An economic evaluation of tranexamic acid to prevent postpartum haemorrhage in women with vaginal delivery: the randomised controlled TRAAP trial.

OBJECTIVE: To estimate the cost-effectiveness of tranexamic acid (TXA) use to prevent postpartum haemorrhage. DESIGN: A trial-based economic evaluation. SETTING: Fifteen French university maternity hospitals. POPULATION: Women enrolled in the TRAAP randomised controlled trial comparing TXA versus placebo in women with vaginal delivery. TRAAP failed to show a reduction in postpartum haemorrhage of at least 500 ml in the intervention arm but evidenced significant lower rates of secondary outcomes related to blood loss. METHODS & MAIN OUTCOME MEASURES: We estimated direct medical costs from within-trial hospital resources collected prospectively from the study report form. All resources were costed at their value to the hospital. We estimated incremental cost per incremental haemorrhage averted. RESULTS: Among the 4079 women in the TRAAP trial, data necessary to calculate costs were available for 3836 (94.0%). The average total costs in the TXA and control groups were €2278 ± 388 and €2288 ± 409 per woman, respectively (P = 0.79). In women with postpartum haemorrhage of at least 500 ml (trial primary endpoint), costs were €2359 ± 354 and €2409 ± 525 (P = 0.14); for provider-assessed clinically significant postpartum haemorrhage and postpartum haemorrhage of at least 1000 ml, costs were respectively €2316 ± 347 versus €2381 ± 521 (P = 0.22) and €2321 ± 318 versus €2411 ± 590 (P = 0.35) in the tranexamic and placebo groups, respectively. The probabilistic sensitivity analysis showed that the use of TXA had a 65-73% probability of saving costs and improving outcome. CONCLUSIONS: Our findings support the use of TXA, as both bleeding events and cost may be reduced three out of four times. TWEETABLE ABSTRACT: Tranexamic acid at vaginal delivery reduces both costs and bleeding events 3 times out of 4.

Thermodynamic and structural properties of binary calcium silicate glasses: insights from molecular dynamics.

We study calcium silicate glass of composition (CaO)X(SiO2)(1-X), where X = 40-70 mol%, by means of molecular dynamics for different cooling rates between 1011-1013 K s-1. The thermodynamic and kinetic properties of calcium silicate materials are determined, discussed, and correlated to local structures at short and intermediate range orders and to the potential energies of the oxygen atoms. We show that the amount of non-bridging oxygens and the appearance of free oxygens are related to the increase of the glass transition temperature for an increasing CaO content. Our results are analyzed and discussed in connection with the available experimental data.

Comparing the broad socio-cognitive profile of youth with Williams syndrome and 22q11.2 deletion syndrome.

BACKGROUND: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. METHODS: Eighty-two children participated in four study groups: WS (n = 18), 22q112.DS (n = 24), age-matched individuals with idiopathic developmental disability (IDD; n = 20) and typically developing (TD) controls (n = 20). Participants completed four socio-cognitive tests: facial emotion recognition, mental state attribution, differentiating real from apparent emotions and trait inference based on motives and actions-outcomes. RESULTS: The current findings demonstrate that children with WS were better in labelling happy faces compared with children with 22q11.2DS, partially reflecting their exaggerated social drive. In the false belief task, however, the WS and IDD groups performed poorly compared with the 22q11.2DS group, possibly due to their difficulty to interpret subtle social cues. When asked to identify the gap between real-negative vs. apparent-positive emotions, the 22q11.2DS group performed similarly to TD children but better than the WS group, possibly due to their anxious personality and their innate bias towards negatively valence cues. Finally, individuals with WS were more willing to become friends with a story character even when the character's motives were negative, reflecting their difficulty to avoid potentially harmful real-life situations. CONCLUSIONS: Overall, our multi-facet socio-cognitive battery uncovered strengths and weaknesses in social cognition that are syndrome-specific, shared among the genetic syndromes, or common to the three clinical groups compared with healthy controls. Our findings underscore the need to devise age-specific and condition-specific assessment tools and intervention programs towards improving these children's socio-cognitive deficits.

Designing heavy metal oxide glasses with threshold properties from network rigidity.

