bluuebunny/crossref_metadata_2025 huggingface dataset:
A support vector regression model for time series forecasting of the COMEX copper spot price
Authors: García-Gonzalo Esperanza , García Nieto Paulino José , Gracia Rodríguez Javier , Sánchez Lasheras Fernando , Fidalgo Valverde Gregorio
Published: January 2022

The price of copper is unstable but it is considered an important indicator of the global economy. Changes in the price of copper point to higher global growth or an impending recession. In this work, the forecasting of the spot prices of copper from the New York Commodity Exchange is studied using a machine learning method, support vector regression coupled with different model schemas (recursive, direct and hybrid multi-step). Using these techniques, three different time series analyses are built and its performance are compared. The numerical results show that the hybrid direct-recursive obtains the best results.
Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer
Authors: Wang Xiao-Shan , Bai Yi-Feng , Verma Vivek , Yu Rui-Lian , Tian Wei , Ao Rui , Deng Ying , Zhu Xue-Qiang , Liu Hao , Pan Hai-Xia , Yang Lan , Bai Han-Song , Luo Xing , Guo Yan , Zhou Ming-Xiu , Sun Yue-Mei , Zhang Zi-Can , Li Si-Min , Cheng Xue , Tan Bang-Xian , Han Liang-Fu , Liu Ying-Yi , Zhang Kai , Zeng Fan-Xin , Jia Lin , Hao Xin-Bao , Wang You-Yu , Feng Gang , Xie Ke , Lu You , Zeng Ming
Published: January 2022

Background

Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.

Methods

Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.

Results

A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.

Conclusions

As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Comparison of pretreatment, preservation and determination methods for foliar pH of plant samples
Authors: Liu Sining , Chen Jiashu , Han Wenxuan
Published: January 2022

To compare current methods of pretreatment/determination for plant foliar pH, we proposed a method for long-period sample preservation with little interference with the stability of foliar pH. Four hundred leaf samples from 20 species were collected and four methods of pH determination were used: refrigerated (stored at 4 °C for 4 days), frozen (stored at −16 °C for 4 days), oven-dried and fresh green-leaf pH (control). To explore the effects of different leaf:water mixing ratio on the pH determination results, we measured oven-dried green-leaf pH by leaf:water volume ratio of 1:8 and mass ratio of 1:10, and measured frozen senesced-leaf pH by mass ratio of 1:10 and 1:15. The standard major axis regression was used to analyze the relationship and the conversion equation between the measured pH with different methods. Foliar pH of refrigerated and frozen green leaves did not significantly differ from that of fresh green-leaf, but drying always overrated fresh green-leaf pH. During the field sampling, cryopreservation with a portable refrigerator was an advisable choice to get a precise pH. For long-duration field sampling, freezing was the optimal choice, and refrigeration is the best choice for the short-time preservation. The different leaf:water mixing ratio significantly influenced the measured foliar pH. High dilution reduced the proton concentration and increased the measured pH. Our findings provide the conversion relationships between the existing pretreatment and measurement methods, and establish a connection among pH determined by different methods. Our study can facilitate foliar pH measurement, thus contributing to understanding of this interesting plant functional trait.
Dual control of MAPK activities by AP2C1 and MKP1 MAPK phosphatases regulates defence responses in Arabidopsis
Authors: Ayatollahi Zahra , Kazanaviciute Vaiva , Shubchynskyy Volodymyr , Kvederaviciute Kotryna , Schwanninger Manfred , Rozhon Wilfried , Stumpe Michael , Mauch Felix , Bartels Sebastian , Ulm Roman , Balazadeh Salma , Mueller-Roeber Bernd , Meskiene Irute , Schweighofer Alois
Published: January 2022

Mitogen-activated protein kinase (MAPK) cascades transmit environmental signals and induce stress and defence responses in plants. These signalling cascades are negatively controlled by specific Ser/Thr protein phosphatases of the type 2C (PP2C) and dual-specificity phosphatase (DSP) families that inactivate stress-induced MAPKs; however, the interplay between phosphatases of these different types has remained unknown. This work reveals that different Arabidopsis MAPK phosphatases, the PP2C-type AP2C1 and the DSP-type MKP1, exhibit both specific and overlapping functions in plant stress responses. Each single mutant, ap2c1 and mkp1, and the ap2c1 mkp1 double mutant displayed enhanced stress-induced activation of the MAPKs MPK3, MPK4, and MPK6, as well as induction of a set of transcription factors. Moreover, ap2c1 mkp1 double mutants showed an autoimmune-like response, associated with increased levels of the stress hormones salicylic acid and ethylene, and of the phytoalexin camalexin. This phenotype was reduced in the ap2c1 mkp1 mpk3 and ap2c1 mkp1 mpk6 triple mutants, suggesting that the autoimmune-like response is due to MAPK misregulation. We conclude that the evolutionarily distant MAPK phosphatases AP2C1 and MKP1 contribute crucially to the tight control of MAPK activities, ensuring appropriately balanced stress signalling and suppression of autoimmune-like responses during plant growth and development.
Xyloglucan remodelling enzymes and the mechanics of plant seed and fruit biology
Authors: Steinbrecher Tina , Leubner-Metzger Gerhard
Published: January 2022

