Shuffling the yeast genome using CRISPR/Cas9-generated DSBs that target the transposable Ty1 elements.

Although homologous recombination between transposable elements can drive genomic evolution in yeast by facilitating chromosomal rearrangements, the details of the underlying mechanisms are not fully clarified. In the genome of the yeast Saccharomyces cerevisiae, the most common class of transposon is the retrotransposon Ty1. Here, we explored how Cas9-induced double-strand breaks (DSBs) directed to Ty1 elements produce genomic alterations in this yeast species. Following Cas9 induction, we observed a significant elevation of chromosome rearrangements such as deletions, duplications and translocations. In addition, we found elevated rates of mitotic recombination, resulting in loss of heterozygosity. Using Southern analysis coupled with short- and long-read DNA sequencing, we revealed important features of recombination induced in retrotransposons. Almost all of the chromosomal rearrangements reflect the repair of DSBs at Ty1 elements by non-allelic homologous recombination; clustered Ty elements were hotspots for chromosome rearrangements. In contrast, a large proportion (about three-fourths) of the allelic mitotic recombination events have breakpoints in unique sequences. Our analysis suggests that some of the latter events reflect extensive processing of the broken ends produced in the Ty element that extend into unique sequences resulting in break-induced replication. Finally, we found that haploid and diploid strain have different preferences for the pathways used to repair double-stranded DNA breaks. Our findings demonstrate the importance of DNA lesions in retrotransposons in driving genome evolution.

Global genomic instability caused by reduced expression of DNA polymerase ε in yeast.

SignificanceAlthough most studies of the genetic regulation of genome stability involve an analysis of mutations within the coding sequences of genes required for DNA replication or DNA repair, recent studies in yeast show that reduced levels of wild-type enzymes can also produce a mutator phenotype. By whole-genome sequencing and other methods, we find that reduced levels of the wild-type DNA polymerase ε in yeast greatly increase the rates of mitotic recombination, aneuploidy, and single-base mutations. The observed pattern of genome instability is different from those observed in yeast strains with reduced levels of the other replicative DNA polymerases, Pol α and Pol δ. These observations are relevant to our understanding of cancer and other diseases associated with genetic instability.

Novel insights into the effects of 5-hydroxymethfurural on genomic instability and phenotypic evolution using a yeast model.

5-Hydroxymethfurural (5-HMF) is naturally found in a variety of foods and beverages and represents a main inhibitor in the lignocellulosic hydrolysates used for fermentation. This study investigated the impact of 5-HMF on the genomic stability and phenotypic plasticity of the yeast Saccharomyces cerevisiae. Using next-generation sequencing technology, we examined the genomic alterations of diploid S. cerevisiae isolates that were subcultured on a medium containing 1.2 g/L 5-HMF. We found that in 5-HMF-treated cells, the rates of chromosome aneuploidy, large deletions/duplications, and loss of heterozygosity were elevated compared with that in untreated cells. 5-HMF exposure had a mild impact on the rate of point mutations but altered the mutation spectrum. Contrary to what was observed in untreated cells, more monosomy than trisomy occurred in 5-HMF-treated cells. The aneuploidy mutant with monosomic chromosome IX was more resistant to 5-HMF than the diploid parent strain because of the enhanced activity of alcohol dehydrogenase. Finally, we found that overexpression of ADH6 and ZWF1 effectively stabilized the yeast genome under 5-HMF stress. Our findings not only elucidated the global effect of 5-HMF on the genomic integrity of yeast but also provided novel insights into how chromosomal instability drives the environmental adaptability of eukaryotic cells.IMPORTANCESingle-cell microorganisms are exposed to a range of stressors in both natural and industrial settings. This study investigated the effects of 5-hydroxymethfurural (5-HMF), a major inhibitor found in baked foods and lignocellulosic hydrolysates, on the chromosomal instability of yeast. We examined the mechanisms leading to the distinct patterns of 5-HMF-induced genomic alterations and discovered that chromosomal loss, typically viewed as detrimental to cell growth under most conditions, can contribute to yeast tolerance to 5-HMF. Our results increased the understanding of how specific stressors stimulate genomic plasticity and environmental adaptation in yeast.

