Letter : anxiety score as a risk factor for radial artery vasospasm during radial interventions : a pilot study

I read with interest the article in Angiology that determined the role of anxiety level on radial artery spasm during transradial coronary angiography.1 As the importance of conducting more randomised controlled trials using anxiolytics to define the relation between anxiety and vasospasm was noted by the authors, I offer the following insights for investigators to consider when conducting such research. While previous research has already identified that moderate procedural sedation and opioid analgesia reduces the incidence of vasospasm,2 the identification of risk factors in the present study is hypothesis generating as to how outcomes might be even further improved. It is possible that selectively applying either even more intensive sedation and analgesia or complementary non-pharmacological stress-reducing therapies, such as music therapy or visualisation and attentive behaviour, to patients ‘at-risk’ of vasospasm (women and those with high levels of anxiety prior to the procedure) might lead to even better patient outcomes...

Poly(2-oxazoline) hydrogels for controlled fibroblast attachment

Currently there is a lack of choice when selecting synthetic materials with the cell-instructive properties demanded by modern biomaterials. The purpose of this study was to investigate the attachment of cells onto hydrogels prepared from poly(2-oxazoline)s selectively-functionalized with cell adhesion motifs. A water-soluble macromer based on the microwave-assisted cationic ring-opening polymerization of 2-methyl-2-oxazoline and 2-(dec-9-enyl)-2-oxazoline was functionalized with the peptide CRGDSG or controls using thiol-ene photochemistry followed by facile crosslinking in the presence of a dithiol crosslinker. The growth of human fibroblasts on the hydrogel surfaces was dictated by the structure and amount of incorporated peptide. Controls without any peptide showed resistance to cellular attachment. The benignity of the crosslinking conditions was demonstrated by the incorporation of fibroblasts within the hydrogels to produce three-dimensional cell-polymer constructs.

Molecular mechanisms of migraine

Migraine is a common complex disorder that affects a large portion of the population and thus incurs a substantial economic burden on society. The disorder is characterized by recurrent headaches that are unilateral and usually accompanied by nausea, vomiting, photophobia, and phonophobia. The range of clinical characteristics is broad and there is evidence of comorbidity with other neurological diseases, complicating both the diagnosis and management of the disorder. Although the class of drugs known as the triptans (serotonin 5-HT1B/1D agonists) has been shown to be effective in treating a significant number of patients with migraine, treatment may in the future be further enhanced by identifying drugs that selectively target molecular mechanisms causing susceptibility to the disease. Genetically, migraine is a complex familial disorder in which the severity and susceptibility of individuals is most likely governed by several genes that may be different among families. Identification of the genomic variants involved in genetic predisposition to migraine should facilitate the development of more effective diagnostic and therapeutic applications. Genetic profiling, combined with our knowledge of therapeutic response to drugs, should enable the development of specific, individually-tailored treatment.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

Development of modified inorganic adsorbents for radioactive iodine removal and biomolecule adsorption

Development and application of inorganic adsorbent materials have been continuously investigated due to their variability and versatility. This Master thesis has expanded the knowledge in the field of adsorption targeting radioactive iodine waste and proteins using modified inorganic materials. Industrial treatment of radioactive waste and safety disposal of nuclear waste is a constant concern around the world with the development of radioactive materials applications. To address the current problems, laminar titanate with large surface area (143 m2 g−1) was synthesized from inorganic titanium compounds by hydrothermal reactions at 433 K. Ag2O nanocrystals of particle size ranging from 5–30 nm were anchored on the titanate lamina surface which has crystallographic similarity to that of Ag2O nanocrystals. Therefore, the deposited Ag2O nanocrystals and titanate substrate could join together at these surfaces between which there forms a coherent interface. Such coherence between the two phases reduces the overall energy by minimizing surface energy and maintains the Ag2O nanocrystals firmly on the outer surface of the titanate structure. The combined adsorbent was then applied as efficient adsorbent to remove radioactive iodine from water (one gram adsorbent can capture up to 3.4 mmol of I- anions) and the composite adsorbent can be recovered easily for safe disposal. The structure changes of the titanate lamina and the composite adsorbent were characterized via various techniques. The isotherm and kinetics of iodine adsorption, competitive adsorption and column adsorption using the adsorbent were studied to determine the iodine removal abilities of the adsorbent. It is shown that the adsorbent exhibited excellent trapping ability towards iodine in the fix-bed column despite the presence of competitive ions. Hence, Ag2O deposited titanate lamina could serve as an effective adsorbent for removing iodine from radioactive waste. Surface hydroxyl group of the inorganic materials is widely applied for modification purposes and modification of inorganic materials for biomolecule adsorption can also be achieved. Specifically, γ-Al2O3 nanofibre material is converted via calcinations from boehmite precursor which is synthesised by hydrothermal chemical reactions under directing of surfactant. These γ-Al2O3 nanofibres possess large surface area (243 m2 g-1), good stability under extreme chemical conditions, good mechanical strength and rich surface hydroxyl groups making it an ideal candidate in industrialized separation column. The fibrous morphology of the adsorbent also guarantees facile recovery from aqueous solution under both centrifuge and sedimentation approaches. By chemically bonding the dyes molecules, the charge property of γ-Al2O3 is changed in the aim of selectively capturing of lysozyme from chicken egg white solution. The highest Lysozyme adsorption amount was obtained at around 600 mg/g and its proportion is elevated from around 5% to 69% in chicken egg white solution. It was found from the adsorption test under different solution pH that electrostatic force played the key role in the good selectivity and high adsorption rate of surface modified γ-Al2O3 nanofibre adsorbents. Overall, surface modified fibrous γ-Al2O3 could be applied potentially as an efficient adsorbent for capturing of various biomolecules.

