Showing papers by "Andrew Collins published in 2011"
TL;DR: A unique nongenomic mechanism of glucocorticoid hormone action in dentate gyrus granule neurons on long-lasting behavioral responses to stress involving direct cross-talk of GRs with ERK1/2–MSK1–Elk-1 signaling to the nucleus is found.
Abstract: Stressful events are known to have a long-term impact on future behavioral stress responses. Previous studies suggested that both glucocorticoid hormones and glutamate acting via glucocorticoid receptors (GRs) and N-methyl d-aspartate (NMDA) receptors, respectively, are of critical importance for the consolidation of these long-lasting behavioral responses at the dentate gyrus, the gateway of the hippocampal formation. We found that an acute psychologically stressful event resulted in ERK1/2 phosphorylation (pERK1/2), which within 15 min led to the activation of the nuclear kinases MSK1 and Elk-1 in granule neurons of the dentate gyrus. Next, MSK1 and Elk-1 activation evoked serine-10 phosphorylation and lysine-14 acetylation in histone H3, resulting in the induction of the neuroplasticity-associated immediate-early genes c-Fos and Egr-1 in these neurons. The pERK1/2-mediated activation of MSK1 and Elk-1 required a rapid protein–protein interaction between pERK1/2 and activated GRs. This is a unique nongenomic mechanism of glucocorticoid hormone action in dentate gyrus granule neurons on long-lasting behavioral responses to stress involving direct cross-talk of GRs with ERK1/2–MSK1–Elk-1 signaling to the nucleus.
133 citations
TL;DR: It is shown that the deletion of genes outside MDRs can influence clinical outcome and larger deletions (class II) were associated with a significantly increased risk of disease progression.
Abstract: Historically, genes targeted by recurrent chromosomal deletions have been identified within the smallest genomic region shared in all patients, the minimally deleted region (MDR). However, deletions this small do not occur in all patients and are a simplification of the impact larger heterogeneous deletions have during carcinogenesis. We use the example of 13q14 deletions in chronic lymphocytic leukemia to show that genes outside MDRs are associated with disease progression. Genomic profiling of 224 patients identified 205 copy number alterations on chromosome 13 in 132 cases. Deletions including DLEU2 were heterogeneous (845 Kb–96.2 Mb) and identified two breakpoint cluster regions within short interspersed nuclear elements proximal to DLEU2 and within long interspersed nuclear elements/L1 repeats distal to GUCY1B2. After defining a deletion class on the basis of size and location, we show that (a) at diagnosis, larger deletions (class II) were associated with a significantly increased risk of disease progression (odds ratio=12.3; P=0.005), (b) in progressive patients, class II deletions were enriched (P=0.02) and (c) this association was independent of IgVH mutational status, ZAP70 expression and ATM/TP53 deletion. Deletion of a 1 Mb gene cluster (48.2–49.2 Mb), including SETDB2, PHF11 and RCBTB1, was significantly associated (P<0.01) with disease progression. Here, we show that the deletion of genes outside MDRs can influence clinical outcome.
111 citations
TL;DR: It is demonstrated how small changes in comet-assay variables may significantly affect the results, by use of two cell types, viz. human peripheral blood lymphocytes and the lymphoblastoid cell line TK-6.
Abstract: The comet assay is now the method of choice for measuring most kinds of DNA damage in cells. However, due to the lack of a standardised protocol inter-laboratory comparisons are of limited value. The aim of this paper is to demonstrate how small changes in comet-assay variables may significantly affect the results. We examined the effect of varying agarose concentrations, alkaline unwinding time, electrophoresis time, voltage and current, by use of two cell types, viz. human peripheral blood lymphocytes and the lymphoblastoid cell line TK-6. All these variables have marked effects on assay performance and, therefore, on the determination of DNA damage. Here we identify factors of particular importance.
109 citations
TL;DR: This project has compared the performance of visual scoring, automated and semi-automated image analysis when assessing comets in the same set of gels from dose-response experiments with typical DNA-damaging agents, and found that heavily damaged comets are less efficiently detected with image analysis.
