bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microquasar Cyg X-3 – a unique jet-wind neutrino factory?
Authors: Koljonen Karri I I , Satalecka Konstancja , Lindfors Elina J , Liodakis Ioannis 
Published: June 2023

ABSTRACT
The origin of astrophysical neutrinos is one of the most debated topics today. Perhaps the most robust evidence of neutrino counterpart comes from supermassive black holes in active galactic nuclei associated with strongly collimated outflows, or jets, that can accelerate particles to relativistic energies and produce neutrinos through hadronic interactions. Similar outflows can also be found from X-ray binaries, or ‘microquasars’, that consist of a neutron star or a stellar-mass black hole accreting matter from a non-degenerate companion star. In some cases, these systems can accelerate particles up to GeV energies implying an efficient acceleration mechanism in their jets. Neutrino production in microquasar jets can be expected with suitable conditions and a hadronic particle population. Microquasar Cyg X-3 is a unique, short orbital period X-ray binary hosting a Wolf–Rayet companion star with a strong stellar wind. The interaction of the dense stellar wind with a relativistic jet leads to particle collisions followed by high-energy gamma-ray and potentially neutrino emission. Here, using the 10-yr neutrino candidate sample of the IceCube neutrino observatory, we find that the events with the highest spatial association with Cyg X-3 occur during short-lived high-energy gamma-ray flaring periods indicating the possible astrophysical nature of these events.
The ages and metallicities of the globular clusters in the Sparkler
Authors: Adamo Angela , Usher Christopher , Pfeffer Joel , Claeyssens Adélaïde 
Published: June 2023

ABSTRACT
JWST observations of the strongly lensed galaxy the Sparkler have revealed a population of gravitationally bound globular cluster (GC) candidates. Different analyses have resulted in broadly similar ages but significantly different metallicities, questioning the assembly history that has led to the formation of such a population. In this letter, we reanalyse the two sets of photometry available in the literature with the code mcmame especially tailored to fit physical properties of GCs. We find the ages and metallicities from both data sets are consistent within 1σ uncertainties. A significant group of GCs is consistent with being old and metal poor ([Fe/H] ∼ −1.7). For this group, the ages do not converge, hence, we conclude that they are definitively older than 1 Gyr and can be as old as the age of the Universe. The remaining GCs have younger ages and a metallicity spread. The ages and metallicities distribution of GCs in the Sparkler are consistent with those observed in Local Group’s galaxies at similar lookback times. Comparing with predictions from E-MOSAICS simulations we confirm that the Sparkler GC population traces the self-enrichment history of a galaxy which might become a few times 109 M⊙ massive system at redshift z = 0.
Catalytic Climate Litigation: Rights and Statutes
Authors: Bookman Sam 
Published: June 2023

Abstract
Rights-based climate litigation has captured the global legal imagination in part because of its aspiration to achieve a certain function: catalysing political and policy processes into more ambitious climate action across the entire government apparatus. But many jurisdictions lack the legal opportunity structure that allows rights to perform this function. Instead, litigants might look to framework statutes as a way to trigger climate catalysis through litigation. Legal and mobilisation strategies drawing on both rights and framework statutes could prove an effective approach in future litigation.
Protein phase separation in plant membrane biology: more than just a compartmentalization strategy
Authors: Dragwidge Jonathan Michael , Van Damme Daniël 
Published: June 2023

Abstract
The formation of biomolecular condensates through phase separation is an important strategy to compartmentalize cellular functions. While it is now well established that condensates exist throughout eukaryotic cells, how condensates assemble and function on lipid membranes is only beginning to be understood. In this perspective, we highlight work from plant, animal, and yeast model systems showing that condensates assemble on many endomembrane surfaces to carry out diverse functions. In vesicle trafficking, condensation has reported roles in the formation of endocytic vesicles and autophagosomes and in the inactivation of secretory COPII vesicles. We briefly discuss how membranes and membrane lipids regulate the formation and function of membrane-associated condensates. This includes how membranes act as surfaces for condensate assembly, with lipids mediating the nucleation of condensates during endocytosis and other processes. Additionally, membrane–condensate interactions give rise to the biophysical property of “wetting”, which has functional importance in shaping autophagosomal and vacuolar membranes. We also speculate on the existence of membrane-associated condensates during cell polarity in plants and discuss how condensation may help to establish functional plasma membrane domains. Lastly, we provide advice on relevant in vitro and in vivo approaches and techniques to study membrane-associated phase separation.
In Vitro Insights Into the Influence of Marrow Mesodermal/Mesenchymal Progenitor Cells on Acute Myelogenous Leukemia and Myelodysplastic Syndromes
Authors: Liesveld Jane , Galipeau Jaques 
Published: June 2023

Abstract
The study of marrow-resident mesodermal progenitors can provide important insight into their role in influencing normal and aberrant hematopoiesis as occurs in acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). In addition, the chemokine competency of these cells provides links to the inflammatory milieu of the marrow microenvironment with additional implications for normal and malignant hematopoiesis. While in vivo studies have elucidated the structure and function of the marrow niche in murine genetic models, corollary human studies have not been feasible, and thus the use of culture-adapted mesodermal cells has provided insights into the role these rare endogenous niche cells play in physiologic, malignant, and inflammatory states. This review focuses on culture-adapted human mesenchymal stem/stromal cells (MSCs) as they have been utilized in understanding their influence in AML and MDS as well as on their chemokine—mediated responses to myeloid malignancies, injury, and inflammation. Such studies have intrinsic limitations but have provided mechanistic insights and clues regarding novel druggable targets.
Two-year Clinical Outcomes Following Photodynamic Acute Exudative Maculopathy in Patients with Chronic Central Serous Chorioretinopathy
Authors: Fernández-Vigo José Ignacio , Moreno-Morillo Francisco Javier , Burgos-Blasco Barbara , Ly-Yang Fernando , Oribio-Quinto Carlos , García-Caride Sara , Donate-López Juan 
Published: June 2023

ABSTRACT

Objective:
To analyze the two-year clinical outcomes following photodynamic therapy (PDT)-induced acute exudative maculopathy (PAEM) in patients with chronic central serous chorioretinopathy (cCSCR).

Methods:
Prospective observational study that included 64 eyes of 64 patients with cCSCR who received half-fluence PDT and had a 2-year follow-up. Patients were classified into 2 groups based on whether they had had PAEM at 3 days after treatment (PAEM+, n=22; ≥50 µm increase in subretinal fluid (SRF) or not (PAEM-, n=42). Best-corrected visual acuity (BCVA) and SRF changes evaluated with optical coherence tomography (OCT) were registered at 3 days, 1 month, 3 months, 1 year and 2 years after PDT. The number of recurrences, the appearance of outer retinal atrophy (ORA) and choroidal neovascularization (CNV) were analyzed.

Results:
BCVA was 75.9±13.6 (20/32) and 82.0±11.0 letters (20/25) at two years in the PAEM+ and PAEM- groups, respectively (p=0.055). There were no differences in the BCVA change (4.2±7.7 vs 3.3±7.1 letters; p=0.654) and the SRF decrease (-117.3±74.2 vs -138.5±83.6 µm; p=0.323) at 2 years between patients with and without PAEM. No differences in the number of recurrences (p=0.267), the appearance of CNV (p=0.155) or ORA (p=0.273) between both groups were noted.

Conclusions:
Patients with cCSCR with and without PAEM presented similar results at 2 years in terms of BCVA gain, SRF reduction and complication rate.
MEDICAL THERAPY FOR LARGE IDIOPATHIC FULL-THICKNESS MACULAR HOLES
Authors: Sheng Young , Jain Mukesh , Sahoo Niroj , Reddy Nikitha , Tyagi Mudit , Narula Ritesh , Stewart Michael W. , Narayanan Raja 
Published: June 2023

Purpose:
To describe the characteristics and outcomes of eyes with idiopathic full-thickness macular holes that underwent initial medical management.

Methods:
This retrospective study included eyes with full-thickness macular holes that were initially managed with 1 month of topical therapy. Eligible subjects were treated with dorzolamide 2% three times a day, nepafenac 0.1% twice a day, and prednisolone acetate 1% four times a day. The primary end points was hole closure at one month and secondary end point was change in best-corrected visual acuity.

