bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations
Authors: Aardema Heleen , Bult Wouter , van Hateren Kai , Dieperink Willem , Touw Daan J , Alffenaar Jan-Willem C , Zijlstra Jan G
Published: October 2019

Background

In critical care patients, reaching optimal β-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population.

Objectives

To assess total and unbound serum levels of cefotaxime and an active metabolite, desacetylcefotaxime, in critically ill patients treated with either continuously or intermittently dosed cefotaxime.

Methods

Adult critical care patients with indication for treatment with cefotaxime were randomized to treatment with either intermittent dosing (1 g every 6 h) or continuous dosing (4 g/24 h, after a loading dose of 1 g). We defined a preset target of reaching and maintaining a total cefotaxime concentration of 4 mg/L from 1 h after start of treatment. CCMO trial registration number NL50809.042.14, Clinicaltrials.gov NCT02560207.

Results

Twenty-nine and 30 patients, respectively, were included in the continuous dosing group and the intermittent dosing group. A total of 642 samples were available for analysis. In the continuous dosing arm, 89.3% met our preset target, compared with 50% in the intermittent dosing arm. Patients not reaching this target had a significantly higher creatinine clearance on the day of admission.

Conclusions

These results support the application of a continuous dosing strategy of β-lactams in critical care patients and the practice of therapeutic drug monitoring in a subset of patients with higher renal clearance and need for prolonged treatment for further optimization, where using total cefotaxime concentrations should suffice.
The Ins and Outs of Conceptualizing Inclusion: Theoretical and Empirical Implications for the Study of Inclusive Approaches to Governance and Peace-building
Authors: Hendrix Cullen S
Published: October 2019

In the field of global security studies, inclusion, both in terms of process and outcomes, is certainly having a moment. Like many terms widely adopted by the international security and development communities, the utility of the discourse around inclusion stems in part from its ambiguity. The various contributions to this special issue make good and productive use of this ambiguity and have moved the discussion of inclusive approaches to governance, violence reduction, and peace-building forward. In doing so, however, they have put forth very different conceptualizations and operationalizations of inclusion and exclusion. Thus, my contribution to this symposium identifies these various conceptualizations, discusses the strengths and weaknesses of proposed measures, and concludes with remarks on the normative implications of these analyses.
Speaking with one voice: simulations and observations discuss the common envelope α parameter
Authors: Iaconi Roberto , De Marco Orsola
Published: October 2019

We present a comparative study between the results of most hydrodynamic simulations of the common envelope binary interaction to date and observations of post-common envelope binaries. The goal is to evaluate whether this data set indicates the existence of a formula that may predict final separations of post-common envelope systems as a function of pre-common envelope parameters. Some of our conclusions are not surprising while others are more subtle. We find that: (i) Values of the final orbital separation derived from common envelope simulations must at this time be considered upper limits. Simulations that include recombination energy do not seem to have systematically different final separations; these and other simulations imply αCE < 0.6–1.0. At least one simulation, applicable to double-degenerate systems, implies αCE < 0.2. (ii) Despite large reconstruction errors, the post-RGB observations reconstructed parameters are in agreement with some of the simulations. The post-AGB observations behave instead as if they had a systematically lower value of αCE. The lack of common envelope simulations with low-mass AGB stars leaves us with no insight as to why this is the case. (iii) The smallest mass companion that survives the common envelope with intermediate mass giants is 0.05–0.1 M⊙. (iv) Observations of binaries with separations larger than ∼10 R⊙, tend to have high M2/M1 mass ratios and may go through a relatively long phase of unstable Roche lobe mass transfer followed by a weakened common envelope (or with no common envelope at all). (v) The effect of the spatial resolution and of the softening length on simulation results remains poorly quantified.
The exceptional X-ray evolution of SN 1996cr in high resolution
Authors: Quirola-Vásquez J , Bauer F E , Dwarkadas V V , Badenes C , Brandt W N , Nymark T , Walton D
Published: October 2019

We present X-ray spectra spanning 18 yr of evolution for SN 1996cr, one of the five nearest SNe detected in the modern era. Chandra HETG exposures in 2000, 2004, and 2009 allow us to resolve spectrally the velocity profiles of Ne, Mg, Si, S, and Fe emission lines and monitor their evolution as tracers of the ejecta-circumstellar medium interaction. To explain the diversity of X-ray line profiles, we explore several possible geometrical models. Based on the highest signal-to-noise 2009 epoch, we find that a polar geometry with two distinct opening angle configurations and internal obscuration can successfully reproduce all of the observed line profiles. The best-fitting model consists of two plasma components: (1) a mildly absorbed (2 × 1021 cm−2), cooler (≈2 keV) with high Ne, Mg, Si, and S abundances associated with a wide polar interaction region (half-opening angle ≈58°); (2) a moderately absorbed (2 × 1022 cm−2), hotter ($\gtrsim$20 keV) plasma with high Fe abundances and strong internal obscuration associated with a narrow polar interaction region (half-opening angle ≈20°). We extend this model to seven further epochs with lower signal-to-noise ratio and/or lower spectral-resolution between 2000 and 2018, yielding several interesting trends in absorption, flux, geometry, and expansion velocity. We argue that the hotter and colder components are associated with reflected and forward shocks, respectively, at least at later epochs. We discuss the physical implications of our results and plausible explosion scenarios to understand the X-ray data of SN 1996cr.
Gravity-mode period spacings and near-core rotation rates of 611 γ Doradus stars with Kepler
Authors: Li Gang , Van Reeth Timothy , Bedding Timothy R , Murphy Simon J , Antoci Victoria , Ouazzani Rhita-Maria , Barbara Nicholas H
Published: October 2019

