Loss of Cpt1a results in elevated glucose-fueled mitochondrial oxidative phosphorylation and defective hematopoietic stem cells.

Hematopoietic stem cells (HSCs) rely on self-renewal to sustain stem cell potential and undergo differentiation to generate mature blood cells. Mitochondrial fatty acid β-oxidation (FAO) is essential for HSC maintenance. However, the role of Carnitine palmitoyl transferase 1a (CPT1A), a key enzyme in FAO, remains unclear in HSCs.

Akkermansia muciniphila induces slow extramedullary hematopoiesis via cooperative IL-1R/TLR signals.

Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear.

Repurposing immunosuppressants for antileukemia therapy.

Drug repurposing, the strategy to identify new therapeutic use for clinically approved drugs has attracted much attention in recent years. This strategy offers various advantages over traditional approaches to develop new drugs, including shorter development timelines, low cost, and reduced risk of failure. In this issue of EMBO Molecular Medicine, Liu et al show that inosine monophosphate dehydrogenase (IMPDH) inhibitors, the well-known immunosuppressants have a potent therapeutic effect on the aggressive blood cancer, acute myeloid leukemia with MLL rearrangements.

Hematopoietic stem and progenitor cells integrate microbial signals to promote post-inflammation gut tissue repair.

Bone marrow (BM)-resident hematopoietic stem and progenitor cells (HSPCs) are often activated following bacterial insults to replenish the host hemato-immune system, but how they integrate the associated tissue damage signals to initiate distal tissue repair is largely unknown. Here, we show that acute gut inflammation expands HSPCs in the BM and directs them to inflamed mesenteric lymph nodes through GM-CSFR activation for further expansion and potential differentiation into Ly6C /G myeloid cells specialized in gut tissue repair. We identified this process to be mediated by Bacteroides, a commensal gram-negative bacteria that activates innate immune signaling.

Quantitative Analysis of Sympathetic and Nociceptive Innervation Across Bone Marrow Regions in Mice.

Bone marrow (BM) innervation regulates the mobilization of hematopoietic stem and progenitor cells (HSPCs) from BM and stress hematopoiesis either by acting directly on HSPCs or by altering the niche function of mesenchymal and endothelial cells. However, the spatial distribution of BM innervation across bone regions is yet to be fully elucidated. Thus, we aimed to characterize the distribution of sympathetic and nociceptive nerves in each bone and BM region using three-dimensional quantitative microscopy.

Remote control of neural function by X-ray-induced scintillation.

Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd(Al,Ga)O (Ce:GAGG), can effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively.

CD271CD51PALLADIN Human Mesenchymal Stromal Cells Possess Enhanced Ossicle-Forming Potential.

Human mesenchymal stem/stromal cells (hMSCs), when engrafted into immunodeficient mice, can form ectopic bone organs with hematopoietic stem cell (HSC) supportive functions. However, the ability to do so, through a cartilage intermediate, appears limited to 30% of donor bone marrow samples. In this study, we characterize the heterogeneous nature of hMSCs and their ability to efficiently form humanized ossicles observed in "good donors" to correlate with the frequency and functionality of chondrocyte progenitors.

Immuno-Modulation of Hematopoietic Stem and Progenitor Cells in Inflammation.

Lifelong blood production is maintained by bone marrow (BM)-residing hematopoietic stem cells (HSCs) that are defined by two special properties: multipotency and self-renewal. Since dysregulation of either may lead to a differentiation block or extensive proliferation causing dysplasia or neoplasia, the genomic integrity and cellular function of HSCs must be tightly controlled and preserved by cell-intrinsic programs and cell-extrinsic environmental factors of the BM. The BM had been long regarded an immune-privileged organ shielded from immune insults and inflammation, and was thereby assumed to provide HSCs and immune cells with a protective environment to ensure blood and immune homeostasis.

Hypnotic effect of thalidomide is independent of teratogenic ubiquitin/proteasome pathway.

Thalidomide exerts its teratogenic and immunomodulatory effects by binding to cereblon (CRBN) and thereby inhibiting/modifying the CRBN-mediated ubiquitination pathway consisting of the Cullin4-DDB1-ROC1 E3 ligase complex. The mechanism of thalidomide's classical hypnotic effect remains largely unexplored, however. Here we examined whether CRBN is involved in the hypnotic effect of thalidomide by generating mice harboring a thalidomide-resistant mutant allele of ( knock-in mice).

Development of the hematopoietic system: Role of inflammatory factors.

Hematopoietic stem cells (HSCs) have two defining features, multipotency and self-renewal, both of which are tightly controlled by cell autonomous programs and environmental factors throughout the lifetime of an organism. During development, HSCs are born in the aorta-gonad-mesonephros region, and migrate to distinct hematopoietic organs such as the placenta, fetal liver and spleen, continuously self-renewing and expanding to reach a homeostatic number. HSCs ultimately seed the bone marrow around the time of birth and become dormant to sustain lifelong hematopoiesis.

Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus-the 'D-shuttle' project.

