Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis.

A small RNA encoded within the nucleus is an essential subunit of a RNA processing endonuclease (RNase MRP) hypothesized to generate primers for mitochondrial DNA replication from the heavy strand origin of replication. Controversy has arisen, however, concerning the authenticity of an intramitochondrial pool of MRP RNA, and has called into question the existence of pathways for nucleo-mitochondrial transport of nucleic acids in animal cells. In an effort to resolve this controversy, we combined ultrastructural in situ hybridization and biochemical techniques to assess the subcellular partitioning of MRP RNA. Cryosections of mouse cardiomyocytes were hybridized with biotin-labeled RNA probes complementary to different regions of MRP RNA and varying in length from 115 to 230 nucleotides, followed by immunogold labeling. In addition, we transfected mouse C2C12 myogenic cells with constructs bearing mutated forms of the mouse MRP RNA gene and compared the relative abundance of the resulting transcripts to that of control RNAs within whole cell and mitochondrial fractions. In the former analysis we observed preferential localization of MRP RNA to nucleoli and mitochondria in comparison to the nucleoplasm and cytoplasm. In the latter series of studies we observed that wild-type MRP RNA partitions to the mitochondrial fraction by comparison to other RNA transcripts that are localized to the extramitochondrial cytoplasmic space (28S rRNA) or to the nucleoplasm (U1 snRNA). Deletions within 5' or 3' regions of the MRP RNA gene produced transcripts that remain competent for mitochondrial targeting. In contrast, deletion of the midportion of the coding region (nt 118 to 175) of the MRP RNA gene resulted in transcripts that fail to partition to the mitochondrial fraction. We conclude that an authentic intramitochondrial pool of MRP RNA is present in these actively respiring cells, and that specific structural determinants within the MRP RNA molecule permit it to be partitioned to mitochondria

Edge Partitions of Optimal 22-plane and 33-plane Graphs

A topological graph is a graph drawn in the plane. A topological graph is $k$-plane, $k>0$, if each edge is crossed at most $k$ times. We study the problem of partitioning the edges of a $k$-plane graph such that each partite set forms a graph with a simpler structure. While this problem has been studied for $k=1$, we focus on optimal $2$-plane and $3$-plane graphs, which are $2$-plane and $3$-plane graphs with maximum density. We prove the following results. (i) It is not possible to partition the edges of a simple optimal $2$-plane graph into a $1$-plane graph and a forest, while (ii) an edge partition formed by a $1$-plane graph and two plane forests always exists and can be computed in linear time. (iii) We describe efficient algorithms to partition the edges of a simple optimal $2$-plane graph into a $1$-plane graph and a plane graph with maximum vertex degree $12$, or with maximum vertex degree $8$ if the optimal $2$-plane graph is such that its crossing-free edges form a graph with no separating triangles. (iv) We exhibit an infinite family of simple optimal $2$-plane graphs such that in any edge partition composed of a $1$-plane graph and a plane graph, the plane graph has maximum vertex degree at least $6$ and the $1$-plane graph has maximum vertex degree at least $12$. (v) We show that every optimal $3$-plane graph whose crossing-free edges form a biconnected graph can be decomposed, in linear time, into a $2$-plane graph and two plane forests

The impacts of corruption on firm performance: some lessons from 40 African countries

The current evidence-base regarding the impacts of corruption on firm performance is based largely on studies of individual countries and contains mixed results. Therefore, the aim of this paper is to achieve a better insight into this relationship by reporting the results of a firm-level analysis of the impacts of corruption on firm performance using World Bank Enterprise Survey (WBES) data across 40 African countries. The clear result is that corruption significantly enhances rather than harms annual sales, employment and productivity growth rates. The outcome is to re-theorize participation in acts of corruption as beneficial for the individual firms engaged in such activity, while recognizing the wider evidence that this is not an optimal strategy at the aggregate country level. The outcome will be to advance knowledge about how corruption needs to be tackled. To eliminate corruption, it is shown here to be necessary for public authorities to recognize that corruption is an efficient strategy at the firm level and to adopt measures to alter the cost/benefit ratio confronting individual enterprises, and at the same time, to address the country-level formal institutional deficiencies that characterize many developing countries and result in the prevalence of corruption

The impact of new water vapor spectroscopy on satellite retrievals

Water vapor, arguably the most important trace gas constituent of Earth atmospheric physics, is also both a retrieval goal and a hindrance in the retrievals of other trace gases from nadir-measuring satellite spectrometers. This is because the atmospherically-attenuated solar spectrum in the visible and shortwave infrared is littered with water vapor bands. The recent plethora of water vapor spectroscopy databases in this spectral region has prompted us to study their utility in satellite retrievals. We consider water vapor spectroscopy compiled from four sources including new spectroscopy due to University College London and Imperial College London. Radiative transfer models of satellite measurements, in combination with accurate retrieval techniques, are quite sensitive to the accuracy and completeness of the water vapor spectroscopy. Notwithstanding the high degree of variability of a number of different factors in satellite measurements we show that retrievals are sensitive to database differences which suggests that our knowledge of water vapor spectroscopy is not as yet complete. In addition, new laboratory measurements indicate that the role of both the far-line wings of water vapor and the cumulative effect of many weak lines each have an important role to play in forming the so-called continuum

