bluuebunny/crossref_metadata_2025 huggingface dataset:
The ages and metallicities of the globular clusters in the Sparkler
Authors: Adamo Angela , Usher Christopher , Pfeffer Joel , Claeyssens Adélaïde
Published: June 2023

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.
Nigerian Politics and Government
Authors: Onapajo Hakeem
Published: June 2023

Nigeria’s status as the “Giant of Africa” is not only an expression suggesting it has the largest population size in the region, but also implies the immense influence the Nigerian state has on African politics and society. It is arguable that a proper understanding of politics and government in Nigeria should provide a good understanding of African politics. Nigeria is a product of British colonialism and gained its independence in 1960. Being a plural society with multiple ethnic groups, the Nigerian political system is built on a three-tier federal system (federal, state, and local governments). Modeled after the American model of democracy, Nigeria operates a presidential system that produces a president exercising enormous executive power at the federal level and a governor as head of the executive in the thirty-six (subnational) states in the federation. The legislative system is bicameral at the federal level and unicameral at the state level. With an estimated 300 ethnic groups, Nigeria is often considered the most diverse society in Africa. Despite the multiple ethnic groupings, three major ethnic groups dominate the political space given their population and linguistic spread over other groups. The majority groups are the Hausa-Fulani (northern region), Yoruba (western region) and the Igbo (eastern region). Besides these majority groups, there are hundreds of minority groups spread across the different regions of the country. In addition to ethnicity, religion represents another significant component of Nigerian society and has a major influence on politics. Nigerians mostly identify with Christianity or Islam, while a few associate with the African Traditional Religion. In geographical spread, there are more Muslims in the northern region and more Christians in the southern region. Over the years, ethnicity and religion have been a major factor in Nigerian politics, determining access to power and distribution of values. These factors have become a major driver of politics and therefore feature prominently in any discourse about politics and government in Nigeria. Politics in Nigeria since independence has oscillated between civilian democracy and military rule. Democracy failed at three different periods before the present democratic regime, which began in 1999. The military interventions and abrupt end to democratic rules give room for the periodization of the First, Second, Third, and Fourth Republics that is often employed as a framework of analysis in the study of Nigerian politics and government.
Actor-Network Theory
Authors: Birkbak Andreas
Published: June 2023

Actor-Network Theory (ANT) is an approach developed in the field of science and technology studies (STS) to avoid purely social and purely technical explanations for scientific and technological developments. ANT offers the departure point of symmetrical constructivism, where there are no primordially social or technical domains, only socio-technical hybrids. As such, ANT is a crucial instigator of a wider turn away from human-centric perspectives in social research. ANT decenters humans by offering an ontological outlook where all actors, humans included, are constituted through their heterogeneous relations with other entities. According to ANT, agency is not a human privilege, but something that emerges in networks of relations between humans and nonhuman alike, thus the name actor-network theory. ANT emerged in France and the United Kingdom in the early 1980s and its influence on STS in the following decades is hard to overestimate. Early ANT brought forward relational, processual, and constructivist studies of scientific practices and technological development. Since around 1990, ANT has been taken up in a wide range of contexts, as the thematic sections below illustrate. This broadening is sometimes associated with the label post-ANT, which signifies a more explicit engagement with the entanglements of multiple practical ontologies, and ethical and political concerns in ANT research, often in conversation with feminist STS and other post-structuralist approaches in the humanities and social sciences. Today, ANT approaches are at work across many scholarly disciplines and fields, where ANT tends to play the role of a heterodox and sometimes even implicit background rather than an explicit theoretical or methodological school. In response to this, the present annotated bibliography seeks to strike a balance between guiding the reader toward classic ANT texts and including some of the trajectories of research that have followed on from ANT in more or less manifest ways. It is not uncommon to omit the label of ANT even in key ANT texts. For example, a central contributor such as Michel Callon refers to the “sociology of translation” instead of ANT. As this lack of fixed vocabulary illustrates, defining the boundaries of the ANT literature is a never-ending task that only has temporary, partial solutions. The aim of this bibliography is not to claim exhaustiveness, but to provide a solid guide for students and researchers who need starting points, either for engaging with ANT in general, or for encountering work within their specific fields of study that have engaged with ANT.
Slang
Authors: Adams Michael
Published: June 2023

