3,914 research outputs found

    Methods matter: A primer on permanent and reversible interference techniques in animals for investigators of human neuropsychology.

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    The study of patients with brain lesions has contributed greatly to our understanding of the biological bases of human cognition, but this approach also has several unavoidable limitations. Research that uses animal models complements and extends human neuropsychology by addressing many of these limitations. In this review, we provide an overview of permanent and reversible animal lesion techniques for researchers of human neuropsychology, with the aim of highlighting how these methods provide a valuable adjunct to behavioural, neuroimaging, physiological, and clinical investigations in humans. Research in animals has provided important lessons about how the limitations of one or more techniques, or differences in their mechanism of action, has impacted upon the understanding of brain organisation and function. These cautionary tales highlight the importance of striving for a thorough understanding of how any intereference technique works (whether in animal or human), and for how to best use animal research to clarify the precise mechanisms underlying temporary lesion methods in humans

    Experiences and perceptions of Spring Lane Sure Start Children's Centre

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    Spring Lane Sure Start Children’s Centre was designated in September 2007, and ‘officially opened’ in February 2009. The Centre is housed in refurbished premises within a nursery/school complex in the heart of Northampton and offers diverse health, childcare, early education and support services delivered by a multi-professional team. These services and activities are available to children aged 0-5 years old, and their parents/carers, residing within a catchment area comprising eight ‘Super Output Areas’ in the Castle and St. James ward of Northampton. In April 2009, the Centre for Children and Youth (CCY) – a research centre based at The University of Northampton – was commissioned by Spring Lane Sure Start Children’s Centre to collate and gather evaluative data regarding experiences and perceptions of the Children’s Centre during its first year of activitie

    The Cochlear Amplifier as a Standing Wave: Squirting Waves Between Rows of Outer Hair Cells?

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    This paper draws attention to symmetric Lloyd-Redwood (SLR) waves-known in ultrasonics as "squirting" waves-and points out that their distinctive properties make them well-suited for carrying positive feedback between rows of outer hair cells. This coul

    Synthesis and fluorescent properties of ÎČ-pyridyl α-amino acids

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    The preparation of a new class of ÎČ-pyridyl α-amino acid is described using a highly regioselective, ytterbium-catalyzed hetero Diels-Alder reaction of enones with vinyl ethers followed by a modified Knoevenagel-Stobbe reaction as the key heterocycle forming steps. Investigation of the properties and applications of these amino acids showed that they could be utilized in solid phase peptide synthesis for the preparation of a biologically relevant hexapeptide, while pyridines bearing electron-rich substituents exhibited strongly fluorescent properties with high quantum yields and MegaStokes shifts. A solvatochromic study with the most fluorogenic amino acid, a p-methoxyphenyl analogue revealed that this charge-transfer based chromophore is highly sensitive to solvent polarity with a bathochromic shift of 115 nm on changing from THF to phosphate-buffered saline

    Crystallographic and magnetic identification of secondary phase in orientated Bi5Fe0.5Co0.5Ti3O15 ceramics

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    Oxide materials which exhibit both ferroelectricity and ferromagnetism are of great interest for sensors and memory applications. Layered bismuth titanates with an Aurivillius structure, (BiFeO3)nBi4Ti3O12, can possess ferroelectric and ferromagnetic order parameters simultaneously. It has recently been demonstrated that one such example, Bi5Fe0.5Co0.5Ti3O15,where n = 1 with half the Fe3+ sites substituted by Co3+ ions, exhibits both ferroelectric and ferromagnetic properties at room temperature. Here we report the fabrication of highly-oriented polycrystalline ceramics of this material, prepared via molten salt synthesis and uniaxial pressing of high aspect ratio platelets. Electron backscatter images showed that there is a secondary phase within the ceramic matrix which is rich in cobalt and iron, hence this secondary phase could contribute in the main phase ferromagnetic property. The concentration of the secondary phase obtained from secondary electron microscopy is estimated at less than 2.5 %, below the detection limit of XRD. TEM was used to identify the crystallographic structure of the secondary phase, which was shown to be cobalt ferrite, CoFe2O4. It is inferred from the data that the resultant ferromagnetic response identified using VSM measurements was due to the presence of the minor secondary phase. The Remanent magnetization at room temperature was Mr ≈ 76 memu/g which dropped down to almost zero (Mr ≈ 0.8 memu/g) at 460 oC, far lower than the anticipated for CoFe2O4

    In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis.

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    UnlabelledToxoplasma gondii is an obligate intracellular parasite that invades host cells and replicates within a unique parasitophorous vacuole. To maintain this intracellular niche, the parasite secretes an array of dense granule proteins (GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the parasite is replicating within the host cell. Despite the central role of GRAs in the Toxoplasma life cycle, only a subset of these proteins have been identified, and many of their roles have not been fully elucidated. In this report, we utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted into the vacuole and then identify those proteins by affinity purification and mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a large number of known and candidate GRAs and verified localization of 13 novel GRA proteins by endogenous gene tagging. We proceeded to functionally characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene knockout. While Δgra38 and Δgra40 parasites showed no altered phenotype, disruption of GRA39 results in slow-growing parasites that contain striking lipid deposits in the parasitophorous vacuole, suggesting a role in lipid regulation that is important for parasite growth. In addition, parasites lacking GRA39 showed dramatically reduced virulence and a lower tissue cyst burden in vivo Together, the findings from this work reveal a partial vacuolar proteome of T. gondii and identify a novel GRA that plays a key role in parasite replication and pathogenesis.ImportanceMost intracellular pathogens reside inside a membrane-bound vacuole within their host cell that is extensively modified by the pathogen to optimize intracellular growth and avoid host defenses. In Toxoplasma, this vacuole is modified by a host of secretory GRA proteins, many of which remain unidentified. Here we demonstrate that in vivo biotinylation of proximal and interacting proteins using the promiscuous biotin ligase BirA* is a powerful approach to rapidly identify vacuolar GRA proteins. We further demonstrate that one factor identified by this approach, GRA39, plays an important role in the ability of the parasite to replicate within its host cell and cause disease

    Stereoselective synthesis of 2,6-trans-4-oxopiperidines using an acid-mediated 6-endo-trig cyclisation

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    An acid-mediated 6-endo-trig cyclisation of amine-substituted enones has been developed for the stereoselective synthesis of trans-6-alkyl-2-methyl-4-oxopiperidines. Performed under conditions that prevent removal of the Boc-protecting group or acetal formation, the key cyclisation was found to generate cleanly the 4-oxopiperidine products in high overall yields from a wide range of alkyl substituted enones. The synthetic utility of the trans-6-alkyl-2-methyl-4-oxopiperidines formed from this process was demonstrated with the total synthesis of the quinolizidine alkaloid, (+)-myrtine and the piperidine alkaloid, (–)-solenopsin A

    The behavioural and neurophysiological modulation of microsaccades in monkeys

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    Systematic modulations of microsaccades have been observed in humans during covert orienting. We show here that monkeys are a suitable model for studying the neurophysiology governing these modulations of microsaccades. Using various cue-target saccade tasks, we observed the effects of visual and auditory cues on microsaccades in monkeys. As in human studies, following visual cues there was an early bias in cue-congruent microsaccades followed by a later bias in cue-incongruent microsaccades. Following auditory cues there was a cue-incongruent bias in left cues only. In a separate experiment, we observed that brainstem omnipause neurons, which gate all saccades, also paused during microsaccade generation. Thus, we provide evidence that at least part of the same neurocircuitry governs both large saccades and microsaccades
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