bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-reactive antibody responses against SARS-CoV-2 and seasonal common cold coronaviruses
Authors: Klompus Shelley , Leviatan Sigal , Vogl Thomas , Kalka Iris N. , Godneva Anastasia , Shinar Eilat , Weinberger Adina , Segal Eran
Published: September 2020

Beyond SARS-CoV-2, six more coronaviruses infect humans (hCoVs), four of which cause only mild symptoms (seasonal/common cold hCoVs) 12. Previous exposures to seasonal hCoVs may elicit immunological memory that could benefit the course of SARS-CoV-2 infections 3. While cross-reactive T cells epitopes of SARS-CoV-2 and seasonal hCoVs have been reported in individuals unexposed to SARS-CoV-2 4-6, potential antibody-based cross-reactivity is incompletely understood.

Here, we have probed for high resolution antibody binding against all hCoVs represented as 1,539 peptides with a phage-displayed 7 antigen library. We detected broad serum antibody responses against peptides of seasonal hCoVs in up to 75% of individuals. Recovered COVID-19 patients exhibited distinct antibody repertoires targeting variable SARS-CoV-2 epitopes, and could be accurately classified from unexposed individuals (AUC=0.96). Up to 50% of recovered patients also mounted antibody responses against unique epitopes of seasonal hCoV-OC43, that were not detectable in unexposed individuals.

These results indicate substantial interindividual variability and antibody cross-reactivity between hCoVs from the direction of SARS-CoV-2 infections towards seasonal hCoVs. Our accurate high throughput assay allows profiling preexisting antibody responses against seasonal hCoVs cost-effectively and could inform on their protective nature against SARS-CoV-2.
Effects of Public Health Interventions on the Epidemiological Spread During the First Wave of the COVID-19 Outbreak in Thailand
Authors: Triukose Sipat , Nitinawarat Sirin , Satian Ponlapat , Somboonsavatdee Anupap , Chotikarn Ponlachart , Thammasanya Thunchanok , Wanlapakorn Nasamon , Sudhinaraset Natthinee , Boonyamalik Pitakpol , Kakhong Bancha , Poovorawan Yong
Published: September 2020

A novel infectious respiratory disease was recognized in Wuhan (Hubei Province, China) in December 2019. In February 2020, the disease was named “coronavirus disease 2019” (COVID-19). COVID-19 became a pandemic in March 2020, and, since then, different countries have implemented a broad spectrum of policies. Thailand is considered to be among the top countries in handling its first wave of the outbreak -- 12 January to 31 July 2020. Here, we illustrate how Thailand tackled the COVID-19 outbreak, particularly the effects of public health interventions on the epidemiologic spread. This study shows how the available data from the outbreak can be analyzed and visualized to quantify the severity of the outbreak, the effectiveness of the interventions, and the level of risk of allowed activities during an easing of a “lockdown.” This study shows how a well-organized governmental apparatus can overcome the havoc caused by a pandemic.
SARS-CoV-2 Protein in Wastewater Mirrors COVID-19 Prevalence
Authors: Neault Nafisa , Baig Aiman Tariq , Graber Tyson E. , D’Aoust Patrick M. , Mercier Elisabeth , Alexandrov Ilya , Crosby Daniel , Baird Stephen , Mayne Janice , Pounds Thomas , MacKenzie Malcolm , Figeys Daniel , MacKenzie Alex , Delatolla Robert
Published: September 2020

The COVID-19 pandemic has given rise to diverse approaches to track infections. The causative agent, SARS-CoV-2, is a fecally-shed RNA virus, and many groups have assayed wastewater for viral RNA fragments by quantitative reverse transcription polymerase chain reaction (qRT-PCR) as a proxy for COVID-19 prevalence in the community. Most groups report low levels of viral RNA that often skirt the method’s theoretical limits of detection and quantitation. Here, we demonstrate the presence of SARS-CoV-2 structural proteins in wastewater using traditional immunoblotting and quantitate them from wastewater solids using an immuno-linked PCR method called Multiplex Paired-antibody Amplified Detection (MPAD). MPAD demonstrated facile detection of SARS-CoV-2 proteins compared with SARS-CoV-2 RNA via qRT-PCR in wastewater. In this longitudinal study, we corrected for stochastic variability inherent to wastewater-based epidemiology using multiple fecal content protein biomarkers. These normalized SARS-CoV-2 protein data correlated well with public health metrics. Our method of assaying SARS-CoV-2 protein from wastewater represents a promising and sensitive epidemiological tool to assess prevalence of fecally-shed pathogens in the community.
Mechanical Loading Recovers Bone but not Muscle Lost During Unloading
Authors: Krause Andrew R. , Speacht Toni A. , Steiner Jennifer L. , Lang Charles H. , Donahue Henry J.
Published: September 2020