Here, we show that a new class of glasses composed of heavy metal oxides involving transition metals (V2O5-TeO2) can surprisingly be designed from very basic tools using topology and rigidity of their underlying molecular networks. When investigated as a function of composition, such glasses display abrupt changes in network packing and enthalpy of relaxation at Tg, underscoring presence of flexible to rigid elastic phase transitions. We find that these elastic phases are fully consistent with polaronic nature of electronic conductivity at high V2O5 content. Such observations have new implications for designing electronic glasses which differ from the traditional amorphous electrolytes having only mobile ions as charge carriers.

Determination of heavy metal content and lipid profiles in mussel extracts from two sites on the moroccan atlantic coast and evaluation of their biological activities on MIN6 pancreatic cells.

Mussels may concentrate pollutants, with possibly significant side effects on human health. Therefore, mussels (Mytilus galloprovincialis) from two sites of the Moroccan Atlantic coast (Jorf Lasfar [JL], an industrial site, and Oualidia [OL], a vegetable-growing area), were subjected to biochemical analyses to quantify the presence of heavy metals (Cd, Cr, and Pb) and to establish the lipid profile: fatty acid, cholesterol, oxysterol, phytosterol and phospholipid content. In addition, mussel lipid extracts known to accumulate numerous toxic components were tested on murine pancreatic ß-cells (MIN6), and their biological activities were measured with various flow cytometric and biochemical methods to determine their impacts on cell death induction, organelle dysfunctions (mitochondria, lysosomes, and peroxisomes), oxidative stress and insulin secretion. The characteristics of JL and OL lipid extracts were compared with those of commercially available mussels from Spain (SP) used for human consumption. OL and JL contained heavy metals, high amounts of phospholipids, and high levels of oxysterols; the [(unsaturated fatty acids)/(saturated fatty acids)] ratio, which can be considered a sign of environmental stress leading to lipid peroxidation, was low. On MIN6 cells, JL and OL lipid extracts were able to trigger cell death. This event was associated with overproduction of H2 O2 , increased catalase activity, a decreased GSH level, lipid peroxidation and stimulation of insulin secretion. These effects were not observed with SP lipid extracts. These data suggest that some components from OL and JL lipid extracts might predispose to pancreatic dysfunctions. Epidemiological studies would be needed to assess the global risk on human health and the metabolic disease incidence in a context of regular seafood consumption from the OL and JL areas.

A Multiphysics Thermoelastoviscoplastic Damage Internal State Variable Constitutive Model including Magnetism.

We present a macroscale constitutive model that couples magnetism with thermal, elastic, plastic, and damage effects in an Internal State Variable (ISV) theory. Previous constitutive models did not include an interdependence between the internal magnetic (magnetostriction and magnetic flux) and mechanical fields. Although constitutive models explaining the mechanisms behind mechanical deformations caused by magnetization changes have been presented in the literature, they mainly focus on nanoscale structure-property relations. A fully coupled multiphysics macroscale ISV model presented herein admits lower length scale information from the nanoscale and microscale descriptions of the multiphysics behavior, thus capturing the effects of magnetic field forces with isotropic and anisotropic magnetization terms and moments under thermomechanical deformations. For the first time, this ISV modeling framework internally coheres to the kinematic, thermodynamic, and kinetic relationships of deformation using the evolving ISV histories. For the kinematics, a multiplicative decomposition of deformation gradient is employed including a magnetization term; hence, the Jacobian represents the conservation of mass and conservation of momentum including magnetism. The first and second laws of thermodynamics are used to constrain the appropriate constitutive relations through the Clausius-Duhem inequality. The kinetic framework employs a stress-strain relationship with a flow rule that couples the thermal, mechanical, and magnetic terms. Experimental data from the literature for three different materials (iron, nickel, and cobalt) are used to compare with the model's results showing good correlations.

Long term experience of robotic retroperitoneal partial nephrectomy as the default approach in the management of renal masses: should the paradigm shift?

