bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term study of reservoir cascade in south-eastern Brazil reveals spatio-temporal gradient in fish assemblages
Authors: Loures Raquel Coelho , Pompeu Paulo Santos
Published: September 2018

In reservoir cascades, effects on fish assemblages are expected to strengthen over time and transfer from one reservoir to an adjacent one. To test this, fish-assemblage data from 23 years of monitoring in the Araguari reservoir cascade system, upper Paraná River basin, were analysed. The results showed a clear reduction in richness of native and migratory fish species and an increase of non-native species, following reservoir formation. Migratory species richness was higher in reservoirs that presented habitats similar to lotic stretches or tributaries upstream of the impounded area. There was a clear tendency for native species to decline and non-native fish species to increase, in a downstream direction. Fish assemblages became increasingly dissimilar as reservoirs became more distant from each other (longitudinal gradient) and were dominated by small and medium-sized species. Alongside longitudinal position, reservoir area, age and the presence of herbivorous non-native fish were found to be important predictors of variation in fish-assemblage structure. Results from the present study help clarify the potential accumulated impacts of reservoir cascades on fish diversity, which must be carefully considered in river-basin inventories for hydropower plants, and reinforce the importance of long-term monitoring, considering longitudinal and lateral dimensions of the basin.
Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus
Authors: Wu Yu-Er , Enoki Ryosuke , Oda Yoshiaki , Huang Zhi-Li , Honma Ken-ichi , Honma Sato
Published: September 2018

Significance

Despite that the various functions in mammals fluctuate in the ultradian fashion, the origin and mechanism of the rhythm are largely unknown. In this study, we found synchronous ultradian calcium rhythms in the hypothalamic paraventricular nucleus (PVN), subparaventricular zone (SPZ), and suprachiasmatic nucleus (SCN). The ultradian rhythms were originated from the SPZ-PVN region and transmitted to the SCN. Neurochemical interventions revealed that the glutamatergic mechanism is critical for generation and a tetrodotoxin-sensitive neural network for synchrony of the ultradian rhythm. The GABAergic system could have a role in refining the circadian output signals. The study provides the first clue to understand the loci and mechanism of ultradian rhythm in the hypothalamus.
Identification of cell populations necessary for leaf-to-leaf electrical signaling in a wounded plant
Authors: Nguyen Chi Tam , Kurenda Andrzej , Stolz Stéphanie , Chételat Aurore , Farmer Edward E.
Published: September 2018

Significance

Numerous modes of long-distance electrical signaling exist in nature. The best known of these, axonal conduction, requires one primary cell population, i.e., neurons. In contrast, the cell types that mediate leaf-to-leaf electrical signaling in wounded plants have not been defined rigorously. Using genetic approaches, we find that two distinct populations of cells in the vasculature matrix are needed to perform this function. Surprisingly, these cells do not contact each other directly. As we further defined the plant wound response, we found that wound-induced membrane depolarizations preceded large intravasculature calcium fluxes. We reveal a two-cell-type mode of electrical signaling in leaves and discuss parallels and differences in electrical signaling outside the plant kingdom.
GIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine-induced locomotor sensitization
Authors: Rifkin Robert A. , Huyghe Deborah , Li Xiaofan , Parakala Manasa , Aisenberg Erin , Moss Stephen J. , Slesinger Paul A.
Published: September 2018

Significance

Activation of G protein-gated inwardly rectifying potassium (GIRK) channels inhibits neuronal activity in the brain, but details are lacking on how this important pathway influences neural circuits in the reward pathway. Here, we provide an example of where control of trafficking of GIRK channels by a cytoplasmic protein, sorting nexin 27, determines the sensitivity of mice to cocaine in a model of addiction known as locomotor sensitization. These results implicate GIRK channels as a therapeutic target for treating addiction, as well as other psychiatric disorders involving dopamine dysregulation.
Designing a century ahead: climate change adaptation in the Dutch Delta
Authors: Bloemen Pieter , Van Der Steen Martijn , Van Der Wal Zeger
Published: September 2018

This article examines policy capacity for dealing with the effects of climate change. The case under study is the Delta Program in the Netherlands; a large-scale policy program to prepare the country for current and anticipated effects of climate change that runs until 2050. Using a qualitative case study approach, we examine how the actors involved design analytical capacity, operational capacity and political capacity to deal with the uncertainty and complexity that are inherent in this policy field. The context of climate change necessitates policy capacity that anticipates effects that are in themselves uncertain and ambiguous, span over decades of time, and involve many stakeholders. Our analysis shows how policy capacity was designed to allow for present-day interventions, while also enabling adaptation to new and emerging developments overtime. We conclude our article with theoretical and practical lessons about policy capacity for dealing with long-term uncertainty and complexity.
Cargo regulates clathrin-coated pit invagination via clathrin light chain phosphorylation
Authors: Maib Hannes , Ferreira Filipe , Vassilopoulos Stéphane , Smythe Elizabeth
Published: September 2018

