bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival dynamical systems: individual-level survival analysis from population-level epidemic models
Authors: KhudaBukhsh Wasiur R. , Choi Boseung , Kenah Eben , Rempała Grzegorz A.
Published: December 2019

In this paper, we show that solutions to ordinary differential equations describing the large-population limits of Markovian stochastic epidemic models can be interpreted as survival or cumulative hazard functions when analysing data on individuals sampled from the population. We refer to the individual-level survival and hazard functions derived from population-level equations as a survival dynamical system (SDS). To illustrate how population-level dynamics imply probability laws for individual-level infection and recovery times that can be used for statistical inference, we show numerical examples based on synthetic data. In these examples, we show that an SDS analysis compares favourably with a complete-data maximum-likelihood analysis. Finally, we use the SDS approach to analyse data from a 2009 influenza A(H1N1) outbreak at Washington State University.
Multi-scale dynamics of infectious diseases
Authors: Garabed Rebecca B. , Jolles Anna , Garira Winston , Lanzas Cristina , Gutierrez Juan , Rempala Grzegorz
Published: December 2019

To address the challenge of multiscale dynamics of infectious diseases, the Mathematical Biosciences Institute organized a workshop at The Ohio State University to bring together scientists from a variety of disciplines to share expertise gained through looking at infectious diseases across different scales. The researchers at the workshop, held in April 2018, were specifically looking at three model systems: foot-and-mouth disease, vector-borne diseases and enteric diseases. Although every multiscale model must be necessarily derived from a multiscale system, not every multiscale system has to lead to multiscale models. These three model systems seem to have produced a variety of both multiscale and integrated single-scale mechanistic models that have developed their own strengths and particular challenges. Here, we present papers from some of the workshop participants to show the breadth of the field.
Mechanisms and drivers of belemnite body-size dynamics across the Pliensbachian–Toarcian crisis
Authors: Rita Patrícia , Nätscher Paulina , Duarte Luís V. , Weis Robert , De Baets Kenneth
Published: December 2019

Body-size reduction is considered an important response to current climate warming and has been observed during past biotic crises, including the Pliensbachian–Toarcian crisis, a second-order mass extinction. However, in fossil cephalopod studies, the mechanisms and their potential link with climate are rarely investigated and palaeobiological scales of organization are not usually differentiated. Here, we hypothesize that belemnites reduce their adult size across the Pliensbachian–Toarcian boundary warming event. Belemnite body-size dynamics across the Pliensbachian–Toarcian boundary in the Peniche section (Lusitanian Basin, Portugal) were analysed based on the newly collected field data. We disentangle the mechanisms and the environmental drivers of the size fluctuations observed from the individual to the assemblage scale. Despite the lack of a major taxonomic turnover, a 40% decrease in rostrum volume is observed across the Pliensbachian–Toarcian boundary, before the Toarcian Oceanic Anoxic Event where belemnites go locally extinct. The pattern is mainly driven by a reduction in adult size of the two dominant species,Pseudohastites longiformisandPassaloteuthis bisulcata.Belemnite-size distribution is best correlated with fluctuations in a palaeotemperature proxy (stable oxygen isotopes); however, potential indirect effects of volcanism and carbon cycle perturbations may also play a role. This highlights the complex interplay between environmental stressors (warming, deoxygenation, nutrient input) and biotic variables (productivity, competition, migration) associated with these hyperthermal events in driving belemnite body-size.
Investigation of the changing patterns of the land use land cover over Osogbo and its environs
Authors: Eresanya Emmanuel Olaoluwa , Daramola Mojooluwa Toluwalase , Durowoju Olufemi Sunday , Awoyele Peace
Published: December 2019

The progressive nature of urbanization plays a prominent role in land–atmosphere processes, which have corresponding impacts on the general environment. This research investigated the changing patterns of the land use land cover over Osogbo and its environs using remote sensing data obtained from Landsat TM, ETM+ and OLI/TIRS sensors. The changes in four land use classes were assessed for the years 1984, 2000 and 2015. The land surface temperature (LST) of the area was estimated from the satellite images covering the study periods, and the surface urban heat island (SUHI) process was also investigated between the city of Osogbo and the surrounding towns. The results showed major urban expansion leading to urban sprawl within the vicinity. Urban area increased by 5106 ha while vegetation decreased by 8653 ha between 1984 and 2015 indicating major variations in the land surface features. This was revealed by the increase in the LST over the locations which ranged between 22.6°C and 30°C (mean, 25.2°C) in 1984 and between 29.3°C and 36.7°C (mean, 31°C) in 2015. The highest SUHI intensity was observed between the major urban area (Osogbo) and least developed towns. The continuous increase in the surface temperature of the environment due to the continuous variations in the land surface properties implies increased risk of heat-related environmental issues such as deterioration of thermal comfort conditions.
Plant–soil–foliage feedbacks on seed germination and seedling growth of the invasive plant
Ageratina adenophora
Authors: Fang Kai , Chen Lin , Zhou Jie , Yang Zhi-Ping , Dong Xing-Fan , Zhang Han-Bo
Published: December 2019

