bluuebunny/crossref_metadata_2025_split huggingface dataset:
Legislation and the Stress of Environmental Problems
Authors: Scotford Eloise 
Published: October 2021

Abstract
For lawyers and legal scholars, legislation seems a known quantity—a relatively permanent, public expression of democratic processes in parliamentary democracies and of the rule of law. This ‘knowable’ character can however be misleading, particularly in the field of environmental law. This article examines why research into environmental legislation is challenging but critically important. A short history of UK environmental law provides salient examples of political stress and highly complex, unsettled, even unknowable, environmental legislation. Collective environmental problems demand legislative responses in shaping individual behaviours and guiding social policies—but knowing how to craft these responses and how to evaluate the resulting legislation is often uncharted legal territory. Navigating that legislative terrain is a vital task for legal scholars and practitioners, particularly to investigate the serious legal problems that can arise from its construction, including poor legibility, legal fragmentation, and concerns about compatibility with the rule of law.
TORC1 signaling modulates Cdk8-dependent GAL gene expression in Saccharomyces cerevisiae
Authors: Horvath Riley , Hawe Nicole , Lam Cindy , Mestnikov Konstantin , Eji-Lasisi Mariam , Rohde John , Sadowski Ivan 
Published: October 2021

Abstract
Cdk8 of the RNA polymerase II mediator kinase complex regulates gene expression by phosphorylating sequence-specific transcription factors. This function is conserved amongst eukaryotes, but the signals and mechanisms regulating Cdk8 activity and phosphorylation of its substrates are unknown. Full induction of the GAL genes in yeast requires phosphorylation of the transcriptional activator Gal4 by Cdk8. We used a screen to identify regulators of the Cdk8-dependent phosphorylation on Gal4, from which we identified multiple mutants with defects in TORC1 signaling. One mutant, designated gal four throttle 1 (gft1) was identified as a recessive allele of hom3, encoding aspartokinase, and mutations in hom3 caused effects typical of inhibition of TORC1, including rapamycin sensitivity and enhanced nuclear localization of the TORC1-responsive transcription factor Gat1. Mutations in hom3 also inhibit phosphorylation of Gal4 in vivo at the Cdk8-dependent site on Gal4, as did mutations of tor1, but these mutations did not affect activity of Cdk8 assayed in vitro. Disruption of cdc55, encoding a regulatory subunit of the TORC1-regulated protein phosphatase PP2A, suppressed the effect of hom3 and tor1 mutations on GAL expression, and also restored phosphorylation of Gal4 at the Cdk8-dependent site in vivo. These observations demonstrate that TORC1 signaling regulates GAL induction through the activity of PP2A/Cdc55 and suggest that Cdk8-dependent phosphorylation of Gal4 is opposed by PP2A/Cdc55 dephosphorylation. These results provide insight into how induction of transcription by a specific inducer can be modulated by global nutritional signals through regulation of Cdk8-dependent phosphorylation.
Constructing a regional human rights legal order: The Inter-American Court, national courts, and judicial dialogue, 1988–2014
Authors: Gonzalez-Ocantos Ezequiel , Sandholtz Wayne 
Published: October 2021

Abstract
Why do courts rely on specific bodies of jurisprudence to justify decisions? We analyze judicial dialogue in the Inter-American System, where the Inter-American Court of Human Rights (IACtHR) has defined its mission as the construction of a regional legal order. This order needs courts at all levels to engage with each other. Original databases of citations by the IACtHR to the judgments of national courts, and in the opposite direction, allow us to establish whether such practices are emerging. Furthermore, the article asks why the IACtHR cites some courts but not others, and to what end. Statistical models reveal that the IACtHR is more likely to cite case law from countries that exhibit characteristics that are more conducive to the creation of a regional human rights legal order, and jurisprudence from countries with which it has had more extensive experience and interaction. Qualitative content analysis suggests that the IACtHR uses citations as a source of persuasive authority, but also to showcase domestic acceptance of its doctrines and decisions. This leads us to characterize citations as an effort to educate courts in the use of Inter-American jurisprudence and thus foster greater integration. At the national level, we find considerable temporal/cross-country variation in openness to the dialogue. We rely on original quantitative indicators and case studies to show this is as a function of the IACtHR’s growing visibility and networking efforts, as well as country-level changes in legal cultures and judicial personnel that push courts away from formalism.
Econazole as adjuvant to conventional antibiotics is able to eradicate starvation-induced tolerant bacteria by causing proton motive force dissipation
Authors: Wang Miaomiao , Chan Edward Wai Chi , Xu Chen , Chen Kaichao , Yang Chen , Chen Sheng 
Published: October 2021