We report our survey of γ Dor stars from the 4-yr Kepler mission. These stars pulsate mainly in g modes and r modes, showing period-spacing patterns in the amplitude spectra. The period-spacing patterns are sensitive to the chemical composition gradients and the near-core rotation, hence they are essential for understanding the stellar interior. We identified period-spacing patterns in 611 γ Dor stars. Almost every star pulsates in dipole g modes, while about 30% of stars also show clear patterns for quadrupole g modes and 16% of stars present r mode patterns. We measure periods, period spacings, and the gradient of the period spacings. These three observables guide the mode identifications and can be used to estimate the near-core rotation rate. We find many stars are hotter and show longer period-spacing patterns than theory. Using the Traditional Approximation of Rotation (TAR), we inferred the asymptotic spacings, the near-core rotation rates, and the radial orders of the g and r modes. Most stars have a near-core rotation rate around 1 d−1and an asymptotic spacing around 4000 s. We also find that many stars rotate more slowly than predicted by theory for unclear reasons. 11 stars show rotational splittings with fast rotation rates. We compared the observed slope–rotation relation with the theory and find a large spread. We detected rotational modulations in 58 stars and used them to derive the core-to-surface rotation ratios. The interiors rotate faster than the cores in most stars, but by no more than 5%.
X-ray signatures of the polar dusty gas in AGN
Authors: Liu Jiren , Hönig Sebastian F , Ricci Claudio , Paltani Stéphane
Published: October 2019

Recent mid-infrared interferometry observations of nearby active galactic nuclei (AGN) revealed that a significant part of the dust emission extends in the polar direction, rather than the equatorial torus/disc direction as expected by the traditional unification model. We study the X-ray signatures of this polar dusty gas with ray-tracing simulations. Different from those from the ionized gas, the scattered emission from the polar dusty gas produces self-absorption and neutral-like fluorescence lines, which are potentially a unique probe of the kinematics of the polar dusty gas. The anomalously small Fe Kα/Si Kα ratios of type 2 AGN observed previously can be naturally explained by the polar dusty gas, because the polar emission does not suffer from heavy absorption by the dense equatorial gas. The observed Si Kα lines of the Circinus galaxy and NGC 1068 show blueshifts with respect to the systemic velocities of the host galaxies, consistent with an outflowing scenario of the Si Kα-emitting gas. The 2.5–3 keV image of the Circinus galaxy is elongated along the polar direction, consistent with an origin of the polar gas. These results show that the polar-gas-scattered X-ray emission of type 2 AGN is an ideal objective for future X-ray missions, such as Athena.
A GMRT 150 MHz search for variables and transients in Stripe 82
Authors: Hajela A , Mooley K P , Intema H T , Frail D A
Published: October 2019

We have carried out a dedicated transient survey of 300 deg2 of the SDSS Stripe 82 region using the Giant Metrewave Radio Telescope (GMRT) at 150 MHz. Our multi-epoch observations, together with the TGSS survey, allow us to probe variability and transient activity on four different time-scales, beginning with 4 h and up to 4 yr. Data calibration, RFI flagging, source finding, and transient search were carried out in a semi-automated pipeline incorporating the SPAM recipe. This has enabled us to produce superior-quality images and carry out reliable transient search over the entire survey region in under 48 h post-observation. Among the few thousand unique point sources found in our 5σ single-epoch catalogues (flux density thresholds of about 24, 20, 16, and 18 mJy on the respective time-scales), we find <0.08 per cent, 0.01 per cent, <0.06 per cent, and 0.05 per cent to be variable (beyond a significance of 4σ and fractional variability of 30 per cent) on time-scales of 4 h, 1 d, 1 month, and 4 yr, respectively. This is substantially lower than that in the GHz sky, where ∼1 per cent of the persistent point sources are found to be variable. Although our survey was designed to probe a superior part of the transient phase space, our transient search did not yield any significant candidates. The transient (preferentially extragalactic) rate at 150 MHz is therefore <0.005 on time-scales of 1 month and 4 yr, and <0.002 on time-scales of 1 d and 4 h, beyond 7σ detection threshold. We put these results in perspective with the previous studies and give recommendations for future low-frequency transient surveys.
A simplified model for the secular dynamics of eccentric discs and applications to planet–disc interactions
Authors: Teyssandier Jean , Lai Dong
Published: October 2019

