bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrostatic engineering of charge clouds around DNA inhibits strand breakages
Authors: Sequeira M. P. , D'Souza J. S. , Dharmadhikari A. K. , Dharmadhikari J. A. , Vasa P. , Mathur D.
Published: September 2018

Femtosecond laser-induced damage to plasmid DNA in aqueous medium manifests itself as strand breaks arising from interactions with slow OH-radicals (and electrons) in the laser-induced plasma generated in water. Such strand breakages are found to be significantly inhibited upon addition of salts (in physiologically significant concentrations) to the aqueous medium. A simple model rationalizes our observations and suggests the feasibility of electrostatically “engineering” DNA's ion atmosphere so as to prevent damage-inducing free radicals accessing DNA strands. These findings may aid development of new strategies for cancer treatment.
Thermal behavior of In impurities in ZnO
Authors: Sato W. , Shimizu H. , Komatsuda S. , Ohkubo Y.
Published: September 2018

Thermally activated association and dissociation behaviors of indium impurities in Zinc oxide (ZnO) were observed on an atomic scale by means of time-differential perturbed angular correlation spectroscopy with the radioactive 111In(→111Cd) probe. We found that In impurities associate in the process of thermal diffusion to form nanoscale clusters in the ZnO matrix under thermal treatment in air, and their structures depend on the concentration of In ions introduced. Heat treatment under vacuum, however, causes dissociation of part of the clusters, suggesting that In ions leave the clusters and migrate into the ZnO matrix. Positron annihilation lifetime spectroscopy performed for the In-doped ZnO also suggests that In ions as impurities migrate into the ZnO matrix by thermal diffusion to settle themselves in Zn vacancies. Dependences of thermal behavior of In impurities on their concentration, treatment temperature, and atmospheric condition are discussed based on the results observed by the nuclear spectroscopic techniques.
Expanding fish productivity in Tasmanian saltmarsh wetlands through tidal reconnection and habitat repair
Authors: Prahalad Vishnu , Harrison-Day Violet , McQuillan Peter , Creighton Colin
Published: September 2018

Fish use of coastal saltmarsh wetlands has been documented for many parts of Australia with the notable exception of Tasmania. An initial investigation to examine the diversity, density and patterns of fish use in the Circular Head coast saltmarshes of north-west Tasmania was undertaken. To aid decision making in repair strategies, the effect of saltmarsh condition on fish assemblages was studied using paired sites of predominantly unaltered and altered saltmarshes where levees were present. In all, 851 fish from 11 species were caught in 37 of the 48 pop nets. Three species, Aldrichetta forsteri, Arripis truttaceus and Rhombosolea tapirina, are important to commercial and recreational fisheries and contributed ~20% of the total catch numbers. The mean density of >72 fish per 100m2 is the highest yet reported from Australian studies and indicates that Tasmanian saltmarshes provide higher value habitat for fish compared with elsewhere in Australia, likely due to more frequent and prolonged flooding, and the lack of adjacent mangroves. There was no significant difference in fish assemblages between unaltered and altered marshes. The results suggest that restoring basic saltmarsh structure through tidal reconnection will deliver substantial benefits for fish productivity through habitat expansion.A
An uncertain future: climate resilience of first-generation ranchers
Authors: Munden-Dixon Kate , Tate Kenneth , Cutts Bethany , Roche Leslie
Published: September 2018

Policymakers and scholars agree that the aging and declining number of ranchers is a serious problem for the future of ranching and range management. Studies show that recruiting and retaining new ranchers is difficult due to a complex mix of start-up costs, knowledge and skill requirements, and regulatory barriers. While research suggests that first-generation farmers are different demographically and require individualised information, there is limited research on first-generation ranchers (FGRs); at best they are generalised as beginning farmers in research and outreach programs. This is surprising given ranchers’ unique knowledge requirements relating to the production of food and fibre, and the management of vast areas of public and private land. Based on a rangeland decision-making survey of 507 California Cattlemen’s Association members, this paper examines similarities and divergences in socioeconomic factors, management practices, drought adaptation strategies, information needs, and values between FGRs and multigenerational ranchers (MGRs). Survey results indicate FGRs and MGRs are not statistically different demographically and have similar values; however, key differences include FGRs using fewer information sources about ranching, fewer general management practices, and fewer drought adaptation practices. FGRs are also more susceptible to drought, and are underserved by organisations. Their vulnerability is particularly concerning, as many have limited drought experience, are more likely to take risks, and are less likely to find value and/or participate in ranching organisations. The future of rangelands requires that organisations interested in conserving rangelands and supporting ranchers re-evaluate assumptions about why FGRs and MGRs have different information needs beyond simplistic demographic identity, and instead focus on their affinity as FGRs in order to understand the complexity of the processes underlying these differences. We end with suggestions for a research agenda to support the climate resiliency of FGRs and increase the efficacy of support organisations.
The impact of US wildland fires on ozone and particulate matter: a comparison of measurements and CMAQ model predictions from 2008 to 2012
Authors: Wilkins Joseph L. , Pouliot George , Foley Kristen , Appel Wyat , Pierce Thomas
Published: September 2018