Abstract

Objectives
Bacterial antibiotic tolerance is responsible for the recalcitrance of chronic infections. This study aims to investigate a potential drug that can effectively kill antibiotic-tolerant bacteria and evaluate the ability of this drug on the eradication of tolerant cells both in vitro and in vivo.

Methods
The in vitro effect of econazole on eradicating starvation-induced tolerant bacterial populations was studied by testing the amount of survival bacteria in the presence of econazole combining conventional antibiotics. Proton motive force (PMF) was determined after econazole treatment by DiOC2(3). Finally, mouse infection models were used to detect the ability of econazole on killing the tolerant populations in vivo.

Results
Econazole eradicated starvation-induced tolerant cells of various bacterial species within 24 or 96 h when used in combination with conventional antibiotics. Moreover, mouse survival rate drastically increased along with the decrease of in vivo bacterial count after treatment of infected mice with the econazole and ceftazidime combination for 72 h. PMF was found to have dissipated almost completely in econazole-treated cells.

Conclusions
Econazole could act in combination with conventional antibiotics to effectively eradicate bacterial tolerant cells. The combined use of econazole and ceftazidime was shown to be effective for eradicating tolerant cells in a mouse infection model. The ability of econazole to eradicate tolerant cells was due to its ability to cause dissipation of bacterial transmembrane PMF. Econazole-mediated PMF disruption is a feasible strategy for the treatment of chronic and recurrent bacterial infections.
Caspofungin-resistance in Candida auris is cell wall-dependent phenotype and potential prevention by zinc oxide nanoparticles
Authors: Fayed Bahgat , Jayakumar Manju Nidagodu , Soliman Sameh S M 
Published: October 2021

Abstract

Candida auris is an emergent nosocomial multi-drug-resistant yeast that represents a global health threat. Recently, C. auris clinical isolates with caspofungin resistance were identified. Mutation in FKS1 gene was determined as a mechanism of resistance. However, the ability of C. auris to develop acquired and cross-resistance has never been investigated. Herein, this resistance ability due to caspofungin and associate mechanisms were investigated. C. auris clinical isolate was successively cultured for ten generations in the presence of caspofungin compared to fluconazole-treatment and untreated controls. This was followed by the analysis of target gene expression and phenotypic changes. The obtained results showed that caspofungin-treated C. auris exhibited elevated MIC50(caspofungin), slower growth, elevated chitin content, overexpression of caspofungin target genes, and cross-resistance to fluconazole. Interestingly, caspofungin exposure induced cell-cell adhesion and biofilm formation. C. auris gradually lost caspofungin resistance after removal of antifungal pressure, while keeping the overexpression of fungal cell wall-related genes including ALS5. We propose that C. auris ageing in the presence of caspofungin caused the development of persistent phenotypic changes in the fungal cell wall, leading to acquired and physical cross-resistance mechanisms. Surprisingly, formulation of caspofungin in zinc oxide nanoparticles prevented the aforementioned behavioral changes regardless of the pathogen generations.

Lay summary
Candida auris developed resistance against caspofungin. Our data indicated that this resistance mechanism is unique because of changes in the genes related to cell wall adhesions. Formulation of caspofungin in ZnO nanoparticles was able to overcome these phenotypic changes.
A new framework for understanding systematic errors in cluster lens modelling – II. Constraint selection
Authors: Zimmerman Dhruv T , Keeton Charles R , Raney Catie A 
Published: October 2021

ABSTRACT
Cluster lens models are affected by a variety of choices in the lens modelling process. We have begun a programme to develop a systematic error budget for cluster lens modelling. Here, we examine the selection of image constraints as a potential systematic effect. For constraining the mass model, we find that it is more important to have images be spatially distributed around the cluster than to have them distributed in redshift. We also find that some image sets appear to be more important than others in terms of how well they constrain the models; the ‘important’ image sets typically include an image that lies close to a lensing critical curve as well as an image that is relatively isolated from other images (providing constraints in a region that would otherwise lack lensing information). These conclusions can help guide observing programmes that seek follow-up data for candidate lensed images.
Tightly Constrained Genome Reduction and Relaxation of Purifying Selection during Secondary Plastid Endosymbiosis
Authors: Uthanumallian Kavitha , Iha Cintia , Repetti Sonja I , Chan Cheong Xin , Bhattacharya Debashish , Duchene Sebastian , Verbruggen Heroen 
Published: October 2021

Abstract
Endosymbiosis, the establishment of a former free-living prokaryotic or eukaryotic cell as an organelle inside a host cell, can dramatically alter the genomic architecture of the endosymbiont. Plastids or chloroplasts, the light-harvesting organelle of photosynthetic eukaryotes, are excellent models to study this phenomenon because plastid origin has occurred multiple times in evolution. Here, we investigate the genomic signature of molecular processes acting through secondary plastid endosymbiosis—the origination of a new plastid from a free-living eukaryotic alga. We used phylogenetic comparative methods to study gene loss and changes in selective regimes on plastid genomes, focusing on green algae that have given rise to three independent lineages with secondary plastids (euglenophytes, chlorarachniophytes, and Lepidodinium). Our results show an overall increase in gene loss associated with secondary endosymbiosis, but this loss is tightly constrained by the retention of genes essential for plastid function. The data show that secondary plastids have experienced temporary relaxation of purifying selection during secondary endosymbiosis. However, this process is tightly constrained, with selection relaxed only relative to the background in primary plastids. Purifying selection remains strong in absolute terms even during the endosymbiosis events. Selection intensity rebounds to pre-endosymbiosis levels following endosymbiosis events, demonstrating the changes in selection efficiency during different origin phases of secondary plastids. Independent endosymbiosis events in the euglenophytes, chlorarachniophytes, and Lepidodinium differ in their degree of relaxation of selection, highlighting the different evolutionary contexts of these events. This study reveals the selection–drift interplay during secondary endosymbiosis and evolutionary parallels during organellogenesis.
Assessing Sex, Gender Identity, Sexual Orientation, Race, Ethnicity, Socioeconomic Status, and Mental Health Concerns in Tobacco Use Disorder Treatment Research: Measurement Challenges and Recommendations From a Society for Research on Nicotine and Tobacco Pre-conference Workshop
Authors: Weinberger Andrea H , Steinberg Marc L , Mills Sarah D , Dermody Sarah S , Heffner Jaimee L , Kong Amanda Y , Pang Raina D , Rosen Rachel L 
Published: October 2021

