Directed polymer in a random medium of dimension 1+1 and 1+3: weights statistics in the low-temperature phase

We consider the low-temperature $T<T_c$ disorder-dominated phase of the directed polymer in a random potentiel in dimension 1+1 (where $T_c=\infty$) and 1+3 (where $T_c<\infty$). To characterize the localization properties of the polymer of length $L$, we analyse the statistics of the weights $w_L(\vec r)$ of the last monomer as follows. We numerically compute the probability distributions $P_1(w)$ of the maximal weight $w_L^{max}= max_{\vec r} [w_L(\vec r)]$, the probability distribution $\Pi(Y_2)$ of the parameter $Y_2(L)= \sum_{\vec r} w_L^2(\vec r)$ as well as the average values of the higher order moments $Y_k(L)= \sum_{\vec r} w_L^k(\vec r)$. We find that there exists a temperature $T_{gap}<T_c$ such that (i) for $T<T_{gap}$, the distributions $P_1(w)$ and $\Pi(Y_2)$ present the characteristic Derrida-Flyvbjerg singularities at $w=1/n$ and $Y_2=1/n$ for $n=1,2..$. In particular, there exists a temperature-dependent exponent $\mu(T)$ that governs the main singularities $P_1(w) \sim (1-w)^{\mu(T)-1}$ and $\Pi(Y_2) \sim (1-Y_2)^{\mu(T)-1}$ as well as the power-law decay of the moments $\bar{Y_k(i)} \sim 1/k^{\mu(T)}$. The exponent $\mu(T)$ grows from the value $\mu(T=0)=0$ up to $\mu(T_{gap}) \sim 2$. (ii) for $T_{gap}<T<T_c$, the distribution $P_1(w)$ vanishes at some value $w_0(T)<1$, and accordingly the moments $\bar{Y_k(i)}$ decay exponentially as $(w_0(T))^k$ in $k$. The histograms of spatial correlations also display Derrida-Flyvbjerg singularities for $T<T_{gap}$. Both below and above $T_{gap}$, the study of typical and averaged correlations is in full agreement with the droplet scaling theory.Comment: 13 pages, 29 figure

Mutation in CEP63 co-segregating with developmental dyslexia in a Swedish family

Developmental dyslexia is the most common learning disorder in children. Problems in reading and writing are likely due to a complex interaction of genetic and environmental factors, resulting in reduced power of studies of the genetic factors underlying developmental dyslexia. Our approach in the current study was to perform exome sequencing of affected and unaffected individuals within an extended pedigree with a familial form of developmental dyslexia. We identified a two-base mutation, causing a p.R229L amino acid substitution in the centrosomal protein 63 kDa (CEP63), co-segregating with developmental dyslexia in this pedigree. This mutation is novel, and predicted to be highly damaging for the function of the protein. 3D modelling suggested a distinct conformational change caused by the mutation. CEP63 is localised to the centrosome in eukaryotic cells and is required for maintaining normal centriole duplication and control of cell cycle progression. We found that a common polymorphism in the CEP63 gene had a significant association with brain white matter volume. The brain regions were partly overlapping with the previously reported region influenced by polymorphisms in the dyslexia susceptibility genes DYX1C1 and KIAA0319. We hypothesise that CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated.Peer reviewe

Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development

Peer reviewe

Pathways and Management of Phosphorus in urban areas

Due to the finite nature of mineral phosphorus reserves, effective management of anthropogenic phosphorus flows is currently under investigation by the international research community. This article emphasizes the importance of urban phosphorus flows, which are often marginalized due to the greater magnitude of agricultural phosphorus flows. A study on phosphorus flows in Gothenburg, Sweden, points out the potential role of solid waste in nutrient management, as the amounts of phosphorus in solid waste and in wastewater were found to be equal. Importation of food commodities accounts for 50% of the total inflow of phosphorus, and food waste is a major contributor of phosphorus to solid waste. The results suggest that solid waste incineration residues represent a large underestimated sink of phosphorus. Focusing on wastewater as the sole source of recovered phosphorus is not sufficient. The Swedish national goal on phosphorus recycling, which is limited to sewage sludge, targets only a part of the total phosphorus flow that can potentially be recovered. In contrast to previous studies, agricultural flows in Gothenburg were marginal compared to flows related to the urban waste management infrastructure. We emphasize the need for debate on preferable routes for disposal of waste with a high phosphorus content. Both recovery potential and usefulness of the recovered product for agricultural purposes have to be considered. Impacts of five waste management strategies on phosphorus flows were evaluated: incineration of all the waste, comprehensive food waste separation, installation of kitchen grinders, urine diversion, and separation of blackwater and food waste

Identification of NCAN as a candidate gene for developmental dyslexia

A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G >A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.Peer reviewe

Case report: a novel deep intronic splice-altering variant in DMD as a cause of Becker muscular dystrophy

We present the case of a male patient who was ultimately diagnosed with Becker muscular dystrophy (BMD; MIM# 300376) after the onset of muscle weakness in his teens progressively led to significant walking difficulties in his twenties. A genetic diagnosis was pursued but initial investigation revealed no aberrations in the dystrophin gene (DMD), although immunohistochemistry and Western blot analysis suggested the diagnosis of dystrophinopathy. Eventually, after more than 10 years, an RNA analysis captured abnormal splicing where 154 nucleotides from intron 43 were inserted between exon 43 and 44 resulting in a frameshift and a premature stop codon. Normal splicing of the DMD gene was also observed. Additionally, a novel variant c.6291–13537A&gt;G in DMD was confirmed in the genomic DNA of the patient. The predicted function of the variant aligns with the mRNA results. To conclude, we here demonstrate that mRNA analysis can guide the diagnosis of non-coding genetic variants in DMD

Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health

<p>Abstract</p> <p>Background</p> <p>An understanding of the relation of commensal microbiota to health is essential in preventing disease. Here we studied the oral microbial composition of children (N = 74, aged 3 - 18 years) in natural transition from their deciduous to a permanent dentition and related the microbial profiles to their oral health status. The microbial composition of saliva was assessed by barcoded pyrosequencing of the V5-V6 hypervariable regions of the 16 S rRNA, as well as by using phylogenetic microarrays.</p> <p>Results</p> <p>Pyrosequencing reads (126174 reads, 1045 unique sequences) represented 8 phyla and 113 higher taxa in saliva samples. Four phyla - Firmicutes, Bacteriodetes, Proteobacteria and Actinobacteria - predominated in all groups. The deciduous dentition harboured a higher proportion of Proteobacteria (Gammaproteobacteria, Moraxellaceae) than Bacteroidetes, while in all other groups Bacteroidetes were at least as abundant as Proteobacteria. Bacteroidetes (mainly genus <it>Prevotella</it>), Veillonellaceae family, Spirochaetes and candidate division TM7 increased with increasing age, reflecting maturation of the microbiome driven by biological changes with age.</p> <p>Microarray analysis enabled further analysis of the individual salivary microbiota. Of 350 microarray probes, 156 gave a positive signal with, on average, 77 (range 48-93) probes per individual sample.</p> <p>A caries-free oral status significantly associated with the higher signal of the probes targeting <it>Porphyromonas catoniae </it>and <it>Neisseria flavescens</it>.</p> <p>Conclusions</p> <p>The potential role of <it>P. catoniae </it>and <it>N. flavescens </it>as oral health markers should be assessed in large-scale clinical studies. The combination of both, open-ended and targeted molecular approaches provides us with information that will increase our understanding of the interplay between the human host and its microbiome.</p

Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2

Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats