bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-451-targeted PSMB8 promotes PRRSV infection by degrading IRF3
Authors: Li Sihan , Guo Shuyuan , Liu Fang , Yao Yao , Zhu Yingqi , Feng Wen-hai 
Published: August 2024

ABSTRACT

Porcine respiratory and reproductive syndrome (PRRS) is one of the most devastating infectious diseases of pigs, causing reproductive failures in sows and severe respiratory symptoms in piglets and growing pigs. MicroRNAs (miRNAs) are reported to play an essential role in virus–host interactions. In this study, we demonstrated that miR-451 enhanced type I interferon (IFN-I) production through targeting proteasome subunit β8 (PSMB8), therefore restricting PRRS virus (PRRSV) replication. We showed that the expression of PSMB8 was upregulated by PRRSV infection, and knockdown of PSMB8 inhibited PRRSV replication by promoting IFN-I production. Moreover, we demonstrated that PSMB8 interacted with the regulatory domain of IRF3 to mediate K48-linked polyubiquitination and degradation of IRF3. Also, importantly, we showed that PSMB8, as a target gene of miR-451, negatively regulated IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to modulate innate immune responses.

IMPORTANCE
Porcine respiratory and reproductive syndrome virus (PRRSV), as a huge threat to the swine industry, is a causative agent that urgently needs to be solved. The dissecting of PRRSV pathogenesis and understanding of the host–pathogen interaction will provide insights into developing effective anti-PRRSV strategies. In this study, we showed that miR-451 dramatically inhibited PRRSV replication by targeting proteasome subunit β8 (PSMB8), a subunit of the immunoproteasome. Mutation of PSMB8 is often related to autoinflammatory diseases due to the elevated IFN production. We revealed that PSMB8 downregulated IFN production by promoting IRF3 degradation. In addition, we showed that PRRSV infection upregulated PSMB8 expression. Taken together, our findings reveal that miR-451 is a negative regulator of PRRSV replication, and PSMB8, a target gene of miR-451, negatively regulates IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to regulate innate immune responses.
Coenzyme A biosynthesis in
Bacillus subtilis
: discovery of a novel precursor metabolite for salvage and its uptake system
Authors: Warneke Robert , Herzberg Christina , Klein Moritz , Elfmann Christoph , Dittmann Josi , Feussner Kirstin , Feussner Ivo , Stülke Jörg 
Published: August 2024

ABSTRACT

The Gram-positive model bacterium
Bacillus subtilis
is used for many biotechnological applications, including the large-scale production of vitamins. For vitamin B5, a precursor for coenzyme A synthesis, there is so far no established fermentation process available, and the metabolic pathways that involve this vitamin are only partially understood. In this study, we have elucidated the complete pathways for the biosynthesis of pantothenate and coenzyme A in
B. subtilis
. Pantothenate can not only be synthesized but also be taken up from the medium. We have identified the enzymes and the transporter involved in the pantothenate biosynthesis and uptake. High-affinity vitamin B5 uptake in
B. subtilis
requires an ATP-driven energy coupling factor transporter with PanU (previously YhfU) as the substrate-specific subunit. Moreover, we have identified a salvage pathway for coenzyme A acquisition that acts on complex medium even in the absence of pantothenate synthesis. This pathway requires rewiring of sulfur metabolism resulting in the increased expression of a cysteine transporter. In the salvage pathway, the bacteria import cysteinopantetheine, a novel naturally occurring metabolite, using the cystine transport system TcyJKLMN. This work lays the foundation for the development of effective processes for vitamin B5 and coenzyme A production using
B. subtilis
.

IMPORTANCE

Vitamins are essential components of the diet of animals and humans. Vitamins are thus important targets for biotechnological production. While efficient fermentation processes have been developed for several vitamins, this is not the case for vitamin B5 (pantothenate), the precursor of coenzyme A. We have elucidated the complete pathway for coenzyme A biosynthesis in the biotechnological workhorse
Bacillus subtilis
. Moreover, a salvage pathway for coenzyme A synthesis was found in this study. Normally, this pathway depends on pantetheine; however, we observed activity of the salvage pathway on complex medium in mutants lacking the pantothenate biosynthesis pathway even in the absence of supplemented pantetheine. This required rewiring of metabolism by expressing a cystine transporter due to acquisition of mutations affecting the regulation of cysteine metabolism. This shows how the hidden “underground metabolism” can give rise to the rapid formation of novel metabolic pathways.
Slow clearance of histidine-rich protein-2 in Gabonese with uncomplicated malaria
Authors: Lamsfus Calle Carlos , Schaumburg Frieder , Rieck Thorsten , Nkoma Mouima Anne Marie , Martinez de Salazar Pablo , Breil Saskia , Behringer Johannes , Kremsner Peter G. , Mordmüller Benjamin , Fendel Rolf 
Published: August 2024

