bluuebunny/crossref_metadata_2025 huggingface dataset:
Penalised semi-parametric copula method for semi-competing risks data: application to hip fracture in elderly
Authors: Sun Tao , Liang Weijie , Zhang Gongzi , Yi Danhui , Ding Ying , Zhang Lihai
Published: November 2023

Hip fracture is a severe complication in the elderly. The affected people are at a higher risk of second fracture and death occurrence, and the best treatment for hip fractures is still being debated. Aside from the treatment, many factors, such as comorbidity conditions, may be associated with second fracture and death occurrence. This study aims to identify effective treatments and important covariates and estimate their effects on the progression of second fracture and death occurrence in hip fracture elderly patients using the semi-competing risks framework, because death dependently censors a second fracture but not vice versa. Due to the complex semi-competing risks data, performing variable selection simultaneously for second fracture and death occurrence is difficult. We propose a penalised semi-parametric copula method for semi-competing risks data. Specifically, we use separate Cox semi-parametric models for both margins and employ a copula to model the two margins’ dependence. We develop a coordinate-wise optimisation algorithm that takes into account the data structure and copula function’s complexities. Simulations show that the proposed method outperforms the traditional penalised marginal method. We apply the proposed method to a population-based cohort study of hip fracture elderly patients, providing new insights into their treatment and clinical management.
Transcription factor PbMYB80 regulates lignification of stone cells and undergoes RING finger protein PbRHY1-mediated degradation in pear fruit
Authors: Wang Han , Zhang Yingjie , Feng Xiaofeng , Hong Jiayi , Aamir Manzoor Muhammad , Zhou Xinyue , Zhou Qifang , Cai Yongping
Published: November 2023

The Chinese white pear (Pyrus bretschneideri) fruit carries a high proportion of stone cells, adversely affecting fruit quality. Lignin is a main component of stone cells in pear fruit. In this study, we discovered that a pear MYB transcription factor, PbMYB80, binds to the promoters of key lignin biosynthesis genes and inhibits their expression. Stable overexpression of PbMYB80 in Arabidopsis showed that lignin deposition and secondary wall thickening were inhibited, and the expression of the lignin biosynthesis genes in transgenic Arabidopsis was decreased. Transient overexpression of PbMYB80 in pear fruit inhibited lignin metabolism and stone cell development, and the expression of some genes in the lignin metabolism pathway was reduced. In contrast, silencing PbMYB80 with VIGS increased the lignin and stone cell content in pear fruit, and increased expression of genes in the lignin metabolism pathway. By screening a pear fruit cDNA library in yeast, we found that PbMYB80 binds to a RING finger (PbRHY1) protein. We also showed that PbRHY1 exhibits E3 ubiquitin ligase activity and degrades ubiquitinated PbMYB80 in vivo and in vitro. This investigation contributes to a better understanding of the regulation of lignin biosynthesis in pear fruit, and provides a theoretical foundation for increasing pear fruit quality at the molecular level.
The wind of rotating B supergiants – II. The δ-slow hydrodynamic regime
Authors: Venero R O J , Curé M , Puls J , Cidale L S , Haucke M , Araya I , Gormaz-Matamala A , Arcos C
Published: November 2023

The theory of line-driven winds can explain many observed spectral features in early-type stars, though our understanding the winds of B supergiants remains incomplete. The hydrodynamic equations for slowly rotating stellar winds predict two regimes based on the line-force parameter δ: the fast and the δ-slow solution. In this paper, we aim to explore the capability of the latter to explain the observed properties of B supergiant winds. We calculate Hα line profiles, the most sensitive wind diagnostics in the optical, for both fast and δ-slow wind models. We fit them to observed data from a well-studied sample of B supergiants, by adapting the line-force parameters (k, α, and δ) of the hydrodynamic model. Unexpectedly, the observed Hα spectra can be reproduced by both hydrodynamic wind regimes with similar precision. We argue that this similarity results from the similar shape of the normalized velocity law produced by both regimes in the lower, Hα-forming wind region. Our findings raise a dichotomy, because mass-loss rates and terminal velocities (v∞) for each solution are quite different. The δ-slow solution predicts maximum values for v∞ that are systematically lower than those measured in the ultraviolet, whereas the v∞ values of the fast solution are closer, and probably more appropriate. However, our results also indicate that the δ-slow solution might better describe the dense winds of B hypergiants. Multiwavelength analyses and a larger sample of stars are needed to reach a definitive conclusion.
Multiwavelength analysis of Fermi-LAT blazars with high-significance periodicity: detection of a long-term rising emission in PG 1553+113
Authors: Peñil P , Westernacher-Schneider J R , Ajello M , Domínguez A , Buson S , Otero-Santos J , Marcotulli L , Torres−Albà N , Zrake J
Published: November 2023

