Combining genotype,phenotype, and environmental data to delineate site‐adjusted provenance strategies for ecological restoration

Despite the importance of climate‐adjusted provenancing to mitigate the effects of environmental change, climatic considerations alone are insufficient when restoring highly degraded sites. Here we propose a comprehensive landscape genomic approach to assist the restoration of moderately disturbed and highly degraded sites. To illustrate it we employ genomic data sets comprising thousands of single nucleotide polymorphisms from two plant species suitable for the restoration of iron‐rich Amazonian Savannas. We first use a subset of neutral loci to assess genetic structure and determine the genetic neighbourhood size. We then identify genotype‐phenotype‐environment associations, map adaptive genetic variation, and predict adaptive genotypes for restoration sites. Whereas local provenances were found optimal to restore a moderately disturbed site, a mixture of genotypes seemed the most promising strategy to recover a highly degraded mining site. We discuss how our results can help define site‐adjusted provenancing strategies, and argue that our methods can be more broadly applied to assist other restoration initiatives.     

The serine peptidase inhibitor N-ρ-tosyl-l-phenylalanine chloromethyl ketone (TPCK) affects the cell biology of Candida haemulonii species complex

Candida haemulonii species complex (C. haemulonii, C. haemulonii var. vulnera and Candida duobushaemulonii) is composed by emerging and multidrug-resistant (MDR) yeasts. Candidiasis, the disease caused by these species, is difficult to treat and culminates in clinical failures and patient death. It is well-known that Candida peptidases play important roles in the fungus–host interactions, and hence these enzymes are promising targets for developing new antifungal drugs. Recently, serine-type peptidases were described in clinical isolates of C. haemulonii complex with the ability to cleave relevant key host proteins. Herein, the effects of serine peptidase inhibitors (SPIs) on the cell biology of this fungal complex were evaluated. Initially, eight distinct SPIs (phenylmethylsulfonyl fluoride – PMSF, 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride – AEBSF, N-α-tosyl-l-lysine chloromethyl ketone hydrochloride – TLCK, N-p-tosyl-l-phenylalanine chloromethyl ketone – TPCK, simeprevir, boceprevir, danoprevir and telaprevir) were tested on the fungal growth. TPCK showed the best efficacy in controlling cell proliferation, being selected for the following experiments. This SPI induced changes in the architecture of yeast cells, as observed by scanning electron microscopy, besides injuries at the plasma membrane and reduction in the ergosterol content. TPCK also diminished the ability of yeasts to adhere to abiotic (polystyrene and glass) and biotic (murine macrophages) surfaces in a typically concentration-dependent manner. In addition, the 24 h-treatment of the mature biofilm promoted a decrease in biomass, viability and extracellular matrix. Altogether, our results highlight that SPIs may be promising new therapeutic agents in the treatment of candidiasis caused by emergent, opportunistic and MDR species forming the C. haemulonii complex.     

Intensity of official Futsal matches

The purpose of this study was to assess the intensity of official Futsal matches, expressed in different ways. Fourteen male professional Futsal players from a First Division Brazilian team volunteered to participate in this study. Maximal oxygen uptake (VO(2)max) and the heart hate (HR) and oxygen uptake (VO(2)) correlation were determined for each player. The match intensity was estimated from the players' average HR measured during 13 National Futsal League matches. The HR measurements were obtained while the players were in the court but the values recorded while the players were sitting on the bench were not considered. In addition, these HR values were used to estimate the intensity of the effort expressed as a percentage of the maximal HR (% HRmax), percentage of VO(2)max (% VO(2)max), kilocalories per minute (kcal·min(-1)), and total caloric expenditure. The mean intensity of the matches was 86.4 ± 3.8% HRmax, 79.2 ± 9.0% VO(2)max, 18.0 ± 2.2 kcal·min(-1), and 313 ± 9.3 kcal. It was concluded that official Futsal matches have high intensity when expressed in the different ways used in this study. The information provided by this research can be used for planning the athletes' workouts, diets, and resting periods.     

Whole-chromosome aneuploidy analysis in human oocytes: focus on comparative genomic hybridization

The study of aneuploidy in human oocytes, discarded from IVF cycles, has provided a better understanding of the incidence of aneuploidy of female origin and the responsible mechanisms. Comparative genomic hybridization (CGH) is an established technique that allows for the detection of aneuploidy in all chromosomes avoiding artifactual chromosome losses. In this review, results obtained using CGH in single cells (1PB and/or MII oocytes) are included. The results of oocyte aneuploidy rates obtained by CGH from discarded oocytes of IVF patients and of oocyte donors are summarized. Moreover, the mechanisms involved in the aneuploid events, e.g. whether alterations occurred due to first meiotic errors or germ-line mitotic errors are also discussed. Finally, the incidence of aneuploid oocyte production due to first meiotic errors and germ-line mitotic errors observed in oocytes coming from IVF patients and IVF oocyte donors was assessed.     

Mapping of disease-associated variants in admixed populations

Recent developments in high-throughput genotyping and whole-genome sequencing will enhance the identification of disease loci in admixed populations. We discuss how a more refined estimation of ancestry benefits both admixture mapping and association mapping, making disease loci identification in admixed populations more powerful.     

