Vasorin (VASN), a transmembrane protein heavily expressed in endothelial cells, has garnered recent interest due to its key role in vascular development and pathology. The oligomeric state of VASN is a crucial piece of knowledge given that receptor clustering is a frequent regulatory mechanism in downstream signaling activation and amplification. However, documentation of VASN oligomerization is currently absent. In this brief report, we describe the measurement of VASN oligomerization in its native membranous environment, leveraging a class of fluorescence fluctuation spectroscopy. Our investigation revealed that the majority of VASN resides in a monomeric state, while a minority of VASN forms homodimers in the cellular membrane. This result raises the intriguing possibility that ligand-independent clustering of VASN may play a role in transforming growth factor signaling.

Sound vibrations generate electrical signals called cochlear potentials, which can reflect cochlear stereocilia movement and outer hair cells (OHC) mechanical activity. However, because the cochlear structure is delicate and complex, it is difficult for existing measurement techniques to pinpoint the origin of potentials. This limitation in measurement capability makes it difficult to fully understand the contribution of stereocilia and transduction channels to cochlear potentials. In view of this, firstly, this article obtains the stereocilia movement generated by basilar membrane (BM) vibration based on the positional relationship between the various structures of the organ Corti. Secondly, Kirchhoff’s law is used to establish an electric field model of the cochlear cavity, and the stereocilia movement is embedded in the electric field by combining the gated spring model. Finally, a force-electric coupling mathematical model of the cochlea is established. The results indicated that the resistance variation between different cavities in the cochlea leads to a sharp tuning curve. As the displacement of the BM increased, the longitudinal potential along the cochlea continued to move toward the base. The decrease in stereocilia stiffness reduced the deflection angle, thereby reducing the transduction current and lymphatic potential.

While bilateral fitting of bone conduction hearing devices (BCHDs) enhances spatial hearing, further improvements are constrained by the unresolved effects of crosstalk – an influential factor that disrupts binaural acoustic cues, such as interaural level difference (ILD) and interaural phase differences (IPD), essential for accurate sound localization. This paper introduces a simplified theoretical model to describe the crosstalk phenomenon and predict the cochlear vibrational responses under bilateral bone conduction (BC) based on principles of wave interference and superposition. The model reveals sound lateralization patterns across different ILD and IPD combinations, different from well‐established principles governing air conduction (AC) sound localization, including the precedence effect and intensity rule. These predicted patterns are experimentally validated through cadaveric vibration measurements and are further corroborated in psychoacoustic sound lateralization tests conducted on healthy volunteers. The findings suggest that crosstalk induces wave interference in the skull and leads to the superposition of bilateral signals at the cochleae, resulting in these atypical lateralization patterns. This evidence highlights the inherent challenges of sound localization under BC compared to AC, identifying crosstalk‐induced wave interference as a primary obstacle to improved spatial hearing for bilateral BCHD users.

Due to ethical issues and the nature of the ear, it is difficult to directly perform experimental measurements on living body elements of the human ear. Therefore, a numerical model has been developed to effectively assess the effect of the replacement of artificial ossicles on hearing in the inner ear. A healthy volunteer’s right ear was scanned to obtain CT data, which were digitalized through the use of a self-compiling program and coalescent Patran-Nastran software to establish a 3D numerical model of the whole ear, and a frequency response of a healthy human ear was analyzed. The vibration characteristics of the basilar membrane (BM) after total ossicular replacement prosthesis (TORP) implantation were then analyzed. The results show that although the sound conduction function of the middle ear was restored after replacement of the TORP, the sensory sound function of the inner ear was affected. In the low frequency and medium frequency range, hearing loss was 5.2~10.7%. Meanwhile, in the middle–high frequency range, the replacement of a middle ear TORP in response to high sound pressure produced a high acoustic stimulation effect in the inner ear, making the inner ear structures susceptible to fatigue and more prone to fatigue damage compared to the structures in healthy individuals. This developed model is able to assess the effects of surgical operation on the entire hearing system.

Alzheimer’s disease is the most common form of dementia, characterized by the pathological accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Triggering receptor expressed on myeloid cells 2 (TREM2) is increasingly recognized as playing a central role in Aβ clearance and microglia activation in AD. The TREM2 gene transcriptional product is alternatively spliced to produce three different protein isoforms. The canonical TREM2 isoform binds to DAP12 to activate downstream pathways. However, little is known about the function or interaction partners of the alternative TREM2 isoforms. The present study utilized a computational approach in a systematic search for new interaction partners of the TREM2 isoforms by integrating several state-of-the-art structural bioinformatics tools from initial large-scale screening to one-on-one corroborative modeling and eventual all-atom visualization. CD9, a cell surface glycoprotein involved in cell–cell adhesion and migration, was identified as a new interaction partner for two TREM2 isoforms, and CALM, a calcium-binding protein involved in calcium signaling, was identified as an interaction partner for a third TREM2 isoform, highlighting the potential role of cell adhesion and calcium regulation in AD.

Background: Alzheimer’s disease (AD) hallmarks are amyloid plaques and tau tangles. APOE and TREM2 are the strongest genetic risk factors for AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is increasingly recognized to play a central role in amyloid beta clearance and microglia activation in AD. TREM2 has several described ligands, including amyloid beta, apoE and tau. It is known that canonical full‐length TREM2 interacts with DAP12 which in turn activates downstream pathways. One study describes TREM2 interaction with TMEM59 as a regulator TMEM59 protein degradation through cell membrane protein–protein interaction. Three TREM2 alternative splicing isoforms have been described. Little is known about protein–protein interactions with all of three of these TREM2 isoforms. The hypothesis of our study is that full‐length TREM2 and its alternative splicing isoforms interact with other undescribed proteins. The aim of this study was to perform a systematic computational search for new interactors of different TREM2 isoforms by employing several state‐of‐the‐art structural bioinformatics tools, from initial large‐scale screening to identify a one‐on‐one corroborative simulation and fine visualization.Method: ProteinPrompt software random forest method was used to scan mega libraries in the Homo sapien proteome to identify potential interactors of TREM2 isoforms. The top 5 predictions from ProteinPrompt were simulated in PEPPI, in order to verify the authenticity of the interactions. The TREM2 isoforms and their newfound interactors, identified by ProteinPrompt and validated by PEPPI, were then built into heterodimeric complex in AlphaFold Multimer.Results: CD9, a cell surface glycoprotein involved in cell‐cell adhesion and migration, was identified as a new interactor for two TREM2 isoforms. CALM, a calcium binding protein involved in calcium metabolism, was identified as a new interactor for a third TREM2 isoform.Conclusion: The predicted interaction of CD9 or CALM with TREM2 isoforms suggests a possible role of TREM2 in cell adhesion and calcium regulation. Both cell adhesion and calcium regulation are two biological systems previously implicated in Alzheimer’s disease.