Some exotic plants become invasive because they partially release from soil-borne enemies and thus benefit from positive plant–soil feedbacks (PSFs) in the introduced range. However, reports that have focused only on PSFs may exaggerate the invader's competitiveness. Here, we conducted three experiments to characterize plant–soil–foliage feedbacks, including mature leaves (ML), leaf litter (LL), rhizosphere soil (RS) and leaves plus soil (LS), on the early growth stages of the invasive plant
Ageratina adenophora
. In general, the feedbacks from aboveground (ML, LL) adversely affected
A. adenophora
by delaying germination time, inhibiting germination rate and reducing seedling growth. The increased invasion history exacerbated the adverse effects of LL and LS feedbacks on seedling growth. These adverse effects were partially contributed by more abundant fungi (e.g.
Didymella
) or/and more virulent fungi (e.g.
Fusarium
) developed in the aboveground part of
A. adenophora
during the invasion. Interestingly, the aboveground adverse effects can be weakened by microbes from RSs. Our novel findings emphasize the important role of aboveground feedbacks in the evaluation of plant invasiveness, and their commonness and significance remain to be explored in other invasive systems.
Algoriphagus aquimaris sp. nov., isolated from seashore sand
Authors: Kim Jinsoo , Yoon Sung-Ho , Yang Keun-Hyeok , Kim Sungchul , Lee Sang-Seob
Published: December 2019

Strain F21T, a marine, aerobic, Gram-negative, rod-shaped bacterium, was isolated from seashore sand sampled in Pohang, Republic of Korea. Cells of strain F21T were non-motile, catalase-positive, oxidase-positive, non-spore-forming and formed pinkish-red colonies on marine agar. The strain grew optimally at 37°C, pH 7 and in the presence of 2–3 % NaCl (w/v). Analysis of the 16S rRNA gene sequence of strain F21T revealed that it belonged to the genus

Algoriphagus

, family

Cyclobacteriaceae

, with similarity values of 98.1 and 96.8 % to

Algoriphagus marincola

DSM 16067T and

Algoriphagus ornithinivorans

IMSNU 14014T, respectively. When comparing the genome sequence of F21 T with those of the type strains of six species of the genus

Algoriphagus

, the values obtained were below the thresholds for analyses of average nucleotide identity (71.8–92.7 %) and in silico DNA–DNA hybridization using the Genome-to-Genome Distance Calculator (14.7–75.2 %). The DNA G+C content of strain F21T was 42.0 mol%. The chemotaxonomic characteristics of F21T included MK-7 as the predominant isoprenoid quinone, iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) as major cellular fatty acids, and phosphatidylcholine and phosphatidylethanolamine as major polar lipids. On the basis of phenotypic and chemotaxonomic properties, phylogenetic distinctiveness, and genomic data, we named strain F21T as Algoriphagus aquimaris sp. nov. and proposed that strain F21T (=KEMB 2250–007T= KCTC 72106T=JCM 33187T) in the genus

Algoriphagus

represents a novel species.
Impact and cost-effectiveness of nonavalent human papillomavirus vaccination in Switzerland: insights from a dynamic transmission model
Authors: Riesen Maurane , Bogaards Johannes A. , Low Nicola , Althaus Christian L.
Published: December 2019

AIM

In Switzerland, human papillomavirus (HPV) vaccination has been implemented using a quadrivalent vaccine that covers HPV types 16 and 18, responsible for about 70% of cervical cancer. The average national uptake was 56% in girls by the age of 16 years in 2014–2016. A nonavalent vaccine, covering five additional oncogenic HPV types was recommended at the end of 2018. The primary aim of this study was to assess the impact and cost-effectiveness of introducing the nonavalent HPV vaccine in Switzerland compared with the quadrivalent vaccine.

METHODS

We developed a dynamic transmission model that describes the spread of 10 high risk HPV types. We informed the model with Swiss data about sexual behaviour and cervical cancer screening, and calibrated the model to cervical cancer incidence in Switzerland. We modelled the impact of quadrivalent and nonavalent vaccines at the achieved (56%) and national recommended uptake (80%) in girls. We calculated the incremental cost-effectiveness ratio (ICER) between the nonavalent vaccine, the quadrivalent vaccine and no vaccination. We evaluated costs linked to cervical cancer screening, treatment of different disease stages and vaccination in a sensitivity analysis.

RESULTS

Compared with quadrivalent HPV vaccination in Switzerland at 56% uptake, vaccinating with the nonavalent vaccine would avert 1,175 cervical cancer deaths, 3,641 cases of cervical cancer and 106,898 CIN treatments over 100 years at 56% uptake. Compared with the quadrivalent vaccine, which would prevent an estimated 67% and 72% of cervical cancer cases at 56% and 80% coverage, the nonavalent vaccine would prevent 83% and 89% of all cervical cancers at the same coverage rates. The sensitivity analysis shows that introducing the nonavalent vaccination should improve health outcomes and offers a cost-saving alternative to the quadrivalent vaccine under the current price difference.

