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Objective Using positron emission tomography (PET) with [11C]flumazenil ([11C]FMZ), an antagonist of the central benzodiazepine site located within the GABAA receptor, we quantified and mapped neuronal damage in the gray matter (GM) of patients with multiple sclerosis (MS) at distinct disease stages. We investigated the relationship between neuronal damage and white matter (WM) lesions and evaluated the clinical relevance of this neuronal PET metric. Methods A cohort of 18 MS patients (9 progressive and 9 relapsing-remitting) was compared to healthy controls and underwent neurological and cognitive evaluations, high-resolution dynamic [11C]FMZ PET imaging and brain magnetic resonance imaging. [11C]FMZ binding was estimated using the partial saturation protocol providing voxel-wise absolute quantification of GABAA receptor concentration. PET data were evaluated using a region of interest (ROI) approach as well as on a vertex-by-vertex basis. Results [11C]FMZ binding was significantly decreased in the cortical GM of MS patients, compared to controls (–10%). Cortical mapping of benzodiazepine receptor concentration ([11C]FMZ Bmax) revealed significant intergroup differences in the bilateral parietal cortices and right frontal areas. ROI analyses taking into account GM volume changes showed extensive decrease in [11C]FMZ binding in bilateral parietal, cingulate, and insular cortices as well as in the thalami, amygdalae, and hippocampi. These changes were significant in both progressive and relapsing-remitting forms of the disease and correlated with WM T2-weighted lesion load. [11C]FMZ cortical binding correlated with cognitive performance. Interpretation This pilot study showed that PET with [11C]FMZ could be a promising and sensitive quantitative marker to assess and map the neuronal substrate of GM pathology in MS. Ann Neurol 2015;78:554–567

Objective Sneddon syndrome (SS) is characterized by the association of a livedo reticularis with stroke. Clinicoradiological features of its neurological manifestations, its prognosis, and the frequency of associated cardiac valvulopathy remain poorly known, particularly in the absence of antiphospholipid antibodies (APL). The objectives were to assess the clinicoradiological pattern of SS without APL (SSAPL−) and its midterm prognosis. Methods Clinical data, transthoracic echocardiograms, and brain imaging of 53 consecutive patients (83% women) with SSAPL−, followed up at our institution between 1991 and 2011, were reviewed. Results Seventy-four strokes were reported; 76% were ischemic strokes (IS), 15% transient ischemic attacks, and 9% hemorrhagic strokes. Heart valve lesions were found in 50% of the cases. Brain imaging showed 177 IS of 3 different types: large territorial (43%), small distal corticosubcortical (14%), and small deep (23%) IS. No significant association was found between the valve involvement and the presence of territorial IS. After a mean follow-up of 7.4 years, 82% of patients had a modified Rankin Scale score ≤ 2. The ischemic event recurrence rate was 20%, with a similar annual rate in the antiplatelet group (3%) compared to the anticoagulation group (2.7%). Interpretation SSAPL− is not only a neurocutaneous disorder, but is frequently associated with heart valve involvement. The latter does not influence the IS type, which suggests that strokes are caused by vasculopathy of the small and medium-size cerebral arteries. Our results show no progression toward a serious disability in the majority of the cases and a moderate recurrence rate under antiplatelet therapy. Ann Neurol 2015;77:817–829

Objective To assess the predictive value of hemoperitoneum for the outcome of methotrexate (MTX) treatment of ectopic pregnancy (EP). Methods This observational prospective single-center study included women presenting with EP treated with MTX from November 2007 to November 2009. The percentage of women with hemoperitoneum at the beginning of MTX treatment was compared between two groups: those whose treatment was successful and those whose treatment failed. The rate of hemoperitoneum in each group and its value in predicting the outcome of MTX treatment of EP were assessed. Results MTX treatment was successful in 69 of 93 (74%) cases. The percentage of women with hemoperitoneum at the beginning of treatment was significantly higher in women in whom MTX treatment failed as compared to those in whom it was successful (15/24 (62.5%) vs 17/69 (24.6%); P = 0.001). The likelihood of requiring surgery following treatment with MTX was higher in women with hemoperitoneum (odds ratio, 5.1; 95% CI, 1.74–15.14). Study of the diagnostic performance of hemoperitoneum in predicting the need for surgical treatment after MTX treatment revealed a sensitivity of 0.63, a specificity of 0.76, a positive predictive value of 0.47 and a negative predictive value of 0.85. Conclusions The presence of hemoperitoneum appears to be a risk factor for MTX treatment failure. It is important to inform women as fully as possible about the risk of such failure. Nonetheless, the predictive value of this sign is insufficient for either routinely excluding women with hemoperitoneum from MTX treatment or omitting post-treatment monitoring. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Zusammenfassung Es wurde der Ruhe-Nuchtern-Sauerstoffverbrauch (RNSV) an unterschiedlich ernahrten und bei 28° C Umgebungstemperatur gehaltenen jugendlichen, mannlichen Albinoratten bestimmt. Unterstellt man eine Abhangigkeit des RNSV von der Korpermasse (M) nach der logarithmischen Funktion ln(RNSV) = ln(a Mb), ergibt sich der Exponent dieser Gleichung bei Latz-Kost mit b = 0,545 ± 0,009 (n = 248), dagegen bei Altromin-Zuchtfutter mitb = 0,481 ± 0,017 (n = 40). Beide b-Werte sind mit P o) nach 4 bis 14 Wochen ein Minimum. Der Exponent dieses RNSV-Minimums berechnet sich mit b = 0,736 ± 0,022 (n = 40). Er ist mit P

SUMMARY The Oomycete genus Aphanomyces houses plant and animal pathogens found in both terrestrial and aquatic habitats. Aphanomyces euteiches Drechs. causes seedling damping off and root rot diseases on many legumes. It is the most devastating pea (Pisum sativum) disease in several countries, causing up to 80% losses each year. This strictly soil-borne pathogen may survive many years in soil and no efficient chemical control is currently available. The only way to control the disease is to avoid cultivating legumes in infested fields for up to 10 years. Although huge research effort has been devoted to the Oomycete genus Phytophthora during the last decade, A. euteiches received has little attention and mechanisms by which it infects its hosts are still unclear. A. euteiches is nevertheless an interesting parasite to study plant–oomycete interactions as it is pathogenic on the model legume Medicago truncatula. This review summarizes knowledge about the main characteristics of A. euteiches and presents research currently developed to find new strategies to control this pathogen and to gain insight into its pathogenicity. Taxonomy: Aphanomyces euteiches Drechs belongs to a kingdom of diverse eukaryotic protists named Chromista or Straminipila. It is a member of the class Oomycetes (syn. Peronosporomycetes), which gathers organisms resembling fungi through morphological and physiological traits, but are phylogenically related to diatoms, chromophyte algae and other heterokont protists. The genus Aphanomyces is classified within the order Saprolegniales, family Saprolegniaceae s.l. or Leptolegniaceae. Host range: Several legumes were found to be hosts for A. euteiches and this pathogen was isolated from field-grown pea, alfafa, snap bean, vetch, clover, sweet clover and several weed species. Disease symptoms: The disease begins with the yellowing of root tissue. At a later stage, infected roots become brown and the hypocotyl darkens at the soil line. The pathogen infects the cortex of primary and lateral roots and oospores are formed within the root tissues. Useful websites: http://www.indexfungorum.org/Names/Names.asp (links to taxonomy data), http://www.eugrainlegumes.org/; http://www.medicago.org/ (links to the European Union ‘Grain Legume’ Integrated Project).

We have tried to elucidate the origin of phytochemical variation in trees by studying concomitantly the chemical and microsatellite variations in Santalum austrocaledonicum. Eight natural populations were sampled in the New-Caledonian archipelago, a total of 157 individuals being analyzed. The main components, as revealed by gas chromatography (GC), were alpha- and beta-santalol (as in other sandalwood species), although the level of (Z)-lanceol was particularly high. Most of the chemical variation was observed within populations (83.7%). With microsatellites, the variation between populations was more pronounced (32% of the total variation). Although the chemical variation between populations was small, we investigated the effects of genetic drift and migration by comparing the chemical- and molecular-differentiation patterns. The poor congruence between neighbor-joining trees, confirmed by the non-significant Mantel test between the molecular and chemical distance matrices (R = 0.26, P = 0.12). showed that genetic drift and migration are not the main evolutionary forces acting on chemical differentiation between populations. We could not find any effect of soil and rainfall conditions neither. Although the impact of drift and migration cannot be discounted in rationalizing between-population differentiation, the low variation among populations could result from a stabilizing selection caused by the same phytopathogen charge across the natural range.

Objective: Previous research has shown that dehydration is associated with impairment of mood. However, the effect of habitual total fluid intake (TFI) on mood in a population of adults with a wide...

We present a study of the genetic diversity and structure of a tropical tree in an insular system. Santalum austrocaledonicum is endemic to the archipelago of New Caledonia and is exploited for oil extraction from heartwood. A total of 431 individuals over 17 populations were analysed for eight polymorphic microsatellite loci. The number of alleles per locus ranged from 3 to 33 and the observed heterozygosity per population ranged from 0.01 in Mare to 0.74 in Ile des Pins. The genetic diversity was lowest in the most recent islands, the Loyautes, and highest in the oldest island, Grande Terre, as well as the nearby small Ile des Pins. Significant departures from panmixia were observed for some loci–population combinations (per population FIS = 0–0.03 on Grande-Terre and Ile des Pins, and 0–0.67 on Loyautes). A strong genetic differentiation among all islands was observed (FST = 0.22), and the amount of differentiation increased with geographic distance in Iles Loyaute and in Grande Terre. At both population and island levels, island age and isolation seem to be the main factors influencing the amount of genetic diversity. In particular, populations from recent islands had large average FIS that could not be entirely explained by null alleles or a Wahlund effect. This result suggests that, at least in some populations, selfing occurred extensively. Conclusively, our results indicate a strong influence of insularity on the genetic diversity and structure of Santalum austrocaledonicum.

The paper presents an overview of the aerothermal plasma simulation facilities in use at the von Karman Institute for Fluid Dynamics and the main research topics that have been followed during 10 years of work in the field. Both numerical simulation of plasma flows and experimental techniques are addressed, with an emphasis of the methodology which allows to relate measurements in the facilities to flight conditions of a space vehicle (re-)entering a planetary atmosphere.

Summary • Phytophthora parasitica var. nicotianae, an oomycete pathogen of tobacco, produces a cell wall glycoprotein named CBEL, which induces necrosis and defence responses in the host plant. Here, we investigated the elicitor activity of CBEL in Arabidopsis thaliana. • CBEL was infiltrated into leaves of Colombia-0, and its effect on defence responses was assessed. Involvement of the signalling pathways mediated by salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) was estimated by using SA-deficient transgenic plants (NahG) and two mutants affected in the perception of JA (coi1) and ET (ein2). • We found that CBEL induced necrosis, ethylene biosynthesis, HRGP accumulation, peroxidase activity and expression of the defence-related genes ACO1, ASA1, Wak1 and PR-1 in Col-0. Necrosis induction was abolished in coi1 and ein2, whereas induction of PR-1 and Wak1 expression, HRGP accumulation and peroxidase activity was affected in NahG plants. • Our results suggest that the three signalling pathways SA, JA and ET are involved differentially in the induction of necrosis and defence by CBEL in A. thaliana.

The genes encoding (2Fe-2S) plant-like ferredoxins were studied in the widely used cyanobacterium Synechocystis PCC6803. The fedl gene (ssI0020) coding for the most abundant ferredoxin product was found to be expressed strongly as a light-induced monocistronic transcript, whereas the other fed genes appeared to be silent (sIr1828) or moderately expressed as polycistronic transcripts regulated by either light fluence (sIr0150, negative control) or glucose availability (sII1382). fedl was found to be critical to Synechocystis PCC6803 viability in spite of sIr0150, sII1382 or flavodoxin induction, even after the addition of glucose that compensates for the loss of photosynthesis. Nevertheless, fedl could be deleted from all chromosome copies in cells propagating a fedl gene (even of heterologous origin) on a replicating plasmid. This strain was used as the host for the subsequent introduction of fedl mutant alleles propagated on a second vector. Analysis of the fedl mutant strains generated after plasmid exchange showed that the C18-C85 disulphide bridge is not central either to the tight compaction of ferredoxin I or to its reduction by photosystem I and demonstrated that the length of the Fedl carboxy terminus is important for effective PSI/FedI interactions. The plasmid-shuffling strategy presently described has general applicability for mutational analysis of essential genes in many organisms, as it is based on promiscuous plasmids.

