bluuebunny/crossref_metadata_2025 huggingface dataset:
The signaling peptide PapR is required for the activity of the quorum-sensor PlcRa in Bacillus thuringiensis
Authors: Huillet Eugénie , Bridoux Ludovic , Barboza Isabelle , Lemy Christelle , André-Leroux Gwenaëlle , Lereclus Didier
Published: February 2020

The transcriptional regulator PlcR, its cognate cell-cell signaling heptapeptide PapR7, and the oligopeptide permease OppABCDF, required for PapR7 import, form a quorum-sensing system that controls the expression of virulence factors in

Bacillus cereus

and

Bacillus thuringiensis

species. In

B. cereus

strain ATCC 14579, the transcriptional regulator PlcRa activates the expression of abrB2 gene, which encodes an AbrB-like transcriptional regulator involved in cysteine biosynthesis. PlcRa is a structural homolog of PlcR: in particular, its C-terminal TPR peptide-binding domain could be similarly arranged as in PlcR. The signaling peptide of PlcRa is not known. As PlcRa is a PlcR-like protein, the cognate PapR7 peptide (ADLPFEF) is a relevant candidate to act as a signaling peptide for PlcRa activation. Also, the putative PapRa7 peptide (CSIPYEY), encoded by the papRa gene adjacent to the plcRa gene, is a relevant candidate as addition of synthetic PapRa7 induces a dose-dependent increase of abrB2 expression. To address the issue of peptide selectivity of PlcRa, the role of PapR and PapRa peptides in PlcRa activity was investigated in

B. thuringiensis

407 strain, by genetic and functional complementation analyses. A transcriptional fusion between the promoter of abrB2 and lacZ was used to monitor the PlcRa activity in various genetic backgrounds. We demonstrated that PapR was necessary and sufficient for PlcRa activity. We showed that synthetic PapRs from pherogroups II, III and IV and synthetic PapRa7 were able to trigger abrB2 expression, suggesting that PlcRa is less selective than PlcR. Lastly, the mode of binding of PlcRa was addressed using an in silico approach. Overall, we report a new role for PapR as a signaling peptide for PlcRa activity and show a functional link between PlcR and PlcRa regulons in

B. thuringiensis

.
Identification of Essential Residues for Ciprofloxacin Resistance of Ciprofloxacin-Modifying Enzyme (CrpP) of pUM505
Authors: Chávez-Jacobo Víctor M. , García Merinos Juan Pablo , López Yliana , Meza-Carmen Victor , Ramírez-Díaz Martha I.
Published: February 2020

The ciprofloxacin-resistance crpP gene, encoded by the pUM505 plasmid, isolated from a

P. aeruginosa

clinical isolate, confers an enzymatic mechanism of antibiotic phosphorylation, which is ATP-dependent, that decreases ciprofloxacin susceptibility. Homologous crpP genes are distributed across extended spectrum beta-lactamase (ESBL)-producing isolates obtained from Mexican hospitals and which confer decreased susceptibility to CIP. The analysis of sequences of the CrpP of proteins showed that the residues Gly7, Thr8, Asp9, Lys33 and Gly34 (located at the N-terminal region) and Cys40 (located at the C-terminal region) are conserved in all proteins, suggesting that these residues could be essential for CrpP function. The aim of this study was to investigate the amino acids essential to ciprofloxacin resistance, which is conferred by the CrpP protein of pUM505 plasmid. Mutations in the codons encoding Gly7, Asp9, Lys33 and Cys40 of CrpP protein from pUM505 were generated by PCR fusion. The results showed that all mutations generated in CrpP proteins increased ciprofloxacin susceptibility in

Escherichia coli

. In addition, the CrpP modified proteins were purified and their enzymatic activity on ciprofloxacin was assayed, showing that these modified proteins do not exert catalytic activity on ciprofloxacin. Moreover, by infrared assays it was determined that the modified proteins were are not able to modify the ciprofloxacin molecule. Our findings are the first report that indicate that the amino acids, namely Gly7, Asp9, Lys33 and Cys40, which are conserved in the CrpP proteins, possess an essential role for the enzymatic mechanism that confers ciprofloxacin resistance.
Rethinking success, integrity, and culture in research (part 1) — A multi-actor qualitative study on success in science
Authors: Bonn Noémie Aubert , Pinxten Wim
Published: February 2020

Background

Success shapes the life and careers of scientists. But success in science is difficult to define, let alone to translate in indicators that can be used for assessment. In the past few years, several groups expressed their dissatisfaction with the indicators currently used for assessing researchers. But given the lack of agreement on what should constitute success in science, most propositions remain unanswered. This paper aims to complement our understanding of success in science and to document areas of tension and conflict in research assessments.

Methods

We conducted semi-structured interviews and focus groups with policy makers, funders, institution leaders, editors or publishers, research integrity office members, research integrity community members, laboratory technicians, researchers, research students, and former-researchers who changed career to inquire on the topics of success, integrity, and responsibilities in science. We used the Flemish biomedical landscape as a baseline to be able to grasp the views of interacting and complementary actors in a system setting.

