A simple model for DNA denaturation

Following Poland and Scheraga, we consider a simplified model for the denaturation transition of DNA. The two strands are modeled as interacting polymer chains. The attractive interactions, which mimic the pairing between the four bases, are reduced to a single short range binding term. Furthermore, base-pair misalignments are forbidden, implying that this binding term exists only for corresponding (same curvilinear abscissae) monomers of the two chains. We take into account the excluded volume repulsion between monomers of the two chains, but neglect intra-chain repulsion. We find that the excluded volume term generates an effective repulsive interaction between the chains, which decays as $1/r^{d-2}$. Due to this long-range repulsion between the chains, the denaturation transition is first order in any dimension, in agreement with previous studies.Comment: 10 page

Emerging Strategies Targeting Catabolic Muscle Stress Relief

Skeletal muscle wasting represents a common trait in many conditions, including aging, cancer, heart failure, immobilization, and critical illness. Loss of muscle mass leads to impaired functional mobility and severely impedes the quality of life. At present, exercise training remains the only proven treatment for muscle atrophy, yet many patients are too ill, frail, bedridden, or neurologically impaired to perform physical exertion. The development of novel therapeutic strategies that can be applied to an in vivo context and attenuate secondary myopathies represents an unmet medical need. This review discusses recent progress in understanding the molecular pathways involved in regulating skeletal muscle wasting with a focus on pro-catabolic factors, in particular, the ubiquitin-proteasome system and its activating muscle-specific E3 ligase RING-finger protein 1 (MuRF1). Mechanistic progress has provided the opportunity to design experimental therapeutic concepts that may affect the ubiquitin-proteasome system and prevent subsequent muscle wasting, with novel advances made in regards to nutritional supplements, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) inhibitors, myostatin antibodies, β2 adrenergic agonists, and small-molecules interfering with MuRF1, which all emerge as a novel in vivo treatment strategies for muscle wasting

Ocular effects caused by viral infections and corresponding vaccines: An overview of varicella zoster virus, measles virus, influenza viruses, hepatitis B viruses, and SARS-CoV-2

Many viral infections can affect vision and the visual system. Vaccination to prevent diseases is commonplace today, acting by stimulating an immune response without developing the pathology. It involves the production of persisting antibodies against the pathogen and the activation of T cells. Certain diseases have already been eradicated by rigorous vaccination campaigns, while others are hoped to be eliminated soon. Vaccines currently available on the market are largely safe, even if they can rarely cause some adverse effects, such as ocular complications. Analyzing existing literature, we aimed to compare the pathological effects on the eye due to the most common viral infections [in particular varicella zoster virus (VZV), measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2] with the possible ocular adverse effects of their relative vaccines, in order to establish a risk-benefit relationship from an ophthalmological point of view

HIV-1 Nucleocapsid Protein Unfolds Stable RNA G-Quadruplexes in the Viral Genome and Is Inhibited by G-Quadruplex Ligands

The G-quadruplexes that form in the HIV-1 RNA genome hinder progression of reverse transcriptase in vitro, but not in infected cells. We investigated the possibility that the HIV-1 nucleocapsid protein NCp7, which remains associated with the viral RNA during reverse transcription, modulated HIV-1 RNA G-quadruplex stability. By electrophoresis, circular dichroism, mass spectrometry, and reverse transcriptase stop assays, we demonstrated that NCp7 binds and unfolds the HIV-1 RNA G-quadruplexes and promotes DNA/RNA duplex formation, allowing reverse transcription to proceed. The G-quadruplex ligand BRACO-19 was able to partially counteract this effect. These results indicate NCp7 as the first known viral protein able to unfold RNA G-quadruplexes, and they explain how the extra-stable HIV-1 RNA G-quadruplexes are processed; they also point out that the reverse transcription process is hindered by G-quadruplex ligands at both reverse transcriptase and NCp7 level. This information can lead to the development of more effective anti-HIV-1 drugs with a new mechanism of action

