Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues.

Dynamin, a membrane-remodelling GTPase

The membrane raft hypothesis postulates the existence of lipid bilayer membrane heterogeneities, or domains, supposed to be important for cellular function, including lateral sorting, signaling, and trafficking. Characterization of membrane lipid heterogeneities in live cells has been challenging in part because inhomogeneity has not usually been definable by optical microscopy. Model membrane systems, including giant unilamellar vesicles, allow optical fluorescence discrimination of coexisting lipid phase types, but thus far have focused on coexisting optically resolvable fluid phases in simple lipid mixtures. Here we demonstrate that giant plasma membrane vesicles (GPMVs) or blebs formed from the plasma membranes of cultured mammalian cells can also segregate into micrometer-scale fluid phase domains. Phase segregation temperatures are widely spread, with the vast majority of GPMVs found to form optically resolvable domains only at temperatures below ≈25°C. At 37°C, these GPMV membranes are almost exclusively optically homogenous. At room temperature, we find diagnostic lipid phase fluorophore partitioning preferences in GPMVs analogous to the partitioning behavior now established in model membrane systems with liquid-ordered and liquid-disordered fluid phase coexistence. We image these GPMVs for direct visual characterization of protein partitioning between coexisting liquid-ordered-like and liquid-disordered-like membrane phases in the absence of detergent perturbation. For example, we find that the transmembrane IgE receptor FceRI preferentially segregates into liquid-disordered-like phases, and we report the partitioning of additional well known membrane associated proteins. Thus, GPMVs now provide an effective approach to characterize biological membrane heterogeneities.

/pdf/large-scale-fluid-fluid-phase-separation-of-proteins-and-2yky3ta3an.pdf

Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles

http://radio.cuci.udg.mx/bch/ES/papers/MembraneModel_BBA_2013-epub.pdf

The Fluid—Mosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years

Membrane deformation is necessary to generate endocytic vesicles, but the molecular mechanisms proposed to drive membrane bending are controversial. Stachowiak and Schmid et al. report that crowding of proteins at the membrane is sufficient to induce curvature in vitro.

Membrane bending by protein-protein crowding

Cell membranes contain a large variety of lipid types and are crowded with proteins, endowing them with the plasticity needed to fulfill their key roles in cell functioning. The compositional complexity of cellular membranes gives rise to a heterogeneous lateral organization, which is still poorly understood. Computational models, in particular molecular dynamics simulations and related techniques, have provided important insight into the organizational principles of cell membranes over the past decades. Now, we are witnessing a transition from simulations of simpler membrane models to multicomponent systems, culminating in realistic models of an increasing variety of cell types and organelles. Here, we review the state of the art in the field of realistic membrane simulations and discuss the current limitations and challenges ahead.

Computational Modeling of Realistic Cell Membranes

Iron promotes ADAM-17 mediated sCD163: TNF-α liberation and modulates inflammation in severe alcoholic hepatitis

Micropipette aspiration technique can be very useful for describing the shape transitions of lipid bilayer vesicles with fluid phase coexistence modulated by the line tension and the bending rigidity. For example, composition dependence of the line tension at the liquid-ordered and liquid-disordered phase interface has been investigated using this technique. Recently, using a very simple mechanical model, the instabilities that occur during suction and release experiments of aspirated vesicles have been discussed. Due to its simplicity the model could not predict the influence of the bending rigidity. In this work, we incorporate the contributions from Helfrich bending energy and the line energy in the vesicle free energy and investigate the shape transitions in micropipette aspirated vesicles. We discuss how the critical aspiration pressure depends on the bending moduli of the phases, the line tension at the interface, and the reduced volume of the vesicle. The ratio of the bending moduli that we predict using the critical aspiration pressure data from recent experiments agrees with the literature.

Influence of the bending rigidity and the line tension on the mechanical stability of micropipette aspirated vesicles.

