Metabolic and cometabolic degradation of herbicides in the fine material of railway ballast

Microbial degradation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron) and mineralization of 4-chloro-2-methylphenoxyacetic acid (MCPA) were studied in soil samples taken from the ballast layers of three Swedish railway embankments. The degradation of diuron followed first-order kinetics and half-lives ranged between 122 and 365 days. The half-lives correlated strongly with microbial biomass estimated by substrate-induced respiration (SIR; R=-0.85; p<0.05) and with the amount of organic matter measured as loss on ignition (R=-0.87; p<0.05). Accumulation of the metabolites 1-(3,4-dichlorophenyl)-3-methyl urea (DCPMU) and 1-(3,4-dichlorophenyl) urea (DCPU) was observed in all samples and these were only detectably degraded in the sample with the highest SIR. Addition of ground lucerne straw to the ballast samples stimulated microbial activity and led to increased formation of metabolites, but further transformation of DCPMU and DCPU was not enhanced. Mineralization of MCPA followed growth-linked kinetics and the time for 50% mineralization was 44.5±7.1 days in samples of previously untreated ballast. In samples of ballast that had been previously treated with the herbicide formulation MCPA 750, the time for 50% mineralization was reduced to 13.7±11.3 days. The number of MCPA degraders, quantified using an MPN technique, was clearly increased but highly variable. An average yield of 0.18 cells pg−1 of MCPA was estimated from the kinetic data. The yield estimates correlated with the amount of nitrogen in the ballast, indicating that mineralization of MCPA was nitrogen-limited in the railway embankments studied. This has practical implications for weed control using herbicides on railways

Liability of a Surgeon for the Extension of an Authorized Operation

Polyunsaturated fatty acids modulate the voltage dependence of several voltage-gated ion channels, thereby being potent modifiers of cellular excitability. Detailed knowledge of this molecular mechanism can be used in designing a new class of small-molecule compounds against hyperexcitability diseases. Here, we show that arginines on one side of the helical K-channel voltage sensor S4 increased the sensitivity to docosahexaenoic acid (DHA), whereas arginines on the opposing side decreased this sensitivity. Glutamates had opposite effects. In addition, a positively charged DHA-like molecule, arachidonyl amine, had opposite effects to the negatively charged DHA. This suggests that S4 rotates to open the channel and that DHA electrostatically affects this rotation. A channel with arginines in positions 356, 359, and 362 was extremely sensitive to DHA: 70 mu M DHA at pH 9.0 increased the current greater than500 times at negative voltages compared with wild type (WT). The small-molecule compound pimaric acid, a novel Shaker channel opener, opened the WT channel. The 356R/359R/362R channel drastically increased this effect, suggesting it to be instrumental in future drug screening

SVenX: A highly parallelized pipeline for structural variation detection using linked read whole genome sequencing data