Although retroperitoneal surgery has demonstrated a better quality of recovery compared to transperitoneal routes, Retroperitoneal Robot Assisted Partial Nephrectomy (RRAPN) remains proportionally infrequent. As the boundaries of what is achievable robotically continue to be pushed, we present our experience at a high-volume tertiary referral centre that specialises in retroperitoneal surgery, exploring its feasibility as standard of care in the management of small renal masses. A prospective database of 784 RAPNs (2009-2020) was reviewed and 721 RRAPNs (92%) were performed at our centre. In our practice, we utilise a four-port approach to RRAPN. Patient, tumour and operative characteristics were assessed and both oncological outcomes and trifecta and pentafecta achievements were determined. Pentafecta was defined as achieving trifecta (negative surgical margin, no post-operative complications and WIT of < 25 min) plus over 90% estimated GFR preservation and no CKD stage upgrading at 1 year. Multivariate analysis was conducted to predict peri-operative factors which may prevent achieving a trifecta/pentafecta outcome. From 784 cases, 112 RAPNs were performed for imperative reasons, whilst the remainder were elective. Mean BMI ± s.d amongst our cohort was 28.6 ± 5.7. Mean tumour size was 3.1 cm (range 0.8-10.5 cm) and 47% of cases were stratified as intermediate/high risk using R.E.N.A.L nephrometry scoring. Forty-six patients had lesions in a hilar location, and 31% were anterior. Median blood loss was 30mls, with an open conversion rate of 1% and transfusion rate of 1.6%. Median warm ischaemic time (WIT) was 21 min, positive surgical margins were found in 4% and our post-operative Clavien 3/ > complication rate was 2.6%. We had a 1-day median length of stay with a 30 day readmission rate of 2%. Of 631 patients (80%) with a definitive histological diagnosis of cancer, 23% had T1b/ > disease. Over a mean 15 month follow-up period (range 1-125 months), 2% of patients developed recurrences and our cohort demonstrated a 99% 5 year cancer specific survival. Trifecta was achieved in 67% of cases and pentafecta in 47%. Age (p = 0.05), operative time (p = 0.008), pT1b tumours (p = 0.03), R.E.N.A.L score and blood loss (p = 0.001) were found to statistically significantly influence achievement of trifecta. Pentafecta achievement was influenced by R.E.N.A.L score (p = 0.008), operative time (p = 0.001) and blood loss (p = 0.001). We demonstrate the retroperitoneal approach in RAPN is feasible and safe irrespective of lesion location and complexity. In the hands of high-volume centres that are skilled in the retroperitoneal approach the benefits of retroperitoneal surgery can be extended even to challenging cohorts of patients without compromising their oncological or functional outcomes.

Characterization of arrowroot (Maranta arundinacea) starch as a potential starch source for the food industry.

Arrowroot is an underutilized tuber crop in Sri Lanka and the characterization of starch was done to identify its nutritional, physicochemical, and functional properties to evaluate its potential for use in the food industry. This study distinctly advances the field of arrowroot starch characterization by providing more characterization techniques for starch samples from Sri Lanka. Arrowroot starch colour was closely similar to colour of wheat flour indicating that the effect of colour is minimum when replacing wheat flour. Oval, spherical, and irregular globular shapes were the predominant starch granule shapes for arrowroot. The average length of starch granules was 44.99 ± 1.27 µm while the width of granules was 31.44 ± 0.58 µm. The least gelation concentration was 8.0% indicating its better gel-forming ability. The nutritional composition of arrowroot starch consisted of low crude protein (0.72 ± 0.02%), crude fat (0.26 ± 0.19%), and crude fiber (1.00 ± 0.09%) contents indicating the purity of starch. Sodium, Potassium, Calcium, Iron, and Zinc contents were 52.6 mg/kg, 4312.95 mg/kg, 382.67 mg/kg, 9.07 mg/kg, and 2.59 mg/kg, respectively. Results of flour densities demonstrated the potential of arrowroot starch to be used in the pharmaceutical industry. Arrowroot starch had high viscosity defining its potential as a thickener. The starch also had high swelling power and solubility indices while solubility was positively correlated with viscosity (0.679; P > 0.05). The low moisture absorbance indicates a longer shelf life of stored arrowroot starch. Onset temperature (To) of 75.02 °C, peak temperature (Tp) of 77.95 °C, and conclusion temperature (Tc) of 82.43 °C were resulted from DSC thermogram. Arrowroot was identified as an A-type starch from x-ray diffractometry and the FT-IR spectrum of arrowroot was identical to starch and presented the carbohydrate nature of starch. Thus, arrowroot starch has a high potential to be used in the food industry based on its functional properties.

Splice variant PRKC-ζ(-PrC) is a novel biomarker of human prostate cancer.

