Glial sulfatides and neuronal complex gangliosides are functionally interdependent in maintaining myelinating axon integrity

Sulfatides and gangliosides are raft-associated glycolipids essential for maintaining myelinated nerve integrity. Mice deficient in sulfatide (cerebroside sulfotransferase knockout, CST-/- ) or complex gangliosides (β-1,4-N-acetylegalactosaminyltransferase1 knockout, GalNAc-T-/- ) display prominent disorganization of proteins at the node of Ranvier (NoR) in early life, and age-dependent neurodegeneration. Loss of neuronal rather than glial complex gangliosides underpins the GalNAc-T-/- phenotype, as shown by neuron or glial-specific rescue, whereas sulfatide is principally expressed and functional in glial membranes. The similarities in NoR phenotype of CST-/- , GalNAc-T-/- and axo-glial protein deficient mice suggests these glycolipids stabilise membrane proteins including neurofascin155 (NF155) and myelin-associated glycoprotein (MAG) at axo-glial junctions. To assess the functional interactions between sulfatide and gangliosides, CST-/- and GalNAc-T-/- genotypes were interbred. CST-/- x GalNAc-T-/- mice develop normally to P10, but all die between P20-P25, coinciding with peak myelination. Ultrastructural, immunohistological and biochemical analysis of either sex reveals widespread axonal degeneration and disruption to the axo-glial junction at the NoR. In addition to sulfatide-dependent loss of NF155, CST-/-x GalNAc-T-/- mice exhibited a major reduction in MAG protein levels in CNS myelin, compared to wild type and single lipid deficient mice. The CST-/- x GalNAc-T-/- phenotype was fully restored to that of CST-/- mice by neuron-specific expression of complex gangliosides, but not by their glial-specific expression nor by the global expression of a-series gangliosides. These data indicate that sulfatide and complex b-series gangliosides on the glial and neuronal membranes respectively act in concert to promote NF155 and MAG in maintaining the stable axo-glial interactions essential for normal nerve function.SIGNIFICANCE STATEMENTSulfatides and complex gangliosides are membrane glycolipids with important roles in maintaining nervous system integrity. Node of Ranvier maintenance in particular requires stable compartmentalisation of multiple membrane proteins. The axo-glial adhesion molecules neurofascin 155 and myelin-associated glycoprotein require membrane microdomains containing either sulfatides or complex gangliosides to localise and function effectively. The co-operative roles of these microdomains and associated proteins are unknown. Here we show vital interdependent roles for sulfatides and complex gangliosides as double (but not single) deficiency causes a rapidly lethal phenotype in early age. These findings suggests that sulfatides and complex gangliosides on opposing axo-glial membranes are responsible for essential tethering of the axo-glial junction proteins, neurofascin155 and myelin-associated glycoprotein that interact to maintain the nodal complex

Achimota Pararubulavirus 3: A New Bat-Derived Paramyxovirus of the Genus Pararubulavirus.

Bats are an important source of viral zoonoses, including paramyxoviruses. The paramyxoviral Pararubulavirus genus contains viruses mostly derived from bats that are common, diverse, distributed throughout the Old World, and known to be zoonotic. Here, we describe a new member of the genus Achimota pararubulavirus 3 (AchPV3) and its isolation from the urine of African straw-coloured fruit bats on primary bat kidneys cells. We sequenced and analysed the genome of AchPV3 relative to other Paramyxoviridae, revealing it to be similar to known pararubulaviruses. Phylogenetic analysis of AchPV3 revealed the failure of molecular detection in the urine sample from which AchPV3 was derived and an attachment protein most closely related with AchPV2-a pararubulavirus known to cause cross-species transmission. Together these findings add to the picture of pararubulaviruses, their sources, and variable zoonotic potential, which is key to our understanding of host restriction and spillover of bat-derived paramyxoviruses. AchPV3 represents a novel candidate zoonosis and an important tool for further study

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Gold nanoparticles supported on magnesium oxide for CO oxidation

