Medicine and Health Sciences Commons^™

Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphologic maturation. Moreover, it remains unknown whether neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and use identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage …

Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis, Rebecca A. Drummond, Jigar V. Desai, Amy P. Hsu, Vasileios Oikonomou, Donald C. Vinh, Joshua A. Acklin, Michael S. Abers, Magdalena A. Walkiewicz, Sarah L. Anzick, Muthulekha Swamydas, Simon Vautier, Mukil Natarajan, Andrew J. Oler, Daisuke Yamanaka, Katrin D. Mayer-Barber, Yoichiro Iwakura, David Bianchi, Brian Driscoll, Ken Hauck, Ahnika Kline, Nicholas S.P. Viall, Christa S. Zerbe, Elise M.N. Ferré, Monica M. Schmitt, Tom Dimaggio, Stefania Pittaluga, John A. Butman, Adrian M. Zelazny, Yvonne R. Shea, Cesar A. Arias, Cameron Ashbaugh, Maryam Mahmood, Zelalem Temesgen, Alexander G. Theofiles, Masayuki Nigo, Varsha Moudgal, Karen C. Bloch, Sean G. Kelly, M. Suzanne Whitworth, Ganesh Rao, Cindy J. Whitener, Neema Mafi, Juan Gea-Banacloche, Lawrence C. Kenyon, William R. Miller, Katia Boggian, Andrea Gilbert, Matthew Sincock, Alexandra F. Freeman, John E. Bennett, Rodrigo Hasbun, Constantinos M. Mikelis, Kyung J. Kwon-Chung, Yasmine Belkaid, Gordon D. Brown, Jean K. Lim, Douglas B. Kuhns, Steven M. Holland, Michail S. Lionakis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, β-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1β in response to β-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1β and …

The Nogo Receptor Ngr2, A Novel Αvβ3 Integrin Effector, Induces Neuroendocrine Differentiation In Prostate Cancer, Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter Mccue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, …

Diagnostic Accuracy Of Macular Thickness Map And Texture En Face Images For Detecting Glaucoma In Eyes With Axial High Myopia, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Mark Christopher, Leslie Hyman, Jost B Jonas, Robert N Weinreb, Linda M Zangwill

Wills Eye Hospital Papers

Purpose: To evaluate the diagnostic accuracy of a novel optical coherence tomography texture-based en face image analysis (SALSA-Texture) that requires segmentation of only 1 retinal layer for glaucoma detection in eyes with axial high myopia, and to compare SALSA-Texture with standard macular ganglion cell-inner plexiform layer (GCIPL) thickness, macular retinal nerve fiber layer (mRNFL) thickness, and ganglion cell complex (GCC) thickness maps.

Design: Comparison of diagnostic approaches.

Methods: Cross-sectional data were collected from 92 eyes with primary open-angle glaucoma (POAG) and 44 healthy control eyes with axial high myopia (axial length >26 mm). Optical coherence tomography texture en face images, …

A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes, Brandie Morris Verdone, Maria Elena Cicardi, Xinmei Wen, Sindhu Sriramoji, Katelyn Russell, Shashirekha S Markandaiah, Brigid K Jensen, Karthik Krishnamurthy, Aaron R. Haeusler, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these …

68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …

When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects Among Individuals With Cancer And Their Caregivers, Brandy-Joe Milliron, Lora Packel, Dan Dychtwald, Cynthia Klobodu, Laura Pontiggia, Ochi Ogbogu, Byron Barksdale, Jonathan Deutsch

Institute of Emerging Health Professions Faculty Papers

Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced …