A5073387001- Hereditary Neurological Disorders
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Neurological diseases and metabolism
- Signaling Pathways in Disease
- Sphingolipid Metabolism and Signaling
- Veterinary Orthopedics and Neurology
- Knee injuries and reconstruction techniques
- Blood Pressure and Hypertension Studies
- Cardiovascular and Diving-Related Complications
- Orthopedic Surgery and Rehabilitation
- Advanced Fluorescence Microscopy Techniques
- Cardiovascular Issues in Pregnancy
- Hippo pathway signaling and YAP/TAZ
- Reproductive System and Pregnancy
- Neuroscience and Neural Engineering
- Skin and Cellular Biology Research
- Cardiac tumors and thrombi
- Prenatal Screening and Diagnostics
- Lipid Membrane Structure and Behavior
- Cardiovascular Health and Disease Prevention
- Pleural and Pulmonary Diseases
- Advanced Electron Microscopy Techniques and Applications
University at Buffalo, State University of New York
2020-2024
University of Cambridge
2024
Royal Hobart Hospital
2024
University College London
2018-2021
National Hospital for Neurology and Neurosurgery
2018-2021
Jacobs Institute
2020-2021
Cancer Research UK
2014
Fluorescence microscopy of GFP-tagged proteins is a fundamental tool in cell biology, but without seeing the structure surrounding cellular space, functional information can be lost. Here we present protocol that preserves GFP and mCherry fluorescence mammalian cells embedded resin with electron contrast to reveal ultrastructure. Ultrathin in-resin (IRF) sections were imaged simultaneously for signals an integrated light scanning microscope. We show, first time, stable active vacuo. applied...
Abstract In peripheral nerves, Schwann cells form myelin and provide trophic support to axons. We previously showed that the mitochondrial protein prohibitin 2 can localize axon-Schwann-cell interface is required for developmental myelination. Whether homologous 1 has a similar role, whether prohibitins also play important roles in cell mitochondria unknown. Here, we show deletion of minimally perturbs development, but later triggers severe demyelinating neuropathy. Moreover, are heavily...
Hereditary sensory neuropathy type 1 (HSN-1) is a peripheral most frequently caused by mutations in the SPTLC1 or SPTLC2 genes, which code for two subunits of enzyme serine palmitoyltransferase (SPT). SPT catalyzes first step de novo sphingolipid synthesis. Mutations result change substrate specificity, causes production atypical deoxysphinganine and deoxymethylsphinganine, rather than normal product, sphinganine. Levels these abnormal compounds are elevated blood HSN-1 patients this thought...
Osteoarthritis (OA) progresses in the canine cranial cruciate ligament (CCL) deficient stifle. Progression of OA is also documented patients after various surgical repair techniques for this injury. We evaluated radiographic arthritic changes stifle joints that have sustained a CCL injury, and compared scores between Tibial Plateau Leveling Osteotomy (TPLO)surgery receiving medial parapatellar exploratory arthrotomy remnant removal versus those limited caudal without remnants. Medial/lateral...
Our study evaluated thigh circumference (TC), stifle range of motion (ROM), and lameness in dogs one to five years after unilateral tibial plateau levelling osteotomy (TPLO). We hypothesised that TC, ROM, would not be different the unoperated limb (control), surgery. Patients were post-TPLO reviewed included if they had a TPLO, no additional clinical evidence orthopaedic disease. Standing mid-thigh TC measurements extension flexion angles made triplicate. Clinical was graded blindly. Data...
Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive causing profound deficits and often severe motor loss. L-serine supplementation possible candidate therapy but the lack of responsive outcome measures barrier for undertaking clinical trials in HSN1. We performed 12-month natural history study to characterise phenotype HSN1 identify measures.Assessments included Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), CMTNSv2-Rasch modified, nerve conduction studies,...
Significance Voltage-gated ion channels contain domains that have discrete functionalities. The central pore domain allows current flow and provides selectivity, whereas peripherally located voltage-sensing (VSDs) are needed for voltage-dependent gating. Certain mutations trigger a leak through VSDs, known as gating current. Hypokalemic periodic paralysis (HypoPP) type 2 is caused by in the skeletal muscle voltage-gated sodium channel Na V 1.4 neutralize positive charges S4 segments of VSDs....
