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Accurate computational design of multipass transmembrane proteins
Lu, Peilong,Min, Duyoung,DiMaio, Frank,Wei, Kathy Y.,Vahey, Michael D.,Boyken, Scott E.,Chen, Zibo,Fallas, Jorge A.,Ueda, George,Sheffler, William,Mulligan, Vikram Khipple,Xu, Wenqing,Bowie, James U. American Association for the Advancement of Scienc 2018 Science Vol.359 No.6379
<P><B>Membrane protein oligomers by design</B></P><P>In recent years, soluble protein design has achieved successes such as artificial enzymes and large protein cages. Membrane proteins present a considerable design challenge, but here too there have been advances, including the design of a zinc-transporting tetramer. Lu <I>et al.</I> report the design of stable transmembrane monomers, homodimers, trimers, and tetramers with up to eight membrane-spanning regions in an oligomer. The designed proteins adopted the target oligomerization state and localized to the predicted cellular membranes, and crystal structures of the designed dimer and tetramer reflected the design models.</P><P><I>Science</I>, this issue p. 1042</P><P>The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer—a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices—are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions.</P>
Ji Hoon Park,Hye Won Yi,Daniel DiMaio,Eun Seong Hwang 한국유전학회 2007 Genes & Genomics Vol.29 No.4
Cellular programs that control lysosome activity and biosynthesis are largely unexplored. We found that the lysosome number and the expression of lysosomal genes increase substantially in normal fibroblasts undergoing replicative or induced senescence and in HeLa cervical carcinoma cells undergoing induced senescence. This suggests that cellular programs that control lysosomogenesis are activated in senescence regardless of the cell type and the nature of the senescence stimulus. However, there was a substantial discordance in the extent of induction among different lysosomal genes and in different types of senescence, suggesting heterogeneity in regulatory mechanisms within the family of lysosomal genes as well as in the senescence programs themselves.
Combined Modality Therapy for Locally Advanced Non-Small Cell Lung Cancer
L.Chinsoo Cho,J.Michael Dimaio,Randall Hughes,Phuc Nguyen,Paula Anderson,Hak Choy 대한암학회 2003 Cancer Research and Treatment Vol.35 No.5
The majority of non-small cell lung cancer patients presentwith locally advanced disease that may not be resectable.A single modality treatment such as thoracic radiotherapyoften results in an inferior outcome when compared tocombined modality treatment. Various combinations ofradiotherapy, chemotherapy, and surgery have beentested in patients with locally advanced non-small-celllungcancer with promising results. The favorable results of thecombined modality treatment are accompanied by acorresponding increase in treatment related morbidity. Inthis article, the results of the application of combinedmodality treatments in the management of locally advancednon-small cell lung cancer are reviewed. (Cancer Res Treat. 2003;35:373-382)
Sunil Amin,Dennis J. Yang,Aimee L. Lucas,Susana Gonzalez,Christopher J. DiMaio 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.4
Background/Aims: Options for the endoscopic management of symptomatic pancreatic fluid collections (PFCs) include transmural drainage (TM) alone, transpapillary drainage (TP) alone, or a combination of both drainage method (CD). There have been conflicting reports about the best method. This study performed a meta-analysis to determine whether CD presents an added clinical benefit over TM. Methods: The included studies compared TM with CD and reported clinical success for both methods. A random-effects model was used to determine the pooled odds ratios (ORs) and the 95% confidence intervals (CIs) for the following outcomes: technical success, clinical success, complications, and recurrence. Results: Nine studies involving a combined total of 604 drainage procedures—373 TMs (62%) and 231 CDs (38%)—were included. CD showed no additional benefit over TM in terms of technical success (OR, 1.12; 95% CI, 0.37–3.37; p=0.85), clinical success (OR, 1.11; 95% CI, 0.65–1.89; p=0.70), recurrence (OR, 1.49; 95% CI, 0.53–4.21; p=0.45), or complications (OR, 1.15; 95% CI, 0.61–2.18; p=0.67). Conclusions: Pancreatic duct (PD) stenting provides no additional clinical benefit for the TM of PFCs (particularly pseudocysts). Patients undergoing the TM of symptomatic pseudocysts may not require endoscopic retrograde pancreatography (ERP).