Chasing Brane Inflation in String-Theory

We investigate the embedding of brane anti-brane inflation into a concrete type IIB string theory compactification with all moduli fixed. Specifically, we are considering a D3-brane, whose position represents the inflaton $\phi$, in a warped conifold throat in the presence of supersymmetrically embedded D7-branes and an anti D3-brane localized at the tip of the warped conifold cone. After presenting the moduli stabilization analysis for a general D7-brane embedding, we concentrate on two explicit models, the Ouyang and the Kuperstein embeddings. We analyze whether the forces, induced by moduli stabilization and acting on the D3-brane, might cancel by fine-tuning such as to leave us with the original Coulomb attraction of the anti D3-brane as the driving force for inflation. For a large class of D7-brane embeddings we obtain a negative result. Cancelations are possible only for very small intervals of $\phi$ around an inflection point but not globally. For the most part of its motion the inflaton then feels a steep, non slow-roll potential. We study the inflationary dynamics induced by this potential.Comment: 34 pages, 4 figures. Final version published in JCA

The Sequence of a 1.8-Mb Bacterial Linear Plasmid Reveals a Rich Evolutionary Reservoir of Secondary Metabolic Pathways

Plasmids are mobile genetic elements that play a key role in the evolution of bacteria by mediating genome plasticity and lateral transfer of useful genetic information. Although originally considered to be exclusively circular, linear plasmids have also been identified in certain bacterial phyla, notably the actinomycetes. In some cases, linear plasmids engage with chromosomes in an intricate evolutionary interplay, facilitating the emergence of new genome configurations by transfer and recombination or plasmid integration. Genome sequencing of Streptomyces clavuligerus ATCC 27064, a Gram-positive soil bacterium known for its production of a diverse array of biotechnologically important secondary metabolites, revealed a giant linear plasmid of 1.8 Mb in length. This megaplasmid (pSCL4) is one of the largest plasmids ever identified and the largest linear plasmid to be sequenced. It contains more than 20% of the putative protein-coding genes of the species, but none of these is predicted to be essential for primary metabolism. Instead, the plasmid is densely packed with an exceptionally large number of gene clusters for the potential production of secondary metabolites, including a large number of putative antibiotics, such as staurosporine, moenomycin, β-lactams, and enediynes. Interestingly, cross-regulation occurs between chromosomal and plasmid-encoded genes. Several factors suggest that the megaplasmid came into existence through recombination of a smaller plasmid with the arms of the main chromosome. Phylogenetic analysis indicates that heavy traffic of genetic information between Streptomyces plasmids and chromosomes may facilitate the rapid evolution of secondary metabolite repertoires in these bacteria

A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy

We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming

Normalization in MALDI-TOF imaging datasets of proteins: practical considerations

Normalization is critically important for the proper interpretation of matrix-assisted laser desorption/ionization (MALDI) imaging datasets. The effects of the commonly used normalization techniques based on total ion count (TIC) or vector norm normalization are significant, and they are frequently beneficial. In certain cases, however, these normalization algorithms may produce misleading results and possibly lead to wrong conclusions, e.g. regarding to potential biomarker distributions. This is typical for tissues in which signals of prominent abundance are present in confined areas, such as insulin in the pancreas or β-amyloid peptides in the brain. In this work, we investigated whether normalization can be improved if dominant signals are excluded from the calculation. Because manual interaction with the data (e.g., defining the abundant signals) is not desired for routine analysis, we investigated two alternatives: normalization on the spectra noise level or on the median of signal intensities in the spectrum. Normalization on the median and the noise level was found to be significantly more robust against artifact generation compared to normalization on the TIC. Therefore, we propose to include these normalization methods in the standard “toolbox” of MALDI imaging for reliable results under conditions of automation

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and objectiveTranscranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. MethdsData from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. ResultsIn M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. ConclusionsOur data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects

A European study on alcohol and drug use among young drivers : The TEND by night study design and methodology

Background. Young individuals are the age group with the highest risk of car accidents. One of main explanations relies on the use of psychoactive substances (alcohol, illegal and medicinal drugs), which are known to be major risk factors of road accidents, and whose consumption is almost universally more common among younger drivers. Although the correlation between psychoactive substances use and decrease in driving performance has been established in controlled experimental or laboratory settings, few studies were conducted in naturalistic circumstances. The TEND by Night project has been designed to evaluate the relationship between driving performance and psychoactive substances assumption in young drivers enrolled at typical places of consumption. Methods/Design. The TEND by Night project, endorsed by the European Commission, is a multidisciplinary, multi-centric, cross-sectional study conducted in six European countries (Italy, Belgium/Netherlands, Bulgaria, Spain, Poland and Latvia). The study population consists of 5000 young drivers aged 16-34 years, attending recreational sites during weekend nights. The intervention is based on the portal survey technique and includes several steps at the entrance and exit of selected sites, including the administration of semi-structured questionnaires, breath alcohol test, several drug assumption test, and measurement of the reaction time using a driving simulator. The main outcome is the difference in reaction time between the entrance and exit of the recreation site, and its correlation with psychoactive substances use. As a secondary outcome it will be explored the relationship between reaction time difference and the amount of consumption of each substance. All analyses will be multivariate. Discussion. The project methodology should provide some relevant advantages over traditional survey systems. The main strengths of the study include the large and multicentric sample, the objective measurement of substance assumption (which is typically self-reported), the application of a portal survey technique and the simultaneous evaluation of several psychoactive substances.publishersversionPeer reviewe

Optical Coherence Tomography in Parkinsonian Syndromes

BACKGROUND/OBJECTIVE: Parkinson's disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases. METHODS: This cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls. RESULTS: The mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%. CONCLUSION: Different parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes

Scientists' warning on climate change and insects

Climate warming is considered to be among the most serious of anthropogenic stresses to the environment, because it not only has direct effects on biodiversity, but it also exacerbates the harmful effects of other human-mediated threats. The associated consequences are potentially severe, particularly in terms of threats to species preservation, as well as in the preservation of an array of ecosystem services provided by biodiversity. Among the most affected groups of animals are insects—central components of many ecosystems—for which climate change has pervasive effects from individuals to communities. In this contribution to the scientists' warning series, we summarize the effect of the gradual global surface temperature increase on insects, in terms of physiology, behavior, phenology, distribution, and species interactions, as well as the effect of increased frequency and duration of extreme events such as hot and cold spells, fires, droughts, and floods on these parameters. We warn that, if no action is taken to better understand and reduce the action of climate change on insects, we will drastically reduce our ability to build a sustainable future based on healthy, functional ecosystems. We discuss perspectives on relevant ways to conserve insects in the face of climate change, and we offer several key recommendations on management approaches that can be adopted, on policies that should be pursued, and on the involvement of the general public in the protection effort