Estrogen receptor ß controls proliferation of enteric glia and differentiation of neurons in the myenteric plexus after damage.

Injury to the enteric nervous system (ENS) can cause several gastrointestinal (GI) disorders including achalasia, irritable bowel syndrome, and gastroparesis. Recently, a subpopulation of enteric glial cells with neuronal stem/progenitor properties (ENSCs) has been identified in the adult ENS. ENSCs have the ability of reconstituting the enteric neuronal pool after damage of the myenteric plexus. Since the estrogen receptor ß (ERß) is expressed in enteric glial cells and neurons, we investigated whether a selective ERß agonist, LY3201, can influence neuronal and glial cell differentiation. Myenteric ganglia from the murine muscularis externa were isolated and cultured in either glial cell medium or neuronal medium. In glial cell medium, the number of glial progenitor cells (Sox10+) was increased by fourfold in the presence of LY3201. In the neuronal medium supplemented with an antimitotic agent to block glial cell proliferation, LY3201 elicited a 2.7-fold increase in the number of neurons (neurofilament+ or HuC/D+). In addition, the effect of LY3201 was evaluated in vivo in two murine models of enteric neuronal damage and loss, namely, high-fat diet and topical application of the cationic detergent benzalkonium chloride (BAC) on the intestinal serosa, respectively. In both models, treatment with LY3201 significantly increased the recovery of neurons after damage. Thus, LY3201 was able to stimulate glial-to-neuron cell differentiation in vitro and promoted neurogenesis in the damaged myenteric plexus in vivo. Overall, our study suggests that selective ERß agonists may represent a therapeutic tool to treat patients suffering from GI disorders, caused by excessive neuronal/glial cell damage.

Assigning a social status from face adornments: an fMRI study.

For at least 150,000 years, the human body has been culturally modified by the wearing of personal ornaments and probably by painting with red pigment. The present study used functional magnetic resonance imaging to explore the brain networks involved in attributing social status from face decorations. Results showed the fusiform gyrus, orbitofrontal cortex, and salience network were involved in social encoding, categorization, and evaluation. The hippocampus and parahippocampus were activated due to the memory and associative skills required for the task, while the inferior frontal gyrus likely interpreted face ornaments as symbols. Resting-state functional connectivity analysis clarified the interaction between these regions. The study highlights the importance of these neural interactions in the symbolic interpretation of social markers on the human face, which were likely active in early Homo species and intensified with Homo sapiens populations as more complex technologies were developed to culturalize the human face.

Bimodal effect of D-aspartate on brain aging processes: insights from animal models.

Nowadays it is widely recognized that D-amino acids are present in bacteria as well as in eukaryotes, including mammals. In particular, free D-serine and D-aspartate are found in the brain of mammals. Notably, D-aspartate occurs at substantial levels in the embryo brain to then consistently decrease at post-natal phases. Temporal regulation of D-aspartate content depends on the post-natal onset of D-aspartate oxidase expression, the only known enzyme able to catabolize this D-amino acid. Pharmacological evidence indicates that D-aspartate binds and activates NMDA receptors (NMDARs). To decipher the physiological function of D-aspartate in mammals, in the last years, genetic and pharmacological mouse models with abnormally higher levels of this D-amino acid have been generated. Overall, these animal models have pointed out a significant neuromodulatory role for D-aspartate in the regulation of NMDAR-dependent functions. Indeed, increased content of D-aspartate are able to increase hippocampal NMDAR-dependent long-term potentiation (LTP) and spatial memory of adult mice. However, if exposure to elevated levels of D-Asp lasts for the entire lifetime of mice, enhancement of synaptic plasticity turns into a dramatic worsening, thus triggering an acceleration of the NMDAR-dependent aging processes in the hippocampus. Nonetheless, administration of D-Asp to old mice can restore the physiological age-related decay of hippocampal NMDA-related LTP. Besides its effect on hippocampus-dependent processes in mouse models, different points of evidence are indicating, today, a potential role for D-Asp in neurologic and psychiatric disorders associated with aberrant signalling of NMDARs.

Transient global amnesia as the first symptom of primary antiphospholipid syndrome: a case report.

