Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity:combined application of atomic force microscopy and modulated Raman spectroscopy

Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM–Raman combined methodologies for cancer profiling and screening with translational significance

The integration of on-line monitoring and reconfiguration functions using IEEE1149.4 into a safety critical automotive electronic control unit.

This paper presents an innovative application of IEEE 1149.4 and the integrated diagnostic reconfiguration (IDR) as tools for the implementation of an embedded test solution for an automotive electronic control unit, implemented as a fully integrated mixed signal system. The paper describes how the test architecture can be used for fault avoidance with results from a hardware prototype presented. The paper concludes that fault avoidance can be integrated into mixed signal electronic systems to handle key failure modes

Identifying car ingress movement strategies before and after total knee replacement

Background: Post-operative performance of knee bearings is typically assessed in activities of daily living by means of motion capture. Biomechanical studies predominantly explore common tasks such as walking, standing and stair climbing, while overlooking equally demanding activities such as embarking a vehicle. Aims: The aim of this work is to evaluate changes in the movement habits of patients after total knee arthroplasty surgery in comparison to healthy age-matched control participants. Methods: A mock-up car was fabricated based on the architecture of a common vehicle. Ten control participants and 10 patients with severe osteoarthritis of the knee attended a single- and three-motion capture session(s), respectively. Participants were asked to enter the car and sit comfortably adopting a driving position. Three trials per session were used for the identification of movement strategies by means of hierarchical clustering. Task completion time was also measured. Results: Patients’ movement behaviour didn’t change significantly following total knee arthroplasty surgery. Control participants favoured different movement strategies compared to patients post-operatively. Group membership, height and sidedness of the affected joint were found to be non-significant in task completion time. Conclusion: This study describes an alternative movement identification technique for the analysis of the ingress movement that may be used to clinically assess knee bearings and aid in movement simulations and vehicle design

Spoken word recognition in adolescents with autism spectrum disorders and specific language impairment

Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied in frequency (low/high) and number of phonological onset neighbors (low/high density). Adolescents with ALI required more speech input to initially identify low-frequency words with low competitor density than those with SLI and those with TLD, who did not differ. These differences may be due to less well specified word form representations in ALI

Implant Design Affects Walking and Stair Navigation after Total Knee Arthroplasty:a double-blinded randomised controlled trial

Background: Dissimilar total knee arthroplasty implant designs offer different functional characteristics. This is the first work in the literature to fully assess the Columbus ultra-congruent mobile (UCR) system with a rotating platform. Methods: This is a double-blinded randomised controlled trial, comparing the functional performance of the low congruent fixed (CR DD), ultra-congruent fixed (UC) and UCR Columbus Total Knee Systems. The pre-operative and post-operative functional performance of twenty-four osteoarthritic patients was evaluated against nine control participants when carrying out everyday tasks. Spatiotemporal, kinematic and kinetic gait parameters in walking and stair navigation were extracted by means of motion capture. Results: The UC implant provided better post-operative function, closely followed by the UCR design. However, both the UC and UCR groups exhibited restricted post-operative sagittal RoM (walking, 52.1 ± 4.4° and 53.2 ± 6.6°, respectively), whilst patients receiving a UCR implant did not show an improvement in their tibiofemoral axial rotation despite the bearing’s mobile design (walking, CR DD 13.2 ± 4.6°, UC 15.3 ± 6.7°, UCR 13.5 ± 5.4°). Patients with a CR DD fixed bearing showed a statistically significant post-operative improvement in their sagittal RoM when walking (56.8 ± 4.6°). Conclusion: It was concluded that both ultra-congruent designs in this study, the UC and UCR bearings, showed comparable functional performance and improvement after TKA surgery. The CR DD group showed the most prominent improvement in the sagittal RoM during walking. Trial registration: The study is registered under the clinical trial registration number: NCT02422251. Registered on April 21, 2015

KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction

Funding: This work was supported by Action Medical Research/ The Chief Scientist (CSO) Office, Scotland [GN 2614], Royal Society [RG160373], Carnegie Trust [50341], Wellcome Trust ISSF grant 105621/Z/14/Z, and RS Macdonald Charitable Trust grants to SP and Engineering and Physical Sciences Research Council [EP/P030017/1], Biotechnology and Biological Sciences Research Council [BB/P027148/1], and the European Research Council Starting Grant ABLASE [640012] grants to MCG. SP is a Royal Society University Research Fellow.Following its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood. We developed the first human cellular knockout model for KIAA0319 in RPE1 retinal pigment epithelia cells via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We observed in the KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that RPE1 cells exert highly dynamic, piconewton vertical pushing forces through actin-rich protrusions that are surrounded by vinculin-rich pulling sites. This protein arrangement and force pattern has previously been associated to podosomes in other cells. KIAA0319 depletion reduces the fraction of cells forming these actin-rich protrusions. Our results suggest an involvement of KIAA0319 in cilia biology and cell–substrate force regulation.Publisher PDFPeer reviewe