CONCLUSIONS

All scenarios with quadrivalent and nonavalent vaccination are likely to be cost-effective compared with no vaccination. Switching to the nonavalent vaccine at current and improved vaccination uptake is likely to be cost-saving under the investigated price difference.
Evolutionary stasis of an RNA virus indicates arbovirus re-emergence triggered by accidental release
Authors: Pascall David J , Nomikou Kyriaki , Bréard Emmanuel , Zientara Stephan , Silva Filipe Ana da , Hoffmann Bernd , Jacquot Maude , Singer Joshua B. , De Clercq Kris , Bøtner Anette , Sailleau Corinne , Viarouge Cyrille , Batten Carrie , Puggioni Giantonella , Ligios Ciriaco , Savini Giovanni , van Rijn Piet A. , Mertens Peter PC , Biek Roman , Palmarini Massimo
Published: December 2019

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an insect-borne virus of ruminants, emerged in livestock in Northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of Euros. Though the outbreak was successfully controlled through vaccination by early 2010, puzzlingly a closely-related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this period without replication, we conclude that the second outbreak was most likely initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.
Cytological abnormalities and pollen abortion in interspecific hybrids ofNicotiana
Authors: Liao Jugou , Chen Zhiyun , Pan Zihui , Niu Yongzhi , Suo Wenlong , Wei Xuemei , Zhen Yunye , Lv Litang , Ma Wenguang , Chen Suiyun
Published: December 2019

Interspecific cross breeding introduces superior agronomic traits into cultivated species; however, problematic pollen sterility occurs in the hybrids. Our previous study obtained interspecific hybrids from the cross between a cytoplasmic male sterility line ofNicotiana tabacumandNicotiana alata, and some of the hybrids were pollen sterile. Here, we conducted an in-depth cellular study to understand the cytological mechanism of pollen abortion in these hybrids (F1-D sterile) compared with pollen development in the fertile hybrids (F1-S sterile) from the same cross. The ultrastructure observation showed that the membrane of microspore in F1-D sterile hybrid was deficient at all represented developmental stages. Chromosome behavior during meiosis was studied by carbol fuchsin staining, which indicated that cytomixis, chromosome leakage and asymmetric callose wall deposition occurred with high frequency in the microsporocyte of F1-D sterile. The results of the ultrastructure and 6-diamidino-2-phenylindole (DAPI) analyses also showed that the cytoplasm and nucleus were unstable and extruded from F1-D sterile microspore during the developmental process, leading to mature pollen grains that were vacuous and collapsed in the aperture region. In addition, delayed tapetum degradation was also detected in the anther of F1-D sterile, and might be associated with irregular sporopollenin deposition in the aperture region of F1-D sterile pollen. Genetic unbalance and cytomembrane deficiency might both be responsible for the instability of the chromosome, nuclear and cytoplasm, and resulted in pollen abortion in F1-D sterile hybrids, and irregular tapetum degradation might also be related with pollen sterility.
Seasonal Variation in the Internet Searches for Cancer Recurrence: An Infodemiological Study
Authors: Lou Xiaoqi , Hu Dingtao , Zhang Man , Xie Qiaomei , Zou Yanfeng , Wang Fang
Published: December 2019

Background

While few clinical and epidemiological studies have assessed how seasonality affects cancer recurrence, it has not been studied with the utility of the internet data. In this study, we aim to test whether cancer recurrence presents seasonality on a population level, utilizing internet search query data.

Methods

This infodemiological study used Google Trends to find query data for the term “cancer recurrence” from January 01, 2004, to December 31, 2018 in the USA, the UK, Canada, and Australia. Time series seasonal decomposition and the cosinor analysis were used to analyze and describe the seasonal trends for cancer recurrence.

Results

A general upward trend in UK and northern hemisphere were observed. Statistically significant seasonal trends on “cancer recurrence” in the USA (p=1.33×10−5), the UK (p=0.012), and northern hemisphere (p=5.67×10−7) were revealed by cosinor analysis, with a peak in early summer and nadir in early winter. Besides, a seasonal variation was also found in Australia (p=2.3×10−4), with a peak in late summer and nadir in late winter.

Conclusions

The evidence from internet search query data showed a seasonal variation in cancer recurrence, with a peak in early summer(northern hemisphere)/late summer(southern hemisphere). Besides, the relative search volume of “cancer recurrence” appeared a general upward trend in UK and northern hemisphere in recent years.
Molybdate to prevent the formation of sulfide during the process of biogas production
Authors: Tenti Pietro , Roman Samuele , Storelli Nicola
Published: December 2019

The process of anaerobic digestion producing biogas is an eco-friendly energy source that promotes recycling from waste biomass such as food chain residues, wet waste, wastewater. In this study, we focused on the problem of the sulfide (H2S) produced by the sulfate-reducing bacteria (SRB) in the presence of sulfate residues. This byproduct is dangerous for human health and an issue due to the highly corrosive effect on metallic components. To this purpose, the Molybdate, a sulfate analog, known in the literature to inhibit SRBs by blocking the first enzyme of the metabolic pathway of anaerobic respiration, was applied. The experiments carried out showed that a concentration of 0.3 mM of molybdate was enough to inhibit the SRB in a complex environment of the anaerobically digested sludge (ADS) took from a real biogas producing bioreactor. During the study, we observed the importance of the sulfate concentration sulfate in the system. Indeed, the production of sulfide was stopped only under the threshold ratio value of 1:10 (molybdate: sulfate). In the short term, the addition of molybdate did not alter the production and quality (% of methane) of the biogas, nor the anaerobic microbial community, including SRB population itself.
High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma
Authors: Vinod Natasha , Hwang Duhyeong , Azam Salma H. , Van Swearingen Amanda E. D. , Wayne Elizabeth , Fussell Sloane C. , Sokolsky-Papkov Marina , Pecot Chad V. , Kabanov Alexander V.
Published: December 2019

