Probabilistic causal reasoning under time pressure.

While causal reasoning is a core facet of our cognitive abilities, its time-course has not received proper attention. As the duration of reasoning might prove crucial in understanding the underlying cognitive processes, we asked participants in two experiments to make probabilistic causal inferences while manipulating time pressure. We found that participants are less accurate under time pressure, a speed-accuracy-tradeoff, and that they respond more conservatively. Surprisingly, two other persistent reasoning errors-Markov violations and failures to explain away-appeared insensitive to time pressure. These observations seem related to confidence: Conservative inferences were associated with low confidence, whereas Markov violations and failures to explain were not. These findings challenge existing theories that predict an association between time pressure and all causal reasoning errors including conservatism. Our findings suggest that these errors should not be attributed to a single cognitive mechanism and emphasize that causal judgements are the result of multiple processes.

Implicit association tests: Stimuli validation from participant responses.

The Implicit Association Test (IAT, Greenwald et al., J. Pers. Soc. Psychol., 74, 1998, 1464) is a popular instrument for measuring attitudes and (stereotypical) biases. Greenwald et al. (Behav. Res. Methods, 54, 2021, 1161) proposed a concrete method for validating IAT stimuli: appropriate stimuli should be familiar and easy to classify - translating to rapid (response times <800 ms) and accurate (error < 10%) participant responses. We conducted three analyses to explore the theoretical and practical utility of these proposed validation criteria. We first applied the proposed validation criteria to the data of 15 IATs that were available via Project Implicit. A bootstrap approach with 10,000 'experiments' of 100 participants showed that 5.85% of stimuli were reliably valid (i.e., we are more than 95% confident that a stimulus will also be valid in a new sample of 18- to 25-year-old US participants). Most stimuli (78.44%) could not be reliably validated, indicating a less than 5% certainty in the outcome of stimulus (in)validity for a new sample of participants. We then explored how stimulus validity differs across IATs. Results show that only some stimuli are consistently (in)valid. Most stimuli show between-IAT variances, which indicate that stimulus validity differs across IAT contexts. In the final analysis, we explored the effect of stimulus type (images, nouns, names, adjectives) on stimulus validity. Stimulus type was a significant predictor of stimulus validity. Although images attain the highest stimulus validity, raw data show large differences within stimulus types. Together, the results indicate a need for revised validation criteria. We finish with practical recommendations for stimulus selection and (post-hoc) stimulus validation.

Contact with soil impacts ferrihydrite and lepidocrocite transformations during redox cycling in a paddy soil.

Iron (Fe) oxyhydroxides can be reductively dissolved or transformed under Fe reducing conditions, affecting mineral crystallinity and the sorption capacity for other elements. However, the pathways and rates at which these processes occur under natural soil conditions are still poorly understood. Here, we studied Fe oxyhydroxide transformations during reduction-oxidation cycles by incubating mesh bags containing ferrihydrite or lepidocrocite in paddy soil mesocosms for up to 12 weeks. To investigate the influence of close contact with the soil matrix, mesh bags were either filled with pure Fe minerals or with soil mixed with 57Fe-labeled Fe minerals. Three cycles of flooding (3 weeks) and drainage (1 week) were applied to induce soil redox cycles. The Fe mineral composition was analyzed with Fe K-edge X-ray absorption fine structure spectroscopy, X-ray diffraction analysis and/or 57Fe Mössbauer spectroscopy. Ferrihydrite and lepidocrocite in mesh bags without soil transformed to magnetite and/or goethite, likely catalyzed by Fe(II) released to the pore water by microbial Fe reduction in the surrounding soil. In contrast, 57Fe-ferrihydrite in mineral-soil mixes transformed to a highly disordered mixed-valence Fe(II)-Fe(III) phase, suggesting hindered transformation to crystalline Fe minerals. The 57Fe-lepidocrocite transformed to goethite and small amounts of the highly disordered Fe phase. The extent of reductive dissolution of minerals in 57Fe-mineral-soil mixes during anoxic periods increased with every redox cycle, while ferrihydrite and lepidocrocite precipitated during oxic periods. The results demonstrate that the soil matrix strongly impacts Fe oxyhydroxide transformations when minerals are in close spatial association or direct contact with other soil components. This can lead to highly disordered and reactive Fe phases from ferrihydrite rather than crystalline mineral products and promoted goethite formation from lepidocrocite.

