BRAF Mutation is Associated with an Improved Survival in Glioma—a Systematic Review and Meta-analysis

Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (HR = 0.60; 95% CI = 0.44–0.80). Results for progression-free survival (PFS), however, were not statistically significant (HR = 1.39; 95% CI = 0.82–2.34). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric and young adult gliomas (under 35 years) but did not have prognostic value in old adult. Additionally, BRAF V600E was only associated with a favorable prognosis in lower grade glioma. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in gliomas and its prognostic value might be dependent on patient age and tumor grade. This mutation can be used as a prognostic factor in glioma but additional studies are required to clarify its prognostic value taking into account other confounding factors.     

Captive breeding—a useful tool in the preservation of biodiversity?

Within the next decades species extinction may eliminate between 20 and 50% of the Earth's species. Captive breeding has often been claimed to be a useful tool in preservation of biodiversity. The role of zoos in conservation work and the value of captive breeding are discussed; the latter exemplified by the Peregrine Falcon (Falco peregrinus) Programme and the Arabian oryx (Oryx leucoryx) Programme. Captive breeding programmes are very resource demanding and can only be afforded for a very small number of species, which limits their value significantly. Zoos deal mainly with vertebrates, but these comprise less than 3% of the described species, and although the 878 zoos considered hold more than 20 000 specimens of 140 threatened mammal species, they probably only contribute to the conservation of 20 full species. The situation for birds, reptiles and amphibians is even worse. Zoos face serious problems with minimum viable population sizes and hybridization. However, zoos can make a major contribution to preservation of biodiversity through educating and informing the public. Today, where the crisis of extinction of species has reached such daunting dimensions, captive breeding and otherex situ conservation tools should be the last resort for preserving biodiversity, and captive breeding must not become an excuse to avoid dealing with preservation of habitats.     

Macroinvertebrate assemblages in an artificial habitat—a settling basin of a hydroelectric power plant: comparison with a natural riffle habitat

The macroinvertebrate assemblages in an artificial habitat, the settling basin of a hydroelectric power plant, were investigated and compared with those in a natural habitat, riffles in a nearby river. This study showed that macroinvertebrate density was much higher in the settling basin than in the riffles. Macroinvertebrate assemblage composition differed between the settling basin and the riffles. The difference was probably due to the widespread bryophyte beds in the settling basin. Cincticostella, Brachycentrus, Ephmerella, and chironomid midges, which are usually abundant in bryophyte beds, were present at much higher densities in the settling basin. Cheumatopsyche and Taeniopterygidae were also present at higher densities in the settling basin than in the natural riffles. In contrast, Epeorus was present at lower density in the settling basin than in the natural riffles. This study suggests that the settling basin increases β-diversity in riverine ecosystems.     

Assessing structural variation in a personal genome—towards a human reference diploid genome

Background

Characterizing large genomic variants is essential to expanding the research and clinical applications of genome sequencing. While multiple data types and methods are available to detect these structural variants (SVs), they remain less characterized than smaller variants because of SV diversity, complexity, and size. These challenges are exacerbated by the experimental and computational demands of SV analysis. Here, we characterize the SV content of a personal genome with Parliament, a publicly available consensus SV-calling infrastructure that merges multiple data types and SV detection methods.

Results

We demonstrate Parliament’s efficacy via integrated analyses of data from whole-genome array comparative genomic hybridization, short-read next-generation sequencing, long-read (Pacific BioSciences RSII), long-insert (Illumina Nextera), and whole-genome architecture (BioNano Irys) data from the personal genome of a single subject (HS1011). From this genome, Parliament identified 31,007 genomic loci between 100 bp and 1 Mbp that are inconsistent with the hg19 reference assembly. Of these loci, 9,777 are supported as putative SVs by hybrid local assembly, long-read PacBio data, or multi-source heuristics. These SVs span 59 Mbp of the reference genome (1.8%) and include 3,801 events identified only with long-read data. The HS1011 data and complete Parliament infrastructure, including a BAM-to-SV workflow, are available on the cloud-based service DNAnexus.

Conclusions

HS1011 SV analysis reveals the limits and advantages of multiple sequencing technologies, specifically the impact of long-read SV discovery. With the full Parliament infrastructure, the HS1011 data constitute a public resource for novel SV discovery, software calibration, and personal genome structural variation analysis.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1479-3) contains supplementary material, which is available to authorized users.     

