New Chiral Phases of Superfluid 3He Stabilized by Anisotropic Silica Aerogel

A rich variety of Fermi systems condense by forming bound pairs, including high temperature [1] and heavy fermion [2] superconductors, Sr2RuO4 [3], cold atomic gases [4], and superfluid 3He [5]. Some of these form exotic quantum states having non-zero orbital angular momentum. We have discovered, in the case of 3He, that anisotropic disorder, engineered from highly porous silica aerogel, stabilizes a chiral superfluid state that otherwise would not exist. Additionally, we find that the chiral axis of this state can be uniquely oriented with the application of a magnetic field perpendicular to the aerogel anisotropy axis. At suffciently low temperature we observe a sharp transition from a uniformly oriented chiral state to a disordered structure consistent with locally ordered domains, contrary to expectations for a superfluid glass phase [6].Comment: 6 pages, 4 figure, and Supplementary Informatio

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Predicting Impaired Extinction of Traumatic Memory and Elevated Startle

Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD). Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological interventions that can reduce the probability of developing pathologic behaviors associated with such disorders

Psychophysical Investigations into the Role of Low-Threshold C Fibres in Non-Painful Affective Processing and Pain Modulation

We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet-stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low-threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain

A Review of Sociological Issues in Fire Safety Regulation

This paper presents an overview of contemporary sociological issues in fire safety. The most obviously social aspects of fire safety—those that relate to the socioeconomic distribution of fire casualties and damage—are discussed first. The means that society uses to mitigate fire risks through regulation are treated next; focusing on the shift towards fire engineered solutions and the particular challenges this poses for the social distribution and communication of fire safety knowledge and expertise. Finally, the social construction of fire safety knowledge is discussed, raising questions about whether the confidence in the application of this knowledge by the full range of participants in the fire safety design and approvals process is always justified, given the specific assumptions involved in both the production of the knowledge and its extension to applications significantly removed from the original knowledge production; and the requisite competence that is therefore needed to apply this knowledge. The overarching objective is to argue that the fire safety professions ought to be more reflexive and informed about the nature of the knowledge and expertise that they develop and apply, and to suggest that fire safety scientists and engineers ought to actively collaborate with social scientists in research designed to study the way people interact with fire safety technology

Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway

Chordomas are radio- and chemo-resistant tumours and metastasise in as many as 40% of patients. The aim of this study was to identify potential molecular targets for the treatment of chordoma. In view of the reported association of chordoma and tuberous sclerosis complex syndrome, and the available therapeutic agents against molecules in the PI3K/AKT/TSC1/TSC2/mTOR pathway, a tissue microarray of 50 chordoma cases was analysed for expression of active molecules involved in this signalling pathway by immunohistochemistry and a selected number by western blot analysis. Chordomas were positive for p-AKT (92%), p-TSC2 (96%), p-mTOR (27%), total mTOR (75%), p-p70S6K (62%), p-RPS6 (22%), p-4E-BP1 (96%) and eIF-4E (98%). Phosphatase and tensin homologue deleted on chromosome 10 expression was lost in 16% of cases. Mutations failed to be identified in PI3KCA and RHEB1 in the 23 cases for which genomic DNA was available. Fluorescence in situ hybridisation analysis for mTOR and RPS6 loci showed that 11 of 33 and 21 of 44 tumours had loss of one copy of the respective genes, results which correlated with the loss of the relevant total proteins. Fluorescence in situ hybridisation analysis for loci containing TSC1 and TSC2 revealed that all cases analysed harboured two copies of the respective genes. On the basis of p-mTOR and or p-p70S6K expression there is evidence indicating that 65% of the chordomas studied may be responsive to mTOR inhibitors, rapamycin or its analogues, and that patients may benefit from combined therapy including drugs that inhibit AKT

Knockdown of the Drosophila Fused in Sarcoma (FUS) Homologue Causes Deficient Locomotive Behavior and Shortening of Motoneuron Terminal Branches

