1,160 research outputs found
Toward the total synthesis of spirastrellolide A. Part 3: Intelligence gathering and preparation of a ring-expanded analogue
Different methods for the formation of the C.25–C.26 bond of spirastrellolide A (1) are evaluated that might qualify for the end game of the projected total synthesis, with emphasis on metathetic ways to forge the macrocyclic frame
Ibuprofen Ameliorates Fatigue- And Depressive-Like Behavior in Tumor-Bearing Mice
Aims: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF.
Main methods: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10 mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis.
Key findings: Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice.
Significance: Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF
Fluoxetine Prevents the Development of Depressive-like Behavior in a Mouse Model of Cancer Related Fatigue
Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue- and depressive-like behaviors. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRIs such as fluoxetine
Mentalization and dissociation in the context of trauma: Implications for child psychopathology
Dissociation is a common reaction subsequent to childhood sexual abuse (CSA) and has been identified as a risk factor for child psychopathology. There is also evidence that mentalization contributes to resilience in the context of abuse. However, at this stage little is known regarding the relationship between mentalization and dissociation, and their respective contributions to psychopathology. The aim of this study was to examine pathways from CSA to depressive symptoms, externalizing behaviour difficulties and sexualized behaviour, through mentalization and dissociation. These pathways were examined in a sample of 168 mother-child dyads including 74 dyads where children (aged 7–12) had histories of sexual abuse. Maternal mentalization was assessed using the Parent Development Interview-Revised and children’s mentalization was assessed using the Child Reflective Functioning Scale. Children completed the Child Depression Inventory and parents completed the Child Dissociative Checklist, the Child Behavior Checklist and the Child Sexual Behavior Inventory. Direct and indirect paths from CSA to child psychopathology via children’s mentalization and dissociation were examined using Mplus. Two distinct paths from abuse to psychopathology were identified. Child mentalization partially mediated the relationship between CSA and depressive symptoms. The effects of CSA on externalizing symptoms and sexualized behaviour difficulties were sequentially mediated through mentalisation and dissociation
Cluster state quantum computing in optical fibers
A scheme for the implementation of the cluster state model of quantum
computing in optical fibers, which enables the feedforward feature, is
proposed. This scheme uses the time-bin encoding of qubits. Following
previously suggested methods of applying arbitrary one-qubit gates in optical
fibers, two different ways for the realization of fusion gate types I and II
for cluster production are proposed: a fully time-bin based encoding scheme and
a combination of time-bin and polarization based encoding scheme. Also the
methods of measurement in any desired bases for the purpose of the processing
of cluster state computing for both these encodings are explained.Comment: 6 pages, 11 figures, submitted to the Optical Quantum-Information
Science focus issue of JOSA
Toward the Total Synthesis of Spirastrellolide A. Part 1: Strategic Considerations and Preparation of the Southern Domain
North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. The southern hemisphere (C1–C25) and the northern hemisphere (including the chlorinated [5,6,6]-bis-spiroacetal entity and the lateral C42–C47 chain) are prepared by concise and efficient routes. Consequently, the entire carbon framework of this potent phosphatase inhibitor, which contains 21 chiral centers, is prepared in an optically active form, and an important step toward structure determination by total synthesis is achieved
Endobronchial ultrasound reliably quantifies airway smooth muscle remodeling in an equine asthma model
Toward the Total Synthesis of Spirastrellolide A. Part 2: Conquest of the Northern Hemisphere
North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. The southern hemisphere (C1–C25) and the northern hemisphere (including the chlorinated [5,6,6]-bis-spiroacetal entity and the lateral C42–C47 chain) are prepared by concise and efficient routes. Consequently, the entire carbon framework of this potent phosphatase inhibitor, which contains 21 chiral centers, is prepared in an optically active form, and an important step toward structure determination by total synthesis is achieved
Tumor Growth Increases Neuroinflammation, Fatigue and Depressive-like Behavior Prior to Alterations in Muscle Function
Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth
Fair Loss-Tolerant Quantum Coin Flipping
Coin flipping is a cryptographic primitive in which two spatially separated
players, who in principle do not trust each other, wish to establish a common
random bit. If we limit ourselves to classical communication, this task
requires either assumptions on the computational power of the players or it
requires them to send messages to each other with sufficient simultaneity to
force their complete independence. Without such assumptions, all classical
protocols are so that one dishonest player has complete control over the
outcome. If we use quantum communication, on the other hand, protocols have
been introduced that limit the maximal bias that dishonest players can produce.
However, those protocols would be very difficult to implement in practice
because they are susceptible to realistic losses on the quantum channel between
the players or in their quantum memory and measurement apparatus. In this
paper, we introduce a novel quantum protocol and we prove that it is completely
impervious to loss. The protocol is fair in the sense that either player has
the same probability of success in cheating attempts at biasing the outcome of
the coin flip. We also give explicit and optimal cheating strategies for both
players.Comment: 12 pages, 1 figure; various minor typos corrected in version
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