bluuebunny/crossref_metadata_2025 huggingface dataset:
Generic person marking in Japhug and other Gyalrong
languages
Authors: Jacques Guillaume
Published: July 2018

This paper discusses the history of generic person marking systems in
several Gyalrong languages. While closely related, Japhug and
Tshobdun differ considerably: the inverse prefix marks generic A in
Japhug, while it appears in the generic P form in Tshobdun. We
propose a historical scenario to explain how such radically
different systems came into being, proposing in particular that one
of the generic human markers was grammaticalized from a nominalizer,
and show that our reconstruction can also explain the origin of the
local scenario portmanteau 1→2 and 2→1 prefixes. These
reconstructions allow us to establish the existence of several
previously unattested grammaticalization pathways.
Characterization and abolishment of the cyclopiazonic acids produced by Aspergillus oryzae HMP-F28
Authors: Cao Ting , Ling Junhong , Liu Yi , Chen Xiaoqi , Tian Xiaoyue , Meng Dali , Pan Huaqi , Hu Jiangchun , Wang Nan
Published: July 2018

Extracellular alkalinization and H2O2 production are important early events during induced resistance establishment in plants. In a screen for metabolites as plant resistance activators from 98 fungal isolates associated with marine sponge Hymeniacidon perleve, the cyclopiazonic acids (CPAs) produced by Aspergillus oryzae HMP-F28 induced significant extracellular alkalinization coupled with augmented H2O2 production in tobacco cell suspensions. Bioassay-guided fractionation led to the isolation and structural elucidation of a new CPA congener (4, 3-hydroxysperadine A) and three known ones (1–3). To construct a mutasynthetic strain to generate unnatural CPA analogues, a hybrid pks-nrps gene (cpaS) was disrupted to abolish the production of the critical precursor of cyclo-acetoacetyl-l-tryptophan (cAATrp) and all the downstream CPA products. Elimination of cAATrp will allow cAATrp mimics being processed by the CPA biosynthetic machinery to produce CPA derivatives with designed structural features.
Forty years of wicked problems literature: forging closer links to policy studies
Authors: Head Brian W
Published: July 2018

Rittel and Webber boldly challenged the conventional assumption that ‘scientific’ approaches to social policy and planning provide the most reliable guidance for practitioners and researchers who are addressing complex, and contested, social problems. This provocative claim, that scientific-technical approaches would not ‘work’ for complex social issues, has engaged policy analysts, academic researchers and planning practitioners since the 1970s. Grappling with the implications of complexity and uncertainty in policy debates, the first generation of ‘wicked problem’ scholars generally agreed that wicked issues require correspondingly complex and iterative approaches. This tended to quarantine complex ‘wicked’ problems as a special category that required special collaborative processes. Most often they recommended the inclusion of multiple stakeholders in exploring the relevant issues, interests, value differences and policy responses. More than four decades later, however, there are strong arguments for developing a second-generation approach which would ‘mainstream’ the analysis of wicked problems in public policy. While continuing to recognize the centrality of complexity and uncertainty, and the need for creative thinking, a broader approach would make better use of recent public policy literatures on such topics as problem framing, policy design, policy capacity and the contexts of policy implementation.
Religiosity and consumer behavior: a summarizing review
Authors: Agarwala Ridhi , Mishra Prashant , Singh Ramendra
Published: July 2018

This article is a summarizing review on religiosity and consumer behavior. Review findings from marketing literature indicate that religiosity influences consumer outcomes like materialism, intolerance, ethics, and risk aversion. It also impacts consumer attitude toward religious products and economic shopping behavior. A conceptual framework is presented to depict how certain dimensions of religion can explain the psychological mechanisms underlying these effects. Specifically, we propose prayer (religious rituals), religious exclusivism and divine retribution (religious beliefs), frugality (religious values) and religious community involvement and religious identity (religious community) as possible antecedents that drive the previously established differences in consumer behavior. For each of these antecedents, we offer definitions and integrate research findings from psychology, religion and marketing to build testable propositions. This essay complements preceding work and at the same time expands and broadens it by developing theory regarding the causal linkages between religiosity and consumer outcomes.
Accurate and adaptive imputation of summary statistics in mixed-ethnicity cohorts
Authors: Togninalli Matteo , Roqueiro Damian ,   COPDGene Investigators, Borgwardt Karsten M
Published: July 2018

Motivation

Methods based on summary statistics obtained from genome-wide association studies have gained considerable interest in genetics due to the computational cost and privacy advantages they present. Imputing missing summary statistics has therefore become a key procedure in many bioinformatics pipelines, but available solutions may rely on additional knowledge about the populations used in the original study and, as a result, may not always ensure feasibility or high accuracy of the imputation procedure.

Results

We present ARDISS, a method to impute missing summary statistics in mixed-ethnicity cohorts through Gaussian Process Regression and automatic relevance determination. ARDISS is trained on an external reference panel and does not require information about allele frequencies of genotypes from the original study. Our method approximates the original GWAS population by a combination of samples from a reference panel relying exclusively on the summary statistics and without any external information. ARDISS successfully reconstructs the original composition of mixed-ethnicity cohorts and outperforms alternative solutions in terms of speed and imputation accuracy both for heterogeneous and homogeneous datasets.