Neurons Activated During Fear Memory Consolidation and Reconsolidation are Mapped to a Common and New Topography in the Lateral Amygdala

A key question in neuroscience is how memory is selectively allocated to neural networks in the brain. This question remains a significant research challenge, in both rodent models and humans alike, because of the inherent difficulty in tracking and deciphering large, highly dimensional neuronal ensembles that support memory (i.e., the engram). In a previous study we showed that consolidation of a new fear memory is allocated to a common topography of amygdala neurons. When a consolidated memory is retrieved, it may enter a labile state, requiring reconsolidation for it to persist. What is not known is whether the original spatial allocation of a consolidated memory changes during reconsolidation. Knowledge about the spatial allocation of a memory, during consolidation and reconsolidation, provides fundamental insight into its core physical structure (i.e., the engram). Using design-based stereology, we operationally define reconsolidation by showing a nearly identical quantity of neurons in the dorsolateral amygdala (LAd) that expressed a plasticity-related protein, phosphorylated mitogen-activated protein kinase, following both memory acquisition and retrieval. Next, we confirm that Pavlovian fear conditioning recruits a stable, topographically organized population of activated neurons in the LAd. When the stored fear memory was briefly reactivated in the presence of the relevant conditioned stimulus, a similar topography of activated neurons was uncovered. In addition, we found evidence for activated neurons allocated to new regions of the LAd. These findings provide the first insight into the spatial allocation of a fear engram in the LAd, during its consolidation and reconsolidation phase.

V: Rewriting and reclaiming history : an analysis of the emergence of restorative justice in western criminal justice systems

During the last three decades, restorative justice has emerged in numerous localities around the world as an accepted approach to responding to crime. This article, which stems from a doctoral study on the history of restorative justice, provides a critical analysis of accepted histories of restorative practices. It revisits the celebrated historical texts of the restorative justice movement, and re-evaluates their contribution to the emergence of restorative justice measures. It traces the emergence of the term 'restorative justice', and reveals that it emerged in much earlier writings than is commonly thought to be the case by scholars in the restorative justice field. It also briefly considers some 'power struggles' in relation to producing an accepted version of the history of restorative justice, and scholars' attempts to 'rewrite history' to align with current views on restorative justice. Finally, this article argues that some histories of restorative justice selectively and inaccurately portray key figures from the history of criminology as restorative justice supporters. This, it is argued, gives restorative justice a false lineage and operates to legitimise the widespread adoption of restorative justice around the globe.

The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule

IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4μ8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.

