An RNA virus hijacks an incognito function of a DNA repair enzyme

A previously described mammalian cell activity, called VPg unlinkase, specifically cleaves a unique protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection. For over three decades, the identity of this cellular activity and its normal role in the uninfected cell had remained elusive. Here we report the purification and identification of VPg unlinkase as the DNA repair enzyme, 5'-tyrosyl-DNA phosphodiesterase-2 (TDP2). Our data show that VPg unlinkase activity in different mammalian cell lines correlates with their differential expression of TDP2. Furthermore, we show that recombinant TDP2 can cleave the protein-RNA linkage generated by different picornaviruses without impairing the integrity of viral RNA. Our results reveal a unique RNA repair-like function for TDP2 and suggest an unusual role in host-pathogen interactions for this cellular enzyme. On the basis of the identification of TDP2 as a potential antiviral target, our findings may lead to the development of universal therapeutics to treat the millions of individuals afflicted annually with diseases caused by picornaviruses, including myocarditis, aseptic meningitis, encephalitis, hepatitis, and the common cold.     

An update on ECARUCA,the European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations

The European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations (ECARUCA, www.ecaruca.net) is an online database initiated in 2003 that collects and provides detailed, curated clinical and molecular information on rare unbalanced chromosome aberrations. ECARUCA now contains over 4800 cases with a total of more than 6600 genetic aberrations and has over 3000 account holders worldwide. Recently, the ECARUCA web site was renewed, including the presentation of interesting case reports in collaboration with the European Journal of Medical Genetics. This article gives an overview of the current status and future plans of the online ECARUCA database.     

Complex craniosynostosis is associated with the 2p15p16.1 microdeletion syndrome

In a screening project of patients with (complex) craniosynostosis using genomic arrays, we identified two patients with craniosynostosis and microcephaly with a deletion in the 2p15p16.1 chromosomal region. This region has been associated with a new microdeletion syndrome, for which patients have various features in common, including microcephaly and intellectual disability. Deletions were identified using Affymetrix 250K SNP array and further characterized by fluorescence in situ hybridization (FISH) analysis and qPCR. The deletions in our two patients overlapped within the 2p15p16.1 microdeletion syndrome area and were 6.8 and 6.9 Mb in size, respectively. FISH and qPCR confirmed the presence of only one copy in this region. Finemapping of the breakpoints indicated precise borders in our patients and were further finemapped in two other previously reported patients. Clinical features of patients with deletions in the 2p15p16.1 region vary. Including data from our patients, now eight out of nine reported patients have microcephaly, one of the major features, and all had intellectual disability. The current reported two patients add different forms of craniosynostosis to the clinical spectrum of this recently recognized microdeletion syndrome. © 2013 Wiley Periodicals, Inc.     

Intraocular pressure variation during colorectal laparoscopic surgery: standard pneumoperitoneum leads to reversible elevation in intraocular pressure

Background

The potential effects of laparoscopic surgery on intra- and postoperative intraocular pressure (IOP) are not completely understood. Although prior studies have reported that pneumoperitoneum may increase IOP, it is not clear whether this increase is related to the effects of pneumoperitoneum or to the patient’s position, such as the Trendelenburg position. This study aimed to evaluate the potential fluctuations of IOP during colorectal laparoscopic surgery in two groups of patients: those with and those without Trendelenburg positioning.

Methods

For this prospective study 45- to 85-year-old patients undergoing laparoscopic colorectal surgery were enrolled after a thorough ophthalmologic assessment. The study protocol included measurement of IOP at eight different time points (before, during, and after surgery) using a contact tonometer in both eyes.

Results

The study enrolled 29 patients: 17 (58.6 %) with Trendelenburg position placement during surgery and 12 (41.4 %) without Trendelenburg positioning. The two groups did not differ in terms of gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, or operative time. In all the patients, pneumoperitoneum induction led to a mild rise in IOP, averaging 4.1 mmHg. The patients with Trendelenburg positioning showed a greater increase than the patients without it (5.05 vs 4.23 mmHg at 45 min; p = 0.179), but IOP evaluation 48 h after surgery showed no substantial differences between the two groups. Among the 29 patients, 17 (58.6 %) showed an increase in IOP of 5 mmHg or more during surgery. A greater percentage of the patients who underwent Trendelenburg positioning showed an IOP increase of 5 mmHg or more (76.5 vs 33.3 %; p = 0.020). At the multivariate analysis, no potential predictors of increased IOP during surgery was identified.

Conclusions

Standard pneumoperitoneum (≤14 mmHg) led to mild and reversible IOP increases. A trend was observed toward a greater IOP increase in patients with Trendelenburg positioning. Thus, the patient’s position during surgery may represent a stronger risk factor for IOP increase than pneumoperitoneum-related intraabdominal pressure.