bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Enhancement via Network-Targeted Cortico-cortical Associative Brain Stimulation
Authors: Momi D , Neri F , Coiro G , Smeralda C , Veniero D , Sprugnoli G , Rossi A , Pascual-Leone A , Rossi S , Santarnecchi E
Published: July 2019

Fluid intelligence (gf) represents a crucial component of human cognition, as it correlates with academic achievement, successful aging, and longevity. However, it has strong resilience against enhancement interventions, making the identification of gf enhancement approaches a key unmet goal of cognitive neuroscience. Here, we applied a spike-timing-dependent plasticity (STDP)-inducing brain stimulation protocol, named cortico-cortical paired associative stimulation (cc-PAS), to modulate gf in 29 healthy young subjects (13 females—mean ± standard deviation, 25.43 years ± 3.69), based on dual-coil transcranial magnetic stimulation (TMS). Pairs of neuronavigated TMS pulses (10-ms interval) were delivered over two frontoparietal nodes of the gf network, based on individual functional magnetic resonance imaging data and in accordance with cognitive models of information processing across the prefrontal and parietal lobe. cc-PAS enhanced accuracy at gf tasks, with parieto-frontal and fronto-parietal stimulation significantly increasing logical and relational reasoning, respectively. Results suggest the possibility of using SPTD-inducing TMS protocols to causally validate cognitive models by selectively engaging relevant networks and manipulating inter-regional temporal dynamics supporting specific cognitive functions.
Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants
Authors: Adachi Kristina , Romero Tahmineh , Nielsen-Saines Karin , Pone Sheila , Aibe Mitsue , Barroso de Aguiar Elisa , Sim Myung , Brasil Patricia , Zin Andrea , Tsui Irena , Gaw Stephanie L , Halai Umme-Aiman , Vasconcelos Zilton , Pereira Jose Paulo , Salles Tania Saad , Barbosa Claudia Neves , Portari Elyzabeth , Cherry James D , Pone Marcos , Moreira Maria Elisabeth
Published: July 2019

Background

Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.

Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes.

Methods

Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed.

Results

Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1–10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2–12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life.

Conclusions

ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.

Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.
Source localization and joint velocity model building using wavefront attributes
Authors: Diekmann Leon , Schwarz Benjamin , Bauer Alexander , Gajewski Dirk
Published: July 2019

The localization of passive seismic sources in form of microseismic tremors as well as large-scale earthquakes is a key issue in seismology. While most previous studies are assuming fairly good knowledge of the underlying velocity model, we propose an automatic spatial localization and joint velocity model building scheme that is independent of detailed a priori information. The first step is a coherence analysis, estimating so-called wavefront attributes to locally describe the wavefield in terms of slopes and curvatures. In a similar fashion, we also obtain an initial guess of the source excitation times of the recorded events. The wavefront attributes constitute the input for wavefront tomography which represents the next step of the workflow and allows for a refinement of the previously evaluated source excitation times while simultaneously approximating the velocity distribution. In a last step, we use the final estimate of the velocity distribution and compute the respective image function by reverse time modelling to gain the source locations. This paper introduces the theoretical concept of our proposed approach for the general 3-D case. We analyse the feasibility of our strategy and the influences of different acquisition settings by means of a synthetic 2-D data example. In a final 3-D field data example we use the workflow to localize a deep earthquake without relying on a given velocity model. The approach can deal with high levels of noise and low signal amplitudes, respectively, as well as sparse geophone sampling. The workflow generally delivers good approximations of the long-wavelength velocity variations along with accurate source locations.
Shallow crustal imaging using distant, high-magnitude earthquakes
Authors: van IJsseldijk Johno , Ruigrok Elmer , Verdel Arie , Weemstra Cornelis
Published: July 2019

Global phases, viz. seismic phases that travel through the Earth’s core, can be used to locally image the crust by means of seismic interferometry. This method is known as Global Phase Seismic Interferometry (GloPSI). Traditionally, GloPSI retrieves low-frequency information (up to 1 Hz). Recent studies, however, suggest that there is high-frequency signal present in the coda of strong, distant earthquakes. This research quantifies the potential of these high-frequency signals, by analysing recordings of a multitude of high-magnitude earthquakes (≥6.4 Mw) and their coda on a selection of permanent USArray stations. Nearly half of the P, PKP and PKIKP phases are recorded with a signal-to-noise ratio of at least 5 dB at 3 Hz. To assess the viability of using the high-frequency signal, the second half of the paper highlights two case studies. First, a known sedimentary structure is imaged in Malargüe, Argentina. Secondly, the method is used to reveal the structure of the Midcontinent Rift below the SPREE array in Minnesota, USA. Both studies demonstrate that structural information of the shallow crust (≤5 km) below the arrays can be retrieved. In particular, the interpreted thickness of the sedimentary layer below the Malargüe array is in agreement with earlier studies in the same area. Being able to use global phases and direct P-phases with large epicentral distances (>80°) to recover the Earth’s sedimentary structure suggests that GloPSI can be applied in an industrial context.
A geothermal application for GOCE satellite gravity data: modelling the crustal heat production and lithospheric temperature field in Central Europe
Authors: Pastorutti A , Braitenberg C
Published: July 2019

