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We propose that the apoptotic function of p53 has an important role in B-cell homeostasis, which is important for the prevention of B-cell lymphomas. We created a mouse model (mΔpro) that lacked residues 58–88 of the proline-rich domain of p53. mΔpro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. mΔpro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, mΔpro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in mΔpro before tumor onset, in which aged mice showed an increased population of inappropriately differentiated B cells in the bone marrow and spleen. We predict that by keeping B-cell populations in check, p53-dependent apoptosis prevents irregular B cells from eventuating in lymphomas. [ABSTRACT FROM AUTHOR]

The clinical importance of assessing and combining data on TP53 mutations and isoforms is discussed in this article. It gives a succinct overview of the structural makeup and key biological roles of the isoforms. It then provides a comprehensive summary of the roles that p53 isoforms play in cancer development, therapy response and resistance. The review provides a summary of studies demonstrating the role of p53 isoforms as potential prognostic indicators. It further provides evidence on how the presence of TP53 mutations may affect one or more of these activities and the association of p53 isoforms with clinicopathological data in various tumour types. The review gives insight into the present diagnostic hurdles for identifying TP53 isoforms and makes recommendations to improve their evaluation. In conclusion, this review offers suggestions for enhancing the identification and integration of TP53 isoforms in conjunction with mutation data within the clinical context., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: This pilot study aimed to develop a methodology characterising the urogenital microbiome as a predictive test in the IVF workup., Methods: Using unique custom qPCRs, we tested for the presence of specific microbial species from vaginal samples and First Catch Urines from the male. The test panel included a range of potential urogenital pathogens, STIs, 'favourable bacteria' (Lactobacillus spp.) and 'unfavourable bacteria' (anaerobes) reported to influence implantation rates. We tested couples attending Fertility Associates, Christchurch, New Zealand for their first round of IVF., Results: We found that some microbial species affected implantation. The qPCR result was interpreted qualitatively using the Z proportionality test. Samples from women at the time of Embryo Transfer who did not achieve implantation had significantly higher percent of samples that were positive for Prevotella bivia and Staphylococcus aureus compared to women who did achieve implantation., Discussion: The results provide evidence that most other microbial species chosen for testing had little functional effect on implantation rates. The addition of further microbial targets (yet to be determined) could be combined in this predictive test for vaginal preparedness on the day of embryo transfer. This methodology has a substantial advantage of being affordable and easily performed in any routine molecular laboratory. This methodology is most suitable as a foundation on which to develop a timely test of microbiome profiling. Using the indicators detected to have a significant influence, these results can be extrapolated., Conclusion: Using a rapid antigen test, a woman can self-sample prior to embryo transfer and obtain an indication of microbial species present which could influence implantation outcome., (© 2023. The Author(s).)

Surface to hand transfer of viruses represents a potential mechanism for human exposure. An experimental process for evaluating the touch transfer of aerosol-deposited material is described based on controlling surface, tribological, and soft matter components of the transfer process. A range of high-touch surfaces were evaluated. Under standardized touch parameters (15 N, 1 s), relative humidity (RH) of the atmosphere around the contact transfer event significantly influenced transfer of material to the finger-pad. At RH < 40%, transfer from all surfaces was <10%. Transfer efficiency increased markedly as RH increased, reaching a maximum of approximately 50%. The quantity of material transferred at specific RHs above 40% was also dependent on roughness of the surface material and the properties of the aerosol-deposited material. Smooth surfaces, such as melamine and stainless steel, generated higher transfer efficiencies compared to those with textured roughness, such as ABS pinseal and KYDEX® plastics. Pooled human saliva was transferred at a lower rate compared to artificial saliva, indicating the role of rheological properties. The artificial saliva data were modeled by non-linear regression and the impact of environmental humidity and temperature were evaluated within a Quantitative Microbial Risk Assessment model using SARS-CoV-2 as an example. This illustrated that the trade-off between transfer efficiency and virus survival may lead to the highest risks of fomite transmissions in indoor environments with higher humidity.

