Mitochondria are not only the powerhouses of the cell. They are also dynamic signaling hubs, playing a key role in cellular metabolism and adaptation. Proper mitochondrial function depends largely on the import of proteins encoded by the nucleus. Using proximity labeling (TurboID), we show that Arabidopsis thaliana FRIENDLY (FMT) protein is in close proximity to several organellar-destined proteins, mostly mitochondrial, during their translation. Many of the corresponding mRNAs are immunoprecipitated with FMT. Remarkably, when FMT is absent, its target mRNAs lose their correct cellular localization. Our TurboID approach, associated with immunoprecipitations and confocal microscopy, also demonstrates the interaction between FMT and the Nascent polypeptide Associated Complex (NAC), a ribosome-associated platform involved in the maturation and sorting of nascent peptides. Taken together, these results suggest that FMT, through its interaction with NAC and the ribosome, is involved in the spatial regulation of translation in the cell.

Founded in 1703, St. Petersburg was the capital of the Russian Empire. Its historic center and associated monuments are inscribed as a UNESCO World Heritage Site. Its components are classified as cultural rather than natural or mixed. We hypothesized that a part of them has an additional ecotourism value. We carried out field observations along with a review of the literature. Our results confirmed the hypothesis: many of these sites retain important elements of biodiversity that can be used for environmental education. Large congregations of birds can be observed in close proximity to Heritage monuments. Wintering bats occupy the interiors of historic fortifications, and in summer, concentrations of feeding bats can be found nearby. Seal haul-out sites have been documented on small islands near the city. The ecotourism and nature-conservation value of these Heritage landscapes is usually linked to the original logic of their selection. The best locations were chosen for palace construction—dry, scenic areas with fertile soils suitable for park creation. Proximity to bodies of water was equally important, both for aesthetic reasons and for sanitation. These same qualities also make such areas highly favorable for biodiversity. Even after centuries of development, many natural features have persisted.

Botryosphaeriaceae pathogens have broad host ranges and can move between hosts, particularly those with overlapping geographic distributions. Cross-infection potential and virulence were assessed for 40 isolates of Botryosphaeria, Diplodia, and Neofusicoccum (11 species), originally isolated from apple, olive, or grapevine crops. Progression of asymptomatic colonization beyond visible necrotic lesions was also assessed, to determine minimum pruning distances required for effective pathogen removal. The assays were conducted using detached lignified stems of apple and olive, and dormant cuttings of grapevine. All the isolates cross-infected and colonized stems or cuttings of the three potential hosts, confirming host-independence of these pathogens. Most of the Neofusicoccum isolates consistently caused the largest lesions across the three inoculated hosts. Asymptomatic colonization was not detected at distances of 20 or 30 cm beyond visible lesions. However, at 10 cm, one isolate of N. parvum colonized the three hosts, and one isolate of D. seriata colonized olive host. These results highlight the challenges for managing these pathogens in fruit crops growing in close proximity, and emphasize the urgency of revising the minimum pruning distances required for successful pathogen removal.

Uncertainty quantification for geospatial prediction models plays a crucial role in evaluating model confidence and supporting informed decision-making. Conformal prediction (CP), as a model-agnostic framework, has recently been introduced into geospatial settings, leading to the development of geospatial conformal prediction (GeoCP). GeoCP considers spatial dependence and incorporates a geographic weighting mechanism into CP to capture spatially varying uncertainty, satisfying the localized exchangeability assumption. In many real-world scenarios, however, spatial processes could exhibit abrupt transitions, such as neighboring regions with distinct land-use types, resulting in significant differences despite close geographic proximity. To address this limitation, we propose geospatial similarity conformal prediction (GeoSIMCP), an extension of GeoCP that jointly considers both geographic distance and feature-space similarity when estimating local uncertainty. We further develop a parameter optimization framework to ensure robust model tuning. Through comprehensive simulation studies under varying spatial structures, we demonstrate the advantages of GeoSIMCP over GeoCP. Additionally, we validate the effectiveness of GeoSIMCP on two real-world prediction tasks—housing prices and PM2.5 concentration—characterized by different spatial processes. Our results highlight the potential of integrating geographic and feature similarity to enhance uncertainty quantification in spatial prediction, offering a more adaptive and reliable framework for geospatial decision-making.

