The Cabrières Biota (France) provides insights into Ordovician polar ecosystems.

Early Palaeozoic sites with soft-tissue preservation are predominantly found in Cambrian rocks and tend to capture past tropical and temperate ecosystems. In this study, we describe the diversity and preservation of the Cabrières Biota, a newly discovered Early Ordovician Lagerstätte from Montagne Noire, southern France. The Cabrières Biota showcases a diverse polar assemblage of both biomineralized and soft-bodied organisms predominantly preserved in iron oxides. Echinoderms are extremely scarce, while sponges and algae are abundantly represented. Non-biomineralized arthropod fragments are also preserved, along with faunal elements reminiscent of Cambrian Burgess Shale-type ecosystems, such as armoured lobopodians. The taxonomic diversity observed in the Cabrières Biota mixes Early Ordovician Lagerstätten taxa with Cambrian forms. By potentially being the closest Lagerstätte to the South Pole, the Cabrières Biota probably served as a biotic refuge amid the high-water temperatures of the Early Ordovician, and shows comparable ecological structuring to modern polar communities.

Impact of global climate cooling on Ordovician marine biodiversity.

Global cooling has been proposed as a driver of the Great Ordovician Biodiversification Event, the largest radiation of Phanerozoic marine animal Life. Yet, mechanistic understanding of the underlying pathways is lacking and other possible causes are debated. Here we couple a global climate model with a macroecological model to reconstruct global biodiversity patterns during the Ordovician. In our simulations, an inverted latitudinal biodiversity gradient characterizes the late Cambrian and Early Ordovician when climate was much warmer than today. During the Mid-Late Ordovician, climate cooling simultaneously permits the development of a modern latitudinal biodiversity gradient and an increase in global biodiversity. This increase is a consequence of the ecophysiological limitations to marine Life and is robust to uncertainties in both proxy-derived temperature reconstructions and organism physiology. First-order model-data agreement suggests that the most conspicuous rise in biodiversity over Earth's history - the Great Ordovician Biodiversification Event - was primarily driven by global cooling.

New fossil assemblages from the Early Ordovician Fezouata Biota.

The Fezouata Biota (Morocco) is a unique Early Ordovician fossil assemblage. The discovery of this biota revolutionized our understanding of Earth's early animal diversifications-the Cambrian Explosion and the Ordovician Radiation-by suggesting an evolutionary continuum between both events. Herein, we describe Taichoute, a new fossil locality from the Fezouata Shale. This locality extends the temporal distribution of fossil preservation from this formation into the upper Floian, while also expanding the range of depositional environments to more distal parts of the shelf. In Taichoute, most animals were transported by density flows, unlike the in-situ preservation of animals recovered in previously investigated Fezouata sites. Taichoute is dominated by three-dimensionally preserved, and heavily sclerotized fragments of large euarthropods-possibly representing nektobenthic/nektic bivalved taxa and/or hurdiid radiodonts. Resolving whether this dominance reflects a legitimate aspect of the original ecosystem or a preservational bias requires an in-depth assessment of the environmental conditions at this site. Nevertheless, Taichoute provides novel preservational and palaeontological insights during a key evolutionary transition in the history of life on Earth.

Importance of Public Transport Networks for Reconciling the Spatial Distribution of Dengue and the Association of Socio-Economic Factors with Dengue Risk in Bangkok, Thailand.