Space travel and prolonged bed rest are examples of mechanical unloading that induce significant muscle and bone loss. To explore interactions between skeletal bone and muscle during reloading, we hypothesized that acute external mechanical loading of bone in combination with re-ambulation facilitates proportional recovery of bone and muscle lost during hind limb suspension (HLS) unloading. Adult male C57Bl/6J mice were assigned to a HLS or time-matched ground control (GC) group. After 2-weeks of HLS, separate groups of mice were studied at day 14 (no re-ambulation), day 28 (14 days re-ambulation) and day 56 (42 days re-ambulation); throughout the re-ambulation period, one limb received mechanical loading and the contralateral limb served as an internal control. HLS induced loss of trabecular bone volume (BV/TV; -51%±2%) and muscle weight (-15%±2%) compared to GC at day 14. At day 28, the left tibia (re-ambulation only) of HLS mice had recovered 20% of BV/TV lost during HLS, while the right tibia (re-ambulation and acute external mechanical loading) recovered to GC values of BV/TV (∼100% recovery). At day 56, the right tibia continued to recover bone for some outcomes (trabecular BV/TV, trabecular thickness), while the left limb did not. Cortical bone displayed a delayed response to HLS, with a 10% greater decrease in BV/TV at day 28 compared to day 14. In contrast to bone, acute external mechanical loading during the re-ambulation period did not significantly increase muscle mass or protein synthesis in the gastrocnemius, compared to re-ambulation alone.
Butyribacter intestinigen. nov., sp. nov., a butyric acid-producing bacterium of the familyLachnospiraceaeisolated from the human faeces, and reclassification ofAcetivibrio ethanolgignensasAcetanaerobacter ethanolgignensgen. nov., comb. nov
Authors: Xue Wenbin , Lin Xiaoqian , Lv Mei , Luo Guangwen , Dai Ying , Sun Haipeng , Xiao Liang , Zou Yuanqiang
Published: September 2020

A novel, non-motile, Gram-stain-positive, non-spore-forming, obligate anaerobic bacterium, designated strain TF01-11T, was isolated from human faeces. The isolate was characterized by phylogenetic and phenotypic properties, as well as by determination of its whole genome sequence. The growth temperature and pH ranges were 30–42 °C and 6.0–8.5, respectively. The end products of glucose fermentation were butyric acid and a small amount of acetic acid. The genome was estimated to be 3.61Mbp with G+C content of 36.79 mol%. Genes related to biosynthesis of diaminopimelic acid, polar lipids, polyamines, teichoic and lipoteichoic acids were present. The predominant fatty acids were C16:0(37.9 %), C14:0(16.4 %), C13:0OH/iso-C15:1H (11.1 %) and C18:1ω9c(10.6 %). Phylogenetic analyses based on 16S rRNA gene sequences, the isolate was a member of familyLachnospiraceae, with the highest sequence similarity to the type strain ofRoseburia intestinalisDSM 14610Tat 92.18 % followed byAcetivibrio ethanolgignensATCC 33324Tat 91.99 %. The average nucleotide identity (ANI) calculated for the genomes between strain TF01-11Tand these closest relatives were 70.5 % and 68.1 %. Based on results of phenotypic characteristics and genotypic properties presented in this study, strain TF01-11Trepresent a novel species in a new genus, for which the nameButyribacter intestinigen. nov., sp. nov. is proposed. The type strain of the type species is TF01-11T(CGMCC 1.5203T= CGMCC 10984T= DSM 105140T). In addition,Acetivibrio ethanolgignensis proposed to be reclassified asAcetanaerobacter ethanolgignensgen. nov., comb. nov.
Genome-wide maps of enhancer regulation connect risk variants to disease genes
Authors: Nasser Joseph , Bergman Drew T. , Fulco Charles P. , Guckelberger Philine , Doughty Benjamin R. , Patwardhan Tejal A. , Jones Thouis R. , Nguyen Tung H. , Ulirsch Jacob C. , Natri Heini M. , Weeks Elle M. , Munson Glen , Kane Michael , Kang Helen Y. , Cui Ang , Ray John P. , Eisenhaure Tom M. , Mualim Kristy , Collins Ryan L. , Dey Kushal , Price Alkes L. , Epstein Charles B. , Kundaje Anshul , Xavier Ramnik J. , Daly Mark J. , Huang Hailiang , Finucane Hilary K. , Hacohen Nir , Lander Eric S. , Engreitz Jesse M.
Published: September 2020

Genome-wide association studies have now identified tens of thousands of noncoding loci associated with human diseases and complex traits, each of which could reveal insights into biological mechanisms of disease. Many of the underlying causal variants are thought to affect enhancers, but we have lacked genome-wide maps of enhancer-gene regulation to interpret such variants. We previously developed the Activity-by-Contact (ABC) Model to predict enhancer-gene connections and demonstrated that it can accurately predict the results of CRISPR perturbations across several cell types. Here, we apply this ABC Model to create enhancer-gene maps in 131 cell types and tissues, and use these maps to interpret the functions of fine-mapped GWAS variants. For inflammatory bowel disease (IBD), causal variants are >20-fold enriched in enhancers in particular cell types, and ABC outperforms other regulatory methods at connecting noncoding variants to target genes. Across 72 diseases and complex traits, ABC links 5,036 GWAS signals to 2,249 unique genes, including a class of 577 genes that appear to influence multiple phenotypes via variants in enhancers that act in different cell types. Guided by these variant-to-function maps, we show that an enhancer containing an IBD risk variant regulates the expression ofPPIFto tune mitochondrial membrane potential. Together, our study reveals insights into principles of genome regulation, illuminates mechanisms that influence IBD, and demonstrates a generalizable strategy to connect common disease risk variants to their molecular and cellular functions.
PhenoImage: an open-source GUI for plant image analysis
Authors: Zhu Feiyu , Saluja Manny , Singh Jaspinder , Paul Puneet , Sattler Scott E. , Staswick Paul , Walia Harkamal , Yu Hongfeng
Published: September 2020