Background/Objectives: Endometrial cancer frequently develops resistance to therapy, partly due to the ability of tumor cells to adapt to cellular stress through non-apoptotic mechanisms. Mitochondrial dysfunction and cytoskeletal remodeling are increasingly recognized as key components of stress adaptation; however, their structural relationship under pharmacological stress in three-dimensional (3D) tumor models remains poorly characterized. The present study aimed to investigate the ultrastructural and phenotypic effects of lithium chloride (LiCl)-induced stress in 3D endometrial cancer spheroids, with a particular focus on mitochondrial alterations and intermediate filament organization. Methods: Three-dimensional spheroids generated from Ishikawa endometrial cancer cells were exposed to lithium chloride at concentrations of 1, 10, or 50 mM for defined time periods. Cell viability, proliferative activity, and clonogenic capacity were assessed using Trypan Blue exclusion, BrdU incorporation, and soft agar assays. Ultrastructural changes were examined by transmission electron microscopy to evaluate mitochondrial morphology, cytoplasmic organization, and intermediate filament distribution. Results: LiCl exposure resulted in a dose- and time-dependent reduction in cell viability, proliferation, and clonogenic potential in 3D spheroids. Ultrastructural analysis revealed pronounced mitochondrial swelling, cristae disorganization, and membrane-associated mitochondrial alterations. These changes were consistently accompanied by conspicuous accumulation and reorganization of intermediate filaments in close spatial proximity to damaged mitochondria, suggesting a structural association between cytoskeletal remodeling and mitochondrial injury. Across all experimental conditions, classical apoptotic ultrastructural features, including chromatin condensation and apoptotic body formation, were not observed. Conclusions: Together, these observations indicate that lithium chloride elicits a stress phenotype in 3D endometrial cancer spheroids that primarily manifests at the organelle and cytoskeletal levels, rather than through classical apoptotic execution. Although descriptive in nature, the present study highlights intermediate filament accumulation as a prominent structural feature of lithium-induced mitochondrial stress and establishes a structural reference point for future studies aimed at further investigating mitochondrial-cytoskeletal relationships during pharmacological stress in endometrial cancer.

Zoonotic diseases account for approximately one billion cases of illness and millions of deaths globally each year. Increasing contact between humans and competent wildlife hosts elevates the risk of zoonotic spillover. Synanthropic bird species are key players in the transmission of zoonotic pathogens, including flaviviruses such as West Nile virus (WNV) and influenza A viruses like Avian Influenza Virus (AIV). Active surveillance of sentinel birds inhabiting urban areas allows for early detection of emerging pathogens before they cause zoonotic outbreaks. Despite nesting in close proximity to humans, the role of the house martin (Delichon urbicum) in the circulation of flaviviruses and AIV remains poorly understood. Here, we analyzed the presence of antibodies against flaviviruses and AIV in a colony of house martins from southwestern Spain. In addition, we aimed to detect amplicons of the matrix and nucleoprotein genes of AIV using RT-qPCR. While none of the samples tested positive for AIV by RT-qPCR, we observed an AIV seroprevalence of 2.13% based on non-subtyped ELISA. Notably, this is the first report of AIV-seropositive D. urbicum individuals captured in Spain. Moreover, we detected a flavivirus-group seroprevalence of 24.34%, similar to rates reported in the same house martin population between 2018 and 2020, suggesting widespread circulation of flaviviruses within this synanthropic species. These results support the hypothesis that house martins may participate in the transmission of these viruses between wild bird populations and humans in urban environments.