Results:
Ten subjects (mean age: 62.80 years; female: 50%) with unilateral full-thickness macular holes were studied. The mean basal diameter of the entire cohort at baseline was 824.1 µm (median 828 µm). Four (40%) of the smaller holes (mean 698 µm; median 698.50 µm) closed after 1 month of topical therapy, whereas larger holes (mean 908.17 µm; median 889.50 µm) did not close. In one eye, the hole reopened 4 months after stopping the medication but closed again at 1 month after restarting the topical treatment. Median best-corrected visual acuity improved from 0.35 logMAR at baseline to 0.05 logMAR in eyes that closed but remained at 0.70 logMAR at 1 month in eyes that did not close.

Conclusion:
Topical corticosteroid, nonsteroidal antiinflammatory, and carbonic anhydrase inhibitor therapy may promote closure of small full-thickness macular holes, but large holes are less likely to respond. One month of topical therapy might avoid subjecting some patients to complex vitreoretinal surgery without compromising visual outcomes. Macular hole may reopen after stopping the topical therapy.
Characterization of cannabinoid plasma concentration, maternal health, and cytokine levels in a rat model of prenatalCannabissmoke exposure
Authors: Black Tallan , Baccetto Sarah L. , Barnard Ilne L. , Finch Emma , McElroy Dan L. , Austin-Scott Faith V. L. , Greba Quentin , Michel Deborah , Zagzoog Ayat , Howland John G. , Laprairie Robert B. 
Published: June 2023

AbstractCannabis sativahas gained popularity as a “natural substance”, leading many to falsely assume that it is not harmful. This assumption has been documented amongst pregnant mothers, many of whom considerCannabisuse during pregnancy as benign. The purpose of this study was to validate aCannabissmoke exposure model in pregnant rats by determining the plasma levels of cannabinoids and associated metabolites in the dams after exposure to eitherCannabissmoke or injected cannabinoids. Maternal and fetal cytokine and chemokine profiles were also assessed after exposure. Pregnant Sprague-Dawley rats were treated daily from gestational day 6 – 20 with either room air,i.p.vehicle, inhaled high-Δ9-tetrahydrocannabinol (THC) (17.98% THC, 0.1% cannabidiol [CBD]) smoke, inhaled high-CBD (0.1% THC, 12.83% CBD) smoke, 3 mg/kgi.p.THC, or 10 mg/kgi.p.CBD. Our data reveal that THC and CBD, but not their metabolites, accumulate in maternal plasma after repeated exposures. Injection of THC or CBD was associated with fewer offspring and increased uterine reabsorption events. For cytokines and chemokines, injection of THC or CBD up-regulated several pro-inflammatory cytokines compared to control or high-THC smoke or high-CBD smoke in placental and fetal brain tissue, whereas smoke exposure was generally associated with reduced cytokine and chemokine concentrations in placental and fetal brain tissue compared to controls. These results support existing, but limited, knowledge on how different routes of administration contribute to inconsistent manifestations of cannabinoid-mediated effects on pregnancy. SmokedCannabisis still the most common means of human consumption, and more preclinical investigation is needed to determine the effects of smoke inhalation on developmental and behavioural trajectories.
Cofea: correlation-based feature selection for single-cell chromatin accessibility data
Authors: Li Keyi , Chen Xiaoyang , Song Shuang , Hou Lin , Chen Shengquan , Jiang Rui 
Published: June 2023

ABSTRACTSingle-cell sequencing technologies have revolutionized the understanding of cellular heterogeneity at an unprecedented resolution. However, the high-noise and high-dimensional nature of single-cell data poses challenges for downstream analysis, and thus increases the demand for selecting biologically informative features when processing and analyzing single-cell data. Such approaches are mature for single-cell RNA sequencing (scRNA-seq) data, while for single-cell chromatin accessibility sequencing data, the epigenomic profiles at the cellular level, there is a significant gap in the availability of effective methods. Here we present Cofea, a correlation-based framework that focuses on the correlation between accessible chromatin regions, to accurately select scCAS data’s features which are highly relevant to biological processes. With various simulated datasets, we quantitively demonstrate the advantages of Cofea for capturing cellular heterogeneity of imbalanced cell populations or differentiation trajectories. We further demonstrate that Cofea outperforms existing feature selection methods in facilitating downstream analysis, particularly in cell clustering, on a wide range of real scCAS datasets. Applying this method to identification of cell type-specific peaks and candidate enhancers, pathway enrichment analysis and partitioned heritability analysis, we show the potential of Cofea to uncover functional biological process and the genetic basis of cellular characteristics.
Genetic Association ofPLAG1Gene Variant 14:25015640G>T with Wither-Height in Pakistani Cattle
Authors: Naeem Muneeba , Zahid Sarosh , Fatima Seemab , Raza Muhammad Hassan , Zafar Muhammad Osama , Saif Rashid 
Published: June 2023