We develop a simplified model for studying the long-term evolution of giant planets in protoplanetary discs. The model accounts for the eccentricity evolution of the planets and the dynamics of eccentric discs under the influences of secular planet–disc interactions and internal disc pressure, self-gravity, and viscosity. Adopting the ansatz that the disc precesses coherently with aligned apsides, the eccentricity evolution equations of the planet–disc system reduce to a set of linearized ordinary differential equations, which allows for fast computation of the evolution of planet–disc eccentricities over long time-scales. Applying our model to ‘giant planet + external disc’ systems, we are able to reproduce and explain the secular behaviours found in previously published hydrodynamical simulations. We re-examine the possibility of eccentricity excitation (due to secular resonance) of multiple planets embedded in a dispersing disc, and find that taking into account the dynamics of eccentric discs can significantly affect the evolution of the planets’ eccentricities.
Gas accretion and galactic fountain flows in the Auriga cosmological simulations: angular momentum and metal redistribution
Authors: Grand Robert J J , van de Voort Freeke , Zjupa Jolanta , Fragkoudi Francesca , Gómez Facundo A , Kauffmann Guinevere , Marinacci Federico , Pakmor Rüdiger , Springel Volker , White Simon D M
Published: October 2019

Using a set of 15 high-resolution magnetohydrodynamic cosmological simulations of Milky Way formation, we investigate the origin of the baryonic material found in stars at redshift zero. We find that roughly half of this material originates from subhalo/satellite systems and half is smoothly accreted from the intergalactic medium. About $90 {{\ \rm per\ cent}}$ of all material has been ejected and re-accreted in galactic winds at least once. The vast majority of smoothly accreted gas enters into a galactic fountain that extends to a median galactocentric distance of ∼20 kpc with a median recycling time-scale of ∼500 Myr. We demonstrate that, in most cases, galactic fountains acquire angular momentum via mixing of low angular momentum, wind-recycled gas with high angular momentum gas in the circumgalactic medium (CGM). Prograde mergers boost this activity by helping to align the disc and CGM rotation axes, whereas retrograde mergers cause the fountain to lose angular momentum. Fountain flows that promote angular momentum growth are conducive to smooth evolution on tracks quasi-parallel to the disc sequence of the stellar mass-specific angular momentum plane, whereas retrograde minor mergers, major mergers, and bar-driven secular evolution move galaxies towards the bulge sequence. Finally, we demonstrate that fountain flows act to flatten and narrow the radial metallicity gradient and metallicity dispersion of disc stars, respectively. Thus, the evolution of galactic fountains depends strongly on the cosmological merger history and is crucial for the chemodynamical evolution of Milky-Way-sized disc galaxies.
Cosmological test of gravity using weak lensing voids
Authors: Davies Christopher T , Cautun Marius , Li Baojiu
Published: October 2019

Modifications to general relativity often incorporate screening mechanisms in order to remain compatible with existing tests of gravity. The screening is less efficient in underdense regions, which suggests that cosmic voids can be a useful cosmological probe for constraining modified gravity models. In particular, weak lensing by voids has been proposed as a promising test of such theories. Usually, voids are identified from galaxy distributions, making them biased tracers of the underlying matter field. An alternative approach is to study voids identified in weak lensing maps – weak lensing voids – which have been shown to better correspond to true underdense regions. In this paper, we study the ability of weak lensing voids to detect the signatures of modified gravity. Focusing on the void abundance and weak lensing profiles, we find that both statistics are sensitive probes of gravity. These are quantified in terms of the signal-to-noise ratios (SNR) with which an LSST-like survey will be able to distinguish between different gravity models. We find that the tangential shear profiles of weak lensing voids are considerably better than galaxy voids at this, though voids have somewhat lower SNR than weak lensing peaks. The abundances of voids and peaks have, respectively, $\rm {SNR} = 50$ and 70 for a popular class of modified gravity in an LSST-like survey.
Inactivation of folylpolyglutamate synthetase Met7 results in genome instability driven by an increased dUTP/dTTP ratio
Authors: Schmidt Tobias T , Sharma Sushma , Reyes Gloria X , Kolodziejczak Anna , Wagner Tina , Luke Brian , Hofer Anders , Chabes Andrei , Hombauer Hans
Published: October 2019

The accumulation of mutations is frequently associated with alterations in gene function leading to the onset of diseases, including cancer. Aiming to find novel genes that contribute to the stability of the genome, we screened the Saccharomyces cerevisiae deletion collection for increased mutator phenotypes. Among the identified genes, we discovered MET7, which encodes folylpolyglutamate synthetase (FPGS), an enzyme that facilitates several folate-dependent reactions including the synthesis of purines, thymidylate (dTMP) and DNA methylation. Here, we found that Met7-deficient strains show elevated mutation rates, but also increased levels of endogenous DNA damage resulting in gross chromosomal rearrangements (GCRs). Quantification of deoxyribonucleotide (dNTP) pools in cell extracts from met7Δ mutant revealed reductions in dTTP and dGTP that cause a constitutively active DNA damage checkpoint. In addition, we found that the absence of Met7 leads to dUTP accumulation, at levels that allowed its detection in yeast extracts for the first time. Consequently, a high dUTP/dTTP ratio promotes uracil incorporation into DNA, followed by futile repair cycles that compromise both mitochondrial and nuclear DNA integrity. In summary, this work highlights the importance of folate polyglutamylation in the maintenance of nucleotide homeostasis and genome stability.
ChimerDB 4.0: an updated and expanded database of fusion genes
Authors: Jang Ye Eun , Jang Insu , Kim Sunkyu , Cho Subin , Kim Daehan , Kim Keonwoo , Kim Jaewon , Hwang Jimin , Kim Sangok , Kim Jaesang , Kang Jaewoo , Lee Byungwook , Lee Sanghyuk
Published: October 2019

