D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2^R140Q and IDH2^R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life span, recapitulating the abnormalities observed in D2HGA patients. The diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant up-regulation of genes involved in glycogen biosynthesis. Notably, mild cardiac hypertrophy was also observed in nude mice implanted with IDH2^R140Q-expressing xenografts, suggesting that 2HG may potentially act in a paracrine fashion. Finally, we show that silencing of IDH2^R140Q in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition.     

Resequencing and association analysis of MIR137 with schizophrenia in a Japanese population

MicroRNA may play a role in the pathophysiology of schizophrenia. A recent meta‐analysis of genome‐wide association studies indicated a significant association between schizophrenia and a common intronic variation in MIR137HG (microRNA 137 host gene) encoding the primary microRNA‐137. To explore additional risk variations for schizophrenia, we resequenced MIR137 and performed an association analysis in 1321 Japanese individuals. By resequencing, we detected four sequence variations in the 5' and 3' flanking regions. There were no significant associations between these variations and schizophrenia. Our resequencing and association analysis of MIR137 failed to find additional risk variations for schizophrenia.     

Dysregulated miR‐98 Contributes to Extracellular Matrix Degradation by Targeting IL‐6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) is associated with dysregulated expression of microRNAs (miRNAs). However, the precise molecular mechanisms underlying this disorder remain unclear. Therefore, we tested the hypothesis that miRNAs modulate IDD through effects on the IL‐6/STAT3 signaling pathway, a potential regulator of IDD. The miRNA expression profile was determined in nucleus pulposus (NP) tissues from patients with IDD and controls, employing miRNA microarray and quantitative real‐time PCR (RT‐qPCR). Biological functions of differential expression miRNAs were further investigated using immunofluorescent staining. Luciferase reporter assays and Western blotting were performed to determine miRNA targets. We identified 41 miRNAs that were differentially expressed in patients compared with controls. Following RT‐qPCR confirmation, miR‐98 was significantly downregulated in degenerative NP tissues. Moreover, its level was inversely correlated with grade of disc degeneration. Through gain‐of‐function and loss‐of‐function studies, miR‐98 was shown to significantly promote type II collagen expression in NP cells. Interleukin‐6 (IL‐6) was identified as a target of miR‐98. Knockdown of IL‐6 induced effects on NP cells similar to those induced by miR‐98. In contrast, IL‐6 treatment abrogated the effects induced by miR‐98 upregulation. Moreover, miR‐98 dramatically suppressed expression of STAT3 target gene, MMP2. IL‐6 treatment antagonized this effect, whereas knockdown of IL‐6 by IL‐6 short hairpin RNA (shIL‐6) induced inhibitory effects on the expression of p‐STAT3 and its main target genes, similar to miR‐98. The mRNA level of IL‐6 was inversely correlated with that of miR‐98 in degenerative NP tissues. These results suggest the downregulation of miR‐98 could promote IDD through the IL‐6/STAT3 signaling pathway. Our findings also highlight miR‐98 as a novel hopeful therapeutic target for IDD. © 2015 American Society for Bone and Mineral Research.     

氢化物原子荧光法测定溪黄草中的硒

目的：建立氢化物原子荧光法测定溪黄草中硒含量的方法。方法：样品经1＋1的硝酸-高氯酸消解完全、6．0mol／L的盐酸预还原后通过氢化物原子荧光法进行测定。结果：方法的检出限为0．02mg／kg，精密度为5．7％，回收率为86％-105％。结论：采用氢化物原子荧光法测定溪黄草中的硒，方法污染少、灵敏度高、准确度较好。     

隐球菌脑膜脑炎MRI不典型表现1例

1　病历简介患者男 ,2 0岁 ,因“头痛近 2个月 ,视力减退 1个月”入院。患者入院前 2个月 :“上感”后出现两颞侧间性胀痛 ,逐渐进展为持续性全头痛 ,阵发性加重伴有头昏、恶心、呕吐 ,1个月后并发视物模糊 ,视力很快下降至眼前 0 5ｍ可见手动。头颅ＭＲＩ示 :Ｔ1ＷＩ无异常信     

A preliminary study into injuries due to non-perforating ballistic impacts into soft body armour over the spine

The UK Home Office test method for ballistic protective police body armours considers anterior torso impacts to be the worst-case scenario and tests rear armour panels to the same standards as front panels. The aim of this paper was to examine the injuries from spinal behind armour blunt trauma (BABT) impacts. This study used a cadaveric 65 kg, female pig barrel and 9 mm Luger ammunition (9 × 19 mm, FMJ Nammo Lapur Oy) into HG1/A + KR1 soft armour panels over the spine. Injuries were inspected and sections removed for x-radiography and micro-CT assessment.All shots over the spine resulted in deep soft tissue injuries from pencilling of the armour and the shirt worn under the armour. The wounds had embedded fabric debris which would require surgery to remove resulting in increased recovery time over injuries usually seen in anterior torso BABT impacts, which are typically haematoma and fractured ribs. The shot with the deepest soft tissue wound (41 mm) also resulted in a fractured spinous process. Shots were also fired at the posterior and anterior rib area of the pig barrel, for comparison to the spine. Similar wounds were seen on the shots to the posterior rib area while shallower, smaller wounds were seen on the anterior and one anterior rib shot resulted in a single, un-displaced rib fracture. The anatomical differences between pigs and humans would most likely mean that injury to a human from these impacts would be more serious.