Stone locales together with continuous maps form a coreflective subcategory of spectral locales and perfect maps. A proof in the internal language of an elementary topos was previously given by the second-named author. This proof can be easily translated to univalent type theory using resizing axioms. In this work, we show how to achieve such a translation without resizing axioms, by working with large, locally small, and small-complete frames with small bases. This requires predicative reformulations of several fundamental concepts of locale theory in predicative HoTT/UF, which we investigate systematically.

The Intergovernmental Negotiating Committee (INC) on plastic pollution are United Nations member states who will convene for the second part of the fifth session of the Intergovernmental Negotiating Committee in Geneva (INC5.2) 5-14 August, 2025 to negotiate a global plastics treaty. The Scientists’ Coalition for an Effective Plastics Treaty (‘The Scientists’ Coalition’) is an international network of independent scientific and technical experts who have been contributing robust science to treaty negotiators since INC1 in 2022. The Scientists’ Coalition established a series of working groups following INC5.1 in Busan, Korea 25 November – 1 December 2024. Each working group has produced science-based responses to the selected articles of ‘the Chair’s text’ (the latest version of the draft global plastics treaty text). This Letter to the Editor summarises those responses.

To achieve infectivity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, must first traverse the upper respiratory tract mucosal barrier. Once infection is established, the cascading complexities of the pathophysiology of COVID-19 makes intervention extremely difficult. Thus, enhancing the defensive properties of the mucosal linings of the upper respiratory tract may reduce infection by SARS-CoV-2 and indeed by other viruses such as influenza, which have been responsible for the two major pandemics of the last century. In this review we summarise potential opportunities for foods and nutrients to promote an adequate mucosal immune preparedness with an aim to assist protection against infection by SARS-CoV-2, to maximise the mucosal vaccination (IgA inducing) response to existing systemic vaccines, and to play a role as adjuvants to intranasal vaccines. We identify opportunities for vitamins A and D, zinc, probiotics, bovine colostrum and resistant starch to promote mucosal immunity and enhance the mucosal response to systemic vaccines, and for vitamin A to also improve the mucosal response to intranasal vaccination. It is possible that an entirely different virus may in the future, by way of convergent evolution, utilise a similar upper respiratory tract infection pathway. A greater research focus on mucosal lymphoid immune protection in partnership with nutrition would result in greater preparedness for such an event.

The cestode Gerbillitaenia psammomi (Cyclophyllidea: Catenotaeniidae: Skrjabinotaeniinae) was found parasitizing fat sand rats (Psammomys obesus) in the south of Tunisia. The species was found previously in P. obesus from Egypt and in Meriones shawi from Morocco. The present finding constitutes the first record of the species in Tunisia. In the present study, G. psammomi was morphologically characterized using light microscopy and compared to previous records of the species. The main differentiating morphological features of G. psammomi with respect to other skrjabinotaenines of North African Gerbillinae murids are, in particular, the shape of strobila, size of suckers, number of testes, absence of an antero-poral ovarian lobe, length of the central uterine stem, and number of primary uterine branches. Negative density-dependent growth (crowding effect) has also been reported. Molecular analysis based on 28S rDNA was performed for G. psammomi and for Skrjabinotaenia oranensis. Thus, both species are grouped in a clade with other species of the subfamily Skrjabinotaeniinae and are clearly separated from the clade that includes species of the subfamily Catenotaeniinae. The molecular study confirmed the previously postulated synonymy of Meggittina numida with S. oranensis.

Major depressive disorder (MDD) is a serious and often chronic illness that requires early and urgent treatment. Failing to provide effective treatment of MDD can worsen the illness trajectory, negatively impact physical health, and even alter brain structure. Early optimized treatment (EOT) of MDD, with a measurement-based approach to diagnosis, rapid treatment initiation with medication dosage optimization, frequent monitoring, and prompt adjustments in treatment planning when indicated, should proceed with a sense of urgency. In this article, we describe common barriers to providing an EOT approach to treating MDD at each phase of care, along with strategies for navigating these obstacles. Approaching the treatment of MDD with a greater sense of urgency increases the likelihood of symptom reduction in MDD, facilitating full functional recovery and a return to life engagement.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

Domestic cats have lived alongside human communities for thousands of years, hunting rats, mice, and other pests and serving as pets and a source of pelts and meat. Cats have received limited archaeological attention because their independence limits direct insight into human societies. An adult and juvenile cat recovered from the Emanuel Point wreck 2 (EP2) reflect what are, most likely, the earliest cats in what is now the United States. Zooarchaeological analyses of these and other archaeological cats in the Americas demonstrate that cats ranged substantially in size: some were comparable to modern house cats, and others were much smaller. Isotopic analyses of the adult cat from EP2 provides insight into early shipboard cat behavior and their diet, which appears to have focused on consumption of fish and possibly domestic meat. Cats accompanied sailors on ships where they were relied on to hunt rats and mice that were infesting ships’ holds. Interestingly, based on these isotopic results, the adult cat from EP2 does not seem to have relied heavily on rats as a source of food. These pests were unintentionally introduced to the New World, and cats would have followed, hunting both native and invasive pests.

