bluuebunny/crossref_metadata_2025 huggingface dataset:
The cost-effectiveness of mammography-based female breast cancer screening in Canadian populations: a systematic review
Authors: Tahir Talha , Wong Melanie Mitsui , Tahir Rabia , Wong Michael Mitsui
Published: January 2020

Introduction

Mammography-based breast cancer screening is an important aspect of female breast cancer prevention within the Canadian healthcare system. The current literature on female breast cancer screening is largely focused on the health outcomes that result from screening. There is comparatively little data on the cost-effectiveness of the screening. Therefore, this paper sought to conduct a systematic review of the literature on the cost effectiveness of mammography-based breast cancer screening within female Canadian populations.

Materials and methods

A systematic review was performed in the PubMed database to identify all studies published within the last 10 years that addressed breast cancer screening and evaluate cost-effectiveness in a Canadian population.

Results

The search yielded five studies for inclusion, only three of which were applicable to average-risk Canadian women. The benefits of mortality reduction rose approximately linearly with costs, while costs were linearly dependent on the number of lifetime screens per woman. Moreover, triennial screening for average-risk women aged 50-69 years was found to be the most cost-effective in terms of cost per quality adjusted life year. The use of MRI in conjunction with mammography for women with the BRCA 1/2 mutation was found to be cost-effective while annual mammography-based screening for women with dense breasts was found to be cost-ineffective.

Conclusion

In spite of the growing interest to enhance breast cancer screening programs, analyses of the cost-effectiveness of mammography-based screening within Canadian populations are scarcely reported and have heterogeneous methodologies. The existing data suggests that Canada’s current breast cancer screening policy to screen average-risk women aged 50-74, biennially or triennially is cost-effective. These findings could be of interest to health policy makers when making decisions regarding resource allocation; however, further studies in this field are required in order to make stronger recommendations regarding cost-effectiveness.
The role of HMGB1 in invasiveCandida albicansinfection
Authors: Wang Jiaojiao , Wu Chuanxin , Wang Yunying , Chen Chongxiang , Cheng Jing , Rao Xiaolong , Sun Hang
Published: January 2020

Background

High mobility group box 1 (HMGB1) is an important “late” inflammatory mediator in bacterial sepsis. Ethyl pyruvate (EP), an inhibitor of HMGB1, can prevent bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated the role of HMGB1 and EP in invasiveC. albicansinfection.

Methods

We measured serum HMGB1 levels in patients with sepsis withC. albicansinfection and without fungal infection, and control subjects. We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice withC. albicansandC. albicans+ EP. Then, we examined HMGB1 levels from serum and tissue, investigated serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), determined pathological changes in tissues, and assessed mortality.

Results

Serum HMGB1 levels in patients with severe sepsis withC. albicansinfection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) andC. albicanssepsis severity. HMGB1 levels in serum and tissues were significantly increased within seven days after mice were infected withC. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.

Conclusions

HMGB1 levels were significantly increased in invasiveC. albicansinfections. EP preventedC. albicanslethality by decreasing HMGB1 expression and release. HMGB1 may provide an effective diagnostic and therapeutic target for invasiveC. albicansinfections.
Did we get sensorimotor adaptation wrong? Implicit adaptation as direct policy updating rather than forward-model-based learning
Authors: Hadjiosif Alkis M. , Krakauer John W. , Haith Adrian M.
Published: January 2020

The human motor system can rapidly adapt its motor output in response to errors. The prevailing theory of this process posits that the motor system adapts an internal forward model that predicts the consequences of outgoing motor commands, and that this forward model is then used to guide selection of motor output. However, although there is clear evidence for the existence of adaptive forward models to help track the state of the body, there is no real evidence that such models influence the selection of motor output. A possible alternative to the forward-model-based theory of adaptation is that motor output could be directly adjusted by movement errors (“direct policy learning”), in parallel with but independent of any updates to a predictive forward model. Here, we show evidence for this latter theory based on the properties of implicit adaptation under mirror-reversed visual feedback. We show that implicit adaptation still occurs under this extreme perturbation but acts in an inappropriate direction, following a pattern consistent with direct policy learning but not forward-model-based learning. We suggest that the forward-model-based theory of adaptation needs to be re-examined and that direct policy learning is a more plausible mechanism of implicit adaptation.
Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially-infected epithelial cells
Authors: Bastounis Effie E. , Alcalde Francisco Serrano , Radhakrishnan Prathima , Engström Patrik , Gómez Benito María J. , Oswald Mackenzi S. , Smith Jason G. , Welch Matthew D. , García Aznar José M. , Theriot Julie A.
Published: January 2020

