Changing minds: Children's inferences about third party belief revision

By the age of 5, children explicitly represent that agents can have both true and false beliefs based on epistemic access to information (e.g., Wellman, Cross, & Watson, 2001). Children also begin to understand that agents can view identical evidence and draw different inferences from it (e.g., Carpendale & Chandler, 1996). However, much less is known about when, and under what conditions, children expect other agents to change their minds. Here, inspired by formal ideal observer models of learning, we investigate children's expectations of the dynamics that underlie third parties' belief revision. We introduce an agent who has prior beliefs about the location of a population of toys and then observes evidence that, from an ideal observer perspective, either does, or does not justify revising those beliefs. We show that children's inferences on behalf of third parties are consistent with the ideal observer perspective, but not with a number of alternative possibilities, including that children expect other agents to be influenced only by their prior beliefs, only by the sampling process, or only by the observed data. Rather, children integrate all three factors in determining how and when agents will update their beliefs from evidence.National Science Foundation (U.S.). Division of Computing and Communication Foundations (1231216)National Science Foundation (U.S.). Division of Research on Learning in Formal and Informal Settings (0744213)National Science Foundation (U.S.) (STC Center for Brains, Minds and Machines Award CCF-1231216)National Science Foundation (U.S.) (0744213

Determining the Nature of the SS 433 Binary Using an X-ray Spectrum During Eclipse

We test the physical model of the relativistic jets in the galactic X-ray binary SS 433 proposed in our previous paper using additional observations from the Chandra High Energy Transmission Grating Spectrometer. These observations sample two new orbital/precessional phase combinations. In the observation near orbital phase zero, the H- and He-like Fe lines from both receding and approaching jets are comparably strong and unocculted while the He-like Si line of the receding jet is significantly weaker than that of the approaching jet. This condition may imply the cooler parts of the receding jet are eclipsed by the companion. The X-ray spectrum from this observation has broader emission lines than obtained in Paper I that may arise from the divergence of a conical outflow or from Doppler shift variations during the observation. Using recent optical results, along with the length of the unobscured portion of the receding jet assuming adiabatic cooling, we calculate the radius of the companion to be 9.6+/-1.0 R_sun, about one third of the Roche lobe radius. For a main sequence star, this corresponds to a companion mass of 35+/-7 M_sun, giving a primary source mass of 20+/-5 M_sun. If our model is correct, this calculation indicates the compact object is a black hole, and accretion occurs through a wind process. In a subsequent paper, we will examine the validity of the adiabatic cooling model of the jets and test the mode of line broadening.Comment: 26 pages, 10 figures, accepted to Ap

The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence

K.L.S. was supported by the Australian National Health and Medical Research Council (NHMRC) C. J. Martin Fellowship and Career Development Fellowship. A.F.H. was supported by a Marie Curie Fellowship (PIEF-GA-2012-328377). F.O., L.F., and S.B. were recipients of Novartis fellowships from the Ph.D. program of the University of Siena (Siena, Italy) and University of Bologna (Bologna, Italy), respectively.GNA2091 is one of the components of the 4-component meningococcal serogroup B vaccine (4CMenB) vaccine and is highly conserved in all meningococcal strains. However, its functional role has not been fully characterized. Here we show that nmb2091 is part of an operon and is cotranscribed with the nmb2089, nmb2090, and nmb2092 adjacent genes, and a similar but reduced operon arrangement is conserved in many other gram-negative bacteria. Deletion of the nmb2091 gene causes an aggregative phenotype with a mild defect in cell separation; differences in the outer membrane composition and phospholipid profile, in particular in the phosphoethanolamine levels; an increased level of outer membrane vesicles; and deregulation of the zinc-responsive genes such as znuD. Finally, the Δ2091 strain is attenuated with respect to the wild-type strain in competitive index experiments in the infant rat model of meningococcal infection. Altogether these data suggest that GNA2091 plays important roles in outer membrane architecture, biogenesis, homeostasis, and in meningococcal survival in vivo, and amodel for its role is discussed. These findings highlight the importance of GNA2091 as a vaccine component.PostprintPeer reviewe

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this “uncultivated majority” remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes. Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages. IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism

TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis

The Endoplasmic Reticulum (ER) is responsible for the folding and post-translational modification of secretory proteins, as well as for triaging misfolded proteins. During folding, there is a complex yet only partially understood interplay between disulfide bond formation, which is an enzyme catalyzed event in the oxidizing environment of the ER, along with other post-translational modifications (PTMs) and chaperone-supported protein folding. Here, we used the glycoprotein torsinA as a model substrate to explore the impact of ER redox homeostasis on PTMs and protein biogenesis. TorsinA is a AAA+ ATPase with unusual oligomeric properties and controversial functions. The deletion of a C-terminal glutamic acid residue (∆E) is associated with the development of Early-Onset Torsion Dystonia, a severe movement disorder. TorsinA differs from other AAA+ ATPases since it is an ER resident, and as a result of its entry into the ER torsinA contains two N-linked glycans and at least one disulfide bond. The role of these PTMs on torsinA biogenesis and function and the identity of the enzymes that catalyze them are poorly defined. Using a yeast torsinA expression system, we demonstrate that a specific protein disulfide isomerase, Pdi1, affects the folding and N-linked glycosylation of torsinA and torsinA∆E in a redox-dependent manner, suggesting that the acquisition of early torsinA folding intermediates is sensitive to perturbed interactions between Cys residues and the quality control machinery. We also highlight the role of specific Cys residues during torsinA biogenesis and demonstrate that torsinA∆E is more sensitive than torsinA when these Cys residues are mutated.Fil: Honer, Jonas. University of Pittsburgh; Estados UnidosFil: Niemeyer, Katie M.. University of Pittsburgh; Estados UnidosFil: Fercher, Christian. The University of Queensland; AustraliaFil: Diez Tissera, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Jaberolansar, Noushin. The University of Queensland; AustraliaFil: Jafrani, Yohaann M.A.. The University of Queensland; AustraliaFil: Zhou, Chun. The University of Queensland; AustraliaFil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shewan, Annette M.. The University of Queensland; AustraliaFil: Schulz, Benjamin L.. The University of Queensland; AustraliaFil: Brodsky, Jeffrey L.. University of Pittsburgh; Estados UnidosFil: Zacchi, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Pittsburgh; Estados Unidos. The University of Queensland; Australi

Mind the Gap: Investigating Toddlers’ Sensitivity to Contact Relations in Predictive Events

Toddlers readily learn predictive relations between events (e.g., that event A predicts event B). However, they intervene on A to try to cause B only in a few contexts: When a dispositional agent initiates the event or when the event is described with causal language. The current studies look at whether toddlers’ failures are due merely to the difficulty of initiating interventions or to more general constraints on the kinds of events they represent as causal. Toddlers saw a block slide towards a base, but an occluder prevented them from seeing whether the block contacted the base; after the block disappeared behind the occluder, a toy connected to the base did or did not activate. We hypothesized that if toddlers construed the events as causal, they would be sensitive to the contact relations between the participants in the predictive event. In Experiment 1, the block either moved spontaneously (no dispositional agent) or emerged already in motion (a dispositional agent was potentially present). Toddlers were sensitive to the contact relations only when a dispositional agent was potentially present. Experiment 2 confirmed that toddlers inferred a hidden agent was present when the block emerged in motion. In Experiment 3, the block moved spontaneously, but the events were described either with non-causal (“here’s my block”) or causal (“the block can make it go”) language. Toddlers were sensitive to the contact relations only when given causal language. These findings suggest that dispositional agency and causal language facilitate toddlers’ ability to represent causal relationships.John Templeton Foundation (#12667)James S. McDonnell Foundation (Causal Learning Collaborative Initiative)National Science Foundation (U.S.) (Career Award (# 0744213

Caracterización hidroquímica e isotópica del agua subterránea en el acuífero de Quemú Quemú, La Pampa, Argentina

Este trabajo presenta una caracterización hidroquímica e isotópica del acuífero de Quemú Quemú, ub icado al Noreste de la provincia de La Pampa, Argentina. Se tomaron muestras de agua subterránea, superficial y lluvias para determinaciones físico-químicas e isotópicas. La zona de recarga se extiende a lo largo de un cordón medanoso donde la composición isotópica del agua subterránea refleja la composición promedio de la precipitación local; la conductividad eléctrica es baja, y las aguas son predominantemente bicarbonatadas sódica/magnésicas y bicarbonatadas sódicas. Las de mayor conductividad eléctrica y similar composición isotópica se relacionan a las áreas de conducción, ubicadas hacia los laterales de este cordón, y las facies son bicarbonatadas sódicas. Las aguas con mayor conductividad eléctrica e isotópicamente enriquecidas se asocian a zonas de descarga, presentando facies cloruradas/sulfatadas sódicas.This paper presents a hydrochemical and isotopic characterization of Quemu Quemu aquifer, located to the northeast of the province of La Pampa. Groundwater, surface water and rains samples were taken in order to analyze their chemistry and isotope composition. The recharge zone extends along the dune area where the groundwater isotope composition reflects the average composition of the local precipitation; electrical conductivity is low and waters are mainly sodium/magnesium bicarbonate and sodium bicarbonate. Those with high electrical conductivity and similar isotope composition are related to conduction zones and are located towards the sides of the dunes, and the facies are sodium bicarbonate. Waters with the highest salinity and isotopical enriched are associated to discharge zones and present sodium chloride/sulfate facies.Universidad Nacional de La Plat

Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment

<p>Abstract</p> <p>Background</p> <p>The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer.</p> <p>Methods</p> <p>Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible.</p> <p>Results</p> <p>Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.</p> <p>Conclusions</p> <p>Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.</p

Circulating Micro-RNAs as Potential Blood-Based Markers for Early Stage Breast Cancer Detection

INTRODUCTION: MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. METHODS: We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). RESULTS: Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. CONCLUSIONS: MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use