Biology subjects

Johnstone, B.

Publications and source records attributed to Johnstone, B..

3 recordsLinked to original sources

bioRxiv2026

Sensory Neuropeptides Dictate Sex-Specific Synovial Immunity and Cartilage Degeneration in Aging Mice

Sensory neuropeptides, particularly Substance P (SP) and -calcitonin gene-related peptide (CGRP), are implicated in osteoarthritis (OA) pathogenesis. This study elucidates their specific roles in spontaneous, age-related OA. Male and female mice deficient in SP (Tac1-/-), CGRP (CGRP-/-), or both (DKO) were evaluated at 6, 12, and 18 months of age. Assessments included histological OARSI scoring for articular cartilage matrix structure, Luminex arrays for systemic serum cytokines, and flow cytometry for local synovial immune cell profiling. Wild type (WT) mice developed early-stage, age-related cartilage degradation, predominantly in the lateral compartment. Conversely, all neuropeptide-deficient strains exhibited significant structural protection against this process. Systemically, SP deficiency distinctly altered cytokine profiles (e.g., decreased IL-23, increased IP-10), whereas CGRP deficiency caused minimal systemic shifts, highlighting a disconnect between circulating markers and local joint preservation. Locally, flow cytometry revealed profound, sexually dimorphic, and age-dependent neuroimmune alterations. In young males, neuropeptide deficiency significantly reduced synovial macrophage counts to levels comparable to those of aged WT mice. Furthermore, male CGRP-/- mice exhibited an age-related accumulation of CD8+ cytotoxic T cells. In contrast to males, young WT females demonstrated higher baseline CD8+ T cell counts that declined with age, whereas these subpopulations remained persistently low in KO mice. SP and CGRP act as critical modulators of age-related cartilage degradation. Their absence provides robust structural protection mediated through highly localized, sexually dimorphic neuroimmune pathways. These findings emphasize the necessity of targeting the local joint microenvironment for future personalized, sex-specific OA therapies.

pathology↗

bioRxiv2025

Autosomal Allelic Inactivation: Variable Replication and Dosage Sensitivity

Autosomal monoallelic gene expression and asynchronous replication between alleles are established features of imprinted genes and genes regulated by allelic exclusion. Inactivation/Stability Centers (I/SCs) are recently described autosomal loci that exhibit epigenetic regulation of allelic expression and replication timing, with differences that can be comparable to those observed between the active and inactive X chromosomes1. Here we characterize >100 autosomal loci with allele-specific epigenetic regulation of replication timing and gene expression, defining them as I/SCs. I/SCs are approximately 1 megabase in size and can contain both protein-coding and noncoding genes. In different single cell derived clones, these genes may be expressed from a single allele, the opposite allele, both alleles, or not expressed at all. This stochastic, yet mitotically stable, pattern indicates that the choice of which allele is expressed is independent of parent of origin and independent of the expression status of the other allele. Similarly, alleles within I/SCs show varying replication timing, either earlier or later, that is also independent of the other allele. Additionally, we identify syntenic loci in the mouse genome that display epigenetic regulation of allelic replication timing, highlighting the genomic organization and conservation of I/SC-associated regulation between human and mouse genomes. The allele-restricted regulation described here creates extensive cellular mosaicism through a stable epigenetic mechanism. This mosaicism impacts numerous dosage-sensitive genes associated with human diseases such as Alzheimer, Parkinson, epilepsy, deafness, and impaired intellectual development.

genomics↗

bioRxiv2019

Abbreviated assessment of psychopathology in patients with suspected seizure disorders

PurposePsychopathology is common in patients undergoing investigation for seizure-related disorders. Psychometric examination using self-report instruments, such as the SCL-90-R, can assist diagnosis. The SCL-90-R, however, is a lengthy instrument and might not be tolerated by all patients. We assessed several abbreviated forms of the SCL-90-R in patients undergoing video encephalographic monitoring (VEM).\n\nMethod687 patients completed the SCL-90-R and scores were computed for the full SCL-90-R and five abbreviated forms. Correlations and mean differences were computed between different forms. Classification accuracy was assessed via receiver operating characteristic (ROC) curves, and measurements models were examined using confirmatory factor analysis (CFA).\n\nResultsAll abbreviated forms were strongly correlated with the SCL-90-R for general psychopathology (r = .93 - .99), depression (r = .89 - .95), anxiety (r = .97 - .98), psychosis (r = .95 - .99), and obsessive-compulsive symptoms (r = .97). Classification performance was similar across forms for depression and anxiety, with high negative predictive values (.90 - .94) and lower positive predictive values (.34 - .38). Classification performance for psychotic and obsessive-compulsive disorders was poor. Differences were observed between the full SCL-90-R and its abbreviated forms across most domains (d = 0.00 - 0.65). The published measurement model was most strongly validated for the SCL-27, SCL-14, and the SCL-K-9.\n\nConclusionsThese five SCL-90-R abbreviated forms show high convergent validity with the full version. In patients undergoing investigation for seizure-related disorders, the BSI or BSI-18 are most appropriate where screening for both depression and anxiety is required. The SCL-K-9 is appropriate when only a single measure of global psychological distress is required. None of the instruments were able to detect psychotic or obsessive-compulsive symptoms with great accuracy. Caution should be exercised when making direct comparisons across the different forms.

neuroscience↗