Multiple distinct types of intracellular bacterial pathogens have been shown to alter the mechanics of their mammalian host cells to promote cell-to-cell spread. Conversely, host cells may respond by altering their own mechanical behavior to limit infection. We monitored epithelial cell monolayers sparsely infected with the intracellular bacterial pathogensListeria monocytogenesorRickettsia parkeriover the course of several days. Under conditions where these pathogens were able to trigger innate immune signaling through the NF-κB pathway and to use actin-based motility to spread non-lytically from cell to cell, domains of infected cells formed enormous three-dimensional mounds, where uninfected cells surrounding the infected cells became stiffer and actively moved toward the site of infection, collectively squeezing the softer and weaker infected cells up and ejecting them from the epithelial monolayer. Bacteria in mounds were less able to spread laterally in the monolayer, limiting the growth of the focus, while mounded cells eventually underwent cell death. Cells in infected monolayers exhibited behavioral and molecular signatures of the epithelial to mesenchymal transition (EMT), such that coordinated forceful action by uninfected bystander cells actively eliminated large domains of infected cells, consistent with the hypothesis that this collective cell response represents an innate immune response.
Cancer PRSweb – an Online Repository with Polygenic Risk Scores (PRS) for Major Cancer Traits and Their Phenome-wide Exploration in Two Independent Biobanks
Authors: Fritsche Lars G. , Patil Snehal , Beesley Lauren J. , VandeHaar Peter , Salvatore Maxwell , Peng Robert B. , Taliun Daniel , Zhou Xiang , Mukherjee Bhramar
Published: January 2020

To facilitate scientific collaboration on polygenic risk scores (PRS) research, we created an extensive PRS online repository for 49 common cancer traits integrating freely available genome-wide association studies (GWAS) summary statistics from three sources: published GWAS, the NHGRI-EBI GWAS Catalog, and UK Biobank-based GWAS. Our framework condenses these summary statistics into PRS using various approaches such as linkage disequilibrium pruning / p-value thresholding (fixed or data-adaptively optimized thresholds) and penalized, genome-wide effect size weighting. We evaluated the PRS in two biobanks: the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort at Michigan Medicine, and the population-based UK Biobank (UKB). For each PRS construct, we provide measures on predictive performance, calibration, and discrimination. Besides PRS evaluation, the Cancer-PRSweb platform features construct downloads and phenome-wide PRS association study results (PRS-PheWAS) for predictive PRS. We expect this integrated platform to accelerate PRS-related cancer research.
Tough and Tunable Scaffold-Hydrogel Composite Biomaterial for Soft-to-Hard Musculoskeletal Tissue Interfaces
Authors: Sun Han Chang Raul A. , Kersh Mariana E. , Harley Brendan A.C.
Published: January 2020

Biological interfaces connecting tissues with dissimilar mechanical and structural properties are ubiquitous throughout the musculoskeletal system. Tendons attach to bone via a fibrocartilaginous interface (enthesis) that reduces mechanical strain and resultant tissue failure. Despite this toughening mechanism, tears at the enthesis occur due to acute (overload) or degradative (aging) processes. Repair involves surgical fixation of the torn tendon to bone, but results in the formation of a narrow fibrovascular scar tissue with inferior biomechanical properties. Progress toward enthesis regeneration requires biomaterial approaches to protect exogenously added or endogenously recruited cells from high levels of strain at the interface between dissimilar materials. Here, we describe an innovative reinforcement strategy to address this need. We report a stratified scaffold containing collagen bone and tendon tissue compartments linked by a continuous polyethylene glycol (PEG) hydrogel interface. Tuning the gelation kinetics of the hydrogel modulates its integration with the surrounding biomaterial compartments and yields biomechanical performance advantages. Notably, the continuous hydrogel interface reduces the deleterious effects of strain concentrations that form between tissue compartments in conventional stratified biomaterials. This design of mechanically robust stratified composite biomaterials may be appropriate for a broad range of tendon and ligament-to-bone insertions.
A universal chromosome identification system for maize and wildZeaspecies
Authors: Braz Guilherme T. , do Vale Martins Lívia , Zhang Tao , Albert Patrice S. , Birchler James A. , Jiang Jiming
Published: January 2020

Maize was one of the first eukaryotic species in which individual chromosomes can be identified cytologically, which made maize one of the oldest models for genetics and cytogenetics research. Nevertheless, consistent identification of all 10 chromosomes from different maize lines as well as from wildZeaspecies remains a challenge. We developed a new technique for maize chromosome identification based on fluorescence in situ hybridization (FISH). We developed two oligonucleotide-based probes that hybridize to 24 chromosomal regions. Individual maize chromosomes show distinct FISH signal patterns, which allow universal identification of all chromosomes from differentZeaspecies. We developed karyotypes from threeZea mayssubspecies and two additional wildZeaspecies based on individually identified chromosomes. A paracentric inversion was discovered on the long arm of chromosome 4 inZ. nicaraguensisandZ. luxuriansbased on modifications of the FISH signal patterns. Chromosomes from these two species also showed distinct distribution patterns of terminal knobs compared to otherZeaspecies. These results support thatZ. nicaraguensisandZ. luxuriansare closely related species.
Genomic and phenotypic evolution ofEscherichia coliin a novel citrate-only resource environment
Authors: Blount Zachary D. , Maddamsetti Rohan , Grant Nkrumah A. , Ahmed Sumaya T. , Jagdish Tanush , Sommerfeld Brooke A. , Tillman Alice , Moore Jeremy , Slonczewski Joan L. , Barrick Jeffrey E. , Lenski Richard E.
Published: January 2020