Abstract: As part of a project to develop high throughput versions of the comet assay (single cell gel electrophoresis), with a consequent need for more efficient scoring, we have compared the performance of visual scoring, automated and semi-automated image analysis when assessing comets in the same set of gels from dose-response experiments with typical DNA-damaging agents. Human lymphoblastoid TK-6 cells were treated with concentrations of methylmethanesulphonate between 0.04 and 0.6 mM, and peripheral human lymphocytes were incubated, after embedding in agarose, with H(2)O(2) concentrations from 2.5 to 160 μM. All three scoring methods proved capable of detecting a significant level of damage at the lowest concentration of each agent. Visual scoring systematically overestimates low levels of damage compared with computerised image analysis; on the other hand, heavily damaged comets are less efficiently detected with image analysis. Overall, the degree of agreement between the scoring methods is within acceptable limits according to a Bland-Altman analysis.
99 citations
TL;DR: The data uncover a new, highly dynamic role for CBG in the regulation of glucocorticoid hormone physiology after acute stress, and it is discovered that CBG is the key player in this delay.
Abstract: A strict control of glucocorticoid hormone responses to stress is essential for health. In blood, glucocorticoid hormones are for the largest part bound to corticosteroid-binding globulin (CBG), and just a minor fraction of hormone is free. Only free glucocorticoid hormone is able to exert biological effects, but little is known about its regulation during stress. We found, using a dual-probe in vivomicrodialysis method, that in rats, the forced-swim stress-induced rise in free corticosterone (its major glucocorticoid hormone) is strikingly similar in the blood and in target compartments such as the subcutaneous tissue and the brain. However, in all compartments, the free corticosterone response was delayed by 20–30 min as compared with the total corticosterone response in the blood. We discovered that CBG is the key player in this delay. Swim stress evoked a fast (within 5 min) and profound rise in CBG protein and binding capacity in the blood through a release of the protein from the liver. Thus, the increase in circulating CBG levels after stress restrains the rise in free corticosterone concentrations for approximately 20 min in the face of mounting total hormonelevelsinthecirculation.Thestress-inducedincreaseinCBGseemstobespecificformoderate and strong stressors. Both restraint stress and forced swimming caused an increase in circulating CBG, whereas its levels were not affected by mild novelty stress. Our data uncover a new, highly dynamic role for CBG in the regulation of glucocorticoid hormone physiology after acute stress. (Endocrinology 152: 3738–3748, 2011)
90 citations
TL;DR: How epigenetic modifications induced by a range of stressors can affect the biological activity of cells is examined and the role of synergetic interactions between these pathways in adaptive responses to stress and learning and memory paradigms is discussed.
Abstract: Epigenetic mechanisms are processes at the level of the chromatin that control the expression of genes but their role in neuro-immuno-endocrine communication is poorly understood. This review focuses on epigenetic modifications induced by a range of stressors, both physical and psychological, and examines how these variations can affect the biological activity of cells. It is clear that epigenetic modifications are critical in explaining how environmental factors, which have no effect on the DNA sequence, can have such profound, long-lasting influences on both physiology and behavior. A signaling pathway involving activation of MEK-ERK1/2, MSK1, and Elk-1 signaling molecules has been identified in the hippocampus which results in the phospho-acetylation of histone H3 and modification of gene expression including up-regulation of immediate early genes such as c-Fos. This pathway can be induced by a range of challenging experiences including forced swimming, Morris water maze learning, fear conditioning and exposure to the radial maze. Glucocorticoid (GC) hormones, released as part of the stress response and acting via glucocorticoid receptors (GRs), enhance signaling through the ERK1/2/MSK1–Elk-1 pathway and thereby increase the impact on epigenetic and gene expression mechanisms. The role of synergetic interactions between these pathways in adaptive responses to stress and learning and memory paradigms is discussed, in addition we speculate on their potential role in immune function.
82 citations
TL;DR: Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage, and plasma vitamin C increased as did resistance towards H2O2-induced DNA damage.
Abstract: Background: The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. Methods: We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. Results: Plasma vitamin C increased after supplementation as did resistance towards H2O2-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. Conclusion: Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.
68 citations
TL;DR: The comet assay is a sensitive electrophoretic method for measuring DNA breaks at the level of single cells, used widely in genotoxicity experiments, biomonitoring, and in fundamental research.
