CLASPs are widely conserved microtubule plus-end-tracking proteins with essential roles in the local regulation of microtubule dynamics. In yeast, Drosophila, and Xenopus, a single CLASP orthologue is present, which is required for mitotic spindle assembly by regulating microtubule dynamics at the kinetochore. In mammals, however, only CLASP1 has been directly implicated in cell division, despite the existence of a second paralogue, CLASP2, whose mitotic roles remain unknown. Here, we show that CLASP2 localization at kinetochores, centrosomes, and spindle throughout mitosis is remarkably similar to CLASP1, both showing fast microtubule-independent turnover rates. Strikingly, primary fibroblasts from Clasp2 knockout mice show numerous spindle and chromosome segregation defects that can be partially rescued by ectopic expression of Clasp1 or Clasp2. Moreover, chromosome segregation rates during anaphase A and B are slower in Clasp2 knockout cells, which is consistent with a role of CLASP2 in the regulation of kinetochore and spindle function. Noteworthy, cell viability/proliferation and spindle checkpoint function were not impaired in Clasp2 knockout cells, but the fidelity of mitosis was strongly compromised, leading to severe chromosomal instability in adult cells. Together, our data support that the partial redundancy of CLASPs during mitosis acts as a possible mechanism to prevent aneuploidy in mammals.

A top priority in biomarker development for Alzheimer’s disease (AD) and Parkinson’s disease (PD) is the focus on early diagnosis, where the use of the retina is a promising avenue of research. We computed fundus images from optical coherence tomography (OCT) data and analysed the structural arrangement of the retinal tissue using texture metrics. We built clinical class classification models to distinguish between healthy controls (HC), AD, and PD, using machine learning (support vector machines). Median sensitivity is 88.7%, 79.5% and 77.8%, for HC, AD, and PD eyes, respectively. When the same subject has the same classification for both eyes, 94.4% (median) of the classifications are correct. A significant amount of information discriminating between multiple neurodegenerative states is conveyed by OCT imaging of the human retina, even when differences in thickness are not yet present. This technique may allow for simultaneously diagnosing Alzheimer’s and Parkinson’s diseases.

Objective: To evaluate the utility of positional testing in peripheral and central acute vestibular syndrome (pAVS, cAVS, respectively). Study design: Prospective; observational. Setting: Tertiary referral center. Patients: Consecutive AVS patients. Interventions: Video-oculography in upright, supine and head hanging positions at presentation, 3-month and 1-year follow-up. Main Outcome Measures: Positional modulation of spontaneous nystagmus; co-occurrence of central paroxysmal positional nystagmus (CPPN). Results: Fifteen pAVS [mean age (SD), 53.3 (16.6) (11 males)] and 15 cAVS [mean age (SD), 56.5 (17.8) (11 males)] patients were included (p=0.49). Acutely, in supine, in patients whose nystagmus was present in both head rotation sides, 12 of 13 (93%) pAVS and only 4 of 12 (33%) cAVS patients showed direction-fixed positional nystagmus which was stronger when turning the head to the slow phase side. The remaining cAVS patients showed either direction-fixed positional nystagmus which was stronger when turning the head to the fast phase side (5), or direction-changing positional geotropic nystagmus (2). One patient in each group showed direction-changing positional apogeotropic nystagmus. During follow-up, direction-changing positional apogeotropic and geotropic nystagmus became common in both groups. Acutely, in head hanging, 5 (33%) cAVS patients showed vertical CPPN and 2 showed positional saccadic intrusions. Positional downbeat nystagmus and saccadic intrusions became chronic. Conclusions: The presence of acute direction-changing positional geotropic nystagmus, stronger direction-fixed positional nystagmus when turning the head to the fast phase side, and acute or chronic head hanging vertical CPPN should raise the suspicion for central AVS. Chronic geotropic and apogeotropic nystagmus following AVS constitute an underrecognized manifestation of vestibular compensation.

Sex and gender, as biological and social factors, significantly influence health outcomes. Among the biological factors, sex differences in vascular physiology may be one specific mechanism contributing to the observed differences in clinical presentation, response to treatment, and clinical outcomes in several vascular disorders. This review focuses on the cerebrovascular bed and summarizes the existing literature on sex differences in cerebrovascular hemodynamics to highlight the knowledge deficit that exists in this domain. The available evidence is used to generate mechanistically plausible and testable hypotheses to underscore the unmet need in understanding sex-specific mechanisms as targets for more effective therapeutic and preventive strategies.

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