Fusion genes represent an important class of biomarkers and therapeutic targets in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data (ChimerSeq) and text mining of publications (ChimerPub) with extensive manual annotations (ChimerKB). In this update, we present all three modules substantially enhanced by incorporating the recent flood of deep sequencing data and related publications. ChimerSeq now covers all 10 565 patients in the TCGA project, with compilation of computational results from two reliable programs of STAR-Fusion and FusionScan with several public resources. In sum, ChimerSeq includes 65 945 fusion candidates, 21 106 of which were predicted by multiple programs (ChimerSeq-Plus). ChimerPub has been upgraded by applying a deep learning method for text mining followed by extensive manual curation, which yielded 1257 fusion genes including 777 cases with experimental supports (ChimerPub-Plus). ChimerKB includes 1597 fusion genes with publication support, experimental evidences and breakpoint information. Importantly, we implemented several new features to aid estimation of functional significance, including the fusion structure viewer with domain information, gene expression plot of fusion positive versus negative patients and a STRING network viewer. The user interface also was greatly enhanced by applying responsive web design. ChimerDB 4.0 is available at http://www.kobic.re.kr/chimerdb/.
Frequent template switching in postreplication gaps: suppression of deleterious consequences by the Escherichia coli Uup and RadD proteins
Authors: Romero Zachary J , Armstrong Thomas J , Henrikus Sarah S , Chen Stefanie H , Glass David J , Ferrazzoli Alexander E , Wood Elizabeth A , Chitteni-Pattu Sindhu , van Oijen Antoine M , Lovett Susan T , Robinson Andrew , Cox Michael M
Published: October 2019

When replication forks encounter template DNA lesions, the lesion is simply skipped in some cases. The resulting lesion-containing gap must be converted to duplex DNA to permit repair. Some gap filling occurs via template switching, a process that generates recombination-like branched DNA intermediates. The Escherichia coli Uup and RadD proteins function in different pathways to process the branched intermediates. Uup is a UvrA-like ABC family ATPase. RadD is a RecQ-like SF2 family ATPase. Loss of both functions uncovers frequent and RecA-independent deletion events in a plasmid-based assay. Elevated levels of crossing over and repeat expansions accompany these deletion events, indicating that many, if not most, of these events are associated with template switching in postreplication gaps as opposed to simple replication slippage. The deletion data underpin simulations indicating that multiple postreplication gaps may be generated per replication cycle. Both Uup and RadD bind to branched DNAs in vitro. RadD protein suppresses crossovers and Uup prevents nucleoid mis-segregation. Loss of Uup and RadD function increases sensitivity to ciprofloxacin. We present Uup and RadD as genomic guardians. These proteins govern two pathways for resolution of branched DNA intermediates such that potentially deleterious genome rearrangements arising from frequent template switching are averted.
Why is the American South Poorer?
Authors: Baker Regina S
Published: October 2019

While American poverty research has devoted greater attention to poverty in the Northeast and Midwest, poverty has been persistently higher in the U.S. South than in the other regions. Thus, this study investigates the enduring question of why poverty is higher in the South. Specifically, it demonstrates the role of power resources as an explanation for this regional disparity, yet also considers family demography, economic structure, and racial/ethnic heterogeneity. Using six waves (2000–2016) of U.S. Census Current Population Survey data from the Luxembourg Income Study (N = 1,157,914), this study employs a triangulation of analytic techniques: (1) tests of means and proportion differences, (2) multilevel linear probability models of poverty, and (3) binary decomposition of the South/non-South poverty gap. The comparison of means associated with the power resource hypothesis yields the largest substantive differences between the South and the non-South. In the multilevel models, adjusting for power resources yields the largest declines in the South coefficient. Binary decomposition results indicate power resources are the second most influential factor explaining the South/non-South poverty gap. Overall, power resources are an important source of the South/non-South poverty gap, though economic structure and other factors certainly also play a role. Results also suggest an important interplay between power resources and race. Altogether, these results underscore the importance of macrolevel characteristics of places, including political and economic contexts, in shaping individual poverty and overall patterns of inequality.
Predator and prey detection in two species of water bear (Tardigrada)
Authors: Meyer Harry A , Larsen Hannah E , Akobi Nézira O , Broussard Garret
Published: October 2019