Improved method of in vitro regeneration in Leucaena leucocephala — a leguminous pulpwood tree species

Leucaena leucocephala is a fast growing multipurpose legume tree used for forage, leaf manure, paper and pulp. Lignin in Leucaena pulp adversely influences the quality of paper produced. Developing transgenic Leucaena with altered lignin by genetic engineering demands an optimized regeneration system. The present study deals with optimization of regeneration system for L. leucocephala cv. K636. Multiple shoot induction from the cotyledonary nodes of L. leucocephala was studied in response to cytokinins, thidiazuron (TDZ) and N⁶-benzyladenine (BA) supplemented in half strength MS (½-MS) medium and also their effect on in vitro rooting of the regenerated shoots. Multiple shoots were induced from cotyledonary nodes at varied frequencies depending on the type and concentration of cytokinin used in the medium. TDZ was found to induce more number of shoots per explant than BA, with a maximum of 7 shoots at an optimum concentration of 0.23 µM. Further increase in TDZ concentration resulted in reduced shoot length and fasciation of the shoots. Liquid pulse treatment of the explants with TDZ did not improve the shoot production further but improved the subsequent rooting of the shoots that regenerated. Regenerated shoots successfully rooted on ½-MS medium supplemented with 0.54 µM α-naphthaleneacetic acid (NAA). Rooted shoots of Leucaena were transferred to coco-peat and hardened plantlets showed ≥ 90 % establishment in the green house.Key words: Cotyledonary nodes, Multiple shoot induction, Pulse treatment, TDZ     

Heat shock proteins in animal neoplasms and human tumours—a comparison

Heat shock proteins (HSPs) are implicated in all phases of cancer from proliferation, impaired apoptosis and sustained angiogenesis to invasion and metastasis. The presence of abnormal HSP levels in several human tumours suggests that these proteins could be used as diagnostic and/or prognostic markers, whilst the direct correlation between HSP expression and drug resistance in neoplastic tissues means they could also be used to predict cancer response to specific treatment. HSPs have also been successfully targeted in clinical trials modifying their expression or chaperone activity. Preliminary studies in veterinary medicine have also demonstrated the presence of altered HSP expression in neoplasms, and the study of carcinogenesis and the role of HSPs in animal models will surely be an additional source of information for clinical cancer research.     

Modeling thermal sensation in a Mediterranean climate—a comparison of linear and ordinal models

A simple thermo-physiological model of outdoor thermal sensation adjusted with psychological factors is developed aiming to predict thermal sensation in Mediterranean climates. Microclimatic measurements simultaneously with interviews on personal and psychological conditions were carried out in a square, a street canyon and a coastal location of the greater urban area of Athens, Greece. Multiple linear and ordinal regression were applied in order to estimate thermal sensation making allowance for all the recorded parameters or specific, empirically selected, subsets producing so-called extensive and empirical models, respectively. Meteorological, thermo-physiological and overall models - considering psychological factors as well - were developed. Predictions were improved when personal and psychological factors were taken into account as compared to meteorological models. The model based on ordinal regression reproduced extreme values of thermal sensation vote more adequately than the linear regression one, while the empirical model produced satisfactory results in relation to the extensive model. The effects of adaptation and expectation on thermal sensation vote were introduced in the models by means of the exposure time, season and preference related to air temperature and irradiation. The assessment of thermal sensation could be a useful criterion in decision making regarding public health, outdoor spaces planning and tourism.     

Monitoring of membrane phospholipid scrambling in human erythrocytes and K562 cells with FM1-43 — a comparison with annexin V-FITC

The styryl dye FM1-43 becomes highly fluorescent upon binding to cell membranes. The breakdown of membrane phospholipid asymmetry in ionophore-stimulated T-lymphocytes further increases this fluorescence [Zweifach, 2000]. In this study, the capacity of FM1-43 to monitor membrane phospholipid scrambling was explored using flow cytometry in human erythrocytes and human erythrocyte progenitor K562 cells. The Ca²⁺-dependent phosphatidylserine-specific probe annexin V-FITC was used for comparison. The presented data show that the loss of phospholipid asymmetry that could be induced in human erythrocytes by elevated intracellular Ca²⁺ or by structurally different membrane intercalated amphiphilic compounds increases the FM1-43 fluorescence two- to fivefold. The profile of FM1-43 fluorescence for various treatments resembles that of phosphatidylserine exposure reported by annexin V-FITC. FM1-43 detected the onset of scrambling more efficiently than annexin V-FITC. The amphiphile-induced scrambling was shown to be a Ca²⁺-independent process. Monitoring of scrambling in K562 cells caused by NEM-induced Ca²⁺-release from intracellular stores and by Ca²⁺ and ionophore A23187 treatment showed that the increase in FM1-43 fluorescence correlated well with the number of annexin V-FITC-detected phosphatidylserine-positive cells. The results presented here show the usefulness of FM1-43 as a Ca²⁺-independent marker of dissipation in asymmetric membrane phospholipid distribution induced by various stimuli in both nucleated and non-nucleated cells.     

