Subtypes of medulloblastoma have distinct developmental origins

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.     

大亚湾石珊瑚群落近25年的变化及其对2008年极端低温事件的响应

在气候变暖、ENSO加剧等导致全球珊瑚礁生态系统严重退化的背景下, 相对高纬度海域的石珊瑚群落被认为是石珊瑚物种延续的最后保留地, 但相对高纬度海域周期性的冬季低温是妨碍其发育的最重要因子之一. 南海北部相对高纬度的大亚湾海区(22°31′~22°50′N)近40年来持续变暖, 珊瑚群落发育但未成礁. 2008年初经历了近50年来罕见的极端低温事件, 持续32 d, 大亚湾海区2008年2月平均SST低于14℃, 连续多天最低SST为12.3℃左右, 低于传统认为的使珊瑚“致命”的温度(13℃), 日最低气温则低达6.6℃. 该海域的石珊瑚群落生态调查显示: (1) 近25年来大亚湾石珊瑚覆盖度从76.6%下降到15.3%, 退化达80%; (2) 石珊瑚群落优势种由霜鹿角珊瑚变成秘密角蜂巢珊瑚; (3) 2008年低温事件对本区石珊瑚群落没有造成明显影响, 活珊瑚覆盖度没有发生明显变化. 总体结果显示, 相对高纬度的大亚湾海区的珊瑚种类已经总体上适应了极端低温的环境, 具有进一步发育的潜力, 可望在全球变暖背景下成为石珊瑚物种的避难所.     

The nature of the solar activity during the Maunder Minimum revealed by the Guliya ice core record

Whether the solar activity was very low, and especially whether the solar cycle existed, during the Maunder Minimum (1645–1715 AD), have been disputed for a long time. In this paper we use the Guliya NO₃ ⁻ data, which can reflect the solar activity, to analyze the characteristics of the solar activity during the Maunder Minimum. The results show that the solar activity was indeed low, and solar cycle displayed normal as present, i.e. about 11a, in that period. Moreover, it was found that the solar activity contains a 36-year periodic component probably, which might be related to the variations in the length of the sunspot cycle. This finding is of importance for the study of the relationship between the sun variability and the Earth climate change.     

Methodology choice in a coercive context

Action research has been conducted into the problem of software usability. Guidance in methodology selection was sought in the work of M. C. Jackson. In the absence of suitable methodology for what was judged to be a systemic-coercive situation, use was made of radical design methods. Both radical design and the theory of Jackson are evaluated in this paper