High-throughput genotyping coupled with molecular breeding approaches has dramatically accelerated crop improvement programs. More recently, improved plant phenotyping methods have led to a shift from manual measurements to automated platforms with increased scalability and resolution. Considerable effort has also gone into the development of large-scale downstream processing of the imaging datasets derived from high-throughput phenotyping (HTP) platforms. However, most available tools require some programing skills. We developedPhenoImage– an open-source GUI based cross-platform solution for HTP image processing with the aim to make image analysis accessible to users with either little or no programming skills. The open-source nature provides the possibility to extend its usability to meet user-specific requirements. The availability of multiple functions and filtering parameters provides flexibility to analyze images from a wide variety of plant species and platforms.PhenoImagecan be run on a personal computer as well as on high-performance computing clusters. To test the efficacy of the application, we analyzed the LemnaTec Imaging system derived RGB and fluorescence shoot images from two plant species: sorghum and wheat differing in their physical attributes. In the study, we discuss the development, implementation, and working of thePhenoImage.

Highlight

PhenoImageis an open-source application designed for analyzing images derived from high-throughput phenotyping.
Whole-brain functional connectivity neuromarkers uncover the cognitive recovery scheme for overt hepatic encephalopathy after liver transplantation
Authors: Cheng Yue , Shen Wen , Xu Junhai , Amey Rachel C. , Huang Li-Xiang , Zhang Xiao-Dong , Li Jing-Li , Akhavan Cameron , Duffy Ben A. , Jiang Wenjuan , Liu Mengting , Kim Hosung
Published: September 2020

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with the overt hepatic encephalopathy (OHE). Liver transplantation (LT) may reverse the impaired brain function. MRI of resting-state functional connectivity can help unravel the underlying mechanisms that lead to these cognitive deficits and recovery. Sixty-four cirrhotic patients (28 with OHE; 36 without) and 32 healthy controls were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated pre- and postsurgical neurocognitive performance in cirrhotic patients using psychomotor tests, i.e. number connection test (NCT) and digit symbol test (DST). Network-based statistics found significant disrupted connectivity in both groups of cirrhosis with OHE and without compared to controls. However, the presurgical connectivity disruption in patients with OHE was included in a greater number of connections than those without (65 vs. 17). The decrease in FC for both OHE and non-OHE patient groups was reversed to the level of controls after LT. An additional hyperconnected network (i.e., higher than controls) was observed in OHE patients after LT (p=0.009). Regarding the neural-behavior relationship, the functional network that predicted cognitive performance in healthy individuals, showed no correlation in presurgical cirrhotic patients. Such an impaired neural-behavior relationship was re-established after LT for non-OHE patients but not for OHE. OHE patients displayed abnormal hyperconnectivity and persistently impaired neural-behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery in comparison to those without, which needs further clarification in the future study.
Prime-boost protein subunit vaccines against SARS-CoV-2 are highly immunogenic in mice and macaques
Authors: Tan Hyon-Xhi , Juno Jennifer A , Lee Wen Shi , Barber-Axthelm Isaac , Kelly Hannah G , Wragg Kathleen M , Esterbauer Robyn , Amarasena Thakshila , Mordant Francesca L , Subbarao Kanta , Kent Stephen J , Wheatley Adam K
Published: September 2020

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assessed prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD was associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augmented neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines were comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
Dengue Disease Dynamics are Modulated by the Combined Influence of Precipitation and Landscapes: A Machine Learning-based Approach
Authors: Francisco Micanaldo Ernesto , Carvajal Thaddeus M. , Ryo Masahiro , Nukazawa Kei , Amalin Divina M. , Watanabe Kozo
Published: September 2020

Background

Dengue is an endemic vector-borne disease influenced by environmental factors such as landscape and climate. Previous studies separately assessed the effects of landscape and climate factors on mosquito occurrence and dengue incidence. However, both factors interact in time and space to affect mosquito development and dengue disease transmission. For example, eggs laid in a suitable environment can hatch after being submerged in rain or flood water.

Objectives

This study aimed to investigate the combined influences of landscape and climate factors on mosquito occurrence and dengue incidence.

Methods

Entomological, epidemiological, and landscape data from the rainy season (July-December) were obtained from respective government agencies in Metro Manila, Philippines, from 2012 to 2014. Temperature, precipitation, and vegetation data were obtained through remote sensing. A random forest algorithm was used to select the landscape and climate variables. Afterwards, using the identified key variables, a model-based (MOB) recursive partitioning was implemented to test the combinatory influences of landscape and climate factors on the ovitrap index and dengue incidence.