Since the completion of the Gravity field and steady-state Ocean Circulation Explorer mission (GOCE), global gravity models of uniform quality and coverage are available. We investigate their potential of being useful tools for estimating the thermal structure of the continental lithosphere, through simulation and real-data test in Central-Eastern Europe across the Trans-European Suture Zone. Heat flow, measured near the Earth surface, is the result of the superposition of a complex set of contributions, one of them being the heat production occurring in the crust. The crust is enriched in radioactive elements respect to the underlying mantle and crustal thickness is an essential parameter in isolating the thermal contribution of the crust. Obtaining reliable estimates of crustal thickness through inversion of GOCE-derived gravity models has already proven feasible, especially when weak constraints from other observables are introduced. We test a way to integrate this in a geothermal framework, building a 3-D, steady state, solid Earth conductive heat transport model, from the lithosphere–asthenosphere boundary to the surface. This thermal model is coupled with a crust-mantle boundary depth resulting from inverse modelling, after correcting the gravity model for the effects of topography, far-field isostatic roots and sediments. We employ a mixed space- and spectral-domain based forward modelling strategy to ensure full spectral coherency between the limited spectral content of the gravity model and the reductions. Deviations from a direct crustal thickness to crustal heat production relationship are accommodated using a subsequent substitution scheme, constrained by surface heat flow measurements, where available. The result is a 3-D model of the lithosphere characterised in temperature, radiogenic heat and thermal conductivity. It provides added information respect to the lithospheric structure and sparse heat flow measurements alone, revealing a satisfactory coherence with the geological features in the area and their controlling effect on the conductive heat transport.
Spurious low velocity zones in joint inversions of surface waves and receiver functions
Authors: Gao Chao , Cunningham Erin , Lekić Vedran
Published: July 2019

Low-velocity layers within the crust can indicate the presence of melt and lithologic differences with implications for crustal composition and formation. Seismic wave conversions and reverberations across the base of the crust or intracrustal discontinuities, analysed using the receiver function method, can be used to constrain crustal layering. This is commonly accomplished by inverting receiver functions jointly with surface wave dispersion. Recently, the proliferation of model-space search approaches has made this technique a workhorse of crustal seismology. We show that reverberations from shallow layers such as sedimentary basins produce spurious low-velocity zones when inverted for crustal structure with surface wave data of insufficiently high frequency. Therefore, reports of such layers in the literature based on inversions using receiver function data should be re-evaluated. We demonstrate that a simple resonance-removal filter can suppress these effects and yield reliable estimates of crustal structure, and advocate for its use in receiver-function based inversions.
Do home pregnancy tests bring women to community health workers for antenatal care counselling? A randomized controlled trial in Madagascar
Authors: Comfort Alison B , Juras Randall C , Bradley Sarah E K , Ranjalahy Rasolofomanana Justin , Noeliarivelo Ranjalahy Anja , Harper Cynthia C
Published: July 2019

Task-shifting the provision of pregnancy tests to community health workers (CHWs) in low-resource settings has the potential to reach significantly more underserved women at risk of pregnancy with essential reproductive health services. This study assessed whether an intervention to supply CHWs with home pregnancy tests brought more clients for antenatal care (ANC) counselling. We implemented a randomized controlled trial among CHWs providing reproductive health services to women in Eastern Madagascar. We used ordinary least squares regressions to estimate the effect of the intervention, with district- and month-fixed effects and CHW baseline characteristics as control variables. Our outcomes of interest included whether the intervention increased: (1) the number of women at risk of pregnancy who sought services from CHWs; (2) the number of these women who knew they were pregnant by the end of visit; and (3) the number of these women who received ANC counselling during visit. We found that providing pregnancy tests to CHWs to distribute to their clients for free significantly increased the number of women at risk of pregnancy who sought services from CHWs. At follow-up, treatment-group CHWs provided services to 6.3 clients compared with 4.2 clients among control-group CHWs, which represents a 50% relative increase from the control-group mean. A significantly higher number of these clients knew they were pregnant by the end of the visit, with a mean of 0.95 in treatment compared with 0.10 in control (Coeff. 0.86; 95% CI 0.59–1.13). A significantly higher number of these clients received antenatal counselling at the visit (Coeff. 0.4; 95% CI 0.14–0.64). Introducing free home pregnancy tests as part of community-based health services can improve pregnancy care by attracting more clients at risk of pregnancy to services at the community level, enabling more women to confirm they are pregnant and receive antenatal counselling.
The disciplined sea: a history of maritime security and zonation
Authors: Ryan Barry J.
Published: July 2019