Wildland fire emissions are routinely estimated in the US Environmental Protection Agency’s National Emissions Inventory, specifically for fine particulate matter (PM2.5) and precursors to ozone (O3); however, there is a large amount of uncertainty in this sector. We employ a brute-force zero-out sensitivity method to estimate the impact of wildland fire emissions on air quality across the contiguous US using the Community Multiscale Air Quality (CMAQ) modelling system. These simulations are designed to assess the importance of wildland fire emissions on CMAQ model performance and are not intended for regulatory assessments. CMAQ ver. 5.0.1 estimated that fires contributed 11% to the mean PM2.5 and less than 1% to the mean O3 concentrations during 2008–2012. Adding fires to CMAQ increases the number of ‘grid-cell days’ with PM2.5 above 35 µg m−3 by a factor of 4 and the number of grid-cell days with maximum daily 8-h average O3 above 70 ppb by 14%. Although CMAQ simulations of specific fires have improved with the latest model version (e.g. for the 2008 California wildfire episode, the correlation r = 0.82 with CMAQ ver. 5.0.1 v. r = 0.68 for CMAQ ver. 4.7.1), the model still exhibits a low bias at higher observed concentrations and a high bias at lower observed concentrations. Given the large impact of wildland fire emissions on simulated concentrations of elevated PM2.5 and O3, improvements are recommended on how these emissions are characterised and distributed vertically in the model.
Predicting human behavior toward members of different social groups
Authors: Jenkins Adrianna C. , Karashchuk Pierre , Zhu Lusha , Hsu Ming
Published: September 2018

Disparities in outcomes across social groups pervade human societies and are of central interest to the social sciences. How people treat others is known to depend on a multitude of factors (e.g., others’ gender, ethnicity, appearance) even when these should be irrelevant. However, despite substantial progress, much remains unknown regarding (
i
) the set of mechanisms shaping people’s behavior toward members of different social groups and (
ii
) the extent to which these mechanisms can explain the structure of existing societal disparities. Here, we show in a set of experiments the important interplay between social perception and social valuation processes in explaining how people treat members of different social groups. Building on the idea that stereotypes can be organized onto basic, underlying dimensions, we first found using laboratory economic games that quantitative variation in stereotypes about different groups’ warmth and competence translated meaningfully into resource allocation behavior toward those groups. Computational modeling further revealed that these effects operated via the interaction of social perception and social valuation processes, with warmth and competence exerting diverging effects on participants’ preferences for equitable distributions of resources. This framework successfully predicted behavior toward members of a diverse set of social groups across samples and successfully generalized to predict societal disparities documented in labor and education settings with substantial precision and accuracy. Together, these results highlight a common set of mechanisms linking social group information to social treatment and show how preexisting, societally shared assumptions about different social groups can produce and reinforce societal disparities.
Universal method for robust detection of circadian state from gene expression
Authors: Braun Rosemary , Kath William L. , Iwanaszko Marta , Kula-Eversole Elzbieta , Abbott Sabra M. , Reid Kathryn J. , Zee Phyllis C. , Allada Ravi
Published: September 2018

Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time of therapeutic treatments. To be useful, such a test must be accurate, minimally burdensome to the patient, and readily generalizable to new data. A major obstacle in development of gene expression biomarker tests is the diversity of measurement platforms and the inherent variability of the data, often resulting in predictors that perform well in the original datasets but cannot be universally applied to new samples collected in other settings. Here, we introduce TimeSignature, an algorithm that robustly infers circadian time from gene expression. We demonstrate its application in data from three independent studies using distinct microarrays and further validate it against a new set of samples profiled by RNA-sequencing. Our results show that TimeSignature is more accurate and efficient than competing methods, estimating circadian time to within 2 h for the majority of samples. Importantly, we demonstrate that once trained on data from a single study, the resulting predictor can be universally applied to yield highly accurate results in new data from other studies independent of differences in study population, patient protocol, or assay platform without renormalizing the data or retraining. This feature is unique among expression-based predictors and addresses a major challenge in the development of generalizable, clinically useful tests.
Describing strong correlation with fractional-spin correction in density functional theory
Authors: Su Neil Qiang , Li Chen , Yang Weitao
Published: September 2018

