bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing human and animal antimicrobial usage: a critical appraisal of the indicators used is needed
Authors: Sanders Pim , van Geijlswijk Ingeborg , Bonten Marc , Mughini-Gras Lapo , van Hout Jobke , Heederik Dick
Published: January 2024

Comparisons between antimicrobial usage (AMU) in humans and food-producing animals are regularly made. The accuracy of such comparisons depends on the indicators used to quantify AMU. Indicators for AMU quantitatively relate use data (the numerator) to population data (the denominator). The denominator should be a proxy for the population at risk in a certain period when comparing the exposure of different populations to antimicrobials. Denominators based on numbers of animals slaughtered, such as the commonly used population correction unit, do not consider the time at risk of antimicrobial treatment. Production-based indicators underestimate animal AMU. Additionally, production-based indicators are fundamentally different from indicators used to quantify human AMU. Using such indicators to compare human and animal AMU therefore leads to biased results. More caution should be taken in selecting the indicator to quantify AMU when comparing AMU in food-producing animals and humans.
Bacillus subtilis NBRI-W9 simultaneously activates SAR and ISR against Fusarium chlamydosporum NBRI-FOL7 to increase wilt resistance in tomato
Authors: Yadav Udit , Anand Vandana , Kumar Sanjeev , Verma Isha , Anshu Anshu , Pandey Ishan Alok , Kumar Manoj , Behera Sandip Kumar , Srivastava Suchi , Singh Poonam C
Published: January 2024

Aims

The study aimed to determine the pathogenicity of Fusarium species currently prevalent in tomato fields having history of chemical fungicide applications and determine the bio-efficacy of Bacillus subtilis NBRI-W9 as a potent biological control agent.

Methods and results

Fusarium was isolated from surface-sterilized infected tomato plants collected from fields. Pathogenicity of 30 Fusarium isolates was determined by in vitro and in vivo assays. Following Koch’s postulates, F. chlamydosporum (FOL7) was identified as a virulent pathogen. The biological control of FOL 7 by B. subtilis NBRI-W9 (W9) and the colonization potential of W9 were established using spontaneous rifampicin-resistant mutants. W9 showed 82% inhibition of FOL7 on a dual-culture plate and colonization levels in tomato plants of ∼5.5, ∼3.3, and ∼2.2 log10 CFU/g in root, stem, and leaf tissue, respectively. Antagonistic activity was shown by scanning electron microscopy (SEM) and cell-wall-degradative enzymes. W9 reduced FOL7 infection in net-house and field experiments by 60% and 41%, respectively. Biochemical investigation, defence enzymes, defence gene expression analysis, SEM, and field studies provide evidence of hyperparasitism and induced resistance as the mode of biological control. The study also demonstrates that the potent biocontrol agent W9, isolated from Piper, can colonize tomato plants, control fungal disease by inducing induced systemic resistance (ISR) and systemic acquired resistance (SAR) simultaneously, and increase crop yield by 21.58% under field conditions.

Conclusions

This study concludes that F. chlamydosporum (NBRI-FOL7) is a potent, fungicide-resistant pathogen causing wilt in tomatoes. NBRI-W9 controlled FOL7 through mycoparasitism and simultaneously activated ISR and SAR in plants, providing an attractive tool for disease control that acts at multiple levels.
Production improvement of an antioxidant in cariogenic Streptococcus mutans UA140
Authors: Li Shuyu , Zhang Yuwei , Zong Jianfa , Liu Yufeng , Tang Yue , Lu Jincai , Chen Yihua
Published: January 2024

Aims

This study aimed to improve the production of mutantioxidin, an antioxidant encoded by a biosynthetic gene cluster (mao) in Streptococcus mutans UA140, through a series of optimization methods.

Method and results

Through the construction of mao knockout strain S. mutans UA140∆mao, we identified mutantioxidin as the antioxidant encoded by mao and verified its antioxidant activity through a reactive oxygen species (ROS) tolerance assay. By optimizing the culture medium and fermentation time, 72 h of fermentation in chemically defined medium (CDM) medium was determined as the optimal fermentation conditions. Based on two promoters commonly used in Streptococcus (ldhp and xylS1p), eight promoter refactoring strains were constructed, nevertheless all showed impaired antioxidant production. In-frame deletion and complementation experiments demonstrated the positive regulatory role of mao1 and mao2, on mao. Afterward, the mao1 and mao2, overexpression strain S. mutans UA140/pDL278:: mao1mao2, were constructed, in which the production of mutantioxidin was improved significantly.

Conclusions

In this study, through a combination of varied strategies such as optimization of fermentation conditions and overexpression of regulatory genes, production of mutantioxidin was increased by 10.5 times ultimately.
Differential consumption of malic acid and fructose in apple musts by Pichia kudriavzevii strains
Authors: Mazzucco María Belén , Rodríguez María Eugenia , Catalina Caballero Adriana , Ariel Lopes Christian
Published: January 2024

Aims

To assess the capability of Pichia kudriavzevii strains isolated from wine, cider, and natural environments in North Patagonia to produce ciders with reduced malic acid levels.