This article details the evolution of maritime security from the perspective of its impact on the historical architecture of sea space. It argues that, as the fundamental unit of governance, zoning provides keen insight into the mechanics of maritime security. The article observes that Britain's Hovering Acts in the late eighteenth century represent the earliest example of modern zonation at sea and that they exhibit a shift from early modern territorial claims based on imperium and dominium. The article explores the way these hovering zones shaped the rationale underlying contemporary maritime security. It finds that maritime security has effectively relegated national security to a minor spatial belt of state power, while elevating non-traditional understandings of security to the level of global existential threat. The future of maritime security is under construction. Increasingly segmented by interconnecting, overlapping, multi-functional zones that seek to regulate all free movement and usage of the sea, security developments are reorganizing the maritime sphere. Nonetheless, the article argues, despite the novelty of this development, a historical military logic persists in new formations of security-oriented practices of maritime governance.
Paternal antidepressant use as a negative control for maternal use: assessing familial confounding on gestational length and anxiety traits in offspring
Authors: Cohen Jacqueline M , Wood Mollie E , Hernández-Díaz Sonia , Ystrom Eivind , Nordeng Hedvig
Published: July 2019

Background

Maternal antidepressant use in pregnancy has been associated with both shorter gestational length and child anxiety. We employed paternal antidepressant use as a negative-control exposure to indirectly assess whether confounding by genetic or shared familial environmental factors associated with depression may explain these associations.

Methods

The study sample came from the population-based Norwegian Mother and Child Cohort Study (MoBa) that recruited participants from 1999 to 2008. We included 70 959 families where the father completed a questionnaire about medication use in the 6 months prior to pregnancy. In 42 511 infants who completed the 3-year follow-up, we computed Z-scores for the anxiety domain of the Child Behavior Checklist. We used linear and logistic regression to assess the association between paternal antidepressant use, gestational age at birth and child anxiety.

Results

Antidepressants were used by 1.1% (n = 755) of fathers. Paternal antidepressant use was not associated with gestational age at birth [β = 0.63 days, 95% confidence interval (CI) –1.56, 0.31] whereas it was positively associated with a child anxiety symptom Z-score and high anxiety symptoms (odds ratio 1.33, 95% CI 0.90, 1.97) in unadjusted analyses. This association was attenuated when controlling for maternal and paternal history of depression and other measured factors (odds ratio 1.14, 95% CI 0.76, 1.69).

Conclusions

These results support the suggested effect of maternal use of antidepressants in pregnancy on shorter gestation; however, they suggest familial confounding could explain the association between maternal use of antidepressants and anxiety traits in the offspring.
Modeling and simulation of a small-scale solar-powered absorption cooling system in three cities with a tropical climate
Authors: Boero Andrea , Agyenim Francis
Published: July 2019

This study assessed through numerical simulations, the technical feasibility of a solar-powered absorption cooling system for a small-scale application in an office building in three different cities with a tropical climate in Ecuador. The model and simulations were performed using the dynamic transient software TRNSYS and were compared and validated using experimental data obtained from a real-life system with main components: 12 m2 vacuum tube solar thermal collector array, a 4.5 kW LiBr/H2O single-effect absorption chiller, a 6 kW fan coil and a 100 l sensible cold store. The results of the simulation showed a good agreement with the experimental data with a deviation of 8.5%.

The validated model was used to undertake a parametric study to determine capacities of systems that will be applicable to three Ecuadorian cities: Guayaquil, Manta and San Cristobal. The system capacity predicted by the model for the Ecuadorian cities has the following components: 24 m2 evacuated tube collector field, a 20 kW heat exchanger, a 15 kW single-stage LiBr/H2O absorption chiller, a 35 kW cooling tower and a cold storage tank of 2 m3. The results showed that the proposed system could meet most of the required cooling load (90% for Guayaquil and San Cristobal, and 71% for Manta, considering a set point of 24°C) of a typical single-story office building with.
Activity of imipenem/relebactam against carbapenemase-producing Enterobacteriaceae with high colistin resistance
Authors: Carpenter Jessica , Neidig Nick , Campbell Alex , Thornsberry Tanner , Truex Taylor , Fortney Tiffany , Zhang Yunliang , Bush Karen
Published: July 2019

Objectives

Imipenem/relebactam, an investigational β-lactam/β-lactamase inhibitor combination for treatment of Gram-negative infections, and comparators including ceftazidime/avibactam, piperacillin/tazobactam and colistin were tested for activity against representative carbapenemase-producing Enterobacteriaceae (CPE) isolates.

Methods

MICs of the antimicrobial agents were determined using standard broth microdilution methodology for CPE isolates collected from Indiana patients, primarily during the time frame of 2013–17 (n = 199 of a total of 200 isolates). Inhibitors were tested at 4 mg/L in all combinations.

Results

Of the CPE in the study, 199 produced plasmid-encoded KPC class A carbapenemases; 1 Serratia marcescens isolate produced the SME-1 chromosomal class A carbapenemase. MIC50/MIC90 values of imipenem/relebactam were ≤0.25/0.5 mg/L, whereas MIC50/MIC90 values of ceftazidime/avibactam were 1/2 mg/L. Resistance to colistin was observed in 54% (n = 97) of 180 non-Serratia isolates tested (MIC50 of 4 mg/L). Colistin resistance mechanisms included production of a plasmid-encoded mcr-1-like gene (n = 2) or an inactivated mgrB gene.