About 40% of the NSCLC patients have Stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure. New immunotherapeutic modalities such as anti-PD1 checkpoint blockade have shown promise; however, response to such strategies is highly variable across patients. Here, we show that our novel poly(2-oxazoline) (POx) based nanomicellar formulation of Resiquimod, an imidazoquinoline TLR 7/8 agonist, had a superior tumor inhibitory effect in a metastatic model of lung adenocarcinoma, relative to anti-PD1 immune checkpoint blockade therapy as well as platinum-based chemotherapy, which is the mainstay of treatment for NSCLC. Investigation of the in vivo immune status following Resiquimod PM (POx micellar formulation of Resiquimod) treatment showed that Resiquimod-based stimulation of antigen-presenting cells in the tumor microenvironment resulted in the mobilization of anti-tumor CD8+immune response. Our study demonstrates the promise of optimally delivered and nano-formulated Resiquimod as a new immunomodulating therapeutic strategy for the treatment of metastatic NSCLC.
Drebrin-like protein regulates body bending ofC. elegansvia suppression of NCA cation leak channels
Authors: Butkevich Eugenia , Weist Peter , Härtter Daniel , Klopfenstein Dieter R. , Garces Renata , Schmidt Christoph F.
Published: December 2019

Drebrin-like protein (DBN-1) inC. elegansis an adaptor protein that connects different cellular pathways to the actin cytoskeleton. Using a CRISPR-Cas9 system, we generated a newdbn-1allele, which lacks 80% of C-terminal part of DBN-1. The mutant displays a striking hyper-bending locomotion phenotype and body posture with two times stronger curvature than wild type. We show by atomic force microscopy that the muscle tone of the mutant remains unaffected. Aiming to track down the cause of hyper-bending, we performed genetic epistasis experiments. We found that mutations in the Rho-specific guanine-nucleotide exchange factor (GEF) domain of UNC-73 (Trio), pan-neuronal expression of dominant negative RHO-1 and mutations in NCA (NALCN) cation leak channels all suppressed hyper-bending in thedbn-1mutant. These data indicate that DBN-1 negatively regulates the activity of both NCA-1 and NCA-2 channels, opposing RHO-1 in the non-canonical Gq pathway. We conclude that DBN-1 is an important component of the neuronal signaling cascade that controls the degree ofC. elegansbody bending during locomotion.
Boron alters carboxyl group binding capacity and Al transport pathway to relieve Al toxicity
Authors: Yan Lei , Riaz Muhammad , Liu Jiayou , Liu Yalin , Zeng Yu , Jiang Cuncang
Published: December 2019

Boron (B) is indispensable for plant growth and has been reported in the mitigation of aluminum (Al) toxicity in different plants. This study unraveled the efficacy of B in reducing the toxicity of Al to trifoliate orange seedlings in a hydroponic experiment. In the current study, B supply had a positive effect on root length and plant growth-related parameters, and attenuated Al-induced inhibition of plasma membrane H+-ATPase activity. The results of XPS and SEM-EDS revealed that B reduces the Al accumulation in root cell wall (CW), especially acts on pectin fractions (alkali-soluble pectin), accompanied by suppressing the pectin synthesis, inhibiting pectin methylesterase (PME) activity andPMEexpression. Furthermore, B application inhibitsNRAT1expression while increasesALS1expression, which are responsible for restraining Al transport from external cells to the cytoplasm and accelerating Al divert to vacuoles, and the results can be further demonstrated by TEM-EDS analysis. Taken together, our results indicated that B mainly promotes the efflux of H+by regulating the plasma membrane H+-ATPase activity, futhur reduce the demethylation of pectin to weaken Al binding ability to carboxyl. More importantly, B alleviated some of the toxic effects of Al by decreasing the deposition of Al in cytoplasm and compartmentalizes Al into vacuoles.

One-sentence summary

Boron can reduce the binding amount of carboxyl group to Al in pectin, decreasing the deposition of Al in cytoplasm and compartmentalizes Al into vacuoles, thereby reduce the toxicity of Al to plants..
Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation
Authors: Halstead Michelle M , Ma Xin , Schultz Richard M , Ross Pablo J
Published: December 2019