Evolutionary innovations allow populations to colonize new, previously inaccessible ecological niches. We previously reported that aerobic growth on citrate (Cit+) evolved in a population ofEscherichia coliduring adaptation to a minimal glucose medium containing citrate (DM25). Cit+can grow in citrate-only medium (DM0), which is a novel environment forE. coli. To study adaptation to this new niche, we evolved one set of Cit+populations for 2,500 generations in DM0 and a control set in DM25. We identified numerous parallel mutations, many mediated by transposable elements. Several lineages evolved multi-copy amplifications containing themaeAgene, constituting up to ∼15% of the genome. We also found substantial cell death in ancestral and evolved clones. Our results demonstrate the importance of copy-number variation and transposable elements in the refinement of the Cit+trait. However, the observed mortality suggests a persistent evolutionary mismatch betweenE. coliphysiology and a citrate-only environment.
AmpliconReconstructor: Integrated analysis of NGS and optical mapping resolves the complex structures of focal amplifications in cancer
Authors: Luebeck Jens , Coruh Ceyda , Dehkordi Siavash R. , Lange Joshua T. , Turner Kristen M. , Deshpande Viraj , Pai Dave A. , Zhang Chao , Rajkumar Utkrisht , Law Julie A. , Mischel Paul S. , Bafna Vineet
Published: January 2020

Oncogene amplification, a major driver of cancer pathogenicity, is often mediated through focal amplification of genomic segments. Recent results implicate extrachromosomal DNA (ecDNA) as the primary mechanism driving focal copy number amplification (fCNA) - enabling gene amplification, rapid tumor evolution, and the rewiring of regulatory circuitry. Resolving an fCNA’s structure is a first step in deciphering the mechanisms of its genesis and the subsequent biological consequences. Here, we introduce a powerful new computational method, AmpliconReconstructor (AR), for integrating optical mapping (OM) of long DNA fragments (>150kb) with next-generation sequencing (NGS) to resolve fCNAs at single-nucleotide resolution. AR uses an NGS-derived breakpoint graph alongside OM scaffolds to produce high-fidelity reconstructions. After validating performance by extensive simulations, we used AR to reconstruct fCNAs in seven cancer cell lines to reveal the complex architecture of ecDNA, breakage-fusion-bridge cycles, and other complex rearrangements. By distinguishing between chromosomal and extrachromosomal origins, and by reconstructing the rearrangement signatures associated with a given fCNA’s generative mechanism, AR enables a more thorough understanding of the origins of fCNAs, and their functional consequences.
High-throughput screens of PAM-flexible Cas9 variants for gene knock-out and transcriptional modulation
Authors: Legut Mateusz , Daniloski Zharko , Xue Xinhe , McKenzie Dayna , Guo Xinyi , Wessels Hans-Hermann , Sanjana Neville E.
Published: January 2020

A key limitation of the commonly-used CRISPR enzymeS. pyogenesCas9 is the strict requirement of an NGG protospacer-adjacent motif (PAM) at the target site, which reduces the number of accessible genomic loci. This constraint can be limiting for genome editing applications that require precise Cas9 positioning. Recently, two Cas9 variants with a relaxed PAM requirement (NG) have been developed (xCas9 and Cas9-NG) but their activity has been measured at only a small number of endogenous sites. Here we devised a high-throughput Cas9 pooled competition screen to compare the performance of both PAM-flexible Cas9 variants and wild-type Cas9 at thousands of genomic loci and across 3 modalities (gene knock-out, transcriptional activation and suppression). We show that PAM flexibility comes at a substantial cost of decreased DNA targeting and cutting. Of the PAM-flexible variants, we found that Cas9-NG outperforms xCas9 regardless of genome engineering modality or PAM. Finally, we combined xCas9 mutations with those of Cas9-NG, creating a stronger transcriptional modulator than existing PAM-flexible Cas9 variants.
S-adenosylhomocysteine hydrolase regulates anterior patterning inDugesia japonica
Authors: Reinmets Kristina , Bischof Johanna , Taketa Emily , Levin Michael , Fuchs Stephen M.
Published: January 2020

Background

Biological methylation requires S-adenosylmethionine (SAM) and participates in a range of processes from modulation of gene expression via histone modifications to neurotransmitter synthesis. An important factor in all methylation reactions is the concentration ratio of SAM to methylation byproduct S-adenosylhomocysteine (SAH). SAH hydrolase, also known as adenosylhomocysteinase, depletes SAH and thereby facilitates metabolite recycling and maintains the methylation permissive SAM/SAH ratio. While the importance of SAH hydrolase in sustaining methylation is obvious on the cellular level, the function of this metabolic process on the organismal scale is not clear.