Changes in seabed morphology, mud temperature and free gas venting at the H ̊akon Mosby mud volcano, offshore northern Norway, over the time period 2003-2006

The HAyenkon Mosby mud volcano is a 1.5-km-diameter geological structure located on the Southwest Barents Sea slope at a water depth of 1,270 m. High-definition seabed mapping of the mud volcano has been carried out in 2003 and 2006. A comparative analysis of the bathymetry and backscatter maps produced from the two surveys shows subtle morphological changes over the entire crater of the mud volcano, interpreted to be the consequence of mud eruption events. Mud temperature measurements point to a persistently warm mud at shallow depth in the crater. This is explained by upward fluid advection, rather than conductive cooling of mud flows. The small-scale spatial variability in the temperature distribution may be related to mud outflows or changes in the fluid flow regime. Furthermore, the locations of free gas venting observed in 2006 were found to differ from those of 2003. Our observations of overall similar topographic profiles across the mud volcano in 2003 and 2006 suggest that eruption events would have been modest. Nevertheless, the data bring evidence of significant change in activity even over short time intervals of only 3 years. This may be a characteristic shared by other submarine mud volcanoes, notably those considered to be in a quiescent stage

Ground State Energy of the One-Component Charged Bose Gas

The model considered here is the `jellium' model in which there is a uniform, fixed background with charge density $-e\rho$ in a large volume $V$ and in which $N=\rho V$ particles of electric charge $+e$ and mass $m$ move --- the whole system being neutral. In 1961 Foldy used Bogolubov's 1947 method to investigate the ground state energy of this system for bosonic particles in the large $\rho$ limit. He found that the energy per particle is $-0.402 r_s^{-3/4} {me^4}/{\hbar^2}$ in this limit, where $r_s=(3/4\pi \rho)^{1/3}e^2m/\hbar^2$. Here we prove that this formula is correct, thereby validating, for the first time, at least one aspect of Bogolubov's pairing theory of the Bose gasComment: 38 pages latex. Typos corrected.Lemma 6.2 change

Mesenchymal stem cell-derived extracellular vesicles protect human corneal endothelial cells from endoplasmic reticulum stress-mediated apoptosis

Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy

gam genomic assemblies merger

Motivations. In the last 3 years more than 20 assemblers have been proposed to tackle the hard task of assembling. Recent evaluation efforts (Assemblathon 1 and GAGE) demonstrated that none of these tools clearly outperforms the others. However, results clearly show that some assemblers performs better than others on specific regions and statistics while poorly performing on other regions and evaluation measures. With this picture in mind we developed GAM (Genomic Assemblies Merger) whose primary goal is to merge two or more assemblies in order to obtain a more contiguous one. Moreover, as a by-product of the merging step, GAM is able to correct mis-assemblies. GAM does not need global alignment between contigs, making it unique among others Assembly Reconciliation tools. In this way a computationally expensive alignment is avoided, and paralog sequences (likely to create false connection among contigs) do not represent a problem. GAM procedure is based only on the information coming from reads used in the assembling phases, and it can be used even on assemblies obtained with different datasets. Methods. Let us concentrate on the the merging of two assemblies, dubbed M and S. As a preprocessing step, that is an almost mandatory analysis, reads (or a subset of them) used in the assembling phase are aligned against M and S using a SAM-compatible aligner (e.g., BWA, rNA). GAM takes as input M, S and the two SAM files produced in the preprocessing step. The main idea is to identify fragments belonging to M and S having high similarity. For this purpose, GAM identifies regions, named blocks, belonging to M and S that share an high enough amount of reads (i.e. regions sharing the same aligned reads). After all blocks are identified the Assembly Graph (AG) is built: each node corresponds to a block and a directed edge connects block A to block B if the first precedes the second in either M or S (see Fig.1). Once AG is available, the merging phase can start. As a first step GAM identifies genomic regions in which assemblies contradict each other (loops, bifurcations, etc.). These areas represent potential inconsistencies between the two sequences. We chose to be as much conservative as possible electing (for example) M to be the Master assembly: all its contigs are supposed to be correct and cannot be contradicted. S becomes the Slave and everywhere an inconsistency is found, M is preferred to S. After the identification and the resolution of problematic regions, GAM visits the simplified graph, merges contigs accordingly to blocks and edges in AG (each merging phase is performed using a Smith-Waterman algorithm variant) and finally outputs the new improved assembly. GAM is not only limited to contigs, it can also work with scaffolds, filling the N's inserted by an assembler and not by the other. Results. GAM has been tested on several real datasets, in particular on Olea's chloroplast (241X Illumina paired reads and 21X 454 paired reads), Populus trichocarpa (82X Illumina paired reads), boa constrictor (40X Illumina paired reads). Illumina reads have average length of 100 bp and insert size of 500 bp. All tests have been performed on a computer equipped with 8 cores and 32GB RAM. ABySS and CLC were selected as assemblers. Results are summarized in Fig. 1. Olea's chloroplast has been used as a proof of concept experiment. The presence of a reference sequence allowed GAM's output validation (using dnadiff). Two assemblies were obtained with CLC using Illumina and 454 data. GAM was used to merge them. Figure 1 shows how GAM assembly is not only more contiguous but also more correct: while Master (CLC-Illumina) and Slave (CLC-454) have 58 and 39 suspicious regions respectively, GAM has only 14 of those. On Populus trichocarpa and Boa constrictor, CLC assemblies were used as master due to their better contiguity. In both cases assemblies returned by GAM were more contiguous (see Fig. 1)

