Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations

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Highlights? Complex chromosomal alterations (chromothripsis) observed in medulloblastomas ? Cancers with such alterations harbor TP53 mutations ? Context-specific link between the status of p53 and likelihood of chromothripsis ? p53 status and chromothripsis also correlate with aggressive acute myeloid leukemia     

Effect of phototherapy on oxidant/antioxidant status: a randomized controlled trial

In order to evaluate the effect of different types of phototherapy on oxidant/antioxidant status in hyperbilirubinemic neonates, an interventional randomized control trial was conducted on 120 neonates ≥35 weeks’ gestational age with indirect hyperbilirubinemia reaching phototherapy level. This study is registered with ClinicalTrials.gov as NCT03074292. Neonates were assigned to three groups; 40 neonates received conventional phototherapy, 40 received intensive phototherapy and 40 received blue light-emitting diodes (LED) phototherapy. Complete blood count (CBC), total serum bilirubin (TSB), total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), copper (Cu), zinc (Zn), and iron (Fe) levels were measured before and 24?hours after phototherapy. TSB decreased postphototherapy in all three groups (p < .05 for all), with significantly lower levels following intensive and LED phototherapy compared to conventional phototherapy (p < .05 for both). TAC decreased postphototherapy in the three groups (p < .05 for all). MDA and NO increased postphototherapy (p < .05 for all), with the intensive phototherapy group having the highest levels followed by the conventional while LED phototherapy group showed the lowest levels in comparison to the other groups (p < .05). Cu, Zn and Fe increased postphototherapy in all three groups (p < .05 for all). Positive correlations were found between postphototherapy TSB with TAC, Cu and Zn (p < .05) and negative correlations with MDA, NO and Fe (p < .05) among neonates of the 3 studied groups. In conclusion, different photo therapies have an impact on oxidant/antioxidant balance and are associated with increased oxidative stress markers with the LED phototherapy being the safest.     

Treatment-resistant schizophrenia and DAT and SERT polymorphisms

One fifth to one third of all patients diagnosed with schizophrenia are resistant to drug treatment, which makes it a major clinical challenge. Genetic studies have focused on the association between treatment resistant schizophrenia (TRS) and a number of candidate genes, including serotonin and dopamine system genes. We explored associations between carefully characterized TRS and DAT–VNTR, SERT-PR and SERT-in2 polymorphisms. There were 173 patients enrolled in the study that were clinically evaluated using Positive and Negative Syndrome Scale and Clinical Global Impressions Scales and divided into two groups based on treatment resistance (92 patients in TRS group). Patients with a combination of SERT-in2 ll and DAT 9/10, 9/11, 9/9 and 6/6 genotypes were more likely to have TRS, compared to those with 10/10 or 10/12 genotype (OR = 5.1; 95% CI = 1.6–16.8). In the group of patients with DAT 10/10 or 10/12 genotype, those who also shared SERT-in2 ls or ss genotype were more likely to have TRS, compared to ll genotype carriers (OR = 2.7; 95% CI = 1.0–7.0). The model in which interaction between SERT-in2 and DAT polymorphisms is linked to TRS can possibly explain contradictory previous results regarding role of DAT and SERT in TRS, but further research is needed.     

Antioxidative response patterns of Norway spruce bark to low-density Ceratocystis polonica inoculation

Key message

Based on time courses of individual antioxidant compounds, bark phenolic metabolism has been recognised to integrate ascorbate–glutathione system as a redox hub in Norway spruce defence against Ceratocystis polonica infection.

Abstract

Temporal courses of individual phenolics, thiols and ascorbate were studied in Norway spruce phloem over a 5-month period after inoculation at low density with Ceratocystis polonica. The initial reaction of Norway spruce 3 days after inoculation was characterised by significantly increased isorhapontin and taxifolin concentrations, accompanied by significantly lowered catechin contents. On later sampling dates, catechin concentrations within infected bark increased until September. The slightly accumulated astringin contents in April and May diminished at later sampling dates in response to infection. The isorhapontin levels strongly raised in April and were slightly lowered from June onwards. Compared to the controls, taxifolin concentrations were higher in the infected samples showing a double peak with maxima in April and June. The taxifolin values eased later but remained above the control levels. The initial response of the ascorbate–glutathione system to fungal infection was characterised by a significantly more oxidised glutathione pool, slightly more reduced ascorbate system and by higher glutathione reductase activity. Three weeks later an accumulation of thiols was observed, whereas total ascorbate was significantly lowered and the ascorbate redox state shifted towards more oxidised values. Until the middle of July a gradual increase of total glutathione was determined within the infected bark, which was accompanied by significantly increased cysteine contents, higher glutathione reductase activity, but significantly lowered total ascorbate contents. The increased pressure on the ascorbate system reflects its interaction with phenolics, as ascorbate is needed for reducing the phenoxyl radicals formed during pathogen defence.     

