Communities, Martin G. Klotz, Donald A. Bryant, Jim K. Fredrickson, William P. Inskeep, Michael Kühl

Publications and Research

No abstract provided.

Toward Repurposing Metformin As A Precision Anti-Cancer Therapy Using Structural Systems Pharmacology, Thomas Hart, Shihab Dider, Weiwei Han, Hua Xu, Zhongming Zhao, Lei Xie

Publications and Research

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally …

Genome Assembly And Geospatial Phylogenomics Of The Bed Bug Cimex Lectularius, Jeffrey A. Rosenfeld, Darryl Reeves, Mercer R. Brugler, Apurva Narechania, Sabrina Simon, Russell Durrett, Jonathan Foox, Kevin Shianna, Michael C. Schatz, Jorge Gandara, Ebrahim Afshinnekoo, Ernest T. Lam, Alex R. Hastie, Saki Chan, Han Cao, Michael Saghbini, Alex Kentsis, Paul J. Planet, Vladyslav Kholodovych, Michael Tessler, Richard Baker, Rob Desalle, Louis N. Sorkin, Sergios-Orestis Kolokotronis, Mark E. Siddall, George Amato, Christopher E. Mason

Publications and Research

The common bed bug (Cimex lectularius) has been a persistent pest of humans for thousands of years, yet the genetic basis of the bed bug’s basic biology and adaptation to dense human environments is largely unknown. Here we report the assembly, annotation and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies. A RNA-seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models. The most pronounced change in gene expression during the life cycle occurs after feeding on …

A Novel Compressed Sensing Method For Magnetic Resonance Imaging: Exponential Wavelet Iterative Shrinkage-Thresholding Algorithm With Random Shift, Yudong Zhang, Jiquan Yang, Jianfei Yang, Aijun Liu, Ping Sun

Publications and Research

Aim. It can help improve the hospital throughput to accelerate magnetic resonance imaging (MRI) scanning. Patients will benefit from less waiting time. Task. In the last decade, various rapid MRI techniques on the basis of compressed sensing (CS) were proposed. However, both computation time and reconstruction quality of traditional CS-MRI did not meet the requirement of clinical use.

Method. In this study, a novel method was proposed with the name of exponential wavelet iterative shrinkagethresholding algorithm with random shift (abbreviated as EWISTARS). It is composed of three successful components: (i) exponential wavelet transform, (ii) iterative shrinkage-thresholding algorithm, and (iii) randomshift. …

Neighborhood Matters: The Impact Of Hispanic Ethnic Density On Future Depressive Symptoms 1-Year Following An Acs Event Among Hispanic Patients, Ellen-Ge Denton, Jonathan Shaffer, Carmela Alcantara, Esteban Cadermil

Publications and Research

The Ethnic Density hypothesis posits that living around others from similar ethnic backgrounds reduces the risk of adverse mental health outcomes such as depression. Contrary to this hypothesis, previous work has shown that Hispanic ethnic density is cross-sectionally associated with increased depressive symptom severity among patients hospitalized with an acute coronary syndrome (ACS; myocardial infarction or unstable angina pectoris). To date, no study has examined the prospective association of Hispanic ethnic density on long-term depressive symptom severity following an acute medical event. We prospectively assessed the impact of Hispanic ethnic density on depressive symptoms, 1-year following an ACS event, among …

Hypersexual, Sexually Compulsive, Or Just Highly Sexually Active? Investigating Three Distinct Groups Of Gay And Bisexual Men And Their Profiles Of Hiv-Related Sexual Risk, Jeffrey T. Parsons, H. Jonathan Rendina, Ana Ventuneac, Raymond L. Moody, Christian Grov

Publications and Research

Emerging research supports the notion that sexual compulsivity (SC) and hypersexual disorder (HD) among gay and bisexual men (GBM) might be conceptualized as comprising three groups—Neither SC nor HD; SC only, and Both SC and HD—that capture distinct levels of severity across the SC/HD continuum. We examined data from 370 highly sexually active GBM to assess how the three groups compare across a range of risk factors for HIV infection. Comparisons focused on psychosexual measures—temptation for condomless anal sex (CAS), self-efficacy for avoiding CAS, sexual excitation and inhibition—as well as reports of actual sexual behavior. Nearly half (48.9%) of this …

Losing It: The Construction And Stigmatization Of Obesity On Reality Television In The United States, Alisa Roost

Publications and Research

No abstract provided.

Hydrodynamic Loading In Concomitance With Exogenous Cytokine Stimulation Modulates Differentiation Of Bovine Mesenchymal Stem Cells Towards Osteochondral Lineages, Stephen M. Goldman, Gilda A. Barabino

Publications and Research

Background: Mesenchymal stem cells (MSCs) are viewed as a having significant potential for tissue engineering and regenerative medicine therapies. Clinical implementation of MSCs, however, demands that their preparation be stable and reproducible. Given that environmental and bioprocessing parameters such as substrate stiffness, seeding densities, culture medium composition, and mechanical loading can result in undirected differentiation of the MSC population, the objective of this study was to systematically investigate how hydrodynamic loading influences the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) towards the osteochondral lineages both in the presence and absence of exogenous, inductive factors.

