Biology subjects

Shulman, A.

Publications and source records attributed to Shulman, A..

4 recordsLinked to original sources

bioRxiv2026

Fidelity-Ensuring Consistency of Mitosis is Safeguarded by the 53BP1-USP28-p53 Pathway

Mitosis is monitored by and mechanically coupled to the spindle assembly checkpoint (SAC), which halts mitotic progression until fidelity is met, disregarding time efficiency. Conversely, there exists SAC-independent, efficiency-promoting surveillance mechanically uncoupled from mitosis. This external mitotic surveillance (EMS), comprising 53BP1, USP28, and p53, induces post-mitotic arrest following prolonged, inefficient mitosis. To explore additional EMS inputs, we performed comparative CRISPR-Cas9 screens for genes functionally safeguarded by EMS, identifying, among others, two components of the RZZ kinetochore complex--KNTC1 and ZWILCH. Depleting KNTC1, which impairs fidelity-ensuring activities of mitosis, including SAC, triggered population-level post-mitotic arrests without widespread, characteristic mitotic delay or catastrophe. Instead, KNTC1 depletion produced mostly viable mitosis and yet activated EMS via ectopic accumulation of 53BP1-USP28-p53 complexes over normal mitotic duration. These results suggest that when the fidelity-ensuring control within mitosis is itself compromised, mitosis is rendered invalid from without by EMS, echoing Godels incompleteness theorems.

cell biology↗

bioRxiv2025

Neurophysiological mechanisms of immersive virtual reality influence segmental motor reflexes

Immersive virtual reality (VR) technologies are being increasingly applied in clinical settings, physiotherapy, and neurorehabilitation due to their potential to modulate neurophysiological functions. However, the mechanistic basis of VRs effects on human motor systems, especially the impact of emotionally charged VR experiences on segmental spinal reflex excitability, remains unclear. This study aimed to compare the effects of immersive VR stimulation with different emotional tones, the Jendrassik maneuver, and transcranial magnetic stimulation on spinal motor center excitability in healthy adults. H-reflex and M-response amplitudes in the soleus muscle were measured during tibial nerve stimulation under control conditions, during the Jendrassik maneuver, subthreshold magnetic stimulation, and while participants viewed VR videos evoking fear, excitement, or relaxation. The experimental design randomized condition order for each participant. The principal finding was that emotionally salient VR content, particularly scenes inducing fear, produced clear lateralized effects on the spinal motor system. Specifically, inhibitory effects on reflex excitability were observed in the dominant limb, while facilitatory changes occurred in the non-dominant limb. These patterns suggest that immersive VR may differentially engage descending modulatory systems, influencing both sympathoadrenal and corticospinal pathways. In contrast, traditional neuromodulatory interventions did not alter reflex parameters compared to control. The results highlight the unique multimodal influence of immersive VR on sensorimotor regulation and support its incorporation into advanced neurorehabilitation protocols.

physiology↗

bioRxiv2025

Centriole biogenesis is seeded by CEP152-CEP63-PCNT aggregates propagating outside the centriole through the Alstrom syndrome protein ALMS1

Biogenesis of subcellular structures like centrioles is viewed as a physical transformation wherein elementary constituents form order without preexisting templates. Centrioles grow with precision from a composite scaffold known as the cartwheel, which is thought to self-assemble without templates and disassemble following centriole growth; however, the mechanism governing cartwheel assembly-disassembly dynamics remains obscure. Here, we identify ALMS1, a disease-linked, intrinsically disordered protein (IDP), as an external mediator of cartwheel dynamics that causes a seed for cartwheel--and thus centriole--formation without itself incorporating into the seed structure. The cartwheel seed (CS), characterized as a dense composite of CEP152/CEP63 protein complexes, forms in interphase and adopts a nanoscale, concentric ring from which the cartwheel grows. Upon mitotic entry, CSs recruit ALMS1 while disassembling into constituents associating with ALMS1 in proximity, correlating with cartwheel assembly-disassembly cycles. Hypomorph, disease-linked ALMS1 mutations trigger cartwheel expansion and shedding by its own grown procentriole, in turn forming ectopic centrioles, leading to perpetual reciprocal amplification. Without ALMS1, CS formation fails, negating centriole biogenesis, whereas reintroducing ALMS1 initializes biogenesis anew, creating diverse yet heritable architectures that evolve through selection, instead of generating a single canonical form. These results suggest that centriole biogenesis is grounded on adaptable transformation cues extrinsic to its constituents, propagating via IDP-mediated CS assembly-disassembly cycles, a process we conjecture involves memory.

cell biology↗

bioRxiv2020

The interaction of curiosity and reward on long-term memory in younger and older adults

Long-term memory is sensitive to both intrinsic and extrinsic motivation, but little is known about the relative influence of these two sources of motivation on memory performance across the adult lifespan. The study examined the effects of extrinsic motivation, manipulated via monetary reward, and curiosity, a form of intrinsic motivation, on long-term memory in healthy younger and older adults. During the incidental encoding phase on Day 1, 60 younger and 53 older participants viewed high- and low-curiosity trivia items as well as unrelated face stimuli. Half of the participants in each age group received financial rewards for correctly guessing trivia answers. On Day 2, participants completed a trivia recall test and an old-new recognition test for the face stimuli. Both curiosity and reward were associated with enhanced trivia recall, but the effects were interactive, such that only low-curiosity items benefitted from monetary reward. Neither curiosity nor reward affected face recognition performance in either age group. These findings indicate that individual and joint effects of intrinsic and extrinsic motivation on long-term memory are relatively preserved in healthy aging, a finding that highlights the viability of motivational strategies for memory enhancement into old age. Identifying conditions under which memory for unrelated information benefits from motivational spillover effects in younger and older adults is a priority for future research.

animal behavior and cognition↗