Transgenic mice provide a unique tool for studying the tissue specificity and mutagenic potential of chemicals. Because 3-methylcholanthrene (3MC) was found mutagenic in bacteria, clastogenic in bone marrow, and induces DNA adducts in animals, we were interested to determinine whether this xenobiotic provokes (1) cell proliferation, (2) transcriptional activity changes, (3) DNA adducts, and (4) hepatic mutations in transgenic Big Blues mice carrying the λLIZ phage shuttle vector. Big Blue C57/Bl male mice were treated with a single intraperitoneal dose of 80 mg/kg 3MC for 1, 3, 6, 14, or 30 days. Cell proliferation was checked by 5-bromo-2-deoxyuridine labeling and immunohistochemical detection. The maximal increase of the mitotic index was evidenced after 3 days (2.9 times the control value; P < 0.01). The relative nucleus area, reflecting the transcriptional activity, was also the highest in the treated group after 3 days: 1.86 times the control value, on average (P < 0.01). Four major DNA adducts, determined according to the [ 32 P]-postlabeling method, were evidenced in liver DNA of treated mice, 6 days after the treatment: the spot intensities increased in a time-dependent manner. The mutant frequency of liver DNA was the highest after 14 days: 20.3 ± 2.9 × 10 -5 in the treated vs. 7.6 ± 2.7 × 10 -5 in the control mice (P < 0.01). Sequencing of the λ lacl mutant plaques showed mainly G:C → T:A and C:G → A:T transversions. In conclusion, 3MC at first induced nuclear enlargement and a slight increase of cell proliferation in liver, followed by parallel formation of DNA adducts and mutations. This study shows how transgenic models allow in vivo evaluation of mechanistically simultaneous endpoints. Environ. Mol. Mutagen. 36:266-273, 2000.

Genomic libraries of Arenaria grandiflora enriched for di- and trinucleotide repeats were used for the development of novel microsatellite markers. The subset of 13 polymorphic markers was characterized on 40 individuals of A. grandiflora originating from lowland locations in France. The loci amplified 3 to 10 alleles per locus and expected heterozygosities ranged from 0.46 to 0.83. The newly developed markers will be used for population genetic studies and for assessing genetic composition of a restoration experiment of lowland A. grandiflora populations that are protected in France.

The forest tree Santalum austrocaledonicum is endemic to the archipelagos of New Caledonia and Vanuatu, and is threatened by the reduction of the populations due to exploitation. In order to investigate the genetic diversity and structure of this species, we developed eight pairs of primers for nuclear microsatellites. These loci were polymorphic in all the populations, with a mean of three to 33 alleles per locus.

The effect of French maritime pine bark extract (PBE) on the gene expression profile of HaCaT human keratinocytes was studied using high density filter arrays. The expression profile of both control and PBE-treated cells was determined. Interestingly, PBE was shown to downregulate both calgranulin A and B genes which are known to be upregulated in psoriasis and various dermatoses. Thus, PBE could be considered in human dermatoses.

Room temperature transient EPR spectra of photosystem I (PS I) particles from Synechocystis 6803 are presented. Native PS I samples and preparations depleted in the A1-acceptor site by solvent extraction and then reconstituted with the quinones (Q) vitamin K1 (VK1), duroquinone (DQ and DQd12) and naphthoquinone (NQ) have been studied. Sequential electron transfer to P+700A−1 (FeS) and P+700A1 (FeS)− is recovered only with VK1. With DQ and NQ electron transfer is restored to form the radical pair P+700Q− as specified by a characteristic electron spin polarization (ESP)-pattern, but further electron transfer is either slowed down or blocked. A qualitative analysis of the K-band spectrum suggests that the orientation of reconstituted NQ in PS I is different from the native acceptor A1 = VK1.

The structure of the carbanionic species 4 formed from diethyl(2-oxopropyl)phosphonate and t-BuOK has been studied by 1H, 13C and 31P NMR. In an associating medium (pyridine), a single chelated (C) carbanionic species 4Z (C) is observed. Two slowly interconverting species 4Z and 4E co-exist when the anion-cation interaction is loose, i.e. in Me2SO and when the gegenion K+ is complexed to (2,2,2)cryptand in Me2SO. The anionic carbon of 4Z and 4E is planar, and they have a strong enolate character as shown by the barrier to rotation around the C-1C-2 bond (ΔGc‡∼92 KJ mol−1). Their structures are compared to those of the related E and Z 1-diethylphosphonato-2-trimethylsilyloxypropenes and to (acetylmethylene)triphenylphosphorane.