GMOseek: a user friendly tool for optimized GMO testing

Background

With the increasing pace of new Genetically Modified Organisms (GMOs) authorized or in pipeline for commercialization worldwide, the task of the laboratories in charge to test the compliance of food, feed or seed samples with their relevant regulations became difficult and costly. Many of them have already adopted the so called "matrix approach" to rationalize the resources and efforts used to increase their efficiency within a limited budget. Most of the time, the "matrix approach" is implemented using limited information and some proprietary (if any) computational tool to efficiently use the available data.

Results

The developed GMOseek software is designed to support decision making in all the phases of routine GMO laboratory testing, including the interpretation of wet-lab results. The tool makes use of a tabulated matrix of GM events and their genetic elements, of the laboratory analysis history and the available information about the sample at hand. The tool uses an optimization approach to suggest the most suited screening assays for the given sample. The practical GMOseek user interface allows the user to customize the search for a cost-efficient combination of screening assays to be employed on a given sample. It further guides the user to select appropriate analyses to determine the presence of individual GM events in the analyzed sample, and it helps taking a final decision regarding the GMO composition in the sample. GMOseek can also be used to evaluate new, previously unused GMO screening targets and to estimate the profitability of developing new GMO screening methods.

Conclusion

The presented freely available software tool offers the GMO testing laboratories the possibility to select combinations of assays (e.g. quantitative real-time PCR tests) needed for their task, by allowing the expert to express his/her preferences in terms of multiplexing and cost. The utility of GMOseek is exemplified by analyzing selected food, feed and seed samples from a national reference laboratory for GMO testing and by comparing its performance to existing tools which use the matrix approach. GMOseek proves superior when tested on real samples in terms of GMO coverage and cost efficiency of its screening strategies, including its capacity of simple interpretation of the testing results.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-258) contains supplementary material, which is available to authorized users.     

Sarcoidosis in Native and Transplanted Kidneys: Incidence,Pathologic Findings,and Clinical Course

Renal involvement by sarcoidosis in native and transplanted kidneys classically presents as non caseating granulomatous interstitial nephritis. However, the incidence of sarcoidosis in native and transplant kidney biopsies, its frequency as a cause of end stage renal disease and its recurrence in renal allograft are not well defined, which prompted this study. The electronic medical records and the pathology findings in native and transplant kidney biopsies reviewed at the Johns Hopkins Hospital from 1/1/2000 to 6/30/2011 were searched. A total of 51 patients with a diagnosis of sarcoidosis and renal abnormalities requiring a native kidney biopsy were identified. Granulomatous interstitial nephritis, consistent with renal sarcoidosis was identified in kidney biopsies from 19 of these subjects (37%). This is equivalent to a frequency of 0.18% of this diagnosis in a total of 10,023 biopsies from native kidney reviewed at our institution. Follow-up information was available in 10 patients with biopsy-proven renal sarcoidosis: 6 responded to treatment with prednisone, one progressed to end stage renal disease. Renal sarcoidosis was the primary cause of end stage renal disease in only 2 out of 2,331 transplants performed. Only one biopsy-proven recurrence of sarcoidosis granulomatous interstitial nephritis was identified.

Conclusions

Renal involvement by sarcoidosis in the form of granulomatous interstitial nephritis was a rare finding in biopsies from native kidneys reviewed at our center, and was found to be a rare cause of end stage renal disease. However, our observations indicate that recurrence of sarcoid granulomatous inflammation may occur in the transplanted kidney of patients with sarcoidosis as the original kidney disease.     

