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  1. Article ; Online: Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency.

    Flynn, Patrick A / Long, Mark D / Kosaka, Yoko / Long, Nicola / Mulkey, Jessica S / Coy, Jesse L / Agarwal, Anupriya / Lind, Evan F

    Frontiers in immunology

    2024  Volume 15, Page(s) 1297338

    Abstract: Dendritic cells (DC) are mediators between innate and adaptive immune responses to pathogens and tumors. DC development is determined by signaling through the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3) in bone marrow myeloid progenitors. ... ...

    Abstract Dendritic cells (DC) are mediators between innate and adaptive immune responses to pathogens and tumors. DC development is determined by signaling through the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3) in bone marrow myeloid progenitors. Recently the naming conventions for DC phenotypes have been updated to distinguish between "Conventional" DCs (cDCs) and plasmacytoid DCs (pDCs). Activating mutations of FLT3, including Internal Tandem Duplication (FLT3-ITD), are associated with poor prognosis for acute myeloid leukemia (AML) patients. Having a shared myeloid lineage it can be difficult to distinguish
    MeSH term(s) Animals ; Humans ; Mice ; Dendritic Cells/pathology ; fms-Like Tyrosine Kinase 3/genetics ; Homeostasis ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Mutation ; Tumor Microenvironment/genetics
    Chemical Substances FLT3 protein, human (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; Flt3 protein, mouse (EC 2.7.10.1)
    Language English
    Publishing date 2024-03-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1297338
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Benchmarking surgical indications for adolescent idiopathic scoliosis across time, region, and patient population: a study of 4229 cases.

    Heyer, Jessica H / Baldwin, Keith D / Shah, Apurva S / Flynn, John M

    Spine deformity

    2022  Volume 10, Issue 4, Page(s) 833–840

    Abstract: Purpose: There is no identified consensus for the curve magnitude at which an adolescent idiopathic scoliosis (AIS) patient is indicated for posterior spinal fusion (PSF). We aimed to identify a benchmark for curve magnitude at which fusion is indicated; ...

    Abstract Purpose: There is no identified consensus for the curve magnitude at which an adolescent idiopathic scoliosis (AIS) patient is indicated for posterior spinal fusion (PSF). We aimed to identify a benchmark for curve magnitude at which fusion is indicated; we also aimed to evaluate which patients were being fused under 50°.
    Methods: A prospective multicenter AIS database was queried to identify patients who underwent PSF for AIS. Clinical outcome and demographic information was collected along with anatomic area of the primary curve. Benchmarking was assessed by median and IQR. Patients were stratified by fusion prior to 50° or at 50° or more, and statistical analysis was performed to assess risk factors for fusion < 50°.
    Results: 4229 patients were included in the analysis. The median indication for PSF in the thoracic curve cohort was 55°, and in the lumbar curve cohort was 51°. Site-specific evaluation showed that two sites were more likely to fuse < 50° compared to all other sites (p < 0.05). Over time, the percentage of patients being fused < 50° has declined (p < 0.05). On univariate and multivariate analysis, lumbar curve location, increasing Risser score and female sex were all risk factors for fusion < 50° (p < 0.05). Low SRS-24 scores did not correlate to fusion below 50°.
    Conclusion: There exist location-specific indications for posterior spinal fusion that vary throughout the country. Additionally, increasing maturity, female sex, and lumbar curve location are independent risk factors for fusion under 50°.
    MeSH term(s) Adolescent ; Benchmarking ; Female ; Humans ; Kyphosis/etiology ; Prospective Studies ; Radiography ; Scoliosis/diagnostic imaging ; Spinal Fusion/adverse effects ; Thoracic Vertebrae/surgery ; Treatment Outcome
    Language English
    Publishing date 2022-03-08
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2717704-X
    ISSN 2212-1358 ; 2212-134X ; 2212-1358
    ISSN (online) 2212-1358 ; 2212-134X
    ISSN 2212-1358
    DOI 10.1007/s43390-022-00480-1
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  3. Article ; Online: Raman spectral imaging of

    Watson, Matthew D / Flynn, Jessica D / Lee, Jennifer C

    Biophysical chemistry

    2020  Volume 269, Page(s) 106528

    Abstract: Parkinson's disease is characterized by the intracellular accumulation of α-synuclein (α-syn) amyloid fibrils, which are insoluble, β-sheet-rich protein aggregates. Raman spectroscopy is a powerful technique that reports on intrinsic molecular vibrations ...