We describe the case of a 45-year-old woman who had drawn our attention for some recent episodes of transient global amnesia that, upon further examination, resulted from ischemic events caused by multiple arterial thrombosis (bilateral internal carotid occlusion, significant stenosis of the right external carotid, mild stenosis of the right vertebral artery, right anterior cerebral artery occlusion and severe stenosis of the anterior descending coronary artery) due to primary antiphospholipid syndrome. Revascularisation of either carotid was not attempted. A percutaneous intervention in the anterior descending coronary artery stenosis was performed successfully. Due to severe arterial thrombosis, the patient was discharged with only duplex antiplatelet treatment and subcutaneous anticoagulant therapy, since immunotherapy is not indicated in primary APS. The occurrence of transient global amnesia should raise the suspicion of APS.

The earliest evidence for the use of human bone as a tool.

We report on the analysis of three human cranial fragments from a Mousterian context at the site of La Quina (France), which show anthropogenic surface modifications. Macroscopic and microscopic analyses, including SEM observation, demonstrate that the modifications visible on one of these fragments are similar to those produced on bone fragments used experimentally to retouch flakes. The microscopic analysis also identified ancient scraping marks, possibly resulting from the cleaning of the skull prior to its breakage and utilisation of a resulting fragment as a tool. The traces of utilisation and the dimensions of this object are compared to those on a sample of 67 bone retouchers found in the same excavation area and layer. Results show that the tool size, as well as the dimensions and location of the utilised area, fall well within the range of variation observed on faunal shaft fragments from La Quina that were used as retouchers. This skull fragment represents the earliest known use of human bone as a raw material and the first reported use of human bone for this purpose by hominins other than modern humans. The two other skull fragments, which probably come from the same individual, also bear anthropogenic surface modifications in the form of percussion, cut, and scraping marks. The deliberate versus unintentional hypotheses for the unusual choice of the bone are presented in light of contextual information, modifications identified on the two skull fragments not used as tools, and data on bone retouchers from the same layer, the same site, and other Mousterian sites.

Anatomic features in SCAD assessed by CCT: A propensity score matching case control study.

PURPOSE: Spontaneous coronary artery dissection (SCAD) may occur in middle age population without any cardiovascular risk factor. We retrospectively evaluated anatomic features of 11 patients with SCAD using a coronary arteries computed tomography (CCT), compared to age and sex balanced patients who underwent CCT. MATERIAL AND METHODS: CCT was performed in 11 patients (7 females and 4 males) as follow-up in patients with SCAD (left anterior descending - LAD or circumflex artery - Cx) and compared, using the propensity score matching analysis, with 11 healthy patients. Several anatomic features were evaluated: Left main (LM) length, angle between descending coronary artery (LAD) and its first branch, angle between LAD and LM, distance from the annulus to RCA (a-RCA distance) and LM (a-LM distance) ostia and their ratio; ratio between LM length and length a-LM and tortuosity score of the vessel with SCAD. A fluid dynamic analysis has been performed to evaluate the effects on shear stress of vessels wall. RESULTS: LM length was significantly shorter in patients with SCAD versus healthy subjects (P=0.01) as well as LM length/a-LM (P=0.03) and the angle between LAD and the first adjacent branch was sharper (P<0.01). Tortuosity score showed a statistically significant difference between groups (P<0.001). Fluid dynamic analysis demonstrates that, in SCAD group, an angle<90 degree is present at the first bifurcation and it can be a cause of increased strain on vessel wall in patients with high tortuosity of coronary artery. CONCLUSION: Tortuosity and angle between the LAD and the adjacent arterial branch combined may determine increased shear stress on the vessel wall that increases the risk of SCAD.

Post-translational modulation of CD133 expression during sodium butyrate-induced differentiation of HT29 human colon cancer cells: implications for its detection.

The CD133 molecule has been proposed as a surface marker of cancer stem cells in several human malignancies, including colon cancers. The function and the mechanisms regulating CD133 expression remain unknown. The HT29 human colon cancer cells undergo differentiation following treatment with various agents and represent a useful in vitro model of colon differentiation. This study evaluated the behavior of CD133 during sodium butyrate-induced differentiation of HT29 cells. Treatment with sodium butyrate induced a progressive decrease of CD133 expression, as assessed by flow cytometry using the AC133 monoclonal antibody. Indeed, expression of CD133, which was about 47% in untreated control cells, gradually decreased down to about 3% after 72 h in a time- and dose-dependent manner. No relationship was observed between CD133 protein evaluated by flow cytometry and mRNA expression level, and no changes were detected in the methylation status of the CD133 gene promoter during HT29 differentiation. Moreover, the expression of the CD133 protein, evaluated by Western blot analysis using a specific anti-CD133 antibody directed against the C-terminal intracytoplasmic region of human CD133 protein, did not correlate with flow cytometry results. Different results were also obtained using the two antibodies to analyze the expression of the CD133 molecule in human colon cancers. These findings demonstrate that membrane expression of the CD133 stem cell marker might undergo a complex regulation during differentiation of colon cells and suggest that HT29 cells are a useful in vitro model to study the mechanisms involved in this regulation which likely occurs at a post-transcriptional level.