Availability and implementation

The proposed method is available at https://github.com/BorgwardtLab/ARDISS.

Supplementary information

Supplementary data are available at Bioinformatics online.
Crumble: reference free lossy compression of sequence quality values
Authors: Bonfield James K , McCarthy Shane A , Durbin Richard
Published: July 2018

Motivation

The bulk of space taken up by NGS sequencing CRAM files consists of per-base quality values. Most of these are unnecessary for variant calling, offering an opportunity for space saving.

Results

On the Syndip test set, a 17 fold reduction in the quality storage portion of a CRAM file can be achieved while maintaining variant calling accuracy. The size reduction of an entire CRAM file varied from 2.2 to 7.4 fold, depending on the non-quality content of the original file (see Supplementary Material S6 for details).

Availability and implementation

Crumble is OpenSource and can be obtained from https://github.com/jkbonfield/crumble.

Supplementary information

Supplementary data are available at Bioinformatics online.
Goblet cell-produced retinoic acid suppresses CD86 expression and IL-12 production in bone marrow-derived cells
Authors: Xiao Yangyan , de Paiva Cintia S , Yu Zhiyuan , de Souza Rodrigo G , Li De-Quan , Pflugfelder Stephen C
Published: July 2018

Conjunctival goblet cell loss in ocular surface diseases is accompanied by increased number of interleukin-12 (IL-12)-producing antigen-presenting cells (APCs) and increased interferon-γ (IFN-γ) expression. This study tested the hypothesis that mouse conjunctival goblet cells produce biologically active retinoic acid (RA) that suppresses CD86 expression and IL-12 production by myeloid cells. We found that conditioned media from cultured conjunctival goblet cells (CjCM) suppressed stimulated CD86 expression, NF-κB p65 activation and IL-12 and IFN-γ production in unstimulated and lipopolysaccharide-stimulated cultured bone marrow-derived cells (BMDCs) containing a mixed population of APCs. Goblet cell-conditioned, ovalbumin-loaded APCs suppressed IFN-γ production and increased IL-13 production in co-cultured OTII cells. The goblet cell suppressive activity is due in part to their ability to synthesize RA from retinol. Conjunctival goblet cells had greater expression of aldehyde dehydrogenases Aldh1a1 and a3 and ALDEFLUOR activity than cornea epithelium lacking goblet cells. The conditioning activity was lost in goblet cells treated with an ALDH inhibitor, and a retinoid receptor alpha antagonist blocked the suppressive effects of CjCM on IL-12 production. Similar to RA, CjCM increased expression of suppressor of cytokine signaling 3 (SOCS3) in BMDCs. SOCS3 silencing reversed the IL-12-suppressive effects of CjCM. Our findings indicate that conjunctival goblet cells are capable of synthesizing RA from retinol secreted by the lacrimal gland into tears that can condition APCs. Evidence suggests goblet cell RA may function in maintaining conjunctival immune tolerance and loss of conjunctival goblet cells may contribute to increased Th1 priming in dry eye.
Electrocochleographic Responses Before and After Short-Term Suprathreshold Electrical Stimulation in Human Cochlear Implant Recipients
Authors: Hoesli Marco , Huber Alexander , Pfiffner Flurin , Veraguth Dorothe , Roosli Christof , Dalbert Adrian
Published: July 2018

Objective:

To assess changes in electrocochleographic (ECoG) responses following short-term suprathreshold electrical stimulation during cochlear implant (CI) telemetry in CI recipients.

Methods:

Extracochlear ECoG recordings were conducted before and after intraoperative short-term suprathreshold electrical stimulation. Tone bursts at 500, 750, and 1000 Hz as well as clicks were used as acoustic stimuli. Changes of ECoG responses were correlated to calculated maximum electrical charge levels.

Results:

Fourteen subjects were included. On average, no significant changes of ECoG responses occurred in the earliest postoperative phase; therefore, also following short-term suprathreshold electrical stimulation. However, one subject (S7) showed a decrease of ECoG responses. Neural as well as hair cell components of the ECoG signal were affected. On average, the maximum electrical charge level was 22 nC (range, 15–37 nC). In S7, the maximum electrical charge level was 17 nC. No correlations were found between maximum electrical charge levels and changes of ECoG signals.

Conclusion:

In a majority of cases, electrophysiological responses to acoustic stimuli remain unchanged in the earliest postoperative phase. However, deterioration of cochlear function occurs in this phase. Neural as well as hair cell components of the ECoG signal are affected. Such deterioration is not associated with unusually high electrical charge levels during CI telemetry. Overall, our results support the notion that an electrical charge applied at levels used in the clinical routine does not have an acute deleterious effect on cochlear function.
The Hand-eye Coordination of Professional Baseball Players: The Relationship to Batting
Authors: Laby Daniel M. , Kirschen David G. , Govindarajulu Usha , DeLand Paul
Published: July 2018

SIGNIFICANCE

A visuomotor skill (eye-hand visual-motor reaction time [EH-VMRT]) important for baseball performance is described. Eye-hand visual-motor reaction time represents the integration of visual information, perceptually based decisions, and motor movements to accomplish a specific task. The speed at which this occurs depends on many factors, some visual, some perceptual, and some motor related.