Results

Given the breadth of our results, we divided our findings in a two-paper series, with the current paper focusing on what defines and determines success in science. Respondents depicted success as a multi-factorial, context-dependent, and mutable factor. Success appeared to be an interaction between characteristics from the researcher (Who), research outputs (What), processes (How), and luck. Interviewees noted that current research assessments overvalued outputs but largely ignored the processes deemed essential for research quality and integrity. Interviewees sustained that we need a diversity of indicators to allow a balanced and diverse view of success; that assessments should not blindly depend on metrics but also value human input; that we must value quality over quantity; and that any indicators used must be transparent, robust, and valid.

Conclusions

The objective of research assessments may be to encourage good researchers, to benefit society, or simply to advance science. Yet we show that current assessments fall short on each of these objectives. Open and transparent inter-actor dialogue is needed to understand what research assessments aim for and how they can best achieve their objective.

Trial Registration

osf.io/33v3m
Clinical Characteristics of 2019 Novel Infected Coronavirus Pneumonia: A Systemic Review and Meta-analysis
Authors: Qian Kai , Deng Yi , Tai Yong-Hang , Peng Jun , Peng Hao , Jiang Li-Hong
Published: February 2020

Background

A novel pneumonia associated with the 2019 coronavirus infected pneumonia (NCIP) suddenly broke out in Wuhan, China in December 2019. 37287 confirmed cases and 813 death case in China (Until 8th/Feb/2019) have been reported in just fortnight. Although this risky pneumonia with high infection rates and high mortality rates need to be resolved immediately, major gaps in our knowledge of clinical characters of it were still not be established. The aim of this study is to summaries and analysis the clinical characteristics of 2019-nCoV pneumonia.

Methods

Literatures have been systematically performed a search on PubMed, Embase, Web of Science, GreyNet International, and The Cochrane Library from inception up to February 8, 2020. The Newcastle-Ottawa Scale was used to assess quality, and publication bias was analyzed by Egger’s test. In the single-arm meta-analysis, A fix-effects model was used to obtain a pooled incidence rate. We conducted subgroup analysis according to geographic region and research scale.

Results

A total of nine studies including 356 patients were included in this study, the mean age was 52.4 years and 221 (62.1%) were male. The pooled incidences rate of symptoms as follows: pharyngalgia (12.2%, 95% CI: 0.087-0.167), diarrhea (9.2%, 95% CI: 0.062-0.133) and headache (8.9%, 95% CI: 0.063-0.125). Meanwhile, 5.7% (95% CI: 0.027-0.114) of patients were found without any symptoms although they were diagnosed by RT-PCR. In the terms of CT imaging examination, the most of patients showed bilateral mottling or ground-glass opacity, 8.6% (95% CI: 0.048-0.148) of patients with crazy-paving pattern, and 11.5% (95% CI: 0.064-0.197) of patients without obvious CT imaging presentations. The pooled incidence of mortality was 8.9% (95% CI: 0.062-0.126).

Conclusions

To our knowledge, this is the first evidence-based medicine research to further elaborate the clinical characteristics of NCIP, which is beneficial to the next step of prevention and treatment.
Estimation of Rift Valley fever virus spillover to humans during the Mayotte 2018-2019 epidemic
Authors: Métras Raphaëlle , Edmunds W John , Youssouffi Chouanibou , Dommergues Laure , Fournié Guillaume , Camacho Anton , Funk Sebastian , Cardinale Eric , Godais Gilles Le , Combo Soihibou , Filleul Laurent , Youssouf Hassani , Subiros Marion
Published: February 2020

Rift Valley fever (RVF) is an emerging, zoonotic, arboviral haemorrhagic fever threatening livestock and humans mainly in Africa. RVF is of global concern, having expanded its geographical range over the last decades. The impact of control measures on epidemic dynamics using empirical data has not been assessed. Here, we combined seroprevalence livestock and human RVF case data from the 2018-2019 epidemic in Mayotte, with a dynamic mathematical model. Using a Bayesian inference framework, we estimated viral transmission potential amongst livestock, and spillover from livestock to humans, through both direct contact and vector-mediated routes. Model simulations were used to assess the impact of vaccination on reducing the human epidemic size. Reactive vaccination immunising 20% of the livestock population reduced the number of human cases by 30%. To achieve a similar impact, delaying the vaccination by one month required using 50% more vaccine doses, and vaccinating only humans required 20 times as more as the number of doses for livestock. Finally, with 53.92% (95%CrI [44.76-61.29]) of livestock estimated to be immune at the end of the epidemic wave, viral re-emergence in the next rainy season (2019-2020) was unlikely. We present the first mathematical model for RVF fitted to real-world data to estimate virus transmission parameters, and able to inform potential control programmes. Human and animal health surveillance, and timely livestock vaccination appear to be key in reducing disease risk in humans. We furthermore demonstrate the value of a One Health quantitative approach to surveillance and control of zoonotic infectious diseases.
The Efficacy of Contact Tracing for the Containment of the 2019 Novel Coronavirus (COVID-19)
Authors: Keeling Matt J , Hollingsworth T Déirdre , Read Jonathan M
Published: February 2020

Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel Coronavirus (COVID-19) from China and elsewhere into the United Kingdom highlights the need to understand the impact of contact tracing as a control measure. Using detailed survey information on social encounters coupled to predictive models, we investigate the likely efficacy of the current UK definition of a close contact (within 2 meters for 15 minutes or more) and the distribution of secondary cases that may go untraced. Taking recent estimates for COVID-19 transmission, we show that less than 1 in 5 cases will generate any subsequent untraced cases, although this comes at a high logistical burden with an average of 36.1 individuals (95th percentiles 0-182) traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we estimate that any definition where close contact requires more than 4 hours of contact is likely to lead to uncontrolled spread.
Adaptive Baseline Fitting for1H MR Spectroscopy Analysis
Authors: Wilson Martin
Published: February 2020

Purpose

Accurate baseline modeling is essential for reliable MRS analysis and interpretation — particularly at short echo-times, where enhanced metabolite information coincides with elevated baseline interference. The degree of baseline smoothness is a key analysis parameter for metabolite estimation, and in this study a new method is presented to estimate its optimal value.

Methods

An adaptive baseline fitting algorithm (ABfit) is described, incorporating a spline basis into a frequency-domain analysis model, with a penalty parameter to enforce baseline smoothness. A series of candidate analyses are performed over a range of smoothness penalties, as part of a four stage algorithm, and the Akaike information criterion is used to estimate the appropriate penalty. ABfit is applied to a set of simulated spectra with differing baseline features and experimentally acquired 2D MRSI — both at a field strength of 3 Tesla.

Results

Simulated analyses demonstrate metabolite errors result from two main sources: bias from an inflexible baseline (underfitting) and increased variance from an overly flexible baseline (over-fitting). In the case of an ideal flat baseline ABfit is shown to correctly estimate a highly rigid baseline, and for more realistic spectra a reasonable compromise between bias and variance is found. Analysis of experimentally acquired data demonstrates good agreement with known correlations between metabolite ratios and the contributing volumes of gray and white matter tissue.

Conclusion

ABfit has been shown to perform accurate baseline estimation and is suitable for fully-automated routine MRS analysis.
Overcoming efflux of fluorescent probes for actin imaging in living cells
Authors: Gerasimaitė Rūta , Seikowski Jan , Schimpfhauser Jens , Kostiuk Georgij , Gilat Tanja , D’Este Elisa , Schnorrenberg Sebastian , Lukinavičius Gražvydas
Published: February 2020

Actin cytoskeleton is crucial for endocytosis, intracellular trafficking, cell shape maintenance and a wide range of other cellular functions. Recently introduced cell-permeable fluorescent actin probes suffer from poor membrane permeability and stain some cell populations inhomogeneously due to the active efflux by the plasma membrane pumps. We addressed this issue by constructing a series of probes which employ modified rhodamine fluorophores. We found that the best performing probes are based on 6-carboxy-carbopyronine scaffold. These probes show preferential binding to F-actin, do not require efflux pumps inhibitors for staining and can be used for 2D and 3D fluorescence nanoscopy at high nanomolar concentrations without significant cytotoxicity. We demonstrate their excellent performance in multiple organisms and cell types: human cell lines, frog erythrocytes, fruit fly tissues and primary neurons.
Anode surface bioaugmentation enhances deterministic biofilm assembly in microbial fuel cells
Authors: Yanuka-Golub Keren , Dubinsky Vadim , Korenblum Elisa , Reshef Leah , Ofek-Lalzar Maya , Rishpon Judith , Gophna Uri
Published: February 2020

Microbial fuel cells (MFCs) are devices that can generate energy while aiding biodegradation of waste through the activity of an electroactive mixed biofilm. Metabolic cooperation is considered essential for MFCs’ efficiency, especially during early-anode colonization. Yet, the specific ecological processes that drive the assembly of an optimized anode-attached community remain unknown. Here, we show, using 16S rRNA gene amplicon and shotgun metagenomic sequencing that bioaugmentation of the anode surface with an electroactive consortium originating from a well-established anodic biofilm, dominated by differentDesulfuromonasstrains, resulted in an extremely rapid voltage generation (reaching maximal voltage within several hours). This was in sharp contrast to the highly stochastic and slower biofilm assembly that occurred when the anode-surface was not augmented. By comparing two inoculation media, wastewater and filtered wastewater, we were able to illustrate two different "source-communities" for newly arriving species that with time colonized the anode surface in a different manner and resulted in dramatically different community assembly processes. Remarkably, an efficient anode colonization process was obtained only if unfiltered wastewater was added, leading to a near-complete replacement of the bioaugmented community byGeobacter lovleyi. We propose that anode bioaugmentation reduced stochasticity by creating available niches that were quickly occupied by specific newly-arriving species that positively supported the fast establishment of a highly-functional anode biofilm.
The Nucleosome Remodeling and Deacetylase complex has an asymmetric, dynamic, and modular architecture
Authors: Low Jason KK , Silva Ana PG , Tabar Mehdi Sharifi , Torrado Mario , Webb Sarah R , Parker Benjamin L , Sana Maryam , Smits Callum , Schmidberger Jason W , Brillault Lou , Jackman Matthew J , Williams David C , Blobel Gerd A. , Hake Sandra B , Shepherd Nicholas E , Landsberg Michael J , Mackay Joel P
Published: February 2020