Results

We used planarianDugesia japonicato investigate the role SAH hydrolase in physiological homeostasis on the body-wide scale. Remarkably, pharmacological inhibition of the SAH hydrolase results in regression of anterior tissues and is accompanied by extensive apoptosis throughout the planarian body. Moreover, exposure to the SAHH inhibitor AdOx leads to changes in brain morphology and spatial shift in the expression of Wnt-modulatorNotum. Strikingly, planarians are able to overcome these destructive patterning defects through regeneration of the anterior tissues and adaptation to the used inhibitor. Transcriptome analysis indicates that resistance to the SAHH inhibitor is at least partly mediated by changes in folate cycle and lipid metabolism.

Conclusions

SAH hydrolase plays a critical role in planarian homeostasis and anterior patterning potentially through modulation of Wnt signaling. Moreover, planarian adaptation to the SAHH inhibitor via metabolic reprogramming suggests potential targets for addressing methylation-related human conditions.
From graph topology to ODE models for gene regulatory networks
Authors: Kang Xiaohan , Hajek Bruce , Hanzawa Yoshie
Published: January 2020

A gene regulatory network can be described at a high level by a directed graph with signed edges, and at a more detailed level by a system of ordinary differential equations (ODEs). The former qualitatively models the causal regulatory interactions between ordered pairs of genes, while the latter quantitatively models the time-varying concentrations of mRNA and proteins. This paper clarifies the connection between the two types of models.

We propose a property, called the constant sign property, for a general class of ODE models. The constant sign property characterizes the set of conditions (system parameters, external signals, or internal states) under which an ODE model is consistent with a signed, directed graph. If the constant sign property for an ODE model holds globally for all conditions, then the ODE model has a single signed, directed graph. If the constant sign property for an ODE model only holds locally, which may be more typical, then the ODE model corresponds to different graphs under different sets of conditions. In addition, two versions of constant sign property are given and a relationship between them is proved.

As an example, the ODE models that capture the effect ofcis-regulatory elements involving protein complex binding, based on the model in the GeneNetWeaver source code, are described in detail and shown to satisfy the global constant sign property with a unique consistent gene regulatory graph. Even a single gene regulatory graph is shown to have many ODE models of GeneNetWeaver type consistent with it due to combinatorial complexity and continuous parameters.

Finally the question of how closely data generated by one ODE model can be fit by another ODE model is explored. It is observed that the fit is better if the two models come from the same graph.
Probing multi-way chromatin interaction with hypergraph representation learning
Authors: Zhang Ruochi , Ma Jian
Published: January 2020

Advances in high-throughput mapping of 3D genome organization have enabled genome-wide characterization of chromatin interactions. However, proximity ligation based mapping approaches for pairwise chromatin interaction such as Hi-C cannot capture multi-way interactions, which are informative to delineate higher-order genome organization and gene regulation mechanisms at single-nucleus resolution. The very recent development of ligation-free chromatin interaction mapping methods such as SPRITE and ChIA-Drop has offered new opportunities to uncover simultaneous interactions involving multiple genomic loci within the same nuclei. Unfortunately, methods for analyzing multi-way chromatin interaction data are significantly underexplored. Here we develop a new computational method, called MATCHA, based on hypergraph representation learning where multi-way chromatin interactions are represented as hyperedges. Applications to SPRITE and ChIA-Drop data suggest that MATCHA is effective to denoise the data and makede novopredictions of multi-way chromatin interactions, reducing the potential false positives and false negatives from the original data. We also show that MATCHA is able to distinguish between multi-way interaction in a single nucleus and combination of pairwise interactions in a cell population. In addition, the embeddings from MATCHA reflect 3D genome spatial localization and function. MATCHA provides a promising framework to significantly improve the analysis of multi-way chromatin interaction data and has the potential to offer unique insights into higher-order chromosome organization and function.
Antigens in water-in-oil emulsion: a simple antigen extraction method for analysis and proof of equal antigen distribution in vaccination syringe after mixture
Authors: Ghosh Michael , Gauger Marion , Denk Monika , Rammensee Hans-Georg , Stevanović Stefan
Published: January 2020

Therapeutic vaccination of antigens in oil emulsions is an approach becoming increasingly popular. Water-in-oil emulsions enable the formation of a depot, a slow passive antigen release and a decelerated antigen degradation. Furthermore, particularly advantageous for peptide vaccinations with a low clinical response rate is the increased immunogenicity and activation of CD8+and CD4+T-cells. Therefore, the use of personalized peptide vaccination cocktails in oil emulsions are tested in the treatment of cancer patients. An equal peptide distribution in the emulsion is striking for a successful depot effect to ensure the optimal efficacy and additionally, to enable reliable drug release analytics. First, the stability of the generated peptide-Montanide ISA™51 emulsion was demonstrated with a cocktail of heterogeneous peptides for 24 h in room temperature. Furthermore, we developed a simple peptide extraction method to investigate the equal peptide distribution in a Montanide ISA™51 emulsion in the syringe after mixing. Peptides were successfully extracted from a peptide-Montanide ISA™51 vaccination cocktail in sufficient volume for analysis and an equal peptide distribution in the syringe was verified via HPLC.
Prolonged disturbance of proteostasis induces cellular senescence via temporal mitochondrial dysfunction and enhanced mitochondrial biogenesis in human fibroblasts
Authors: Takenaka Yasuhiro , Inoue Ikuo , Nakano Takanari , Ikeda Masaaki , Kakinuma Yoshihiko
Published: January 2020