Preliminary study on AI-assisted diagnosis of bone remodeling in chronic maxillary sinusitis.

OBJECTIVE: To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. METHODS: Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. RESULTS: Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. CONCLUSION: It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

Ribodysgenesis: sudden genome instability in the yeast Saccharomyces cerevisiae arising from RNase H2 cleavage at genomic-embedded ribonucleotides.

Ribonucleotides can be incorporated into DNA during replication by the replicative DNA polymerases. These aberrant DNA subunits are efficiently recognized and removed by Ribonucleotide Excision Repair, which is initiated by the heterotrimeric enzyme RNase H2. While RNase H2 is essential in higher eukaryotes, the yeast Saccharomyces cerevisiae can survive without RNase H2 enzyme, although the genome undergoes mutation, recombination and other genome instability events at an increased rate. Although RNase H2 can be considered as a protector of the genome from the deleterious events that can ensue from recognition and removal of embedded ribonucleotides, under conditions of high ribonucleotide incorporation and retention in the genome in a RNase H2-negative strain, sudden introduction of active RNase H2 causes massive DNA breaks and genome instability in a condition which we term 'ribodysgenesis'. The DNA breaks and genome instability arise solely from RNase H2 cleavage directed to the ribonucleotide-containing genome. Survivors of ribodysgenesis have massive loss of heterozygosity events stemming from recombinogenic lesions on the ribonucleotide-containing DNA, with increases of over 1000X from wild-type. DNA breaks are produced over one to two divisions and subsequently cells adapt to RNase H2 and ribonucleotides in the genome and grow with normal levels of genome instability.

Radical Homopolymerization of Linear α-Olefins Enabled by 1,4-Cyano Group Migration.

α-Olefins are valued and abundant building blocks from fossil resources. They are widely used to provide small-molecule or polymeric products. Despite numerous advantages of radical polymerization, it has been well-documented as textbook knowledge that α-olefins and their functionalized derivatives cannot be radically homopolymerized because of the degradative chain transfer side reactions. Herein, we report our studies on the homopolymerization of thiocyanate functionalized α-olefins enabled by 1,4-cyano group migration under radical conditions. By this approach, a library of ABC sequence-controlled polymers with high molecular weights can be prepared. We can also extend this strategy to the homopolymerization of α-substituted styrenic and acylate monomers which are known to be challenging to achieve. Overall, the demonstrated functional group migration radical polymerization could provide new possibilities to synthesize polymers with unprecedented main chain sequences and structures. These polymers are promising candidates for novel polymeric materials.

Nanoscale effects of TiO2 nanoparticles on the rheological behaviors of ultra-high molecular weight polyethylene (UHMWPE).

Considering the molar mass between entanglements to be an intrinsic property of ultra-high molecular weight polyethylene (UHMWPE), the number of entanglements per chain increases with increasing molar mass, correspondingly making the UHMWPE intractable. Herein, we dispersed TiO2 nanoparticles with different characteristics into UHMWPE solutions to disentangle the molecular chains. Compared with the UHMWPE pure solution, the viscosity of the mixture solution declines by 91.22%, and the critical overlap concentration increases from 1 wt% to 1.4 wt%. A rapid precipitation method was utilized to obtain UHMWPE and UHMWPE/TiO2 composites from the solutions. The melting index of UHMWPE/TiO2 is 68.85 mg, which is in sharp contrast to that of UHMWPE which is 0 mg. We characterized the microstructures of UHMWPE/TiO2 nanocomposites using TEM, SAXS, DMA, and DSC. Accordingly, this significant improvement in processability contributed to the reduction of entanglements and a schematic model was proposed to explain the mechanism by which nanoparticles disentangle molecular chains. Simultaneously, the composite demonstrated better mechanical properties than UHMWPE. In summary, we provide a strategy to promote the processability of UHMWPE without sacrificing its outstanding mechanical properties.