Methods and results

Fermentation kinetics and malic acid consumption were assessed in synthetic media and in regional acidic apple musts. All P. kudriavzevii strains degraded malic acid and grew in synthetic media with malic acid as the sole carbon source. Among these strains, those isolated from cider exhibited higher fermentative capacity, mainly due to increased fructose utilization; however, a low capacity to consume sucrose present in the must was also observed for all strains. The NPCC1651 cider strain stood out for its malic acid consumption ability in high-malic acid Granny Smith apple must. Additionally, this strain produced high levels of glycerol as well as acceptable levels of acetic acid. On the other hand, Saccharomyces cerevisiae ÑIF8 reference strain isolated from Patagonian wine completely consumed reducing sugars and sucrose and showed an important capacity for malic acid consumption in apple must fermentations.

Conclusions

Pichia kudriavzevii NPCC1651 strain isolated from cider evidenced interesting features for the consumption of malic acid and fructose in ciders.
Screening of astaxanthin-overproducing Xanthophyllomyces dendrorhous strains via iterative ARTP mutagenesis and cell sorting by flow cytometry
Authors: Ding Ruirui , Huang Ruilin , Su Hang , Li Jiawen , Li Fuli , Wang Shi'an
Published: January 2024

Aims

The astaxanthin-producing yeast Xanthophyllomyces dendrorhous is widely used in aquaculture. Due to the production of carotenoid, this yeast shows visible color; however, high-throughput approaches for identification of astaxanthin-overproducing strains remain rare.

Methods and results

This study verified an effective approach to identify astaxanthin-overproducing mutants of X. dendrorhous by flow cytometry (FCM) and cell sorting. First, the mutant libraries were generated by atmospheric and room-temperature plasma (ARTP) mutagenesis. Second, a highly direct correlation between the concentrations of intracellular astaxanthin and the levels of emitting fluorescence was constructed by testing a variety of astaxanthin-contained populations via FCM and cell sorting. Third, iterative cell sorting efficiently improves the identification of astaxanthin-overproducing strains. Finally, two mutants producing 4.96 mg astaxanthin g−1 DCW (dry cell weight) and 5.30 mg astaxanthin g−1 DCW were obtained, which were 25.3% and 33.8% higher than that of the original strain, respectively.

Conclusions

This study demonstrated that iterative ARTP mutagenesis along with cell sorting by FCM is effective for identifying astaxanthin-overproduction strains.
Biometric contrastive learning for data-efficient deep learning from electrocardiographic images
Authors: Sangha Veer , Khunte Akshay , Holste Gregory , Mortazavi Bobak J , Wang Zhangyang , Oikonomou Evangelos K , Khera Rohan
Published: January 2024

Objective

Artificial intelligence (AI) detects heart disease from images of electrocardiograms (ECGs). However, traditional supervised learning is limited by the need for large amounts of labeled data. We report the development of Biometric Contrastive Learning (BCL), a self-supervised pretraining approach for label-efficient deep learning on ECG images.

Materials and Methods

Using pairs of ECGs from 78 288 individuals from Yale (2000-2015), we trained a convolutional neural network to identify temporally separated ECG pairs that varied in layouts from the same patient. We fine-tuned BCL-pretrained models to detect atrial fibrillation (AF), gender, and LVEF < 40%, using ECGs from 2015 to 2021. We externally tested the models in cohorts from Germany and the United States. We compared BCL with ImageNet initialization and general-purpose self-supervised contrastive learning for images (simCLR).

Results

While with 100% labeled training data, BCL performed similarly to other approaches for detecting AF/Gender/LVEF < 40% with an AUROC of 0.98/0.90/0.90 in the held-out test sets, it consistently outperformed other methods with smaller proportions of labeled data, reaching equivalent performance at 50% of data. With 0.1% data, BCL achieved AUROC of 0.88/0.79/0.75, compared with 0.51/0.52/0.60 (ImageNet) and 0.61/0.53/0.49 (simCLR). In external validation, BCL outperformed other methods even at 100% labeled training data, with an AUROC of 0.88/0.88 for Gender and LVEF < 40% compared with 0.83/0.83 (ImageNet) and 0.84/0.83 (simCLR).

Discussion and Conclusion

A pretraining strategy that leverages biometric signatures of different ECGs from the same patient enhances the efficiency of developing AI models for ECG images. This represents a major advance in detecting disorders from ECG images with limited labeled data.
Sedentary behavior does not predict low BMD nor fracture—population-based Canadian Multicentre Osteoporosis Study
Authors: Guðmundsdóttir Sigríður Lára , Berger Claudie , Macdonald Heather , Adachi Jonathan D , Hopman Wilma M , Kaiser Stephanie M , Kovacs Christopher S , Davison Kenneth Shawn , Morin Suzanne N , Goltzman David ,   CaMos Research Group, Goltzman David , Kreiger Nancy , Tenenhouse Alan , Rahme Elham , Brent Richards J , Morin Suzanne N , Berger Claudie , Joyce Carol , Kovacs Christopher S , Kirkland Susan , Kaiser Stephanie M , Brown Jacques P , Bessette Louis , Anastassiades Tassos P , Towheed Tanveer , Hopman Wilma M , Cheung Angela M , Josse Robert G , Kin On Wong Andy , Adachi Jonathan D , Papaioannou Alexandra , Olszynski Wojciech P , Shawn Davison K , Hanley David A , Boyd Steven K , Prior Jerilynn C , Kalyan Shirin , Lentle Brian , Patel Millan S , Jackson Stuart D , Leslie William D , Prior Jerilynn C
Published: January 2024

Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1–L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture.
First-line nivolumab plus ipilimumab with or without chemotherapy for Japanese patients with non-small cell lung cancer: LIGHT-NING study
Authors: Imai Hisao , Kijima Takashi , Azuma Koichi , Kishi Kazuma , Saito Haruhiro , Yamaguchi Teppei , Tanizaki Junko , Yoneshima Yasuto , Fujita Kohei , Watanabe Satoshi , Kitazono Satoru , Fukuhara Tatsuro , Hataji Osamu , Toi Yukihiro , Mizutani Hideaki , Hamakawa Yusuke , Maemondo Makoto , Ohsugi Tomoyuki , Suzuki Keisuke , Horinouchi Hidehito , Ohe Yuichiro
Published: January 2024

Objective

As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited.

Methods

LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information.

Results

We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0–9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3–4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3–4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2–7.6) and 5.8 (4.3–7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively.

Conclusions

LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings.
Availability of cancer survivorship support services across the National Cancer Institute Community Oncology Research Program network
Authors: Faro Jamie M , Dressler Emily V , Kittel Carol , Beeler Dori M , Bluethmann Shirley M , Sohl Stephanie J , McDonald Andrew M , Weaver Kathryn E , Nightingale Chandylen ,   Landscape Committee, Neuman Heather B , Nightingale Chandylen L , Parsons Susan K , Obeng-Gyasi Samilia , Cooley Mary E , Loh Kah Poh , Ramsey Scott D , McDonald Andrew M , Foust Melyssa , Braun-Inglis Christa , Kyono Wade T , Drescher Charles W , Wood Eden G , Dressler Emily V
Published: January 2024

Background

National cancer organizations recommend provision of nutrition, physical activity, and mental health supportive services to cancer survivors. However, the availability of these services across diverse community oncology settings remains unclear.

Methods

The National Cancer Institute Community Oncology Research Program (NCORP) is a national network of community oncology practices engaged in cancer research. The 2022 NCORP Landscape Assessment (5UG1CA189824) assessed individual practices’ establishment of survivorship clinics and nutrition, physical activity, and mental health services, resources, and/or referrals. Descriptive statistics summarized and logistic regression quantified the association between services, practice, and patient characteristics.

Results

Of 46 NCORP community sites, 45 (98%) responded to the survey, representing 259 adult practice groups. A total of 41% had a survivorship clinic; 96% offered mental health, 94% nutrition, and 53% physical activity services, resources, and/or referrals. All 3 services were offered in various formats (eg, in-house, referrals, education) by 51% and in-house only by 25% of practices. Practices with advanced practice providers were more likely to have a survivorship clinic (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.04 to 9.76). Practices with at least 30% Medicare patients (OR = 2.54, 95% CI = 1.39 to 4.66) and more oncology providers (OR = 1.02, 95% CI = 1.01 to 1.04) were more likely to have all 3 services in any format. Practices with at least 30% Medicare patients (OR = 3.41, 95% CI = 1.50 to 7.77) and a survivorship clinic (OR = 2.84, 95% CI = 1.57 to 5.14) were more likely to have all 3 services in-house.

Conclusions

Larger oncology practices and those caring for more survivors on Medicare provided more supportive services, resources, and/or referrals. Smaller practices and those without survivorship clinics may need strategies to address potential gaps in supportive services.
Noncognitive religious influence and initiation in Tillson’s Children, Religion and the Ethics of Influence
Authors: Wareham Ruth J
Published: January 2024

In Children, Religion and the Ethics of Influence, John Tillson sets out a clear and convincing case for the view that children ought not to be initiated into religious faith by their parents or others with the relevant ‘extra-parental responsibilities’. However, by predicating his thesis on an understanding of illegitimate religious influence that largely equates initiation into faith with the inculcation of a distinctive type of propositional content, I contend that Tillson misses some of the potential harms such initiation may engender. Here I briefly explain why this is a problem before suggesting three ways he might respond to the criticism.
Damping of disco-seismic C-mode oscillations at the sonic radius of discs
Authors: Kato Shoji
Published: January 2024

