Molecular profiling has refined risk stratification in meningioma, but the biological relevance of associated transcriptional changes remains incompletely understood. Calbindin D28K (Calb), encoded by CALB1, is a calcium-binding protein with reported anti-apoptotic and cytoprotective functions. Previous unsupervised transcriptomic analysis identified CALB1 upregulation in meningiomas with aggressive cellular features, but its biological and clinical relevance remains unresolved. We analysed Calb immunoreactivity in 231 meningioma tissue microarray (TMA) cores from 147 patients and evaluated CALB1 transcript expression, DNA methylation and copy-number alterations in an independent cohort of 110 primary meningiomas. Calb immunoreactivity was detected in approximately 30
Intranuclear localization of the affected protein ataxin-3 is critical for the pathogenesis of spinocerebellar ataxia type 3 (SCA3). The nuclear–cytoplasmic transporter karyopherin alpha 3 (KPNA3) has been demonstrated to play an essential role in the pathophysiology of this disorder. In this study, we characterized the single nucleotide polymorphism (SNP) rs11618521, located in the KPNA3 promoter, as a genetic modifier of the age at onset in SCA3 and a regulator of the KPNA3 promoter activity. Moreover, we identified the transcription factor Nanog homeobox (NANOG) as a key regulator exerting allele-specific modulatory effects on the KPNA3 promoter activity, thereby modulating expression and contributing to SCA3-associated pathogenic mechanisms. Pharmacological inhibition of NANOG reduced KPNA3 levels and ameliorated aggregate formation. In conclusion, we identified variant rs11618521 as a regulator of KPNA3 promoter activity and as a genetic modifier of SCA3. Moreover, we provide mechanistic insights that may guide future-targeted therapeutic strategies.
Cerebrospinal fluid cytology remains a cornerstone of diagnostic evaluation in infectious, autoimmune, haemorrhagic, and neoplastic disorders of the central nervous system despite advances in neuroimaging, molecular diagnostics, and digital technologies. This narrative review summarises established principles of cerebrospinal fluid cytology, highlights methodological limitations and diagnostic pitfalls, and integrates emerging developments, including automated cell counting, artificial intelligence, and telecytology. Pre-analytical factors are critical determinants of diagnostic accuracy. Delayed sample processing promotes pH-dependent autolysis and substantial cell loss, whereas rapid cytocentrifugation preserves cellular morphology and facilitates reliable assessment. Automated cell counters are increasingly implemented in routine laboratories and offer advantages in settings with limited technical staffing. However, current systems show limited precision in samples with low and slightly elevated cell counts and limited morphological evaluation. Manual chamber counting, particularly in the normal and low-cell-count range, remains the gold standard for quantitative CSF cell assessment, whereas expert microscopic examination remains the reference standard for qualitative cytomorphological assessment. Although the sensitivity of neuroimaging continues to improve, cerebrospinal fluid cytology retains a unique diagnostic role in the detection of infectious and neoplastic conditions and in the evaluation of subarachnoid haemorrhage. Cytological detection of erythrophages, siderophages, and haematoidin crystals can reveal haemorrhage and provide clues to its temporal stage. Overall, cerebrospinal fluid cytology remains a valuable diagnostic tool when integrated with clinical, laboratory, microbiological, immunological, and imaging findings. Careful recognition of common pitfalls is essential. We recommend rapid cerebrospinal fluid processing, routine preparation of cytospin-based stained slides with expert microscopic review, and the implementation of automated or digital methods only within clearly validated workflows.
A major challenge for identifying a disease-modifying cure for Parkinson’s disease (PD) is creating models resembling key features of the disease including resting tremor, bradykinesia, muscle rigidity and gait disturbances. In addition, PD patients often develop cognitive symptoms that are associated with pathology in neocortical areas. Initially, PD rodent models were generated primarily by chemical neurotoxins that induce an acute loss of dopaminergic neurons. Upon discovery of familial-PD-linked genetic mutations in the SNCA gene—encoding α-synuclein (αS)—mice carrying these mutations provided deeper insight into the pathologic role of this synaptic protein throughout the brain. αS transgenic mouse models stand out for their ability to develop intraneuronal lesions that are rich in αS phospho-serine 129, a histopathological signature of the human PD brain. Recent advances in αS protein biochemistry led to the generation of mice carrying strategic amplifications of familial-PD-linked αS mutants, resulting in more pronounced neurodegeneration and progressive phenotype development. Here we review advances of αS transgenic mouse model development with a focus on strategic mutations that may have greater potential for identifying underlying disease mechanisms than classical single-mutant and wild-type αS overexpressing mice. We also present how the mice are currently used in testing drug efficacy and target engagement for PD drug discovery and outline strategies for utilizing such mice in basic and translational research.
Pineal region tumors are rare neoplasms that occur in all ages and account for less than 1
