The difficult legacy of Turing’s wager

Neuron modeling may be said to have originated with the Hodgkin and Huxley action potential model in 1952 and Rall’s models of integrative activity of dendrites in 1964. Over the ensuing decades, these approaches have led to a massive development of increasingly accurate and complex data-based models of neurons and neuronal circuits. ModelDB was founded in 1996 to support this new field and enhance the scientific credibility and utility of computational neuroscience models by providing a convenient venue for sharing them. It has grown to include over 1100 published models covering more than 130 research topics. It is actively curated and developed to help researchers discover and understand models of interest. ModelDB also provides mechanisms to assist running models both locally and remotely, and has a graphical tool that enables users to explore the anatomical and biophysical properties that are represented in a model. Each of its capabilities is undergoing continued refinement and improvement in response to user experience. Large research groups (Allen Brain Institute, EU Human Brain Project, etc.) are emerging that collect data across multiple scales and integrate that data into many complex models, presenting new challenges of scale. We end by predicting a future for neuroscience increasingly fueled by new technology and high performance computation, and increasingly in need of comprehensive user-friendly databases such as ModelDB to provide the means to integrate the data for deeper insights into brain function in health and disease.     

Water availability drives stem growth and stem water deficit of <Emphasis Type="Italic">Pinus canariensis</Emphasis> in a drought-induced treeline in Tenerife

Tree growth of Pinus canariensis at treeline in Tenerife, Canary Islands, is thought to be primarily controlled by wet season precipitation (P) prior to the current year´s growth. Therefore, we investigated the inter-annual variations in stem water deficit (ΔW) and radial growth (RG) during two consecutive years differing in wet season P. ΔW was extracted from stem circumference variations, and the influence of environmental variables was evaluated by Pearson correlation statistics. Wet season P was considerably lower in 2008 than in 2009; despite this difference in P between both years, shallow soil water availability was almost exhausted during both summers. However, the effect of shallow soil drought showing a clear seasonality of ΔW and RG was only detected in 2008. In summer 2009, RG rates were highest during the summer indicating that P. canariensis was able to tap water from deep soil layers originating from P prior to the current year´s growth. The ability to use deep soil water during extended periods of shallow soil water deficit was also reflected in a close positive correlation between RG and whole-tree water use. In our study, the effect of only one hydrological dry year resulted in a severe reduction in annual RG. Thus, when wet season P is low for a number of years, chronic drought may have negative implications for tree growth at treeline in Tenerife.     

Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering

Chinese hamster ovary (CHO) cells are the predominant cell factory for the production of recombinant therapeutic proteins. Nevertheless, the lack in publicly available sequence information is severely limiting advances in CHO cell biology, including the exploration of microRNAs (miRNA) as tools for CHO cell characterization and engineering. In an effort to identify and annotate both conserved and novel CHO miRNAs in the absence of a Chinese hamster genome, we deep-sequenced small RNA fractions of 6 biotechnologically relevant cell lines and mapped the resulting reads to an artificial reference sequence consisting of all known miRNA hairpins. Read alignment patterns and read count ratios of 5' and 3' mature miRNAs were obtained and used for an independent classification into miR/miR* and 5p/3p miRNA pairs and discrimination of miRNAs from other non-coding RNAs, resulting in the annotation of 387 mature CHO miRNAs. The quantitative content of next-generation sequencing data was analyzed and confirmed using qPCR, to find that miRNAs are markers of cell status. Finally, cDNA sequencing of 26 validated targets of miR-17-92 suggests conserved functions for miRNAs in CHO cells, which together with the now publicly available sequence information sets the stage for developing novel RNAi tools for CHO cell engineering.     

Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins

Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing-proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence.     

Effects of temperature on allocation of metabolic energy in perch (Perca fluviatilis) fed submaximal rations

Growth and long-term trends of oxygen consumption were monitored at 15 and 20° C in spontaneously swimming juvenile perch fed a fixed daily submaximal ration. The average rate as well as the efficiency of assimilation were the same at the two temperatures but a much higher proportion of food energy was allocated to activity and maintenance, and a correspondingly lower proportion to growth, at 20 than at 15° C. By computing average specific rates of oxygen consumption separately for all light and dark periods, it was found that at 20, but not at 15° C, the' scope for spontaneous activity' of two consecutive (dark and light) phases of a diurnal cycle was indirectly proportional to the average rate of oxygen consumption in the dark phase. This indicates that at 20° C the perch displayed partial compensation for a high metabolic rate in the dark by reducing swimming activity in the following light phase. However, the overall effect of this behaviour was probably too small to make a noticeable impact on the low conversion efficiency in the juvenile perch at 20 as compared to 15° C.