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Never-in-mitosis A (NIMA)-related kinases (NEKs) regulate a series of mitotic events in fungi and animals, whereas plant NEKs have been shown to control the growth direction of cells and organs. Plant NEKs are highly expressed in the meristem, but whether they regulate meristematic activity remains unknown. The liverwort Marchantia polymorpha has a single functional MpNEK1 gene, and its knockout results in twisted rhizoid growth. For a gain-of-function approach, we generated lines for the inducible expression of MpNEK1 using an estrogen receptor-mediated system. Estradiol treatment effectively induced the accumulation of MpNEK1 mRNA and MpNEK1-Citrine fusion protein throughout the plant. MpNEK1 overexpression severely suppressed rhizoid and thallus growth, ultimately leading to the lethality of juvenile plants. This severe effect was observed even at the nanomolar level of estradiol. EdU (5-ethynyl-2'-deoxyuridine) staining and microtubule imaging clearly indicated suppression of cell division by estradiol-induced MpNEK1. MpNEK1 induction also reduced cortical microtubule density and dynamics but did not severely affect cell growth and morphology in thalli. Overexpression of kinase-deficient MpNEK1 also suppressed thallus and rhizoid growth, although to a slightly lesser extent than wild-type MpNEK1, indicating a phosphorylation-independent mechanism of growth suppression. Furthermore, Mpnek1 mutants exhibited growth suppression in their reproductive organs, the gametangiophores. This supports the role of MpNEK1 in cell division, as observed in both fungi and animals.
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http://dx.doi.org/10.1093/pcp/pcaf021 | DOI Listing |
Haematologica
September 2025
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Okayama.
Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), exhibit distinct pathophysiologic mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, the differences in IL-6 production sources between subtypes remain unclear.
View Article and Find Full Text PDFHaematologica
September 2025
Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel.
We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors.
View Article and Find Full Text PDFHaematologica
September 2025
Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan; Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke.
Patient age might influence donor selection priorities in allogeneic hematopoietic stem cell transplantation (allo-HCT), due to the differences in donor age, organ function, and resistance to graft-versus-host disease between younger and older patients. We compared the transplant outcomes among human leukocyte antigen (HLA)-matched related donors (M-RDs, n=4,106), HLA 1-antigen-mismatched related donors (1MM-RDs, n=592), HLA 2-3-antigen-mismatched related donors (23MM-RDs, n=882), HLA-matched unrelated donors (M-UDs, n=3,927), HLA 1-locus-mismatched unrelated donors (1MM-UDs, n=2,474), and unrelated cord blood units (U-CBs, n=5,867) between patients aged.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
September 2025
Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, MA (K. Cui, B.Z., B.W., S.E.-B., A.V., H.C.).
Background: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-laden foam cells and plaques within the arterial wall. Dysfunctional vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells, and macrophages contribute to disease progression. Here, we report that macrophage-specific expression of epsins, highly conserved endocytic adaptor proteins involved in clathrin-mediated endocytosis, accelerates atherosclerosis in Western diet-fed mice.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
September 2025
Department of Medicine/Division of Cardiology, University of California Los Angeles. (S.S., C.R.S., L.F., M.P., C.P., Z.Z., J.J.M., R.C.D., D.S., A.J.L.).
Background: In genetic studies with the Hybrid Mouse Diversity Panel, we previously identified a chromosome 9 locus for atherosclerosis. We now identify NNMT (nicotinamide -methyltransferase), an enzyme that degrades nicotinamide, as the causal gene in the locus and show that the underlying mechanism involves salvage of nicotinamide to nicotinamide adenine dinucleotide (NAD).
Methods: Gain/loss of function studies in macrophages were performed to examine the role of NAD levels in macrophage proliferation and apoptosis in atherosclerosis.