Results

The MOB recursive partitioning for the ovitrap index indicated that mosquito occurrence was higher in high residential density areas, where industrial areas also exist and are well connected with roads. Precipitation was another key covariate modulating the effects of landscape factors, possibly by expanding breeding sites and activating mosquito reproduction. Moreover, the MOB recursive partitioning indicated that precipitation was the main predictor of dengue incidence, with a stronger effect in high residential density and commercial areas.

Discussion

Precipitation with floods has epidemiologically important implications by damaging shelters and causing population displacement, thus increasing exposure to dengue vectors. Our findings suggest that the intensification of vector control during the rainy season can be prioritized in residential and commercial areas to better control dengue disease dynamics.
Comparison of transcriptional responses and metabolic alterations in three multidrug resistant model microorganisms,Staphylococcus aureusATCC BAA-39,Escherichia coliATCC BAA-196 andAcinetobacter baumanniiATCC BAA-1790, on exposure to iodine-containing nano-micelle drug FS-1
Authors: Korotetskiy Ilya S. , Shilov Sergey V. , Kuznetsova Tatyana V. , Ilin Aleksandr I. , Joubert Monique , Taukobong Setshaba , Reva Oleg N.
Published: September 2020

Iodine is one of the oldest antimicrobial agents. Till now there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection:Escherichia coliBAA-196,Staphylococcus aureusBAA-39 andAcinetobacter baumanniiBAA-1790. These cultures were treated by a 5 min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging and the mid of the logarithmic growth phases. Complete genome sequences of these strains were obtained in the previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in central metabolic pathways; however, alterations of the gene expression profiles were species-specific and depended on the growth phase. Disruption of respiratory electron-transfer membrane complexes, increased penetrability of bacterial cell walls, osmotic and oxidative stresses leading to DNA damaging were the major factors influencing the treated bacteria.

IMPORTANCE

Infections caused by antibiotic resistant bacteria threaten the public health worldwide. Combinatorial therapy when antibiotics are administrated together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered as a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic resistant infections.
Vertical transmission at the pathogen-symbiont interface:Serratia symbioticaand aphids
Authors: Perreau Julie , Patel Devki J. , Anderson Hanna , Maeda Gerald P. , Elston Katherine M. , Barrick Jeffrey E. , Moran Nancy A.
Published: September 2020

Many insects possess beneficial bacterial symbionts that occupy specialized host cells and are maternally transmitted. As a consequence of their host-restricted lifestyle, these symbionts often possess reduced genomes and cannot be cultured outside hosts, limiting their study. The bacterial speciesSerratia symbioticawas originally described by noncultured strains that live as mutualistic symbionts of aphids and are vertically transmitted through transovarial endocytosis within the mother’s body. More recently, culturable strains ofS. symbioticawere discovered that retain a larger set of ancestralSerratiagenes, are gut pathogens in aphid hosts, and are principally transmitted via a fecal-oral route. We find that these culturable strains, when injected into pea aphids, replicate in the hemolymph and are pathogenic. Unexpectedly, they are also capable of maternal transmission via transovarial endocytosis: using GFP-tagged strains, we observe that pathogenicS. symbiotica, but notEscherichia coli, are endocytosed into early embryos. Furthermore, pathogenicS. symbioticastrains are compartmentalized into specialized aphid cells in a similar fashion to mutualisticS. symbioticastrains during later stages of embryonic development. Thus, cultured, pathogenic strains ofS. symbioticahave the latent capacity to transition to lifestyles as mutualistic symbionts of aphid hosts. This capacity is blocked by pathogenicity: their hosts die before infected progeny are born. To transition into stably inherited symbionts, culturableS. symbioticastrains may need to adapt to regulate their titer, limit their pathogenicity, and/or provide benefits to aphids that outweigh their cost.

Importance

Insects have evolved various mechanisms to reliably transmit their beneficial bacterial symbionts to the next generation. Sap-sucking insects, including aphids, transmit symbionts by endocytosis of the symbiont into cells of the early embryo within the mother’s body. Experimental studies of this process are hampered by the inability to culture or genetically manipulate host-restricted, symbiotic bacteria.Serratia symbioticais a bacterial species that includes strains ranging from obligate, heritable symbionts to culturable gut pathogens. We demonstrate that culturableS. symbioticastrains, that are aphid gut pathogens, can be maternally transmitted by endocytosis. CulturedS. symbioticatherefore possess a latent capacity for evolving a host-restricted lifestyle and can be used to understand the transition from pathogenicity to beneficial symbiosis.
Trends in cardiovascular disease risk factors by body mass index category among adults in England 2003-18: analysis of repeated cross-sectional national health surveys
Authors: Scholes Shaun , Fat Linda Ng , Mindell Jennifer S
Published: September 2020

Objective

Favourable trends in cardiovascular disease (CVD) risk factors at the population level potentially mask differences within high- and low-risk groups. Data from annual, repeated cross-sectional surveys (Health Survey for England 2003-18) was used to examine trends in the prevalence of key CVD risk factors by body mass index (BMI) category among adults aged 16 years or older (n = 115,860).