Dengue is the most widespread mosquito-borne viral disease of man and spreading at an alarming rate. Socio-economic inequality has long been thought to contribute to providing an environment for viral propagation. However, identifying socio-economic (SE) risk factors is confounded by intra-urban daily human mobility, with virus being ferried across cities. This study aimed to identify SE variables associated with dengue at a subdistrict level in Bangkok, analyse how they explain observed dengue hotspots and assess the impact of mobility networks on such associations. Using meteorological, dengue case, national statistics, and transport databases from the Bangkok authorities, we applied statistical association and spatial analyses to identify SE variables associated with dengue and spatial hotspots and the extent to which incorporating transport data impacts the observed associations. We identified three SE risk factors at the subdistrict level: lack of education, % of houses being cement/brick, and number of houses as being associated with increased risk of dengue. Spatial hotspots of dengue were found to occur consistently in the centre of the city, but which did not entirely have the socio-economic risk factor characteristics. Incorporation of the intra-urban transport network, however, much improved the overall statistical association of the socio-economic variables with dengue incidence and reconciled the incongruous difference between the spatial hotspots and the SE risk factors. Our study suggests that incorporating transport networks enables a more real-world analysis within urban areas and should enable improvements in the identification of risk factors.

Contrasting Early Ordovician assembly patterns highlight the complex initial stages of the Ordovician Radiation.

The Early Ordovician is a key interval for our understanding of the evolution of life on Earth as it lays at the transition between the Cambrian Explosion and the Ordovician Radiation and because the fossil record of the late Cambrian is scarce. In this study, assembly processes of Early Ordovician trilobite and echinoderm communities from the Central Anti-Atlas (Morocco), the Montagne Noire (France), and the Cordillera Oriental (Argentina) are explored. The results show that dispersal increased diachronically in trilobite communities during the Early Ordovician. Dispersal did not increase for echinoderms. Dispersal was most probably proximally triggered by the planktic revolution, the fall in seawater temperatures, changes in oceanic circulation, with an overall control by tectonic frameworks and phylogenetic constraints. The diachronous increase in dispersal within trilobite communities in the Early Ordovician highlights the complexity of ecosystem structuring during the early stages of the Ordovician Radiation. As Early Ordovician regional dispersal was followed by well-documented continental dispersal in the Middle/Late Ordovician, it is possible to consider that alongside a global increase in taxonomic richness, the Ordovician Radiation is also characterized by a gradual increase in dispersal.

Assessing healthcare access using the Levesque's conceptual framework- a scoping review.

INTRODUCTION: Countries are working hard to improve access to healthcare through Universal Healthcare Coverage. To genuinely address the problems of healthcare access, we need to recognize all the dimensions and complexities of healthcare access. Levesque's Conceptual Framework of Access to Health introduced in 2013 provides an interesting and comprehensive perspective through the five dimensions of access and the five abilities of the population to access healthcare. The objectives of this paper are to identify and analyze all empirical studies that applied Levesque's conceptual framework for access to healthcare and to explore the experiences and challenges of researchers who used this framework in developing tools for assessing access. METHODS: A scoping review was conducted by searching through four databases, for studies citing Levesque et al. 2013 to select all empirical studies focusing on healthcare access that applied the framework. An initial 1838 documents underwent title screening, followed by abstract screening, and finally full text screening by two independent reviewers. Authors of studies identified from the scoping review were also interviewed. RESULTS: There were 31 studies identified on healthcare access using the Levesque framework either a priori, to develop assessment tool/s (11 studies), or a posteriori, to organize and analyze collected data (20 studies). From the tools used, 147 unique questions on healthcare access were collected, 91 of these explored dimensions of access while 56 were about abilities to access. Those that were designed from the patient's perspective were 73%, while 20% were for health providers, and 7% were addressed to both. Interviews from seven out of the 26 authors, showed that while there were some challenges such as instances of categorization difficulty and unequal representation of dimensions and abilities, the overall experience was positive. CONCLUSION: Levesque's framework has been successfully used in research that explored, assessed, and measured access in various healthcare services and settings. The framework allowed researchers to comprehensively assess the complex and dynamic process of access both in the health systems and the population contexts. There is still potential room for improvement of the framework, particularly the incorporation of time-related elements of access.

A Scoping Review on Air Quality Monitoring, Policy and Health in West African Cities.

