Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Antimicrobial resistance profile and presence of class I integrongs among Salmonella enterica serovars isolated from human clinical specimens in Tehran, Iran

International audienceBACKGROUND AND OBJECTIVES: Salmonella is one of the leading causes of food-borne diseases. Increasing occurrence of antimicrobial resistance, especially multidrug-resistance, in Salmonella serovars is a major public health problem worldwide. This study was carried out to detect class I integrons and antibiotic resistance profiles in clinical isolates of Salmonella serovars collected from seven hospitals in Tehran during November 2009 to June 2010. MATERIALS AND METHODS: Antibiotic susceptibility profile of 19 antibiotics against 58 Salmonella isolates commonly used in humans was determined using disk diffusion assay. Minimum inhibitory concentration against ceftriaxone and ciprofloxacin was studied. PCR assays were used to detect class I integrons. RESULTS: Among 58 Salmonella isolates, 72.4% were Salmonella enterica serovar Enteritidis, 8.7% were Salmonella enterica serovar Typhimurium and 18.9% were other serovars. Of the total 58 Salmonella serovars, 43 (74.1%) were multidrug-resistant and showed resistance to three or more antibiotic families. Class I integrons were identified in 38 (88.3%) MDR Salmonella isolates. Ciprofloxacin minimum inhibitory concentration ranged between 0.125-2 g/ml for four isolates and other four isolates exhibited resistance to ceftriaxone (MIC 64-256 g /ml). CONCLUSION: The high prevalence of class I integrons was seen in our MDR Salmonella isolates and class I integrons might play an important role in the dissemination of antimicrobial resistance determinants

The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides

BACKGROUND: RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which they derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants.  RESULTS: Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which can be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway.  CONCLUSION: This work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous genes in M. circinelloides during exponential and stationary growth phases and opens up an important avenue for in-depth study of genes involved in the regulation of physiological and developmental processes in this fungal model

"Acute pseudo-pericardial tamponade": the compression of the thoracal inferior vena cava – a case report

We describe a case of 68-year-old woman which was admitted to our hospital for mitral valve replacement (MVR), in whom acute compresion of the vena cava inferior developed after repair of lacerated atrio-caval junction with hemostatic tissue sealant, biologic glue (BioGlue, Cryolife, ınc, Kennesaw, Ga). Removal of the BioGlue relieved the unexpected problem

Developments in the Photonic Theory of Fluorescence

Conventional fluorescence commonly arises when excited molecules relax to their ground electronic state, and most of the surplus energy dissipates in the form of photon emission. The consolidation and full development of theory based on this concept has paved the way for the discovery of several mechanistic variants that can come into play with the involvement of laser input – most notably the phenomenon of multiphoton-induced fluorescence. However, other effects can become apparent when off-resonant laser input is applied during the lifetime of the initial excited state. Examples include a recently identified scheme for laser-controlled fluorescence. Other systems of interest are those in which fluorescence is emitted from a set of two or more coupled nanoemitters. This chapter develops a quantum theoretical outlook to identify and describe these processes, leading to a discussion of potential applications ranging from all-optical switching to the generation of optical vortices

Issues in the management of simple and complex meconium ileus

Various surgical methods are used to treat meconium ileus (MI), including resection with enterostomy (RES), primary anastomosis (RPA), and purse-string enterotomy with intra-operative lavage (PSI). The aim of this study is to discuss the surgical treatment of MI, based on our experience. Of the 41 MI patients treated at our institution between 1984 and 2007, 18 had simple MI and 23 had complex MI. These groups were analyzed according to treatment modality, concentrating on length of hospital stay, complications [peritonitis, septicemia, adhesive small bowel obstruction (ASBO), and malabsorption/diarrhea], need for additional surgical procedures, mortality. Of the 18 patients with simple MI, 7 (39%) were successfully treated with diluted Gastrografin® enema. The remaining 11 patients were treated surgically: two underwent RPA, of whom one died; five had RES, of whom one developed ASBO; four underwent PSI, of whom two developed peritonitis. In the complex MI group, 14 patients underwent RPA, with peritonitis occurring in three (one died); nine underwent RES, of whom two developed ASBO. In patients with simple MI, conservative treatment with diluted Gastrografin® enema is an effective initial treatment in our hands. In case of failure, RES is advisable. Patients with complex MI are candidates for RES. RPA and PSI seem to have higher complication rate

Nanotechnology and global energy demand: challenges and prospects for a paradigm shift in the oil and gas industry.