Blazars display variable emission across the entire electromagnetic spectrum, with time-scales that can range from a few minutes to several years. Our recent work has shown that a sample of five blazars exhibit hints of periodicity with a global significance ${\gtrsim}2\, \sigma$ at γ-ray energies, in the range of 0.1 GeV < E < 800 GeV. In this work, we study their multiwavelength emission, covering the X-ray, ultraviolet, optical, and radio bands. We show that three of these blazars present similar periodic patterns in the optical and radio bands. Additionally, fluxes in the different bands of the five blazars are correlated, suggesting a co-spatial origin. Moreover, we detect a long-term (≈10 yr) rising trend in the light curves of PG 1553+113, and we use it to infer possible constraints on the binary black hole hypothesis.
Microphysical parameter variation in gamma-ray burst stratified afterglows and closure relations: from sub-GeV to TeV observations
Authors: Fraija Nissim , Dainotti Maria G , Betancourt Kamenetskaia Boris , Galván-Gámez Antonio , Aguilar-Ruiz Edilberto
Published: November 2023

Gamma-ray bursts (GRBs) are one of the most exciting sources that offer valuable opportunities for investigating the evolution of energy fraction given to magnetic fields and particles through microphysical parameters during relativistic shocks. The delayed onset of GeV–TeV radiation from bursts detected by the Fermi Large Area Telescope and Cherenkov Telescopes provide crucial information in favour of the external-shock model. Derivation of the closure relations (CRs) and the light curves in external shocks requires knowledge of GRB afterglow physics. In this manuscript, we derive the CRs and light curves in a stratified medium with variations of microphysical parameters of the synchrotron and synchrotron self-Compton (SSC) afterglow model radiated by an electron distribution with a hard and soft spectral index. Using Markov chain Monte Carlo simulations, we apply the current model to investigate the evolution of the spectral and temporal indices of those GRBs reported in the Second Gamma-ray Burst Catalog (2FLGC), which comprises 29 bursts with photon energies above 10 GeV and of those bursts (GRB 180720B, 190114C, 190829A, and 221009A) with energetic photons above 100 GeV, which can hardly be modelled with the CRs of the standard synchrotron scenario. The analysis shows that (i) the most likely afterglow model using synchrotron and SSC emission on the 2FLGC corresponds to the constant-density scenario, and (ii) variations of spectral (temporal) index keeping the temporal (spectral) index constant could be associated with the evolution of microphysical parameters, as exhibited in GRB 190829A and GRB 221009A.
Investigating the multidrifting behaviour of subpulses in PSR J2007 + 0910 with the FAST
Authors: Xu Xin , Shang Lunhua , Zhi Qijun , Dang Shijun , Dai Shi , Tian Jie , Yu Yan , Li Qingying , Xiao Shuo , Zhang Dandan
Published: November 2023

The multidrifting subpulse behaviours in PSR J2007 + 0910 have been studied carefully with the high sensitivity observations of the Five-hundred-meter Aperture Spherical radio Telescope (FAST) at 1250 MHz. We found that there are at least six different single emission modes in PSR J2007 + 0910 are observed, four of which show significant subpulse drifting behaviours (modes A, B, C, and D), and the remaining two (modes E1 and E2) show stationary subpulse structures. The subpulse drifting periods of modes A, B, C, and D are P3,A = 8.7 ± 1.6P, P3,B = 15.8 ± 1.2P, P3,C = 21.6 ± 1.3P, and P3,D = 32.3 ± 0.9P, respectively, where P represents the pulse period of this pulsar. The subpulse separation is almost the same for all modes P2 = 6.01 ± 0.18°. Deep analysis suggests that the appearance and significant changes in the drifting period of multidrifting subpulse emission modes for a pulsar may originate from the aliasing effect. The observed non-drifting modes may be caused by the spark point move with a period ∼P2. Our statistical analysis shows that the drift mode of this pulsar almost always switches from slower to faster drifts in the mode change. The interesting subpulse emission phenomenon of PSR J2007 + 0910 provides a unique opportunity to understand the switching mechanism of multidrift mode.
Unsupervised machine learning classification of Fermi gamma-ray bursts using spectral parameters
Authors: Chen Jia-Ming , Zhu Ke-Rui , Peng Zhao-Yang , Zhang Li
Published: November 2023

A thorough analysis of 2297 gamma-ray bursts (GRBs) in the Fermi catalogue is performed by using unsupervised machine learning algorithms in this paper. In our analysis, for two spectral parameter samples, namely for the peak-flux and time-integrated spectral fits, two dimensionality reduction algorithms, t-distributed stochastic neighbour embedding (t-SNE), and uniform manifold approximation and projection (UMAP), are used to generate four embedding maps; further, K-means algorithm is used for searching for the optimal clustering on the four maps. Our results show that Fermi GRBs can be well separated into two groups. For the time-integrated spectral parameters, both UMAP and t-SNE algorithms classify 372 bursts as short GRBs and 1925 bursts as long GRBs, and 384 bursts as short GRBs and 1913 bursts as long GRBs for the peak-time spectral parameters. This new classification method differs from traditional long and short classifications because it is not based on duration. In addition, it is found that the classification results of 11 GRBs are inconsistent between the integrated and peak-time spectral samples. GRB200826A is the first confirmed short GRB of collapsar origin, and the physical origins of these GRBs may be similar to it.
Not gone with the wind: survival of high-velocity molecular clouds in the galactic centre
Authors: Zhang Mengfei , Li Miao
Published: November 2023

High-velocity atomic clouds in the Galactic centre have attracted significant attention due to their enigmatic formation process, which is potentially linked to the starburst or supermassive black hole activities in the region. Further, the discovery of high-velocity molecular clouds (HVMCs) presents a greater puzzle, because they are much denser and more massive. If the HVMCs were accelerated by the strong activities in the Galactic centre, they are expected to be destroyed before they reach such a high velocity. To shed light on this phenomenon, we perform 3D numerical simulations to investigate the origin and hydrodynamic evolution of HVMCs during a starburst in the Galactic centre. We find that the presence of a magnetic field provides effective protection and acceleration to molecular clouds (MCs) within the galactic winds. Consequently, the MCs can attain latitudes of approximately 1 kpc with velocities around 200 km s−1, consistent with the observed characteristics of HVMCs. The consistency of our findings across a wide parameter space supports the conclusion that HVMCs can indeed withstand the starburst environment in the Galactic centre, providing valuable insights into their survival mechanisms.
Impact of tidal environment on galaxy clustering in GAMA
Authors: Alam Shadab , Paranjape Aseem , Peacock John A
Published: November 2023

We constrain models of the galaxy distribution in the cosmic web using data from the Galaxy and Mass Assembly (GAMA) survey. We model the redshift-space behaviour of the 2-point correlation function (2pcf) and the recently proposed Voronoi volume function (VVF) – which includes information beyond two-point statistics. We extend the standard halo model using extra satellite degrees of freedom and two assembly bias parameters: αcen and αsat, which correlate the occupation numbers of central and satellite galaxies with their host halo’s tidal environment, respectively. We measure $\alpha _{\rm sat}=1.44^{+0.25}_{-0.43}$ and $\alpha _{\rm cen}=-0.79^{+0.29}_{-0.11}$ using a combination of 2pcf and VVF measurements, representing a detection of assembly bias at the 3.3σ (2.4σ) significance level for satellite (central) galaxies. This result remains robust to possible anisotropies in the halocentric distribution of satellites as well as technicalities of estimating the data covariance. We show that the growth rate (fσ8) deduced using models with assembly bias is about 7 per cent (i.e. 1.5σ) lower than if assembly bias is ignored. When projected on to the Ωm–σ8 plane, the model constraints without assembly bias overlap with Planck expectations, while allowing assembly bias introduces significant tension with Planck, preferring either a lower Ωm or a lower σ8. Finally, we find that the all-galaxy weak-lensing signal is unaffected by assembly bias, but the central and satellite sub-populations individually show significantly different signals in the presence of assembly bias. Our results illustrate the importance of accurately modelling galaxy formation for cosmological inference from future surveys.
The H i-rich ultra-diffuse galaxies follow the extended Schmidt law
Authors: Zhai Sai , Shi Yong , Zhang Zhi-Yu , Wang Jun-Zhi , Gao Yu , Gu Qiusheng , Wang Tao , Du Kaiyi , Yu Xiaoling , Li Xin
Published: November 2023

The ${\rm H\, {\small I}}$-rich ultra-diffuse galaxies (HUDGs) offer a unique case for studies of star formation laws as they host low star formation efficiency and low-metallicity environments where gas is predominantly atomic. We collect a sample of six HUDGs in the field and investigate their location in the extended Schmidt law ($\Sigma _{\text{SFR }} \propto \left(\Sigma _{\text{star}}^{0.5} \Sigma _{\text{gas}}\right)^{1.09}$). They are consistent with this relationship well (with deviations of only 1.1σ). Furthermore, we find that HUDGs follow the tight correlation between the hydrostatic pressure in the galaxy mid-plane and the quantity on the x-axis ($\rm log(\Sigma _{star}^{0.5}\Sigma _{gas})$) of the extended Schmidt law. This result indicates that these HUDGs can be self-regulated systems that reach the dynamical and thermal equilibrium. In this framework, the stellar gravity compresses the disc vertically and counteracts the gas pressure in the galaxy mid-plane to regulate the star formation as suggested by some theoretical models.
The physical origins of gas in the circumgalactic medium using observationally motivated TNG50 mocks
Authors: Weng Simon , Péroux Céline , Ramesh Rahul , Nelson Dylan , Sadler Elaine M , Zwaan Martin , Bollo Victoria , Casavecchia Benedetta
Published: November 2023

Absorbers in the spectrum of background objects probe the circumgalactic medium (CGM) surrounding galaxies, but its physical properties remain unconstrained. We use the cosmological hydrodynamical simulation TNG50 to statistically trace the origins of ${\rm H\, {\small I}}$ Ly α absorbers around galaxies at z = 0.5 with stellar masses ranging from 108 to 1011 M⊙. We emulate observational CGM studies by considering all gas within a line of sight velocity range of ±500 kms−1 from the central, to quantitatively assess the impact of other galaxy haloes and overdense gas in the IGM that intersect sightlines. We find that 75 per cent of ${\rm H\, {\small I}}$ absorbers with column densities $\log [N(\mbox{${\rm H\, {\small I}}$})/\rm {cm}^{-2}]\gt 16.0$ trace the central galaxy within ±150 (80) kms−1 of M* = 1010(108) M⊙ central galaxies. The impact of satellites to the total absorber fraction is most significant at impact parameters 0.5Rvir < b < Rvir, and satellites with masses below typical detection limits (M* < 108 M⊙) account for 10 (40) per cent of absorbers that intersect any satellite bound to 1010 and 1011 (109) M⊙ centrals. After confirming outflows are more dominant along the minor axis, we additionally show that at least 20 per cent of absorbers exhibit no significant radial movement, indicating that absorbers can also trace quasi-static gas. Our work shows that determining the stellar mass of galaxies at zabs is essential to constrain the physical origin of the gas traced in absorption, which in turn is key to characterizing the kinematics and distribution of gas and metals in the CGM.
The giant nature of WD 1856 b implies that transiting rocky planets are rare around white dwarfs
Authors: Kipping David
Published: November 2023