The maternal-to-zygotic transition (MZT) is underpinned by wide-spread transcriptomic and epigenomic remodeling that facilitates totipotency acquisition. Factors regulating MZT vary across species and differences in timing of developmental transitions and motif enrichment at accessible chromatin between human and mouse embryos suggest a distinct regulatory circuitry. Profiling accessible chromatin in bovine preimplantation embryos—timing of developmental transitions in bovine closely resembles that in human—indicated that prior to embryonic genome activation (EGA) accessible chromatin is enriched in maternal transcription factor recognition sites, e.g., CTCF, KLFs, NFY, and SP1, echoing observations in humans and mice, and suggesting that a conserved set of maternal factors regulate chromatin remodeling prior to EGA. In contrast, open chromatin established during EGA was primarily enriched for homeobox motifs and showed remarkable similarities between cattle and humans, indicating that cattle could be a more relevant model for human preimplantation development than mice.
Context-specific control of the neural dynamics of temporal attention by the human cerebellum
Authors: Breska Assaf , Ivry Richard B.
Published: December 2019

Physiological methods have identified a number of signatures of temporal prediction, a core component of attention. While the underlying neural dynamics have been linked to activity within cortico-striatal networks, recent work has shown that the behavioral benefits of temporal prediction causally rely on the cerebellum. Here we examine the involvement of the human cerebellum in the generation and/or temporal adjustment of anticipatory neural dynamics, measuring scalp electroencephalography in individuals with cerebellar degeneration. When the temporal prediction relied on an interval representation, duration-dependent adjustments were impaired in the cerebellar group compared to matched controls. This impairment was evident in ramping activity, beta-band power, and phase locking of delta-band activity. Remarkably, these same neural adjustments were preserved when the prediction relied on a rhythmic stream. Thus, the cerebellum has a context-specific causal role in the adjustment of anticipatory neural dynamics of temporal prediction, providing the requisite modulation to optimize behavior.
Mechanism of action of rigosertib does not involve tubulin binding
Authors: Baker Stacey J. , Cosenza Stephen C. , Athuluri-Divakar Saikrishna , Reddy M.V. Ramana , Vasquez-Del Carpio Rodrigo , Jain Rinku , Aggarwal Aneel K , Reddy E. Premkumar
Published: December 2019

Rigosertib is a novel benzyl styryl sulfone that inhibits the growth of a wide variety of human tumor cellsin vitroandin vivoand is currently in Phase III clinical trials. We recently provided structural and biochemical evidence to show that rigosertib acts as a RAS-mimetic by binding to Ras Binding Domains (RBDs) of the RAF and PI3K family proteins and disrupts their binding to RAS. In a recent study, Jost et al (2017) attributed the mechanism of action of rigosertib to microtubule-binding. In these studies, rigosertib was obtained from a commercial vendor. We have been unable to replicate the reported results with clinical grade rigosertib, and hence compared the purity of clinical grade and commercially sourced rigosertib. We find that the commercially sourced rigosertib contains approximately 5% ON01500, a potent inhibitor of tubulin polymerization. Clinical grade rigosertib, which is free of this impurity, does not exhibit tubulin binding activity.In vivo, cell lines that express mutant β-tubulin (TUBBL240F) were also reported to be resistant to the effects of rigosertib. However, our studies showed that both wild-type and TUBBL240F-expressing cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. Morphologically, we find that rigosertib, at lethal concentrations, induced a senescence-like phenotype in the small percentage of both wild-type and TUBBL240F-expressing cells that survive in the presence of rigosertib. Our results suggest that TUBBL240F expressing cells are more prone to undergo senescence in the presence of rigosertib as well as BI2536, an unrelated ATP-competitive pan-PLK inhibitor. The appearance of these senescent cells could be incorrectly scored as resistant cells in flow cytometric assays using short term cultures.
WITHDRAWN: Oligomerization of the antimalarial drug targetPfATP4 is essential for parasite survival
Authors: Ramanathan Aarti A. , Morrisey Joanne M. , Daly Thomas M. , Bergman Lawrence W. , Mather Michael W. , Vaidya Akhil B.
Published: December 2019

Withdrawal Statement

The authors have withdrawn their manuscript owing to further investigations on PfATP4 that have revealed that the main conclusion of the preprint that PfATP4 forms oligomers is incorrect. Initial cryogenic electron microscopy observations showed a large detergent belt that surrounds monomers of PfATP4, which could have affected migration of the molecule on blue-native polyacrylamide gels. This gave an incorrect impression of the molecule to be in a dimeric or oligomeric state. Authors regret this error in interpreting the data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Integration of system phenotypes in microbiome networks to identify candidate synthetic communities: a study of the grafted tomato rhizobiome
Authors: Poudel Ravin , Jumpponen Ari , Kennelly Megan M. , Rivard Cary , Gomez-Montano Lorena , Garrett Karen A.
Published: December 2019

Understanding factors influencing microbial interactions, and designing methods to identify key taxa, are complex challenges for achieving microbiome-based agriculture. Here we study how grafting and the choice of rootstock influence root-associated fungal communities in a grafted tomato system. We studied three tomato rootstocks (BHN589, RST-04-106 and Maxifort) grafted to a BHN589 scion and profiled the fungal communities in the endosphere and rhizosphere by sequencing the Internal Transcribed Spacer (ITS2). The data provided evidence for a rootstock effect (explaining ~2% of the total captured variation, p < 0.01) on the fungal community. Moreover, the most productive rootstock, Maxifort, supported greater fungal species richness than the other rootstocks or controls. We then constructed a phenotype-OTU network analysis (PhONA) using an integrated machine learning and network analysis approach based on sequence-based fungal Operational Taxonomic Units (OTUs) and associated tomato yield data. PhONA provides a graphical framework to select a testable and manageable number of OTUs to support microbiome-enhanced agriculture. We identified differentially abundant OTUs specific to each rootstock in both endosphere and rhizosphere compartments. Subsequent analyses using PhONA identified OTUs that were directly associated with tomato fruit yield, and others that were indirectly linked to yield through their links to these OTUs. Fungal OTUs that are directly or indirectly linked with tomato yield may represent candidates for synthetic communities to be explored in agricultural systems.

