CXCR2 inhibition in G-MDSCs enhances CD47 blockade for melanoma tumor cell clearance.

The use of colony-stimulating factor-1 receptor (CSF1R) inhibitors has been widely explored as a strategy for cancer immunotherapy due to their robust depletion of tumor-associated macrophages (TAMs). While CSF1R blockade effectively eliminates TAMs from the solid tumor microenvironment, its clinical efficacy is limited. Here, we use an inducible CSF1R knockout model to investigate the persistence of tumor progression in the absence of TAMs.

A rhodium(II)/rhodium(III) redox couple for C-H bond amination with alkylazides: a rhodium(III)-nitrenoid intermediate with a tetradentate [14]-macrocyclic ligand.

The catalytic activity of a rhodium(II) dimer complex, [Rh(TMAA)] (TMAA = tetramethyltetraaza[14]annulene), in C-H amination reactions with organic azides is explored. Organic azides (N-R) with an electron-withdrawing group such as a sulfonyl group (trisylazide; R = S(O)CH (Trs)) and a simple alkyl group (R = (CH)Ph, (CH)OCHPh, CHPh, or CHNO) are employed in intra- and intermolecular C-H bond amination reactions. The spectroscopic analysis using ESI-mass and EPR spectroscopy techniques on the reaction intermediate generated from [Rh(TMAA)] and N-R reveals that a rhodium(III)-nitrenoid species is an active oxidant in the C-H bond amination reaction.

Isolation Method for Long-Term and Short-Term Hematopoietic Stem Cells.

Self-renewal capacity and multi-lineage differentiation potential are generally regarded as the defining characteristics of hematopoietic stem cells (HSCs). However, numerous studies have suggested that functional heterogeneity exists in the HSC compartment. Recent single-cell analyses have reported HSC clones with different cell fates within the HSC compartment, which are referred to as biased HSC clones.

gen. nov., sp. nov., a novel bacterium isolated from the brain of the squid, and reclassification of two species as comb. nov. and comb. nov.

A Gram-stain-positive, non-motile, mesophilic, aerobic, coccus-shaped bacterium, designated strain Y7R2, was isolated from the brain of a squid living in mesopelagic water near Muroto, Kochi, Japan. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain was most closely related to the genus (96.1 % similarity to the type strain of the type species ) and formed a separate distinct cluster in a stable, deep-branching lineage with the type strains of and (98.

A Computational Study on the Mechanism of Catalytic Cyclopropanation Reaction with Cobalt N-Confused Porphyrin: The Effects of Inner Carbon and Intramolecular Axial Ligand.

The factors that affect acceleration and high / selectivity in the catalytic cyclopropanation reaction of styrene with ethyl diazoacetate by cobalt N-confused porphyrin (NCP) complexes were investigated using density functional theory calculations. The reaction rate was primarily related to the energy gap between the cobalt-carbene adduct intermediates, and , which was affected by the NCP skeletons and axial pyridine ligands more than the corresponding porphyrin complex. In addition, high / stereoselectivity was determined at the and, in part, in the isomerization process at the carbon-centered radical intermediates, and .

C(sp)-H bond activation by the carboxylate-adduct of osmium tetroxide (OsO).

The reaction of osmium tetroxide (OsO) and carboxylate anions (acetate: X = AcO and benzoate: X = BzO) gave 1 : 1 adducts, [OsO(X)] (1X), the structures of which were determined by X-ray crystallographic analysis. In both cases, the carboxylate anion X coordinates to the osmium centre to generate a distorted trigonal bipyramidal osmium(VIII) complex. The carboxylate adducts show a negative shift of the redox potentials () and a red shift of the stretches as compared to those of tetrahedral OsO itself.

Establishment of a predictive model for GVHD-free, relapse-free survival after allogeneic HSCT using ensemble learning.

Graft-versus-host disease-free, relapse-free survival (GRFS) is a useful composite end point that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS. This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT within the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group of 17 transplantation centers in Japan.

Identification of the minimum requirements for successful haematopoietic stem cell transplantation.

Historically, defining haematopoietic subsets, including self-renewal, differentiation and lineage restriction, has been elucidated by transplanting a small number of candidate cells with many supporting bone marrow (BM) cells. While this approach has been invaluable in characterising numerous distinct subsets in haematopoiesis, this approach is arguably flawed. The haematopoietic stem cell (HSC) has been proposed as the critical haematopoietic subset necessary for transplantation.

Tin(II)-Nitrene Radical Complexes Formed by Electron Transfer from Redox-Active Ligand to Organic Azides and Their Reactivity in C(sp)-H Activation.

A tin(II) complex coordinated by a sterically demanding -phenylenediamido ligand is synthesized. The ligand is redox-active to reach a tin(II) complex with the diiminobenzosemiquinone radial anion in the oxidation by AgPF. The tin(II) complex reacts with a series of nosylazides (-NOCH-SO-N; = , , or ) at -30 °C to yield the corresponding nitrene radical bound tin(II) complexes.

OPERA tau neutrino charged current interactions.

The OPERA experiment was designed to discover the v appearance in a v beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors.

Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment.

Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field have allowed us to analyze HSCs with single cell resolution and implicate that functional heterogeneity may exist even within the highly purified HSC compartment.

Photocatalytic hydrogen evolution using a Ru(ii)-bound heteroaromatic ligand as a reactive site.

A Ru complex, [Ru(tpphz)(bpy)] (1) (tpphz = tetrapyridophenazine, bpy = 2,2'-bipyridine), whose tpphz ligand has a pyrazine moiety, is converted efficiently to [Ru(tpphz-HH)(bpy)] (2) having a dihydropyrazine moiety upon photoirradiation of a water-methanol mixed solvent solution of 1 in the presence of an electron donor. In this reaction, the triplet metal-to-ligand charge-transfer excited state (MLCT*) of 1 is firstly formed upon photoirradiation and the MLCT* state is reductively quenched with an electron donor to afford [Ru(tpphz˙)(bpy)], which is converted to 2 without the observation of detectable reduced intermediates by nano-second laser flash photolysis. The inverse kinetic isotope effect (KIE) was observed to be 0.

Low Multiplication Value of Absolute Monocyte Count and Absolute Lymphocyte Count at Diagnosis May Predict Poor Prognosis in Neuroblastoma.

Despite the growing evidences that immune dysfunction contributes to tumor progression, the prognostic value in patients with neuroblastoma regarding circulating immune blood cell counts has not been well characterized. To answer this, we conducted a retrospective study to evaluate the prognostic value of the circulating immune cell counts at diagnosis in a cohort of 55 patients with neuroblastoma. Based on a novel index by multiplying the absolute monocyte count (AMC)/μl and absolute lymphocyte count (ALC)/μl, we sub-grouped patients with AMC × ALC ≥ 1 × 10 (/μl) as high group and patients with AMC × ALC < 1 × 10 (/μl) as low group.

[Significance and purification of long-term hematopoietic stem cells in the hematopoietic system].

The hematopoietic stem cells, defined as blood stem cells with self-replication ability and multipotency, are key to successful hematopoietic stem cell transplantation. With the history of transplantation in the past 60 years and advances in stem cell technologies, our understanding of the hematopoietic system has deepened. However, the molecular mechanisms of self-renewal and pluripotency, which are the essence of the hematopoietic stem cells, remain poorly understood.

Neutrophil and monocyte kinetics play critical roles in mouse peritoneal adhesion formation.

Peritoneal adhesions are pathological fibroses that ensnare organs after abdominal surgery. This dense connective tissue can cause small bowel obstruction, female infertility, and chronic abdominal pain. The pathogenesis of adhesions is a fibrotic response to tissue damage coordinated between mesothelial cells, fibroblasts, and immune cells.

Role of Amino Acid Residues for Dioxygen Activation in the Second Coordination Sphere of the Dicopper Site of pMMO.

Formation of an active oxygen species at the dicopper site of pMMO is studied by using density functional theory (DFT) calculations. The role of the amino acid residues of tyrosine (Tyr374) and glutamate (Glu35) located in the second coordination sphere of the dicopper site is discussed in detail. The phenolic proton of the tyrosine residue is transferred to the CuO core in a two-step manner via the glutamate residue, and an electron is directly transferred to the CuO core.

Galactosyl carbohydrate residues on hematopoietic stem/progenitor cells are essential for homing and engraftment to the bone marrow.

The role of carbohydrate chains in leukocyte migration to inflamed sites during inflammation and trafficking to the lymph nodes under physiological conditions has been extensively characterized. Here, we report that carbohydrate chains also mediate the homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow (BM). In particular, we found that transplanted BM cells deficient in β-1,4-galactosyltransferase-1 (β4GalT-1) could not support survival in mice exposed to a lethal dose of irradiation.

Final Results of the OPERA Experiment on ν_{τ} Appearance in the CNGS Neutrino Beam.

The OPERA experiment was designed to study ν_{μ}→ν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target.

Where Hematopoietic Stem Cells Live: The Bone Marrow Niche.

Hematopoietic stem cells (HSCs) can sustain the production of blood throughout one's lifetime. However, for proper self-renewal of its own population and differentiation to blood, the HSC requires a specialized microenvironment called the "niche." Recent Advances: Recent studies using novel mouse models have shed new light on the cellular architecture and function of the HSC niche.

Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche.

Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{μ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions.

Do pluripotent stem cells exist in adult mice as very small embryonic stem cells?

Very small embryonic-like stem cells (VSELs) isolated from bone marrow (BM) have been reported to be pluripotent. Given their nonembryonic source, they could replace blastocyst-derived embryonic stem cells in research and medicine. However, their multiple-germ-layer potential has been incompletely studied.

Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response.

Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody-mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response.

Synergistic effect of Tim4 and MFG-E8 null mutations on the development of autoimmunity.

Phagocytes, including macrophages, recognize phosphatidylserine exposed on apoptotic cells as an "eat me" signal. Milk Fat Globule EGF Factor VIII (MFG-E8) is secreted by one subset of macrophages, whereas Tim4, a type I membrane protein, is expressed by another. These proteins bind tightly to phosphatidylserine on apoptotic cells and enhance their engulfment by macrophages.