Starch determination in Chlorella vulgaris—a comparison between acid and enzymatic methods

Different methods for estimating starch in Chlorella vulgaris were compared with the view of establishing a procedure suitable for rapid and accurate determination of starch content in this microalgal species. A close agreement was observed between methods that use perchloric acid and enzymatic methods that use α-amylase and amyloglucosidase to hydrolyze the starch of microalgae grown under different nitrogen culture conditions. Starch values obtained by these methods were significantly higher than those estimated by using hydrochloric acid as solubilizing and hydrolyzing agent. The enzymatic method (EM1) proved to be the most rapid and precise method for microalgal starch quantification. Furthermore, the evaluation of resistant starch by enzymatic methods assayed in nitrogen-sufficient and nitrogen-starved cells showed that no formation of this type of starch occurred in microalgae, meaning that this should not interfere with starch content determinations.     

Mycorrhizal symbiosis and Lygodium microphyllum Invasion in South Florida—a biogeographic comparison

Lygodium microphyllum (Old World Climbing Fern) is one of the most problematic weeds in south Florida, invading numerous habitats from mangroves to pine flatwoods natural ecosystems. Much of the research efforts on L. microphyllum has been focused on reproductive potential, spore release, growth under different environmental conditions, belowground rhizome dormancy and survival strategies that describes its invasiveness. However, the role of an important mutualistic association with arbuscular mycorrhizal fungi (AMF) in the competitive ability and successful invasion of L. microphyllum by enhancing nutrient uptake has not been previously considered. Analysis of field root and soil samples from the ferns introduced and native range as well as a 7-week growth chamber experiment were done to determine the level of mycorrhizal colonization in the roots of L. microphyllum and the dependency on mycorrhizal fungi for growth and phosphorus (P) uptake. The field root samples showed that L. microphyllum was heavily colonized by AMF in relatively drier conditions, which are commonly found on some Florida sites compared to more common wetter sites where the fern is found in its native Australia. The results from the growth chamber experiment showed that the mycorrhizal treatment plants had significantly higher relative growth rate and biomass compared to the non-mycorrhizal plants. Similarly, L. microphyllum was highly dependent on the mycorrhizal fungi for growth and P uptake. Our results suggest that AMF play a significant role in vegetative reproduction and likely enhance the invasiveness of L. microphyllum in south Florida natural areas.     

Error propagation methods for LCA—a comparison

Purpose

The analysis of uncertainty in life cycle assessment (LCA) studies has been a topic for more than 10 years, and many commercial LCA programs now feature a sampling approach called Monte Carlo analysis. Yet, a full Monte Carlo analysis of a large LCA system, for instance containing the 4,000 unit processes of ecoinvent v2.2, is rarely carried out by LCA practitioners. One reason for this is computation time. An alternative faster than Monte Carlo method is analytical error propagation by means of a Taylor series expansion; however, this approach suffers from being explained in the literature in conflicting ways, hampering implementation in most software packages for LCA. The purpose of this paper is to compare the two different approaches from a theoretical and practical perspective.

Methods

In this paper, we compare the analytical and sampling approaches in terms of their theoretical background and their mathematical formulation. Using three case studies—one stylized, one real-sized, and one input–output (IO)-based—we approach these techniques from a practical perspective and compare them in terms of speed and results.

Results

Depending on the precise question, a sampling or an analytical approach provides more useful information. Whenever they provide the same indicators, an analytical approach is much faster but less reliable when the uncertainties are large.

Conclusions

For a good analysis, analytical and sampling approaches are equally important, and we recommend practitioners to use both whenever available, and we recommend software suppliers to implement both.     