Abstract: The comet assay is a sensitive electrophoretic method for measuring DNA breaks at the level of single cells, used widely in genotoxicity experiments, in biomonitoring, and in fundamental research. Its sensitivity and range of application are increased by the incorporation of an extra step, after lysis of agarose-embedded cells, in which the DNA is digested with lesion-specific endonucleases (DNA repair enzymes of bacterial or phage origin). Enzymes with specificity for oxidized purines, oxidized pyrimidines, alkylated bases, UV-induced cyclobutane pyrimidine dimers, and misincorporated uracil have been employed. The additional enzyme-sensitive sites, over and above the strand breaks detected in the standard comet assay, give a quantitative estimate of the number of specific lesions present in the cells.
51 citations
TL;DR: Evidence is presented that its selective removal by ethylenediaminetetraacetic acid (EDTA) leaves the gum substantially intact, preventing collapse and entanglement of the network of fibroin brins, enabling wet reeling and this method clearly differs from the standard "degumming" and should be referred to as "demineralizing".
45 citations
TL;DR: Dementia ascertainment to age about 88 years was completed in the 1921 birth cohort and was underway in the 1936 born cohort and these databases are available to other bone fide research groups wishing to test specific hypotheses that may either replicate their own findings or make best use of the data collected in the Aberdeen studies.
42 citations
TL;DR: Targeting more ‘extreme’ breast cancer phenotypes, particularly cases with early-onset disease, a strong family history (not accounted for by BRCA mutations), and with specific tumor subtypes, provides a route to progress using next-generation sequencing methods.
Abstract: The genetic factors known to be involved in breast cancer risk comprise about 30 genes. These include the high-penetrance early-onset breast cancer genes, BRCA1 and BRCA2, a number of rare cancer syndrome genes, and rare genes with more moderate penetrance. A larger group of common variants has more recently been identified through genome-wide association studies. Quite a number of these common variants are mapped to genomic regions without being firmly associated with specific genes. It is thought that most of these variants have gene regulatory functions, but their precise roles in disease susceptibility are not well understood. Common variants account for only a small percentage of the risk of disease because they have low penetrance. Collectively, the breast cancer genes identified to date contribute only ~30% of the familial risk. Therefore, there is much interest in accounting for the missing heritability, and possible sources include loss of information through ignoring phenotype heterogeneity (disease subtypes have genetic differences), gene–gene and gene–environment interaction, and rarer forms of variation. Identification of these rarer variations in coding regions is now feasible and cost effective through exome sequencing, which has already identified high-penetrance variants for some rare diseases. Targeting more ‘extreme’ breast cancer phenotypes, particularly cases with early-onset disease, a strong family history (not accounted for by BRCA mutations), and with specific tumor subtypes, provides a route to progress using next-generation sequencing methods.
TL;DR: In this paper, the EnbioJet® Microwave Flow Pasteurizer was used to examine the preservation of plant phytochemicals and bioactivity upon sterilization.
TL;DR: It is demonstrated that DNA repair is affected by diet and that modified versions of the comet assay can be used to assess activity of different DNA repair pathways in human biomonitoring studies.
Abstract: Lack of reliable assays for DNA repair has largely prevented measurements of DNA repair from being included in human biomonitoring studies. Using newly developed modifications of the comet assay we tested whether a fruit- and antioxidant-rich plant-based intervention could affect base excision repair (BER) and nucleotide excision repair (NER) in a group of 102 male volunteers. BER and NER repair capacities were measured in lymphocytes before and after a dietary intervention lasting 8 weeks. The study had one control group, one group consuming three kiwifruits per day and one group consuming a variety of antioxidant-rich fruits and plant products in addition to their normal diet. DNA strand breaks were reduced following consumption of both kiwifruits (13%, p = 0.05) and antioxidant-rich plant products (20%, p = 0.02). Increased BER (55%, p = 0.01) and reduced NER (−39%, p < 0.01) were observed in the group consuming a wide variety of plant products. Reduced NER was also observed in the kiwifruit group (−38%, p = 0.05), but BER was not affected in this group. Here we have demonstrated that DNA repair is affected by diet and that modified versions of the comet assay can be used to assess activity of different DNA repair pathways in human biomonitoring studies. Copyright © 2010 John Wiley & Sons, Ltd.
TL;DR: The comet assay as discussed by the authors is a simple and sensitive method for measuring DNA damage, which can be used to examine DNA damage and repair at the level of single genes or DNA sequences.