Methods: Expanded bovine MSCs were …

Are We Overestimating The Niche? Removing Marginal Localities Helps Ecological Niche Models Detect Environmental Barriers, Mariano Soley-Guardia, Eliécer E. Gutiérrez, Darla M. Thomas, José Ochoa-G, Marisol Aguilera, Robert P. Anderson

Publications and Research

Correlative ecological niche models (ENMs) estimate species niches using occurrence records and environmental data. These tools are valuable to the field of biogeography, where they are commonly used to infer potential connectivity among populations. However, a recent study showed that when locally relevant environmental data are not available, records from patches of suitable habitat protruding into otherwise unsuitable regions (e.g., gallery forests within dry areas) can lead to overestimations of species niches and their potential distributions. Here, we test whether this issue obfuscates detection of an obvious environmental barrier existing in northern Venezuela – that of the hot and xeric …

The Ubiquitin-Proteasome System: Potential Therapeutic Targets For Alzheimer’S Disease And Spinal Cord Injury, Bing Gong, Miroslav Radulovic, Maria E. Figueiredo-Pereira, Christopher Cardozo

Publications and Research

The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in eukaryotes. Herein, we will review advances in the understanding of the role of several proteins of the UPS in Alzheimer’s disease (AD) and functional recovery after spinal cord injury (SCI). The UPS consists of many factors that include E3 ubiquitin ligases, ubiquitin hydrolases, ubiquitin and ubiquitin-like molecules, and the proteasome itself. An extensive body of work links UPS dysfunction with AD pathogenesis and progression. More recently, the UPS has been shown to have vital roles in recovery of function after SCI. The ubiquitin hydrolase (Uch-L1) has been proposed to …

Characterization Of Induced Pluripotent Stem Cell Microvesicle Genesis, Morphology And Pluripotent Content, Jing Zhou, Shima Ghoroghi, Alberto Benito-Martin, Hao Wu, Uchenna John Unachukwu, Linda Saxe Einbond, Sara Guariglia, Hector Peinado, Stephen Redenti

Publications and Research

Microvesicles (MVs) are lipid bilayer-covered cell fragments that range in diameter from 30 nm–1uM and are released from all cell types. An increasing number of studies reveal that MVs contain microRNA, mRNA and protein that can be detected in the extracellular space. In this study, we characterized induced pluripotent stem cell (iPSC) MV genesis, content and fusion to retinal progenitor cells (RPCs) in vitro. Nanoparticle tracking revealed that iPSCs released approximately 2200 MVs cell/hour in the first 12 hrs with an average diameter of 122 nm. Electron and light microscopic analysis of iPSCs showed MV release via lipid bilayer budding. …

Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response To Pulmonary Tuberculosis In A Rabbit Model, Selvakumar Subbian, Liana Tsenova, Jennifer Holloway, Blas Peixoto, Paul O'Brien, Veronique Dartois, Vikram Khetani, Jerome B. Zeldis, Gilla Kaplan

Publications and Research

Objectives: Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB).We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection.

Methods: A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with orwithout CC-11050, starting at fourweeks post infection. The …

The Human Disease-Associated Ab Amyloid Core Sequence Forms Functional Amyloids In A Fungal Adhesin, Rachele D. Rameau, Desmond N. Jackson, Audrey Beaussary, Yves F. Dufrêne, Peter N. Lipke

Publications and Research

There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human A protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein …

Targeted Curing Of All Lysogenic Bacteriophage From Streptococcus Pyogenes Using A Novel Counter-Selection Technique, Chad W. Euler, Barbara Juncosa, Patricia A. Ryan, Douglas R. Deutsch, W. Michael Mcshan, Vincent A. Fischetti

Publications and Research

Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease- causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach …

Site-Specifically Labeled Immunoconjugates For Molecular Imaging—Part 1: Cysteine Residues And Glycans, Pierre Adumeau, Sai Kiran Sharma, Colleen Brent, Brian M. Zeglis

Publications and Research

Due to their remarkable selectivity and specificity for cancer biomarkers, immunoconjugates have emerged as extremely promising vectors for the delivery of diagnostic radioisotopes and fluorophores to malignant tissues. Paradoxically, however, these tools for precision medicine are synthesized in a remarkably imprecise way. Indeed, the vast majority of immunoconjugates are created via the random conjugation of bifunctional probes (e.g., DOTA-NCS) to amino acids within the antibody (e.g., lysines). Yet antibodies have multiple copies of these residues throughout their macromolecular structure, making control over the location of the conjugation reaction impossible. This lack of site specificity can lead to the formation of …