Occurrence, genes and expression of the W/Se-containing class II benzoyl-coenzyme A reductases in anaerobic bacteria

Benzoyl-coenzyme A (CoA) reductases (BCRs) are key enzymes in the anaerobic degradation of aromatic compounds and catalyse the reductive dearomatization of benzoyl-CoA to cyclohexa-1,5-dienoyl-1-carboxyl-CoA. Class I BCRs are ATP-dependent FeS enzymes, whereas class II BCRs are supposed to be ATP-independent and contain W, FeS clusters, and most probably selenocysteine. The active site components of a putative eight subunit class II BCR, BamBCDEFGHI, were recently characterized in Geobacter metallireducens. In this organism bamB was identified as structural gene for the W-containing active site subunit; bamF was predicted to code for a selenocysteine containing electron transfer subunit. In this work the occurrence and expression of BCRs in a number of anaerobic, aromatic compound degrading model microorganisms was investigated with a focus on the BamB and BamF components. Benzoate-induced class II BCR in vitro activities were determined in the soluble protein fraction in all obligately anaerobic bacteria tested. Where applicable, the results were in agreement with Western blot analysis using BamB targeting antibodies. By establishing a specific bamB targeting PCR assay, bamB homologues were identified in all tested obligately anaerobic bacteria with the capacity to degrade aromatic compounds; a number of bamB sequences from Gram-negative/positive sulfate-reducing bacteria were newly sequenced. In several organisms at least two bamB paralogues per genome were identified; however, in nearly all cases only one of them was transcribed during growth on an aromatic substrate. These benzoate-induced bamB genes are proposed to code for the active site subunit of class II BCRs; the major part of them group into a phylogenetic subcluster within the bamB homologues. Results from in silico analysis suggested that all class II BCRs contain selenocysteine in the BamF, and in many cases also in the BamE subunit. The results obtained indicate that the distribution of the two classes of BCRs in anaerobic bacteria appears to be strictly ruled by the available free energy from the oxidation of the aromatic carbon source rather than by phylogenetic relationships.     

Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

Background

Is Impulse Oscillometry System (IOS) a valuable tool to measure respiratory system function in Children?Asthma (A) is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation.IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI) and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC) and augmented RIC (aRIC) models have emerged, which offer advantages over earlier models.

Methods

IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B) and post- bronchodilation (post-B) conditions over a period of 2 years.

Results and Discussion

Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress?Children were classified into two main categories: Healthy (H) and Small Airway-Impaired (SAI). The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children.The two model parameters: peripheral compliance (Cp) and peripheral resistance (Rp) tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle") showed good correlations.

Conclusions

What are the most useful IOS and model parameters?In this work we demonstrate that IOS parameters such as resistance at 5 Hz (R5), frequency-dependence of resistance (fdR: R5-R20), reactance area (AX), and parameter estimates of respiratory system such as Cp and Rp provide sensitive indicators of lung function and have the capacity to differentiate between obstructed and non-obstructed airway conditions. They are also capable of demonstrating airway growth-related changes over a two-year period.We conclude that the IOS parameters AX and the eRIC model derived parameter Cp are the most reliable parameters to track lung function in children before and after bronchodilator and over a time period (2 years).Which model is more suitable for interpreting IOS data?IOS data are equally well-modelled by eRIC and aRIC models, based on the close correlations of their corresponding parameters - excluding upper airway shunt compliance. The eRIC model is a more parsimonious and equally powerful model in capturing the differences in IOS indices between SAI and H children. Therefore, it may be considered a clinically-preferred model of lung function.

     

The Protein Information and Property Explorer 2: gaggle-like exploration of biological proteomic data within one webpage

The Protein Information and Property Explorer 2 (PIPE2) is an enhanced software program and updated web application that aims at providing the proteomic researcher a simple, intuitive user interface through which to begin inquiry into the biological significance of a list of proteins typically produced by MS/MS proteomic processing software. PIPE2 includes an improved interface, new data visualization options, and new data analysis methods for combining disparate, but related, data sets. In particular, PIPE2 has been enhanced to handle multi-dimensional data such as protein abundance, gene expression, and/or interaction data. The current architecture of PIPE2, modeled after that of Gaggle (a programming infrastructure for interoperability between separately developed software tools), contains independent functional units that can be instantiated and pieced together at the user's discretion to form a pipelined analysis workflow. Among these functional units is the Network Viewer component, which adds rich network analysis capabilities to the suite of existing proteomic web resources. Additionally, PIPE2 implements a framework within which new analysis procedures can be easily deployed and distributed over the World Wide Web. PIPE2 is available as a web service at http://pipe2.systemsbiology.net/.     

Nuclear insertions of mitochondrial origin: Database updating and usefulness in cancer studies

Nuclear insertions of mitochondrial origin (NUMTs) can be useful tools in evolution and population studies. However, due to their similarity to mitochondrial DNA (mtDNA), NUMTs may also be a source of contamination in mtDNA studies. The main goal of this work is to present a database of NUMTs, based on the latest version of the human genome—GRCh37 draft. A total of 755 insertions were identified. There are 33 paralogous sequences with over 80% sequence similarity and of a greater length than 500 bp. The non-identical positions between paralogous sequences are listed for the first time. As an application example, the described database is used to evaluate the impact of NUMT contamination in cancer studies. The evaluation reveals that 220 positions from 256 with zero hits in the current mtDNA phylogeny could in fact be traced to one or more nuclear insertions of mtDNA. This is due to they are located in non-identical positions between mtDNA and nuclear DNA (nDNA). After in silico primer validation of each revised cancer study, risk of co-amplification between mtDNA and nDNA was detected in some cases, whereas in others no risk of amplification was identified. This approach to cancer studies clearly proves the potential of our NUMT database as a valuable new tool to validate mtDNA mutations described in different contexts. Moreover, due to the amount of information provided for each nuclear insertion, this database should play an important role in designing evolutionary, phylogenetic and epidemiological studies.