A New Approach for Investigating Iron Mineral Transformations in Soils and Sediments Using 57Fe-Labeled Minerals and 57Fe Mössbauer Spectroscopy.

Iron minerals in soils and sediments play important roles in many biogeochemical processes and therefore influence the cycling of major and trace elements and the fate of pollutants in the environment. However, the kinetics and pathways of Fe mineral recrystallization and transformation processes under environmentally relevant conditions are still elusive. Here, we present a novel approach enabling us to follow the transformations of Fe minerals added to soils or sediments in close spatial association with complex solid matrices including other minerals, organic matter, and microorganisms. Minerals enriched with the stable isotope 57Fe are mixed with soil or sediment, and changes in Fe speciation are subsequently studied by 57Fe Mössbauer spectroscopy, which exclusively detects 57Fe. In this study, 57Fe-labeled ferrihydrite was synthesized, mixed with four soils differing in chemical and physical properties, and incubated for 12+ weeks under anoxic conditions. Our results reveal that the formation of crystalline Fe(III)(oxyhydr)oxides such as lepidocrocite and goethite was strongly suppressed, and instead formation of a green rust-like phase was observed in all soils. These results contrast those from Fe(II)-catalyzed ferrihydrite transformation experiments, where formation of lepidocrocite, goethite, and/or magnetite often occurs. The presented approach allows control over the composition and crystallinity of the initial Fe mineral, and it can be easily adapted to other experimental setups or Fe minerals. It thus offers great potential for future investigations of Fe mineral transformations in situ under environmentally relevant conditions, in both the laboratory and the field.

Ferrihydrite transformations in flooded paddy soils: rates, pathways, and product spatial distributions.

Complex interactions between redox-driven element cycles in soils influence iron mineral transformation processes. The rates and pathways of iron mineral transformation processes have been studied intensely in model systems such as mixed suspensions, but transformation in complex heterogeneous porous media is not well understood. Here, mesh bags containing 0.5 g of ferrihydrite were incubated in five water-saturated paddy soils with contrasting microbial iron-reduction potential for up to twelve weeks. Using X-ray diffraction analysis, we show near-complete transformation of the ferrihydrite to lepidocrocite and goethite within six weeks in the soil with the highest iron(II) release, and slower transformation with higher ratios of goethite to lepidocrocite in soils with lower iron(II) release. In the least reduced soil, no mineral transformations were observed. In soils where ferrihydrite transformation occurred, the transformation rate was one to three orders of magnitude slower than transformation in comparable mixed-suspension studies. To interpret the spatial distribution of ferrihydrite and its transformation products, we developed a novel application of confocal micro-Raman spectroscopy in which we identified and mapped minerals on selected cross sections of mesh bag contents. After two weeks of flooded incubation, ferrihydrite was still abundant in the core of some mesh bags, and as a rim at the mineral-soil interface. The reacted outer core contained unevenly mixed ferrihydrite, goethite and lepidocrocite on the micrometre scale. The slower rate of transformation and uneven distribution of product minerals highlight the influence of biogeochemically complex matrices and diffusion processes on the transformation of minerals, and the importance of studying iron mineral transformation in environmental media.

Stabilization of Ferrihydrite and Lepidocrocite by Silicate during Fe(II)-Catalyzed Mineral Transformation: Impact on Particle Morphology and Silicate Distribution.

