Volatile Organic Compounds in Uremia

Background

Although “uremic fetor” has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia.

Methods

Breath analysis was performed in 28 adults with an eGFR ≥60 ml/min per 1.73 m², 26 adults with chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m², and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry.

Results

Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10–59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis.

Conclusion

Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules.     

Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.     

Neonate human remains: a window of opportunity to the molecular study of ancient syphilis

Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of "La Ermita de la Soledad" (XVI-XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals.     

Number concepts without number lines in an indigenous group of Papua New Guinea

Background

The generic concept of number line, which maps numbers to unidimensional space, is a fundamental concept in mathematics, but its cognitive origins are uncertain. Two defining criteria of the number line are that (i) there is a mapping of each individual number (or numerosity) under consideration onto a specific location on the line, and (ii) that the mapping defines a unidimensional space representing numbers with a metric — a distance function. It has been proposed that the number line is based on a spontaneous universal human intuition, rooted directly in brain evolution, that maps number magnitude to linear space with a metric. To date, no culture lacking this intuition has been documented.

Methodology/Principal Findings

By means of a number line task, we investigated the universality proposal with the Yupno of Papua New Guinea. Unschooled adults did exhibit a number-to-space mapping (criterion i) but, strikingly, despite having precise cardinal number concepts, they located numbers only on the endpoints, thus failing to use the extent of the line. The produced mapping was bi-categorical and metric-free, in violation of criterion ii. In contrast, Yupnos with scholastic experience used the extent of the segment according to known standards, but they did so not as evenly as western controls, exhibiting a bias towards the endpoints.

Conclusions/Significance

Results suggest that cardinal number concepts can exist independently from number line representations. They also suggest that the number line mapping, although ubiquitous in the modern world, is not universally spontaneous, but rather seems to be learned through — and continually reinforced by — specific cultural practices.     

The Density of Knobs on Plasmodium falciparum-Infected Erythrocytes Depends on Developmental Age and Varies among Isolates

Background

The virulence of Plasmodium falciparum malaria is related to the parasite’s ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on dome-shaped protrusions called knobs on the IE surface is central to both. Differences in receptor specificity and affinity of expressed PfEMP1 are important for IE adhesiveness, but it is not known whether differences in the number and size of the knobs on which the PfEMP1 proteins are expressed also play a role. Therefore, the aim of this study was to provide detailed information on isolate- and time-dependent differences in knob size and density.

Methodology/Principal Findings

We used atomic force microscopy to characterize knobs on the surface of P. falciparum-infected erythrocytes. Fourteen ex vivo isolates from Ghanaian children with malaria and 10 P. falciparum isolates selected in vitro for expression of a particular PfEMP1 protein (VAR2CSA) were examined. Knob density increased from ∼20 h to ∼35 h post-invasion, with significant variation among isolates. The knob density ex vivo, which was about five-fold higher than following long-term in vitro culture, started to decline within a few months of culture. Although knob diameter and height varied among isolates, we did not observe significant time-dependent variation in these dimensions.

Conclusions/Significance

The density of knobs on the P. falciparum-IE surface depends on time since invasion, but is also determined by the infecting isolate in a time-independent manner. This is the first study to quantitatively evaluate knob densities and dimensions on different P. falciparum isolates, to examine ex vivo isolates from humans, and to compare ex vivo and long-term in vitro-cultured isolates. Our findings contribute to the understanding of the interaction between P. falciparum parasites and the infected host.     

Amphidoma languida sp. nov. (Dinophyceae) reveals a close relationship between Amphidoma and Azadinium

Toxic algae such as Alexandrium and Azadinium have an important ecological impact and have originated several times independently within the dinophytes. Their closest relatives, however, are mostly unknown at present. A new dinophyte species, Amphidoma languida sp. nov., was isolated from Bantry Bay (Ireland) during a period of elevated azaspiracid toxicity in mussels. The new species was described in detail, and its phylogenetic position was analysed, by using a combination of light and electron microscopy, chemical detection methods, and sequence comparison of concatenated ribosomal RNA sequence data. Morphological similarities, such as cingular and hypothecal plates, the number and arrangement of sulcal plates, and the characteristic apical pore complex with a small X-plate centrally invading the first apical plate, indicated a close relationship between Amphidoma and Azadinium. However, no known azaspiracid analogues were detected in A. languida by liquid chromatography coupled with tandem mass-spectrometry. In a molecular phylogeny, the Amphidomataceae including Amphidoma and Azadinium were an independent lineage among other monophyletic major groups of the dinophytes such as the Suessiales, Prorocentrales, Gonyaulacales, and Peridiniales. Thus, the taxonomic affiliation of Azadinium is clarified, and our data may prove helpful in the development of specific and reliable molecular detection methods of toxic Azadinium.     

New records of rhodolith-forming species (Corallinales, Rhodophyta) from deep water in Espírito Santo State, Brazil

Little is known about the diversity of non-geniculate coralline red algae (Rhodophyta, Corallinophycidae) from deep waters in Brazil. Most surveys undertaken in this country have been carried out in shallow waters. In 1994, however, the REVIZEE program surveyed the sustainable living resources potential of the Brazilian exclusive economic zone to depths of 500?m. In the present study, the rhodolith-forming coralline algae from the continental shelf of Espírito Santo State were identified. Samples were taken from 54 to 60?m depth by dredging during ship cruises in 1997. Three rhodolith-forming species were found: Spongites yendoi (Foslie) Chamberlain, Lithothamnion muelleri Lenormand ex Rosanoff and Lithothamnion glaciale Kjellman. These records extend the distribution ranges of these species into Brazilian waters and extend the depth distribution of non-geniculate coralline red algae into Brazilian water to 58?m.