BACKGROUND: Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues. METHODS: Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ. Hydropathy analysis was employed to analyse the hypothetical protein sequence subsequently translated and to identify an appropriate epitope to generate a specific monoclonal antibody. RESULTS: A novel sequence was identified within the 3'-terminal domain of human PRKCZ that, in prostate cancer cell lines and tissues, is expressed during transcription and thereafter translated into protein (designated PKC-ζ(-PrC)) independent of conventional PKC-ζ(-a). The monoclonal antibody detected expression of this 96 kD protein only within malignant prostatic epithelium. INTERPRETATION: Transcription and translation of this gene sequence, including previous intronic sequences, generates a novel specific biomarker of human prostate cancer. The presence of catalytic domains characteristic of classic PKC-ß and atypical PKC-ι within PKC-ζ(-PrC) provides a potential mechanism for this PRKCZ variant to modulate the malignant prostatic phenotype out-with normal cell-regulatory control.

Hexavalent Chromium Reduction and Accumulation by Acinetobacter AB1 Isolated from Fez Tanneries in Morocco.

Hexavalent chromium reduction and accumulation by Acinetobacter AB1 isolated from Fez tanneries effluents were tested. The effects of some environmental factors such as pH, temperature, and exposure time on Cr(VI) reduction and resistance were investigated. We found that this strain was able to resist to concentrations as high as 400 mg/l of Cr(VI). Moreover, pH 10 and the temperature 30°C constitute favourable conditions to the growth and reduction of Acinetobacter AB1. Complete reduction of Cr(VI) was observed at low initial Cr(VI) concentrations of 50 mg/l after 72 h of incubation. Furthermore, Transmission electron microscope (TEM) analysis showed morphological changes in AB1 strain due 48H exposure to 100 mg/l chromate concentration and revealed circular electron dense (dark black point) inclusion within the cell cytoplasm suggesting chromium deposition within the cells.

The impact of a fellow on a regional robotic-assisted partial nephrectomy service.

INTRODUCTION: Training a fellow has a cost in time and effort for the surgeon and their team. Their relative inexperience may also negatively affect the patient. The aim of this study was to determine and quantify the impact of a fellow on a regional robotic-assisted partial nephrectomy service and on perioperative outcomes. MATERIALS AND METHODS: We reviewed the prospectively collected data for 522 patients who had undergone robotic-assisted partial nephrectomy since 2015 during the tenure of six fellows. Perioperative outcomes for three groups were compared: group A (no fellow participation), group B (some participation) and group C (fellow completed entire operation). We also reviewed progression over 12 months. RESULTS: Demographics were similar in all groups apart from the percentage of men, which was lower in group C (p < 0.05). Operative time was 27 minutes longer for group B (p < 0.001). Warm ischaemia time was significantly shorter for group A but the difference was only four minutes (p < 0.001). Length of stay was slightly shorter for group C compared with the other groups (p < 0.01). Trifecta achievement was greatest for group A (p < 0.001). There were no perioperative deaths in any group and positive margins, complications and readmissions were low and similar in all groups. Towards the end of their fellowship, fellows performed more operations independently. CONCLUSION: There is a measurable, but small, negative impact of a fellow on a robotic-assisted partial nephrectomy service, which reduces with experience. With appropriate supervision and patient selection, a fellow can be taught robotic-assisted partial nephrectomy without affecting patient safety or treatment outcome.

From Río Tinto to Mars: the terrestrial and extraterrestrial ecology of acidophiles.

The recent geomicrobiological characterization of Río Tinto, Iberian Pyrite Belt (IPB), has proven the importance of the iron cycle, not only in generating the extreme conditions of the habitat (low pH, high concentration of toxic heavy metals) but also in maintaining the high level of microbial diversity, both prokaryotic and eukaryotic, detected in the water column and the sediments. The extreme conditions of the Tinto basin are not the product of industrial contamination but the consequence of the presence of an underground bioreactor that obtains its energy from the massive sulfide minerals of the IPB. To test this hypothesis, a drilling project was carried out to intersect ground waters that interact with the mineral ore in order to provide evidence of subsurface microbial activities and the potential resources to support these activities. The oxidants that drive the system appear to come from the rock matrix, contradicting conventional acid mine drainage models. These resources need only groundwater to launch microbial metabolism. There are several similarities between the vast deposits of sulfates and iron oxides on Mars and the main sulfide-containing iron bioleaching products found in the Tinto. Firstly, the short-lived methane detected both in Mars' atmosphere and in the sediments and subsurface of the IPB and secondly, the abundance of iron, common to both. The physicochemical properties of iron make it a source of energy, a shield against radiation and oxidative stress as well as a natural pH controller. These similarities have led to Río Tinto's status as a Mars terrestrial analogue.

