bluuebunny/crossref_metadata_2025 huggingface dataset:
Queering Lists: Culinary and Literary Modernism in The Book of Salt
Authors: Cheng Julia
Published: August 2019

Lists, and the practice of listing, provide avenues of insight into Bình, the protagonist in Monique Truong’s The Book of Salt (2003). Working as a cook in the infamous Stein Salon in Old World Paris, Bình, a narrative footnote extracted from The Alice B. Cook Book (1954), exercises a linguistic and culinary grasp shown to rival the resident darling couple’s own modernist projects. Demonstrating the narrator’s artistry under the radar, the list represents a formal feature that stages the particularities of queer aesthetics against the humanist backdrop represented by Gertrude Stein and Alice Toklas. As the novel spans geographical coordinates and varied temporalities, Bình’s curious expression of choice prompts narratological overlooking even as it tracks the desires of diasporic bodies and the taste of cherished dishes. Exercised with remarkable restraint, the generative accretions of running catalogs and errant recipes represent small acts of creativity in the novel. Simultaneously, the practice of listing foregrounds the enumerations as tactical sites of interruption and deferral, to constitute a critical methodology that reflects the list-maker’s precarity as a queer Vietnamese exile. This essay attends to the achievements of a minoritarian character who casts a shadow in the familiar archives of high modernism, as the “superficial” stylistic feature of the list opens up The Book of Salt to larger reflections on the intimate ties between coloniality and avant-garde experimentation.
The isolation of luminous blue variables resembles aging B-type supergiants, not the most massive unevolved stars
Authors: Smith Nathan
Published: August 2019

Luminous blue variables (LBVs) are suprisingly isolated from the massive O-type stars that are their putative progenitors in single-star evolution, implicating LBVs as binary evolution products. Aadland et al. found that LBVs are, however, only marginally more dispersed than a photometrically selected sample of bright blue stars (BBS) in the Large Magellanic Cloud (LMC), leading them to suggest that LBV environments may not exclude a single-star origin. In both comparisons, LBVs have the same median separation, confirming that any incompleteness in the O-star sample does not fabricate LBV isolation. Instead, the relative difference arises because the photometric BBS sample is far more dispersed than known O-type stars. Evidence suggests that the large BBS separation arises because it traces less massive (∼20 M⊙), aging blue supergiants. Although photometric criteria used by A19 aimed to select only the most massive unevolved stars, visual-wavelength colour selection cannot avoid contamination because O and early B stars have almost the same intrinsic colour. Spectral types confirm that the BBS sample contains many B supergiants. Moreover, the observed BBS separation distribution matches that of spectroscopically confirmed early B supergiants, not O-type stars, and matches predictions for a roughly 10 Myr population, not a 3–4 Myr population. A broader implication for ages of stellar populations is that bright blue stars are not a good tracer of the youngest massive O-type stars. Bright blue stars in nearby galaxies (and unresolved blue light in distant galaxies) generally trace evolved blue supergiants akin to SN 1987A’s progenitor.
New evidence for the ubiquity of prominent polar dust emission in AGN on tens of parsec scales
Authors: Asmus D
Published: August 2019

The key ingredient of active galactic nuclei (AGN) unification, the dusty obscuring torus was so far held responsible for the observed mid-infrared (MIR) emission of AGN. However, the best studied objects with Very Large Telescope Interferometer (VLTI)/MID-infrared Interferometric instrument (MIDI) show that instead a polar dusty wind is dominating these wavelengths, leaving little room for a torus contribution. But is this wind a ubiquitous part of the AGN? To test this, we conducted a straightforward detection experiment, using the upgraded Very Large Telescope (VLT)/VLT Imager and Spectrometer for mid-InfraRed (VISIR) for deep subarcsecond resolution MIR imaging of a sample of nine [O iv]-bright, obscured AGN, all of which were predicted to have detectable polar emission. Indeed, the new data reveal such emission in all objects but one. We further estimate lower limits on the extent of the polar dust and show that the polar dust emission is dominating the total MIR emission of the AGN. These findings support the scenario that polar dust is not only ubiquitous in AGN but also an integral part of its structure, processing a significant part of the primary radiation. The polar dust has to be optically thin on average, which explains e.g. the small dispersion in the observed MIR–X-ray luminosity correlation. At the same time, it has to be taken into account when deriving covering factors of obscuring material from MIR to bolometric luminosity ratios. Finally, we find a new tentative trend of increasing MIR emission size with increasing Eddington ratio.
Insights into telomeric G-quadruplex DNA recognition by HMGB1 protein
Authors: Amato Jussara , Cerofolini Linda , Brancaccio Diego , Giuntini Stefano , Iaccarino Nunzia , Zizza Pasquale , Iachettini Sara , Biroccio Annamaria , Novellino Ettore , Rosato Antonio , Fragai Marco , Luchinat Claudio , Randazzo Antonio , Pagano Bruno
Published: August 2019