IMPORTANCE

The realized benefits of microbiome analyses for plant health and disease management are often limited by the lack of methods to select manageable and testable synthetic microbiomes. We evaluated the composition and diversity of root-associated fungal communities from grafted tomatoes. We then constructed a phenotype-OTU network analysis (PhONA) using these linear and network models. By incorporating yield data in the network, PhONA identified OTUs that were directly predictive of tomato yield, and others that were indirectly linked to yield through their links to these OTUs. Follow-up functional studies of taxa associated with effective rootstocks, identified using approaches like PhONA, could support the design of synthetic fungal communities for microbiome-based crop production and disease management. The PhONA framework is flexible for incorporation of other phenotypic data and the underlying models can readily be generalized to accommodate other microbiome or other ‘omics data.
mtDNA-based reconstructions of change in effective population sizes of Holarctic birds do not agree with their reconstructed range sizes based on paleoclimates
Authors: Miller Eleanor F. , Green Rhys E. , Balmford Andrew , Beyer Robert , Somveille Marius , Leonardi Michela , Amos William , Manica Andrea
Published: December 2019

During the Quaternary, large climate oscillations had profound impacts on the distribution, demography and diversity of species globally. Birds offer a special opportunity for studying these impacts because surveys of geographical distributions, publicly-available genetic sequence data, and the existence of species with adaptations to life in structurally different habitats, permit large-scale comparative analyses. We use Bayesian Skyline Plot (BSP) analysis of mitochondrial DNA to reconstruct profiles depicting how effective population size (Ne) may have changed over time, focussing on variation in the effect of the last deglaciation among 102 Holarctic species. Only 3 species showed a decline inNesince the Last Glacial Maximum (LGM) and 7 showed no sizeable change, whilst 92 profiles revealed an increase inNe. Using bioclimatic Species Distribution Models (SDMs), we also estimated changes in species potential range extent since the LGM. Whilst most modelled ranges also increased, we found no correlation across species between the magnitude of change in range size and change inNe. The lack of correlation between SDM and BSP reconstructions could not be reconciled even when range shifts were considered. We suggest the lack of agreement between these measures might be linked to changes in population densities which can be independent of range changes. We caution that interpreting either SDM or BSPs independently is problematic and potentially misleading. Additionally, we found thatNeof wetland species tended to increase later than species from terrestrial habitats, possibly reflecting a delayed increase in the extent of this habitat type after the LGM.
YBEY is an essential biogenesis factor for mitochondrial ribosomes
Authors: Summer Sabrina , Smirnova Anna , Gabriele Alessandro , Toth Ursula , Mandela Fasemore , Förstner Konrad U. , Kuhn Lauriane , Chicher Johana , Hammann Philippe , Mitulović Goran , Entelis Nina , Tarassov Ivan , Rossmanith Walter , Smirnov Alexandre
Published: December 2019

Ribosome biogenesis requires numerous trans-acting factors, some of which are deeply conserved. In Bacteria, the endoribonuclease YbeY is believed to be involved in 16S rRNA 3’-end processing and its loss was associated with ribosomal abnormalities. In Eukarya, YBEY appears to generally localize to mitochondria (or chloroplasts). Here we show that the deletion of human YBEY results in a severe respiratory deficiency and morphologically abnormal mitochondria as an apparent consequence of impaired mitochondrial translation. Reduced stability of 12S rRNA and the deficiency of several proteins of the small ribosomal subunit inYBEYknockout cells pointed towards a defect in mitochondrial ribosome biogenesis. The specific interaction of mitoribosomal protein uS11m with YBEY suggests that the latter recruits uS11m to the nascent small subunit in its late assembly stage. This scenario shows similarities with final stages of cytosolic ribosome biogenesis, and may represent a late checkpoint before the mitoribosome engages in translation.
Polyandry is extremely rare in the firefly squid,Watasenia scintillans
Authors: Sato Noriyosi , Tsuda Sei-Ichiro , Alam Nur E , Sasanami Tomohiro , Iwata Yoko , Kusama Satoshi , Inamura Osamu , Yoshida Masa-aki , Hirohashi Noritaka
Published: December 2019