This article comments on:

Di Marzo M, Ebeling Viana V, Banfi C, Cassina V, Corti R, Herrera-Ubaldo H, Babolin N, Guazzotti A, Kiegle E, Gregis V, de Folter S, Sampedro J, Mantegazza F, Colombo L, Ezquer I. 2022. Cell wall modifications by α-XYLOSIDASE1 are required for the control of seed and fruit size. Journal of Experimental Botany 73, 1499–1515.
Jasmonic acid is involved in root cell wall phosphorus remobilization through the nitric oxide dependent pathway in rice
Authors: Tao Ye , Huang Jing , Jing Huai Kang , Shen Ren Fang , Zhu Xiao Fang
Published: January 2022

Jasmonic acid (JA) is involved in phosphorus (P) stress in plants, but its underlying molecular mechanisms are still elusive. In this study, we found root endogenous JA content in rice increased under P deficiency (-P), suggesting that JA might participate in P homeostasis in plants. This hypothesis was further confirmed through the addition of exogenous JA (+JA), as this could increase both the root and shoot soluble P content through regulating root cell wall P reutilization. In addition, –P+JA treatment significantly induced the expression of P transporter gene OsPT2, together with increased xylem P content, implying that JA is also important for P translocation from the root to the shoot in P-deficient rice. Furthermore, the accumulation of the molecular signal nitric oxide (NO) was enhanced under –P+JA treatment when compared with –P treatment alone, while the addition of c-PTIO, a scavenger of NO, could reverse the P-deficient phenotype alleviated by JA. Taken together, our results reveal a JA-NO-cell wall P reutilization pathway under P deficiency in rice.
MeJA-responsive bHLH transcription factor LjbHLH7 regulates cyanogenic glucoside biosynthesis in Lotus japonicus
Authors: Chen Cheng , Liu Fu , Zhang Kaixuan , Niu Xiaolei , Zhao Hui , Liu Qiuxu , Georgiev Milen I , Xu Xiaoheng , Zhang Xinquan , Zhou Meiliang
Published: January 2022

Cyanogenic glucosides (CNglcs) play an important role in plant defense response; however, the mechanism of regulation of CNglc synthesis by the external environment and endogenous hormones is largely unclear. In this study, we found that jasmonates (JAs) promoted the synthesis of CNglcs by activating the expression of CNglc biosynthesis genes in Lotus japonicus. Several differentially expressed basic helix–loop–helix (bHLH) family genes related to the synthesis of CNglcs were identified by RNA-seq. LjbHLH7 can directly activate the expression of CYP79D3 gene, the first step of CNglc synthesis, by binding to the G-box sequence of its promoter. Transgenic plants overexpressing LjbHLH7 exhibited higher relative CNglc content and enhanced insect resistance compared with the wild type. Furthermore, the transcriptional activity of LjbHLH7 was suppressed by the interaction with the L. japonicus JASMONATE-ZIM DOMAIN protein LjJAZ4. Based on these results, we propose that LjbHLH7 acts as an activator and LjJAZ4 acts as a repressor of JA-induced regulation of CNglc biosynthesis in L. japonicus.
Charting galactic accelerations – II. How to ‘learn’ accelerations in the solar neighbourhood
Authors: Naik A P , An J , Burrage C , Evans N W
Published: January 2022

Gravitational acceleration fields can be deduced from the collisionless Boltzmann equation, once the distribution function is known. This can be constructed via the method of normalizing flows from data sets of the positions and velocities of stars. Here, we consider application of this technique to the solar neighbourhood. We construct mock data from a linear superposition of multiple ‘quasi-isothermal’ distribution functions, representing stellar populations in the equilibrium Milky Way disc. We show that given a mock data set comprising a million stars within 1 kpc of the Sun, the underlying acceleration field can be measured with excellent, sub-per cent level accuracy, even in the face of realistic errors and missing line-of-sight velocities. The effects of disequilibrium can lead to bias in the inferred acceleration field. This can be diagnosed by the presence of a phase space spiral, which can be extracted simply and cleanly from the learned distribution function. We carry out a comparison with two other popular methods of finding the local acceleration field (Jeans analysis and 1D distribution function fitting). We show our method most accurately measures accelerations from a given mock data set, particularly in the presence of disequilibria.
Time-resolved spectroscopy on the heartbeat state of GRS 1915+105 using AstroSat
Authors: Rawat Divya , Misra Ranjeev , Jain Pankaj , Yadav J S
Published: January 2022

AstroSat spectra of the black hole system GRS 1915+105 during the heartbeat state (with a varying oscillation period from 150 to 100 s) were analysed using a truncated relativistic disc model along with a Comptonization component. Spectra were fitted for segments of length ∼24 s. The oscillation can be described as coordinated variations of the accretion rate, Comptonized flux, and the inner disc radius, with the latter ranging from 1.235 to 5 gravitational radii. Comparison with results from the χ and intermediate states shows that while the accretion rate and the high-energy photon index were similar, the inner disc radius and the fraction of Comptonized photons were larger for these states than for the heartbeat one. The coronal efficiency $\eta \equiv L_{ac}/\dot{M} c^2$, where Lac is the radiative luminosity generated in the corona, is found to be approximately ${\propto}\dot{M}^{-2/3}$ for all the observations. The efficiency decreases with inner radii for the heartbeat state but has similar values for the χ and intermediate states where the inner radii are larger. The implications of these results are discussed.
Multiscale magnetic fields in the central molecular zone: inference from the gradient technique
Authors: Hu Yue , Lazarian A , Wang Q Daniel
Published: January 2022