Proteolytic activities decline with age, resulting in the accumulation of aggregated proteins in aged organisms. To investigate how disturbance in proteostasis causes cellular senescence, we developed a stress-induced premature senescence (SIPS) model, in which normal human fibroblast MRC-5 cells were treated with either the proteasome inhibitor MG132 or the V-ATPase inhibitor bafilomycin A1 (BAFA1) for 5 days. Time-course studies revealed significant increase in intracellular and mitochondrial reactive oxygen species (ROS) during and after drug treatment. Mitochondrial membrane potential initially decreased, but recovered along with PGC-1α-mediated mitochondrial biogenesis, especially after drug treatment. Mitochondrial antioxidant enzymes SOD2 and GPx4 were temporally depleted in mitochondria on day 1 of the treatment, which in turn could cause excess production of mitochondrial ROS. Extra-mitochondrial SOD2 colocalized with protein aggregates and lysosomes in MG132-treated cells on day 1. SOD2 partially interacted with HSC70 and LAMP2, implying that dysfunctional SOD2 was degraded through chaperon-mediated autophagy (CMA) and caused SOD2 depletion in mitochondria. SIPS induction by MG132 or BAFA1 was partially attenuated by co-treatment with rapamycin, in which generation of excess ROS and mitochondrial biogenesis were suppressed. Rapamycin co-treatment also augmented the upregulation of HSP70 and decreased protein aggregates after drug treatment. Our study proposes a possible pathway from the disturbance of proteostasis to cellular senescence via functional changes in mitochondria.
Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions
Authors: Read Jonathan M. , Bridgen Jessica R.E. , Cummings Derek A.T. , Ho Antonia , Jewell Chris P.
Published: January 2020

Since first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. using a transmission model, we estimate a basic reproductive number of 3.11 (95%CI, 2.39–4.13); 58–76% of transmissions must be prevented to stop increasing; Wuhan case ascertainment of 5.0% (3.6–7.4); 21022 (11090–33490) total infections in Wuhan 1 to 22 January.

Changes to previous version

case data updated to include 22 Jan 2020; we did not use cases reported after this period as cases were reported at the province level hereafter, and large-scale control interventions were initiated on 23 Jan 2020;

improved likelihood function, better accounting for first 41 confirmed cases, and now using all infections (rather than just cases detected) in Wuhan for prediction of infection in international travellers;

improved characterization of uncertainty in parameters, and calculation of epidemic trajectory confidence intervals using a more statistically rigorous method;

extended range of latent period in sensitivity analysis to reflect reports of up to 6 day incubation period in household clusters;

removed travel restriction analysis, as different modelling approaches (e.g. stochastic transmission, rather than deterministic transmission) are more appropriate to such analyses.
Machine-learning forecasting for Dengue epidemics - Comparing LSTM, Random Forest and Lasso regression
Authors: Mussumeci Elisa , Coelho Flávio Codeço
Published: January 2020

Effective management of seasonal diseases such as dengue fever depends on timely deployment of control measures prior to the high transmission season. As the epidemic season fluctuates from year to year, the availability of accurate forecasts of incidence can be decisive in attaining control of such diseases. Obtaining such forecasts from classical time series models has proven a difficult task. Here we propose and compare machine learning models incorporating feature selection,such as LASSO and Random Forest regression with LSTM a deep recurrent neural network, to forecast weekly dengue incidence in 790 cities in Brazil. We use multivariate time-series as predictors and also utilize time series from similar cities to capture the spatial component of disease transmission. Among the compared models, the LSTM recurrent neural network model displayed the smallest predictive errors in predicting incidence of dengue out of sample, in cities of different sizes.
Food for the Empire: dietary pattern of Imperial Rome inhabitants.
Authors: De Angelis Flavio , Varano Sara , Battistini Andrea , Di Giannantonio Stefania , Ricci Paola , Lubritto Carmine , Facchin Giulia , Brancazi Luca , Santangeli Valenzani Riccardo , Catalano Paola , Gazzaniga Valentina , Rickards Olga , Martinez-Labarga Cristina
Published: January 2020