In a previous paper we have suggested that two-armed disc deformation excites two- or three-armed disco-seismic c-mode oscillations by three-mode resonant coupling processes. This might be one of possible causes of the QPOs observed in low-mass X-ray binaries and in black-hole sources. In another previous paper we showed that for these c-mode oscillations to be time periodic, they must satisfy some boundary conditions (regularity conditions) at the sonic point where accretion speed becomes transonic. In this paper we show that these boundary conditions acts so as to dampen the oscillations. This might be favourable for explaining why the QPOs are quasi-periodic.
A catalogue of Galactic GEMS: Globular cluster Extra-tidal Mock Stars
Authors: Grondin Steffani M , Webb Jeremy J , Lane James M M , Speagle Joshua S , Leigh Nathan W C
Published: January 2024

This work presents the Globular cluster Extra-tidal Mock Star (GEMS) catalogue of extra-tidal stars and binaries created via three-body dynamical encounters in globular cluster cores. Using the particle-spray code Corespray, we sample $N=50\, 000$ extra-tidal stars and escaped recoil binaries for 159 Galactic globular clusters. Sky positions, kinematics, stellar properties, and escape information are provided for all simulated stars. Stellar orbits are integrated in seven different static and time-varying Milky Way gravitational potential models where the structure of the disc, perturbations from the Large Magellanic Cloud and the mass and sphericity of the Milky Way’s dark matter halo are all investigated. We find that the action coordinates of the mock extra-tidal stars are largely Galactic model independent, where minor offsets and broadening of the distributions between models are likely due to interactions with substructure. Importantly, we also report the first evidence for stellar stream contamination by globular cluster core stars and binaries for clusters with pericentre radii larger than five kiloparsecs. Finally, we provide a quantitative tool that uses action coordinates to match field stars to host clusters with probabilities. Ultimately, combining data from the GEMS catalogue with information of observed stars will allow for association of extra-tidal field stars with any Galactic globular cluster; a requisite tool for understanding population-level dynamics and evolution of clusters in the Milky Way.
Uncovering the formation of the counter-rotating stellar discs in SDSS J074834.64+444117.8
Authors: Bao Min , Chen Yanmei , Yang Meng , Zhu Ling , Shi Yong , Gu Qiusheng
Published: January 2024

Using the integral field spectroscopic data from Mapping Nearby Galaxies at Apache Point Observatory survey, we study the kinematics and stellar population properties of the two counter-rotating stellar discs in a nearby galaxy SDSS J074834.64+444117.8. We disentangle the two stellar discs by three methods, including Ca ii λ8542 double Gaussian fit, penalized pixel fitting (pPXF) spectral decomposition, and orbit-based dynamical model. These three different methods give consistent stellar kinematics. The pPXF spectral decomposition provides the spectra of two stellar discs, with one being more luminous across the whole galaxy named primary disc, and the other named secondary disc. The primary disc is counter-rotating with ionized gas, while the secondary disc is co-rotating with ionized gas. The secondary disc has younger stellar population and poorer stellar metallicity than the primary disc. We estimate the stellar mass ratio between the primary and secondary discs to be ∼5.2. The DESI g, r, z colour image does not show any merger remnant feature in this galaxy. These findings support a scenario that the counter-rotating stellar discs in SDSS J074834.64+444117.8 formed through gas accretion from the cosmic web or a gas-rich companion.
Implication of kilometre-scale fluctuations on the MGS radio-occultation-derived electron density profiles: artefacts or ionospheric wave-like structures
Authors: Wan Xin , Zhong Jiahao , Wu Zhaopeng , Hao Yongqiang , Xiong Chao , Wang Hui , He Maosheng , Cui Jun , Liu Yiwen , Li Qiaoling , Kuai Jiawei
Published: January 2024

This study investigates the vertical kilometre-scale fluctuations (KSFs) seen on the Mars Global Surveyor (MGS) radio-occultation (RO)-derived electron density profiles (EDPs) by wavelet spectrum analysis. A delicate five-peak signature is revealed: in the northern polar region near the dawn–dusk terminator, the amplitudes of the KSF peak at fixed altitudes with a constant separation of approximately 28 km. The feature could not be noticed on a single EDP; averaging with at least tens of continuously collected EDPs is needed, suggesting that the phenomenon is not instantaneous (time duration of each RO event is ∼7 min), but on a time-scale of days (observation time for tens of continuous RO events). Applying similar background criteria, Mars Atmosphere and Volatile EvolutioN (MAVEN) Radio Occultation Science Experiment derived EDPs could also occasionally capture similar multipeak features, indicating either that it is a natural ionospheric structure or that both MGS and MAVEN suffer the same artefact. The two indications are discussed, and a preliminary hypothesis is raised. A linear superposition with a 28 km standing wave might modulate the amplitude of KSF, and the 28 km standing wave might be associated with the ionospheric buoyancy waves disturbed by the upstream solar wind, while the plasma instabilities might trigger the KSF in the backgrounds of the draped magnetic field and day-to-night neutral winds.
Spin state and convex shape inversion from light curves of fast-rotating asteroids
Authors: Feng Shuai , Hu Shaoming , Chen Xu , Li Yang , Du Junju , Yang Zhitao , Cao Hai , Gan Qingbo , Liu Shuqi , Jiang Yuchen
Published: January 2024

