bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of tit-for-tat in bacteria via the type VI secretion system
Authors: Smith William P. J. , Brodmann Maj , Unterweger Daniel , Davit Yohan , Comstock Laurie E. , Basler Marek , Foster Kevin R. 
Published: October 2020

AbstractTit-for-tat is a familiar principle from animal behavior: individuals respond in kind to being helped or harmed by others. Remarkably some bacteria appear to display tit-for-tat behavior, but how this evolved is not understood. Here we combine evolutionary game theory with agent-based modelling of bacterial tit-for-tat, whereby cells stab rivals with poisoned needles (the type VI secretion system) after being stabbed themselves. Our modelling shows tit-for-tat retaliation is a surprisingly poor evolutionary strategy, because tit-for-tat cells lack the first-strike advantage of preemptive attackers. However, if cells retaliate strongly and fire back multiple times, we find that reciprocation is highly effective. We test our predictions by competing Pseudomonas aeruginosa (a tit-for-tat species) with Vibrio cholerae (random-firing), revealing that P. aeruginosa does indeed fire multiple times per incoming attack. Our work suggests bacterial competition has led to a particular form of reciprocation, where the principle is that of strong retaliation, or ‘tits-for-tat’.
Automated and optimally FRET-assisted structural modeling
Authors: Dimura Mykola , Peulen Thomas-Otavio , Sanabria Hugo , Rodnin Dmitro , Hemmen Katherina , Hanke Christian A. , Seidel Claus A. M. , Gohlke Holger 
Published: October 2020

AbstractFRET experiments can provide state-specific structural information of complex dynamic biomolecular assemblies. However, to overcome the sparsity of FRET experiments, they need to be combined with computer simulations. We introduce a program suite with (i) an automated design tool for FRET experiments, which determines how many and which FRET pairs should be used to minimize the uncertainty and maximize the accuracy of an integrative structure, (ii) an efficient approach for FRET-assisted coarse-grained structural modeling, and all-atom molecular dynamics simulations-based refinement, and (iii) a quantitative quality estimate for judging the accuracy of FRET-derived structures as opposed to precision. We benchmark our tools against simulated and experimental data of proteins with multiple conformational states and demonstrate an accuracy of ~3 Å RMSDCα against X-ray structures for sets of 15 to 23 FRET pairs. Free and open-source software for the introduced workflow is available at https://github.com/Fluorescence-Tools. A web server for FRET-assisted structural modeling of proteins is available at http://nmsim.de.
Detecting and tracking drift in quantum information processors
Authors: Proctor Timothy , Revelle Melissa , Nielsen Erik , Rudinger Kenneth , Lobser Daniel , Maunz Peter , Blume-Kohout Robin , Young Kevin 
Published: October 2020

AbstractIf quantum information processors are to fulfill their potential, the diverse errors that affect them must be understood and suppressed. But errors typically fluctuate over time, and the most widely used tools for characterizing them assume static error modes and rates. This mismatch can cause unheralded failures, misidentified error modes, and wasted experimental effort. Here, we demonstrate a spectral analysis technique for resolving time dependence in quantum processors. Our method is fast, simple, and statistically sound. It can be applied to time-series data from any quantum processor experiment. We use data from simulations and trapped-ion qubit experiments to show how our method can resolve time dependence when applied to popular characterization protocols, including randomized benchmarking, gate set tomography, and Ramsey spectroscopy. In the experiments, we detect instability and localize its source, implement drift control techniques to compensate for this instability, and then demonstrate that the instability has been suppressed.
Vortex phase matching as a strategy for schooling in robots and in fish
Authors: Li Liang , Nagy Máté , Graving Jacob M. , Bak-Coleman Joseph , Xie Guangming , Couzin Iain D. 
Published: October 2020

AbstractIt has long been proposed that flying and swimming animals could exploit neighbour-induced flows. Despite this it is still not clear whether, and if so how, schooling fish coordinate their movement to benefit from the vortices shed by others. To address this we developed bio-mimetic fish-like robots which allow us to measure directly the energy consumption associated with swimming together in pairs (the most common natural configuration in schooling fish). We find that followers, in any relative position to a near-neighbour, could obtain hydrodynamic benefits if they exhibit a tailbeat phase difference that varies linearly with front-back distance, a strategy we term ‘vortex phase matching’. Experiments with pairs of freely-swimming fish reveal that followers exhibit this strategy, and that doing so requires neither a functioning visual nor lateral line system. Our results are consistent with the hypothesis that fish typically, but not exclusively, use vortex phase matching to save energy.
Neglecting uncertainties biases house-elevation decisions to manage riverine flood risks
Authors: Zarekarizi Mahkameh , Srikrishnan Vivek , Keller Klaus 
Published: October 2020