The biocompatibility of adhesive systems is essential for the long-term success of restorative dental procedures due to their close proximity to dentin and pulpal tissues. This study aimed to evaluate the cytotoxic effects of adhesive systems with different pH values on L929 mouse fibroblast cells under in vitro conditions. Four commercially available adhesive systems with different pH values-All-Bond Universal, G-Premio Bond, Tokuyama Bond Force II, and Clearfil Universal Bond Quick-were evaluated. Cytotoxicity was assessed using the MTT assay at four different concentrations (0.1%, 0.01%, 0.001%, and 0.0001%) and three incubation periods (24, 48, and 72 h). Cell viability data were analyzed using two-way analysis of variance followed by Bonferroni post hoc tests. Cytotoxicity was interpreted according to ISO 10993-5 criteria. All adhesive systems exhibited concentration-dependent cytotoxicity, with significant reductions in cell viability observed only at the highest concentration (0.1%). At lower concentrations, no cytotoxic effects were detected. Despite having the highest pH value, All-Bond Universal consistently demonstrated the lowest cell viability. In contrast, Tokuyama Bond Force II showed the most favorable cytocompatibility profile, with relatively higher cell viability values over time. Morphological analysis supported the quantitative findings, revealing pronounced cellular alterations at high concentrations and preserved fibroblastic morphology at lower concentrations. adhesive systems demonstrate cytotoxic effects in a concentration-dependent manner, and pH alone is insufficient to predict their biocompatibility. Monomer composition and formulation characteristics appear to play a more critical role in determining cytotoxic behavior. These findings emphasize the importance of appropriate adhesive handling and isolation techniques to minimize tissue exposure and enhance clinical safety.

Antimicrobial resistance and transmission potential of pet-derived Providencia spp. in China.

Retail food outlets are commonly located in close proximity to schools, providing students with opportunities to purchase and consume food enroute to or from school. These outlets are typically unhealthy and disproportionately clustered near schools, and this trend has been increasing over time. While quantitative studies have established associations between school food environments and adolescent dietary behaviours, little is known about how school personnel perceive and experience their impacts. This qualitative study explored perspectives of school personnel (n = 9) from a secondary school in Perth, Western Australia, located 150 m from two retail food precincts (areas with a high concentration of food outlets, such as fast-food outlets, restaurants, cafés, and convenience stores). Semi-structured interviews were conducted, transcribed verbatim, and analysed thematically. School personnel described the nearby outlets as exerting a strong influence on students’ food choices, behaviours, and routines before and after school. Participants reported that nearby outlets increased students’ consumption of unhealthy food and drinks, contributed to classroom disruption, and undermined the school's health promotion efforts. The outlets also influenced the dietary practices of school personnel and increased their workload through the enforcement of school policies concerning external food. Broader community impacts, including loitering and shoplifting, created reputational issues for the school. While employment opportunities were acknowledged, overall sentiment from school personnel was overwhelmingly negative. Participants advocated for planning regulations to restrict the development of food outlets near schools and called for alternative youth-focused community infrastructure. Policy reform to limit outlets near schools, supported by cross-sector collaboration between education, health, and urban planning, is urgently needed to create healthier school food environments.

