Medicine and Health Sciences Commons^™

Fungal Melanin: What Do We Know About Structure?, Joshua D. Nosanchuk, Ruth E. Stark, Arturo Casadevall

Publications and Research

The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.

Pvt1 Exon 9: A Potential Biomarker Of Aggressive Prostate Cancer?, Adeodat Ilboudo, Jyoti Chouhan, Brian K. Mcneil, Joseph R. Osborne, Olorunseun O. Ogunwobi

Publications and Research

Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are …

Impact Of Executive Order 13211 On Environmental Regulation: An Empirical Study, Elizabeth Ann Glass Geltman

Publications and Research

A great deal has been written about the Energy Policy Act of 2005 exempting oil and gas operations using hydraulic fracturing from the purview of certain federal environmental laws. Far less attention has been paid to George W. Bush’s Executive Order 13211 (EO 13211), entitled “Actions Concerning Regulations that Significantly Affect Energy Supply, Distribution or Use.” The executive order requires federal agencies to evaluate the impact of federal regulations on “supply, distribution and use of energy.” This study examined the impact of EO 13211 on United States environmental and conservation regulations proposed and promulgated by federal agencies. The study found …

Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman

Publications and Research

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …

Common Cell Shape Evolution Of Two Nasopharyngeal Pathogens, Frédéric J. Veyrier, Nicolas Biais, Pablo Morales, Nouria Belkacem, Cyril Guilhen, Sylvia Ranjeva, Odile Sismeiro, Gérard Péhau-Arnaudet, Eduardo P. Rocha, Catherine Werts, Muhamed-Kheir Taha, Ivo G. Boneca

Publications and Research

Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Rationale, Design And Respondent Characteristics Of The 2013–2014 New York City Health And Nutrition Examination Survey (Nyc Hanes 2013–2014), Lorna E. Thorpe, Carolyn Greene, Amy Freeman, Elisabeth Snell, Jesica S. Rodriguez-Lopez, Martin Frankel, Amado Punsalang Jr., Claudia Chernov, Elizabeth Lurie, Mark Friedman, Ram Koppaka, Sharon E. Perlman

Publications and Research

Purpose. Capacity to monitor non-communicable diseases (NCDs) at state or local levels is limited. Emerging approaches include using biomeasures and electronic health record (EHR) data. In 2004, New York City (NYC) performed a population-based health study on adult residents using biomeasures (NYC Health and Nutrition Examination Study, or NYC HANES), modeled after NHANES. A second NYC HANES was launched in 2013 to examine change over time, evaluate municipal policies, and validate a proposed EHR-based surveillance system. We describe the rationale and methods of NYC HANES 2013–2014.

Methods. NYC HANES was a population-based, cross-sectional survey of NYC adults using three-stage cluster …

Lesion-Specific Immune Response In Granulomas Of Patients With Pulmonary Tuberculosis: A Pilot Study, Selvakumar Subbian, Liana Tsenova, Mi-Jeong Kim, Helen C. Wainwright, Annalie Visser, Nirmalya Bandyopadhyay, Joel S. Bader, Petros C. Karakousis, Gabriele B. Murrmann, Linda-Gail Bekker, David G. Russell, Gilla Kaplan

Publications and Research

The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different …

The Regulatory Function Of Sphingosine-1-Phosphate Signaling Axis On Regulatory T Cells In Colorectal Cancer, Andrew V. Nguyen, Yuan-Yuan Wu, Elaine Y. Lin

Publications and Research

In tumors associated with inflammation such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), high numbers of regulatory T cells (Tregs) are associated with both favorable and poor prognoses. The functions of Tregs in CRC remain elusive and have yet to be clearly defined. With new evidence supporting many subsets of Tregs, the research on the development and functions of these cells has begun to come to fruition. The sphingosine 1 phosphate (S1P) pathway was recently reported to regulate the development and function of regulatory T cells. This pathway may shine new light into the pleiotropic nature of these …

Orbitofrontal 18f-Dopa Uptake And Movement Preparation In Parkinson’S Disease, Lucio Marinelli, Arnoldo Piccardo, Laura Mori, Silvia Morbelli, Nicola Girtler, Antonio Castaldi, Agnese Picco, Carlo Trompetto, Maria Felice Ghilardi, Giovanni Abbruzzese, Flavio Nobili

Publications and Research

In Parkinson’s disease (PD) degeneration of mesocortical dopaminergic projections may determine cognitive and behavioral symptoms. Choice reaction time task is related to attention, working memory, and goal-directed behavior. Such paradigm involves frontal cortical circuits receiving mesocortical dopamine which are affected early in PD. The aim of this study is to characterize the role of dopamine on the cognitive processes that precede movement in a reaction time paradigm in PD.We enrolled 16 newly diagnosed and untreated patientswith PDwithout cognitive impairment or depression and 10 control subjectswith essential tremor. They performed multiple-choice reaction time task with the right upper limb and brain …

Nosh-Aspirin (Nbs-1120), A Dual Nitric Oxide And Hydrogen Sulfide-Releasing Hybrid, Reduces Inflammatory Pain, Miriam D. Fonseca, Fernando Q. Cunha, Khosrow Kashfi, Thiago M. Cunha

Publications and Research

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dosedependent (5–150 lmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin’s antinociceptive effect was also …