AbstractHomeowners around the world elevate houses to manage flood risks. Deciding how high to elevate a house poses a nontrivial decision problem. The U.S. Federal Emergency Management Agency (FEMA) recommends elevating existing houses to the Base Flood Elevation (the elevation of the 100-year flood) plus a freeboard. This recommendation neglects many uncertainties. Here we analyze a case-study of riverine flood risk management using a multi-objective robust decision-making framework in the face of deep uncertainties. While the quantitative results are location-specific, the approach and overall insights are generalizable. We find strong interactions between the economic, engineering, and Earth science uncertainties, illustrating the need for expanding on previous integrated analyses to further understand the nature and strength of these connections. Considering deep uncertainties surrounding flood hazards, the discount rate, the house lifetime, and the fragility can increase the economically optimal house elevation to values well above FEMA’s recommendation.
Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort
Authors: Moen Gunn-Helen , Brumpton Ben , Willer Cristen , Åsvold Bjørn Olav , Birkeland Kåre I. , Wang Geng , Neale Michael C. , Freathy Rachel M. , Smith George Davey , Lawlor Deborah A. , Kirkpatrick Robert M. , Warrington Nicole M. , Evans David M. 
Published: October 2020

AbstractThere is a robust observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero increase future risk of cardiometabolic disease. Here, we explore if a genetic risk score (GRS) of maternal SNPs associated with offspring birthweight is also associated with offspring cardiometabolic risk factors, after controlling for offspring GRS, in up to 26,057 mother–offspring pairs (and 19,792 father–offspring pairs) from the Nord-Trøndelag Health (HUNT) Study. We find little evidence for a maternal (or paternal) genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring GRS. In contrast, offspring GRS is strongly related to many cardiometabolic risk factors, even after conditioning on maternal GRS. Our results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals.
Objective assessment of tumor regression in post-neoadjuvant therapy resections for pancreatic ductal adenocarcinoma: comparison of multiple tumor regression grading systems
Authors: Matsuda Yoko , Ohkubo Satoshi , Nakano-Narusawa Yuko , Fukumura Yuki , Hirabayashi Kenichi , Yamaguchi Hiroshi , Sahara Yatsuka , Kawanishi Aya , Takahashi Shinichiro , Arai Tomio , Kojima Motohiro , Mino-Kenudson Mari 
Published: October 2020

AbstractNeoadjuvant therapy is increasingly used to control local tumor spread and micrometastasis of pancreatic ductal adenocarcinoma (PDAC). Pathology assessments of treatment effects might predict patient outcomes after surgery. However, there are conflicting reports regarding the reproducibility and prognostic performance of commonly used tumor regression grading systems, namely College of American Pathologists (CAP) and Evans’ grading system. Further, the M.D. Anderson Cancer Center group (MDA) and the Japan Pancreas Society (JPS) have introduced other grading systems, while we recently proposed a new, simple grading system based on the area of residual tumor (ART). Herein, we aimed to assess and compare the reproducibility and prognostic performance of the modified ART grading system with those of the four grading systems using a multicenter cohort. The study cohort consisted of 97 patients with PDAC who had undergone post-neoadjuvant pancreatectomy at four hospitals. All patients were treated with gemcitabine and S-1 (GS)-based chemotherapies with/without radiation. Two pathologists individually evaluated tumor regression in accordance with the CAP, Evans’, JPS, MDA and ART grading systems, and interobserver concordance was compared between the five systems. The ART grading system was a 5-tiered system based on a number of 40× microscopic fields equivalent to the surface area of the largest ART. Furthermore, the final grades, which were either the concordant grades of the two observers or the majority grades, including those given by the third observer, were correlated with patient outcomes in each system. The interobserver concordance (kappa value) for Evans’, CAP, MDA, JPS and ART grading systems were 0.34, 0.50, 0.65, 0.33, and 0.60, respectively. Univariate analysis showed that higher ART grades were significantly associated with shorter overall survival (p = 0.001) and recurrence-free survival (p = 0.005), while the other grading systems did not show significant association with patient outcomes. The present study revealed that the ART grading system that was designed to be simple and more objective has achieved high concordance and showed a prognostic value; thus it may be most practical for assessing tumor regression in post-neoadjuvant resections for PDAC.
Markers of neutrophil activation and extracellular traps formation are predictive of appendicitis in mice and humans: a pilot study
Authors: Boettcher Michael , Esser Melina , Trah Julian , Klohs Stefan , Mokhaberi Nariman , Wenskus Julia , Trochimiuk Madgalena , Appl Birgit , Reinshagen Konrad , Raluy Laia Pagerols , Klinke Michaela 
Published: October 2020

