bluuebunny/crossref_metadata_2025_split huggingface dataset:
AAV-HBV mouse model replicates immune exhaustion patterns of chronic HBV patients at single-cell level
Authors: Conceição-Neto Nádia , Han Qinglin , Yao Zhiyuan , Pierson Wim , Wu Qun , Dockx Koen , Aerts Liese , De Maeyer Dries , Van den Berge Koen , Li Chris , Kukolj George , Zhu Ren , Podlaha Ondřej , Nájera Isabel , Van Gulck Ellen 
Published: August 2023

AbstractBackground and AimsUnresolved hepatitis B virus (HBV) infection leads to a progressive state of immune exhaustion that impairs resolution of infection, leading to chronic infection (CHB). The immune-competent AAV-HBV mouse is a common HBV preclinical immune competent model, though a comprehensive characterization of the liver immune microenvironment and its translatability to human infection is still lacking. We investigated the intrahepatic immune profile of the AAV-HBV mouse model at a single-cell level and compared with data from CHB patients in immune tolerant (IT) and immune active (IA) clinical stages.MethodsImmune exhaustion was profiled through an iterative subclustering approach for cell-typing analyses of single-cell RNA-sequencing data in CHB donors and compared to the AAV-HBV mouse model 24-weeks post-transduction to assess its translatability. This was validated using an exhaustion flow cytometry panel at 40 weeks post-transduction.ResultsUsing single-cell RNA-sequencing, CD8 pre-exhausted T-cells with self-renewing capacity (TCF7+), and terminally exhausted CD8 T-cells (TCF7-) were detected in the AAV-HBV model. These terminally exhausted CD8 T-cells (expressingPdcd1,Tox,Lag3,Tigit) were significantly enriched versus control mice and independently identified through flow cytometry. Importantly, comparison to CHB human data showed a similar exhausted CD8 T-cell population in IT and IA donors, but not in healthy individuals.ConclusionsLong term high titer AAV-HBV mouse liver transduction led to T-cell exhaustion, as evidenced by expression of classical immune checkpoint markers at mRNA and protein levels. In both IT and IA donors, a similar CD8 exhausted T-cell population was identified, with increased frequency observed in IA donors. These data support the use of the AAV-HBV mouse model to study T-cell exhaustion in HBV infection and the effect of immune-based therapeutic interventions.Lay SummaryThe AAV-HBV mouse model is used as a research tool to study hepatitis B infection. In this study we evaluated the translation value from mouse to human with regards to T-cell exhaustion.HighlightsAAV-HBV mice transduced with a high titer vector showed presence of CD8 exhausted T-cells after 24 weeks.High titer transduced mice, but not lower titer show increased expression of LAG-3, TOX, TIM-3 and TIGIT in CD8 T-cells. PD-1 was increased in CD8 T-cells, independent of HBV transduction titer.A similar exhausted CD8 T-cell population could be found in chronic HBV donors, but not in healthy individuals.Graphical abstract
Discovery of a Well-Folded Protein Interaction Hub Within the Human Long Non-Coding RNANORAD
Authors: Kumar Ananthanarayanan , Wan Han , Perry Zion , Patel Shivali , Tavares Rafael , Pyle Anna Marie 
Published: August 2023

ABSTRACTThe long non-coding RNANORADfunctions in maintaining genomic stability in humans via sequestering Pumilio proteins from the cytoplasm, and thereby modulating the gene expression of mRNA targets of Pumilio proteins. Despite its role in fundamental cellular pathways including chromosome segregation and DNA damage response, there have been limited structural and biophysical descriptions ofNORAD. Here, using an integrative approach combining chemical probing coupled to high throughput sequencing, and RNA-pull downs coupled with mass spectrometry, we discovered a well-folded and structured protein interaction hub within the functional core ofNORAD. Ourin vitrobiochemical reconstitutions using purified recombinant proteins and aNORADrepeat unit region within this hub reveal the assembly of a higher-order multimeric RNA-protein complex.
Unravelling the complex biogeographic and anthropogenic history of Alaska’s mountain goats
Authors: Young Kiana B. , White Kevin S. , Shafer Aaron B.A. 
Published: August 2023

