A New Chytridiomycete Fungus Intermixed with Crustacean Resting Eggs in a 407-Million-Year-Old Continental Freshwater Environment

Copyright: © 2016 Strullu-Derrien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Faster algorithms for 1-mappability of a sequence

In the k-mappability problem, we are given a string x of length n and integers m and k, and we are asked to count, for each length-m factor y of x, the number of other factors of length m of x that are at Hamming distance at most k from y. We focus here on the version of the problem where k = 1. The fastest known algorithm for k = 1 requires time O(mn log n/ log log n) and space O(n). We present two algorithms that require worst-case time O(mn) and O(n log^2 n), respectively, and space O(n), thus greatly improving the state of the art. Moreover, we present an algorithm that requires average-case time and space O(n) for integer alphabets if m = {\Omega}(log n/ log {\sigma}), where {\sigma} is the alphabet size

Photoionization and transient Wannier-Stark ladder in silicon: First-principles simulations versus Keldysh theory

Nonlinear photoionization of dielectrics and semiconductors is widely treated in the framework of the Keldysh theory whose validity is limited to photon energies that are small compared to the band gap and relatively low laser intensities. The time-dependent density functional theory (TDDFT) simulations, which are free of these limitations, enable one to gain insight into nonequilibrium dynamics of the electronic structure. Here we apply TDDFT to investigate the photoionization of silicon crystal by ultrashort laser pulses in a wide range of laser wavelengths and intensities and compare the results with predictions of the Keldysh theory. Photoionization rates derived from the simulations considerably exceed the data obtained with the Keldysh theory within the validity range of the latter. Possible reasons for the discrepancy are discussed and we provide fundamental data on the photoionization rates beyond the limits of the Keldysh theory. By investigating the features of the Stark shift as a function of photon energy and laser field strength, a manifestation of the transient Wannier-Stark ladder states is revealed, which become blurred with increasing laser field strength. Finally, it is shown that the TDDFT simulations can potentially provide reliable data on the electron damping time that is of high importance for large-scale modeling

The origins, evolution, and functional potential of alternative splicing in vertebrates.

Alternative splicing (AS) has the potential to greatly expand the functional repertoire of mammalian transcriptomes. However, few variant transcripts have been characterized functionally, making it difficult to assess the contribution of AS to the generation of phenotypic complexity and to study the evolution of splicing patterns. We have compared the AS of 309 protein-coding genes in the human ENCODE pilot regions against their mouse orthologs in unprecedented detail, utilizing traditional transcriptomic and RNAseq data. The conservation status of every transcript has been investigated, and each functionally categorized as coding (separated into coding sequence [CDS] or nonsense-mediated decay [NMD] linked) or noncoding. In total, 36.7% of human and 19.3% of mouse coding transcripts are species specific, and we observe a 3.6 times excess of human NMD transcripts compared with mouse; in contrast to previous studies, the majority of species-specific AS is unlinked to transposable elements. We observe one conserved CDS variant and one conserved NMD variant per 2.3 and 11.4 genes, respectively. Subsequently, we identify and characterize equivalent AS patterns for 22.9% of these CDS or NMD-linked events in nonmammalian vertebrate genomes, and our data indicate that functional NMD-linked AS is more widespread and ancient than previously thought. Furthermore, although we observe an association between conserved AS and elevated sequence conservation, as previously reported, we emphasize that 30% of conserved AS exons display sequence conservation below the average score for constitutive exons. In conclusion, we demonstrate the value of detailed comparative annotation in generating a comprehensive set of AS transcripts, increasing our understanding of AS evolution in vertebrates. Our data supports a model whereby the acquisition of functional AS has occurred throughout vertebrate evolution and is considered alongside amino acid change as a key mechanism in gene evolution

A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome

Although incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18–58)) and 20 HC (60% female, mean age 26.8 (range 23–41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based “permeability cluster” was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based “immune-enteroendocrine cluster” was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type

The dynamics of the non-heme iron in bacterial reaction centers from Rhodobacter sphaeroides

AbstractWe investigate the dynamical properties of the non-heme iron (NHFe) in His-tagged photosynthetic bacterial reaction centers (RCs) isolated from Rhodobacter (Rb.) sphaeroides. Mössbauer spectroscopy and nuclear inelastic scattering of synchrotron radiation (NIS) were applied to monitor the arrangement and flexibility of the NHFe binding site. In His-tagged RCs, NHFe was stabilized only in a high spin ferrous state. Its hyperfine parameters (IS=1.06±0.01mm/s and QS=2.12±0.01mm/s), and Debye temperature (θD0~167K) are comparable to those detected for the high spin state of NHFe in non-His-tagged RCs. For the first time, pure vibrational modes characteristic of NHFe in a high spin ferrous state are revealed. The vibrational density of states (DOS) shows some maxima between 22 and 33meV, 33 and 42meV, and 53 and 60meV and a very sharp one at 44.5meV. In addition, we observe a large contribution of vibrational modes at low energies. This iron atom is directly connected to the protein matrix via all its ligands, and it is therefore extremely sensitive to the collective motions of the RC protein core. A comparison of the DOS spectra of His-tagged and non-His-tagged RCs from Rb. sphaeroides shows that in the latter case the spectrum was overlapped by the vibrations of the heme iron of residual cytochrome c2, and a low spin state of NHFe in addition to its high spin one. This enabled us to pin-point vibrations characteristic for the low spin state of NHFe

Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo

Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins