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  1. Article ; Online: Measurement of Molecular Height Using Cell Surface Optical Profilometry (CSOP).

    Son, Sungmin / Fletcher, Daniel A

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2654, Page(s) 113–122

    Abstract: The plasma membrane of cells is covered by proteins, glycoproteins, and glycolipids with molecular heights ranging from just a few nanometers to hundreds of nanometers. Formation of cell-cell contacts and signal transduction by individual receptors can ... ...

    Abstract The plasma membrane of cells is covered by proteins, glycoproteins, and glycolipids with molecular heights ranging from just a few nanometers to hundreds of nanometers. Formation of cell-cell contacts and signal transduction by individual receptors can be dependent on both the average height of a cell's glycocalyx and the specific height of individual receptors, sometimes with nanometer-scale sensitivity. While super-resolution imaging techniques allow molecular distances to be measured with the sub-diffraction limited resolution, typically 10 nm in the lateral direction and 100 nm in the axial direction, measurements of molecular heights at the single nanometer scale on native cell membranes have been difficult to obtain. Cell surface optical profilometry (CSOP) is a simple and rapid method that achieves nanometer height resolution by localizing fluorophores at the tip and base of cell surface molecules and determining their separation with high precision by radially averaging across many molecules. Here we describe how to make CSOP measurements of multi-domain proteins on model membrane surfaces as well as native cell surfaces.
    MeSH term(s) Cell Membrane/metabolism ; Glycocalyx ; Glycoproteins/metabolism ; Signal Transduction
    Chemical Substances Glycoproteins
    Language English
    Publishing date 2023-04-27
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3135-5_7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Approaching future rewards or waiting for them to arrive: Spatial representations of time and intertemporal choice.

    Fletcher, Daniel / Houghton, Robert / Spence, Alexa

    PloS one

    2024  Volume 19, Issue 4, Page(s) e0301781

    Abstract: Our mental representation of the passage of time is structured by concepts of spatial motion, including an ego-moving perspective in which the self is perceived as approaching future events and a time-moving perspective in which future events are ... ...

    Abstract Our mental representation of the passage of time is structured by concepts of spatial motion, including an ego-moving perspective in which the self is perceived as approaching future events and a time-moving perspective in which future events are perceived as approaching the self. While previous research has found that processing spatial information in one's environment can preferentially activate either an ego-moving or time-moving temporal perspective, potential downstream impacts on everyday decision-making have received less empirical attention. Based on the idea people may feel closer to positive events they see themselves as actively approaching rather than passively waiting for, in this pre-registered study we tested the hypothesis that spatial primes corresponding to an ego-moving (vs. time-moving) perspective would attenuate temporal discounting by making future rewards feel more proximal. 599 participants were randomly assigned to one of three spatial prime conditions (ego-moving, time-moving, control) resembling map-based tasks people may engage with on digital devices, before completing measures of temporal perspective, perceived wait time, perceived control over time, and temporal discounting. Partly consistent with previous research, the results indicated that the time-moving prime successfully activated the intended temporal perspective-though the ego-moving prime did not. Contrary to our primary hypotheses, the spatial primes had no effect on either perceived wait time or temporal discounting. Processing spatial information in a map-based task therefore appears to influence how people conceptualise the passage of time, but there was no evidence for downstream effects on intertemporal preferences. Additionally, exploratory analysis indicated that greater perceived control over time was associated with lower temporal discounting, mediated by a reduction in perceived wait time, suggesting a possible area for future research into individual differences and interventions in intertemporal decision-making.
    MeSH term(s) Humans ; Reward ; Delay Discounting/physiology ; Time Perception/physiology ; Emotions ; Individuality
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0301781
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Engineered molecular sensors for quantifying cell surface crowding.

    Takatori, Sho C / Son, Sungmin / Lee, Daniel S W / Fletcher, Daniel A

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 21, Page(s) e2219778120

    Abstract: Cells mediate interactions with the extracellular environment through a crowded assembly of transmembrane proteins, glycoproteins and glycolipids on their plasma membrane. The extent to which surface crowding modulates the biophysical interactions of ... ...