AbstractAimWe used genetic tools to examine the population structure of mountain goats in Alaska, USA and assessed the demographic history of this species in relation to the natural and anthropogenic forces.LocationAlaska, USATaxonNorth American mountain goat (Oreamnos americanus)MethodsSamples were collected between 2006 - 2020 from harvested animals and live captures. We genotyped 816 mountain goats at 18 microsatellite loci and identified the number of genetically distinct subpopulations across the state and assessed their genetic diversity. We used Bayesian computation software to investigate the demographic history relative to the known biogeographic history of the state. We also simulated island translocation events and compared simulations to empirical data to address the hypothesis that Baranof Island was a cryptic refugia.ResultsWe showed that Alaska has four genetically distinct subpopulations of mountain goats with some additional genetic structure within those subpopulations. The main split of mountain goats between Southcentral and Southeast Alaska occurred ∼14,000 years ago. Simulations of translocation events largely aligned with the current populations observed today except for Baranof Island which showed greater diversity than the translocation simulation.Main ConclusionsThe distribution and genetic structure of mountain goats in Alaska reflects a combination of natural and anthropogenic forces. A rapid northerly expansion through an ice-free corridor in combination with the isolated nature of the landscape led to low diversity and isolation 14,000 years ago in Southcentral Alaska and higher diversity in Southeast Alaska. Two of the three islands where mountain goat translocations have occurred match genetically with their source population, while Baranof Island appears to have a divergent population, consistent with the hypothesis of an endemic or cryptic population prior to the translocation event. This study highlights the value of considering both the natural and anthropogenic forces when assessing the biogeographic history of a species.
Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules
Authors: Toledano Ignasi , Supek Fran , Lehner Ben 
Published: August 2023

AbstractPremature termination codons (PTCs) cause ∼10-20% of Mendelian diseases and are the major mechanism of tumor suppressor gene inactivation in cancer. A general strategy to alleviate the effects of PTCs would be to promote translational readthrough. Nonsense suppression by small molecules has proven effective in diverse disease models, but translation into the clinic is hampered by ineffective readthrough of many PTCs. Here we directly tackle the challenge of defining drug efficacy by quantifying readthrough of ∼5,800 human pathogenic stop codons by 8 drugs. We find that different drugs promote readthrough of complementary subsets of PTCs defined by local sequence context. This allows us to build interpretable models that accurately predict drug-induced readthrough genome-wide. Accurate readthrough quantification and prediction will empower clinical trial design and the development of personalized nonsense suppression therapies.
Deep learning reduces data requirements and allows real-time measurements in Imaging Fluorescence Correlation Spectroscopy
Authors: Tang Wai Hoh , Sim Shao Ren , Aik Daniel Ying Kia , Nelanuthala Ashwin Venkata Subba , Athilingam Thamarailingam , Röllin Adrian , Wohland Thorsten 
Published: August 2023

AbstractImaging Fluorescence Correlation Spectroscopy (Imaging FCS) is a powerful tool to extract information on molecular mobilities, actions and interactions in live cells, tissues and organisms. Nevertheless, several limitations restrict its applicability. First, FCS is data hungry, requiring 50,000 frames at 1 ms time resolution to obtain accurate parameter estimates. Second, the data size makes evaluation slow. Thirdly, as FCS evaluation is model-dependent, data evaluation is significantly slowed unless analytic models are available. Here we introduce two convolutional neural networks (CNNs) –FCSNetandIm-FCSNet– for correlation and intensity trace analysis, respectively.FCSNetrobustly predicts parameters in 2D and 3D live samples.ImFCSNetreduces the amount of data required for accurate parameter retrieval by at least one order of magnitude and makes correct estimates even in moderately defocused samples. Both CNNs are trained on simulated data, are model-agnostic, and allow autonomous, real-time evaluation of Imaging FCS measurements.
Single-molecule analysis of transcription activation: dynamics of SAGA co-activator recruitment
Authors: Jeon Jongcheol , Friedman Larry J. , Seo Hogyu David , Adeleke Augustus , Graham Bria , Patteson Emily , Gelles Jeff , Buratowski Stephen 
Published: August 2023