The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for development in complex animals but has been refractory to biochemical analysis. We present the first integrated analysis of the architecture of the native mammalian NuRD complex, combining quantitative mass spectrometry, covalent cross-linking, protein biochemistry and electron microscopy. NuRD is built around a 2:2:4 pseudo-symmetric deacetylase module comprising MTA, HDAC and RBBP subunits. This module interacts asymmetrically with a remodeling module comprising one copy each of MBD, GATAD2 and CHD subunits. The previously enigmatic GATAD2 controls the asymmetry of the complex and directly recruits the ATP-dependent CHD remodeler. Unexpectedly, the MTA-MBD interaction acts as a point of functional switching. The transcriptional regulator PWWP2A modulates NuRD assembly by competing directly with MBD for binding to the MTA-HDAC-RBBP subcomplex, forming a ‘moonlighting’ PWWP2A-MTA-HDAC-RBBP complex that likely directs deacetylase activity to PWWP2A target sites. Taken together, our data describe the overall architecture of the intact NuRD complex and reveal aspects of its structural dynamics and functional plasticity.
Assessing predictors for new post translational modification sites: a case study on hydroxylation
Authors: Piovesan Damiano , Hatos Andras , Minervini Giovanni , Quaglia Federica , Monzon Alexander Miguel , Tosatto Silvio C.E.
Published: February 2020

Post-translational modification (PTM) sites have become popular for predictor development. However, with the exception of phosphorylation and a handful of other examples, PTMs suffer from a limited number of available training examples and their sparsity in protein sequences. Here, proline hydroxylation is taken as an example to compare different methods and evaluate their performance on new experimentally determined sites. As a proxy for an effective experimental design, predictors require both high specificity and sensitivity. However, the self-reported performance is often not indicative of prediction quality and detection of new sites is not guaranteed. We have benchmarked seven published hydroxylation site predictors on two newly constructed independent datasets. The self-reported performance widely overestimates the real accuracy measured on independent datasets. No predictor performs better than random on new examples, indicating the refined models are not sufficiently general to detect new sites. The number of false positives is high and precision low, in particular for non-collagen proteins whose motifs are not conserved. In short, existing predictors for hydroxylation sites do not appear to generalize to new data. Caution is advised when dealing with PTM predictors in the absence of independent evaluations, in particular for unique specific sites such as those involved in signalling.

Author Summary

Machine learning methods are extensively used by biologists to design and interpret experiments. Predictors which take the only sequence as input are of particular interest due to the large amount of sequence data available and self-reported performance is often very high. In this work, we evaluated post-translational modification (PTM) predictors for hydroxylation sites and found that they perform no better than random, in strong contrast to performances reported in the original publications. PTMs are chemical amino acids alterations providing the cell with conditional mechanisms to fine tune protein function, thereby regulating complex biological processes such as signalling and cell cycle. Hydroxylation sites are a good PTM test case due to the availability of a range of predictors and an abundance of newly experimentally detected modification sites. Poor performances in our results highlight the overlooked problem of predicting PTMs when best practices are not followed and training data are likely incomplete. Experimentalists should be careful when using PTM predictors blindly and more independent assessments are needed to separate the wheat from the chaff in the field.
Genome-scale conserved molecular principles of mRNA half-life regulation
Authors: Basu Sudipto , Mallik Saurav , Hait Suman , Kundu Sudip
Published: February 2020

Precise control of protein and mRNA degradation is essential for cellular metabolism and homeostasis. Controlled and specific degradation of both molecular species necessitates their engagements with the respective degradation machineries; this engagement involves a disordered/unstructured segment of the substrate traversing the degradation tunnel of the machinery and accessing the catalytic sites. Here, we report that mRNAs comprising longer terminal and/or internal unstructured segments have significantly shorter half-lives; the lengths of the 5′ terminal, 3′ terminal and internal unstructured segments that affect mRNA half-life are compatible with molecular structures of the 5′ exo- 3′ exo- and endo-ribonuclease machineries. Sequestration into ribonucleoprotein complexes elongates mRNA half-life, presumably by burying ribonuclease engagement sites under oligomeric interfaces. After gene duplication, differences in terminal unstructured lengths, proportions of internal unstructured segments and oligomerization modes result in significantly altered half-lives of paralogous mRNAs. Side-by-side comparison of molecular principles underlying controlled protein and mRNA degradation unravels their remarkable mechanistic similarities, and suggests how the intrinsic structural features of the two molecular species regulate their half-lives on genome-scale and during evolution.
IRE1α regulates macrophage polarization, PD-L1 expression and tumor survival
Authors: Batista Alyssa , Rodvold Jeffrey J. , Xian Su , Searles Stephen , Lew Alyssa , Iwawaki Takao , Almanza Gonzalo , Waller T. Cameron , Lin Jonathan , Jepsen Kristen , Carter Hannah , Zanetti Maurizio
Published: February 2020

