julilili42/papers huggingface dataset:
Anaphylaxis: opportunities of stratified medicine for diagnosis and risk assessment
2013-11-22

The risk to develop anaphylaxis depends on the sensitization pattern, the proportion of the involved immunoglobulin classes, the avidity and affinity of immunoglobulins to bind an allergen, characteristics of the allergen, the route of allergen application, and, last but not least, the presence of cofactors of anaphylaxis. To be able to calculate the risk to develop anaphylaxis and to anticipate the severity of the reactions under certain conditions, it is necessary to understand how all these factors interact with each other. Important progress for risk assessment in anaphylaxis is based on component-resolved stratified diagnostics, which allow to (i) determine a patient's sensitization pattern on a molecular basis, (ii) correlate clinical responses to defined sensitization patterns, and (iii) better identify cross-reactive allergens. Together with the increasing knowledge regarding the role and mode of action of cofactors of anaphylaxis, these data pave the way to unscramble the complex interactions determining the clinical relevance of sensitizations, the risk of anaphylaxis, and the severity of reactions. As a consequence, this understanding allows to better determine the individual risk in response to an identified allergen and results in more specific advices and education for our patients to prevent further life-threatening anaphylactic reactions.
Cemetery or sacrifice? Infant burials at the Carthage Tophet
2013-11-22

Even if the foundation, rise and eventual demise of Carthage and its overseas territories in the West Mediterranean occurred in much the same space and time as the glory days of Archaic, Classical and Hellenistic Greece and Rome, there is no doubt that the Phoenicians and their Punic successors (to use the conventional terms) have rarely been regarded as fully signed-up members of the ancient world. Reduced to walk-on cameos as skilled silversmiths, agricultural experts, shrewd traders or military strategists, Phoenician and Punic representations tend to be rather stereotypical (Prag 2010, with earlier bibliography), which perhaps should not come as a surprise, as nearly all these portraits have been sketched by outsiders; they certainly do not add up to a coherent ethnographic or political description.
Emotion through Locomotion: Gender Impact
2013-11-22

Body language reading is of significance for daily life social cognition and successful social interaction, and constitutes a core component of social competence. Yet it is unclear whether our ability for body language reading is gender specific. In the present work, female and male observers had to visually recognize emotions through point-light human locomotion performed by female and male actors with different emotional expressions. For subtle emotional expressions only, males surpass females in recognition accuracy and readiness to respond to happy walking portrayed by female actors, whereas females exhibit a tendency to be better in recognition of hostile angry locomotion expressed by male actors. In contrast to widespread beliefs about female superiority in social cognition, the findings suggest that gender effects in recognition of emotions from human locomotion are modulated by emotional content of actions and opposite actor gender. In a nutshell, the study makes a further step in elucidation of gender impact on body language reading and on neurodevelopmental and psychiatric deficits in visual social cognition.
Nitrate/oxygen co‐sensing by an NreA/NreB sensor complex of Staphylococcus carnosus
2013-11-22

Summary In S taphylococci maximal induction of nitrate reductase ( narGHJI genes) requires anaerobic conditions, the presence of nitrate, and the NreABC regulatory system. Aerobic regulation is effected by the NreB / NreC two‐component system. The role of the nitrate receptor NreA in nitrate induction and its relation to aerobic regulation was analysed in S taphylococcus carnosus . Nitrate induction of a narG‐lip reporter gene required presence of NreB / NreC . When nreA was deleted, nitrate was no longer required for maximal induction, suggesting that NreA is a nitrate regulated inhibitor of NreB / NreC . I n vitro , NreA and mutant NreA ( Y95A ) decreased NreB phosphorylation in part or completely, which was due to the inhibition of the autophosphorylating activity rather than an increase of phosphatase activity. Inhibition of phosphorylation was relieved completely when the nitrate‐bound NreA was used instead of the nitrate‐free form. In the bacterial two‐hybrid BACTH system and HPINE interaction assays, NreA interacted with NreB , but not with NreC , and the interaction was diminished by nitrate. In summary, NreA interacts with NreB and controls its phosphorylation level in a nitrate dependent manner. In this way nitrate and NreA modulate the function of the oxygen sensor NreB , resulting in nitrate/oxygen co‐sensing by an NreA / NreB sensor unit as part of the NreABC ‐system.
Crustal-scale folding: Palaeozoic deformation of the Mt Painter Inlier, South Australia
2013-11-22

