The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.This work is part of the SIGMA project with the reference FCT-ANR/NEU-OSD/0258/2012, co-financed by the French public funding agency ANR (Agence Nationale pour laRecherche, APP Blanc International II 2012), the Portuguese FCT (Fundação para aCiência e Tecnologia) and the Portuguese North Regional Operational Program (ON.2—O Novo Norte) under the National Strategic Reference Framework (QREN), through theEuropean Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional DevelopmentFund COMPETE (FCOMP-01-0124-FEDER-037298). D.A.B. and A.N. were funded bygrants from FCT-ANR/NEU-OSD/0258/2012. R.M. was supported by the FCT fellow-ship grant with the reference PDE/BDE/113604/2015 from the PhDiHES program. A.C.was supported by a grant from the foundation NRJ. P.M. was funded by FundaçãoCalouste Gulbenkian (Portugal;‘Better mental health during ageing based on temporalprediction of individual brain ageing trajectories TEMPO’) with Grant Number P-139977. France Life Imaging is acknowledged for its support in funding the NeuroSpinplatform of preclinical MRI scanners. The authors also acknowledge and thank EdwardGanz, MD, for proof reading our work

The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.This work is part of the Sigma project with the reference FCT-ANR/NEU-OSD/ 0258/2012 co-financed by the French public funding agency ANR (Agence National pour la Recherche, APP Blanc International II 2012), the Portuguese FCT (Fundação para a Ciência e Tecnologia) and by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298). DAB and AN were funded by grants from FCT-ANR/NEU-OSD/0258/2012. RM is supported by the FCT fellowship grant with the reference PDE/BDE/113604/2015 from the PhDiHES program; AC was supported by a grant from the foundation NRJ. PM was funded by Fundação Calouste Gulbenkian (Portugal; ‘Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)’), Grant Number P-139977. We thank Drs Patrício Costa and Pedro Moreira for support on the various statistical analyses.info:eu-repo/semantics/publishedVersio