Since 1774, the word slang has referred to a type of informal speech not quite distinct from cant, an earlier term for cryptolects (secret languages) employed by rogues, vagabonds, and thieves in early modern England. The word slang thus suggests a broadening of users, contexts, and ultimately the term’s meaning, though after a century and more of argument, we have not yet arrived at a satisfactory definition or agreement about the slang concept. Indeed, since the rise of sociolinguistics, which tends to see language continua rather than categories, legitimacy of the slang concept has been challenged and dismissed by many linguists. Nevertheless, speakers of English and many other languages recognize a register that they call slang, and it thus deserves attention, if not as a linguistic, at least as a cultural phenomenon—one hopes that, if it is a linguistic thing, linguists can arrive at a plausible theory of slang. In the meantime, slang has some theory behind it, a long history, can be described in terms of various populations and places, and is well documented over the centuries in dictionaries of various types. Slang develops in subcultures and is thus an essential object of study, a way to understand the subcultures in which all people live and their relationship to “mainstream” culture. Study of the relationship between subcultural language and “mainstream” language is also important, including, of course, standard varieties, which some have argued serve not only as points of departure for slang, but as the very thing from which slang dissents, both linguistically and ideologically. Other sorts of niche vocabularies sometimes parallel and sometimes overlap with slang, including jargon—the vocabularies of vocations and avocations—ethnic and racial slurs, and, arguably, profanity, although much of what we have called “profanity” over the ages is now slang in use, often hyperexpressive slang, itself a development in the history and structure of slang. This bibliography avoids slurs—as an altogether different type of language pragmatically—and jargon—because the function of jargon is often different from that of slang, besides which there is little recent scholarly attention paid to it—but it does include a brief section on profanity, which, while relevant here, nonetheless probably deserves its own bibliography.
Positive Discourse Analysis
Authors: Mallet Aurelie , Mahboob Ahmar
Published: June 2023

Positive discourse analysis (PDA) falls under the broader umbrella of discourse analysis and privileges discourses that promote empowerment and social change. PDA is often viewed as a complementary approach to critical discourse analysis (CDA) which aims to expose hegemonic discourses and discourses of disempowerment. While CDA has been useful in bringing to light discriminatory discourse practices, it has been less reliable at providing the means to change such hegemonic practices. PDA on the other hand, not only promotes positive discourse, it also advocates for design and interventions that empowers people and brings about social change. Since being first coined in 2002, PDA has been employed in many linguistic subfields including media discourse, ecolinguistics, and educational linguistics. And more recently, PDA has been developed as a tool for community members to use to address issues in their local communities. The major theory underpinning PDA is Systemic Functional Linguistics (SFL). SFL provides a functional theory of how language is used in social context and models language according to its three general social functions: to represent experience, to enact social relationships, and to organize these experiences and social relationships. But first and foremost, SFL is concerned with redressing inequality. For this reason, SFL frameworks are often used in PDA studies, in text analyses, and in designing materials and interventions. This bibliography explores some of the main linguistics subfields where positive discourse analysis has taken ground over the past two decades. However, there are plenty of studies that would be considered PDA prior to its coinage as a methodological approach. Therefore, this bibliography presents a variety of studies that either explicitly use PDA as a methodological approach or others that have not necessarily employed the term PDA, but would nevertheless be considered PDA since they advocate for positive discourses, social change and empowerment.
Video Games and Violent Content
Authors: Rogojina Alena , Kim El-Lim , Miles-Novelo Andreas , Gentile Douglas A.
Published: June 2023

Scientific inquiry into the effects of violent video games emerged in the 1980s as a focused area of media violence research. Early studies on media-based effects examined how individuals observed media content and learned attitudes and behaviors depicted in the media. Pioneering studies on video game violence adapted a similar research framework. However, a marked difference between video games and other forms of media (e.g., television, movies, music) is that the former requires the user to be an active participant—exploring the world, controlling the avatar, making choices, and earning rewards. This greater level of involvement theoretically should facilitate greater learning. As video games became more popular, technologically advanced, and immersive, research into their effects grew and evolved. Although the often fast-paced nature of violent video games seems to have a positive effect on players’ cognitive abilities, such as distraction filtering, the violent content also negatively affects social and emotional outcomes, such as increased aggressive cognitions and behaviors. Such negative outcomes may be particularly salient in early adolescence. This article provides a review of the theoretical foundations of, and early findings in, the field of violent video game effects research and a listing of relevant up-to-date empirical studies as well as a broader overview of the field through relevant reviews and meta-analyses.
Catalytic Climate Litigation: Rights and Statutes
Authors: Bookman Sam
Published: June 2023

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

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

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.
Sleep
Authors: Venneman Sandy S.
Published: June 2023

Sleep can impact health and performance. With increased knowledge about sleep hygiene and sleep disorders, nurses can teach patients practical behaviors and strategies to promote healthy sleep habits and assist their journey to healing and recovery.
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

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.
Drug Formulation for Pediatric Oral Antimicrobial Agents in Japan: Current Status, Prospects, and Challenges
Authors: Saito Jumpei , Shoji Kensuke , Miyairi Isao , Yamatani Akimasa
Published: June 2023

The development of antibiotics that are acceptable and easy for children to take and use is highly desirable. As advocated by the World Health Organization, solid oral formulations with excellent shelf-life, taste masking and dose adjustment are attracting attention as appropriate pediatric oral antimicrobial formulations, but liquid formulations remain the most common worldwide. Apparently unique to Japan, the most common formulations of oral antimicrobials for pediatric use are dispensed as a powder with most being flavored powders. Powdered formulations are packaged in single doses, which eliminates the need for parents to weigh them before administration and may reduce the possibility of dosage errors. On the other hand, there are some formulations that require large doses of powder due to inappropriate concentrations, granular formulations that have a rough texture that affects palatability, and some formulations that require flavoring agents to mask the bitter taste of the main drug. Such inappropriate formulations have a significant impact on adherence to antimicrobial therapy. It remains unclear whether solid oral dosage forms might be as acceptable worldwide as in Japan. To ensure that appropriate antimicrobials are delivered to children worldwide, a direction for the development of appropriate dosage forms in children needs to be established.
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

Cannabis 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.
Physiological phenotypes differ among color morphs in introduced populations of the common wall lizard,Podarcis muralis
Authors: Amer Ali , Spears Sierra , Vaughn Princeton L. , Colwell Cece , Livingston Ethan H. , McQueen Wyatt , Schill Anna , Reichard Dustin , Gangloff Eric J. , Brock Kinsey M
Published: June 2023

Many species exhibit color polymorphisms which have distinct physiological and behavioral characteristics. However, the consistency of morph trait covariation patterns across species, time, and ecological contexts remains unclear. This trait covariation is especially relevant in the context of invasion biology and urban adaptation. Specifically, physiological and behavioral traits pertaining to energy maintenance are crucial to fitness, given their immediate ties to individual reproduction, growth, and population establishment. We investigated the physiological and behavioral traits ofPodarcis muralis, a versatile color polymorphic species that thrives in urban environments (including invasive populations in Ohio, USA). We measured five physiological and behavioral traits (circulating corticosterone and triglycerides, hematocrit, body condition, and field body temperature) which compose an integrated multivariate phenotype. We then tested variation among stable color polymorphisms in the context of establishment in an urban environment. We found that the traits describing physiological status and strategy shifted across the active season in a morph-dependent manner - the white and yellow morphs exhibited clearly different multivariate physiological phenotypes, characterized primarily by differences in circulating corticosterone. This suggests that morphs have different strategies in physiological regulation, the flexibility of which is crucial to urban adaptation. The white-yellow morph exhibited an intermediate phenotype, suggesting an intermediary energy maintenance strategy. Orange morphs also exhibited distinct phenotypes, but the low prevalence of this morph in our study populations precludes clear interpretation. Our work provides insight into how differences among stable polymorphisms exist across axes of the phenotype and how this variation may aid in establishment within novel environments.
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

Single-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

The 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

The 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

Many 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

Alzheimer’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

We 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 audience

We 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.
Cross-species comparison of pregnancy-induced GDF15
Authors: Klein Anders Bue , Ranea-Robles Pablo , Nicolaisen Trine Sand , Gil Claudia , Johann Kornelia , Quesada Júlia Prats , Pistolevij Nina , Hviid Kathrine V.R. , Olsen Line F. , Offersen Simone M. , Helge Jørn Wulff , Svarre-Nielsen Henriette , Bakker Jaco , Kleinert Maximillian , Clemmensen Christoffer
Published: June 2023

GDF15 (growth differentiation factor 15) is a stress-induced cytokine. Although the exact physiological function of GDF15 is not yet fully comprehended, the significant elevation of circulating GDF15 levels during gestation suggests a potential role for this hormone in pregnancy. This is corroborated by genetic association studies in which GDF15 and the GDF15 receptor, GDNF Family Receptor Alpha Like (GFRAL) have been linked to morning sickness and hyperemesis gravidarum (HG) in humans. Here, we studied GDF15 biology during pregnancy in mice, rats, macaques, and humans. In contrast to macaques and humans, mice and rats exhibited an underwhelming induction in plasma GDF15 levels in response to pregnancy (∼75-fold increase in macaques vs. ∼2-fold increase in rodents). The changes in circulating GDF15 levels were corroborated by the magnitude ofGdf15mRNA and GDF15 protein expression in placentae from mice, rats, and macaques. These species-specific findings may help guide future studies focusing on GDF15 in pregnancy and on the evaluation of pharmacological strategies to interfere with GDF15-GFRAL signaling to treat severe nausea and HG.
Seq-InSite: sequence supersedes structure for protein interaction site prediction
Authors: Hosseini SeyedMohsen , Golding G. Brian , Ilie Lucian
Published: June 2023

Proteins accomplish cellular functions by interacting with each other, which makes the prediction of interaction sites a fundamental problem. Computational prediction of the interaction sites has been studied extensively, with the structure-based programs being the most accurate, while the sequence-based ones being much more widely applicable, as the sequences available outnumber the structures by two orders of magnitude. We provide here the first solution that achieves both goals. Our new sequence-based program, Seq-InSite, greatly surpasses the performance of sequence-based models, matching the quality of state-of-the-art structure-based predictors, thus effectively superseding the need for models requiring structure. Seq-InSite is illustrated using an analysis of four protein sequences. Seq-InSite is freely available as a web server atseq-insite.csd.uwo.caand as free source code, including trained models and all datasets used for training and testing, atgithub.com/lucian-ilie/seq-insite.
Increased reliance on temporal coding when target sound is softer than the background
Authors: Alamatsaz Nima , Rosen Merri J. , Ihlefeld Antje
Published: June 2023

Everyday environments often contain multiple concurrent sound sources that fluctuate over time. Normally hearing listeners can benefit from high signal-to-noise ratios (SNRs) in energetic dips of temporally fluctuating background sound, a phenomenon called dip-listening. Specialized mechanisms of dip-listening exist across the entire auditory pathway. Both the instantaneous fluctuating and the long-term overall SNR shape dip-listening. An unresolved issue regarding cortical mechanisms of dip-listening is how target perception remains invariant to overall SNR, specifically, across different tone levels with an ongoing fluctuating masker. Equivalent target detection over both positive and negative overall SNRs (SNR invariance) is reliably achieved in highly-trained listeners. Dip-listening is correlated with the ability to resolve temporal fine structure, which involves temporally-varying spike patterns. Thus the current work tests the hypothesis that at negative SNRs, neuronal readout mechanisms need to increasingly rely on decoding strategies based on temporal spike patterns, as opposed to spike count. Recordings from chronically implanted electrode arrays in core auditory cortex of trained and awake Mongolian gerbils that are engaged in a tone detection task in 10 Hz amplitude-modulated background sound reveal that rate-based decoding is not SNR-invariant, whereas temporal coding is informative at both negative and positive SNRs.
Gamma-Oscillation Plasticity Is Mediated by Parvalbumin Interneurons
Authors: Hadler Michael D. , Tzilivaki Alexandra , Schmitz Dietmar , Alle Henrik , Geiger Jörg R. P.
Published: June 2023

Understanding the plasticity of neuronal networks is an emerging field of (patho-)physiological research, yet little is known about the underlying cellular mechanisms. Gamma-oscillations (30 – 80 Hz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. Inex vivolocal field potential recordings, we demonstrate long-term potentiation of hippocampal gamma-power. Gamma-potentiation obeys established rules of PVI plasticity, requiring calcium-permeable AMPA receptors (CP-AMPARs) and metabotropic glutamate receptors (mGluRs). A microcircuit model of CA3 gamma-oscillations predicts CP-AMPAR plasticity onto PVIs critically outperforms pyramidal cell plasticity in increasing gamma-power and completely accounts for gamma-potentiation. We re-affirm this ex vivo in three PVI-targeting animal models, demonstrating that gamma-potentiation requires PVI-specific metabotropic signaling via a Gq/PKC-pathway comprising mGluR5 and a Gi-sensitive, PKA-dependent pathway. Gamma-activity dependent, metabotropically mediated CP-AMPAR plasticity on PVIs may serve as a guiding principle in understanding network plasticity in health and disease.
Solvent influence on the crystal structures of new cadmium tri-tert-butoxysilanethiolate complexes with 1,4-bis(3-aminopropyl)piperazine: luminescence and antifungal activity
Authors: Kowalkowska-Zedler Daria , Bruździak Piotr , Hnatejko Zbigniew , Łyszczek Renata , Brillowska-Dąbrowska Anna , Ponikiewski Łukasz , Cieśla Bartosz , Pladzyk Agnieszka
Published: June 2023