This paper aims to provide a broad diet reconstruction for people buried in archaeologically defined contexts in Rome (1st-3rd centuries CE), in order to combine archaeological and biological evidence focusing on dietary preferences in Imperial Rome. A sample of 214 human bones recovered from 6 funerary contexts were selected for carbon and nitrogen stable isotope analysis. The baseline for the terrestrial protein component of the diet was set using 17 coeval faunal remains recovered from excavations at Rome supplemented by previously published data for the same geographic and chronological frames. δ13C ranges from -19.95permil to -14.78 permil, whereas δ15N values are between 7.17permil and 10.00permil. The values are consistent with an overall diet mainly based on terrestrial resources. All the human samples rely on a higher trophic level than the primary consumer faunal samples. Certainly, C3 plants played a pivotal role in the dietary habits. However, C4 plants also seem to have been consumed, albeit they were not as widespread and were not always used for human consumption. The environment played a critical role also for Romans of lower social classes. The topographical location determined the preferential consumption of food that people could obtain from their neighborhood.
Large-scale DNA-based phenotypic recording and deep learning enable highly accurate sequence-function mapping
Authors: Höllerer Simon , Papaxanthos Laetitia , Gumpinger Anja Cathrin , Fischer Katrin , Beisel Christian , Borgwardt Karsten , Benenson Yaakov , Jeschek Markus
Published: January 2020

Predicting quantitative effects of gene regulatory elements (GREs) on gene expression is a longstanding challenge in biology. Machine learning models for gene expression prediction may be able to address this challenge, but they require experimental datasets that link large numbers of GREs to their quantitative effect. However, current methods to generate such datasets experimentally are either restricted to specific applications or limited by their technical complexity and error-proneness. Here we introduce DNA-based phenotypic recording as a widely applicable and practical approach to generate very large datasets linking GREs to quantitative functional readouts of high precision, temporal resolution, and dynamic range, solely relying on sequencing. This is enabled by a novel DNA architecture comprising a site-specific recombinase, a GRE that controls recombinase expression, and a DNA substrate modifiable by the recombinase. Both GRE sequence and substrate state can be determined in a single sequencing read, and the frequency of modified substrates amongst constructs harbouring the same GRE is a quantitative, internally normalized readout of this GRE’s effect on recombinase expression. Using next-generation sequencing, the quantitative expression effect of extremely large GRE sets can be assessed in parallel. As a proof of principle, we apply this approach to record translation kinetics of more than 300,000 bacterial ribosome binding sites (RBSs), collecting over 2.7 million sequence-function pairs in a single experiment. Further, we generalize from these large-scale datasets by a novel deep learning approach that combines ensembling and uncertainty modelling to predict the function of untested RBSs with high accuracy, substantially outperforming state-of-the-art methods. The combination of DNA-based phenotypic recording and deep learning represents a major advance in our ability to predict quantitative function from genetic sequence.
Improved accuracy and precision of bioprinting through progressive cavity pump-controlled extrusion
Authors: Fisch Philipp , Holub Martin , Zenobi-Wong Marcy
Published: January 2020

3D bioprinting has seen a tremendous growth in recent years in a variety of fields such as tissue and organ models, drug testing and regenerative medicine. This growth has led researchers and manufacturers to continuously advance and develop novel bioprinting techniques and materials. Although new bioprinting methods are emerging (e.g. contactless and volumetric bioprinting), micro-extrusion bioprinting remains the most widely used method. Micro-extrusion bioprinting, however, is still largely dependent on the conventional pneumatic extrusion process, which relies heavily on homogenous biomaterial inks and bioinks to maintain a constant material flowrate. Augmenting the functionality of the bioink with the addition of nanoparticles, cells or biopolymers can induce inhomogeneities resulting in uneven material flow during printing and/or clogging of the nozzle, leading to defects in the printed construct. In this work, we evaluated a novel extrusion technique based on a miniaturized progressive cavity pump. We compared the accuracy and precision of this system to the pneumatic extrusion system and tested both for their effect on cell viability after extrusion. The progressive cavity pump achieved a significantly higher accuracy and precision compared to the pneumatic system while maintaining good viability and was able to maintain its reliability independently of the bioink composition, printing speed or nozzle size. Progressive cavity pumps are a promising tool for bioprinting and could help provide standardized and validated bioprinted constructs while leaving the researcher more freedom in the design of the bioinks with increased functionality.
Multiple streams of genetic diversity in Japonica rice
Authors: Santos João D. , Billot Claire , Chebotarov Dmytro , Droc Gaëtan , Lorieux Mathias , McNally Kenneth L. , Glaszmann Jean Christophe
Published: January 2020