In the tumor microenvironment local immune dysregulation is driven in part by macrophages and dendritic cells that are polarized to a mixed proinflammatory/immune suppressive phenotype. The unfolded protein response (UPR) is emerging as the possible origin of these events. Here we report that the inositol-requiring enzyme 1 (IRE1α) branch of the UPR is directly involved in the polarization of macrophagesin vitroandin vivo,including the upregulation of IL-6, IL-23, Arginase1, as well as surface expression of CD86 and PD-L1. Macrophages in which the IRE1α/Xbp1 axis is blocked pharmacologically or deleted genetically have significantly reduced polarization, and CD86 and PD-L1 expression, which was induced independent of IFNγ signaling suggesting a novel mechanism in PD-L1 regulation in macrophages. Mice with IRE1α- but not Xbp1-deficient macrophages showed greater survival than controls when implanted with B16.F10 melanoma cells. Remarkably, we found a significant association between the IRE1α gene signature andCD274gene expression in tumor-infiltrating macrophages in humans. RNASeq analysis showed that bone marrow derived macrophages with IRE1α deletion lose the integrity of the gene connectivity characteristic of regulated IRE1α-dependent decay (RIDD) and the ability to activateCD274gene expression. Thus, the IRE1α/Xbp1 axis drives the polarization of macrophages in the tumor microenvironment initiating a complex immune dysregulation leading to failure of local immune surveillance.
Common postzygotic mutational signature in multiple healthy adult tissues related to embryonic hypoxia
Authors: Hong Yaqiang , Zhang Dake , Zhou Xiangtian , Chen Aili , Abliz Amir , Bai Jian , Wang Liang , Hu Qingtao , Gong Kenan , Guan Xiaonan , Liu Mengfei , Zheng Xinchang , Lai Shujuan , Qu Hongzhu , Zhao Fuxin , Hao Shuang , Wu Zhen , Cai Hong , Hu Shaoyan , Ma Yue , Zhang Junting , Ke Yang , Wang Qianfei , Chen Wei , Zeng Changqing
Published: February 2020

Postzygotic mutations are acquired in all of the normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenesis causing factors. The process and underlying mechanism of postzygotic mutations in normal tissues is still poorly understood. In this study, we investigated postzygotic mutation spectra in healthy individuals by optimized ultra-deep exome sequencing of time series samples from the same volunteer and samples from different individuals. In cells of blood, sperm, and muscle, we resolved three common types of mutational signature. Two of them are known to represent clock-like mutational processes, and their proportions in mutation profiles associated with polymorphisms of epigenetic regulation genes, suggesting the contribution of personal genetic backgrounds to underlying biological process. Notably, the third signature, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type were likely to occur early in embryo development even before the tissue differentiation, as indicated by their relatively high allele frequencies, sharing variants between multiple tissues, and lacking of age-related accumulation. Almost all tumors shown in public datasets did not have this signature detected except for 19.6% of clear cell renal cell carcinoma samples, which featured by activation of the hypoxia-induced signaling pathway. Moreover, in vitro activation of HIF signaling pathway successfully introduced the corresponding mutation profile of this signature in a culture-expanded human embryonic stem cell line. Therefore, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggest hypoxic conditions in the early stage of embryo development may be a crucial factor for the C>T transitions at GpCpN sites and individual genetic background also related to shaping human postzygotic mutation profiles.
Transcriptome analysis reveals the effects of transgenic expression of the Gal4 protein on normal gene expression in silkworm tissues
Authors: Chen Tao , Ma Yan , Liu Rongpeng , Tan Tingting , Huang Lihua , Xu Hanfu
Published: February 2020