Clathrin light chains (CLCs) control selective uptake of a range of G protein–coupled receptors (GPCRs), although the mechanism by which this occurs has remained elusive thus far. In particular, site-specific phosphorylation of CLCb controls the uptake of the purinergic GPCR P2Y12, but it is dispensable for the constitutive uptake of the transferrin receptor (TfR). We demonstrate that phosphorylation of CLCb is required for the maturation of clathrin-coated pits (CCPs) through the transition of flat lattices into invaginated buds. This transition is dependent on efficient clathrin exchange regulated by CLCb phosphorylation and mediated through auxilin. Strikingly, this rearrangement is required for the uptake of P2Y12 but not TfR. These findings link auxilin-mediated clathrin exchange to early stages of CCP invagination in a cargo-specific manner. This supports a model in which CCPs invaginate with variable modes of curvature depending on the cargo they incorporate.
Tatsushi Igaki: Flying up the research summits
Authors: O’Donnell Marie Anne
Published: September 2018

Igaki explores how cell–cell communication directs tissue and tumor development.
Powerful and efficient SNP-set association tests across multiple phenotypes using GWAS summary data
Authors: Guo Bin , Wu Baolin
Published: September 2018

Motivation

Many GWAS conducted in the past decade have identified tens of thousands of disease related variants, which in total explained only part of the heritability for most traits. There remain many more genetics variants with small effect sizes to be discovered. This has motivated the development of sequencing studies with larger sample sizes and increased resolution of genotyped variants, e.g., the ongoing NHLBI Trans-Omics for Precision Medicine (TOPMed) whole genome sequencing project. An alternative approach is the development of novel and more powerful statistical methods. The current dominating approach in the field of GWAS analysis is the “single trait single variant” association test, despite the fact that most GWAS are conducted in deeply-phenotyped cohorts with many correlated traits measured. In this paper, we aim to develop rigorous methods that integrate multiple correlated traits and multiple variants to improve the power to detect novel variants. In recognition of the difficulty of accessing raw genotype and phenotype data due to privacy and logistic concerns, we develop methods that are applicable to publicly available GWAS summary data.

Results

We build rigorous statistical models for GWAS summary statistics to motivate novel multi-trait SNP-set association tests, including variance component test, burden test and their adaptive test, and develop efficient numerical algorithms to quickly compute their analytical P-values. We implement the proposed methods in an open source R package. We conduct thorough simulation studies to verify the proposed methods rigorously control type I errors at the genome-wide significance level, and further demonstrate their utility via comprehensive analysis of GWAS summary data for multiple lipids traits and glycemic traits. We identified many novel loci that were not detected by the individual trait based GWAS analysis.

Availability and implementation

We have implemented the proposed methods in an R package freely available at http://www.github.com/baolinwu/MSKAT.

Supplementary information

Supplementary data are available at Bioinformatics online.
CINNA: an R/CRAN package to decipher Central Informative Nodes in Network Analysis
Authors: Ashtiani Minoo , Mirzaie Mehdi , Jafari Mohieddin
Published: September 2018

Motivation

Centrality analysis involves a series of ambiguities in that there are numerous well-known centrality measures with differing algorithms for establishing which nodes in a network are essential. There is no clearly preferred measure or means of deciding which measure is most germane to a given network with respect to node essentiality vis-à-vis topological features. Our aim here was to develop an instrument that enables comparisons among potentially appropriate centrality measures to be made with respect to network structure and thereby to support the identification of the most informative measure according to dimensional reduction methods.

Methods

The Central Informative Nodes in Network Analysis (CINNA) package introduced herein gathers all required functions for centrality analysis in weighted/unweighted and directed/undirected networks. Then, it compares, assorts and visualizes centrality measures to select which best describes the node importance.

Availability and implementation

CINNA is available in CRAN, including a tutorial. URL: https://cran.r-project.org/web/packages/CINNA/index.html.
Saccadic Adaptation Boosts Ongoing Gamma Activity in a Subsequent Visuoattentional Task
Authors: Nicolas Judith , Bompas Aline , Bouet Romain , Sillan Olivier , Koun Eric , Urquizar Christian , Bidet-Caulet Aurélie , Pélisson Denis
Published: September 2018

Attention and saccadic adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy toward them. Recent studies propelled the hypothesis of a tight functional coupling between these mechanisms, possibly due to shared neural substrates. Here, we used magnetoencephalography to investigate for the first time the neurophysiological bases of this coupling and of SA per se. We compared visual discrimination performance of 12 healthy subjects before and after SA. Eye movements and magnetic signals were recorded continuously. Analyses focused on gamma band activity (GBA) during the pretarget period of the discrimination and the saccadic tasks. We found that GBA increases after SA. This increase was found in the right hemisphere for both postadaptation saccadic and discrimination tasks. For the latter, GBA also increased in the left hemisphere. We conclude that oculomotor plasticity involves GBA modulation within an extended neural network which persists after SA, suggesting a possible role of gamma oscillations in the coupling between SA and attention.
Gestational Stress Augments Postpartum β-Amyloid Pathology and Cognitive Decline in a Mouse Model of Alzheimer’s Disease
Authors: Jafari Zahra , Mehla Jogender , Kolb Bryan E , Mohajerani Majid H
Published: September 2018

Besides well-known risk factors for Alzheimer’s disease (AD), stress, and in particular noise stress (NS), is a lifestyle risk factor common today. It is known that females are at a significantly greater risk of developing AD than males, and given that stress is a common adversity in females during pregnancy, we hypothesized that gestational noise exposure could exacerbate the postpartum development of the AD-like neuropathological changes during the life span. Pregnant APPNL-G-F/NL-G-F mice were randomly assigned to either the stress condition or control group. The stress group was exposed to the NS on gestational days 12–16, which resulted in a markedly higher hypothalamic–pituitary–adrenal (HPA) axis responsivity during the postpartum stage. Higher amyloid-β (Aβ) deposition and larger Aβ plaque size in the olfactory area were the early onset impacts of the gestational stress (GS) seen at the age of 4 months. This pattern of increased Aβ aggregation and larger plaque size were observed in various brain areas involved in both AD and stress regulation, especially in limbic structures, at the age of 6 months. The GS also produced anxiety-like behavior, deficits in learning and memory, and impaired motor coordination. The findings suggest that environmental stresses during pregnancy pose a potential risk factor in accelerating postpartum cognitive decline and AD-like neuropathological changes in the dams (mothers) later in life.
Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam Against Pseudomonas aeruginosa: PRIMERS IV
Authors: Evans Scott R , Tran Thuy Tien T , Hujer Andrea M , Hill Carol B , Hujer Kristine M , Mediavilla Jose R , Manca Claudia , Domitrovic T Nicholas , Perez Federico , Farmer Michael , Pitzer Kelsey M , Wilson Brigid M , Kreiswirth Barry N , Patel Robin , Jacobs Michael R , Chen Liang , Fowler Vance G , Chambers Henry F , Bonomo Robert A
Published: September 2018

Background

Overcoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa.

Methods

In this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO).

Results

We found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA).

Conclusions

The diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.
Extensive evaluation of the generalized relevance network approach to inferring gene regulatory networks
Authors: Kuzmanovski Vladimir , Todorovski Ljupčo , Džeroski Sašo
Published: September 2018

Background

The generalized relevance network approach to network inference reconstructs network links based on the strength of associations between data in individual network nodes. It can reconstruct undirected networks, i.e., relevance networks, sensu stricto, as well as directed networks, referred to as causal relevance networks. The generalized approach allows the use of an arbitrary measure of pairwise association between nodes, an arbitrary scoring scheme that transforms the associations into weights of the network links, and a method for inferring the directions of the links. While this makes the approach powerful and flexible, it introduces the challenge of finding a combination of components that would perform well on a given inference task.

Results

We address this challenge by performing an extensive empirical analysis of the performance of 114 variants of the generalized relevance network approach on 47 tasks of gene network inference from time-series data and 39 tasks of gene network inference from steady-state data. We compare the different variants in a multi-objective manner, considering their ranking in terms of different performance metrics. The results suggest a set of recommendations that provide guidance for selecting an appropriate variant of the approach in different data settings.

Conclusions

The association measures based on correlation, combined with a particular scoring scheme of asymmetric weighting, lead to optimal performance of the relevance network approach in the general case. In the two special cases of inference tasks involving short time-series data and/or large networks, association measures based on identifying qualitative trends in the time series are more appropriate.
Development of epibenthic assemblages on artificial habitat associated with marine renewable infrastructure
Authors: Sheehan E V , Cartwright A Y , Witt M J , Attrill M J , Vural M , Holmes L A
Published: September 2018

Offshore marine renewable energy installations (MREI) introduce structure into the marine environment and can locally exclude destructive, bottom trawl fishing. These effects have the potential to aid restoration of degraded seabed habitats but may be constrained by timescales of ecological succession following MREI construction, and the removal of infrastructure during decommissioning. To inform managers about appropriate decommissioning strategies, a 25 km cable and associated rock armouring (Wave Hub, UK), installed on rocky reef, was monitored up to 5 years post-deployment. The epibenthic Assemblage composition, and Number of taxa remained significantly different from surrounding controls, while Abundance was similar in all survey years between the cable and controls. Six morphotaxa showed four patterns of colonization on cable plots compared to the controls: (i) Early colonization, which remained in greater abundances (Porifera), (ii) early colonization, converging (Turf), (iii) slow colonization, converging Anthozoa and Vertebrata), and (iv) slow colonization, remaining lower in abundance (Tunicata and Echinodermata). The environmental relevance of this MREI is considered relatively benign as it covers 0.01% of the surrounding bioregion, appears to be supporting similar assemblages to the surrounding habitat, and exhibited minimal evidence of invasive species (three records of two non-native species). Longer monitoring timescales are required to provide comprehensive, site-specific decommissioning advice.
Emergent three-dimensional sperm motility: coupling calcium dynamics and preferred curvature in a Kirchhoff rod model
Authors: Carichino Lucia , Olson Sarah D
Published: September 2018

