bluuebunny/crossref_metadata_2025 huggingface dataset:
Noise-driven multistability versus deterministic chaos in phenomenological semi-empirical models of whole-brain activity
Authors: Piccinini Juan , Ipina Ignacio Perez , Laufs Helmut , Kringelbach Morten , Deco Gustavo , Perl Yonatan Sanz , Tagliazucchi Enzo
Published: August 2020

An outstanding open problem in neuroscience is to understand how neural systems are capable of producing and sustaining complex spatiotemporal dynamics. Computational models that combine local dynamics within vivomeasurements of anatomical and functional connectivity can be used to test potential mechanisms underlying this complexity. We compared two conceptually different mechanisms: noise-driven switching between equilibrium solutions (modeled by coupled Stuart-Landau oscillators) and deterministic chaos (modeled by coupled Rossler oscillators). We found that both models struggled to simultaneously reproduce multiple observables computed from the empirical data. This issue was especially manifest in the case of noise-driven dynamics close to a bifurcation, which imposed overly strong constraints on the optimal model parameters. In contrast, the chaotic model could produce complex behavior over an ampler range of parameters, thus being capable of capturing multiple observables at the same time with good performance. Our observations support the view of the brain as a non-equilibrium system able to produce endogenous variability. We presented a simple model capable of jointly reproducing functional connectivity computed at different temporal scales. Besides adding to our conceptual understanding of brain complexity, our results inform and constraint the future development of biophysically realistic large-scale models.

The quote“What I cannot create, I do not understand”was found written in the blackboard of celebrated physicist Richard Feynman at the time of his death. This sentence suggests a way forward for neuroscientists interested in unravelling the principles behind the richness and complexity of spontaneous brain dynamics. Over the last decades, tremendous advances in neuroimaging enabled the construction of whole-brain activity models with real predictive power in the statistical sense. It is now possible tocreaterealistic complex dynamics, instead of passively screening for their presence in neuroimaging data. We contrasted two different types of building blocks (i.e. two choices of local dynamics) and tested their capacity to reproduce the empirical data, with the purpose of increasing our conceptual understanding of the mechanisms behind large-scale spontaneous activity in the human brain.
The Incubation Period of Severe Acute Respiratory Syndrome Coronavirus 2:A Systematic Review
Authors: Li Zhiyao , Zhang Yu , Wang Chenchen , Peng Liuqing , Gao Rongrong , Jing Jiarui , Ren Binzhi , Xu Jianguo , Wang Tong
Published: August 2020

While the novel coronavirus continues to spread worldwide, the reported incubation period has varied between studies and is imprecise due to limited data. A literature search with certain selection criteria was conducted on May 30, 2020. In total, sixty-four articles were included, and 854 individual-level data were extracted from 30 studies for pooled analysis. Of these studies, 72% of them reported a median or mean incubation period of 4-7 days, while our estimated median was 4.9 days (95% confidence interval [CI]: 4.6-5.2). However, the inclusion of 81 asymptomatic and presymptomatic patients, as well as 31 cases with incubation periods exceeding 14 days, led to our estimation of 97.5 th percentile with 19.3 days (95% CI: 17.4-21.4), beyond the currently suggested 14-day quarantine period. Therefore, we appeal to prolong the quarantine duration, especially for areas that have insufficient testing resources, to protect susceptible populations from being infected.

Article Summary Line

This article reviewed the COVID-19 studies involving incubation period and provided pooled estimation based on available data from these studies.The result showed that our estimated median incubation period is consistent with the estimates of formal studies but the 97.5 percentile is larger than ever on account of including a number of asymptomatic and presymptomatic patients.These finds suggested that we should properly prolong the isolation or quarantine period in order to identify more patients with longer incubation period and those without any symptoms.
Highly performing point-of-care molecular testing for SARS-CoV-2 with RNA extraction and isothermal amplification
Authors: Garneret Pierre , Coz Etienne , Martin Elian , Manuguerra Jean-Claude , Brient-Litzler Elodie , Enouf Vincent , González Obando Daniel Felipe , Olivo-Marin Jean-Christophe , Monti Fabrice , Van der Werf Sylvie , Vanhomwegen Jessica , Tabeling Patrick
Published: August 2020

In order to respond to the urgent request of massive testing, developed countries perform nucleic acid amplification tests (NAAT) of SARS-CoV-2 in centralized laboratories. Real-time RT - PCR (Reverse transcription - Polymerase Chain Reaction) is used to amplify the viral RNA and enable its detection. Although PCR is 37 years old, it is still considered, without dispute, as the gold standard. PCR is an efficient process, but the complex engineering required for automated RNA extraction and temperature cycling makes it incompatible for use in point of care settings. In the present work, by harnessing progress made in the past two decades in DNA amplification, microfluidics and membrane technologies, we succeeded to create a portable test, in which SARS-CoV-2 RNA is extracted, amplified isothermally by RT - LAMP (Loop-mediated Isothermal Amplification), and detected using intercalating dyes or highly fluorescent probes. Depending on the viral load, the detection takes between twenty minutes and one hour. Using pools of naso-pharyngal clinical samples, we estimated a sensitivity comparable to RT-qPCR (up to a Cycle threshold of 39, equivalent to <0.1 TCID50 per mL) and a 100% specificity, for other human coronaviruses and eight respiratory viruses currently circulating in Europe. We designed and fabricated an easy-to-use portable device called “COVIDISC” to carry out the test at the point of care. The low cost of the materials along with the absence of complex equipment paves the way towards a large dissemination of this device. The perspective of a reliable SARS-CoV-2 point of care detection, highly performing, that would deliver on-site results in less than one hour, with a self-testing potential, opens up a new efficient approach to manage the pandemics.
The Cone Method: Inferring Decision Times from Single-Trial 3D Movement Trajectories in Choice Behavior
Authors: Ulbrich Philipp , Gail Alexander
Published: August 2020

