A Myosin Nanomotor Essential for Stereocilia Maintenance Expands the Etiology of Hereditary Hearing Loss DFNB3.

Cochlear hair cells transduce sound using stereocilia, and disruption to these delicate mechanosensors is a significant cause of hearing loss. Stereocilia architecture is dependent upon the nanomotor myosin 15. A short isoform (MYO15A-2) drives stereocilia development by delivering an elongation-promoting complex (EC) to stereocilia tips, and an alternatively spliced long isoform (MYO15A-1) tunes postnatal size in shorter stereocilia, which possess mechanosensitive ion channels.

The risk of complications after hip fracture.

Aims: The risk of mortality after a hip fracture has been extensively investigated, but there is little high-quality information available dealing with the overall risk of complications. The aim of this study was to report the risk of complications in the first 120 days after a hip fracture.

Methods: This was a multicentre, prospective cohort study of patients aged > 60 years with a hip fracture, involving 77 hospitals in England, Wales, and Northern Ireland, between January 2015 and 2022.

A mutation in Tmem135 causes progressive sensorineural hearing loss.

Transmembrane protein 135 (TMEM135) is a highly conserved 52 kDa protein with five predicted transmembrane domains that colocalizes with mitochondria and peroxisomes. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism across multiple tissues and species; however, its role in the inner ear and auditory system remains unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 (FUN025) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain.

Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing.

Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism.

Unconventional Anomalous Hall Effect Driven by Self-Intercalation in Covalent 2D Magnet CrTe.

Covalent 2D magnets such as CrTe, which feature self-intercalated magnetic cations located between monolayers of transition-metal dichalcogenide material, offer a unique platform for controlling magnetic order and spin texture, enabling new potential applications for spintronic devices. Here, it is demonstrated that the unconventional anomalous Hall effect (AHE) in CrTe, characterized by additional humps and dips near the coercive field in AHE hysteresis, originates from an intrinsic mechanism dictated by the self-intercalation. This mechanism is distinctly different from previously proposed mechanisms such as topological Hall effect, or two-channel AHE arising from spatial inhomogeneities.

No differences between remote and laboratory-based testing of cardiac interoceptive accuracy using the phase adjustment task.

In recent years, there has been an increased interest in remote testing methods for quantifying individual differences in interoception, the perception of the body's internal state. Hampering the adoption of remote methods are concerns as to the quality of data obtained remotely. Using data from several studies, we sought to compare the performance of individuals who completed the Phase Adjustment Task-a new measure of cardiac interoceptive accuracy that can be administered via a smartphone application-supervised in a laboratory against those who completed the task remotely.

Exploring sex differences in cardiac interoceptive accuracy using the phase adjustment task.

Previous evidence suggests males and females differ with respect to interoception-the processing of internal bodily signals-with males typically outperforming females on tasks of interoceptive accuracy. However, interpretation of existing evidence in the cardiac domain is hindered by the limitations of existing tools. In this investigation, we pooled data from several samples to examine sex differences in cardiac interoceptive accuracy on the phase adjustment task, a new measure that overcomes several limitations of the existing tools.

A Mutation in Causes Progressive Sensorineural Hearing Loss.

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and ( ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain.

An optimized approach to study nanoscale sarcomere structure utilizing super-resolution microscopy with nanobodies.

The sarcomere is the fundamental contractile unit in skeletal muscle, and the regularity of its structure is critical for function. Emerging data demonstrates that nanoscale changes to the regularity of sarcomere structure can affect the overall function of the protein dense ~2μm sarcomere. Further, sarcomere structure is implicated in many clinical conditions of muscle weakness.

Large-scale annotated dataset for cochlear hair cell detection and classification.

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment.

Heightened interoception in adults with fibromyalgia.

Previous research suggests that the processing of internal body sensations (interoception) affects how we experience pain. Some evidence suggests that people with fibromyalgia syndrome (FMS) - a condition characterised by chronic pain and fatigue - may have altered interoceptive processing. However, extant findings are inconclusive, and some tasks previously used to measure interoception are of questionable validity.