Attenuation of 7-ketocholesterol- and 7ß-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases.

Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7ß-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7ß-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7ß-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer's disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7ß-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7ß-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7ß-hydroxycholesterol.

Direct evidence of a characteristic length scale of a dynamical nature in the Boolchand phase of glasses.

The ac conductivity spectra of xAgI-(1 - x)AgPO(3) fast-ion conducting glasses spanning the flexible, intermediate (isostatically rigid), and stressed rigid phases are analyzed. The rescaled frequency-dependent spectra are mapped into time-dependent mean-square displacements out of which a typical length scale characterizing the spatial extent sqrt[(R(2)(∞))] of nonrandom subdiffusive regions of ionic motions is computed. The latter quantity is studied as a function of AgI compositions, and is found to display a maximum isostatic compositions, providing the first clear evidence of a typical length scale of a dynamical nature when a system becomes isostatically rigid and enters that phase.

Road traffic fatalities in Qatar, Jordan and the UAE: estimates using regression analysis and the relationship with economic growth.

Smeed's equation is a widely used model for prediction of traffic fatalities but has been inadequate for use in developing countries. We applied regression analysis to time-series data on vehicles, exponential models for fatality prediction, producing an average absolute error of 20.9% for Qatar, 10.9% for population and traffic fatalities in the United Arab Emirates (UAE), Jordan and Qatar. The data were fitted to Jordan and 5.5% for the UAE. We found a strong linear relationship between gross domestic product and fatality rate.

Elastic flexibility, fast-ion conduction, boson and floppy modes in AgPO(3)-AgI glasses.

Raman scattering, IR reflectance and modulated-DSC measurements are performed on specifically prepared dry (AgI)(x)(AgPO(3))(1-x) glasses over a wide range of compositions 0%37.8% are elastically flexible. Raman optical elasticity power laws, trends in the nature of the glass transition endotherms, corroborate the three elastic phase assignments. Ionic conductivities reveal a step-like increase when glasses become stress-free at x>x(c)(1) = 9.5% and a logarithmic increase in conductivity (σ∼(x-x(c)(2))(µ)) once they become flexible at x>x(c)(2) = 37.8% with a power law µ = 1.78. The power law is consistent with percolation of 3D filamentary conduction pathways. Traces of water doping lower T(g) and narrow the reversibility window, and can also completely collapse it. Ideas on network flexibility promoting ion conduction are in harmony with the unified approach of Ingram et al (2008 J. Phys. Chem. B 112 859), who have emphasized the similarity of process compliance or elasticity relating to ion transport and structural relaxation in decoupled systems. Boson mode frequency and scattering strength display thresholds that coincide with the two elastic phase boundaries. In particular, the scattering strength of the boson mode increases almost linearly with glass composition x, with a slope that tracks the floppy mode fraction as a function of mean coordination number r predicted by mean-field rigidity theory. These data suggest that the excess low frequency vibrations contributing to the boson mode in flexible glasses come largely from floppy modes.

Extraction of extracellular polymeric substances from the acidophilic bacterium Acidiphilium 3.2Sup(5).

Extraction of extracellular polymeric substances (EPS) from Acidiphilium 3.2Sup(5) was investigated using five methods: EDTA, NaOH, ion exchange resin, heating and centrifugation. The bacterium studied presents promising application in microbial fuel cells (MFCs). The degree of cellular lysis provoked by each method was determined by UV-visible spectroscopy of cultures before and after EPS extraction. In addition, two electron microscopy techniques (TEM and SEM) were employed to determine the degree of attachment and the growth of the biofilm overtime on two solid supports: carbon fibre cloth and graphite rods. The main constituents of the EPS extracted by all methods were proteins and carbohydrates, as confirmed by FT-IR analysis, showing the major presence of carboxylic, hydroxylic and amino groups. The greater extractions of EPS were obtained using EDTA. This method also produced a less degree of cellular lysis. Furthermore, both the amount and the chemical composition of EPS strongly depended on the extraction method used.