As part of a broad survey of the trematodes of damselfishes (Pomacentridae) in the tropical Indo-West Pacific, zoogonids were collected from multiple localities in Australia, New Caledonia, and French Polynesia. All zoogonid specimens collected were consistent with the subfamily Lecithostaphylinae, and morphological and molecular data (ITS2 and 28S rDNA, and cox1 mtDNA) were generated for most host-locality combinations to enable an integrative species delimitation. The collection comprised three species: Deretrema stratiotes n. sp. from four species of Abudefduf Forsskål from Ningaloo Reef in Western Australia, and two species consistent with the genus Lecithostaphylus Odhner, 1911 for which Innuptacola n. gen. is proposed based on phylogenetic and morphological distinction, the type-species I. gibsoni (Cribb, Bray & Barker, 1992) n. comb. (= L. gibsoni) from six species of Abudefduf in Ningaloo Reef, Queensland and New Caledonia, and I. torquata n. sp. from 12 pomacentrid species in Ningaloo Reef, the Great Barrier Reef in Queensland, and the Gambier Islands in French Polynesia. The new collection demonstrates that some zoogonid species are geographically widespread (from the Pacific Ocean to the Indian Ocean) and can infect a broad range of hosts (multiple genera within a family), whereas others are apparently geographically restricted and exhibit higher host-specificity (fishes within a single genus).

This study compares the design practices and performance of ChatGPT 4.0, a large language model (LLM), against graduate engineering students in a 48-h prototyping hackathon, based on a dataset comprising more than 100 prototypes. The LLM participated by instructing two participants who executed its instructions and provided objective feedback, generated ideas autonomously and made all design decisions without human intervention. The LLM exhibited similar prototyping practices to human participants and finished second among six teams, successfully designing and providing building instructions for functional prototypes. The LLM’s concept generation capabilities were particularly strong. However, the LLM prematurely abandoned promising concepts when facing minor difficulties, added unnecessary complexity to designs, and experienced design fixation. Communication between the LLM and participants was challenging due to vague or unclear descriptions, and the LLM had difficulty maintaining continuity and relevance in answers. Based on these findings, six recommendations for implementing an LLM like ChatGPT in the design process are proposed, including leveraging it for ideation, ensuring human oversight for key decisions, implementing iterative feedback loops, prompting it to consider alternatives, and assigning specific and manageable tasks at a subsystem level.

This paper studies reversibility and transitivity of semigroups acting on homogeneous spaces. Properties of the reversor set of a subsemigroup acting on homogeneous spaces are presented. Let G be a topological group and L a subgroup of G. Assume that S is a subsemigroup of G with nonempty interior. It is presented a study of the reversibility of the S-action on $G/L$ in terms of the actions of S and L on homogeneous spaces of G. The results relate the reversibility and the transitivity of S in $G/L$ with the minimality of the action of L on homogeneous spaces of G. In addition, sufficient conditions for S to be right reversible in G if S is reversible in $G/L$ are presented.

Leptospira are bacteria that cause leptospirosis in both humans and animals. Human Leptospira infections in Uganda are suspected to arise from animal–human interactions. From a nationwide survey to determine Leptospira prevalence and circulating sequence types in Uganda, we tested 2030 livestock kidney samples, and 117 small mammals (rodents and shrews) using real-time PCR targeting the lipL32 gene. Pathogenic Leptospira species were detected in 45 livestock samples but not in the small mammals. The prevalence was 6.12% in sheep, 4.25% in cattle, 2.08% in goats, and 0.46% in pigs. Sequence typing revealed that Leptospira borgpetersenii, Leptospira kirschneri, and Leptospira interrogans are widespread across Uganda, with 13 novel sequence types identified. These findings enhance the East African MLST database and support the hypothesis that domesticated animals may be a source of human leptospirosis in Uganda, highlighting the need for increased awareness among those in close contact with livestock.