Bacillus anthracis Diversity and Geographic Potential across Nigeria, Cameroon and Chad: Further Support of a Novel West African Lineage.

Zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries. Anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in Nigeria. Here we describe the genetic diversity of Bacillus anthracis in Nigeria and compare it to Chad, Cameroon and a broader global dataset based on the multiple locus variable number tandem repeat (MLVA-25) genetic typing system. Nigerian B. anthracis isolates had identical MLVA genotypes and could only be resolved by measuring highly mutable single nucleotide repeats (SNRs). The Nigerian MLVA genotype was identical or highly genetically similar to those in the neighboring countries, confirming the strains belong to this unique West African lineage. Interestingly, sequence data from a Nigerian isolate shares the anthrose deficient genotypes previously described for strains in this region, which may be associated with vaccine evasion. Strains in this study were isolated over six decades, indicating a high level of temporal strain stability regionally. Ecological niche models were used to predict the geographic distribution of the pathogen for all three countries. We describe a west-east habitat corridor through northern Nigeria extending into Chad and Cameroon. Ecological niche models and genetic results show B. anthracis to be ecologically established in Nigeria. These findings expand our understanding of the global B. anthracis population structure and can guide regional anthrax surveillance and control planning.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Geomorphology of the Imhotep region on comet 67P/Churyumov-Gerasimenko from OSIRIS observations

Context. Since August 2014, the OSIRIS Narrow Angle Camera (NAC) onboard the Rosetta spacecraft has acquired high spatial resolution images of the nucleus of comet 67P/Churyumov-Gerasimenko, down to the decimeter scale. This paper focuses on the Imhotep region, located on the largest lobe of the nucleus, near the equator. Aims. We map, inventory, and describe the geomorphology of the Imhotep region. We propose and discuss some processes to explain the formation and ongoing evolution of this region. Methods. We used OSIRIS NAC images, gravitational heights and slopes, and digital terrain models to map and measure the morphologies of Imhotep. Results. The Imhotep region presents a wide variety of terrains and morphologies: smooth and rocky terrains, bright areas, linear features, roundish features, and boulders. Gravity processes such as mass wasting and collapse play a significant role in the geomorphological evolution of this region. Cometary processes initiate erosion and are responsible for the formation of degassing conduits that are revealed by elevated roundish features on the surface. We also propose a scenario for the formation and evolution of the Imhotep region; this implies the presence of large primordial voids inside the nucleus, resulting from its formation process.

Insolation, erosion, and morphology of comet 67P/Churyumov-Gerasimenko

Context. The complex shape of comet 67P and its oblique rotation axis cause pronounced seasonal effects. Irradiation and hence activity vary strongly. Aims. We investigate the insolation of the cometary surface in order to predict the sublimation of water ice. The strongly varying erosion levels are correlated with the topography and morphology of the present cometary surface and its evolution. Methods. The insolation as a function of heliocentric distance and diurnal (spin dependent) variation is calculated using >10(5) facets of a detailed digital terrain model. Shading, but also illumination and thermal radiation by facets in the field of view of a specific facet are iteratively taken into account. We use a two-layer model of a thin porous dust cover above an icy surface to calculate the water sublimation, presuming steady state and a uniform surface. Our second model, which includes the history of warming and cooling due to thermal inertia, is restricted to a much simpler shape model but allows us to test various distributions of active areas. Results. Sublimation from a dirty ice surface yields maximum erosion. A thin dust cover of 50 pm yields similar rates at perihelion. Only about 6% of the surface needs to be active to match the observed water production rates at perihelion. A dust layer of 1 mm thickness suppresses the activity by a factor of 4 to 5. Erosion on the south side can reach more than 10 m per orbit at active spots. The energy input to the concave neck area (Hapi) during northern summer is enhanced by about 50% owing to self-illumination. Here surface temperatures reach maximum values along the foot of the Hathor wall. Integrated over the whole orbit this area receives the least energy input. Based on the detailed shape model, the simulations identify "hot spots" in depressions and larger pits in good correlation with observed dust activity. Three-quarters of the total sublimation is produced while the sub-solar latitude is south, resulting in a distinct dichotomy in activity and morphology. Conclusions. The northern areas display a much rougher morphology than what is seen on Imhotep, an area at the equator that will be fully illuminated when 67P is closer to the Sun. Self-illumination in concave regions enhance the energy input and hence erosion. This explains the early activity observed at Hapi. Cliffs are more prone to erosion than horizontal, often dust covered, areas, which leads to surface planation. Local activity can only persist if the forming cliff walls are eroding. Comet 67P has two lobes and also two distinct sides. Transport of material from the south to the north is probable. The morphology of the Imhotep plain should be typical for the terrains of the yet unseen southern hemisphere.