Tardigrade behavioural studies have focused on responses to abiotic environmental conditions. Predator–prey interactions have received some attention, but not how predators and prey might detect one another. Here, we investigate whether a predatory tardigrade species is attracted to, and a potential prey tardigrade avoids, areas previously occupied by the other. In our experiments, Milnesium lagniappe was the predator and Macrobiotus acadianus the prey. Petri dishes with non-nutrient agar were used as experimental arenas. In one treatment, we allowed Macrobiotus to roam over half of the agar for 20 h, while leaving the other half free of Macrobiotus. We then removed the prey and introduced the predator. In the control treatment, no prey were added. Results indicated that Milnesium individuals were significantly concentrated in the area previously occupied by Macrobiotus, whereas no such concentration was evident when Macrobiotus had not been present. A similar protocol was used to test whether Macrobiotus avoided areas previously occupied by the predator. As expected, Macrobiotus were significantly concentrated in the area never occupied by Milnesium, unlike the control treatment. These results suggest that both species can detect the other without physical contact and react accordingly. Given that the experiments were conducted in darkness, detection is probably olfactory.
Determining nicotine-related behavior changes in juvenile female rats through long-term maternal nicotine exposure
Authors: Jang Minji , Jung Taesub , Kim Woonhee , Kim Inyong , Jeong Yoonhwa , Noh Jihyun
Published: October 2019

Nicotine replacement therapy (NRT) has been developed as a drug therapy for smoking cessation and has been considered a safe alternative to smoking during pregnancy. However, the effects of long-term nicotine exposure via NRT on the fetus are still being debated. Here, we determined the effects of long-term maternal nicotine exposure in gestation and lactation on nicotine-related behavior and drug vulnerability in dams and offspring rats. To expose long-term nicotine, on gestation day 14, pregnant rats were implanted with osmotic minipumps releasing nicotine tartrate (6 mg/kg/day, subcutaneously, equivalent to 2 mg nicotine-freebase) for 28 days. The concentration of cotinine in blood was 373.0 ± 109.0 ng/ml in dams and 12.50 ± 1.19 ng/ml in offspring rats. In dams, we found no significant differences in anxiety-like behaviors and various maternal behaviors such as touching, sniffing, pup licking, laying on pups, and retrieval between saline- and nicotine-exposed groups. Adolescent offspring female rats showed no significant differences in anxiety-like behavior and forced alcohol consumption between saline- and nicotine-exposed groups. Nicotine-exposed offspring rats showed more increased nicotine aversion than saline-exposed groups, but the effect was disturbed in the forced alcohol consumption condition on the first day of the nicotine consumption test. Taken together, these results suggest that, in the last gestation and lactation period corresponding to the second and third trimester of human pregnancy, long-term maternal nicotine exposure has a minor effect on dam and female offspring health and does not involve serious pathological changes in rat offspring, despite the presence of nicotine in their blood.
An online cognitive bias task: the Rough Estimation Task using Qualtrics
Authors: Wilcockson Thomas D.W. , Emmanuel M. Pothos , Cox W. Miles
Published: October 2019

Measurement of cognitive bias typically relies on laboratory-based tasks. In order for cognitive bias measures to be useful outside of laboratory settings, a simple measure is required which does not rely on precise measurement tools, for example, precise reaction time measurement (which can be done only with specialized software typically running through either dedicated hardware or specifically configured computers). The Rough Estimation Task is a simple reading task which has been previously shown to be an effective measure of alcohol-related cognitive bias. We conducted an online version of the Rough Estimation Task, so that we could measure cognitive bias away from a laboratory environment. We also measured whether baseline Rough Estimation Task scores could predict future drinking and Rough Estimation Task scores. A sample of undergraduate participants completed the study online. We found that the online Rough Estimation Task was associated with both current and future drinking, as measured in a follow-up online task. The results imply that the online Rough Estimation Task could be used as a simple online measure of cognitive bias for both concurrent and future drinking behavior, and so raises hope for employing this measure outside of laboratory settings and possibly even in clinical applications.
Two simple criteria to estimate an objective’s performance when imaging in non design tissue clearing solutions
Authors: Asteriti Sabrina , Ricci Valeria , Cangiano Lorenzo
Published: October 2019

Tissue clearing techniques are undergoing a renaissance motivated by the need to image fluorescence deep in biological samples without physical sectioning. Optical transparency is achieved by equilibrating tissues with high refractive index (RI) solutions, which require expensive optimized objectives to avoid aberrations. One may thus need to assess whether an available objective is suitable for a specific clearing solution, or the impact on imaging of small mismatches between cleared sample and objective design RIs. We derived closed form approximations for image quality degradation versus RI mismatch and other parameters available to the microscopist. We validated them with computed (and experimentally confirmed) aberrated point spread functions, and by imaging fluorescent neurons in high RI solutions. Crucially, we propose two simple numerical criteria to establish: (i) the degradation in image quality (brightness and resolution) from optimal conditions of any clearing solution/objective combination; (ii) which objective, among several, achieves the highest resolution in a given immersion medium. These criteria apply directly to the widefield fluorescent microscope but are also closely relevant to more advanced microscopes.
Cerebellar-recipient motor thalamus drives behavioral context-specific movement initiation
Authors: Dacre Joshua , Colligan Matt , Ammer Julian , Schiemann Julia , Clarke Thomas , Chamosa-Pino Victor , Claudi Federico , Harston J. Alex , Eleftheriou Constantinos , Pakan Janelle M.P. , Huang Cheng-Chiu , Hantman Adam , Rochefort Nathalie L. , Duguid Ian
Published: October 2019

