bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of gene expression noise due to nonspecific transcription factor binding
Authors: Dey Supravat , Soltani Mohammad , Singh Abhyudai 
Published: December 2019

ABSTRACTThe genome contains several high-affinity non-functional binding sites for transcription factors (TFs) creating a hidden and unexplored layer of gene regulation. We investigate the role of such “decoy sites” in controlling noise (random fluctuations) in the level of a TF that is synthesized in stochastic bursts. Prior studies have assumed that decoy-bound TFs are protected from degradation, and in this case decoys function to buffer noise. Relaxing this assumption to consider arbitrary degradation rates for both bound/unbound TF states, we find rich noise behaviors. For low-affinity decoys, noise in the level of unbound TF always monotonically decreases to the Poisson limit with increasing decoy numbers. In contrast, for high affinity decoys, noise levels first increase with increasing decoy numbers, before decreasing back to the Poisson limit. Interestingly, while protection of bound TFs from degradation slows the time-scale of fluctuations in the unbound TF levels, decay of bounds TFs leads to faster fluctuations and smaller noise propagation to downstream target proteins. In summary, our analysis reveals stochastic dynamics emerging from nonspecific binding of TFs, and highlight the dual role of decoys as attenuators or amplifiers of gene expression noise depending on their binding affinity and stability of the bound TF.
The Drosophila MLR COMPASS-like complex regulatesbantammiRNA expression differentially in the context of cell fate
Authors: Ford David J. , Zraly Claudia B. , Perez John Hertenstein , Dingwall Andrew K. 
Published: December 2019

AbstractThe conserved MLR COMPASS-like complexes are histone modifiers that are recruited by a variety of transcription factors to enhancer regions where they act as necessary epigenetic tools for enhancer establishment and function. A criticalin vivotarget of the Drosophila MLR complex is thebantammiRNA that regulates cell survival and functions in feedback regulation of cellular signaling pathways during development. We determine that loss of Drosophila MLR complex function in developing wing and eye imaginal discs results in growth and patterning defects that are sensitive tobantamlevels. Consistent with an essential regulatory role in modulatingbantamtranscription, the MLR complex binds to tissue-specificbantamenhancers and contributes to fine-tuning expression levels during larval tissue development. In wing imaginal discs, the MLR complex attenuatesbantamenhancer activity by negatively regulating expression; whereas, in differentiating eye discs, the complex exerts either positive or negative regulatory activity onbantamtranscription depending on cell fate. Furthermore, while the MLR complex is not required to controlbantamlevels in undifferentiated eye cells anterior to the morphogenetic furrow, it serves to prepare critical enhancer control ofbantamtranscription for later regulation upon differentiation. Our investigation into the transcriptional regulation of a single target in a developmental context has provided novel insights as to how the MLR complex contributes to the precise timing of gene expression, and how the complex functions to help orchestrate the regulatory output of conserved signaling pathways during animal development.
Targeted mutagenesis using CRISPR-Cas9 in the chelicerate herbivoreTetranychus urticae
Authors: Dermauw Wannes , Jonckheere Wim , Riga Maria , Livadaras Ioannis , Vontas John , Van Leeuwen Thomas 
Published: December 2019

AbstractThe use of CRISPR-Cas9 has revolutionized functional genetic work in many organisms, including more and more insect species. However, successful gene editing or genetic transformation has not yet been reported for chelicerates, the second largest group of terrestrial animals. Within this group, some mite and tick species are economically very important for agriculture and human health, and the availability of a gene-editing tool would be a significant advancement for the field. Here, we report on the use of CRISPR-Cas9 to create gene knock-outs in the spider miteTetranychus urticae. The ovary of virgin adult females was injected with a mix of Cas9 and sgRNAs targeting the phytoene desaturase gene. Natural mutants of this gene have previously shown an easy-to-score albino phenotype. Albino sons of injected virgin females were mated with wild-type females, and two independent transformed lines where created and further characterized. Albinism inherited as a recessive monogenic trait. Sequencing of the complete target-gene of both lines revealed two different lesions at expected locations near the PAM site in the target-gene. Both lines did not genetically complement each other in dedicated crosses, nor when crossed to a reference albino line with a known genetic defect in the same gene. In conclusion, two independent mutagenesis events were induced in the spider miteT. urticaeusing CRISPR-Cas9, providing an impetus for genetic transformation in chelicerates and paving the way for functional studies using CRISPR-Cas9 inT. urticae.
Single cell transcriptome analysis reveals RGS1 as a new marker and promoting factor for T cell exhaustion in multiple cancers
Authors: Bai Yunmeng , Hu Meiling , Chen Zixi , Wei Jinfen , Du Hongli 
Published: December 2019