Significance

The static correlation error inherent in commonly used density functional approximations (DFAs) has seriously hindered the application of density functional theory (DFT) to strongly correlated systems. Here, an effective fractional-spin correction against the important issue of static/strong correlation in DFT is developed. With this, the flat-plane behavior of various DFAs is largely restored, and the potential energy curves of dissociation of ionic species, single bonds, and multiple bonds are properly described, which demonstrates great improvement in the treatment of strong correlation. This work should have a significant impact on the development and application of DFT.
High nitrous oxide fluxes from rice indicate the need to manage water for both long- and short-term climate impacts
Authors: Kritee Kritee , Nair Drishya , Zavala-Araiza Daniel , Proville Jeremy , Rudek Joseph , Adhya Tapan K. , Loecke Terrance , Esteves Tashina , Balireddygari Shalini , Dava Obulapathi , Ram Karthik , S. R. Abhilash , Madasamy Murugan , Dokka Ramakrishna V. , Anandaraj Daniel , Athiyaman D. , Reddy Malla , Ahuja Richie , Hamburg Steven P.
Published: September 2018

Significance

Methane from global rice cultivation currently accounts for one-half of all crop-related greenhouse gas emissions. Several international organizations are advocating reductions in methane emissions from rice by promoting intermittent flooding without accounting for the possibility of large emissions of nitrous oxide (N
2
O), a long-lived greenhouse gas. Our experimental results suggest that the Indian subcontinent’s N
2
O emissions from intermittently flooded rice fields could be 30–45 times higher than reported under continuous flooding. Net climate impacts of rice cultivation could be reduced by up to 90% through comanagement of water, nitrogen, and carbon. To do this effectively will require a careful ongoing global assessment of N
2
O emissions from rice, or we will risk ignoring a very large source of climate impact.
Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo
Authors: Yarrington Robert M. , Verma Surbhi , Schwartz Shaina , Trautman Jonathan K. , Carroll Dana
Published: September 2018

Significance

The efficiency of genome editing with CRISPR-Cas9 can vary widely at different targets and in different cells. Some of this variability may be due to the inherent quality of different guide RNAs, but it may also depend on the cellular context of the genomic target DNA. In this report, we demonstrate that targets bound by nucleosomes are cut much less efficiently than targets from which nucleosomes are absent or have been depleted. This information can inform target selection, particularly in cases where cells are quiescent or nucleosome mobility is limited.
Goal realization
Authors: Georgakopoulos Thanasis , Härtl Holden , Sioupi Athina
Published: September 2018

Drawing upon recent insights into the role of Goal preference as reflector of cross-linguistic differences, this paper investigates the factors affecting the realization of Goals in motion event descriptions. In particular, it examines the interplay between the lexicalization pattern of a language, on the one hand, and grammatical viewpoint aspect, on the other – factors which have commonly been treated in isolation. In so doing, three typologically distinct languages were examined: English, German and Greek. The empirical basis of this paper includes: (a) a corpus study, in which we examined the distribution of Goals in a small set of verbs, and (b) an experimental verbalization study, from which we elicited descriptions of different motion event types. While the former does not give a clear picture concerning the cross-linguistic differences in Goal prominence, the latter indicates that lexicalization pattern assumes a more prominent role than grammatical viewpoint aspect in affecting Goal realization.
Biochemical characteristics of cellulose and a green alga degradation by Gilvimarinus japonicas 12-2T, and its application potential for seaweed saccharification
Authors: Kouzuma Shousei , Fujii Katsuhiko
Published: September 2018

Cellulose is one of the major constituents of seaweeds, but reports of mechanisms in microbial seaweed degradation in marine environment are limited, in contrast to the multitude of reports for lignocellulose degradation in terrestrial environment. We studied the biochemical characteristics for marine cellulolytic bacterium Gilvimarinus japonicas 12-2T in seaweed degradation. The bacterial strain was found to degrade green and red algae, but not brown algae. It was shown that the bacterial strain employs various polysaccharide hydrolases (endocellulase, agarase, carrageenanase, xylanase, and laminarinase) to degrade seaweed polysaccharides. Electrophoretic analysis and peptide sequencing showed that the major protein bands on the electrophoresis gel were homologous to known glucanases and glycoside hydrolases. A seaweed hydrolysate harvested from the bacterial culture was found useful as a substrate for yeasts to produce ethanol. These findings will provide insights into possible seaweed decomposition mechanisms of Gilvimarinus, and its biotechnological potential for ethanol production from inedible seaweeds.
Is sports science answering the call for interdisciplinary research? A systematic review
Authors: Piggott Ben , Müller Sean , Chivers Paola , Papaluca Carmen , Hoyne Gerard
Published: September 2018

Sports science research is traditionally monodisciplinary despite calls for an interdisciplinary focus. The primary purpose of this systematic review was to identify studies on talent identification, talent selection and competition performance to determine whether interdisciplinary research is being conducted. Thirty‐six studies met the selection criteria. These studies were critiqued relative to sport, skill level, sport science sub‐disciplines included, and whether the research was multidisciplinary or interdisciplinary. The secondary purpose of the review was to critique the level of analysis and level of representative task design in performance tests used in the studies. Twenty‐five studies were categorised as interdisciplinary, with 11 categorised as multidisciplinary. Thirteen sports were represented with soccer the most frequent followed by field hockey, Australian Rules football, handball and rugby league. Thirty‐two studies completed their analysis at a group level and four at an individual level. A total of 337 performance tests were rated for representative task design with 64 categorised as low, 123 as medium and 150 as high. The results pertaining to interdisciplinary studies and individual analyses are discussed in relation to constraints theory, which predicts that interacting variables can explain sport performance. Sports science research is beginning to fulfil the call for interdisciplinary research. Future research, however, needs to consider individual analyses and representative task design of tests to progress sports science knowledge.
Plague and Violence in Early Modern Italy
Authors: Rose Colin
Published: September 2018