Conclusions

Imipenem/relebactam was the most potent agent tested against CPE in this study and may be a useful addition to the antimicrobial armamentarium to treat infections caused by these pathogens.
High-redshift quasars and their host galaxies – I. Kinematical and dynamical properties and their tracers
Authors: Lupi Alessandro , Volonteri Marta , Decarli Roberto , Bovino Stefano , Silk Joseph , Bergeron Jacqueline
Published: July 2019

Observations of high-redshift quasars provide information on the massive black holes (MBHs) powering them and the galaxies hosting them. Current observations of z ≳ 6 hosts, at sub-millimetre wavelengths, trace the properties of cold gas, and these are used to compare with the correlations between MBHs and galaxies characterizing the z = 0 population. The relations at z = 0, however, rely on stellar-based tracers of the galaxy properties. We perform a very high resolution cosmological zoom-in simulation of a z = 7 quasar including state-of-the-art non-equilibrium chemistry, MBH formation, growth, and feedback, to assess the evolution of the galaxy host and the central MBH, and compare the results with recent ALMA observations of high-redshift quasars. We measure both the stellar-based quantities used to establish the z = 0 correlations, as well as the gas-based quantities available in z ≳ 6 observations, adopting the same assumptions and techniques used in observational studies. The high-redshift studies argued that MBHs at high redshift deviate from the local MBH–galaxy correlations. In our analysis of the single galaxy we evolve, we find that the high-redshift population sits on the same correlations as the local one, when using the same tracers used at z = 0. When using the gas-based tracers, however, MBHs appear to be overmassive. The discrepancy between local and high-redshift MBHs seems to be caused by the different tracers employed, and the necessary assumptions, and not by an intrinsic difference. Better calibration of the tracers, higher resolution data, and availability of facilities that can probe the stellar population will be crucial to assess precisely and accurately high-redshift quasar hosts.
How low does it go? Too few Galactic satellites with standard reionization quenching
Authors: Graus Andrew S , Bullock James S , Kelley Tyler , Boylan-Kolchin Michael , Garrison-Kimmel Shea , Qi Yuewen
Published: July 2019

A standard prediction of galaxy formation theory is that the ionizing background suppresses galaxy formation in haloes with peak circular velocities smaller than $V_{\rm peak}\simeq 20 \, \rm km \, s^{-1}$, rendering the majority of haloes below this scale completely dark. We use a suite of cosmological zoom simulations of Milky Way-like haloes that include central Milky Way disc galaxy potentials to investigate the relationship between subhaloes and ultrafaint galaxies. We find that there are far too few subhaloes within 50 kpc of the Milky Way that had $V_{\rm peak}\gtrsim 20\, \rm km \, s^{-1}$ to account for the number of ultrafaint galaxies already known within that volume today. In order to match the observed count, we must populate subhaloes down to $V_{\rm peak}\simeq 6\, \rm km \, s^{-1}$ with ultrafaint dwarfs. The required haloes have peak virial temperatures as low as 1500 K, well below the atomic hydrogen cooling limit of 104 K. Allowing for the possibility that the Large Magellanic Cloud contributes several of the satellites within 50 kpc could potentially raise this threshold to $10\, \rm km \, s^{-1}$ (4000 K), still below the atomic cooling limit and far below the nominal reionization threshold.
Bolometric corrections of stellar oscillation amplitudes as observed by the Kepler, CoRoT, and TESS missions
Authors: Lund Mikkel N
Published: July 2019

A better understanding of the amplitudes of stellar oscillation modes and surface granulation is essential for improving theories of mode physics and the properties of the outer convection zone of solar-like stars. A proper prediction of these amplitudes is also essential for appraising the detectability of solar-like oscillations for asteroseismic analysis. Comparisons with models, or between different photometric missions, are enabled by applying a bolometric correction, which converts mission-specific amplitudes to their corresponding bolometric (full light) values. We derive the bolometric correction factor for amplitudes of radial oscillation modes and surface granulation as observed by the Kepler, CoRoT, and TESS missions. The calculations are done assuming a stellar spectrum given by a black-body as well as by synthetic spectral flux densities from 1D model atmospheres. We derive a power-law and polynomial relations for the bolometric correction as a function of temperature from the black-body approximation and evaluate the deviations from adopting a more realistic spectrum. Across the full temperature range from 4000 to 7500 K, the amplitudes from TESS are in the black-body approximation predicted to be a factor ∼0.83–0.84 times those observed by Kepler. We find that using more realistic flux spectra over the black-body approximation can change the bolometric correction by as much as ${\sim }30{{\ \rm per\ cent}}$ at the lowest temperatures, but with a change typically within ${\sim }5\!-\!10 {{\ \rm per\ cent}}$ around a Teff of 5500–6000 K. We find that after Teff, the bolometric correction most strongly depends on $\rm [M/H]$, which could have an impact on reported metallicity dependences of amplitudes reported in the literature.
Detection of metal-rich, cool-warm gas in the outskirts of galaxy clusters
Authors: Pradeep Jayadev , Narayanan Anand , Muzahid Sowgat , Nagai Daisuke , Charlton Jane C , Srianand Raghunathan
Published: July 2019