PURPOSE

The purpose of this study was to describe the EH-VMRT ability and evaluate its relationship to the baseball batting performance of professional baseball players.

METHODS

A commercially available EH-VMRT system was used on 450 professional baseball players. Results were retrospectively compared with standard, career, plate discipline metrics.

RESULTS

Statistically significant correlations were found between the EH-VMRT metrics and plate discipline batting metrics. Better EH-VMRT ability also correlated with longer service in, and likelihood to achieve, the major-league level. The better (top 20%) EH-VMRT group had three fewer at bats before gaining a walk (22% decrease), as well as swinging 10 to 12% less often at pitches outside the strike zone and 6 to 7% less often at pitches in the strike zone as compared with the bottom 20% group. In addition, EH-VMRT displays a threshold-like relationship with the ability to gain a walk.

CONCLUSIONS

These results describe the EH-VMRT ability of professional baseball players and show a significant relationship between the EH-VMRT ability and batting performance. These results may suggest a possible role in player selection, indicating that batters with better EH-VMRT may be more likely to reach the major-league level and be more productive for their team. Further studies will be needed to demonstrate whether training better EH-VMRT results in improved batting performance.
Branch/mode competition in the flow-induced vibration of a square cylinder
Authors: Zhao Jisheng , Nemes András , Lo Jacono David , Sheridan John
Published: July 2018

The flow-induced vibration response of a square cross-sectional cylinder with low mass and damping ratio is analysed using continuous wavelet transforms (CWT) for three representative angles of attack of the cylinder to the incoming flow. The amplitude and frequency responses over a range of flow velocities map out multiple regimes (branches) of oscillation. Analysis of the time–frequency domain for boundary regions between branches using CWT reveals intermittency at the synchronization region boundaries as well as mode competition at branch boundaries. Complementary recurrence analysis shows that periodic dynamical states are interrupted by chaotic bursts in the transition regions around the higher branch at an angle of attack of
α
 = 20° (a new branch first observed by Nemes
et al.
(2012
J. Fluid Mech.
710
, 102–130 (
doi:10.1017/jfm.2012.353
))), supporting the CWT-based frequency–time analysis.

This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
Wavelet-based analysis of time-variant adaptive structures
Authors: Dziedziech Kajetan , Nowak Alexander , Hasse Alexander , Uhl Tadeusz , Staszewski Wiesław J.
Published: July 2018

Wavelet analysis is applied to identify the time-variant dynamics of adaptive structures. The wavelet-based power spectrum of the structural response, wavelet-based frequency response function (FRF) and wavelet-based coherence are used to identify continuously and abruptly varying natural frequencies. A cantilever plate with surface-bonded macro fibre composite—which alters the structural stiffness—is used to demonstrate the application of the methods. The results show that the wavelet-based input–output characteristics—i.e. the FRF and coherence—can identify correctly the dynamics of the analysed time-variant system and reveal the varying natural frequency. The wavelet-based coherence can be used not only for the assessment of the quality of the wavelet-based FRF but also for the identification.

This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
Continuous wavelet transform in the study of the time-scale properties of intracranial pressure in hydrocephalus
Authors: García María , Poza Jesús , Santamarta David , Romero-Oraá Roberto , Hornero Roberto
Published: July 2018

Normal pressure hydrocephalus (NPH) encompasses a heterogeneous group of disorders generally characterized by clinical symptoms, ventriculomegaly and anomalous cerebrospinal fluid (CSF) dynamics. Lumbar infusion tests (ITs) are frequently performed in the preoperatory evaluation of patients who show NPH features. The analysis of intracranial pressure (ICP) signals recorded during ITs could be useful to better understand the pathophysiology underlying NPH and to assist treatment decisions. In this study, 131 ICP signals recorded during ITs were analysed using two continuous wavelet transform (CWT)-derived parameters: Jensen divergence (JD) and spectral flux (SF). These parameters were studied in two frequency bands, associated with different components of the signal:
B
1
(0.15–0.3 Hz), related to respiratory blood pressure oscillations; and
B
2
(0.67–2.5 Hz), related to ICP pulse waves. Statistically significant differences (
p
 < 1.70 × 10
−3
, Bonferroni-corrected Wilcoxon signed-rank tests) in pairwise comparisons between phases of ITs were found using the mean and standard deviation of JD and SF. These differences were mainly found in
B
2
, where a lower irregularity and variability, together with less prominent time-frequency fluctuations, were found in the hypertension phase of ITs. Our results suggest that wavelet analysis could be useful for understanding CSF dynamics in NPH.