Abstract The Mt Painter Inlier (Northern Flinders Ranges, South Australia) was exhumed in the Yankaninna Anticline, in the hanging wall of the major NE–SW-running Paralana Fault System. Regional north–south compression resulted in SE-directed oblique and lateral ramping on to the rigid Curnamona Province. Formation of the crustal-scale anticline caused exhumation of up to 15 km of basement rocks in the core of the anticline. Currently exposed rocks reached the surface in Permian times. Folding and thrusting commenced between c. 500 and c. 450 Ma and lasted until the Permian Period. Contrary to previous studies, only a minor part of the deformation can be attributed to the c. 500 Ma Delamerian Orogeny, with most of the tectonic activity being contemporaneous with the Alice Springs and Lachlan Orogenies. New Permo-Triassic zircon and apatite (U–Th)/He ages, as well as a titanite fission-track age point to a long-lived near-surface hydrothermal event that overprinted the basement and cover rocks. Hydrothermal reheating and burial below the Mesozoic Eromanga Basin sediments, to a depth of no more than 2 km, resulted in partial or full rejuvenation of the apatite (U–Th)/He system.
Potential Role of Nitrite for Abiotic Fe(II) Oxidation and Cell Encrustation during Nitrate Reduction by Denitrifying Bacteria
2013-11-23

ABSTRACT Microorganisms have been observed to oxidize Fe(II) at neutral pH under anoxic and microoxic conditions. While most of the mixotrophic nitrate-reducing Fe(II)-oxidizing bacteria become encrusted with Fe(III)-rich minerals, photoautotrophic and microaerophilic Fe(II) oxidizers avoid cell encrustation. The Fe(II) oxidation mechanisms and the reasons for encrustation remain largely unresolved. Here we used cultivation-based methods and electron microscopy to compare two previously described nitrate-reducing Fe(II) oxidizers ( Acidovorax sp. strain BoFeN1 and Pseudogulbenkiania sp. strain 2002) and two heterotrophic nitrate reducers ( Paracoccus denitrificans ATCC 19367 and P. denitrificans Pd 1222). All four strains oxidized ∼8 mM Fe(II) within 5 days in the presence of 5 mM acetate and accumulated nitrite (maximum concentrations of 0.8 to 1.0 mM) in the culture media. Iron(III) minerals, mainly goethite, formed and precipitated extracellularly in close proximity to the cell surface. Interestingly, mineral formation was also observed within the periplasm and cytoplasm; intracellular mineralization is expected to be physiologically disadvantageous, yet acetate consumption continued to be observed even at an advanced stage of Fe(II) oxidation. Extracellular polymeric substances (EPS) were detected by lectin staining with fluorescence microscopy, particularly in the presence of Fe(II), suggesting that EPS production is a response to Fe(II) toxicity or a strategy to decrease encrustation. Based on the data presented here, we propose a nitrite-driven, indirect mechanism of cell encrustation whereby nitrite forms during heterotrophic denitrification and abiotically oxidizes Fe(II). This work adds to the known assemblage of Fe(II)-oxidizing bacteria in nature and complicates our ability to delineate microbial Fe(II) oxidation in ancient microbes preserved as fossils in the geological record.
The Processing Domain of Scope Interaction
2013-11-23

The present study investigates whether quantifier scope is computed incrementally during online sentence processing. We exploited the free word order in German to manipulate whether the verbal predicate preceded or followed the second quantifier in doubly quantified sentences that required the computation of inverse scope. A possessive pronoun in the first quantifier that had to be bound by the second quantifier was used to enforce scope inversion. We tested whether scope inversion causes difficulty and whether this difficulty emerges even at a point before comprehenders have encountered the main verb. We report three pretests and two reading time experiments. The first two pretests were offline tests that established (1) that the sentences exhibited the assumed scope preferences and (2) that variable binding forced scope inversion. The third pretest employed self-paced reading to show that interpreting a bound variable is not difficult per se and that difficulty in the critical construction must thus be due to inverting scope. Incremental processing of quantifier scope was investigated in a self-paced reading experiment. We observed difficulty right after the second quantifier, but only if it appeared after the main verb, that is, after the predication was complete. Further evidence for late scope inversion comes from an eyetracking experiment. Again, a scope inversion effect could only be observed at the end of the sentence. Taken together, our study demonstrates that in German inverse scope is only computed at the sentence boundary.
A HumanIn VitroModel That Mimics the Renal Proximal Tubule
2013-11-24

Human in vitro-manufactured tissue and organ models can serve as powerful enabling tools for the exploration of fundamental questions regarding cell, matrix, and developmental biology in addition to the study of drug delivery dynamics and kinetics. To date, the development of a human model of the renal proximal tubule (PT) has been hindered by the lack of an appropriate cell source and scaffolds that allow epithelial monolayer formation and maintenance. Using extracellular matrices or matrix proteins, an in vivo-mimicking environment can be created that allows epithelial cells to exhibit their typical phenotype and functionality. Here, we describe an in vitro-engineered PT model. We isolated highly proliferative cells from cadaveric human kidneys (human kidney-derived cells [hKDCs]), which express markers that are associated with renal progenitor cells. Seeded on small intestinal submucosa (SIS), hKDCs formed a confluent monolayer and displayed the typical phenotype of PT epithelial cells. PT markers, including N-cadherin, were detected throughout the hKDC culture on the SIS, whereas markers of later tubule segments were weak (E-cadherin) or not (aquaporin-2) expressed. Basement membrane and microvilli formation demonstrated a strong polarization. We conclude that the combination of hKDCs and SIS is a suitable cell-scaffold composite to mimic the human PT in vitro.
GRIN2B mutations in west syndrome and intellectual disability with focal epilepsy
2013-11-25