The central molecular zone (CMZ) plays an essential role in regulating the nuclear ecosystem of our Galaxy. To get an insight into magnetic fields of the CMZ, we employ the gradient technique (GT), which is rooted in the anisotropy of magnetohydrodynamic turbulence. Our analysis is based on the data of multiple wavelengths, including molecular emission lines, radio 1.4 GHz continuum image, and Herschel $70\, {\mu }{\rm m}$ image, as well as ionized [Ne ii] and Paschen-alpha emissions. The results are compared with the observations of Planck 353 GHz and High-resolution Airborne Wideband Camera Plus (HWAC+) $53\, {\mu }{\rm m}$ polarized dust emissions. We map the magnetic fields orientation at multiple wavelength across the central molecular zone, including close-ups of the Radio Arc and Sagittarius A West regions, on multiscales from ∼0.1 pc to 10 pc. The magnetic fields towards the central molecular zone traced by the GT are globally compatible with the polarization measurements, accounting for the contribution from the galactic foreground and background. This correspondence suggests that the magnetic field and turbulence are dynamically crucial in the galactic center. We find that the magnetic fields associated with the Arched filaments and the thermal components of the Radio Arc are in good agree with the HAWC+ polarization. Our measurement towards the non-thermal Radio Arc reveals the poloidal magnetic field components in the galactic center. For Sagittarius A West region, we find a great agreement between the GT measurement using [Ne ii] emission and HWAC+ $53\, {\mu }{\rm m}$ observation. We use the GT to predict the magnetic fields associated with ionized Paschen-alpha gas down to scales of 0.1 pc.
The origin of the high-mass X-ray binary 4U 2206+54/BD+532790
Authors: Hambaryan V , Stoyanov K A , Mugrauer M , Neuhäuser R , Stenglein W , Bischoff R , Michel K-U , Geymeier M , Kurtenkov A , Kostov A
Published: January 2022

Based on the Gaia EDR3 astrometric parameters and our new systemic radial velocity of the high-mass X-ray binary 4U 2206+54/BD+532790, we studied the trace back motion of the system and propose that it originated in the subgroup of the Cepheus OB1 association (Age ∼4–10 Myr) with its brightest star, BD+532820 (B0V; ${\cal L}$∼104.7${\cal L}$⊙). The kinematic age of 4U  2206+54 is about 2.8 ± 0.4 Myr, it is at a distance of 3.1–3.3 kpc and has a space velocity of 75–100 km s−1 with respect to this member star (BD+532820) of the Cep OB1 association. This runaway velocity indicates that the progenitor of the neutron star hosted by 4U 2206+54 lost about 4–9 M⊙ during the supernova explosion and the latter one received a kick velocity of at least 200–350 km s−1 . Since the high-mass X-ray binary 4U 2206+54/BD+532790 was born as a member of a subgroup of Cep OB1, the initially most massive star in the system terminated its evolution within $\lesssim 7-9$ Myr, corresponding to an initial mass $\gtrsim 32$ M⊙.
Cool outflows in MaNGA: a systematic study and comparison to the warm phase
Authors: Avery Charlotte R , Wuyts Stijn , Förster Schreiber Natascha M , Villforth Carolin , Bertemes Caroline , Hamer Stephen L , Sharma Raman , Toshikawa Jun , Zhang Junkai
Published: January 2022

This paper investigates the neutral gas phase of galactic winds via the Na i Dλλ5890, 5895Å feature within z ∼ 0.04 MaNGA galaxies and directly compares their incidence and strength to the ionized winds detected within the same parent sample. We find evidence for neutral outflows in 127 galaxies (∼5 per cent of the analysed line-emitting sample). ${\rm Na\, \small {\rm I}\ D}$ winds are preferentially seen in galaxies with dustier central regions and both wind phases are more often found in systems with elevated star formation rate (SFR) surface densities, especially when there has been a recent upturn in the star formation activity according to the $\rm SFR_{5 \, Myr}/SFR_{800 \, Myr}$ parameter. We find the ionized outflow kinematics to be in line with what we measure in the neutral phase. This demonstrates that, despite their small contributions to the total outflow mass budget, there is value to collecting empirical measurements of the ionized wind phase to provide information on bulk motion in the outflow. Depending on dust corrections applied to the ionized gas diagnostics, the neutral phase has ∼1.2−1.8 dex higher mass outflow rates ($\dot{M}_{\rm out}$), on average, compared to the ionized phase. We quantify scaling relations between $\dot{M}_{\rm out}$ and the strengths of the physical wind drivers (SFR, LAGN). Using a radial–azimuthal stacking method, and by considering inclination dependencies, we find results consistent with biconical outflows orthogonal to the disc plane. Our work complements other multiphase outflow studies in the literature that consider smaller samples, more extreme objects, or proceed via stacking of larger samples.
Compact groups from semi-analytical models of galaxy formation – III. Purity and completeness of Hickson-like catalogues
Authors: Taverna A , Díaz-Giménez E , Zandivarez A , Mamon G A
Published: January 2022

