Snm1B Interacts with PSF2

The protein Snm1B plays a key role in interstrand crosslink (ICL) repair. In a yeast two-hybrid screen we identified the protein PSF2 to bind Snm1B. PSF2 is a member of the GINS complex involved in replication initiation and elongation, and is known to play a role in ICL repair. Snm1B was shown to bind PSF2 in human cells through two regions, strongly to a 144 amino acid N-terminal region and weakly to a second smaller 37 amino acid C-terminal region. Ectopic expression of PSF2 increased the amount of Mus81, a protein component of the endonucleolytic complex involved in ICL repair, co-immunoprecipitating with Snm1B. Moreover, deleting the N-terminal, but not C-terminal region of Snm1B reduced the amount of co-immunoprecipitated Mus81. Conversely, the telomere-binding protein TRF2 competed with PSF2 for binding to the C-terminus of Snm1B, and deletion of this region, but not the N-terminal region, reduced Snm1B chromatin association. We speculate that the N-terminal region of Snm1B forms a complex containing PSF2 and Mus81, while the C-terminal region is important for PSF2-mediated chromatin association.     

Health facility characteristics and their relationship to coverage of PMTCT of HIV services across four African countries: the PEARL study

Background

Health facility characteristics associated with effective prevention of mother-to-child transmission of HIV (PMTCT) coverage in sub-Saharan are poorly understood.

Methodology/Principal Findings

We conducted surveys in health facilities with active PMTCT services in Cameroon, Cote d''Ivoire, South Africa, and Zambia. Data was compiled via direct observation and exit interviews. We constructed composite scores to describe provision of PMTCT services across seven topical areas: antenatal quality, PMTCT quality, supplies available, patient satisfaction, patient understanding of medication, and infrastructure quality. Pearson correlations and Generalized Estimating Equations (GEE) to account for clustering of facilities within countries were used to evaluate the relationship between the composite scores, total time of visit and select individual variables with PMTCT coverage among women delivering.Between July 2008 and May 2009, we collected data from 32 facilities; 78% were managed by the government health system. An opt-out approach for HIV testing was used in 100% of facilities in Zambia, 63% in Cameroon, and none in Côte d''Ivoire or South Africa. Using Pearson correlations, PMTCT coverage (median of 55%, (IQR: 33–68) was correlated with PMTCT quality score (rho = 0.51; p = 0.003); infrastructure quality score (rho = 0.43; p = 0.017); time spent at clinic (rho = 0.47; p = 0.013); patient understanding of medications score (rho = 0.51; p = 0.006); and patient satisfaction quality score (rho = 0.38; p = 0.031). PMTCT coverage was marginally correlated with the antenatal quality score (rho = 0.304; p = 0.091). Using GEE adjustment for clustering, the, antenatal quality score became more strongly associated with PMTCT coverage (p<0.001) and the PMTCT quality score and patient understanding of medications remained marginally significant.

Conclusions/Results

We observed a positive relationship between an antenatal quality score and PMTCT coverage but did not identify a consistent set of variables that predicted PMTCT coverage.     

Cullin RING Ligases: Glommed by Glomulin

Cullin ring ligases (CRLs) constitute the largest group of RING finger ubiquitin ligases. Two recent studies in?Molecular Cell describe glomulin as a CRL1 inhibitor that blocks interactions with its ubiquitin-conjugating enzyme (E2) (Duda et?al., 2012; Tron et?al., 2012). These findings and their significance are discussed.     

Histomorphometric evidence of growth plate recovery potential after fractionated radiotherapy: an in vivo model

Damron, T. A., Horton, J. A., Pritchard, M. R., Stringer, M. T., Margulies, B. S., Strauss, J. A., Spadaro, J. A. and Farnum, C. E. Histomorphometric Evidence of Recovery Potential after Fractionated Radiotherapy: An In Vivo Model. Radiat. Res. 170, 284-291 (2008).This study evaluated the hypothesis that early growth plate radiorecovery is evident by growth rate, histomorphometric and immunohistochemical end points after exposure to clinically relevant fractionated radiation in vivo. Twenty-four weanling 5-week-old male Sprague-Dawley rats were randomized into eight groups. In each animal, the right distal femur and proximal tibia were exposed to five daily fractions of 3.5 Gy (17.5 Gy) with the left leg serving as a control. Rats were killed humanely at 7, 8, 9, 10, 11, 14, 15 and 16 days after the first day of radiation exposure. Quantitative end points calculated included individual zonal and overall growth plate heights, area matrix fraction, OTC-labeled growth rate, chondrocyte clone volume and numeric density, and BrdU immunohistochemical labeling for proliferative index. Transient postirradiation reductions occurred early and improved during observation for growth rate, proliferative indices, transitional/hypertrophic zone matrix area fraction, proliferative height, and clonal volume. Reserve and hypertrophic zone height remained increased during the period of observation. The current model, using a more clinically relevant fractionation scheme than used previously, shows early evidence of growth plate recovery and provides a model that can be used to correlate temporal changes in RNA and protein expression during the early period of growth plate recovery.     

Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53–1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO°II vs. °III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additonal risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.     

ESR and U-series analyses of enamel and dentine fragments of the Banyoles mandible

The Banyoles mandible presents a puzzle. Its anatomy has been described as pre-Neandertal, but the travertine in which it was found has been dated to 45,000 +/- 4000 years. By this time, any pre-Neandertals had supposedly been absent from the European fossil record for more than 100,000 years. It was therefore proposed that the age of the travertine may represent a minimum age estimate, with the mandible possibly having been reworked from older deposits. We carried out a non-destructive ESR analysis of an enamel fragment removed from a molar and performed a series of in situ laser ablation U-series analyses on dentine fragments adjacent to the enamel piece. The analyses resulted in an apparent combined ESR-U-series age of 66,000 +/- 7000 years. The encasing travertine matrix was also analyzed for U-series isotopes and showed signs of U-mobilization. It cannot be excluded that the travertine matrix is older than the previously determined age. If the mandible was not reworked, then the combined ESR-U-series result on the tooth enamel would give its best age estimate. If, on the other hand, the mandible was reworked from another deposit, the actual ESR-U-series age will depend on the external dose rate from the previous matrix and the depth of its burial, which controls the degree of the attenuation of the cosmic dose rate over time. Considering a range of possible burial histories, the mean age of the mandible would lie somewhere between the combined ESR-U-series age and the previously determined age of the travertine matrix. Regarding the morphology of the mandible, a review of its features in the context of larger Neandertal samples indicates that the anatomy of the specimen is not incompatible with such a young age determination, although it further highlights morphological variation in the late Neandertal sample.     

Visualizing loss of heterozygosity in living mouse cells and tissues

Chronic exposure to oxidative stress especially to highly reactive hydroxyl radicals (HO*) could damage biomolecules, particularly DNA, that in turn would accelerate onset of degenerative diseases. In the present study a few standard phytochemicals (vitamin C, gallic acid, catechin, apigenin, naringenin and naringin) and plant extracts (Hippophae rhamnoides kernel (HRK), Syzygium cumini kernel (SCK) and Punica granatum pericarp (PGP)) were evaluated for their potential to protect/damage DNA in Fenton's system using in vitro models. The results indicated a significant DNA protective effect for naringin and PGP whereas other phytochemicals/extracts showed DNA damaging effect similar to or more than that of control value. The phytochemicals/extracts were also evaluated for their antioxidant and iron chelation properties. In general, the phytochemicals/extracts with high antioxidant activity but without iron chelation capacity failed to protect DNA in Fenton's system, suggesting that iron chelation was an essential requirement for the phytochemicals studied here to retard HO* generation by Fenton's reaction. This was demonstrated by the high iron chelation capacity of naringin and PGP (83.67% and 68.67% respectively) and their DNA protective effect. Commonly consumed phytochemicals such as vitamin C and gallic acid with their high reducing power and at higher physiological concentration, could regenerate free iron for Fenton's reaction leading to DNA damage as shown here.     

Effectiveness of journal ranking schemes as a tool for locating information

Background

The rise of electronic publishing [1], preprint archives, blogs, and wikis is raising concerns among publishers, editors, and scientists about the present day relevance of academic journals and traditional peer review [2]. These concerns are especially fuelled by the ability of search engines to automatically identify and sort information [1]. It appears that academic journals can only remain relevant if acceptance of research for publication within a journal allows readers to infer immediate, reliable information on the value of that research.

Methodology/Principal Findings

Here, we systematically evaluate the effectiveness of journals, through the work of editors and reviewers, at evaluating unpublished research. We find that the distribution of the number of citations to a paper published in a given journal in a specific year converges to a steady state after a journal-specific transient time, and demonstrate that in the steady state the logarithm of the number of citations has a journal-specific typical value. We then develop a model for the asymptotic number of citations accrued by papers published in a journal that closely matches the data.

Conclusions/Significance

Our model enables us to quantify both the typical impact and the range of impacts of papers published in a journal. Finally, we propose a journal-ranking scheme that maximizes the efficiency of locating high impact research.     

Ingestible insecticides for spotted wing Drosophila control: a polyol,Erythritol, and an insect growth regulator,Lufenuron

Bioassays tested insecticidal activity of Erythritol from the nutritive sweetener, Truvia, and an insect growth regulator, Lufenuron, against life stages (eggs, larvae, pupae, adults) of Drosophila melanogaster (Meigen) and Drosophila suzukii (Matsumura), the spotted wing Drosophila (SWD). These compounds were chosen for their demonstrated acute toxicity to adult and larval Drosophila and potential use on organic fruit farms. D. melanogaster fed on standard Drosophila diet media moistened with water containing known concentrations of Erythritol. Likewise, SWD consumed standard diet media as well as thawed host fruit (blackberries and blueberries) treated with solutions of Erythritol, Lufenuron or both. During the first bioassay, Erythritol at lower concentrations between 0 and 500 mm (~61 000 ppm) in water and mixed with instant diet media increased adult survival from ~80% to 97% for D. melanogaster and SWD. However, from aqueous concentrations ranging from 1750 (~414 000 ppm) to 2000 mm (~244 000 ppm), Erythritol killed 100% of adult Drosophila in culture vials. One hundred per cent mortality for SWD and D. melanogaster occurred at ≥0.5 m (~61 000 ppm) Erythritol added to diet media or topically applied to host fruit. In a second bioassay, 0.013–1.000 ppm of aqueous Lufenuron, a chitin synthase inhibitor, when added to dry diet media prevented 90–99% of SWD from reaching the pupal stage. In another assay, ~67% of SWD eggs or neonates (early first instars) died inside blackberries pre‐treated with (dipped in) a soapy solution of 10 ppm Lufenuron. Pre‐treating blackberry fruit with an Erythritol–Lufenuron mixture reduced SWD brood survival by 99%. Likewise, during our last fruit‐based bioassay, 98% of eggs and neonates died inside blueberries similarly pre‐treated. During the last experiment, Lufenuron in diet media also rendered adult females sterile. Sterility, however, dissipated over 7 days once females began feeding on a Lufenuron‐free diet media.