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YY1 Regulates the Germinal Center Reaction by Inhibiting Apoptosis

Thu, 10/13/2016 - 8:53pm

The germinal center (GC) reaction produces high-affinity Abs for a robust adaptive immune response. When dysregulated, the same processes cause GC B cells to become susceptible to lymphomagenesis. It is important to understand how the GC reaction is regulated. In this study, we show that transcription factor YY1 is required to maintain a robust GC reaction in mice. Selective ablation of YY1 significantly decreased in the frequency and number of GC B cells during the GC reaction. This decrease of GC B cells was accompanied by increased apoptosis in these cells. Furthermore, we found that loss of YY1 disrupted the balance between dark zones and light zones, leading to a preferential decrease in dark zone cells. Collectively, these results indicate that YY1 plays an important role in regulating the balance between dark zone and light zone cells in GCs and between survival and death of GC B cells.

Prion-like domains as epigenetic regulators, scaffolds for subcellular organization, and drivers of neurodegenerative disease

Thu, 10/13/2016 - 8:53pm

Key challenges faced by all cells include how to spatiotemporally organize complex biochemistry and how to respond to environmental fluctuations. The budding yeast Saccharomyces cerevisiae harnesses alternative protein folding mediated by yeast prion domains (PrDs) for rapid evolution of new traits in response to environmental stress. Increasingly, it is appreciated that low complexity domains similar in amino acid composition to yeast PrDs (prion-like domains; PrLDs) found in metazoa have a prominent role in subcellular cytoplasmic organization, especially in relation to RNA homeostasis. In this review, we highlight recent advances in our understanding of the role of prions in enabling rapid adaptation to environmental stress in yeast. We also present the complete list of human proteins with PrLDs and discuss the prevalence of the PrLD in nucleic-acid binding proteins that are often connected to neurodegenerative disease, including: ataxin 1, ataxin 2, FUS, TDP-43, TAF15, EWSR1, hnRNPA1, and hnRNPA2. Recent paradigm-shifting advances establish that PrLDs undergo phase transitions to liquid states, which contribute to the structure and biophysics of diverse membraneless organelles. This structural functionality of PrLDs, however, simultaneously increases their propensity for deleterious protein-misfolding events that drive neurodegenerative disease. We suggest that even these PrLD-misfolding events are not irreversible and can be mitigated by natural or engineered protein disaggregases, which could have important therapeutic applications. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.

Biorepository Booth at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Biorepository booth at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Arlene Ash, PhD, at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Arlene Ash, PhD, at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Chancellor Michael F. Collins, MD, at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Chancellor Michael F. Collins, MD, at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Faculty at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Faculty at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Dean Terence Flotte, MD at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Dean Terence Flotte, MD at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Keynote Address at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Keynote address at the 6th annual UMass Center for Clinical and Translational Science Research Retreat held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Katherine Luzuriaga, MD, at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

Katherine Luzuriaga, MD at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

David McManus, Vasan S. Ramachandran, and Nate Hafer at 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:06pm

David McManus, MD, Keynote speaker Vasan S. Ramachandran, MD, and Nate Hafer, PhD, at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Mary Lee, MD, at Mini Symposia Presentation at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Mary Lee, MD, at a Mini Symposia presentation at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Mini Symposia Presentation at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Mini Symposia presentation at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Mini Symposia Presentation at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Mini Symposia Presentation at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Mini Symposia Presentation at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Mini Symposia Presentation at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Dean Terence R. Flotte, MD during Mini Symposia Presentation at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Dean Terence Flotte during Mini Symposia presentation at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Mini Symposia Presentation at the 2016 UMCCTS Research Retreat

Thu, 10/13/2016 - 7:05pm

Mini Symposia presentation at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

2016 UMCCTS Research Retreat Poster Session

Thu, 10/13/2016 - 7:05pm

Poster Session at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

2016 UMCCTS Research Retreat Poster Session

Thu, 10/13/2016 - 7:05pm

Poster Session at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

2016 UMCCTS Research Retreat Poster Session

Thu, 10/13/2016 - 7:05pm

Poster Session at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

2016 UMCCTS Research Retreat Poster Session

Thu, 10/13/2016 - 7:05pm

Poster Session at the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.