Methods

Six risk factors were investigated: (i) current cigarette smoking; (ii) physical inactivity (< 30 minutes of moderate-to-vigorous physical activity per week); (iii) drinking above recommended daily alcohol limits; (iv) hypertension (measured blood pressure ≥140/90mmHg or use of medicine prescribed for high blood pressure); (v) total diabetes (reported diagnosed or elevated glycated haemoglobin); and (vi) raised total cholesterol (≥5mmol/L). Age-standardised risk factor prevalence was computed in each four-year time period (2003-06; 2007-10; 2011-14; 2015-18) in all adults and by BMI category (normal-weight; overweight; obesity). Change in risk factor prevalence on the absolute scale was computed as the difference between the first and last time-periods, expressed in percentage points (PP).

Results

Risk factor change varied by BMI category in a number of cases. Current smoking prevalence fell more sharply for normal-weight men (−8.1 PP; 95% CI: -10.3, -5.8) versus men with obesity (−3.8 PP; 95% CI: -6.2, -1.4). Hypertension remained at a stable level among normal-weight men but decreased among men with obesity (−4.1 PP; 95% CI: -7.1, -1.0). Total diabetes remained at a stable level among normal-weight adults, but increased among adults with obesity (men: 3.5 PP; 95% CI: 1.2, 5.7; women: 3.6 PP; 95% CI: 1.8, 5.4). Raised total cholesterol decreased in all BMI groups, but fell more sharply among women with obesity (−21 PP; 95% CI: -25, -17) versus their normal-weight counterparts (−16 PP; 95% CI: -18, -14).

Conclusions

Relative to adults with normal weight, greater reductions in hypertension and raised total cholesterol among adults with overweight and obesity reflect at least in part improvements in screening, treatment and control among those at highest cardiovascular risk. Higher levels of risk factor prevalence among adults with overweight and obesity, in parallel with rising diabetes, highlight the importance of national prevention efforts to combat the public health impact of excess adiposity.
Modelling the impact of travel restrictions on COVID-19 cases in Newfoundland and Labrador
Authors: Hurford Amy , Rahman Proton , Loredo-Osti J. Concepción
Published: September 2020

In many jurisdictions, public health authorities have implemented travel restrictions to reduce coronavirus disease 2019 (COVID-19) spread. Policies that restrict travel within countries have been implemented, but the impact of these restrictions is not well known. On May 4th, 2020, Newfoundland and Labrador (NL) implemented travel restrictions such that non-residents required exemptions to enter the province. We fit a stochastic epidemic model to data describing the number of active COVID-19 cases in NL from March 14th to June 26th. We predicted possible outbreaks over 9 weeks, with and without the travel restrictions, and for contact rates 40% to 70% of pre-pandemic levels. Our results suggest that the travel restrictions reduced the mean number of clinical COVID-19 cases in NL by 92%. Furthermore, without the travel restrictions there is a substantial risk of very large outbreaks. Using epidemic modelling, we show how the NL COVID-19 outbreak could have unfolded had the travel restrictions not been implemented. Both physical distancing and travel restrictions affect the local dynamics of the epidemic. Our modelling shows that the travel restrictions are a plausible reason for the few reported COVID-19 cases in NL after May 4th.
Cross-ecosystem transcriptomics identifies distinct genetic modules for nutrient acquisition in maize
Authors: Sugimura Yusaku , Kawahara Ai , Maruyama Hayato , Ezawa Tatsuhiro
Published: September 2020

Plants have evolved diverse strategies for the acquisition of the macro-nutrients phosphorus and nitrogen; e.g., mycorrhizal formation, root development, and secretion of chelators/hydrolases to liberate inorganic phosphate. Despite the extensive studies on the individual strategies, there is little information about how plants regulate these strategies in response to fluctuating environment. We approached this issue via profiling transcriptomes of plants grown in large environmental gradients. Roots, leaves, and root-zone soils of 251 maize plants were collected across the US Corn Belt and Japan. RNA was extracted from the roots and sequenced, and the leaves and soils were analyzed. Nineteen genetic modules were defined by weighted gene coexpression network analysis and functionally characterized according to gene ontology analysis, by which we found three modules that are directly involved in nutrient acquisition: mycorrhizal formation, phosphate-starvation response (PSR), and root development. Correlation analysis with soil and plant factors revealed that both phosphorus and nitrogen deficiencies upregulated the mycorrhizal module, whereas the PSR module was upregulated mainly by deficiency in phosphorus relative to nitrogen. Expression levels of the root development module were negatively correlated with those of the mycorrhizal module, suggesting that nutrient acquisition through the two pathways, mycorrhizas and roots, are opposite strategies that are employed under nutrient-deficient and -enriched conditions, respectively. The identification of the soil and plant factors that drive the modules has implications for sustainable agriculture; activation/optimization of the strategies is feasible via manipulating the factors. Overall, our study opens a new window for understanding plant response to complex environments.
MetaFunc: Taxonomic and Functional Analyses of High Throughput Sequencing for Microbiomes
Authors: Sulit Arielle Kae , Kolisnik Tyler , Frizelle Frank A , Purcell Rachel , Schmeier Sebastian
Published: September 2020

The identification of functional processes taking place in microbiome communities augment traditional microbiome taxonomic studies, giving a more complete picture of interactions taking place within the community. While there are applications that perform functional annotation on metagenomes or metatranscriptomes, very few of these are able to link taxonomic identity to function or are limited by their input types or databases used. Here we present MetaFunc, a workflow which takes input reads, and from these 1) identifies species present in the microbiome sample and 2) provides gene ontology (GO) annotations associated with the species identified. In addition, MetaFunc allows for host gene analysis, mapping the reads to a host genome, and separating these reads, prior to microbiome analyses. Differential abundance analysis for microbe taxonomies, and differential gene expression analysis and gene set enrichment analysis may then be carried out through the pipeline. A final correlation analysis between microbial species and host genes can also be performed. Finally, MetaFunc builds an R shiny application that allows users to view and interact with the microbiome results. In this paper, we showed how MetaFunc can be applied to metatranscriptomic datasets of colorectal cancer.
Adaptation to plant shade relies on rebalancing the transcriptional activity of the PIF-HFR1 regulatory module
Authors: Paulišić Sandi , Then Christiane , Alary Benjamin , Nogue Fabien , Tsiantis Miltos , Martínez-García Jaime F.
Published: September 2020

Shade caused by the proximity of neighboring vegetation triggers a set of acclimation responses to either avoid or tolerate shade. Comparative analyses between the shade avoiderArabidopsis thalianaand the shade tolerantCardamine hirsuta, revealed a role for the atypical basic-helix-loop-helix LONG HYPOCOTYL IN FR 1 (HFR1) in maintaining the shade-tolerance inC. hirsuta, inhibiting hypocotyl elongation in shade and constraining expression profile of shade induced genes. We showed thatC. hirsutaHFR1 protein is more stable than itsA. thalianacounterpart, contributing to enhance its biological activity. The enhanced HFR1 activity is accompanied by an attenuated PHYTOCHROME INTERACTING FACTOR (PIF) activity inC. hirsuta. As a result, the PIF-HFR1 module is imbalanced, causing a reduced PIF activity and attenuating other PIF-mediated responses such as warm temperature-induced hypocotyl elongation (thermomorphogenesis) and dark-induced senescence. By this mechanism and that of the already-known of phytochrome A photoreceptor, plants might ensure to properly adapt and thrive in habitats with disparate light amounts.
Distinct neural substrates of individual differences in components of reading comprehension in adults with or without dyslexia
Authors: Ozernov-Palchik O , Centanni TM , Beach SD , May S , Hogan T , Gabrieli JDE
Published: September 2020

Reading comprehension is a complex task that depends on multiple cognitive and linguistic processes. According to the updated Simple View of Reading framework, in adults, individual variation in reading comprehension can be largely explained by combined variance in three component abilities: (1) decoding accuracy, (2) fluency, and (3) language comprehension. Here we asked whether the neural correlates of the three components are different in adults with dyslexia as compared to typically-reading adults and whether the relative contribution of these correlates to reading comprehension is similar in the two groups. We employed a novel naturalistic fMRI reading task to identify the neural correlates of individual differences in the three components using whole-brain and literature-driven regions-of-interest approaches. Across all participants, as predicted by the simple view framework, we found distinct patterns of associations with linguistic and domain-general regions for the three components, and that the left-hemispheric neural correlates of language comprehension in the angular and posterior temporal gyri made the largest contributions to explaining out-of-scanner reading comprehension performance. These patterns differed between the two groups. In typical adult readers, better fluency was associated with greater activation of left occipitotemporal regions, better comprehension with lesser activation in prefrontal and posterior parietal regions, and there were no significant associations with decoding. In adults with dyslexia, better fluency was associated with greater activation of bilateral inferior parietal regions, better comprehension was associated with greater activation in some prefrontal clusters and lower in others, and better decoding skills were associated with lesser activation of bilateral prefrontal and posterior parietal regions. Extending the behavioral findings of skill-level differences in the relative contribution of the three components to reading comprehension, the relative contributions of the neural correlates to reading comprehension differed based on dyslexia status. These findings reveal some of the neural correlates of individual differences in the three components and the underlying mechanisms of reading comprehension deficits in adults with dyslexia.
Shoot-derived miR2111 controls legume root and nodule development
Authors: Zhang Mengbai , Su Huanan , Gresshoff Peter M. , Ferguson Brett J.
Published: September 2020