AbstractT cell exhaustion is one of the main reasons of tumor immune escape. Using single cell transcriptome data of CD8+ T cells in multiple cancers, we identified different cell types, in which Pre_exhaust and exhausted T cells participated in negative regulation of immune system process. By analyzing the co-expression network patterns and differentially expressed genes of Pre_exhaust, exhausted and effector T cells, we identified 35 genes related to T cell exhaustion, which high GSVA scores were associated with significantly poor prognosis in various cancers. In the differentially expressed genes,RGS1showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression ofRGS1was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore,RGS1displayed positive correlation with the 35 genes, especially highly correlated withPDCD1, CTLA4, HAVCR2andTNFRSF9in CD8+ T cells and cancer tissues, indicating important roles ofRGS1in CD8+ T cell exhaustion. Considering the GTP-hydrolysis activity ofRGS1and significantly high mRNA and protein expression in cancer tissues, we speculated thatRGS1potentially mediate the T cell retention to lead to the persistent antigen stimulation, resulting in T cell exhaustion. In conclusion, our findings suggest that RGS1 is a new marker and promoting factor for CD8+ T cell exhaustion, and provide theoretical basis for research and immunotherapy of exhausted cells.
Resurrecting immortal‐time bias in the study of readmissions
Authors: Hugar Lee A. , Borza Tudor , Oerline Mary K. , Hollenbeck Brent K. , Skolarus Ted A. , Jacobs Bruce L. 
Published: December 2019

AbstractObjectiveTo compare readmission rates as measured by the Centers for Medicare and Medicaid Services and the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) methods.Data Sources20 percent sample of national Medicare data for patients undergoing cystectomy, colectomy, abdominal aortic aneurysm (AAA) repair, and total knee arthroplasty (TKA) between 2010 and 2014.Study DesignRetrospective cohort study comparing 30‐day readmission rates.Data Collection/Extraction MethodsPatients undergoing cystectomy, colectomy, abdominal aortic aneurysm repair, and total knee arthroplasty between 2010 and 2014 were identified.Principal FindingsCystectomy had the highest and total knee arthroplasty had the lowest readmission rate. The NSQIP measure reported significantly lower rates for all procedures compared to the CMS measure, which reflects an immortal‐time bias.ConclusionsWe found significantly different readmission rates across all surgical procedures when comparing CMS and NSQIP measures. Longer length of stay exacerbated these differences. Uniform outcome measures are needed to eliminate ambiguity and synergize research and policy efforts.
Plant–herbivorous insect networks: who is eating what revealed by long barcodes using high‐throughput sequencing and Trinity assembly
Authors: Zhang Xiao‐Man , Shi Zhi‐Yong , Zhang Shao‐Qian , Zhang Peng , Wilson John‐James , Shih Chungkun , Li Jing , Li Xue‐Dong , Yu Guo‐Yue , Zhang Ai‐Bing 
Published: December 2019

