bluuebunny/crossref_metadata_2025_split huggingface dataset:
[Ne v] emission from a faint epoch of reionization-era galaxy: evidence for a narrow-line intermediate-mass black hole
Authors: Chisholm J , Berg D A , Endsley R , Gazagnes S , Richardson C T , Lambrides E , Greene J , Finkelstein S , Flury S , Guseva N G , Henry A , Hutchison T A , Izotov Y I , Marques-Chaves R , Oesch P , Papovich C , Saldana-Lopez A , Schaerer D , Stephenson M  G 
Published: September 2024

ABSTRACT
Here, we present high spectral resolution ${\it JWST}$ NIRSpec observations of GN 42437, a low-mass (log(M$_\ast /{\rm M}_\odot)=7.9$), compact ($r_e \lt 500$pc), extreme starburst galaxy at $z=5.59$ with 13 emission-line detections. GN 42437 has a low metallicity (5–10 per cent Z$_\odot$) and its rest-frame H$\alpha$ equivalent width suggests nearly all of the observed stellar mass formed within the last 3 Myr. GN 42437 has an extraordinary 7$\sigma$ significant [Ne v] 3427 Å detection. The [Ne v] line has a rest-frame equivalent width of $11\pm 2$Å, [Ne v]/H$\alpha =0.04\pm 0.007$, [Ne v]/[Ne iii] 3870Å $= 0.26\pm 0.04$, and [Ne v]/He ii 4687Å $ = 1.2\pm 0.5$. Ionization from massive stars, shocks, or high-mass X-ray binaries cannot simultaneously produce these [Ne v] and other low-ionization line ratios. Reproducing the complete nebular structure requires both massive stars and accretion on to a black hole. We do not detect broad lines nor do the traditional diagnostics indicate that GN 42437 has an accreting black hole. Thus, the very high-ionization emission lines powerfully diagnose faint narrow-line black holes at high redshift. We approximate the black hole mass in a variety of ways as log(M$_{\rm BH}/{\rm M}_\odot) \sim 5{-}7$. This black hole mass is consistent with local relations between the black hole mass and the observed velocity dispersion, but significantly more massive than the stellar mass would predict. Very high-ionization emission lines may reveal samples to probe the formation and growth of the first black holes in the universe.
Hierarchical three-body problem at high eccentricities = simple pendulum II: octupole including Brown’s Hamiltonian
Authors: Klein Ygal Y , Katz Boaz 
Published: September 2024

ABSTRACT
The very long-term evolution of the hierarchical restricted three-body problem with a massive perturber is analysed analytically in the high eccentricity regime. Perturbations on the time-scale of the outer orbit can accumulate over long time-scales and be comparable to the effect of the octupole term. These perturbations are described by Brown’s Hamiltonian – having different forms in the literature. We show that at the high eccentricity regime – the effect of Brown’s Hamiltonian is an azimuthal precession of the eccentricity vector and can be solved analytically. In fact, the dynamics are equivalent to a simple pendulum model allowing an explicit flip criterion.
Chem-CRISPR/dCas9FCPF: a platform for chemically induced epigenome editing
Authors: Altinbay Mukaddes , Wang Jianhui , Chen Jie , Schäfer Daniel , Sprang Maximilian , Blagojevic Biljana , Wölfl Stefan , Andrade-Navarro Miguel A , Dikic Ivan , Knapp Stefan , Cheng Xinlai 
Published: September 2024

Abstract
Epigenetic aberration is one of the major driving factors in human cancer, often leading to acquired resistance to chemotherapies. Various small molecule epigenetic modulators have been reported. Nonetheless, outcomes from animal models and clinical trials have underscored the substantial setbacks attributed to pronounced on- and off-target toxicities. To address these challenges, CRISPR/dCas9 technology is emerging as a potent tool for precise modulation of epigenetic mechanism. However, this technology involves co-expressing exogenous epigenetic modulator proteins, which presents technical challenges in preparation and delivery with potential undesirable side effects. Recently, our research demonstrated that Cas9 tagged with the Phe-Cys-Pro-Phe (FCPF)-peptide motif can be specifically targeted by perfluorobiphenyl (PFB) derivatives. Here, we integrated the FCPF-tag into dCas9 and established a chemically inducible platform for epigenome editing, called Chem-CRISPR/dCas9FCPF. We designed a series of chemical inhibitor-PFB conjugates targeting various epigenetic modulator proteins. Focusing on JQ1, a panBET inhibitor, we demonstrate that c-MYC-sgRNA-guided JQ1-PFB specifically inhibits BRD4 in close proximity to the c-MYC promoter/enhancer, thereby effectively repressing the intricate transcription networks orchestrated by c-MYC as compared with JQ1 alone. In conclusion, our Chem-CRISPR/dCas9FCPF platform significantly increased target specificity of chemical epigenetic inhibitors, offering a viable alternative to conventional fusion protein systems for epigenome editing.
FRAME: flap endonuclease 1-engineered PAM module for precise and sensitive modulation of CRISPR/Cas12a trans-cleavage activity
Authors: Zuo Tongshan , Shen Chen , Xie Zhen , Xu Guanhong , Wei Fangdi , Yang Jing , Zhu Xiaolei , Hu Qin , Zhao Zheng , Tang Ben Zhong , Cen Yao 
Published: September 2024

Abstract
CRISPR/Cas12a system, renowned for its precise recognition and efficient nucleic acid cleavage capabilities, has demonstrated remarkable performance in molecular diagnostics and biosensing. However, the reported Cas12a activity regulation methods often involved intricate CRISPR RNA (crRNA) structural adjustments or costly chemical modifications, which limited their applications. Here, we demonstrated a unique enzyme activity engineering strategy using flap endonuclease 1 (FEN1) to regulate the accessibility of the protospacer adjacent motif (PAM) module in the double-stranded DNA activator (FRAME). By identifying the three-base overlapping structure between the target inputs and substrate, FEN1 selectively cleaved and released the 5′-flap containing the ‘TTTN’ sequence, which triggered the secondary cleavage of FEN1 while forming a nicked PAM, ultimately achieving the sensitive switching of Cas12a’s activity. The FRAME strategy exemplified the ‘two birds with one stone’ principle, as it not only precisely programmed Cas12a’s activity but also simultaneously triggered isothermal cyclic amplification. Moreover, the FRAME strategy was applied to construct a sensing platform for detecting myeloperoxidase and miR-155, which demonstrated high sensitivity and specificity. Importantly, it proved its versatility in detecting multiple targets using a single crRNA without redesign. Collectively, the FRAME strategy opens up a novel avenue for modulating Cas12a’s activity, promising immense potential in the realm of medical diagnostics.
p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis
Authors: Elfar Gamal Ahmed , Aning Obed , Ngai Tsz Wai , Yeo Pearlyn , Chan Joel Wai Kit , Sim Shang Hong , Goh Leonard , Yuan Ju , Phua Cheryl Zi Jin , Yeo Joanna Zhen Zhen , Mak Shi Ya , Goh Brian Kim Poh , Chow Pierce Kah-Hoe , Tam Wai Leong , Ho Ying Swan , Cheok Chit Fang 
Published: September 2024

Abstract
Mechanisms underlying p53-mediated protection of the replicating genome remain elusive, despite the quintessential role of p53 in maintaining genomic stability. Here, we uncover an unexpected function of p53 in curbing replication stress by limiting PARP1 activity and preventing the unscheduled degradation of deprotected stalled forks. We searched for p53-dependent factors and elucidated RRM2B as a prime factor. Deficiency in p53/RRM2B results in the activation of an NRF2 antioxidant transcriptional program, with a concomitant elevation in basal PARylation in cells. Dissecting the consequences of p53/RRM2B loss revealed a crosstalk between redox metabolism and genome integrity that is negotiated through a hitherto undescribed NRF2-PARP1 axis, and pinpoint G6PD as a primary oxidative stress-induced NRF2 target and activator of basal PARylation. This study elucidates how loss of p53 could be destabilizing for the replicating genome and, importantly, describes an unanticipated crosstalk between redox metabolism, PARP1 and p53 tumor suppressor pathway that is broadly relevant in cancers and can be leveraged therapeutically.
Phage defence loci of Streptococcus thermophilus—tip of the anti-phage iceberg?
Authors: Kelleher Philip , Ortiz Charneco Guillermo , Kampff Zoe , Diaz-Garrido Natalia , Bottacini Francesca , McDonnell Brian , Lugli Gabriele A , Ventura Marco , Fomenkov Alexey , Quénée Pascal , Kulakauskas Saulius , de Waal Paul , van Peij Noël N M E , Cambillau Christian , Roberts Richard John , van Sinderen Douwe , Mahony Jennifer 
Published: September 2024

Abstract
Bacteria possess (bacterio)phage defence systems to ensure their survival. The thermophilic lactic acid bacterium, Streptococcus thermophilus, which is used in dairy fermentations, harbours multiple CRISPR-Cas and restriction and modification (R/M) systems to protect itself against phage attack, with limited reports on other types of phage-resistance. Here, we describe the systematic identification and functional analysis of the phage resistome of S. thermophilus using a collection of 27 strains as representatives of the species. In addition to CRISPR-Cas and R/M systems, we uncover nine distinct phage-resistance systems including homologues of Kiwa, Gabija, Dodola, defence-associated sirtuins and classical lactococcal/streptococcal abortive infection systems. The genes encoding several of these newly identified S. thermophilus antiphage systems are located in proximity to the genetic determinants of CRISPR-Cas systems thus constituting apparent Phage Defence Islands. Other phage-resistance systems whose encoding genes are not co-located with genes specifying CRISPR-Cas systems may represent anchors to identify additional Defence Islands harbouring, as yet, uncharacterised phage defence systems. We estimate that up to 2.5% of the genetic material of the analysed strains is dedicated to phage defence, highlighting that phage-host antagonism plays an important role in driving the evolution and shaping the composition of dairy streptococcal genomes.
3,N4-Etheno-5-methylcytosine blocks TET1-3 oxidation but is repaired by ALKBH2, 3 and FTO
Authors: Ma Jian , Qi Rui , Harcourt Emily M , Chen Yi-Tzai , Barbosa Giovannia M , Peng Zhiyuan , Howarth Samuel , Delaney Sarah , Li Deyu 
Published: September 2024

Abstract
5-Methyldeoxycytidine (5mC) is a major epigenetic marker that regulates cellular functions in mammals. Endogenous lipid peroxidation can convert 5mC into 3,N4-etheno-5-methylcytosine (ϵ5mC). ϵ5mC is structurally similar to the mutagenic analog 3,N4-ethenocytosine (ϵC), which is repaired by AlkB family enzymes in the direct reversal repair (DRR) pathway and excised by DNA glycosylases in the base excision repair (BER) pathway. However, the repair of ϵ5mC has not been reported. Here, we examined the activities against ϵ5mC by DRR and BER enzymes and TET1-3, enzymes that modify the 5-methyl group in 5mC. We found that the etheno modification of 5mC blocks oxidation by TET1-3. Conversely, three human homologs in the AlkB family, ALKBH2, 3 and FTO were able to repair ϵ5mC to 5mC, which was subsequently modified by TET1 to 5-hydroxymethylcytosine. We also demonstrated that ALKBH2 likely repairs ϵ5mC in MEF cells. Another homolog, ALKBH5, could not repair ϵ5mC. Also, ϵ5mC is not a substrate for BER glycosylases SMUG1, AAG, or TDG. These findings indicate DRR committed by ALKBH2, 3 and FTO could reduce the detrimental effects of ϵ5mC in genetics and epigenetics and may work together with TET enzymes to modulate epigenetic regulations.
scMMO-atlas: a single cell multimodal omics atlas and portal for exploring fine cell heterogeneity and cell dynamics
Authors: Cheng Wenwen , Yin Changhui , Yu Shiya , Chen Xi , Hong Ni , Jin Wenfei 
Published: September 2024

Abstract
Single-cell multimodal sequencing parallelly captures multiple modalities of the same cell, providing unparalleled insights into cell heterogeneity and cell dynamics. For example, joint profiling of chromatin accessibility and transcriptome from the same single cell (scATAC + RNA) identified new cell subsets within the well-defined clusters. However, lack of single-cell multimodal omics (scMMO) database has led to data fragmentation, seriously hindering access, utilization and mining of scMMO data. Here, we constructed a scMMO atlas by collecting and integrating various scMMO data, then constructed scMMO database and portal called scMMO-atlas (https://www.biosino.org/scMMO-atlas/). scMMO-atlas includes scATAC + RNA (ISSAAS-seq, SNARE-seq, paired-seq, sci-CAR, scCARE-seq, 10X Multiome and so on), scRNA + protein, scATAC + protein and scTri-modal omics data, with 3 168 824 cells from 27 cell tissues/organs. scMMO-atlas offered an interactive portal for visualization and featured analysis for each modality and the integrated data. Integrated analysis of scATAC + RNA data of mouse cerebral cortex in scMMO-atlas identified more cell subsets compared with unimodal omics data. Among these new cell subsets, there is an early astrocyte subset highly expressed Grm3, called Astro-Grm3. Furthermore, we identified Ex-L6-Tle4-Nrf1, a progenitor of Ex-L6-Tle4, indicating the statistical power provided by the big data in scMMO-atlas. In summary, scMMO-atlas offers cell atlas, database and portal to facilitate data utilization and biological insight.
Disparate requirements for RAD54L in replication fork reversal
Authors: Uhrig Mollie E , Sharma Neelam , Maxwell Petey , Gomez Jordi , Selemenakis Platon , Mazin Alexander V , Wiese Claudia 
Published: September 2024

Abstract
RAD54L is a DNA motor protein with multiple roles in homologous recombination DNA repair. In vitro, RAD54L was shown to also catalyze the reversal and restoration of model replication forks. In cells, however, little is known about how RAD54L may regulate the dynamics of DNA replication. Here, we show that RAD54L restrains the progression of replication forks and functions as a fork remodeler in human cancer cell lines and non-transformed cells. Analogous to HLTF, SMARCAL1 and FBH1, and consistent with a role in fork reversal, RAD54L decelerates fork progression in response to replication stress and suppresses the formation of replication-associated ssDNA gaps. Interestingly, loss of RAD54L prevents nascent strand DNA degradation in both BRCA1/2- and 53BP1-deficient cells, suggesting that RAD54L functions in both pathways of RAD51-mediated replication fork reversal. In the HLTF/SMARCAL1 pathway, RAD54L is critical, but its ability to catalyze branch migration is dispensable, indicative of its function downstream of HLTF/SMARCAL1. Conversely, in the FBH1 pathway, branch migration activity of RAD54L is essential, and FBH1 engagement is dependent on its concerted action with RAD54L. Collectively, our results reveal disparate requirements for RAD54L in two distinct RAD51-mediated fork reversal pathways, positing its potential as a future therapeutic target.
Severe Optic Neuropathy Induced by Very Prolonged Tedizolid as Suppressive Therapy: Description of a Case Report and Implication for Better Assessment
Authors: Coustilleres F , Thillard E M , Khanna R K , Olivereau S , Ouaissi M , Pansu N , Le Lez M L 
Published: September 2024

AbstractThe long-term tolerability of linezolid is low because of mitochondrial toxicity, whereas tedizolid may represent a better option for suppressive therapy. We report a first presumed case of tedizolid-associated optic neuropathy after a very prolonged (18-month) intake and believe that screening for optic neuropathy should be considered for patients undergoing tedizolid suppression.
The ubiquitin E3 ligase RZFP1 affects drought tolerance in poplar by mediating the degradation of the protein phosphatase PP2C-9
Authors: He Fang , Niu Meng-Xue , Wang Ting , Li Jun-Lin , Shi Yu-Jie , Zhao Jiu-Jiu , Li Hao , Xiang Xiang , Yang Peng , Wei Shu-Ying , Lin Tian-Tian , Huang Xiong , Xia Xinli , Wan Xue-Qin 
Published: September 2024

Abstract
Abscisic acid (ABA) signaling has been implicated in plant responses to water deficit-induced osmotic stress. However, the underlying molecular mechanism remains unelucidated. This study identified the RING-type E3 ubiquitin ligase RING ZINC FINGER PROTEIN1 (PtrRZFP1) in poplar (Populus trichocarpa), a woody model plant. PtrRZFP1 encodes an ubiquitin E3 ligase that participates in protein ubiquitination. PtrRZFP1 mainly functions in the nucleus and endoplasmic reticulum and is activated by drought and ABA. PtrRZFP1-overexpressing transgenic poplars (35S:PtrRZFP1) showed greater tolerance to drought, whereas PtrRZFP1-knockdown lines (KD-PtrRZFP1) showed greater sensitivity to drought. Under treatment with polyethylene glycol and ABA, PtrRZFP1 promoted the production of nitric oxide and hydrogen peroxide in stomatal guard cells, ultimately enhancing stomatal closure and improving drought tolerance. Additionally, PtrRZFP1 physically interacted with the clade A Protein Phosphatase 2C protein PtrPP2C-9, a core regulator of ABA signaling, and mediated its ubiquitination and eventual degradation through the ubiquitination-26S proteasome system, indicating that PtrRZFP1 positively regulates the ABA signaling pathway. Furthermore, the PtrPP2C-9-overexpression line was insensitive to ABA and more sensitive to drought than the wild-type plants, whereas the opposite phenotype was observed in 35S:PtrRZFP1 plants. In general, PtrRZFP1 negatively regulates the stability of PtrPP2C-9 to mediate poplar drought tolerance. The results of this study provide a theoretical framework for the targeted breeding of drought-tolerant traits in perennial woody plants.
Every History
Authors: Knutzen Jonathan 
Published: September 2024

