Biology subjects

Schinke, T.

Publications and source records attributed to Schinke, T..

3 recordsLinked to original sources

bioRxiv2023

Increased beta2-adrenergic signaling is a targetable stimulus essential for bone healing by promoting callus neovascularization

Traumatic brain injury (TBI) is associated with a hyperadrenergic state and paradoxically causes systemic bone loss while accelerating fracture healing. Here, we identify the beta2-adrenergic receptor (Adrb2) as a central mediator of these skeletal manifestations. While the negative effects of TBI on the unfractured skeleton can be explained by the established impact of Adrb2 signaling on bone formation, Adrb2 promotes neovascularization of the fracture callus under conditions of high sympathetic tone, including TBI and advanced age. Mechanistically, norepinephrine stimulates the expression of Vegfa and Cgrp primarily in periosteal cells via Adrb2, both of which synergistically promote the formation of osteogenic type-H vessels in the fracture callus. Accordingly, the beneficial effect of TBI on bone repair is abolished in mice lacking Adrb2 or Cgrp, and aged Adrb2-deficient mice without TBI develop fracture nonunions despite high bone formation in uninjured bone. Pharmacologically, the Adrb2 antagonist propranolol impairs, and the agonist formoterol promotes fracture healing in aged mice by regulating callus neovascularization. Clinically, intravenous beta-adrenergic sympathomimetics are associated with improved callus formation in trauma patients with long bone fractures. Thus, Adrb2 is a novel target for promoting bone healing, and widely used beta-blockers may cause fracture nonunion under conditions of increased sympathetic tone. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/548550v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@cea57corg.highwire.dtl.DTLVardef@d29642org.highwire.dtl.DTLVardef@186ea5aorg.highwire.dtl.DTLVardef@83eaae_HPS_FORMAT_FIGEXP M_FIG Artwork was created in BioRender. C_FIG

cell biology↗

bioRxiv2023

Pupil dilation scales with movement distance of real but not of imagined reaching movements

Pupillary responses have now been reliably identified for cognitive and motor tasks, but less is known about their relation to mentally simulating movements (known as motor imagery). Previous work found pupil dilations during the performance of simple finger movements, where peak pupillary dilation scaled with the complexity of the finger movement and force required. Recently, pupillary dilations were reported during imagery of grasping and piano playing. Here we examined whether pupillary responses are sensitive to the dynamics of the underlying motor task for both executed and imagined reach movements. Participants reached or imagined reaching to one of three targets placed at different distances from a start position. Both executed and imagined movement times scaled with target distance, and they were highly correlated, confirming previous work and suggesting that participants did imagine the respective movement. Increased pupillary dilation was evident during motor execution compared to rest, with stronger dilations for larger movements. Pupil dilations also occurred during motor imagery, however they were generally weaker than during motor execution and they were not influenced by imagined movement distance. Instead, dilations during motor imagery resembled pupil responses obtained during a non-motor imagery task (imagining a previously viewed painting). Our results demonstrate that pupillary responses can reliably capture the dynamics of an executed goal-directed reaching movement, but suggest that pupillary responses during imagined reaching movements reflect general cognitive rather than motor-specific components of the motor imagery process. New and noteworthyPupil size is influenced by the performance of cognitive tasks. Here we demonstrate that pupil size increases during execution and mental simulation of goal-directed reaching movements compared to rest. Pupil dilations scale with movement amplitude only during motor execution, whereas they are similar during motor imagery and a non-motor imagery, cognitive task.

neuroscience↗

bioRxiv2021

G6b-B regulates an essential step in megakaryocyte maturation

G6b-B is a megakaryocyte lineage-specific immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor, essential for platelet homeostasis. Mice with a genomic deletion of the entire Mpig6b locus develop severe macrothrombocytopenia and myelofibrosis, which is reflected in humans with null-mutations in MPIG6B. The current model proposes that megakaryocytes lacking G6b-B develop normally, while proplatelet release is hampered, but the underlying molecular mechanism remains unclear. Here, we report on a spontaneous recessive single nucleotide mutation in C57BL/6 mice, localized within the intronic region of the Mpig6b locus that abolishes G6b-B expression and reproduces macrothrombocytopenia, myelofibrosis and osteosclerosis. As the mutation is based on a single nucleotide exchange, Mpig6bmut mice represent an ideal model to study the role of G6b-B. Megakaryocytes from these mice were smaller in size, displayed a less developed demarcation membrane system and reduced expression of receptors. RNA sequencing revealed a striking global reduction in the level of megakaryocyte-specific transcripts, in conjunction with decreased protein levels of the transcription factor GATA-1, and impaired thrombopoietin signaling. The reduced number of mature MKs in the bone marrow was corroborated on a newly developed Mpig6b null mouse strain. Our findings highlight an unexpected essential role of G6b-B in the early differentiation within the megakaryocytic lineage.

cell biology↗