Legumes control their nodule numbers through the Autoregulation Of Nodulation (AON). Rhizobia infection stimulates the production of root-derived CLE peptide hormones that are translocated to the shoot where they regulate a new signal. We used soybean to demonstrate that this shoot-derived signal is miR2111, which is transported via phloem to the root where it targets transcripts ofToo Much Love(TML), a negative regulator of nodulation. Shoot perception of rhizobia-induced CLE peptides suppresses miR2111 expression, resulting in TML accumulation in roots and subsequent inhibition of nodule organogenesis. Feeding synthetic mature miR2111 via the petiole increased nodule numbers per plant. Likewise, elevating miR2111 availability by over-expression promoted nodulation, while target mimicry ofTMLinduced the opposite effect on nodule development in wild-type plants and alleviated the supernodulating and stunted root growth phenotypes of AON-defective mutants. Additionally, in non-nodulating wild-type plants, ectopic expression of miR2111 significantly enhanced lateral root emergence with a decrease in lateral root length and average root diameter. In contrast, hairy roots constitutively expressing the target mimic construct exhibited reduced lateral root density. Overall, these findings demonstrate that miR2111 is both the critical shoot-to-root factor that positively regulates root nodule development, and also acts to shape root system architecture via orchestrating the degree of root branching, as well as the length and thickness of lateral roots.
Temporal variabilities provide additional category-related information in object category decoding: a systematic comparison of informative EEG features
Authors: Karimi-Rouzbahani Hamid , Shahmohammadi Mozhgan , Vahab Ehsan , Setayeshi Saeed , Carlson Thomas
Published: September 2020

How does the human brain encode visual object categories? Our understanding of this has advanced substantially with the development of multivariate decoding analyses. However, conventional electroencephalography (EEG) decoding predominantly use the “mean” neural activation within the analysis window to extract category information. Such temporal averaging overlooks the within-trial neural variability which is suggested to provide an additional channel for the encoding of information about the complexity and uncertainty of the sensory input. The richness of temporal variabilities, however, has not been systematically compared with the conventional “mean” activity. Here we compare the information content of 31 variability-sensitive features against the “mean” of activity, using three independent highly-varied datasets. In whole-trial decoding, the classical event-related potential (ERP) components of “P2a” and “P2b” provided information comparable to those provided by “Original Magnitude Data (OMD)” and “Wavelet Coefficients (WC)”, the two most informative variability-sensitive features. In time-resolved decoding, the “OMD” and “WC” outperformed all the other features (including “mean”), which were sensitive to limited and specific aspects of temporal variabilities, such as their phase or frequency. The information was more pronounced in Theta frequency band, previously suggested to support feed-forward visual processing. We concluded that the brain might encode the information in multiple aspects of neural variabilities simultaneously e.g. phase, amplitude and frequency rather than “mean” per se. In our active categorization dataset, we found that more effective decoding of the neural codes corresponds to better prediction of behavioral performance. Therefore, the incorporation of temporal variabilities in time-resolved decoding can provide additional category information and improved prediction of behavior.
A mesh microelectrode array for non-invasive electrophysiology within neural organoids
Authors: McDonald Matthew , Sebinger David , Brauns Lisa , Gonzalez-Cano Laura , Menuchin-Lasowski Yotam , Mierzejewski Michael , Psathaki Olympia-Ekaterini , Stumpf Angelika , Wickham Jenny , Rauen Thomas , Schöler Hans , Jones Peter D.
Published: September 2020

Organoids are emergingin vitromodels of human physiology. Neural models require the evaluation of functional activity of single cells and networks, which is best measured by microelectrode arrays. The characteristics of organoids clash with existingin vitroorin vivomicroelectrode arrays. With inspiration from implantable mesh electronics and growth of organoids on polymer scaffolds, we fabricated suspended hammock-like mesh microelectrode arrays for neural organoids. We have demonstrated the growth of organoids enveloping these meshes and the culture of organoids on meshes for up to one year. Furthermore, we present proof-of-principle recordings of spontaneous electrical activity across the volume of an organoid. Our concept enables a new class of microelectrode arrays forin vitromodels of three-dimensional electrically active tissue.
Submesoscale dynamics directly shape bacterioplankton community structure in space and time
Authors: Fadeev Eduard , Wietz Matthias , von Appen Wilken-Jon , Nöthig Eva-Maria , Engel Anja , Grosse Julia , Graeve Martin , Boetius Antje
Published: September 2020

Submesoscale eddies and fronts are recognized as important components of oceanic mixing and energy fluxes. These submesoscale phenomena occur in the surface ocean for a period of a few days on scales between several hundred meters and a few tens of kilometers. Remote sensing and modeling suggest that they may influence marine ecosystem dynamics, but their limited temporal and spatial scales make them challenging for observation and in situ sampling. Here, the study of a submesoscale filament in summerly Arctic waters (depth 0 - 400 m) revealed enhanced vertical mixing of Polar and Atlantic water masses, resulting in a ca. 4 km wide and ca. 50 km long filament with distinct physical and biogeochemical conditions. Compared to the surrounding waters the filament was characterized by a distinct phytoplankton bloom dominated by diatoms and two-fold higher bacterioplankton cell densities. High-throughput 16S rRNA gene sequencing of both bacterioplankton communities revealed 3-4 orders of magnitude higher sequence abundance ofSynechococcusinside the filament, as well as tenfold higher sequence abundance of taxonomic groups typically found during summertime in aging phytoplankton blooms (e.g.,Flavobacteriales). In contrast, the surrounding waters contained severalfold higher sequence abundance of winterly taxonomic groups that are also associated with polar water masses (e.g., SAR202 clade). Altogether, our results show that physical submesoscale processes in the ocean can shape distinct biogeochemical conditions and microbial communities within a few kilometers. Furthermore, our results underline the importance of such submesoscale features for our understanding of surface ocean diversity and biogeochemical processes.
Robust spatial ventriloquism effect and aftereffect under memory interference
Authors: Park Hame , Kayser Christoph
Published: September 2020