Wildfires generate large, spatially heterogeneous patches in boreal forests, providing a unique opportunity to investigate the spatial pattern of saproxylic beetle colonization. In this study, we analyzed spatial patterns of beetle assemblages within a 76,483 ha wildfire in northern Québec in 2005. Using a spatial modeling approach (Principal Coordinate of Neighboring Matrices, PCNM), we examined how beetle abundance patterns were structured at different spatial scales and whether these patterns were explained by plot-level variables, landscape-scale burn severity, or proximity to potential source habitats. Our results showed that most common saproxylic species exhibited significant spatial structure, primarily at a very large scale (> 2 km), with additional contributions from medium and small scales. These patterns were largely explained by environmental variables, particularly landscape-level attributes such as fire severity, rather than by distance to potential source habitats. While some mycophagous species showed reduced abundance with increasing distance from a recent (2002) burn, overall, distance to unburned or previously burned areas did not strongly constrain colonization. Our findings suggest that early post-fire beetle colonizers possess high dispersal capacities, allowing them to track suitable habitats across large distances. At a close proximity to suitable habitats, fine-scale environmental conditions, such as local fire severity and substrate characteristics, also played an important role, especially for xylophagous and predaceous species. These findings indicate that post-fire saproxylic beetle colonization is driven by a complex interplay of large-scale environmental heterogeneity and species-specific responses to fine-scale habitat features. Our study underscores the importance of incorporating broad spatial extents when studying post-fire colonization dynamics and highlights how spatial modeling can help disentangle the relative influence of environmental structure and dispersal processes.

Domain interactions in neuronal nitric oxide synthase identified by time-resolved fluorescence.

Coronary artery abnormalities (CAAs) are frequently encountered in common arterial trunk (CAT), with an estimated incidence of 5%-20%. However, their prognostic implications remain unclear. Surgical challenges potentially arise due to coronary arteries crossing the right ventricular outflow tract (RVOT), close proximity of the coronary and pulmonary orifices, and distortion to the proximal coronary segments and ostia during arch reconstruction or truncal valve replacement. Some studies have demonstrated that CAAs confer worse outcomes after CAT repair, while others have reported no significant prognostic impact. Both the number and subtype of CAAs may influence outcomes, but heterogeneous categorization limits the conclusions that can be drawn from existing studies. A uniform classification of CAAs in CAT is warranted to better ascertain the prognostic impact of CAA burden and morphology. This may enable more focused decision-making in clinical scenarios where a high-risk CAA pattern is suspected. For example, it may help inform the intraoperative trade-off between probing the coronaries to define their precise morphology against the risk of causing damage. We propose a classification consisting of 6 abnormalities: (1) single coronary artery, (2) ostial stenosis, (3) intramural course, (4) juxtacommissural origin, (5) coronary crossing RVOT, and (6) close proximity of coronary and pulmonary orifices.

Stochastic partial differential equations (SPDEs) have become key tools for modeling randomly disturbed systems in a broad spectrum of scientific and engineering disciplines. Among them, the optical soliton propagation in birefringent fibers has been of great interest because of the natural stochastic effects present in real optical communication systems. Although some research has been conducted on soliton dynamics in deterministic and integer-order models, the literature has few studies focusing on fractional stochastic frameworks coupled with M-truncated fractional operators. This paper fills this gap by proposing and studying the fractional stochastic Biswas–Arshed equation (FSBAE) that includes multiplicative white noise to represent random perturbations during optical signal propagation. We employ the [Formula: see text] method with Itô calculus and M-truncated fractional derivatives: in order to arrive at three different classes of solutions: stochastic optical breather solitons, M-shaped solitons, and singular solitons. The first contribution of this work consists in the combination of M-truncated fractional calculus — a not extensively developed operator in stochastic nonlinear optics — within the FSBAE, for the first time applied to this model. Comparative graphical analysis under conditions of different levels of white noise and fractional orders also identifies the robustness and stability of the solutions in close proximity to the zero-noise limit. This research adds to the development of soliton theory in that it has proposed a new mathematical model that can capture both nonlocal memory effect and stochastic variability, which are essential in real optical systems. The efficiency, simplicity, and flexibility of the approach make it an effective tool in solving a wider class of nonlinear stochastic issues in optical engineering and other fields dealing with stochastic partial differential equations.

ABSTRACT The Second Siege of Malta during the Second World War witnessed a huge amount of aerial activity, with over 3300 air raids from June 1940 to August 1944. The close proximity of the islands with the airbases of their attackers, separated only by a relatively small passage of water, the irregular nature of resupply to an island under siege, its size and even its geology; all had a profound effect on the nature and deployment of its anti-aircraft (AA) defences. In this paper, the background to Malta’s considerable investment in its anti-aircraft defences (in particular Heavy Anti-Aircraft defences) will be explicated, followed by examining how that coverage evolved to adapt to the changes both in the course of the war and those who were responsible for prosecuting it.

