Calponin-homology domain of GAS2L1 promotes formation of stress fibers and focal adhesions.

Growth arrest-specific 2-like 1 protein (GAS2L1) binds both actin and microtubules through its unique structural domains: a calponin-homology (CH) domain for actin binding and a GAS2-related (GAR) domain for microtubule interaction. In this study, we demonstrate that GAS2L1 promotes stress fiber assembly, enhances focal adhesion formation, and stabilizes cytoskeletal networks against mechanical perturbation through its CH domain. Remarkably, we show that the CH domain dimerizes and induces actin filament bundling and stabilization both in cells and in vitro.

A Flipped Classroom Model to Enhance Simulation Education for Percutaneous Renal Surgery.

Introduction: The limitations of lectures are magnified when teaching technical skills. A "flipped classroom" (FC) model allows learners to first review material and replaces lectures with active teacher-learner engagement. FC has been shown to improve knowledge retention, but its impact on skill acquisition is unknown.

Ethnic density and first episode psychosis in the British Pakistani population: findings from the East Lancashire Early Intervention Service.

Background: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups.

Aims: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire.

Initial Experience and Clinical Assessment of the Karl Storz FLEX-XC1 Single-Use Flexible Ureteroscope.

Introduction: The Karl Storz FLEX-XC1 is a novel single-use flexible ureteroscope that uses the same videographics platform as its reusable digital counterpart. We evaluated the technical performance of the FLEX-XC1 in its initial clinical use.

Methods: We reviewed a series of consecutive ureteroscopy procedures performed by 2 endourologists using the FLEX-XC1 for indications for which we typically use a single-use device: total stone burden > 15 mm or > 10 mm in the lower pole, anticipated case duration > 60 minutes, bilateral procedure, or upper tract urothelial cancer procedures.

Developmental Outcomes for Children With Unoperated Metopic or Sagittal Craniosynostosis: Findings at 3 and 7 Years From the Craniofacial Collaboration UK.

The Craniofacial Collaboration UK (CC-UK) is a shared initiative with the aim of addressing key limitations in the existing literature and examining the development of homogenous samples of children with craniosynostosis. This article preliminarily describes developmental, behavioral, and cognitive outcomes for children with either metopic synostosis (MS) or sagittal synostosis (SS), who were unoperated and managed conservatively under the CC-UK protocol. A total of 112 patients were included, and assessments conducted at 3 and/or 7 years of age are presented.

Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex.

The γ-tubulin ring complex (γTuRC) is the principal nucleator of cellular microtubules, and the microtubule-nucleating activity of the complex is stimulated by binding to the γTuRC-mediated nucleation activator (γTuNA) motif. The γTuNA is part of the centrosomin motif 1 (CM1), which is widely found in γTuRC stimulators, including CDK5RAP2. Here, we show that a conserved segment within CM1 binds to the γTuNA and blocks its association with γTuRCs; therefore, we refer to this segment as the γTuNA inhibitor (γTuNA-In).

Apicosome: Newly identified cell-type-specific organelle in mouse cochlear and vestibular hair cells.

Cochlear and vestibular hair cells are highly specialized sensory receptors for hearing and balance. Here, we report a serendipitous identification of a hair-cell-specific organelle in neonatal mouse inner ear, which we name "apicosome." The apicosome is ∼500 nm in diameter and shows itinerant nature and transient appearance during development in cochlear hair cells.

Understanding the identity of lived experience researchers and providers: a conceptual framework and systematic narrative review.

Background: Identity is how we understand ourselves and others through the roles or social groups we occupy. This review focuses on lived experience researchers and providers and the impact of these roles on identity. Lived experience researchers and providers use their lived experience of mental or physical disability either as experts by experience, researchers, peer workers, or mental health professionals with lived experience.

THY1 (CD90) Maintains the Adherens Junctions in Nasopharyngeal Carcinoma via Inhibition of SRC Activation.

