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Intracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment
Get PDFV-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms of regulation of VISTA activity and functions by factors of tumour microenvironment (TME) remain unclear and understanding these processes is required in order to develop successful personalised cancer immunotherapeutic strategies and approaches. Here we report for the very first time that VISTA interacts with another immune checkpoint protein galectin-9 inside the cell most likely facilitating its interaction with TGF-β-activated kinase 1 (TAK1). This process is required for protection of lysosomes, which is crucial for many cell types and tissues. We found that VISTA expression can be differentially controlled by crucial factors present in TME, such as transforming growth factor beta type 1 (TGF-β) and hypoxia as well as other factors activating hypoxic signalling. We confirmed that involvement of these important pathways modulated by TME differentially influences VISTA expression in different cell types. These networks include: TGF-β-Smad3 pathway, TAK1 (TGF-β-activated kinase 1) or apoptosis signal-regulating kinase 1 (ASK1)-induced activation of activating transcription factor 2 (ATF-2) and hypoxic signalling pathway. Based on this work we determined the five critical functions of VISTA and the role of TME factors in controlling (modulating or downregulating) VISTA expression
‘Who has been denied equality and why?’ – Disability movements in changing and eroding democracies of Central and Eastern Europe
Get PDFDisability is rarely studied in the context of democracy even though disabled people represent 16% of the population and the disabled people’s movement has been influencing laws and policies in all modern democracies. This study explored how disability movements work in changing and eroding democracies in Central and Eastern Europe (CEE). Data was collected in Bulgaria, Hungary, Romania and Serbia.
The study confirms that democratization and de-democratization influence disability movements and their position. Although the inclusion of disability movements in policy-making has been established through formal consultative and monitoring platforms, disability movements’ participation in policy-making remains mostly tokenistic in CEE. Democratic backsliding affects movements’ coalition-building capacities, and mobilization becomes harder. Where democratic erosion is stronger, movement organizations exercise self-censorship and avoid open criticism of government politics. The study argues that reactions to democratic erosion are influenced by movement organizations’ resources, their embeddedness in state structures, and other factors. The paper offers a typology of disability movement organizations in CEE and points at potential risks for re-democratization efforts
Evidential Pluralism and accounts of establishing
Get PDFIn Evidential Pluralism in the Social Sciences, Yafeng Shan and Jon Williamson do a great job of clarifying, motivating, and defending the commitments of Evidential Pluralism. In this commentary, I will show that one of their clarifications commits Evidential Pluralism to a particular account of establishing. And I will argue that a non-committal account of establishing would better promote the main message of the book
Outcomes of orangutan wild-to-wild translocations reveal conservation and welfare risks
Get PDFWild orangutans (Pongo spp.) are captured and moved (wild-to-wild translocated) primarily to prevent crop foraging or out of concern for orangutans' survival in fragmented habitat. Little is known about wild-to-wild translocation frequency, circumstances, and possible species conservation and individual welfare outcomes. We investigated orangutan wild-to-wild translocations in Indonesia from 2005 to 2022 using primarily data from public sources and consultation with practitioners. At least 988 wild orangutans were captured for translocation during the study period, including many reproductively valuable resident females and adult males removed from unprotected fragmented forests and forest patches. Data on health condition (n = 808) indicated 81.7% were reported as healthy at time of capture. Information on post-capture disposition (n = 268) showed that only 23% were translocated immediately. Mean estimated killing combined with reported translocation removals was calculated to affect 3.3% of orangutans in Kalimantan, and 11.6% in Sumatra, both higher than the threshold of mortality from human actions expected to drive populations to extinction. Negative impacts are likely compounded where multiple individuals are translocated from the same area, and for the Tapanuli orangutan (P. tapanuliensis), which has the smallest population and range of all orangutan species. Data on reasons for capture (n = 743) indicated most translocations (69%) were conducted to address crop foraging and orangutan presence in or around croplands and plantations. Forest cover analysis around 104 orangutan capture sites with high resolution spatial information indicated that deforestation levels in the year preceding capture were not significantly associated with likelihood of captures for translocation. To improve conservation outcomes, wild-to-wild translocations should be used only in exceptional circumstances. Most orangutans should instead be monitored and protected in situ by addressing conflicts and maintaining the forests, including forest fragments, they are using. When translocation is necessary, post-release survival and potential conservation impacts must be monitored. [Abstract copyright: Copyright: © 2025 Sherman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Global landscape of infection-induced pulmonary hypertension