Au was loaded (1 wt%) on a commercial MgO support by three different methods: double impregnation, liquid-phase reductive deposition and ultrasonication. Samples were characterised by adsorption of N2 at -96°C, temperature-programmed reduction, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction. Upon loading with Au, MgO changed into Mg(OH)2 (the hydroxide was most likely formed by reaction with water, in which the gold precursor was dissolved). The size range for gold nanoparticles was 2-12 nm for the DIM method and 3-15 nm for LPRD and US. The average size of gold particles was 5.4 nm for DIM and larger than 6.5 for the other methods. CO oxidation was used as a test reaction to compare the catalytic activity. The best results were obtained with the DIM method, followed by LPRD and US. This can be explained in terms of the nanoparticle size, well known to determine the catalytic activity of gold catalysts

Simple Metals at High Pressure

In this lecture we review high-pressure phase transition sequences exhibited by simple elements, looking at the examples of the main group I, II, IV, V, and VI elements. General trends are established by analyzing the changes in coordination number on compression. Experimentally found phase transitions and crystal structures are discussed with a brief description of the present theoretical picture.Comment: 22 pages, 4 figures, lecture notes for the lecture given at the Erice course on High-Pressure Crystallography in June 2009, Sicily, Ital

Hospital characteristics associated with highly automated and usable clinical information systems in Texas, United States

<p>Abstract</p> <p>Background</p> <p>A hospital's clinical information system may require a specific environment in which to flourish. This environment is not yet well defined. We examined whether specific hospital characteristics are associated with highly automated and usable clinical information systems.</p> <p>Methods</p> <p>This was a cross-sectional survey of 125 urban hospitals in Texas, United States using the Clinical Information Technology Assessment Tool (CITAT), which measures a hospital's level of automation based on physician interactions with the information system. Physician responses were used to calculate a series of CITAT scores: automation and usability scores, four automation sub-domain scores, and an overall clinical information technology (CIT) score. A multivariable regression analysis was used to examine the relation between hospital characteristics and CITAT scores.</p> <p>Results</p> <p>We received a sufficient number of physician responses at 69 hospitals (55% response rate). Teaching hospitals, hospitals with higher IT operating expenses (>$1 million annually), IT capital expenses (>$75,000 annually) and hospitals with larger IT staff (≥ 10 full-time staff) had higher automation scores than hospitals that did not meet these criteria (p < 0.05 in all cases). These findings held after adjustment for bed size, total margin, and ownership (p < 0.05 in all cases). There were few significant associations between the hospital characteristics tested in this study and usability scores.</p> <p>Conclusion</p> <p>Academic affiliation and larger IT operating, capital, and staff budgets are associated with more highly automated clinical information systems.</p

Retroperitoneal abscess complicated with necrotizing fasciitis of the thigh in a patient with sigmoid colon cancer

<p>Abstract</p> <p>Background</p> <p>Necrotizing fasciitis of the thigh due to the colon cancer, especially during chemotherepy, has not been previously reported.</p> <p>Case presentation</p> <p>A 67-year-old man admitted to the hospital was diagnosed with sigmoid colon cancer that had spread to the left psoas muscle. Multiple hepatic metastases were also found, and combination chemotherapy with irinotecan and S-1 was administered. Four months after the initiation of chemotherapy, the patient developed gait disturbance and high fever and was therefore admitted to the emergency department of our hospital. Blood examination revealed generalized inflammation with a high C-reactive protein level. Computed tomography of the abdomen and pelvis showed gas and fluid collection in the retroperitoneum adjacent to the sigmoid colon cancer. The abscess was locally drained under computed tomographic guidance; however, the infection continued to spread and necrotizing fasciitis developed. Consequently, emergent debridement was performed. The patient recovered well, and the primary tumor was resected after remission of the local inflammation.</p> <p>Conclusion</p> <p>Necrotizing fasciitis of the thigh due to the spread of sigmoid colon cancer is unusual, but this fatal complication should be considered during chemotherapy for patients with unresectable colorectal cancer.</p

Selective IgA Deficiency

Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions