Global maps of the magnetic thickness and magnetization of the Earth’s lithosphere

International audienceWe have constructed global maps of the large-scale magnetic thickness and magnetization of Earth's lithosphere. Deriving such large-scale maps based on lithospheric magnetic field measurements faces the challenge of the masking effect of the core field. In this study, the maps were obtained through analyses in the spectral domain by means of a new regional spatial power spectrum based on the Revised Spherical Cap Harmonic Analysis (R-SCHA) formalism. A series of regional spectral analyses were conducted covering the entire Earth. The R-SCHA surface power spectrum for each region was estimated using the NGDC-720 spherical harmonic (SH) model of the lithospheric magnetic field, which is based on satellite, aeromagnetic, and marine measurements. These observational regional spectra were fitted to a recently proposed statistical expression of the power spectrum of Earth's lithospheric magnetic field, whose free parameters include the thickness and magnetization of the magnetic sources. The resulting global magnetic thickness map is compared to other crustal and magnetic thickness maps based upon different geophysical data. We conclude that the large-scale magnetic thickness of the lithosphere is on average confined to a layer that does not exceed the Moho

Some methods for blindfolded record linkage

BACKGROUND: The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. METHODS: A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. RESULTS: The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. CONCLUSION: Although the protocols described in this paper are not unconditionally secure, they do suggest the feasibility, with the aid of modern cryptographic techniques and high speed communication networks, of a general purpose probabilistic record linkage system which permits record linkage studies to be carried out with negligible risk of invasion of personal privacy

Preclinical Evidence Supporting Early Initiation of Citalopram Treatment in Machado-Joseph Disease

Spinocerebellar ataxias are dominantly inherited neurodegenerative disorders with no disease-modifying treatment. We previously identified the selective serotonin reuptake inhibitor citalopram as a safe and effective drug to be repurposed for Machado-Joseph disease. Pre-symptomatic treatment of transgenic (CMVMJD135) mice strikingly ameliorated mutant ataxin-3 (ATXN3) pathogenesis. Here, we asked whether citalopram treatment initiated at a post-symptomatic age would still show efficacy. We used a cohort of CMVMJD135 mice that shows increased phenotypic severity and faster disease progression (CMVMJD135hi) compared to the mice used in the first trial. Groups of hemizygous CMVMJD135hi mice were orally treated with citalopram. Behavior, protein analysis, and pathology assessment were performed blindly to treatment. Our results show that even when initiated after symptom onset, treatment of CMVMJD135hi mice with citalopram ameliorated motor coordination and balance, attenuating disease progression, albeit to a lesser extent than that seen with pre-symptomatic treatment initiation. There was no impact on ATXN3 aggregation, which contrasts with the robust reduction in ATXN3-positive inclusions observed in CMVMJD135 mice, when treated pre-symptomatically. Post-symptomatic treatment of CMVMJD135hi mice revealed, however, a limited neuroprotective effect by showing a tendency to repair cerebellar calbindin staining, and to increase the number of motor neurons and of NeuN-positive cells in certain brain regions. While supporting that early initiation of treatment with citalopram leads to a marked increase in efficacy, these results strengthen our previous observation that modulation of serotonergic signaling by citalopram is a promising therapeutic approach for Machado-Joseph disease even after symptom onset.European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to PM) and [EXPL/BIM-MEC/0239/2012] (to AT-C), by FCT through the project [POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to PM), by National Ataxia foundation (to PM and to AT-C), and by Ataxia UK (to PM). SE, SD-S, SO, and AT-C were supported by the FCT individual fellowships, SFRH/BD/78554/2011, SFRH/BD/78388/2011, PD/BD/127818/2016, and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa, and EU/FSEinfo:eu-repo/semantics/publishedVersio

A multilevel analysis of neighborhood and individual effects on individual smoking and drinking in Taiwan

<p>Abstract</p> <p>Background</p> <p>We assessed direct effects of neighborhood-level characteristics and interactive effects of neighborhood-level characteristics and individual socioeconomic position on adult smoking and drinking, after consideration of individual-level characteristics in Taiwan.</p> <p>Methods</p> <p>Data on individual sociodemographic characteristics, smoking, and drinking were obtained from Taiwan Social Change Survey conducted in 1990, 1995, and 2000. The overall response rate was 67%. A total of 5883 women and men aged over 20 living in 434 neighborhoods were interviewed. Participants' addresses were geocoded and linked with Taiwan census data for measuring neighborhood-level characteristics including neighborhood education, neighborhood concentration of elderly people, and neighborhood social disorganization. The data were analyzed with multilevel binomial regression models.</p> <p>Results</p> <p>Several interaction effects between neighborhood characteristics and individual socioeconomic status (SES) were found in multilevel analyses. Our results indicated that different neighborhood characteristics led to different interaction patterns. For example, neighborhood education had a positive effect on smoking for low SES women, in contrast to a negative effect on smoking for high SES women. This result supports the hypothesis of "relative deprivation," suggesting that poor people living in affluent neighborhoods suffer from relative deprivation and relative standing. On the other hand, neighborhood social disorganization has positive effects on drinking for low SES individuals, but not for high SES individuals. These interactive effects support the hypothesis of the double jeopardy theory, suggesting that living in neighborhoods with high social disorganization will intensify the effects of individual low SES.</p> <p>Conclusion</p> <p>The findings of this study show new evidence for the effects of neighborhood characteristics on individual smoking and drinking in Taiwan, suggesting that more studies are needed to understand neighborhood effects in Asian societies.</p

SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli

Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo

Protein Phosphatase 2A Interacts with the Na+,K+-ATPase and Modulates Its Trafficking by Inhibition of Its Association with Arrestin

Background: The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na +,K +-ATPase. The catalytic subunit of the Na +,K +-ATPase includes several functional domains that determine its enzymatic and trafficking properties. Methodology/Principal Findings: Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na +,K +-ATPase interacting protein. PP-2A C-subunit interacted with the Na +,K +-ATPase, but not with the homologous sequences of the H +,K +-ATPase. We confirmed that the Na +,K +-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na +,K +-ATPase trafficking through direct association. PP2A inhibits association between the Na +,K +-ATPase and arrestin, and diminishes the effect of arrestin on Na +,K +-ATPase trafficking. GRK phosphorylates the Na +,K +-ATPase and PP2A can at least partially reverse this phosphorylation. Conclusions/Significance: Taken together, these data demonstrate that the sodium pump belongs to a growing list of io