bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummarySARS-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

ABSTRACTBackgroundDengue 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.ObjectivesThis study aimed to investigate the combined influences of landscape and climate factors on mosquito occurrence and dengue incidence.MethodsEntomological, 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.ResultsThe 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.DiscussionPrecipitation 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

AbstractIodine 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.IMPORTANCEInfections 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

AbstractMany 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.ImportanceInsects 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

AbstractObjectiveFavourable 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).MethodsSix 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).ResultsRisk 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).ConclusionsRelative 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

AbstractIn 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

AbstractPlants 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

AbstractThe 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

ABSTRACTShade 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

AbstractReading 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

AbstractLegumes 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.