Pathological changes are associated with shifts in the employment of synonymous codons at the transcriptome level

The usage of different synonymous codons reflects the genome organization and has been connected to parameters such as mRNA abundance and protein folding. It is also been established that mutations targeting specific synonymous codons can trigger disease. We performed a systematic meta-analysis of transcriptome results from 75 datasets representing 40 pathologies. We found that a subset of codons was preferentially employed in abundant transcripts, while other codons were preferentially found in low-abundance transcripts. By comparing control and pathological transcriptomes, we observed a shift in the employment of synonymous codons for every analyzed disease. For example, cancerous tissue employed preferentially A- or U-ending codons, shifting from G- or C-ending codons, which were preferred by control tissues. This analysis was able to discriminate patients and controls with high specificity and sensitivity. Here we show that the employment of specific synonymous codons, quantified at the whole transcriptome level, changes profoundly in many diseases. We propose that the changes in codon employment offer a novel perspective for disease studies, and could be used to design new diagnostic tools

Overvoltages in DC Urban Light Railway Systems: Statistical Analysis and Possible Causes

In DC light railway systems the equipment in the power substations and certain devices along the lines are protected against lightning overvoltages thanks to surge arresters. This paper analyses the overvoltages occurring on the tram network of Torino, Italy to discover the causes that brought to the explosion of several surge arresters in the past years. The cause is found to be the regenerative breaking of a particular type of vehicles, in conditions of low load in the system. The benefits of regenerative breaking are discussed in the light of the possible problems introduced. Finally, possible solutions are proposed

Updated version of final design and of the architecture of SEAMLESS-IF

Agricultural and Food Policy, Environmental Economics and Policy, Farm Management, Land Economics/Use, Livestock Production/Industries,

Memory-based immigrants for ant colony optimization in changing environments

Copyright @ 2011 SpringerAnt colony optimization (ACO) algorithms have proved that they can adapt to dynamic optimization problems (DOPs) when they are enhanced to maintain diversity. DOPs are important due to their similarities to many real-world applications. Several approaches have been integrated with ACO to improve their performance in DOPs, where memory-based approaches and immigrants schemes have shown good results on different variations of the dynamic travelling salesman problem (DTSP). In this paper, we consider a novel variation of DTSP where traffic jams occur in a cyclic pattern. This means that old environments will re-appear in the future. A hybrid method that combines memory and immigrants schemes is proposed into ACO to address this kind of DTSPs. The memory-based approach is useful to directly move the population to promising areas in the new environment by using solutions stored in the memory. The immigrants scheme is useful to maintain the diversity within the population. The experimental results based on different test cases of the DTSP show that the memory based immigrants scheme enhances the performance of ACO in cyclic dynamic environments.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/2

The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

Modeling the response of top-down control exerted by gelatinous carnivores on the Black Sea pelagic food web

Recent changes in structure and functioning of the interior Black Sea ecosystem are studied by a series of simulations using a one-dimensional, vertically resolved, coupled physical-biochemical model. The simulations are intended to provide a better understanding of how the pelagic food web structure responds to increasing grazing pressure by gelatinous carnivores (medusae Aurelia aurita and ctenophore Mnemiopsis leidyi) during the past 2 decades. The model is first shown to represent typical eutrophic ecosystem conditions of the late 1970s and early 1980s. This simulation reproduces reasonably well the observed planktonic food web structure at a particular location of the Black Sea for which a year-long data set is available from 1978. Additional simulations are performed to explore the role of the Mnemiopsis-dominated ecosystem in the late 1980s. They are also validated by extended observations from specific years. The results indicate that the population outbreaks of the gelatinous species, either Aurelia or Mnemiopsis, reduce mesozooplankton grazing and lead to increased phytoplankton blooms as observed throughout the 1980s and 1990s in the Black Sea. The peaks of phytoplankton, mesozooplankton, Noctiluca, and gelatinous predator biomass distributions march sequentially as a result of prey-predator interactions. The late winter diatom bloom and a subsequent increase in mesozooplankton stocks are robust features common to all simulations. The autotrophs and heterotrophs, however, have different responses during the rest of the year, depending on the nature of grazing pressure exerted by the gelatinous predators. In the presence of Mnemiopsis, phytoplankton have additional distinct and pronounced bloom episodes during the spring and summer seasons. These events appear with a 2 month time shift in the ecosystem prior to introduction of Mnemiopsis

A mass spectrometry workflow for measuring protein turnover rates in vivo

Proteins are continually produced and degraded, to avoid the accumulation of old or damaged molecules and to maintain the efficiency of physiological processes. Despite its importance, protein turnover has been difficult to measure in vivo. Previous approaches to evaluating turnover in vivo have required custom labeling approaches, involved complex mass spectrometry (MS) analyses, or used comparative strategies that do not allow direct quantitative measurements. Here, we describe a robust protocol for quantitative proteome turnover analysis in mice that is based on a commercially available diet for stable isotope labeling of amino acids in mammals (SILAM). We start by discussing fundamental concepts of protein turnover, including different methodological approaches. We then cover in detail the practical aspects of metabolic labeling and explain both the experimental and computational steps that must be taken to obtain accurate in vivo results. Finally, we present a simple experimental workflow that enables measurement of precise turnover rates in a time frame of similar to 4-5 weeks, including the labeling time. We also provide all the scripts needed for the interpretation of the MS results and for comparing turnover across different conditions. Overall, the workflow presented here comprises several improvements in the determination of protein lifetimes with respect to other available methods, including a minimally invasive labeling strategy and a robust interpretation of MS results, thus enhancing reproducibility across laboratories

Socioeconomic and living conditions are determinants of hip fracture incidence and age occurrence among community-dwelling elderly

Summary: In this prospective, 10-year study in community-dwelling elderly aged 50years and over, hip fracture incidence and accordingly age at hip fracture were inversely associated with the area-level income, independently of the geographical area. Age at hip fracture also depended of marital status but in a gender-specific way. Purpose: The purpose of this study is to investigate the impact of socioeconomic and living conditions on hip fracture incidence and age occurrence among community-dwelling elderly. Method: Between January 1991 and December 2000, 2,454 hip fractures were recorded in community-dwelling adults aged 50years and over in the Geneva University Hospital, State of Geneva, Switzerland. Median annual household income by postal code of residence (referred to as area-level income) based on the 1990 Census was used as a measure of socioeconomic condition and was stratified into tertiles (<53,170; 53,170-58,678; and ≥58,678 CHF). Hip fracture incidence and age occurrence were calculated according to area-level income categories and adjusted for confounding factors among community-dwelling elderly. Results: Independently of the geographical area (urban versus rural), community-dwelling persons residing in areas with the medium income category presented a lower hip fracture incidence [OR 0.91 (0.82-0.99), p = 0.049] compared to those from the lowest income category. Those in the highest income category had a hip fracture at a significant older age [+1.58 (0.55-2.61) year, p = 0.003] as compared to those in the lowest income category. Age at hip fracture also depended on marital status but in a gender-specific way, with married women fracturing earlier. Conclusions: These results indicate that incidence and age occurrence of hip fracture are influenced by area-level income and living conditions among community-dwelling elderly. Prevention programs may be encouraged in priority in communities with low incom