528 research outputs found
A pathogenicity determinant maps to the N-terminal coat protein region of the <i>Pepino mosaic virus</i> genome
Multiplex ligation-dependent probe amplification (MLPA) analysis is an effective tool for the detection of novel intragenic PLA2G6 mutations: Implications for molecular diagnosis
Phospholipase associated neurodegeneration (PLAN) comprises a heterogeneous group of autosomal recessive neurological disorders caused by mutations in the PLA2G6 gene. Direct gene sequencing detects 85% mutations in infantile neuroaxonal dystrophy. We report the novel use of multiplex ligation-dependent probe amplification (MLPA) analysis to detect novel PLA2G6 duplications and deletions. The identification of such copy number variants (CNVs) expands the PLAN mutation spectrum and may account for up to 12.5% of PLA2G6 mutations. MLPA should thus be employed to detect CNVs of PLA2G6 in patients who show clinical features of PLAN but in whom both disease-causing mutations cannot be identified on routine sequencin
The diverse roles of mononuclear phagocytes in prion disease pathogenesis
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurological diseases that can be transmitted through a number of different routes. A wide range of mammalian species are affected by the disease. After peripheral exposure, some TSE agents accumulate in lymphoid tissues at an early stage of disease prior to spreading to the nerves and the brain. Much research has focused on identifying the cells and molecules involved in the transmission of TSE agents from the site of exposure to the brain and several crucial cell types have been associated with this process. The identification of the key cells that influence the different stages of disease transmission might identify targets for therapeutic intervention. This review highlights the involvement of mononuclear phagocytes in TSE disease. Current data suggest these cells may exhibit a diverse range of roles in TSE disease from the transport or destruction of TSE agents in lymphoid tissues, to mediators or protectors of neuropathology in the brain
Reviews
George MacDonald: Divine Carelessness and Fairytale Levity. Daniel Gabelman. Reviewed by Bonnie Gaarden.
The Gender Dance: Ironic Subversion in C.S. Lewis\u27s Cosmic Trilogy. Monika B. Hilder. Preface by Matthew Dickerson. Reviewed by Joe R. Christopher.
Sir Gawain and the Green Knight: In a Modern English Version with a Critical Introduction. John Gardner. Reviewed by Perry Neil Harrison.
Myths of Light: Eastern Metaphors of the Eternal. Joseph Campbell. Reviewed by Christopher Tuthill.
The Riddles of the Hobbit. Adam Roberts. Reviewed by Jon Garrad.
The Modern Literary Werewolf: A Critical Study of the Mutable Motif. Brent A. Stypczynski. Reviewed by Sharon L. Bolding.
Fairy Tales Reimagined: Essays on New Retellings. Ed. by Susan Redington Bobby. Reviewed by Kazia Estrada.
C.S. Lewis\u27s Perelandra: Reshaping the Image of the Cosmos. Ed. Judith Wolfe and Brendan Wolfe. Reviewed by Holly Ordway.
The Ideal of Kingship in the Writings of Charles Williams, C.S. Lewis, and J.R.R. Tolkien: Divine Kingship is Reflected in Middle-Earth. Christopher Scarf. Reviewed by Melody Green.
The Ring of Words: Tolkien and the Oxford English Dictionary. By Peter Gilliver, Jeremy Marshall, and Edmund Weiner. Reviewed by Mike Foster.
Tolkien: The Forest and the City. Ed. Helen Conrad-O\u27Briain and Gerard Hynes. Reviewed by T.S. Miller.
Tolkien Studies X. Edited by Michael D.C. Drout, Verlyn Flieger, and David Bratman. Reviewed by Janet Brennan Croft.
Seven: An Anglo-American Literary Review 30. Edited by Marjorie Lamp Mead. Reviewed by Janet Brennan Croft
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All-optical detection of neuronal membrane depolarization in live cells using colloidal quantum dots
Luminescent semiconductor quantum dots (QDs) have recently been suggested as novel probes for imaging and sensing cell membrane voltages. However, a key bottleneck for their development is a lack of techniques to assess QD responses to voltages generated in the aqueous electrolytic environments typical of biological systems. Even more generally, there have been relatively few efforts to assess the response of QDs to voltage changes in live cells. Here, we develop a platform for monitoring the photoluminescence (PL) response of QDs under AC and DC voltage changes within aqueous ionic environments. We evaluate both traditional CdSe/CdS and more biologically compatible InP/ZnS QDs at a range of ion concentrations to establish their PL/voltage characteristics on chip. Wide-field, few-particle PL measurements with neuronal cells show the QDs can be used to track local voltage changes with greater sensitivity (ΔPL up to twice as large) than state-of-the-art calcium imaging dyes, making them particularly appealing for tracking sub-threshold events. Additional physiological observation studies showed that whilst CdSe/CdS dots have greater PL responses on membrane depolarization, their lower cytotoxicity makes InP/ZnS far more suitable for voltage sensing in living systems. Our results provide a methodology for the rational development of QD voltage sensors and highlight their potential for imaging changes in cell membrane voltage.EPSRC Doctoral Training Award (EP/L016087/1
Stair-specific algorithms for identification of touch-down and foot-off when descending or ascending a non-instrumented staircase.
yesThe present study introduces four event detection algorithms for defining touch-down and foot-off during stair descent and stair ascent using segmental kinematics. For stair descent, vertical velocity minima of the whole body center-of-mass was used to define touch-down, and foot-off was defined as the instant of trail limb peak knee flexion. For stair ascent, vertical velocity local minima of the lead-limb toe was used to define touch-down, and foot-off was defined as the local maxima in vertical displacement between the toe and pelvis. The performance of these algorithms was determined as the agreement in timings of kinematically derived events to those defined kinetically (ground reaction forces). Data were recorded while 17 young and 15 older adults completed stair descent and ascent trials over a four-step instrumented staircase. Trials were repeated for three stair riser height conditions (85 mm, 170 mm, and 255 mm). Kinematically derived touch-down and foot-off events showed good agreement (small 95% limits of agreement) with kinetically derived events for both young and older adults, across all riser heights, and for both ascent and descent. In addition, agreement metrics were better than those returned using existing kinematically derived event detection algorithms developed for overground gait. These results indicate that touch-down and foot-off during stair ascent and descent of non-instrumented staircases can be determined with acceptable precision using segmental kinematic data
Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence
Peer reviewedPublisher PD
Synthesis of monodisperse Iron oxide nanoparticles without surfactants
Monodisperse iron oxide nanoparticles could be successfully synthesized with two kinds of precipitants through a precipitation method. As-prepared nanoparticles in the size around 10 nm with regular spherical-like shape were achieved by adjusting pH values. NaOH and NH 3 ⋅H 2 O were used as two precipitants for comparison. The average size of nanoparticles with NH 3 ⋅H 2 O precipitant got smaller and represented better dispersibility, while nanoparticles with NaOH precipitant represented better magnetic property. This work provided a simple method without using any organic solvents, organic metal salts, or surfactants which could easily obtain monodisperse nanoparticles with tunable morphology
The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK
Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England.
Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data.
All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan.
The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks
Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control
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