Introduction: The pandemic COVID-19 has emerged from Wuhan city of China in December 2019 and now spread all around the world till the end of March 2020. The World Health Organization (WHO) has named this corona virus disease as COVID-19 and defined it as the disease caused by severe acute respiratory syndrome corona virus -2 (SARS-CoV-2). Aim: The aim of this study was to find out a possibility for the treatment of a patient infected with SARS-CoV-2 (COVID-19) using high energy ionizing radiation, 10-15 MV X-ray photon, based on biological facts and scientific evidences. Materials and Methods: RNA is the integral part of SARS-CoV-2. And it is wellknown fact that high energy ionizing radiation is able to break strand of both RNA and DNA causing cell death. SARS-CoV-2 enters into host cells using spikeglycoprotein consists of a large ectodomain. The ectodomain contains a receptorbinding unit S1 and a membrane-fusion unit S2. Results: Severalstudiesshowed thatthere are basic similaritiesin chemical bonding of base of RNA and DNA. Adenine, Guanine, Cytocine and Uracil are common and identical components. These common components have weak hydrogen bonds. Single-stranded RNA (ss RNA) is the major structural component of SARS-CoV-2. Discussion: The pandemic COVID-19 has panicked the world. There is no clinically approved medicine for this deadly disease up till now in the medical science. Only symptomatic treatment is given to the patients. On analyzing the several studies and literatures related to radio-biology, molecular biology, virology and radiation oncology, our medical physicist team found that DNA and RNA have many identical and common features. And high energy ionizing radiation (IR) is capable to break the strand of RNA, spike-protein, lipids and kill the viruses. Conclusion: High energy ionizing radiation has a peculiar capability to damage the strand of RNA, proteins and lipids which are the integral parts of SARS-CoV-2. It is able to break the bond between ACE-2 of host cell and Spike- protein of SARSCoV-2. Hence, it is concluded that 10-15 MV X-ray photon should be used for the treatment of patientsinfected with SARS-CoV-2 and it willsurely give better result.

/pdf/covid-19-the-scientific-modality-of-treatment-using-high-2odzaofyqd.pdf

COVID-19: The Scientific Modality of Treatment Using High Energy Ionizing Radiation 10-15 MV X-ray Photon

Dear Editor, Tissue Patch Dural is a synthetic Cerebrospinal Fluid (CSF) sealant used most commonly by neurosurgeons. Its use has previously been reported in the anterior skull base by ENT surgeons. We have found it a useful material to have available during middle ear and mastoid surgery and have not identified any publications reporting its potential applications here. We describe our experience. The proximity of the middle and posterior cranial fossa dura to the mastoid cavity makes it vulnerable both to disease and instrumentation during mastoid surgery. Breach of the dura will result in a CSF leak, which may present as CSF otorrhoea, otorhinorrhoea or meningitis if not repaired. Most causes of CSF leaks are acquired. Iatrogenic causes are more common than trauma. CSF leakage into the middle ear is a recognised complication of trans-mastoid lateral skull base surgery and less commonly occurs as a result of mastoid explorations and approaches to the petrous apex. Blunt trauma to the skull leading to a fracture of the temporal bone is the commonest cause of traumatic CSF otorrhoea. Other rare causes include erosion by cholesteatoma, infection or neoplasm. A breach of the round or oval windows may lead to a perilymph fistula with associated vertigo and changes to hearing. Semicircular canal wall dehiscence may also give rise to vertigo and changes to hearing. These defects may arise de novo, as a result of pathology (eg cholesteatoma or trauma) or be iatrogenic. Repairs of dural and bony defects of the mastoid cavity have been addressed by varied techniques. Autologous materials including temporalis fascia, cartilage, bone dust and cortical bone are commonly used. The best results are seen in multilayer closure. Synthetic materials including hydroxyapatite cement and titanium meshes have been used in the past. SerenoCem granules require caution given recent reports of subsequent bony erosion (communication with The British Society of Otology and MHRA Alert—August, 2016). In the case of larger defects leading to CSF leaks, a “blind sac closure” with abdominal fat graft to pack the mastoid cavity may be employed. A high-resolution CT scan is the primary form of imaging to identify a bony defect. This may be supplemented by an MRI Scan. We report our experience of Tissue Patch Dural (TPD) to repair defects in the mastoid cavity to manage CSF and perilymph leaks.

Novel middle ear applications for a synthetic cerebrospinal fluid (CSF) sealant.

When a stack consisting of layers of soft elastomer and thin metallic film is subjected to low intensity impact by releasing an axisymmetric spherical indenter from a vertical height, the foils buried within the stack undergoes large deformation and fracture. The shape of the deformed area nevertheless remains circular, its radius first increases with the depth from the surface of the stack and then decreases. In contrast, here we show that the symmetry of the deformed area breaks down when instead of a smooth elastomeric layer, one with topographical patterns is used in the stack. The metallic foil deforms through a polygonal area. The size and shape of the polygonal area vary with the flexibility of foil, geometry and dimension of the patterns and the intensity of the impact. For example, for one elastomeric layer decorated with pillars arranged in a square array, the damaged area turns rectangular to hexagonal and then to octagonal with increasing severity of impact, very much similar to polygo...

S. Das

Papers

Iron promotes ADAM-17 mediated sCD163: TNF-α liberation and modulates inflammation in severe alcoholic hepatitis

Influence of the bending rigidity and the line tension on the mechanical stability of micropipette aspirated vesicles.

COVID-19: The Scientific Modality of Treatment Using High Energy Ionizing Radiation 10-15 MV X-ray Photon

Novel middle ear applications for a synthetic cerebrospinal fluid (CSF) sealant.

Polygonal deformation of a metallic foil subjected to impact by an axisymmetric indenter