In-depth studies on the genetic diversity of crops indicate that domestication is likely a drawn-out process that differs from the traditional representation of a simple rapid bottleneck. Asian cultivated rice provides a clear picture of multiple foundations of crop diversity. Among them, Japonica rice is likely the group derived from the first human manipulations of this species. We make use of the 3,000 Rice Genomes (3K RG) data set, first described in 2018, to explore the genetic diversity of traditional Japonica rice. After delineating introgressions from the Indica andcAus cultivar groups, we mask these traces to analyse Japonica diversity in more depth. We find differentiation between the established “temperate”, “subtropical” and “tropical” subgroups, and identify stream-like traces of highly divergent sources from broad geographic ranges and subgroups. We characterize five such streams, most visible respectively in: 1) Indonesia, 2) continental Southeast Asia, 3) China, 4) uplands of Japan, and 5) Bhutan. These streams likely consist of ancient alien introgressions propagated through geneflow to different degrees. They currently appear as long genome segments conserved among specific germplasm groups, as well as shorter segments more broadly distributed across diverse germplasm along what could be adaptive corridors. They are all represented in the Japonica component ofcBasmati varieties, thought to have emerged over two millennia ago. We thus provide strong evidence that Japonica, the group posited as being the most direct product of a simple domestication process in China, is an aggregate derived from multiple waves of admixture and represents a composite gene pool with ancient Asia-wide population dynamics.
Establishment gaps in species-poor grasslands: artificial biodiversity hotspots to support the colonization of target species
Authors: Kiss Réka , Deák Balázs , Tóthmérész Béla , Miglécz Tamás , Tóth Katalin , Török Péter , Lukács Katalin , Godó Laura , Körmöczi Zsófia , Radócz Szilvia , Kelemen András , Sonkoly Judit , Kirmer Anita , Tischew Sabine , Švamberková Eva , Valkó Orsolya
Published: January 2020

Sowing of grass seed mixtures is a feasible and cost-effective method for landscape-scale grassland restoration. However, sowing only grasses usually leads to species-poor and dense grass sward, where the establishment of target forbs is hampered both by microsite and propagule limitation. To overcome these limitations and increase the diversity of species-poor sown grasslands we developed a novel method by creating ‘establishment gaps’. We used tillage to open gaps of 1 m2, 4 m2and 16 m2size in the dense grass sward of six species-poor sown grasslands in the Great Hungarian Plain. We sowed high-diversity seed mixtures of 35 native species into all gaps. We analyzed vegetation development during the first five years after setting up the trial. We also studied the colonization dynamics of the sown species along four 20-m transects around each gap, resulting in a total of 1440 plots of 1 m2size that were studied. Our results indicated that most of the sown species were able to establish permanently in the establishment gaps. The total cover and the cover of perennial sown species increased independently of gap size. Meanwhile the cover of short-lived sown species decreased during the five years. There was only a moderate level of weed abundance in the gaps, and weed cover decreased over the years. The sown target species started to colonize the species-poor grasslands surrounding the establishment gaps within five years. The highest number of species and individuals dispersed from the 4 m2-sized gaps, as they had a more stable development than small gaps and were exposed to lower grazing pressure than large ones.

Implications for practice

Establishment gaps are widely applicable tools to increase the diversity of species-poor grasslands. Gaps of 4 m2represent a more feasible solution compared to larger openings also for the farmers, because there is only a moderate level of weed encroachment and smaller soil disturbance occurs during their creation.

We recommend sowing high-diversity seed mixtures containing both short-lived species that can establish in the first year and perennial species, which guarantee a high cover of target species later on.

Gaps sown with high-diversity seed mixture are highly resistant to unfavorable climatic conditions: increasing grass abundance in dry years does not hamper the recovery of target grassland species in the following years.
Unidirectional response to bidirectional selection on body size II Quantitative genetics
Authors: Rouzic Arnaud Le , Renneville Clémentine , Millot Alexis , Agostini Simon , Carmignac David , Édeline Éric
Published: January 2020

Anticipating the genetic and phenotypic changes induced by natural or artificial selection requires reliable estimates of trait evolvabilities (genetic variances and covariances). However, whether or not multivariate quantitative genetics models are able to predict precisely the evolution of traits of interest, especially fitness-related, life-history traits, remains an open empirical question. Here, we assessed to what extent the response to bivariate artificial selection on both body size and maturity in the medakaOryzias latipes, a model fish species, fits the theoretical predictions. Three lines (Large, Small, and Control lines) were differentially selected for body length at 75 days of age, conditional on maturity. As maturity and body size were phenotypically correlated, this selection procedure generated a bi-dimensional selection pattern on two life history traits. After removal of non-heritable trends and noise with a random effect (’animal’) model, the observed selection response did not match the expected bidirectional response. For body size, Large and Control lines responded along selection gradients (larger body size and stasis, respectively), but, surprisingly, the Small did not evolve a smaller body length, and remained identical to the Control line throughout the experiment. The magnitude of the empirical response was smaller than the theoretical prediction in both selected directions. For maturity, the response was opposite to the expectation (the Large line evolved late maturity compared to the Control line, while the Small line evolved early maturity, while the opposite pattern was predicted due to the strong positive genetic correlation between both traits). The mismatch between predicted and observed response was substantial and could not be explained by usual sources of uncertainties (including sampling effects, genetic drift, and error in G matrix estimates).
Genome-Wide Identification, Characterization and Expression Analysis of Non-Arginine Aspartate Receptor like kinase gene family underColletotrichum truncatumstress conditions in Hot pepper
Authors: Srideepthi R , Krishna MSR , Suneetha P , Krishna R Sai , Karthikeyan S
Published: January 2020