Changes in calcium concentration along the sperm flagellum regulate sperm motility and hyperactivation, characterized by an increased flagellar bend amplitude and beat asymmetry, enabling the sperm to reach and penetrate the ovum (egg). The signalling pathways by which calcium increases within the flagellum are well established. However, the exact mechanisms of how calcium regulates flagellar bending are still under investigation. We extend our previous model of planar flagellar bending by developing a fluid-structure interaction model that couples the 3D motion of the flagellum in a viscous Newtonian fluid with the evolving calcium concentration. The flagellum is modelled as a Kirchhoff rod: an elastic rod with preferred curvature and twist. The calcium dynamics are represented as a 1D reaction–diffusion model on a moving domain, the flagellum. The two models are coupled assuming that the preferred curvature and twist of the sperm flagellum depend on the local calcium concentration. To investigate the effect of calcium on sperm motility, we compare model results of flagellar bend amplitude and swimming speed for three cases: planar, helical (spiral with equal amplitude in both directions), and quasi-planar (spiral with small amplitude in one direction). We observe that for the same parameters, the planar swimmer is faster and a turning motion is more clearly observed when calcium coupling is accounted for in the model. In the case of flagellar bending coupled to the calcium concentration, we observe emergent trajectories that can be characterized as a hypotrochoid for both quasi-planar and helical bending.
Rationalizing phonon dispersion for lattice thermal conductivity of solids
Authors: Chen Zhiwei , Zhang Xinyue , Lin Siqi , Chen Lidong , Pei Yanzhong
Published: September 2018

Lattice thermal conductivity (κL) is one of the most fundamental properties of solids. The acoustic–elastic-wave assumption, proposed by Debye (Debye P. Ann Phys 1912; 344: 789–839), has led to linear phonon dispersion being the most common approximation for understanding phonon transport over the past century. Such an assumption does not take into account the effect of a periodic boundary condition on the phonon dispersion, originating from the nature of periodicity on atomic arrangements. Driven by modern demands on the thermal functionality of materials, with κL ranging from ultra-low to ultra-high, any deviation from the Debye approximation in real materials becomes more and more significant. This work takes into account the periodic boundary condition, and therefore rationalizes the phonon dispersion to be more realistic. This significantly improves the precision for quickly predicting κL without any fitting parameters, as demonstrated in hundreds of materials, and offers a theoretical basis rationalizing κL to be lower than the minimum currently accepted based on the Debye dispersion. This work paves the way for designing solids with expected κL and particularly inspires the advancement of low-κL materials for thermal energy applications.
Innovation and Policing: Factors Influencing the Adoption of Social Medias by Members of Quebec Police Organizations
Authors: Delle Donne Julie , Fortin Francis
Published: September 2018

The literature on members of police organizations adopting new technology is generally descriptive and rarely explanatory. However, the Diffusion of Innovation Theory and the studies that have grown out of it have contributed to creation of a model that helps explain adoption rates of new technology by individuals working in an organization. To verify whether this model can be used to study the adoption of technology in police organizations, our study examines the factors that influence the adoption of social media (SM) by members (n = 177) of Quebec police organizations. Our findings confirm that the factors identified in the literature on innovation—the perception that potential users have of the new technology as well as organizational factors, such as the respondent’s role in the organization—can also help explain why and how frequently a member uses SM in his or her work.
How Do Police Officers Cope with Police Corruption and Corrupt Peers? A Typology in the Making
Authors: Constantinou Angelo G
Published: September 2018

The phenomenon of police corruption has received a significant share of attention by both scholars and practitioners. However, although notable knowledge has been built on a corpus of circumferential issues in and determinants of corruption, the array of coping strategies of police officers who encounter corrupt practices and interact with corrupt colleagues has evaded empirical analysis. That said, this article sets out to do that and draws on data collected from a web survey, based on a sample of 446 Cypriot police officers. In the main, it is argued that inertia and apathy are embedded in the preponderance of police officers’ attitudes towards their corrupt peers. Also, for delineating (and somewhat explicating) the coping strategies of police officers who share workplaces with corrupt peers, a typology based on the COPE Inventory is introduced.
Changes in physical activity, weight and wellbeing outcomes among attendees of a weekly mass participation event: a prospective 12-month study
Authors: Stevinson C , Hickson M
Published: September 2018

Background

Mass participation events are recognized as a way of engaging low-active individuals in health-enhancing physical activity, but there is a need to investigate the sustained effects on behaviour and health. This study aimed to examine changes in self-reported physical activity, weight and wellbeing over 12 months in participants of parkrun, a weekly mass participation 5 km running event.