Genomic rearrangements larger than 50 bp are called structural variants. As a group, they affect the phenotypic diversity among humans and have been associated with many human disorders including neurodevelopmental disorder and cancer. Recent advances in whole genome sequencing (WGS) technologies have made it possible to identify many more disease-causing genetic variants relevant in clinical diagnostics and sometimes affecting treatment. Numerous approaches have been proposed to detect structural variants, but to acquire and filter out the most significant information from the multitude of called variants in the sequencing data has shown to be a challenge. Another obstacle is the high computational cost of data analyses and difficulties in configuring and operating the softwares and databases. Here, we present SVenX, a highly automated and parallelized pipeline that analyzes and call structural variants using linked read WGS data. It performs variant calling using three different approaches, as well as annotation of variants and variant filtering. We also introduce a new tool, SVGenT, that reanalyzes the called structural variants by performing de novo assembly using the aligned reads at the identified breakpoint junctions. By comparing assembled contigs and analyzing the read coverage between the breakpoint junctions, SVGenT improves both variant and genotype classification and the breakpoint localization.Tool for detection of genomic rearrangements in humans Genomic rearrangements larger than 50 base pairs are referred to as structural variants (SVs), and impact phenotypic differences between humans. Some of these variants have been associated with human diseases such as cancer and neurodevelopmental disorders. Recent advances in whole genome sequencing (WGS) technologies have made it possible to analyze and identify many structural variants. Yet, the existing tools used for analyzing these data are not perfect, and require a fair amount of knowledge in bioinformatics to operate. SVenX is a highly parallelized and automated pipeline, executing all steps from whole genome sequencing data to filtered SVs. This includes 1) verifying that all required data exist, 2) making sure no data duplications exist, 3) finding variants using different methods, and 4) annotating and filtering the detected SVs. SVenX performs 10 separate steps including 3 different variant detection tools (also known as variant callers). Normally, these steps are performed one by one, waiting for the output before running the next. Not only does it take longer for the programs to run with this approach, it also requires an employee to execute the steps. Except from the installation, SVenX takes at the most a few minutes to setup and launch and can analyze multiple samples of WGS data at the same time. The whole pipeline takes about 4 to 5 days to complete, requiring minimal work effort and bioinformatic knowledge. Another challenge in SV research is not only detecting the variants, but also to be confident that the detected SVs are true calls. The performance of existing variant callers differ significantly between each other. One tool can perform really good using one dataset and fail totally in detecting SVs in another dataset, while a second tool might be good in detecting only a single type of SV. Using multiple bioinformatics methods to detect SVs have shown to result in a higher detection rate. We have created a novel tool, SVGenT, that re-analyzes already detected SVs by doing de novo assembly. SVGenT classifies the SV type (deletion, duplication, inversion or break-end), genotype (homozygous or heterozygous), and update the genomic position of the SV breakpoints. SVGenT has been tested using two datasets: one public large-scale WGS dataset and one simulated dataset with 4000 SVs. Three different variant callers were used to detect the variants before SVGenT was run on the output files. The detection rate was calculated before and after SVGenT was applied. In most cases, SVGenT improved the classification of both SV-type and SV-genotype. Master’s Degree Project in Biology/Molecular Biology/Bioinformatics 60 credits 2017 Department of Biology, Lund University Advisor: Anna Lindstrand M.D., Ph.D. Karolinska Institutet

Side effects and experiences of doping with anabolic androgenic steroids in men and women