This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
California's carbon market and energy prices: a wavelet analysis
Authors: Aguiar-Conraria Luís , Joana Soares Maria , Sousa Rita
Published: July 2018

Carbon price is a key variable in management and risk decisions in activities related to the burning of fossil fuels. Different major players in this market, such as polluters, regulators and financial actors, have different time horizons. We use innovative multivariate wavelet analysis tools, including partial wavelet coherence and partial wavelet gain, to study the link between carbon prices and final energy prices in the time and frequency dimensions in California's carbon market, officially known as the California cap-and-trade programme. We find that gasoline prices lead an anti-phase relation with carbon prices. This result is very stable at lower frequencies (close to 1-year period cycles), and it is also present before mid-2015 in the 20–34 weeks frequency band. Regarding electricity, we find that at about a 1-year period, a rise in carbon prices is reflected in higher electricity prices. We conclude that the first 5 years of compliance of the California cap-and-trade programme show that emissions trading is a significant measure for climate change mitigation, with visible rising carbon prices. The quantitative financial analytics we present supports the recent decision to extend the current market to 2030 without the need for complementary carbon pricing schemes.

This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
A review of Morlet wavelet analysis of radial profiles of Saturn's rings
Authors: Tiscareno Matthew S. , Hedman Matthew M.
Published: July 2018

Spiral waves propagating in Saturn's rings have wavelengths that vary with radial position within the disc. The best-quality observations of these waves have the form of radial profiles centred on a particular azimuth. In that context, the wavelength of a given spiral wave is seen to change substantially with position along the one-dimensional profile. In this paper, we review the use of Morlet wavelet analysis to understand these waves. When signal to noise is high and the cause of the wave is well understood, wavelet analysis has been used to solve for wave parameters that are diagnostic of local disc properties. Waves that are not readily perceptible in the spatial domain signal can be clearly identified. Furthermore, filtering in wavelet space, followed by the reverse wavelet transform, has been used to isolate the part of the signal that is of interest. When the cause of the wave is not known, comparing the phases of the complex-valued wavelet transforms from many profiles has been used to determine wave parameters that cannot be determined from any single profile. When signal to noise is low, co-adding wavelet transforms while manipulating the phase has been used to boost a wave's signal above detection limits.

This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
Aptamer-based biosensor for food allergen determination using graphene oxide/gold nanocomposite on a paper-assisted analytical device
Authors: Tah Amit , Olmos Cordero Jorge M. , Weng Xuan , Neethirajan Suresh
Published: July 2018

The detection of allergens in food are currently conducted by techniques that are time-consuming and complicated which can deter consistent sampling for allergens, which could potentially cause an anaphylactic shock in the consumer by cross-contamination. The need for a technique that is rapid, on-site, cost-effective, disposable, highly sensitive and accurate to identify these molecules urges the development of a point-of-care device. The aim of this work is to develop a microfluidic paper-assisted analytical device (PAD) using hydrophobic channels, set by a wax printer on filter paper, and functionalized gold nanoparticles (AuNP) to help identify the allergens arachin (Ara h 1) for peanuts, β-lactoglobulin (β LG) for milk, and tropomyosin (Pen a 1) for shrimp and other shellfish presence by a colorimetric test. Synthesized AuNP were conjugated with biotinylated aptamers, using the biotin-streptavidin interaction, to make the specific detection of target allergens. Functionalized AuNP are incubated with the sample and are absorbed by graphene oxide (GO), creating GO-AuNP complexes, if the aptamers have not become structured due to conjugation with allergenic proteins. The PAD device is used to filter the resultant mixture which provides superior sensitivity to detect the allergens present down to the nanogram range (allergens were measured from 25 nM - 1000 nM with a LOD of 7.8 nM, 12.4 nM and 6.2 nM for peanut, milk and shrimp allergens respectively), in contrast to the microgram range of commonly used enzymatic immunoassays. The simple color indicator, varying from clear to pink in the presences of allergens allows the readout to be utilized without the need for highly specific equipment or training. Alternatively, the results can be quantified by taking a picture and measuring the color. This presented PAD can provide results in real time and has the potential to become a rapid, low-cost, and accurate portable point-of-care device to avoid cross-reactivity of food-borne allergens.
Genomic inversion drives small colony variant formation and increased virulence inP. aeruginosa
Authors: Irvine Sharon , Bunk Boyke , Bayes Hannah K. , Sprӧer Cathrin , Connolly James P. R. , Six Anne , Evans Thomas J. , Roe Andrew J. , Overmann Jӧrg , Walker Daniel
Published: July 2018

Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronicPseudomonas aeruginosalung infection in patients with cystic fibrosis, well-characterised phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoidP. aeruginosastrain NH57388A. Here we show, using a combination of singlemolecule real-time (PacBio) and Illumina sequencing that the genetic switch for conversion to the SCV phenotype is a large genomic inversion through recombination between homologous regions of two rRNA operons. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance since the appearance of SCVs during chronic infection is associated with declining lung function.
Transcriptional regulatory mechanisms of fibrosis development in mouse lung tissue exposed to carbon nanotubes
Authors: Zhernovkov Vadim , Santra Tapesh , Cassidy Hilary , Rukhlenko Oleksii , Matallanas David , Krstic Aleksandar , Kolch Walter , Lobaskin Vladimir , Kholodenko Boris N.
Published: July 2018

Background

Carbon nanotubes (CNTs) usage has rapidly increased in the last few decades due to their unique properties, exploited in various industrial and commercial products. Certain types of CNTs cause adverse health effects, including chronic inflammation and fibrosis. Despite the large number of in vitro and in vivo studies evaluating these effects, many important questions remain unanswered due to a lack of mechanistic understanding of how CNTs induce cellular stress responses. In order to predict CNT toxicity, it is important to understand which transcriptional programs are specifically activated in response to CNTs, and what similarities and differences exist in relation to other toxic inducers exerting similar adverse effects.