HMGB1 is a ubiquitous non-histone protein, which biological effects depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription and telomere maintenance. HMGB1 has been reported to bind preferentially to bent DNA as well as to noncanonical DNA structures like 4-way junctions and, more recently, to G-quadruplexes. These are four-stranded conformations of nucleic acids involved in important cellular processes, including telomere maintenance. In this frame, G-quadruplex recognition by specific proteins represents a key event to modulate physiological or pathological pathways. Herein, to get insights into the telomeric G-quadruplex DNA recognition by HMGB1, we performed detailed biophysical studies complemented with biological analyses. The obtained results provided information about the molecular determinants for the interaction and showed that the structural variability of human telomeric G-quadruplex DNA may have significant implications in HMGB1 recognition. The biological data identified HMGB1 as a telomere-associated protein in both telomerase-positive and -negative tumor cells and showed that HMGB1 gene silencing in such cells induces telomere DNA damage foci. Altogether, these findings provide a deeper understanding of telomeric G-quadruplex recognition by HMGB1 and suggest that this protein could actually represent a new target for cancer therapy.
Detection of internal N7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing
Authors: Enroth Christel , Poulsen Line Dahl , Iversen Søren , Kirpekar Finn , Albrechtsen Anders , Vinther Jeppe
Published: August 2019

Methylation of guanosine on position N7 (m7G) on internal RNA positions has been found in all domains of life and have been implicated in human disease. Here, we present m7G Mutational Profiling sequencing (m7G-MaP-seq), which allows high throughput detection of m7G modifications at nucleotide resolution. In our method, m7G modified positions are converted to abasic sites by reduction with sodium borohydride, directly recorded as cDNA mutations through reverse transcription and sequenced. We detect positions with increased mutation rates in the reduced and control samples taking the possibility of sequencing/alignment error into account and use replicates to calculate statistical significance based on log likelihood ratio tests. We show that m7G-MaP-seq efficiently detects known m7G modifications in rRNA with mutational rates up to 25% and we map a previously uncharacterised evolutionarily conserved rRNA modification at position 1581 in Arabidopsis thaliana SSU rRNA. Furthermore, we identify m7G modifications in budding yeast, human and arabidopsis tRNAs and demonstrate that m7G modification occurs before tRNA splicing. We do not find any evidence for internal m7G modifications being present in other small RNA, such as miRNA, snoRNA and sRNA, including human Let-7e. Likewise, high sequencing depth m7G-MaP-seq analysis of mRNA from E. coli or yeast cells did not identify any internal m7G modifications.
Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease
Authors: Lee Yu Ho , Kim Ki Pyo , Park Sun-Hwa , Kim Dong-Jin , Kim Yang-Gyun , Moon Ju-Young , Jung Su-Woong , Kim Jin Sug , Jeong Kyung-Hwan , Lee So-Young , Yang Dong-Ho , Lim Sung-Jig , Woo Jeong-Taek , Rhee Sang Youl , Chon Suk , Choi Hoon-Young , Park Hyeong-Cheon , Jo Young-Il , Yi Joo-Hark , Han Sang-Woong , Lee Sang-Ho
Published: August 2019

Background

Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis.

Methods

Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes.

Results

Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070–3.455, P = 0.029).

Conclusions

Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.
Trends in Attempts to Quit Smoking in England Since 2007: A Time Series Analysis of a Range of Population-Level Influences
Authors: Beard Emma , Jackson Sarah E , West Robert , Kuipers Mirte A G , Brown Jamie
Published: August 2019

Aim

To quantify population-level associations between quit attempts and factors that have varied across 2007–2017 in England.

Methods

Data from 51 867 past-year smokers participating in the Smoking Toolkit Study (a monthly cross-sectional survey of individuals aged 16+) were aggregated over an 11-year period. Time series analysis was undertaken using ARIMAX modeling. The input series were: (1) prevalence of smoking reduction using (a) e-cigarettes and (b) nicotine replacement therapy; (2) prevalence of roll-your-own tobacco use; (3) prevalence of (a) smoking and (b) non-daily smoking; (4) mass media expenditure; (5) average expenditure on smoking; (6) characteristics in the form of (a) prevalence of high motivation to quit, (b) average age, (c) proportion from lower social grades, and (d) average number of cigarettes smoked; and (7) implementation of tobacco control policies.

Results

There was a decline in the prevalence of quit attempts from 44.6% to 33.8% over the study period. The partial point-of-sale ban was associated with a temporary increase in quit attempt prevalence (Badjusted = 0.224%; 95% confidence interval [CI] 0.061 to 0.388). Quit attempts were positively associated with the prevalence of high motivation to quit (Badjusted = 0.165%;95% CI 0.048 to 0.282) and negatively associated with the mean age of smokers (Badjusted = −1.351%; 95% CI −2.168 to −0.534). All other associations were nonsignificant.