For fast-rotating asteroids, observed light curves could be very different from real light curves due to long exposure time. We present an improved observed light-curve model that accounts for long exposure time often encountered in observations of fast-rotating asteroids. By integrating brightness over time, we derive a more accurate observed light-curve model, allowing for better shape and spin state inversion results. Our analysis demonstrates that the fast-rotating model is more suitable for spin state inversion with longer exposure time, while the Kaasalainen model suffices for shorter exposure time. For spin state and shape inversion, exposure times of approximately 0.4P and 0.2P represent critical thresholds, respectively, beyond which the fast-rotating model exhibits superior performance. Notably, scattering parameters have minimal impact on the shape inversion results. These findings contribute valuable insights to the determination of shape and spin states for fast-rotating asteroids, shedding light on the challenges posed by long exposure time in such investigations.
On an apparent dearth of recurrent nova super-remnants in the Local Group
Authors: Healy-Kalesh M W , Darnley M J , Shara M M
Published: January 2024

The Andromeda Galaxy is home to the annually erupting recurrent nova (RN) M 31N 2008-12a (12a); the first nova found to host a nova super-remnant (NSR). An NSR is an immense structure surrounding a RN, created from many millions of eruptions sweeping up material in the local environment to form a shell tens of parsecs across. Theory has demonstrated that NSRs should be found around all recurrent novae (RNe), even those systems with long periods between eruptions. Befittingly, the second NSR was found around the Galactic classical (and long suspected recurrent) nova, KT Eridani. In this Paper, we aim to find more of these phenomena through conducting the first ever survey for NSRs in M 31 and the Large Magellanic Cloud (LMC). We find that the surroundings of fourteen RNe in M 31 as well as the surroundings of the four RNe in the LMC do not show any evidence of vast parsec-scale structures in narrow-band (H α and $[{\rm S\, {\small II}}]$) images, unlike the one clearly seen around 12a, and therefore conclude that observable NSRs are either rare structures, or they are too faint (or small) to be detected in our existing data sets. Yet, the NSR surrounding 12a would also likely to have been overlooked in our study if it were approximately one magnitude fainter. Searches for NSRs around other RNe ‘masquerading’ as classical novae may prove to be fruitful as would whole surveys of other Local Group galaxies.
The VLBA CANDELS GOODS-North Survey – I. survey design, processing, data products, and source counts
Authors: Deane Roger P , Radcliffe Jack F , Njeri Ann , Akoto-Danso Alexander , Bernardi Gianni , Smirnov Oleg M , Beswick Rob , Garrett Michael A , Jarvis Matt J , Whittam Imogen H , Bourke Stephen , Paragi Zsolt
Published: January 2024

The past decade has seen significant advances in wide-field cm-wave very long baseline interferometry (VLBI), which is timely given the wide-area, synoptic survey-driven strategy of major facilities across the electromagnetic spectrum. While wide-field VLBI poses significant post-processing challenges that can severely curtail its potential scientific yield, many developments in the km-scale connected-element interferometer sphere are directly applicable to addressing these. Here we present the design, processing, data products, and source counts from a deep (11 μJy beam−1), quasi-uniform sensitivity, contiguous wide-field (160 arcmin2) 1.6 GHz VLBI survey of the CANDELS GOODS-North field. This is one of the best-studied extragalactic fields at milli-arcsecond resolution and, therefore, is well-suited as a comparative study for our Tera-pixel VLBI image. The derived VLBI source counts show consistency with those measured in the COSMOS field, which broadly traces the AGN population detected in arcsecond-scale radio surveys. However, there is a distinctive flattening in the S1.4GHz ∼100–500 μJy flux density range, which suggests a transition in the population of compact faint radio sources, qualitatively consistent with the excess source counts at 15 GHz that is argued to be an unmodelled population of radio cores. This survey approach will assist in deriving robust VLBI source counts and broadening the discovery space for future wide-field VLBI surveys, including VLBI with the Square Kilometre Array, which will include new large field-of-view antennas on the African continent at ≳1000 km baselines. In addition, it may be useful in the design of both monitoring and/or rapidly triggered VLBI transient programmes.
X-ray variability of SDSS quasars based on the SRG/eROSITA all-sky survey
Authors: Prokhorenko S A , Sazonov S Yu , Gilfanov M R , Balashev S A , Bikmaev I F , Ivanchik A V , Medvedev P S , Starobinsky A A , Sunyaev R A
Published: January 2024