On Presence, Collective Performance and Assumptions of Causality

The ways we assume, observe and model “presence” and its effects are the focus in this paper. Entities with selectively shared presences are the basis of any collective, and of attributions (such as “humorous”, “efficient” or “intelligent”). The subtleties of any joint presence can markedly influence potentials, perceptions and performance of the collective as demonstrated when a humorous tale is counterpoised with disciplined thought. Disciplines build on presences assumed known or knowable while fluid and interpretable presences pervade humor. Explorations in this paper allow considerations of collectives, causality and the philosophy of computing. Economics has long considered issues of collective action in ways circumscribed by assumptions about the presence of economic entities. Such entities are deemed rational but they are clearly not intelligent. To reach its potential, collective intelligence research needs more adequate considerations of alternate presences and their impacts.

miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2

We demonstrate that in zebrafish, the microRNA miR-451 plays a crucial role in promoting erythroid maturation, in part via its target transcript gata2. Zebrafish miR-144 and miR-451 are processed from a single precursor transcript selectively expressed in erythrocytes. In contrast to other hematopoietic mutants, the ze-brafish mutant meunier (mnr) showed intact erythroid specification but diminished miR-144/451 expression. Although erythropoiesis initiated normally in mnr, erythrocyte maturation was morphologically retarded. Morpholino knockdown of miR-451 increased erythrocyte immaturity in wild-type embryos, and miR-451 RNA duplexes partially rescued erythroid maturation in mnr, demonstrating a requirement and role for miR-451 in erythro-cyte maturation. mnr provided a selectively miR-144/451-deficient background, facilitating studies to discern miRNA function and validate candidate targets. Among computer-predicted miR-451 targets potentially mediating these biologic effects, the pro-stem cell transcription factor gata2 was an attractive candidate. In vivo reporter assays validated the predicted miR-451/gata2-3'UTR interaction, gata2 down-regulation was delayed in miR-451-knockdown and mnr embryos, and gata2 knockdown partially restored erythroid maturation in mnr, collectively confirming gata2down-regulation as pivotal for miR-451-driven erythroid maturation. These studies define a new genetic pathway promoting erythroid maturation (mnr/miR-451/gata2) and provide a rare example of partial rescue of a mutant phenotype solely by miRNA overexpression. © 2009 by The American Society of Hematology.

Measuring dietary intake in remote Australian Aboriginal communities

This paper reports a comparison of the practicality, acceptability and face validity of five dietary intake methods in two remote Australian Aboriginal communities: weighed dietary intake, 24‐hour recall, ‘store‐turnover’, diet history and food frequency methods. The methods used to measure individual dietary intake were poorly accepted by the communities. Quantitative data were obtained only from the first three methods. The 24‐hour recall method tended to produce higher nutrient intakes than the weighed intake method and certain foods appeared to be selectively recalled according to perceived nutritional desirability. The ‘store‐turnover’ method was most acceptable to the communities and had less potential for bias than the other methods. It was also relatively objective, non‐intrusive, rapid, easy and inexpensive. However, food distribution patterns within the communities could not be assessed by this method. Nevertheless, other similarly isolated communities may benefit by use of the ‘store‐turnover’ method.

A novel protecting group methodology for syntheses using nitroxides

The methoxyamine group represents an ideal protecting group for the nitroxide moiety. It can be easily and selectively introduced in high yield (typically >90%) to a range of functionalised nitroxides using FeSO4.7H2O and H2O2 in DMSO. Its removal is readily achieved under mild conditions in high yield (70-90%) using mCPBA in a Cope-type elimination process.

Orchids : My Intersex Adventure

Orchids: My Intersex Adventure is a multi-award winning autobiographical documentary film. The film follows documentary filmmaker, Phoebe Hart, as she comes clean on her journey of self-discovery to embrace her future and reconcile the past shame and family secrecy surrounding her intersex condition. Despite her mother’s outright refusal to be in the film, Phoebe decides she must push on with her quest to resolve her life story and connect with other intersex people on camera. With the help of her sister Bonnie and support from her partner James, she hits the open road and reflects on her youth. Phoebe’s happy and carefree childhood came to an abrupt end at puberty when she was told she would never menstruate nor have children. But the reasons why were never discussed and the topic was taboo. At the age of 17, Phoebe’s mother felt she was old enough to understand the true nature of her body and the family secret was finally revealed. Phoebe then faced an orchidectomy, invasive surgery to remove her undescended testes, the emotional scars of which are still raw today. Phoebe’s road trip around Australia exposes her to the stories of other intersex people and holds a mirror to her own experience. She learns valuable lessons in resilience and healing but also sees the pervasive impact her condition has on all her relationships. At home, Phoebe and James want to start a family but dealing with infertility and the stress of the adoption process puts pressure on their marriage. Phoebe also starts to understand the difficult decisions her parents faced and is excited but apprehensive when they eventually agree to be interviewed. Will talking openly with her mother give Phoebe the answers she has been looking for? The film was produced and directed by Phoebe Hart and commissioned by the Australian Broadcasting Commission. The film premiered at the Brisbane International Film Festival in 2010 where it was voted the number one film of the festival by audiences. Orchids was broadcast on ABC1 in Australia in 2012, appeared in more than 50 film festivals internationally and has since been broadcast nationally in Switzerland, Sweden, Israel, Spain, France, Russia, Poland, Germany and the USA.