Conclusion

Increases in the prevalence of high motivation to quit was associated with higher prevalence of attempts to quit smoking, while an increase in the mean age of smokers was associated with lower prevalence. The introduction of the partial point-of-sale ban appeared to have a temporary positive impact.

Implications

This study provides insight into how monthly changes in a wide range of population-level factors are associated with changes in quit attempts over an extended time period in a country with a strong tobacco control climate. The findings suggest a need for intervention or policy to stimulate quit attempts in older smokers. Otherwise, increases in the mean age of a smokers appears likely to undermine wider efforts to promote quit attempts in a population.
THE USE OF DECONVOLUTION TECHNIQUE FOR THE ANALYSIS OF GAMMA SPECTROMETRY DATA FROM FIELD MONITORING USING UNMANNED AERIAL VEHICLES
Authors: Klusoň Jaroslav , Thinová Lenka
Published: August 2019

Airborne gamma spectrometry is an effective tool for prompt monitoring and mapping of large areas contaminated after NPP accident, radionuclides leakage cases, an impact of uranium ore mining and processing, etc. Airborne spectrometry data analysis using deconvolution technique enables to calculate air kerma rates and/or radionuclides concentrations as well as identification of radionuclides. Application of this technique on the airborne data (from manned as well as an unmanned survey using drones) is rather specific due to the requirements for short time of one scan data acquisition, a relatively long distance from the source and small detector size, due to the limited payload of the usually used drones. Application of deconvolution techniques for analysis of spectra with very poor statistics, methods and possibilities to improve the processing of such spectra are discussed.
ANALYSIS OF RADON TIME SERIES RECORDED IN SLOVAK AND CZECH CAVES FOR THE DETECTION OF ANOMALIES DUE TO SEISMIC PHENOMENA
Authors: Ambrosino Fabrizio , Thinová Lenka , Briestenský Miloš , Sabbarese Carlo
Published: August 2019

Anomalies in the radon (222Rn) releases in underground environments are one of the phenomena that can be observed before earthquake occurrence. Continuous measurements of radon activity concentration, and of meteorological parameters that influence the gas emission, were performed in three Slovak and Czech caves during 1-y period (1 July 2016–30 June 2017). The radon activity concentration in caves shows seasonal variations, with maxima reached during summer months. The anomalies in the radon time series are identified using a combination of three mathematical methods: multiple linear regression, empirical mode decomposition and support vector regression. The radon anomaly periods were compared with earthquake occurrences in Europe. Coincidences between both phenomena were found, since all monitored caves reflect contemporaneous local tectonic changes. The results indicate that radon continuous monitoring could assist a better understanding of radon emissions, along active tectonic structures, during seismic events.
Phylogenetic Trees and Networks Can Serve as Powerful and Complementary Approaches for Analysis of Genomic Data
Authors: Blair Christopher , Ané Cécile
Published: August 2019

Genomic data have had a profound impact on nearly every biological discipline. In systematics and phylogenetics, the thousands of loci that are now being sequenced can be analyzed under the multispecies coalescent model (MSC) to explicitly account for gene tree discordance due to incomplete lineage sorting (ILS). However, the MSC assumes no gene flow post divergence, calling for additional methods that can accommodate this limitation. Explicit phylogenetic network methods have emerged, which can simultaneously account for ILS and gene flow by representing evolutionary history as a directed acyclic graph. In this point of view, we highlight some of the strengths and limitations of phylogenetic networks and argue that tree-based inference should not be blindly abandoned in favor of networks simply because they represent more parameter rich models. Attention should be given to model selection of reticulation complexity, and the most robust conclusions regarding evolutionary history are likely obtained when combining tree- and network-based inference.
Technical Note: The use of iSperm technology for on-farm measurement of equine sperm motility and concentration
Authors: Moraes Christa R , Runcan Erin E , Blawut Bryan , Coutinho da Silva Marco A
Published: August 2019