The Gal4/upstream activating sequence(UAS) system, a well-known genetic tool, has been widely used to analyze gene function in many organisms, including the silkworm (Bombyx mori), a model lepidopteran insect. Several studies have suggested that Gal4 protein activation in tissues can negatively affect transgenic individuals; however, whether and to what extent the Gal4 protein affects normal endogenous gene expression have rarely been studied. Here, we analyzed the transcriptomes of transgenic silkworms expressing the Gal4 protein at high levels in both the wing disc (WD) and epidermis (EP) and investigated gene expression changes in both tissues. Overall, 24,593 genes were identified in the WD and EP libraries, and 2,025 and 2,488 were identified as significant differentially expressed genes(DEGs) in the WD and EP between the transgenic and control groups, respectively. These DEGs were further annotated by gene function classification and pathway assessment using public databases. In addition, 506 DEGs were shared (common) between both tissues. Of these, 97 genes were commonly upregulated, and 234 were commonly downregulated; many of them were annotated to be involved in metabolic processes such as “fat digestion and absorption”, “glycine, serine and threonine metabolism” and “glutathione metabolism” and in signal transduction pathways such as the “Rap1 signaling pathway”, “MAPK signaling pathway” and “Hippo signaling pathway”. Overall, this work enhances understanding of the effects of transgenic Gal4 protein expression on normal gene expression in silkworm tissues and suggests that researchers should pay attention to unexpected effects when using the Gal4/UAS system to study gene function.
Microhabitat and ectomycorrhizal effects on the establishment, growth and survival ofQuercus ilexL. seedlings under drought
Authors: García de Jalón Laura , Limousin Jean-Marc , Richard Franck , Gessler Arthur , Peter Martina , Hättenschwiler Stephan , Milcu Alexandru
Published: February 2020

The success of tree recruitment in MediterraneanQuercus ilexforests is threatened by the increasing intensity, duration and frequency of drought periods. Seedling germination and growth are modulated by complex interactions between abiotic (microhabitat conditions) and biotic factors (mycorrhiza association) that may mitigate the impacts of climate change on tree recruitment. To better understand and anticipate these effects, we conducted a germination experiment in a long-term precipitation reduction (PR) field experiment where we monitored seedling establishment and survival, micro-environmental conditions and ectomycorrhizal (ECM) colonization by different mycelia exploration types during the first year of seedling growth. We hypothesized that (i) the PR treatment decreases seedling survival relative to the control with ambient conditions, (ii) the underlying mechanisms for seedling survival are better understood with detailed information of microhabitat water and light availability irrespective of the PR treatment, (iii) the PR treatment will favour the development of ECM exploration types with drought-resistance traits such as differentiated rhizomorphs. Contrary to our first hypothesis, seedling survival was lower in control plots with overall higher soil moisture. Micro-site light and soil moisture conditions were better predictors of seedling survival and growth than the plot-level PR treatment, confirming our second hypothesis. Furthermore, in line with our third hypothesis, we found that ECM with longer extramatrical mycelia were more abundant in the PR treatment plots and were positively correlated to survival, which suggests a potential role of this ECM exploration type in seedling survival and recruitment. Although summer drought was the main cause of seedling mortality, our study indicates that drier conditions in spring can increase seedling survival, presumably through a synergistic effect of drought adapted ECM species and less favourable conditions for root pathogens.
Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats
Authors: Logan Carly N. , Bechard Allison R. , Hamor Peter U. , Wu Lizhen , Schwendt Marek , Knackstedt Lori A.
Published: February 2020

Rationale

The beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine-seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement.

Aims

Here, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core.

Methods

Male and female rats self-administered cocaine for 12 days followed by 2-3 weeks of extinction training. During the last 6-10 days of extinction, rats received ceftriaxone (200 mg/kg IP) or vehicle. In experiment 1, rats were killed, and NA core tissue was biotinylated for assessment of total and surface expression of mGlu2 and mGlu3 via western blotting. In experiment 2, we tested the hypothesis that mGlu2/3 signaling is necessary for ceftriaxone to attenuate cue- and cocaine-primed reinstatement by administering bilateral intra-NA core infusion of mGlu2/3 antagonist LY341495 or vehicle immediately prior to reinstatement testing.

Results

mGlu2 expression was reduced by cocaine and restored by ceftriaxone. There were no effects of cocaine or ceftriaxone on mGlu3 expression. We observed no effects of estrus on expression of either protein. The antagonism of mGlu2/3 in the NA core during both cue- and cocaine-primed reinstatement tests prevented ceftriaxone from attenuating reinstatement.

Conclusions

These results indicate that ceftriaxone’s effects depend on mGlu2/3 function and possibly mGlu2 receptor expression. Future work will test this hypothesis by manipulating mGlu2 expression in pathways that project to the NA core.
Proteomic and phosphoproteomic analysis identifies novel liver-related signaling in retinal pigment epithelial cells during epithelial-mesenchymal transition
Authors: Mertz Joseph L. , Sripathi Srinivas , Yang Xue , Chen Lijun , Esumi Noriko , Zhang Hui , Zack Donald J.
Published: February 2020

Epithelial–mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is associated with several potentially blinding retinal diseases. Proteomic and phosphoproteomic studies were performed on human pluripotent stem cell-derived RPE (hPSC-RPE) monolayers to better understand the pathways mediating RPE EMT. EMT was induced by enzymatic dissociation or by co-treatment with transforming growth factor beta (TGFβ) and tumor necrosis factor alpha (TNFα; TGNF). The global and phosphoproteomes were analyzed at 1 hr post EMT induction to capture early events in kinase/phosphatase signaling cascades and at 12 hrs to define early changes in protein abundance. Pathway enrichment analysis revealed that TGNF and Dissociation rapidly perturbed signaling in many of the same pathways, with striking similarity in the phosphoproteome at 1 hr. Surprisingly, functions related to liver cell proliferation and hyperplasia were strongly enriched in the phosphosites altered by both treatments at 1 hr and in protein abundance changes at 12 hrs. Hepatocyte Growth Factor-cMET signaling exhibited the strongest overall enrichment in both treatments. These signaling pathways may serve as suitable targets for the development of therapeutic strategies for the inhibition of RPE EMT, and thus progression of several debilitating visual diseases.
Prefrontal cortex projections to the nucleus reuniens suppress freezing following two-way signaled avoidance training
Authors: Moscarello Justin M.
Published: February 2020