We present an ultraviolet quasar absorption line analysis of metal lines associated with three strong intervening H i absorbers (with $N(\rm {{H}\,{\small I}})$ > 1016.5 cm−2) detected in the outskirts of Sunyaev–Zel’dovich (SZ) effect-selected galaxy clusters (zcl ∼ 0.4–0.5), within clustocentric impact parameters of ρcl ∼ (1.6–4.7)r500. Discovered in a recent set of targeted far-UV HST/COS spectroscopic observations, these absorbers have among the highest H  i column densities ever observed in the outskirts of galaxy clusters, and are also rich in metal absorption lines. Photoionization models yield single phase solutions for the three absorbers with gas densities of nH  ∼ 10−3–10−4 cm−3 and metallicities of [X/H] > −1.0 (from one-tenth solar to near-solar). The widths of detected absorption lines suggest gas temperatures of T ∼ 104 K. The inferred densities (temperatures) are significantly higher (lower) compared to the X-ray emitting intracluster medium in cluster cores. The absorbers are tracing a cool phase of the intracluster gas in the cluster outskirts, either associated with gas stripped from cluster galaxies via outflows, tidal streams or ram-pressure forces, or denser regions within the intracluster medium that were uniformly chemically enriched from an earlier epoch of enhanced supernova and Active Galactic Nucleus (AGN) feedback.
SuperWASP dispositions and false positive catalogue
Authors: Schanche N , Collier Cameron A , Almenara J M , Alsubai K A , Anderson D R , Armstrong D J , Barkaoui K , Barros S C C , Bochiński J , Bonomo A S , Bouchy F , Brown D J A , Burdanov A , Busuttil R , Deleuil M , Delrez L , Faedi F , Gillon M , Hay K , Hebb L , Hébrard G , Jehin E , Kolb U , Maxted P F L , Miller G , Nielsen L D , Pollacco D L , Pozuelos F J , Queloz D , Relles H , Smalley B , Triaud A H M J , Udry S , West R , Wheatley P J
Published: July 2019

SuperWASP, the Northern hemisphere WASP observatory, has been observing the skies from La Palma since 2004. In that time, more than 50 planets have been discovered with data contributions from SuperWASP. In the process of validating planets, many false-positive candidates have also been identified. The TESS telescope is set to begin observations of the northern sky in 2019. Similar to the WASP survey, the TESS pixel size is relatively large (13 arcsec for WASP and 21 arcsec for TESS), making it susceptible to many blended signals and false detections caused principally by grazing and blended stellar eclipsing binary systems. In order to reduce duplication of effort on targets, we present a catalogue of 1 041 Northern hemisphere SuperWASP targets that have been rejected as planetary transits through follow-up observation.
Rad5 dysregulation drives hyperactive recombination at replication forks resulting in cisplatin sensitivity and genome instability
Authors: Bryant Eric E , Šunjevarić Ivana , Berchowitz Luke , Rothstein Rodney , Reid Robert J D
Published: July 2019

The postreplication repair gene, HLTF, is often amplified and overexpressed in cancer. Here we model HLTF dysregulation through the functionally conserved Saccharomyces cerevisiae ortholog, RAD5. Genetic interaction profiling and landscape enrichment analysis of RAD5 overexpression (RAD5OE) reveals requirements for genes involved in recombination, crossover resolution, and DNA replication. While RAD5OE and rad5Δ both cause cisplatin sensitivity and share many genetic interactions, RAD5OE specifically requires crossover resolving genes and drives recombination in a region of repetitive DNA. Remarkably, RAD5OE induced recombination does not require other post-replication repair pathway members, or the PCNA modification sites involved in regulation of this pathway. Instead, the RAD5OE phenotype depends on a conserved domain necessary for binding 3′ DNA ends. Analysis of DNA replication intermediates supports a model in which dysregulated Rad5 causes aberrant template switching at replication forks. The direct effect of Rad5 on replication forks in vivo, increased recombination, and cisplatin sensitivity predicts similar consequences for dysregulated HLTF in cancer.
A 212-nt long RNA structure in the Tobacco necrosis virus-D RNA genome is resistant to Xrn degradation
Authors: Gunawardene Chaminda D , Newburn Laura R , White K Andrew
Published: July 2019

Plus-strand RNA viruses can accumulate viral RNA degradation products during infections. Some of these decay intermediates are generated by the cytosolic 5′-to-3′ exoribonuclease Xrn1 (mammals and yeast) or Xrn4 (plants) and are formed when the enzyme stalls on substrate RNAs upon encountering inhibitory RNA structures. Many Xrn-generated RNAs correspond to 3′-terminal segments within the 3′-UTR of viral genomes and perform important functions during infections. Here we have investigated a 3′-terminal small viral RNA (svRNA) generated by Xrn during infections with Tobacco necrosis virus-D (family Tombusviridae). Our results indicate that (i) unlike known stalling RNA structures that are compact and modular, the TNV-D structure encompasses the entire 212 nt of the svRNA and is not functionally transposable, (ii) at least two tertiary interactions within the RNA structure are required for effective Xrn blocking and (iii) most of the svRNA generated in infections is derived from viral polymerase-generated subgenomic mRNA1. In vitro and in vivo analyses allowed for inferences on roles for the svRNA. Our findings provide a new and distinct addition to the growing list of Xrn-resistant viral RNAs and stalling structures found associated with different plant and animal RNA viruses.
Loss of NLRP6 expression increases the severity of acute kidney injury
Authors: Valiño-Rivas Lara , Cuarental Leticia , Nuñez Gabriel , Sanz Ana B , Ortiz Alberto , Sanchez-Niño Maria Dolores
Published: July 2019

Background

Nlrp6 is a nucleotide-binding oligomerization domain-like receptor (NLR) that forms atypical inflammasomes. Nlrp6 modulates the gut epithelium interaction with the microbiota. However, the expression and function of Nlrp6 in the kidney, a sterile environment, have not been characterized. We explored the role of Nlrp6 in acute kidney injury (AKI).