The iSperm is a newly released semen analysis tool from Aidmics Biotechnology Co. LTD, which allows an iPad Mini to be transformed into a handheld microscope with objective semen analysis software for equine available through the Apple Store (version 4.5.2). The aim of this study was to compare iSperm values for sperm motility and sperm concentration to current acceptable methods for semen analysis and to determine the agreement with these methods using statistical methods. Two ejaculates from each of five Standardbred stallions were used to compare sperm motility (computer-assisted semen analysis [CASA] vs. iSperm) and concentration (NucleoCounter SP-100 [NC] vs. hemocytometer vs. iSperm). Data were analyzed by first testing for the differences between the means of each method using a linear mixed-effects model. The agreement between the two continuous measurements for each method was then investigated by computing Lin’s concordance correlation coefficient (CCC), with a value of 1 indicating perfect agreement between methods. Results are reported as the CCC with the associated 95% confidence interval in parentheses. Means for both total motility (TM) and progressive motility (PM) were equal between CASA and iSperm values (P = 0.0741 and P = 0.725, respectively). However, means for all velocity measurements were significantly different between CASA and iSperm readings (P < 0.001). For concentration, means were equal between NC and iSperm values (P = 0.748) and for hemocytometer and iSperm values (P = 0.953). The CCC for TM was 0.871 (0.788, 0.923) and for PM was 0.916 (0.847, 0.955) indicating good agreement between methods. Low levels of agreement were observed for all velocity measurements. Finally, the CCC for concentration compared by iSperm and NC was 0.970 (0.949, 0.982) and for iSperm and hemocytometer it was 0.962 (0.934, 0.978), both close to the line of perfect concordance. Although more work is needed to improve the iSperm software for velocity measurements to be acceptable by research standards, in its present form the iSperm will introduce a low-cost and affordable method for on-farm semen analysis (TM, PM, concentration) for breeders and veterinarians. As a result, more farms will have access to accurate sperm analysis tools which will help to standardize semen processing procedures leading to better overall quality of semen used for artificial insemination.
Dynamic dengue haemorrhagic fever calculators as clinical decision support tools in adult dengue
Authors: Tan Ken Wei , Tan Ben , Thein Tun L , Leo Yee-Sin , Lye David C , Dickens Borame L , Wong Joshua Guo Xian , Cook Alex R
Published: August 2019

Background

The objective of this study was to develop multiple prediction tools that calculate the risk of developing dengue haemorrhagic fever.

Methods

Training data consisted of 1771 individuals from 2006–2008 admitted with dengue fever whereby 304 developed dengue haemorrhagic fever during hospitalisation. Least absolute shrinkage and selection operator regression was used to construct three types of calculators, static admission calculators and dynamic calculators that predict the risk of developing dengue haemorrhagic fever for a subsequent day (DAily Risk Tomorrow [DART]) or for any future point after a specific day since fever onset (DAily Risk Ever [DARE]).

Results

From 119 admission covariates, 35 were in at least one of the calculators, which reported area under the curve (AUC) values of at least 0.72. Addition of person-time data for DART improved AUC to 0.76. DARE calculators displayed a large increase in AUC to 0.79 past day 7 with the inclusion of a strong predictor, maximum temperature on day 6 since onset, indicative of a saddleback fever.

Conclusions

All calculators performed well when validated with 2005 data. Addition of daily variables further improved the accuracy. These calculators can be used in tandem to assess the risk of dengue haemorrhagic fever upon admission and updated daily to obtain more precise risk estimates.
A synthetic cervix model and the impact of softness on cerclage integrity
Authors: Baumer Alexa , Gimovsky Alexis C. , Gallagher Michael , Leftwich Megan C.
Published: August 2019

Cervical insufficiency is a medical condition of pregnancy which causes the cervix to soften, shorten and dilate before full term, typically between 18 and 22 weeks of gestation, such that a preterm birth occurs. It is a common cause of second trimester pregnancy loss. Before meeting the diagnostic criteria, a patient that experiences early cervical remodelling or the development of a short cervix may receive surgical intervention. Once detected, the typical treatment is a cerclage procedure (a purse string suture to close the cervix) and progesterone medication. There are conflicting studies on the efficacy of the cerclage procedure, with conclusions drawn from clinical evidence as opposed to mechanical properties. The purpose of this study is to understand the mechanical limitations of the cerclage procedure. Working with physicians at George Washington University School of Medicine and Health Sciences, we created generalized three dimensional models of the cervix from ultrasound images. To fabricate the synthetic cervices, we used a silicone rubber to mimic the qualitative feel of the cervix according to collaborating physicians. Using this qualitative information, we performed material testing for quantitative analysis. The synthetic cervices were then sutured using clinical techniques. The maximum force required for the synthetic tissue to rupture due to the cerclage stitch was recorded. The impact of material softness on the integrity of the cerclage is investigated.
The global phylogeny of Plum pox virus is emerging
Authors: Hajizadeh Mohammad , Gibbs Adrian J. , Amirnia Fahimeh , Glasa Miroslav
Published: August 2019

The 206 complete genomic sequences ofPlum pox virusin GenBank (January 2019) were downloaded. Their main open reading frames (ORF)s were compared by phylogenetic and population genetic methods. All fell into the nine previously recognized strain clusters; the PPV-Rec and PPV-T strain ORFs were all recombinants, whereas most of those in the PPV-C, PPV-CR, PPV-CV, PPV-D, PPV-EA, PPV-M and PPV-W strain clusters were not. The strain clusters ranged in size from 2 (PPV-CV and PPV-EA) to 74 (PPV-D). The isolates of eight of the nine strains came solely from Europe and the Levant (with an exception resulting from a quarantine breach), but many PPV-D strain isolates also came from east and south Asia and the Americas. The estimated time to the most recent common ancestor (TMRCA) of all 134 non-recombinant ORFs was 820 (865–775) BCE. Most strain populations were only a few decades old, and had small intra-strain, but large inter-strain, differences; strain PPV-W was the oldest. Eurasia is clearly the ‘centre of emergence’ of PPV and the several PPV-D strain populations found elsewhere only show evidence of gene flow with Europe, so have come from separate introductions from Europe. All ORFs and their individual genes show evidence of strong negative selection, except the positively selectedpipogene of the recently migrant populations. The possible ancient origins of PPV are discussed.
Why Westerners Are Dissatisfied: A Cross-Sectional Study Identifying State-Level Factors Associated with Variation in Private Health Insurance Satisfaction
Authors: McLeod Megan , Berinstein Jeffrey A. , Steiner Calen A. , Cushing Kelly , Cohen Mekelburg Shirley A. , Higgins Peter D.R.
Published: August 2019

