Epigenetic dysregulation is a common mechanism shared by molecularly and clinically heterogenous neurodegenerative diseases (NDs). Histone acetylation homeostasis, maintained by the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), is necessary for appropriate gene expression and neuronal function. Disruption of neural acetylation homeostasis has been implicated in multiple types of NDs including Alzheimer’s disease (AD), yet mechanisms underlying alterations remain unclear. We show that like AD, disruption of Tip60 HAT/HDAC2 balance with concomitant epigenetic repression of common Tip60 target neuroplasticity genes occurs early in multiple types of Drosophila ND models such as Parkinson’s Disease (PD), Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Repressed neuroplasticity genes show reduced enrichment of Tip60 and epigentic acetylation signatures at all gene loci examined with certain genes showing inappropriate HDAC2 repressor enrichment. Functional neuronal consequences for these disease conditions are reminiscent of human pathology and include locomotion, synapse morphology, and short-term memory deficits. Increasing Tip60 HAT levels specifically in the mushroom body learning and memory center in the Drosophila brain protects against locomotion and short-term memory function deficits in multiple NDs. Together, our results support a model by which Tip60 protects against neurological impairments in different NDs via similar modes of action.

Mycobacteriophage Superphikiman is a cluster J bacteriophage which was isolated from soil collected in Philadelphia, PA. Superphikiman has a 109,799-bp genome with 239 predicted genes, including 2 tRNA genes.

Introduction and Importance. Rosai-Dorfman disease (RDD) is a rare, benign type II histiocytosis characterized by the infiltration of S100+ histiocytes and emperipolesis. The disease may present in the lymph nodes (nodal RDD), in extranodal sites, or in both nodal and extranodal sites. Among those patients who present exclusively in extranodal sites, only a minority of cases present in the soft tissue. Case Presentation. An 18-year-old female presented to orthopedic oncology clinic with a chief complaint of a mass located in her lower back. The patient underwent excision of the lumbosacral mass. Pathologic review demonstrated emperipolesis of lymphocytes and plasma cells within enlarged, eosinophilic histiocytes in a background of lymphoplasmacytic infiltration and collagenous stroma. Immunohistochemical staining demonstrated S100+ and CD163+ histiocytes, consistent with diagnosis of soft tissue RDD. Clinical Discussion. Histologically, RDD is generally characterized by emperipolesis—the presence of intact lymphocytes within the histiocyte cytoplasm—and a mixed infiltrate of S100+ histiocytes, mononuclear cells, plasma cells, and lymphocytes. Although soft tissue RDD may histologically resemble nodal RDD, soft tissue RDD also demonstrates some notable histologic differences including the lack of nodal architecture, the presence of increased fibrosis and collagen deposition, and generally fewer RDD cells. Conclusion. This case presentation demonstrates one few reports of isolated soft tissue RDD within the lumbosacral region without associated lymphadenopathy or skin changes and highlights the heterogeneity that still exists in the treatment paradigm of extranodal RDD.