Interactions between aqueous ferrous iron (Fe(II)) and secondary Fe oxyhydroxides catalyze mineral recrystallization and/or transformation processes in anoxic soils and sediments, where oxyanions, such as silicate, are abundant. However, the effect and the fate of silicate during Fe mineral recrystallization and transformation are not entirely understood and especially remain unclear for lepidocrocite. In this study, we reacted (Si-)ferrihydrite (Si/Fe = 0, 0.05, and 0.18) and (Si-)lepidocrocite (Si/Fe = 0 and 0.08) with isotopically labeled 57Fe(II) (Fe(II)/Fe(III) = 0.02 and 0.2) at pH 7 for up to 4 weeks. We followed Fe mineral transformations with X-ray diffraction and tracked Fe atom exchange by measuring aqueous and solid phase Fe isotope fractions. Our results show that the extent of ferrihydrite transformation in the presence of Fe(II) was strongly influenced by the solid phase Si/Fe ratio, while increasing the Fe(II)/Fe(III) ratio (from 0.02 to 0.2) had only a minor effect. The presence of silicate increased the thickness of newly formed lepidocrocite crystallites, and elemental distribution maps of Fe(II)-reacted Si-ferrihydrites revealed that much more Si was associated with the remaining ferrihydrite than with the newly formed lepidocrocite. Pure lepidocrocite underwent recrystallization in the low Fe(II) treatment and transformed to magnetite at the high Fe(II)/Fe(III) ratio. Adsorbed silicate inactivated the lepidocrocite surfaces, which strongly reduced Fe atom exchange and inhibited mineral transformation. Collectively, the results of this study demonstrate that Fe(II)-catalyzed Si-ferrihydrite transformation leads to the redistribution of silicate in the solid phase and the formation of thicker lepidocrocite platelets, while lepidocrocite transformation can be completely inhibited by adsorbed silicate. Therefore, silicate is an important factor to include when considering Fe mineral dynamics in soils under reducing conditions.

Schwann Cells Provide Iron to Axonal Mitochondria and Its Role in Nerve Regeneration.

Iron is an essential cofactor for several metabolic processes, including the generation of ATP in mitochondria, which is required for axonal function and regeneration. However, it is not known how mitochondria in long axons, such as those in sciatic nerves, acquire iron in vivo Because of their close proximity to axons, Schwann cells are a likely source of iron for axonal mitochondria in the PNS. Here we demonstrate the critical role of iron in promoting neurite growth in vitro using iron chelation. We also show that Schwann cells express the molecular machinery to release iron, namely, the iron exporter, ferroportin (Fpn) and the ferroxidase ceruloplasmin (Cp). In Cp KO mice, Schwann cells accumulate iron because Fpn requires to partner with Cp to export iron. Axons and Schwann cells also express the iron importer transferrin receptor 1 (TfR1), indicating their ability for iron uptake. In teased nerve fibers, Fpn and TfR1 are predominantly localized at the nodes of Ranvier and Schmidt-Lanterman incisures, axonal sites that are in close contact with Schwann cell cytoplasm. We also show that lack of iron export from Schwann cells in Cp KO mice reduces mitochondrial iron in axons as detected by reduction in mitochondrial ferritin, affects localization of axonal mitochondria at the nodes of Ranvier and Schmidt-Lanterman incisures, and impairs axonal regeneration following sciatic nerve injury. These finding suggest that Schwann cells contribute to the delivery of iron to axonal mitochondria, required for proper nerve repair.SIGNIFICANCE STATEMENT This work addresses how and where mitochondria in long axons in peripheral nerves acquire iron. We show that Schwann cells are a likely source as they express the molecular machinery to import iron (transferrin receptor 1), and to export iron (ferroportin and ceruloplasmin [Cp]) to the axonal compartment at the nodes of Ranvier and Schmidt-Lanterman incisures. Cp KO mice, which cannot export iron from Schwann cells, show reduced iron content in axonal mitochondria, along with increased localization of axonal mitochondria at Schmidt-Lanterman incisures and nodes of Ranvier, and impaired sciatic nerve regeneration. Iron chelation in vitro also drastically reduces neurite growth. These data suggest that Schwann cells are likely to contribute iron to axonal mitochondria needed for axon growth and regeneration.

Variations in strain affect friction and microstructure evolution in copper under a reciprocating tribological load.

The microstructure of the materials constituting a metallic frictional contact strongly influence tribological performance. Being able to tailor friction and wear is challenging due to the complex microstructure evolution associated with tribological loading. Here, we investigate the effect of the strain distribution on these processes. High-purity copper plates were morphologically surface textured with two parallel rectangles - referred to as membranes - over the entire sample length by micro-milling. By keeping the width of these membranes constant and only varying their height, reciprocating tribological loading against sapphire discs resulted in different elastic and plastic strains. Finite element simulations were carried out to evaluate the strain distribution in the membranes. It was found that the maximum elastic strain increases with decreasing membrane stiffness. The coefficient of friction decreases with increasing membrane aspect ratio. By analyzing the microstructure and local crystallographic orientation, we found that both show less change with decreasing membrane stiffness.

