A Fat Body-Derived IGF-like Peptide Regulates Postfeeding Growth in Drosophila

SummaryMembers of the insulin family of peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. Here we show that Drosophila insulin-like peptide 6 (DILP6), which is structurally similar to vertebrate insulin-like growth factor (IGF), is predominantly expressed in the fat body, a functional equivalent of the vertebrate liver and adipocytes. This expression occurs during the postfeeding stage under the direct regulation of ecdysteroid. We further reveal that dilp6 mutants show growth defects during the postfeeding stage, which results in reduced adult body size through a decrease in cell number. This phenotype is rescued by fat body-specific expression of dilp6. These data indicate that DILP6 is a functional, as well as a structural, counterpart of vertebrate IGFs. Our data provide in vivo evidence for a role of ILPs in determining adult body size through the regulation of postfeeding growth

Phenethyl iosothiocyanate activates leptin signaling

Obesity, a principal risk factor for the development of diabetes mellitus, heart disease, and hypertension, is a growing and serious health problem all over the world. Leptin is a weight-reducing hormone produced by adipose tissue, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. In this study, we revealed that phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate in certain cruciferous vegetables, potently inhibits recombinant PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in differentiated human SH-SY5Y neuronal cells. PEITC treatment also induced nuclear accumulation of phosphorylated STAT3, resulting in enhanced anorexigenic POMC expression and suppressed orexigenic NPY/AGRP expression. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity

Macrophage HIF-1α increases liver tumor

Aims/Introduction: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of liver cancer. Recently, it was reported that hypoxia‐inducible factor‐1α (HIF‐1α) is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity‐ and diabetes‐associated liver cancer using macrophage‐specific HIF‐1α knockout (KO) mice. Materials and Methods: To induce liver cancer in the mice, diethylnitrosamine, a chemical carcinogen, was used. Both KO mice and wild‐type littermates were fed either a high‐fat diet (HFD) or normal chow. They were mainly analyzed 6 months after HFD feeding. Results: Development of liver cancer after HFD feeding was 45% less in KO mice than in wild‐type littermates mice. Phosphorylation of extracellular signal‐regulated kinase 2 was also lower in the liver of KO mice. Those effects of HIF‐1α deletion in macrophages were not observed in normal chow‐fed mice. Furthermore, the size of liver tumors did not differ between KO and wild‐type littermates mice, even those on a HFD. These results suggest that the activation of macrophage HIF‐1α by HFD is involved not in the growth, but in the development of liver cancer with the enhanced oncogenic extracellular signal‐regulated kinase 2 signaling in hepatocytes. Conclusions: The activation of macrophage HIF‐1α might play important roles in the development of liver cancer associated with diet‐induced obesity and diabetes

Analysis software for upper atmospheric data developed by the IUGONET project and its application to polar science

To comprehensively understand the Arctic and Antarctic upper atmosphere, it is often crucial to analyze various data that are obtained from many regions. Infrastructure that promotes such interdisciplinary studies on the upper atmosphere has been developed by a Japanese inter-university project called the Inter-university Upper atmosphere Global Observation Network (IUGONET). The objective of this paper is to describe the infrastructure and tools developed by IUGONET. We focus on the data analysis software. It is written in Interactive Data Language (IDL) and is a plug-in for the THEMIS Data Analysis Software suite (TDAS), which is a set of IDL libraries used to visualize and analyze satellite- and ground-based data. We present plots of upper atmospheric data provided by IUGONET as examples of applications, and verify the usefulness of the software in the study of polar science. We discuss IUGONET’s new and unique developments, i.e., an executable file of TDAS that can run on the IDL Virtual Machine, IDL routines to retrieve metadata from the IUGONET database, and an archive of 3-D simulation data that uses the Common Data Format so that it can easily be used with TDAS

A novel transgenic chimaeric mouse system for the rapid functional evaluation of genes encoding secreted proteins

A major challenge of the post-genomic era is the functional characterization of anonymous open reading frames (ORFs) identified by the Human Genome Project. In this context, there is a strong requirement for the development of technologies that enhance our ability to analyze gene functions at the level of the whole organism. Here, we describe a rapid and efficient procedure to generate transgenic chimaeric mice that continuously secrete a foreign protein into the systemic circulation. The transgene units were inserted into the genomic site adjacent to the endogenous immunoglobulin (Ig) κ locus by homologous recombination, using a modified mouse embryonic stem (ES) cell line that exhibits a high frequency of homologous recombination at the Igκ region. The resultant ES clones were injected into embryos derived from a B-cell-deficient host strain, thus producing chimaerism-independent, B-cell-specific transgene expression. This feature of the system eliminates the time-consuming breeding typically implemented in standard transgenic strategies and allows for evaluating the effect of ectopic transgene expression directly in the resulting chimaeric mice. To demonstrate the utility of this system we showed high-level protein expression in the sera and severe phenotypes in human EPO (hEPO) and murine thrombopoietin (mTPO) transgenic chimaeras