Abstract
This paper focuses on an underexplored challenge in infinite ethics. On realistic assumptions, if our universe is infinite, every nomologically possible history is actual and nothing we ever do makes a difference to the moral quality of the world as a whole. Call this thought Every History. This paper unpacks Every History and explores some of its ethical implications. Specifically, I argue that if Every History is true and the universe turns out to be infinite (1) our lives are globally insignificant, (2) moral principles enjoining the promotion of value need to be given an appropriately scope-restricted interpretation, and (3) impersonal consequentialism faces a serious challenge.
Emotional unreliability and epistemic defeat
Authors: Magalotti Tricia 
Published: September 2024

Abstract
Among those who think that emotions can provide epistemic reasons for belief, there is disagreement about whether emotions provide foundational reasons (ones that are not based on further reasons) or non-foundational reasons (ones that are based on further reasons). I argue in this paper that considerations about evidence of emotional unreliability favour the non-foundational view of emotional reasons. The argument starts with a set of counterexamples to the claim that evidence of emotional unreliability always defeats emotional justification. I then show why only the non-foundational picture of emotional reasons is compatible with this finding. The upshot is 2-fold: first, the commonly held assumption that evidence of emotional unreliability always defeats emotional justification is false; and, second, this gives us a reason for preferring a non-foundational picture of emotional reasons.
Capital Investment, Equity Returns, and Aggregate Dynamics in Oligopolistic Production Economies
Authors: Doshi Hitesh , Kumar Praveen 
Published: September 2024

Abstract
We analyze effects of tacit collusion in a dynamic general equilibrium model of oligopolistic sectors with capital investment and real frictions. Through their effects on equilibrium- and off-equilibrium stock prices, fundamental shocks affect incentives for defection from tacit collusion, amplifying the interaction between the real economy and financial markets as well as firms’ risk exposure. The model implies ambiguous relationship between industry concentration and equity returns depending on operating leverage, which helps reconcile conflicting evidence in the literature. We find quantitative and empirical support for novel theoretical predictions regarding the effects of concentration on returns and investment.
Electrochemical impedance spectroscopy unmasks high‐risk atherosclerotic features in human coronary artery disease
Authors: Chen Michael , Suwannaphoom Krit , Sanaiha Yas , Luo Yuan , Benharash Peyman , Fishbein Michael C. , Packard René R. Sevag 
Published: September 2024

AbstractCoronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture‐prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high‐risk atherosclerotic features that portend rupture risk. In this single‐center, prospective study, n = 26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N = 61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture‐risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas‐under‐the‐curve (AUC). Necrotic cores were identified in n = 19 vessels (median area 1.53 mm2) with a median fibrous cap thickness of 62 μm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm2 versus <1.75 mm2 (19.8 ± 4.4 kΩ vs. 7.2 ± 1.0 kΩ, p = .019), fibrous cap thickness ≤65 μm versus >65 μm (19.1 ± 3.5 kΩ vs. 6.5 ± 0.9 kΩ, p = .004), and ≥20 macrophages per 0.3 mm‐diameter high‐power field (HPF) versus <20 macrophages per HPF (19.8 ± 4.1 kΩ vs. 10.2 ± 0.9 kΩ, p = .002). Impedance identified necrotic core area ≥1.75 mm2, fibrous cap thickness ≤65 μm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716–1.000) (p = .013), 0.852 (0.646–1.000) (p = .025), and 0.835 (0.577–1.000) (p = .028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573–0.962) (p = .035). EIS discriminates high‐risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography‐guided atherosclerosis evaluation.
Celiac disease
Authors: Olmstead Jill 
Published: September 2024

ABSTRACT
The American College of Gastroenterology revised its recommendations for diagnosing and managing celiac disease in its updated 2023 clinical guideline. Celiac disease is an autoimmune disorder causing malabsorption following exposure to gluten. A wide range of both gastrointestinal and nongastrointestinal signs and symptoms can occur. This article provides an overview of the diagnosis and management of celiac disease, aiding the NP in developing a greater awareness of the condition both to diagnose it and to refer patients as needed to gastroenterology for evaluation.