Ongoing goal-directed movements can be rapidly adjusted following new environmental information, e.g. when chasing pray or foraging. This makes movement trajectories in go-before-you-know decision-making a suitable behavioral readout of the ongoing decision process. Yet, existing methods of movement analysis are often based on statistically comparing two groups of trial-averaged trajectories and are not easily applied to three-dimensional data, preventing them from being applicable to natural free behavior. We developed and tested thecone methodto estimate the point of overt commitment (POC) along a single two- or three-dimensional trajectory, i.e. the position where movement is adjusted towards a newly selected spatial target. In Experiment 1, we established a “ground truth” data set in which the cone method successfully identified the experimentally constrained POCs across a wide range of all but the shallowest adjustment angles. In Experiment 2, we demonstrate the power of the method in a typical decision-making task with expected decision time differences known from previous findings. The POCs identified by cone method matched these expected effects. In both experiments, we compared the cone method’s single trial performance with a trial-averaging method and obtained comparable results. We discuss the advantages of the single-trajectory cone method over trial-averaging methods and possible applications beyond the examples presented in this study. The cone method provides a distinct addition to existing tools used to study decisions during ongoing movement behavior, which we consider particularly promising towards studies of non-repetitive free behavior.
Prediction of type 2 diabetes mellitus onset using logistic regression-based scoreboards
Authors: Edlitz Yochai , Segal Eran
Published: August 2020

Type 2 diabetes mellitus (T2DM) accounts for ∼90% of all cases of diabetes which are estimated with an annual world death rate of 1.6 million in 2016. Early detection of T2D high-risk patients can reduce the incidence of the disease through a change in lifestyle, diet, or medication. Since populations of lower socio-demographic status are more susceptible to T2D and might have limited resources for laboratory testing, there is a need for accurate yet accessible prediction models based on non-laboratory parameters. This paper introduces one non-laboratory model which is highly accessible to the general population and one highly precise yet simple laboratory model. Both models are provided as an accessible scoreboard form and also as a logistic regression model. We based the models on data from 44,879 non-diabetic, UK Biobank participants, aged 40-65, predicting the risk of T2D onset within the next 7.3 years (SD 2.3). The non-laboratory prediction model for T2DM onset probability incorporated the following covariates: sex, age, weight, height, waist, hips-circumferences, waist-to-hip Ratio (WHR) and Body-Mass Index (BMI). This logistic regression model achieved an Area Under the Receiver Operating Curve (auROC) of 0.82 (0.79-0.85 95% CI) and an odds ratio (OR) between the upper and lower prevalence deciles of x77 (28-98). We further analysed the contribution of laboratory-based parameters and devised a blood-test model based on just five blood tests. In this model, we included age, sex, Glycated Hemoglobin (HbA1c%), reticulocyte count, Gamma Glutamyl-Transferase, Triglycerides, and HDL cholesterol to predict T2D onset. This logistic-regression model achieved an auROC of 0.89 (0.86-0.91) and a deciles’ OR of x87 (27-152). Using the scoreboard results, the Anthropometrics model classified three risk groups, a group with 1%(1-2%); a group with 9% (7-11%) probability, and a group with a 15% (7-23%) risk of developing T2D. The Five blood tests scoreboard model, further classified into four risk groups: 0.9% (0.7%-1%); 8%(6-11%); 18%(14-22%) and a high risk group of 38%(23-54%) of developing T2D. We analysed several more comprehensive models which included genotyping data and other environmental factors and found that it did not provide cost efficient benefits over the five blood tests model. The Five blood tests and anthropometric models, both in their logistic regression form and scoreboard form, outperform the commonly used non-laboratory models, the Finnish Diabetes Risk Score (FINDRISC) and the German Diabetes Risk Score (GDRS). When trained using our data, the FINDRISC achieved an auROC of 0.75 (0.71-0.78), and the GDRS auROC resulted in 0.58 (0.54-0.62), respectively.
SARS-CoV-2 Seroprevalence in Relation to Timing of Symptoms
Authors: Ebinger Joseph E. , Botwin Gregory J. , Albert Christine M. , Alotaibi Mona , Arditi Moshe , Berg Anders H. , Binek Aleksandra , Botting Patrick , Fert-Bober Justyna , Figueiredo Jane C. , Grein Jonathan D. , Hasan Wohaib , Henglin Mir , Hussain Shehnaz K. , Jain Mohit , Joung Sandy , Karin Michael , Kim Elizabeth H. , Li Dalin , Liu Yunxian , Luong Eric , McGovern Dermot P.B. , Merchant Akil , Merin Noah , Miles Peggy B. , Nguyen Trevor-Trung , Raedschelders Koen , Rashid Mohamad A. , Riera Celine E. , Riggs Richard V. , Sharma Sonia , Sobhani Kimia , Sternbach Sarah , Sun Nancy , Tourtellotte Warren G. , Eyk Jennifer E. Van , Braun Jonathan G. , Cheng Susan
Published: August 2020

Of individuals with SARS-CoV-2 IgG antibody testing performed, those who contemporaneously experienced a cluster of Covid-19 relevant symptoms in the 1-2 months preceding the antibody assay were more likely to test positive whereas those who experienced the symptom clustering in the prior 3-6 months were more likely to test negative. These findings suggest that antibodies likely wane over a period of months, particularly in relation to the timing of symptoms.
Impacts of people’s learning behavior in fighting the COVID-19 epidemic
Authors: Cheng Baolian , Wang Yi-Ming
Published: August 2020

This work presents a mathematical model that captures time-dependent social-distancing effects and presents examples of the consequences of relaxing social-distancing restrictions in the fight against the novel coronavirus epidemic. Without social distancing, the spread of COVID-19 will grow exponentially, but social distancing and people’s learning behavior (isolating, staying at home, wearing face masks, washing hands, restricting the size and frequency of group gatherings, etc.) can significantly impede the epidemic spread, flatten the infection curve, and change the final outcome of the COVID-19 outbreak. Our results demonstrate that strict social distancing and people’s learning behavior can be effective in slowing the spread rate and significantly reducing the total number of infections, daily infection rate, peak of daily infections, and duration of the epidemic. Under strict social distancing, the rise and fall of infections would be nearly symmetric about the peak of of daily infections, and the epidemic spread would be essentially over within 60 days. Relaxing social distancing and people learning behaviors will significantly increase the total and daily numbers of infections and prolong the course of the outbreak. These results have immediate applications for the implementation of various social-distancing policies and general significance for ongoing outbreaks and similar infectious disease epidemics in the future (LA-UR 20-22877).

Disclaimer

This material is not final and is subject to be updated any time. Contact information:bcheng@lanl.gov.)
The Effect of Introgression of an R2R3 MYB Transcription Factor on Sulphur Metabolism inBrassica oleracea
Authors: Neequaye Mikhaela , Saha Shikha , Trick Martin , Steuernagel Burkhard , Troncoso-Rey Perla , van den Bosch Frans , Stephenson Pauline , Traka Maria H , Østergaard Lars , Mithen Richard
Published: August 2020

Background

A diet rich in cruciferous vegetables is reported to have beneficial health effects, partially mediated by 4-methylsulfinylbutyl glucosinolate, or glucoraphanin, which is predominantly found within broccoli (Brassica oleracea var italica). We describe the downstream effects on transcription and metabolism in broccoli following the introgression of a genetic variant of MYB28 into broccoli from a wildBrassicarelative which has previously been associated with enhancement of glucoraphanin.

Results

Whole genome sequencing, RNA expression and metabolite analyses were used to characterise the consequences of the introgression of either one or two copies of a genetic variant of the MYB28 transcription factor into a commercial broccoli genetic background. The introgression of the variant of MYB28 resulted in enhanced expression of genes involved in primary sulphate assimilation, sulphur metabolism and aliphatic glucosinolate biosynthesis, and enhanced accumulation of 4-methylsulphinyl butyl glucosinolate in florets. Other changes in transcription that may be related to non-targeted introgression events are reported. There were no consistent effects upon sulphur metabolites pools, apart from methionine-derived glucosinolates.

Conclusion

This study illustrates the downstream effects on transcription and metabolism of the introgression of a genetic variant of MYB28 from a wild species into a commercial broccoli genotype.
Increasing temperature threatens an already endangered coastal dune plant
Authors: Compagnoni Aldo , Pardini Eleanor , Knight Tiffany M.
Published: August 2020

Climate change has the potential to reduce the abundance and distribution of species and threaten global biodiversity, but it is typically not listed as a threat in classifying species conservation status. This likely occurs because demonstrating climate change as a threat requires data-intensive demographic information. Moreover, the threat from climate change is often studied in specific biomes, such as polar or arid ones. Other biomes, such as coastal ones, have received little attention, despite being currently exposed to substantial climate change effects. We forecast the effect of climate change on the demography and population size of a federally endangered coastal dune plant (Lupinus tidestromii). We use data from a 14-year demographic study across seven extant populations of this endangered plant. Using model selection, we found that survival and fertility measures responded negatively to temperature anomalies. We then produced forecasts based on stochastic individual based population models that account for uncertainty in demographic outcomes. Despite large uncertainties, we predict that all populations will decline if temperatures increase by 1° Celsius. Considering the total number of individuals across all seven populations, the most likely outcome is a population decline of 90%. Moreover, we predict extinction is certain for one of our seven populations. These results demonstrate that climate change will profoundly decrease the current and future population growth rates of this plant, and its chance of persistence. Thus, our study provides the first evidence that climate change is an extinction threat for a plant species classified as endangered under the USA Endangered Species Act.
An MRI protocol for anatomical and functional evaluation of the California sea lion brain
Authors: Cook Peter , Hoard Vanessa , Dolui Sudipto , Frederick Blaise , Redfern Richard , Dennison Sophie , Halaska Barbie , Bloom Josh , Kruse-Elliott Kris , Whitmer Emily , Trumbull Emily , Berns Greg , Detre John , D’Esposito Mark , Gulland Frances , Reichmuth Colleen , Johnson Shawn , Field Cara , Inglis Ben
Published: August 2020

We describe a research MRI protocol forin vivoevaluation of pinniped brains using standard human clinical MRI hardware and pulse sequences. Our intended application is to study development of California sea lions (Zalophus californianus) exposedin uteroto domoic acid (DOM) produced by harmful algae blooms in the coastal Pacific Ocean. In cases where the fetus survives to birth, exposure to the toxinin uterocould result in developmental abnormalities leading to neurological and behavioral deficits. Prior studies on sea lions naturally exposed to DOM as adults have demonstrated hippocampal atrophy and altered mesial temporal connectivity. This MRI protocol is therefore intended to depict the hippocampal formation as the primary region of interest, and to provide longitudinal measures of brain functional and structural connectivity as well as quantitative anatomical evaluations. Scan quality and utility are assessed by comparison with prior studies in live and post mortem sea lion brains. We include the first determination of cerebral blood flow mapping using MRI, and also the first fiber tractography using diffusion-weighted imaging from a live sea lion brain. The protocol also facilitates screening for common neurological pathologies, including tumors, trauma and hemorrhages. We believe the protocol would be suitable for any pinniped that can fit inside a human MRI scanner.
RobMixReg: an R package for robust, flexible and high dimensional mixture regression
Authors: Chang Wennan , Wan Changlin , Yu Chun , Yao Weixin , Zhang Chi , Cao Sha
Published: August 2020

Motivation

Mixture regression has been widely used as a statistical model to untangle the latent subgroups of the sample population. Traditional mixture regression faces challenges when dealing with: 1) outliers and versatile regression forms; and 2) the high dimensionality of the predictors. Here, we develop an R package called RobMixReg, which provides comprehensive solutions for robust, flexible as well as high dimensional mixture modeling.

Availability and Implementation

RobMixReg R package and associated documentation is available at CRAN:https://CRAN.R-project.org/package=RobMixReg.
Risk of hospitalisation with coronavirus disease 2019 in healthcare workers and their households: a nationwide linkage cohort study
Authors: Shah ASV , Wood R , Gribben C , Caldwell D , Bishop J , Weir A , Kennedy S , Martin R , Smith-Palmer A , Goldberg D , McMenamin J , Fischbacher C , Robertson C , Hutchinson S , McKeigue P , Helen C , McAllister DA
Published: August 2020

Objective

Many healthcare staff work in high-risk settings for contracting and transmitting Severe Acute Respiratory Syndrome Coronavirus 2. Their risk of hospitalisation for coronavirus disease 2019 (COVID-19), and that of their households, is poorly understood.

Design and settings and participants

During the peak period for COVID-19 infection in Scotland (1st March 2020 to 6th June 2020) we conducted a national record linkage study to compare the risk of COVID-19 hospitalisation among healthcare workers (age: 18-65 years), their households and other members of the general population.

Main outcome

Hospitalisation with COVID-19

Results

The cohort comprised 158,445 healthcare workers, the majority being patient facing (90,733 / 158,445; 57.3%), and 229,905 household members. Of all COVID-19 hospitalisations in the working age population (18-65-year-old), 17.2% (360 / 2,097) were in healthcare workers or their households. Adjusting for age, sex, ethnicity, socio-economic deprivation and comorbidity, the risk of COVID-19 hospitalisation in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazards ratio [HR] 0.81; 95%CI 0.52-1.26 and 0.86; 95%CI 0.49-1.51 respectively). In models adjusting for the same covariates however, patient facing healthcare workers, compared to non-patient facing healthcare workers, were at higher risk (HR 3.30; 95%CI 2.13-5.13); so too were household members of patient facing healthcare workers (HR 1.79; 95%CI 1.10-2.91). On sub-dividing patient-facing healthcare workers into those who worked in front-door, intensive care and non-intensive care aerosol generating settings and other, those in ‘front door’ roles were at higher risk (HR 2.09; 95%CI 1.49-2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of COVID-19 hospitalisation was less than 0.5% but was 1% and above in older men with comorbidity.

Conclusions

Healthcare workers and their households contribute a sixth of hospitalised COVID-19 cases. Whilst the absolute risk of hospitalisation was low overall, patient facing healthcare workers and their households had 3- and 2-fold increased risks of COVID-19 hospitalisation.
The impact of relaxing interventions on human contact patterns and SARS- CoV-2 transmission in China
Authors: Zhang Juanjuan , Litvinova Maria , Liang Yuxia , Zheng Wen , Shi Huilin , Vespignani Alessandro , Viboud Cecile , Ajelli Marco , Yu Hongjie
Published: August 2020

Non-pharmaceutical interventions to control COVID-19 spread have been implemented in several countries with different intensity, timing, and impact on transmission. As a result, post-lockdown COVID-19 dynamics are heterogenous and difficult to interpret. Here we describe a set of contact surveys performed in four Chinese cities (Wuhan, Shanghai, Shenzhen, and Changsha) during the pre-pandemic, lockdown, and post-lockdown period to quantify the transmission impact of relaxing interventions via changes in age-specific contact patterns. We estimate that the mean number of contacts increased 5%-17% since the end of the lockdown but are still 3-7 times lower than their pre-pandemic levels. We find that post-lockdown contact patterns in China are still sufficiently low to keep SARS-CoV-2 transmission under control. We also find that the impact of school interventions depends non-linearly on the share of other activities being resumed. When most community activities are halted, school closure leads to a 77% decrease in the reproductive number; in contrast, when social mixing outside of schools is at pre-pandemic level, school closure leads to a 5% reduction in transmission. Moving forward, to control COVID-19 spread without resorting to a lockdown, it will be key to dose relaxation in social mixing in the community and strengthen targeted interventions.

One Sentence Summary

Social contacts estimated in the post-lockdown period in four large Chinese cities are not sufficient to sustain local SARS-CoV-2 transmission.
Automated generation of context-specific Gene Regulatory Networks with a weighted approach in D. melanogaster
Authors: Murgas Leandro , Contreras-Riquelme Sebastian , Martínez J. Eduardo , Villaman Camilo , Santibáñez Rodrigo , Martin Alberto J.M.
Published: August 2020

Motivation

The regulation of gene expression is a key factor in the development and maintenance of life in all organisms. This process is carried out mainly through the action of transcription factors (TFs), although other actors such as ncRNAs are involved. In this work, we propose a new method to construct Gene Regulatory Networks (GRNs) depicting regulatory events in a certain context forDrosophila melanogaster. Our approach is based on known relationships between epigenetics and the activity of transcription factors.

Results

We developed method, Tool for Weighted Epigenomic Networks inD. melanogaster(Fly T-WEoN), which generates GRNs starting from a reference network that contains all known gene regulations in the fly. Regulations that are unlikely taking place are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility, histone modifications, and gene expression. Fly T-WEoN is based on heuristic rules that reflect current knowledge on gene regulation inD. melanogasterobtained from literature. Experimental data files can be generated with several standard procedures and used solely when and if available.Fly T-WEoN is available as a Cytoscape application that permits integration with other tools, and facilitates downstream network analysis. In this work, we first demonstrate the reliability of our method to then provide a relevant application case of our tool: early development ofD. melanogaster.

Availability

Fly T-WEoN, together with its step-by-step guide is available athttps://weon.readthedocs.io

Contact

alberto.martin@umayor.cl
Bio-Inspired Molecular Bridging in a Hybrid Perovskite Leads to Enhanced Stability and Tunable Properties
Authors: Lang Arad , Polishchuk Iryna , Seknazi Eva , Feldmann Jochen , Katsman Alexander , Pokroy Boaz
Published: August 2020

Hybrid organic-inorganic halide perovskites demonstrate high potential in several applications such as solar cells, field-effect transistors, light-emitting diodes and more. However, the main drawback which limits their use in such applications is their low stability in humid conditions. In this paper we implement one of Nature’s strategies found in bio-crystals in order to improve the stability of the hybrid perovskite methylammonium lead bromide (MAPbBr3) in water, as well as to tune its structure, optical and thermal properties. This was achieved, for the first time, by the incorporation of amino acids into the lattice of MAPbBr3. The amino acid lysine, which possesses two NH3+groups, is incorporated into the hybrid unit cell, by substituting two methylammonium ions and serves as a “molecular bridge”. This incorporation induces a decrease in the lattice parameter of the host, accompanied with an increase in the band gap and noticeable changes in its morphology. Furthermore, we observed an increase in thermal expansion coefficient and a shift of the phase transformation temperature of the hybrid crystal. The level of amino acid incorporation depends on the conditions of crystallization, which also influence the extent of MAPbBr3band gap changes. Notably, lysine incorporation strongly increases the perovskite stability in water. This study demonstrates the unique and promising approach to tune the properties and stability of hybrid perovskites via this novel bio-inspired route.
Drought and rewetting events enhance nitrate leaching and seepage-mediated translocation of microbes from beech forest soils
Authors: Krüger Markus , Potthast Karin , Michalzik Beate , Tischer Alexander , Küsel Kirsten , Deckner Florian F. K. , Herrmann Martina
Published: August 2020