We examine the long-term (rest-frame time-scales from a few months to ∼20 yr) X-ray variability of a sample of 2344 X-ray bright quasars from the Sloan Digital Sky Survey (SDSS) data release 14 quasar (DR14Q) catalogue, based on the data of the Spectrum-Roentgen-Gamma (SRG)/eROSITA All-Sky Survey complemented for ∼7 per cent of the sample by archival data from the XMM–Newton Serendipitous Source Catalogue. We characterize variability by a structure function, SF2(Δt). We confirm the previously known anticorrelation of the X-ray variability amplitude with luminosity. We also study the dependence of X-ray variability on black hole mass, MBH, and on an X-ray-based proxy of the Eddington ratio, λX. Less massive black holes prove to be more variable for given Eddington ratio and time-scale. X-ray variability also grows with decreasing Eddington ratio and becomes particularly strong at λX of less than a few per cent. We confirm that the X-ray variability amplitude increases with increasing time-scale. The SF2(Δt) dependence can be satisfactorily described by a power law, with the slope ranging from ∼0 to ∼0.4 for different (MBH, λX) subsamples (except for the subsample with the lowest black hole mass and Eddington ratio, where it is equal to 1.1 ± 0.4).
Two-dimensional kinematics and dynamical modelling of the ‘Jackpot’ gravitational lens from deep MUSE observations
Authors: Turner Hannah C , Smith Russell J , Collett Thomas E
Published: January 2024

We present results from the first spatially resolved kinematic and dynamical modelling analysis of the unique SDSSJ0946+1006 (‘Jackpot’) triple-source lens system, where a single massive foreground $z\, =\, 0.222$ galaxy multiple-images three background sources at different redshifts. Deep integral field unit spectroscopic data were obtained using the MUSE instrument on the VLT, which, compared to previous single-slit observations, provides full azimuthal area coverage, high sensitivity (5 h integration) and high angular resolution (0.5 arcsec full width at half-maximum). To account for the strong continuum contributions from the $z\, =\, 0.609$ source, a multiple-component stellar template fitting technique is adopted to fit to the spectra of both the lens galaxy and the bright lensed background arc simultaneously. Through this, we robustly measure the first and second moments of the 2D stellar kinematics out to about 10 kpc from the centre of the lens, as well as resolving the inner profile inwards to ∼1 kpc. The 2D kinematic maps show a steep velocity dispersion gradient and a clear rotational component. We constrain the characteristic properties of the stellar and dark matter (DM) mass components with a sufficiently flexible parametrised dynamical model and an imposed lensing mass and find a DM density slope of $\gamma \, =\, 1.73\substack{+0.17 \\ -0.26}$, i.e. significantly steeper than an unmodified NFW profile ($\gamma \, =\, 1$) and consistent with a contracted DM halo. Our fitted models have a lensing-equivalent density slope of $\eta \, =\, 0.96\pm 0.02$, and thus we confirm most pure lensing results in finding a near isothermal profile for this galaxy.
The variable magnetic field of V889 Her and the challenge of detecting exoplanets around young Suns using Gaussian process regression
Authors: Brown E L , Marsden S C , Jeffers S V , Heitzmann A , Barnes J R , Folsom C P
Published: January 2024

Discovering exoplanets orbiting young Suns can provide insight into the formation and early evolution of our own solar system, but the extreme magnetic activity of young stars obfuscates exoplanet detection. Here we monitor the long-term magnetic field and chromospheric activity variability of the young solar analogue V889 Her, model the activity-induced radial velocity variations, and evaluate the impacts of extreme magnetism on exoplanet detection thresholds. We map the magnetic field and surface brightness for 14 epochs between 2004 and 2019. Our results show potential 3–4 yr variations of the magnetic field that evolves from weak and simple during chromospheric activity minima to strong and complex during activity maxima but without any polarity reversals. A persistent, temporally varying polar spot coexists with weaker, short-lived lower-latitude spots. Due to their different decay time-scales, significant differential rotation, and the limited temporal coverage of our legacy data, we were unable to reliably model the activity-induced radial velocity using Gaussian Process regression. Doppler Imaging can be a useful method for modelling the magnetic activity jitter of extremely active stars using data with large phase gaps. Given our data and using Doppler Imaging to filter activity jitter, we estimate that we could detect Jupiter-mass planets with orbital periods of $\sim$3 d. A longer baseline of continuous observations is the best observing strategy for the detection of exoplanets orbiting highly active stars.
The radio to GeV picture of PSR B1259-63 during the 2021 periastron passage
Authors: Chernyakova M , Malyshev D , van Soelen B , Mc Keague S , O’Sullivan S P , Buckley D
Published: January 2024

PSR B1259-63 is a gamma-ray binary system with a radio pulsar orbiting an O9.5Ve star, LS 2883, with a period of ${\sim} 3.4$ yr. Close to the periastron the system is detected at all wavelengths, from radio to the TeV energies. The emission in this time period is believed to originate from the interaction of LS 2883 and pulsar’s outflows. The observations of four periastra passages taken in 2010–2021 show strong correlation of the radio and X-ray light curves with two peaks just before and after the periastron. The observations of the latest 2021 periastron passage reveal the presence of the 3rd X-ray peak and subsequent disappearance of radio/X-ray flux correlation. In this paper, we present the results of our optical, radio, and X-ray observational campaigns on PSR B1259-63 performed in 2021 accompanied with the analysis of the publicly available GeV Fermi/LAT data. We compare the properties of different periastron passages, discuss the obtained results and show that they can be explained in terms of the 2-zone emission model proposed by us previously.
Diurnal Rhythms in the Red Seaweed Gracilariopsis chorda are Characterized by Unique Regulatory Networks of Carbon Metabolism
Authors: Lee JunMo , Yang Ji Hyun , Weber Andreas P M , Bhattacharya Debashish , Kim Woe-Yeon , Yoon Hwan Su
Published: January 2024