Following the plague of 1630, which struck Northern Italy particularly hard, the erosion of social norms and hierarchies led to an outbreak of homicidal violence in the city and province of Bologna. In particular, urban nobility resumed practices of vendetta and revenge as politics that had lain dormant for some decades; while in the countryside, the heightened stresses of endemic rural poverty led to homicides over resources such as land, food, and employment. This article examines that outbreak of violence in the context of natural disaster, employing a selection of seventy-seven homicide trials prosecuted by the Tribunale del Torrone, the criminal court of Bologna, in 1632.
Squeezing, Squirting, Spilling Milk: The Lactation of Saint Bernard and the FlemishMadonna Lactans(ca. 1430–1530)
Authors: Sperling Jutta
Published: September 2018

The focus on three drops of milk issuing from the Virgin’s breast in “The Virgin in Front of a Fire Screen” was inspired by contemporary representations of the Lactation of Saint Bernard. This latter iconography provides the visual context for the vivid address of eroticized depictions of the Madonna’s “one bare breast” in Flemish art and shows the intricate connections between visuality and materiality in fifteenth-century Flemish religious art. Some depictions of Saint Bernard’s lactation transform the Madonna’s jets of milk into rays of light aiming for his eyes, stressing the interchangeability of materiality and visuality as modes that were expected to facilitate and/or authenticate miraculous appearances of the Madonna.
Investigating the impact of cigarette smoking behaviours on DNA methylation patterns in adolescence
Authors: Prince Claire , Hammerton Gemma , Taylor Amy E , Anderson Emma L , Timpson Nicholas J , Davey Smith George , Munafò Marcus R , Relton Caroline L , Richmond Rebecca C
Published: September 2018

Smoking usually begins in adolescence, and early onset of smoking has been linked to increased risk of later life disease. There is a need to better understand the biological impact of cigarette smoking behaviours in adolescence. DNA methylation profiles related to smoking behaviours and cessation in adulthood have been previously identified, but alterations arising from smoking initiation have not been thoroughly investigated. We aimed to investigate DNA methylation in the Avon Longitudinal Study of Parents and Children in relation to (1) different smoking measures, (2) time since smoking initiation and frequency of smoke exposure and (3) latent classes of smoking behaviour. Using 2620 CpG sites previously associated with cigarette smoking, we investigated DNA methylation change in relation to own smoking measures, smoke exposure duration and frequency, and using longitudinal latent class analysis of different smoking behaviour patterns in 968 adolescents. Eleven CpG sites located in seven gene regions were differentially methylated in relation to smoking in adolescence. While only AHRR (cg05575921) showed a robust pattern of methylation in relation to weekly smoking, several CpGs showed differences in methylation among individuals who had tried smoking compared with non-smokers. In relation to smoke exposure duration and frequency, cg05575921 showed a strong dose–response relationship, while there was evidence for more immediate methylation change at other sites. Our findings illustrate the impact of cigarette smoking behaviours on DNA methylation at some smoking-responsive CpG sites, even among individuals with a short smoking history.
Contextualizing selection bias in Mendelian randomization: how bad is it likely to be?
Authors: Gkatzionis Apostolos , Burgess Stephen
Published: September 2018

Background

Selection bias affects Mendelian randomization investigations when selection into the study sample depends on a collider between the genetic variant and confounders of the risk factor–outcome association. However, the relative importance of selection bias for Mendelian randomization compared with other potential biases is unclear.

Methods

We performed an extensive simulation study to assess the impact of selection bias on a typical Mendelian randomization investigation. We considered inverse probability weighting as a potential method for reducing selection bias. Finally, we investigated whether selection bias may explain a recently reported finding that lipoprotein(a) is not a causal risk factor for cardiovascular mortality in individuals with previous coronary heart disease.

Results

Selection bias had a severe impact on bias and Type 1 error rates in our simulation study, but only when selection effects were large. For moderate effects of the risk factor on selection, bias was generally small and Type 1 error rate inflation was not considerable. Inverse probability weighting ameliorated bias when the selection model was correctly specified, but increased bias when selection bias was moderate and the model was misspecified. In the example of lipoprotein(a), strong genetic associations and strong confounder effects on selection mean the reported null effect on cardiovascular mortality could plausibly be explained by selection bias.