    Abstract Parkinson's disease is characterized by the intracellular accumulation of α-synuclein (α-syn) amyloid fibrils, which are insoluble, β-sheet-rich protein aggregates. Raman spectroscopy is a powerful technique that reports on intrinsic molecular vibrations such as the coupled vibrational modes of the polypeptide backbone, yielding secondary structural information. However, in order to apply this method in cells, spectroscopically unique frequencies are necessary to resolve proteins of interest from the cellular proteome. Here, we report the use of
    MeSH term(s) Amyloid/chemistry ; Isotope Labeling ; Protein Aggregates ; Spectrum Analysis, Raman ; alpha-Synuclein/chemistry
    Chemical Substances Amyloid ; Protein Aggregates ; alpha-Synuclein
    Language English
    Publishing date 2020-12-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 185052-0
    ISSN 1873-4200 ; 0301-4622
    ISSN (online) 1873-4200
    ISSN 0301-4622
    DOI 10.1016/j.bpc.2020.106528
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1147: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  4. Article ; Online: Raman fingerprints of amyloid structures.

    Flynn, Jessica D / Lee, Jennifer C

    Chemical communications (Cambridge, England)

    2018  Volume 54, Issue 51, Page(s) 6983–6986

    Abstract: Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, ... ...

    Abstract Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, spatially resolved Raman spectra reveal molecular heterogeneity in amyloid structures.
    MeSH term(s) Amides/analysis ; Amyloid beta-Peptides/chemistry ; Humans ; Particle Size ; Protein Conformation ; Spectrum Analysis, Raman ; Surface Properties
    Chemical Substances Amides ; Amyloid beta-Peptides
    Language English
    Publishing date 2018-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/c8cc03217c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Physical Chemistry in Biomedical Research: From Cuvettes toward Cellular Insights.

    Flynn, Jessica D / Lee, Jennifer C

    The journal of physical chemistry letters

    2017  Volume 8, Issue 9, Page(s) 1943–1945

    MeSH term(s) Amyloid/chemistry ; Biomedical Research ; Brain/cytology ; Chemistry, Physical ; Protein Aggregates ; alpha-Synuclein/chemistry
    Chemical Substances Amyloid ; Protein Aggregates ; alpha-Synuclein
    Language English
    Publishing date 2017-05-03
    Publishing country United States
    Document type Journal Article
    ISSN 1948-7185
    ISSN (online) 1948-7185
    DOI 10.1021/acs.jpclett.7b00549
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  6. Article: Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency.

    Flynn, Patrick A / Long, Mark D / Kosaka, Yoko / Mulkey, Jessica S / Coy, Jesse L / Agarwal, Anupriya / Lind, Evan F

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Dendritic cells (DC) are mediators of adaptive immune responses to pathogens and tumors. DC development is determined by signaling through the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3) in bone marrow myeloid progenitors. Recently the ... ...

    Abstract Dendritic cells (DC) are mediators of adaptive immune responses to pathogens and tumors. DC development is determined by signaling through the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3) in bone marrow myeloid progenitors. Recently the naming conventions for DC phenotypes have been updated to distinguish between "Conventional" DCs (cDCs) and plasmacytoid DCs (pDCs). Activating mutations of FLT3, including Internal Tandem Duplication (FLT3-ITD), are associated with poor prognosis for leukemia patients. To date, there is little information on the effects of FLT3-ITD in DC biology. We examined the cDC phenotype and frequency in bone marrow aspirates from patients with acute myeloid leukemia (AML) to understand the changes to cDCs associated with FLT3-ITD. When compared to healthy donor (HD) we found that a subset of FLT3-ITD+ AML patient samples have overrepresented populations of cDCs and disrupted phenotypes. Using a mouse model of FLT3-ITD+ AML, we found that cDCs were increased in percentage and number compared to control wild-type (WT) mice. Single cell RNA-seq identified FLT3-ITD+ cDCs as skewed towards a cDC2 T-bet
    Language English
    Publishing date 2023-09-22
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.19.558512
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  7. Article ; Online: A systematic review on the biochemical threshold of mitochondrial genetic variants.

    Smith, Karan K / Moreira, Jesse D / Wilson, Callum R / Padera, June O / Lamason, Ashlee N / Xue, Liying / Gopal, Deepa M / Flynn, David B / Fetterman, Jessica L

    Genome research

    2024  Volume 34, Issue 3, Page(s) 341–365

    Abstract: Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a ... ...

    Abstract Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58,
    MeSH term(s) Humans ; DNA, Mitochondrial/genetics ; Oxidative Phosphorylation ; Mitochondria/metabolism ; Mitochondria/genetics ; Gene Frequency ; Mitochondrial Diseases/genetics ; Mitochondrial Diseases/metabolism ; Genetic Variation
    Chemical Substances DNA, Mitochondrial
    Language English
    Publishing date 2024-04-25
    Publishing country United States
    Document type Journal Article ; Systematic Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.278200.123
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3729: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 8: Show issues

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  8. Article ; Online: How do implants overlying the spine influence "The Law of Diminishing Returns" in early-onset scoliosis patients?