Improved survival in both men and women with diabetes between 1980 and 2004 – a cohort study in Sweden

Background

In Sweden, diabetes prevalence is increasing in spite of unchanged incidence, indicating improved survival. In recent US studies mortality in diabetic subjects has decreased over three decades, but only in men. Our aim was to study mortality over time in diabetic subjects.

Methods

The annual Swedish Living Conditions Survey from 1980 to 2004 has been record-linked to the Cause of Death Register in order to study trends in mortality risk for those reporting diabetes as a chronic illness. Survival and the relative mortality risk within 5 years of follow-up have been calculated for a random sample of men and women aged 40–84 years with (n = 3,589) and without diabetes (n = 85,685) for the period 1980 to 2004. Poisson regression models were used.

Results

The age-adjusted mortality risk relative to non-diabetics within 5 years of follow-up for men was doubled during all periods. The relative risk for women was initially about 2.5, with a substantial drop in mortality in 1995–1999 to 1.45 although it increased to 1.90 in the last period. Using models that took into consideration the presence of heart disease, hypertension, daily smoking, and socio-economic status at the initial interview did not change the relative mortality risk. The age-adjusted 10-year observed survival rate for men with diabetes increased from 41.4% 1980–1984 to 51.5% in 1995–1999. The observed survival for women increased from 43.7% to 61.0%.

Conclusion

Survival rates have improved in subjects with diabetes since the early 1980s, more so in women than in men, thereby decreasing the gap to non-diabetic women.

     

Utilization of recovered wood in cascades versus utilization of primary wood—a comparison with life cycle assessment using system expansion

Purpose

A cascading utilization of resources is encouraged especially by legislative bodies. However, only few consecutive assessments of the environmental impacts of cascading are available. This study provides answers to the following questions for using recovered wood as a secondary resource: (1) Does cascading decrease impacts on the environment compared to the use of primary wood resources? (2) What aspects of the cascading system are decisive for the life cycle assessment (LCA) results?

Methods

We conducted full LCAs for cascading utilization options of waste wood and compared the results to functionally equivalent products from primary wood, thereby focusing on the direct effects cascading has on the environmental impacts of the systems. In order to compare waste wood cascading to the use of primary wood with LCA, a functional equivalence of the systems has to be achieved. We applied a system expansion approach, considering different options for providing the additionally needed energy for the cascading system.

Results and discussion

We found that the cascading systems create fewer environmental impacts than the primary wood systems, if system expansion is based on wood energy. The most noticeable advantages were detected for the impact categories of land transformation and occupation and the demand of primary energy from renewable sources. The results of the sensitivity analyses indicate that the advantage of the cascading system is robust against the majority of considered factors. Efficiency and the method of incineration at the end of life do influence the results.

Conclusions

To maximize the benefits and minimize the associated environmental impacts, cascading proves to be a preferable option of utilizing untreated waste wood.     

A comparison of head-out mist bathing,with or without facial fanning,with head-out half-body low-water level bathing in humans—a pilot study

To reduce the risks of Japanese-style bathing, half-body bathing (HBLB) has been recommended in Japan, but discomfort due to the cold environment in winter prevents its widespread adoption. The development of the mist sauna, which causes a gradual core temperature rise with sufficient thermal comfort, has reduced the demerits of HBLB. We examined head-out 42 °C mist bathing with 38 °C HBLB up to the navel to see if it could improve thermal comfort without detracting from the merits of HBLB, with and without the effects of facial fanning (FF). The subjects were seven healthy males aged 22–25 years. The following bathing styles were provided: (1) HBLB—head-out half-body low bathing of 38 °C up to the navel (20 min); (2) HOMB—head-out mist bathing of 42 °C and HBLB of 38 °C (20 min); and (3) HOMBFF—HOMB with FF (20 min). HOMB raised the core temperature gradually. HOMBFF suppressed the core temperature rise in a similar fashion to HOMB. Increases in blood pressure and heart rate usually observed in Japanese traditional-style bathing were less marked in HOMBs with no significant difference with and without FF. The greatest body weight loss was observed after Japanese traditional-style bathing, with only one-third of this amount lost after mist bathing, and one-sixth after HBLB. HOMB increased thermal sensation, and FF also enhanced post-bathing invigoration. We conclude that HOMB reduces the risks of Japanese traditional style bathing by mitigating marked changes in the core temperature and hemodynamics, and FF provides thermal comfort and invigoration.     