Methods

New parkrun registrants (n = 354) completed self-reported measures of physical activity, weight, happiness and stress, at registration, 6 months and 12 months. Objective data on attendance and fitness (i.e. run dates and finishing times) were obtained from the parkrun database.

Results

Overall physical activity levels were high at baseline, but significantly increased over the first 6 months, before declining. By 12 months, weekly physical activity was 39 min higher than baseline. Significant reductions in body mass index were observed over 12 months, with a weight loss of 1.1% in the whole sample, and 2.4% among overweight participants. Modest increases in happiness and decreases in perceived stress were recorded. Run times suggested a 12% improvement in fitness during the study.

Conclusion

Significant changes in weight, fitness and wellbeing outcomes indicate the public health benefits of regular participation in parkrun.
Frictional Labour Mobility
Authors: Schmutz Benoît , Sidibé Modibo
Published: September 2018

We build a dynamic model of migration where, in addition to standard relocation costs, workers face spatial frictions that decrease their ability to compete for distant job opportunities. We estimate the model on a matched employer–employee panel dataset describing labour market transitions within and between the 100 largest French cities. Our identification strategy is based on the premise that frictions affect the frequency of job transitions, while mobility costs impact the distribution of accepted wages. We find that: (1) controlling for spatial frictions reduces mobility cost estimates by one order of magnitude; (2) the urban wage premium is driven by better opportunities for local job-to-job transitions in larger cities; (3) migration reduces lifetime inequalities by providing insurance against unsatisfactory initial location draws; (4) labour mobility policies based on relocation subsidies are inefficient, unlike switching from nationwide to local minimum wages.
RADIATION DOSE TO PATIENTS IN CORONARY INTERVENTIONAL PROCEDURES: A SURVEY
Authors: Brindhaban A
Published: September 2018

The objective of this study was to evaluate dose–area product (DAP) and peak skin dose (PSD) for coronary angiography (CA) and percutaneous coronary intervention (PCI). The DAP and PSD of 300 randomly selected patients who were referred to CA and/or PCI, over a period of 3 months were recorded and analyzed. The mean DAP of 32 Gy cm2 and mean PSD of 412 mGy for CA were lower than 118 Gy cm2 and 857 mGy, respectively, for PCI. The DAP range of 2–84 Gy cm2 for CA and 12–378 mGy for PCI were also established. The maximum value of PSD for PCI procedures reached above the 2 Gy threshold for erythema. However, these values are similar to those available in literature. Periodic surveys may be required to monitor and/or reduce radiation doses in coronary interventional procedures.
Population-level Mortality Associated with HIV Exposure in HIV-uninfected Infants in Botswana and South Africa: A Model-based Evaluation
Authors: Slogrove Amy L , Johnson Leigh F , Powis Kathleen M
Published: September 2018

We aimed to quantify the contribution of excess mortality in HIV-exposed uninfected (HEU) infants to total mortality in HIV-uninfected infants in Botswana and South Africa in 2013. Population attributable fractions (PAFs) and excess infant deaths associated with HIV exposure in HIV-uninfected infants were estimated. Additionally, the Thembisa South African demographic model estimated the proportion of all infant mortality associated with excess mortality in HEU infants from 1990 to 2013. The PAF (lower bound; upper bound) of mortality associated with HIV exposure in HIV-uninfected infants was 16.8% (2.5; 31.2) in Botswana and 15.1% (2.2; 28.2) in South Africa. Excess infant deaths (lower bound; upper bound) associated with HIV exposure in 2013 were estimated to be 5.6 (0.5; 16.6)/1000 and 4.9 (0.6; 11.2)/1000 HIV-uninfected infants in Botswana and South Africa, respectively. In South Africa, the proportion of all infant (HIV-infected and HIV-uninfected) mortality associated with excess HEU infant mortality increased from 0.4% in 1990 to 13.8% in 2013.
Influence of Irrigation and Wetting Agent on Fungicide Residues in Creeping Bentgrass
Authors: Latin Richard , Ou Ling
Published: September 2018

Fungicides (azoxystrobin, propiconazole, pyraclostrobin, and thiophanate-methyl) were applied to field plots of creeping bentgrass established on a sand-based root zone substrate and maintained at a cutting height of 0.34 cm. The wetting agent, a modified alkylated polyol, was applied 24 h prior to fungicide application. Irrigation (0.51 cm) was applied to plots immediately after the fungicide spray. Turf was sampled nine times over 42 days to examine fungicide residues in three components of the turf profile: verdure/thatch, roots, and soil. Residues were extracted from samples and then quantified using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The experiment was run twice. Wetting agent had little or no effect on fungicide distribution in any of the turf components. Postapplication irrigation had little effect on residues observed in the verdure/thatch component. Significant irrigation treatment effects were observed in root and soil components, but results varied among fungicides and sampling dates. Where significant effects were observed for the irrigation plus wetting agent treatment, results generally mirrored outcomes for irrigation treatment.
Early postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons
Authors: Krajeski Rohan N. , Macey-Dare Anežka , van Heusden Fran , Ebrahimjee Farid , Ellender Tommas J.
Published: September 2018