We had previously shown that THY1 (CD90) is a tumor suppressor in nasopharyngeal carcinoma (NPC) and that its down-regulation and loss of expression are associated with tumor metastasis, yet the mechanism leading to such effects remains unknown. In this study we show that tumor invasion could be suppressed by THY1 via adherens junction formation in a few NPC cell lines, and knockdown of THY1 would disrupt this cell-cell adhesion phenotype. Mechanistically, the activity of the SRC family kinase (SFK) member, SRC, and canonical Wnt signaling were dramatically reduced when THY1 was constitutively expressed.

CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma.

In oral squamous cell carcinoma (OSCC), a highly aggressive and frequently lethal malignancy, the role and action mechanism of the microtubule regulatory protein CDK5RAP2 have not been fully understood. Here, we show that CDK5RAP2 is highly expressed in OSCC and its expression correlates with clinical stage and lymph node metastasis of the disease. The expression of CDK5RAP2 is regulated by the Wnt signaling pathway.

Detection and Analysis of Microtubule Nucleator γ-Tubulin Ring Complex.

Golgi-derived microtubules constitute an asymmetrical microtubule network that drives polarized transport of vesicles to support cell polarization and directional migration. Golgi-based microtubule nucleation requires the γ-tubulin ring complex (γTuRC), the principal microtubule nucleator in animal cells. In this chapter, we present methods for detecting γTuRC components and associated proteins on the Golgi, examining Golgi-based microtubule nucleation, and measuring the microtubule-nucleating activity of isolated γTuRCs.

Protocol to measure inter-centrosome distance in adherent cells using epifluorescence microscopy.

We present here a protocol to assay the centrosome separation events at late-G2 phase of the cell cycle by immunofluorescence microscopy. We describe the steps required for imaging and measurement of inter-centrosome distance. Here, we use GAS2L1 as an example, but the protocol can be used to test any protein for a role in centrosome separation and cohesion.

Comparison of Different Pulse Modulation Modes for Holmium:Yttrium-Aluminum-Garnet Laser Lithotripsy Ablation in a Benchtop Model.

Manipulation of Holmium:Yttrium-Aluminum-Garnet laser parameters such as pulse energy (PE), frequency, and duration can impact laser lithotripsy ablation efficiency. In 2017, Lumenis introduced Moses™ Technology, which uses pulse modulation to enhance the delivery of energy from fiber to stone as well as to minimize stone retropulsion. Since the introduction of Moses Technology, other companies have brought additional pulse modulation concepts to market.

Proteolysis of γ-tubulin small complex proteins is mediated by the ubiquitin-proteasome system.

Microtubule nucleation is mainly mediated by the γ-tubulin ring complex (γTuRC), whose core components are γ-tubulin and γ-tubulin complex proteins GCP2-6. A substantial fraction of γ-tubulin also exists with GCP2 and GCP3 in a tetramer called the γ-tubulin small complex (γTuSC). To date, the mechanisms underlying the turnover of γ-tubulin and GCPs have remained unclear.

The Role of Cavitation in Energy Delivery and Stone Damage During Laser Lithotripsy.

Although cavitation during laser lithotripsy (LL) contributes to the Moses effect, the impact of cavitation on stone damage is less clear. Using different laser settings, we investigate the role of cavitation bubbles in energy delivery and stone damage. The role of cavitation in laser energy delivery was characterized by using photodetector measurements synced with high-speed imaging for laser pulses of varying durations.

Benchtop Assessment of a New Single-Use Flexible Ureteroscope.

Single-use flexible ureteroscopes are an increasingly popular alternative to reusable ureteroscopes. In this study, we performed a benchtop examination of the physical and optical properties of the new Dornier Axis™ (Webling, Germany) single-use ureteroscope. Ten new, never-used Dornier Axis ureteroscopes were assessed for optical performance, maximal tip deflection, and irrigation flow rate with an empty working channel and with insertion of 200 and 365 μm laser fibers, and a 1.