Our brain adapts to discrepancies in the sensory inputs. One example is provided by the ventriloquism effect, experienced when the sight and sound of an object are displaced. Here the discrepant multisensory stimuli not only result in a biased localization of the sound, but also recalibrate the perception of subsequent unisensory acoustic information in the so-called ventriloquism aftereffect. This aftereffect has been linked to memory-related processes based on its parallels to general sequential effects in perceptual decision making experiments and insights obtained in neuroimaging studies. For example, we have recently implied memory-related medial parietal regions in the trial-by-trial ventriloquism aftereffect. Here, we tested the hypothesis that the ventriloquism aftereffect is indeed susceptible to manipulations interfering with working memory. Across three experiments we systematically manipulated the temporal delays between stimuli and response for either the ventriloquism or the aftereffect trials, or added a sensory-motor masking trial in between. Our data reveal no significant impact of either of these manipulations on the aftereffect, suggesting that the recalibration reflected by the ventriloquism aftereffect is surprisingly resilient to manipulations interfering with memory-related processes.
Comparative analysis of human brain organoids of brainstem and midbrain at single-cell resolution
Authors: Kinugawa Kaoru , Luginbühl Joachim , Matsui Takeshi K. , Eura Nobuyuki , Sakaguchi Yoshihiko M. , Shin Jay W , Sugie Kazuma , Schwamborn Jens C. , Mori Eiichiro
Published: September 2020

Human brain organoids provide us the means to investigate human brain development and neurological diseases, and single-cell RNA-sequencing (scRNA-seq) technologies allow us to identify homologous cell types and the molecular heterogeneity between individual cells. Previously established human brain organoids of brainstem (hBSOs) and midbrain (hMBOs) were analyzed by scRNA-seq, but the difference in cellular composition between these organoids remains unclear. Here, we integrated and compared the single-cell transcriptome of hBSOs and hMBOs. Our analysis demonstrated that the hBSOs and hMBOs contain some unique cell types, including inflammatory and mesenchymal cells. Further comparison of the hBSOs and hMBOs with publicly available scRNA-seq dataset of human fetal midbrain (hMB) showed high similarity in their neuronal components. These results provide new insights into human brain organoid technologies.
Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease
Authors: Caetano Ana J. , Yianni Val , Volponi Ana A. , Booth Veronica , D’Agostino Eleanor M. , Sharpe Paul T.
Published: September 2020

Human oral soft tissues provide the first barrier of defence against chronic inflammatory disease and hold a remarkable scarless wounding phenotype. Tissue homeostasis requires coordinated actions of epithelial, mesenchymal and immune cells. However, the extent of heterogeneity within the human oral mucosa and how tissue cell types are affected during the course of disease progression is unknown. Using single cell transcriptome profiling we reveal a striking remodelling of the epithelial and mesenchymal niches with a decrease in functional populations that are linked to the aetiology of the disease. Analysis of ligand-receptor interaction pairs identify potential intercellular hubs driving the inflammatory component of the disease. Our work establishes a reference map of the human oral mucosa in health and disease, and a framework for the development of new therapeutic strategies.
Gaze Behaviour Reveals Flexible Encoding of Competing Reach Goals Under Conditions of Target Uncertainty
Authors: de Brouwer Anouk J. , Carter Michael J. , Smail Lauren C. , Wolpert Daniel M. , Gallivan Jason P. , Flanagan J. Randall
Published: September 2020

In daily tasks, we are often confronted with competing potential targets and must select one to act on. It has been suggested that, prior to target selection, the human brain encodes the motor goals of multiple, potential targets. However, this view remains controversial and it has been argued that only a single motor goal is encoded, or that motor goals are only specified after target selection. To investigate this issue, we measured participants’ gaze behaviour while viewing two potential reach targets, one of which was cued after a preview period. We applied visuomotor rotations to dissociate each visual target location from its corresponding motor goal location; i.e., the location participants needed to aim their hand toward to bring the rotated cursor to the target. During the preview period, participants most often fixated both motor goals but also frequently fixated one, or neither, motor goal location. Further gaze analysis revealed that on trials in which both motor goals were fixated, both locations were held in memory simultaneously. These findings show that, at the level of single trials, the brain most often encodes multiple motor goals prior to target selection, but may also encode either one or no motor goals. This result may help reconcile a key debate concerning the specification of motor goals in cases of target uncertainty.