To initiate goal-directed behavior, animals must transform sensory cues into motor commands that generate appropriately timed actions. Sensorimotor transformations along the cerebellar-thalamocortical pathway are thought to shape motor cortical output and movement timing, but whether this pathway initiates goal-directed movement remains poorly understood. Here, we recorded and perturbed activity in cerebellar-recipient regions of motor thalamus (dentate / interpositus nucleus-recipient regions, MThDN/IPN) and primary motor cortex (M1) in mice trained to execute a cued forelimb lever push task for reward. MThDN/IPN population responses were dominated by a time-locked increase in activity immediately prior to movement that was temporally uncoupled from cue presentation, providing a fixed latency feedforward motor timing signal to M1FL. Blocking MThDN/IPN output suppressed cued movement initiation. Stimulating the MThDN/IPN thalamocortical pathway in the absence of the cue recapitulated cue-evoked M1 membrane potential dynamics and forelimb behavior in the learned behavioral context, but generated semi-random movements in an altered behavioral context. Thus, cerebellar-recipient motor thalamocortical input to M1 is indispensable for the generation of motor commands that initiate goal-directed movement, refining our understanding of how the cerebellar-thalamocortical pathway contributes to movement timing.
Deletion of M-opsin prevents “M cone” degeneration in a mouse model of Leber congenital amaurosis
Authors: Xu Hui , Enemchukwu Nduka , Zhong Xiaoyue , Zhang Olivia , Fu Yingbin
Published: October 2019

Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal synthesis and cause Leber congenital amaurosis (LCA). In Lrat−/− mouse model, mislocalized medium (M)-wavelength sensitive opsin was degraded whereas mislocalized short (S)-wavelength sensitive opsin accumulated before the onset of cone degeneration. The mechanism for the foveal medium (M)/long (L)-wavelength-sensitive cone degeneration in LCA is unknown. By crossing Lrat−/− mice with a proteasome reporter mouse line, we showed that M-opsin enriched dorsal cones in Lrat−/− mice exhibit proteasome stress due to the degradation of large amounts of M-opsin. Deletion of M-opsin relieves the proteasome stress and completely prevents “M cone” degeneration in Lrat−/−Opn1sw−/− mice (a pure “M cone” LCA model, Opn1sw−/− encoding S-opsin) for at least 12 months. Our results suggest that M-opsin degradation associated proteasome stress plays a major role in “M cone” degeneration in Lrat−/− model. This finding may represent a general mechanism for “M cone” degeneration for multiple forms of cone degeneration due to M-opsin mislocalization and degradation. Our results have important implications for the current gene therapy strategy for LCA that emphasizes the need for a combinatorial therapy to both improve vision and slow photoreceptor degeneration.
Distribution of members of the Anopheles gambiae complex in selected forested tourist areas of Cross River State, Nigeria
Authors: Oduwole OA , Oduola AO , Oringanje CM , Nwachuku NS , Meremikwu MM , Useh MF , Alaribe AAA
Published: October 2019

Background

The Anopheles gambiae mosquitoes are the most abundant, efficient and widely distributed vectors of the malaria parasite in sub-Saharan Africa. In most African countries, where malaria control programmes are focused on the use of long-lasting insecticide treated bed net, there is need to evaluate the biting behaviour and the identity of such mosquitoes to determine the relevance and appropriateness of the control measure implemented.

Method

This study investigated the distribution and molecular characteristics of the Anopheles species in selected forested areas in Cross River State, Nigeria. Mosquitoes were collected using pyrethrum spray catch and Centre for Disease Control light traps modified with yeast and sugar to generate carbon dioxide (CO2). Anopheles gambiae complex was identified using multiplex polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) for molecular forms characterization.

Results

One hundred and four Anopheles gambiae s.l. were collected during the study. Multiplex PCR showed 75% of the species complex were A. gambiae s.s. and further characterization using PCR-RFLP showed that 53.8% of the A. gambiae s.l. identified were A. gambiae s.s.while 24.4% were A.coluzzii. The two species of the A. gambiae s.l. were found to be most abundant. The study also reported a 1.3% hybrid form of Anopheles gambiae s.s.and Anopheles coluzzii.