Although polygamy has versatile benefits for both sexes, many species favor monogamy for reasons with the clarity or unclarity. In cephalopods, all species are regarded to be polygamous, which could be attributed to their common life-history traits. Contrary to this prediction, we show empirical evidence for monogamy in the firefly squid,Watasenia scintillans. The peak spawning season comes after male disappearance owning to long-reserved spermatangia deposited by male at exact locations (bilateral pouches under neck collar) on female with a symmetric distribution. Such a non-random placement of spermatangia prompted us to hypothesize that females engage in lifetime monoandry. Hence we assigned genotypes of female-stored spermatangia and offspring. We found that in 94.7 % females, the spermatangia were delivered from a single male and all embryos in the same egg string sired by sperm from stored spermatangia. Throughout the season, relative testes mass was much smaller inW. scintillansthan all other cephalopods previously examined. The mean number of male-stored spermatophores was approximately 30, the equivalent to 2.5 mates. Our demographic and morphometrical data agree with the prediction that monogyny is favored when potential mates are scarce such as absence of female remating. Together, these results suggest the likelihood of mutual monogamy.
A comprehensive study of Phospholipid fatty acid rearrangements in the early onset of the metabolic syndrome: correlations to organ dysfunction
Authors: Bacle Amélie , Kadri Linette , Khoury Spiro , Ferru-Clément Romain , Faivre Jean-François , Cognard Christian , Bescond Jocelyn , Krzesiak Amandine , Contzler Hugo , Delpech Nathalie , Colas Jenny , Vandebrouck Clarisse , Sébille Stéphane , Ferreira Thierry
Published: December 2019

The balance within phospholipids (PL) between Saturated Fatty Acids (SFA) and mono- or poly-Unsaturated Fatty Acids (UFA), is known to regulate the biophysical properties of cellular membranes. As a consequence, perturbating this balance alters crucial cellular processes in many cell types, such as vesicular budding and the trafficking/function of membrane-anchored proteins. The worldwide spreading of the Western-diet, which is specifically enriched in saturated fats, has been clearly correlated with the emergence of a complex syndrome, known as the Metabolic Syndrome (MetS), which is defined as a cluster of risk factors for cardiovascular diseases, type 2 diabetes and hepatic steatosis. However, no clear correlations between diet-induced fatty acid redistribution within cellular PL, the severity/chronology of the symptoms associated to MetS and the function of the targeted organs, particularly in the early onset of the disease, have been established. In an attempt to fill this gap, we analyzed in the present study PL remodeling in rats exposed during 15 weeks to a High Fat/High Fructose diet (HFHF) in several organs, including known MetS targets. We show that fatty acids from the diet can distribute within PL in a very selective way, with PhosphatidylCholine being the preferred sink for this distribution. Moreover, in the HFHF rat model, most organs are protected from this redistribution, at least during the early onset of MetS, at the exception of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs.
Recent hybridization and allopolyploidy reprogrammedSpartinamicroRNA expression under xenobiotic induced stress
Authors: Cavé-Radet Armand , Salmon Armel , Tran Van Canh Loup , Moyle Richard L. , Pretorius Lara-Simone , Lima O. , Ainouche Malika L. , El Amrani Abdelhak
Published: December 2019

Xenobiotic detoxification is a common trait of all living organisms, necessary for developmental plasticity and stress tolerance. The gene set involved in this biological process is dubbed the xenome (i.e.involved in drug metabolism in mammals, degradation of allelochemicals and environmental pollutants by bacteria and plant communities). Recently, we found that allopolyploidy increased tolerance to xenobiotics (phenanthrene) inSpartina. To decipher the molecular mechanisms underlying this process, we examined how interspecific hybridization and genome doubling impact miRNAs expression under xenobiotic induced stress. In this work we used a deep sequencing approach, and analyzed the parental speciesS. alternifloraandS. maritima, their F1 hybridS. x townsendiiand the allopolyploidS. anglicaunder phenanthrene exposure. We found that hybridization and genome doubling reprogrammed a myriad of miRNAs under phenanthrene-induced stress. Hence, to identify the master miRNAs involved in phenanthrene tolerance, we performed experimental functional validation of phenanthrene-responsive Spar-miRNAs using Arabidopsis T-DNA mutant lines inserted in homologous MIR genes, 39 knock out T-DNAArabidopsismutants, tagged in the most conserved miRNAs genes in vascular plants were screened. Development of MIR159 and MIR156 mutants was significantly affected under phenanthrene-induced stress. Subsequently, we performedin plantaexperimental validation to confirm the interaction between these miRNAs and their targets. These analyses suggest that MIR159 and MIR156 regulatory modules were targeted to induce the xenome relaxation and impact developmental plasticity responses in phylogenetically distant species under xenobiotic-induced stress.

Graphical abstract
BZIP Transcription Factors Modulate DNA Supercoiling Transitions
Authors: Hörberg Johanna , Reymer Anna
Published: December 2019