AbstractTranscription activators are said to stimulate gene expression by “recruiting” coactivators to promoters, yet this term fits several different kinetic models. To directly analyze dynamics of activator-coactivator interactions, single-molecule microscopy was used to image promoter DNA, a transcription activator, and the Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex within nuclear extract. SAGA readily, but transiently, binds nucleosome-free DNA without activator, while chromatin template association occurs nearly exclusively when activator is present. On both templates, activator increases SAGA association rates by up to an order of magnitude, and dramatically extends its dwell times. These effects reflect direct interactions with the transactivation domain, as VP16 or Rap1 activation domains produce different SAGA dynamics. Despite multiple bromodomains, acetyl-CoA or histone H3/H4 tail acetylation only modestly improves SAGA binding. Unexpectedly, histone acetylation more strongly affects activator residence. Our studies thus reveal two modes of SAGA interaction with the genome: a short-lived activator-independent interaction with nucleosome-free DNA, and a state tethered to promoter-bound transcription activators that can last up to several minutes.
A novel lncRNA PROCA11 regulates cell plasticity in response to androgen deprivation of prostate cancer cells
Authors: Cipolla Rocco , Gabriel Marc , Regin Giorgia Ianese , Piemontese Micaela , Szachnowski Ugo , Firlej Virginie , Pinskaya Marina , Morillon Antonin 
Published: August 2023

AbstractLong non-coding RNAs (lncRNAs) represent vast and yet poorly characterized family of genes that can fine tune cellular plasticity, thereby allowing the emergence of aggressive therapy-resistant and metastatic cancers. Androgen deprivation therapies (ADT) are commonly used to treat prostate cancer by inactivating the Androgen Receptor (AR). However, castration-resistant prostate cancer (CRPC) with neuroendocrine subtypes (NEPC) often emerge. In this study, we explore the role of lncRNAs in response to androgen deprivation. Using a dynamic prostate cancer cell system mimicking the CRPC and NEPC onset, we identified 15 novel lncRNAs, with PROCA11 standing out as a first-choice candidate, being also highly abundant in high-risk prostate cancer tumors. This majorly nuclear lncRNA is expressed at low levels in androgen-dependent conditions of growth and strongly activated upon hormone withdrawal, preceding neuroendocrine genes and persisting at high levels in neuroendocrine cells. Extensive computational analysis of clinical data and functional studies in cells revealed PROCA11 association with basal-to-luminal transformation of the transcriptomic landscape and activation of metabolic and signaling pathways reminiscent of neurogenesis and of maintenance of AR signaling. We propose that PROCA11 is involved in the intricate circuits regulating cellular plasticity enabling cell survival and proliferation and emergence of the NE phenotype in response to ADT.
Season of transmission of Ross River/Barmah Forest Virus andMycobacterium ulceransclosely align in southeastern Australia, supporting mosquitoes as the vector of Buruli ulcer
Authors: Buultjens Andrew H. , Tay Ee Laine , Yuen Aidan , Friedman N. Deborah , Stinear Timothy P. , Johnson Paul D.R. 
Published: August 2023

AbstractRoss River Virus and Barmah Forest Virus infections (alphaviruses) have short incubation periods and are transmitted to humans by mosquitoes.Mycobacterium ulceransinfection (Buruli ulcer) has a much longer incubation period and its mode of transmission is contested. We studied the relationship between month of notification of alphavirus infections and Buruli ulcer in the temperate Australian state of Victoria over the six-year period, 2017-2022. Usingcross-correlation, a signal processing technique, we found that a five-month temporal shift in month of Buruli ulcer notification provided optimal alignment with month of alphavirus notification. This closely matches the previously determined 5-month Buruli ulcer incubation period. Inferred transmission of both conditions showed coordinated maxima in summer and autumn and coordinated minima in winter and spring. The close alignment in season of transmission of alphavirus infection and Buruli ulcer in Victoria supports mosquitoes as the primary local vector ofM. ulcerans.
Does cooperative membership stabilize farm income volatility? Evidence from the pig sector in China
Authors: Ji Chen , Zhuo Ni , Jin Songqing 
Published: August 2023