ABSTRACT

Malaria rapid diagnostic tests (RDTs), which detect
Plasmodium falciparum
(Pf)-specific histidine-rich protein-2 (HRP2), have increasing importance for the diagnosis and control of malaria, especially also in regions where routine diagnosis by microscopy is not available. HRP2-based RDTs have a similar sensitivity to expert microscopy, but their reported low specificity can lead to high false positivity rates, particularly in high-endemic areas. Despite the widespread use of RDTs, models investigating the dynamics of HRP2 clearance following Pf treatment focus rather on short-term clearance of the protein. The goal of this observational cohort study was to determine the long-term kinetic of HRP2-levels in peripheral blood after treatment of uncomplicated malaria cases with Pf mono-infection using a 3-day course of artesunate/amodiaquine. HRP2 levels were quantified at enrollment and on days 1, 2, 3, 5, 7, 12, 17, 22, and 28 post-treatment initiation. The findings reveal an unexpectedly prolonged clearance of HRP2 after parasite clearance from capillary blood. Terminal HRP2 half-life was estimated to be 9 days after parasite clearance using a pharmacokinetic two-compartmental elimination model. These results provide evidence that HRP2 clearance has generally been underestimated, as the antigen remains detectable in capillary blood for up to 28 days following successful treatment, influencing RDT-based assessment following a malaria treatment for weeks. A better understanding of the HRP2 clearance dynamics is critical for guiding the diagnosis of malaria when relying on RDTs.

IMPORTANCE

Detecting
Plasmodium falciparum
, the parasite responsible for the severest form of malaria, typically involves microscopy, polymerase chain reaction (PCR), or rapid diagnostic tests (RDTs) targeting the histidine-rich protein 2 or 3 (HRP2/3). While microscopy and PCR quickly turn negative after the infection is cleared, HRP2 remains detectable for a prolonged period. The exact duration of HRP2 persistence had not been well defined. Our study in Gabon tracked HRP2 levels over 4 weeks, resulting in a new model for antigen clearance. We discovered that a two-compartment model accurately predicts HRP2 levels, revealing an initial rapid reduction followed by a much slower elimination phase that can take several weeks. These findings are crucial for interpreting RDT results, as lingering HRP2 can lead to false positives, impacting malaria diagnosis and treatment decisions.
Desertic siliciclastic stromatolites in the Upper Jurassic Guará Formation from southwestern Gondwana: Trapping and binding in a non-marine setting
Authors: Angonese Bruno S. , Scherer Claiton M.S. , De Ros Luiz F. , Michel Rossano D.L. , Sipp Gabriel S. , Ferronato João P.F. 
Published: August 2024

Abstract
Siliciclastic stromatolites are rare in the geologic record, and their occurrence recorded in the literature is restricted to marine and coastal environments. The Upper Jurassic Guará Formation, from the Paraná Basin in southern Brazil, hosts unique non-marine siliciclastic stromatolites, providing a rare opportunity to study trapping and binding mechanisms by microbial mats in a continental setting. These microbialites occur interbedded with eolian and fluvial facies. The structural layering of the stromatolite domes is formed by the intercalation of sandy layers, resulting from trapping and binding of siliciclastic grains by microbial mats and in situ precipitation of amorphous to cryptocrystalline silica, which directly replaced the microbial colonies. The silica layers contain partially preserved spherical to ovoid bodies interpreted as colonies of coccoid microorganisms. These siliciclastic stromatolites were formed due to a specific balance of environmental factors, namely water chemistry and sediment supply, which enhanced the processes of trapping and binding and in situ precipitation. They record the presence of microbial life in a non-marine, silica-rich, fluvial-eolian environment in which there were no previous published occurrences of agglutinated stromatolites. These specimens record macroscopically identifiable evidence of microbial life in a continental environment that must be accounted for in the search for ancient life on Earth and Mars.
Denoising and Augmented Negative Sampling for Collaborative Filtering
Authors: Zhao Yuhan , Chen Rui , Lai Riwei , Han Qilong , Song Hongtao , Chen Li 
Published: August 2024

