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Resistance Is Futile

Omar D Perez, Garry P Nolan
2001 Immunity  
P(T/S)AP), YPDL (consensus YXXL), and PPPY (consensus PxPY), represent three types of retroviral Gag L Exploitation of cellular resources by viruses, namely domain proteins.  ...  the P(T/S)AP motif of the HIV-1 p6 Gag , the PPPPY motif of the avian retrovirus p2b Gag , the PY motif of the murine moloney leukemia virus (MMLV) p12 Gag and the pp16 Gag HIV-1 budding appears to require  ... 
doi:10.1016/s1074-7613(01)00238-2 pmid:11728331 fatcat:gdi4y2q77zdv5aq53ooqdb2hn4

Transcription and the broken heart

Garry P. Nolan
1998 Nature  
Debenedetti is in the Chemical Engineering Department, Princeton University, Princeton, New Jersey 08544-5263, USA. e-mail: pdebene@pucc.princeton.edu Transcription and the broken heart Garry P.  ...  Nolan C ongenital heart defects occur in an astonishing 1% of live births 1,2 , and fetal heart malformations are implicated in many pregnancies that end in stillbirth or spontaneous abortion 2 .  ... 
doi:10.1038/32290 pmid:9515954 fatcat:qixj5uhaejgzrmd2i7ro6izz2a

Spatial epitope barcoding reveals subclonal tumor patch behaviors [article]

Xavier Rovira-Clavé, Alexandros P. Drainas, Sizun Jiang, Yunhao Bai, Maya Baron, Bokai Zhu, Maxim Markovic, Garry L. Coles, Michael C. Bassik, Julien Sage, Garry P. Nolan
2021 bioRxiv   pre-print
Maria Angulo-Ibanez and Pablo Domizi for critical discussions and reading the manuscript, and all the members of the Bassik, Sage and Nolan labs for their help throughout this study.  ...  P-adj: 0.05-0.01:*, 0.01-0.001:**, <0.001:***. ingly, not in vivo in the context studied.  ...  Single-cell technologies provide opportunities to investigate whether inherent order exists in tumor samples (reviewed in (González-Silva, Quevedo, and Varela 2020; Irish, Kotecha, and Nolan 2006) ).  ... 
doi:10.1101/2021.06.29.449991 fatcat:6kjpipijubhk3mortja3czpdba

In Reply

Martin S. Angst, Gabriela K. Fragiadakis, Brice Gaudillière, Nima Aghaeepour, Garry P. Nolan
2016 Anesthesiology  
We appreciate the opportunity to respond to Dr. Laudanski's critical commentary. The key result of our study suggests that signaling activity of the Toll-like receptor 4 (TLR4) in a pre-surgical whole blood sample predicts the speed at which patients regain function of their operated hip. 1 We agree with Dr. Laudanski that NFkB is ubiquitous. However, our findings are related to specific signaling events downstream of TLR4, including MAPKAPK2, CREB, and rpS6, that occurred in a precisely
more » ... ped subset of monocytes. 1,2 The detected signaling patterns were highly specific with respect to pathway and cell type, which diverges from Dr. Laudanski's view that "activation of the immune system is often nonspecific". Our findings further highlight the sentinel role of TLR4 in detecting tissue damage and mediating sterile inflammation, and extend previous work by linking TLR4 activation patterns to patients' functional recovery. 3, 4 Functional recovery is at the very core of current ERAS (enhanced recovery after surgery) protocols, and delays of weeks, as reported by us and others, matter greatly to patients and health care providers. 2,5,6 A blood test identifying patients at risk for delayed functional recovery is an important step toward providing individualized, effective, cost-conscious, and high-value care in the context of the perioperative surgical home. 7 While we agree that the blood test used an external or "artificial" TLR4 ligand (LPS) that may not recapitulate biology as it unfolds during surgery, the use of LPS to activate a specific signaling pathway does not negate the predictive value of the test. The scientific endeavor never stops and interesting results will always trigger the next set of important questions. While our strong correlative findings provide a link to relevant biology, we agree that they do not prove cause and effect -and we never in our report suggested such a relationship. This is the next obvious question that we need to address. The prospect of validating TLR4 as a therapeutic target is exciting in light of preclinical studies suggesting that preemptive dampening of TLR4 with a non-toxic agonist attenuated pro-inflammatory ‡
doi:10.1097/aln.0000000000001091 pmid:27187126 pmcid:PMC4914362 fatcat:auqie27mgzf3vpuj5uizrviik4

Mass Cytometry: Single Cells, Many Features

Matthew H. Spitzer, Garry P. Nolan
2016 Cell  
Spitzer and Nolan Page 6 Cell. Author manuscript; available in PMC 2017 May 05. Spitzer and Nolan Page 7 Cell. Author manuscript; available in PMC 2017 May 05.  ...  Spitzer and Nolan Page 20 Cell. Author manuscript; available in PMC 2017 May 05. Figure 3.  ... 
doi:10.1016/j.cell.2016.04.019 pmid:27153492 pmcid:PMC4860251 fatcat:ycxsomdogve37jnom3eelbfebi

