Scientific Advisory Board Member Research Articles

Interview with FocalPlane Scientific Advisory Board member Kota Miura

ABSTRACT Kota Miura is the Vice-Chair of the Network of European Bioimage Analysts (NEUBIAS) and a freelance bioimage analyst. For his PhD, Kota studied cell migration in true and cellular slime molds where he was introduced to bioimage analysis, which became the focus of his research. After moving to EMBL at Heidelberg in Germany, Kota was instrumental in running the EMBL bioimages analysis courses and in founding NEUBIAS. We caught up with Kota to discuss his career, his hopes for the future of bioimage analysis and how FocalPlane can benefit the microscopy community.

Interview with FocalPlane Scientific Advisory Board member Jennifer Waters

ABSTRACT Jennifer Waters is Director of the Nikon Imaging Center and Lecturer in Cell Biology at Harvard Medical School, USA. Jennifer started using microscopes during her undergraduate studies and continued developing her technical skills during her PhD at University of North Carolina (UNC) at Chapel Hill. After completing her PhD, Jennifer was appointed to a faculty position teaching microscopy at Wake Forest before she moved to her current position at Harvard Medical School. We caught up with Jennifer to discuss her career, her passion for microscopy education, and the merger of Microlist and FocalPlane, the microscopy community site hosted by The Company of Biologists (https://focalplane.biologists.com/).

Interview with FocalPlane Scientific Advisory Board member Lucy Collinson

ABSTRACT Lucy Collinson is Head of the Electron Microscopy (EM) Science Technology Platform (STP) at The Francis Crick Institute (the Crick), London, UK. Lucy completed her PhD in microbiology before switching to cell biology and microscopy for her postdoc with Colin Hopkins. Her first core facility position was as Head of EM at the Laboratory for Molecular Cell Biology (LMCB) at University College London before moving to the Cancer Research UK London Research Institute (LRI) and then the Crick. We caught up with Lucy to discuss her career, the volume EM revolution, FocalPlane and the upcoming JCS Special Issue on ‘Imaging Cell Dynamics’, which she'll be guest editing with Guillaume Jacquemet.

OR16-02 Histone ADP-Ribosylation Site Mutations As Oncogenic Drivers In Breast And Ovarian Cancers

Abstract Disclosure: D. Huang: None. C.V. Camacho: None. A. Nagari: None. W.L. Kraus: Other; Self; - Founder and stockholder for Ribon Therapeutics, Inc. - Founder, stockholder, scientific advisory board member, member of the board of directors for ARase Therapeutics, Inc. - Coholder of U.S. Patent. Recent studies have identified oncohistones, which are encoded by histone genes that harbor missense mutations, as a new class of cancer drivers. We found that many of the oncohistone mutations identified with the highest frequencies in human cancers occur on glutamate (Glu, E) and aspartate (Asp, D) residues, which are potential sites of ADP-ribosylation (ADPRylation). ADPRylation is a post-translational modification, which is catalyzed by the PARP family of ADP-ribosyl transferases and results in the covalent attachment of ADP-ribose on protein substrates. Unlike other well characterized histone modifications, the functions of histone ADPRylation are poorly characterized. Mass spectrometry analyses confirmed that 20 Glu or Asp residues subjected to oncohistone mutation are bona fide sites of ADPRylation by PARP-1. Ectopic expression of each of six different oncohistone mutants from three different core histones (H2B, H3, and H4) altered the proliferation of at least 2 out of 3 cancer cell lines, including MCF-7 and MDA-MB-231 breast cancer cells, as well as OVCAR-3 ovarian cancer cells. We focused on H2B-D51, whose mutation resulted in enhanced cell proliferation in both of the breast cancer cell lines for further characterization of its potential transcription regulatory effects. Proteomic (histone PTMs) and genomic (ATAC-Seq, ChIP-Seq and RNA-Seq) analyses revealed that loss of ADPRylation on H2B-D51 by mutation to alanine (Ala, A) or asparagine (Asn, N) dramatically enhanced p300-mediated acetylation of H2B, altered chromatin accessibility, and changed the pattern of gene expression in MDA-MB-231 cells. To determine the effects of H2B-D51 ADPRylation on cancer cell growth in vivo and their responses to the FDA-approved PARP inhibitor Niraparib, we performed xenograft tumor growth assays in immunocompromised mice using MDA-MB-231 cells ectopically expressing wild-type or D51A mutant histone H2B. Ectopic expression of the H2B-D51A mutant led to a significant increase in tumor growth versus wild-type H2B. Interestingly, these effects were inhibited by treatment with Niraparib, suggesting that the H2B-D51A mutant alone does not confer resistance to PARP inhibitor. Taken together, this study demonstrates that functional sites of Glu/Asp ADPRylation on histones are mutated in cancers, allowing cancer cells to escape the growth-regulating effects of ADPRylation. (This work was supported by grants from the NIH/NIDDK and CPRIT, and funds from the Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment to W.L.K.) Presentation: Friday, June 16, 2023