Nitrification in forest soils is often associated with increased leaching of nitrate to deeper soil layers with potential impacts on groundwater resources, further enhanced under scenarios of anthropogenic atmospheric nitrogen deposition and predicted weather extremes. We aimed to disentangle the relationships between soil nitrification potential, seepage-mediated nitrate leaching and the vertical translocation of nitrifiers in soils of a temperate mixed beech forest in central Germany before, during and after the severe summer drought 2018. Leaching of nitrate assessed below the litter layer and in 4, 16 and 30 cm soil depth showed high temporal and vertical variation with maxima at 16 and 30 cm during and after the drought period. Maximum of soil potential nitrification activity of 4.4 mg N kg-1d-1only partially coincided with maximum nitrate leaching of 10.5 kg N ha-2. Both ammonia oxidizing bacteria (AOB) and ammonia oxidizing archaea (AOA) were subject to translocation by seepage, and AOB decreased at least by half and AOA increased by one to three orders of magnitude in their abundance in seepage with increasing soil depth. On the level of the total bacterial population, an increasing trend with depth was also observed forCand. Patescibacteria while Bacteroidetes were strongly mobilized from the litter layer but poorly transported further down. Despite stable population densities in soil over time, abundances of AOA, AOB and total bacteria in seepage increased by one order of magnitude after the onset of autumn rewetting. Predicted future higher frequency of drought periods in temperate regions may result in more frequent seepage-mediated seasonal flushes of nitrate and bacteria from forest soils. Moreover, the observed translocation patterns point to taxon-specific differences in the susceptibility to mobilization, suggesting that only selected topsoil derived microbial groups are likely to affect subsoil or groundwater microbial communities and their functional potential.
Power-law scaling of brain wave activity associated with mental fatigue
Authors: Anh Vo V. , Nguyen Hung T. , Craig Ashley , Tran Yvonne , Wang Yu Guang
Published: August 2020

This paper investigates the cause and detection of power-law scaling of brain wave activity due to the heterogeneity of the brain cortex, considered as a complex system, and the initial condition such as the alert or fatigue state of the brain. Our starting point is the construction of a mathematical model of global brain wave activity based on EEG measurements on the cortical surface. The model takes the form of a stochastic delay-differential equation (SDDE). Its fractional diffusion operator and delay operator capture the responses due to the heterogeneous medium and the initial condition. The analytical solution of the model is obtained in the form of a Karhunen-Loève expansion. A method to estimate the key parameters of the model and the corresponding numerical schemes are given. Real EEG data on driver fatigue at 32 channels measured on 50 participants are used to estimate these parameters. Interpretation of the results is given by comparing and contrasting the alert and fatigue states of the brain.

The EEG time series at each electrode on the scalp display power-law scaling, as indicated by their spectral slopes in the low-frequency range. The diffusion of the EEG random field is non-Gaussian, reflecting the heterogeneity of the brain cortex. This non-Gaussianity is more pronounced for the alert state than the fatigue state. The response of the system to the initial condition is also more significant for the alert state than the fatigue state. These results demonstrate the usefulness of global SDDE modelling complementing the time series approach for EEG analysis.
Knock-in of labeled proteins into 5’UTR enables highly efficient generation of stable cell lines
Authors: Ijaz Faryal , Ikegami Koji
Published: August 2020

Stable cell lines and animal models expressing tagged proteins are important tools for studying behaviors of cells and molecules. Several molecular biological technologies have been applied with varying degrees of success and efficiencies to establish cell lines expressing tagged proteins. Here we applied CRISPR/Cas9 for the knock-in of tagged proteins into the 5’UTR of the endogenous gene loci. With this 5’UTR-targeting knock-in strategy, stable cell lines expressing Arl13b-Venus, Reep6-HA, and EGFP-alpha-tubulin were established with high knock-in efficiencies ranging from 50 to 80%. The localization of the knock-in proteins were identical to that of the endogenous proteins in wild-type cells and showed homogenous expression. Moreover, the expression of knock-in EGFP-alpha-tubulin from the endogenous promoter was stable over long-term culture. We further demonstrated that the fluorescent signals were enough for a long time time-lapse imaging. The fluorescent signals were distinctly visible during the whole duration of the time-lapse imaging and showed specific subcellular localizations. Altogether, our strategy demonstrates that 5’UTR is a ‘hotspot’ for targeted insertion of gene sequences and allows the stable expression of tagged proteins from endogenous loci in mammalian cells.
A dynamic, spatially periodic, micro-pattern of HES5 underlies neurogenesis in the mouse spinal cord
Authors: Biga V , Hawley J , Soto X , Johns E , Han D , Bennett H , Adamson AD , Kursawe J , Glendinning P , Manning C.S , Papalopulu N
Published: August 2020

Ultradian oscillations of HES Transcription Factors (TFs) at the single cell level, enable cell state transitions. However, the tissue level organisation of HES5 dynamics in neurogenesis is unknown. Here, we analyse the expression of HES5 ex-vivo in the developing mouse ventral spinal cord and identify microclusters of 4-6 cells with positively correlated HES5 level and ultradian dynamics. These microclusters are spatially periodic along the dorsoventral axis and temporally dynamic, alternating between high and low expression with a supra-ultradian persistence time. We show that Notch signaling is required for temporal dynamics but not the spatial periodicity of HES5. Few Neurogenin-2 cells are observed per cluster, irrespective of high or low state, suggesting that the microcluster organization of HES5 enables the stable selection of differentiating cells. Computational modelling predicts that different cell coupling strengths underlie the HES5 spatial patterns and rate of differentiation, which is consistent with comparison between the motoneuron and interneuron progenitor domains. Our work shows a previously unrecognised spatiotemporal organisation of neurogenesis, emergent at the tissue level from the synthesis of single cell dynamics.