PurposeFarm income in the agricultural sector is susceptible to natural and market risks. A large body of literature has studied the effects of cooperative membership on household welfare, technical efficiency, productivity and production behavior, yet little has been known about the impact of cooperative membership on farm income volatility. This paper aims to fill this research gap by investigating the relationship between cooperative membership and farm income volatility of Chinese pig farmers and drawing policy implications.Design/methodology/approachThis paper examines the effect of cooperative membership on farm income volatility, using data from a two-round survey of pig farmers in China. The authors employ an endogenous switching regression model to address the selection bias issues associated with unobserved factors simultaneously affecting farmers' participation in agricultural cooperatives and income earning activities.FindingsUsing household panel from a two-round survey of 193 pig farmers in China, this analysis highlights two key findings: (1) agricultural cooperative membership has significant and positive effect on farm income stability and (2) the impact of cooperative membership on farm income stability varies with production scale.Originality/valueThis research makes two contributions to the literature. First, this study contributes to the scant literature exploring the relationship between agricultural cooperatives and farm income stability. Second, to the best of the authors' knowledge, this is the first study that explores such relationship in a livestock sector. The pig sector in China and around the developing world has been increasingly challenged by multifaceted risks (e.g. price fluctuations, epidemic diseases, environmental regulations), and understanding the role of agricultural cooperatives in farm income stability of pig farmers is of great practical and policy significance.
Informality in strategic communication. Making the case for a forgotten concept
Authors: Hoffjann Olaf 
Published: August 2023

PurposeAlthough current strategic communication research is particularly interested in deviations from normative ideals, there is a surprising lack of interest in the structures that lead to such deviations from formal specifications. To this end, this paper explores the classic, but of late largely forgotten concept of informality. The aim is to develop a theoretical framework and a systematization that can be used to answer central questions in strategic communication research. The focus is on three research questions: How can formal and informal structures of strategic organizational communication be systematized? How are formal and informal organizational structures thematized in strategic organizational communication? What is the relationship between (in)formal structures of strategic organizational communication and the thematization of (in)formal organizational structures?Design/methodology/approachThe conceptual contribution is based on systems theoretical organization theory, which understands formal structures as decided decision premises and informal structures as undecided decision premises.FindingsThe understanding of informal expectation structures presented here has enormous potential for describing and researching central issues in strategic communication research in a far more significant way, both theoretically and empirically. For example, decoupling can be described in a much more differentiated way than is possible using the neo-institutionalist perspective.Practical implicationsThe systematizing framework for researching informal structures enables a deeper understanding of informal structures and thus a better handling of them in practice. In addition, the framework provides a basis for future empirical studies.Originality/valueInformal phenomena and structures seem to be the elephant in the room in many discourses in strategic communication research. With the theoretical perspective and systematization presented here, these phenomena can finally be explored in a differentiated and meaningful way.
No escape from the No.10. bunker? UK government news management under siege: John Major (1990–97) and Boris Johnson (2019–2022)
Authors: Garland Ruth 
Published: August 2023

PurposeThis study draws parallels between the Major and Johnson eras to reclaim a discursive space beyond the media and political battlefields to examine long-term systemic failure of government PR.Design/methodology/approachAs part of a wider study into government communications from 1979 to date, this paper draws on evidence from government archives from the 1990s, as well as contemporary accounts, official documents, media accounts, memoirs and biographies, to examine the PR record of two Conservative administrations divided by three decades.FindingsNews management during the Major premiership is worth serious scrutiny, not just as an interlude between two media-friendly Prime Ministers, Thatcher and Blair, but in comparison to Boris Johnson's struggle to contain the news narrative between 2019 and 2022. Both administrations experienced terminal reputational crises during their closing years but their means of managing the news were counter-productive and damaging to public trust (65).Practical implicationsDoes this failure in public communication illustrate a systemic dysfunction in government-media relations and, if so, what is the role of government PR in these circumstances?Originality/valueThis article uses a comparison between fixed and moving variables associated with two very different administrations to identify the causes of ongoing systemic failure in government communication.
Measuring differences-in-differences of crimes: a case of Dolphin Force in Punjab
Authors: Mazhar Ummad 
Published: August 2023

