bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implication of polymerase recycling for nascent transcript quantification by live cell imaging
Authors: Kindongo Olivia , Lieb Guillaume , Skaggs Benjamin , Dusserre Yves , Vincenzetti Vincent , Pelet Serge 
Published: September 2023

AbstractTranscription enables the production of RNA from a DNA template. Due to the highly dynamic nature of transcription, live-cell imaging methods play a crucial role in measuring the kinetics of this process. For instance, transcriptional bursts have been visualized using fluorescent phage-coat proteins that associate tightly with mRNA stem loops formed on nascent transcripts. To convert the signal emanating from a transcription site into meaningful estimates of transcription dynamics, the influence of various parameters on the measured signal must be evaluated. Here, the effect of gene length on the intensity of the transcription site focus was analyzed. Intuitively, a longer gene can support a larger number of transcribing polymerases, thus leading to an increase in the measured signal. However, measurements of transcription induced by hyper-osmotic stress responsive promoters display independence from gene length. A mathematical model of the stress-induced transcription process suggests that the formation of gene loops that favor the recycling of polymerase from the terminator to the promoter can explain the observed behavior. One experimentally validated prediction from this model is that the amount of mRNA produced from a short gene should be higher than for a long one as the density of active polymerase on the short gene will be increased by polymerase recycling. Our data suggest that this recycling contributes significantly to the expression output from a gene and that polymerase recycling is modulated by the promoter identity and the cellular state.Take away- Quantification of stress-induced promoter transcription dynamics using a live assays reporter system displays no dependence of signal intensity with gene length.- Mathematical modeling predicts that the formation of gene loops leading to the recycling of polymerases can explain the observed behavior.- More prevalent polymerase recycling on short genes results in a higher transcriptional output.
Tenofovir Activation is Diminished in the Brain and Liver of Creatine Kinase Brain-Type Knockout Mice
Authors: Eberhard Colten D. , Mosher Eric P. , Bumpus Namandjé N. , Orsburn Benjamin C. 
Published: September 2023

ABSTRACTTenofovir (TFV) is a nucleotide reverse transcriptase inhibitor prescribed for the treatment and prevention of human immunodeficiency virus infection, and the treatment of chronic hepatitis B virus infection. Here, we demonstrate that creatine kinase brain-type (CKB) can form tenofovir-diphosphate (TFV-DP), the pharmacologically active metabolite, in vitro, and identify nine missense mutations (C74S, R96P, S128R, R132H, R172P, R236Q, C283S, R292Q, and H296R) that diminish this activity. Additional characterization of these mutations reveal that five (R96P, R132H, R236Q, C283S, and R292Q) have ATP dephosphorylation catalytic efficiencies less than 20% of wild-type (WT), and seven (C74S, R96P, R132H, R172P, R236Q, C283S, and H296P) induce thermal instabilities. To determine the extent CKB contributes to TFV activation in vivo, we generated a CKB knockout mouse strain,Ckbtm1Nnb. Using an in vitro assay, we show that brain lysates ofCkbtm1Nnbmale and female mice form 70.5% and 77.4% less TFV-DP than wild-type brain lysates of the same sex, respectively. Additionally, we observe thatCkbtm1Nnbmale mice treated with tenofovir disoproxil fumarate for 14 days exhibit a 22.8% reduction in TFV activation in liver compared to wild-type male mice. Lastly, we utilize mass spectrometry-based proteomics to elucidate the impact of the knockout on the abundance of nucleotide and small molecule kinases in the brain and liver, adding to our understanding of how loss of CKB may be impacting tenofovir activation in these tissues. Together, our data suggest that disruptions in CKB may lower levels of active drug in brain and liver.ABSTRACT GRAPHIC
Microbially-catalyzed conjugation of GABA and tyramine to bile acids
Authors: Mullowney Michael W. , Fiebig Aretha , Schnizlein Matthew K. , McMillin Mary , Rose Amber R. , Koval Jason , Rubin David , Dalal Sushila , Sogin Mitchell L. , Chang Eugene B. , Sidebottom Ashley M. , Crosson Sean 
Published: September 2023

AbstractBile acids (BAs) are cholesterol-derived molecules that aid in digestion and nutrient absorption, regulate host metabolic processes, and influence physiology of the gut microbiota. Both the host and its microbiome contribute to enzymatic modifications that shape the chemical diversity of BAs in the gut. Several bacterial species have been reported to conjugate standard amino acids to BAs, but it was not known if bacteria conjugate BAs to other amine classes. Here, we show thatBacteroides fragilisstrain P207, isolated from a bacterial bloom in the J-pouch of a patient with ulcerative colitis (UC) pouchitis, conjugates standard amino acids and the neuroactive amines γ-aminobutyric acid (GABA) and tyramine to deoxycholic acid. We extended this analysis to other human gut isolates and identified species that are competent to conjugate GABA and tyramine to primary and secondary BAs, and further identified diverse BA-GABA and BA-tyramine amides in human stool. A longitudinal metabolomic analysis of J-pouch contents of the patient from whomB. fragilisP207 was isolated revealed highly reduced levels of secondary bile acids and a shifting BA amide profile before, during, and after onset of pouchitis, including temporal changes in several BA-GABA amides. Treatment of pouchitis with ciprofloxacin was associated with a marked reduction of nearly all BA amides in the J-pouch. Our study expands the known repertoire of conjugated bile acids produced by bacteria to include BA conjugates to GABA and tyramine and demonstrates that these molecules are present in the human gut.ImportanceBile acids (BAs) are modified in multiple ways by host enzymes and the microbiota to produce a chemically diverse set of molecules that assist in the digestive process and impact many physiological functions. This study reports the discovery of bacteria isolated from the gut of human patients that conjugate the neuroactive amines, GABA and tyramine, to BAs and demonstrates that BA-GABA and BA-tyramine amides are present in the human gut. GABA and tyramine are common metabolic products of the gut microbiota and potent neuroactive molecules, and their conjugation to BAs may influence receptor-mediated regulatory mechanisms of humans and their gut microbes.
Cyclodipeptide oxidase is an enzyme filament
Authors: Andreas Michael P. , Giessen Tobias W. 
Published: September 2023

AbstractModified cyclic dipeptides represent a widespread class of secondary metabolites with diverse pharmacological activities, including antibacterial, antifungal, and antitumor. Here, we report the structural characterization of theStreptomyces nourseienzyme AlbAB, a cyclodipeptide oxidase (CDO) carrying out α,β-dehydrogenations during the biosynthesis of the antibiotic albonoursin. We show that AlbAB is a megadalton heterooligomeric enzyme filament containing covalently bound flavin mononucleotide cofactors. We highlight that AlbAB filaments consist of alternating dimers of AlbA and AlbB and that enzyme activity is crucially dependent on filament formation. We show that AlbA-AlbB interactions are highly conserved suggesting that all CDO-like enzymes are likely enzyme filaments. Our work represents the first structural characterization of a CDO. As CDOs have been employed in the structural diversification of cyclic dipeptides, our results will be useful for future applications of CDOs in biocatalysis and chemoenzymatic synthesis.
Species- and strain-effects in interferon, innate immunity, and barrier transcriptional response of microbiome interactions of 3D respiratory epithelial cultures
Authors: Horvath Mian , Yang Ruoyu , Castaneda Diana Cadena , Callender Megan , Fleming Elizabeth , Voigt Anita , Caldwell Ryan , Fachi José , Di Luccia Blanda , Scholar Zoe , Yu Peter , Salner Andrew , Colonna Marco , Palucka Karolina , Oh Julia 
Published: September 2023

AbstractThe microbiome modulates the respiratory epithelium’s immunomodulatory functions. To explore how the microbiome’s biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on tracheobronchial air-liquid interface cell (ALI) cultures. We found distinct species- and strain-level differences in host innate immunity, and epithelial barrier response. Strikingly, we found that host interferon, an antiviral immune response, was one of the most variable host processes, and this variability was not driven by microbial phylogenetic diversity, bioburden, nor by the microbe’s ability to stimulate other innate immunity pathways. Our study provides a foundation for understanding how the respiratory microbiome’s biodiversity affects epithelial, and particularly, antiviral innate immunity.
Organelle landscape analysis using a multi-parametric particle-based method
Authors: Kurikawa Yoshitaka , Koyama-Honda Ikuko , Igarashi Keiko , Tamura Norito , Koike Seiichi , Mizushima Noboru 
Published: September 2023