A microglial cell model for acyl-CoA oxidase 1 deficiency.

Acyl-CoA oxidase 1 (ACOX1) deficiency is a rare and severe peroxisomal leukodystrophy associated with a very long-chain fatty acid (VLCFA) ß-oxidation defect. This neurodegenerative disease lacks relevant cell models to further decipher the pathomechanisms in order to identify novel therapeutic targets. Since peroxisomal defects in microglia appear to be a key component of peroxisomal leukodystrophies, we targeted the Acox1 gene in the murine microglial BV-2 cell line. Using CRISPR/Cas9 gene editing, we generated an Acox1-deficient cell line and validated the allelic mutations, which lead to the absence of ACOX1 protein and enzymatic activity. The activity of catalase, the enzyme degrading H2O2, was increased, likely in response to the alteration of redox homeostasis. The mutant cell line grew more slowly than control cells without obvious morphological changes. However, ultrastructural analysis revealed an increased number of peroxisomes and mitochondria associated with size reduction of mitochondria. Changes in the distribution of lipid droplets containing neutral lipids have been observed in mutant cells; lipid analysis revealed the accumulation of saturated and monounsaturated VLCFA. Besides, expression levels of genes encoding interleukin-1 beta and 6 (IL-1ß and IL-6), as well as triggering receptor expressed on myeloid cells 2 (Trem2) were found modified in the mutant cells suggesting modification of microglial polarization and phagocytosis ability. In summary, this Acox1-deficient cell line presents the main biochemical characteristics of the human disease and will serve as a promising model to further investigate the consequences of a specific microglial peroxisomal ß-oxidation defect on oxidative stress, inflammation and cellular functions.

Stability domains of actin genes and genomic evolution.

In eukaryotic genes, the protein coding sequence is split into several fragments, the exons, separated by noncoding DNA stretches, the introns. Prokaryotes do not have introns in their genomes. We report calculations of the stability domains of actin genes for various organisms in the animal, plant, and fungi kingdoms. Actin genes have been chosen because they have been highly conserved during evolution. In these genes, all introns were removed so as to mimic ancient genes at the time of the early eukaryotic development, i.e., before intron insertion. Common stability boundaries are found in evolutionarily distant organisms, which implies that these boundaries date from the early origin of eukaryotes. In general, the boundaries correspond with intron positions in the actins of vertebrates and other animals, but not much for plants and fungi. The sharpest boundary is found in a locus where fungi, algae, and animals have introns in positions separated by one nucleotide only, which identifies a hot spot for insertion. These results suggest that some introns may have been incorporated into the genomes through a thermodynamically driven mechanism, in agreement with previous observations on human genes. They also suggest a different mechanism for intron insertion in plants and animals.

Mineralization and Preservation of an extremotolerant Bacterium Isolated from an Early Mars Analog Environment.

The artificial mineralization of a polyresistant bacterial strain isolated from an acidic, oligotrophic lake was carried out to better understand microbial (i) early mineralization and (ii) potential for further fossilisation. Mineralization was conducted in mineral matrixes commonly found on Mars and Early-Earth, silica and gypsum, for 6 months. Samples were analyzed using microbiological (survival rates), morphological (electron microscopy), biochemical (GC-MS, Microarray immunoassay, Rock-Eval) and spectroscopic (EDX, FTIR, RAMAN spectroscopy) methods. We also investigated the impact of physiological status on mineralization and long-term fossilisation by exposing cells or not to Mars-related stresses (desiccation and radiation). Bacterial populations remained viable after 6 months although the kinetics of mineralization and cell-mineral interactions depended on the nature of minerals. Detection of biosignatures strongly depended on analytical methods, successful with FTIR and EDX but not with RAMAN and immunoassays. Neither influence of stress exposure, nor qualitative and quantitative changes of detected molecules were observed as a function of mineralization time and matrix. Rock-Eval analysis suggests that potential for preservation on geological times may be possible only with moderate diagenetic and metamorphic conditions. The implications of our results for microfossil preservation in the geological record of Earth as well as on Mars are discussed.