Importance

Large regional variations in consumer satisfaction with private health insurance plans have been observed, but the factors driving this variation are unknown.

Objective

To identify explanatory state-level and insurance family-level predictors of satsifaction with private health insurance.

Design

Cross-sectional study examining regional and state variations in consumer health insurance plan satisfaction using National Committee for Quality Assurance data from 2015 to 2018, state-level health data and parent insurance family.

Setting

US Population

Participants

Privately insured individuals.

Exposure

One of 2176 private health insurance plans.

Main Outcome

Consumer satisfaction with the health insurance plan on a 0-5 scale.

RESULTS

Consumer satisfaction with health insurance was consistently lowest in the West (p<0.0001). Lower private health insurance plan satisfaction was associated with the percentage of the population without a place of usual medical care, the percentage of the state population that is Hispanic, and the percentage of the population reporting any mental illness. Factors associated with increasing insurance satisfaction included higher healthcare spending per capita, a higher number of for-profit beds per capita, and an increased cancer death rate. Increased consumer satisfaction was associated with the Kaiser and Anthem insurance plan families.

Conclusions and Relevance

State and insurer family factors are predictive of private health insurance plan satisfaction. Potentially modifiable factors include access to primary care, healthcare spending per capita, and numbers of for-profit hospital beds. This information will help consumers hold insurance providers accountable to provide higher quality and more desirable coverage and provide actionable items to improve health insurance satisfaction.
Factors associated with opioid cessation: a machine learning approach
Authors: Cox Jiayi W. , Sherva Richard M. , Lunetta Kathryn L. , Saitz Richard , Kon Mark , Kranzler Henry R. , Gelernter Joel E. , Farrer Lindsay A.
Published: August 2019

Background and Aims

People with opioid use disorder (OUD) can stop using opioids on their own, with help from groups and with treatment, but there is limited research on the factors that influence opioid cessation.

Methods

We employed multiple machine learning prediction algorithms (LASSO, random forest, deep neural network, and support vector machine) to assess factors associated with ceasing opioid use in a sample comprised of African Americans (AAs) and European Americans (EAs) who met DSM-5 criteria for mild to severe OUD. Values for several thousand demographic, alcohol and other drug use, general health, and behavioral variables, as well as diagnoses for other psychiatric disorders, were obtained for each participant from a detailed semi-structured interview.

Results

Support vector machine models performed marginally better on average than those derived using other machine learning methods with maximum prediction accuracies of 75.4% in AAs and 79.4% in EAs. Subsequent stepwise regression analyses that considered the 83 most highly ranked variables across all methods and models identified less recent cocaine use (p<5×10−8), a shorter duration of opioid use (p<5×10−6), and older age (p<5×10−9) as the strongest independent predictors of opioid cessation. Factors related to drug use comprised about half of the significant independent predictors, with other predictors related to non-drug use behaviors, psychiatric disorders, overall health, and demographics.

Conclusions

These proof-of-concept findings provide information that can help develop strategies for improving OUD management and the methods we applied provide a framework for personalizing OUD treatment.
Extreme genome selection towards complete antimicrobial resistance in a nosocomial strain ofStenotrophomonas maltophiliacomplex
Authors: Kumar Sanjeet , Bansal Kanika , Patil Prashant P. , Kaur Amandeep , Kaur Satinder , Gautam Vikas , Patil Prabhu B.
Published: August 2019

We report first complete genome sequence and analysis of an extreme drug resistance (XDR) nosocomialStenotrophomonas maltophiliathat is resistant to the mainstream drugs i.e. trimethoprim/sulfamethoxazole (TMP/SXT) and levofloxacin. Taxonogenomic analysis revealed it to be a novel genomospecies of theStenotrophomonas maltophiliacomplex (Smc). Comprehensive genomic investigation revealed fourteen dynamic regions (DRs) exclusive to SM866, consisting of diverse antibiotic resistance genes, efflux pumps, heavy metal resistance, various transcriptional regulators etc. Further, resistome analysis of Smc clearly depicted SM866 to be an enriched strain, having diversified resistome consisting ofsul1andsul2genes. Interestingly, SM866 does not have any plasmid but it harbors two diverse super-integrons of chromosomal origin. Apart from genes for sulfonamide resistance (sul1andsul2), both of these integrons harbor an array of antibiotic resistance genes linked to ISCR (IS91-like elements common regions) elements. These integrons also harbor genes encoding resistance to commonly used disinfectants like quaternary ammonium compounds and heavy metals like mercury. Hence, isolation of a novel strain belonging to a novel sequence type (ST) and genomospecies with diverse array of resistance from a tertiary care unit of India indicates extent and nature of selection pressure driving XDRs in hospital settings. There is an urgent need to employ complete genome based investigation using emerging technologies for tracking emergence of XDR at the global level and designing strategies of sanitization and antibiotic regime.