The exploitation of new hydrocarbon discoveries in meeting the present global energy demand is a function of the availability and application of new technologies. The relevance of new technologies is borne out of the complex subsurface architecture and conditions of offshore petroleum plays. Conventional techniques, from drilling to production, for exploiting these discoveries may require adaption for such subsurface conditions as they fail under conditions of high pressure and high temperature. The oil and gas industry over the past decades has witnessed increased research into the use of nanotechnology with great promise for drilling operations, enhanced oil recovery, reservoir characterization, production, etc. The prospect for a paradigm shift towards the application of nanotechnology in the oil and gas industry is constrained by evolving challenges with its progression. This paper gave a review of developments from nano-research in the oil and gas industry, challenges and recommendations

Gene Properties and Chromatin State Influence the Accumulation of Transposable Elements in Genes

Transposable elements (TEs) are mobile DNA sequences found in the genomes of almost all species. By measuring the normalized coverage of TE sequences within genes, we identified sets of genes with conserved extremes of high/low TE density in the genomes of human, mouse and cow and denoted them as ‘shared upper/lower outliers (SUOs/SLOs)’. By comparing these outlier genes to the genomic background, we show that a large proportion of SUOs are involved in metabolic pathways and tend to be mammal-specific, whereas many SLOs are related to developmental processes and have more ancient origins. Furthermore, the proportions of different types of TEs within human and mouse orthologous SUOs showed high similarity, even though most detectable TEs in these two genomes inserted after their divergence. Interestingly, our computational analysis of polymerase-II (Pol-II) occupancy at gene promoters in different mouse tissues showed that 60% of tissue-specific SUOs show strong Pol-II binding only in embryonic stem cells (ESCs), a proportion significantly higher than the genomic background (37%). In addition, our analysis of histone marks such as H3K4me3 and H3K27me3 in mouse ESCs also suggest a strong association between TE-rich genes and open-chromatin at promoters. Finally, two independent whole-transcriptome datasets show a positive association between TE density and gene expression level in ESCs. While this study focuses on genes with extreme TE densities, the above results clearly show that the probability of TE accumulation/fixation in mammalian genes is not random and is likely associated with different factors/gene properties and, most importantly, an association between the TE insertion/fixation rate and gene activity status in ES cells

Retrotransposon-Induced Heterochromatin Spreading in the Mouse Revealed by Insertional Polymorphisms

The “arms race” relationship between transposable elements (TEs) and their host has promoted a series of epigenetic silencing mechanisms directed against TEs. Retrotransposons, a class of TEs, are often located in repressed regions and are thought to induce heterochromatin formation and spreading. However, direct evidence for TE–induced local heterochromatin in mammals is surprisingly scarce. To examine this phenomenon, we chose two mouse embryonic stem (ES) cell lines that possess insertionally polymorphic retrotransposons (IAP, ETn/MusD, and LINE elements) at specific loci in one cell line but not the other. Employing ChIP-seq data for these cell lines, we show that IAP elements robustly induce H3K9me3 and H4K20me3 marks in flanking genomic DNA. In contrast, such heterochromatin is not induced by LINE copies and only by a minority of polymorphic ETn/MusD copies. DNA methylation is independent of the presence of IAP copies, since it is present in flanking regions of both full and empty sites. Finally, such spreading into genes appears to be rare, since the transcriptional start sites of very few genes are less than one Kb from an IAP. However, the B3galtl gene is subject to transcriptional silencing via IAP-induced heterochromatin. Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness