bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Mars co-orbitals to estimate the importance of rotation-induced YORP break-up events in Earth co-orbital space
Authors: de la Fuente Marcos C , de la Fuente Marcos R 
Published: January 2021

ABSTRACT
Both Earth and Mars host populations of co-orbital minor bodies. A large number of present-day Mars co-orbitals is probably associated with the fission of the parent body of Mars Trojan 5261 Eureka (1990 MB) during a rotation-induced Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) break-up event. Here, we use the statistical distributions of the Tisserand parameter and the relative mean longitude of Mars co-orbitals with eccentricity below 0.2 to estimate the importance of rotation-induced YORP break-up events in Martian co-orbital space. Machine-learning techniques (k-means++ and agglomerative hierarchical clustering algorithms) are applied to assess our findings. Our statistical analysis identified three new Mars Trojans: 2009 SE, 2018 EC4, and 2018 FC4. Two of them, 2018 EC4 and 2018 FC4, are probably linked to Eureka but we argue that 2009 SE may have been captured, so it is not related to Eureka. We also suggest that 2020 VT1, a recent discovery, is a transient Martian co-orbital of the horseshoe type. When applied to Earth co-orbital candidates with eccentricity below 0.2, our approach led us to identify some clustering, perhaps linked to fission events. The cluster with most members could be associated with Earth quasi-satellite 469219 Kamo‘oalewa (2016 HO3) that is a fast rotator. Our statistical analysis identified two new Earth co-orbitals: 2020 PN1, which follows a horseshoe path, and 2020 PP1, a quasi-satellite that is dynamically similar to Kamo‘oalewa. For both Mars and Earth co-orbitals, we found pairs of objects whose values of the Tisserand parameter differ by very small amounts, perhaps hinting at recent disruption events. Clustering algorithms and numerical simulations both suggest that 2020 KZ2 and Kamo‘oalewa could be related.
Weighing Milky Way satellites with LISA
Authors: Korol Valeriya , Belokurov Vasily , Moore Christopher J , Toonen Silvia 
Published: January 2021

ABSTRACT
White dwarf stars are a well-established tool for studying Galactic stellar populations. Two white dwarfs in a tight binary system offer us an additional messenger – gravitational waves – for exploring the Milky Way and its immediate surroundings. Gravitational waves produced by double white dwarf (DWD) binaries can be detected by the future Laser Interferometer Space Antenna (LISA). Numerous and widespread DWDs have the potential to probe shapes, masses, and formation histories of the stellar populations in the Galactic neighbourhood. In this work we outline a method for estimating the total stellar mass of Milky Way satellite galaxies based on the number of DWDs detected by LISA. To constrain the mass we perform a Bayesian inference using binary population synthesis models and considering the number of detected DWDs associated with the satellite and the measured distance to the satellite as the only inputs. Based on a fiducial binary population synthesis model we find that for large satellites the stellar masses can be recovered to within (1) a factor 2 if the star formation history (SFH) is known and (2) an order of magnitude when marginalizing over different SFH models. For smaller satellites we can place upper limits on their stellar mass. Gravitational wave observations can provide mass measurements for large satellites that are comparable, and in some cases more precise, than standard electromagnetic observations.
Invasive growth associated with cold-inducible RNA-binding protein expression drives recurrence of surgically resected brain metastases
Authors: Dankner Matthew , Caron Maxime , Al-Saadi Tariq , Yu WenQing , Ouellet Véronique , Ezzeddine Rima , Maritan Sarah M , Annis Matthew G , Le Phuong Uyen , Nadaf Javad , Neubarth Noah S , Savage Paul , Zuo Dongmei , Couturier Charles P , Monlong Jean , Djambazian Haig , Altoukhi Huda , Bourque Guillaume , Ragoussis Jiannis , Diaz Roberto J , Park Morag , Guiot Marie-Christine , Lam Stephanie , Petrecca Kevin , Siegel Peter M 
Published: January 2021

Abstract

Background
Sixty percent of surgically resected brain metastases (BrM) recur within 1 year. These recurrences have long been thought to result from the dispersion of cancer cells during surgery. We tested the alternative hypothesis that invasion of cancer cells into the adjacent brain plays a significant role in local recurrence and shortened overall survival.

