Domain structure of human complement C4b extends with increasing NaCl concentration: implications for its regulatory mechanism

During the activation of complement C4 to C4b, the exposure of its thioester domain (TED) is crucial for the attachment of C4b to activator surfaces. In the C4b crystal structure, TED forms an Arg(104)-Glu(1032) salt bridge to tether its neighbouring macroglobulin (MG1) domain. Here, we examined the C4b domain structure to test whether this salt bridge affects its conformation. Dual polarisation interferometry of C4b immobilised at a sensor surface showed that the maximum thickness of C4b increased by 0.46 nm with increase in NaCl concentration from 50 mM to 175 mM NaCl. Analytical ultracentrifugation showed that the sedimentation coefficient s20, w of monomeric C4b of 8.41 S in 50 mM NaCl buffer decreased to 7.98 S in 137 mM NaCl buffer, indicating that C4b became more extended. Small angle X-ray scattering reported similar RG values of 4.89-4.90 nm for C4b in 137-250 mM NaCl. Atomistic scattering modelling of the C4b conformation showed that TED and the MG1 domain were separated by 4.7 nm in 137-250 mM NaCl, this being greater than that of 4.0 nm in the C4b crystal structure. Our data reveal that in low NaCl concentrations, both at surfaces and in solution, C4b forms compact TED-MG1 structures. In solution, physiologically-relevant NaCl concentrations lead to the separation of the TED and MG1 domain, making C4b less able to bind to its complement regulators. These conformational changes are similar to those seen previously for complement C3b, confirming the importance of this salt bridge for regulating both C4b and C3b

Decoding intentions of self and others from fMRI activity patterns

Previous studies using multi-voxel pattern analysis have decoded the content of participants' delayed intentions from patterns of fMRI data. Here we investigate whether this technique can be used to decode not only participants' own intentions, but also their representation of the intentions held by other people. In other words: if Sam is thinking about Hoki, can we decode the content of Hoki's intention by scanning Sam's brain? We additionally distinguished two components of intentions: action-plans versus goals, and included novel control analyses that allowed us to distinguish intending an outcome from simply expecting it to occur or simulating its consequences. Regions of frontal, parietal, and occipital cortex contained patterns from which it was possible to decode intentions of both self and other. Furthermore, crossclasification between self and other was possible, suggesting overlap between the two. Control analyses suggested that these results reflected visuo-spatial processes by which intentions were generated in our paradigm, rather than anything special about intentions per se. There was no evidence for any representation of intentions as mental states distinct from visuospatial processes involved in generating their content and/or simulating their outcomes. These findings suggest that the brain activity patterns decoded in intention-decoding fMRI studies may reflect domain-general processes rather than being intention-specific

Altered Patterns of Fungal Keratitis at a London Ophthalmic Referral Hospital: An Eight-Year Retrospective Observational Study

PURPOSE: In previous studies of fungal keratitis (FK) from temperate countries, yeasts were the predominant isolates, with ocular surface disease (OSD) being the leading risk factor. Since the 2005–2006 outbreak of contact lens (CL)-associated Fusarium keratitis, there may have been a rise in CL-associated filamentary FK in the United Kingdom. This retrospective case series investigated the patterns of FK from 2007 to 2014. We compared these to 1994–2006 data from the same hospital. DESIGN: Retrospective observational study. METHODS: All cases of FK presenting to Moorfields Eye Hospital between 2007 and 2014 were identified. The definition of FK was either a fungal organism isolated by culture or fungal structures identified by light microscopy (LM) of scrape material, histopathology, or in vivo corneal confocal microscopy (IVCM). Main outcome measure was cases of FK per year. RESULTS: A total of 112 patients had confirmed FK. Median age was 47.2 years. Between 2007 and 2014, there was an increase in annual numbers of FK (Poisson regression, P [ .0001). FK was confirmed using various modalities: 79 (70.5%) by positive culture, 16 (14.3%) by LM, and 61 (54.5%) by IVCM. Seventy-eight patients (69.6%) were diagnosed with filamentary fungus alone, 28 (25%) with yeast alone, and 6 (5.4%) with mixed filamentary and yeast infections. This represents an increase in the proportion of filamentary fungal infections from the pre-2007 data. Filamentary fungal and yeast infections were associated with CL use and OSD, respectively. CONCLUSIONS: The number of FK cases has increased. This increase is due to CL-associated filamentary FK. Clinicians should be aware of these changes, which warrant epidemiologic investigations to identify modifiable risk factors