White dwarfs (WDs) have roughly Earth-sized radii – a fact long recognized to facilitate the potential discovery of sub-Earth-sized planets via transits, as well as atmospheric characterization including biosignatures. Despite this, the first (and still only) transiting planet discovered in 2020 was a roughly Jupiter-sized world, found using Transiting Exoplanet Survey Satellite (TESS) photometry. Given the relative paucity of giant planets compared to terrestrials indicated by both exoplanet demographics and theoretical simulations (a ‘bottom-heavy’ radius distribution), this is perhaps somewhat surprising. Here, we quantify the surprisingness of this fact accounting for geometric bias and detection bias assuming (1) a bottom-heavy Kepler-derived radius distribution and (2) a top-heavy radial velocity-inspired radius distribution. Both are concerning, with the latter implying that rocky planets are highly unusual and the former implying that WD 1856 b would have to be highly surprising event at the <0.5 per cent level. Using a hierarchical Bayesian model, we infer the implied power-law radius distribution conditioned upon WD 1856 b and arrive at a top-heavy distribution, such that 0.1–2 R⊕ planets are an order-of-magnitude less common than 2–20 R⊕ planets in the period range of 0.1–10 d. The implied hypothesis is that transiting WD rocky planets are rare. We discuss ways to reconcile this with other evidence for minor bodies around WDs, and ultimately argue that it should be easily testable.
Detection of X-ray/UV delay in NGC 4051 using AstroSat observations
Authors: Kumari Kavita , Dewangan G C , Papadakis I E , Singh K P
Published: November 2023

We study the connection between the variations in the far-ultraviolet (FUV), near-ultraviolet (NUV), and X-ray band emission from NGC 4051 using 4 d long AstroSat observations performed during 5–9 June 2016. NGC 4051 showed rapid variability in all three bands with the strongest variability amplitude in the X-ray band ($F_{\mathrm{ var}} \sim 37~{{\ \rm per\ cent}}$) and much weaker variability in the UV bands ($F_{\mathrm{ var}} \sim 3{\!-\!}5~{{\ \rm per\ cent}}$). Cross-correlation analysis performed using interpolated cross-correlation functions and discrete cross-correlation functions revealed a robust correlation (∼0.75) between the UV and X-ray light curves. The variations in the X-ray band are found to lead those in the FUV and NUV bands by ∼7.4 ks and ∼24.2 ks, respectively. The UV lags favour the thermal disc reprocessing model. The FUV and NUV bands are strongly correlated (∼0.9) and the variations in the FUV band lead those in the NUV band by ∼13 ks. Comparison of the UV lags found using the AstroSat observations with those reported earlier and the theoretical model for thermal reverberation timelag suggests a possible change in either the geometry of the accretion disc/corona or the height of the corona.
Infrared spectroscopy of SWIFT J0850.8−4219: identification of the second red supergiant X-ray binary in the Milky Way
Authors: De Kishalay , Daly Fiona A , Soria Roberto
Published: November 2023

High-mass X-ray binaries hosting red supergiant (RSG) donors are a rare but crucial phase in massive stellar evolution, with only one source previously known in the Milky Way. In this letter, we present the identification of the second Galactic RSG X-ray binary SWIFT J0850.8−4219. We identify the source 2MASS 08504008−4211514 as the likely infrared counterpart with a chance coincidence probability ≈5 × 10−6. We present a $1.0{\!-\!}2.5\, \mu$m spectrum of the counterpart, exhibiting features characteristic of late-type stars and an exceptionally strong He i emission line, corroborating the identification. Based on i) the strength of the 12CO(2,0) band, ii) strong CN bandheads and absent TiO bandheads at ≈1.1 µm and iii) equivalent width of the Mg i$1.71\, \mu$m line, we classify the counterpart to be a K3–K5 type RSG with an effective temperature of 3820 ± 100 K, located at a distance of ≈12 kpc. We estimate the source X-ray luminosity to be (4 ± 1) × 1035 erg s−1, with a hard photon index (Γ < 1), arguing against a white dwarf accretor but consistent with a magnetized neutron star in the propeller phase. Our results highlight the potential of systematic near-infrared spectroscopy of Galactic hard X-ray sources in completing our census of the local X-ray binary population.
Metagenomics harvested genus-specific single-stranded DNA-annealing proteins improve and expand recombineering in Pseudomonas species
Authors: Asin-Garcia Enrique , Garcia-Morales Luis , Bartholet Tessa , Liang Zhuobin , Isaacs Farren J , Martins dos Santos Vitor A P
Published: November 2023

The widespread Pseudomonas genus comprises a collection of related species with remarkable abilities to degrade plastics and polluted wastes and to produce a broad set of valuable compounds, ranging from bulk chemicals to pharmaceuticals. Pseudomonas possess characteristics of tolerance and stress resistance making them valuable hosts for industrial and environmental biotechnology. However, efficient and high-throughput genetic engineering tools have limited metabolic engineering efforts and applications. To improve their genome editing capabilities, we first employed a computational biology workflow to generate a genus-specific library of potential single-stranded DNA-annealing proteins (SSAPs). Assessment of the library was performed in different Pseudomonas using a high-throughput pooled recombinase screen followed by Oxford Nanopore NGS analysis. Among different active variants with variable levels of allelic replacement frequency (ARF), efficient SSAPs were found and characterized for mediating recombineering in the four tested species. New variants yielded higher ARFs than existing ones in Pseudomonas putida and Pseudomonas aeruginosa, and expanded the field of recombineering in Pseudomonas taiwanensisand Pseudomonas fluorescens. These findings will enhance the mutagenesis capabilities of these members of the Pseudomonas genus, increasing the possibilities for biotransformation and enhancing their potential for synthetic biology applications.
COLOCdb: a comprehensive resource for multi-model colocalization of complex traits
Authors: Pan Siyu , Kang Hongen , Liu Xinxuan , Li Shuhua , Yang Peng , Wu Mingqiu , Yuan Na , Lin Shiqi , Zheng Qiwen , Jia Peilin
Published: November 2023

Large-scale genome-wide association studies (GWAS) have provided profound insights into complex traits and diseases. Yet, deciphering the fine-scale molecular mechanisms of how genetic variants manifest to cause the phenotypes remains a daunting task. Here, we present COLOCdb (https://ngdc.cncb.ac.cn/colocdb), a comprehensive genetic colocalization database by integrating more than 3000 GWAS summary statistics and 13 types of xQTL to date. By employing two representative approaches for the colocalization analysis, COLOCdb deposits results from three key components: (i) GWAS-xQTL, pair-wise colocalization between GWAS loci and different types of xQTL, (ii) GWAS–GWAS, pair-wise colocalization between the trait-associated genetic loci from GWASs and (iii) xQTL–xQTL, pair-wise colocalization between the genetic loci associated with molecular phenotypes in xQTLs. These results together represent the most comprehensive colocalization analysis, which also greatly expands the list of shared variants with genetic pleiotropy. We expect that COLOCdb can serve as a unique and useful resource in advancing the discovery of new biological mechanisms and benefit future functional studies.
Rapid in situ RNA imaging based on Cas12a thrusting strand displacement reaction
Authors: Cheng Xiaoxue , Li Xiaosong , Kang Yuexi , Zhang Decai , Yu Qiubo , Chen Junman , Li Xinyu , Du Li , Yang Tiantian , Gong Yao , Yi Ming , Zhang Songzhi , Zhu Shasha , Ding Shijia , Cheng Wei
Published: November 2023

RNA In situ imaging through DNA self-assembly is advantaged in illustrating its structures and functions with high-resolution, while the limited reaction efficiency and time-consuming operation hinder its clinical application. Here, we first proposed a new strand displacement reaction (SDR) model (Cas12a thrusting SDR, CtSDR), in which Cas12a could overcome the inherent reaction limitation and dramatically enhance efficiency through energy replenishment and by-product consumption. The target-initiated CtSDR amplification was established for RNA analysis, with order of magnitude lower limit of detection (LOD) than the Cas13a system. The CtSDR-based RNA in situ imaging strategy was developed to monitor intra-cellular microRNA expression change and delineate the landscape of oncogenic RNA in 66 clinic tissue samples, possessing a clear advantage over classic in situ hybridization (ISH) in terms of operation time (1 h versus 14 h) while showing comparable sensitivity and specificity. This work presents a promising approach to developing advanced molecular diagnostic tools.
Structural basis for the allosteric regulation and dynamic assembly of DNMT3B
Authors: Lu Jiuwei , Fang Jian , Zhu Hongtao , Liang Kimberly Lu , Khudaverdyan Nelli , Song Jikui
Published: November 2023

Oligomerization of DNMT3B, a mammalian de novo DNA methyltransferase, critically regulates its chromatin targeting and DNA methylation activities. However, how the N-terminal PWWP and ADD domains interplay with the C-terminal methyltransferase (MTase) domain in regulating the dynamic assembly of DNMT3B remains unclear. Here, we report the cryo-EM structure of DNMT3B under various oligomerization states. The ADD domain of DNMT3B interacts with the MTase domain to form an autoinhibitory conformation, resembling the previously observed DNMT3A autoinhibition. Our combined structural and biochemical study further identifies a role for the PWWP domain and its associated ICF mutation in the allosteric regulation of DNMT3B tetramer, and a differential functional impact on DNMT3B by potential ADD–H3K4me0 and PWWP–H3K36me3 bindings. In addition, our comparative structural analysis reveals a coupling between DNMT3B oligomerization and folding of its substrate-binding sites. Together, this study provides mechanistic insights into the allosteric regulation and dynamic assembly of DNMT3B.
Accumulation of 8-oxodG within the human mitochondrial genome positively associates with transcription
Authors: Scala Giovanni , Ambrosio Susanna , Menna Margherita , Gorini Francesca , Caiazza Carmen , Cooke Marcus S , Majello Barbara , Amente Stefano
Published: November 2023

Mitochondrial DNA (mtDNA) can be subject to internal and environmental stressors that lead to oxidatively generated damage and the formation of 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxodG). The accumulation of 8-oxodG has been linked to degenerative diseases and aging, as well as cancer. Despite the well-described implications of 8-oxodG in mtDNA for mitochondrial function, there have been no reports of mapping of 8-oxodG across the mitochondrial genome. To address this, we used OxiDIP-Seq and mapped 8-oxodG levels in the mitochondrial genome of human MCF10A cells. Our findings indicated that, under steady-state conditions, 8-oxodG is non-uniformly distributed along the mitochondrial genome, and that the longer non-coding region appeared to be more protected from 8-oxodG accumulation compared with the coding region. However, when the cells have been exposed to oxidative stress, 8-oxodG preferentially accumulated in the coding region which is highly transcribed as H1 transcript. Our data suggest that 8-oxodG accumulation in the mitochondrial genome is positively associated with mitochondrial transcription.
Limited Clinical Utility of Routine Mycobacterial Cultures for the Management of Diabetic Foot Infections
Authors: Castellino Laila M , McCormick-Baw Clare , Coye Tyler , Crisologo Peter A , Hanna John J , Lee Francesca , Clark Andrew , Fanning Michael , Killeen Amanda L
Published: November 2023

Mycobacterial infections of the foot and ankle are uncommon. In a cohort of 2340 patients with diabetic foot infection (DFI) in a region with increased prevalence of mycobacterial disease, we identified no clinically significant positive cultures over a 3-year period. Routine mycobacterial culture of DFIs is of limited clinical utility.
H2 supplied via ammonia borane stimulates lateral root branching via phytomelatonin signaling
Authors: Wang Yueqiao , Jin Shanshan , Liu Ziyu , Chen Genmei , Cheng Pengfei , Li Longna , Xu Sheng , Shen Wenbiao
Published: November 2023

A reliable and stable hydrogen gas (H2) supply will benefit agricultural laboratory and field trials. Here, we assessed ammonia borane (AB), an efficient hydrogen storage material used in the energy industry, and determined its effect on plant physiology and the corresponding mechanism. Through hydroponics and pot experiments, we discovered that AB increases tomato (Solanum lycopersicum) lateral root (LR) branching and this function depended on the increased endogenous H2 level caused by the sustainable H2 supply. In particular, AB might trigger LR primordia initiation. Transgenic tomato and Arabidopsis (Arabidopsis thaliana) expressing hydrogenase1 (CrHYD1) from Chlamydomonas reinhardtii not only accumulated higher endogenous H2 and phytomelatonin levels but also displayed pronounced LR branching. These endogenous H2 responses achieved by AB or genetic manipulation were sensitive to the pharmacological removal of phytomelatonin, indicating the downstream role of phytomelatonin in endogenous H2 control of LR formation. Consistently, extra H2 supply failed to influence the LR defective phenotypes in phytomelatonin synthetic mutants. Molecular evidence showed that the phytomelatonin-regulated auxin signaling network and cell-cycle regulation were associated with the AB/H2 control of LR branching. Also, AB and melatonin had little effect on LR branching in the presence of auxin synthetic inhibitors. Collectively, our integrated approaches show that supplying H2 via AB increases LR branching via phytomelatonin signaling. This finding might open the way for applying hydrogen storage materials to horticultural production.
Quantifying leadership in climate negotiations: A social power game
Authors: Bernardo Carmela , Wang Lingfei , Fridahl Mathias , Altafini Claudio
Published: November 2023

We consider complex multistage multiagent negotiation processes such as those occurring at climate conferences and ask ourselves how can an agent maximize its social power, intended as influence over the outcome of the negotiation. This question can be framed as a strategic game played over an opinion dynamics model, in which the action of an agent consists in stubbornly defending its own opinion. We show that for consensus-seeking opinion dynamics models in which the interaction weights are uniform, the optimal action obeys to an early mover advantage principle, i.e. the agents behaving stubbornly in the early phases of the negotiations achieve the highest social power. When looking at data collected from the climate change negotiations going on at the United Nations Framework Convention on Climate Change, we find evidence of the use of the early mover strategy. Furthermore, we show that the social powers computed through our model correlate very well with the perceived leadership roles assessed through independent survey data, especially when non-uniform weights incorporating economical and demographic factors are considered.
Hardiness and baton performance among police student trainees
Authors: Skoglund Tom Hilding , Lie Anders Lohne , Kristian Jakobsen Einar , Risan Patrick
Published: November 2023

Following Kobasa’s seminal description of hardiness in 1979, this psychological construct has attained an increased research focus in law enforcement. The present study adds to this research focus by sampling 156 Norwegian police student trainees to investigate whether trainees’ hardiness levels were related to their performance in a high-stress baton exercise. The Dispositional Resilience Scale-15-R was used to measure hardiness and its three components: commitment, challenge, and control. Baton performance was independently evaluated by two examiners. The results of a regression analysis controlling for age and sex revealed that, among the three components, commitment significantly predicted baton performance. Considerable sex differences were observed in the performance scores, where men outperformed women. An interaction model treating sex as a moderator showed that the commitment prediction was aligned across men and women. In conclusion, police educators should increase their focus on hardiness—especially the commitment component—to facilitate the police student trainees’ operational skill training.
Physical Therapist Interventions to Reduce Headache Intensity, Frequency, and Duration in Patients With Cervicogenic Headache: A Systematic Review and Network Meta-Analysis
Authors: Jung Andres , Carvalho Gabriela F , Szikszay Tibor M , Pawlowsky Vera , Gabler Tom , Luedtke Kerstin
Published: November 2023

Objective

The aim of this study was to assess the efficacy of physical therapist interventions on the intensity, frequency, and duration of headaches, as well as on the quality of life of patients with cervicogenic headache.