Negative sampling plays a crucial role in implicit-feedback-based collaborative filtering, where it leverages massive unlabeled data to generate negative signals for guiding supervised learning. The current state-of-the-art approaches focus on utilizing hard negative samples that contain more information to establish a better decision boundary. To strike a balance between efficiency and effectiveness, most existing methods adopt a two-pass approach: in the first pass, a fixed number of unobserved items are sampled using a simple static distribution, while, in the second pass, a more sophisticated negative sampling strategy is employed to select the final negative items. However, selecting negative samples solely from the original items in a dataset is inherently restricted due to the limited available choices, and thus may not be able to effectively contrast positive samples. In this paper, we empirically validate this observation through meticulously designed experiments and identify three major limitations of existing solutions: ambiguous trap, information discrimination, and false negative samples.
Our response to such limitations is to introduce “denoised” and “augmented” negative samples that may not exist in the original dataset. This direction renders a few substantial technical challenges. First, constructing augmented negative samples may introduce excessive noise that eventually distorts the decision boundary. Second, the scarcity of supervision signals hampers the denoising process. To this end, we introduce a novel generic denoising and augmented negative sampling (DANS) paradigm and provide a concrete instantiation. First, we disentangle the hard and easy factors of negative items. Then, we regulate the augmentation of easy factors by carefully considering the direction and magnitude. Next, we propose a reverse attention mechanism to learn a user’s negative preference, which allows us to perform a dimension-level denoising procedure on hard factors. Finally, we design an advanced negative sampling strategy to identify the final negative samples, taking into account both the score function used in existing methods and a novel metric called synthesization gain. Through extensive experiments on real-world datasets, we demonstrate that our method substantially outperforms state-of-the-art baselines. Our code is publicly available at https://github.com/Asa9aoTK/ANS-Recbole.
O Estado e a produção de convenções sociais acerca do mercado de armas de fogo no Brasil
Authors: Vieira Mateus Tobias , Jardim Maria Chaves 
Published: August 2024

The article analyzes the role of the state in formulating social conventions about firearms in Brazil. We selected Law 10.826/2003, passed during the first Lula Government (2003-2006),as the empirical dispute, and also we analyzed eight presidential decrees from the first year ofthe Bolsonaro Government (2019). In the methodology, we analyzed the legal framework based on the studies of Steiner and Trespeuch, about contested markets; Bourdieu, about the state and the concept of social convention, by Mary Douglas. The results indicate that the state has influenced the production of predispositions and that the disarmamentist social convention, produced during the Lula Government, has been challenged, generating disputes that go beyond the normative perspective.
Fábrica de líderes: a influência da USP na formação da elite dirigente nacional
Authors: Loureiro Maria Rita , Codato Adriano , Rodrigues Viegas Rafael , Silva Rodrigo 
Published: August 2024

The University of São Paulo (USP) is acknowledged for its scientific and cultural significance. This article investigates the extent of USP’s influence on the shaping of Brazil’s governing elites. The study is founded on a quantitative analysis of the academic background of individuals occupying top positions in the federal public administration (Presidents of the Republic, Presidents of the Central Bank, Ministers of State, leaders of the Legislative, Judiciary, and the Public Prosecutor Service) from the 1930s to the present day. The data reveals that usp has made a significant contribution to the education of high-ranking federal members across various spheres, with its influence being predominant. The participation of USP alumni varies over time and between different political regimes, being more pronounced during democratic periods. Moreover, other higher education institutions have also played crucial roles in the formation of governing elites. The diversity of institutions attended by government members reflects the complexity and dynamics of the formation of Brazilian elites, influenced by political and social changes over time.
Dária Jaremtchuk. Políticas de atração: relações artístico-culturais entre Estados Unidos e Brasil (1960-1970)
Authors: Carvalho Paula Costa Nunes de 
Published: August 2024

Book review: Políticas de atração: relações artístico-culturais entre Estados Unidos e Brasil (1960-1970)", São paulo, Editora Unesp, 2023, by Dária Jaremtchuk.
Changing Nepali children’s attitudes toward conservation through a participatory education program
Authors: Phillips John A. , Rijal Bishwanath , Tan Chia L. 
Published: August 2024

Abstract
People’s attitude toward wildlife is known to affect the success of conservation programs. Public education can increase support for conservation measures by providing the knowledge necessary to make informed decisions, improve pro-environmental behaviour and potentially enlist participation. To that end, we developed a participatory conservation education program in Nepal with a target audience of secondary school students. Our lessons emphasized ecological balance by highlighting the roles of individual species, including the rhesus macaque (Macaca mulatta). This species presents a challenge for educating the public about maintaining balance in nature, because although an important seed disperser and species of religious significance, macaques are frequently involved in human-wildlife conflict and considered a pest species. We evaluated the impact of our program by surveying students from six socioeconomically similar schools, four that participated in our program and two that had not. Our questionnaire was comprised of knowledge questions about local wildlife and conservation issues, an open-ended listing exercise to determine species preferences, and statements that elicited students’ opinions regarding empathy toward animals. Knowledge about and attitude toward wildlife, including M. mulatta, were greater in students that participated in the program. More importantly, these students were more likely to understand the role individual species play in a balanced ecosystem, how human behaviour can negatively impact wildlife, and how they could participate in conservation efforts. Gender was not a factor in any response. We discuss the merits of using a participatory learning platform in a standalone education program that has long-term purpose, funding, and buy-in.
Fire-Faith and the Gnostic Neo-Templars
Authors: Hedenborg White Manon 
Published: August 2024