Financial reimbursement - irrelevant for GPs' readiness to implement brief intervention to reduce alcohol consumption? A cross-sectional vignette study.

BACKGROUND: General Practitioners' (GPs) readiness to implement screening and brief intervention (SBI) to treat patients with excessive alcohol consumption is low. Several studies identified crucial barriers such as insufficient financial reimbursement. In contrast to the barriers-account, we assume that low implementation readiness of GPs may be less attributed to external barriers but rather more so to inherent characteristics of SBI. To test our assumption, we conducted a vignette study assessing the GPs' readiness to implement SBI in comparison to a pharmacological intervention also designed for the treatment of excessive drinkers in relation to standard or above-standard financial reimbursement. According to our hypothesis GPs should be less ready to implement SBI regardless of financial reimbursement. METHODS: A convenience sample of GPs was recruited to answer the questionnaire. To assess the GPs' implementation readiness a 4-item 6-point Likert scale was developed and pretested. RESULTS: One hundred forty GPs completed the questionnaire. GPs were more ready to implement the pharmacological intervention than SBI, F(1,132) = 27.58, p > .001 (main effect). We found no effect for financial reimbursement, F(1,132) = 3.60, ns, and no interaction effect, F(1,132) = 2.20, ns. CONCLUSIONS: Further research should investigate more thoroughly the crucial characteristics of SBI to initiate a modification process finally leading to more effective primary care dependency prevention.

Generics and Alternatives.

In this paper we argue that for the (probabilistic) interpretation of generic sentences of the form "Gs are f," three types of alternatives play a role: (i) alternative features of f, (ii) alternative groups, or kinds, of G, and (iii) alternative causal background factors. In the first part of this paper we argue for the relevance of these alternatives. In the second part, we describe the results of some experiments that empirically tested in particular the second use of alternatives.

Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study.

Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently.

The Everyday Moral Judge - Autobiographical Recollections of Moral Emotions.

Moral emotions are typically elicited in everyday social interactions and regulate social behavior. Previous research in the field of attribution theory identified ought (the moral standard of a given situation or intended goal), goal-attainment (a goal can be attained vs. not attained) and effort (high vs. low effort expenditure) as cognitive antecedents of moral emotions. In contrast to earlier studies, mainly relying on thought experiments, we investigated autobiographical recollections of N = 312 participants by means of an online study. We analyzed a diverse range of moral emotions, i.e., admiration, anger, contempt, indignation, pride, respect, schadenfreude, and sympathy, by using a mixed-method approach. Qualitative and quantitative methods clearly corroborate the important role of ought, goal-attainment, and effort as eliciting conditions of moral emotions. Furthermore, we built categorical systems based on our participants' descriptions of real-life situations, allowing for more fine-grained distinctions between seemingly similar moral emotions. We thus identify additional prerequisites explaining more subtle differences between moral emotion clusters as they emerge from our analyses (i.e., cluster 1: admiration, pride, and respect; cluster 2: anger, contempt, and indignation; cluster 3: schadenfreude and sympathy). Results are discussed in the light of attributional theories of moral emotions, and implications for future research are derived.

Molecular Epidemiology of Staphylococcus aureus in the General Population in Northeast Germany: Results of the Study of Health in Pomerania (SHIP-TREND-0).