AbstractInteractions between plants and insects are among the most important life functions for all organism at a particular natural community. Usually a large number of samples are required to identify insect diets in food web studies. Previously, Sanger sequencing and next generation sequencing (NGS) with short DNA barcodes were used, resulting in low species‐level identification; meanwhile the costs of Sanger sequencing are expensive for metabarcoding together with more samples. Here, we present a fast and effective sequencing strategy to identify larvae of Lepidoptera and their diets at the same time without increasing the cost on Illumina platform in a single HiSeq run, with long‐multiplex‐metabarcoding (COI for insects, rbcL, matK, ITS and trnL for plants) obtained by Trinity assembly (SHMMT). Meanwhile, Sanger sequencing (for single individuals) and NGS (for polyphagous) were used to verify the reliability of the SHMMT approach. Furthermore, we show that SHMMT approach is fast and reliable, with most high‐quality sequences of five DNA barcodes of 63 larvae individuals (54 species) recovered (full length of 100% of the COI gene and 98.3% of plant DNA barcodes) using Trinity assembly (up‐sized to 1015 bp). For larvae diets identification, 95% are reliable; the other 5% failed because their guts were empty. The diets identified by SHMMT approach are 100% consistent with the host plants that the larvae were feeding on during our collection. Our study demonstrates that SHMMT approach is reliable and cost‐effective for insect‐plants network studies. This will facilitate insect‐host plant studies that generally contain a huge number of samples.
Effect of ultra‐fine friction grinding on the physical and chemical properties of curcuma (Curcuma longa L.) suspensions
Authors: Serpa Guerra A. M. , Gómez Hoyos C. , Velásquez‐Cock J. A. , Vélez Penagos L. , Gañán Rojo P. , Vélez Acosta L. , Pereira M. A. , Zuluaga R. 
Published: December 2019

AbstractCurcuma longa is a rhizome used for the extraction of curcumin, a yellow colorant that only represents 3 wt% of the dried rhizome. To increase the possibility of using the entire rhizome as a food colorant, in the present investigation, the effect of ultra‐fine friction grinding (supermasscolloider) to obtain turmeric suspensions was evaluated. To achieve this goal, two distances between the grinding stones or Gap were evaluated (G of –1 and –1.5), and the obtained suspensions were characterized by infrared spectroscopy and through the determination of curcumin content, color, particle size, sedimentation index, serum cloudiness, and microstructure. The results establish that a lower G contributes to an increase in the release of curcumin in the suspension up to 21%, which is related to a greater tendency for yellow coloration, observed in the increase of the *b coordinate of color (from 61.588 to 66.497). Additionally, it was found that a lower G generates smaller particle sizes, which is related to a lower turbidity.Practical ApplicationThis research shows that ultra‐fine friction grinding (UFFG) has great potential for the development of turmeric suspensions. The results have applications in the food industry sector, because UFFG could be used to produce different types of vegetable suspensions.
Visible and eco‐friendly immunoassays for the detection of cyclopiazonic acid in maize and rice
Authors: Li Yue , Liu Liqiang , Kuang Hua , Xu Chuanlai 
Published: December 2019

AbstractCyclopiazonic acid (CPA) is an indole‐tetramine mycotoxin commonly produced by Penicillium and Aspergillus and is widely found in agricultural products, fermented food, and feed. Food contaminated with CPA poses a substantial health risk to consumers. Therefore, eco‐friendly immunoassays, including an indirect competitive enzyme‐linked immunosorbent assay (ic‐ELISA) and a lateral flow immunochromatographic strip (LFICS), were developed to monitor CPA in maize and rice samples. For this purpose, a monoclonal antibody (3H12) posed highly resistant to pH (5.6 to 9.6) and ethanol (≤50%) was generated by mouse immunization. Negative maize and rice samples or samples spiked with CPA were extracted with ethanol/0.01 M sodium borate buffer (4/1, v/v, pH 8.4). For ic–ELISA analysis, the limits of detection (LODs) were 0.48 and 0.28 ng/g for maize and rice samples, respectively. The recovery for spiked maize was 76.9% to 83.5% with the highest variable coefficient (CVmax) being 9.32%. For spiked rice, the recovery was 85.3% to 105.1% with a CVmax of 8.56%. For LFICS analysis, the visible LODs were 2.5 and 1 ng/g and cutoff values were 5 and 2.5 ng/g for maize and rice samples, respectively. The LFICS method gave results within 5 to 10 min, providing an auxiliary analytical tool for the rapid, sensitive, and portable screening of the massive samples onsite.
Unraveling the genetic diversity of Belgian Milk Sheep using medium‐density SNP genotypes
Authors: Meyermans R. , Gorssen W. , Wijnrocx K. , Lenstra J. A. , Vellema P. , Buys N. , Janssens S. 
Published: December 2019