Monocrystals of dinuclear μ-1,4-bis(3-aminopropyl)piperazine-κ4
N
1,N
1′:N
4,N
4′-bis[bis(tri-tert-butoxysilanethiolato-κS)cadmium(II)], [Cd2(C12H27O3SSi)4(C10H24N4)] or [Cd2{SSi(OtBu)3}4(μ-BAPP)], 1, and polynuclear catena-poly[[bis(tri-tert-butoxysilanethiolato-κS)cadmium(II)]-μ-1,4-bis(3-aminopropyl)piperazine-κ2
N
1′:N
4′], [Cd(C12H27O3SSi)2(C10H24N4)]
n
or [Cd{SSi(OtBu)3}2(μ-BAPP)]
n
, 2, with 1,4-bis(3-aminopropyl)piperazine (BAPP) and tri-tert-butoxysilanethiolate ligands, were obtained from the same ratio of reactants, but with different solvents used for the crystallization processes. The structures and properties of both complexes were characterized using elemental analysis, X-ray diffraction and FT–IR, 1H NMR and luminescence spectroscopy. Applied density functional theory (DFT) computational methods and noncovalent interaction (NCI) analysis were used for geometry optimization and visualization of the interactions between the metallic centres and their surroundings. The X-ray analysis revealed four-coordinate CdII centres bound to two S atoms of the silanethiolate groups and two N atoms of the BAPP ligand; however, it chelates to tertiary and primary N atoms in 1, whilst in 2 it does not chelate and bonds only to RNH2. The photoluminescence properties of complexes 1 and 2 result from free-ligand emission and differ significantly from each other with respect to emission intensity. Additionally, antifungal activity was investigated against 18 isolates of fungi. Compound 1 strongly inhibited the growth of three dermatophytes: Epidermophyton floccosum, Microsporum canis and Trichophyton rubrum.
Algorithms for magnetic symmetry operation search and identification of magnetic space group from magnetic crystal structure
Authors: Shinohara Kohei , Togo Atsushi , Tanaka Isao
Published: June 2023

A crystal symmetry search is crucial for computational crystallography and materials science. Although algorithms and implementations for the crystal symmetry search have been developed, their extension to magnetic space groups (MSGs) remains limited. In this paper, algorithms for determining magnetic symmetry operations of magnetic crystal structures, identifying magnetic space-group types of given MSGs, searching for transformations to a Belov–Neronova–Smirnova (BNS) setting, and symmetrizing the magnetic crystal structures using the MSGs are presented. The determination of magnetic symmetry operations is numerically stable and is implemented with minimal modifications from the existing crystal symmetry search. Magnetic space-group types and transformations to the BNS setting are identified by a two-step approach combining space-group-type identification and the use of affine normalizers. Point coordinates and magnetic moments of the magnetic crystal structures are symmetrized by projection operators for the MSGs. An implementation is distributed with a permissive free software license inspglibv2.0.2: https://github.com/spglib/spglib.
Internal audit function, audit report lag and audit fee: evidence from the early stage of COVID-19 pandemic
Authors: Harymawan Iman , Putri Fiona Vista
Published: June 2023

Purpose

How does the internal audit function make external auditors work more efficiently at the early stage of the COVID-19 pandemic? This study examines the relationship between internal audit function, audit report lag and audit fee at the early stage of the COVID-19 pandemic.

Design/methodology/approach

This study uses data from all public firms listed on the Indonesia Stock Exchange from 2018 to 2019 using the difference-in-difference test technique to answer the proposed hypothesis. In addition, this study also tested the issue of endogeneity using Coarsened Exact Matching (CEM) and Two-Stage Least Square (Heckman, 1979).

Findings

This study finds that, at the early stage of the COVID-19 pandemic, a good internal audit function significantly reduced audit report lag and audit fee. These findings indicate that good corporate governance implemented through an internal audit function during the COVID-19 pandemic can give assurance to prevent and mitigate the firm's risk so that external auditors can work more efficiently. Furthermore, this study also carries out an additional analysis by subsampling the high and low technological industries. Based on the robustness test, it is revealed that the results of this study are consistent.

Originality/value

This study contributes to the novelty of literature in auditing studies that highlights the audit process at the early stage of the COVID-19 pandemic