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Kokkalis, A.

Publications and source records attributed to Kokkalis, A..

2 recordsLinked to original sources

Repurposed macroH2A Chromatin Landscapes Guide Cellular Reprogramming

Cellular reprogramming converts differentiated cells into a pluripotent state through extensive chromatin remodeling. The histone variant macroH2A has classically viewed as an epigenetic barrier stabilizing somatic identity and restricting pluripotency gene activation. Here, we show that during reprogramming, macroH2A1 nucleosomes undergo functional repurposing. Early in the process, mH2A1 nucleosomes act as a barrier to cellular plasticity, but later facilitate the establishment and maintenance of pluripotency by reshaping the epigenetic landscape. High-resolution chromatin profiling reveals that mH2A1.2 nucleosomes undergo rapid, large-scale repositioning, dissociating from promoters and reassembling [~]30 bp away, frequently near NRF-1 binding sites. This repositioning occludes E2F4 binding, relieving cell-cycle arrest thereby enabling reprogramming. Likewise, mH2A1.1 nucleosomes display extensive mobility that culminates in deposition at pluripotency genes in ESCs, where they sustain their expression by assembling promoter transcriptional hubs. In this later role, mH2A1.1 functions as a chromatin bookmark stabilizing the Nanog, Sox2, and Oct4 network. These findings suggest that mH2A1 nucleosomal mobility underlines its context-dependent functional repurposing from reprogramming inhibitor to facilitator, illustrating how chromatin components evolve dynamic roles to coordinate cell-state transitions.

molecular biology↗

Implementing the precautionary approach into fisheries management: Making the case for probability-based harvest control rules

The precautionary approach to fisheries management advocates for risk-averse management strategies that include biological reference points as well as decision rules and account for scientific uncertainty. In this regard, two approaches have been recommended: (i) harvest control rules (HCRs) with threshold reference points to safeguard against low stock biomass, and (ii) the P* method, a probability-based HCR that reduces the catch limit as a function of scientific uncertainty (i.e. process, model, and observation uncertainty). This study compares the effectiveness of these precautionary approaches in recovering over-exploited fish stocks with various life-history traits and under a wide range of levels of scientific uncertainty. We use management strategy evaluation based on a stochastic, age-based operating model with quarterly time steps and a stochastic surplus production model. The results show that the most effective HCR includes both a biomass threshold as well as the P* method, and leads to high and stable long-term yield with a decreased risk of low stock biomass. For highly dynamics stocks, management strategies that aim for higher biomass targets than the traditionally used BMSY result in higher long-term yield. This study makes the case for probability-based HCRs by demonstrating their benefit over deterministic HCRs and provides a list of recommendations regarding their definition and implementation.

ecology↗