Many catalogues of isolated compact groups of galaxies (CGs) have been extracted using Hickson’s criteria to identify isolated, dense systems of galaxies, with at least three or four galaxies concordant in magnitude and redshift. But is not clear to what extent the catalogues of CGs are complete and reliable, relative to 3D truly isolated, dense groups. Using five different semi-analytical models of galaxy formation (SAMs), we identify isolated dense groups in 3D real space, containing at least three galaxies. We then build mock redshift space galaxy catalogues and run a Hickson-like CG finder. We find that the Hickson-like algorithm in redshift space is poor at recovering 3D CGs of at least three galaxies, with a purity of $\sim 10{{\ \rm per \, cent}}$ and a completeness of $\sim 22{{\ \rm per \, cent}}$. Among the $\sim 90{{\ \rm per \, cent}}$ of spurious systems, typically $60{{\ \rm per\ cent}}$ are dense structures that failed the 3D isolation criteria, while the remaining $40{{\ \rm per \, cent}}$ are chance alignments of galaxies along the line of sight, nearly all of which are within regular groups, with some variation with the SAM used for the analysis. In other words, while only 10 per cent of CGs are isolated dense groups, as intended, half are dense structures embedded within larger groups, and one-third are chance alignments within larger groups. The low completeness of the extracted CG sample is mainly due to the flux limits of the selection criteria. Our results suggest that a new observational algorithm to identify compact groups in redshift space is required to obtain dense isolated galaxy systems.
Mapping the cosmic expansion history from LIGO-Virgo-KAGRA in synergy with DESI and SPHEREx
Authors: Cigarrán Díaz Cristina , Mukherjee Suvodip
Published: January 2022

The measurement of the expansion history of the Universe from the redshift unknown gravitational wave (GW) sources (dark GW sources) detectable from the network of LIGO-Virgo-KAGRA (LVK) detectors depends on the synergy with the galaxy surveys having accurate redshift measurements over a broad redshift range, large sky coverage, and detectability of fainter galaxies.In this work, we explore the possible synergy of the LVK with the spectroscopic galaxy surveys, such as DESI and SPHEREx, to measure the cosmological parameters which are related to the cosmic expansion history and the GW bias parameters. We show that by using the 3D spatial cross-correlation between the dark GW sources and the spectroscopic galaxy samples, we can measure the value of Hubble constant with about $2{{\ \rm per\ cent}}$ and $1.5{{\ \rm per\ cent}}$ precision from LVK+DESI and LVK+SPHEREx, respectively within the 5 yr of observation time with $50{{\ \rm per\ cent}}$ duty-cycle. Similarly, the dark energy equation of state can be measured with about $10{{\ \rm per\ cent}}$ and $8{{\ \rm per\ cent}}$ precision from LVK+DESI and LVK+SPHEREx, respectively. We find that due to the large sky coverage of SPHEREx than DESI, performance in constraining the cosmological parameters is better from the former than the latter. By combining Euclid along with DESI and SPHEREx, a marginal gain in the measurability of the cosmological parameters is possible from the sources at high redshift (z ≥ 0.9).
Decomposition of stellar populations in CosmoDC2 galaxies using SCARLET and Deep Learning
Authors: Kunsági-Máté Sándor , Csabai István
Published: January 2022

We are presenting a novel, Deep Learning based approach to estimate the normalized broad-band spectral energy distribution (SED) of different stellar populations in synthetic galaxies. In contrast to the non-parametric multiband source separation algorithm, SCARLET – where the SED and morphology are simultaneously fitted, in our study we provide a morphology-independent, statistical determination of the SEDs, where we only use the colour distribution of the galaxy. We developed a neural network (sedNN) that accurately predicts the SEDs of the old, red and young, blue stellar populations of realistic synthetic galaxies from the colour distribution of the galaxy-related pixels in simulated broad-band images. We trained and tested the network on a subset of the recently published CosmoDC2 simulated galaxy catalogue containing about 3600 galaxies. The model performance was compared to the results of SCARLET, where we found that sedNN can predict the SEDs with 4–5 per cent accuracy on average, which is about two times better than applying SCARLET. We also investigated the effect of this improvement on the flux determination accuracy of the bulge and disc. We found that using more accurate SEDs decreases the error in the flux determination of the components by approximately 30 per cent.
The first days of Type II-P core collapse supernovae in the gamma-ray range
Authors: Cristofari P , Marcowith A , Renaud M , Dwarkadas V V , Tatischeff V , Giacinti G , Peretti E , Sol H
Published: January 2022

Type II-P supernovæ (SNe), the most common core-collapse SNe type, result from the explosions of red supergiant stars. Their detection in the radio domain testifies of the presence of relativistic electrons, and shows that they are potentially efficient energetic particle accelerators. If hadrons can also be accelerated, these energetic particles are expected to interact with the surrounding medium to produce a gamma-ray signal even in the multi–TeV range. The intensity of this signal depends on various factors, but an essential one is the density of the circumstellar medium. Such a signal should however be limited by electron–positron pair production arising from the interaction of the gamma-ray photons with optical photons emitted by the supernova photosphere, which can potentially degrade the gamma-ray signal by over ten orders of magnitude in the first days/weeks following the explosion. We calculate the gamma-gamma opacity from a detailed modelling of the time evolution of the forward shock and supernova photosphere, taking a full account of the non-isotropy of the photon interactions. We discuss the time-dependent gamma-ray TeV emission from Type II-P SNe as a function of the stellar progenitor radius and mass-loss rate, as well as the explosion energy and mass of the ejected material. We evaluate the detectability of the SNe with the next generation of Cherenkov telescopes. We find that, while most extragalactic events may be undetectable, Type II-P SNe exploding in our Galaxy or in the Magellanic Clouds should be detected by gamma-ray observatories such as the upcoming Cherenkov Telescope Array.
Two evolved close binary stars: GALEX J015054.4+310745 and the central star of the planetary nebula Hen 2-84
Authors: Hillwig Todd C , Reindl Nicole , Rotter Hannah M , Rengstorf Adam W , Heber Ulrich , Irrgang Andreas
Published: January 2022

As part of a survey to find close binary systems among central stars of planetary nebula, we present two newly discovered binary systems. GALEX J015054.4+310745 is identified as the central star of the possible planetary nebula Fr 2-22. We find it to be a single-lined spectroscopic binary with an orbital period of 0.2554435(10) d. We support the previous identification of GALEX J015054.4+310745 as an sdB star and provide physical parameters for the star from spectral modelling. We identify its undetected companion as a likely He white dwarf. Based on this information, we find it unlikely that Fr 2-22 is a true planetary nebula. In addition, the central star of the true planetary nebula Hen 2-84 is found to be a photometric variable, likely due to the irradiation of a cool companion. The system has an orbital period of 0.485645(30) d. We discuss limits on binary parameters based on the available light-curve data. Hen 2-84 is a strongly shaped bipolar planetary nebula, which we now add to the growing list of axially or point-symmetric planetary nebulae with a close binary central star.
The Role of DNA Methylation in Genome Defense in Cnidaria and Other Invertebrates
Authors: Ying Hua , Hayward David C , Klimovich Alexander , Bosch Thomas C G , Baldassarre Laura , Neeman Teresa , Forêt Sylvain , Huttley Gavin , Reitzel Adam M , Fraune Sebastian , Ball Eldon E , Miller David J
Published: January 2022

Considerable attention has recently been focused on the potential involvement of DNA methylation in regulating gene expression in cnidarians. Much of this work has been centered on corals, in the context of changes in methylation perhaps facilitating adaptation to higher seawater temperatures and other stressful conditions. Although first proposed more than 30 years ago, the possibility that DNA methylation systems function in protecting animal genomes against the harmful effects of transposon activity has largely been ignored since that time. Here, we show that transposons are specifically targeted by the DNA methylation system in cnidarians, and that the youngest transposons (i.e., those most likely to be active) are most highly methylated. Transposons in longer and highly active genes were preferentially methylated and, as transposons aged, methylation levels declined, reducing the potentially harmful side effects of CpG methylation. In Cnidaria and a range of other invertebrates, correlation between the overall extent of methylation and transposon content was strongly supported. Present transposon burden is the dominant factor in determining overall level of genomic methylation in a range of animals that diverged in or before the early Cambrian, suggesting that genome defense represents the ancestral role of CpG methylation.
Zinc sequestration by human calprotectin facilitates manganese binding to the bacterial solute-binding proteins PsaA and MntC
Authors: Rosen Tomer , Hadley Rose C , Bozzi Aaron T , Ocampo Daniel , Shearer Jason , Nolan Elizabeth M
Published: January 2022

Zinc is an essential transition metal nutrient for bacterial survival and growth but may become toxic when present at elevated levels. The Gram-positive bacterial pathogen Streptococcus pneumoniae is sensitive to zinc poisoning, which results in growth inhibition and lower resistance to oxidative stress. Streptococcus pneumoniae has a relatively high manganese requirement, and zinc toxicity in this pathogen has been attributed to the coordination of Zn(II) at the Mn(II) site of the solute-binding protein (SBP) PsaA, which prevents Mn(II) uptake by the PsaABC transport system. In this work, we investigate the Zn(II)-binding properties of pneumococcal PsaA and staphylococcal MntC, a related SBP expressed by another Gram-positive bacterial pathogen, Staphylococcus aureus, which contributes to Mn(II) uptake. X-ray absorption spectroscopic studies demonstrate that both SBPs harbor Zn(II) sites best described as five-coordinate, and metal-binding studies in solution show that both SBPs bind Zn(II) reversibly with sub-nanomolar affinities. Moreover, both SBPs exhibit a strong thermodynamic preference for Zn(II) ions, which readily displace bound Mn(II) ions from these proteins. We also evaluate the Zn(II) competition between these SBPs and the human S100 protein calprotectin (CP, S100A8/S100A9 oligomer), an abundant host-defense protein that is involved in the metal-withholding innate immune response. CP can sequester Zn(II) from PsaA and MntC, which facilitates Mn(II) binding to the SBPs. These results demonstrate that CP can inhibit Zn(II) poisoning of the SBPs and provide molecular insight into how S100 proteins may inadvertently benefit bacterial pathogens rather than the host.
Transcription-replication coordination revealed in single live cells
Authors: Tsirkas Ioannis , Dovrat Daniel , Thangaraj Manikandan , Brouwer Ineke , Cohen Amit , Paleiov Zohar , Meijler Michael M , Lenstra Tineke , Aharoni Amir
Published: January 2022

The coexistence of DNA replication and transcription during S-phase requires their tight coordination to prevent harmful conflicts. While extensive research revealed important mechanisms for minimizing these conflicts and their consequences, little is known regarding how the replication and transcription machinery are coordinated in real-time. Here, we developed a live-cell imaging approach for the real-time monitoring of replisome progression and transcription dynamics during a transcription-replication encounter. We found a wave of partial transcriptional repression ahead of the moving replication fork, which may contribute to efficient fork progression through the transcribed gene. Real-time detection of conflicts revealed their negative impact on both processes, leading to fork stalling or slowdown as well as lower transcription levels during gene replication, with different trade-offs observed in defined subpopulations of cells. Our real-time measurements of transcription-replication encounters demonstrate how these processes can proceed simultaneously while maintaining genomic stability, and how conflicts can arise when coordination is impaired.
SLX4 dampens MutSα-dependent mismatch repair
Authors: Guervilly Jean-Hugues , Blin Marion , Laureti Luisa , Baudelet Emilie , Audebert Stéphane , Gaillard Pierre-Henri
Published: January 2022

The tumour suppressor SLX4 plays multiple roles in the maintenance of genome stability, acting as a scaffold for structure-specific endonucleases and other DNA repair proteins. It directly interacts with the mismatch repair (MMR) protein MSH2 but the significance of this interaction remained unknown until recent findings showing that MutSβ (MSH2-MSH3) stimulates in vitro the SLX4-dependent Holliday junction resolvase activity. Here, we characterize the mode of interaction between SLX4 and MSH2, which relies on an MSH2-interacting peptide (SHIP box) that drives interaction of SLX4 with both MutSβ and MutSα (MSH2-MSH6). While we show that this MSH2 binding domain is dispensable for the well-established role of SLX4 in interstrand crosslink repair, we find that it mediates inhibition of MutSα-dependent MMR by SLX4, unravelling an unanticipated function of SLX4.
Liquid Biopsy-based Precision Therapy in Patients with Advanced Solid Tumors: A Real-world Experience from a Community-based Oncology Practice
Authors: Choucair Khalil , Mattar Bassam Ibrahim , Van Truong Quoc , Koeneke Travis , Van Truong Phu , Dakhil Christopher , Cannon Michael W , Page Seth Joel , Deutsch Jeremy Michael , Carlson Eric , Moore Dennis Frederic , Nabbout Nassim H , Kallail K James , Dakhil Shaker R , Reddy Pavan S
Published: January 2022

Background

Liquid biopsy testing offers a significant potential in selecting signal-matched therapies for advanced solid malignancies. The feasibility of liquid biopsy testing in a community-based oncology practice, and its actual impact on selecting signal-matched therapies, and subsequent survival effects have not previously been reported.

Patients and Methods

A retrospective chart review was conducted on adult patients with advanced solid cancer tested with a liquid-biopsy assay between December 2018 and 2019, in a community oncology practice. The impact of testing on treatment assignment and survival was assessed at 1-year follow-up.

Results

A total of 178 patients underwent testing. A positive test was reported in 140/178 patients (78.7%), of whom 75% had an actionable mutation. The actual overall signal-based matching rate was 17.8%. While 85.7% of patients with no actionable mutation had a signal-based clinical trial opportunity, only 10% were referred to a trial. Survival analysis of lung, breast, and colorectal cancer patients with actionable mutations who received any therapy (n = 66) revealed a survival advantage for target-matched (n = 22) compared to unmatched therapy (n = 44): patients who received matched therapy had significantly longer progression-free survival (PFS) (mPFS: 12 months; 95%CI, 10.6-13.4 vs. 5.0 months; 95%CI, 3.4-6.6; P = .029), with a tendency towards longer overall survival (OS) (mOS: 15 months; 95%CI, 13.5-16.5 vs. 13 months; 95%CI: 11.3-14.7; P = .087).

Conclusions

Implementation of liquid biopsy testing is feasible in a US community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched therapies conferred added survival benefits.
Comparing Barriers and Facilitators to Adolescent and Young Adult Clinical Trial Enrollment Across High- and Low-Enrolling Community-Based Clinics
Authors: Siembida Elizabeth J , Loomans-Kropp Holli A , Tami-Maury Irene , Freyer David R , Sung Lillian , Crosswell Howland E , Pollock Brad H , Roth Michael E
Published: January 2022

Background

Adolescent and young adult (AYA) patients with cancer are underrepresented on cancer clinical trials (CCTs), and most AYAs are treated in the community setting. Past research has focused on individual academic institutions, but factors impacting enrollment vary across institutions. Therefore, we examined the patterns of barriers and facilitators between high- and low-AYA enrolling community-based clinics to identify targets for intervention.