Comparative study and multi-parameter analysis to optimize device structure of triboelectric nanogenerators.

Triboelectric nanogenerator is becoming one of the most efficient energy harvesting device among all mechanical energy harvesters. This device consists of dielectric friction layers and metal electrode which generates electrical charges using electrostatic induction effect. There are several factors influencing the performance of this generator which needs to be evaluated prior to experiment. The absence of a universal technique for TENG simulation makes the device design and optimization hard before practical fabrication, which also lengthens the exploration and advancement cycle and hinders the arrival of practical applications. In order to deepen the understanding the core physic behind the working process of this device, this work will provide comparative analysis on different modes of TENG. Systematic investigation on different material combination, effect of material thickness, dielectric constant and impact of surface patterning is evaluated to shortlist the best material combination. COMSOL Multiphysics simulating environment is used to design, model and analyze factor affecting the overall output performance of TENG. The stationary study in this simulator is performed using 2D geometry structure with higher mesh density. During this study short circuit and open circuit condition were applied to observe the behavior of charge and electric potential produced. This observation is analyzed by plotting charge transfer/electric potential against various displacement distances of dielectric friction layers. The ouput is then provided to load ciruitary to measure the maximum output power of the models. Overall, this study provides an excellent understanding and multi-parameter analysis on basic theoretical and simulation modeling of TENG device.

Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases.

Yeast strains with low levels of the replicative DNA polymerases (alpha, delta, and epsilon) have high levels of chromosome deletions, duplications, and translocations. By examining the patterns of mutations induced in strains with low levels of DNA polymerase by the human protein APOBEC3B (a protein that deaminates cytosine in single-stranded DNA), we show dramatically elevated amounts of single-stranded DNA relative to a wild-type strain. During DNA replication, one strand (defined as the leading strand) is replicated processively by DNA polymerase epsilon and the other (the lagging strand) is replicated as short fragments initiated by DNA polymerase alpha and extended by DNA polymerase delta. In the low DNA polymerase alpha and delta strains, the APOBEC-induced mutations are concentrated on the lagging-strand template, whereas in the low DNA polymerase epsilon strain, mutations occur on the leading- and lagging-strand templates with similar frequencies. In addition, for most genes, the transcribed strand is mutagenized more frequently than the nontranscribed strand. Lastly, some of the APOBEC-induced clusters in strains with low levels of DNA polymerase alpha or delta are greater than 10 kb in length.

Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells.

Genomic alterations including single-base mutations, deletions and duplications, translocations, mitotic recombination events, and chromosome aneuploidy generate genetic diversity. We examined the rates of all of these genetic changes in a diploid strain of Saccharomyces cerevisiae by whole-genome sequencing of many independent isolates (n = 93) subcloned about 100 times in unstressed growth conditions. The most common alterations were point mutations and small (<100 bp) insertion/deletions (n = 1,337) and mitotic recombination events (n = 1,215). The diploid cells of most eukaryotes are heterozygous for many single-nucleotide polymorphisms (SNPs). During mitotic cell divisions, recombination can produce derivatives of these cells that have become homozygous for the polymorphisms, termed loss-of-heterozygosity (LOH) events. LOH events can change the phenotype of the cells and contribute to tumor formation in humans. We observed two types of LOH events: interstitial events (conversions) resulting in a short LOH tract (usually less than 15 kb) and terminal events (mostly cross-overs) in which the LOH tract extends to the end of the chromosome. These two types of LOH events had different distributions, suggesting that they may have initiated by different mechanisms. Based on our results, we present a method of calculating the probability of an LOH event for individual SNPs located throughout the genome. We also identified several hotspots for chromosomal rearrangements (large deletions and duplications). Our results provide insights into the relative importance of different types of genetic alterations produced during vegetative growth.

Radical chemistry in polymer science: an overview and recent advances.

