Structure, function, and evolution of plant NIMA-related kinases: implication for phosphorylation-dependent microtubule regulation

icrotubules are highly dynamic structures that control the spatiotemporal pattern of cell growth and division. Microtubule dynamics are regulated by reversible protein phosphorylation involving both protein kinases and phosphatases. Never in mitosis A (NIMA)-related kinases (NEKs) are a family of serine/threonine kinases that regulate microtubule-related mitotic events in fungi and animal cells (e.g. centrosome separation and spindle formation). Although plants contain multiple members of the NEK family, their functions remain elusive. Recent studies revealed that NEK6 of Arabidopsis thaliana regulates cell expansion and morphogenesis through β-tubulin phosphorylation and microtubule destabilization. In addition, plant NEK members participate in organ development and stress responses. The present phylogenetic analysis indicates that plant NEK genes are diverged from a single NEK6-like gene, which may share a common ancestor with other kinases involved in the control of microtubule organization. On the contrary, another mitotic kinase, polo-like kinase, might have been lost during the evolution of land plants. We propose that plant NEK members have acquired novel functions to regulate cell growth, microtubule organization, and stress responses

COMPARISON OF VIRTUAL UNENHANCED AND TRUE UNENHANCED ATTENUATION VALUES BY DUAL-ENERGY CT FOR DETECTING INDISTINCT LIVER METASTASES ON CONTRAST-ENHANCED CT

Purpose : We aimed to evaluate the differences between true unenhanced (TUE) and virtual unenhanced (VUE) computed tomography (CT) performed by contrast-enhanced CT with dualenergy CT in the assessment of liver metastases that were difficult to visually identify with contrast- enhanced CT. Materials and methods : Between April 2018 and September 2019, we identified 266 patients with liver metastases who underwent unenhanced and contrast-enhanced CT with dual-energy CT at our institution, and enrolled 43 liver metastases in 19 patients (7.1%) that were indistinct on contrast-enhanced CT.　Mean CT attenuation values for liver metastases and liver parenchyma were measured, and differences between the CT attenuation values for liver metastases and liver parenchyma were analyzed using VUE CT and TUE CT. Results : The mean CT attenuation values for liver metastases and liver parenchyma in VUE CT versus TUE CT were 51.0 vs. 41.0 HU (p<0.001) and 58.2 HU vs. 61.2 HU (p=0.027), respectively.　The differences in CT attenuation values between liver metastases and liver parenchyma were 10.1 HU on VUE CT vs. 19.3 HU on TUE CT (p<0.001). Conclusion : The contrast between lesions and liver parenchyma on VUE CT was significantly lower than that on TUE CT.　VUE CT cannot currently replace TUE CT

Extracellular DJ-1 induces sterile inflammation in the ischemic brain.

Inflammation is implicated in the onset and progression of various diseases, including cerebral pathologies. Here, we report that DJ-1, which plays a role within cells as an antioxidant protein, functions as a damage-associated molecular pattern (DAMP) and triggers inflammation if released from dead cells into the extracellular space. We first found that recombinant DJ-1 protein induces the production of various inflammatory cytokines in bone marrow-derived macrophages (BMMs) and dendritic cells (BMDCs). We further identified a unique peptide sequence in the αG and αH helices of DJ-1 that activates Toll-like receptor 2 (TLR2) and TLR4. In the ischemic brain, DJ-1 is released into the extracellular space from necrotic neurons within 24 h after stroke onset and makes direct contact with TLR2 and TLR4 in infiltrating myeloid cells. Although DJ-1 deficiency in a murine model of middle cerebral artery occlusion did not attenuate neuronal injury, the inflammatory cytokine expression in infiltrating immune cells was significantly decreased. Next, we found that the administration of an antibody to neutralize extracellular DJ-1 suppressed cerebral post-ischemic inflammation and attenuated ischemic neuronal damage. Our results demonstrate a previously unknown function of DJ-1 as a DAMP and suggest that extracellular DJ-1 could be a therapeutic target to prevent inflammation in tissue injuries and neurodegenerative diseases