    Abstract Cells mediate interactions with the extracellular environment through a crowded assembly of transmembrane proteins, glycoproteins and glycolipids on their plasma membrane. The extent to which surface crowding modulates the biophysical interactions of ligands, receptors, and other macromolecules is poorly understood due to the lack of methods to quantify surface crowding on native cell membranes. In this work, we demonstrate that physical crowding on reconstituted membranes and live cell surfaces attenuates the effective binding affinity of macromolecules such as IgG antibodies in a surface crowding-dependent manner. We combine experiment and simulation to design a crowding sensor based on this principle that provides a quantitative readout of cell surface crowding. Our measurements reveal that surface crowding decreases IgG antibody binding by 2 to 20 fold in live cells compared to a bare membrane surface. Our sensors show that sialic acid, a negatively charged monosaccharide, contributes disproportionately to red blood cell surface crowding via electrostatic repulsion, despite occupying only ~1% of the total cell membrane by mass. We also observe significant differences in surface crowding for different cell types and find that expression of single oncogenes can both increase and decrease crowding, suggesting that surface crowding may be an indicator of both cell type and state. Our high-throughput, single-cell measurement of cell surface crowding may be combined with functional assays to enable further biophysical dissection of the cell surfaceome.
    MeSH term(s) Cell Membrane/metabolism ; Membrane Proteins/metabolism ; Macromolecular Substances/metabolism ; Erythrocytes/metabolism
    Chemical Substances Membrane Proteins ; Macromolecular Substances
    Language English
    Publishing date 2023-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2219778120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Low-Fidelity Assembly of Influenza A Virus Promotes Escape from Host Cells.

    Vahey, Michael D / Fletcher, Daniel A

    Cell

    2020  Volume 180, Issue 1, Page(s) 205

    Language English
    Publishing date 2020-01-07
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2019.12.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Opening up autism research: Bringing open research methods to our field.

    Hobson, Hannah / Poole, Daniel / Pearson, Amy / Fletcher-Watson, Sue

    Autism : the international journal of research and practice

    2022  Volume 26, Issue 5, Page(s) 1011–1013

    MeSH term(s) Autism Spectrum Disorder ; Autistic Disorder ; Humans ; Research Design
    Language English
    Publishing date 2022-07-28
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1338513-6
    ISSN 1461-7005 ; 1362-3613
    ISSN (online) 1461-7005
    ISSN 1362-3613
    DOI 10.1177/13623613221105385
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Low-Fidelity Assembly of Influenza A Virus Promotes Escape from Host Cells.

    Vahey, Michael D / Fletcher, Daniel A

    Cell

    2019  Volume 176, Issue 3, Page(s) 678

    Language English
    Publishing date 2019-01-22
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2019.01.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bottom-Up Biology: Harnessing Engineering to Understand Nature.

    Fletcher, Daniel A

    Developmental cell

    2016  Volume 38, Issue 6, Page(s) 587–589

    Abstract: Engineering as a field has fundamentally different goals than biology, but the perspective that engineers take-that systems can be designed and built-is helping to advance biological sciences by motivating and equipping efforts to construct biological ... ...

    Abstract Engineering as a field has fundamentally different goals than biology, but the perspective that engineers take-that systems can be designed and built-is helping to advance biological sciences by motivating and equipping efforts to construct biological systems from the bottom up.
    MeSH term(s) Bioengineering/trends ; Genetic Engineering ; Models, Biological ; Systems Biology/trends
    Language English
    Publishing date 2016-09-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2016.09.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Digital spatial profiling of intraductal papillary mucinous neoplasms: Toward a molecular framework for risk stratification.

    Iyer, Matthew K / Shi, Chanjuan / Eckhoff, Austin M / Fletcher, Ashley / Nussbaum, Daniel P / Allen, Peter J

    Science advances

    2023  Volume 9, Issue 11, Page(s) eade4582

    Abstract: The histopathologic heterogeneity of intraductal papillary mucinous neoplasms (IPMN) complicates the prediction of pancreatic ductal adenocarcinoma (PDAC) risk. Intratumoral regions of pancreaticobiliary (PB), intestinal (INT), and gastric foveolar (GF) ... ...

    Abstract The histopathologic heterogeneity of intraductal papillary mucinous neoplasms (IPMN) complicates the prediction of pancreatic ductal adenocarcinoma (PDAC) risk. Intratumoral regions of pancreaticobiliary (PB), intestinal (INT), and gastric foveolar (GF) epithelium may occur with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). We used digital spatial RNA profiling of dysplastic epithelium (83 regions) from surgically resected IPMN tissues (12 patients) to differentiate subtypes and predict genes associated with malignancy. The expression patterns of PB and GF lesions diverged from INT, suggesting that PB and GF arise from a common lineage. Transcriptional dysregulation within PB lesions mirrored that of PDAC, whereas INT and GF foci did not. Tumor necrosis factor/nuclear factor κB (TNF-NFκB) and cell cycle (cycling S and cycling G
    MeSH term(s) Humans ; Pancreatic Intraductal Neoplasms/genetics ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Neoplasms, Cystic, Mucinous, and Serous ; Risk Assessment ; Pancreatic Neoplasms
    Language English
    Publishing date 2023-03-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.ade4582
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Perspective: Biochemical and Physical Constraints Associated With Preparing Thin Specimens for Single-Particle Cryo-EM.