Torsional stress on DNA, introduced by molecular motors, constitutes an important regulatory mechanism of transcriptional control. Torsional stress can modulate specific binding of transcription factors to DNA and introduce local conformational changes that facilitate the opening of promoters and nucleosome remodeling. Using all-atom microsecond scale molecular dynamics simulations together with a torsional restraint that controls the total helical twist of a DNA fragment, we addressed the impact of torsional stress on DNA complexation with a human BZIP transcription factor, MafB. We gradually over- and underwind DNA alone and in complex with MafB by 5° per dinucleotide step, monitoring the evolution of the protein-DNA contacts at different degrees of torsional strain. Our computations show that MafB changes the DNA sequence-specific response to torsional stress. The dinucleotide steps that are susceptible to absorb most of the torsional stress become more torsionally rigid, as they are involved in the protein-DNA contacts. Also, the protein undergoes substantial conformational changes to follow the stress-induced DNA deformation, but mostly maintains the specific contacts with DNA. This results in a significant asymmetric increase of free energy of DNA twisting transitions, relative to free DNA, where overtwisting is more energetically unfavorable. Our data suggest that MafB could act as a torsional stress insulator, modulating the propagation of torsional stress along the chromatin fiber, which might promote cooperative binding of other transcription factors.
Regional glia-related metabolite levels are higher at older age and scale negatively with visuo-spatial working memory: A cross-sectional proton MR spectroscopy study at 7 tesla on normal cognitive ageing
Authors: Lind Anna , Boraxbekk Carl-Johan , Petersen Esben Thade , Paulson Olaf Bjarne , Siebner Hartwig Roman , Marsman Anouk
Published: December 2019

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field strength, we performed 1H-MRS in 60 healthy volunteers to asses age-related differences in neuron- and glia-related metabolite levels and their relation to cognitive ageing. Gender was balanced and participants were assigned to a younger, middle and older group according to their age, ranging from 18 to 79 years. They underwent 1H-MRS of anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus and thalamus and performed a visuo-spatial working memory task outside the scanner. Multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all brain regions of interest. Considering specific metabolites, elevated levels of glia-related metabolites in older age groups were observed in all brain regions. For the neuron-related metabolites, differences among age groups were only observed in two regions. We found higher levels of total N-acetyl aspartate in hippocampus for the older than the middle group, and lower levels of glutamate in DLPFC in the older than the younger group. Working memory performance correlated negatively with levels of glia-related metabolites for total creatine and total choline in ACC and myo-inositol in hippocampus and thalamus, but not with neuron-related metabolites. Together, the results show that age effects on glia-related metabolites scale with cognitive ageing in multiple brain regions. We conclude that 1H-MRS-derived glia-related markers may be of value in longitudinal studies of brain ageing.

Significance statement

Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. Due to the higher spectral resolution and sensitivity, 7 tesla 1H-MRS has potential to improve consistency of the results. Here we apply this technique to demonstrate that glia-related metabolites are elevated in older age in anterior cingulate cortex, hippocampus and thalamus with a novel link to cognitive ageing of visuo-spatial working memory. This study is the first to investigate normal ageing in these brain regions using 7 tesla 1H-MRS and the results indicate that glia-related metabolites could be of value in longitudinal studies of cognitive ageing.
Thousands of missing variants in the UK BioBank are recoverable by genome realignment
Authors: Jia Tongqiu , Munson Brenton , Allen Hana Lango , Ideker Trey , Majithia Amit R.
Published: December 2019

The UK Biobank is an unprecedented resource for human disease research. In March 2019, 49,997 exomes were made publicly available to investigators. Here we note that thousands of variant calls are unexpectedly absent from the current dataset, with 641 genes showing zero variation. We show that the reason for this was an erroneous read alignment to the GRCh38 reference. The missing variants can be recovered by modifying read alignment parameters to correctly handle the expanded set of contigs available in the human genome reference.
Detection of active Granzyme A in NK92 cells with fluorescent activity-based probe
Authors: Kołt Sonia , Janiszewski Tomasz , Kaiserman Dion , Modrzycka Sylwia , Snipas Scott J. , Salvesen Guy , Drąg Marcin , Bird Phillip I. , Kasperkiewicz Paulina
Published: December 2019

Cytotoxic T-lymphocytes (CTLs) and natural killer cells (NKs) kill compromised cells to defend against tumor and viral infections. Both effector cell types use multiple strategies to induce target cell death including Fas/CD95 activation; and the release of perforin and a group of lymphocyte granule serine proteases called granzymes. Granzymes have relatively broad and overlapping substrate specificities and may hydrolyze a wide range of peptidic epitopes; it is therefore challenging to identify their natural and synthetic substrates and to distinguish their localization and functions. Here, we present a specific and potent substrate, an inhibitor, and an activity-based probe of Granzyme A (GrA) that can be used to follow functional GrA in cells.
Continuous, multidimensional coding of 3D complex tactile stimuli by primary sensory neurons of the vibrissal system
Authors: Bush Nicholas E. , Solla Sara A. , Hartmann Mitra J. Z.
Published: December 2019

To reveal the full representational capabilities of sensory neurons, it is essential to observe their responses to complex stimuli. In the rodent vibrissal system, mechanical information at the whisker base drives responses of primary sensory neurons in the trigeminal ganglion (Vg). Studies of how Vg neurons encode stimulus properties are typically limited to 2D analyses and restricted stimulus sets. Here we record from Vg neurons during 3D stimulation while quantifying the complete 3D whisker shape and mechanics. Results show that individual Vg neurons simultaneously represent multiple mechanical features of the stimulus, do not preferentially encode principal components of the stimuli, and represent continuous and tiled variations of all available mechanical information. As a population, the neurons span a continuum of rapid and slow adaptation properties; a binary distinction between these adaptation classes is oversimplified. These results contrast with proposed codes in which Vg neurons segregate into functional classes.