Selective regulation of p38β protein and signaling by integrin-linked kinase mediates bladder cancer cell migration

Integrin-linked kinase (ILK) and p38MAPK are protein kinases that transduce extracellular signals regulating cell migration and actin cytoskeletal organization. ILK-dependent regulation of p38MAPK is critical for mammalian kidney development and in smooth muscle cell migration, however, specific p38 isoforms has not been previously examined in ILK-regulated responses. Signaling by ILK and p38MAPK is often dysregulated in bladder cancer, and here we report a strong positive correlation between protein levels of ILK and p38β, which is the predominant isoform found in bladder cancer cells, as well as in patient-matched normal bladder and tumor samples. Knockdown by RNA interference of either p38β or ILK disrupts serum-induced, Rac1-dependent migration and actin cytoskeletal organization in bladder cancer cells. Surprisingly, ILK knockdown causes the selective reduction in p38β cellular protein level, without inhibiting p38β messenger RNA (mRNA) expression. The loss of p38β protein in ILK-depleted cells is partially rescued by the 26S proteasomal inhibitor MG132. Using co-precipitation and bimolecular fluorescent complementation assays, we find that ILK selectively forms cytoplasmic complexes with p38β. In situ proximity ligation assays further demonstrate that serum-stimulated assembly of endogenous ILK–p38β complexes is sensitive to QLT-0267, a small molecule ILK kinase inhibitor. Finally, inhibition of ILK reduces the amplitude and period of serum-induced activation of heat shock protein 27 (Hsp27), a target of p38β implicated in actin cytoskeletal reorganization. Our work identifies Hsp27 as a novel target of ILK–p38β signaling complexes, playing a key role in bladder cancer cell migration.

Photocatalysis on supported gold and silver nanoparticles under ultraviolet and visible light irradiation

Studies of the optical properties and catalytic capabilities of noble metal nanoparticles (NPs), such as gold (Au) and silver (Ag), have formed the basis for the very recent fast expansion of the field of green photocatalysis: photocatalysis utilizing visible and ultraviolet light, a major part of the solar spectrum. The reason for this growth is the recognition that the localised surface plasmon resonance (LSPR) effect of Au NPs and Ag NPs can couple the light flux to the conduction electrons of metal NPs, and the excited electrons and enhanced electric fields in close proximity to the NPs can contribute to converting the solar energy to chemical energy by photon-driven photocatalytic reactions. Previously the LSPR effect of noble metal NPs was utilized almost exclusively to improve the performance of semiconductor photocatalysts (for example, TiO2 and Ag halides), but recently, a conceptual breakthrough was made: studies on light driven reactions catalysed by NPs of Au or Ag on photocatalytically inactive supports (insulating solids with a very wide band gap) have demonstrated that these materials are a class of efficient photocatalysts working by mechanisms distinct from those of semiconducting photocatalysts. There are several reasons for the significant photocatalytic activity of Au and Ag NPs. (1) The conduction electrons of the particles gain the irradiation energy, resulting in high energy electrons at the NP surface which is desirable for activating molecules on the particles for chemical reactions. (2) In such a photocatalysis system, both light harvesting and the catalysing reaction take place on the nanoparticle, and so charge transfer between the NPs and support is not a prerequisite. (3) The density of the conduction electrons at the NP surface is much higher than that at the surface of any semiconductor, and these electrons can drive the reactions on the catalysts. (4) The metal NPs have much better affinity than semiconductors to many reactants, especially organic molecules. Recent progress in photocatalysis using Au and Ag NPs on insulator supports is reviewed. We focus on the mechanism differences between insulator and semiconductor-supported Au and Ag NPs when applied in photocatalytic processes, and the influence of important factors, light intensity and wavelength, in particular estimations of light irradiation contribution, by calculating the apparent activation energies of photo reactions and thermal reactions.