Results

A systems biology approach was applied to reveal complex interactions at the molecular level in mouse lung tissue in response to different fibrosis inducers: two types of multi-walled CNTs, NM-401 and NRCWE-26, and bleomycin (BLM). Based on mRNA gene expression profiles, we inferred gene regulatory networks (GRNs) to capture functional hierarchical regulatory structures between genes and their regulators. We found that activities of the transcription factors (TFs) Myc, Arid5a and Mxd1 were associated with the regulation of cytokine transcription in response to CNTs, while in response to BLM treatment, Myc was associated with p53 signaling. TF Litaf was identified as the essential regulator for noncanonical signaling of TLR2/4 driven by CNTs. Despite the different nature of the lung injury caused by CNTs and BLM, we identified common stress response modules, that included DNA damage (TFs: E2f8, E2f1, Foxm1), M1/M2 macrophage polarization (TF: Mafb), Interferon response (TFs: Irf7, Stat2 and Irf9) for all agents.

Conclusions

These results suggest that the reconstruction and analysis of TF-centric gene interaction networks can reveal key targets and regulators of cellular stress responses to toxic agents.
Conserved SQ and QS motifs in bacterial effectors suggest pathogen interplay with the ATM kinase family during infection
Authors: Sampietro Davide , Sámano-Sánchez Hugo , Davey Norman E. , Sharan Malvika , Mészáros Bálint , Gibson Toby J. , Kumar Manjeet
Published: July 2018

Understanding how bacteria hijack eukaryotic cells during infection is vital to develop better strategies to counter the pathologies that they cause. ATM kinase family members phosphorylate eukaryotic protein substrates on Ser or Thr residues followed by Gln. The kinases are active under oxidative stress conditions and/or the presence of ds-DNA breaks. While examining the protein sequences of well-known bacterial effector proteins such as CagA and Tir, we noticed that they often show conserved (S/TQ) motifs, even though the evidence for effector phosphorylation by ATM has not been reported. We undertook a bioinformatics analysis to examine effectors for their potential to mimic the eukaryotic substrates of the ATM kinase. The candidates we found could interfere with the host’s intracellular signaling network upon interaction, which might give an advantage to the pathogen inside the host. Further, the putative phosphorylation sites should be accessible, conserved across species and, in the vicinity to the phosphorylation sites, positively charged residues should be depleted. We also noticed that the reverse motif (QT/S) is often also conserved and located close to (S/TQ) sites, indicating its potential biological role in ATM kinase function. Our findings could suggest a mechanism of infection whereby many pathogens inactivate/modulate the host ATM signaling pathway.
A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis
Authors: Hercyk Brian S. , Rich-Robinson Julie T. , Mitoubsi Ahmad S. , Harrell Marcus A. , Das Maitreyi E.
Published: July 2018

Cdc42, a conserved regulator of cell polarity, is activated by two GEFs, Gef1 and Scd1, in fission yeast. Whilegef1andscd1mutants exhibit distinct phenotypes, how they do so is unclear given that they activate the same GTPase. Using the GEF localization pattern during cytokinesis as a paradigm, we report a novel interplay between Gef1 and Scd1 that spatially modulates Cdc42. We find that Gef1 promotes Scd1 localization to the division site during cytokinesis and to the new end during polarized growth through the recruitment of the scaffold Scd2 via a Cdc42 feedforward pathway. Gef1-mediated Scd1 recruitment at the new end enables the transition from monopolar to bipolar growth. Reciprocally, Scd1 restricts Gef1 localization to prevent ectopic Cdc42 activation during cytokinesis to promote cell separation and during interphase to maintain cell shape. Our findings reveal an elegant regulatory pattern in which Gef1 establishes new sites of Scd1-mediated Cdc42 activity, while Scd1 restricts Gef1 to functional sites. We propose that crosstalk between GEFs is a conserved mechanism that orchestrates Cdc42 activation during complex cellular processes.

Summary Statement

Cdc42 GEFs Gef1 and Scd1 crosstalk to fine-tune Cdc42 activity. This crosstalk promotes bipolar growth and maintains cell shape in fission yeast.
Deep learning for inferring gene relationships from single-cell expression data
Authors: Yuan Ye , Bar-Joseph Ziv
Published: July 2018

Several methods were developed to mine gene-gene relationships from expression data. Examples include correlation and mutual information methods for co-expression analysis, clustering and undirected graphical models for functional assignments and directed graphical models for pathway reconstruction. Using a novel encoding for gene expression data, followed by deep neural networks analysis, we present a framework that can successfully address all these diverse tasks. We show that our method, CNNC, improves upon prior methods in tasks ranging from predicting transcription factor targets to identifying disease related genes to causality inference. CNNC’s encoding provides insights about some of the decisions it makes and their biological basis. CNNC is flexible and can easily be extended to integrate additional types of genomics data leading to further improvements in its performance.

