Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain

© 2017 The Royal Society of Chemistry. Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson's disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson's disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder

Shunting of recurrent post-traumatic syringomyelia into the fourth ventricle: a case report

<p>Abstract</p> <p>Introduction</p> <p>Post-traumatic syringomyelia is a progressive degenerative disorder that is a well-recognized sequela of spinal cord injury. There is currently no optimal intervention capable of producing satisfactory long-term clinical results.</p> <p>Case presentation</p> <p>In this report, we present a 55-year-old Asian man with recurrent syringomyelia after shunt treatment. The syrinx extended from the thoracic cord into the medulla. We used a silicone tube to create a channel connecting the syrinx cavity directly to the fourth ventricle. The patient made a good recovery and follow-up magnetic resonance imaging revealed a considerable diminution in the size of the syrinx.</p> <p>Conclusions</p> <p>We present a new approach that has the potential to improve the outcome of patients with recurrent post-traumatic syringomyelia, who cannot be treated by conventional methods.</p

Invariant Synthesis for Incomplete Verification Engines

We propose a framework for synthesizing inductive invariants for incomplete verification engines, which soundly reduce logical problems in undecidable theories to decidable theories. Our framework is based on the counter-example guided inductive synthesis principle (CEGIS) and allows verification engines to communicate non-provability information to guide invariant synthesis. We show precisely how the verification engine can compute such non-provability information and how to build effective learning algorithms when invariants are expressed as Boolean combinations of a fixed set of predicates. Moreover, we evaluate our framework in two verification settings, one in which verification engines need to handle quantified formulas and one in which verification engines have to reason about heap properties expressed in an expressive but undecidable separation logic. Our experiments show that our invariant synthesis framework based on non-provability information can both effectively synthesize inductive invariants and adequately strengthen contracts across a large suite of programs

Resilience to obesity among socioeconomically disadvantaged women : the READI study

Objective: This cross-sectional study aimed to identify sociodemographic and behavioural characteristics of &lsquo;overweight-resilient&rsquo; women, that is, women who were in a healthy body weight range, despite living in socioeconomically disadvantaged neighbourhoods that place them at increased risk of obesity. The study also aimed to test a comprehensive theoretically derived model of the associations between intrapersonal, social and environmental factors and obesity among this target group.Participants: A total of 3235 women aged 18&ndash;45 years from 80 urban and rural neighbourhoods throughout Victoria, Australia, participated in the Resilience for Eating and Activity Despite Inequality study.Measurements: Women reported height, weight, sociodemographic characteristics, leisure-time physical activity, dietary behaviours and a range of theoretically derived cognitive, social and neighbourhood environmental characteristics hypothesized to influence obesity risk. A theoretical model predicting body mass index (BMI) was tested using structural equation models.Results: Women classified as &lsquo;resilient&rsquo; to obesity tended to be younger, born overseas, more highly educated, unmarried and to have higher or undisclosed household incomes. They engaged in more leisure-time physical activity and consumed less fast foods and soft drinks than overweight/obese women. Neighbourhood characteristics, social characteristics and cognitive characteristics all contributed to explaining variation in BMI in the hypothesized directions.Conclusions: These results demonstrate several characteristics of women appearing &lsquo;resilient&rsquo; to obesity, despite their increased risk conferred by residing in socioeconomically disadvantaged neighbourhoods. Acknowledging the cross-sectional study design, the results advance theoretical frameworks aimed at investigating obesity risk by providing evidence in support of a comprehensive model of direct and indirect effects on obesity of neighbourhood, as well as social, cognitive and behavioural characteristics

Lewis X antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involvement of the endothelial scavenger receptor C-Type lectin

Lewis x (Lex, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Lex in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Lex-dependent PMN interaction with HUVEC. Although both anti-Lex mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Lex-trisaccharide, interacts with specific glycoproteins of Mr␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.Fil: Elola, Maria Teresa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capurro, Mariana Isabel. University of Toronto; CanadáFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; ArgentinaFil: Coombs, Peter J.. Imperial College London; Reino UnidoFil: Taylor, Maureen E.. Imperial College London; Reino UnidoFil: Drickamer, Kurt. Imperial College London; Reino UnidoFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentin

The gray matter volume of the amygdala is correlated with the perception of melodic intervals: a voxel-based morphometry study

Music is not simply a series of organized pitches, rhythms, and timbres, it is capable of evoking emotions. In the present study, voxel-based morphometry (VBM) was employed to explore the neural basis that may link music to emotion. To do this, we identified the neuroanatomical correlates of the ability to extract pitch interval size in a music segment (i.e., interval perception) in a large population of healthy young adults (N = 264). Behaviorally, we found that interval perception was correlated with daily emotional experiences, indicating the intrinsic link between music and emotion. Neurally, and as expected, we found that interval perception was positively correlated with the gray matter volume (GMV) of the bilateral temporal cortex. More important, a larger GMV of the bilateral amygdala was associated with better interval perception, suggesting that the amygdala, which is the neural substrate of emotional processing, is also involved in music processing. In sum, our study provides one of first neuroanatomical evidence on the association between the amygdala and music, which contributes to our understanding of exactly how music evokes emotional responses

Danger Invariants

Static analysers search for overapproximating proofs of safety commonly known as safety invariants. Conversely, static bug finders (e.g. Bounded Model Checking) give evidence for the failure of an assertion in the form of a counterexample trace. As opposed to safety invariants, the size of a counterexample is dependent on the depth of the bug, i.e., the length of the execution trace prior to the error state, which also determines the computational effort required to find them. We propose a way of expressing danger proofs that is independent of the depth of bugs. Essentially, such danger proofs constitute a compact representation of a counterexample trace, which we call a danger invariant. Danger invariants summarise sets of traces that are guaranteed to be able to reach an error state. Our conjecture is that such danger proofs will enable the design of bug finding analyses for which the computational effort is independent of the depth of bugs, and thus find deep bugs more efficiently. As an exemplar of an analysis that uses danger invariants, we design a bug finding technique based on a synthesis engine. We implemented this technique and compute danger invariants for intricate programs taken from SV-COMP 2016

Conceptualising Gamification Risks to Teamwork within Enterprise

Gamification in businesses refers to the use of technology-assisted solutions to boost or change staff attitude, perception and behaviour, in relation to certain business goals and tasks, individually or collectively. Previous research indicated that gamification techniques can introduce risks to the business environment, and not only fail to make a positive change, but also raise concerns in relation to ethics, quality of work, and well-being at a workplace. Although the problem is already recognised in principle, there is still a need to clarify and concretise those risks, their factors and their relation to the gamification dynamics and mechanics. To address this, we conducted multi-staged empirical research, including two months’ observation and interview study, in two large-scale businesses using gamification in their workplace. In this paper, we focus on gamification risks related to teamwork within the enterprise. We outline various risk mitigation strategies and map them to primary types of gamification risks. By accomplishing such conceptualisation, we pave the way towards methods to model, detect and predict gamification risks on teamwork and recommend and design practices and strategies to tackle them

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

<p>Abstract</p> <p>Background</p> <p>Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.</p> <p>Objective</p> <p>To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.</p> <p>Methods</p> <p>129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (<it>V</it>_T) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with <it>V</it>_T8 mL/kg and PEEP 5 cmH₂0 for 2 h 45 min.</p> <p>Results</p> <p>High V_Tventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.</p> <p>Conclusions</p> <p>Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.</p