Synopsis

Live imaging of HES5 expression in the ventral mouse spinal cord together with computational modelling is used to identify and analyse spatially periodic HES5 micro-patterns that emerge from the synthesis of single cell dynamics.

HES5 is expressed in spatially periodic microclusters along the dorsal-ventral axis in spinal cord that are dynamically maintained by Notch signalling.

Microclusters can arise, in part, from single cell oscillators that are synchronous and weakly coupled via Notch.

Spatial patterns are different between motorneuron and interneuron progenitor domains and the probability for progenitor differentiation is regulated by the coupling strength between cells.

NGN2 is also spatially periodic along the dorso-ventral axis and microclusters of HES5 may act to pick a single NGN2 high cell for differentiation.
UV and bacteriophages as a chemical-free approach for cleaning membranes from anaerobic bioreactors
Authors: Scarascia Giantommaso , Fortunato Luca , Myshkevych Yevhen , Cheng Hong , Leiknes TorOve , Hong Pei-Ying
Published: August 2020

Anaerobic membrane bioreactor (AnMBR) for wastewater treatment has attracted much interest due to its efficacy in providing high quality effluent with minimal energy costs. However, membrane biofouling represents the main bottleneck for AnMBR because it diminishes flux and necessitates frequent replacement of membranes. In this study, we assessed the feasibility of combining bacteriophages and UV-C irradiation to provide a chemical-free approach to remove biofoulants on the membrane. The combination of bacteriophage and UV-C resulted in better log cells removal and twice higher extracellular polymeric substance (EPS) concentration reduction in mature biofoulants compared to UV-C. A reduction in the relative abundance ofAcinetobacterspp. and selected gram-positive bacteria associated with the membrane biofilm was also achieved by the new cleaning approach. Microscopic analysis further revealed the formation of cavities in the biofilm due to bacteriophages and UV-C irradiation, which would be beneficial to maintain water flux through the membrane. When the combined treatment was further compared with the common chemical cleaning procedure, a similar reduction on the cell numbers was observed (1.4 log). However, combined treatment was less effective in removing EPS compared with chemical cleaning. These results suggest that the combination of UV-C and bacteriophage have an additive effect in biofouling reduction, representing a potential chemical-free method to remove reversible biofoulants on membrane fitted in an anaerobic membrane bioreactor.

SIGNIFICANCE

Anaerobic membrane bioreactors can achieve high quality effluent with a reduced energy consumption. However, biofouling represents the main bottleneck for membrane filtration efficiency. Biofouling is commonly reduced through chemical treatment. These agents are often detrimental for the environment and health safety due to the formation of toxic byproducts. Therefore, we present a new approach, based on the additive antifouling action of bacteriophages infection and UV-C irradiation, to reduce anaerobic membrane biofouling. This new strategy could potentially delay the occurrence of membrane fouling by removing the reversible fouling layers on membranes, in turn reducing the frequencies and amount of chemicals needed throughout the course of wastewater treatment.
New insights into the influence of plant and microbial diversity on denitrification rates in a salt marsh
Authors: Mason Olivia U. , Chanton Patrick , Knobbe Loren N. , Zaugg Julian , Mortazavi Behzad
Published: August 2020

Coastal salt marshes are some of the most productive ecosystems on Earth, providing numerous services such as soil carbon storage, flood protection and nutrient filtering, several of which are mediated by the sediment microbiome associated with marsh vegetation. Here, nutrient filtering (nitrate removal through denitrification) was examined by determining microbial community structure (16S rRNA gene iTag sequencing), diversity, denitrification rates and metabolic potential (assembled metagenomic sequences) in collocated patches ofSpartina alterniflora(Spartina) andJuncus roemerianus(Juncus) sediments. The iTag data showed that diversity and richness inSpartinaandJuncussediment microbial communities were highly similar. However, microbial community evenness differed significantly, with the most even communities observed inJuncussediments. Further, denitrification rates were significantly higher inJuncuscompared toSpartina, suggesting oscillations in microbial abundances and in particular the core microbiome identified herein, along with plant diversity influence marsh nitrogen (N) removal. Amplicon and assembled metagenome sequences pointed to a potentially important, yet unappreciated Planctomycetes role in N removal in the salt marsh. Thus, perturbations, such as sea-level rise, that can alter marsh vegetation distribution could impact microbial diversity and may ultimately influence the ecologically important ecosystem functions the marsh sediment microbiome provides.
A Multi-Gene Synaptic Plasticity Array Identifies Candidate Molecular Underpinnings of Cognitive and Mood Deficits in Rats with Heart Failure
Authors: Parent Marise B. , Ferreira-Neto Hildebrando Candido , Kruemmel Ana Rafaela , Althammer Ferdinand , Patel Atit A. , Keo Sreinick , E.Whitley Kathryn , Cox Daniel N. , Stern Javier E.
Published: August 2020