Population-based studies on Staphylococcus aureus nasal colonization are scarce. We examined the prevalence, resistance, and molecular diversity of S. aureus in the general population in Northeast Germany. Nasal swabs were obtained from 3,891 adults in the large-scale population-based Study of Health in Pomerania (SHIP-TREND). Isolates were characterized using spa genotyping, as well as antibiotic resistance and virulence gene profiling. We observed an S. aureus prevalence of 27.2%. Nasal S. aureus carriage was associated with male sex and inversely correlated with age. Methicillin-resistant S. aureus (MRSA) accounted for 0.95% of the colonizing S. aureus strains. MRSA carriage was associated with frequent visits to hospitals, nursing homes, or retirement homes within the previous 24 months. All MRSA strains were resistant to multiple antibiotics. Most MRSA isolates belonged to the pandemic European hospital-acquired MRSA sequence type 22 (HA-MRSA-ST22) lineage. We also detected one livestock-associated MRSA ST398 (LA-MRSA-ST398) isolate, as well as six livestock-associated methicillin-susceptible S. aureus (LA-MSSA) isolates (clonal complex 1 [CC1], CC97, and CC398). spa typing revealed a diverse but also highly clonal S. aureus population structure. We identified a total of 357 spa types, which were grouped into 30 CCs or sequence types. The major seven CCs (CC30, CC45, CC15, CC8, CC7, CC22, and CC25) included 75% of all isolates. Virulence gene patterns were strongly linked to the clonal background. In conclusion, MSSA and MRSA prevalences and the molecular diversity of S. aureus in Northeast Germany are consistent with those of other European countries. The detection of HA-MRSA and LA-MRSA within the general population indicates possible transmission from hospitals and livestock, respectively, and should be closely monitored.

[General practitioners' commitment to treating excessive alcohol consumption: A question of role security in treating affected patients?]. / Hausärztliche Bereitschaft zur Intervention bei zu hohem Alkoholkonsum: Eine Frage der Sicherheit im Umgang mit betroffenen Patienten?

Only a few general practitioners (GPs) are committed to screen their patients for alcohol consumption and, in case of excessive alcohol consumption conduct by a brief intervention according to WHO recommendations. Apart from inadequate compensation and work load, another barrier identified by the GPs was their uncertainty about how to deal with affected patients. Most German universities presently spend no more than 90minutes lecture time on addiction medicine teaching. Our research aims to investigate the question whether medical studies and advanced medical education increases the role security of medical students and physicians and their commitment to implementing alcohol screening and brief intervention. Moreover, we will explore whether lack of therapeutic commitment can be related to lack of role security. Questionnaires were administered to pre-clinical and clinical medical students as well as senior house officers. Role security and therapeutic commitment of students and senior house officers were assessed using the Alcohol and Alcohol Problems Questionnaire (SAAPPQ) subscales "Role Security" and "Therapeutic Commitment". Analysis was based on 367 questionnaires. As expected, senior house officers reported more Role Security than clinical medical students who showed a higher level of Role Security than pre-clinical medical students. No differences could be found for Therapeutic Commitment. An association between Role Security and Therapeutic Commitment was only revealed for clinical medical students. Medical studies and advanced medical education can increase students' and senior house officers' Role Security to treat patients with excessive alcohol consumption, but not Therapeutic Commitment. Moreover, no association between Role Security and Therapeutic Commitment could be found for senior house officers. Hence, it may be assumed that educational activities aiming to increase Role Security do not promote the development of motivational aspects such as Therapeutic Commitment to the management of patients with excessive alcohol intake.

Ceruloplasmin gene-deficient mice with experimental autoimmune encephalomyelitis show attenuated early disease evolution.

We conducted a microarray study to identify genes that are differentially regulated in the spinal cords of mice with the inflammatory disease experimental autoimmune encephalomyelitis (EAE) relative to healthy mice. In total 181 genes with at least a two-fold increase in expression were identified, and most of these genes were associated with immune function. Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord. Expression of Cp protein is known to be increased in several neurological conditions, but the role of Cp regulation in CNS autoimmune disease is not known. To investigate this, we induced EAE in Cp gene knockout, heterozygous, and wild-type mice. Cp knockout mice were found to have slower disease evolution than wild-type mice (EAE days 13-17; P = 0.05). Interestingly, Cp knockout mice also exhibited a significant increase in the number of astrocytes with reactive morphology in early EAE compared with wild-type mice at the same stage of disease. CNS iron levels were not increased with EAE in these mice. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.

Reassortants of the pandemic (H1N1) 2009 virus and establishment of a novel porcine H1N2 influenza virus, lineage in Germany.

The incursion of pandemic (H1N1) 2009 virus (pdmH1N1) into the German pig population was investigated in a serosurvey and by virological means between June 2009 and December 2012. Analysis of 23,116 pig sera from a total of 2,666 herds revealed 224 herds that reacted with pdmH1N1 but not with the prevalent avian-like H1N1 swine influenza virus. Sixty-six pdmH1N1 strains and their reassortant derivatives (pdmH1huN2, huH3pdmN1) have been collected since November 2009. Sequencing of three pdmH1N1, 20 pdmH1huN2 and one huH3pdmN1 strains with conventional and next generation sequencing techniques and subsequent phylogenetic analyses with available sequence data revealed the emergence of five distinct reassortant genotypes in Europe. The most frequent genotype emerged at least three times independently, one of which (Papenburg lineage) established a stable infection chain and became more prevalent in pigs than pdmH1N1 in Germany.

Daniel has fallen into a muddy puddle--schadenfreude or sympathy?

The present study investigated the experience of schadenfreude among children. Participants were 4- to 8-year-old children (n = 100) who were told stories of another child experiencing a misfortune while pursuing a morally positive versus morally negative goal. Schadenfreude, sympathy, and helping behaviour towards the suffering child were assessed. Results showed that beginning at the age of 4, emotional and behavioural reactions towards a misfortune of another child were predicted by the moral valence of the other child's goal. Furthermore, morally negative goals decreased helping behaviour and morally positive goals increased helping behaviour. Multilevel mediation analysis revealed that the relation between goal valence and helping behaviour was mediated by both schadenfreude and sympathy. However, those effects were especially pronounced in older children.

Iron efflux from astrocytes plays a role in remyelination.

How iron is delivered to the CNS for myelination is not well understood. We assessed whether astrocytes can provide iron to cells in the CNS for remyelination. To study this we generated a conditional deletion of the iron efflux transporter ferroportin (Fpn) in astrocytes, and induced focal demyelination in the mouse spinal cord dorsal column by microinjection of lysophosphatidylcholine (LPC). Remyelination assessed by electron microscopy was reduced in astrocyte-specific Fpn knock-out mice compared with wild-type controls, as was proliferation of oligodendrocyte precursor cells (OPCs). Cell culture work showed that lack of iron reduces the ability of microglia to express cytokines (TNF-α and IL-1ß) involved in remyelination. Furthermore, astrocytes in culture express high levels of FGF-2 in response to IL-1ß, and IGF-1 in response to TNF-α stimulation. FGF-2 and IGF-1 are known to be important for myelination. Reduction in IL-1ß and IGF-1 were also seen in astrocyte-specific Fpn knock-out mice after LPC-induced demyelination. These data suggest that iron efflux from astrocytes plays a role in remyelination by either direct effects on OPCs or indirectly by affecting glial activation.

Toxoplasmosis after allogeneic stem cell transplantation--a single centre experience.

Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.

Iron efflux from oligodendrocytes is differentially regulated in gray and white matter.

Accumulation of iron occurs in the CNS in several neurodegenerative diseases. Iron is essential for life but also has the ability to generate toxic free radicals if not properly handled. Iron homeostasis at the cellular level is therefore important to maintain proper cellular function, and its dysregulation can contribute to neurodegenerative diseases. Iron export, a key mechanism to maintain proper levels in cells, occurs via ferroportin, a ubiquitously expressed transmembrane protein that partners with a ferroxidase. A membrane-bound form of the ferroxidase ceruloplasmin is expressed by astrocytes in the CNS and regulates iron efflux. We now show that oligodendrocytes use another ferroxidase, called hephaestin, which was first identified in enterocytes in the gut. Mice with mutations in the hephaestin gene (sex-linked anemia mice) show iron accumulation in oligodendrocytes in the gray matter, but not in the white matter, and exhibit motor deficits. This was accompanied by a marked reduction in the levels of the paranodal proteins contactin-associated protein 1 (Caspr) and reticulon-4 (Nogo A). We show that the sparing of iron accumulation in white matter oligodendrocytes in sex-linked anemia mice is due to compensatory upregulation of ceruloplasmin in these cells. This was further confirmed in ceruloplasmin/hephaestin double-mutant mice, which show iron accumulation in both gray and white matter oligodendrocytes. These data indicate that gray and white matter oligodendrocytes can use different iron efflux mechanisms to maintain iron homeostasis. Dysregulation of such efflux mechanisms leads to iron accumulation in the CNS.