Mirk/Dyrk1B controls ventral spinal cord development via Shh pathway.

Cross-talk between Mirk/Dyrk1B kinase and Sonic hedgehog (Shh)/Gli pathway affects physiology and pathology. Here, we reveal a novel role for Dyrk1B in regulating ventral progenitor and neuron subtypes in the embryonic chick spinal cord (SC) via the Shh pathway. Using in ovo gain-and-loss-of-function approaches at E2, we report that Dyrk1B affects the proliferation and differentiation of neuronal progenitors at E4 and impacts on apoptosis specifically in the motor neuron (MN) domain. Especially, Dyrk1B overexpression decreases the numbers of ventral progenitors, MNs, and V2a interneurons, while the pharmacological inhibition of endogenous Dyrk1B kinase activity by AZ191 administration increases the numbers of ventral progenitors and MNs. Mechanistically, Dyrk1B overexpression suppresses Shh, Gli2 and Gli3 mRNA levels, while conversely, Shh, Gli2 and Gli3 transcription is increased in the presence of Dyrk1B inhibitor AZ191 or Smoothened agonist SAG. Most importantly, in phenotype rescue experiments, SAG restores the Dyrk1B-mediated dysregulation of ventral progenitors. Further at E6, Dyrk1B affects selectively the medial lateral motor neuron column (LMCm), consistent with the expression of Shh in this region. Collectively, these observations reveal a novel regulatory function of Dyrk1B kinase in suppressing the Shh/Gli pathway and thus affecting ventral subtypes in the developing spinal cord. These data render Dyrk1B a possible therapeutic target for motor neuron diseases.

Combining elemental and immunochemical analyses to characterize diagenetic alteration patterns in ancient skeletal remains.

Bones and teeth are biological archives, but their structure and composition are subjected to alteration overtime due to biological and chemical degradation postmortem, influenced by burial environment and conditions. Nevertheless, organic fraction preservation is mandatory for several archeometric analyses and applications. The mutual protection between biomineral and organic fractions in bones and teeth may lead to a limited diagenetic alteration, promoting a better conservation of the organic fraction. However, the correlation between elemental variations and the presence of organic materials (e.g., collagen) in the same specimen is still unclear. To fill this gap, chemiluminescent (CL) immunochemical imaging analysis has been applied for the first time for collagen localization. Then, Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) and CL imaging were combined to investigate the correlation between elemental (i.e., REE, U, Sr, Ba) and collagen distribution. Teeth and bones from various archeological contexts, chronological periods, and characterized by different collagen content were analyzed. Immunochemical analysis revealed a heterogeneous distribution of collagen, especially in highly degraded samples. Subsequently, LA-ICP-MS showed a correlation between the presence of uranium and rare earth elements and areas with low amount of collagen. The innovative integration between the two methods permitted to clarify the mutual relation between elemental variation and collagen preservation overtime, thus contributing to unravel the effects of diagenetic alteration in bones and teeth.

Marine reservoir effect on the Southeastern coast of Brazil: results from the Tarioba shellmound paired samples.

On the Southeastern coast of Brazil the presence of many archaeological shellmounds offers a great potential for studying the radiocarbon marine reservoir effect (MRE). However, very few such studies are available for this region. These archaeological settlements, mostly dating from 5 to 2 kyr cal BP, include both terrestrial and marine remains in good stratigraphic context and secure association, enabling the comparison of different carbon reservoirs. In a previous study the chronology of the Sambaqui da Tarioba, located in Rio de Janeiro state, Brazil, was established based on marine mollusc shells and charcoal samples from hearths, from several layers in two excavated sectors. We now compare the different materials with the aim of studying the MRE in this region. Calibration was performed with Oxford software OxCal v4.2.3 using the marine curve Marine13 with an undetermined offset to account for local corrections for shell samples, and the atmospheric curve SHCal13 for charcoal samples. The distribution of results considering a phase model indicates a ΔR value of -127 ± 67 (14)C yr in the 1 sigma range and the multi-paired approach leads to a mean value of -110 ± 94 (14)C yr.