Schwann cell (SC) mitochondria are quickly emerging as an important regulator of myelin maintenance in the peripheral nervous system (PNS). However, mechanisms underlying demyelination context mitochondrial dysfunction PNS incompletely understood. We recently showed that conditional ablation protein Prohibitin 1 (PHB1) SCs causes a severe and fast progressing demyelinating neuropathy mice, but mechanism failure remained unknown. Here, we report mTORC1 c-Jun continuously activated absence...
Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage subsequent degeneration. Studies utilizing genetic (CNPase-, MAG-, PLP-null mice) naturally occurring neuropathy models suggest that myelinating glia also support axons independently from myelin. protein zero (MPZ P0), which expressed only by Schwann cells, critical formation the peripheral nervous system. Many mutations MPZ...
Neural Crest cells (NC) are a multipotent cell population that give rise to multitude of types including Schwann (SC) in the peripheral nervous system (PNS). Immature SC interact with neuronal axons via neuregulin 1 (NRG1) ligand present on surface and ultimately form myelin sheath. Multiple attempts derive functional from pluripotent stem have met challenges respect expression mature markers axonal sorting. Here, they hypothesized sustained signaling immobilized NRG1 (iNRG1) might enhance...
The O2 dependence of mitochondrial cytochromes was studied in suspensions isolated rat kidney cells to examine the determinants renal function. Direct spectroscopy oxidation c + c1, a a3, and b561 b566 showed that oxidation-reduction changes entire electron transport chain occur over same range concentrations; this suggests function as single unit response changes. Half-maximal (P50 value) cytochrome c1 intact 3.6 microM but only 0.45 cortex mitochondria under state 3 conditions. This is...
Schwann cells are critical for the proper development and function of peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that pair proteins called prohibitins play major roles in cell biology. Prohibitins ubiquitously expressed versatile proteins. We previously shown while crucial role mitochondria long-term myelin maintenance axon health, may also be present at cell-axon interface during development. Here, we expand on...
Abstract Schwann cells are critical for the proper development and function of peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that pair proteins called prohibitins play major roles in cell biology. Prohibitins ubiquitously expressed versatile proteins. We have previously shown while crucial role mitochondria long‐term myelin maintenance axon health, may also be present at cell‐axon interface during development. Here, we...
Systemic air embolism is a rare but potentially life-threatening complication of computed tomography (CT)-guided lung biopsy. The largest biopsy audits report an incidence rate approximately 0.061% for systemic embolism, with mortality 0.07–0.15%. A prompt diagnosis high index suspicion essential, and hyperbaric oxygen treatment (HBOT) the definitive management. We case 44-year-old lady who developed lateral ST elevation myocardial infarction from coronary artery following CT-guided...
This study was conducted to evaluate the clinical application of computed tomography canine femoral intercondylar notch. The notch is angled 12 degrees from dorsal plane and obliqued 7 proximolateral distomedial in sagittal plane. Measurements were performed with eight, 12, 16 gantry tilt. With exception proximal opening angle, significant differences not detected measurements referenced Evidence this indicated that a +/- 4 degree variation tilt angle desired did significantly affect...
Abstract Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage subsequent degeneration. Studies utilizing genetic (CNPase-, MAG-, PLP-null mice) naturally occurring neuropathy models suggest that myelinating glia also support axons independently from myelin. protein zero (MPZ P0), which expressed only by Schwann cells, critical formation the peripheral nervous system. Many...
In this report, we present a challenging case of pedunculated left atrial myxoma which was initially diagnosed on Transthoracic Echocardiography (TTE) at 39 weeks and 2 days gestation in grand-multigravida woman with previous normal deliveries. She delivered by urgent caesarean section resection the following day. had an unremarkable recovery.
Abstract Schwann cell (SC) mitochondria are quickly emerging as an important regulator of myelin maintenance in the peripheral nervous system (PNS). However, mechanisms underlying demyelination context mitochondrial dysfunction PNS incompletely understood. We recently showed that conditional ablation protein Prohibitin 1 ( Phb1 ) SCs causes a severe and fast progressing demyelinating neuropathy, but mechanism failure remained unknown. Here, we report mTORC1 JUN continuously activated absence...
Abstract Myelin is required for nervous system function. In the peripheral system, Schwann cells (SCs) form myelin and trophically support axons they ensheath. We previously showed that mitochondrial protein prohibitin 2 (PHB2) can localize to axon-SC interface developmental myelination. Whether homologous PHB1 has a similar role, whether prohibitins also play important roles in SC mitochondria unknown. Here we show deletion of Phb1 SCs only minimally perturbs development, but later triggers...