All living organisms have developed processes to sense and address environmental changes to maintain a stable internal state (homeostasis). When activated, the p53 tumour suppressor maintains cell and organ integrity and functions in response to homeostasis disruptors (stresses) such as infection, metabolic alterations and cellular damage. Thus, p53 plays a fundamental physiological role in maintaining organismal homeostasis. The TP53 gene encodes a network of proteins (p53 isoforms) with similar and distinct biochemical functions. The p53 network carries out multiple biological activities enabling cooperation between individual cells required for long-term survival of multicellular organisms (animals) in response to an ever-changing environment caused by mutation, infection, metabolic alteration or damage. In this review, we suggest that the p53 network has evolved as an adaptive response to pathogen infections and other environmental selection pressures., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion., (© 2021. The Author(s).)

Every autumn rail networks across the world suffer delays, accidents and schedule changes due to low friction problems caused by leaves landing on the rails. These leaves form a layer that can reduce the friction between the wheel and the rail to a similar level as that between ice and an ice-skate ( μ = 0.01 - 0.05 ). Previous works have generated several hypotheses for the chemical reactions and low friction mechanism associated with these layers. In this work, the reaction between an aqueous extract of sycamore leaves and metallic iron is investigated. This reaction has been shown to produce a black precipitate, which matches field observations of leaf layers, while friction tests with these extracts produce characteristic ultra low friction. The reaction is investigated through FTIR, XPS, CHNS and ICP-MS analysis as well as wet chemical testing. The impact of the reaction on friction is investigated through three rounds of tribological testing. The results indicate that the black precipitate produced is iron tannate, formed by complexation of tannins with dissolved iron ions. Friction testing showed that eliminating tannins from the leaf extract resulted in a significant increase in the friction coefficient compared with the control., Competing Interests: We declare we have no competing interests., (© 2020 The Author(s).)

Due to their design, hollow cavity and filled sodium, hollow head and sodium filled engine valves (HHSVs) have superior performance to traditional solid valves in terms of mass and temperature reduction. This paper presents a new manufacturing method for 42Cr9Si2 steel hollow head and sodium filled valves. An inertia friction welding process parameter optimization was conducted to obtain a suitable process parameter range. The fatigue strength of 42Cr9Si2 steel at elevated temperatures was evaluated by rotating bending fatigue test with material specimens. Performance evaluation tests for real valve components were then carried out using a bespoke bench-top apparatus, as well as a stress evaluation utilizing a finite element method. It was proved that the optimized friction welding parameters of HHSV can achieve good welding quality and performance, and the HHSV specimen successfully survived defined durability tests proving the viability of this new method. The wear resistance of the HHSV specimens was evaluated and the corresponding wear mechanisms were found to be those classically defined in automotive valve wear.

This data article presents data on machining trials that were carried out using 0.5 mm micro-end-mills with different coatings to characterize their wear. The data take the following forms: Tabulated wear measurements, cutting force measurements and graphs of wear against sliding distance. Three materials were machined: titanium grade 2, Hastelloy and Brass (CuZn37). Wear is measured on the flank, rake face and outside edge of the tools. Two coatings were used for each material, with wear data plotted for each material. For further information on experimental methods please refer to "Protocol for Tool Wear Measurement in Micro-milling" (Alhadeff et al., 2018).

Background and Purpose: In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages., Materials and Methods: Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features., Results: Tumors with a regular margin and those lacking a fungating margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more frequent in the subgroup of ALT+/M- ( P < .05). Radiologic necrosis, lack of cystic component (by both criteria), and extensive peritumoral edema were more frequent in ALT-/M+ tumors ( P < .05). Multivariate testing with a Cox regression analysis found the cystic imaging feature was additive to tumor subtype, and O6-methylguanine methyltransferase ( MGMT ) status to predict improved patient survival ( P < .05)., Conclusions: Glioblastomas with tumor-associated macrophages are associated with routine MR imaging features consistent with these tumors being more aggressive. Inclusion of cystic change with molecular subtypes and MGMT status provided a better estimate of survival., (© 2018 by American Journal of Neuroradiology.)