Conclusion

The findings suggest the first documented evidence of hybrid forms of A. gambiae s.s./A.coluzzii in South Eastern Nigeria although its epidemiological implication is still not clear.
miR-181a Regulates p62/SQSTM1, Parkin and Protein DJ-1 Promoting Mitochondrial Dynamics in Skeletal Muscle Ageing
Authors: Goljanek-Whysall Katarzyna , Soriano-Arroquia Ana , McCormick Rachel , Chinda Caroline , McDonagh Brian
Published: October 2019

One of the key mechanisms underlying skeletal muscle functional deterioration during ageing is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria, however the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during ageing concomitant with dysregulation of miR-181a target interactions. Using functional approaches and mitoQc assay, we have established that miR-181a is an endogenous regulator of mitochondrial dynamics through concerted regulation of Park2, p62/SQSTM1 and DJ-1 in vitro. Downregulation of miR-181a with age was associated with an accumulation of autophagy-related proteins and abnormal mitochondria. Restoring miR-181a levels in old mice prevented accumulation of p62, DJ-1 and PARK2, improved mitochondrial quality and muscle function. These results provide physiological evidence for the potential of microRNA-based interventions for age-related muscle atrophy and of wider significance for diseases with disrupted mitochondrial dynamics.
Novel step selection analyses on energy landscapes reveal how linear features alter migrations of soaring birds
Authors: Eisaguirre Joseph M. , Booms Travis L. , Barger Christopher P. , Lewis Stephen B. , Breed Greg A.
Published: October 2019

Human modification of landscapes includes extensive addition of linear features, such as roads and transmission lines. These can alter animal movement and space use and affect the intensity of interactions among species, including predation and competition. Effects of linear features on animal movement have seen relatively little research in avian systems, despite ample evidence of their effects in mammalian systems and that some types of linear features, including both roads and transmission lines, are substantial sources of mortality. Here, we used satellite telemetry combined with step-selection functions designed to explicitly incorporate the energy landscape (el-SSFs) to investigate the effects of linear features and habitat on movements and space use of a large soaring bird, the golden eagleAquila chrysaetos, during migration. Our sample consisted of 32 adult eagles tracked for 45 spring and 39 fall migrations from 2014-2017. Fitted el-SSFs indicated eagles had a strong general preference for south-facing slopes, where thermal uplift develops predictably, and that these areas are likely important aspects of migratory pathways. el-SSFs also revealed that roads and railroads affected movement during both spring and fall migrations, but eagles selected areas near roads to a greater degree in spring compared to fall and at higher latitudes compared to lower latitudes. During spring, time spent near linear features often occurred during slower-paced or stopover movements, perhaps in part to access carrion produced by vehicle collisions. Regardless of the behavioral mechanism of selection, use of these features could expose eagles and other soaring species to elevated risk via collision with vehicles and/or transmission lines. Linear features have been previously documented to affect the ecology of terrestrial species (e.g., large mammals) by modifying individuals’ movement patterns; our work shows these effects on movement extend to avian taxa.
Inhibition of ATR Reverses a Mitochondrial Respiratory Insufficiency
Authors: Borror Megan B. , Girotti Milena , Kar Adwitiya , Cain Meghan , Gao Xiaoli , MacKay Vivian L. , Herron Brent , Bhaskaran Shylesh , Becerra Sandra , Novy Nate , Ventura Natascia , Johnson Thomas E. , Kennedy Brian K. , Rea Shane L.
Published: October 2019

Diseases that affect the mitochondrial electron transport chain (ETC) often manifest as threshold effect disorders, meaning patients only become symptomatic once a certain level of ETC dysfunction is reached. Multiple processes work to control proximity to the critical ETC threshold and as a consequence there can be significant variability in disease presentation among patients. Identification of such control processes remains an ongoing goal. Checkpoint signaling comprises a collection of alert mechanisms activated in cells in response to nuclear DNA damage. Well-defined hierarchies of proteins are involved in both sensing and signaling DNA damage, with ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) acting as pivotal signaling kinases. In the nematode C. elegans, severe reduction of mitochondrial ETC activity shortens life, as in humans, but mild reduction extends life as a consequence of survival strategies that are invoked under these circumstances. Here we show that removal of ATL-1, the worm ortholog of ATR, unexpectedly lessens the severity of ETC dysfunction, but removal of ATM does not. Multiple genetic and biochemical tests show no evidence for increased mutation or DNA breakage in animals exposed to ETC disruption. Instead, we find that reduced ETC function alters nucleotide ratios within both the ribo- and deoxyribo-nucleotide pools, and causes stalling of RNA polymerase, which is also known to activate ATR. Unexpectedly, atl-1 mutants confronted with mitochondrial ETC disruption maintain normal levels of oxygen consumption and have an increased abundance of translating ribosomes. This suggests checkpoint signaling by ATL-1 normally dampens cytoplasmic translation. Taken together, our data suggests a model whereby ETC insufficiency in C. elegans results in nucleotide imbalances leading to stalling of RNA polymerase, activation of ATL-1, dampening of global translation and magnification of ETC dysfunction. Loss of ATL-1 effectively reverses the severity of ETC disruption so that animals become phenotypically closer to wild type.
Demonstration of altruistic behaviour in rats
Authors: Das Ushnik , Kumari Anshu , Sharma Shruthi , Rao Laxmi T.
Published: October 2019

A pilot study demonstrating complex cognitive abilities of altruism in rats by observing if rats would voluntarily put themselves in distress solely in order to help another conspecific irrespective of kinship and without any expectation of reward in terms of food or mate in return.
Tunings for leapfrog integration of Hamiltonian Monte Carlo for estimating genetic parameters
Authors: Arakawa Aisaku , Hayashi Takeshi , Taniguchi Masaaki , Mikawa Satoshi , Nishio Motohide
Published: October 2019

