1,242 research outputs found

    Protein aggregate formation permits millennium-old brain preservation

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    Human proteins have not been reported to survive in free nature, at ambient temperature, for long periods. Particularly, the human brain rapidly dissolves after death due to auto-proteolysis and putrefaction. The here presented discovery of 2600-year-old brain proteins from a radiocarbon dated human brain provides new evidence for extraordinary long-term stability of non-amyloid protein aggregates. Immunoelectron microscopy confirmed the preservation of neurocytoarchitecture in the ancient brain, which appeared shrunken and compact compared to a modern brain. Resolution of intermediate filaments (IFs) from protein aggregates took 2–12 months. Immunoassays on micro-dissected brain tissue homogenates revealed the preservation of the known protein topography for grey and white matter for type III (glial fibrillary acidic protein, GFAP) and IV (neurofilaments, Nfs) IFs. Mass spectrometry data could be matched to a number of peptide sequences, notably for GFAP and Nfs. Preserved immunogenicity of the prehistoric human brain proteins was demonstrated by antibody generation (GFAP, Nfs, myelin basic protein). Unlike brain proteins, DNA was of poor quality preventing reliable sequencing. These long-term data from a unique ancient human brain demonstrate that aggregate formation permits for the preservation of brain proteins for millennia

    Fibroblast Activation Protein specific optical imaging in Non-Small Cell Lung Cancer

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    Fibroblast activation protein (FAP) is a cell surface propyl-specific serine protease involved in the regulation of extracellular matrix. Whilst expressed at low levels in healthy tissue, upregulation of FAP on fibroblasts can be found in several solid organ malignancies, including non-small cell lung cancer, and chronic inflammatory conditions such as pulmonary fibrosis and rheumatoid arthritis. Their full role remains unclear, but FAP expressing cancer associated fibroblasts (CAFs) have been found to relate to a poor prognosis with worse survival rates in breast, colorectal, pancreatic, and non-small cell lung cancer (NSCLC). Optical imaging using a FAP specific chemical probe, when combined with clinically compatible imaging systems, can provide a readout of FAP activity which could allow disease monitoring, prognostication and potentially stratify therapy. However, to derive a specific signal for FAP any sequence must retain specificity over closely related endopeptidases, such as prolyl endopeptidase (PREP), and be resistant to degradation in areas of active inflammation. We describe the iterative development of a FAP optical reporter sequence which retains FAP specificity, confers resistance to degradation in the presence of activated neutrophil proteases and demonstrates clinical tractability ex vivo in NSCLC samples with an imaging platform

    Perceptions and Determinants of Eating for Health and Performance in High-Level Male Adolescent Rugby Union Players

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    Sports nutrition recommendations provide guidance on dietary strategies to optimise sports performance. However, research indicates that young athletes often find it difficult to follow these guidelines in practice. Limited research exists on the determinants that influence adherence to sports nutrition guidelines. This study aimed to explore the perceptions and determinants of eating for health and performance in high-level male adolescent rugby union players. Determinants were explored using semi-structured individual interviews in New Zealand high-level male rugby union players (n = 20, 16⁻18 years). Interviews were recorded, transcribed, and then underwent thematic analysis. Perceptions of eating for health and performance included balance and variety, appropriate portions, and specific foods. Both adolescent- and sport-specific determinants influenced the food choices of participants. Determinants relevant to adolescent lifestyles included the influence of significant others such as peers and family but also included the taste, cost, convenience, and availability of food. Sports-specific determinants revolved around the desire to enhance sports performance, motivation to perform, and team culture. The media (mainstream and social media), physical appearance, and feeling good were identified as both adolescent- and sport-specific factors influencing food choice. These findings highlight the importance of having support and positive role modelling to help young athletes make optimal food choices for health and performance. Strategies to further enable healthy eating practices should aim to strengthen the support available to young athletes in the home, school, and sporting environments and should include education on appropriate social media use to inform eating for health and performance

    Unveiling the structure of the planetary nebula M 2-48: Kinematics and physical conditions