Chemical labeling strategies for cell biology

Kevin M Marks, Garry P Nolan
2006 Nature Methods  
Methods to visualize, track, measure and perturb proteins in living cells are central to biomedicine's efforts to characterize and understand the spatial and temporal underpinnings of life inside cells. Although fluorescent proteins have revolutionized such studies, they have shortcomings, which have spurred the creation of alternative approaches to chemically label proteins in live cells. In this review we highlight research questions that can be addressed using site-specific chemical labeling
more » ... and present a comparison of the various labeling techniques that have been developed. We also provide a 'roadmap' for selection of appropriate labeling techniques(s) and outline generalized strategies to validate and troubleshoot chemical labeling experiments. Rationale for chemical labeling in cell biology In the past decade, fluorescent variants of Aequorea victoria green fluorescent protein have allowed a wide range of studies in live cells, leading to a greater appreciation that cell biology is coordinated via the spatial and temporal organization of proteins and their activities 1 . A key feature of fluorescent proteins is that they are genetically encoded and thus can be used to label proteins in live cells with absolute specificity. Absent proteolysis, fluorescent proteins are colocalized with the fusion protein they were designed to study. In addition to this genetic encoding, fluorescent proteins are highly stable proteins, and the chromophore is sheltered by the protein's barrel structure, making fluorescent proteins ideal reagents to track the localization and movement of fusion proteins in cells. Although this genetic encoding and stable structure provides some key advantages, the system also has several potential disadvantages. First, the ~235-aminoacid proteins are large enough that they can interfere with the localization, structure or activity of the proteins to which they are fused 2 . Second, despite efforts to modulate the environmental sensitivity of fluorescent proteins, the barrel structure isolates the chromophore from the cellular environment making fluorescent proteins poor probes for environmental cues like pH, hydrophobicity and ion concentrations 3 . In contrast, many families of organic fluorescent dyes possess far greater sensitivity to their environment than has been achieved with fluorescent proteins. For example, there are several classes of organic calcium dyes that increase in fluorescence as much as 100-fold in the presence of calcium, whereas fluorescent proteins are limited to a much smaller dynamic range 4 . As uniquely useful as the internal fluorophore in fluorescent proteins have been, there appears to be a finite potential for modifications to their spectral and biochemical properties. In one such example, considerable efforts were required to convert the tetrameric red fluorescent protein into a monomeric form-involving the stepwise mutation of 33 amino acids to achieve a desired result. This mutagenesis resulted in an 80% loss in fluorescence, demonstrating that modification of fluorescent proteins can result in substantial trade-offs 5 . Lastly, fluorescent proteins are not as bright or photostable as some smallmolecule fluorophores and therefore are not ideal for single-molecule labeling studies. Applications enabled by chemical labeling These shortcomings have led to the development of alternative chemical labeling approaches that combine the genetic targeting of fluorescent proteins with the diversity and environmental sensitivity of fluorescent small molecules. These chemical labeling techniques have recently been used to overcome major challenges in cell biology. For example, a pulse-chase approach developed by Roger Tsien and colleagues was used to label newly synthesized connexin43 protein one color and 'older' connexin43
doi:10.1038/nmeth906 pmid:16862131 fatcat:oksnyjn5ljhixo732cmmkgzrhi

Plasmid mapping computer program

Garry P. Nolan, Claude V. Maina, Aladar A. Szalay
1984 Nucleic Acids Research  
Three new computer algorithms are described which rapidly order the restriction fragments of a plasmid DNA which has been cleaved with two restriction endonucleases in single and double digestions. Two of the algorithms are contained within a single computer program (called MPCIRC). The Rule-Oriented algorithm, constructs all logical circular map solutions within sixty seconds (14 double-digestion fragments) when used in conjunction with the Permutation method. The program is written in Apple
more » ... scal and runs on an Apple II Plus Microcomputer with 64K of memory. A third algorithm is described which rapidly maps double digests and uses the above two algorithms as adducts. Modifications of the algorithms for linear mapping are also presented.
doi:10.1093/nar/12.1part2.717 pmid:6320105 pmcid:PMC321087 fatcat:42gqimpo2vfm5g6fsioybeuvba

Mitogen-independent cell cycle progression in B lymphocytes [article]

Amit Singh, Matthew H Spitzer, Jaimy P Joy, Mary Kaileh, Xiang Qiu, Garry P Nolan, Ranjan Sen
2019 bioRxiv   pre-print
Data were considered statistically significant at *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001. All rights reserved. No reuse allowed without permission.  ...  Behbehani, G.K., Bendall Sc Fau -Clutter, M.R., Clutter Mr Fau -Fantl, W.J., Fantl Wj Fau -Nolan, G.P. & Nolan, G.P. Single-cell mass cytometry adapted to measurements of the cell cycle. 34.  ... 
doi:10.1101/796904 fatcat:cqlt3k7fyvfbhnbguwzh3gksnq