Poor availability of context-specific evidence hampers decision-making in conservation

Evidence-based conservation relies on reliable and relevant evidence. Practitioners often prefer locally relevant studies whose results are more likely to be transferable to the context of planned conservation interventions. To quantify the availability of relevant evidence for amphibian and bird conservation we reviewed Conservation Evidence, a database of quantitative tests of conservation interventions. Studies were geographically clustered, and few locally conducted studies were found in Western sub-Saharan Africa, Russia, South East Asia, and Eastern South America. Globally there were extremely low densities of studies per intervention - fewer than one study within 2000 km of a given location. The availability of relevant evidence was extremely low when we restricted studies to those studying biomes or taxonomic orders containing high percentages of threatened species, compared to the most frequently studied biomes and taxonomic orders. Further constraining the evidence by study design showed that only 17–20% of amphibian and bird studies used reliable designs. Our results highlight the paucity of evidence on the effectiveness of conservation interventions, and the disparity in evidence for local contexts that are frequently studied and those where conservation needs are greatest. Addressing the serious global shortfall in context-specific evidence requires a step change in the frequency of testing conservation interventions, greater use of reliable study designs and standardized metrics, and methodological advances to analyze patchy evidence bases

Assessment of the impact of the scanner-related factors on brain morphometry analysis with Brainvisa.

BACKGROUND: Brain morphometry is extensively used in cross-sectional studies. However, the difference in the estimated values of the morphometric measures between patients and healthy subjects may be small and hence overshadowed by the scanner-related variability, especially with multicentre and longitudinal studies. It is important therefore to investigate the variability and reliability of morphometric measurements between different scanners and different sessions of the same scanner. METHODS: We assessed the variability and reliability for the grey matter, white matter, cerebrospinal fluid and cerebral hemisphere volumes as well as the global sulcal index, sulcal surface and mean geodesic depth using Brainvisa. We used datasets obtained across multiple MR scanners at 1.5 T and 3 T from the same groups of 13 and 11 healthy volunteers, respectively. For each morphometric measure, we conducted ANOVA analysis and verified whether the estimated values were significantly different across different scanners or different sessions of the same scanner. The between-centre and between-visit reliabilities were estimated from their contribution to the total variance, using a random-effects ANOVA model. To estimate the main processes responsible for low reliability, the results of brain segmentation were compared to those obtained using FAST within FSL. RESULTS: In a considerable number of cases, the main effects of both centre and visit factors were found to be significant. Moreover, both between-centre and between-visit reliabilities ranged from poor to excellent for most morphometric measures. A comparison between segmentation using Brainvisa and FAST revealed that FAST improved the reliabilities for most cases, suggesting that morphometry could benefit from improving the bias correction. However, the results were still significantly different across different scanners or different visits. CONCLUSIONS: Our results confirm that for morphometry analysis with the current version of Brainvisa using data from multicentre or longitudinal studies, the scanner-related variability must be taken into account and where possible should be corrected for. We also suggest providing some flexibility to Brainvisa for a step-by-step analysis of the robustness of this package in terms of reproducibility of the results by allowing the bias corrected images to be imported from other packages and bias correction step be skipped, for example.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

Systemic immunosuppression depletes peripheral blood regulatory B cells in patients with immune thrombocytopenia

Regulatory B (Breg) cells are potentially implicated in the pathogenesis of immune thrombocytopenia (ITP). We analysed a prospective cohort of newly diagnosed steroid naïve ITP patients enrolled in the multicentre FLIGHT trial and found that the numbers of Bregs in their peripheral blood were similar to healthy controls. In contrast, Breg numbers were significantly reduced in ITP patients treated with systemic immunosuppression (glucocorticoids or mycophenolate mofetil). We also demonstrate that glucocorticoid treatment impairs Breg interleukin-10 production via an indirect T-cell-mediated mechanism

Multiple parallel skin markers for minimal incision lumbar disc surgery; a technical note

BACKGROUND: Spinal surgery depends on accurate localization to prevent incorrect surgical approaches. The trend towards minimally invasive surgery that minimizes surgical exposure and reduces postoperative pain increasingly requires surgeons to accurately determine the operative level before an incision is made. Preoperative localization with a C-arm image intensifier is popular, but the exposure of both patients and theatre staff to radiation is a disadvantage, as well as being time-consuming. METHODS: We describe a simple surgical tool developed to help localize exact spinal levels in conjunction with a simple AP X-ray film immediately before surgery. Multiple parallel skin markers were made using a circular oven rack comprising multiple 1.5 cm spaced parallel wires attached to a circular outside rim. The longest line was placed on the line of the postero-superior iliac spine (PSIS) over the junction of the L5-S1 region. RESULTS AND CONCLUSIONS: Based on the film taken, the incision can be accurately made at the intended level. The incision wound can be minimized to 3.0 cm even when using conventional disc surgery instruments