Materials and Methods

We conducted 34 semi-structured interviews with stakeholders employed used at National Cancer Institute Community Oncology Research Program (NCORP) affiliate sites (“clinics”). Stakeholders (eg, clinical research associates, patient advocates) were recruited from high- and low-AYA enrolling clinics. We conducted a content analysis and calculated the percentage of stakeholders from each clinic type that reported the barrier or facilitator. A 10% gap between high- and low-enrollers was considered the threshold for differences.

Results

Both high- and low-enrollers highlighted insufficient resources as a barrier and the presence of a patient eligibility screening process as a facilitator to AYA enrollment. High-enrolling clinics reported physician gatekeeping as a barrier and the improvement of departmental collaboration as a facilitator. Low-enrollers reported AYAs’ uncertainty regarding the CCT process as a barrier and the need for increased physician endorsement of CCTs as a facilitator.

Conclusions

High-enrolling clinics reported more barriers downstream in the enrollment process, such as physician gatekeeping. In contrast, low-enrolling clinics struggled with the earlier steps in the CCT enrollment process, such as identifying eligible trials. These findings highlight the need for multi-level, tailored interventions rather than a “one-size-fits-all” approach to improve AYA enrollment in the community setting.
Developmental Traditions in the Study of Persons with Down Syndrome
Authors: Burack Jacob A. , Lai Jessica , Stewart Jillian , Landry Oriane
Published: January 2022

This chapter is focused on two lines of pioneering scholarship that were initiated more than a half century ago but continue to resonate in the contemporary study and understanding of the development of persons with Down syndrome. In one line, Janet Carr followed a cohort of persons with Down syndrome from infancy through well into adulthood and provided data about virtually every aspect of their lives, as well as the lives of their families. In a second line, Edward Zigler articulated a developmental approach to the study of persons with intellectual disability that was expanded by Dante Cicchetti and colleagues to also encompass persons with Down syndrome, and by extension persons with other specific physiological etiologies associated with intellectual disability. Both these lines of work contributed to the revised scholarly and lay narratives about persons with Down syndrome in which the emphasis is on the whole person and ways of being rather than on defects and differences.
Digital Platforms and Antitrust
Authors: Parker Geoffrey , Petropoulos Georgios , Van Alstyne Marshall W.
Published: January 2022

At the heart of economic activity, digital platforms connect multi-sided markets of producers and consumers of various goods and services. Their market power and privileged ecosystem position raise concerns that they may engage in anti-competitive practices that reduce innovation and consumer welfare. This chapter deals with the role of market competition and regulation in addressing these concerns. Traditional (ex post) antitrust intervention will be less effective in markets driven by network effects unless it is combined with a proper (ex ante) regulatory framework. Antitrust tools should focus on value creation and its distribution before focusing on competition. The scope of regulatory intervention should satisfy three criteria: (1) value creation from operation of the platforms does not decrease due to the policy intervention; (2) allocative efficiency is based on distributing the value created in a fair way among market participants; (3) dynamic efficiency and competition ensure that incentives for market misconduct and anti-competitive strategies such as artificial entry barriers are eliminated. Market interventions that target a firm’s market power should ideally retain value creation while also encouraging small firm entry and innovation. Data has a central role in online markets. Value creation is reinforced through a recursive data capture and data deployment feedback loop enabled by machine learning technologies. A regulatory intervention that facilitates data sharing mechanisms, such that data will not only confer value to market leaders but also to their competitors to the benefit of consumers, is crucial for creating more competitive and innovative digital markets.
Charles W. Mills,The Racial Contract
Authors: Marwah Inder S.
Published: January 2022

Charles Mills’ The Racial Contract (TRC) was a landmark intervention that set itself no less a task than raising the topic of race up to mainstream philosophical investigation. As remarkable in its scope as in its perspicacity, the book re-envisions modern political theory by centering its racialized constitution and imbrications in Euro-American practices of racial exploitation. Taking a half-millennium of global white supremacy as its point of departure, it both exposes racial divides encoded within social contractarianism and lays the groundwork for a non-ideal theory of justice, conjoining a penetrating critique of white domination with a methodologically innovative liberalism. This chapter (a) situates TRC’s main arguments within their contexts of emergence, (b) considers certain lines of criticism to which it has been subjected, along with Mills’ adaptations to them, and (c) reflects on its downstream impacts, in terms of Mills’ own trajectory and of the discipline’s grappling with race.
The TGN/EE SNARE protein SYP61 and the ubiquitin ligase ATL31 cooperatively regulate plant responses to carbon/nitrogen conditions in Arabidopsis
Authors: Hasegawa Yoko , Huarancca Reyes Thais , Uemura Tomohiro , Baral Anirban , Fujimaki Akari , Luo Yongming , Morita Yoshie , Saeki Yasushi , Maekawa Shugo , Yasuda Shigetaka , Mukuta Koki , Fukao Yoichiro , Tanaka Keiji , Nakano Akihiko , Takagi Junpei , Bhalerao Rishikesh P , Yamaguchi Junji , Sato Takeo
Published: January 2022

