Impacts of biodiversity on the emergence and transmission of infectious diseases

Current unprecedented declines in biodiversity reduce the ability of ecological communities to provide many fundamental ecosystem services. Here we evaluate evidence that reduced biodiversity affects the transmission of infectious diseases of humans, other animals and plants. In principle, loss of biodiversity could either increase or decrease disease transmission. However, mounting evidence indicates that biodiversity loss frequently increases disease transmission. In contrast, areas of naturally high biodiversity may serve as a source pool for new pathogens. Overall, despite many remaining questions, current evidence indicates that preserving intact ecosystems and their endemic biodiversity should generally reduce the prevalence of infectious diseases.     

Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice

Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X?chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X?chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X?chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X?chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.     

Genomic and functional adaptation in surface ocean planktonic prokaryotes

The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0?μm size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass.     

Ⅱ,Ⅲ期乳腺癌综合疗法对比分析（附69例报告）

对Ⅱ、Ⅲ期乳腺癌６９例综合方法疗效对比分析。全组５年生存率５３６％，Ⅱ期７８％，Ⅲ期４７２％，Ⅱ期各组（Ｓ，Ｓ＋Ｃ，Ｓ＋Ｒ，Ｓ＋Ｒ＋Ｃ）无显著差别；Ⅲ期各组Ｓ１４２％，Ｓ＋Ｃ３３％，Ｓ＋Ｒ４７３％，Ｓ＋Ｒ＋Ｃ６０％（Ｐ＜００５）说明综合治疗方法对生存率有影响，增加放疗对Ⅲ期尤为显著；加放组淋巴区胸壁３年复发率与未加放组比为１∶２（９／５０：７／１９），其复发平均时间为３１８∶１３５（月），说明加放对局部控制效果的肯定。增加化疗（ＣＭＦ／ＣＡＦ／ＣＥＦ）与未加化疗比生存率有改变，前者为５９５％（２２／３７），后者为３３３％（３／９），而除Ｓ组外，增加化疗使Ｓ＋Ｒ＋Ｃ达６０％，Ｓ＋Ｒ４７３％组无显著性差别（０２５＞Ｐ＞０１０）。Ｓ＋（Ｓ＋Ｃ）与（Ｓ＋Ｒ）＋（Ｓ＋Ｒ＋Ｃ）组５年生存率，前者为３６８％（７／１９），后者为６０％（３０／５０）。     

Prediction of central nervous system embryonal tumour outcome based on gene expression.

Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.     

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.