Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction

<p>Abstract</p> <p>Background</p> <p>When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown.</p> <p>Results</p> <p>We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of <it>Arabidopsis thaliana </it>and published EST datasets from commercially relevant species (rice and papaya).</p> <p>Conclusion</p> <p>We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.</p

Sedimentary ancient DNA shows terrestrial plant richness continuously increased over the Holocene in northern Fennoscandia

The effects of climate change on species richness are debated but can be informed by the past. Here, we generated a sedimentary ancient DNA dataset covering 10 lakes and applied novel methods for data harmonization. We assessed the impact of Holocene climate changes and nutrients on terrestrial plant richness in northern Fennoscandia. We find that richness increased steeply during the rapidly warming Early Holocene. In contrast to findings from most pollen studies, we show that richness continued to increase thereafter, although the climate was stable, with richness and the regional species pool only stabilizing during the past three millennia. Furthermore, overall increases in richness were greater in catchments with higher soil nutrient availability. We suggest that richness will increase with ongoing warming, especially at localities with high nutrient availability and assuming that human activity remains low in the region, although lags of millennia may be expected.The effects of climate change on species richness are debated but can be informed by the past. Here, we generated a sedimentary ancient DNA dataset covering 10 lakes and applied novel methods for data harmonization. We assessed the impact of Holocene climate changes and nutrients on terrestrial plant richness in northern Fennoscandia. We find that richness increased steeply during the rapidly warming Early Holocene. In contrast to findings from most pollen studies, we show that richness continued to increase thereafter, although the climate was stable, with richness and the regional species pool only stabilizing during the past three millennia. Furthermore, overall increases in richness were greater in catchments with higher soil nutrient availability. We suggest that richness will increase with ongoing warming, especially at localities with high nutrient availability and assuming that human activity remains low in the region, although lags of millennia may be expected.Peer reviewe

Stable cerebrospinal fluid neurogranin and β-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients

Cerebrospinal fluid (CSF) β-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer’s disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T−/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer’s disease cases (n = 176) [including cases that progressed to dementia (n = 10)] and controls (n = 74) from the Norwegian Dementia Disease Initiation cohort. We selected cases at the presumed early (A+/T−/N−, n = 86) and late stages (A+/T+/N+, n = 90) of the Alzheimer’s disease continuum and controlled with normal markers (A−/T−/N−, n = 74). A subset of subjects in all A/T/N groups underwent repeat CSF sampling at approximately 2-year intervals up to 6 years from baseline. Using linear mixed models, longitudinal measurements of CSF BACE1 and neurogranin levels in A+/T−/N− and A+/T+/N+ as compared to A−/T−/N− healthy controls were performed. Next, we measured changes in CSF BACE1 and neurogranin levels in cases that progressed from A−/T−/N− to A+/T−/N− (n = 12), from A+/T−/N− to A+/T or N+ (n = 12), remained stable A+/T−/N− (n = 26), remained stable A+/T+/N+ (n = 28) compared with controls remaining stable A−/T−/N− (n = 33). Lastly, associations between these markers and memory decline were assessed. Compared with A−/T−/N− healthy controls, neurogranin was unaltered in A+/T−/N− (n.s.) but higher in A+/T+/N+ (P < 0.0001). In contrast, BACE1 was lower in A+/T−/N− (P < 0.05) and higher in A+/T+/N+ (P < 0.0001). The neurogranin/BACE1 ratio was increased in both A+/T−/N− (P < 0.05) and A+/T+/N+ (P < 0.0001) groups as compared to A-/T-/N- healthy controls and was more strongly associated with memory decline (b = −0.29, P = 0.0006) than neurogranin (b = −0.20, P = 0.002) and BACE1 (b = −0.13, P = 0.046). Neurogranin and BACE1 level differences remained stable over time not only within A/T/N groups but also in patients progressing to more pathological A/T/N stages (e.g. progressing from A+/T−/N− to A + T or N+) and in cases progressing to dementia. Our results suggest that neurogranin and BACE1 levels may differentiate pathomechanistic Alzheimer’s disease subgroups, putatively with different options for treatment

Postglacial species arrival and diversity buildup of northern ecosystems took millennia

What drives ecosystem buildup, diversity, and stability? We assess species arrival and ecosystem changes across 16 millennia by combining regional-scale plant sedimentary ancient DNA from Fennoscandia with near-complete DNA and trait databases. We show that postglacial arrival time varies within and between plant growth forms. Further, arrival times were mainly predicted by adaptation to temperature, disturbance, and light. Major break points in ecological trait diversity were seen between 13.9 and 10.8 calibrated thousand years before the present (cal ka BP), as well as break point in functional diversity at 12.0 cal ka BP, shifting from a state of ecosystem buildup to a state where most habitat types and biotic ecosystem components were in place. Trait and functional diversity stabilized around 8 cal ka BP, after which both remained stable, although changes in climate took place and species inflow continued. Our ecosystem reconstruction indicates a millennial-scale time phase of formation to reach stable and resilient levels of diversity and functioning.publishedVersio

Effects of nitrogen and sulfur fertilization on free amino acids, sugars, and acrylamide-forming potential in potato