Conclusions

Selection bias can adversely affect Mendelian randomization investigations, but its impact is likely to be less than other biases. Selection bias is substantial when the effects of the risk factor and confounders on selection are particularly large.
The structure behind the Galactic bar traced by red clump stars in the VVV survey
Authors: Gonzalez Oscar A , Minniti Dante , Valenti Elena , Alonso-García Javier , Debattista Victor P , Zoccali Manuela , Rejkuba Marina , Dias Bruno , Surot Francisco , Hempel Maren , Saito Roberto K
Published: September 2018

Red clump stars are commonly used to map the reddening and morphology of the inner regions of the Milky Way. We use the new photometric catalogues of the VISTA Variables in the Vía Láctea survey to achieve twice the spatial resolution of previous reddening maps for Galactic longitudes $\rm -10^{\circ }\lt l\lt 10^{\circ }$ and latitudes $\rm -1.5^{\circ }\lt b\lt 1.5^{\circ }$. We use these de-reddened catalogues to construct the $\rm K_{s}$ luminosity function around the red clump in the Galactic plane. We show that the secondary peak (fainter than the red clump) detected in these regions does not correspond to the bulge red-giant branch bump alone, as previously interpreted. Instead, this fainter clump corresponds largely to the over-density of red clump stars tracing the spiral arm structure behind the Galactic bar. This result suggests that studies aiming to characterize the bulge red-giant branch bump should avoid low galactic latitudes ($\rm |b|\lt 2^{\circ }$), where the background red clump population contributes significant contamination. It furthermore highlights the need to include this structural component in future modelling of the Galactic bar.
Safety of Delafloxacin: Focus on Adverse Events of Special Interest
Authors: Lodise Thomas , Corey Ralph , Hooper David , Cammarata Sue
Published: September 2018

Background

Fluoroquinolones have been widely used for a variety of Gram-positive and Gram-negative infections, and by 2002 they had become the most commonly prescribed class of antibiotics for adults in the United States. With widespread use, the class has become associated with a range of adverse events. Delafloxacin is a fluoroquinolone approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs). Delafloxacin is differentiated from other fluoroquinolones due to structural differences and in its activity against methicillin-resistant Staphylococcus aureus, including quinolone-resistant strains. This paper reviews the safety profile of delafloxacin across clinical studies with an emphasis on the incidence of adverse events of special interest that are associated with fluoroquinolones.

Methods

Data from 2 completed phase III studies of delafloxacin for the treatment of ABSSSIs were pooled and are the primary focus of this paper. Additional support from the full safety analysis set (30 completed phase I to phase III clinical studies) is included where applicable.

Results

Fewer patients in the pooled delafloxacin group had AESIs than in the comparator group (7.0% vs 9.2%, respectively). Delafloxacin had a low rate of discontinuations due to treatment-related adverse events (<1%). Serious adverse events occurred at similar rates in patients treated with delafloxacin vs comparators.

Conclusions

Serious adverse events occurred at similar rates in patients treated with delafloxacin vs nonquinolone comparators used to treat ABSSSIs.

Clinicaltrials.gov identifier

NCT01984684 and NCT01811732
CO observations of the molecular gas in the Galactic H ii region Sh2-48: Evidence for cloud–cloud collision as a trigger of high-mass star formation
Authors: Torii Kazufumi , Hattori Yusuke , Matsuo Mitsuhiro , Fujita Shinji , Nishimura Atsushi , Kohno Mikito , Kuriki Mika , Tsuda Yuya , Minamidani Tetsuhiro , Umemoto Tomofumi , Kuno Nario , Yoshiike Satoshi , Ohama Akio , Tachihara Kengo , Fukui Yasuo , Shima Kazuhiro , Habe Asao , Haworth Thomas J
Published: September 2018

Sh2-48 is a Galactic H ii region, 3.8 kpc distant, with an O9.5-type star identified at its center. As a part of the FOREST Unbiased Galactic plane Imaging survey using the Nobeyama 45 m telescope (FUGIN) project, we obtained a CO J = 1–0 data set for a large area of Sh2-48 at a spatial resolution of 21″ (∼0.4 pc), and used it to find a molecular cloud with a total molecular mass of ∼3.8 × 104 M⊙ associated with Sh2-48. The molecular cloud has a systematic velocity shift in a velocity range of ∼42–47 km s−1. On the lower-velocity side the CO emission spatially corresponds to the bright 8 μm filament at the western rim of Sh2-48; however, the CO emission with higher velocities separates into the eastern and western sides of the 8 μm filament. This velocity variation forms a V-shaped feature in the east–west direction on the position–velocity diagram. We found that these lower- and higher-velocity components are, unlike the infrared and radio-continuum data, physically associated with Sh2-48. To interpret the observed V-shaped velocity distribution, we assess a cloud–cloud collision scenario, and found, from a comparison between observations and simulations, that the velocity distribution is an expected outcome of a collision between a cylindrical cloud corresponding to the lower-velocity component and a spherical cloud, and that the two separate higher-velocity components are interpretable as collision-broken remnants of the spherical cloud. Based on the consistency between an estimated formation timescale of the H ii region, ∼1.3 Myr, and a timescale of the collision, we conclude that the high-mass star formation in Sh2-48 was triggered by the collision.
Mimicking the Host Regulation of Salicylic Acid: A Virulence Strategy by the Clubroot Pathogen Plasmodiophora brassicae
Authors: Djavaheri Mohammad , Ma Lisong , Klessig Daniel F. , Mithöfer Axel , Gropp Gordon , Borhan Hossein
Published: September 2018

