Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation.

RNA Polymerase II (Pol II) and transcription factors form concentrated hubs in cells via multivalent protein-protein interactions, often mediated by proteins with intrinsically disordered regions. During Herpes Simplex Virus infection, viral replication compartments (RCs) efficiently enrich host Pol II into membraneless domains, reminiscent of liquid-liquid phase separation. Despite sharing several properties with phase-separated condensates, we show that RCs operate via a distinct mechanism wherein unrestricted nonspecific protein-DNA interactions efficiently outcompete host chromatin, profoundly influencing the way DNA-binding proteins explore RCs. We find that the viral genome remains largely nucleosome-free, and this increase in accessibility allows Pol II and other DNA-binding proteins to repeatedly visit nearby DNA binding sites. This anisotropic behavior creates local accumulations of protein factors despite their unrestricted diffusion across RC boundaries. Our results reveal underappreciated consequences of nonspecific DNA binding in shaping gene activity, and suggest additional roles for chromatin in modulating nuclear function and organization

Effect of membrane exposure on guided bone regeneration: A systematic review and metaâ analysis

AimsThis review aimed at investigating the effect of membrane exposure on guided bone regeneration (GBR) outcomes at periâ implant sites and edentulous ridges.Material and MethodsElectronic and manual literature searches were conducted by two independent reviewers using four databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for articles up to February 2017. Articles were included if they were human clinical trials or case series reporting outcomes of GBR procedures with and without membrane exposure. A randomâ effects metaâ analysis was conducted, and the weighted mean difference (WMD) between the two groups and 95% confidence interval (CI) were reported.ResultsOverall, eight articles were included in the quantitative analysis. The WMD of the horizontal bone gain at edentulous ridges was â 76.24% (95% CI = â 137.52% to â 14.97%, p = .01) between sites with membrane exposure and without exposure. In addition, the WMD of the dehiscence reduction at periâ implant sites was â 27.27% (95% CI of â 45.87% to â 8.68%, p = .004). Both analyses showed significantly favorable outcomes at the sites without membrane exposure.ConclusionBased on the findings of this study, membrane exposure after GBR procedures has a significant detrimental influence on the outcome of bone augmentation. For the edentulous ridges, the sites without membrane exposure achieved 74% more horizontal bone gain than the sites with exposure. For periâ implant dehiscence defects, the sites without membrane exposure had 27% more defect reduction than the sites with exposure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142961/1/clr13121.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142961/2/clr13121_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142961/3/clr13121-sup-0003-checklist.pd

The significance of surgically modifying soft tissue phenotype around fixed dental prostheses: An American Academy of Periodontology best evidence review

BackgroundThis systematic review endeavored to investigate the effect of soft tissue phenotype modification therapy (PhMT- s) at sites with a tooth or an implant supported fixed dental prosthesis.MethodsA comprehensive literature search was conducted by two independent examiners to identify relevant studies reporting differences in clinical, esthetic, or radiographic outcomes of interest between sites underwent PhMT- s and sites that remained untreated. Risk of bias assessment was calculated for all included studies. Meta- analyses involving endpoints of interest were performed when feasible.ResultsNo controlled studies pertaining to tooth sites were identified. A total of six articles reporting on the outcomes of buccal soft tissue phenotype modification around implants were selected, of which, five were included in the meta- analyses. Quantitative analyses showed a weighted mean difference (WMD) of 0.98 mm (95% CI = 0.25 to 1.72 mm, P = 0.009) for change of tissue thickness; a WMD of - 4.87% (95% CI = - 34.27 to 24.53%, P = 0.75) for bleeding on probing (BOP); a WMD of 0.36 mm (95% CI = 0.12 to 0.59 mm, P = 0.003) for mucosal recession (MR); a WMD of 0.13 mm (95% CI = - 0.11 to 0.36 mm, P = 0.30 for probing depth (PD); a WMD of 1.08 (95% CI = - 0.39 to 2.55, P = 0.15) for pink esthetic score (PES), and a WMD of 0.40 mm (95% CI = - 0.34 to 1.14 mm, P = 0.28) for marginal bone loss (MBL).ConclusionsSurgical modification of peri- implant soft tissue phenotype via PhMT- s may decrease the amount of MR. Future clinical trials are needed to warrant the clinical benefits of modifying soft tissue phenotype around tooth- supported restorations.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/1/jper10458-sup-0006-figureS1F.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/2/jper10458_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/3/jper10458-sup-0001-figureS1A.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/4/jper10458-sup-0005-figureS1E.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/5/jper10458-sup-0004-figureS1D.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/6/jper10458-sup-0003-figureS1C.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/7/jper10458-sup-0002-figureS1B.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/8/jper10458.pd

2015-2016 Master Class - Penderecki String Quartet

The Penderecki String Quartet Performance (February 27, 2016) - Programhttps://spiral.lynn.edu/conservatory_masterclasses/1020/thumbnail.jp

Structure and function of the bacterial heterodimeric ABC transporter CydDC: stimulation of ATPase activity by thiol and heme compounds.

In Escherichia coli, the biogenesis of both cytochrome bd-type quinol oxidases and periplasmic cytochromes requires the ATP-binding cassette-type cysteine/GSH transporter, CydDC. Recombinant CydDC was purified as a heterodimer and found to be an active ATPase both in soluble form with detergent and when reconstituted into a lipid environment. Two-dimensional crystals of CydDC were analyzed by electron cryomicroscopy, and the protein was shown to be made up of two non-identical domains corresponding to the putative CydD and CydC subunits, with dimensions characteristic of other ATP-binding cassette transporters. CydDC binds heme b. Detergent-solubilized CydDC appears to adopt at least two structural states, each associated with a characteristic level of bound heme. The purified protein in detergent showed a weak basal ATPase activity (approximately 100 nmol Pi/min/mg) that was stimulated ∼3-fold by various thiol compounds, suggesting that CydDC could act as a thiol transporter. The presence of heme (either intrinsic or added in the form of hemin) led to a further enhancement of thiol-stimulated ATPase activity, although a large excess of heme inhibited activity. Similar responses of the ATPase activity were observed with CydDC reconstituted into E. coli lipids. These results suggest that heme may have a regulatory role in CydDC-mediated transmembrane thiol transport

One-step Preparation of ZnO Electron Transport Layers Functionalized with Benzoic Acid Derivatives

We present a "one-step" approach to modify ZnO electron transport layers (ETLs) used in organic solar cells. This approach involves adding benzoic acid (BZA) derivatives directly to the ZnO precursor solution, which are then present at the surface of the resulting ZnO film. We demonstrate this approach for three different BZA derivatives, namely benzoic acid, chlorobenzoic acid, and 4-hydrazinobenzoic acid. For all molecules, improved device performance and stability is demonstrated in solar cells using an active layer blend of PTQ10 (donor) and ITIC-Br (non-fullerene acceptor) compared to such cells prepared using untreated ZnO. Furthermore, similar or improved device performance and stability is demonstrated compared to conventional PEIE treatment of ZnO. The presence of the BZA derivatives at the surface after processing is established using X-ray photoelectron spectroscopy and near-edge X-ray absorption fine-structure spectroscopy. From atomic force microscopy analysis and X-ray diffraction studies, the addition of BZA derivatives appears to restrict ZnO grain growth; however, this does not negatively impact device performance. ZnO layers treated with BZA derivatives also exhibit higher water contact angle and lower work function compared to untreated ZnO. This approach enables simplification of device manufacture while still allowing optimization of the surface properties of metal oxide ETLs. Keywords: electron transport layers, zinc oxide, organic solar cells, surface modificationComment: Manuscript: 25 pages, 8 figures, 5 tables. Supplementary Material: 36 pages, 22 figures, 13 tables. Submitted to Solar Energy Materials and Solar Cell

2015-2016 Dean\u27s Showcase No. 2

https://spiral.lynn.edu/conservatory_deansshowcase/1007/thumbnail.jp

Lynn Chamber Music Competition 2015

Judges Daniel Andai Janet Harris Joan Kretschmer Winners Alla Sorokoletova (flute), John Weisberg (oboe), Jackie Gillette (clarinet), Sebastian Castellanos (bassoon), Mileidy Gonzales (French Horn), and Chance Israel (piano)https://spiral.lynn.edu/conservatory_chamber-music-competition/1000/thumbnail.jp

HER2-Specific Chimeric Antigen Receptor–Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial

Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients <18 years [median age, 14 years; range, 10-17 years]) with progressive HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR VSTs (1 × 106/m2 to 1 × 108/m2) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma. Further evaluation of HER2-CAR VSTs in a phase 2b study is warranted as a single agent or in combination with other immunomodulatory approaches for glioblastoma

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma

We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids’ quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.Medicin