Comet 67P/Churyumov-Gerasimenko: Constraints on its origin from OSIRIS observations

Context. One of the main aims of the ESA Rosetta mission is to study the origin of the solar system by exploring comet 67P/Churyumov-Gerasimenko at close range. Aims. In this paper we discuss the origin and evolution of comet 67P/Churyumov-Gerasimenko in relation to that of comets in general and in the framework of current solar system formation models. Methods. We use data from the OSIRIS scientific cameras as basic constraints. In particular, we discuss the overall bi-lobate shape and the presence of key geological features, such as layers and fractures. We also treat the problem of collisional evolution of comet nuclei by a particle-in-a-box calculation for an estimate of the probability of survival for 67P/Churyumov-Gerasimenko during the early epochs of the solar system. Results. We argue that the two lobes of the 67P/Churyumov-Gerasimenko nucleus are derived from two distinct objects that have formed a contact binary via a gentle merger. The lobes are separate bodies, though sufficiently similar to have formed in the same environment. An estimate of the collisional rate in the primordial, trans-planetary disk shows that most comets of similar size to 67P/Churyumov-Gerasimenko are likely collisional fragments, although survival of primordial planetesimals cannot be excluded. Conclusions. A collisional origin of the contact binary is suggested, and the low bulk density of the aggregate and abundance of volatile species show that a very gentle merger must have occurred. We thus consider two main scenarios: the primordial accretion of planetesimals, and the re-accretion of fragments after an energetic impact onto a larger parent body. We point to the primordial signatures exhibited by 67P/Churyumov-Gerasimenko and other comet nuclei as critical tests of the collisional evolution.

Rotating dust particles in the coma of comet 67P/Churyumov-Gerasimenko

Context. During September and October 2014, the OSIRIS cameras onboard the ESA Rosetta mission detected millions of single particles. Many of these dust particles appear as long tracks (due to both the dust proper motion and the spacecraft motion during the exposure time) with a clear brightness periodicity. Aims. We interpret the observed periodic features as a rotational and translational motion of aspherical dust grains. Methods. By counting the peaks of each track, we obtained statistics of a rotation frequency. We compared these results with the rotational frequency predicted by a model of aspherical dust grain dynamics in a model gas flow. By testing many possible sets of physical conditions and grain characteristics, we constrained the rotational properties of dust grains. Results. We analyzed on the motion of rotating aspherical dust grains with different cross sections in flow conditions corresponding to the coma of 67P/Churyumov-Gerasimenko qualitatively and quantitatively. Based on the OSIRIS observations, we constrain the possible physical parameters of the grains.

MECHANISMS OF SPECIES DIFFERENCES IN BRAIN ACETYLCHOLINESTERASE SENSITIVITY TO ORGANOPHOSPHATE INHIBITION

In vitro incubation of acetylcholinesterase from brain tissue of several species with organophosphate compounds indicated that the concentrations required to inhibit 50% of acetylcholinesterase activity (IC(,50)) differed from species to species for the same compound (Murphy, et al., 1968; Andersen, et al., 1972, 1977 and 1978).^ The hypothesis that non-specific binding proteins (Lauwerys and Murphy, 1969a,b) exerts a protective effect on acetylcholinesterase, and thus cause the differences observed in IC(,50) studies was tested by a ('3)H-DFP binding experiment. It was found that differences in the amount of non-specific binding protein cannot explain the observed differences observed in IC(,50) studies.^ An alternative hypothesis, that acetylcholinesterase from different species have different affinities for binding and/or different rates of phosphorylation by organophosphate insecticides was tested by determining the apparent affinity constant (k(,a)) and apparent rate of phosphorylation (k(,p)). Kinetic studies indicated that acetylcholinesterases from different species have different sensitivities to inhibition by organophosphate insecticides, and the differences are due to different affinities for binding and/or different rates of phosphorylation by the same organophosphate compound.^ Studies of the spontaneous reactivation of acetylcholinesterase after inhibition by organophosphate insecticides also indicated that acetylcholinesterases from different species have different rates and extents of spontaneous reactivation. This further substantiates the hypothesis that acetylcholinesterases from different species have different kinetic characteristics with respect to organophosphate insecticides inhibition.^ Eleven paraoxon analogs were synthesized for a quantitative structure-activity relationship study. It was found that the electron-withdrawing power ((sigma)) and hydrophobicity ((PARAGR)) of the substituent are important in determining the anti-cholinesterase activity of paraoxon analogs. Thus, predictions of species differences in acetylcholinesterase sensitivities to paraoxon analogs can be made if the physicochemical parameters ((sigma) and (PARAGR)) of the substituents are known.^ In another approach, i.e. enzyme modeling, the sensitivity of rat brain acetylcholinesterase to organophosphate insecticides was used as the independent variable to predict the sensitivities of acetylcholinesterases from other species to the same compound. Regression equations were derived for each species based on nineteen organophosphate insecticides studied. It was found, that in addition to paraoxon analogs, this method is also applicable to other organophosphate compounds with wide variations in structure. Thus, the sensitivities of acetylcholinesterases from other species can also be predicted from the sensitivity of rat brain acetylcholinesterase. ^