Methods

The following databases were searched up to October 2022: Physiotherapy Evidence Database, Web of Science, Pubmed, and Cochrane Library. Randomized controlled trials assessing the effect of physical therapist interventions on adults with cervicogenic headache were included. Quality appraisal was conducted using the Cochrane risk of bias 2.0 tool and the Confidence in Network Meta-analysis web app. Synthesis methods were conducted in accordance with the Cochrane Handbook.

Results

Of the 28 identified reports, 23 were included in the quantitative synthesis. Manipulation plus dry needling was the highest-ranked intervention to reduce the short-term headache intensity (mean difference [MD] = −4.87; 95% CI = −8.51 to −1.24) and frequency (MD = −3.09; 95% CI = −4.93 to −1.25) when compared to a control intervention. Other high-ranked and clinically effective interventions (when compared to a control intervention) were muscle–energy technique plus exercise (MD = 4.37; 95% CI = −8.01 to −0.74), as well as soft tissue techniques plus exercise (MD = −3.01; 95% CI = −5.1 to −0.92) to reduce short-term headache intensity, and dry needling plus exercise (MD = −2.92; 95% CI = −4.73 to −1.11) to reduce short-term headache frequency. These results were based on a low certainty of evidence.

Conclusion

The 4 most highly ranked interventions can be considered in clinical practice. However, no conclusive recommendation can be made due to the low certainty of evidence.

Impact

Combined interventions such as spinal joint manipulation plus dry needling and muscle–energy technique or soft tissue techniques or dry needling plus exercises seem to be the best interventions to reduce short-term cervicogenic headache intensity and/or frequency.
Telehealth Walking Self-Management for Individuals With Amputation: A Qualitative Study of Therapist Perspectives on Adoption
Authors: Swink Laura A , Mealer Meredith L , Miller Matthew J , Anderson Chelsey B , Cook Paul F , Stevens-Lapsley Jennifer E , Christiansen Cory L
Published: November 2023

Objective

The aim of this study was to understand therapist-identified factors influencing clinical adoption of a telehealth walking self-management intervention for individuals with lower limb amputation.

Methods

Semi-structured focus groups were completed with actively practicing physical and occupational therapists treating populations that are medically complex. A qualitative explorative design was employed with conventional content analysis and iterative independent parallel coding using 2 analysts. Themes and subthemes were generated with a consensus building process identifying patterns and collapsing codes to represent participant perspectives.

Results

Thematic saturation was met after 5 focus groups (24 therapists). Therapists were on average 34 years old and predominantly female (n = 19; 79%) physical therapists (n = 17; 71%). Three primary facilitator and barrier themes were identified for intervention adoption: system, therapist, and person. System considerations included telehealth support and interprofessional care coordination. Therapist facilitators included self-management programming that overlapped with standard of care and personalization methods. However, limited behavioral theory training was a therapist level barrier. Finally, person factors such as patient activation could influence both positively and negatively. Person facilitators included social support and barriers included the complex health condition.

Conclusion

System, therapist, and person facilitators and barriers must be considered to maximize the adoption of similar telehealth walking self-management interventions and prior to larger scale implementation of the current intervention for individuals with lower limb amputation.

Impact

A telehealth walking self-management intervention has potential impact for individuals with lower limb amputation and must be considered in terms of optimizing system, therapist, and person level facilitators and barriers to implementation.
Tripping on the edge of consciousness
Authors: Krueger James M
Published: November 2023

Herein the major accomplishments, trials and tribulations, and epiphanies experienced by James M. Krueger over the course of his career in sleep research are presented. They include the characterization of a) the supranormal EEG delta waves occurring during NREMS post sleep loss, b) Factor S as a muramyl peptide, c) the physiological roles of cytokines in sleep regulation, d) multiple other sleep regulatory substances, e) the dramatic changes in sleep over the course of infectious diseases, and f) sleep initiation within small neuronal/glial networks. The theory that the preservation of brain plasticity is the primordial sleep function is briefly discussed. These accomplishments resulted from collaborations with many outstanding scientists including James M. Krueger’s mentors (John Pappenheimer and Manfred Karnovsky) and collaborators later in life, including Charles Dinarello, Louis Chedid, Mark Opp, Ferenc Obal jr., Dave Rector, Ping Taishi, Linda Toth, Jeannine Majde, Levente Kapas, Eva Szentirmai, Jidong Fang, Chris Davis, Sandip Roy, Tetsuya Kushikata, Fabio Garcia-Garcia, Ilia Karatsoreos, Mark Zielinski, and Alok De, plus many students, e.g. Jeremy Alt, Kathryn Jewett, Erika English, and Victor Leyva-Grado.
Metabolic reprograming and increased inflammation by cadmium exposure following early-life respiratory syncytial virus infection: the involvement of protein S-palmitoylation
Authors: Jarrell Zachery R , Lee Choon-Myung , Kim Ki-Hye , He Xiaojia , Smith Matthew R , Raha Jannatul R , Bhatnagar Noopur , Orr Michael , Kang Sang-Moo , Chen Yan , Jones Dean P , Go Young-Mi
Published: November 2023

Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV reprograms metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV reprograms metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/l) in drinking water for 6 weeks (RSV + Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines, and inflammatory cells were highest in the RSV + Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. The BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV + Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target.
Fetoplacental disposition and toxicity of cadmium in mice lacking the Bcrp transporter
Authors: Kozlosky Danielle , Doherty Cathleen , Buckley Brian , Goedken Michael J , Miller Richard K , Huh Dan Dongeun , Barrett Emily S , Aleksunes Lauren M
Published: November 2023

The environmental toxicant cadmium (Cd) impairs the growth of rodents and humans in utero which in turn heightens susceptibility to diseases later in life. We previously demonstrated that the maternal-facing efflux transporter, breast cancer resistance protein (human BCRP/ABCG2, mouse Bcrp/Abcg2) confers resistance against Cd toxicity in human trophoblasts. In the current study, we sought to determine whether the absence of Bcrp alters the fetoplacental disposition and toxicity of Cd in mice. Pregnant female wild-type (WT) and Bcrp-null mice (n = 9–10/group) were administered a single injection of saline (5 ml/kg) or CdCl2 (5 mg/kg) on gestational day (GD) 9. Following Cd treatment, Bcrp-null offspring were shorter and accumulated more Cd in their placentas on GD 17 compared with WT mice. Because Cd can adversely impact placentation and transplacental nutrient delivery in mice, multiple pathways were assessed using morphometrics and immunohistochemistry including placenta zonation, vasculature development, and nutrient transporter expression. Most notably, the placentas of Bcrp-null mice had reduced immunostaining of the cell adhesion marker, β-catenin, and the trophoblast marker, cytokeratin, as well as decreased expression of divalent metal nutrient transporters (Dmt1, Zip14, and ZnT1) following Cd treatment. In summary, the absence of Bcrp expression increased placental concentrations of Cd which was associated with shorter fetal size that may be related to differential changes in molecular patterns of placental development and nutrition.
Mono-(2-ethylhexyl) phthalate reversibly disrupts the blood-testis barrier in pubertal rats
Authors: Tiwary Richa , Richburg John H
Published: November 2023

The blood-testis barrier (BTB) is constituted by tight junctions between adjacent Sertoli cells (SCs) that create a specialized adluminal microenvironment to foster the development of spermatocytes and spermatids. The BTB is a well-studied target of numerous environmental toxicants, including di-(2-ethylhexyl) phthalate (DEHP), a compound widely used in various consumer products. Mono-(2-ethylhexyl) phthalate (MEHP) is the active toxic metabolite of DEHP that has long been recognized in postnatal rodents to disrupt SC function. This study evaluates the impact of MEHP on the integrity of the BTB in both pubertal and adult rats and the signal transduction pathways known to be involved in the disruption of the BTB. Treatment of prepubertal rats with 700 mg/kg MEHP for 24 h functionally disrupted the BTB integrity. A similar treatment of adult rats with MEHP did not disrupt the integrity of the BTB. The observed disruption of the BTB integrity in the MEHP-treated prepubertal rats occurred concomitantly with a decreased expression and mislocalization of both the ZO1 and occludin tight junction-associated proteins, as well as sloughing of spermatocytes and spermatids. At this same time, MEHP treatment induced a transient surge of p44/42 mitogen-activated protein kinase (MAPK) pathway. Interestingly, after a recovery period of 5 weeks, the BTB recovered and was functionally intact. This is the first report to indicate that acute MEHP exposure of prepubertal rats, but not adult rats, disrupts the functional integrity of the BTB and that this effect on the BTB is reversible.
Rat deconvolution as knowledge miner for immune cell trafficking from toxicogenomics databases
Authors: Morita Katsuhisa , Mizuno Tadahaya , Azuma Iori , Suzuki Yutaka , Kusuhara Hiroyuki
Published: November 2023

Toxicogenomics databases are useful for understanding biological responses in individuals because they include a diverse spectrum of biological responses. Although these databases contain no information regarding immune cells in the liver, which are important in the progression of liver injury, deconvolution that estimates cell-type proportions from bulk transcriptome could extend immune information. However, deconvolution has been mainly applied to humans and mice and less often to rats, which are the main target of toxicogenomics databases. Here, we developed a deconvolution method for rats to retrieve information regarding immune cells from toxicogenomics databases. The rat-specific deconvolution showed high correlations for several types of immune cells between spleen and blood, and between liver treated with toxicants compared with those based on human and mouse data. Additionally, we found 4 clusters of compounds in Open TG-GATEs database based on estimated immune cell trafficking, which are different from those based on transcriptome data itself. The contributions of this work are 3-fold. First, we obtained the gene expression profiles of 6 rat immune cells necessary for deconvolution. Second, we clarified the importance of species differences in deconvolution. Third, we retrieved immune cell trafficking from toxicogenomics databases. Accumulated and comparable immune cell profiles of massive data of immune cell trafficking in rats could deepen our understanding of enable us to clarify the relationship between the order and the contribution rate of immune cells, chemokines and cytokines, and pathologies. Ultimately, these findings will lead to the evaluation of organ responses in adverse outcome pathway.