Molecular weight determination program

Claude V. Maina, Garry P. Nolan, Aladar A. Szalay
1984 Nucleic Acids Research  
A computer program is described that will determine the molecular weight of DNA, RNA or protein molecules separated according to size by gel electrophoresis. It uses the sizes and migration distances of known molecules in a reference lane to compute a second or third order equation whose curve best fits the data points. It then computes the sizes of all molecules from this equation. Migration distances are measured and entered using an analog tablet. The program is written in Apple Pascal and
more » ... signed to run on an Apple II Plus computer. © I R L Press Limited, Oxford, England.
doi:10.1093/nar/12.1part2.695 pmid:6198629 pmcid:PMC321085 fatcat:tpe4lsve7fcwrhkcy4hdiggpoe

One-Way Matching of Datasets with Low Rank Signals [article]

Shuxiao Chen, Sizun Jiang, Zongming Ma, Garry P. Nolan, Bokai Zhu
2022 arXiv   pre-print
∧ β 2 p 1/4 ∧ β 2 p 0 ∧ σ max σ min • β 2 p 1 ∧ β 2 p 5/8 ∧ β 2 p 1/2 ∧ β 2 p 3/8 = β d 1 /σ max ∧ β 2 p 1/2 ∧ 1 ∧ σ max β 2 σ min p ∧ σ max σ min β 2 p 3/8 and E unif 1.  ...  T 2 1 T 4/3 2 = β 8/3 p 4/3 • p d 2 1 /σ 2 max ∧ β 10/3 p 5/3 • p d 2 1 /σ 2 max • σ 4/3 max σ 4/3 min ∧ β 3 p 3/2 • p d 2 1 /σ β 2 p d 2 1 /σ 2 max p • E 2 unif E 4/3 loco 3/4 ∨ d 2 1 /σ 2 max p • σ 4  ...  ) 3/8 + p 1/2 k 1/2 (log(1/δ)) 1/4 + p 1/2 k 1/4 (log(1/δ)) 1/2 + p 3/8 k 3/8 (log(1/δ)) 3/8 + p 3/8 k 1/8 (log(1/δ)) 5/8 + p 1/4 k 1/4 (log(1/δ)) 1/2 + p 1/4 (log(1/δ)) 3/4 + k 1/2 (log(1/δ)) 1/2  ... 
arXiv:2204.13858v1 fatcat:yt6zmao23bchjlo4vrzubnmywu

Continuous visualization of differences between biological conditions in single-cell data [article]

Tyler J Burns, Garry P Nolan, Nikolay Samusik
2018 bioRxiv   pre-print
The resulting output is the per-sample comparison p-values.  ...  Like the paired sample p-values, they are corrected for false discovery rate using the Benjamini-Hochberg methods within the p.adjust function in the R stats package.  ... 
doi:10.1101/337485 fatcat:mcbgulfaiffo5g2gztypixp47q

Ion beam subcellular tomography [article]

Ahmet F Coskun, Guojun Han, Shih-Yu Chen, Xavier Rovira-Clave, Sizun Jiang, Christian M. Schuerch, Yunhao Bai, Chuck Hitzman, Garry P Nolan
2019 bioRxiv   pre-print
Lower images: 3D render of 31 P (blue) across 800 slices.  ...  S. & Fraser, P. Replication and transcription: Shaping the landscape of the genome. Nat. Rev. Genet. 6, 669-677 (2005). 30. Brueckner, F. & Cramer, P.  ... 
doi:10.1101/557728 fatcat:ducvbbzmxbhyxfxb67ba5ms5u4

From single cells to deep phenotypes in cancer

Sean C Bendall, Garry P Nolan
2012 Nature Biotechnology  
P Nolan In recent years, major advances in single-cell measurement systems have included the introduction of high-throughput versions of traditional flow cytometry that are now capable of measuring intracellular  ...  have not had the tools to characterize the crucial differences, and just as importantly, sort out which differences are causal and which From single cells to deep phenotypes in cancer Sean C Bendall & Garry  ... 
doi:10.1038/nbt.2283 pmid:22781693 fatcat:2casoq2anvgqhiuu24t7cl3fdq

Recognizing a Something When Your Library Sees It

Jean-Francois Fortin, Garry P Nolan
2002 Chemistry and Biology  
At present, the P., Liu, J., Kouzarides, T., and Schreiber, S. (2002). Methylation most promising method for addressing the issue of temof histone H3 lys 4 in coding regions of active genes. Proc.  ...  Jean-Francois Fortin and Garry P. Nolan  ... 
doi:10.1016/s1074-5521(02)00159-x pmid:12079777 fatcat:er6qzumr4zcjfjzjgtpsqhiisy

A deep profiler's guide to cytometry

Sean C. Bendall, Garry P. Nolan, Mario Roederer, Pratip K. Chattopadhyay
2012 Trends in immunology  
doi:10.1016/j.it.2012.02.010 pmid:22476049 pmcid:PMC3383392 fatcat:6yczeod375fnncy3sk3nf654gq
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