Get PDFIntroduction: Infectious diseases significantly impact pulmonary vascular disorders, particularly in developing countries where parasitic infections remain prevalent. These infections constitute a substantial yet frequently overlooked contributor to pulmonary hypertension. Discussion: This review examines the prevalence of parasitic lung diseases in regions where communicable infections are endemic and highlights their pathophysiological links to pulmonary hypertension. Schistosomiasis and HIV notably increase pulmonary hypertension risk in these areas. While other infectious diseases may also cause pulmonary vascular lesions, most remain insufficiently studied. The review addresses global epidemiological trends, diagnostic challenges, and recent advancements in understanding the multifaceted origins of pulmonary hypertension. Conclusion: The association between parasitic infections and pulmonary hypertension is significant, necessitating a high index of suspicion for pulmonary hypertension in patients with a history of parasitic diseases, especially in endemic regions. More research is needed to understand infection-related pulmonary hypertension mechanisms and reduce its global impact
Exemplary Ascetics: Ethical Instruction in Theodoret of Cyrrhus’s Religious History
Get PDFThis article reappraises Theodoret of Cyrrhus’s Religious History to show that the Syrian bishop engages his audience in a process of reflective emulation by rhetorically presenting the ascetics he describes as exemplars. In so doing, Theodoret’s sketches act as ethical stories. I highlight their cultural value and also underline their didactic function by demonstrating how the bishop invites his readers to meditate on the complex life choices the ascetics make. This prompts his audience to reassess their ideas of holiness and selfhood. Theodoret’s emphasis on critical judgement could be read as part of his practice of writing compilations with a didactic aim. It could also be viewed as a plea for thoughtful consideration during a time of significant doctrinal controversies in which he played a key role in his Antiochene network. “Antiochene” was coined by Adam Schor when describing the social networks forged between Syrian bishops and lay civil leaders. Finally, the article shows that by promoting the language of exemplarity in his text, which partially focuses on commemoration, Theodoret fulfills the desire he expresses in his Prologue: for the Religious History to become part of cultural memory
'Only joking' Negotiating offensive humour in interaction
No full textIn this special issue, we view ‘offensive humour’ as a purposefully broad, catch-all category that includes teasing, sarcasm, put downs and jocular insults (e.g., Dynel & Sinkeviciute 2021). While both ‘offence’ and ‘humour’ are notoriously difficult to define, across the papers in this collection we find the common threads that identify offensive humour are (a) a speaker’s (assumed) intent to amuse, and (b) recipients’ judgements or reactions to the humour as offensive. Crucially, offensive humour typically focuses on attempts to produce amusement through a seemingly faux negative attitude towards some target but without claimed malicious intent, differentiating offensive humour from insults proper, which purposefully — or at least overtly — seek to offend (cf. Dynel & Poppi 2020).
This issue raises a number of interrelated theoretical questions regarding the nature of offensive humour and how it is negotiated by participants across different communicative domains. From the outset, characterising offensive humour through a speaker’s humorous intent presents an immediate — practical and theoretical — challenge: since neither recipients nor analysts have access to a speaker’s private intentions, was the denigrating humour meant to be offensive (e.g., Zajdman 1995)? One difficulty for recipients is that by framing (purposefully) offensive messages through the lens ofhumour offers perpetrators deniability for having intended any offence, and hence relieves them from being held accountable for the problematic content of their joke: they can always claim to be ‘only joking’. Indeed, it is exactly by invoking a non-serious frame that a speaker may disguise any disparaging and discriminatory attitudes (e.g., racism, sexism, ableism, homophobia), which may be present at a conscious or unconscious level. However, the ‘only joking’ defence is not always successful, leaving open the question of how far this strategy is truly plausible as deniable (see Haugh & Márquez Reiter, this issue; Horn, this issue).