AbstractThe cow is one of the most valuable domesticated animals, producing milk, meat, fiber, hide and manure for agricultural purposes to serve humanity. Particularly, first two production traits are significantly linked with the physical characteristics of the animal e.g., wither-height, large body-size and skeletal frame are positively correlated with these production traits. ThePLAG1is one of the many genes that has been associated with the aforementioned trait in many livestock and human species. So, the current study was conducted on a total of 50 cattles using ARMS-PCR genotyping technique followed by genetic association testing of the 14:25015640G>T variant using PLINK data analysis toolset. Our findings showed that 24% of the sampled Pakistani cow population are homozygous wild-type (GG), 12% homozygous mutant (TT), while 64% found heterozygous (GT). Sampled cows were obeying Hardy Weinberg Equilibrium (HWE) withχ2 (2, N = 50) = 10.39,p= 0.049. Similarly, Chi-square variant association was also observed significant withp-value of 1.267×10−3having minor-allele frequency of 0.60 and 0.28 in heighted (cases) and control cohorts respectively. Additionally, a positive odds-ratio of 3.85 is also evident that the subject variant is under-selection and showing the tendency of the mutant allele almost 4-times higher in cases vs control groups. This pilot scale study would be helpful to gain insight of variability of the subject SNP in the sampled cow population but further functional studies on larger sample size may be conducted for validation and subsequent results can be disseminated to improve this valued trait of the indigenous cows for gaining maximum milk and meat production from this esteemed species.
An EGF-modified PLGA-lanthanide nanoplatform for combined NIR-II cancer imaging and targeted drug delivery
Authors: He Yuanyuan , Yu Zhenfeng , Schomann Timo , Zhang Hong , Eich Christina , Cruz Luis J. 
Published: June 2023

AbstractThe use of multifunctional nanoplatforms for synergistic therapy and imaging is a promising approach in cancer treatment. In this study, we exploited the imaging properties of lanthanides by encapsulating CaF2:Y, Nd along with the chemotherapeutic drug doxorubicin (DOX) into poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to prepare a nanoplatform suitable for imaging in the second near-infrared (NIR-II) window and simultaneous anti-cancer therapy. To facilitate the accumulation of CaF2:Y, Nd+DOX@PLGA NPs in breast cancer cells, we modified the NPs with EGF. The diameter of the obtained CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs was approximately 150 nm, with a nearly round shape and homogeneous size distribution. In addition, analysis of the drug release behaviour showed that DOX was released more readily and had a longer release time in acidic environments. Accordingly, MTS results indicated that DOX-loaded NPs were significantly cytotoxic. Furthermore, fluorescence microscopy and flow cytometry studies revealed that CaF2:Y, Nd+DOX@PLGA/PEG and CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs were gradually taken up by 4T1 breast cancer cells over time, and EGF-coated Nd+DOX@PLGA NPs exhibited increased uptake rates after 72 h. Moreover, we found that EGF increased the solubility of Nd+DOX@PLGA NPs in water by comparing the aqueous solutions of the different NPs formulations. Finally, NIR imaging demonstrated strong fluorescence of PLGA NPs carrying CaF2:Y, Nd NPs at 900-1200 nm under 808 nm laser excitation. In conclusion, the developed CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs could be monitored for an extended period of time, and co-encapsulated DOX could be efficiently released to kill breast cancer cells.
Spatially clustered pattern of transcription factor binding reveals phase-separated transcriptional condensates at super-enhancers
Authors: Wang Zhenjia , Wang Shengyuan , Zang Chongzhi 
Published: June 2023