Signaled active avoidance (SAA) behavior requires the suppression of defensive reactions, such as freezing, that conflict with the avoidance response. The neural mechanisms of this inhibitory process are not well understood. Here, we demonstrate that ventromedial prefrontal cortex projections to the nucleus reuniens of the thalamus are recruited following SAA training to suppress freezing in rats. This projection may serve as a crucial common pathway for the inhibition of innate defensive reactions that interfere with proactive behavior, thus facilitating adaptive coping.
Under the condition of unitization at encoding rather than unitization at retrieval, familiarity could support associative recognition and the relationship between unitization and recollection was moderated by unitization-congruence
Authors: Liu Zejun , Wang Yujuan , Guo Chunyan
Published: February 2020

It is widely accepted that associative recognition can be supported by familiarity through integrating more than two stimuli into a unit, but there are still three unsolved questions: (1) how unitization affects recollection-based associative recognition; (2) whether it is necessary to match the level of unitization (LOU) between original and rearranged pairs, which was term as unitization-congruence (UC); (3) whether unitization can occur at encoding or at retrieval. The purposes of this study are to try to answer these questions. During the encoding phase, the participants were asked to learn compound words and unrelated word pairs, and during the retrieval phase, they needed to distinguish intact pairs from rearranged consistent and rearranged inconsistent pairs with “remember/know” paradigm. The results showed that (1) the role of unitization in recollection was moderated by UC; (2) Under the consistent UC condition, unitization could improve familiarity-based associative recognition without affecting recollection-based associative recognition, while under the inconsistent UC condition, unitization could improve familiarity-based and recollection-based associative recognition simultaneously, these results indicated that it was necessary to match the LOU between original and rearranged pairs; (3) unitization at encoding could support familiarity-based associative recognition, while unitization at retrieval did not. In briefly, unitization at encoding could improve associative recognition and this effect was moderated by UC, while unitization at retrieval did not affect associative recognition.
RADDOSE-XFEL: femtosecond time-resolved dose estimates for macromolecular X-ray free-electron laser experiments
Authors: Dickerson Joshua L. , McCubbin Patrick T. N. , Garman Elspeth F.
Published: February 2020

For macromolecular structure determination at synchrotron sources, radiation damage remains a major limiting factor. Estimation of the absorbed dose (J kg−1) during data collection at these sources by programs such asRADDOSE-3Dhas allowed direct comparison of radiation damage between experiments carried out with different samples and beam parameters. This has enabled prediction of roughly when radiation damage will manifest so it can potentially be avoided. X-ray free-electron lasers (XFELs), which produce intense X-ray pulses only a few femtoseconds in duration, can be used to generate diffraction patterns before most of the radiation damage processes have occurred and hence hypothetically they enable the determination of damage-free atomic resolution structures. In spite of this, several experimental and theoretical studies have suggested that structures from XFELs are not always free of radiation damage. There are currently no freely available programs designed to calculate the dose absorbed during XFEL data collection. This article presents an extension toRADDOSE-3DcalledRADDOSE-XFEL, which calculates the time-resolved dose during XFEL experiments. It is anticipated thatRADDOSE-XFELcould be used to facilitate the study of radiation damage at XFELs and ultimately be used prior to data collection so that experimenters can plan their experiments to avoid radiation damage manifesting in their structures.
Enhancing physical activity knowledge exchange strategies for Canadian long-haul truck drivers
Authors: Gorczynski Paul F. , Edmunds Sarah , Lowry Ruth
Published: February 2020

Purpose

Canadian long-haul truck drivers lead sedentary lives, but are receptive to receiving physical activity information to address health risks. This study examined how Canadian long-haul truck drivers would like to receive physical activity information in order to improve their overall health. The purpose of this study was twofold: 1) explore barriers Canadian long-haul truck drivers have to receiving and using physical activity information and 2) understand how physical activity information should be structured and delivered to these drivers to overcome these barriers.

Design/methodology/approach

Semi-structured interviews were conducted with 12 Canadian long-haul truck drivers. Drivers had, on average, 14.3 years of professional long-haul driving experience.

Findings

Few drivers had received any physical activity information. Drivers discussed a culture where they perceived both employers and drivers to be lacking awareness of the importance of physical activity and its impact on health. Drivers explained they were too busy, stressed or tired to be active or to learn about physical activity. Information received by some drivers on this topic was too general to be helpful in changing physical activity behaviours. Drivers mentioned that personalized and accessible physical activity information should be provided to them through multiple methods by their employers, as an aspect of occupational health and safety.