Last Interglacial Iberian Neandertals as fisher-hunter-gatherers.

Marine food-reliant subsistence systems such as those in the African Middle Stone Age (MSA) were not thought to exist in Europe until the much later Mesolithic. Whether this apparent lag reflects taphonomic biases or behavioral distinctions between archaic and modern humans remains much debated. Figueira Brava cave, in the Arrábida range (Portugal), provides an exceptionally well preserved record of Neandertal coastal resource exploitation on a comparable scale to the MSA and dated to ~86 to 106 thousand years ago. The breadth of the subsistence base-pine nuts, marine invertebrates, fish, marine birds and mammals, tortoises, waterfowl, and hoofed game-exceeds that of regional early Holocene sites. Fisher-hunter-gatherer economies are not the preserve of anatomically modern people; by the Last Interglacial, they were in place across the Old World in the appropriate settings.

Dosimetric and chemical characteristics of Fricke gels based on PVA matrices cross-linked with glutaraldehyde.

Fricke gel radiochemical sensors based on various matrices have been studied for decades as 3D dosimeters for radiotherapy. Despite their many appealing features, progressive aging and blurring of the signal have prevented the widespread use of these dosimeters, so far. We have addressed these shortcomings and hereby present our development of a Fricke gel based on a chemically cross-linked PVA matrix. We investigated the influence of several parameters of the polymeric matrix on sensitivity, diffusion coefficient and spontaneous oxidation of the proposed gel dosimeter. Based on these findings, we optimized the gel compositions. Our new gel formulation combines transparency, high sensitivity and simple production method, typical of gels based on natural polymers, with low diffusion coefficient and slow spontaneous oxidation typical of PVA gels made by freezing-thawing.

Neuroimaging supports the representational nature of the earliest human engravings.

The earliest human graphic productions, consisting of abstract patterns engraved on a variety of media, date to the Lower and Middle Palaeolithic. They are associated with anatomically modern and archaic hominins. The nature and significance of these engravings are still under question. To address this issue, we used functional magnetic resonance imaging to compare brain activations triggered by the perception of engraved patterns dating between 540 000 and 30 000 years before the present with those elicited by the perception of scenes, objects, symbol-like characters and written words. The perception of the engravings bilaterally activated regions along the ventral route in a pattern similar to that activated by the perception of objects, suggesting that these graphic productions are processed as organized visual representations in the brain. Moreover, the perception of the engravings led to a leftward activation of the visual word form area. These results support the hypothesis that these engravings have the visual properties of meaningful representations in present-day humans, and could have served such purpose in early modern humans and archaic hominins.

Comparison of double dosimetry algorithms for estimating the effective dose in occupational dosimetry of interventional radiology staff.

'Double dosimetry' i.e. measurement with two dosemeters, one located above the protective apron and one under has been recommended in interventional radiology (IR) to determine the effective dose to staff. Several algorithms have been developed to calculate the effective dose from the readings of the two dosemeters, but there is no international consensus on what is the best algorithm. In this work, a few of the most recently developed algorithms have been tested in typical IR conditions. The effective dose and personnel dosemeter readings were obtained experimentally by using thermoluminescent dosemeters in and on a Rando-Alderson phantom provided with a lead apron. In addition, the effective dose and personnel dosemeter readings were calculated by the Monte Carlo method for the same irradiation geometry. The results suggest that most of the algorithms overestimate effective dose in the selected IR conditions, but there is also a risk of underestimation by using the least conservative algorithms. Two of the algorithms seem to comply best with the chosen criteria of performance, i.e. no underestimation, minimum overestimation and close estimation of effective dose in typical IR conditions. However, it might not be justified to generalise the results. It is recommended that whenever personnel doses approach or exceed the dose limit, IR conditions should be further investigated and the possibility of over- or under-estimation of effective dose by the algorithm used should be considered.

Overview of double dosimetry procedures for the determination of the effective dose to the interventional radiology staff.