Ambient air pollution is a global health threat that causes severe mortality and morbidity from respiratory, cardiovascular, and other diseases. Its impact is especially concerning in cities; as the urban population increases, especially in low- and middle-income countries, large populations risk suffering from these health effects. The Economic Community of West African States (ECOWAS) comprises 15 West African countries, in which many cities are currently experiencing fast growth and industrialization. However, government-led initiatives in air quality monitoring are scarce in ECOWAS countries, which makes it difficult to effectively control and regulate air quality and subsequent health issues. A scoping study was performed following the Arksey and O'Malley methodological framework in order to assess the precise status of air quality monitoring, related policy, and legislation in this region. Scientific databases and gray literature searches were conducted, and the results were contrasted through expert consultations. It was found that only two ECOWAS countries monitor air quality, and most countries have insufficient legislation in place. Public health surveillance data in relation to air quality data is largely unavailable. In order to address this, improved air quality surveillance, stricter and better-enforced regulations, regional cooperation, and further research are strongly suggested for ECOWAS.

Biogenic Iron Preserves Structures during Fossilization: A Hypothesis: Iron from Decaying Tissues May Stabilize Their Morphology in the Fossil Record.

It is hypothesized that iron from biological tissues, liberated during decay, may have played a role in inhibiting loss of anatomical information during fossilization of extinct organisms. Most tissues in the animal kingdom contain iron in different forms. A widely distributed iron-bearing molecule is ferritin, a globular protein that contains iron crystallites in the form of ferrihydrite minerals. Iron concentrations in ferritin are high and ferrihydrites are extremely reactive. When ancient animals are decaying on the sea floor under anoxic environmental conditions, ferrihydrites may initialize the selective replication of some tissues in pyrite FeS2 . This model explains why some labile tissues are preserved, while other more resistant structures decay and are absent in many fossils. A major implication of this hypothesis is that structures described as brains in Cambrian arthropods are not fossilization artifacts, but are instead a source of information on anatomical evolution at the dawn of complex animal life.

Is plasma GABA level a biomarker of Post-Traumatic Stress Disorder (PTSD) severity? A preliminary study.

OBJECTIVES: An increased reactivity to the environment is observed in Post-Traumatic Stress Disorder (PTSD). It would be related to impairment of the Gamma Amino Butyric Acid (GABA) neurotransmission. The study aimed to evaluate plasma GABA concentration as a candidate for PTSD severity biomarker. METHODS: This hypothesis was studied in 17 PTSD patients and 17 healthy Controls using classic and emotional Stroop paradigms. Plasma GABA concentrations were assessed before and after both Stroop tests to evaluate GABA basal tone and GABA reactivity (change in GABAp), respectively. RESULTS: During baseline, PTSD had lower plasma GABA concentrations than the Controls. After the Stroop conflicts GABA reactivity was also lower in PTSD than in the Controls. The GABA baseline tone was negatively correlated with the severity of the PTSD symptoms. This relation was only marginally observed for GABA reactivity. The results produced a trend due to the small size of the sample compared to the number of statistical results given. CONCLUSION: Altogether, the reduced GABA concentration observed in PTSD could be considered as a possible biomarker for PTSD severity.

4-hydroxyphenylpyruvate dioxygenase catalysis: identification of catalytic residues and production of a hydroxylated intermediate shared with a structurally unrelated enzyme.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the conversion of 4-hydroxyphenylpyruvate (HPP) into homogentisate. HPPD is the molecular target of very effective synthetic herbicides. HPPD inhibitors may also be useful in treating life-threatening tyrosinemia type I and are currently in trials for treatment of Parkinson disease. The reaction mechanism of this key enzyme in both plants and animals has not yet been fully elucidated. In this study, using site-directed mutagenesis supported by quantum mechanical/molecular mechanical theoretical calculations, we investigated the role of catalytic residues potentially interacting with the substrate/intermediates. These results highlight the following: (i) the central role of Gln-272, Gln-286, and Gln-358 in HPP binding and the first nucleophilic attack; (ii) the important movement of the aromatic ring of HPP during the reaction, and (iii) the key role played by Asn-261 and Ser-246 in C1 hydroxylation and the final ortho-rearrangement steps (numbering according to the Arabidopsis HPPD crystal structure 1SQD). Furthermore, this study reveals that the last step of the catalytic reaction, the 1,2 shift of the acetate side chain, which was believed to be unique to the HPPD activity, is also catalyzed by a structurally unrelated enzyme.

