Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms

Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously.     

RNAi-mediated gene silencing in non-human primates

The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.     

从克隆羊多利到个性化治疗

 从1865年到世界上首个克隆动物--"克隆羊"诞生的100多年间，人类一直在进行相关研究。有一个问题直到现在仍未得到完全的回答--人类来自于一个单一的细胞，但现在还不完全清楚的是，这样一个单个细胞是如何产生胚胎并形成其他器官的。1865年，著名科学家韦斯曼（Weissmann）认为，细胞的分裂是不平均的，这样导致在细胞分裂之后所获得的结果有各自不同的特点。那么，把细胞分离进行移植到底会产生什么样的结果?正是这样一种对换，导致了克隆技术的研发和发展。     

Microbiome–health interactions in older people

Alterations in the composition and function of the gut microbiome have been implicated in a range of conditions and diseases. Culture-dependent and culture-independent studies both showed that older people harbour a gut microbiome that differs in composition from that of younger adults. Detailed analyses have identified discrete microbiota subtypes that characterize intermediates between a high diversity microbiota found in healthy community-dwelling subjects and a low diversity microbiota typical for elderly living in long-term residential care. There are also alterations in the microbiome composition associated with biological age, independent of health status. Even after adjusting for confounding factors such as age and medication, trends in microbiota composition correlate with gradients in clinical metadata particularly frailty and inflammatory status. There are few known mechanisms by which these associations might be causative rather than consequential, and this is a subject of intensive research. The strongest candidate effectors are microbial metabolites that could impact host energy balance, act as signalling molecules to modulate host metabolism or inflammation, and potentially also impact on the gut–brain axis.     

Combining exchange rate forecasts: What is the optimal consensus measure?

In this paper a high-quality disaggregate database is utilized to examine whether individual forecasters produce efficient exchange rate predictions and also if the properties of the forecasts change when they are combined. The paper links a number of themes in the exchange rate literature and examines various methods of forecast combination. It is demonstrated, inter alia, that some forecasters are better than others, but that most are not as good as a naive no-change prediction. Combining forecasts adds to the accuracy of the predictions, but the gains mainly reflect the removal of systematic and unstable bias.     

Instrumentalizing Failure: Edison's Invention of the Carbon Microphone

For Thomas Edison, experiencing a failure did not mean that he had failed. Through an examination of the process that led to his invention of the carbon microphone, I argue that his positive approach to failure contributed both to his success as an inventor and to the functional success of his inventions. Edison's laboratory notebooks and legal testimony reveal that his seemingly erratic approach and reliance on trial and error methods in fact had a consistent direction and a rational basis, well suited to the under-determined problems he faced. The outcome of this process, the carbon microphone, contributed significantly to the commercial success of the telephone and remains in use today. Thomas Hughes has observed that nineteenth century inventors made use of the unexpected behaviour of their inventions as sources of novel phenomena to exploit in new inventions. This paper identifies other ways in which Edison made use of failure and proposes that, paradoxically, the success of technological artefacts can be determined by the thoroughness with which failure is pursued in their creation. It also notes a parallel between Edison's instrumentalizing of failure and the way in which recent philosophers of science have proposed that scientists should make use of error.