In interventional radiology, for an accurate determination of effective dose to the staff, measurements with two dosemeters have been recommended, one located above and one under the protective apron. Such 'double dosimetry' practices and the algorithms used for the determination of effective dose were reviewed in this study by circulating a questionnaire and by an extensive literature search. The results indicated that regulations for double dosimetry almost do not exist and there is no firm consensus on the most suitable calculation algorithms. The calculation of effective dose is mainly based on the single dosemeter measurements, in which either personal dose equivalent, directly, (dosemeter below the apron) or a fraction of personal dose equivalent (dosemeter above the apron) is taken as an assessment of effective dose. The most recent studies suggest that there might not be just one double dosimetry algorithm that would be optimum for all interventional radiology procedures. Further investigations in several critical configurations of interventional radiology procedures are needed to assess the suitability of the proposed algorithms.

Evaluation of the calibration procedure of active personal dosemeters for interventional radiology.

An overview of the use of active personal dosemeters (APD) in interventional radiology is presented. It is based on the work done by the working package 7 of the CONRAD coordinated action supported by the EC within the frame of the 6th FP. This study was done in collaboration with the working package 4 of CONRAD to deal with the calculations required for studying the new calibration facility. The main requirements of the standard for the APD and the difficulties caused by the use of pulsed radiations are presented through the results of an intercomparison organised in a realistic calibration facility similar to the workplace situation in interventional radiology. The main characteristics of this facility are presented.

Advanced readout methods for superheated emulsion detectors.

Superheated emulsions develop visible vapor bubbles when exposed to ionizing radiation. They consist in droplets of a metastable liquid, emulsified in an inert matrix. The formation of a bubble cavity is accompanied by sound waves. Evaporated bubbles also exhibit a lower refractive index, compared to the inert gel matrix. These two physical phenomena have been exploited to count the number of evaporated bubbles and thus measure the interacting radiation flux. Systems based on piezoelectric transducers have been traditionally used to acquire the acoustic (pressure) signals generated by bubble evaporation. Such systems can operate at ambient noise levels exceeding 100 dB; however, they are affected by a significant dead time (>10 ms). An optical readout technique relying on the scattering of light by neutron-induced bubbles has been recently improved in order to minimize measurement dead time and ambient noise sensitivity. Beams of infra-red light from light-emitting diode (LED) sources cross the active area of the detector and are deflected by evaporated bubbles. The scattered light correlates with bubble density. Planar photodiodes are affixed along the detector length in optimized positions, allowing the detection of scattered light from the bubbles and minimizing the detection of direct light from the LEDs. A low-noise signal-conditioning stage has been designed and realized to amplify the current induced in the photodiodes by scattered light and to subtract the background signal due to intrinsic scattering within the detector matrix. The proposed amplification architecture maximizes the measurement signal-to-noise ratio, yielding a readout uncertainty of 6% (±1 SD), with 1000 evaporated bubbles in a detector active volume of 150 ml (6 cm detector diameter). In this work, we prove that the intensity of scattered light also relates to the bubble size, which can be controlled by applying an external pressure to the detector emulsion. This effect can be exploited during the readout procedure to minimize shadowing effects between bubbles, which become severe when the latter are several thousands. The detector we used in this work is based on superheated C-318 (octafluorocyclobutane), emulsified in 100 µm ± 10% (1 SD) diameter drops in an inert matrix of approximately 150 ml. The detector was operated at room temperature and ambient pressure.

NEW DEVELOPMENTS AND APPLICATIONS OF SUPERHEATED EMULSIONS: WARHEAD VERIFICATION AND SPECIAL NUCLEAR MATERIAL INTERDICTION.

In recent years, neutron detection with superheated emulsions has received renewed attention thanks to improved detector manufacturing and read-out techniques, and thanks to successful applications in warhead verification and special nuclear material (SNM) interdiction. Detectors are currently manufactured with methods allowing high uniformity of the drop sizes, which in turn allows the use of optical read-out techniques based on dynamic light scattering. Small detector cartridges arranged in 2D matrices are developed for the verification of a declared warhead without revealing its design. For this application, the enabling features of the emulsions are that bubbles formed at different times cannot be distinguished from each other, while the passive nature of the detectors avoids the susceptibility to electronic snooping and tampering. Large modules of emulsions are developed to detect the presence of shielded special nuclear materials hidden in cargo containers 'interrogated' with high energy X-rays. In this case, the enabling features of the emulsions are photon discrimination, a neutron detection threshold close to 3 MeV and a rate-insensitive read-out.