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    The kinematics and physical conditions of the bipolar planetary nebula M 2-48 are analysed from high and low dispersion long-slit spectra. Previous CCD narrow-band optical observations have suggested that this nebula is mainly formed by a pair of symmetric bow-shocks, an off-center semi-circular shell, and an internal bipolar structure. The bipolar outflow has a complex structure, characterised by a series of shocked regions located between the bright core and the polar tips. There is an apparent kinematic discontinuity between the bright bipolar core and the outer regions. The fragmented ring around the bright bipolar region presents a low expansion velocity and could be associated to ejection in the AGB-PN transition phase, although its nature remains unclear. The chemical abundances of the central region are derived, showing that M 2-48 is a Type I planetary nebula (PN)

    Genetic influences on cost-efficient organization of human cortical functional networks

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    The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09–0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization

    Longitudinal Study on Trace Mineral Compositions (Selenium, Zinc, Copper, Manganese) in Korean Human Preterm Milk

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    We measured selenium, zinc, copper and manganese concentrations in the human milk of Korean mothers who gave birth to preterm infants, and compared these measurements with the recommended daily intakes. The samples of human milk were collected postpartum at week-1, -2, -4, -6, -8, and -12, from 67 mothers who gave birth to preterm infants (< 34 weeks, or birth weight < 1.8 kg). All samples were analyzed using atomic absorption spectrophotometry. The concentrations of selenium were 11.8 ± 0.5, 11.4 ± 0.8, 12.7 ± 0.9, 11.4 ± 0.8, 10.8 ± 0.9, and 10.5 ± 1.3 ”g/L, zinc were 7.8 ± 0.5, 9.1 ± 0.8, 7.2 ± 0.9, 8.0 ± 0.8, 7.4 ± 0.9, and 6.6 ± 1.2 mg/L, copper were 506 ± 23.6, 489 ± 29.4, 384 ± 33.6, 356 ± 32.9, 303 ± 35.0, and 301 ± 48.0 ”g/L and manganese were 133 ± 4.0, 127 ± 6.0, 125 ± 6.0, 123 ± 6.0, 127 ± 6.0, and 108 ± 9.0 ”g/L at week-1, -2, -4, -6, -8, and -12, respectively. The concentrations of selenium and zinc meet the daily requirements but that of copper is low and of manganese exceeds daily requirements recommended by the American Academy of Pediatrics, Committee on Nutrition

    Earthworms and mesofauna from an isolated, alkaline chemical waste site in Northwest England

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    Post-industrial sites across Europe may have developed over periods in excess of a century, often leading to poor nutrient soils with noxious constituents and extreme pH values. One such site, Nob End (Bolton, UK), a toxic tip created in the 1800s from a sodium carbonate factory, represents an “island of alkalinity in an acidic sea” where the weathering process (from pH 12) has provided a suitable environment for a rich alkali-loving flora and hence, deserving its designation as a Site of Special Scientific Interest. Despite their importance, the belowground communities have not been investigated and for this reason, in this study, we explored how soil macro- and mesofauna communities respond to extreme pH values in a system that has also experienced recent changes in management practices. As expected, earthworms, mites, insects and woodlice numbers were significantly higher and the community diversity enriched at the (now pH 8) alkaline sites, whereas in areas where acidic boiler waste was historically deposited, enchytraeids, collembolans and dipteran larvae populations dominated the soil communities. Surprisingly, site management (cutting back of scrub) in the alkaline soil areas had a significant positive effect on soil macro-fauna by promoting numbers and biomass, but severely reduced the microarthropod populations. A transect investigation across an increasing pH gradient (from 4.5 to 8.0) was mirrored by a rise in earthworm numbers and species richness. Earthworms were further investigated surrounding the site, seeking potential sources of colonisation, with the majority of species at Nob End also present in adjacent non-industrially-influenced areas. This work demonstrates that soil fauna can ultimately colonise extreme edaphic conditions and these extreme environments have not prompted the development of specific faunal communities. As management of above-ground communities significantly influenced soil invertebrate communities, this could represent an important restoration practice to improve soil structure and fertility at this polluted site
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