Practical implications

Future physical activity information strategies should use both passive and interactive mediums to promote physical activity to Canadian long-haul truck drivers.

Originality/value

This is the first study to assess how Canadian long-haul truck drivers would like to receive trustworthy information that can lead to healthful improvements in physical activity behaviour.
An empirical evaluation of interpersonal deception theory in a real-world, high-stakes environment
Authors: Thomas Joseph York , Biros David P.
Published: February 2020

Purpose

The study of deception and the theories, which have been developed have relied heavily on laboratory experiments in controlled environments, using American college students participating in mock scenarios. The purpose of this paper is to validate previous deception detection research in a real-world, high stakes environment where the unit of analysis is the question–response pair.

Design/methodology/approach

The study used previously confirmed linguistic and paralinguistic speech cues and the constructs of deception in an attempt to validate a leading deception theory, interpersonal deception theory (IDT). A combination of descriptive and predictive analysis was conducted to best understand the relationship between speech cues and changes in the subjects’ behavior.

Findings

The result validates IDT with mixed results on individual measures and their constructs. However, there is clear evidence across the 711 question-response pairs that not only was it possible to differentiate truth from deceptive behavior but also patterns of behavior can be seen over time.

Research limitations/implications

Because of the real-world nature of the study, it is difficult to generalize the results to a larger population. However, one implication for future research is the development of methods to capture, process and prepare raw speech into data ready for analysis.

Originality/value

This paper attempts to fill the gap between the controlled mock scenarios and the harsh reality of real-world deception.
Swipe right on personality: a mobile response latency measure
Authors: Weidner Nathan W. , Landers Richard N.
Published: February 2020

Purpose

While high-stakes mobile assessment is increasing, researchers have done little to adapt traditional assessments to this new medium. The present study developed and tested a new response method for personality assessment using a mobile-first gamification design paradigm.

Design/methodology/approach

Participants used smartphones to “swipe” right or left to indicate agreement or disagreement with Goldberg's (1992) Big Five adjective indicators. These scores were correlated with responses to a Likert-type measure and participants provided reactions to both measures.

Findings

Each of the swipe-based measures was found to be a reliable and valid predictor of the corresponding dimensions measured using the Likert-type scale. Reactions to the swipe measure were mixed when compared to a traditional Likert-type measure. Response latencies of swipes were used as an indicator of self-schema beliefs. Transformed latency scores contributed incremental variance to the prediction of Likert responses beyond the dichotomous responses alone for some personality dimensions.

Research limitations/implications

Convergent validity between the two measures was likely attenuated due to differences in scales, response methods, devices, connection speeds, and social desirability effects indicating that the present results may constitute a lower-bound estimate of convergent validity between the two measurement styles.

Practical implications

Designing assessments for mobile administration requires balancing trade-offs in speed, ease of use, and number of items relative to the reliability and validity of the measures.

Originality/value

Mobile-first designs such as swipe-based responses show potential to enhance future mobile assessment practices with further development.
Down‐regulation of FOXR2 inhibits hypoxia‐driven ROS‐induced migration and invasion of thyroid cancer cells via regulation of the hedgehog pathway
Authors: Liao Chong‐Wu , Zheng Chen , Wang Le
Published: February 2020

Forkhead box R2 (FOXR2), a new member of the FOX family, is involved in a wide range of biological processes such as embryogenesis, differentiation, transformation and metabolic homeostasis. Recently, FOXR2 has been reported to be aberrantly expressed in a variety of cancers and correlated with cancer development. However, the specific role of FOXR2 in thyroid cancer (TC) remains unclear. In this study, we showed that FOXR2 was highly expressed in TC tissues and cell lines. Moreover, down‐regulation of FOXR2 inhibited hypoxia‐induced reactive oxygen species (ROS) production and migration/invasion of TC cells. We also found that the hedgehog pathway was responsible for the partial mechanisms underlying the inhibitory effect. Taken together, these findings indicated that down‐regulation of FOXR2 inhibits hypoxia‐driven ROS‐induced migration and invasion of TC cells via regulation of the hedgehog pathway. Thus, FOXR2 may hold great potential for TC treatment.
The signal is clear: It's noisy in the emergency department
Authors: Fatovich Daniel M
Published: February 2020

EDs are noisy and the noise levels exceed regulatory recommendations. Noise distracts us during any task and can saturate our attentional demand and impair our thinking and decision‐making. This is a systematic problem that is consistently ignored by accreditation bodies. Many of our patients are vulnerable to the adverse impact of noise including the elderly, people with mental health problems, migraine and those with sensory impairments. Our noise levels are equivalent to a noisy restaurant. When noise levels are reduced, staff report less stress and better work conditions. Noise is a patient safety issue, as excessive noise impairs good communication, which is essential for patient care. Good acoustic design and management is achievable, but needs to be explicitly assessed as a part of accreditation standards. This would promote wellness for both patients and staff.