SummaryThe present study focuses on the Belgian Milk Sheep in Flanders (Belgium) and compares its genetic diversity and relationship with the Flemish Sheep, the Friesian Milk Sheep, the French Lacaune dairy sheep and other Northern European breeds. For this study, 94 Belgian Milk Sheep, 23 Flemish Sheep and 22 Friesian Milk Sheep were genotyped with the OvineSNP50 array. In addition, 29 unregistered animals phenotypically similar to Belgian Milk Sheep were genotyped using the 15K ISGC chip. Both Belgian and Friesian Milk Sheep as well as the East Friesian Sheep were found to be less diverse than the other seven breeds included in this study. Genomic inbreeding coefficients based on runs of homozygosity (ROH) were estimated at 14.5, 12.4 and 10.2% for Belgian Milk Sheep, Flemish Sheep and Friesian Milk Sheep respectively. Out of 29 unregistered Belgian Milk Sheep, 28 mapped in the registered Belgian Milk Sheep population. Ancestry analysis, PCA and FST calculations showed that Belgian Milk Sheep are more related to Friesian Milk Sheep than to Flemish Sheep, which was contrary to the breeders' expectations. Consequently, breeders may prefer to crossbreed Belgian Milk Sheep with Friesian sheep populations (Friesian Milk Sheep or East Friesian Sheep) in order to increase diversity. This research underlines the usefulness of SNP chip genotyping and ROH analyses for monitoring genetic diversity and studying genetic links in small livestock populations, profiting from internationally available genotypes. As assessment of genetic diversity is vital for long‐term breed survival, these results will aid flockbooks to preserve genetic diversity.
Critical care burden of skin and soft tissue infection in Central Australia: More than skin deep
Authors: Secombe Paul , Planche Yannick , Athan Eugene , Ollapallil Jacob 
Published: December 2019

AbstractObjectiveTo describe the epidemiology, critical care resource use of and outcomes from an intensive care admission for a skin or soft tissue infection in Central Australia.DesignRetrospective database review of prospectively collected data identifying all patients requiring admission for a life‐threatening illness related to a skin or soft tissue infection.SettingIntensive care unit Alice Springs Hospital.ParticipantsAll patients admitted with a primary diagnosis of skin or soft tissue infection between 2010 and 2016.Main outcome measureAnnualised incidence of skin or soft tissue infection requiring intensive care. Secondary outcomes examined resource use (length of stay, mechanical ventilation) and a description of the microbiology of skin or soft tissue infection in Central Australia.ResultsThere were 80 admissions to the intensive care unit over the sampling period, yielding an annualised incidence of 24.2 intensive care unit admissions per 100 000 population. Eighty‐five per cent were Indigenous with high rates of co‐morbid disease including poorly controlled type 2 diabetes, haemodialysis‐dependent chronic kidney disease and co‐infection with human T‐cell lymphocytic virus. The predominant type of skin or soft tissue infection was abscess, predominantly below the waist. Gram‐positive cocci comprised 50% of the organisms cultured, and 20% of organisms were multi‐resistant. Mortality was 0% and 1.3% at 28 and 90 days respectively.ConclusionThe annualised incidence of skin or soft tissue infection requiring intensive care support in Central Australia is higher than expected. This probably reflects the high burden of chronic disease and poor living conditions. While there is no mortality burden associated with skin or soft tissue infection in Central Australia, there is substantial morbidity. The data from this study adds weight to the call for improved primary health resources for this group.
Laser‐facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation
Authors: Korotchenko Evgeniia , Moya Raquel , Scheiblhofer Sandra , Joubert Isabella A , Horejs‐Hoeck Jutta , Hauser Michael , Calzada David , Iraola Víctor , Carnés Jerónimo , Weiss Richard 
Published: December 2019