Laboratory measurements of electrostatic solitary structures generated by beam injection.

Electrostatic solitary structures are generated by injection of a suprathermal electron beam parallel to the magnetic field in a laboratory plasma. Electric microprobes with tips smaller than the Debye length (λDe) enabled the measurement of positive potential pulses with half-widths 4 to 25λDe and velocities 1 to 3 times the background electron thermal speed. Nonlinear wave packets of similar velocities and scales are also observed, indicating that the two descend from the same mode which is consistent with the electrostatic whistler mode and result from an instability likely to be driven by field-aligned currents.

Ordovician faunas of Burgess Shale type.

The renowned soft-bodied faunas of the Cambrian period, which include the Burgess Shale, disappear from the fossil record in the late Middle Cambrian, after which the Palaeozoic fauna dominates. The disappearance of faunas of Burgess Shale type curtails the stratigraphic record of a number of iconic Cambrian taxa. One possible explanation for this loss is a major extinction, but more probably it reflects the absence of preservation of similar soft-bodied faunas in later periods. Here we report the discovery of numerous diverse soft-bodied assemblages in the Lower and Upper Fezouata Formations (Lower Ordovician) of Morocco, which include a range of remarkable stem-group morphologies normally considered characteristic of the Cambrian. It is clear that biotas of Burgess Shale type persisted after the Cambrian and are preserved where suitable facies occur. The Fezouata biota provides a link between the Burgess Shale communities and the early stages of the Great Ordovician Biodiversification Event.

Application of laccase-mediator system (LMS) for the degradation of organophosphorus compounds.

Degradation of organophosphorus compounds was achieved in the presence of purified fungal laccase from Trametes versicolor and a small molecular weight redox mediator (ABTS). This laccase-mediator system (LMS) catalyzed degradation of VX, PhX and VR while had no apparent effect on CVX, ecothiophate or demeton. Inhibition of ABTS oxidation was shown with VX, PhX, VR and CVX. Results with CVX suggest either no degradation subsequent to interaction with the laccase active site or the formation of a new toxic compound. PhX degradation was also monitored by mass spectroscopy, a method that allowed us to identify certain intermediates formed during OP degradation. Altogether, results underline the importance of the OP nitrogen atom at beta-position and of its substituents, even though the intimate mechanism of laccase-catalyzed degradation is not yet known.

Physicochemical properties and membrane interactions of anti-apoptotic derivatives 2-(4-fluorophenyl)-3-(pyridin-4-yl)imidazo[1,2-a]pyridine depending on the hydroxyalkylamino side chain length and conformation: an NMR and ESR study.

Three imidazo[1,2-a]pyridine derivatives 3a-c have been synthesized from p38 kinase inhibitor structures and evaluated as anti-apoptosis agents. These drugs were designed to interact with nucleic acids and membrane interactions by varying the chain length in position 6, from hydroxyethylamino (3a), to hydroxybutylamino (3b) and hydroxyhexylamino (3c). First experiments showed that 3a and 3b were insoluble in water while 3c could be solubilized in water despite its partition coefficient (logP=3.2). This latter feature was explained by the formation of a fifth intramolecular cycle thus allowing supramolecular structure formation (NMR and MD calculations). The interactions with membranes have been studied using (1)H, (2)H, (31)P Nuclear Magnetic Resonance (NMR), Electron Spin Resonance (ESR) and High Resolution-Magic Angle Spinning (HR-MAS). Despite the insolubility of 3a and 3b in water, these derivatives could be partially solubilized by synthetic phospholipidic model membranes (small unilamellar vesicles, SUV). (1)H NMR paramagnetic broadening experiments performed on the same models showed that 3a was located in the external layer, probably close to the surface while 3b only formed external superficial adducts. Supplementary (31)P, (2)H NMR and ESR experiments on phospholipid dispersions confirmed the location of 3a close to the polar headgroup of the external layer of the membrane, this resulting in a 2K lowering of the transition temperature. Moreover, no significant interaction was detected on the deep part of the layer ((2)H NMR and 16NS ESR experiments). This binding was also found in the presence of cell cultures, as revealed by HR-MAS NMR experiments. Conversely, no significant interaction with membranes was found with 3b or 3c. From both the unexpected solubility of 3c and 3a interactions with membranes, further chemical modifications were finally proposed.