Radical chemistry is one of the most important methods used in modern polymer science and industry. Over the past century, new knowledge on radical chemistry has both promoted and been generated from the emergence of polymer synthesis and modification techniques. In this review, we discuss radical chemistry in polymer science from four interconnected aspects. We begin with radical polymerization, the most employed technique for industrial production of polymeric materials, and other polymer synthesis involving a radical process. Post-polymerization modification, including polymer crosslinking and polymer surface modification, is the key process that introduces functionality and practicality to polymeric materials. Radical depolymerization, an efficient approach to destroy polymers, finds applications in two distinct fields, semiconductor industry and environmental protection. Polymer chemistry has largely diverged from organic chemistry with the fine division of modern science but polymer chemists constantly acquire new inspirations from organic chemists. Dialogues on radical chemistry between the two communities will deepen the understanding of the two fields and benefit the humanity.

Uncovering Bleomycin-Induced Genomic Alterations and Underlying Mechanisms in the Yeast Saccharomyces cerevisiae.

Bleomycin (BLM) is a widely used chemotherapeutic drug. BLM-treated cells showed an elevated rate of mutations, but the underlying mechanisms remained unclear. In this study, the global genomic alterations in BLM-treated cells were explored in the yeast Saccharomyces cerevisiae. Using genetic assay and whole-genome sequencing, we found that the mutation rate could be greatly elevated in S. cerevisiae cells that underwent Zeocin (a BLM member) treatment. One-base deletion and T-to-G substitution at the 5'-GT-3' motif represented the most striking signature of Zeocin-induced mutations. This was mainly the result of translesion DNA synthesis involving Rev1 and polymerase ζ. Zeocin treatment led to the frequent loss of heterozygosity and chromosomal rearrangements in the diploid strains. The breakpoints of recombination events were significantly associated with certain chromosomal elements. Lastly, we identified multiple genomic alterations that contributed to BLM resistance in the Zeocin-treated mutants. Overall, this study provides new insights into the genotoxicity and evolutional effects of BLM. IMPORTANCE Bleomycin is an antitumor antibiotic that can mutate genomic DNA. Using yeast models in combination with genome sequencing, the mutational signatures of Zeocin (a member of the bleomycin family) are disclosed. Translesion-synthesis polymerases are crucial for the viability of Zeocin-treated yeast cells at the sacrifice of a higher mutation rate. We also confirmed that multiple genomic alterations were associated with the improved resistance to Zeocin, providing novel insights into how bleomycin resistance is developed in cells.

AIoT enabled resampling filter for temperature extraction of the Brillouin gain spectrum.

The Artificial Intelligence of Things (AIoT) turns passive fiber sensors into learning machines. It can be used to integrate intelligent nodes into a multi-dimensional sensing system. In this study, the temperature measurement system based on Brillouin Gain Spectrum (BGS) test setup is creatively implemented with the AIoT architecture; the training and testing stages of the neural network are divided into different layers of equipment to improve performance and reduce the network traffic. To enable the lightweight and low-power consumption edge computing device to extract accurate temperature from the BGS during testing, we have integrated the post-processing method inspired by curve fitting into the machine learning and proposed the efficient digital resampling filter. The resampling filter approach is achieved by the peak range algorithm with Gauss differential operator and digital band-pass filter. The evaluation results for different methods on the BGS datasets show the superior performance of our approach. Notably, the approach can increase temperature extraction accuracy and compress the sampling data. The RMSEA of the extraction temperature is 0.5635, which can bring an almost 21% accuracy increase over the classic method. Compared with the classic method of processing the original data on the same hardware platform, the amount of data post-processed by the filter is reduced by 75%; the time consumption is reduced by 22%.

[Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology].

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Sweep frequency method with variance weight probability for temperature extraction of the Brillouin gain spectrum based on an artificial neural network.