Abstract: The comet assay is a simple and sensitive method for measuring DNA damage. Cells are embedded in agarose on a microscope slide, lysed, and electrophoresed; the presence of strand breaks allows the DNA to migrate, giving the appearance of a comet tail, the percentage of DNA in the tail reflecting the break frequency. Lesion-specific endonucleases extend the usefulness of the method to investigate different kinds of damage. DNA repair can be studied by treating cells with damaging agent and monitoring the damage remaining at intervals during incubation. An important feature of the assay is that damage is detected at the level of individual cells. By combining the comet assay with fluorescent in situ hybridization (FISH), using labeled probes to particular DNA sequences, we can examine DNA damage and repair at the level of single genes or DNA sequences. Here we provide protocols for the comet assay and the FISH modification, answer some technical questions, and give examples of applications of the technique.
TL;DR: It is concluded that GABA tonically controls epigenomic responses to psychologically salient events in dentate gyrus granule neurons and appears to exert its controller activity through modulation of NMDA receptor function.
15 Dec 2011
TL;DR: The development of the method, its principles, applications, and limitations are discussed, and some fallacies that trouble the assay are attempted to dispel, including a recent modification that increases the assay's throughput.
Abstract: The comet assay (single-cell gel electrophoresis) is a simple method for measuring DNA strand breaks in cells that are embedded in agarose and lysed to remove membranes and soluble cell constituents (including most histones). The assay depends on the ability of breaks to relax supercoiling, which allows DNA still attached to a nuclear matrix to move toward the anode under electrophoresis, forming a ‘comet tail’ when viewed by fluorescence microscopy. The percentage of DNA in the tail indicates the frequency of DNA breaks. An additional step — digestion with lesion-specific endonucleases — is introduced after lysis in order to detect different kinds of DNA damage. The assay can be calibrated to give quantitative measures of DNA damage. It has been widely used in genotoxicity testing and human biomonitoring, and also in ecogenotoxicology, as well as in basic research. We here discuss the development of the method, its principles, applications, and limitations, and attempt to dispel some fallacies that trouble the assay. We provide a detailed protocol, including a recent modification that increases the assay's throughput.
07 Nov 2011
TL;DR: The stability of the genome is of crucial importance, and yet the DNA molecule is prone to spontaneous loss of bases, and damage from exogenous and endogenous sources – with potentially mutagenic consequences.
Abstract: The stability of the genome is of crucial importance, and yet the DNA molecule is prone to spontaneous loss of bases, and damage from exogenous and endogenous sources – with potentially mutagenic consequences Damage can take the form of small alterations to bases (alkylation or oxidation); breaks in the sugar-phosphate backbone involving one or both strands (single or double strand breaks – SSBs or DSBs); bulky adducts combined with bases; and covalent bonds between adjacent bases (intra-strand cross-links), across the double helix (inter-strand cross-links), or between DNA and protein These lesions can disrupt replication, or cause incorporation of the wrong base Cells possess repair enzymes that correct almost all the damage before it can result in permanent change to the genome Different pathways deal with the various kinds of damage Repair of SSBs is in most cells a rapid process, consisting of little more than ligation DSBs are more complicated (and potentially more serious) since the continuity of the double helix is disrupted Homologous recombination ensures restoration of the correct DNA sequence by using the DNA of the sister chromatid or homologous chromosome as a template, while non-homologous end-rejoining is less precise and can entail loss of sequence Base excision repair (BER) is concerned with small base alterations and starts with removal of the damaged base by a more or less specific glycosylase, leaving a base-less sugar or AP-site (apurinic/apyrimidinic site) An AP endonuclease or lyase cleaves the DNA at this site, and – after trimming of the broken ends of DNA – the one-nucleotide gap is filled by DNA polymerase ┚ Ligation is the final stage Nucleotide excision repair (NER) is a more complex affair, involving recognition of a bulky adduct or helix distortion (such as is caused by the dimerisation of adjacent pyrimidines by UV(C) radiation), endonucleolytic incision on each side of the lesion, and removal of an oligonucleotide containing the damage This is then filled in by DNA polymerase ├, κ or ┝ and the new patch of nucleotides is ligated into the DNA, completing the repair NER enzymes are also involved in repair of inter-strand cross-links, removing the linking molecule from one strand, leaving it attached to the other strand as a mono-adduct to be removed in a second NER reaction (according to the simplest, and possibly simplistic, model) Individual DNA repair capacity is regarded as a biomarker of susceptibility to mutation and cancer A person with high repair rate is assumed to be at lower risk than one with low repair rate DNA repair is partially determined genetically, and polymorphisms in repair
TL;DR: The present study is the first to demonstrate the tolerability and safety of dietary antioxidants at levels similar to dosages provided in RCT using supplements, and may be useful in future studies investigating whether dietary antioxidants may reduce oxidative stress and related diseases.