Supporting website with software and data:https://github.com/xiaoyeye/CNNC.
Orthogonal Representations of Reward Magnitude, Certainty, and Volatility in the Macaque Orbitofrontal Cortex
Authors: Yang Tianming , Murray Elisabeth A.
Published: July 2018

Categorical knowledge about the probabilistic and volatile nature of resource availability can improve foraging strategies, yet we have little understanding of how the brain represents such knowledge. Neurons in the orbitofrontal cortex (OFC) of macaques encode several decision variables (e.g., reward magnitude, probability) that could influence choice behavior. Here we investigated whether OFC neurons also represent two aspects of reward predictability: certainty and volatility. Rhesus monkeys performed a visual stimulus-reward association task in which a set of simple shapes preceded the delivery of reward, and they learned the nature of each shape’s reward association along two dimensions. One involved the certainty of a reward outcome; rewards can be either deterministic (and therefore certain) or probabilistic (uncertain). A second dimension reflected the volatility of an outcome; reward schedules can be either stable over time or volatile. During stimulus presentation, the activity of OFC neurons reflected both categorical certainty and categorical volatility, in addition to reward magnitude. These three characteristics were represented orthogonally by three distinct neural populations of similar size. These findings point to a more general role for OFC in processing reward information than one restricted to encoding parametric valuations such as reward magnitude and probability.
Extensive recoding of dengue virus type 2 specifically reduces replication in primate cells without gain-of-function in Aedes aegypti mosquitoes
Authors: Stauft Charles B. , Shen Sam H. , Song Yutong , Gorbatsevych Oleksandr , Asare Emmanuel , Futcher Bruce , Mueller Steffen , Payne Anne , Brecher Matthew , Kramer Laura , Wimmer Eckard
Published: July 2018

Dengue virus (DENV), an arthropod-borne (“arbovirus”) virus causing a range of human maladies ranging from self-limiting dengue fever to the life-threatening dengue shock syndrome, proliferates well in two different taxa of the Animal Kingdom, mosquitoes and primates. Unexpectedly, mosquitoes and primates have distinct preferences when expressing their genes by translation, e.g. members of these taxa show taxonomic group-specific intolerance to certain codon pairs. This is called “codon pair bias”. By necessity, arboviruses evolved to delicately balance this fundamental difference in their ORFs. Using the mosquito-borne human pathogen DENV we have undone the evolutionarily conserved genomic balance in its ORF sequence and specifically shifted the encoding preference away from primates. However, this recoding of DENV raised concerns of ‘gain-of-function,’ namely whether recoding could inadvertently increase fitness for replication in the arthropod vector. Using mosquito cell cultures and two strains of Aedes aegypti we did not observe any increase in fitness in DENV2 variants codon pair deoptimized for humans. This ability to disrupt and control an arbovirus’s host preference has great promise towards developing the next generation of synthetic vaccines not only for DENV but for other emerging arboviral pathogens such as chikungunya virus and Zika virus.
A statistical note on the detection of autoassociative dynamics in hippocampal place-cell sequences
Authors: Gönner Lorenz , Vitay Julien , Hamker Fred
Published: July 2018

The sequential activity of hippocampal place cells observed during sleep and awake resting is widely viewed as a neural correlate of memory processes. While recent work has advanced our understanding of the content represented during rest-related place-cell sequences, the nature of hippocampal population dynamics during sequential activity remains poorly understood. A recent experimental study has reported that place-cell sequences show a pattern of step-like movement, reminiscent of transitions between discrete attractor states (Pfeiffer and Foster, 2015). By contrast, previous theoretical models predict that the spatiotemporal structure of place-cell sequences should reflect the disribution of place fields, typically observed to be spatially smooth.

Motivated by this discrepancy between models and experimental data, we performed a quantitative comparison between these results and the spike trains generated by a network model for the generation of place-cell sequences (Gönner et al., 2017). Although the model is based on continuous attractor network dynamics, we observed that the movement of sequential place representations was phase-locked to the population oscillation, highly similar to the experimental data interpreted as evidence for discrete attractor dynamics. To resolve this potential contradiction, we performed a detailed analysis of the methodology used to identify discrete attractor dynamics. Our results show that a previous approach to step size decoding is prone to a decoding artefact. We propose a modified approach to estimate step sizes which may help to characterize the underlying circuit dynamics in vivo.
Measuring Orangutan nest structure using Unmanned Aerial Vehicle (UAV) and ImageJ
Authors: Kamaruszaman Salniza Akmar , Fadzly Nik , Abd Mutalib Aini Hasanah , Muslim Aidy M. , Atmoko Sri Suci Utami , Mansor Mashhor , Mansor Asyaf , Rupert Nadine , Zakaria Rahmad , Hashim Zarul Hazrin , Md Sah Amir Shah Ruddin , Jamsari Fadhirul Fitri , Azman Nur Munira
Published: July 2018