Mutations in the fused in sarcoma/translated in liposarcoma gene (FUS/TLS, FUS) have been identified in sporadic and familial forms of amyotrophic lateral sclerosis (ALS). FUS is an RNA-binding protein that is normally localized in the nucleus, but is mislocalized to the cytoplasm in ALS, and comprises cytoplasmic inclusions in ALS-affected areas. However, it is still unknown whether the neurodegeneration that occurs in ALS is caused by the loss of FUS nuclear function, or by the gain of toxic function due to cytoplasmic FUS aggregation. Cabeza (Caz) is a Drosophila orthologue of human FUS. Here, we generated Drosophila models with Caz knockdown, and investigated their phenotypes. In wild-type Drosophila, Caz was strongly expressed in the central nervous system of larvae and adults. Caz did not colocalize with a presynaptic marker, suggesting that Caz physiologically functions in neuronal cell bodies and/or their axons. Fly models with neuron-specific Caz knockdown exhibited reduced climbing ability in adulthood and anatomical defects in presynaptic terminals of motoneurons in third instar larvae. Our results demonstrated that decreased expression of Drosophila Caz is sufficient to cause degeneration of motoneurons and locomotive disability in the absence of abnormal cytoplasmic Caz aggregates, suggesting that the pathogenic mechanism underlying FUS-related ALS should be ascribed more to the loss of physiological FUS functions in the nucleus than to the toxicity of cytoplasmic FUS aggregates. Since the Caz-knockdown Drosophila model we presented recapitulates key features of human ALS, it would be a suitable animal model for the screening of genes and chemicals that might modify the pathogenic processes that lead to the degeneration of motoneurons in ALS

Quality of Reporting on the Vegetative State in Italian Newspapers. The Case of Eluana Englaro

Background: Media coverage of the vegetative state (VS) includes refutations of the VS diagnosis and describes behaviors inconsistent with VS. We used a quality score to assess the reporting in articles describing the medical characteristics of VS in Italian newspapers. Methodology/Principal Findings: Our search covered a 7-month period from July 1, 2008, to February 28, 2009, using the online searchable databases of four major Italian newspapers: Corriere della Sera, La Repubblica, La Stampa, and Avvenire. Medical reporting was judged as complete if three core VS characteristics were described: patient unawareness of self and the environment, preserved wakefulness (eyes open), and spontaneous respiration (artificial ventilator not needed). We retrieved 2,099 articles, and 967 were dedicated to VS. Of these, 853 (88.2%) were non-medical and mainly focused on describing the political, legal, and ethical aspects of VS. Of the 114 (11.8%) medical articles, 53 (5.5%) discussed other medical problems such as death by dehydration, artificial nutrition, neuroimaging, brain death, or uterine hemorrhage, and 61 (6.3%) described VS. Of these 61, only 18 (1.9%) reported all three CORE characteristics and were judged complete. We found no differences among the four investigated newspapers (Fisher’s exact = 0.798), and incomplete articles were equally distributed between journalistic pieces and expert opinions (x 2 = 1.8854, P = 0.170). Incorrect descriptions of VS were significantly more common among incomplete articles (13 of 43 vs. 1 of 18; Fisher’s exact P = 0.047)

Neuronal sensitivity to TDP-43 overexpression is dependent on timing of induction

Ubiquitin-immunoreactive neuronal inclusions composed of TAR DNA binding protein of 43 kDa (TDP-43) are a major pathological feature of frontotemporal lobar degeneration (FTLD-TDP). In vivo studies with TDP-43 knockout mice have suggested that TDP-43 plays a critical, although undefined role in development. In the current report, we generated transgenic mice that conditionally express wild-type human TDP-43 (hTDP-43) in the forebrain and established a paradigm to examine the sensitivity of neurons to TDP-43 overexpression at different developmental stages. Continuous TDP-43 expression during early neuronal development produced a complex phenotype, including aggregation of phospho-TDP-43, increased ubiquitin immunoreactivity, mitochondrial abnormalities, neurodegeneration and early lethality. In contrast, later induction of hTDP-43 in the forebrain of weaned mice prevented early death and mitochondrial abnormalities while yielding salient features of FTLD-TDP, including progressive neurodegeneration and ubiquitinated, phospho-TDP-43 neuronal cytoplasmic inclusions. These results suggest that neurons in the developing forebrain are extremely sensitive to TDP-43 overexpression and that timing of TDP-43 overexpression in transgenic mice must be considered when distinguishing normal roles of TDP-43, particularly as they relate to development, from its pathogenic role in FTLD-TDP and other TDP-43 proteinopathies. Finally, our adult induction of hTDP-43 strategy provides a mouse model that develops critical pathological features that are directly relevant for human TDP-43 proteinopathies