The plant hormone salicylic acid (SA) plays a critical role in defense against biotrophic pathogens such as Plasmodiophora brassicae, which is an obligate pathogen of crucifer species and the causal agent of clubroot disease of canola (Brassica napus). P. brassicae encodes a protein, predicted to be secreted, with very limited homology to benzoic acid (BA)/SA–methyltransferase, designated PbBSMT. PbBSMT has a SA- and an indole-3-acetic acid–binding domain, which are also present in Arabidopsis thaliana BSMT1 (AtBSMT1) and, like AtBSMT1, has been shown to methylate BA and SA. In support of the hypothesis that P. brassicae uses PbBSMT to overcome SA-mediated defenses by converting SA into inactive methyl salicylate (MeSA), here, we show that PbBSMT suppresses local defense and provide evidence that PbBSMT is much more effective than AtBSMT1 at suppressing the levels of SA and its associated effects. Basal SA levels in Arabidopsis plants that constitutively overexpress PbBSMT compared with those in Arabidopsis wild-type Col-0 (WT) were reduced approximately 80% versus only a 50% reduction in plants overexpressing AtBSMT1. PbBSMT-overexpressing plants were more susceptible to P. brassicae than WT plants; they also were partially compromised in nonhost resistance to Albugo candida. In contrast, AtBSMT1-overexpressing plants were not more susceptible than WT to either P. brassicae or A. candida. Furthermore, transgenic Arabidopsis and tobacco plants overexpressing PbBSMT exhibited increased susceptibility to virulent Pseudomonas syringae pv. tomato DC3000 (DC3000) and virulent Pseudomonas syringae pv. tabaci, respectively. Gene-mediated resistance to DC3000/AvrRpt2 and tobacco mosaic virus (TMV) was also compromised in Arabidopsis and Nicotiana tabacum ‘Xanthi-nc’ plants overexpressing PbBSMT, respectively. Transient expression of PbBSMT or AtBSMT1 in lower leaves of N. tabacum Xanthi-nc resulted in systemic acquired resistance (SAR)-like enhanced resistance to TMV in the distal systemic leaves. Chimeric grafting experiments revealed that, similar to SAR, the development of a PbBSMT-mediated SAR-like phenotype was also dependent on the MeSA esterase activity of NtSABP2 in the systemic leaves. Collectively, these results strongly suggest that PbBSMT is a novel effector, which is secreted by P. brassicae into its host plant to deplete pathogen-induced SA accumulation.
Caenorhabditis elegans
excitatory ventral cord motor neurons derive rhythm for body undulation
Authors: Wen Quan , Gao Shangbang , Zhen Mei
Published: September 2018

The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of
Caenorhabditis elegans
motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the
C. elegans
sensorimotor system.
C. elegans
exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems.
C. elegans
has manifested itself as a compact model to search for general principles of sensorimotor behaviours.

This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling
C. elegans
at cellular resolution’.
From head to tail: a neuromechanical model of forward locomotion inCaenorhabditis elegans
Authors: Izquierdo Eduardo J. , Beer Randall D.
Published: September 2018

With 302 neurons and a near-complete reconstruction of the neural and muscle anatomy at the cellular level,Caenorhabditis elegansis an ideal candidate organism to study the neuromechanical basis of behaviour. Yet despite the breadth of knowledge about the neurobiology, anatomy and physics ofC. elegans, there are still a number of unanswered questions about one of its most basic and fundamental behaviours: forward locomotion. How the rhythmic pattern is generated and propagated along the body is not yet well understood. We report on the development and analysis of a model of forward locomotion that integrates the neuroanatomy, neurophysiology and body mechanics of the worm. Our model is motivated by experimental analysis of the structure of the ventral cord circuitry and the effect of local body curvature on nearby motoneurons. We developed a neuroanatomically grounded model of the head motoneuron circuit and the ventral nerve cord circuit. We integrated the neural model with an existing biomechanical model of the worm's body, with updated musculature and stretch receptors. Unknown parameters were evolved using an evolutionary algorithm to match the speed of the worm on agar. We performed 100 evolutionary runs and consistently found electrophysiological configurations that reproduced realistic control of forward movement. The ensemble of successful solutions reproduced key experimental observations that they were not designed to fit, including the wavelength and frequency of the propagating wave. Analysis of the ensemble revealed that head motoneurons SMD and RMD are sufficient to drive dorsoventral undulations in the head and neck and that short-range posteriorly directed proprioceptive feedback is sufficient to propagate the wave along the rest of the body.