The nest is one of the crucial elements in orangutan daily activities. Previously, most of the nest structure studies were done manually by estimating measurement directly from visual observation. However, using the latest unmanned aerial vehicle (UAV) technology, we can reduce the workforce, time and energy while simultaneously ensuring the safety of the researcher conducting nest structure analysis. We recorded 49 pictures of orangutan nests at Sepilok Orangutan Rehabilitation Centre (SORC) using UAV (DJI Phantom 3 Quadcopter). The nest structure (length, depth, and width) was digitally measured by using ImageJ. Most of the nests were built at a strong, stable, and comfortable position at the top of the tree. Most orangutans chose Eusideroxylon zwageri to build nest compared to other tree species because of the strong and durable wood characteristic which would create a sturdy, strong and comfortable nest. We propose the use of drone with digital image analysis could provide a more accurate, less time consuming and safe method for studying orangutan nest structure.
Delayed differentiation of vaginal and uterine microbiomes in dairy cows developing postpartum endometritis
Authors: Miranda-CasoLuengo Raúl , Lu Junnan , Williams Erin J. , Miranda-CasoLuengo Aleksandra A. , Carrington Stephen D. , Evans Alexander C.O. , Meijer Wim G.
Published: July 2018

Bacterial infection of the uterus is a normal event after parturition. While the healthy cow achieves uterine clearance early postpartum, cows unable to control the infection within 21 days after calving develop postpartum endometritis. Studies on the Microbial Ecology of the bovine reproductive tract have focused on either vaginal or uterine microbiomes. This is the first study that compares both microbiomes in the same animals. Terminal Restriction Fragment Length Polymorphism of the 16S rRNA gene showed that despite large differences associated to individuals, a shared community exist in vagina and uterus during the postpartum period. The largest changes associated with development of endometritis were observed at 7 days postpartum, a time when vaginal and uterine microbiomes were most similar. 16S rRNA Pyrosequencing of the vaginal microbiome at 7 days postpartum showed at least three different microbiome types that were associated with postpartum endometritis. All three microbiome types featured reduced bacterial diversity. Taken together, the above findings support a scenario where disruption of the compartmentalization of the reproductive tract during parturition results in the dispersal and mixing of the vaginal and uterine microbiomes, which subsequently are subject to differentiation. This microbial succession is likely associated to early clearance in the healthy cow. In contrast, loss of bacterial diversity and dominance of the microbiome by few bacterial taxa were related to a delayed succession in cows developing endometritis at 7 DPP.
Young Children Integrate Current Observations, Priors and Agent Information to Build Predictive Models of Others’ Actions
Authors: Kayhan E. , Heil L. , Kwisthout J. , van Rooij I. , Hunnius S. , Bekkering H.
Published: July 2018

From early on in life, children are able to use information from their environment to form predictions about events. For instance, they can use statistical information about a population to predict the sample drawn from that population and infer an agent’s preferences from systematic violations of random sampling. We investigated how young children build and update models of an agent’s sampling actions over time, and whether a computational model based on the causal Bayesian network formalization of predictive processing can explain this process.

We formalized three hypotheses about how different explanatory variables (i.e., prior probabilities, current observations, and agent characteristics) are used to build predictive models of others’ actions. We measured pupillary responses as a behavioral marker of ‘prediction errors’ (i.e., the perceived mismatch between what one’s model of an agent predicts and what the agent actually does), as described in the predictive processing framework. Pupillary responses of 24-month-olds, but not 18-month-olds, showed that young children integrated information about current observations, priors and agents to generate predictive models of agents and their actions.

These findings shed light on the mechanisms behind toddlers’ inferences about agent-caused events. To our knowledge, this is the first study in which young children’s pupillary responses are used as markers of prediction errors, and explained by a computational model based on the causal Bayesian network formalization of predictive processing. We argue that the predictive processing framework provides a promising explanation of the way in which young children process other persons’ actions.

Highlights

We present three formalized hypotheses on how young children generate predictive models of others’ sampling actions.

We measured pupillary responses of children as a behavioral marker of prediction errors as described in the predictive processing framework.

Results showed that young children integrated information about current observations, prior probabilities and agents to generate predictive models about others’ actions.

A computational model based on the causal Bayesian network formalization of predictive processing can explain this process.
Quantitative and qualitative evaluation of the impact of the G2 enhancer, bead sizes and lysing tubes on the bacterial community composition during DNA extraction from recalcitrant soil core samples based on community sequencing and qPCR
Authors: Gobbi Alex , Santini Rui G. , Filippi Elisa , Jensen Lea Ellegaard- , Jacobsen Carsten S. , Hansen Lars H.
Published: July 2018

Soil DNA extraction encounters numerous challenges that can affect both yield and purity of the recovered DNA. Clay particles lead to reduced DNA extraction efficiency, and PCR inhibitors from the soil matrix can negatively affect downstream analyses when applying DNA sequencing. Further, these effects impede molecular analysis of bacterial community compositions in lower biomass samples, as often observed in deeper soil layers. Many studies avoid these complications by using indirect DNA extraction with prior separation of the cells from the matrix, but such methods introduce other biases that influence the resulting microbial community composition.