Nitrogen (N) fertilizer is used routinely in potato (Solanum tuberosum) cultivation to maximize yield. However, it also affects sugar and free amino acid concentrations in potato tubers, and this has potential implications for food quality and safety because free amino acids and reducing sugars participate in the Maillard reaction during high-temperature cooking and processing. This results in the formation of color, aroma, and flavor compounds, but also some undesirable contaminants, including acrylamide, which forms when the amino acid that participates in the final stages of the reaction is asparagine. Another mineral, sulfur (S), also has profound effects on tuber composition. In this study, 13 varieties of potato were grown in a field trial in 2010 and treated with different combinations of N and S. Potatoes were analyzed immediately after harvest to show the effect of N and S fertilization on concentrations of free asparagine, other free amino acids, sugars, and acrylamide-forming potential. The study showed that N application can affect acrylamide-forming potential in potatoes but that the effect is type- (French fry, chipping, and boiling) and variety-dependent, with most varieties showing an increase in acrylamide formation in response to increased N but two showing a decrease. S application reduced glucose concentrations and mitigated the effect of high N application on the acrylamide-forming potential of some of the French fry-type potatoes

The positive effect of plant diversity on soil carbon depends on climate

Little is currently known about how climate modulates the relationship between plant diversity and soil organic carbon and the mechanisms involved. Yet, this knowledge is of crucial importance in times of climate change and biodiversity loss. Here, we show that plant diversity is positively correlated with soil carbon content and soil carbon-to-nitrogen ratio across 84 grasslands on six continents that span wide climate gradients. The relationships between plant diversity and soil carbon as well as plant diversity and soil organic matter quality (carbon-to-nitrogen ratio) are particularly strong in warm and arid climates. While plant biomass is positively correlated with soil carbon, plant biomass is not significantly correlated with plant diversity. Our results indicate that plant diversity influences soil carbon storage not via the quantity of organic matter (plant biomass) inputs to soil, but through the quality of organic matter. The study implies that ecosystem management that restores plant diversity likely enhances soil carbon sequestration, particularly in warm and arid climates

Six pelagic seabird species of the North Atlantic engage in a fly-and-forage strategy during their migratory movements

Funding Information: We thank all the fieldworkers for their hard work collecting data. Funding for this study was provided by the Norwegian Ministry for Climate and the Environment, the Norwegian Ministry of Foreign Affairs and the Norwegian Oil and Gas Association along with 8 oil companies through the SEATRACK project (www. seapop. no/ en/ seatrack). Fieldwork in Norwegian colonies (incl. Svalbard and Jan Mayen) was supported by the SEAPOP program (www.seapop.no, grant no. 192141). The French Polar Institute (IPEV project 330 to O.C.) supported field operation for Kongsfjord kittiwakes. The work on the Isle of May was also supported by the Natural Environment Research Council (Award NE/R016429/1 as part of the UK-SCaPE programme delivering National Capability). We thank Maria Bogdanova for field support and data processing. Finally, we thank 3 anonymous reviewers for their help improving the first version of the manuscript.Peer reviewedPublisher PD

Pastoral Herding Strategies and Governmental Management Objectives: Predation Compensation as a Risk Buffering Strategy in the Saami Reindeer Husbandry

Previously it has been found that an important risk buffering strategy in the Saami reindeer husbandry in Norway is the accumulation of large herds of reindeer as this increases long-term household viability. Nevertheless, few studies have investigated how official policies, such as economic compensation for livestock losses, can influence pastoral strategies. This study investigated the effect of received predation compensation on individual husbandry units’ future herd size. The main finding in this study is that predation compensation had a positive effect on husbandry units’ future herd size. The effect of predation compensation, however, was nonlinear in some years, indicating that predation compensation had a positive effect on future herd size only up to a certain threshold whereby adding additional predation compensation had little effect on future herd size. More importantly, the effect of predation compensation was positive after controlling for reindeer density, indicating that for a given reindeer density husbandry units receiving more predation compensation performed better (measured as the size of future herds) compared to husbandry units receiving less compensation

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information

Quantitative EEG findings in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

<p>Abstract</p> <p>Background</p> <p>Patients with brief depressive episodes and concurrent rapidly fluctuating psychiatric symptoms do not fit current diagnostic criteria and they can be difficult to diagnose and treat in an acute psychiatric setting. We wanted to study whether these patients had signs of more epileptic or organic brain dysfunction than patients with depression without additional symptomatology.</p> <p>Methods</p> <p>Sixteen acutely admitted patients diagnosed with a brief depressive episode as well as another concurrent psychiatric diagnosis were included. Sixteen patients with major depression served as controls. Three electroencephalographic studies (EEG) were visually interpreted and the background activity was also analysed with quantitative electroencephalography (QEEG).</p> <p>Results</p> <p>The group with brief depression and concurrent symptoms had multiple abnormal features in their standard EEG compared to patients with major depression, but they did not show significantly more epileptiform activity. They also had significantly higher temporal QEEG delta amplitude and interhemispheric temporal delta asymmetry.</p> <p>Conclusion</p> <p>Organic brain dysfunction may be involved in the pathogenesis of patients with brief depressive episodes mixed with rapidly fluctuating psychiatric symptoms. This subgroup of depressed patients should be investigated further in order to clarify the pathophysiology and to establish the optimal evaluation scheme and treatment in an acute psychiatric setting.</p