OR29-01 Deleting Salt Inducible Kinases In Osteoprogenitor Cells Increases Trabecular Bone

Abstract Disclosure: G. Papaioannou: None. A. Morellato Alcantara: None. K. Strauss: None. H.M. Kronenberg: None. M.N. Wein: Other; Self; Radius Health, Inc, research funding and patent royalties, holds equity in and is a scientific advisory board member of Relation Therapeutics, consultant for AstraZeneca, Guidepoint LLC, and Aditum Bio. Introduction: Osteoblasts are continuously generated by the differentiation of skeletal progenitor cells. Osx positive cells are committed osteoprogenitors. Ebf3 positive cells are a group of bone marrow stromal cells marked by CXCL12 expression that are thought to contribute to osteoblasts in adult mice. Salt-inducible kinases (SIKs) are key kinases that control the skeletal actions of parathyroid hormone. We previously reported that deletion of SIK genes in osteoblasts/osteocytes (using Dmp1-Cre) or ubiquitously (using Ub-CreERt2) causes dramatic increases of trabecular bone and stromal cells. However, the specific osteoblast progenitor populations through which SIKs control bone homeostasis downstream of PTH signaling are still to be determined. Methods: SIK genes were deleted from Osx or Ebf3 positive cells in 3-day-old, 6- or 9-week-old mice using the CreERt2 (tamoxifen inducible) system. OsxCreERt2 mice were crossed with animals harboring floxed Sik2 and Sik3 genes. Ebf3CreERt2 mice were crossed with Sik1, Sik2, and Sik3 floxed mice. These mice also bear a tdTomato reporter that labels cells and their descendants upon Cre recombination. After sacrifice, tibiae were fixed in paraformaldehyde or formalin and decalcified in EDTA for frozen or paraffin sections respectively. Results: In OsxCreERt2; Sik2f/f;Sik3f/f;R26R-Tomato mice tamoxifen was injected at 6 weeks old or P3 and tibias were harvested 4 weeks later. In both cases there was a dramatic increase in trabecular bone mass, that filled a large part of the bone marrow, and an increase in stromal cells. Most of the osteoblasts and many of the stromal cells were tomato positive, indicating that they derive from the osteoprogenitors in which SIKs were deleted. In Ebf3CreERt2;Sik1f/f;Sik2f/f;Sik3f/f;R26R-Tomato mice, tamoxifen was injected at 9-weeks of age and tibiae examined 3 and 9 weeks later, or tamoxifen was given at 3 days of age and tibiae examined 4 weeks later. There were no obvious differences in H/E staining and no significant differences in the number or localization of cells labeled with tomato reporter. The number of tomato positive cells was small (compared to the OsxCreER model) at all ages examined. Some of these cells, were lining the bone, presumably becoming osteoblasts, but interestingly did not increase their number despite SIK deletion and in contrast with the OsxCreER model. Conclusion: Conditional deletion of SIK genes in Osx positive cells leads to a dramatic increase of trabecular bone and stromal cells in long bones suggesting a crucial role for SIKs in more committed osteoprogenitors and their descendants. The SIK pathway may not play a role in the subset of mesenchymal progenitor cells labeled with Ebf3CreERt2. Presentation: Sunday, June 18, 2023