The development of optical fiber sensors has led to the possibility of accumulating vast, real-time databases of acoustic and other measurements throughout fiber networks, which brings even more widespread concern on improving the sampling effectiveness. In this paper, we present two kinds of sweep frequency methods based on using a neural network to extract temperature from the Brillouin gain spectrum (BGS). Gauss centralization and variance weight probability methods are proposed to compare with the uniform sweep frequency method. By analyzing formulas of the ideal BGS model, we find the gain near the peak of Brillouin gain spectrum has greater correlation with temperature extraction than other positions. Therefore, the Gaussian centralized sweep method is proposed. We further investigate the variation of the weights in the neural network and Brillouin data distribution in different positions and find that the variance is positively correlated with the weights in hidden layers. So, we propose the sweep frequency method based on variance weight probability and make a complement to interpret the rationality of this method in neural network. In all the aforementioned approaches, 281 points are obtained between the 9.07 GHz to 9.35 GHz range under the same condition. The data of each method is trained ten times and tested through the same neural network structure. All the RMSE of each test stage covers all data collecting the passage. The result shows that the RMSE of variance weight probability sweep frequency method is 0.5277, which is superior to the Gauss centralization sweep frequency method that was 0.6864 and the uniform sweep frequency method that was 0.9140.

CXCL1 stimulates decidual angiogenesis via the VEGF-A pathway during the first trimester of pregnancy.

Angiogenesis is critical to establishing a successful pregnancy. The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that is an important chemokine involved in the processes of angiogenesis and arteriogenesis; however, little is known about its role in decidual angiogenesis. Effects of CXCL1 on cell proliferation and migration (propidium iodide staining and wound healing assays) of HUVEC cells were determined. The angiogenesis roles of CXCL1 in HUVEC-HTR8/SVneo co-culture system were detected by the tube formation assay. Signal transduction pathways in HUVEC cells in response to CXCL1 were determined by in-cell western analyses. In vivo, mice were injected with (1) PBS (Group A) or (2) CXCL1-neutralizing antibody (Group B) or (3) CXCL1-neutralizing antibody plus recombinant VEGF-A protein (Group C) from E1 to E5 and sacrificed at E6.5 of pregnancy. The decidual angiogenesis in mice was examined by immunohistochemistry of cluster designation 34 (CD34), and the expression levels of vascular endothelial growth factor-A (VEGF-A) in the decidual cells and vascular endothelial growth factor receptor 2 (VEGFR2) in decidual vascular endothelial cells were also tested. Exogenous recombinant human CXCL1 supported endothelial cell proliferation and migration, and this effect was blocked by CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. The tube formation of HUVEC-HTR8/SVneo co-culture system was significantly stimulated by CXCL1, but this effect was markedly abrogated once they were pretreated with CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. In addition, the level of vascular endothelial growth factor A (VEGF-A) expression in HUVEC cells was increased by CXCL1, and this level was suppressed by CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. In vivo, compared with Group A (n = 3), decidual angiogenesis was significantly reduced in Group B by CD34 immunostaining. But compared with Group B, decidual angiogenesis was significantly increased in Group C. In addition, the expression of VEGF-A and VEGFR2 was significantly increased after neutralizing of CXCL1 in Group B. In conclusions, CXCL1 may play essential roles in decidual angiogenesis during the first trimester, and this function may be mediated in part via altering VEGF-A expression.

Genome-wide analysis of genomic alterations induced by oxidative DNA damage in yeast.

Oxidative DNA damage is a threat to genome stability. Using a genetic system in yeast that allows detection of mitotic recombination, we found that the frequency of crossovers is greatly elevated when cells are treated with hydrogen peroxide (H2O2). Using a combination of microarray analysis and genomic sequencing, we mapped the breakpoints of mitotic recombination events and other chromosome rearrangements at a resolution of about 1 kb. Gene conversions and crossovers were the two most common types of events, but we also observed deletions, duplications, and chromosome aneuploidy. In addition, H2O2-treated cells had elevated rates of point mutations (particularly A to T/T to A and C to G/G to C transversions) and small insertions/deletions (in/dels). In cells that underwent multiple rounds of H2O2 treatments, we identified a genetic alteration that resulted in improved H2O2 tolerance by amplification of the CTT1 gene that encodes cytosolic catalase T. Lastly, we showed that cells grown in the absence of oxygen have reduced levels of recombination. This study provided multiple novel insights into how oxidative stress affects genomic instability and phenotypic evolution in aerobic cells.

Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast Saccharomyces cerevisiae.

Chromosomal rearrangements comprise unbalanced structural variations resulting in gain or loss of DNA copy numbers, as well as balanced events including translocation and inversion that are copy number neutral, both of which contribute to phenotypic evolution in organisms. The exquisite genetic assay and gene editing tools available for the model organism Saccharomyces cerevisiae facilitate deep exploration of the mechanisms underlying chromosomal rearrangements. We discuss here the pathways and influential factors of chromosomal rearrangements in S. cerevisiae. Several methods have been developed to generate on-demand chromosomal rearrangements and map the breakpoints of rearrangement events. Finally, we highlight the contributions of chromosomal rearrangements to drive phenotypic evolution in various S. cerevisiae strains. Given the evolutionary conservation of DNA replication and recombination in organisms, the knowledge gathered in the small genome of yeast can be extended to the genomes of higher eukaryotes.

Retraction: The "Other Face" of Research Collaboration?

The last two decades have witnessed the rising prevalence of both co-publishing and retraction. Focusing on research collaboration, this paper utilizes a unique dataset to investigate factors contributing to retraction probability and elapsed time between publication and retraction. Data analysis reveals that the majority of retracted papers are multi-authored and that repeat offenders are collaboration prone. Yet, all things being equal, collaboration, in and of itself, does not increase the likelihood of producing flawed or fraudulent research, at least in the form of retraction. That holds for all retractions and also retractions due to falsification, fabrication, and plagiarism (FFP). The research also finds that publications with authors from elite universities are less likely to be retracted, which is particularly true for retractions due to FFP. China stands out with the fastest retracting speed compared to other countries. Possible explanations, limitations, and policy implications are also discussed.

Global Analysis of Furfural-Induced Genomic Instability Using a Yeast Model.

Furfural is an important renewable precursor for multiple commercial chemicals and fuels; a main inhibitor existing in cellulosic hydrolysate, which is used for bioethanol fermentation; and a potential carcinogen, as well. Using a genetic system in Saccharomyces cerevisiae that allows detection of crossover events, we observed that the frequency of mitotic recombination was elevated by 1.5- to 40-fold when cells were treated with 0.1 g/liter to 20 g/liter furfural. Analysis of the gene conversion tracts associated with crossover events suggested that most furfural-induced recombination resulted from repair of DNA double-strand breaks (DSBs) that occurred in the G1 phase. Furfural was incapable of breaking DNA directly in vitro but could trigger DSBs in vivo related to reactive oxygen species accumulation. By whole-genome single nucleotide polymorphism (SNP) microarray and sequencing, furfural-induced genomic alterations that range from single base substitutions, loss of heterozygosity, and chromosomal rearrangements to aneuploidy were explored. At the whole-genome level, furfural-induced events were evenly distributed across 16 chromosomes but were enriched in high-GC-content regions. Point mutations, particularly the C-to-T/G-to-A transitions, were significantly elevated in furfural-treated cells compared to wild-type cells. This study provided multiple novel insights into the global effects of furfural on genomic stability.IMPORTANCE Whether and how furfural affects genome integrity have not been clarified. Using a Saccharomyces cerevisiae model, we found that furfural exposure leads to in vivo DSBs and elevation in mitotic recombination by orders of magnitude. Gross chromosomal rearrangements and aneuploidy events also occurred at a higher frequency in furfural-treated cells. In a genome-wide analysis, we show that the patterns of mitotic recombination and point mutations differed dramatically in furfural-treated cells and wild-type cells.