Dynamics of Podospora anserina Genome Evolution in a Long-Term Experiment.

The Podospora anserina long-term evolution experiment (PaLTEE) is the only running filamentous fungus study, which is still going on. The aim of our work is to trace the evolutionary dynamics of the accumulation of mutations in the genomes of eight haploid populations of P. anserina. The results of the genome-wide analysis of all of the lineages, performed 8 years after the start of the PaLTEE, are presented. Data analysis detected 312 single nucleotide polymorphisms (SNPs) and 39 short insertion-deletion mutations (indels) in total. There was a clear trend towards a linear increase in the number of SNPs depending on the experiment duration. Among 312 SNPs, 153 were fixed in the coding regions of P. anserina genome. Relatively few synonymous mutations were found, exactly 38; 42 were classified as nonsense mutations; 72 were assigned to missense mutations. In addition, 21 out of 39 indels identified were also localized in coding regions. Here, we also report the detection of parallel evolution at the paralog level in the P. anserina model system. Parallelism in evolution at the level of protein functions also occurs. The latter is especially true for various transcription factors, which may indicate selection leading to optimization of the wide range of cellular processes under experimental conditions.

Complete minicircle genome of Leptomonas pyrrhocoris reveals sources of its non-canonical mitochondrial RNA editing events.

Uridine insertion/deletion (U-indel) editing of mitochondrial mRNA, unique to the protistan class Kinetoplastea, generates canonical as well as potentially non-productive editing events. While the molecular machinery and the role of the guide (g) RNAs that provide required information for U-indel editing are well understood, little is known about the forces underlying its apparently error-prone nature. Analysis of a gRNA:mRNA pair allows the dissection of editing events in a given position of a given mitochondrial transcript. A complete gRNA dataset, paired with a fully characterized mRNA population that includes non-canonically edited transcripts, would allow such an analysis to be performed globally across the mitochondrial transcriptome. To achieve this, we have assembled 67 minicircles of the insect parasite Leptomonas pyrrhocoris, with each minicircle typically encoding one gRNA located in one of two similar-sized units of different origin. From this relatively narrow set of annotated gRNAs, we have dissected all identified mitochondrial editing events in L. pyrrhocoris, the strains of which dramatically differ in the abundance of individual minicircle classes. Our results support a model in which a multitude of editing events are driven by a limited set of gRNAs, with individual gRNAs possessing an inherent ability to guide canonical and non-canonical editing.

Characterization of Mutational Tolerance of a Viral RNA-Protein Interaction.

Replication of RNA viruses is generally markedly error-prone. Nevertheless, these viruses usually retain their identity under more or less constant conditions due to different mechanisms of mutation tolerance. However, there exists only limited information on quantitative aspects of the mutational tolerance of distinct viral functions. To address this problem, we used here as a model the interaction between a replicative cis-acting RNA element (oriL) of poliovirus and its ligand (viral protein 3CD). The mutational tolerance of a conserved tripeptide of 3CD, directly involved in this interaction, was investigated. Randomization of the relevant codons and reverse genetics were used to define the space of viability-compatible sequences. Surprisingly, at least 11 different amino acid substitutions in this tripeptide were not lethal. Several altered viruses exhibited wild-type-like phenotypes, whereas debilitated (but viable) genomes could increase their fitness by the acquisition of reversions or compensatory mutations. Together with our study on the tolerance of oriL (Prostova et al., 2015), the results demonstrate that at least 42 out of 51 possible nucleotide replacements within the two relevant genomic regions are viability-compatible. These results provide new insights into structural aspects of an important viral function as well as into the general problems of viral mutational robustness and evolution.

Trypanosomatid mitochondrial RNA editing: dramatically complex transcript repertoires revealed with a dedicated mapping tool.

RNA editing by targeted insertion and deletion of uridine is crucial to generate translatable mRNAs from the cryptogenes of the mitochondrial genome of kinetoplastids. This type of editing consists of a stepwise cascade of reactions generally proceeding from 3' to 5' on a transcript, resulting in a population of partially edited as well as pre-edited and completely edited molecules for each mitochondrial cryptogene of these protozoans. Often, the number of uridines inserted and deleted exceed the number of nucleotides that are genome-encoded. Thus, analysis of kinetoplastid mitochondrial transcriptomes has proven frustratingly complex. Here we present our analysis of Leptomonas pyrrhocoris mitochondrial cDNA deep sequencing reads using T-Aligner, our new tool which allows comprehensive characterization of RNA editing, not relying on targeted transcript amplification and on prior knowledge of final edited products. T-Aligner implements a pipeline of read mapping, visualization of all editing states and their coverage, and assembly of canonical and alternative translatable mRNAs. We also assess T-Aligner functionality on a more challenging deep sequencing read input from Trypanosoma cruzi. The analysis reveals that transcripts of cryptogenes of both species undergo very complex editing that includes the formation of alternative open reading frames and whole categories of truncated editing products.

Improved exposure for carotid endarterectomy.

Carotid endarterectomy continues to be an operation that is widely employed and associated with excellent outcomes. Challenges to attain adequate field visualization do occur. A new retracting device is described that vastly improves operative field visualization, particularly in the upper area where high lesions and limited cervical mobility can restrict or hamper technical maneuvers. Complex maneuvers such as mandibular subluxation or osteotomy may be obviated.

Treatment of portal venous gas embolism with hyperbaric oxygen after accidental ingestion of hydrogen peroxide: a case report and review of the literature.

BACKGROUND: It is well known that hydrogen peroxide ingestion can cause gas embolism. OBJECTIVE: To report a case illustrating that the definitive, most effective treatment for gas embolism is hyperbaric oxygen therapy. CASE REPORT: We present a case of a woman who presented to the Emergency Department with acute abdominal pain after an accidental ingestion of concentrated hydrogen peroxide. Complete recovery from her symptoms occurred quickly with hyperbaric oxygen therapy. CONCLUSION: This is a case report of the successful use of hyperbaric oxygen therapy to treat portal venous gas embolism caused by hydrogen peroxide ingestion. Hyperbaric oxygen therapy can be considered for the treatment of symptomatic hydrogen peroxide ingestion.

Malignant mucosal melanoma of the paranasal sinuses: Two case presentations.

Primary mucosal melanoma of the paranasal sinuses is a rare tumor of the head and neck which can be a devastating disease. Cancers arising in the sinonasal cavity are extremely rare, with a poor survival rate. There is inherent difficulty in diagnosing these lesions due to their complex anatomic locations and symptoms which are often confused with more common benign processes. The primary treatment of this rare disease process is resection, except in advanced stages where surgical resection is not an option. Diagnostic accuracy in consideration of size, location, and presence of metastatic disease of these malignant tumors tailors individual patients to different management in order to achieve the longest possible survival.

Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Aripiprazole is a newer atypical antipsychotic agent used for effective treatment of schizophrenia. It significantly reduces unwanted side effects of older typical antipsychotics by targeting, with high affinity, dopamine D2/D3 and serotonin 5-HT1A/5-HT-2A receptors. Its documented mechanism of action makes it an unlikely agent to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the first reported case of SIADH caused by aripiprazole in a patient with history of schizophrenia without other precipitating factors to explain hyponatremia or SIADH.