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Full-Text Articles in Medicine and Health Sciences
Sparse Recurrent Excitatory Connectivity In The Microcircuit Of The Adult Mouse And Human Cortex., Stephanie C Seeman, Luke Campagnola, Pasha A Davoudian, Alex Hoggarth, Travis A Hage, Alice Bosma-Moody, Christopher A Baker, Jung Hoon Lee, Stefan Mihalas, Corinne Teeter, Andrew L Ko, Jeffrey G Ojemann, Ryder P Gwinn, Daniel L Silbergeld, Charles Cobbs, John Phillips, Ed Lein, Gabe Murphy, Christof Koch, Hongkui Zeng, Tim Jarsky
Sparse Recurrent Excitatory Connectivity In The Microcircuit Of The Adult Mouse And Human Cortex., Stephanie C Seeman, Luke Campagnola, Pasha A Davoudian, Alex Hoggarth, Travis A Hage, Alice Bosma-Moody, Christopher A Baker, Jung Hoon Lee, Stefan Mihalas, Corinne Teeter, Andrew L Ko, Jeffrey G Ojemann, Ryder P Gwinn, Daniel L Silbergeld, Charles Cobbs, John Phillips, Ed Lein, Gabe Murphy, Christof Koch, Hongkui Zeng, Tim Jarsky
Articles, Abstracts, and Reports
Generating a comprehensive description of cortical networks requires a large-scale, systematic approach. To that end, we have begun a pipeline project using multipatch electrophysiology, supplemented with two-photon optogenetics, to characterize connectivity and synaptic signaling between classes of neurons in adult mouse primary visual cortex (V1) and human cortex. We focus on producing results detailed enough for the generation of computational models and enabling comparison with future studies. Here, we report our examination of intralaminar connectivity within each of several classes of excitatory neurons. We find that connections are sparse but present among all excitatory cell classes and layers we sampled, …
Novel Tnf Receptor-1 Inhibitors Identified As Potential Therapeutic Candidates For Traumatic Brain Injury, Rachel K. Rowe, Jordan L. Harrison, Hongtao Zhang, Adam D. Bachstetter, David P. Hesson, Bruce F. O'Hara, Mark I. Greene, Jonathan Lifshitz
Novel Tnf Receptor-1 Inhibitors Identified As Potential Therapeutic Candidates For Traumatic Brain Injury, Rachel K. Rowe, Jordan L. Harrison, Hongtao Zhang, Adam D. Bachstetter, David P. Hesson, Bruce F. O'Hara, Mark I. Greene, Jonathan Lifshitz
Sanders-Brown Center on Aging Faculty Publications
Background: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel …
Specificity In Sociality: Mice And Prairie Voles Exhibit Different Patterns Of Peer Affiliation, Annaliese K. Beery, Jennifer D. Christensen, Nicole S. Lee, Katrina L. Blandino
Specificity In Sociality: Mice And Prairie Voles Exhibit Different Patterns Of Peer Affiliation, Annaliese K. Beery, Jennifer D. Christensen, Nicole S. Lee, Katrina L. Blandino
Psychology: Faculty Publications
Social behavior is often described as a unified concept, but highly social (group- living) species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex) during extended choice tests, although short-term preferences are not known. Mice (Mus musculus) are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie …
Spatial Relationship Between Bone Formation And Mechanical Stimulus Within Cortical Bone: Combining 3d Fluorochrome Mapping And Poroelastic Finite Element Modelling, Alessandra Carriero, A. F. Pereira, A. J. Wilson, S. Castagno, B. Javaheri, A. A. Pitsillides, M. Marenzana, S. J. Shefelbine
Spatial Relationship Between Bone Formation And Mechanical Stimulus Within Cortical Bone: Combining 3d Fluorochrome Mapping And Poroelastic Finite Element Modelling, Alessandra Carriero, A. F. Pereira, A. J. Wilson, S. Castagno, B. Javaheri, A. A. Pitsillides, M. Marenzana, S. J. Shefelbine
Publications and Research
Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing ‘slice and view’3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average …
Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta
Department of Cancer Biology Faculty Papers
Philadelphia chromosome–positive acute lymphoblastic leukemia (Phþ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Phþ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Phþ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …
Response And Resistance To Paradox-Breaking Braf Inhibitor In Melanomas, Edward J. Hartsough, Curtis H. Kugel, Michael J. Vido, Adam C. Berger, Timothy J. Purwin, Allison F. Goldberg, Michael A. Davies, Matthew J. Schiewer, Karen E. Knudsen, Gideon Bollag, Andrew E. Aplin
Response And Resistance To Paradox-Breaking Braf Inhibitor In Melanomas, Edward J. Hartsough, Curtis H. Kugel, Michael J. Vido, Adam C. Berger, Timothy J. Purwin, Allison F. Goldberg, Michael A. Davies, Matthew J. Schiewer, Karen E. Knudsen, Gideon Bollag, Andrew E. Aplin
Department of Cancer Biology Faculty Papers
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was …