From the perspective of the recipient, feelings of offence may be experienced without necessarily either (a) attributing offensive intentions to the speaker, or even (b) attributing a clear offensive meaning to the speaker’s utterance. Of course, what counts as ‘offensive’ is subjective, and what might be considered offensive in one context may be viewed as playful teasing in another (Biri & Tanskanen, this issue). The ‘intergroup sensitivity effect’ means that it is more permissible for an in-group member to make a joke at that group’s expense than it is for an out-group member to do so (Thai et al. 2019). The matter of ‘who’s listening’ is equally important: while some people — who are typically not the targets of the joke — may fin d it funny, others may be offended (Dynel 2013). And while some might be offended, others may not be, simply because they don’t understand the (potential) offensive import of what has been said (Howes et al, this issue). For those recipients who experience feelings of offence, the guise of humour can make it difficult for them to flag and register having taken offence (Haugh 2015). This is partly because offensive content is often backgrounded as an under-lying prejudiced attitude, which makes the act of explicitly calling out the offensive content interactionally difficult (Elder 2021). Furthermore, while what counts as funny is both context-dependent and subject to individual interpretation, to take offence is generally met with disapproval in society (Stollznow 2020). To criticise offensive humour can be seen as ‘political correctness gone too far’, encouraging censorship and posing a threat to free speech, and to refuse to laugh is to be charged as lacking a sense of humour. The so-called ‘snowflake generation’ are labelled by their supposed sensitivity and proneness to offence, being associated with terms such as ‘sensitive’ and ‘triggered’. At the same time, in the wake of #MeToo and global awareness of the Black Lives Matter movement in the past decade, there is greater sensitivity in society towards certain kinds of humour, and it can be argued that making the jokes in the fir st place contributes to shaping and reinforcing broader societal attitudes towards certain social identities. Indeed, psychological studies have shown that humour that disparages particular groups of people can evidence tolerance and even encouragement of discrimination towards social groups who are the target of such humour (e.g., Ford & Ferguson 2004), and to laugh at a joke can be considered a way of endorsing its ideology. This opens the question of how far speakerscan and should be held accountable for their (potentially) offensive humour, especially when that humour is aired in the public domain (see Assimakopoulos et al., this issue; Kapogianni et al., this issue). Finally, it has to be acknowledged that humorous frames arising in spontaneous interaction, whether that is face-to-face or in written communication, differ from the humorous frame in scripted and/or live-performed comedy. While the humorous frame in spontaneous interaction is under constant negotiation, in comedic settings, the audience opts-in to the humorous frame (Kapogianni et al., this issue). However, live audiences and post-performance audiences opt-in to the humorous frame in different ways. Several papers in this special issue focus on offensive humour in both scripted and live-performance comedy, addressing how offensive humour is viewed and received is relative to joker persona and identity.
Bookended by two papers that survey offensive humour occurring in a range of private and public settings (Haugh & Márquez Reiter; Horn), the publications in this issue also focus on comedic live performance (Kapogianni et al.; Constantinescu; Filani), scripted TV dialogue (Saloustrou & Tsami), online platforms (Tanskanen & Biri), and political discourse (Assimakopoulos et al.; Howes et al.), thus covering a wealth of contextual and discursive perspectives
Fire regimes drive population trends of a threatened lizard in the central and western deserts of Australia
Get PDFContext
Animal and plant populations in arid regions fluctuate in size and extent in response to rainfall, fire and predation. Understanding the influence of these drivers on the status and trends of populations is crucial to implementing effective conservation actions.
Aims
In this study, we quantified the long-term drivers and trends in populations of a threatened lizard, the great desert skink (Liopholis kintorei; Tjakura), in the central and western deserts of Australia.
Methods
We collated 23 years (2002–2023) of active Tjakuṟa burrow count data from 31 sites clustered in the following four regions: Yulara, Newhaven Wildlife Sanctuary, Uluṟu–Kata Tjuṯa National Park and Kiwirrkurra Indigenous Protected Area. We fitted a negative binomial regression model in a Bayesian framework to estimate trends in active burrow counts over time and quantified the effect of rainfall, mean annual normalised difference vegetation index (NDVI), time since fire and fire extent on active burrow counts.