AbstractBackgroundSkin‐based immunotherapy of type 1 allergies has recently been re‐investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)‐induced lung inflammation to explore the potential of laser‐facilitated epicutaneous allergen‐specific treatment.MethodsMice were sensitized against native Dermatophagoides pteronyssinus extract and repeatedly treated by application of depigmented D pteronyssinus extract via laser‐generated skin micropores or by subcutaneous injection with or without alum. Following aerosol challenges, lung function was determined by whole‐body plethysmography and bronchoalveolar lavage fluid was analyzed for cellular composition and cytokine levels. HDM‐specific IgG subclass antibodies were determined by ELISA. Serum as well as cell‐bound IgE was measured by ELISA, rat basophil leukemia cell assay, and ex vivo using a basophil activation test, respectively. Cultured lymphocytes were analyzed for cytokine secretion profiles and cellular polarization by flow cytometry.ResultsImmunization of mice by subcutaneous injection or epicutaneous laser microporation induced comparable IgG antibody levels, but the latter preferentially induced regulatory T cells and in general downregulated T cell cytokine production. This effect was found to be a result of the laser treatment itself, independent from extract application. Epicutaneous treatment of sensitized animals led to induction of blocking IgG, and improvement of lung function, superior compared to the effects of subcutaneous therapy. During the whole therapy schedule, no local or systemic side effects occurred.ConclusionAllergen‐specific immunotherapy with depigmented HDM extract via laser‐generated skin micropores offers a safe and effective treatment option for HDM‐induced allergy and lung inflammation.
Letter: is tenofovir superior to entecavir for hepatocellular carcinoma prevention in chronic hepatitis B?
Authors: Yuan Bao‐Hong , Zhu Yan‐Kun , Li Ru‐Hong 
Published: December 2019

LINKED CONTENTThis article is linked to Brancaccio et al and Yip and Wong papers. To view these articles, visit https://doi.org/10.1111/apt.15188 and https://doi.org/10.1111/apt.15614.
Letter: the Shock Index and predicting outcomes in patients with upper gastrointestinal bleeding
Authors: McPherson Simon J , Hammond Christopher J 
Published: December 2019

LINKED CONTENTThis article is linked to Saffouri et al and Stanley papers. To view these articles, visit https://doi.org/10.1111/apt.15541 and https://doi.org/10.1111/apt.15615.
Letter: the Shock Index and predicting outcomes in patients with upper gastrointestinal bleeding. Author’s reply
Authors: Stanley Adrian 
Published: December 2019

LINKED CONTENTThis article is linked to Saffouri et al and McPherson and Hammond papers. To view these articles, visit https://doi.org/10.1111/apt.15541 and https://doi.org/10.1111/apt.15605.
Cross‐national assessment of the effects of income level, socialization process, and social conditions on employees’ ethics
Authors: Tuliao Kristine Velasquez , Chen Chung‐wen , Yeh Ying‐Jung 
Published: December 2019

AbstractEmployees often experience ethical dilemmas throughout their service in an organization. This study utilized a multilevel standpoint to address employees’ differences in ethical reasoning. Hierarchical linear modeling was used to analyze responses from 40,485 full‐time employees across 54 countries. Drawing from Durkheim's concepts of the homo duplex, socialization process, and social conditions, this study found a positive relationship between employees’ income level and unethical reasoning. Furthermore, the results indicate that modern social regulation, technological advancement, economic development, and economic change moderate the relationship between income and ethical judgment. The study findings contribute to the Durkheimian model by validating the effects of individual‐ and country‐level factors on employees’ ethicality. Considering that the results contradict Durkheim's initial propositions, another concept and theory are proposed, which may complement Durkheim's arguments. Practical implications for organizations and society are further discussed to reinforce employees’ ethics.