Abstract: It has been suggested that antioxidants attenuate oxidative stress and prevent oxidative stress-related diseases. Paradoxically, randomised controlled trials (RCT) using pharmacological doses of antioxidant supplements have demonstrated harmful effects in smokers. The aim of the present study was to test the compliance, tolerability and safety of two food-based antioxidant-rich diets in smokers. One of the diets provided antioxidants at levels similar to that used in RCT using supplements which previously have generated harmful effects. The present study followed a randomised, parallel-arm dietary intervention for 8 weeks (n 102) in male smokers (age ≥ 45 years). Participants were randomised to either antioxidant-rich diet, kiwi fruit or control groups. The antioxidant-rich foods provided about 300 mmol antioxidants/week from a wide range of plant-based food items. The kiwi fruit group consumed three kiwi fruits/d. Compliance to both diets was good. Only mild, undesirable events were reported by a minority of the participants. The safety of both diets was demonstrated as no potentially harmful or pro-oxidative effects were observed. In the antioxidant-rich diet group, the mean intake of antioxidants increased from 30 mmol/d at baseline to 62 mmol/d during the intervention. In conclusion, we have demonstrated that male smokers can comply with two food-based antioxidant-rich diets. Furthermore, the present study is the first to demonstrate the tolerability and safety of dietary antioxidants at levels similar to dosages provided in RCT using supplements. Such diets may be useful in future studies investigating whether dietary antioxidants may reduce oxidative stress and related diseases.
TL;DR: Phaeobacter gallaeciensis strain ANG1 represents the dominant member of the bacterial consortium within the reproductive accessory nidamental gland of the squid Euprymna scolopes and a 4.59-Mb assembly of its genome is presented, which may provide clues as to how it benefits its host.
Abstract: Phaeobacter gallaeciensis strain ANG1 represents the dominant member of the bacterial consortium within the reproductive accessory nidamental gland (ANG) of the squid Euprymna scolopes. We present a 4.59-Mb assembly of its genome, which may provide clues as to how it benefits its host.
TL;DR: Alu repeat containing DNA was repaired rapidly in comparison with total genomic DNA, and the studied genes were generally repaired more rapidly than the Alu repeats, which could provide insights on the organisation of genomic DNA in the comet tail.
TL;DR: Meta-analysis, which combines weighted evidence from composite likelihood in different samples, and refines putative disease locations, is facilitated through defining fixed regions on an underlying LD map, which delimit comparable levels of LD.
Abstract: We describe composite likelihood-based analysis of a genome-wide breast cancer case–control sample from the Cancer Genetic Markers of Susceptibility project. We determine 14 380 genome regions of fixed size on a linkage disequilibrium (LD) map, which delimit comparable levels of LD. Although the numbers of single-nucleotide polymorphisms (SNPs) are highly variable, each region contains an average of ∼35 SNPs and an average of ∼69 after imputation of missing genotypes. Composite likelihood association mapping yields a single P-value for each region, established by a permutation test, along with a maximum likelihood disease location, SE and information weight. For single SNP analysis, the nominal P-value for the most significant SNP (msSNP) requires substantial correction given the number of SNPs in the region. Therefore, imputing genotypes may not always be advantageous for the msSNP test, in contrast to composite likelihood. For the region containing FGFR2 (a known breast cancer gene) the largest χ2 is obtained under composite likelihood with imputed genotypes (χ22 increases from 20.6 to 22.7), and compares with a single SNP-based χ22 of 19.9 after correction. Imputation of additional genotypes in this region reduces the size of the 95% confidence interval for location of the disease gene by ∼40%. Among the highest ranked regions, SNPs in the NTSR1 gene would be worthy of examination in additional samples. Meta-analysis, which combines weighted evidence from composite likelihood in different samples, and refines putative disease locations, is facilitated through defining fixed regions on an underlying LD map.
TL;DR: A composite likelihood-based method is applied, which models association with disease in regions defined on a linkage disequilibrium map and combines the evidence across multiple genome-wide samples, and the FGFR2 gene has the highest rank.
Abstract: For detecting low risk disease variants in genome-wide association panels, meta-analysis is a powerful strategy to increase power. We apply a composite likelihood-based method, which models association with disease in regions defined on a linkage disequilibrium map and combines the evidence across multiple genome-wide samples. This fixed region approach has the advantage that, as only one statistical test is made per region, there is no increased multiple testing penalty in higher marker density panels. Imputation of missing genotypes is also advantageous to increase coverage. Meta-analysis of three breast cancer data sets combines evidence from samples that show heterogeneity in phenotype and, particularly, in marker coverage. The FGFR2 gene has the highest rank, consistent with previous analysis of one of these samples and supported by the small number of early-onset breast cancer cases included. The 8q24 breast cancer region also ranks highly and is supported by evidence from both early-onset and post-menopausal breast cancer samples. The PIK3AP1 gene region is highlighted in this analysis as a strong candidate for further study.
TL;DR: Therapeutically useful concentrations of the water-insoluble organometallic drug, tris(8-hydroxyquinolinato)gallium(III), are delivered to haematological cell lines without the need for toxic cosolvents and cause cell death by a dose-dependent increase in apoptosis.
Abstract: Therapeutically useful concentrations of the water-insoluble organometallic drug, tris(8-hydroxyquinolinato)gallium(III), are delivered to haematological cell lines without the need for toxic cosolvents. Delivery is by sequestration into aqueous micelles of a poly(ethylene glycol)/poly(propylene glycol)/poly(ethylene glycol) triblock copolymer using a facile method based on emulsion-mediated evaporation. The drug-loaded micelles function as a cell cycle inhibitor and cause cell death by a dose-dependent increase in apoptosis.
TL;DR: In this article, the authors examine the impact of social networks on strategic default behavior and show that in fragile markets, advice by those considered to be experts can result in a flood of strategic defaults, causing a contagious downward spiral of home prices and potentially a market collapse.
Abstract: The paper examines the impact of social networks on strategic default behavior. Given the difficulties in empirically modeling this phenomenon, the paper takes a simulation approach, utilizing techniques from epidemiology. The concept is that ideas can travel through a population in the same manner that a disease does. Homeowners learn about strategic default either from their neighbors or from real estate “mavens” who provide information, or in some cases misinformation. The modeling indicates that in fragile markets, advice by those considered to be experts can result in a flood of strategic defaults, causing a contagious downward spiral of home prices and potentially a market collapse.
Patent•
31 Oct 2011
TL;DR: A method for demineralizing wild silk cocoons under mild conditions making it possible both to reel cocoon from species which can only be carded with the prior arts and to wet reel cocoons from species that can either be dry reeled or semi-dry reeled with prior arts.
Abstract: A method for demineralizing wild silk cocoons under mild conditions making it possible both to reel cocoons from species which can only be carded with the prior arts and to wet reel cocoons from species which can only be dry reeled or semi-dry reeled with the prior arts. This, in both cases reduces damage caused in processing and results in single brins and baves with markedly improved consistency in mechanical properties and increased strength and elongation to break. The method also allows substantially all of the silk to be wet reeled from cocoons. For species where the current invention enables silk to be reeled where the prior arts only enabled the carding and spinning of silk the invention makes it possible to form singles, twists and yarns with very long staple lengths and hence greatly superior properties including greater strength, toughness, consistency of diameter, and lustre compared with the short staple fibres prepared according to the prior arts. Demineralisation according to the invention also enables regenerated silk solutions to be prepared under milder conditions compared with the prior arts reducing costs and improving the properties of materials formed from the regenerated silk. The method of demineralizing wild silks according to the present invention also produces materials with reduced or abolished toxicity and allergenicity.
01 Jan 2011
TL;DR: Exercised rodents display reduced anxiety and impulsivity in a variety of behavioral paradigms, and epigenetic and gene expression mechanisms at the dentate gyrus (DG) after long-term voluntary exercise seem to modulate the number of epigenetically marked neurons in the DG, improving cognitive responses to a stress-related event.