Key results
Our results showed contrasting trends in Tjakuṟa active burrow counts across the four regions. At Kiwirrkurra, Newhaven Wildlife Sanctuary and Yulara, active burrow counts increased consistently at rates of 35% (0.298; 95% CI 0.099–0.471), 18% (0.168; 95% CI 0.029, 0.314) and 5% per year (0.045; 95% CI 0.017, 0.073) respectively. In contrast, active burrow counts in Uluṟu–Kata Tjuṯa National Park increased from 2002 to 2012 before steadily decreasing. Across all sites, fire was the most important predictor of active Tjakuṟa burrow counts, with a significant positive effect of time since fire (0.108; 95% CI 0.014–0.204) and a strong negative effect of fire extent in the previous year (−0.111; 95% CI −0.243 to −0.026).
Conclusions
Our results have highlighted the importance of delivering ongoing planned fire management programs that avoid burning vegetation directly at and around Tjakura burrow systems, while providing a patch mosaic across the surrounding landscape.
Implications
We recommend that monitoring of Tjakura burrows be standardised across regions and that site covariates, especially measures of predation pressure, be monitored to further understand drivers of population trends
Safe, sustainable, legal use and trade in wild species: testing a new five-dimensional sustainability assessment
Get PDFThe Kunming Montreal Global Biodiversity Framework, adopted by the UN Convention on Biological Diversity in 2022, sets ambitious targets to ensure that the use, harvesting and trade of wild species is sustainable, safe and legal. While the definition of ‘sustainable’ is traditionally inclusive of ecological, social, and economic dimensions, many practically applied standards and regulations often exclude non-ecological perspectives such as human health and animal welfare. Recognising the challenge of assessing sustainability in a comprehensive, but accessible, way, a five-dimensional sustainability assessment framework (5DSAF) was developed, explicitly focusing on social, ecological, economic, animal welfare, and human health dimensions of sustainability. This paper documents the experiences of applying and testing the 5DSAF in multiple species use examples: geographically, by different sectors, and socio-economically. Its application in the United Republic of Tanzania (game meat industry), in South Africa (game meat sector), in Indonesia (reticulated python skins), and in Zimbabwe (Nile crocodile) is discussed. It proposes the steps for the future adaptations, and application of 5DSAF beyond the initial case studies aiming to assist conservation practitioners, policymakers, as well as indigenous peoples and local communities and private sector actors to demonstrate that the use of wild animal species and products is safe, legal and sustainable and, meeting the objectives of One Health approach, and where it is not, to identify the necessary improvements that need to be made
Bacterial microcompartments and energy metabolism drive gut colonization by Bilophila wadsworthia.
Get PDFHigh-fat diets reshape gut microbiota composition and promote the expansion of Bilophila wadsworthia, a sulfidogenic bacterium linked to inflammation and gut barrier dysfunction. The genetic basis for its colonisation and physiological effects remain poorly understood. Here, we show that B. wadsworthia colonises the gut of germ-free male mice fed a high-fat diet by relying on genes involved in microcompartment formation and anaerobic energy metabolism. Using genome-wide transposon mutagenesis, metatranscriptomics and metabolomics, we identify 34 genes essential for gut colonisation, including two clusters encoding a bacterial microcompartment (BMC), and a NADH dehydrogenase (hdrABC-flxABCD) complex. These systems enable B. wadsworthia to metabolise taurine and isethionate, producing H S, acetate, and ethanol. We further demonstrate that B. wadsworthia can produce and consume ethanol depending on the available electron donors. While B. wadsworthia reached higher abundance and H₂S production in the absence of the simplified microbiota, its co-colonisation with the defined microbial consortium exacerbated host effects, including increased gut permeability, slightly elevated liver ethanol concentrations, and hepatic macrophage infiltration. Our findings reveal how microbial interactions and metabolic flexibility -including using alternative energy sources such as formate- rather than H₂S alone, shape B. wadsworthia's impact on host physiology, with implications for understanding diet-driven microbiome-host interactions
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