Biology subjects

Konig, S.

Publications and source records attributed to Konig, S..

3 recordsLinked to original sources

bioRxiv2026

Cortical bursts provide spatio-temporal frames for the large-scale phase synchrony emerging across the birth transition

Structural corticocortical connectivity grows rapidly around birth, but how it establishes the large-scale neuronal interactions needed for lifelong neurocognitive performance remains unclear. Using repeated high-density EEG from 233 preterm-born infants recorded at 33-45 weeks postmenstrual age, we characterized the development of three phase-based interaction modes with distinct temporal relationships to cortical bursts: burst-based, burst-framed, and general phase-based connectivity. Burst-framed connectivity was quantified with a novel metric, nested phase-phase correlation. All three modes declined globally with age but differed spatially: burst-based connectivity became more confined, burst-framed connectivity reorganized towards sensorimotor-association connectivity, whereas general phase-based connectivity retained a stable modular organization. General phase-based connectivity was initially concentrated along burst-framed connections, but this coupling weakened with age. Its greater persistence around term age was associated with poorer neurocognitive outcomes, suggesting delayed network maturation. These findings suggest that bursting may transiently scaffold the maturation of large-scale corticocortical phase synchrony across the birth transition.

neuroscience↗

bioRxiv2024

Structural basis of archaeal RNA polymerase transcription elongation and Spt4/5 recruitment

Archaeal transcription is carried out by a multi-subunit RNA polymerase (RNAP) that is highly homologous in structure and function to eukaryotic RNAP II. Among the set of basal transcription factors, only Spt5 is found in all domains of life but Spt5 has been shaped during evolution, which is also reflected in the heterodimerization of Spt5 with Spt4 in Archaea and Eukaryotes. To unravel the mechanistic basis of Spt4/5 function in Archaea, we performed structure-function analyses using the archaeal transcriptional machinery of Pyrococcus furiosus (Pfu). We report single-particle cryo-electron microscopy reconstructions of apo RNAP and the archaeal elongation complex (EC) in the absence and presence of Spt4/5. Surprisingly, Pfu Spt4/5 also binds the RNAP in the absence of nucleic acids in a distinct super-contracted conformation. We show that the RNAP clamp/stalk module exhibits conformational flexibility in the apo state of RNAP and that the enzyme contracts upon EC formation or Spt4/5 engagement. We furthermore identified a contact of the Spt5-NGN domain with the DNA duplex that stabilizes the upstream boundary of the transcription bubble and impacts Spt4/5 activity in vitro. This study, therefore, provides the structural basis for Spt4/5 function in archaeal transcription and reveals a potential role beyond the well-described support of elongation.

biochemistry↗

bioRxiv2019

Cell culture dimensionality influences mesenchymal stem cell fate through cadherin-2 and cadherin-11

The acquisition of a specific cell fate is one of the core aims of tissue engineering and regenerative medicine. Significant evidence shows that aggregate cultures have a positive influence on fate decisions, presumably through cell-cell interactions, but little is known about the specific mechanisms. To investigate the difference between cells cultured as a monolayer and as aggregates, we started by looking at cadherin expression, an important protein involved in cell adhesion, during the differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in aggregate and monolayer cultures. We observed that proliferating hMSCs in monolayer culture express cadherin-2 and undergo a switch to cadherin-11 over time, which was not evident in the aggregate cultures. By knocking down cadherin-2 and cadherin-11, we found that both cadherins were required for adipogenic differentiation in a monolayer as well as aggregate culture. However, during osteogenic differentiation, low levels of cadherin-2 were found to be favorable for cells cultured as a monolayer and as aggregates, whereas cadherin-11 was dispensable for cells cultured as aggregates. Together, these results provide compelling evidence for the important role that cadherins play in regulating the differentiation of hMSCs and how this is affected by the dimensionality of cell culture.

cell biology↗