    Mitchell, Stuart L / Heyer, Jessica H / Anari, Jason B / Baldwin, Keith D / Kodali, Pranav / Ramo, Brandon S / Flynn, Jack M / Fitzgerald, Ryan / Truong, Walter / Li, Ying / Andras, Lindsay / Brooks, Jaysson / Cahill, Patrick J

    Spine deformity

    2024  

    Abstract: Purpose: The "law of diminishing returns" (LODR) in early-onset scoliosis (EOS) is well-known. We hypothesized that previously observed variations between constructs may be related to the lateral distance that each construct lies from the spine. We ... ...

    Abstract Purpose: The "law of diminishing returns" (LODR) in early-onset scoliosis (EOS) is well-known. We hypothesized that previously observed variations between constructs may be related to the lateral distance that each construct lies from the spine. We therefore sought to determine whether the curve magnitude improvement and spinal length gains for distraction-based constructs in EOS are positively correlated with the collinearity of the spine and the convex-sided implant on posteroanterior radiographs.
    Methods: A prospectively-collected, multicenter EOS registry was queried for all patients who underwent non-fusion, distraction-based instrumentation surgery. Post-index radiographs were graded from 1 to 5 based on amount of overlap between the convex-sided rod and the apical vertebra. Grade 1: convex rod is lateral to convex-sided pedicle; Grade 2: overlaps the convex-sided pedicle; Grade 3: lies between pedicles; Grade 4: overlaps concave-sided pedicle; Grade 5: medial to concave-sided pedicle. ANOVA assessed the correlations between post-index overlap grade and change in (a) curve magnitude and (b) T1-T12 height. Multivariable regression modeling further assessed these associations.
    Results: 284 patients met all selection criteria and were included. On ANOVA, post-index grade was associated with curve magnitude (p <0.001) and T1-12 height (p = 0.028) change. Better curve correction and height change were associated with higher grade. On regression modeling, curve correction (R = 0.574) and T1-T12 height change (R = 0.339) remained significantly associated with grade when controlling for time, anchor locations, age, underlying diagnosis, and pre-index curve magnitude.
    Conclusion: More apical overlap by the convex rod was associated with better spinal deformity control and improved height gain.
    Level of evidence iii: Therapeutic.
    Language English
    Publishing date 2024-05-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2717704-X
    ISSN 2212-1358 ; 2212-134X ; 2212-1358
    ISSN (online) 2212-1358 ; 2212-134X
    ISSN 2212-1358
    DOI 10.1007/s43390-024-00885-0
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  9. Article ; Online: Segmental

    Flynn, Jessica D / Jiang, Zhiping / Lee, Jennifer C

    Angewandte Chemie (International ed. in English)

    2018  Volume 57, Issue 52, Page(s) 17069–17072

    Abstract: Mapping conformational changes of α-synuclein (α-syn) from soluble, unstructured monomers to β-sheet- rich aggregates is crucial towards understanding amyloid formation. Raman microspectroscopy is now used to spatially resolve conformational ... ...

    Abstract Mapping conformational changes of α-synuclein (α-syn) from soluble, unstructured monomers to β-sheet- rich aggregates is crucial towards understanding amyloid formation. Raman microspectroscopy is now used to spatially resolve conformational heterogeneity of amyloid aggregates and monitor amyloid formation of segmentally
    MeSH term(s) Amyloid/chemical synthesis ; Amyloid/chemistry ; Carbon Isotopes ; Humans ; Particle Size ; Spectrum Analysis, Raman ; alpha-Synuclein/chemical synthesis ; alpha-Synuclein/chemistry
    Chemical Substances Amyloid ; Carbon Isotopes ; alpha-Synuclein ; Carbon-13 (FDJ0A8596D)
    Language English
    Publishing date 2018-11-27
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201809865
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  10. Article: Raman fingerprints of amyloid structures

    Flynn, Jessica D / Lee, Jennifer C

    Chemical communications. 2018 June 21, v. 54, no. 51

    2018  

    Abstract: Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, ... ...

    Abstract Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, spatially resolved Raman spectra reveal molecular heterogeneity in amyloid structures.
    Keywords Raman spectroscopy ; amyloid ; chemical compounds ; chemical reactions
    Language English
    Dates of publication 2018-0621
    Size p. 6983-6986.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/c8cc03217c
    Database NAL-Catalogue (AGRICOLA)

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