Climatic change and the Mediterranean

The temperature and precipitation scenarios for the Malta region developed by the Climate Research Unit of the University of East Anglia suggest that annual temperature will increase by 0.8 to 0.9°C per degree Celsius of global change and that there will be little if any change in the annual rainfall amounts around Malta. A statistical analysis of past meteorological data for Malta indicates an existing trend towards increasing extremes of temperature; namely an increase in the maximum and a decrease in the minimum temperatures. The mean annual temperature is also apparently increasing. These data also suggest a trend towards lower total annual rainfall; an increase in the atmospheric pressure; an increase in the number of days with thunderstorms; and decreases in cloud cover and the number of hours of bright sunshine. These trends suggest that a process of desertification is already occurring in Malta, and that there is an increase in the suspended particle concentration including pollutants, in the atmosphere over the island. The hydrological cycle will be significantly affected by global warming. In Malta, natural sources of freshwater account for about 37% of all potable water in the public supply and for 84% of all irrigation water. Global warming will affect the freshwater supply through changes to relative sea level, and through changes in rainfall and evapotranspiration. A eustatic rise in sea level of around 65 ± 35 cm by the year 2100 would adversely affect the existing extraction rates from Malta's principal aquifer and make it more vulnerable to sea water intrusion. In contrast, the direct climatic effect will be less pronounced, since only a small change in local precipitation is predicted to accompany global warming. Climate is a fundamental factor influencing the nature of the soils of Malta. Since an increase in temperature with little change in the total rainfall is anticipated, evapotranspiration will increase, leading to an increase in aridity, and to soil degradation mainly due to salinization and alkalinization. The anticipated increase in temperature; a shift in precipitation patterns; a decrease in soil water availability; and a rise in sea level, will have negative impacts on agriculture, natural vegetation and associated fauna, favouring an increase in xerophilic, thermophilic and halophilic species. Such species are likely to be introduced ones, thriving at the expense of native species. It is predicted that the character of the vegetation will change from that typical of Mediterranean coastal lowlands, to associations more typical of deserts. This shift in vegetation pattern would be enhanced by soil erosion and increased soil salinity. Remedial action at a local level could include measures to prevent soil erosion by gradually changing to crops and trees that stabilize soils and which tolerate the new climatic conditions. A change in temperature could possibly lead to an increase in agricultural pests, whilst sea level rise may cause inundation of low-lying agricultural land such as that at Pwales and of groves such as those at Salina Bay. The impacts on fisheries may be less dramatic but changes in migration patterns of important fish such as lampuki might happen; and the potentially adverse effects which competitive thermophilic seaweeds may have on the important Posidonia meadows may be of concern in the future. The effects on aquaculture are difficult to assess but may include an increase in pathogens. The control of pollutants and protection of the Posidonia meadows are recommended, together with development of more sustainable use of fisheries resources. The present coastal, near-shore and freshwater ecosystems are threatened by a number of anthropogenic, non-climatic changes. Any additional impacts on these ecosystems resulting from climatic changes will have to be assessed in the light of such nonclimatic effects, if the overall projections of future changes are to be accurate. Increased eutrophic conditions and increased water stratification are likely to occur under conditions of global change in certain localities already influenced by other non-climatic human activities. Non-linear biological responses to climatic changes are discussed and may prove to be quite significant but difficult to predict with the present state of knowledge. Coastal sandy beaches, sand dunes and saline marsh habitats are considered to be sensitive to predicted climate change impacts, through increased erosion, enhanced shoreline recession and increased environmental fluctuations. The extent of impacts on such habitats, under less severe climatic change scenarios, will depend largely on present and future land-use management practices. Given the coastal topography, present drainage patterns and negligible tectonic movements in Malta, the predicted rise in sea level will have coast and especially those in the main drainage basins will become more susceptible to periodic rainfall-induced flooding and anticipatory action will be needed to address the consequential economic and social disruption. Impacts on coastal settlements are expected as a result of tidal and storm surges rather than from permanent inundation. A rise in sea level may cause sewage systems to flood, and new systems may have to be developed to reduce public health risks from such a hazard, including the increased risk of epidemics of enteric disorders such as typhoid fever. Salt water intrusion into aquifers will reduce the quantity and quality of potable water resources. Temperature rise and an increased frequency of extreme high temperatures, especially when combined with high humidity, will put some population groups such as the elderly and infants at risk from heat stress. Diseases presently confined to the tropics may spread to higher latitudes, and tropical and sub-tropical vector borne diseases may become more widespread, partly because vector survival will increase and partly because the parasites may be able to complete their life cycle more easily. Malaria may reappear in Europe, whilst Leishmaniasis, which has been under control in the recent past, already seems to be on the increase, possibly as a result of recent increases in temperature and humidity. Increased exposure to the sun when combined with possible ozone layer depletion may result in a further rise in the incidence of both melanomas and non-melanotic skin cancers. Exposure to increased ultraviolet (UV) radiation is expected to cause damage to the cornea and lens and an increased incidence of cataracts. The effect of UVB radiation on the human immune system is far less well understood, but it is a well accepted fact however, that UV, possibly acting through DNA damage, is an important precipitating factor of the auto-immune condition, systemic lupus erythematosus. The tourist industry has, for many years, been one of the Islands' most important economic activities, employing 5.8% of the total working population. If the climate conditions of the Maltese Islands change, the tourist industry could suffer, causing disruption to the Maltese economy and hardship to the population. Sea level rise will certainly have an impact on this site-dependent and coastal industry, which would be adversely affected by the loss of sandy beaches and the reduction in potable water supply. The tourist industry, is by its very nature, fragile and susceptible to political, economic and social changes. Climate change will add another element of uncertainty to this sector. Transport in Malta depends entirely on roads, whilst a ferry service connects the islands of Malta, Gozo and Comino and is also used around the Grand Harbour area. Road traffic would suffer in the event of flooding of the main traffic arteries as a result of severe rain storms, which will probably increase along with the anticipated increase in autumn precipitation. Changes in climate are expected to have an effect on the patterns of energy demand to heat and cool buildings. Electricity generation, which accounts for almost two thirds of primary energy consumption, has grown on average by about 8.5% per year in recent years. The predicted average temperature increases would, theoretically, reduce the need to provide heating, thereby saving energy. Given the low thermal performance of Maltese buildings, an increase in ambient temperature may merely result in a more thermally comfortable interior, rather than a saving of energy. · In the commercial and industrial sectors, the interhal heat generated by the use of machinery is high and an increase in ambient temperature, may result in a need for cooling through increased ventilation and possibly an extension of the air conditioning season. The introduction of thermal insulation to the building envelope, would reduce both the heating demand in winter as well as the cooling demand in summer. The displacement of fossil fuels by renewable energy sources particularly biomass and hydro power would reduce carbon dioxide emissions. In Malta there is good potential for development of solar energy, although land availability is a major obstacle. There is less possibility of harnessing wind energy on a large scale although wind energy is already widely used for water pumping in agriculture.peer-reviewe

Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G

LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP) and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4+CD25+Foxp3+ regulatory T cells (Tregs) and CD4+CD25+Foxp3− helper T cells after in vitro (re)stimulation of mesenteric lymph node cells with the antigen (2/6-VLP), the adjuvant (LT-R192G) or both. 2/6-VLP did not activate CD4+CD25+Foxp3− nor Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice, whereas they did activate both subsets from mice immunized with 2/6-VLP in the presence of adjuvant. LT-R192G dramatically decreased CD4+CD25+Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice but not from mice immunized with 2/6-VLP and adjuvant. Moreover, in this case, LT-R192G increased Foxp3 expression on CD4+CD25+Foxp3+ cells, suggesting specific Treg activation during the recall. Finally, when both 2/6-VLP and LT-R192G were used for restimulation, LT-R192G clearly suppressed both 2/6-VLP-specific CD4+CD25+Foxp3− and Foxp3+ T cells. All together, these results suggest that LT-R192G exerts different effects on CD4+CD25+Foxp3+ T cells, depending on a first or a second contact. The unexpected immunomodulation observed during the recall should be considered in designing vaccination protocols

Physicians' migration in Europe: an overview of the current situation

<p>Abstract</p> <p>Background</p> <p>The migration of medical professionals as a result of the expansion of the European Union is cause for concern. But there is a significant lack of information available about this phenomenon.</p> <p>Methods</p> <p>Search of secondary databases about the presence of european doctors working abroad, through two search engines in the Internet (Google and Pubmed) and a survey of professional organisations and regulators in countries of the European Union.</p> <p>Results</p> <p>The United Kingdom has more foreign doctors than all other European countries for which figures are available (Ireland, France, Germany, Norway, Portugal, Italy, Austria and Poland). Some 74,031 foreign doctors are registered in the UK, 30.94% of the total. European countries with the highest percentage of doctors working abroad are Ireland (47.5%, or 10,065 doctors) and Malta (23.1%, 376 doctors). The data obtained from Norway, France and Germany do not indicate an increase in the migration of professionals from countries recently incorporated into the EU.</p> <p>Conclusion</p> <p>There is significant mobility and heterogeneous distribution of doctors within the EEA and it should be cause for concern among health care authorities. However, there is no evidence about a possible increase in this phenomenon after the recent expansion of the EU.</p