Learning outcomes
The case has the following learning objectives:
1. understand the various types of comparisons that are possible between groups over time and across space;
2. evaluate a policy intervention using relevant data and different methods; and
3. understand the meaning of the phrase “controlling for other relevant factors” in regression and non-regression contexts.

Case overview/synopsis
The difference-in-differences (DID) approach is a useful tool for making meaningful comparisons. This case tries to provide a non-technical introduction to the approach using a basic comparison of crime rates among districts in Punjab (Pakistan's largest province). Being the most populous region of the country, Punjab faces many governance challenges, and street crime is one of them. (Exhibit 5 provides additional information about the geographical and administrative setting used in this case study.) In 2016, Chief Minister Shahbaz Sharif established the Dolphin (police) Force in different locations to improve urban patrolling and reduce street crime. There were debates about the effectiveness of the Dolphin Force (DF).
Those who are skeptical of DF point to various situations that were handled incorrectly by DF personnel, as well as other administrative and operational problems in the initiative. Optimists believe it is beneficial and want it to be expanded to other districts and regions. The threat of street crime claims many lives and, according to optimists, necessitates the formation of a special force. Whether the huge resources invested in the DF worth their lot or not can be known through sound statistical analysis that can identify the difference in the rate of crime because of the DF. In this instance, the case provides information to answer the following question:
Is there a significant difference in crime rates between areas where the DF is operating and districts where it has not yet been installed?

Complexity academic level
In quantitative/statistical analysis classes, the case can be used to teach the DID technique to MBA/MS Applied Statistics/Applied Data Analysis students. It can also be used in undergraduate Econometrics classes.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 7: Management Science.
Strategic closed-loop supply chain configuration in the transition towards the circular economy of EV batteries: an evolutionary analytical framework
Authors: Chizaryfard Armaghan , Lapko Yulia , Trucco Paolo 
Published: August 2023

PurposeThis study advocates the importance of taking an evolutionary perspective in the strategic configuration of closed-loop supply chains (CLSC) in the transition to a circular economy. Building on the supply chain management and industrial dynamics research domains, an evolutionary analytical framework was developed and applied in the empirical context of the ongoing industrial transition to e-mobility.Design/methodology/approachThis study is designed as an in-depth exploratory case study to capture the multi-layer dynamic complexities and their interplay in CSLC development. The empirical investigation was based on two-year interactions between the authors and various departments in a leading European heavy vehicle manufacturer. The proposed evolutionary analytical framework was used for investigating the dynamics of four CLSC configurations through ten possible trajectories.FindingsThe findings demonstrate that the evolution of each CLSC configuration comes with multiple challenges and requirements and point out the necessity for the co-development of technologies, product design and production, and infrastructure through long-term relationships among key supply chain actors. However, this evolutionary journey is associated with multiple dilemmas caused by uncertainties in the market and technology developments. All these factors were properly captured and critically analyzed, along with their interactions, thanks to the constructs included in the proposed evolutionary analytical framework.Research limitations/implicationsThe proposed evolutionary framework is applicable for examination of SC transformation in the context of market and technology development, and is particularly relevant for transitioning from linear SC to CLSC. The framework offers a single actor perspective, as it does not directly tackle dynamics and effects of actions taken by SC actors.Practical implicationsThe developed framework can support SC managers in identifying, framing, and comparing alternative strategies for CLSC configuration in the transition process.Originality/valueThis study proposes the framework for understanding and guiding the evolutionary process of CLSC development. Its uniqueness lies in the integration of concepts from innovation and evolutionary theories coming from industrial dynamics and SCM literature streams.