Abstract
The article analyses the early development of Aleister Crowley’s (1875–1947) Gnostic Catholic Mass and its c. 1917 German translation by Theodor Reuss (1855–1923), the founder and first international head of the initiatory fraternity Ordo Templi Orientis. Crowley’s Gnostic Mass is an influential and important example of esoteric group ritual still celebrated across the globe today. Reuss’s translated ritual holds historical interest, being the first published version of the ritual (1918) and containing a number of editorial innovations. The article discusses Crowley’s and Reuss’s collaboration and their respective masses in context, suggesting Reuss’s innovations to the Gnostic Mass shed light on his own interests in phallicism and neo-Gnosticism as well as his wish to promote Crowley’s teachings to the continental European esoteric milieu.
The Conjuring Girdles of King Solomon and Doctor Faustus in Early Modern Material Magic
Authors: Skemer Don C. 
Published: August 2024

Abstract
The article concerns conjuring girdles in early modern material magic, particularly in Central Europe during the long eighteenth century (c. 1660–c. 1820). Magicians in ritual circles could wear such girdles on the body as belts or sashes to conjure and command angels, spirits, and demons. Emphasis in the article is on anonymous German manuscript books of learned magic dating from the late seventeenth and early eighteenth century, with pseudepigraphal attributions to King Solomon and Doctor Faustus. These manuscripts explain the design, text, imagery, materials, measurements, production, and applications of conjuring girdles. The article also discusses what is known about their compilers, end-users, and readers during a period marked by hybridizing, variability, and democratization in material magic. The article includes three illustrations in books of learned magic with designs for conjuring girdles (Göttingen, Niedersächsische Staats- und Universitätsbibliothek, Cod. Ms. Hist. Nat. 80; Leipzig, Universitätsbibliothek, Cod. Mag. 6 [no. 51]; Leipzig, Universitätsbibliothek, Cod. Mag. 133 [no. 27]); and two conjuring scenes from the legends of Doctor Faustus and his apprentice Christoph Wagner.
The Notion of Textual Comparison between the Judean Desert Biblical Texts and of Variant Readings
Authors: Tov Emanuel 
Published: August 2024

Abstract
Were there any so-called “variants” in the scrolls? The assumption of contact between any two scrolls has been inferred from corrective additions and deletions. It has usually been claimed that corrections were based on MT. I divide the scrolls into different groups because in each group there could have been a different incentive for correction towards an external source. The strength of the argument depends on this division. In an analysis of the evidence (see the Appendix) in each of the groups, a different correction pattern was detected, and often the corrections were revised towards a text different from MT. In all these cases, the corrections were not made towards external sources, but the source of the scrolls. Strengthened by theoretical arguments, we suggest that the scrolls contain no notations of variants, that is, elements that were copied as variants from other scrolls or were corrected according to external sources.
Gender bias in generative artificial intelligence text-to-image depiction of medical students
Authors: Currie Geoffrey , Currie Josie , Anderson Sam , Hewis Johnathan 
Published: August 2024

Introduction: In Australia, 54.3% of medical students are women yet they remain under-represented in stereotypical perspectives of medicine. While potentially transformative, generative artificial intelligence (genAI) has the potential for errors, misrepresentations and bias. GenAI text-to-image production could reinforce gender biases making it important to evaluate DALL-E 3 (the text-to-image genAI supported through ChatGPT) representations of Australian medical students. Method: In March 2024, DALL-E 3 was utilised via GPT-4 to generate a series of individual and group images of medical students, specifically Australian undergraduate medical students to eliminate potential confounders. Multiple iterations of images were generated using a variety of prompts. Collectively, 47 images were produced for evaluation of which 33 were individual characters and the remaining 14 images were comprised of multiple (5 to 67) characters. All images were independently analysed by three reviewers for apparent gender and skin tone. Consequently, 33 feature individuals were evaluated and a further 417 characters in groups were evaluated ( N = 448). Discrepancies in responses were resolved by consensus. Results: Collectively (individual and group images), 58.8% ( N = 258) of medical students were depicted as men, 39.9% ( N = 175) as women, 92.0% ( N = 404) with a light skin tone, 7.7% ( N = 34) with mid skin tone and 0% with dark skin tone. The gender distribution was a statistically significant variation from that of actual Australian medical students for individual images, for group images and for collective images. Among the images of individual medical students ( N = 25), DALL-E 3 generated 92% ( N = 23) as men and 100% were of light skin tone ( N = 25). Conclusion: This evaluation reveals the gender associated with genAI text-to-image generation using DALL-E 3 among Australian undergraduate medical students. Generated images included a disproportionately high proportion of white male medical students which is not representative of the diversity of medical students in Australia. The use of DALL-E 3 to produce depictions of medical students for education or promotion purposes should be done with caution.