Surface antigens (SAGs) are a class of membrane proteins anchored to the parasite surface via glycosylphosphatidylinositol (GPI) anchors. These antigens play critical roles in parasite adhesion and host cell invasion. However, studies on SAGs from Eimeria necatrix remain limited. In this study, two sag genes, which exhibit differential expression in SZ and MZ-2 stages of E. necatrix, were cloned and expressed. The Ensag8 (XM_013584257.1) and Ensag36 (XM_013577436.1) genes, encoding proteins of 263 and 265 amino acids with predicted molecular weights of 27.83 kDa and 28.66 kDa, respectively. Bioinformatic analysis indicated that neither protein contains transmembrane domains, and phylogenetic classification placed both within the SAGA sub-family, with EnSAG8 showing close evolutionary proximity to EtSAG8. Recombinant proteins rEnSAG8 and rEnSAG36 were expressed predominantly as inclusion bodies in Escherichia coli, with apparent molecular weights of approximately 32 kDa and 36 kDa, respectively. Both rEnSAG8 and rEnSAG36 were recognized by a mouse anti-His tag monoclonal antibody and by convalescent serum from chickens infected with E. necatrix and E. tenella. The native EnSAG8 protein was detected in MZ-2 with an observed molecular weight of ~ 35 kDa, and EnSAG36 was detected in both SZ and MZ-2 at ~ 36 kDa. Immunolocalization analysis revealed that both native proteins are localized on the membranes of SZ and MZ-2. Transcriptional analysis indicated that Ensag8 is more highly expressed in MZ-2 than in SZ, whereas Ensag36 shows higher transcriptional levels in SZ than in MZ-2. Following the E. necatrix challenge, the anticoccidial index (ACI) of both the rEnSAG8- and rEnSAG36-immunized groups exceeded 160 at an immunization dose of 100 µg per chicken per immunization, with the rEnSAG8 group achieving a higher ACI than the rEnSAG36 group. Combined immunization with rEnSAG8 and rEnSAG36 conferred greater protection than immunization with either antigen alone. This study provides insights into the characterization of SAGs from E. necatrix. The differential expression of Ensag8 and Ensag36 highlights their potential roles in different parasite stages. Immunization with these recombinant proteins demonstrated significant anticoccidial protection, with combined immunization offering the best results.

Cellular myelocytomatosis oncogene (MYC) transcription factors are encoded by a family of genes that include the prototype member MYC, MYCN and MYCL, and most human cancers display expression alterations of MYC genes. MYC is regulated at multiple levels, and its stability and activity are modulated by protein phosphorylation. Although there is a reasonable knowledge of the kinases required for MYC modifications, the counteracting phosphatases have been understudied. Here, we have investigated the role of the chromatin-associated protein phosphatase 1 (PP1) regulatory subunit CDCA2, also known as Repo-Man, in the regulation of MYC proteins in cancer cells. Using RNA interference and degron-mediated degradation of CDCA2, we have demonstrated that the PP1 subunit is required for cMYC and MYCN stabilization and viability of triple-negative breast cancer, neuroblastoma and colon cancer cells. Proximity ligation assays indicate that both cMYC and MYCN are in close proximity to CDCA2 in vivo. Furthermore, we have shown that CDC2A is a bona fide MYC target gene in cancer cells, revealing a reciprocal regulatory loop that could be exploited for therapeutic purposes.

S5D mutation of NLRP3 revealed its role in NLRP3 inflammasome complex using split-luciferase complementation assay.