Impact Statement

The hospital settings in India have one of the highest usage of antimicrobials and heavy patient load. Our finding of a novel clinical isolate ofS. maltophiliacomplex with two super-integrons harbouring array of antibiotic resistance genes along with antimicrobials resistance genes indicates the extent and the nature of selection pressures in action. Further, the presence of ISCR type of transposable elements on both integrons not only indicates its propensity to transfer resistome but also their chromosomal origin suggests possibilities for further genomic/phenotypic complexities. Such complex cassettes and strain are potential threat to global health care. Hence, there is an urgent need to employ cost-effective long read technologies to keep vigilance on novel and extreme antimicrobial resistance pathogens in populous countries. There is also need for surveillance for usage of antimicrobials for hygiene and linked/rapid co-evolution of extreme drug resistance in nosocomial pathogens. Our finding of the chromosomal encoding XDR will shed a light on the need of hour to understand the evolution of an opportunistic nosocomial pathogen belonging toS. maltophilia.

Repositories

Complete genome sequence ofStenotrophomonas maltophiliaSM866: CP031058
Low FoxO expression inDrosophilasomatosensory neurons protects dendrite growth under nutrient restriction
Authors: Poe Amy R. , Xu Yineng , Zhang Christine , Li Kailyn , Labib David , Han Chun
Published: August 2019

During prolonged nutrient restriction, developing animals redistribute vital nutrients to favor brain growth at the expense of other organs. InDrosophila, such brain sparing relies on a glia-derived growth factor to sustain proliferation of neural stem cells. However, whether other aspects of neural development are also spared under nutrient restriction is unknown. Here we show that dynamically growing somatosensory neurons in theDrosophilaperipheral nervous system exhibit organ sparing at the level of arbor growth: Under nutrient stress, sensory dendrites preferentially grow as compared to neighboring non-neural tissues, resulting in dendrite overgrowth. Underlying this neuronal nutrient-insensitivity is the lower expression of the stress sensor FoxO in neurons. Consequently, nutrient restriction suppresses Tor signaling less and does not induce autophagy in neurons. Preferential dendrite growth is functional desirable because it results in heightened animal responses to sensory stimuli, indicative of a potential survival advantage under environmental challenges.
Gene copy number is associated with phytochemistry inCannabis sativa
Authors: Vergara Daniela , Huscher Ezra L. , Keepers Kyle G. , Givens Robert M. , Cizek Christian G. , Torres Anthony , Gaudino Reggie , Kane Nolan C.
Published: August 2019

Gene copy number variation is known to be important in nearly every species where it has been examined. Alterations in gene copy number may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species.Cannabis sativaplants produce a distinguishing set of secondary metabolites, the cannabinoids, many having medicinal utility. Two major cannabinoids -- THCA and CBDA -- are products of a three-step biochemical pathway. Using genomic data for 69Cannabiscultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in copy number, and that the cannabinoid paralogs may be differentially expressed. We also found that copy number partially explains variation in cannabinoid content levels amongCannabisplants.
Berberine delays onset of collagen induced arthritis through T cell suppression
Authors: Vita Alexandra A. , Aljobaily Hend , Lyons David O. , Pullen Nicholas A.
Published: August 2019

Previous evidence suggests that berberine (BBR), a clinically relevant plant-derived alkaloid, alleviates symptoms of clinically apparent collagen induced arthritis (CIA), and may have a prophylactic role fromin vitrostudies. Thus, we used a CIA model to determine if BBR merits further exploration as a prophylactic treatment for rheumatoid arthritis. Mice were treated with either 1 mg/kg/day of BBR or a vehicle (PBS) control via IP injections from day 0 to day 28, were left untreated (CIA control), or were in a non-arthritic control group. Incidence of arthritis in BBR mice was 40%, compared to 90% in the CIA and 80% in the PBS controls. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from mice across treatment groups on day 14 and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. BBR-treated mice had significantly reduced populations of CD4+T cells, CXCR5+Tfhcells, and an increased proportion of Tregat both day 14 and day 28 endpoints, as well as decreased CD28+and CD154+CD4+T cells at day 14. BBR-treated mice also experienced a significant reduction of CD19+B cells in LNs at day 28. Additionally, BBR treatment resulted in significantly lower anti-collagen type II-specific (anti-CII) IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement, and that its effect may be mediated through T cell suppression, which indirectly affects B cell activity.
Measuring Perceptual Distance of Organismal Color Pattern using the Features of Deep Neural Networks
Authors: Wham Drew C. , Ezray Briana , Hines Heather M.
Published: August 2019