Mechanism of hydrolysis of dicholine esters with long polymethylene chain by human butyrylcholinesterase.

Human butyrylcholinesterase hydrolyzes long chain dicholine esters more rapidly than short chain dicholine esters. The active site of butyrylcholinesterase is deeply buried within the enzyme molecule and there is limited space for binding of large compounds. Our goal was to understand how butyrylcholinesterase accommodates long chain dicholine esters to make them better substrates than short chain dicholine esters. For this purpose we studied the rate of hydrolysis of adipyldicholine (n=4) and sebacyldicholine (n=8) with mass spectrometry, a method that allowed monitoring the dicholine substrates, the monocholine intermediates, the dicarboxylic acid and choline products. It was shown that hydrolysis of adipyldicholine involves two consecutive steps, dicholine ester hydrolysis followed by relatively slow monocholine ester hydrolysis. However, sebacyldicholine was hydrolyzed at both choline ester sites, though hydrolysis of dicholine was faster than hydrolysis of monocholine. Sebacyldicholine was completely converted to sebacic acid and choline within 90 min, whereas only 15% of the adipyldicholine was converted to adipic acid in this time. Molecular modeling indicated that these dicholine esters can bind to butyrylcholinesterase in two energetically equivalent alternative conformations that may theoretically lead to hydrolysis. The long chain dicholine ester makes closer contact than the short chain ester between one of its carbonyl carbons and the catalytic Ser198, thus explaining why long-chain dicholine esters are hydrolyzed more rapidly by butyrylcholinesterase.

Electrochemical and chemical formation of [Mn4(IV)O5(terpy)4(H2O)2]6+, in relation with the photosystem II oxygen-evolving center model [Mn2(III,IV)O2(terpy)2(H2O)2]3+.

To examine the real ability of the binuclear di-mu-oxo complex [Mn2(III,IV)O2(terpy)2(H2O)2]3+ (2) to act as a catalyst for water oxidation, we have investigated in detail its redox properties and that of its mononuclear precursor complex [Mn(II)(terpy)2]2+ (1) in aqueous solution. It appears that electrochemical oxidation of 1 allows the quantitative formation of 2 and, most importantly, that electrochemical oxidation of 2 quantitatively yields the stable tetranuclear Mn(IV) complex, [Mn4(IV)O5(terpy)4(H2O)2]6+ (4), having a linear mono-mu-oxo{Mn2(mu-oxo)2}2 core. Therefore, these results show that the electrochemical oxidation of 2 in aqueous solution is only a one-electron process leading to 4 via the formation of a mono-mu-oxo bridge between two oxidized [Mn2(IV,IV)O2(terpy)2(H2O)2]4+ species. 4 is also quantitatively formed by dissolution of the binuclear complex [Mn2(IV,IV)O2(terpy)2(SO4)2] (3) in aqueous solutions. Evidence of this work is that 4 is stable in aqueous solutions, and even if it is a good synthetic analogue of the "dimers-of-dimers" model compound of the OEC in PSII, this complex is not able to oxidize water. As a consequence, since 4 results from an one-electron oxidation of 2, 2 cannot act as an efficient homogeneous electrocatalyst for water oxidation. This work demonstrates that a simple oxidation of 2 cannot produce molecular oxygen without the help of an oxygen donor.