A dysfunctional striatum is thought to contribute to neurodevelopmental disorders such as ADHD, Tourette’s syndrome and OCD. Insight into these disorders is reliant on an understanding of the normal development of the striatal cellular and circuit properties. Here we combined whole-cell patch-clamp electrophysiology and anatomical reconstructions of D1 and D2 striatal projection neurons (SPNs) in brain slices to characterize the development of the electrophysiological and morphological properties as well as their long-range and local inputs during the first three postnatal weeks. Overall, we find that many properties develop in parallel but we make several key observations. Firstly, that the electrophysiological properties of young D1 SPNs are more mature and that distinctions between D1 and D2 SPNs become apparent in the second postnatal week. Secondly, that dendrites and spines as well as excitatory inputs from cortex develop in parallel with cortical inputs exhibiting a prolonged period of maturation involving changes in postsynaptic glutamate receptors. Lastly, that initial local connections between striatal SPNs consist of gap junctions, which are gradually replaced by inhibitory synaptic connections. Interestingly, relative biases in inhibitory synaptic connectivity seen between SPNs in adulthood, such as a high connectivity between D2 SPNs, are already evident in the second postnatal week. Combined, these results provide an experimental framework for future investigations of striatal neurodevelopmental disorders and show that many of the cellular and circuit properties are established in the first and second postnatal weeks suggesting intrinsic programs guide their development.

Significance Statement

Normal brain development involves the formation of neurons, which develop correct electrical and morphological properties and are precisely connected with each other in a neural circuit. In neurodevelopmental disorders these processes go awry leading to behavioral and cognitive problems later in life. Here we provide for the first time a detailed quantitative description of the cellular and circuit properties of the two main neuron types of the striatum during the first postnatal weeks. This can form an experimental framework for future studies into neurodevelopmental disorders. We find that most of the properties for both types of striatal neuron develop in parallel and are already established by the second postnatal week suggesting a key role for intrinsic programs in guiding their development.
The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency
Authors: Sohre Selina , Moosmann Bernd
Published: September 2018

Alzheimer’s disease is characterized by intracellular aggregates of hyperphosphorylated tau protein and extracellular plaques of amyloid β peptide, a product of APP processing. The origin of these pathological hallmarks has remained elusive. Here, we have tested the idea that both alterations, at the onset of the disease, may constitute compensatory responses to the same causative and initial trigger, namely NMDA receptor insufficiency. Treatment of rat cortical neurons with the specific NMDA receptor antagonist AP5 within 4 h caused a significant increase in tau phosphorylation at the AT8 and S404 epitopes as well as an increase in APP expression and Aβ40secretion. Single intraperitoneal injections of the NMDA receptor open channel blocker MK-801 into wild-type mice reproduced all of these changes in a brain region-specific fashion either at latency 4 h or 24 h. Subchronic treatment with MK-801 for 6 weeks induced AT8, S404 and S396 immunoreactivity selectively in female mice. We conclude that the pivotal pathological alterations in Alzheimer’s disease represent runaway physiological responses to persistently insufficient excitatory neurotransmission. In view of the evidence for excitatory insufficiency in trisomy 21 patients, PS1 mutation carriers and ApoE4 carriers, our data suggest a common pathomechanism behind familial, sporadic, and risk allele-triggered Alzheimer’s disease. The potential of this mechanism to reconcile previous conflicting observations is discussed.
Phylotastic: improving access to tree-of-life knowledge with flexible, on-the-fly delivery of trees
Authors: Nguyen Van D. , Nguyen Thanh H. , Md. Tayeen Abu Saleh , Laughinghouse H. Dail , Sánchez-Reyes Luna L. , Pontelli Enrico , Mozzherin Dmitry , O’Meara Brian , Stoltzfus Arlin
Published: September 2018

(1) A comprehensive phylogeny of species, i.e., a tree of life, has potential uses in a variety of contexts in research and education. This potential is limited if accessing the tree of life requires special knowledge, complex software, or long periods of training.

(2) The Phylotastic project aims to use web-services technologies to lower the barrier for accessing phylogenetic knowledge, making it as easy to get a phylogeny of species as it is to get online driving directions. In prior work, we designed an open system of web services to validate and manage species names, find phylogeny resources, extract subtrees matching a user’s species list, calibrate them, and mash them up with images and information from online resources.