Chronic heart failure (HF) is a serious disorder that afflicts more than 26 million patients worldwide. HF is comorbid with depression, anxiety and memory deficits that have serious implications for quality of life and self-care in patients who have HF. Despite evidence that cognitive performance is worse in HF patients with reduced ejection fraction than in HF patients with preserved cardiac function, there are few studies that have assessed the effects of severely reduced ejection fraction (≤40%) on cognition in non-human animal models. Moreover, very limited information is available regarding the effects of HF on genetic markers of synaptic plasticity in brain areas critical for memory and mood regulation. We induced HF in male rats and tested mood and anxiety (sucrose preference and elevated plus maze) and memory (spontaneous alternation and inhibitory avoidance) and measured the simultaneous expression of 84 synaptic plasticity-associated genes in dorsal (DH) and ventral hippocampus (VH), basolateral (BLA) and central amygdala (CeA,) and prefrontal cortex (PFC). We also included the hypothalamic paraventricular nucleus (PVN), which has been implicated in neurohumoral activation in HF. Our results show that rats with severely reduced ejection fraction displayed signs of polydipsia, anhedonia, increased anxiety, and impaired memory in both tasks. HF also produced a drastic downregulation of synaptic-plasticity genes in PFC and PVN, moderate decreases in DH and CeA and minimal effects in BLA and VH. Collectively, these findings identify candidate brain areas and molecular mechanisms underlying HF-induced disturbances in mood and memory.
The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans
Authors: Chaves Daniel A , Dai Hui , Li Lichao , Moresco James J , Oh Myung Eun , Conte Darryl , Yates John R , Mello Craig C , Gu Weifeng
Published: August 2020

Eukaryotic cells regulate 5’ triphosphorylated (ppp-) RNAs to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR1 family of RNA polyphosphatases remove both the β and γ phosphates from ppp-RNAs. Here we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RdRPs and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in both somatic and germline development. Our findings suggest that PIR-1 modulates both Dicer-dependent and - independent Argonaute pathways, and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species.
PR-DUB maintains the expression of critical genes through FOXK1/2- and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination
Authors: Kolovos Petros , Nishimura Koutarou , Sankar Aditya , Sidoli Simone , Cloos Paul A. , Helin Kristian , Christensen Jesper
Published: August 2020

Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive deubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A (H2AK119ub1) through a multiprotein core comprised of BAP1, HCFC1, FOXK1/2, and OGT in combination with either of ASXL1, 2, or 3. Mutations in PR-DUB components are frequent in cancer. However, mechanistic understanding of PR-DUB function in gene regulation is limited. Here, we show that BAP1 is dependent on the ASXL proteins and FOXK1/2 in facilitating gene activation across the genome. Although PR-DUB was previously shown to cooperate with PRC2, we observed minimal overlap and functional interaction between BAP1 and PRC2 in embryonic stem cells. Collectively, these results demonstrate that PR-DUB, by counteracting accumulation of H2AK119ub1, maintains chromatin in an optimal configuration ensuring expression of genes important for general functions such as cell metabolism and homeostasis.
[2,2′-Bis(diphenylphosphanyl)-1,1′-binaphthyl-κ2
P,P′]dichloridoplatinum(II) acetonitrile trisolvate
Authors: Braun Jason D. , Uppal Guneet , Herbert David E.
Published: August 2020

The crystal structure (150 K) of the racemic title compound, [PtCl2(C44H32P2)]·3CH3CN, has been determined. The asymmetric unit comprises a single molecule of the title compound co-crystallized with three acetonitrile solvent molecules. Four molecules are observed in the unit cell, with R and S enantiomers present in a 2:2 ratio. Evidence of intramolecular π-stacking is observed with no discernable intermolecular interactions.
Strengthening the weak link of Macao's responsible gambling practices: a consumer education perspective
Authors: Ji Chunli , Kale Sudhir H.
Published: August 2020

Purpose

The purpose of this paper is to assess the current state of consumer education in the context of responsible gambling in Macao and to suggest ways in which Macao could enhance its consumer education efforts to meet its challenges with regard to responsible gambling.

Design/methodology/approach

Exploratory and interpretative approaches have been adopted to suggest why and how Macao should strengthen responsible gambling education. The methodology involved extensive review of relevant academic research, government documents and reports related to Macao's responsible gambling initiatives.

Findings

Effective long-term responsible gambling education is needed in Macao to further people's understanding of gambling and gambler's fallacy. The government should take leadership in influencing all stakeholders toward effective initiatives and behaviors related to responsible gambling education.

Originality/value

Although research on responsible gambling education is still in its infancy, its importance in reducing common misconceptions about gambling has already been established. This study contributes to strengthen Macao's responsible gambling practices by proposing several changes needed to provide desired outcomes through consumer education.