Inhaled Treprostinil is the primary treatment of pulmonary hypertension related to interstitial lung disease (PH-ILD). Despite treatment effectiveness in clinical trials, the real-world safety and tolerability of this therapy remains unclear. We conducted a multicenter, retrospective review of adults with PH-ILD who were prescribed inhaled treprostinil. We assessed clinical outcomes, 6 min walk distance (6MWD) and changes in natriuretic peptides (BNP, NT-proBNP), as well as medication tolerance. Eighty-three patients met the inclusion criteria. The 6MWD data was collected but a limited number of patients had results within close proximity to initiation of inhalational treprostinil with only seven patients having assessments within the 3 months prior to initiation as well as 3 months post therapy. Limited 6MWD data is likely due, in part, to coinciding with the COVID pandemic, limiting face-to-face interactions and exercise testing. The majority of our subjects, 63%, had an absolute improvement in their BNP level, over a mean duration of 170 days. However, no significant difference was detected between baseline and follow-up natriuretic peptide levels. Adherence was assessed and the majority (77%) of patients remained on therapy at the time of censoring, with three-quarters (75%) meeting the target dose. Of the 15 patients intolerant to nebulized treprostinil who were transitioned to a dry powder inhaler, the majority (87%) were able to tolerate the other formulation. The medication was well-tolerated with a large percentage of patients remaining on therapy indefinitely and reaching the targeted therapeutic dose.

Inositol polyphosphate-5-phosphatase E (INPP5E) encodes the ciliary protein INPP5E, which plays an important role in regulating the phospholipid membrane makeup of the primary cilium. Here we utilize proximity labelled proteomics of INPP5E to broaden the functional modules working within close proximity to the protein. In doing so, we identified the EH binding protein EHBP1 as a ciliary protein that localizes to the basal body and ciliary compartment of the primary cilium in human-derived fibroblasts and RPE cells. Additionally, we show that EHBP1 localizes to the outer membrane of developing photoreceptors in mature retinal organoids. Dysfunction of INPP5E - either due to patient-specific mutations in fibroblasts or a CRISPR/Cas9 generated knock-out in retinal organoids - causes the localization of EHBP1 to be altered. This suggests that EHBP1 functions at the primary cilium and photoreceptors where it is regulated by INPP5E. This provides further insights into the disease pathogenesis of retinal ciliopathies caused by mutations in INPP5E, and suggests that EHBP1 might be a candidate protein for retinitis pigmentosa and retinal ciliopathies.

The Neoarchean Mentor anorthosite intrusive complex (MAIC) lies within the Wawa subprovince in northwestern Minnesota, in a region where the Wawa, Quetico, and Wabigoon subprovinces are juxtaposed in close proximity. Archean rocks are entirely concealed, and interpretations are developed from aeromagnetic, gravity, and borehole samples. The MAIC includes both anorthosite (dense, weakly magnetized) and oxide-rich gabbro (strongly magnetized) lithologies. Anorthosite is coarse-grained to megacrystic, intensely altered, and locally brecciated. Pervasive epidote alteration enhanced the density of the anorthosite via introduction of higher-density mineral assemblages, explaining why the MAIC produces a significant gravity high. Oxide-rich gabbro forms a border phase of the MAIC and has potential for vanadium, chromium, and titanium mineralization, and produces a strong aeromagnetic high. The MAIC is interpreted to extend over an area of 640 km2, making it the largest known anorthosite complex of the Superior Province, as measured by preserved areal extent. Modeling indicates the MAIC extends more than 6 km into the subsurface. A new Pb-Pb zircon age of 2737.2 ± 4.5 Ma is interpretated as the crystallization age of anorthosite within the MAIC, showing that the MAIC formed well before the ca. 2690 Ma Shebandowanian orogeny, and raising new questions about correlations with other parts of the Wawa subprovince. A low-density batholith, here informally called the Fertile batholith, is interpreted to intrude the southern part of the MAIC. A new Pb-Pb zircon age of 2701.1 ± 6 Ma is interpreted as the magmatic age of the Fertile batholith.