Abstract: Poor stress-coping is associated with a greater chance of developing a psychiatric illness such as post-traumatic stress disorder (PTSD) or depression. Lifestyle interventions which facilitate more appropriate responses to stress are much sought after. Exercise is one such intervention and is now commonly being prescribed as a cotreatment along with drugs for treating depression. Exercised rodents display reduced anxiety and impulsivity in a variety of behavioral paradigms. Rats exposed to psychological stress show differential epigenetic and gene expression mechanisms at the dentate gyrus (DG) after long-term voluntary exercise. Alterations within ERK MAPK signalling to chromatin seem to modulate the number of epigenetically marked neurons in the DG, improving cognitive responses to a stress-related event. Other lifestyle interventions such as nutrition or better maternal care in early life have been shown to induce changes at the epigenome which impact positively on mental health.
01 Jan 2011
TL;DR: In this paper, the glucocorticoid receptor (GR) and the NMDA/ERK/MSK1 and Elk-1 signaling pathways were identified as playing an important role in the acquisition and consolidation of such memories.
Abstract: Formation of memories of events in our lives is one of the principal functions of the brain. We make particularly strong memories of events with an emotional impact. Glucocorticoid hormones, secreted in response to the stressful event, have been identified as playing an important role in the acquisition and consolidation of such memories. In recent years, significant advances have been made in the identification of the signaling and epigenomic mechanisms in the hippocampus underlying memory formation. Evidence has been accumulating for a principal role of the NMDA–ERK MAPK signaling pathway and its downstream effector molecules MSK1 and Elk-1. Activation of this signaling cascade results in the phosphorylation, acetylation, and possibly methylation of histone molecules within the chromatin structure and in the induction of immediate-early (e.g., c-Fos) and many other genes required for the molecular and cellular adaptation of the affected neurons. Glucocorticoid hormones via the glucocorticoid receptor (GR) enhance memory formation through facilitation of ERK MAPK signaling to the chromatin leading to the enhancement of epigenomic mechanisms and cognitive performance. Thus, formation of strong memories of emotional events involves an interaction between the GR and the NMDA/ERK/MSK1 and Elk-1 signaling pathways resulting in optimization of epigenomic changes in hippocampal neurons to allow the induction of required neuroplasticity changes.
TL;DR: As well as sequence-oriented resources this review presents databases providing genotypic and common disease phenotype data, copy number variation, genetic maps, cytogenetic data, and gives an overview of key software tools, with the emphasis on analysis of the genetic basis of common disease.
Abstract: An enormous number of high-quality Web-based resources are now available to facilitate research into genome variation. Although identification of the most appropriate and informative resources can be challenging, a number of key sites provide links to more specialized resources that may be useful to follow up. Given ongoing research, focussing on the sequencing of many different genomes, we can expect sequence databases and their associated polymorphism-based resources to greatly increase in depth and complexity in a relatively short period of time. However, databases and tools developed to date, and described here, provide a sound basis for accommodating this next generation of genomic data. As well as sequence-oriented resources this review presents databases providing genotypic and common disease phenotype data, copy number variation, genetic maps, cytogenetic data, and gives an overview of key software tools, with the emphasis on analysis of the genetic basis of common disease.
01 Jan 2011
TL;DR: In this article, the authors employ a methodology from the field of epidemiology to measure how quickly this disease can spread throughout a society and find that in our current fragile market, advice by influential Mavens could result in a flood of strategic defaults causing a contagious downward spiral of market prices leading to a potential eventual full market collapse.
Abstract: The most serious and imminent threat to a recovery of the global recession comes in the form of a burgeoning financial contagion known as strategic default. Recognizing that the decision to strategically default goes beyond purely economic considerations, we theorize that the advocacy of strategic default can be likened to a disease, and as such, we employ a methodology from the field of epidemiology to measure how quickly this disease can spread throughout a society. We find that in our current fragile market, advice by influential Mavens could result in a flood of strategic defaults causing a contagious downward spiral of market prices leading to a potential eventual full market collapse. We find that the most critical variable to avoid a financial market collapse is disposition time – the number of months it takes to resolve a foreclosure. The most important social network variable is susceptibility of the general population to adopting the advocacy of strategic default. With these two findings in mind, we conclude with policy recommendations aimed at stemming the tide of this mounting financial concern.