Interplay of Packing and Flip-flop in Local Bilayer Deformation. How Phosphatidylglycerol Could Rescue Mitochondrial Function in a Cardiolipin-deficient Yeast Mutant

In a previous work, we have shown that a spatially localized transmembrane pH gradient, produced by acid micro-injection near the external side of cardiolipin-containing giant unilamellar vesicles, leads to the formation of tubules that retract after the dissipation of this gradient. These tubules have morphologies similar to mitochondrial cristae. The tubulation effect is attributable to direct phospholipid packing modification in the outer leaflet, that is promoted by protonation of cardiolipin headgroups. In this study, we compare the case of cardiolipin-containing giant unilamellar vesicles with that of giant unilamellar vesicles that contain phosphatidylglycerol (PG). Local acidification also promotes formation of tubules in the latter. However, compared with cardiolipin-containing giant unilamellar vesicles the tubules are longer, exhibit a visible pearling, and have a much longer lifetime after acid micro-injection is stopped. We attribute these differences to an additional mechanism that increases monolayer surface imbalance, namely inward PG flip-flop promoted by the local transmembrane pH gradient. Simulations using a fully nonlinear membrane model as well as geometrical calculations are in agreement with this hypothesis. Interestingly, among yeast mutants deficient in cardiolipin biosynthesis, only the crd1-null mutant, which accumulates phosphatidylglycerol, displays significant mitochondrial activity. Our work provides a possible explanation of such a property and further emphasizes the salient role of specific lipids in mitochondrial function.     

Assessment of the influence of different sample processing and cold storage duration on plant free proline content analyses

Introduction – A method which is widely accepted for the analysis of free proline content in plant tissues is based on the use of 3% sulfosalicylic acid as an extractant, followed by spectrophotometric quantification of a proline–ninhydrin complex in toluene. However, sample preparation and storage may influence the proline actually measured. This may give misleading or difficult to compare data. Objective and Methodology – To evaluate free proline levels fresh and frozen strawberry (Fragaria × ananassa Duch.) leaves and soybean [Glycine max (L.) Merr.] hypocotyl tissues were used. These were ground with or without liquid nitrogen and proline extracted with sulfosalicylic acid. A particular focus was the influence of plant sample cold storage duration (1, 4 and 12 weeks at ?20°C) on tissue proline levels measured. Results – The free proline content analyses, carried out in leaves of Fragaria × ananassa Duch. as well as in hypocotyls of Glycine max (L.) Merr., showed a significant influence of the sample preparation method and cold storage period. Long‐term storage of up to 12 weeks at ?20°C led to a significant increase in the measured proline in all samples analysed. Conclusion – The observed changes in proline content in plant tissue samples stored at ?20°C indicate the likelihood of the over‐estimation of the proline content if the proline analyses are delayed. Plant sample processing and cold storage duration seem to have an important influence on results of proline analyses. Therefore it is recommended that samples should be ground fresh and analysed immediately. Copyright © 2010 John Wiley & Sons, Ltd.     

Ultrastructure and mineral distribution in the tergal cuticle of the terrestrial isopod Titanethes albus. Adaptations to a karst cave biotope

Composition and spatial distribution of organic and inorganic materials within the cuticle of isopods vary between species. These variations are related to the behaviour and habitat of the animal. The troglobiotic isopod Titanethes albus lives in the complete darkness of caves in the Slovenian Karst. This habitat provides constant temperature and saturated humidity throughout the year and inconsistent food supply. These conditions should have lead to functional adaptations of arthropod cuticles. However, studies on structure and composition of cave arthropod cuticles are rare and lacking for terrestrial isopods. We therefore analysed the tergite cuticle of T. albus using transmission and field-emission electron microscopy, confocal μ-Raman spectroscopic imaging, quantitative X-ray diffractometry, thermogravimetric analysis and atomic absorption spectroscopy. The ultrastructure of the epicuticle suggests a poor resistance against water loss. A weak interconnection between the organic and mineral phase within the endo- and exocuticle, a comparatively thin apical calcite layer, and almost lack of magnesium within the calcite crystal lattice suggest that the mechanical strength of the cuticle is low in the cave isopod. This may possibly be of advantage in maintaining high cuticle flexibility and reducing metabolic expenditures.