Research excellence and scientific advisory boards

Abstract Scientific advisory boards are frequently established to provide scientific insights and advice to policymakers. Advisory board appointing bodies often state that research excellence and scientific seniority are the main grounds on which advisory board members are selected. Many authors have pointed out that there is more to giving good scientific advice than just being an expert for a specific research field. The aim of this study is to analyse if and how research excellence correlates with the probability of being appointed as a scientific advisory board member. We collected data for scientific advisory boards from both the USA and Germany. We use logit regression models to analyse how research excellence correlates with the probability of appointment to a scientific advisory board. Our results suggest that research excellence is insignificant or even correlates negatively with the probability of being appointed to a scientific advisory board.

Association of perception of patient-centered care with hearing loss by race.

Association of perception of patient-centered care with hearing loss by race.

Ten deprescribing articles you should know about: A guide for newcomers to the field.

Authors on this article have authored and collaborated with authors of several of the studies mentioned in this commentary. Dr. Reeve is supported by an NHMRC Investigator Grant (GNT1195460) and grants from the National Institute on Aging (R33-AG057289 and R01-AG070047-01). She also receives royalties for co-authoring a chapter on deprescribing in UpToDate and honorarium from the Society of Hospital Pharmacists of Australia (leading workshops on deprescribing). Sion Scott has/has had research collaborations with INVISIO Pharmaceuticals, Desitin Pharma and iEthico but has no financial interest in the organizations. Michael A. Steinman is supported by grants from the US National Institute on Aging (R24AG064025, K24AG049057, P30AG044281) and receives honoraria from the American Geriatrics Society and from UpToDate for chapter authorship. Dr. McDonald is the creator and owner of the software MedSafer, licenced for used by MedSafer Corp. MedSafer provides electronic decision support for deprescribing. Dr. Farrell has received honoraria from the American College of Clinical Pharmacy for a textbook chapter and from the United States Deprescribing Research Network as a Scientific Advisory Board Member. Dr. Thompson has received a grant from the US Deprescribing Network (US National Institute on Aging).

Patient Reported Impact of Symptoms in Spinal Bulbar Muscular Atrophy (PRISM-SBMA) (S33.007)

Patient Reported Impact of Symptoms in Spinal Bulbar Muscular Atrophy (PRISM-SBMA) (S33.007)

NF1 Recommendation-Based Care Delivery: A Survey of Patients and Caregivers (P3-7.002)

NF1 Recommendation-Based Care Delivery: A Survey of Patients and Caregivers (P3-7.002)

Barriers to participation in a prospective clinical trial for schwannomatosis-related pain (P7-13.003)

Barriers to participation in a prospective clinical trial for schwannomatosis-related pain (P7-13.003)

Comparison of a STIR- and T1-based radiomics model to differentiate between plexiform neurofibromas and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 (NF1) (S17.010)

Comparison of a STIR- and T1-based radiomics model to differentiate between plexiform neurofibromas and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 (NF1) (S17.010)

Assessing Sex Differences in Individuals with Tourette Syndrome and Persistent Motor or Vocal Tic Disorder (S42.009)