Landmarking the brain for geometric morphometric analysis: An error study

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is limited in that it is unable to quantify changes in shape, to describe how regions are interrelated, or to determine whether changes in size are global or local. Statistical shape analysis using coordinate data from biologically relevant landmarks is the preferred method for testing these aspects of phenotype. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that have used landmark-based statistical shape analysis of the brain, most have not published protocols for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two-fold: (1) to collaboratively develop detailed data collection protocols for a set of brain landmarks, and (2) to complete an intra- and inter-observer validation study of the set of landmarks. Detailed protocols were developed for 29 cortical and subcortical landmarks using a sample of 10 boys aged 12 years old. Average intra-observer error for the final set of landmarks was 1.9 mm with a range of 0.72 mm-5.6 mm. Average inter-observer error was 1.1 mm with a range of 0.40 mm-3.4 mm. This study successfully establishes landmark protocols with a minimal level of error that can be used by other researchers in the assessment of neuroanatomic phenotypes. © 2014 Chollet et al

Self-structuring of lamellar bridged silsesquioxanes with long side spacers

Diurea cross-linked bridged silsesquioxanes (BSs) C(10)C(11)C(10) derived from organosilane precursors, including decylene chains as side spacers and alkylene chains with variable length as central spacers (EtO)(3)Si- (CH(2))(10)-Y(CH(2))(n)-Y-(CH(2))(10)-Si(OEt)(3) (n = 7, 9-12; Y = urea group and Et = ethyl), have been synthesized through the combination of self-directed assembly and an acid-catalyzed sol gel route involving the addition of dimethylsulfoxide (DMSO) and a large excess of water. This new family of hybrids has enabled us to conclude that the length of the side spacers plays a unique role in the structuring of alkylene-based BSs, although their morphology remains unaffected. All the samples adopt a lamellar structure. While the alkylene chains are totally disordered in the case of the C(10)C(7)C(10) sample, a variable proportion of all-trans and gauche conformers exists in the materials with longer central spacers. The highest degree of structuring occurs for n = 9. The inclusion of decylene instead of propylene chains as side spacers leads to the formation of a stronger hydrogen-bonded urea-urea array as evidenced by two dimensional correlation Fourier transform infrared spectroscopic analysis. The emission spectra and emission quantum yields of the C(10)C(n)C(10) Cm materials are similar to those reported for diurea cross-linked alkylene-based BSs incorporating propylene chains as side spacers and prepared under different experimental conditions. The emission of the C(10)C(n)C(10) hybrids is ascribed to the overlap of two distinct components that occur within the urea cross-linkages and within the siliceous nanodomains. Time-resolved photoluminescence spectroscopy has provided evidence that the average distance between the siliceous domains and the urea cross-links is similar in the C(10)C(n)C(10) BSs and in oxyethylene-based hybrid analogues incorporating propylene chains as side spacers (diureasils), an indication that the longer side chains in the former materials adopt gauche conformations. It has also allowed us to demonstrate for the first time that the emission features of the urea-related component of the emission of alkylene-based BSs depend critically on the length of the side spacers

Cortical Gyrification and Sulcal Spans in Early Stage Alzheimer's Disease

Alzheimer's disease (AD) is characterized by an insidious onset of progressive cerebral atrophy and cognitive decline. Previous research suggests that cortical folding and sulcal width are associated with cognitive function in elderly individuals, and the aim of the present study was to investigate these morphological measures in patients with AD. The sample contained 161 participants, comprising 80 normal controls, 57 patients with very mild AD, and 24 patients with mild AD. From 3D T1-weighted brain scans, automated methods were used to calculate an index of global cortex gyrification and the width of five individual sulci: superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure. We found that global cortex gyrification decreased with increasing severity of AD, and that the width of all individual sulci investigated other than the intra-parietal sulcus was greater in patients with mild AD than in controls. We also found that cognitive functioning, as assessed by Mini-Mental State Examination (MMSE) scores, decreased as global cortex gyrification decreased. MMSE scores also decreased in association with a widening of all individual sulci investigated other than the intra-parietal sulcus. The results suggest that abnormalities of global cortex gyrification and regional sulcal span are characteristic of patients with even very mild AD, and could thus facilitate the early diagnosis of this condition