Dichotomy Between Orbital and Magnetic Nematic Instabilities in BaFe2S3

Nematic orders emerge nearly universally in iron-based superconductors, but elucidating their origins is challenging because of intimate couplings between orbital and magnetic fluctuations. The iron-based ladder material BaFe2S3, which superconducts under pressure, exhibits antiferromagnetic order below TN ~ 117K and a weak resistivity anomaly at T* ~ 180K, whose nature remains elusive. Here we report angle-resolved magnetoresistance (MR) and elastoresistance (ER) measurements in BaFe2S3, which reveal distinct changes at T*. We find that MR anisotropy and ER nematic response are both suppressed near T*, implying that an orbital order promoting isotropic electronic states is stabilized at T*. Such an isotropic state below T* competes with the antiferromagnetic order, which is evidenced by the nonmonotonic temperature dependence of nematic fluctuations. In contrast to the cooperative nematic orders in spin and orbital channels in iron pnictides, the present competing orders can provide a new platform to identify the separate roles of orbital and magnetic fluctuations.Comment: 7 pages 5 figures, to be published in Phys. Rev. Re

Cytomegalovirus-associated biliary atresia

The pathogenesis of biliary atresia (BA) is propounded to be an immunological process, but the detailed mechanisms remain unclear. In recent studies with abnormal immunological findings, T cells have drawn attention in the mechanism of BA pathogenesis. Furthermore, cytomegalovirus (CMV) infection in BA patients resulted in elevated levels of helper T cells (Th1 and Th17) and reduction of regulatory T cells. Thus, CMV infection is considered as a cause of BA.We present the case of a 3-month-old boy who presented with intracerebral hemorrhage and finally died of liver failure. BA was diagnosed on autopsy and serum CMV-IgM was positive, but CMV antigen in the liver tissue was negative.Because CMV-associated BA has poor prognosis, compared with BA not associated with CMV, accurate classification of the type of BA is essential. Keywords: Biliary atresia, Cytomegalovirus, Cytomegalovirus-associated biliary atresi

Association of Type 2 Deiodinase Thr92Ala Polymorphism with Pediatric Obesity in Japanese Children: A Case-Control Study

Genetic factors play critical roles in the onset and progression of obesity. Brown adipose tissue (BAT) activity is also critical for adiposity. The objective of this study was to evaluate the prevalence and effects of BAT gene polymorphisms in pediatric obesity. This case-control study included 270 non-obese and 86 obese children. All participants underwent genotyping for type 2 deiodinase (DIO2) Thr92Ala (rs225014). The prevalence of the homozygous Ala/Ala allele of the DIO2 gene in the obese group was 15.1% versus 6.3% in the non-obese group, resulting in an odds ratio (OR) of 3.393 (p = 0.003). The results of this study indicate that the homozygous Ala/Ala allele of the DIO2 gene is associated with an increased risk of pediatric obesity and suggest that pediatric obesity might be suitable for assessing the association with gene polymorphisms related to BAT, especially DIO2 Thr92Ala

Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice

<div><p>Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO’s anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO’s suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT’s endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO’s improvement of obesity and glucose homeostasis can be attributed to increased iBAT thermogenic capacity and activation of BAT’s endocrine functions.</p></div

Using patient-derived iPSCs to develop humanized mouse models for chronic myelomonocytic leukemia and therapeutic drug identification, including liposomal clodronate

Chronic myelomonocytic leukemia (CMML) is an entity of myelodysplastic syndrome/myeloproliferative neoplasm. Although CMML can be cured with allogeneic stem cell transplantation, its prognosis is generally very poor due to the limited efficacy of chemotherapy and to the patient’s age, which is usually not eligible for transplantation. Comprehensive analysis of CMML pathophysiology and the development of therapeutic agents have been limited partly due to the lack of cell lines in CMML and the limited developments of mouse models. After successfully establishing patient’s derived disease-specific induced pluripotent stem cells (iPSCs) derived from a patient with CMML, we utilized these CMML-iPSCs to achieve hematopoietic re-differentiation in vitro, created a humanized CMML mouse model via teratomas, and developed a drug-testing system. The clinical characteristics of CMML were recapitulated following hematopoietic re-differentiation in vitro and a humanized CMML mouse model in vivo. The drug-testing system using CMML-iPSCs identified a MEK inhibitor, a Ras inhibitor, and liposomal clodronate as potential drugs for treating CMML. Clodronate is a drug commonly used as a bisphosphonate for osteoporosis. In this study, the liposomalization of clodronate enhanced its effectiveness in these assays, suggesting that this variation of clodronate may be adopted as a repositioned drug for CMML therapy

Effect of erythropoietin (EPO) on differentiation related genes in interscapular BAT (iBAT).

<p>Histology of iBAT was examined by HE staining (Scale bar = 50 μm). <b>(A)</b> Macroscopic images of iBAT. <b>(B)</b> Representative histology of iBAT in normal chow diet mice (NC-Con), high-fat diet mice (HFD-Con), and EPO-treated high-fat diet mice (HFD-EPO). <b>(C)</b> The number of cells/area in iBAT was counted. <b>(D)</b> Real-time PCR experiments. <b>(E)</b> Western blot analysis. Values are mean ± SE for 4–8 mice. ^a<i>P</i> < 0.05 or ^aa<i>P</i> < 0.01, vs. NC-Con. ^bP < 0.05 or ^bbP < 0.01, vs. mice fed normal chow diet plus EPO (NC-EPO). ^cP < 0.05 or ^ccP < 0.01, vs. mice HFD-Con.</p

Effect of erythropoietin (EPO) on the expressions of PGC1α and UCP1 in interscapular BAT (iBAT).

<p><b>(A)</b> Real-time PCR experiments. <b>(B)</b> Western blot analysis. <b>(C)</b> Arbitrary unit multiplied by iBAT weight. Values shown are mean ± SE for 4–8 mice. ^a<i>P</i> <0 .05 or ^aa<i>P</i> < 0.01, vs, mice fed normal chow diet (NC-Con). ^bP < 0.05 or ^bbP < 0.01, vs. mice fed normal chow diet plus EPO (NC-EPO). ^cP < 0.05 or ^ccP < 0.01, vs. mice fed a high-fat diet alone (HFD-Con).</p