Preclinical research using different rodent model systems has largely contributed to the scientific progress in the pain field, however, it suffers from interspecies differences, limited access to human models, and ethical concerns. Human induced pluripotent stem cells (iPSCs) offer major advantages over animal models, i.e., they retain the genome of the donor (patient), and thus allow donor-specific and cell-type specific research. Consequently, human iPSC-derived nociceptors (iDNs) offer intriguingly new possibilities for patient-specific, animal-free research. In the present study, we characterized iDNs based on the expression of well described nociceptive markers and ion channels, and we conducted a side-by-side comparison of iDNs with mouse sensory neurons. Specifically, immunofluorescence (IF) analyses with selected markers including early somatosensory transcription factors (BRN3A/ISL1/RUNX1), the low-affinity nerve growth factor receptor (p75), hyperpolarization-activated cyclic nucleotide-gated channels (HCN), as well as high voltage-gated calcium channels (VGCC) of the Ca_V2 type, calcium permeable TRPV1 channels, and ionotropic GABA_A receptors, were used to address the characteristics of the iDN phenotype. We further combined IF analyses with microfluorimetric Ca²⁺ measurements to address the functionality of these ion channels in iDNs. Thus, we provide a detailed morphological and functional characterization of iDNs, thereby, underpinning their enormous potential as an animal-free alternative for human specific research in the pain field for unveiling pathophysiological mechanisms and for unbiased, disease-specific personalized drug development.

Atlantic herring (Clupea harengus), an ecologically and economically important species in the northern hemisphere, shows pronounced seasonal migratory behaviour. To follow distinctive migration patterns over hundreds of kilometers between feeding, overwintering and spawning grounds, they are probably guided by orientation mechanisms. We tested whether juvenile spring-spawning Atlantic herring, caught in the western Baltic, use a sun compass for orientation just before they start leaving their hatching area. Fish were randomly divided into two groups, one of them clock-shifted 6 h backwards, to investigate whether they shift their orientation direction accordingly. Individual fish were placed in a circular bowl and their orientation was tested multiple times with the sun as a sole visual orientational cue. Our results show for the first time that juvenile Atlantic herring use a time-compensated sun compass during their migration. Their swimming direction was impaired, but still present, even when the sky was very cloudy, indicating additional orientation capabilities.

Background. Long‐term hematopoietic stem cells (LT‐HSCs) reside in bone marrow niches with tightly controlled reactive oxygen species (ROS) levels. ROS increase results into LT‐HSC differentiation and stem cell exhaustion. Paraoxonase 2 (PON2) has been shown to be important for ROS control. Objectives. We investigate the effects of inactivation of the PON2 gene on hematopoietic cell differentiation and activity. Methods and Results. In young mice with inactivated Pon2 gene (Pon2^-/-, 9 months), Pon2 depletion caused an increase in LT‐HSCs as well as increased levels of granulocyte/macrophage progenitors (GMPs) and myeloid skewing, indicating a premature aging phenotype. No significant changes in ROS levels in old Pon2^-/- LT‐ and short‐term (ST‐) HSCs were observed, but a significant reduction of spontaneous apoptotic cell death was measured. RNA‐seq analysis in Pon2^-/- LT‐HSCs identified overrepresentation of genes involved in the C‐X‐C chemokine receptor type 4 (Cxcr4) signaling, suggesting compensatory mechanisms to overcome ROS‐mediated accelerated aging in hematopoietic progenitor cells. Conclusions. In summary, our current data indicate that PON2 is involved in the regulation of HSC functions.

Sprat (Sprattus sprattus) is one of the most commercially exploited fish species in the Baltic Sea and expresses a pronounced seasonal migration pattern. Spawning takes place, among other places, in the Kiel Bight and Kiel Fjord in early summer. Juvenile sprat leave the nursery areas in late summer/early autumn to move to their feeding and overwintering grounds. What kind of orientation mechanisms sprat use for migration is not known yet. This study shows that juvenile sprat can use a time-compensated sun compass, heading towards the northeast, in the direction of their proposed overwintering grounds in Bornholm Basin. The sprats tested at the end of August oriented themselves in the predicted direction, whereas the sprats tested at the beginning of August only showed a random orientation. For the first time, this demonstrates the onset of migratory readiness in juvenile sprat, indicating the preparation for starting their migration.

Millions of minute, newly hatched coral reef fish larvae get carried into the open ocean by highly complex and variable currents. To survive, they must return to a suitable reef habitat within a species-specific time. Strikingly, previous studies have demonstrated that return to home reefs is much more frequent than would be expected by chance. It has been shown that magnetic and sun compass orien-tation can help cardinalfish maintain their innate swimming direction but do they also have a navigational map to cope with unexpected displacements? If dis-placed settling-stage cardinalfish Ostorhinchus doederleini use positional infor-mation during their pelagic dispersal, we would expect them to re-orient toward their home reef. However, after physical displacement by 180 km, the fish showed a swimming direction indistinguishable from original directions near the capture site. This suggests that the tested fish rely on innate or learned com-pass directions and show no evidence for map-based navigation.