8,026 research outputs found
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Evidence for symmetric chromosomal inversions around the replication origin in bacteria.
BackgroundWhole-genome comparisons can provide great insight into many aspects of biology. Until recently, however, comparisons were mainly possible only between distantly related species. Complete genome sequences are now becoming available from multiple sets of closely related strains or species.ResultsBy comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure. Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment. The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species. Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well.ConclusionsThe most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication. The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution
Uplift histories of Africa and Australia from linear inverse modeling of drainage inventories
We describe and apply a linear inverse model which calculates
spatial and temporal patterns of uplift rate by minimizing the misfit between
inventories of observed and predicted longitudinal river profiles. Our approach
builds upon a more general, non-linear, optimization model, which suggests
that shapes of river profiles are dominantly controlled by upstream advec-
tion of kinematic waves of incision produced by spatial and temporal changes
in regional uplift rate. Here, we use the method of characteristics to solve
a version of this problem. A damped, non-negative, least squares approach
is developed that permits river profiles to be inverted as a function of up-
lift rate. An important benefit of a linearized treatment is low computational
cost. We have tested our algorithm by inverting 957 river profiles from both
Africa and Australia. For each continent, the drainage network was constructed
from a digital elevation model. The fidelity of river profiles extracted from
this network was carefully checked using satellite imagery. River profiles were
inverted many times to systematically investigate the trade-off between model
misfit and smoothness. Spatial and temporal patterns of both uplift rate and
cumulative uplift were calibrated using independent geologic and geophys-
ical observations. Uplift patterns suggest that the topography of Africa and
Australia grew in Cenozoic times. Inverse modeling of large inventories of
river profiles demonstrates that drainage networks contain coherent signals
that record the regional growth of elevation.This is the final version. It first appeared at http://onlinelibrary.wiley.com/wol1/doi/10.1002/2014JF003297/abstract
Duplicated network meta-analysis in advanced prostate cancer: a case study and recommendations for change
Background: Research overlap and duplication is a recognised problem in the context of both pairwise and network systematic reviews and meta-analyses. As a case study, we carried out a scoping review to identify and examine duplicated network meta-analyses (NMAs) in a specific disease setting where several novel therapies have recently emerged: hormone-sensitive metastatic prostate cancer (mHSPC). Methods: MEDLINE and EMBASE were systematically searched, in January 2020, for indirect or mixed treatment comparisons or network meta-analyses of the systemic treatments docetaxel and abiraterone acetate in the mHSPC setting, with a time-to-event outcome reported on the hazard-ratio scale. Eligibility decisions were made, and data extraction performed, by two independent reviewers. Results: A total of 13 eligible reviews were identified, analysing between 3 and 8 randomised comparisons, and comprising between 1773 and 7844 individual patients. Although the included trials and treatments showed a high degree of overlap, we observed considerable variation between identified reviews in terms of review aims, eligibility criteria and included data, statistical methodology, reporting and inference. Furthermore, crucial methodological details and specific source data were often unclear. Conclusions and recommendations: Variation across duplicated NMAs, together with reporting inadequacies, may compromise identification of best-performing treatments. Particularly in fast-moving fields, review authors should be aware of all relevant studies, and of other reviews with potential for overlap or duplication. We recommend that review protocols be published in advance, with greater clarity regarding the specific aims or scope of the project, and that reports include information on how the work builds upon existing knowledge. Source data and results should be clearly and completely presented to allow unbiased interpretation
Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3-day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia.