AbstractOrganelles have unique structures and molecular compositions for their functions and have been classified accordingly. However, many organelles are heterogeneous and in the process of maturation and differentiation. Because traditional methods have a limited number of parameters and spatial resolution, they struggle to capture the heterogeneous landscapes of organelles. Here, we present a method for multi-parametric particle-based analysis of organelles. After disrupting cells, fluorescence microscopy images of organelle particles labeled with six to eight different organelle markers were obtained, and their multi-dimensional data were represented in intuitive two-dimensional UMAP (uniform manifold approximation and projection) spaces. This method enabled visualization of landscapes of seven major organelles as well as the transitional states of endocytic organelles directed to the recycling and degradation pathways. Furthermore, endoplasmic reticulum–mitochondria contact sites were detected in these maps. Our proposed method successfully detects a wide array of organelles simultaneously, enabling the analysis of heterogeneous organelle landscapes.
Barriers and facilitators to women general practitioners’ career progression: a systematic review
Authors: Jefferson Laura , Webster Elin , Golder Su , Barnett Katie , Greenwood Nicola , Dale Veronica , Bloor Karen 
Published: September 2023

AbstractObjectiveTo identify barriers and facilitators to women GPs’ career progression.DesignSystematic review of qualitative and quantitative studies.SettingStudies conducted in the UK NHS general practice setting.ParticipantsGeneral practitioners.Main outcome measuresBarriers and facilitators mapped thematically to the COM-B model, including Capability, Opportunity and Motivation as influencers of Behaviour.Results21 articles were included in this review, with varied study designs. No relevant intervention studies were identified. There was a lack of recent research evidence; over half were conducted over 20 years ago. Most studies met quality criteria, though there were some problems with reporting and adjustment for potential confounders. Barriers at personal, socio-cultural and system levels were found that inhibit women GPs’ career progression. While some positive changes have been documented across studies that span some thirty years, many challenges remain.ConclusionDespite general practice being one of the more female-dominated medical specialties, barriers at personal, socio-cultural and system levels continue to inhibit women GPs’ careers. The COM-B model of behaviour change was used to group thematic findings according to the barriers women may face in terms of their capabilities, opportunities and motivations and identify potential policies that could be evaluated as options to support women GPs’ career progression.
The adoption of the green label by SMEs in the hotel sector: a leverage for reassuring their customers
Authors: Yildiz Helene , Tahali Sara , Trichina Eleni 
Published: September 2023

PurposeIn the era of new technological revolution, seeking to survive and guarantee business sustainability in their digital internationalization, enterprises choose to become environmentally oriented. The need for new green business models has become evident in recent years, and enterprises offer green services in creative and eco-friendly ways. However, does the display of a green label on hotels' websites really promote the eco-conscious tourists' online booking intention? This study aims to examine the impact of the perceived label on the online sustainable hotel booking intention of the eco-conscious tourists, using the foundations of signal theory.Design/methodology/approachThis study adopted a structural equation model to integrate several constructs with a sample of 349 validated responses.FindingsThe empirical results highlight, the importance of the green label perception on the eco-conscious tourists' booking intention of online sustainable hotel and the role that green trust and green perceived risk play as a mediating variable between the perception of the exposed label and the booking intention. Indeed, when booking a sustainable hotel online, the tourists may be sensitive to the exposure of a green label. Therefore, this signal decreases the perceived risk of unsustainability and ultimately increases the trust in hotel's sustainability.Research limitations/implicationsThe first limitation is related to the sample employed in this study. Given that most of the participants were residents of France, the results of this study may not be generalized to the entire population. Secondly, a range of other factors can affect the eco-conscious tourists' intentions to book online a hotel with green label, such as their attitude, social media influence, tourists' satisfaction, etc. Indeed, other variables and/or signals could be adopted to study online booking intention in the pandemic era.Practical implicationsIn light of these results, theoretical and managerial implications are discussed. The findings make an important contribution to SMEs sustainability and internationalization by exploring new ties. This study considers how SMEs and specifically hotels start following green practices (e.g. adoption of an eco-label) relevant to their international environment where they operate and in response to global pressures. SMEs can survive better in the highly competitive global environment where they need to employ more green practices, however, managers should consider how green trust and green perceived risk can affect customer behavior. It also adds to the existing literature by dealing with customer perceptions about the green label of sustainable hotels and its subsequent effect on booking intention.Originality/valueThis study had shown the importance of the display of green label on the eco-conscious tourist's online booking intention.
Predicting plant species climate niches on the basis of mechanistic traits
Authors: Medeiros Camila D. , Henry Christian , Trueba Santiago , Anghel Ioana , Guerrero Samantha Dannet Diaz de Leon , Pivovaroff Alexandria , Fletcher Leila R. , John Grace P. , Lutz James A. , Méndez Alonzo Rodrigo , Sack Lawren 
Published: September 2023

Abstract

Improved estimation of climate niches is critical, given climate change. Plant adaptation to climate depends on their physiological traits and their distributions, yet traits are rarely used to inform the estimation of species climate niches, and the power of a trait‐based approach has been controversial, given the many ecological factors and methodological issues that may result in decoupling of species' traits from their native climate.

For 107 species across six ecosystems of California, we tested the hypothesis that mechanistic leaf and wood traits can robustly predict the mean of diverse species' climate distributions, when combining methodological improvements from previous studies, including standard trait measurements and sampling plants growing together at few sites. Further, we introduce an approach to quantify species' trait‐climate mismatch.

We demonstrate a strong power to predict species mean climate from traits. As hypothesized, the prediction of species mean climate is stronger (and mismatch lower) when traits are sampled for individuals closer to species' mean climates.

Improved resolution of species' climate niches based on mechanistic traits can importantly inform conservation of vulnerable species under the threat of climatic shifts in upcoming decades.

Read the free Plain Language Summary for this article on the Journal blog.
Catalyzing alignment and systems transformation through cross‐sector partnerships: Findings from the California Accountable Communities for Health Initiative
Authors: Angus Lisa , Dall Alaina , Ghosal Ritu 
Published: September 2023

AbstractObjectivesTo describe the impact of Accountable Communities of Health (ACHs) on organizational and community partnerships and explore how ACHs contribute to systems change.Data Sources and Study SettingThe California Accountable Communities of Health Initiative (CACHI) was a 5‐year, $17 M investment in community health transformation in 13 ACH sites. Data sources include two surveys, key informant interviews, small group conversations, and ACH meeting observations and document review.Study DesignThis was a mixed‐methods, observational study. Surveys conducted in 2021 and 2022 focused on ACH progress in building organizational and community partnerships and ACH impact on partners and systems, respectively. Interviews and small group conversations were conducted toward the end of the CACHI grant period and designed to complement the surveys.Data CollectionSurvey respondents included ACH backbone agency staff and partner organization representatives (n = 141 in 2021 and 88 in 2022). Semistructured individual interviews and group conversations were conducted with 40 ACH backbone staff and partners. Documents were collected via grant reporting and directly from ACH staff. Data were analyzed descriptively and thematically.Principal FindingsACHs appear to have supported organizational partnerships and collaboration. Seventy‐six percent of survey respondents reported that their ACH had strengthened organizations' ability to work together and 65% reported developing new or deepened connections. While ACH participants reported a better understanding of community needs and priorities, progress on community relationships, and greater attention to equity and racial justice, many saw room for improvement on meaningful community engagement. Systems changes and precursors of systems change observed across ACH sites included strengthened partnerships, enhanced knowledge, increased capacity, more collaborative ways of working, and new funding streams.ConclusionsThe ACH model is effective at strengthening organizational partnerships and catalyzing other systems changes and precursors including enhanced knowledge, increased capacity, more collaborative ways of working, and new funding.
Corporate R&D Investments Following Competitors’ Voluntary Disclosures: Evidence from the Drug Development Process
Authors: ZHANG YUE 
Published: September 2023

ABSTRACTThis paper examines the role of peer firm disclosures in shaping corporate research and development (R&D) investments. Drawing on models of two‐stage R&D races, I hypothesize that a firm could be either deterred or encouraged by peer disclosure of interim R&D success, depending on peer firms’ R&D strength in the race. Using granular, project‐level data on clinical trials in the drug development process, I find that a firm's R&D investments in a specific therapeutic area are deterred by disclosures of early‐phase trial initiation from strong rivals in the same area but encouraged by disclosures from weak rivals. Cross‐sectional analyses show that focal firm strength and disclosure relevance moderate the effects of peer firm disclosure. Overall, my evidence suggests that peer firms’ R&D disclosures can have both proprietary costs and deterrence benefits.
Enhancement effect of odor and multi‐sensory superposition on sweetness
Authors: Zhang Donghao , Lao Fei , Pan Xin , Li Jing , Yuan Lin , Li Meilun , Cai Yanpei , Wu Jihong 
Published: September 2023

AbstractThe impact of sugary foods on public health has contributed to the development of low‐sugar and sugar‐substituted products, and sugar reduction has become a major challenge for the food industry. There is growing empirical evidence that odor can enhance the perception of sweetness without increasing the caloric load. This current review summarizes the researches on odor‐induced sweetness enhancement published in recent years and discusses the mechanisms and influencing factors of odor‐sweetness interactions. In addition, by combing existing studies, this paper also summarizes the research methods and strategies to investigate odor‐induced sweetness enhancement. Finally, the feasibility of synergistic enhancement of sweetness through the superposition of odor with other senses (texture, visual, etc.) is also discussed and analyzed. In conclusion, odor‐induced sweetness enhancement may present an alternative or complementary approach for developing foods with less sugar.
Senolytic treatment reduces oxidative protein stress in an aging male murine model of post‐traumatic osteoarthritis
Authors: Chin Alexander F. , Han Jin , Clement Cristina C. , Choi Younghwan , Zhang Hong , Browne Maria , Jeon Ok Hee , Elisseeff Jennifer H. 
Published: September 2023

AbstractSenolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro‐regenerative response, but the therapeutic benefit is reduced in aged mice. Increased oxidative stress is a hallmark of advanced age. Therefore, here we investigate whether senolytic treatment differentially affects joint oxidative load in young and aged animals. We find that senolysis by a p53/MDM2 interaction inhibitor, UBX0101, reduces protein oxidative modification in the aged arthritic knee joint. Mass spectrometry coupled with protein interaction network analysis and biophysical stability prediction of extracted joint proteins revealed divergent responses to senolysis between young and aged animals, broadly suggesting that knee regeneration and cellular stress programs are contrarily poised to respond as a function of age. These opposing responses include differing signatures of protein‐by‐protein oxidative modification and abundance change, disparate quantitative trends in modified protein network centrality, and contrasting patterns of oxidation‐induced folding free energy perturbation between young and old. We develop a composite sensitivity score to identify specific key proteins in the proteomes of aged osteoarthritic joints, thereby nominating prospective therapeutic targets to complement senolytics.
Agency, aspirations and citizenship: Non‐formal education from the perspective of children in street situations in Pakistan
Authors: Kushtiwala Nermeen Khalid , Iqbal Humera 
Published: September 2023

AbstractThis paper explores an NGO‐based non‐formal education (NFE) intervention in Pakistan from the perspective of its recipients, children in street situations. Recognizing children as agential beings, we draw on participant observation and in‐depth semi‐structured interviews with 20 children, aged 10–19 years. Young people discussed the impact of the intervention on their self‐worth and future aspirations. They also reflected on their growing awareness of civic issues and citizenship rights. The study emphasizes the importance of NFE in providing opportunities to the most marginalized and those without adequate documentation, particularly in a context when state support can be lacking.