Objective To identify novel epilepsy genes using a panel approach and describe the functional consequences of mutations. Methods Using a panel approach, we screened 357 patients comprising a vast spectrum of epileptic disorders for defects in genes known to contribute to epilepsy and/or intellectual disability (ID). After detection of mutations in a novel epilepsy gene, we investigated functional effects in Xenopus laevis oocytes and screened a follow‐up cohort. Results We revealed de novo mutations in GRIN2B encoding the NR2B subunit of the N‐methyl‐D‐aspartate (NMDA) receptor in 2 individuals with West syndrome and severe developmental delay as well as 1 individual with ID and focal epilepsy. The patient with ID and focal epilepsy had a missense mutation in the extracellular glutamate‐binding domain (p.Arg540His), whereas both West syndrome patients carried missense mutations within the NR2B ion channel‐forming re‐entrant loop (p.Asn615Ile, p.Val618Gly). Subsequent screening of 47 patients with unexplained infantile spasms did not reveal additional de novo mutations, but detected a carrier of a novel inherited GRIN2B splice site variant in close proximity (c.2011‐5_2011‐4delTC). Mutations p.Asn615Ile and p.Val618Gly cause a significantly reduced Mg 2+ block and higher Ca 2+ permeability, leading to a dramatically increased Ca 2+ influx, whereas p.Arg540His caused less severe disturbance of channel function, corresponding to the milder patient phenotype. Interpretation We identified GRIN2B gain‐of‐function mutations as a cause of West syndrome with severe developmental delay as well as of ID with childhood onset focal epilepsy. Severely disturbed channel function corresponded to severe clinical phenotypes, underlining the important role of facilitated NMDA receptor signaling in epileptogenesis. ANN NEUROL 2014;75:147–154
rAAV2/7 vector-mediated overexpression of alpha-synuclein in mouse substantia nigra induces protein aggregation and progressive dose-dependent neurodegeneration
2013-11-25

Abstract Background Alpha-synuclein is a key protein implicated in the pathogenesis of Parkinson's disease (PD). It is the main component of the Lewy bodies, a cardinal neuropathological feature in the disease. In addition, whole locus multiplications and point mutations in the gene coding for alpha-synuclein lead to autosomal dominant monogenic PD. Over the past decade, research on PD has impelled the development of new animal models based on alpha-synuclein. In this context, transgenic mouse lines have failed to reproduce several hallmarks of PD, especially the strong and progressive dopaminergic neurodegeneration over time that occurs in the patients. In contrast, viral vector-based models in rats and non-human primates display prominent, although highly variable, nigral dopaminergic neuron loss. However, the few studies available on viral vector-mediated overexpression of alpha-synuclein in mice report a weak neurodegenerative process and no clear Lewy body-like pathology. To address this issue, we performed a comprehensive comparative study of alpha-synuclein overexpression by means of recombinant adeno-associated viral vectors serotype 2/7 (rAAV2/7) at different doses in adult mouse substantia nigra. Results We noted a significant and dose-dependent alpha-synucleinopathy over time upon nigral viral vector-mediated alpha-synuclein overexpression. We obtained a strong, progressive and dose-dependent loss of dopaminergic neurons in the substantia nigra, reaching a maximum of 82% after 8 weeks. This effect correlated with a reduction in tyrosine hydroxylase immunoreactivity in the striatum. Moreover, behavioural analysis revealed significant motor impairments from 12 weeks after injection on. In addition, we detected the presence of alpha-synuclein-positive aggregates in the remaining surviving neurons. When comparing wild-type to mutant A53T alpha-synuclein at the same vector dose, both induced a similar degree of cell death. These data were supported by a biochemical analysis that showed a net increase in soluble and insoluble alpha-synuclein expression over time to the same extent for both alpha-synuclein variants. Conclusions In conclusion, our in vivo data provide evidence that strong and significant alpha-synuclein-induced neuropathology and progressive dopaminergic neurodegeneration can be achieved in mouse brain by means of rAAV2/7.
Fate of Cd during Microbial Fe(III) Mineral Reduction by a Novel and Cd-Tolerant Geobacter Species
2013-11-25

Fe(III) (oxyhydr)oxides affect the mobility of contaminants in the environment by providing reactive surfaces for sorption. This includes the toxic metal cadmium (Cd), which prevails in agricultural soils and is taken up by crops. Fe(III)-reducing bacteria can mobilize such contaminants by Fe(III) mineral dissolution or immobilize them by sorption to or coprecipitation with secondary Fe minerals. To date, not much is known about the fate of Fe(III) mineral-associated Cd during microbial Fe(III) reduction. Here, we describe the isolation of a new Geobacter sp. strain Cd1 from a Cd-contaminated field site, where the strain accounts for 10(4) cells g(-1) dry soil. Strain Cd1 reduces the poorly crystalline Fe(III) oxyhydroxide ferrihydrite in the presence of at least up to 112 mg Cd L(-1). During initial microbial reduction of Cd-loaded ferrihydrite, sorbed Cd was mobilized. However, during continuous microbial Fe(III) reduction, Cd was immobilized by sorption to and/or coprecipitation within newly formed secondary minerals that contained Ca, Fe, and carbonate, implying the formation of an otavite-siderite-calcite (CdCO3-FeCO3-CaCO3) mixed mineral phase. Our data shows that microbially mediated turnover of Fe minerals affects the mobility of Cd in soils, potentially altering the dynamics of Cd uptake into food or phyto-remediating plants.
Human Infant Faces Provoke Implicit Positive Affective Responses in Parents and Non-Parents Alike
2013-11-25

Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors.
Altered growth and improved resistance of Arabidopsis against Pseudomonas syringae by overexpression of the basic amino acid transporter AtCAT1
2013-11-25

Abstract Amino acid transporters in plants are crucial for distributing amino acids between plant organs and cellular compartments. The H + ‐coupled plasma membrane transporter CAT1 (cationic amino acid transporter 1) facilitates the high‐affinity uptake of basic amino acids. The uptake of lysine ( L ys) via the roots was not altered in loss‐of‐function mutants, in accordance with the minor expression of CAT1 in roots, but plants ectopically overexpressing CAT1 incorporated L ys at higher rates. Exogenous L ys inhibited the primary root of A rabidopsis , whereas lateral roots were stimulated. These effects were augmented by the presence or absence of CAT1 . Furthermore, the total biomass of soil‐grown plants ectopically overexpressing CAT1 was reduced and the time to flowering was accelerated. These effects were accompanied by only minor changes in the overall amino acid profile. Interestingly, CAT1 belongs to a specific small cluster of nitrogen‐containing metabolite transporter genes that are rapidly up‐regulated upon infection with P seudomonas syringae and that may participate in the systemic response of plants to pathogen attack. The overexpression of CAT1 indeed enhanced the resistance to the hemibiotrophic bacterial pathogen P . syringae via a constitutively activated salicylic acid ( SA ) pathway, which is consistent with the developmental defects and the resistance phenotype.
Multiresponse, multiobjective calibration as a diagnostic tool to compare accuracy and structural limitations of five coupled soil-plant models and CLM3.5
2013-11-25

Six models with differing representation of the physical process in the coupled soil-plant system are tested to simultaneously reproduce the dynamics of soil water contents, evapotranspiration, and leaf area index during a growing season of winter wheat at two contrasting field plots in the Kraichgau and the Swabian Alb regions in South-West Germany. The main aim of the study is the assessment of the performance and the identification of structural deficits of the models LEACHN, SUCROS, CERES, GECROS, and SPASS as well as the land-surface model CLM3.5. The calibration of each model is posed in a multiobjective framework with three different objective functions that summarize the fit between model simulations and the three observation types. The AMALGAM evolutionary search algorithm is utilized to simultaneously estimate the most important soil hydraulic and plant parameters. The six models exhibit a wide variability in the trade-offs between the fitting to the data types. Mechanistic process description, particularly of the root system, reduces the trade-off considerably for the SPASS and GECROS models. These models adequately simulate the reduction of root water uptake and transpiration during senescence under nonlimited soil water supply. The SPASS model in particular shows an overall better performance as compared to the more simpler models which is related to an adequate level of structural complexity in the interplay of all model compartments combined with a relatively low parameter sensitivity to the weighting scheme in the multiobjective optimization. The dynamic consideration of the root system formation is particularly important, which is simulated quite detailed in the SPASS model as a function of nitrogen (N) and water availability in the different soil horizons. The proposed multiobjective calibration procedure proved to be very useful to identify processes that are important to adequately simulate the coupled soil-plant system. The consideration of these processes and our insights about the value of different data types for model calibration is expected to lead to more accurate, predictive land-surface models.
Mice with Deficient BK Channel Function Show Impaired Prepulse Inhibition and Spatial Learning, but Normal Working and Spatial Reference Memory
2013-11-26

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.