(3) Here we report a publicly accessible system for on-the-fly delivery of phylogenetic knowledge, developed with user feedback on what types of functionality are considered useful by researchers and educators. The system currently consists of a web portal that implements 3 types of workflows to obtain species phylogenies (scaled by geologic time and decorated with thumbnail images); 19 underlying web services accessible via a common registry; and toolbox code in R and Python so that others can create applications that leverage these services. These resources cover most of the use-cases identified in our analysis of user needs.

(4) The Phylotastic system, accessible viahttp://www.phylotastic.org, provides a unique resource to access the current state of phylogenetic knowledge, useful for a variety of cases in which a tree extracted quickly from online resources (as distinct from a tree custom-made from character data) is sufficient, as it is for many casual uses of trees identified here.
Non-driver somatic alteration burden confers good prognosis in non-small cell lung cancer
Authors: Wang Dennis , Pham Nhu-An , Freeman Timothy M. , Raghavan Vibha , Navab Roya , Pasko Elena , Chang Jonathan , Zhu Chang-Qi , Ly Dalam , Tong Jiefei , Wouters Bradly G. , Pintilie Melania , Moran Michael F. , Shepherd Frances A. , Tsao Ming-Sound
Published: September 2018

Background

Genomic profiling of patient tumors has linked somatic driver mutations to survival outcomes of non-small cell lung cancer (NSCLC) patients, especially for those receiving targeted therapies. However, it remains unclear whether specific non-driver mutations have any prognostic utility.

Methods

Whole exomes and transcriptomes were measured from NSCLC xenograft models of patients with diverse clinical outcomes. Penalised regression analysis was performed to identify a set of 865 genes associated with patient survival. The number of somatic copy number aberrations, point mutations and associated expression changes within the 865 genes were used to stratify independent NSCLC patient populations, filtered for chemotherapy naive and early-stage. In-depth genomic analysis and functional testing was conducted on the genomic alterations to understand their effect on improving survival.

Results

High burden of somatic alterations are associated with longer disease-free survival (HR=0.153, P=1.48×10-4) in NSCLC patients. When somatic alterations burden was integrated with gene expression, we were able to predict prognosis in three independent patient datasets. Patients with high alteration burden could be further stratified based on the presence of immunogenic mutations, revealing another subgroup of patients with even better prognosis (85% with >5 years survival), and associated with cytotoxic T-cell expression. In addition, 95% of these 865 genes lack documented activity relevant to cancer, but are in pathways regulating cell proliferation, motility and immune response were implicated.

Conclusion

Our results demonstrate that non-driver somatic alterations may influence the outcome of cancer patients by increasing beneficial immune response and inhibiting processes associated to tumorigenesis.
Bacteriology and Antibiotic Prescription Patterns in a Malawian Tertiary Hospital Burns Unit
Authors: Kasenda Stephen , Mategula Donnie , Manda Geoffrey Elihu , Chokotho Tilinde Keith
Published: September 2018

Introduction

Infections are responsible for up to 85% of deaths in patients with burn injuries. Proper management of infections in patients with burns requires knowledge of local microbial landscape and antimicrobial resistance patterns. Most burns units in low to middle income countries lack this data to guide patient management.

Methods and results

We conducted a retrospective audit of adult (≥17 years) patient records admitted between at 1st June 2007 and May 2017 at Queen Elizabeth Central Hospital Burns unit in Blantyre Malawi with an index complaint of burn injury. Descriptive statistical analysis was performed to determine antibiotic prescription patterns, microbial isolates and antimicrobial resistance patterns on the 500 patient files that met the inclusion criteria. Cephalosporin’s and Penicillin’s constituted 72.3% of the 328 antibiotic prescriptions given to 212 patients and 84% of all prescriptions were potentially inappropriate. A total of 102 bacterial isolates were identified and a majority (30.4%; n=31) were resistant to Aminoglycosides and Aminocyclitols (23.5%; n=24); seconded by Penicillin’s at 19.6% (n=20). Pseudomonas, staphylococcus and streptococcus species constituted 36.1%, 25% and 16.7% of all resistant bacteria that were isolated and they were thus the most common bacterial isolates. Drug resistance was more common among gram negative bacteria (48.8% versus 26.2%) and a greater proportion of patients (74.1%) that had antibiotic sensitivity testing were affected by drug resistant gram negative bacteria which appear on the World Health Organisation list of priority pathogens.