The role of metallothionein and astrocyte-neuron interactions in injury to the CNS

Metallothioneins (MTs) represent a large family of proteins characterized by high heavy metal content (mainly CuII and ZnII) and by an unusual cysteine abundance. They have a powerful protective function in all animal tissues, due most likely to their properties as free radical scavengers protecting against oxidative damage. Moreover, the presence and overexpression of MTs in various pathological conditions, such as metal dyshomeostasis, cell proliferation, neurological disorders, and chemotherapy and radiotherapy resistance, could be used as an important prognostic marker, as a histopathological diagnostic tool, and to follow specific pharmacological treatments

The depth-profiled carrier concentration and scattering mechanism in undoped GaN film grown on sapphire

The carrier concentration and scattering mechanism in undoped GaN film grown on sapphire were investigated. The film was grown on sapphire using metal organic chemical vapor deposition (MOCVD). Confocal micro-Raman spectroscopic measurements and temperature-dependant Hall (TDH) measurements were performed for the study of the depth distribution of the carrier density across the GaN film. The existence of a nonuniform spatial distribution of free carriers in the film with a highly conductive layer of ∼1 μm thickness near the GaN sapphire boundary was confirmed from the study. The electron mobility limiting effect of nitrogen vacancies on GaN bulk film was also discussed.published_or_final_versio

Probing deep level centers in GaN epilayers with variable-frequency capacitance-voltage characteristics of AuGaN Schottky contacts

Under identical preparation conditions, AuGaN Schottky contacts were prepared on two kinds of GaN epilayers with significantly different background electron concentrations and mobility as well as yellow emission intensities. Current-voltage (I-V) and variable-frequency capacitance-voltage (C-V) characteristics show that the Schottky contacts on the GaN epilayer with a higher background carrier concentration and strong yellow emission exhibit anomalous reverse-bias I-V and C-V characteristics. This is attributed to the presence of deep level centers. Theoretical simulation of the low-frequency C-V curves leads to a determination of the density and energy level position of the deep centers. © 2006 American Institute of Physics.published_or_final_versio

Probing deep level centers in GaN epilayers with variable-frequency capacitance-voltage characteristics of Au/GaN Schottky contacts

Author name used in this publication: X. M. Tao2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Deep level defect in Si-implanted GaN n +-p junction

The results of deep level transient spectroscopy (DLTS) experiments on GaN junctions, fabricated by silicon implantation, were discussed. An unusual appearance of a minority peak in the majority carrier DLTS spectra within the interfacial region of the junctions was observed. The presence of this minority peak suggested a high concentration of a deep level defect within the interfacial region.published_or_final_versio

Influence of indium-tin-oxide thin-film quality on reverse leakage current of indium-tin-oxide/n-GaN Schottky contacts

Author name used in this publication: X. M. Tao2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Raman scattering and X-ray diffraction study of neutron irradiated GaN epilayers

Neutron irradiation induced defects and their effects on the carrier concentration of GaN epilayers are investigated with Raman scattering and X-ray diffraction techniques. Relative to the as-grown sample, the neutronirradiated samples exhibit a clear variation in the position and lineshape of the A 1(LO)-mode Raman peak as well as in the fullwidth at half-maximum height (FWHM) of the XRD rocking curves. Careful curve fitting and adequate calculations give the carrier concentrations of the irradiated GaN. It is found that the defects induced by neutron irradiation act as carrier trap centres which capture the electron carriers so that the carrier concentration of the irradiated GaN is reduced. © 2005 IEEE.published_or_final_versio