Königin Christine [Rezension]

K. P.

Mutagenicity study of the urinary metabolites of 2-aminonaphthalene

The mutagenicity study of the urinary metabolites of 2-aminonaphthalene was conducted to determine whether differences in metabolism between different acetylator phenotypes could account for a proposed mechanism of bladder carcinogenesis. This required the use of fast and slow acetylator rabbits with phenotypic similarities to humans. In the absence of available slow acetylators, it was necessary to inhibit fast acetylators. The proposed mechanism was that slow acetylators were at greater potential risk of bladder carcinogenesis due to low rates of acetylation, a detoxification mechanism for certain aromatic amines. The alternate metabolic pathway will be hydroxylation. The fast acetylators were proposed to exhibit lower risk of bladder carcinogenicity as a result of higher acetylation rates and less mutagenic metabolites.^ This hypothesis was approached by determining from in vitro mutagenicity assays with Salmonella typhimurium strains TA98 and TA100 whether different metabolites were mutagenic. The acetylation rate of each rabbit and a suitable method of acetylation inhibition were determined through oral exposure to dapsone and the acetylation inhibitor, K-p-aminosalicylic acid. Residues of dapsone and its acetylated metabolite were extracted from blood samples and analyzed by ultra-violet spectrometry using standard curves for each metabolite. The urine samples were concentrated on XAD-2 resin and analyzed both as whole urine concentrates and as isolated metabolites from spots on high performance thin layer chromatography plates. The major isolated spots were identified and quantified through extraction and analysis by high performance liquid chromatography when possible.^ Acetylation rate determination and inhibition were successfully demonstrated in rabbits. Significant mutagenicity was noted for several critical metabolites. None of the mutagenic metabolites were detected in higher concentration in the inhibited acetylators and thus, no clear relationship of metabolite concentration to bladder carcinogenesis was evident for the compounds analyzed. There was some evidence that the inhibitor may have affected critical enzyme systems other than acetylation alone. This would account for the lower concentrations of mutagenic hydroxylated compounds observed. ^

Deuterium analysis of ice core GISP2

The Greenland Ice Sheet Project 2 (GISP2) core can enhance our understanding of the relationship between parameters measured in the ice in central Greenland and variability in the ocean, atmosphere, and cryosphere of the North Atlantic Ocean and adjacent land masses. Seasonal (summer, winter) to annual responses of dD and deuterium excess isotopic signals in the GISP2 core to the seesaw in winter temperatures between West Greenland and northern Europe from A.D. 1840 to 1970 are investigated. This seesaw represents extreme modes of the North Atlantic Oscillation, which also influences sea surface temperatures (SSTs), atmospheric pressures, geostrophic wind strength, and sea ice extents beyond the winter season. Temperature excursions inferred from the dD record during seesaw/extreme NAO mode years move in the same direction as the West Greenland side of the seesaw. Symmetry with the West Greenland side of the seesaw suggests a possible mechanism for damping in the ice core record of the lowest decadal temperatures experienced in Europe from A.D. 1500 to 1700. Seasonal and annual deuterium excess excursions during seesaw years show negative correlation with dD. This suggests an isotopic response to a SST/ land temperature seesaw. The isotopic record from GISP2 may therefore give information on both ice sheet and sea surface temperature variability. Cross-plots of dD and d show a tendency for data to be grouped according to the prevailing mode of the seesaw, but do not provide unambiguous identification of individual seesaw years. A combination of ice core and tree ring data sets may allow more confident identification of GA and GB (extreme NAO mode) years prior to 1840.