Methods

In a transcriptomics array of murine nephrotoxic AKI, Nlrp6 and Naip3 were the only significantly downregulated NLR genes. The functional implications of Nlrp6 downregulation were explored in mice and in cultured murine tubular cells.

Results

Nlrp6 was expressed by healthy murine and human kidney tubular epithelium, and expression was reduced during human kidney injury or murine nephrotoxic AKI induced by cisplatin or a folic acid overdose. Genetic Nlrp6 deficiency resulted in upregulation of kidney extracellular signal–regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) phosphorylation and more severe AKI and kidney inflammation. In cultured tubular cells, Nlrp6 downregulation induced by specific small interfering RNA resulted in upregulation of ERK1/2 and p38 phosphorylation and chemokine messenger RNA expression and downregulation of the nephroprotective gene Klotho. MAPK inhibition prevented the inflammatory response in Nlrp6-deficient cells.

Conclusion

Nlrp6 dampens sterile inflammation and has a nephroprotective role during nephrotoxic kidney injury through suppression of MAP kinase activation.
Immobilization of functional nano-objects in living engineered bacterial biofilms for catalytic applications
Authors: Wang Xinyu , Pu Jiahua , Liu Yi , Ba Fang , Cui Mengkui , Li Ke , Xie Yu , Nie Yan , Mi Qixi , Li Tao , Liu Lingli , Zhu Manzhou , Zhong Chao
Published: July 2019

Nanoscale objects feature very large surface-area-to-volume ratios and are now understood as powerful tools for catalysis, but their nature as nanomaterials brings challenges including toxicity and nanomaterial pollution. Immobilization is considered a feasible strategy for addressing these limitations. Here, as a proof-of-concept for the immobilization of nanoscale catalysts in the extracellular matrix of bacterial biofilms, we genetically engineered amyloid monomers of the Escherichia coli curli nanofiber system that are secreted and can self-assemble and anchor nano-objects in a spatially precise manner. We demonstrated three scalable, tunable and reusable catalysis systems: biofilm-anchored gold nanoparticles to reduce nitro aromatic compounds such as the pollutant p-nitrophenol, biofilm-anchored hybrid Cd0.9Zn0.1S quantum dots and gold nanoparticles to degrade organic dyes and biofilm-anchored CdSeS@ZnS quantum dots in a semi-artificial photosynthesis system for hydrogen production. Our work demonstrates how the ability of biofilms to grow in scalable and complex spatial arrangements can be exploited for catalytic applications and clearly illustrates the design utility of segregating high-energy nano-objects from injury-prone cellular components by engineering anchoring points in an extracellular matrix.
Intraoperative Computed Tomography and Finite Element Modelling for Multimodal Image Fusion in Brain Surgery
Authors: Riva Marco , Hiepe Patrick , Frommert Mona , Divenuto Ignazio , Gay Lorenzo G , Sciortino Tommaso , Nibali Marco Conti , Rossi Marco , Pessina Federico , Bello Lorenzo
Published: July 2019

BACKGROUND

intraoperative computer tomography (iCT) and advanced image fusion algorithms could improve the management of brainshift and the navigation accuracy.

OBJECTIVE

To evaluate the performance of an iCT-based fusion algorithm using clinical data.

METHODS

Ten patients with brain tumors were enrolled; preoperative MRI was acquired. The iCT was applied at the end of microsurgical resection. Elastic image fusion of the preoperative MRI to iCT data was performed by deformable fusion employing a biomechanical simulation based on a finite element model. Fusion accuracy was evaluated: the target registration error (TRE, mm) was measured for rigid and elastic fusion (Rf and Ef) and anatomical landmark pairs were divided into test and control structures according to distinct involvement by the brainshift. Intraoperative points describing the stereotactic position of the brain were also acquired and a qualitative evaluation of the adaptive morphing of the preoperative MRI was performed by 5 observers.

RESULTS

The mean TRE for control and test structures with Rf was 1.81 ± 1.52 and 5.53 ± 2.46 mm, respectively. No significant change was observed applying Ef to control structures; the test structures showed reduced TRE values of 3.34 ± 2.10 mm after Ef (P < .001). A 32% average gain (range 9%-54%) in accuracy of image registration was recorded. The morphed MRI showed robust matching with iCT scans and intraoperative stereotactic points.

