Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

Activities related with electricity consumption in the Spanish residential sector: variations between days of the week, Autonomous Communities and size of towns

Nowadays the electricity consumption in the residential sector attracts policy and research efforts, in order to propose saving strategies and to attain a better balance between production and consumption, by integrating renewable energy production and proposing suitable demand side management methods. To achieve these objectives it is essential to have real information about household electricity demand profiles in dwellings, highly correlated, among other aspects, with the active occupancy of the homes and to the personal activities carried out in homes by their occupants. Due to the limited information related to these aspects, in this paper, behavioral factors of the Spanish household residents, related to the electricity consumption, have been determined and analyzed, based on data from the Spanish Time Use Surveys, differentiating among the Autonomous Communities and the size of municipalities, or the type of days, weekdays or weekends. Activities involving a larger number of houses are those related to Personal Care, Food Preparation and Washing Dishes. The activity of greater realization at homes is Watching TV, which together with Using PC, results in a high energy demand in an aggregate level. Results obtained enable identify prospective targets for load control and for efficiency energy reduction recommendations to residential consumers.

Centennial variations in sunspot number, open solar flux and streamer belt width: 1. correction of the sunspot number record since 1874

We analyse the widely-used international/ Zürich sunspot number record, R, with a view to quantifying a suspected calibration discontinuity around 1945 (which has been termed the “Waldmeier discontinuity” [Svalgaard, 2011]). We compare R against the composite sunspot group data from the Royal Greenwich Observatory (RGO) network and the Solar Optical Observing Network (SOON), using both the number of sunspot groups, N{sub}G{\sub}, and the total area of the sunspots, A{sub}G{\sub}. In addition, we compare R with the recently developed interdiurnal variability geomagnetic indices IDV and IDV(1d). In all four cases, linearity of the relationship with R is not assumed and care is taken to ensure that the relationship of each with R is the same before and after the putative calibration change. It is shown the probability that a correction is not needed is of order 10{sup}−8{\sup} and that R is indeed too low before 1945. The optimum correction to R for values before 1945 is found to be 11.6%, 11.7%, 10.3% and 7.9% using A{sub}G{\sub}, N{sub)G{\sub}, IDV, and IDV(1d), respectively. The optimum value obtained by combining the sunspot group data is 11.6% with an uncertainty range 8.1-14.8% at the 2σ level. The geomagnetic indices provide an independent yet less stringent test but do give values that fall within the 2σ uncertainty band with optimum values are slightly lower than from the sunspot group data. The probability of the correction needed being as large as 20%, as advocated by Svalgaard [2011], is shown to be 1.6 × 10{sup}−5{\sup}.

Centennial variations in sunspot number, open solar flux and streamer belt width: 2. Comparison with the geomagnetic data

We investigate the relationship between interdiurnal variation geomagnetic activity indices, IDV and IDV(1d), corrected sunspot number, R{sub}C{\sub}, and the group sunspot number R{sub}G{\sub}. R{sub}C{\sub} uses corrections for both the “Waldmeier discontinuity”, as derived in Paper 1 [Lockwood et al., 2014c], and the “Wolf discontinuity” revealed by Leussu et al. [2013]. We show that the simple correlation of the geomagnetic indices with R{sub}C{\sub}{sup}n{\sup} or R{sub}G{\sub}{sup}n{\sup} masks a considerable solar cycle variation. Using IDV(1d) or IDV to predict or evaluate the sunspot numbers, the errors are almost halved by allowing for the fact that the relationship varies over the solar cycle. The results indicate that differences between R{sub}C{\sub} and R{sub}G{\sub} have a variety of causes and are highly unlikely to be attributable to errors in either R{sub}G{\sub} alone, as has recently been assumed. Because it is not known if R{sub}C{\sub} or R{sub}G{\sub} is a better predictor of open flux emergence before 1874, a simple sunspot number composite is suggested which, like R{sub}G{\sub}, enables modelling of the open solar flux for 1610 onwards in Paper 3, but maintains the characteristics of R{sub}C{\sub}.

Centennial variations in sunspot number, open solar flux and streamer belt width: 3. Modelling

From the variation of near-Earth interplanetary conditions, reconstructed for the mid-19th century to the present day using historic geomagnetic activity observations, Lockwood and Owens [2014] have suggested that Earth remains within a broadened streamer belt during solar cycles when the Open Solar Flux (OSF) is low. From this they propose that the Earth was immersed in almost constant slow solar wind during the Maunder minimum (c. 1650-1710). In this paper, we extend continuity modelling of the OSF to predict the streamer belt width using both group sunspot numbers and corrected international sunspot numbers to quantify the emergence rate of new OSF. The results support the idea that the solar wind at Earth was persistently slow during the Maunder minimum because the streamer belt was broad.

C. colchicum - variation measured by DNA sequence

Cyclamen colchicum has a mixed history in the hands of botanists. This paper examines the genetic identity of a group of wild Cyclamen populations from the Caucasus to discover whther they are Cyclamen colchicum, C. purpurascens or a mixture of the two. The collections supplemented by material collected at the type locality for C. colchicum, proved to be a single but variable genetic group of C. colchicum that was distinct from C. purpurascens.