    Han, Bong-Gyoon / Armstrong, Max / Fletcher, Daniel A / Glaeser, Robert M

    Frontiers in molecular biosciences

    2022  Volume 9, Page(s) 864829

    Abstract: While many aspects of single-particle electron cryo-microscopy (cryo-EM) of biological macromolecules have reached a sophisticated level of development, this is not yet the case when it comes to preparing thin samples on specimen grids. As a result, ... ...

    Abstract While many aspects of single-particle electron cryo-microscopy (cryo-EM) of biological macromolecules have reached a sophisticated level of development, this is not yet the case when it comes to preparing thin samples on specimen grids. As a result, there currently is considerable interest in achieving better control of both the sample thickness and the amount of area that is useful, but this is only one aspect in which improvement is needed. This Perspective addresses the further need to prevent the macromolecular particles from making contact with the air-water interface, something that can result in preferential orientation and even structural disruption of macromolecular particles. This unwanted contact can occur either as the result of free diffusion of particles during the interval between application, thinning and vitrification of the remaining buffer, or-when particles have been immobilized-by the film of buffer becoming too thin prior to vitrification. An opportunity now exists to apply theoretical and practical insights from the fields of thin-film physical chemistry and interfacial science, in an effort to bring cryo-EM sample preparation to a level of sophistication that is comparable to that of current data collection and analysis.
    Language English
    Publishing date 2022-04-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2022.864829
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Pickleball- and Paddleball-Related Injuries in the Lower Extremity: Description, Treatment Options, and Return to Play.

    Opara, Olivia A / Brush, Parker L / Pohl, Nicholas / Fras, Sebastian / Aita, Daren / Hornstein, Joshua / Fletcher, Daniel / Parekh, Selene

    Cureus

    2024  Volume 16, Issue 2, Page(s) e53954

    Abstract: Background Pickleball and paddleball are the fastest-growing sports in the United States. However, there are limited studies on the types of lower extremity injuries and treatment options in an outpatient clinic setting. Hypothesis/purpose This study ... ...

    Abstract Background Pickleball and paddleball are the fastest-growing sports in the United States. However, there are limited studies on the types of lower extremity injuries and treatment options in an outpatient clinic setting. Hypothesis/purpose This study reports the incidence rate, treatments, and return-to-play (RTP) outcomes for patients presenting to a single orthopedic outpatient center with pickleball- and paddleball-related lower extremity injuries. Study design This study is a retrospective case series, with level IV evidence. Methods A database search of our multispecialty electronic medical record (EMR) system from 2015 to 2023 identified 166 patients with outpatient pickleball- and paddleball-related lower extremity injuries. The retrospective data were reviewed for patient demographics, injury type, mechanism of injury, surgical or non-surgical treatment, and return-to-play recommendations. Results We observed that the majority of the patients with pickleball- and paddleball-related injuries in the lower extremities were over 60 years of age, with more males. Additionally, most injuries encountered were ankle sprain/strain from a twisting mechanism, which was treated non-surgically. Additionally, a significant number of patients suffered an Achilles tendon rupture (12.0%), which was treated surgically with an Achilles tendon repair (88.1%), accounting for the most common surgical treatment performed in this study. Of the 166 patients who were seen and treated, 68 (40.9%) returned to play, and 93 (56.3%) were lost to follow-up. Conclusion Most of these injuries were seen in the older population and caused by a sprain or strain due to sudden changes in direction, which were treated non-surgically. The most common surgical treatment was an Achilles tendon repair due to an Achilles tendon rupture. Although a relatively good number of patients were cleared to return to play, some patients were lost to follow-up. Meanwhile, some patients were advised to stop playing pickleball or paddleball due to the severity of their injuries. As this sport continues to rise in popularity and with the incidence rate of lower extremity injuries increasing over time, orthopedic surgeons should be aware of the types of injuries, treatment options, and outcomes, as well as ways to advise patients on prevention. Therefore, further research on the standard treatments and outcomes of pickleball- and paddleball-related injuries in the lower extremities is encouraged.
    Language English
    Publishing date 2024-02-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2747273-5
    ISSN 2168-8184
    ISSN 2168-8184
    DOI 10.7759/cureus.53954
    Database MEDical Literature Analysis and Retrieval System OnLINE

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