To address these issues, a direct DNA extraction method was applied in combination with the use of a commercial product, the G2 DNA/RNA Enhancer®, marketed as being capable of improving the amount of DNA recovered after the lysis step. The results showed that application of G2 increased DNA yields from the studied clayey soils from layers between 1.00 and 2.20 m below ground level.

Importantly, the use of G2 did not introduce bias, as it did not result in any significant differences in the biodiversity of the bacterial community measured in terms of alpha and beta diversity and taxonomical composition.

Finally, this study considered a set of customised lysing tubes for evaluating possible influences on the DNA yield. Tubes customization included different bead sizes and amounts, along with lysing tubes coming from two suppliers. Results showed that the lysing tubes with mixed beads allowed greater DNA recovery compared to the use of either 0.1 or 1.4 mm beads, irrespective of the tube supplier.

These outcomes may help to improve commercial products in DNA/RNA extraction kits, besides raising awareness about the optimal choice of additives, offering opportunities for acquiring a better understanding of topics such as vertical microbial characterisation and environmental DNA recovery in low biomass samples.
Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects underlying impaired adult neurogenesis
Authors: Zywitza Vera , Misios Aristotelis , Bunatyan Lena , Willnow Thomas E. , Rajewsky Nikolaus
Published: July 2018

Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs are crucial for regulating stem cell self-renewal and differentiation. We used single-cell RNA profiling to generate an unbiased molecular atlas of all cell types in the largest neurogenic niche of the adult mouse brain, the subventricular zone (SVZ). We characterized > 20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we apply our single-cell approach to mice lacking LRP2, an endocytic receptor required for SVZ maintenance. The number of NSCs and proliferating progenitors was significantly reduced. Moreover, Wnt and BMP4 signaling was perturbed. We provide a valuable resource for adult neurogenesis, insights into SVZ neurogenesis regulation by LRP2, and a proof-of-principle demonstrating the power of single-cell RNA-seq in pinpointing neural cell type-specific functions in loss-of-function models.

HIGHLIGHTS

unbiased single-cell transcriptomics characterizes adult NSCs and their niche

cell type-specific signatures and marker genes for 22 SVZ cell types

Free online tool to assess gene expression across 9,804 single cells

cell type-specific dysfunctions underlying impaired adult neurogenesis
Yeast Genomic Screens Identify Kinesins as Potential Targets of the Pseudomonas syringae Type III Effector, HopZ1a
Authors: Lee Amy Huei-Yi , Bastedo D. Patrick , Lo Timothy , Middleton Maggie A. , Youn Ji-Young , Kireeva Inga , Lee Jee Yeon , Sharifpoor Sara , Baryshnikova Anastasia , Zhang Jianfeng , Wang Pauline W. , Peisajovich Sergio G. , Constanzo Michael , Andrews Brenda J. , Boone Charles M. , Desveaux Darrell , Guttman David S.
Published: July 2018

Gram-negative bacterial pathogens inject type III secreted effectors (T3SEs) directly into host cells to promote pathogen fitness by manipulating host cellular processes. Despite their crucial role in promoting virulence, relatively few T3SEs have well-characterized enzymatic activities or host targets. This is in part due to functional redundancy within pathogen T3SE repertoires as well as promiscuous individual T3SEs that can have multiple host targets. To overcome these challenges, we conducted heterologous genetic screens in yeast, a non-host organism, to identify T3SEs that target conserved eukaryotic processes. We screened 75 T3SEs from the plant pathogen Pseudomonas syringae and identified 16 that inhibited yeast growth on rich media and eight that inhibited growth on stress-inducing media, including the acetyltransferase HopZ1a. We focused our further analysis on HopZ1a, which interacts with plant tubulin and alters microtubule networks. We first performed a Pathogenic Genetic Array (PGA) screen of HopZ1a against ~4400 yeast carrying non-essential mutations and found 95 and 10 deletion mutants which reduced or enhanced HopZ1a toxicity, respectively. To uncover putative HopZ1a host targets, we interrogated both the genetic- and physical-interaction profiles of HopZ1a by identifying yeast genes with PGA profiles most similar (i.e. congruent) to that of HopZ1a, performing a functional enrichment analysis of these HopZ1a-congruent genes, and by analyzing previously described HopZ physical interaction datasets. Finally, we demonstrated that HopZ1a can target kinesins by acetylating the plant kinesins HINKEL and MKRP1.

ARTICLE SUMMARY

Bacterial pathogens utilize secretion systems to directly deliver effector proteins into host cells, with the ultimate goal of promoting pathogen fitness. Despite the central role that effectors play in infection, the molecular function and host targets of most effectors remain uncharacterized. We used yeast genomics and protein interaction data to identify putative virulence targets of the effector HopZ1a from the plant pathogen Pseudomonas syringae. HopZ1a is an acetyltransferase that induces plant microtubule destruction. We showed that HopZ1a acetylated plant kinesin proteins known to regulate microtubule networks. Our study emphasizes the power of yeast functional genomic screens to characterize effector functions.