AbstractAppendicitis is one of the most frequent emergencies in pediatric surgery, yet current biomarkers for diagnosis are unspecific and have low predictive values. As neutrophils and extracellular traps (ETs) are an essential component of the immune defense against bacterial infections, and appendicitis is considered an inflammation reaction of the appendix, we hypothesized that neutrophil activation and NET formation play an essential role in appendicitis development and maintenance. Therefore, this pilot study aimed to establish a murine model of appendicitis and to evaluate ETs markers to diagnose appendicitis in mice and humans. The study used 20 (12 appendicitis- and 8 controls) 6-week old mice which underwent advanced appendicitis induction using a modified caecal ligation puncture procedure. During the study, cell-free DNA, neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated Histone H3 (H3cit) were assessed. Additionally, samples of 5 children with histologically confirmed appendicitis and 5 matched controls with catarrhal appendicitis, were examined for the same biomarkers. Moreover, NE, MPO, and H3cit were assessed histologically via immunofluorescence in mice and humans. All mice in the appendicitis group developed an advanced form of appendicitis with focal peritonitis. In mice and humans with appendicitis, markers of neutrophil activation and ETs formation (especially cfDNA, NE and H3cit) were significantly elevated in blood and tissue compared to controls. Ultimately, biomarkers correlated extremely well with tissue expression and thus disease severity. It appears that neutrophil activation and possibly NETs contribute to appendicitis development and biomarkers of neutrophil activation and ET formation reflect disease severity and thus could be used as biomarkers for appendicitis. However, large prospective clinical studies are needed to confirm our findings.
MutSignatures: an R package for extraction and analysis of cancer mutational signatures
Authors: Fantini Damiano , Vidimar Vania , Yu Yanni , Condello Salvatore , Meeks Joshua J. 
Published: October 2020

AbstractCancer cells accumulate somatic mutations as result of DNA damage, inaccurate repair and other mechanisms. Different genetic instability processes result in characteristic non-random patterns of DNA mutations, also known as mutational signatures. We developed mutSignatures, an integrated R-based computational framework aimed at deciphering DNA mutational signatures. Our software provides advanced functions for importing DNA variants, computing mutation types, and extracting mutational signatures via non-negative matrix factorization. Specifically, mutSignatures accepts multiple types of input data, is compatible with non-human genomes, and supports the analysis of non-standard mutation types, such as tetra-nucleotide mutation types. We applied mutSignatures to analyze somatic mutations found in smoking-related cancer datasets. We characterized mutational signatures that were consistent with those reported before in independent investigations. Our work demonstrates that selected mutational signatures correlated with specific clinical and molecular features across different cancer types, and revealed complementarity of specific mutational patterns that has not previously been identified. In conclusion, we propose mutSignatures as a powerful open-source tool for detecting the molecular determinants of cancer and gathering insights into cancer biology and treatment.
Qualitative and quantitative differences in endometrial inflammatory gene expression precede the development of bovine uterine disease
Authors: Brewer Amy , Cormican Paul , Lim Joseph J. , Chapwanya Aspinas , O’Farrelly Cliona , Meade Kieran G. 
Published: October 2020

AbstractThe transcriptome of the endometrium early postpartum was profiled to determine if inflammatory gene expression was elevated in cows which subsequently developed uterine disease. Endometrial cytobrush samples were collected at 7 days postpartum (DPP) from 112 Holstein–Friesian dairy cows, from which 27 were retrospectively chosen for RNA-seq on the basis of disease classification [ten healthy and an additional 17 diagnosed with cytological endometritis (CYTO), or purulent vaginal discharge (PVD)] at 21 DPP. 297 genes were significantly differentially expressed between cows that remained healthy versus those that subsequently developed PVD, including IL1A and IL1B (adjusted p < 0.05). In contrast, only 3 genes were significantly differentially expressed in cows which subsequently developed CYTO. Accounting for the early physiological inflammatory status present in cows which do not develop disease enhanced the detection of differentially expressed genes associated with CYTO and further expression profiling in 51 additional cows showed upregulation of multiple immune genes, including IL1A, IL1B and TNFA. Despite the expected heterogeneity associated with natural infection, enhanced activation of the inflammatory response is likely a key contributory feature of both PVD and CYTO development. Prognostic biomarkers of uterine disease would be particularly valuable for seasonal-based dairy systems where any delay to conception undermines sustainability.
GSK-3β activation is required for ZIP-induced disruption of learned fear
Authors: Song Sukwoon , Kim Jihye , Park Kyungjoon , Lee Junghwa , Park Sewon , Lee Sukwon , Kim Jeongyeon , Hong Ingie , Song Beomjong , Choi Sukwoo 
Published: October 2020