CONCLUSIONS

The evaluated method increased the registration accuracy of preoperative MRI and iCT data. The iCT-based non-linear morphing of the preoperative MRI can potentially enhance the consistency of neuronavigation intraoperatively.
Development of a Heat-Inducible Gene Expression System Using Female Gametophytes of Arabidopsis thaliana
Authors: Hwang Dukhyun , Wada Satomi , Takahashi Azusa , Urawa Hiroko , Kamei Yasuhiro , Nishikawa Shuh-ichi
Published: July 2019

Female gametophyte (FG) is crucial for reproduction in flowering plants. Arabidopsis thaliana produces Polygonum-type FGs, which consist of an egg cell, two synergid cells, three antipodal cells and a central cell. Egg cell and central cell are the two female gametes that give rise to the embryo and surrounding endosperm, respectively, after fertilization. During the development of a FG, a single megaspore produced by meiosis undergoes three rounds of mitosis to produce an eight-nucleate cell. A seven-celled FG is formed after cellularization. The central cell initially contains two polar nuclei that fuse during female gametogenesis to form the secondary nucleus. In this study, we developed a gene induction system for analyzing the functions of various genes in developing Arabidopsis FGs. This system allows transgene expression in developing FGs using the heat-inducible Cre-loxP recombination system and FG-specific embryo sac 2 (ES2) promoter. Efficient gene induction was achieved in FGs by incubating flower buds and isolated pistils at 35ï¿½C for short periods of time (1–5 min). Gene induction was also induced in developing FGs by heat treatment of isolated ovules using the infrared laser-evoked gene operator (IR-LEGO) system. Expression of a dominant-negative mutant of Sad1/UNC84 (SUN) proteins in developing FGs using the gene induction system developed in this study caused defects in polar nuclear fusion, indicating the roles of SUN proteins in this process. This strategy represents a new tool for analyzing the functions of genes in FG development and FG functions.
Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy
Authors: Abe Yoshiyuki , Kusaoi Makio , Tada Kurisu , Yamaji Ken , Tamura Naoto
Published: July 2019

Objectives

We examined the effectiveness of plasma exchange (PE) therapy to reduce the mortality of rapidly progressive interstitial lung disease (RP-ILD) in patients positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies.

Methods

Among 142 patients newly diagnosed with PM/DM or clinically amyopathic DM from 2008 to 2019 at our hospital, 10 were diagnosed with refractory RP-ILD and were positive for anti-MDA5 antibodies. PE was used as an adjunct to standard therapy and consisted of fresh frozen plasma as replacement solution. The primary outcome was non-disease-specific mortality.

Results

Anti-MDA5 antibodies were detected in 28 patients, of whom 21 were diagnosed with RP-ILD and 10 were refractory to intensive immunosuppressive therapy. Six patients received PE (PE group) and four did not (non-PE group). The 1-year survival rate of the PE group was higher than that of the non-PE group (100% and 25%, respectively, P = 0.033). Regarding adverse events associated with PE, two patients had anaphylactic shock, one had high fever due to fresh frozen plasma allergy and one had a catheter infection. All adverse events resolved with appropriate treatment.

Conclusion

We evaluated the association between 1-year survival rate and PE for refractory RP-ILD in patients positive for anti-MDA5 antibodies. Intensive immunosuppressive therapy improved the survival rate in RP-ILD patients with anti-MDA5 antibodies, but 20–30% of cases were still fatal. PE could be administered to patients with active infectious disease who were immunocompromised by intensive immunosuppressive therapy. PE may be considered in refractory RP-ILD patients positive for anti-MDA5 antibodies.
Experimental investigations on the partner-finding behaviour of Isohypsibius dastychi (Isohypsibiidae: Tardigrada)
Authors: Bartel Sandra , Hohberg Karin
Published: July 2019

The present study gives the first detailed results on the partner-finding behaviour of tardigrades. We investigated whether the finding of mating partners by Isohypsibius dastychi followed certain criteria that are expected if pheromone signals are involved. For this purpose, tardigrade pairs were positioned in an arena, at a range of distances from each other. Only those females that were ready for mating attracted the male. The smaller the initial distance between them, the more directly the male headed for the female. The route travelled and time taken increased exponentially with increasing initial distance between partners, which means that the male lost orientation with respect to the female the larger the distance between the pair became. The findings indirectly suggest a yet undetermined female pheromone, which produces a concentration gradient in the water and loses strength quickly in terms of distance. Our assumption is supported by rare observations of sperm release without direct contact between partners that nevertheless resulted in fertile offspring. The observation that the female partners in this no-contact mating behaviour then deposited their eggs (a behaviour that was never seen when males were absent) suggests that they, likewise, can sense a fresh ejaculate of spermatozoa in their direct vicinity.
Quantification of Optical Coherence Tomography Angiography in Age and Age-related Macular Degeneration using Vessel Density analysis
Authors: Vaghefi Ehsan , Hill Sophie , Kersten Hannah M , Squirrell David
Published: July 2019

Purpose

To determine whether vessel density (VD) as measured by optical coherence tomography angiography (OCT-A) provide insights into retinal and choriocapillaris vascular changes with ageing and intermediate dry age related macular degeneration (AMD).