Receptor Like kinases (RLKs) are conserved upstream signaling molecules that regulate several biological processes, including plant development and stress adaptation. Non arginine aspartate (non-RD) an important class of RLKs plays a vital role in disease resistance and apoptosis in plants. In present investigation, a comprehensive Insilco analysis for non-RD Kinase gene family including identification, sequence similarity, phylogeny, chromosomal localization, gene structures, gene duplication analysis, promoter analysis and transcript expression profiles were elucidated. In this study twenty six genes were observed on nine out of twelve chromosomes. All these genes were clustered into seven subfamilies under large monophyletic group termed as Interleukin-1 Receptor-Associated Kinase (IRAK) family. Structural diversity in genomic structure among non-RD kinase gene family were identified and presence of pathogen inducedcisregulatory elements like STRE, MYC, MYB,W box were found. Expression profiles of genes involved in providing resistance to anthracnose pathogenColletotrichum truncatumin hot pepper were analyzed at different infective stages in both resistant and susceptible genotypes. Among twenty six genes,CaRLK1gene belonging to LRRXII subfamily was up regulated under severe stress after infection in resistant genotype PBC-80. This integrative approach has helped us to identify candidate genes involved in disease resistance which would be helpful in future crop improvement programs.
Diversity increases the stability of ecosystems
Authors: Arese Lucini Francesca , Morone Flaviano , Tomassone Maria S. , Makse Hernán A.
Published: January 2020

In 1972, Robert May showed that diversity is detrimental to an ecosystem since, as the number of species increases, the ecosystem is less stable. This is the so-called diversity-stability paradox, which has been derived by considering a mathematical model with linear interactions between the species. Despite being in contradiction with empirical evidence, the diversity-stability paradox has survived the test of time for over 40+ years. In this paper we first show that this paradox is a conclusion driven solely by the linearity of the model employed in its derivation which allows for the neglection of the fixed point solution in the stability analysis. The linear model leads to an ill-posed solution and along with it, its paradoxical stability predictions. We then consider a model ecosystem with nonlinear interactions between species, which leads to a stable ecosystem when the number of species is increased. The saturating non linear term in the species interaction is analogous to a Hill function appearing in systems like gene regulation, neurons, diffusion of information and ecosystems The exact fixed point solution of this model is based onk-core percolation and shows that the paradox disappears. This theoretical result, which is exact and non-perturbative, shows that diversity is beneficial to the ecosystem in agreement with analyzed experimental evidence
Effects of sustained inflation pressure during neonatal cardiopulmonary resuscitation of asphyxiated piglets
Authors: Shim Gyu-Hong , Kim Seung Yeon , Cheung Po-Yin , Lee Tze-Fun , O’Reilly Megan , Schmölzer Georg M
Published: January 2020

Objective

Sustained inflation (SI) during chest compression (CC = CC+SI) significantly reduces time to return of spontaneous circulation (ROSC) compared to 3:1 compression-to-ventilation ratio during neonatal resuscitation. However, the optimal peak inflation pressure (PIP) of SI during CC+SI to improve ROSC and hemodynamic recovery in severely asphyxiated piglets is unknown.

Aim

To examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets.

Intervention and measurements

Twenty-nine newborn piglets (1-3 days old) were anesthetized, intubated, instrumented and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into four groups: CC+SI with a PIP of 10 cmH2O (CC+SI_PIP_10, n=8), a PIP of 20 cmH2O (CC+SI_PIP_20, n=8), a PIP of 30 cmH2O (CC+SI_PIP_30, n=8), and a sham-operated control group (n=5). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment.

Main results

Baseline parameters were similar between all groups. There was no difference in asphyxiation (duration and degree) between intervention groups. PIP correlated positively with tidal volume and inversely with exhaled CO2 during cardiopulmonary resuscitation. Time to ROSC and rate of ROSC were similar between piglets resuscitated with CC+SI_PIP_10, CC+SI_PIP_20, and CC+SI_PIP_30 cmH2O: median (IQR) 75 (63-193) sec, 94 (78-210) sec, and 85 (70-90) sec; 5/8 (63%), 7/8 (88%), and 3/8 (38%) (p=0.56 and p=0.12, respectively). All piglets that achieved ROSC survived to four hours post-resuscitation. Piglets resuscitated with CC+SI_PIP_30 cmH2O exhibited increased concentrations of pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α in the frontoparietal cerebral cortex (both p<0.05 vs. sham-operated controls).

Conclusions

In asphyxiated term newborn piglets resuscitated by CC+SI, the use of different PIPs resulted in similar time to ROSC, but PIP at 30 cmH2O showed a larger VT delivery, lower exhaled CO2 and increased tissue inflammatory markers in the brain.