Methods
We determined the invasion pattern of 164 surgically resected BrM and correlated with local recurrence and overall survival. We performed single-cell RNA sequencing (scRNAseq) of &gt;15,000 cells from BrM and adjacent brain tissue. Validation of targets was performed with a novel cohort of BrM patient-derived xenografts (PDX) and patient tissues.

Results
We demonstrate that invasion of metastatic cancer cells into the adjacent brain is associated with local recurrence and shortened overall survival. scRNAseq of paired tumor and adjacent brain samples confirmed the existence of invasive cancer cells in the tumor-adjacent brain. Analysis of these cells identified cold-inducible RNA-binding protein (CIRBP) overexpression in invasive cancer cells compared to cancer cells located within the metastases. Applying PDX models that recapitulate the invasion pattern observed in patients, we show that CIRBP is overexpressed in highly invasive BrM and is required for efficient invasive growth in the brain.

Conclusions
These data demonstrate peritumoral invasion as a driver of treatment failure in BrM that is functionally mediated by CIRBP. These findings improve our understanding of the biology underlying postoperative treatment failure and lay the groundwork for rational clinical trial development based upon invasion pattern in surgically resected BrM.
PARP-mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma
Authors: Wu Shaofang , Li Xiaolong , Gao Feng , de Groot John F , Koul Dimpy , Yung W K Alfred 
Published: January 2021

Abstract

Background
Temozolomide (TMZ) resistance in glioblastoma multiforme (GBM) is mediated by the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). MGMT promoter methylation (occurs in about 40% of patients) is associated with loss of MGMT expression (MGMT−) that compromises DNA repair, leading to a favorable response to TMZ therapy. The 60% of patients with unmethylated MGMT (MGMT+) GBM experience resistance to TMZ; in these patients, understanding the mechanism of MGMT-mediated repair and modulating MGMT activity may lead to enhanced TMZ activity. Here, we report a novel mode of regulation of MGMT protein activity by poly(ADP-ribose) polymerase (PARP).

Methods
MGMT-PARP interaction was detected by co-immunoprecipitation. PARylation of MGMT and PARP was detected by co-immunoprecipitation with anti-PAR antibody. O6-methylguanine (O6-MetG) adducts were quantified by immunofluorescence assay. In vivo studies were conducted in mice to determine the effectiveness of PARP inhibition in sensitizing GBM to TMZ.

Results
We demonstrated that PARP physically binds with MGMT and PARylates MGMT in response to TMZ treatment. In addition, PARylation of MGMT by PARP is required for MGMT binding to chromatin to enhance the removal of O6-MetG adducts from DNA after TMZ treatment. PARP inhibitors reduced PARP-MGMT binding and MGMT PARylation, silencing MGMT activity to repair O6-MetG. PARP inhibition restored TMZ sensitivity in vivo in MGMT-expressing GBM.

Conclusion
This study demonstrated that PARylation of MGMT by PARP is critical for repairing TMZ-induced O6-MetG, and inhibition of PARylation by PARP inhibitor reduces MGMT function rendering sensitization to TMZ, providing a rationale for combining PARP inhibitors to sensitize TMZ in MGMT-unmethylated GBM.
Light-adapted charge-separated state of photosystem II: structural and functional dynamics of the closed reaction center
Authors: Sipka G�bor , Magyar Melinda , Mezzetti Alberto , Akhtar Parveen , Zhu Qingjun , Xiao Yanan , Han Guangye , Santabarbara Stefano , Shen Jian-Ren , Lambrev Petar H , Garab Győző 
Published: January 2021

Abstract
Photosystem II (PSII) uses solar energy to oxidize water and delivers electrons for life on Earth. The photochemical reaction center of PSII is known to possess two stationary states. In the open state (PSIIO), the absorption of a single photon triggers electron-transfer steps, which convert PSII into the charge-separated closed state (PSIIC). Here, by using steady-state and time-resolved spectroscopic techniques on Spinacia oleracea and Thermosynechococcus vulcanus preparations, we show that additional illumination gradually transforms PSIIC into a light-adapted charge-separated state (PSIIL). The PSIIC-to-PSIIL transition, observed at all temperatures between 80 and 308 K, is responsible for a large part of the variable chlorophyll-a fluorescence (Fv) and is associated with subtle, dark-reversible reorganizations in the core complexes, protein conformational changes at noncryogenic temperatures, and marked variations in the rates of photochemical and photophysical reactions. The build-up of PSIIL requires a series of light-induced events generating rapidly recombining primary radical pairs, spaced by sufficient waiting times between these events—pointing to the roles of local electric-field transients and dielectric relaxation processes. We show that the maximum fluorescence level, Fm, is associated with PSIIL rather than with PSIIC, and thus the Fv/Fm parameter cannot be equated with the quantum efficiency of PSII photochemistry. Our findings resolve the controversies and explain the peculiar features of chlorophyll-a fluorescence kinetics, a tool to monitor the functional activity and the structural-functional plasticity of PSII in different wild-types and mutant organisms and under stress conditions.
Declining carbohydrate content of Sitka-spruce treesdying from seawater exposure
Authors: Zhang Peipei , McDowell Nate G , Zhou Xuhui , Wang Wenzhi , Leff Riley T , Pivovaroff Alexandria L , Zhang Hongxia , Chow Pak S , Ward Nicholas D , Indivero Julia , Yabusaki Steven B , Waichler Scott , Bailey Vanessa L 
Published: January 2021

Abstract
Increasing sea levels associated with climate change threaten the survival of coastal forests, yet the mechanisms by which seawater exposure causes tree death remain poorly understood. Despite the potentially crucial role of nonstructural carbohydrate (NSC) reserves in tree survival, their dynamics in the process of death under seawater exposure are unknown. Here we monitored progressive tree mortality and associated NSC storage in Sitka-spruce (Picea sitchensis) trees dying under ecosystem-scale increases in seawater exposure in western Washington, USA. All trees exposed to seawater, because of monthly tidal intrusion, experienced declining crown foliage during the sampling period, and individuals with a lower percentage of live foliated crown (PLFC) died faster. Tree PLFC was strongly correlated with subsurface salinity and needle ion contents. Total NSC concentrations in trees declined remarkably with crown decline, and reached extremely low levels at tree death (2.4% and 1.6% in leaves and branches, respectively, and 0.4% in stems and roots). Starch in all tissues was almost completely consumed, while sugars remained at a homeostatic level in foliage. The decreasing NSC with closer proximity to death and near zero starch at death are evidences that carbon starvation occurred during Sitka-spruce mortality during seawater exposure. Our results highlight the importance of carbon storage as an indicator of tree mortality risks under seawater exposure.
Heat stress interferes with formation of double-strand breaks and homolog synapsis
Authors: Ning Yingjie , Liu Qingpei , Wang Chong , Qin Erdai , Wu Zhihua , Wang Minghui , Yang Ke , Elesawi Ibrahim Eid , Chen Chunli , Liu Hong , Qin Rui , Liu Bing 
Published: January 2021

Abstract
Meiotic recombination (MR) drives novel combinations of alleles and contributes to genomic diversity in eukaryotes. In this study, we showed that heat stress (36°C–38°C) over the fertile threshold fully abolished crossover formation in Arabidopsis (Arabidopsis thaliana). Cytological and genetic studies in wild-type plants and syn1 and rad51 mutants suggested that heat stress reduces generation of SPO11-dependent double-strand breaks (DSBs). In support, the abundance of recombinase DMC1, which is required for MR-specific DSB repair, was significantly reduced under heat stress. In addition, high temperatures induced disassembly and/or instability of the ASY4- but not the SYN1-mediated chromosome axis. At the same time, the ASY1-associated lateral element of the synaptonemal complex (SC) was partially affected, while the ZYP1-dependent central element of SC was disrupted, indicating that heat stress impairs SC formation. Moreover, expression of genes involved in DSB formation; e.g. SPO11-1, PRD1, 2, and 3 was not impacted; however, recombinase RAD51 and chromosome axis factors ASY3 and ASY4 were significantly downregulated under heat stress. Taken together, these findings revealed that heat stress inhibits MR via compromised DSB formation and homolog synapsis, which are possible downstream effects of the impacted chromosome axis. Our study thus provides evidence shedding light on how increasing environmental temperature influences MR in Arabidopsis.
Meta-Metasemantics, or the Quest for the One True Metasemantics
Authors: Nowak Ethan , Michaelson Eliot 
Published: January 2021

Abstract
What determines the meaning of a context-sensitive expression in a context? It is standardly assumed that, for a given expression type, there will be a unitary answer to this question; most of the literature on the subject involves arguments designed to show that one particular metasemantic proposal is superior to a specific set of alternatives. The task of the present essay will be to explore whether this is a warranted assumption, or whether the quest for the one true metasemantics might be a Quixotic one. We argue that there are good reasons—much better than are commonly appreciated—for thinking the latter, but that there nevertheless remains significant scope for metasemantic theorizing. We conclude by outlining our preferred option, metasemantic pluralism.
Neurocognitive processing of infant stimuli in mothers and non-mothers: psychophysiological, cognitive and neuroimaging evidence
Authors: Bjertrup Anne , Friis Nellie , Væver Mette , Miskowiak Kamilla 
Published: January 2021

AbstractEmerging evidence indicates that mothers and non-mothers show different neurocognitive responses to infant stimuli. This study investigated mothers’ psychophysiological, cognitive and neuronal responses to emotional infant stimuli. A total of 35 mothers with 4-month-old infants and 18 control women without young children underwent computerized tests assessing neurocognitive processing of infant stimuli. Their eye gazes and eye fixations, galvanic skin responses (GSRs) and facial expressions towards infant emotional stimuli were recorded during the tasks. Participants underwent functional magnetic resonance imaging during which they viewed pictures of an unknown infant and, for mothers, their own infants. Mothers gazed more and had increased GSR towards infant stimuli and displayed more positive facial expressions to infant laughter, and self-reported more positive ratings of infant vocalizations than control women. At a neural level, mothers showed greater neural response in insula, dorsolateral prefrontal cortex and occipital brain regions within a predefined ‘maternal neural network’ while watching images of their own vs unknown infants. This specific neural response to own infants correlated with less negative ratings of own vs unknown infants’ signals of distress. Differences between mothers and control women without young children could be interpreted as neurocognitive adaptation to motherhood in the mothers.
Intersecting Boundaries: Comparing Stereotypes of Native- and Foreign-Born Members of Ethnoracial Groups
Authors: Schachter Ariela 
Published: January 2021

AbstractPast research finds that Americans hold biased stereotypes about ethnoracial groups and about immigrants, but we lack an understanding of how these group identities intersect. Immigration theories offer opposing predictions; while the straight-line assimilation model predicts Americans will hold weaker ethnoracial stereotypes about the native-born compared to their immigrant coethnics, theories of racialized assimilation suggest that the enduring power of race will limit any differential stereotyping of immigrant and native-born members of racialized groups. I use an original survey experiment to compare Americans’ stereotypes of native- and foreign-born members of the four largest ethnoracial groups in the United States—Whites, Blacks, Latinos, and Asians. As predicted by straight-line assimilation theory, I find that Whites’ negative stereotypes of Latinos fade away with nativity; however, White Americans do not substantially alter their stereotypes of Asians and Blacks based on nativity status. Moreover, native-born Black and Latino Americans do not appear to hold differential stereotypes of ethnoracial groups based on their nativity status. This research highlights both the importance and limitations of accounting for nativity status to understand ethnoracial group boundaries in the United States.
Mitochondrial Membrane Potential Drives Early Change in Mitochondrial Morphology After Acetaminophen Exposure
Authors: Umbaugh David S , Nguyen Nga T , Jaeschke Hartmut , Ramachandran Anup 
Published: January 2021

Abstract
Mitochondrial morphology plays a critical role in regulating mitochondrial and cellular function. It is well established that oxidative stress and mitochondrial injury are central to acetaminophen (APAP) hepatotoxicity. However, the role of mitochondrial dynamics, namely the remodeling of mitochondrial morphology through fusion and fission, has largely gone unexplored. To investigate this, we used primary mouse hepatocytes treated with APAP which allowed for real-time visualization of mitochondrial morphology using mitotracker green. We found that alterations in mitochondrial morphology were dose dependent, with a biphasic response in mitochondrial shape at higher APAP doses. Importantly, these two distinct mitochondrial morphologies corresponded with differences in mitochondrial respiratory function and polarization. The early change in mitochondrial morphology can be reversible and appears to be an adaptive response caused by alterations in membrane potential, which ultimately help preserve mitochondrial function. The later delayed change in mitochondrial morphology is irreversible and is driven by loss of mitochondrial membrane potential, decreased canonical fusion proteins, and alterations in mitochondrial lipid composition. Collectively, these later changes tilt the scales toward mitochondrial fission resulting in fragmented mitochondria with reduced functionality. This work provides evidence of adaptive early changes in mitochondrial morphology, which results in functional consequences that are dictated by the severity of APAP overdose.
Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair
Authors: Pope Quintin , Rand Matthew D 
Published: January 2021

Abstract
The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 &lt; 30 to &gt; 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25–35 years) and child (4 − 6 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1/2 of 46.9, 38.9, and 31.5 days and steady-state blood MeHg of 2.6, 2.6, and 2.3 µg/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7 µg/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child). Local and global sensitivity analyses of model parameters reveal that variation in biotransformation rate in the gut lumen, and rates of transport between gut lumen and gut tissue, have the greatest influence on MeHg t1/2. Volume and partition coefficients for skeletal muscle (SM) and gut tissue also show significant sensitivity affecting model output of MeHg t1/2. Our results emphasize the role of gut microbiota in MeHg biotransformation, transport kinetics at the level of the gut, and SM mass as moderators of MeHg kinetics in the human body.
Generation of an Allelic Series at the Ahr Locus Using an Edited Recombinant Approach
Authors: Wilson Rachel H , Carney Patrick R , Glover Edward , Parrott Jessica C , Rojas Brenda L , Moran Susan M , Yee Jeremiah S , Nukaya Manabu , Goetz Nicholas A , Rubinstein Clifford D , Krentz Kathy J , Xing Yongna , Bradfield Christopher A 
Published: January 2021

Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and a member of the PER-ARNT-SIM (PAS) superfamily of environmental sensors. The AHR is involved in a series of biological processes including adaptive metabolism of xenobiotics, toxicity of certain environmental pollutants, vascular development, fertility, and immune function. Mouse models, including the Ahr null and Ahr conditional null (Ahrfx) mice, are widely used for the study of AHR-mediated biology and toxicity. The Ahr conditional null mouse harbors the low-affinity Ahrd allele that exhibits approximately a 10-fold lower binding affinity for certain xenobiotic AHR ligands than the widely used C57BL/6 mouse that harbors the higher affinity Ahrb1 allele. Here, we report a novel mouse model that introduces a V375A polymorphism that converts the low-affinity allele into a high-affinity allele, offering a more sensitive conditional model. In the generation of this novel conditional allele, two additional mutants arose, including a 3-bp deletion in the PAS-B domain (AhrNG367R) and an early termination codon in the PAS-B domain (AhrTer383). The AhrNG367R allele presents as a phenocopy of the null and the AhrTer383 allele presents as an antimorph when assessing for the ductus venosus and liver lobe weight endpoints. These new models represent a series of tools that will be useful in further characterizing AHR biology.