ABSTRACTMany transcription factors (TFs) have been shown to bind at super-enhancers, forming transcriptional condensates to activate transcription in many cellular systems. Genomic and epigenomic determinants of phase-separated transcriptional condensates are not well understood. Here we systematically analyzed DNA sequence motifs and TF binding profiles across human cell types to identify the molecular features that contribute to the formation of transcriptional condensates. We found that most DNA sequence motifs are not distributed randomly in the genome, but exhibiting spatially clustered patterns associated with super-enhancers. TF binding sites are further clustered and enriched at cell-type-specific super-enhancers. TFs exhibiting clustered binding patterns also have high liquid-liquid phase separation abilities. Compared to regular TF binding, densely clustered TF binding sites are more enriched at cell-type-specific super-enhancers with higher chromatin accessibility, higher chromatin interaction, and higher association with cancer outcome. Our results indicate that the clustered pattern of genomic binding and the phase separation properties of TFs collectively contribute to the formation of transcriptional condensates.
A comprehensive analysis ofAPOEgenotype effects on human brain structure in the UK Biobank
Authors: Heise Verena , Offer Alison , Whiteley William , Mackay Clare E , Armitage Jane M , Parish Sarah 
Published: June 2023

AbstractAlzheimer’s disease (AD) risk is increased in carriers of the apolipoprotein E (APOE) ε4 allele and decreased in ε2 allele carriers compared with the ε3ε3 genotype. The aim of this study was to determine whether:APOEgenotype affects brain grey (GM) or white matter (WM) structure; and if differences exist, the age when they become apparent and whether there are differential effects by sex. We used cross-sectional magnetic resonance imaging data from ~43,000 (28,494 after pre-processing) white British cognitively healthy participants (7,446APOEε4 carriers) aged 45-80 years from the UK Biobank cohort and investigated image-derived phenotypes (IDPs). We observed no statistically significant effects ofAPOEgenotype on GM structure volumes or median T2* in subcortical structures, a measure related to iron content. Volume of white matter hyperintensities differed significantly betweenAPOEgenotype groups with higher volumes inAPOEε4ε4 (effect size 0.14 standard deviations [SD]) and ε3ε4 carriers (effect size 0.04 SD) but no differences in ε2 carriers compared with ε3ε3 carriers. WM integrity measures in the dorsal (mean diffusivity [MD]) and ventral cingulum (MD and intracellular volume fraction), posterior thalamic radiation (MD and isotropic volume fraction) and sagittal stratum (MD) indicated lower integrity inAPOEε4ε4 carriers (effect sizes around 0.2-0.3 SD) and ε3ε4 (effect sizes around 0.05 SD) carriers but no differences in ε2 carriers compared with theAPOEε3ε3 genotype. Effects did not differ between men and women.APOEε4 homozygotes appeared to have lower WM integrity specifically at older ages with a potentially steeper decline of WM integrity from the age of 60 that corresponds to around 5 years greater “brain age”.APOEgenotype affects various white matters measures, which might be indicative of preclinical AD processes. This hypothesis can be assessed in future when clinical outcomes become available.
A geometrical framework for thinking about proteins
Authors: Banavar Jayanth R. , Giacometti Achille , Hoang Trinh X. , Maritan Amos , Škrbić Tatjana 
Published: June 2023

AbstractWe present a model, based on symmetry and geometry, for proteins. Using elementary ideas from mathematics and physics, we derive the geometries of discrete helices and sheets. We postulate a compatible solvent-mediated emergent pairwise attraction that assembles these building blocks, while respecting their individual symmetries. Instead of seeking to mimic the complexity of proteins, we look for a simple abstraction of reality that yet captures the essence of proteins. We employ analytic calculations and detailed Monte Carlo simulations to explore some consequences of our theory. The predictions of our approach are in accord with experimental data. Our framework provides a rationalization for understanding the common characteristics of proteins. Our results show that the free energy landscape of a globular protein is pre-sculpted at the backbone level, sequences and functionalities evolve in the fixed backdrop of the folds determined by geometry and symmetry, and that protein structures are unique in being simultaneously characterized by stability, diversity, and sensitivity.Statement for broader audienceWe present a simple geometrical model of a chain, which captures the essential features of globular proteins, and explore its consequences. Our model marries the ideas of Kepler, of objects touching each other, and Pauling, of hydrogen bonds providing scaffolding for helices and sheets. We suggest a poking potential for a chain, whose deployment yields the correct structures of both helices and sheets, while promoting the assembly of the building blocks into the tertiary structure.