A case of indeterminate cell histiocytosis with ETV3-NCOA2 translocation.

Indeterminate cell histiocytosis (ICH) is a rare histiocytic disorder characterized by a proliferation of CD1a and CD207/langerin cells. Recent molecular analyses have identified ETV3-NCOA2 translocation as a possible aetiopathogenesis of ICH. Herein, we describe the first Japanese case of ICH with ETV3-NCOA2 translocation.

Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer.

Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 ≥15% (CD8-high) received nivolumab monotherapy.

The Neurog2-Tbr2 axis forms a continuous transition to the neurogenic gene expression state in neural stem cells.

Neural stem cells (NSCs) differentiate into neuron-fated intermediate progenitor cells (IPCs) via cell division. Although differentiation from NSCs to IPCs is a discrete process, recent transcriptome analyses identified a continuous transcriptional trajectory during this process, raising the question of how to reconcile these contradictory observations. In mouse NSCs, Hes1 expression oscillates, regulating the oscillatory expression of the proneural gene Neurog2, while Hes1 expression disappears in IPCs.

The significance of ultradian oscillations in development.

Genes regulating developmental processes have been identified, but the mechanisms underlying their expression with the correct timing are still under investigation. Several genes show oscillatory expression that regulates the timing of developmental processes, such as somitogenesis and neurogenesis. These oscillations are also important for other developmental processes, such as cell proliferation and differentiation.

Transcriptional control of neural stem cell activity.

In the adult brain, neural stem cells (NSCs) are under the control of various molecular mechanisms to produce an appropriate number of neurons that are essential for specific brain functions. Usually, the majority of adult NSCs stay in a non-proliferative and undifferentiated state known as quiescence, occasionally transitioning to an active state to produce newborn neurons. This transition between the quiescent and active states is crucial for the activity of NSCs.

Elucidating the Quenching Mechanism of Tris(2,2'-bipyridyl)ruthenium(II) Complex in the Water-Glycerol Binary System Based on the Microscopic Structure of the Media.

Kinetic studies on the photochemical quenching reaction of the tris(2,2'-bipyridyl) ruthenium(II) complex ([Ru(bpy)]) in water-glycerol binary media were conducted based on the Einstein-Smoluchowski (E-S) theory. Dynamic and static quenching behaviors were analyzed by comparing results from time-resolved spectroscopy and emission spectroscopy. While the dynamic quenching reaction aligns well with the E-S theory, static quenching was observed, leading to a notable increase in the overall photoquenching reaction rate constant.

Fluctuation of lysosomal protein degradation in neural stem cells of the postnatal mouse brain.

Lysosomes are intracellular organelles responsible for degrading diverse macromolecules delivered from several pathways, including the endo-lysosomal and autophagic pathways. Recent reports have suggested that lysosomes are essential for regulating neural stem cells in developing, adult and aged brains. However, the activity of these lysosomes has yet to be monitored in these brain tissues.

An essential role for miR-15/16 in Treg suppression and restriction of proliferation.

The miR-15/16 family targets a large network of genes in T cells to restrict their cell cycle, memory formation, and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained response. Here, we used conditional deletion of miR-15/16 in regulatory T cells (Tregs) to identify immune functions of the miR-15/16 family in T cells.

SUMOylation effects on neural stem cells self-renewal, differentiation, and survival.

SUMO (small ubiquitin-like modifier) conjugation or SUMOylation, a post-translational modification, is a crucial regulator of protein function and cellular processes. In the context of neural stem cells (NSCs), SUMOylation has emerged as a key player, affecting their proliferation, differentiation, and survival. By modifying transcription factors, such as SOX1, SOX2, SOX3, SOX6, Bmi1, and Nanog, SUMOylation can either enhance or impair their transcriptional activity, thus impacting on NSCs self-renewal.

Efficient use of all ports of a 3 × 3 coupler in a nonlinear amplifying loop mirror-based fiber laser.

We present an all-polarization-maintaining mode-locked fiber laser based on a nonlinear amplifying loop mirror utilizing a 3 × 3 coupler. A pump laser diode placed outside the cavity pumps both the oscillator and fiber amplifier. This laser configuration effectively utilizes all ports of the coupler, making the laser compact and low-cost, and has great potential as a seed laser for ultrashort pulse lasers.

Differential cell-cycle control by oscillatory versus sustained Hes1 expression via p21.

Oscillatory Hes1 expression activates cell proliferation, while high and sustained Hes1 expression induces quiescence, but the mechanism by which Hes1 differentially controls cell proliferation depending on its expression dynamics is unclear. Here, we show that oscillatory Hes1 expression down-regulates the expression of the cyclin-dependent kinase inhibitor p21 (Cdkn1a), which delays cell-cycle progression, and thereby activates the proliferation of mouse neural stem cells (NSCs). By contrast, sustained Hes1 overexpression up-regulates p21 expression and inhibits NSC proliferation, although it initially down-regulates p21 expression.

A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Napabucasin Combined with Sorafenib in Japanese Patients with Unresectable Hepatocellular Carcinoma.

Background And Objective: For patients with advanced hepatocellular carcinoma (HCC), the standard of care for many years has been sorafenib. Preliminary data have suggested that the combination of the NAD(P)H:quinone oxidoreductase 1 bioactivatable agent napabucasin plus sorafenib may improve clinical outcomes in patients with HCC. In this phase I, multicenter, uncontrolled, open-label study, we evaluated napabucasin (480 mg/day) plus sorafenib (800 mg/day) in Japanese patients with unresectable HCC.

An essential role for miR-15/16 in Treg suppression and restriction of proliferation.

The miR-15/16 family is a highly expressed group of tumor suppressor miRNAs that target a large network of genes in T cells to restrict their cell cycle, memory formation and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained immune response. Here, using conditional deletion of miR-15/16 in immunosuppressive regulatory T cells (Tregs) that express FOXP3, we identify new functions of the miR-15/16 family in T cell immunity.

Forced expression of the non-coding RNA miR-17∼92 restores activation and function in CD28-deficient CD4 T cells.

CD28 provides the prototypical costimulatory signal required for productive T-cell activation. Known molecular consequences of CD28 costimulation are mostly based on studies of protein signaling molecules. The microRNA cluster miR-17∼92 is induced by T cell receptor stimulation and further enhanced by combined CD28 costimulation.

Biological Significance of the Coupling Delay in Synchronized Oscillations.

The significance of the coupling delay, which is the time required for interactions between coupled oscillators, in various oscillatory dynamics has been investigated mathematically for more than three decades, but its biological significance has been revealed only recently. In the segmentation clock, which regulates the periodic formation of somites in embryos, Hes7 expression oscillates synchronously between neighboring presomitic mesoderm (PSM) cells, and this synchronized oscillation is controlled by Notch signaling-mediated coupling between PSM cells. Recent studies have shown that inappropriate coupling delays dampen and desynchronize Hes7 oscillations, as simulated mathematically, leading to the severe fusion of somites and somite-derived tissues such as the vertebrae and ribs.