フククウキョウ シュジュツカ ニ セイフクシタ Sジョウ ケッチョウ カンマク レッコウ ヘルニア ノ 1レイ

症例は45歳、女性。深夜に突然、左下腹部痛を認め近医受診し、当院紹介となった。造影CTを行ったところ、腹水および小腸ループの拡張が認められた。絞扼性腸閉塞の診断のもと、緊急手術を施行した。腹腔鏡下に腹腔内を観察すると、血性腹水を認め、S状結腸間膜に直径約3cmの異常裂孔が存在し、小腸が貫通して脱出しており、S状結腸間膜裂孔ヘルニアによる腸閉塞と診断した。小腸の整復は比較的容易で、小腸の色調も問題なく、腸切除をすることなく裂孔を体内結紮縫合閉鎖し手術を終了した。術後経過は良好で、術後5日目に退院となった。A 45-year-old woman admitted with left abdominal pain. Abdominal computed tomography revealed ascites and mechanical obstruction of small intestine. Urgent laparoscopic surgery was performed. Laparoscopy showed　bloody ascites and an oval hernial orifice about 3 cm diameter in the mesentery of sigmoid colon. Small intestine invaginated through this orifice. The reduction in small intestine was easy relatively, and the color tone of the small intestine was also no problem. Intraabdominal ligation suture closes this hiatus, and an operation has been ended without resection of small intestine. This patient had a good clinical course and was discharged 5 days after operation

ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation

ERAL1, a homologue of Era protein in Escherichia coli, is a member of conserved GTP-binding proteins with RNA-binding activity. Depletion of prokaryotic Era inhibits cell division without affecting chromosome segregation. Previously, we isolated ERAL1 protein as one of proteins which were associated with mitochondrial transcription factor A by using immunoprecipitation. In this study, we analysed the localization and function of ERAL1 in mammalian cells. ERAL1 was localized in mitochondrial matrix and associated with mitoribosomal proteins including the 12S rRNA. siRNA knockdown of ERAL1 decreased mitochondrial translation, caused redistribution of ribosomal small subunits and reduced 12S rRNA. The knockdown of ERAL1 in human HeLa cells elevated mitochondrial superoxide production and slightly decreased mitochondrial membrane potential. The knockdown inhibited the growth of HeLa cells with an accumulation of apoptotic cells. These results suggest that ERAL1 is localized in a small subunit of the mitochondrial ribosome, plays an important role in the small ribosomal constitution, and is also involved in cell viability

ハンカイ シンケイ ドウテイ ニ NIMシステム オ モチイタ Zenkerケイシツ ノ 1レイ

　Zenker憩室はKillian’s間隙に発生した憩室であり，全消化管憩室の0.1%の頻度と稀である．今回われわれは，術中神経モニタリングシステムであるNIMシステム(NERVE INTEGRITY MONITORING SYSTEM；以下，NIMと略記)をZenker憩室の手術で使用し，反回神経を容易に同定することが可能であったので報告する．　症例は67歳，女性．数年前から咽頭部の違和感を自覚し，２カ月前から増悪したため当院外来を受診した．精査の結果，症状を認めるZenker憩室と診断し，手術を施行した．NIMを使用して反回神経の走行を確認しつつ憩室を同定した．憩室を切除後，二層縫合(Albert-Lembert吻合)して閉鎖した．術中内視鏡検査を施行し，食道に狭窄や漏れがないことを確認した．輪状咽頭筋切開を追加し，甲状腺を縫合部の前面で固定して縫合部を補強した．ドレーンを留置して手術を終了した．術後経過は良好で手術から14日目に退院とし，退院後１ヶ月の時点で症状は改善していることを確認した．　Zenker憩室の手術で反回神経損傷は回避すべき合併症のひとつである．甲状腺手術で使用するNIMはZenker憩室の手術においても反回神経の同定に使用することで，神経損傷のリスクを下げる可能性がある．　Zenker’s diverticulum is a diverticulum that develops in the Killian’s gap. The frequency of its occurrence is 0.1% of all digestive tract diverticulum. The present study reports that the NIM system can be useful during Zenker’s diverticulum surgery for easily identifying recurrent laryngeal nerve.　The present case is of a 67-year-old woman. She was aware of discomfort in her pharyngeal region for several years. She had been aggrieved for the past 2 months, and therefore was admitted to our hospital’s outpatient clinic. Following examination, we diagnosed Zenker’s diverticulum and performed surgery. We identified recurrent laryngeal nerve using NIM. We dissected the diverticulum and sutured in layers and closed. Intraoperative endoscopy was performed to confirm that there was no stenosis or leakage in the esophagus. We performed ring pharyngeal muscle incision. We fixed the thyroid gland in front of the suture to reinforce it. There was no untoward event postoperatively, and the patient was discharged from the hospital on day 14 after the surgery. We confirmed that the symptom had improved at 1 month after discharge.　NIM used in thyroid surgery is also useful in identifying the recurrent laryngeal nerve during Zenker’s diverticula surgery and may help reduce the risk of nerve damage