Ubiquitination is a post-translational modification involving the reversible attachment of the small protein ubiquitin to a target protein. Ubiquitination is involved in numerous cellular processes, including the membrane trafficking of cargo proteins. However, the ubiquitination of the trafficking machinery components and their involvement in environmental responses are not well understood. Here, we report that the Arabidopsis thaliana trans-Golgi network/early endosome localized SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein SYP61 interacts with the transmembrane ubiquitin ligase ATL31, a key regulator of resistance to disrupted carbon (C)/nitrogen/(N)-nutrient conditions. SYP61 is a key component of membrane trafficking in Arabidopsis. The subcellular localization of ATL31 was disrupted in knockdown mutants of SYP61, and the insensitivity of ATL31-overexpressing plants to high C/low N-stress was repressed in these mutants, suggesting that SYP61 and ATL31 cooperatively function in plant responses to nutrient stress. SYP61 is ubiquitinated in plants, and its ubiquitination level is upregulated under low C/high N-nutrient conditions. These findings provide important insights into the ubiquitin signaling and membrane trafficking machinery in plants.
Recombinase-mediated gene stacking in cotton
Authors: Li Yamei , Li Ruyu , Han Zhiguo , Wang Haitang , Zhou Sixian , Li Yongqing , Wang Yumei , Qi Junsheng , Ow David W
Published: January 2022

Site-specific gene stacking could reduce the number of segregating loci and expedite the introgression of transgenes from experimental lines to field lines. Recombinase-mediated site-specific gene stacking provides a flexible and efficient solution, but this approach requires a recombinase recognition site in the genome. Here, we describe several cotton (Gossypium hirsutum cv. Coker 312) target lines suitable for Mycobacteriophage Bxb1 recombinase-mediated gene stacking. Obtained through the empirical screening of random insertion events, each of these target lines contains a single intact copy of the target construct with precise sequences of RS2, lox, and attP sites that is not inserted within or close to a known gene or near a centromere and shows good expression of the reporter gene gfp. Gene stacking was tested with insertion of different combinations of three candidate genes for resistance to verticillium wilt into three cotton target lines: CTS1, CTS3, and CTS4. Nine site-specific integration events were recovered from 95 independently transformed embryogenic calluses. Southern and DNA sequence analyses of regenerated plants confirmed precise site-specific integration, and resistance to verticillium wilt was observed for plant CTS1i3, which has a single precise copy of site-specifically integrated DNA. These cotton target lines can serve as foundation lines for recombinase-mediated gene stacking to facilitate precise DNA integration and introgression to field cultivars.
Ethylene response factor MdERF4 and histone deacetylase MdHDA19 suppress apple fruit ripening through histone deacetylation of ripening-related genes
Authors: Hu Yanan , Han Zhenyun , Wang Ting , Li Hua , Li Qiqi , Wang Shuai , Tian Ji , Wang Yi , Zhang Xinzhong , Xu Xuefeng , Han Zhenhai , Lü Peitao , Wu Ting
Published: January 2022

Histone deacetylase enzymes participate in the regulation of many aspects of plant development. However, the genome-level targets of histone deacetylation during apple (Malus domestica) fruit development have not been resolved in detail, and the mechanisms of regulation of such a process are unknown. We previously showed that the complex of ethylene response factor 4 (MdERF4) and the TOPLESS co-repressor (MdTPL4; MdERF4–MdTPL4) is constitutively active during apple fruit development (Hu et al., 2020), but whether this transcriptional repression complex is coupled to chromatin modification is unknown. Here, we show that a histone deacetylase (MdHDA19) is recruited to the MdERF4–MdTPL4 complex, thereby impacting fruit ethylene biosynthesis. Transient suppression of MdHDA19 expression promoted fruit ripening and ethylene production. To identify potential downstream target genes regulated by MdHDA19, we conducted chromatin immunoprecipitation (ChIP) sequencing of H3K9 and ChIP-quantitative polymerase chain reaction assays. We found that MdHDA19 affects ethylene production by facilitating H3K9 deacetylation and forms a complex with MdERF4–MdTPL4 to directly repress MdACS3a expression by decreasing the degree of acetylation. We demonstrate that an early-maturing-specific acetylation H3K9ac peak in MdACS3a and expression of MdACS3a were specifically up-regulated in fruit of an early-maturing, but not a late-maturing, cultivar. We provide evidence that a C-to-G mutation in the ethylene-responsive element binding factor-associated amphiphilic repression motif of MdERF4 reduces the repression of MdACS3a by the MdERF4–MdTPL4–MdHDA19 complex. Taken together, our results reveal that the MdERF4–MdTPL–MdHDA19 repressor complex participates in the epigenetic regulation of apple fruit ripening.
Fixed point structure of the gradient flow exact renormalization group for scalar field theories
Authors: Abe Yoshihiko , Hamada Yu , Haruna Junichi
Published: January 2022

The gradient flow exact renormalization group (GFERG) is a framework for defining the Wilson action via a gradient flow equation. We study the fixed point structure of the GFERG equation associated with a general gradient flow equation for scalar field theories, and show that it is the same as that of the conventional Wilson–Polchinski (WP) equation in general. Furthermore, we see that the GFERG equation has a similar RG flow structure around a fixed point to the WP equation. We illustrate these results with the O(N) non-linear sigma model in 4 − ϵ dimensions and the Wilson–Fisher fixed point.