A new neutron monitor and extended conversion coefficients for HP(10).

A new personal dose equivalent monitor for neutrons, the 'HpSLAB', is introduced. The device consists of a 30x30x15 cm3 polymethyl-methacrylate slab hosting a superheated drop detector embedded at a depth of 10 mm. The personal dose equivalent monitor was characterised experimentally with fast neutron calibrations in the 0.144-14.8 MeV range and numerically with Monte Carlo simulations. In order to evaluate the performance of the device, its response was compared to the fluence-to-directional dose equivalent conversion coefficients, hp(10;alpha,E). Since published coefficients only cover neutron angles of incidence up to 75 degrees, a new extended set of coefficients was computed for angles of incidence up to 180 degrees. The method used in these calculations was the very same used in the generation of the dose equivalent coefficients recommended by International Commission on Radiological Protection publication 74. The response of the HpSLAB follows with good approximation the trend of the conversion coefficients for monoenergetic neutrons above approximately 0.5 MeV. The device was extensively tested in broad-spectrum workplace-fields encountered at nuclear installations and its response was on average within a factor 1.4 of the reference personal dose equivalent values, regardless of angle and energy distribution of the neutron fluence.

The problems associated with the monitoring of complex workplace radiation fields at European high-energy accelerators and thermonuclear fusion facilities.

The European Commission is funding within its Sixth Framework Programme a three-year project (2005-2007) called CONRAD, COordinated Network for RAdiation Dosimetry. The organisational framework for this project is provided by the European Radiation Dosimetry Group EURADOS. One task within the CONRAD project, Work Package 6 (WP6), was to provide a report outlining research needs and research activities within Europe to develop new and improved methods and techniques for the characterisation of complex radiation fields at workplaces around high-energy accelerators, but also at the next generation of thermonuclear fusion facilities. The paper provides an overview of the report, which will be available as CERN Yellow Report.

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part II: Conclusions and recommendations.

The paper presents the main conclusions and recommendations derived from the EVIDOS project, which is supported by the European Commission within the 5th Framework Programme. EVIDOS aims at evaluating state of the art neutron dosimetry techniques in representative workplaces of the nuclear industry with complex mixed neutron-photon radiation fields. This analysis complements a series of individual papers which present detailed results and it summarises the main findings from a practical point of view. Conclusions and recommendations are given concerning characterisation of radiation fields, methods to derive radiation protection quantities and dosemeter results.

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part I: Scope and methods of the project.

Supported by the European Commission, the EVIDOS project started in November 2001 with the broad goal of evaluating state of the art dosimetry techniques in representative workplaces of the nuclear industry. Seven European institutes joined efforts with end users at nuclear power plants, at fuel processing and reprocessing plants, and at transport and storage facilities. A comprehensive programme was devised to evaluate capabilities and limitations of standard and innovative personal dosemeters in relation to the mixed neutron-photon fields of concern to the nuclear industry. This paper describes the criteria behind the selection of dosimetry techniques and workplaces that were analysed, as well as the organisation of the measurement campaigns. Particular emphasis was placed on the evaluation of a variety of electronic personal dosemeters, either commercially available or previously developed by the partners. The estimates provided by these personal dosemeters were compared to reference values of dose equivalent quantities derived from spectrometry and fluence-to-dose equivalent conversion coefficients. Spectrometry was performed both with conventional multisphere and with some original instrumentation providing energy and direction resolution, based on silicon detectors and superheated drop detectors mounted on or in spherical moderators. The results were collected in a large, searchable database and are intended to be used in the harmonisation of dosimetric procedures for mixed radiation fields and for the approval of dosimetry services in Europe.

Direction distributions of neutrons and reference values of the personal dose equivalent in workplace fields.

Within the EC project EVIDOS, double-differential (energy and direction) fluence spectra were determined by means of novel direction spectrometers. By folding the spectra with fluence-to-dose equivalent conversion coefficients, contributions to H*(10) for 14 directions, and values of the personal dose equivalent Hp(10) and the effective dose E for 6 directions of a person's orientation in the field were determined. The results of the measurements and calculations obtained within the EVIDOS project in workplace fields in nuclear installations in Europe, i.e., at Krümmel (boiling water reactor and transport cask), at Mol (Venus research reactor and fuel facility Belgonucléaire) and at Ringhals (pressurised reactor and transport cask) are presented.