Hermit crabs (<i>Pagurus bernhardus</i>) use visual contrast in self- assessment of camouflage

Animals can make use of camouflage to reduce the likelihood of visual detection or recognition and thus improve their chances of survival. Background matching, where body colouration is closely matched to the surrounding substrate, is one form of camouflage. Hermit crabs have the opportunity to choose their camouflage independently of body colouration as they inhabit empty gastropod shells, making them ideal to study their choice of camouflage. We used 3D-printed artificial shells of varying contrasts against a grey substrate to test whether hermit crabs prefer shells that they perceive as less conspicuous. Contrast-minimising shells were chosen for Weber contrasts stronger than −0.5. However, in looming experiments, animals responded to contrasts as weak as −0.2, indicating that while they can detect differences between shells and the background, they are only motivated to move into those shells when the alternatives contrast strongly. This suggests a trade-off between camouflage and vulnerability introduced by switching shells

Advances in the use of virtual reality to treat mental health conditions

Virtual reality (VR) has emerged as a promising tool in the field of mental health. Central to this technology are immersive environments, which enable exposure to highly controlled virtual experiences that feel real. In this Review, we elaborate on the active elements of immersive experiences and how VR-based treatments work. We provide an overview of developments in the use of VR to treat mental health conditions (anxiety, psychotic symptoms, post-traumatic stress, eating disorders, depression and stress management) with a focus on the core mechanisms that drive effective interventions. Artificial intelligence, biofeedback and gamification are emerging areas of development, and we discuss how they might enhance the accessibility, engagement and effectiveness of psychological treatments. Conducting rigorous studies with user-centred designs in diverse populations is a key research priority. As the use of VR in mental health continues to evolve, addressing ethical and implementation considerations is critical for ensuring ongoing treatment improvements.</p

Defining the miRnome of Saphenous Vein Smooth Muscle Cells from Patients with Type 2 Diabetes Mellitus

Citation: Hussain, A.; Asare-Amankwah, Y.; Qureshi, S.; Thornton, M.J.; Palmer, T.M.; Bolanle, I.O.; Wood, I.C.; Turner, N.A.; Porter, K.E.; Tedder, A.; et al. Defining the miRnome of Saphenous Vein Smooth Muscle Cells from Patients with Type 2 Diabetes Mellitus. Diabetology 2024, 5, 178-189. https://doi. Abstract: Type 2 diabetes mellitus (T2DM) patients suffer premature development of cardiovascular disease and commonly require cardiac revascularization using the autologous saphenous vein (SV). Smooth muscle cells (SMCs) are the principal cell type within the vascular wall and are dysfunctional in T2DM SV-SMCs, yet the mechanisms underpinning this are incompletely understood. The purpose of this study was to interrogate differential microRNA (miRNA) expression in SV-SMCs to enhance our understanding of T2DM SV-SMC phenotypic change. miRNA expression in primary human SV-SMCs from T2DM and non-diabetic (ND) donors was determined using an array (n = 6 each of ND and T2DM SV-SMCs). Differentially expressed miRNAs were ranked, and functional annotation of the 30 most differentially expressed miRNAs using DAVID and KEGG analysis revealed pathways related to SMC phenotype, including proliferation, migration, cytokine production and cell signaling. After selecting miRNAs known to be involved in SMC phenotypic regulation, miR-17, miR-29b-2, miR-31, miR-130b and miR-491 were further validated using qRT-PCR (n = 5 each of ND and T2DM SV-SMC), with miR-29b-2 subsequently being removed from further investigation. Potential mRNA targets were identified using mirDIP. Predicted target analysis highlighted likely dysregulation in transcription, epigenetic regulation, cell survival, intracellular signaling and cytoskeletal regulation, all of which are known to be dysfunctional in T2DM SV-SMCs. In conclusion, this paper identified four miRNAs that are dysregulated in T2DM SV-SMCs and are implicated in functional changes in the behavior of these cells. This provides a step forward in our understanding of the molecular and epigenetic regulation of vascular dysfunction in T2DM