Cellular and physiological cycles are driven by endogenous pacemakers, the diurnal and circadian rhythms. Key functions such as cell cycle progression and cellular metabolism are under rhythmic regulation, thereby maintaining physiological homeostasis. The photoreceptors phytochrome and cryptochrome, in response to light cues, are central input pathways for physiological cycles in most photosynthetic organisms. However, among Archaeplastida, red algae are the only taxa that lack phytochromes. Current knowledge about oscillatory rhythms is primarily derived from model species such as Arabidopsis thaliana and Chlamydomonas reinhardtii in the Viridiplantae, whereas little is known about these processes in other clades of the Archaeplastida, such as the red algae (Rhodophyta). We used genome-wide expression profiling of the red seaweed Gracilariopsis chorda and identified 3,098 rhythmic genes. Here, we characterized possible cryptochrome-based regulation and photosynthetic/cytosolic carbon metabolism in this species. We found a large family of cryptochrome genes in G. chorda that display rhythmic expression over the diurnal cycle and may compensate for the lack of phytochromes in this species. The input pathway gates regulatory networks of carbon metabolism which results in a compact and efficient energy metabolism during daylight hours. The system in G. chorda is distinct from energy metabolism in most plants, which activates in the dark. The green lineage, in particular, land plants, balance water loss and CO2 capture in terrestrial environments. In contrast, red seaweeds maintain a reduced set of photoreceptors and a compact cytosolic carbon metabolism to thrive in the harsh abiotic conditions typical of intertidal zones.
Encyclopedia of Family A DNA Polymerases Localized in Organelles: Evolutionary Contribution of Bacteria Including the Proto-Mitochondrion
Authors: Harada Ryo , Hirakawa Yoshihisa , Yabuki Akinori , Kim Eunsoo , Yazaki Euki , Kamikawa Ryoma , Nakano Kentaro , Eliáš Marek , Inagaki Yuji
Published: January 2024

DNA polymerases synthesize DNA from deoxyribonucleotides in a semiconservative manner and serve as the core of DNA replication and repair machinery. In eukaryotic cells, there are 2 genome-containing organelles, mitochondria, and plastids, which were derived from an alphaproteobacterium and a cyanobacterium, respectively. Except for rare cases of genome-lacking mitochondria and plastids, both organelles must be served by nucleus-encoded DNA polymerases that localize and work in them to maintain their genomes. The evolution of organellar DNA polymerases has yet to be fully understood because of 2 unsettled issues. First, the diversity of organellar DNA polymerases has not been elucidated in the full spectrum of eukaryotes. Second, it is unclear when the DNA polymerases that were used originally in the endosymbiotic bacteria giving rise to mitochondria and plastids were discarded, as the organellar DNA polymerases known to date show no phylogenetic affinity to those of the extant alphaproteobacteria or cyanobacteria. In this study, we identified from diverse eukaryotes 134 family A DNA polymerase sequences, which were classified into 10 novel types, and explored their evolutionary origins. The subcellular localizations of selected DNA polymerases were further examined experimentally. The results presented here suggest that the diversity of organellar DNA polymerases has been shaped by multiple transfers of the PolI gene from phylogenetically broad bacteria, and their occurrence in eukaryotes was additionally impacted by secondary plastid endosymbioses. Finally, we propose that the last eukaryotic common ancestor may have possessed 2 mitochondrial DNA polymerases, POP, and a candidate of the direct descendant of the proto-mitochondrial DNA polymerase I, rdxPolA, identified in this study.
Measurement of chromosomal instability and level of DNA damage in peripheral blood mononuclear cells of endometrial cancer patients
Authors: Marković Aleksandra , Grujičić Darko , Živković Radojević Marija , Milošević-Djordjević Olivera
Published: January 2024

Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries. The aim of this study was to evaluate chromosomal instability and level of DNA damage in peripheral blood mononuclear cells (PBMCs) of newly diagnosed endometrial cancer patients in relation to health status (diagnosis), age, histological grade of cancer, residence, smoking, number of pregnancies, miscarriages, and abortions. The analyzed sample consisted of 60 individuals, 30 endometrial cancer patients with an average age of 64.37 ± 7.08, and 30 healthy control women with an average age of 60.23 ± 11.55. Chromosomal instability was evaluated by the cytokinesis-block micronucleus (CBMN) assay, and the level of DNA damage by the single-cell gel electrophoresis (comet) assay in PBMCs. The average frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) as well as nuclear buds (NBUDs) were significantly higher in cancer patients compared to controls (P < .0005). There was no difference in the nuclear division index (NDI) among the analyzed samples. The comet assay showed that the patients had a significantly increased genetic damage index (GDI) compared with controls (P < .0005). Using linear regression analysis, we found that health status (diagnosis) had the strongest influence on the MN frequency as well as GDI (P < .0005). Our results indicated that there is a high level of genetic damage in both the level of DNA and the level of chromosomes in the PBMCs of newly diagnosed patients with endometrial cancer, where the frequency and level of damage were significantly affected by health status, grade of cancer, residence, number of pregnancies, miscarriages, and abortions.
Geno2pheno: recombination detection for HIV-1 and HEV subtypes
Authors: Pirkl Martin , Büch Joachim , Friedrich Georg , Böhm Michael , Turner Dan , Degen Olaf , Kaiser Rolf , Lengauer Thomas
Published: January 2024