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter 'D-shuttle' for two weeks, and kept a journal of his/her whereabouts and activities.

Cellular analysis of cleavage-stage chick embryos reveals hidden conservation in vertebrate early development.

Birds and mammals, phylogenetically close amniotes with similar post-gastrula development, exhibit little conservation in their post-fertilization cleavage patterns. Data from the mouse suggest that cellular morphogenesis and molecular signaling at the cleavage stage play important roles in lineage specification at later (blastula and gastrula) stages. Very little is known, however, about cleavage-stage chick embryos, owing to their poor accessibility.

HINTW, a W-chromosome HINT gene in chick, is expressed ubiquitously and is a robust female cell marker applicable in intraspecific chimera studies.

Grafting and transplantation experiments in embryology require proper distinction between host and donor tissues. For the avian model this has traditionally been achieved by using two closely related species (e.g.

Extending the limits of avian embryo culture with the modified Cornish pasty and whole-embryo transplantation methods.

The New and Early Chick (EC) methods, two commonly used techniques for ex ovo culture of early-stage avian embryos, are limited by poor survivability after initiation of circulation. This limitation is circumvented with two recent technical advancements: the modified Cornish pasty culture and whole-embryo transplantation. The former supports optimal ex ovo growth till stage HH18, and the latter allows ex-ovo-manipulated embryos to have long-term in ovo-survivability.

Versatile roles of R-Ras GAP in neurite formation of PC12 cells and embryonic vascular development.

Ras GTPase-activating proteins (GAP) are negative regulators of Ras that convert active Ras-GTP to inactive Ras-GDP. R-Ras GAP is a membrane-associated molecule with stronger GAP activity for R-Ras, an activator of integrin, than H-Ras. We found that R-Ras GAP is down-regulated during neurite formation in rat pheochromocytoma PC12 cells by nerve growth factor (NGF), which is blocked by the transient expression of R-Ras gap or dominant negative R-ras cDNA.

A transposable element-mediated gene divergence that directly produces a novel type bovine Bcnt protein including the endonuclease domain of RTE-1.

Ruminant Bcnt protein with a molecular mass of 97 kDa (designated p97Bcnt) includes a region derived from the endonuclease domain of a retrotransposable element RTE-1. Human and mouse Bcnt proteins lack the corresponding region but have a highly conserved 82-amino acid region at the C-terminus that is not present in p97Bcnt. By screening a bovine BAC library, we found two more bcnt-related genes: human-type bcnt (h-type bcnt) and its processed pseudogene.

Arsenic contamination in groundwater of Samta, Bangladesh.

In March 1997, we analyzed the water of all tubewells used for drinking in Samta village in the Jessore district, Bangladesh. It has been confirmed from the survey that the arsenic contamination in Samta was one of the worst in the Ganges basin including West Bengal, India. 90% of the tubewells had arsenic concentrations above the Bangladesh standard of 0.

Gene organization of bovine BCNT that contains a portion corresponding to an endonuclease domain derived from an RTE-1 (Bov-B LINE), non-LTR retrotransposable element: duplication of an intramolecular repeat unit downstream of the truncated RTE-1.

BCNT (a protein named after Bucentaur or craniofacial development protein 1) has a unique structure in Ruminantia. Bovine BCNT contains a region of the endonuclease domain derived from a truncated RTE-1 (previously called Bov-B LINE), a non-LTR retrotransposable repetitive element, and two repeat units (intramolecular repeat, IR) each with 40 amino acids in the C-terminal region. In contrast the human and mouse BCNT proteins contain one repeat unit and lack the RTE-1-derived portion.

Mutations in the novel membrane protein spinster interfere with programmed cell death and cause neural degeneration in Drosophila melanogaster.

Mutations in the spin gene are characterized by an extraordinarily strong rejection behavior of female flies in response to male courtship. They are also accompanied by decreases in the viability, adult life span, and oviposition rate of the flies. In spin mutants, some oocytes and adult neural cells undergo degeneration, which is preceded by reductions in programmed cell death of nurse cells in ovaries and of neurons in the pupal nervous system, respectively.

Expression of a mouse zinc finger protein gene in both spermatocytes and oocytes during meiosis.

In order to identify genes regulating meiosis, a mouse spermatocyte cDNA library was screened for sequences encoding proteins with C2H2-type zinc finger motifs which are typically expressed by the Drosophila Krüppel gene. Three new cDNAs were isolated, and they were designated CTfin33, CTfin51, and CTfin92. Among them, CTfin51 was selected for further study.

A new tetracycline antibiotic with antitumor activity. II. The structural elucidation of SF2575.

The structure of a new antitumor antibiotic SF2575, has been determined by spectroscopic analyses of the antibiotic and its alkaline degradation products. The relative stereochemistry has been confirmed by X-ray crystallographic analysis. The antibiotic has a 2-naphthacenecarboxamide carbon skelton which is structurally related to the tetracycline antibiotics and it is unique by bearing C-glycoside, salicyclic acid and angelic acid moieties.