<h3>Objective:</h3> To examine sex differences in Tourette Syndrome (TS) and Persistent Motor or Vocal Tic Disorder (PMVT) individuals. <h3>Background:</h3> TS and PMVT are more prevalent in males compared to females. Females with TS may have a delayed diagnosis and more complex tics than males. Obsessive-compulsive disorder (OCD) is more prevalent in females; attention-deficit hyperactivity disorder (ADHD) is more prevalent in males. This study analyzes sex differences in outcomes among TS and PMVT. <h3>Design/Methods:</h3> Data from 2405 individuals (N=2109 TS; N=168 PMVT) from the Tourette Association of America International Consortium for Genetics were analyzed to explore the relationship between sex and TS or PMVT outcomes: 1) age at tic onset; 2) time-to-diagnosis; 3) tic severity; and 4) comorbidity rates. Regression models adjusted for age, sex, and family relationships. <h3>Results:</h3> Females with TS (25.5% of the sample) compared to males had a later age of symptom onset (6.5±2.8 vs. 6.0±2.7; p=0.001), and a longer time-to-diagnosis [3 (1,7) vs. 2 (1,5), p=0.01]. OCD was more prevalent in females (55% vs. 48.7%; p=0.01) as well as ADHD (61.1% vs. 55.7%; p&lt;0.001). After adjusting for sex, age, and family relationships, females had lower odds of ADHD [0.6 (0.5, 0.7)]. Females with PMVT (42.9% of the sample) compared to males had an earlier age of symptom onset (7.9±3.3 vs. 8.9±3.7; p=0.05). OCD was more prevalent in females (41.9% vs. 22.2%; p&lt;0.001), but not ADHD. Results were significant after adjusting for sex, age, and family relationships. <h3>Conclusions:</h3> Females with TS may be clinically different than males with TS. ADHD appeared more prevalent in females with TS in univariate analyses, but less prevalent in regression models. In contrast, females with PMVT appear similar compared to males with PMVT. Age of symptom onset is later in females with TS, but earlier in females with PMVT. Meta-analyses may help to better understand these findings. <b>Disclosure:</b> The institution of Dr. Dy-Hollins has received research support from CNCDP-K12. Lori B. Chibnik has nothing to disclose. Lisa Osiecki has nothing to disclose. Dr. Sharma has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Sharma has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Sharma has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cambridge Expert Witness. The institution of Dr. Sharma has received research support from NIH. The institution of Carol Mathews has received research support from NIH. Carol Mathews has received publishing royalties from a publication relating to health care. The institution of Dr. Scharf has received research support from the TLC Foundation for Body-Focused Repetitive Behaviors. Dr. Scharf has received personal compensation in the range of $500-$4,999 for serving as a Speaker for a TAA/CDC Family Day Symposium with the Tourette Association of America. Dr. Scharf has a non-compensated relationship as a Scientific Advisory Board Member with the Tourette Association of America that is relevant to AAN interests or activities.

Design of a Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Nipocalimab in Participants with Active Idiopathic Inflammatory Myopathies (SPIREA) (P10-5.007)

Design of a Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Nipocalimab in Participants with Active Idiopathic Inflammatory Myopathies (SPIREA) (P10-5.007)

Black and Hispanic Individuals with Tourette Syndrome are Under-Represented in Specialty Clinics (P11-11.016)

<h3>Objective:</h3> To examine the racial and ethnic distribution of Tourette Syndrome (TS) individuals presenting for care in the Massachusetts General Brigham System (MGB). <h3>Background:</h3> TS is thought to occur with similar frequencies across racial and ethnic groups. However, we observed a low representation of racial and ethnic minority TS individuals in our specialty clinic at the MGB Tourette Syndrome Center of Excellence (TS-COE). We hypothesized that Black and Hispanic TS individuals are under-represented in specialty clinics compared to white and Non-Hispanic individuals. <h3>Design/Methods:</h3> We extracted patient registry aggregate data for individuals ages 4–21 years who were seen in outpatient Pediatrics, Pediatric Neurology, and TS-COE clinics between 01/01/2015–11/17/2021 with a TS diagnosis (ICD-9:307.23; ICD-10:F95.2) and compared to all individuals seen for any type of outpatient clinical care within the MGB Healthcare System. Chi-square goodness-of-fit testing was performed to examine the racial and ethnic proportion of TS individuals seen in the specialty clinics and across MGB (reference group). Statistical significance was set at p=0.05 level for overall group comparisons and at p=0.0125 (race) and p=0.025 (ethnicity) for post-hoc testing. <h3>Results:</h3> All group comparisons were significant for race (p-values &lt;0.05). For ethnicity, group comparisons were significant for MGB vs. Pediatrics (p=0.01) and MGB vs. TS-COE (p=0.03). The proportion of: 1) Black TS individuals was lower in all clinics than in MGB, 2) white TS individuals was higher in the TS-COE (89.6%) compared to MGB (74.6%), and 3) Hispanic TS individuals was higher in Pediatrics (9.3%), but lower in the TS-COE (2.6%) when compared to those within MGB (5.2%). <h3>Conclusions:</h3> A more marked disparity is seen with lower proportions for Black TS individuals than Hispanic TS individuals across the clinics and in the TS-COE. Our findings illustrate the need for further research to identify relevant multi-level barriers to care for Black and Hispanic TS individuals. <b>Disclosure:</b> The institution of Dr. Dy-Hollins has received research support from CNCDP-K12. Lori B. Chibnik has nothing to disclose. Mr. Realbuto has nothing to disclose. Dr. Rao has received research support from National Institute for Health. Dr. Rao has received research support from National Institute for Drug Abuse. Dr. Sharma has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Sharma has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Sharma has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cambridge Expert Witness. The institution of Dr. Sharma has received research support from NIH. Elyse Park has received publishing royalties from a publication relating to health care. The institution of Carol Mathews has received research support from NIH. Carol Mathews has received publishing royalties from a publication relating to health care. The institution of Dr. Scharf has received research support from the TLC Foundation for Body-Focused Repetitive Behaviors. Dr. Scharf has received personal compensation in the range of $500-$4,999 for serving as a Speaker for a TAA/CDC Family Day Symposium with the Tourette Association of America. Dr. Scharf has a non-compensated relationship as a Scientific Advisory Board Member with the Tourette Association of America that is relevant to AAN interests or activities.

