Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.     

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus

TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.     

基于区域增长及边缘检测的一种图象分割方法

提出一种图象分割算法．这种算法综合了三种算法，即区域增长、边缘检测及保持边界平滑方法．它可以明显地克服区域增长及边缘检测各自的缺点．在这种方法中还引进了边界平滑算法使得分割所产生的边界更可靠．可直接应用到三图象分割、医学图象分割的实验中，证明了这种方法的有效性     

Reconsidering the Fresnel–Maxwell theory shift: how the realist can have her cake and EAT it too

This paper takes another look at a case study which has featured prominently in a variety of arguments for rival realist positions. After critically reviewing the previous commentaries of the theory shift that took place in the transition from Fresnel’s ether to Maxwell’s electromagnetic theory of optics, it will defend a slightly different reading of this historical case study. Central to this task is the notion of explanatory approximate truth, a concept which must be carefully analysed to begin with. With this notion properly understood, it will be finally argued, the popular Fresnel–Maxwell case study points towards a novel formulation of scientific realism.     

城市用水:21世纪的挑战

世界城市人口的不断增加，给即将到来的下个世纪带来了一些极为严重的环境问题——最显而易见的是，到2Z25年，必须为5亿城市居民（是目前的两倍）提供安全、纯净的用水。1997年，LjNU（联合国大学）在东京组织了一个主题为“对世纪的城市用水”的讨论会，会议云集了8位世界顶尖专家，分别来自亚洲、欧洲。北美洲、拉丁美洲和世界银行，本文摘录了会上的主要观点。JuhaIUitto博士是UNU总部的高级学术计划官员，AsitK．Biswas教授，本次会议的召集人，是国际水资源协会（IWRA）国际合作委员会的主席。CeciliaTor－tajada是墨西哥第三…     

Revised rates for the stellar triple-alpha process from measurement of 12C nuclear resonances

In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form 12C because of a resonant reaction leading to a nuclear excited state. (Stars with masses greater than approximately 0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.) Although the reaction rate is of critical significance for determining elemental abundances in the Universe, and for determining the size of the iron core of a star just before it goes supernova, it has hitherto been insufficiently determined. Here we report a measurement of the inverse process, where a 12C nucleus decays to three alpha-particles. We find a dominant resonance at an energy of approximately 11 MeV, but do not confirm the presence of a resonance at 9.1 MeV (ref. 3). We show that interference between two resonances has important effects on our measured spectrum. Using these data, we calculate the triple-alpha rate for temperatures from 10(7) K to 10(10) K and find significant deviations from the standard rates. Our rate below approximately 5 x 10(7) K is higher than the previous standard, implying that the critical amounts of carbon that catalysed hydrogen burning in the first stars are produced twice as fast as previously believed. At temperatures above 10(9) K, our rate is much less, which modifies predicted nucleosynthesis in supernovae.     

Generation time and temporal scaling of bird population dynamics

Theoretical studies have shown that variation in density regulation strongly influences population dynamics, yet our understanding of factors influencing the strength of density dependence in natural populations still is limited. Consequently, few general hypotheses have been advanced to explain the large differences between species in the magnitude of population fluctuations. One reason for this is that the detection of density regulation in population time series is complicated by time lags induced by the life history of species that make it difficult to separate the relative contributions of intrinsic and extrinsic factors to the population dynamics. Here we use population time series for 23 bird species to estimate parameters of a stochastic density-dependent age-structured model. We show that both the strength of total density dependence in the life history and the magnitude of environmental stochasticity, including transient fluctuations in age structure, increase with generation time. These results indicate that the relationships between demographic and life-history traits in birds translate into distinct population dynamical patterns that are apparent only on a scale of generations.     

Estimating the strength of expert judgement: The case of US mortality forecasts

The use of expert judgement is an important part of demographic forecasting. However, because judgement enters into the forecasting process in an informal way, it has been very difficult to assess its role relative to the analysis of past data. The use of targets in demographic forecasts permits us to embed the subjective forecasting process into a simple time-series regression model, in which expert judgement is incorporated via mixed estimation. The strength of expert judgement is denned, and estimated using the official forecasts of cause-specific mortality in the United States. We show that the weight given to judgement varies in an improbable manner by age. Overall, the weight given to judgement appears too high. An alternative approach to combining expert judgement and past data is suggested.     

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.