A Hamiltonian Monte Carlo algorithm is a Markov Chain Monte Carlo method that is considered more effective than the conventional Gibbs sampling method. Hamiltonian Monte Carlo is based on Hamiltonian dynamics, and it follows Hamilton’s equations, which are expressed as two differential equations. In the sampling process of Hamiltonian Monte Carlo, a numerical integration method called leapfrog integration is used to approximately solve Hamilton’s equations, and the integration is required to set the number of discrete time steps and the integration stepsize. These two parameters require some amount of tuning and calibration for effective sampling. In this study, we applied the Hamiltonian Monte Carlo method to animal breeding data and identified the optimal tunings of leapfrog integration for normal and inverse chi-square distributions. Then, using real pig data, we revealed the properties of the Hamiltonian Monte Carlo method with the optimal tuning by applying models including variance explained by pedigree information or genomic information. Compared with the Gibbs sampling method, the Hamiltonian Monte Carlo method had superior performance in both models. We have provided the source codes of this method written in the R language.
A meta-analysis of global avian survival across species and latitude
Authors: Scholer Micah N. , Strimas-Mackey Matt , Jankowski Jill E.
Published: October 2019

Tropical birds are purported to be longer lived than temperate species of similar size, but it has not been shown whether avian survival rates covary with a latitudinal gradient worldwide. Here, we perform a global-scale meta-analysis to investigate the extent of the latitudinal survival gradient. We modeled survival as a function of latitude for the separate northern and southern hemispheres, and considered phylogenetic relationships and extrinsic (climate) and intrinsic (life history) predictors hypothesized to moderate these effects. Using a database of 1,004 estimates from 246 studies of avian survival, we demonstrate that in general a latitudinal survival gradient exists in the northern hemisphere, is dampened or absent for southern hemisphere species, and that survival rates of passerine birds largely account for these trends. We found no indication that the extrinsic climate factors were better predictors of survival than latitude alone, but including species’ intrinsic traits improved model predictions. Notably, species with smaller clutch size and larger body mass showed higher survival. Our results illustrate that while some tropical birds may be longer lived than their temperate counterparts, the shape of the latitude-survival gradient differs by geographic region and is strongly influenced by species’ intrinsic traits.
Automating the analysis of fish abundance using object detection: optimising animal ecology with deep learning
Authors: Ditria Ellen M. , Lopez-Marcano Sebastian , Sievers Michael K. , Jinks Eric L. , Brown Christopher J. , Connolly Rod M.
Published: October 2019

Aquatic ecologists routinely count animals to provide critical information for conservation and management. Increased accessibility to underwater recording equipment such as cameras and unmanned underwater devices have allowed footage to be captured efficiently and safely. It has, however, led to immense volumes of data being collected that require manual processing, and thus significant time, labour and money. The use of deep learning to automate image processing has substantial benefits, but has rarely been adopted within the field of aquatic ecology. To test its efficacy and utility, we compared the accuracy and speed of deep learning techniques against human counterparts for quantifying fish abundance in underwater images and video footage. We collected footage of fish assemblages in seagrass meadows in Queensland, Australia. We produced three models using a MaskR-CNN object detection framework to detect the target species, an ecologically important fish, luderick (Girella tricuspidata). Our models were trained on three randomised 80:20 ratios of training:validation data-sets from a total of 6,080 annotations. The computer accurately determined abundance from videos with high performance using unseen footage from the same estuary as the training data (F1 = 92.4%, mAP50 = 92.5%), and from novel footage collected from a different estuary (F1 = 92.3%, mAP50 = 93.4%). The computer’s performance in determining MaxN was 7.1% better than human marine experts, and 13.4% better than citizen scientists in single image test data-sets, and 1.5% and 7.8% higher in video data-sets, respectively. We show that deep learning is a more accurate tool than humans at determining abundance, and that results are consistent and transferable across survey locations. Deep learning methods provide a faster, cheaper and more accurate alternative to manual data analysis methods currently used to monitor and assess animal abundance. Deep learning techniques have much to offer the field of aquatic ecology.
Environmental correlates of the European common toad hybrid zone
Authors: Arntzen Jan W. , Canestrelli Daniele , Martínez-Solano Iñigo
Published: October 2019

The interplay between intrinsic (development, physiology, behavior) and extrinsic (landscape features, climate) factors determines the outcome of admixture processes in hybrid zones, in a continuum from complete genetic merger to full reproductive isolation. Here we assess the role of environmental correlates in shaping admixture patterns in the long hybrid zone formed by the toadsBufo bufoandB. spinosusin western Europe. We used species-specific diagnostic SNP markers to genotype 6584 individuals from 514 localities to describe the contact zone and tested for association with topographic, bioclimatic and land use variables. Variables related to temperature and precipitation contributed to accurately predict the distribution of pure populations of each species, but the models did not perform well in areas where genetically admixed populations occur. A sliding window approach proved useful to identify different sets of variables that are important in different sections of this long and heterogeneous hybrid zone, and offers good potential to predict the fate of moving contact zones in global change scenarios.