A wide range of research relies upon the accurate and repeatable measurement of the degree to which organisms resemble one another. Here, we present an unsupervised workflow for analyzing the relationships between organismal color patterns. This workflow utilizes several recent advancements in deep learning based computer vision techniques to calculate perceptual distance. We validate this approach using previously published datasets surrounding diverse applications of color pattern analysis including mimicry, population differentiation, heritability, and development. We demonstrate that our approach is able to reproduce the biologically relevant color pattern relationships originally reported in these studies. Importantly, these results are achieved without any task-specific training. In many cases, we were able to reproduce findings directly from original photographs or plates with minimum standardization, avoiding the need for intermediate representations such as a cartoonized images or trait matrices. We then present two artificial datasets designed to highlight how this approach handles aspects of color patterns, such as changes in pattern location and the perception of color contrast. These results suggest that this approach will generalize well to support the study of a wide range of biological processes in a diverse set of taxa while also accommodating a variety of data formats, preprocessing techniques, and study designs.
Shared neural codes for eye-gaze and valence
Authors: Pryluk Raviv , Shohat Yosef , Morozov Anna , Friedman Dafna , Taub Aryeh H. , Paz Rony
Published: August 2019

The eye-gaze of others is a prominent social cue in primates and crucial for communication1-7, and atypical processing occurs in several conditions as autism-spectrum-disorder (ASD)1,9-14. The neural mechanisms that underlie eye-gaze remain vague, and it is still debated if these computations developed in dedicated neural circuits or shared with non-social elements. In many species, eye-gaze signals a threat and elicits anxiety, yet can also serve as a predictor for the outcome of the encounter: negative or positive2,4,8. Here, we hypothesized and find that neural codes overlap between eye-gaze and valence. Monkeys participated in a modified version of the human-intruder-test8,15 that includes direct and averted eye-gaze and interleaved with blocks of aversive and appetitive conditioning16,17. We find that single-neurons in the amygdala encode gaze18, whereas neurons in the anterior-cingulate-cortex encode the social context19,20 but not gaze. We identify a shared amygdala circuitry where neural responses to averted and direct gaze parallel the responses to appetitive and aversive value, correspondingly. Importantly, we distinguish two shared coding mechanisms: a shared-intensity scheme that is used for gaze and the unconditioned-stimulus, and a shared-activity scheme that is used for gaze and the conditioned-stimulus. The shared-intensity points to overlap in circuitry, whereas the shared-activity requires also correlated activity. Our results demonstrate that eye-gaze is coded as a signal of valence, yet also as the expected value of the interaction. The findings may suggest new insights into the mechanisms that underlie the malfunction of eye-gaze in ASD and the comorbidity with impaired social skills and anxiety.
A CRISPR-based method for measuring the essentiality of a gene
Authors: You Yan , Ramachandra Sharmila G. , Jin Tian
Published: August 2019

The CRISPR/Cas9 system is a powerful method of editing genes by randomly introducing errors into the target sites. Here, we describe a CRISPR-based test for gene essentiality (CRISPR-E test) that allows the identification of essential genes. Specifically, we use sgRNA-mediated CRISPR/Cas9 to target the open reading frame of a gene in the genome and analyze the in-frame (3n) and frameshift (3n+1 and 3n+2) mutations on the target region of the gene in surviving cells. If the gene is non-essential, the cells would carry both in-frame (3n) and frameshift (3n+1 and 3n+2) mutations. In contrast, the cells would carry only in-frame (3n) mutations if the targeted gene is essential, and this selective elimination of frameshift (3n+1 and 3n+2) mutations of the gene indicate its essentiality. As a proof of concept, we have used this CRISPR-E test in the model organism Dictyostelium discoideum to demonstrate that Dync1li1 is an essential gene while KIF1A and fAR1 are not. We further propose a simple method for quantifying the essentiality of a gene using the CRISPR-E test.