Even after three decades of antiretroviral therapy for HIV-1 (human immunodeficiency virus 1), therapy failure is a continual challenge. This is especially so if the viral variant is a recombinant of subtypes. Thus, improved diagnosis of recombined subtypes can help with the selection of therapy. We are using a new implementation of the previously published computational method recco to detect de novo recombination of known subtypes, independent of and in addition to known circulating recombinant forms (CRFs). We detect an optimal path in a multiple alignment of viral reference sequences based on mutation calls and probable breakpoints for recombination. A tuning parameter is used to favor either mutation calls or breakpoints. Besides novel recombinants, our tool g2p-recco integrated in the geno2pheno web service (https://geno2pheno.org) can successfully detect known recombinant events given only the full consensus references (without CRFs) of the involved subtypes with breakpoints. In addition, the tool can be applied to other viruses, i.e. hepatitis E virus (HEV). In this fashion, we could also detect several previously unknown recombinations in HEV.
Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes
Authors: Dankner Matthew , Maritan Sarah M , Priego Neibla , Kruck Georgia , Nkili-Meyong Andriniaina , Nadaf Javad , Zhuang Rebecca , Annis Matthew G , Zuo Dongmei , Nowakowski Alexander , Biondini Marco , Kiepas Alexander , Mourcos Caitlyn , Le Phuong , Charron François , Inglebert Yanis , Savage Paul , Théret Louis , Guiot Marie-Christine , McKinney R Anne , Muller William J , Park Morag , Valiente Manuel , Petrecca Kevin , Siegel Peter M
Published: January 2024

Background

Compared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether the BrM invasion pattern is influenced by pSTAT3+ RAs and may serve as a predictive biomarker for STAT3 inhibition.

Methods

We used immunohistochemistry to identify pSTAT3+ RAs in HI and MI human and patient-derived xenograft (PDX) BrM. Using PDX, syngeneic, and transgenic mouse models of HI and MI BrM, we assessed how pharmacological STAT3 inhibition or RA-specific STAT3 genetic ablation affected BrM growth in vivo. Cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay. We performed single-cell RNA sequencing of human BrM and adjacent brain tissue.

Results

RAs expressing pSTAT3 are situated at the brain–tumor interface and drive BrM invasive growth. HI BrM invasion pattern was associated with delayed growth in the context of STAT3 inhibition or genetic ablation. We demonstrate that pSTAT3+ RAs secrete Chitinase 3-like-1 (CHI3L1), which is a known STAT3 transcriptional target. Furthermore, single-cell RNA sequencing identified CHI3L1-expressing RAs in human HI BrM. STAT3 activation, or recombinant CHI3L1 alone, induced cancer cell invasion into the brain parenchyma using a brain slice-tumor plug co-culture assay.

Conclusions

Together, these data reveal that pSTAT3+ RA-derived CHI3L1 is associated with BrM invasion, implicating STAT3 and CHI3L1 as clinically relevant therapeutic targets for the treatment of HI BrM.
Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma
Authors: Patel Kunal S , Tessema Kaleab K , Kawaguchi Riki , Dudley Lindsey , Alvarado Alvaro G , Muthukrishnan Sree Deepthi , Perryman Travis , Hagiwara Akifumi , Swarup Vivek , Liau Linda M , Wang Anthony C , Yong William , Geschwind Daniel H , Nakano Ichiro , Goldman Steven A , Everson Richard G , Ellingson Benjamin M , Kornblum Harley I
Published: January 2024

Background

Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma.

Methods

We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas (n = 5) to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining to validate RNA findings.

Results

Tumor cells in NE regions are enriched in neural progenitor cell-like cellular states, while CE regions are enriched in mesenchymal-like states. NE glioma cells have similar proportions of proliferative and putative glioma stem cells relative to CE regions, without significant differences in % Ki-67 staining. Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Our findings in recurrent GBM paralleled some of the findings in a re-analysis of a dataset from primary GBM. Cell-, gene-, and pathway-level analyses of the tumor microenvironment in the NE region reveal relative downregulation of tumor-mediated neovascularization and cell-mediated immune response, but increased glioma-to-nonpathological cell interactions.

Conclusions

This comprehensive analysis illustrates differing tumor and nontumor landscapes of CE and NE regions in high-grade gliomas, highlighting the NE region as an area harboring likely initiators of recurrence in a pro-tumor microenvironment and identifying possible targets for future design of NE-specific adjuvant therapy. These findings also support the aggressive approach to resection of tumor-bearing NE regions.