This article is part of a discussion meeting issue ‘Connectome to behaviour: modellingC. elegansat cellular resolution’.
Powerful and interpretable behavioural features for quantitative phenotyping ofCaenorhabditis elegans
Authors: Javer Avelino , Ripoll-Sánchez Lidia , Brown André E.X.
Published: September 2018

Behaviour is a sensitive and integrative readout of nervous system function and therefore an attractive measure for assessing the effects of mutation or drug treatment on animals. Video data provide a rich but high-dimensional representation of behaviour, and so the first step of analysis is often some form of tracking and feature extraction to reduce dimensionality while maintaining relevant information. Modern machine-learning methods are powerful but notoriously difficult to interpret, while handcrafted features are interpretable but do not always perform as well. Here, we report a new set of handcrafted features to compactly quantifyCaenorhabditis elegansbehaviour. The features are designed to be interpretable but to capture as much of the phenotypic differences between worms as possible. We show that the full feature set is more powerful than a previously defined feature set in classifying mutant strains. We then use a combination of automated and manual feature selection to define a core set of interpretable features that still provides sufficient power to detect behavioural differences between mutant strains and the wild-type. Finally, we apply the new features to detect time-resolved behavioural differences in a series of optogenetic experiments targeting different neural subsets.

This article is part of a discussion meeting issue ‘Connectome to behaviour: modellingC. elegansat cellular resolution’.
Developing a unique medical-grade honey which maximizes glucose oxidase activity
Authors: Li Zhiyuan , Parikh Rohan
Published: September 2018

In the fight against cancer and infection, honey is a compelling solution by virtue of its unique chemical composition; however, current medical-grade honeys are expensive and limited in their scope. In this study, a novel medical-grade honey was developed by maximizing the activity of glucose oxidase (GOX), an enzyme in honey that synthesizes hydrogen peroxide; maximization was done by neutralizing the effects of catalase and methylglyoxal (MGO), compounds in honey that interfere with H2O2 accumulation. Expressed GOX activity was quantified via H2O2 accumulation in honey after catalase, MGO, or both were inhibited. Results indicate the honeys tested have significant quantities of H2O2 inhibitors, greatly affecting expressed GOX activity; neutralization resulted in at least a 100% increase in H2O2 accumulation in all honeys. Blueberry honey with catalase inhibition by EGCG saw a 938% increase in H2O2 accumulation, reaching nearly three times the H2O2 accumulation in current medical grade honey for a tenth of the cost. This research presents a novel and readily reproducible method for maximizing H2O2 accumulation in any honey through neutralization of GOX inhibitors. GOX activity enhancement, combined with honey’s diverse antioxidants, enables the emergence of global low-cost medical-grade honeys with immense potential to revolutionize cancer and infection treatment.

This paper is based on work presented at the Regional Science and Engineering Fair on March 15, 2018 at Riverside High School (Loudoun County, Virginia), the Virginia State Science and Engineering Fair on April 14, 2018 at the Virginia Tech Carilion School of Medicine (Roanoke, Virginia).

Author Summary

With cancer and post-operative infections on the rise, a natural, low-cost alternative treatment is necessary. Honey is an ideal candidate due to its diverse antioxidants and glucose oxidase, an enzyme that produces hydrogen peroxide. The purpose of this research was to maximize glucose oxidase activity by neutralizing compounds that interfere with H2O2 accumulation. This research yielded medical-grade honeys that are economical and more effective than current ones, presenting a novel method that is reproducible on a large scale, scalable to different needs, and applicable to any honey to create low-cost medical-grade honeys that can revolutionize cancer and infection treatment globally.
Nuclear transcriptomes of the seven neuronal cell types that constitute theDrosophilamushroom bodies
Authors: Shih Meng-Fu Maxwell , Davis Fred P. , Henry Gilbert Lee , Dubnau Josh
Published: September 2018

The insect mushroom body (MB) is a conserved brain structure that plays key roles in a diverse array of behaviors. TheDrosophila melanogasterMB is the primary invertebrate model of neural circuits related to memory formation and storage, and its development, morphology, wiring, and function has been extensively studied. MBs consist of intrinsic Kenyon Cells that are divided into three major neuron classes (γ, α’/β’ and α/β) and 7 cell subtypes (γd, γm, α’/β’ap, α’/β’m, α/βp, α/βs and α/βc) based on their birth order, morphology, and connectivity. These subtypes play distinct roles in memory processing, however the underlying transcriptional differences are unknown. Here, we used RNA sequencing (RNA-seq) to profile the nuclear transcriptomes of each MB neuronal cell subtypes. We identified 350 MB class- or subtype-specific genes, including the widely used α/β class markerFas2and the α’/β’ class markertrio. Immunostaining corroborates the RNA-seq measurements at the protein level for several cases. Importantly, our data provide a full accounting of the neurotransmitter receptors, transporters, neurotransmitter biosynthetic enzymes, neuropeptides, and neuropeptide receptors expressed within each of these cell types. This high-quality, cell type-level transcriptome catalog for theDrosophilaMB provides a valuable resource for the fly neuroscience community.
Camouflaging of repetitive movements in autistic female and transgender adults
Authors: Wiskerke Joost , Stern Heléne , Igelström Kajsa
Published: September 2018