Nek2-mediated GAS2L1 phosphorylation and centrosome-linker disassembly induce centrosome disjunction.

Centrosome disjunction occurs in late G2 to facilitate bipolar spindle formation and is mediated by the NIMA-related kinase Nek2. Here, we show that GAS2L1, a microtubule- and F-actin-binding protein required for centrosome disjunction, undergoes Nek2-mediated phosphorylation at Ser352 in G2/M. The phosphorylation is essential for centrosome disjunction in late G2 and for proper spindle assembly and faithful chromosome segregation in mitosis.

Cytolinker Gas2L1 regulates axon morphology through microtubule-modulated actin stabilization.

Crosstalk between the actin and microtubule cytoskeletons underlies cellular morphogenesis. Interactions between actin filaments and microtubules are particularly important for establishing the complex polarized morphology of neurons. Here, we characterized the neuronal function of growth arrest-specific 2-like 1 (Gas2L1), a protein that can directly bind to actin, microtubules and microtubule plus-end-tracking end binding proteins.

Sexual minority status and symptoms of psychosis: The role of bullying, discrimination, social support, and drug use - Findings from the Adult Psychiatric Morbidity Survey 2007.

Objective: Sexual minorities have an increased risk of psychosis, potentially explained by experiences of social adversity. Sexual minorities may also have a specific risk of paranoid symptoms. The current study aimed to determine whether sexual minorities have increased risk of psychosis, whether they have a specific increased risk of paranoia when compared to auditory verbal hallucinations (AVHs), and whether social adversity such as bullying, recent discrimination, lack of social support, and drug use can explain this risk.

The catalytic subunit of DNA polymerase δ is a nucleocytoplasmic shuttling protein.

The DNA polymerase δ catalytic subunit (PolD1) is a highly conserved protein with established functions in both the nucleus and the cytoplasm: whereas PolD1 participates in the replication and repair of nuclear DNA, it plays a role in the control of cytoplasmic microtubule growth by directly acting on microtubule-nucleator γ-tubulin ring complexes. Here, we show that PolD1 shuttles between the nucleus and the cytoplasm. PolD1 harbors two nuclear localization signals that mediate the active transport of PolD1 to the nucleus; conversely, PolD1 is exported from the nucleus by the exportin CRM1-dependent mechanism, a major nuclear-export pathway that mediates the export of various cargos.

A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission.

Endoplasmic reticulum (ER) membrane contact sites (MCSs) mark positions where endosomes undergo fission for cargo sorting. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to cargo-sorting domains on endosome buds. This strategy identified the ER membrane protein TMCC1, a member of a conserved protein family.

Most Gleason 8 Biopsies are Downgraded at Prostatectomy-Does 4 + 4 = 7?

Purpose: Nonrepresentative biopsy sampling of prostate cancers with a biopsy Gleason score of 8 can adversely influence decisions regarding androgen deprivation in men receiving primary radiation therapy. The frequency of and factors associated with downgrading Gleason 8 biopsies at prostatectomy are not well known.

Materials And Methods: We used records from NCDB (National Cancer Database), a hospital based registry in the United States, of 72,556 men with prostate cancer diagnosed from 2010 to 2013, including 5,474 with Gleason 8 biopsies and no other high progression risk criteria according to NCCN (National Comprehensive Cancer Network®) Guidelines®.

Over half of contemporary clinical Gleason 8 on prostate biopsy are downgraded at radical prostatectomy.

Introduction: Contemporary clinical guidelines utilize the highest Gleason sum (HGS) in any one core on prostate biopsy to determine prostate cancer treatment. Here, we present a large discrepancy between prostate cancer risk stratified as high risk on biopsy and their pathology after radical prostatectomy.

Materials And Methods: We retrospectively reviewed 1424 men who underwent either open or robotic-assisted prostatectomy between 2004 and 2015.