Anabolic androgenic steroids (AAS) are mainly used in non-medical conditions for aesthetic and performance- enhancing purposes. The use of AAS is a growing public health problem and a concern in society due to side effects. Men and women use AAS despite their known negative effects and unknown long-term risks. The research in this thesis aimed to study somatic and psychiatric side effects, describe patterns of use, compare self-reported doping agent use with urine test results and to describe AAS usersʼ lived experiences. The approaches in this thesis have been both quantitative (Studies I-IV) and qualitative (Studies V-VI) and were focused on use of AAS outside the field of sports. Study I was an experimental study and included eleven healthy male volunteers administered with a single dose of nandrolone. The aim was to study endocrine and cardiovascular effects. The results showed that luteinising hormone, follicle stimulating hormone and testosterone were suppressed for 14 days after administration. Cholesterol and an enzyme involved in the cholesterol synthesis were increased and hence AAS may be a risk factor for cardiovascular diseases even in low doses. Studies II and III were descriptive studies with eight women and fifty-six men who contacted healthcare (Anti-Doping Hot-Line) on their own initiative. The aim was to identify the pattern of doping agent use in women and compare with similar data reported in men. We also aimed to identify psychiatric and personality disorders and to measure anxiety and depression in men using Structured Clinical Interviews Diagnosis -I and -II, the Brief Scale for Anxiety and the Montgomery Asberg Depression Rating Scale. The participants were interviewed about demographics, details of their AAS use and other co-used substances. They were also asked about motives, side effects they experienced and family background. Both men and women expressed a concern for side effects but there were very few who wanted professional help to terminate their AAS use. Classical side effects of AAS were reported and women contacted healthcare at an earlier stage of use. Women were introduced to AAS by a man in a close relationship. Male individuals diagnosed with a personality disorder showed a significantly increased risk of reporting aggressive feelings/behaviour, suicidal thoughts/attempts and criminality. It was more common that men used injections, higher doses of AAS and several different AAS substances per cycle compared with women. Study IV was an experimental and descriptive study with thirty men and six women who self-reported use of AAS and other performance-enhancing substances within the past year. Our aim was to identify which doping agents could be detected in doping test. The results showed that as many as 50% and 100 % respectively of current male and female testosterone users may escape a doping test. This indicates that AAS users outside the field of sports using only testosterone as a doping agent may not be identified by the routine tests currently used. In men, luteinising hormone and follicle stimulating hormone were normalised within 6-12 months. Haematocrit and haemoglobin values were shown to be high in male current users compared with previous users whereas all women displayed normal values. Thus, cessation of AAS use may reduce the risk of cardiovascular diseases relatively fast. Studies V and VI were qualitative studies with twelve women and twelve men using AAS. The studies applied a phenomenological approach aimed to describe AAS usersʼ lived experiences of using AAS. Our aim was to deepen the understanding about womenʼs and menʼs use of AAS. The results showed that it is an existential challenge to achieve the perfect body. Body dissatisfaction were mastered by hard training, strict diet and the use of AAS. Low self-esteem is compensated for by self-control, discipline and performance. For women it is an arduous endeavour to balance the substances’ side effects with desired femininity. For men the new self-identity stimulates respect by being impressive, prominent and dominant. The use of AAS means living with lies and the fear of being discovered, which may lead to consequences and feelings of not being genuine. The built-up body is fragile from both an existential and a biological perspective, self-esteem can quickly be destroyed in the absence of confirmation and acceptance from others or the substances may damage the body in the form of side effects. Conclusions and reflection: Our studies show that AAS use is associated with many somatic and psychiatric side effects. However, regardless of the perceived side effects, many choose to continue with their AAS use. The fact that the use of AAS is illegal does not prevent those who want to from achieving their goals. A non-judgemental attitude would facilitate the meeting between AAS users and healthcare as it could lead to users experiencing trust and security and would encourage open and honest communication

Two Component Heat Diffusion Observed in CMR Manganites

We investigate the low-temperature electron, lattice, and spin dynamics of LaMnO_3 (LMO) and La_0.7Ca_0.3MnO_3 (LCMO) by resonant pump-probe reflectance spectroscopy. Probing the high-spin d-d transition as a function of time delay and probe energy, we compare the responses of the Mott insulator and the double-exchange metal to the photoexcitation. Attempts have previously been made to describe the sub-picosecond dynamics of CMR manganites in terms of a phenomenological three temperature model describing the energy transfer between the electron, lattice and spin subsystems followed by a comparatively slow exponential decay back to the ground state. However, conflicting results have been reported. Here we first show clear evidence of an additional component in the long term relaxation due to film-to-substrate heat diffusion and then develop a modified three temperature model that gives a consistent account for this feature. We confirm our interpretation by using it to deduce the bandgap in LMO. In addition we also model the non-thermal sub-picosecond dynamics, giving a full account of all observed transient features both in the insulating LMO and the metallic LCMO.Comment: 6 pages, 5 figures http://link.aps.org/doi/10.1103/PhysRevB.81.064434 v2: Abstract correcte

Understanding attitudes towards congestion pricing: a latent variable investigation with data from four cities

Numerous cities around the world are considering the implementation of road pricing to ease urban traffic congestion, following on from the success in cities such as London and Singapore. However, policy makers are also all too aware of the generally negative public opinion towards such measures. This study makes use of data collected in four cities (two in Sweden, one in Finland and one in France) using a very consistent survey probing for citizens' attitudes towards pricing. We find very strong similarities across the four cities in terms of a number of underlying attitudinal constructs that help explain people's answers in a hypothetical referendum on congestion pricing. The similarities across cities indicate that the increase in the opinion towards congestion pricing once they are introduced is not primarily an effect of changes in underlying attitudes, changes in how the underlying attitudes influence the support for congestion pricing, or differences in anticipated versus experienced or perceived self - interest. Instead this effect seems to be caused by a status quo acceptance, tending to increase the support for the current situation