One Sentence Summary

CRISPR-E measures a gene’s essentiality
Motor-mediated clustering at microtubule plus ends facilitates protein transfer to a bio-mimetic cortex
Authors: Taberner Núria , Dogterom Marileen
Published: August 2019

Polarized protein distributions at the cortex play an important role in the spatial organization of cells. In S. pombe, growing microtubule ends contribute to the establishment and maintenance of such distributions by delivering specific factors to membrane receptors at the poles of the cell. It is however unclear how microtubule plus-end tracking of proteins favours protein accumulation at the cell cortex compared to proteins arriving directly from the cytoplasm. To address this question, we developed an in vitro assay, where microtubules were made to deliver His-tagged plus-end tracking proteins to functionalized microchamber walls. We found that motor-mediated protein clusters formed at microtubule ends were able to transfer to the walls, but non-clustered proteins were not. We further show that this transfer mechanism leads to preferential cluster accumulation at chamber poles, when microtubules are confined to elongated microfabricated chambers with sizes and shapes similar to S. pombe.
ARAD9-dependent cell cycle arrest in response to unresolved recombination intermediates inSaccharomyces cerevisiae
Authors: Kaur Hardeep , Krishnaprasad GN , Lichten Michael
Published: August 2019

InSaccharomyces cerevisiae, the conserved Sgs1-Top3-Rmi1 helicase-decatenase regulates homologous recombination by limiting accumulation of recombination intermediates that are precursors of crossovers.In vitrostudies have suggested that the dissolution of double-Holliday junction joint molecules by Sgs1-driven convergent junction migration and Top3-Rmi1 mediated strand decatenation could be responsible for this. To ask if dissolution occursin vivo, we conditionally depleted Sgs1 and/or Rmi1 during return to growth, a procedure where recombination intermediates formed during meiosis are resolved when cells resume the mitotic cell cycle. Sgs1 depletion during return to growth delayed joint molecule resolution, but ultimately most were resolved and cells divided normally. In contrast, Rmi1 depletion resulted in delayed and incomplete joint molecule resolution, and most cells did not divide.rad9Δmutation restored cell division in Rmi1-depleted cells, indicating that the DNA damage checkpoint caused this cell cycle arrest. Restored cell division inrad9Δ, Rmi1-depleted cells frequently produced anucleate cells, consistent with the suggestion that persistent recombination intermediates prevented chromosome segregation. Our findings indicate that Sgs1-Top3-Rmi1 actsin vivo, as it doesin vitro, to promote recombination intermediate resolution by dissolution. They also indicate that, in the absence of Top3-Rmi1 activity, unresolved recombination intermediates persist and activate the DNA damage response, which is usually thought to be activated by much earlier DNA damage-associated lesions.
Detecting Inversions with PCA in the Presence of Population Structure
Authors: Nowling Ronald J. , Manke Krystal R. , Emrich Scott J.
Published: August 2019

Chromosomal inversions are associated with reproductive isolation and adaptation in insects such as Drosophila melanogaster and the malaria vectors Anopheles gambiae and Anopheles coluzzii. While methods based on read alignment have been useful in humans for detecting inversions, these methods are less successful in insects due to long repeated sequences at the breakpoints. Alternatively, inversions can be detected using principal component analysis (PCA) of single nucleotide polymorphisms (SNPs). We apply PCA-based inversion detection to a simulated data set and real data from multiple insect species, which vary in complexity from a single inversion in samples drawn from a single population to analyzing multiple overlapping inversions occurring in closely-related species, samples of which that were generated from multiple geographic locations. We show empirically that proper analysis of these data can be challenging when multiple inversions or populations are present, and that our alternative framework is more robust in these more difficult scenarios.
Bound-state diffusion due to binding to flexible polymers in a selective biofilter
Authors: Maguire L. , Betterton M. D. , Hough L. E.
Published: August 2019

Selective biofilters are used by cells to control the transport of proteins, nucleic acids, and other macromolecules. Biological filters demonstrate both high specificity and rapid motion or high flux of proteins. In contrast, high flux comes at the expense of selectivity in many synthetic filters. Binding can lead to selective transport in systems in which the bound particle can diffuse, but the mechanisms that lead to bound diffusion remain unclear. Previous theory has proposed a molecular mechanism of bound-state mobility based only on transient binding to flexible polymers. However, this mechanism has not been directly tested in experiments. We demonstrate that bound mobility via tethered diffusion can be engineered into a synthetic gel using protein fragments derived from the nuclear pore complex. The resulting bound-state diffusion is quantitatively consistent with theory. Our results suggest that synthetic biological filters can be designed to to take advantage of tethered diffusion to give rapid, selective transport.

SIGNIFICANCE

Biological filters control the passage of proteins and other macromolecules between compartments of living systems. Determination of molecular mechanisms giving selective transport would enable the design of both selective filters and particles designed to penetrate biological barriers for drug delivery. One such mechanism arises from transient binding to dynamic polymer tethers. We designed a biomaterial which supports this type of tethered diffusion, demonstrating the potential to engineer bio-inspired filters.
Cellular heterogeneity and lineage restriction during mouse digit tip regeneration at single cell resolution
Authors: Johnson Gemma L. , Masias Erick J. , Lehoczky Jessica A.
Published: August 2019

Innate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restricted progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restriction of closely related cell types. In this report we present single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration. We define the differentiation trajectories of vascular, monocytic, and fibroblastic lineages over regeneration, and while our data confirm broad lineage restriction of progenitors, our analysis reveals an early blastema fibroblast population expressing a novel regeneration-specific gene,Mest.