Repetitive movements (RMs), colloquially called “stimming” among adult autistic people and “motor stereotypies” among scientists, are common in autism. These behaviors fall under the domain of restricted and repetitive behaviors in the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). RMs can be socially disruptive or cause self-harm, but can also be experienced as cognitively or emotionally helpful and even enjoyable. Overt RMs are less common in females than in males, which could contribute to clinical difficulties in detecting their autism. In the social domain, autistic people with intact intelligence can often mask their social difficulties through various compensation strategies, and females appear especially skilled at it. Subjective report from verbally able adults may be useful as a first step in detecting potential camouflaging of RMs, and to provide a foundation for further studies. We founded an Internet-based outreach platform that became particularly successful in reaching female and transgender individuals. We recruited 342 individuals to an anonymous online questionnaire, collected data about self-reported RMs and probed for potential camouflaging. The cohort comprised 56% formally diagnosed participants and 44% who self-identified as autistic, and 17% of all participants reported non-cisgender identity. Thus, in addition to diagnosed women, we reached two populations that would normally be excluded from autism studies: transgender and undiagnosed participants. We found high rates of RMs in both diagnosed and self-identifying participants, and a striking prevalence of camouflaging. We suggest that camouflaging of RMs may contribute to underdiagnosis of autism, at least in females and transgender people, and that further studies on this topic are exceptionally important.
Group decision-making is optimal in adolescence
Authors: Haller Simone PW , Bang DAN , Bahrami Bahador , Lau Jennifer YF
Published: September 2018

Group decision-making is required in early life in educational settings and central to a well-functioning society. However, there is little research on group decision-making in adolescence, despite the significant neuro-cognitive changes during this period. Researchers have studied adolescent decision-making in ‘static’ social contexts, such as risk-taking in the presence of peers, and largely deemed adolescent decision-making ‘sub-optimal.’ It is not clear whether these findings generalise to more dynamic social contexts, such as the discussions required to reach a group decision. Here we test the optimality of group decision-making at different stages of adolescence. Pairs of male pre-to-early adolescents (8 to 13 years of age) and mid-to-late adolescents (14 to 17 years of age) together performed a low-level, perceptual decision-making task. Whenever their individual decisions differed, they were required to negotiate a joint decision. While there were developmental differences in individual performance, the joint performance of both adolescent groups was at adult levels (data obtained from a previous study). Both adolescent groups achieved a level of joint performance expected under optimal integration of their individual information into a joint decision. Young adolescents’ joint, but not individual, performance deteriorated over time. The results are consistent with recent findings attesting to the competencies, rather than the shortcomings, of adolescent social behaviour.
Management of Hsp90-Dependent Protein Folding by Small Molecule Targeting the Aha1 Co-Chaperone
Authors: Singh Jay , Tait Bradley , Guy Naihsuan , Sivils Jeffrey C. , Culbertson David , Dickey Chad , Kuo Szu Yu , Gestwicki Jason E. , Hutt Darren M. , Dyson Jane H. , Cox Marc B. , Balch William E.
Published: September 2018

The core cytosolic Hsp90 chaperone/co-chaperone complex plays a critical role in proteostasis management of human health and disease. To identify novel compounds that alter the ability of the Hsp90 co-chaperone Aha1 to modulate the ATPase activity found in multiple folding diseases ranging from steroid hormone receptor (SHR) sensitive prostate cancer to tauopathies associated with neurodegenerative diseases, we employed a high throughput screening (HTS) assay to monitor selectively Aha1-stimulated Hsp90 (ASH) ATPase activity. The ASH assay identified SEW04784 (SEW), a small molecule that disrupts ASH activity without inhibiting the basal Hsp90 ATPase activity. NMR analysis reveals that SEW binds to the C-terminal domain of Aha1 to disrupt its asymmetric binding to Hsp90 leading to abrogation of its chaperoning activity of Hsp90. SEW exhibits therapeutic potential by blocking the transcriptional activity of prostate cancer (PCa) associated variants of the androgen receptor (AR) in a cell-based model of PCa. Additionally, SEW exhibits the ability to clear toxic, phosphorylated tau aggregated species associated with tauopathies. By not directly impacting the basal ATPase function of the abundant and ubiquitous Hsp90, SEW could provide a therapeutic approach for mitigation of client-specific proteostatic disease.