Abstract
This paper reports on topics discussed at a Society for Research on Nicotine and Tobacco pre-conference workshop at the 2019 annual Society for Research on Nicotine and Tobacco meeting. The goal of the pre-conference workshop was to help develop a shared understanding of the importance of several tobacco-related priority groups in tobacco use disorder (TUD) treatment research and to highlight challenges in measurement related to these groups. The workshop focused on persons with minoritized sex, gender identity, and sexual orientation identities; persons with minoritized racial and ethnic backgrounds; persons with lower socioeconomic status (SES); and persons with mental health concerns. In addition to experiencing commercial tobacco-related health disparities, these groups are also underrepresented in tobacco research, including TUD treatment studies. Importantly, there is wide variation in how and whether researchers are identifying variation within these priority groups. Best practices for measuring and reporting sex, gender identity, sexual orientation, race, ethnicity, SES, and mental health concerns in TUD treatment research are needed. This paper provides information about measurement challenges when including these groups in TUD treatment research and specific recommendations about how to measure these groups and assess potential disparities in outcomes. The goal of this paper is to encourage TUD treatment researchers to use measurement best practices in these priority groups in an effort to conduct meaningful and equity-promoting research. Increasing the inclusion and visibility of these groups in TUD treatment research will help to move the field forward in decreasing tobacco-related health disparities.
Implications: Tobacco-related disparities exist for a number of priority groups including, among others, women, individuals with minoritized sexual and gender identities, individuals with minoritized racial and ethnic backgrounds, individuals with lower SES, and individuals with mental health concerns. Research on TUD treatments for many of these subgroups is lacking. Accurate assessment and consideration of these subgroups will provide needed information about efficacious and effective TUD treatments, about potential mediators and moderators, and for accurately describing study samples, all critical elements for reducing tobacco-related disparities, and improving diversity, equity, and inclusion in TUD treatment research.
Scaling Up the Discovery of Hesitancy Profiles by Identifying the Framing of Beliefs towards Vaccine Confidence in Twitter Discourse
Authors: Weinzierl Maxwell A. , Hopfer Suellen , Harabagiu Sanda M. 
Published: October 2021

AbstractOur study focused on the inference of the framing of confidence in the HPV vaccine throughout a collection of 422,078 tweets as well as the framing of confidence in the COVID-19 vaccines through a collection of 5,865,046 tweets. The vaccine confidence framings were inferred by using a novel Question/Answering framework enabling the derivation of a misinformation taxonomy as well as trust taxonomies for these two vaccines. These taxonomies, along with the analysis of vaccine literacy, the implied moral foundations and the tension between vaccine mandates and civil rights allowed us to discover several profiles of hesitancy for each vaccine across 138,779 Twitter users referring to confidence in HPV vaccine and 665,798 users referring to confidence in COVID-19 vaccines. These hesitancy profiles inform public health messaging approaches to effectively reach Twitter users with promise to shift or bolster vaccine attitudes.
Characterization and Structural Prediction of ORF10, ORF7b, ORF7a, ORF6, Membrane Glycoprotein, and Envelope Protein in SARS-CoV-2 Bangladeshi Variant through Bioinformatics Approach
Authors: Debnath Pinky , Khan Umama , Khan Md. Salauddin 
Published: October 2021

AbstractThe acute respiratory disease induced by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a global epidemic in just less than a year by the first half of 2020. The subsequent efficient human-to-human transmission of this virus eventually affected millions of people worldwide. The most devastating thing is that the infection rate is continuously uprising and resulting in significant mortality especially among the older age population and those with health co-morbidities. This enveloped, positive-sense RNA virus is chiefly responsible for the infection of the upper respiratory system. The virulence of the SARS-CoV-2 is mostly regulated by its proteins like entry to the host cell through fusion mechanism, fusion of infected cells with neighboring uninfected cells to spread the virus, inhibition of host gene expression, cellular differentiation, apoptosis, mitochondrial biogenesis, etc. But very little is known about the protein structures and functionalities. Therefore, the main purpose of this study is to learn more about these proteins through bioinformatics approaches. In this study, ORF10, ORF7b, ORF7a, ORF6, membrane glycoprotein, and envelope protein have been selected from a Bangladeshi Corona-virus strain G039392 and a number of bioinformatics tools (MEGA-X-V10.1.7, PONDR®, ProtScale, ProtParam, SCRIBER, NetSurfP v2.0, IntFOLD, UCSF Chimera, and PyMol) and strategies were implemented for multiple sequence alignment and phylogeny analysis with 9 different variants, predicting hydropathicity, amino acid compositions, protein-binding propensity, protein disorders, 2D and 3D protein modeling. Selected proteins were characterized as highly flexible, structurally and electrostatically extremely stable, ordered, biologically active, hydrophobic, and closely related to the proteins of different variants. This detailed information regarding the characterization and structure of proteins of SARS-CoV-2 Bangladeshi variant was performed for the first time ever to unveil the deep mechanism behind the virulence features and also, this robust appraisal paves the future way for molecular docking, vaccine development targeting these characterized proteins.
The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities
Authors: Jiménez-Panizo Alba , Alegre-Martí Andrea , Fettweis Gregory , Abella Montserrat , Antón Rosa , Tettey Theophilus , Schiltz Louis R. , Johnson Thomas A , Nuñez-Barrios Israel , Font-Díaz Joan , Caelles Carme , Valledor Annabel F. , Pérez Paloma , Rojas Ana M. , Fernández-Recio Juan , Presman Diego M. , Hager Gordon L. , Fuentes-Prior Pablo , Estébanez-Perpiñá Eva 
Published: October 2021