In the Maheba Refugee Settlement, in the clinics supported by Medecins Sans Frontieres, all children aged up to 5 years with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulfadoxine/pyrimethamine (SP) and artesunate (AS). We compared the treatment's efficacy and effectiveness. Patients were randomized in order to receive the treatment supervised (efficacy) or unsupervised (effectiveness). Therapeutic response was determined after 28 days of follow up. The difference between recrudescence and re-infection was ascertained by polymerase chain reaction (PCR). We also assessed genetic markers associated to SP resistance (dhfr and dhps). Eighty-five patients received treatment under supervision and 84 received it unsupervised. On day 28, and after PCR adjustment, efficacy was found to be 83.5% (95% CI: 74.1-90.5), and effectiveness 63.4% (95% CI: 52.6-73.3) (P < 0.01). Point mutations on dhfr (108) and dhps (437) were found for 92.0% and 44.2% respectively of the PCR samples analysed. The significant difference in therapeutic response after supervised and unsupervised treatment intake can only be explained by insufficient patient adherence. When implementing new malaria treatment policies, serious investment in ensuring patient adherence is essential to ascertain the effectiveness of the new treatment schedules
Autistic traits and mental health in women with the fragile-X premutation: maternal status versus genetic risk
BACKGROUND: Research on women with the fragile-X premutation (FX-p) has been underrepresented within the field of behavioural phenotypes. AIMS: To understand whether the FX-p confers risk for autistic traits, depression and anxiety, independent of maternal status. METHOD: In study 1, mothers of children with fragile-X syndrome (M-FXp; n = 51, mean age 43 years (s.d. = 5.80)) were compared with mothers of autistic children (M-ASD; n = 59, mean age 42 (s.d. = 5.80)), mothers of children with Smith-Magenis syndrome (M-SMS; n = 27, mean age 39 (s.d. = 7.20)) and mothers of typically developing children (M-TD; n = 44, mean age 40 (s.d. = 4.90)). In study 2, the M-FXp group were compared with non-mothers with the FX-p (NM-FXp; n = 17, mean age 32 (s.d. = 9.20)), typically developed non-mothers (NM-TD; n = 28, mean age 31 (s.d. = 6.80)) and the M-TD group. All participants completed an online survey, including measures of IQ, autistic traits, anxiety, depression and positive affect. RESULTS: In study 1: the M-FXp group reported more autistic traits than the M-TD group (P < 0.05, η2 = 0.046). Anxiety and parental stress were elevated in the M-FXp, M-SMS and M-ASD groups relative to the M-TD group (all P ≤ 0.003, η2 = 0.079-0.322). In study 2: a main effect of premutation status indicated that women with the FX-p report elevated autistic traits and anxiety (P ≤ 0.007, η2 = 0.055-0.060); this did not interact with maternal status. CONCLUSIONS: The findings indicate that women with the FX-p show an increased risk for autistic traits and anxiety. This risk is specific to the presence of the FX-p and is not fully accounted for by maternal status or the stress of caring for children with neurodevelopmental disorders
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Quantum networks in the UK
We describe recent progress in quantum secured optical networks in the UK. The Cambridge Quantum Network has been operating for several years with 3 nodes separated by between 5-10 km of installed fibre. All links are secured by QKD systems operating with secure key rates in excess of 1 Mb/s, the highest recorded long term key rates in a deployed network. The network operates in the presence of 100Gb/s classical traffic with no significant reduction of secure key generation rate. In addition, the Bristol Quantum Network has four nodes 1-3km apart connected in a mesh protected by two pairs of QKD systems. The network is designed to be very dynamic, switching both QKD and WDM classical traffic to enable rapid reconfiguration and is used as a testbed for QKD protected dynamic applications. The two metropolitan networks are being connected by a 410 km QKD link, with 4 spans, the longest of which operates over 129km of fibre with an attenuation of 28dB achieving secure key rates of 2.7kb/s, the longest and highest loss QKD field trial to date. A 120km extension of the UK quantum network from Cambridge to BT Labs, Adastral Park operates with fully commercially available components and is an important testbed comprising 3 intermediate nodes and operates with 5 x 100Gb/s classical channels. This helps determine how to proceed with a large-scale commercial deployment of QKD
The Imprint of Galaxy Formation on X-ray Clusters
It is widely believed that structure in the Universe evolves hierarchically,
as primordial density fluctuations, amplified by gravity, collapse and merge to
form progressively larger systems. The structure and evolution of X-ray
clusters, however, seems at odds with this hierarchical scenario for structure
formation. Poor clusters and groups, as well as most distant clusters detected
to date, are substantially fainter than expected from the tight relations
between luminosity, temperature and redshift predicted by these models. Here we
show that these discrepancies arise because, near the centre, the entropy of
the hot, diffuse intracluster medium (ICM) is higher tha possible if the ICM
is heated at modest redshift (z \ltsim 2) but prior to cluster collapse,
indicating that the formation of galaxies precedes that of clusters and that
most clusters have been assembled very recently.Comment: 5 pages, plus 2 postscript figures (one in colour), accepted for
publication in Natur
Renewing Criminalized and Hegemonic Cultural Landscapes
The Mafia's long historical pedigree in Mezzogiorno, Southern Italy, has empowered the Mafioso as a notorious, uncontested, and hegemonic figure. The counter-cultural resistance against the mafiosi culture began to be institutionalized in the early 1990s. Today, Libera Terra is the largest civil society organization in the country that uses the lands confiscated from the Mafia as a space of cultural repertoire to realize its ideals. Deploying labor force through volunteer participation, producing biological fruits and vegetables, and providing information to the students on the fields are the principal cultural practices of this struggle. The confiscated lands make the Italian experience of anti-Mafia resistance a unique example by connecting the land with the ideals of cultural change. The sociocultural resistance of Libera Terra conveys a political message through these practices and utters that the Mafia is not invincible. This study draws the complex panorama of the Mafia and anti-Mafia movement that uses the ‘confiscated lands’ as cultural and public spaces for resistance and socio-cultural change. In doing so, this article sheds new light on the relationship between rural criminology and crime prevention policies in Southern Italy by demonstrating how community development practice of Libera Terra changes the meaning of landscape through iconographic symbolism and ethnographic performance
Using zeta-potential measurements to quantify peptide partition to lipid membranes
© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively
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