Rev3, the catalytic subunit of Polζ, is required for maintaining fragile site stability in human cells

It has been long speculated that mammalian Rev3 plays an important, yet unknown role(s) during mammalian development, as deletion of Rev3 causes embryonic lethality in mice, whereas no other translesion DNA synthesis polymerases studied to date are required for mouse embryo development. Here, we report that both subunits of Polζ (Rev3 and Rev7) show an unexpected increase in expression during G₂/M phase, but they localize independently in mitotic cells. Experimental depletion of Rev3 results in a significant increase in anaphase bridges, chromosomal breaks/gaps and common fragile site (CFS) expression, whereas Rev7 depletion primarily causes lagging chromosome defect with no sign of CFS expression. The genomic instability induced by Rev3 depletion seems to be related to replication stress, as it is further enhanced on aphidicolin treatment and results in increased metaphase-specific Fanconi anemia complementation group D type 2 (FANCD2) foci formation, as well as FANCD2-positive anaphase bridges. Indeed, a long-term depletion of Rev3 in cultured human cells results in massive genomic instability and severe cell cycle arrest. The aforementioned observations collectively support a notion that Rev3 is required for the efficient replication of CFSs during G₂/M phase, and that the resulting fragile site instability in Rev3 knockout mice may trigger cell death during embryonic development.     

A Systematic Review of MicroRNA in Glioblastoma Multiforme: Micro-modulators in the Mesenchymal Mode of Migration and Invasion

Glioblastoma multiforme (GBM) is an incurable form of brain cancer with a very poor prognosis. Because of its highly invasive nature, it is impossible to remove all tumor cells during surgical resection, making relapse inevitable. Further research into the regulatory mechanism underpinning GBM pathogenesis is therefore warranted, and over the past decade, there has been an increased focus on the functional role of microRNA (miRNA). This systematic review aims to present a comprehensive overview of all the available literature on the expression profiles and function of miRNA in GBM. Here, we have reviewed 163 papers and identified 253 upregulated, 95 downregulated, and 17 disputed miRNAs with respect to expression levels; 85 % of these miRNAs have not yet been functionally characterized. A focus in this study has been 26 interesting miRNAs involved in the mesenchymal mode of migration and invasion, demonstrating the importance of miRNAs in the context of the cellular niche. Both oncogenic and tumor-suppressive miRNAs were found to affect target genes involved in cell migration, cytoskeletal rearrangement, invasiveness, and angiogenesis. Clearly, the distinct functional properties of these miRNAs need further investigation and might hold a great potential in future molecular therapies targeting GBM.     

Pressure pain sensitivity and hardness along human normal and sensitized muscle

The spatial distribution of pressure sensitivity and muscle hardness was examined on normal muscle tissue and muscle tissue after induction of delayed onset muscle soreness (DOMS). The pressure sensitivity and muscle hardness were assessed at nine sites on the tibialis muscle from the proximal to distal tendon on two separate days. In total 37 healthy volunteers participated in three experiments. In the first experiment pressure pain threshold (PPT) and pressure pain tolerance (PPTO) were assessed. Decreased PPT and PPTO were found on day 2, 7 days after day 1. Proximal and distal stimulation sites were harder compared to muscle belly sites. In a second experiment two different probe sizes were used. Variation in PPT between the nine sites was found for the large probe with muscle belly being less sensitive to pressure stimulation compared to proximal and distal sites. The most proximal stimulation site was harder compared to muscle belly sites. In a third experiment PPT and muscle hardness were assessed before and 48?h after eccentric exercise. PPT at two muscle belly sites was significantly decreased during DOMS. No specific sites were harder during DOMS, the average muscle hardness across sites was however significantly increased. Decreased PPT and increased muscle hardness did not correlate. In conclusion, within subjects the pressure sensitivity varies along the musculoskeletal unit. In DOMS, specific muscle belly sites were more sensitive to pressure stimulation. Muscle–tendon sites were harder compared to muscle belly sites.     

The Fire Refuge Value of Patches of a Fire‐Sensitive Tree in Fire‐prone Savannas: Callitris intratropica in Northern Australia

Patches of fire‐sensitive vegetation often occur within fire‐prone tropical savannas, and are indicative of localized areas where fire regimes are less severe. These may act as important fire refugia for fire‐sensitive biota. The fire‐sensitive tree Callitris intratropica occurs in small patches throughout the fire‐prone northern Australian savannas, and is widely seen as an indicator of low‐severity fire regimes and of good ecosystem health. Here, we address the question: to what extent do Callitris patches act as refuges for other fire‐sensitive biota, and therefore play a broader conservation role? We contrast floral and faunal species composition between Callitris patches and surrounding eucalypt savanna, using three case studies. In the first case study, a floristic analysis of 47 Callitris patches across Western Australia's Kimberley region showed that woody species in these patches were overwhelmingly widespread, fire‐tolerant savanna taxa. No species of special conservation concern occurred disproportionately within Callitris patches. Similarly, there was no concentration of fire‐sensitive fauna or flora in five Callitris patches in the East Kimberley. Finally, there was no difference in ant species composition among 12 Callitris patches and surrounding eucalypt savannas in Kakadu National Park, Northern Territory, and there were no fire‐sensitive ant species in Callitris patches. Our three case studies from throughout the northwestern Australia provide no evidence that Callitris patches act as important refuges for fire‐sensitive flora or fauna within fire‐prone eucalypt savannas. This calls into question the notion that Callitris is a strong indicator of general ecosystem health.     

Alexander Böhm (1971–2012)

On November 28, 2012 Alexander (Alex) Böhm, a bacterial geneticist, died at age 41, only a few months after taking up a position as an assistant professor at the LOEWE Center for Synthetic Microbiology in Marburg, Germany. Earlier in 2012 Alex had been diagnosed with an aggressive form of thyroid cancer that left him little time to live his scientific and personal dreams.     

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 August 2012 – 30 September 2012

This article documents the addition of 83 microsatellite marker loci and 96 pairs of single‐nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Bembidion lampros, Inimicus japonicus, Lymnaea stagnalis, Panopea abbreviata, Pentadesma butyracea, Sycoscapter hirticola and Thanatephorus cucumeris (anamorph: Rhizoctonia solani). These loci were cross‐tested on the following species: Pentadesma grandifolia and Pentadesma reyndersii. This article also documents the addition of 96 sequencing primer pairs and 88 allele‐specific primers or probes for Plutella xylostella.     

Methicillin-Resistant Staphylococcus aureus (MRSA) Is Increasing in Norway: A Time Series Analysis of Reported MRSA and Methicillin-Sensitive S. aureus Cases, 1997–2010

Background

Accurate estimates of the incidence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections are needed to inform public health policies. In Norway, where both MRSA infection and carriage are notifiable conditions, the reported incidence of MRSA is slowly increasing. However, the proportion of MRSA in relation to all S. aureus isolates is unknown, making it difficult to determine if the rising incidence is real or an artifact of an increasing number of tests performed.

Aim

To characterize recent trends in MRSA infections and obtain a more complete understanding of the MRSA level in Norway.

Methods

All reported cases of MRSA and methicillin-sensitive S. aureus (MSSA) from Oslo County (1997–2010) and Health Region East (2008–2008), representing approximately 11% and 36% of the Norwegian population, respectively, were analyzed using a stochastic time series analysis to characterize trends.

Results

In Oslo County, the proportion of methicillin-resistant cases increased from 0.73% to 3.78% during the study period and was well modeled by an exponential growth with a doubling constant of 5.7 years (95% CI 4.5–7.4 years). In Health Region East, the proportion of MRSA cases increased from 0.4% to 2.1% from 2002 to 2008, with a best-fitting linear increase of 0.26% (95% CI 0.21–0.30%) per year. In both cases, the choice of a linear or exponential model for the time trend produced only marginally different model fits. We found no significant changes due to revised national MRSA guidelines published in June 2009. Significant variations in the increasing time trend were observed in the five hospitals within the region. The yearly reported incidence of MSSA was relatively stable in both study areas although we found seasonal patterns with peaks in August.

Conclusion

The level of MRSA is increasing in Norway, and the proportion of methicillin resistance in all S. aureus isolates are higher than the reported proportion of MRSA in invasive infections.