Annalen der Physik – Wiley's Physics Forum and Center of Excellence

<i>Annalen der Physik</i> – Wiley's Physics Forum and Center of Excellence

3MO Genomic evolution of non-small cell lung cancer during the establishment and propagation of patient-derived xenograft models

3MO Genomic evolution of non-small cell lung cancer during the establishment and propagation of patient-derived xenograft models

2MO Tracking immunoediting from early to late-stage lung cancer

2MO Tracking immunoediting from early to late-stage lung cancer

Hemodynamic Aberrancies in Left Ventricular Assist Device–Associated Heart Failure Syndromes

Hemodynamic Aberrancies in Left Ventricular Assist Device–Associated Heart Failure Syndromes

1395. Epidemiology of Non-Tuberculous Mycobacteria Infection Among Immunocompromised Children: A Single Center Experience

BackgroundNontuberculous mycobacteria (NTM) infection is associated with high rates of morbidity and mortality among immunocompromised adults. However, sparse data exists regarding clinical outcomes among immunocompromised (IC) children with NTM infection. We sought to characterize clinical features and outcomes among IC children at our institution with microbiologically confirmed NTM disease.MethodsRetrospective review of cases of microbiologically confirmed NTM infection among IC children between January 2017 and December 2020. Children (≤21y.o) with microbiologically confirmed NTM disease and known primary or secondary immunodeficiency diagnosed between January 1, 2017 and December 20, 2020 were included in the study. All subjects with a positive NTM microbiologic stain or culture but no subsequent treatment for NTM infection were excluded. Demographic and clinical characteristics were assessed and risk factors for mortality were evaluated.ResultsOf 147 mycobacterial cultures sent during the study period, 72 subjects had a positive microbiologically confirmed NTM species, with 10 subjects meeting all inclusion and no exclusion criteria. Median age was 16 years old, with 40 percent being female and 50 percent of Hispanic ethnicity. NTM disease was distributed among patients with primary immunodeficiency (30%), solid organ transplantation (20%), hematopoietic stem cell transplant (20%), rheumatologic disease on immunosuppressive therapy (10%), and hematologic malignancy (10%). Bacteremia was common, with blood cultures positive in 70% of cases, and M. abscessus (50%) and M. avium complex (30%) the most frequently implicated pathogens. Hospital acquired infection was common (60%). 2 year mortality following invasive NTM infection was high at 40%. ConclusionWhile rare, NTM infections are associated with significant morbidity and mortality among immunocompromised children. Additional investigations are needed to assess for risk factors associated with NTM and severe NTM disease.Disclosures Laura Filkins, PhD, Avsana Labs (Board Member, Scientific advisory board member)Biofire Diagnostics (Grant/Research Support)