Methods

Seventy-five participants were recruited into three cohorts; young healthy (YH) group, old healthy (OH) and those at high-risk for exudative AMD. Raw OCT and OCT-A data from TOPCON DRI OCT Triton were exported using Topcon IMAGENET 6.0 software, and 3D datasets were analysed to determine retinal thickness and vessel density.

Results

Central macular thickness measurements revealed a trend of overall retinal thinning with increasing age. VD through the full thickness of the retina was highest in ETDRS sector 4 (the inferior macula) in all the cohorts. Mean VD was significantly higher in the deep capillary plexus than the superficial capillary plexus in all ETDRS sectors in all cohorts but there was no significant difference noted between groups. Choriocapillaris VD was significantly lower in all ETDRS sectors in the in the AMD group compared with the YH and the OH groups.

Conclusions

Retinal vessel density maps, derived from the retinal plexi are not reliable biomarkers for assessing the ageing macular. Our non-proprietary analysis of the vascular density of the choriocapillaris revealed a significant drop off of VD with age and disease but further work is required to corroborate this finding. If repeatable, choriocapillaris VD may provide a non-invasive biomarker of healthy ageing and disease.

Brief Summary

In this manuscript, we have studied the potential of retinal vessel density as measured by optical coherence tomography angiography (OCT-A), as a biomarker for detection of high-risk of developing exudative age-related macular degeneration (AMD).
Modeling the interplay between plastic tradeoffs and evolution in changing environments
Authors: Tikhonov Mikhail , Kachru Shamit , Fisher Daniel S.
Published: July 2019

Performance tradeoffs are ubiquitous in both ecological and evolutionary modeling, yet are usually postulated and built into fitness and ecological landscapes. But tradeoffs depend on genetic background and evolutionary history, and can themselves evolve. We present a simple model capable of capturing the key feedback loop: evolutionary history shapes tradeoff strength, which, in turn, shapes evolutionary future. One consequence of this feedback is that genomes with identical fitness can have different evolutionary properties, shaped by prior environmental exposure. Another is that, generically, the best adaptations to one environment may evolve in another. Our minimal model highlights the need for analysis of simple models capable of incorporating explicit dependence on environment, and can serve as a rich playground for investigating evolution in multiple or changing environments.
Genome Complexity Browser: estimation and visualization of prokaryote genome variability
Authors: Manolov Alexander I , Konanov Dmitry N , Fedorov Dmitry E , Osmolovsky Ivan S , Ilina Elena N
Published: July 2019

Motivation

Comparative genomics studies may be used to acquire new knowledge about chromosomal architecture - the rules to combine a set of genes in a genome of a living organism. Hundreds of thousands of prokaryote genomes were sequenced and assembled. Still, there is a lack of computational tools able to compare hundreds of genomes simultaneously, i.e. to find hotspots of genome rearrangements and horizontal gene transfer or to analyze which part of an operon is conservative and which is variable.

Results

We developed Genomic Complexity Browser (GCB), a tool that allows to visualize gene contexts in a graph form and evaluate genome variability of different parts of a prokaryotic chromosome. We introduce a measure called complexity, which is an indirect measure of genome variability. Intraspecies and interspecies comparisons reveal that regions with high complexity tend to be located in a similar context in different strains and species. While many of such hot spots are associated with prophages and pathogenicity islands, some of them lack these determinants and mechanisms that govern their dynamics are to be elucidated.

Availability

GCB is freely available as a web server athttp://gcb.rcpcm.organd as a stand-alone application athttps://github.com/DNKonanov/GCB

Contact

paraslonic@gmail.com
Emergence of B2-ST131-C2 and A-ST617 Escherichia coli clones producing both CTX-M-15- and CTX-M-27 and ST147 NDM-1 positive Klebsiella pneumoniae in the Tunisian community
Authors: Mhaya Amel , Trabelsi Rahma , Begu Dominique , Aillerie Sabine , M’zali Fatima , Tounsi Slim , Gdoura Radhouane , Arpin Corinne
Published: July 2019

CTX-M ESBLs have been increasingly reported from human enterobacteria isolates in Tunisia. NDM-1 carbapenemase was recently reported in isolates from Tunisian Hospitals. During a 2-month period (December 2017 to January 2018), we have collected 23 ESBL-producing Enterobacteriaceae (ESBL-E) from urines of patients hospitalized in three health care facilities and from community, situated in two distinct Tunisian geographical regions. They were divided into 15 Escherichia coli and eight Klebsiella pneumoniae. The aim of this study was to characterize ESBL-E with regard to their β-lactamase content and their epidemiological relationship. The results indicated a high rate (47%) of E. coli producing both CTX-M group-1 and −9. For the first time, we demonstrated the presence of E. coli having concomitantly CTX-M-15 and CTX-M-27 which belong to two sequences types (ST), ie. A-ST617 (2 isolates) and B2-ST131 subclade C2 (2 isolates). All four E. coli isolates carried a multireplicon IncF with an identical allelic combination, F31:A4:B1. This study reports also the first description of K. pneumoniae belonging to the clone ST147 carrying the carbapenemase NDM-1 in the Tunisian community. In conclusion, our data confirms the need for monitoring the resistance to extended-spectrum cephalosporins and to carbapenems among enterobacteria in Tunisia.