The importance of wind and buoyancy forcing for the boundary density variations and the geostrophic component of the AMOC at 26°N

It is widely thought that changes in both the surface buoyancy fluxes and wind stress drive variability in the Atlantic meridional overturning circulation (AMOC), but that they drive variability on different time scales. For example, wind forcing dominates short-term variability through its effects on Ekman currents and coastal upwelling, whereas buoyancy forcing is important for longer time scales (multiannual and decadal). However, the role of the wind forcing on multiannual to decadal time scales is less clear. Here the authors present an analysis of simulations with the Nucleus for European Modelling of the Ocean (NEMO) ocean model with the aim of explaining the important drivers of the zonal density gradient at 26°N, which is directly related to the AMOC. In the experiments, only one of either the wind stress or the buoyancy forcing is allowed to vary in time, whereas the other remains at its seasonally varying climatology. On subannual time scales, variations in the density gradient, and in the AMOC minus Ekman, are driven largely by local wind-forced coastal upwelling at both the western and eastern boundaries. On decadal time scales, buoyancy forcing related to the North Atlantic Oscillation dominates variability in the AMOC. Interestingly, however, it is found that wind forcing also plays a role at longer time scales, primarily impacting the interannual variability through the excitation of Rossby waves in the central Atlantic, which propagate westward to interact with the western boundary, but also by modulating the decadal time-scale response to buoyancy forcing.

A new South American network to study the atmospheric electric field and its variations related to geophysical phenomena

In this paper we present the capability of a new network of field mill sensors to monitor the atmospheric electric field at various locations in South America; we also show some early results. The main objective of the new network is to obtain the characteristic Universal Time diurnal curve of the atmospheric electric field in fair weather, known as the Carnegie curve. The Carnegie curve is closely related to the current sources flowing in the Global Atmospheric Electric Circuit so that another goal is the study of this relationship on various time scales (transient/monthly/seasonal/annual). Also, by operating this new network, we may also study departures of the Carnegie curve from its long term average value related to various solar, geophysical and atmospheric phenomena such as the solar cycle, solar flares and energetic charged particles, galactic cosmic rays, seismic activity and specific meteorological events. We then expect to have a better understanding of the influence of these phenomena on the Global Atmospheric Electric Circuit and its time-varying behavior.

Self-assembly of a Model Peptide incorporating a Hexa-Histidine sequence attached to an Oligo-Alanine sequence, and binding to Gold NTA/Nickel nanoparticles

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexahistidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac’s), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome

Background Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. Methods The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. Results There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs2268490-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). Conclusions This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS.

Study of picosecond processes of an intercalated dipyridophenazine Cr(iii) complex bound to defined sequence DNAs using transient absorption and time-resolved infrared methods

Picosecond transient absorption (TA) and time-resolved infrared (TRIR) measurements of rac-[Cr(phen)2(dppz)]3+ (1) intercalated into double-stranded guanine-containing DNA reveal that the excited state is very rapidly quenched. As no evidence was found for the transient electron transfer products, it is proposed that the back electron transfer reaction must be even faster (<3 ps).

Extended cusp-like regions and their dependence on the Polar orbit, seasonal variations, and interplanetary conditions

Extended cusp-like regions (ECRs) are surveyed, as observed by the Magnetospheric Ion Composition Sensor (MICS) of the Charge and Mass Magnetospheric Ion Composition Experiment (CAMMICE) instrument aboard Polar between 1996 and 1999. The first of these ECR events was observed on 29 May 1996, an event widely discussed in the literature and initially thought to be caused by tail lobe reconnection due to the coinciding prolonged interval of strong northward IMF. ECRs are characterized here by intense fluxes of magnetosheath-like ions in the energy-per-charge range of _1 to 10 keV e_1. We investigate the concurrence of ECRs with intervals of prolonged (lasting longer than 1 and 3 hours) orientations of the IMF vector and high solar wind dynamic pressure (PSW). Also investigated is the opposite concurrence, i.e., of the IMF and high PSW with ECRs. (Note that these surveys are asking distinctly different questions.) The former survey indicates that ECRs have no overall preference for any orientation of the IMF. However, the latter survey reveals that during northward IMF, particularly when accompanied by high PSW, ECRs are more likely. We also test for orbital and seasonal effects revealing that Polar has to be in a particular region to observe ECRs and that they occur more frequently around late spring. These results indicate that ECRs have three distinct causes and so can relate to extended intervals in (1) the cusp on open field lines, (2) the magnetosheath, and (3) the magnetopause indentation at the cusp, with the latter allowing magnetosheath plasma to approach close to the Earth without entering the magnetosphere.

Long-term variations in the open solar flux and possible links to Earth’s climate

Recent paleoclimate studies provide strong evidence for an association between cosmogenic isotope production and Earth’s climate throughout the holecene. These isotopes are generated by the bombardment of Earth’s atmosphere by galactic cosmic rays, the fluxes of which vary in approximately inverse proportion to the total open magnetic flux of the Sun. This paper discusses how results from the Ulysses spacecraft allow us to quantify the open solar flux from observations of near-Earth interplanetary space and to study its long-term variations using the homogeneous record of geomagnetic activity. A study of the results and of their accuracy is presented. The two proposed mechanisms that could lead to the open solar flux being a good proxy for solar-induced climate change are discussed: the first is the modulation of the production of some types of cloud by the air ions produced by cosmic rays; the second is a variation in the total or spectral solar irradiance, in association with changes in the open flux. Some implications for our understanding of anthropogenic climate change are discussed.