Predictors of mortality in periprosthetic fractures of the hip: Results from the national PPF study.

Introduction: Periprosthetic fractures (PPFs) around the hip joint are increasing in prevalence. In this collaborative study, we aimed to investigate the impact of patient demographics, fracture characteristics, and modes of management on in-hospital mortality of PPFs involving the hip.

Methods: Using a multi-centre cohort study design, we retrospectively identified adults presenting with a PPF around the hip over a 10-year period.

Dynamic mechanisms of exercise to improve body satisfaction: Perceived or actual fat loss?

We examined the dynamic mechanisms of aerobic training (AT) and strength training (ST) to improve body satisfaction. Sixty-six participants were randomised to either the AT or ST condition and completed an 8-week intervention. Participants completed 3 weekly, 30-minute sessions of moderate intensity AT (65-75% VO max) or ST (65-75% 1-RM).

Large-scale annotated dataset for cochlear hair cell detection and classification.

Our sense of hearing is mediated by cochlear hair cells, localized within the sensory epithelium called the organ of Corti. There are two types of hair cells in the cochlea, which are organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains a few thousands of hair cells, and their survival is essential for our perception of sound because they are terminally differentiated and do not regenerate after insult.

The actin cytoskeleton in hair bundle development and hearing loss.

Inner ear hair cells assemble mechanosensitive hair bundles on their apical surface that transduce sounds and accelerations. Each hair bundle is comprised of ∼ 100 individual stereocilia that are arranged into rows of increasing height and width; their specific and precise architecture being necessary for mechanoelectrical transduction (MET). The actin cytoskeleton is fundamental to establishing this architecture, not only by forming the structural scaffold shaping each stereocilium, but also by composing rootlets and the cuticular plate that together provide a stable foundation supporting each stereocilium.

Correlated insulator collapse due to quantum avalanche via in-gap ladder states.

The significant discrepancy observed between the predicted and experimental switching fields in correlated insulators under a DC electric field far-from-equilibrium necessitates a reevaluation of current microscopic understanding. Here we show that an electron avalanche can occur in the bulk limit of such insulators at arbitrarily small electric field by introducing a generic model of electrons coupled to an inelastic medium of phonons. The quantum avalanche arises by the generation of a ladder of in-gap states, created by a multi-phonon emission process.

Signatures of hot carriers and hot phonons in the re-entrant metallic and semiconducting states of Moiré-gapped graphene.

Stacking of graphene with hexagonal boron nitride (h-BN) can dramatically modify its bands from their usual linear form, opening a series of narrow minigaps that are separated by wider minibands. While the resulting spectrum offers strong potential for use in functional (opto)electronic devices, a proper understanding of the dynamics of hot carriers in these bands is a prerequisite for such applications. In this work, we therefore apply a strategy of rapid electrical pulsing to drive carriers in graphene/h-BN heterostructures deep into the dissipative limit of strong electron-phonon coupling.

Myosin motors in sensory hair bundle assembly.

Mechanosensory hair bundles are assembled from actin-based stereocilia that project from the apical surface of hair cells in the inner ear. Stereocilia architecture is critical for the transduction of sound and accelerations, and structural defects in these mechano-sensors are a clinical cause of hearing and balance disorders in humans. Unconventional myosin motors are central to the assembly and shaping of stereocilia architecture.

Self-Forming p-n Junction Diode Realized with WSe Surface and Edge Dual Contacts.

Owing to their practical applications, two-dimensional semiconductor p-n diodes have attracted enormous attention. Over the past decade, various methods, such as chemical doping, heterojunction structures, and metallization using metals with different work functions, have been reported for fabrication of such devices. In this study, a lateral p-n junction diode is formed in tungsten diselenide (WSe ) using a combination of edge and surface contacts.

Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia.

The motor protein myosin-15 is necessary for the development and maintenance of mechanosensory stereocilia, and mutations in myosin-15 cause hereditary deafness. In addition to transporting actin regulatory machinery to stereocilia tips, myosin-15 directly nucleates actin filament ("F-actin") assembly, which is disrupted by a progressive hearing loss mutation (p.D1647G, "").