Conclusion

The results of our preliminary study point towards nosocomial gram negative bacteria which appear on the World Health Organisations list of priority pathogens as the more common sources of antibiotic resistance. This scenario is potentially driven by inappropriate antibiotic prescriptions as well as clinical and laboratory diagnostic imprecision in addition to the universally recognised post burn pathophysiological changes of hypermetabolism and immunosuppression. Improvements in the areas of antimicrobial stewardship, diagnostic capacity and burns related research are needed in order to achieve optimal therapeutic outcomes and resource utilisation.
Biolistic transformation of Haematococcus pluvialis with constructs based on the flanking sequences of its endogenous alpha tubulin gene
Authors: Yuan Guanhua , Zhang Wenlei , Xu Xiaoying , Zhang Wei , Cui Yulin , Liu Tianzhong
Published: September 2018

The complete sequence information of the alpha tubulin (tub) genes was obtained from both Haematococcus pluvialis NIES144 and SCCAP K0084., Putative transcriptional elements and polyadenylation signals were identified respectively in their 5’ and 3’ flanking regions. Three selection cassettes of tub/aadA, tub/hyr and tub/ble with 3 different antibiotic-resistant genes fused between the 5’ and 3’ flanking sequences of the tub gene were constructed and utilized for biolistic transformation of H.pluvialis. Antibiotic resistant transformants were obtained in the bombardments with the tub/aadA cassette in 2 strains. It was found that, the foreign tub/aadA DNA could be completely transferred and inherited in their genome through non-homologous recombination. Moreover, transcripts of the insert and spectinomycin resistance were identified. Transformation efficiencies up to 3×10-5 per μg DNA could be obtained in H.pluvialis NIES144 or SCCAP K0084 through utilization of a culture with a high percentage of flagellate cells and by optimizing bombarding protocol. The presented selection marker and optimized transforming procedures in this report should strengthen the platform technology for genetical manipulation and modification of H.pluvialis.
Open prediction of polysaccharide utilisation loci (PUL) in 5414 publicBacteroidetesgenomes using PULpy
Authors: Stewart Rob D. , Auffret Marc D. , Roehe Rainer , Watson Mick
Published: September 2018

Polysaccharide utilisation loci (PUL) are regions within bacterial genomes that encode all the necessary machinery for the cleavage of particular carbohydrates. For theBacteroidetesphylum, prediction of PUL from genomic data alone involves the identification of carbohydrate-active enzymes (CAZymes) co-localised withsusCDgene pairs. Here we present the open prediction of PUL in 5414 publicBacteroidetesgenomes, and an open-source pipeline to reproduce or extend the results.
Determinants of CpG Islands: Expression in Early Embryo and Isochore Structure
Authors: Ponger Loïc , Duret Laurent , Mouchiroud Dominique
Published: September 2018

In an attempt to understand the origin of CpG islands (CGIs) in mammalian genomes, we have studied their location and structure according to the expression pattern of genes and to the G + C content of isochores in which they are embedded. We show that CGIs located over the transcription start site (named start CGIs) are very different structurally from the others (named no-start CGIs): (1) 61.6% of the no-start CGIs are due to repeated sequences (79 % are due to Alus), whereas only 5.6% of the start CGIs are due to such repeats; (2) start CGIs are longer and display a higher CpGo/e ratio and G + C level than no-start CGIs. The frequency of tissue-specific genes associated to a start CGI varies according to the genomic G + C content, from 25% in G + C-poor isochores to 64% in G + C-rich isochores. Conversely, the frequency of housekeeping genes associated to a start CGI (90%) is independent of the isochore context. Interestingly, the structure of start CGIs is very similar for tissue-specific and housekeeping genes. Moreover, 93% of genes expressed in early embryo are found to exhibit a CpG island over their transcription start point. These observations are consistent with the hypothesis that the occurrence of these CGIs is the consequence of gene expression at this stage, when the methylation pattern is installed.
The Contribution of Exon-Skipping Events on Chromosome 22 to Protein Coding Diversity
Authors: Hide Winston A. , Babenko Vladimir N. , van Heusden Peter A. , Seoighe Cathal , Kelso Janet F.
Published: September 2018

Completion of the human genome sequence provides evidence for a gene count with lower bound 30,000–40,000. Significant protein complexity may derive in part from multiple transcript isoforms. Recent EST based studies have revealed that alternate transcription, including alternative splicing, polyadenylation and transcription start sites, occurs within at least 30–40% of human genes. Transcript form surveys have yet to integrate the genomic context, expression, frequency, and contribution to protein diversity of isoform variation. We determine here the degree to which protein coding diversity may be influenced by alternate expression of transcripts by exhaustive manual confirmation of genome sequence annotation, and comparison to available transcript data to accurately associate skipped exon isoforms with genomic sequence. Relative expression levels of transcripts are estimated from EST database representation. The rigorous in silico method accurately identifies exon skipping using verified genome sequence. 545 genes have been studied in this first hand-curated assessment of exon skipping on chromosome 22. Combining manual assessment with software screening of exon boundaries provides a highly accurate and internally consistent indication of skipping frequency. 57 of 62 exon skipping events occur in the protein coding regions of 52 genes. A single gene, (FBXO7) expresses an exon repetition. 59% of highly represented multi-exon genes are likely to express exon-skipped isoforms in ratios that vary from 1:1 to 1:>100. The proportion of all transcripts corresponding to multi-exon genes that exhibit an exon skip is estimated to be 5%.