AbstractThe glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution and quantitative fluorescence microscopy in living cells. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work unveils likely pathophysiologically relevant quaternary assemblies of the nuclear receptor with important implications for glucocorticoid action and drug design.
A NYN domain protein directly interacts with DCP1 and is required for phyllotactic pattern in Arabidopsis
Authors: Schiaffini Marlene , Chicois Clara , Pouclet Aude , Chartier Tiphaine , Ubrig Elodie , Gobert Anthony , Zuber Hélène , Mutterer Jérôme , Chicher Johana , Kuhn Lauriane , Hammann Philippe , Gagliardi Dominique , Garcia Damien 
Published: October 2021

ABSTRACTIn eukaryotes, general mRNA decay requires the decapping complex. The activity of this complex depends on its catalytic subunit, DCP2 and its interaction with decapping enhancers, including its main partner DCP1. Here, we report that in Arabidopsis, DCP1 also interacts with a NYN domain endoribonuclease, hence named DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1). Interestingly, we find DNE1 predominantly associated with DCP1 but not with DCP2 and reciprocally, suggesting the existence of two distinct protein complexes. We also show that the catalytic residues of DNE1 are required to repress the expression of mRNAs in planta upon transient expression. The overexpression of DNE1 in transgenic lines leads to growth defects and transcriptomic changes related to the one observed upon inactivation of the decapping complex. Finally, the combination of dne1 and dcp2 mutations, revealed a functional redundancy between DNE1 and DCP2 in controlling phyllotactic pattern formation in Arabidopsis. Our work identifies DNE1, a hitherto unknown DCP1 protein partner highly conserved in the plant kingdom and identifies its importance for developmental robustness.One-sentence summaryDNE1, a NYN domain protein interacts with the decapping activator DCP1 and, together with DCP2, specify phyllotactic patterns in Arabidopsis.
Dietary vitamin B12 regulates chemosensory receptor gene expression via the MEF2 transcription factor in Caenorhabditis elegans
Authors: McDonagh Aja , Crew Jeannette , van der Linden Alexander M. 
Published: October 2021

ABSTRACTDynamic changes in chemoreceptor gene expression levels in sensory neurons is one strategy that an animal can use to modify their responses to dietary changes. However, the mechanisms underlying diet-dependent modulation of chemosensory gene expression are unclear. Here, we show that the expression of the srh-234 chemoreceptor gene localized in a single ADL sensory neuron type of C. elegans is downregulated when animals are fed a Comamonas bacterial diet, but not on an E. coli diet. Remarkably, this diet-modulated effect on srh-234 gene expression levels is dependent on the micronutrient vitamin B12 endogenously produced by Comamonas bacteria. Excess propionate and genetic perturbations in the canonical and shunt propionate breakdown pathways are able to override the repressing effects of vitamin B12 on srh-234 expression. The vitamin B12-mediated regulation of srh-234 expression levels in ADL requires the MEF-2 transcription factor, providing a potential mechanism by which dietary vitamin B12 may transcriptionally tune individual chemoreceptor genes in a single sensory neuron type, which in turn may change animal responses to biologically relevant chemicals in their diet.