Improved cytologic localisation ofβ-glucuronidase in sections treated with ethanol

Summary Treatment of fixed frozen sections of rat kidney with 40–60% ethanol for 2 minutes at 0° C improved the cytologic localisation of-glucuronidase in naphthol AS-BI post-coupling technique. Concentration of ethanol, duration of treatment and temperature are critical. Higher concentrations of ethanol, longer treatment and higher temperatures deteriorate the normal localisation of the enzyme. Such pretreatment can he introduced as a step in the original histochemical technique.     

Assembly of nucleosomal DNA in a cell-free extract from wild-type and top1− strains ofUstilago maydis

An in vitro nucleosome assembly system has been established from cell-free extracts of the fungusUstilago maydis. The extract catalyzed DNA supercoiling in the absence of exogenously added co-factors such as ATP and MgCl₂ and was inhibited by moderate concentrations (200 mM) of KCl or NaCl. DNA supercoiling occurs via the formation of nucleosomes. Similar extracts, displaying the same activity, were prepared fromSaccharomyces cerevisiae andCandida albicans, suggesting that the extract preparation protocol may be useful for many lower eukaryotic systems. An extract prepared from a strain ofU. maydis lacking topoisomerase I failed to catalyze nucleosome assembly, clearly implicating this enzyme in this process. Addition of purified topoisomerase I, and, to a lesser extent, topoisomerase II, to the top1^? extract regenerated the supercoiling activity. Our results provide a method for preparing assembly extracts from organisms, that are particularly amenable to genetic manipulation.     

Subtilisin DY—Kinetic characterization and comparison with related proteinases

Subtilisin DY, a serine proteinase fromBacillus subtilis, variant DY, is compared with subtilisin Carlsberg, proteinase K, thermitase, as well as with -chymotrypsin by use of kinetic parameters of the reactions with the synthetic peptidyl substrates succinyl-Ala₃-4-nitroanilide, succinyl-Ala₂-Phe-4-nitroanilide, MeO-succinyl-Ala₂-Phe-4-nitroanilide, and with the irreversible inhibitors of the general structure benzyloxycarbonyl-Ala_n-PheCH₂Cl (n=0, 1, 2, 3, 4) and benzyloxycarbonyl-Ala-AaCH₂Cl (Aa=Gly, Ala, Val, Leu, Phe), respectively. The data demonstrated that subtilisin DY is very closely related to the Carlsberg enzyme. Thermitase and -chymotrypsin deviate in their behavior from that of subtilisin DY more than proteinase K. The best inhibitor (highest k_inact/K_i) for the two subtilisins and proteinase K is benzyloxycarbonyl-Ala₂-PheCH₂Cl; for thermitase and -chymotrypsin, benzyloxycarbonyl-Ala₃-PheCH₂Cl. In the series of the benzyloxycarbonyl-protected dipeptidyl chloromethyl ketones, the following order of reactivity was obtained for subtilisin DY as well as for subtilisin Carlsberg and proteinase K: Aa=LeuPhe>AlaVal>Gly. Thermitase and -chymotrypsin prefer the aromatic phenylalanyl rather than the also hydrophobic leucyl residue at S₁. Succinyl-Ala₂-Phe-4-nitroanilide was the most suitable substrate to indicate the inhibition reactions.     

Selection response for part period egg number and egg mass in chickens — a comparison

Summary Two sublines from each of four flocks of White Leghorn were subjected to two cycles of selection for part year egg number and part year egg mass. A family index (combined selection) was the selection criterion for each of the two traits. The generation means of an unselected pedigreed randombred control, bred and maintained along with the selected sub-lines, were used for correcting short term environmental trends. The sublines selected for a common selection criterion were considered as replicates. The control corrected generation means, when averaged over replicates, gave the mean direct and correlated responses for the selected and different unselected traits. The average genetic change per generation was 2.16 eggs in egg number selected sublines and 146 g of egg mass in egg mass selected sublines. The direct response marginally exceeded the correlated response for both part period egg number and egg mass seen in the corresponding sublines. Except for egg weight the correlated responses for different unselected traits were in the same direction in both egg number and egg mass selected sublines. While the egg weight in egg number lines did not change, its response was positive in egg mass selected lines. A comparison between the lines revealed that the egg mass selected lines matured later and laid heavier but slightly less numerous eggs than the egg number selected sub-lines.