AbstractThe myristoylated zeta inhibitory peptide (ZIP), which was originally developed as a protein kinase C/Mζ (PKCζ/PKMζ) inhibitor, is known to produce the loss of different forms of memories. However, ZIP induces memory loss even in the absence of PKMζ, and its mechanism of action, therefore, remains elusive. Here, through a kinome-wide screen, we found that glycogen synthase kinase 3 beta (GSK-3β) was robustly activated by ZIP in vitro. ZIP induced depotentiation (a cellular substrate of memory erasure) of conditioning-induced potentiation at LA synapses, and the ZIP-induced depotentiation was prevented by a GSK-3β inhibitor, 6-bromoindirubin-3-acetoxime (BIO-acetoxime). Consistently, GSK-3β inhibition by BIO-acetoxime infusion or GSK-3β knockdown by GSK-3β shRNA in the LA attenuated ZIP-induced disruption of learned fear. Furthermore, conditioned fear was decreased by expression of a non-inhibitable form of GSK-3β in the LA. Our findings suggest that GSK-3β activation is a critical step for ZIP-induced disruption of memory.
Strap muscle invasion in differentiated thyroid cancer does not impact disease-specific survival: a population-based study
Authors: Yoon Ja Kyung , Lee Jandee , Kim Eun-Kyung , Yoon Jung Hyun , Park Vivian Youngjean , Han Kyunghwa , Kwak Jin Young 
Published: October 2020

AbstractThe American Joint Committee on Cancer (AJCC) 8thTNM staging system of differentiated thyroid cancer defines gross strap muscle invasion as T3b stage. However, the impact of strap muscle invasion on disease-specific survival (DSS) remains controversial. To elucidate the survival impact of strap muscle invasion of any degree in thyroid cancers, the Surveillance, Epidemiology, and End Results (SEER) database (1973–2018) was queried for thyroid cancer only patients on July 2019 (n = 19,914). The Cox proportional hazard analysis with multivariable adjustment revealed that strap muscle invasion was not a significant factor for DSS in tumors equal to or smaller than 40 mm (hazard ratio (HR) = 1.620 [confidence interval (CI) 0.917 – 2.860];p = 0.097). The competing risk analysis with multivariable adjustment showed that strap muscle invasion did not significantly impact DSS regardless of tumor size or cause of death (cancer-caused death (Subdistribution HR (SDHR) = 1.567 [CI 0.984 – 2.495];p = 0.059); deaths to other causes (SDHR = 1.155 [CI 0.842 – 1.585];p = 0.370). A “modified” staging schema discarding strap muscle invasion as a T stage criterion showed better 10-year DSS distinction between T stages. The modified staging schema may better reflect cancer-caused death risk and may prevent potential overstaging.
Addition of anaerobic electron acceptors to solid media did not enhance growth of 125 spacecraft bacteria under simulated low-pressure Martian conditions
Authors: Schwendner Petra , Jobson Mary-Elizabeth , Schuerger Andrew C. 
Published: October 2020

AbstractTo protect Mars from microbial contamination, research on growth of microorganisms found in spacecraft assembly clean rooms under simulated Martian conditions is required. This study investigated the effects of low atmospheric pressure on the growth of chemoorganotrophic spacecraft bacteria and whether the addition of Mars relevant anaerobic electron acceptors might enhance growth. The 125 bacteria screened here were recovered from actual Mars spacecraft. Growth at 7 hPa, 0 °C, and a CO2-enriched anoxic atmosphere (called low-PTA conditions) was tested on five TSA-based media supplemented with anaerobic electron acceptors. None of the 125 spacecraft bacteria showed active growth under the tested low-PTA conditions and amended media. In contrast, a decrease in viability was observed in most cases. Growth curves of two hypopiezotolerant strains, Serratia liquefaciens and Trichococcus pasteurii, were performed to quantify the effects of the added anaerobic electron acceptors. Slight variations in growth rates were determined for both bacteria. However, the final cell densities were similar for all media tested, indicating no general preference for any specific anaerobic electron acceptor. By demonstrating that a broad diversity of chemoorganotrophic and culturable spacecraft bacteria do not grow under the tested conditions, we conclude that there may be low risk of growth of chemoorganotrophic bacteria typically recovered from Mars spacecraft during planetary protection bioburden screenings.
The association between thyroid function biomarkers and attention deficit hyperactivity disorder
Authors: Albrecht Diana , Ittermann Till , Thamm Michael , Grabe Hans-Jörgen , Bahls Martin , Völzke Henry 
Published: October 2020

AbstractThe relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81–1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (β 0.08; 95% CI 0.03–0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD.
Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease
Authors: Stan Tiberiu Loredan , Soylu-Kucharz Rana , Burleigh Stephen , Prykhodko Olena , Cao Ling , Franke Naomi , Sjögren Marie , Haikal Caroline , Hållenius Frida , Björkqvist Maria 
Published: October 2020

AbstractHuntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.