The peculiar landscape of repetitive sequences in the olive (Olea europaea L.) genome

Analyzing genome structure in different species allows to gain an insight into the evolution of plant genome size. Olive (Olea europaea L.) has a medium-sized haploid genome of 1.4 Gb, whose structure is largely uncharacterized, despite the growing importance of this tree as oil crop. Next-generation sequencing technologies and different computational procedures have been used to study the composition of the olive genome and its repetitive fraction. A total of 2.03 and 2.3 genome equivalents of Illumina and 454 reads from genomic DNA, respectively, were assembled following different procedures, which produced more than 200,000 differently redundant contigs, with mean length higher than 1,000 nt. Mapping Illumina reads onto the assembled sequences was used to estimate their redundancy. The genome data set was subdivided into highly and medium redundant and nonredundant contigs. By combining identification and mapping of repeated sequences, it was established that tandem repeats represent a very large portion of the olive genome (∼31% of the whole genome), consisting of six main families of different length, two of which were first discovered in these experiments. The other large redundant class in the olive genome is represented by transposable elements (especially long terminal repeat-retrotransposons). On the whole, the results of our analyses show the peculiar landscape of the olive genome, related to the massive amplification of tandem repeats, more than that reported for any other sequenced plant genome

The Peculiar Landscape of Repetitive Sequences in the Olive (Olea europaea L.) Genome

Analyzing genome structure in different species allows to gain an insight into the evolution of plant genome size. Olive (Olea europaea L.) has a medium-sized haploid genome of 1.4 Gb, whose structure is largely uncharacterized, despite the growing importance of this tree as oil crop. Next-generation sequencing technologies and different computational procedures have been used to study the composition of the olive genome and its repetitive fraction. A total of 2.03 and 2.3 genome equivalents of Illumina and 454 reads from genomic DNA, respectively, were assembled following different procedures, which produced more than 200,000 differently redundant contigs, with mean length higher than 1,000 nt. Mapping Illumina reads onto the assembled sequences was used to estimate their redundancy. The genome data set was subdivided into highly and medium redundant and nonredundant contigs. By combining identification and mapping of repeated sequences, it was established that tandem repeats represent a very large portion of the olive genome (∼31% of the whole genome), consisting of six main families of different length, two of which were first discovered in these experiments. The other large redundant class in the olive genome is represented by transposable elements (especially long terminal repeat-retrotransposons). On the whole, the results of our analyses show the peculiar landscape of the olive genome, related to the massive amplification of tandem repeats, more than that reported for any other sequenced plant genome