Comparison and Mapping Facilitate Relation Discovery and Predication

Relational concepts play a central role in human perception and cognition, but little is known about how they are acquired. For example, how do we come to understand that physical force is a higher-order multiplicative relation between mass and acceleration, or that two circles are the same-shape in the same way that two squares are? A recent model of relational learning, DORA (Discovery of Relations by Analogy; Doumas, Hummel & Sandhofer, 2008), predicts that comparison and analogical mapping play a central role in the discovery and predication of novel higher-order relations. We report two experiments testing and confirming this prediction

Desmocollin switching in colorectal cancer

The desmocollins are members of the desmosomal cadherin family of cell–cell adhesion molecules. They are essential constituents of desmosomes, intercellular junctions that play a critical role in the maintenance of tissue integrity in epithelia and cardiac muscle. In humans, three desmocollins (Dsc1, Dsc2 and Dsc3) have been described. The desmocollins exhibit tissue-specific patterns of expression; only Dsc2 is expressed in normal colonic epithelium. We have found switching between desmocollins in sporadic colorectal adenocarcinoma with a reduction in Dsc2 protein (in 8/16 samples analysed by immunohistochemistry) being accompanied by de novo expression of Dsc1 (16/16) and Dsc3 (7/16). Similar results were obtained by western blotting of a further 16 samples. No change was found in Dsc2 mRNA, but de novo expression of Dscs 1 and 3 was accompanied by increased message levels. Loss of Dsc2 (8/19) and de novo expression of Dsc1 (11/19) and Dsc3 (6/19) was also found in colorectal adenocarcinomas on a background of colitis. The data raise the possibility that switching of desmocollins could play an important role in the development of colorectal cancer

Same/Different Concept Learning by Capuchin Monkeys in Matching-to-Sample Tasks

The ability to understand similarities and analogies is a fundamental aspect of human advanced cognition. Although subject of considerable research in comparative cognition, the extent to which nonhuman species are capable of analogical reasoning is still debated. This study examined the conditions under which tufted capuchin monkeys (Cebus apella) acquire a same/different concept in a matching-to-sample task on the basis of relational similarity among multi-item stimuli. We evaluated (i) the ability of five capuchin monkeys to learn the same/different concept on the basis of the number of items composing the stimuli and (ii) the ability to match novel stimuli after training with both several small stimulus sets and a large stimulus set. We found the first evidence of same/different relational matching-to-sample abilities in a New World monkey and demonstrated that the ability to match novel stimuli is within the capacity of this species. Therefore, analogical reasoning can emerge in monkeys under specific training conditions

The relationship between fertility and lifespan in humans

Evolutionary theories of aging predict a trade-off between fertility and lifespan, where increased lifespan comes at the cost of reduced fertility. Support for this prediction has been obtained from various sources. However, which genes underlie this relationship is unknown. To assess it, we first analyzed the association of fertility with age at menarche and menopause, and with mortality in 3,575 married female participants of the Rotterdam Study. In addition, we conducted a candidate gene study where 1,664 single nucleotide polymorphisms (SNPs) in 25 candidate genes were analyzed in relation to number of children as a measure of fertility. SNPs that associated with fertility were analyzed for association with mortality. We observed no associations between fertility and age at menarche (p = 0.38) and menopause (p = 0.07). In contrast, fertility was associated with mortality. Women with two to three children had significantly lower mortality (hazard ratio (HR), 0.82; 95% confidence interval (95% CI), 0.69–0.97) compared to women with no children. No such benefit was observed for women with four or more children, who had a similar mortality risk (HR, 0.93; 95% CI, 0.76–1.13) as women with no children. The analysis of candidate genes revealed four genes that influence fertility after correction for multiple testing: CGB/LHB gene cluster (p = 0.0036), FSHR (p = 0.023), FST (p = 0.023), and INHBA (p = 0.021). However, none of the independent SNPs in these genes predicted mortality. In conclusion, women who bear two to three children live longer than those who bear none or many children, but this relationship was not mediated by the candidate genes analyzed in this study

CD4(+)CD25(+)FOXP3(+) Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer

BACKGROUND: A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients. METHODOLOGY AND PRINCIPAL FINDINGS: Treg were identified and characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group. CONCLUSIONS/SIGNIFICANCE: Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy

Human-Like Receptor Specificity Does Not Affect the Neuraminidase-Inhibitor Susceptibility of H5N1 Influenza Viruses

If highly pathogenic H5N1 influenza viruses acquire affinity for human rather than avian respiratory epithelium, will their susceptibility to neuraminidase (NA) inhibitors (the likely first line of defense against an influenza pandemic) change as well? Adequate pandemic preparedness requires that this question be answered. We generated and tested 31 recombinants of A/Vietnam/1203/04 (H5N1) influenza virus carrying single, double, or triple mutations located within or near the receptor binding site in the hemagglutinin (HA) glycoprotein that alter H5 HA binding affinity or specificity. To gain insight into how combinations of HA and NA mutations can affect the sensitivity of H5N1 virus to NA inhibitors, we also rescued viruses carrying the HA changes together with the H274Y NA substitution, which was reported to confer resistance to the NA inhibitor oseltamivir. Twenty viruses were genetically stable. The triple N158S/Q226L/N248D HA mutation (which eliminates a glycosylation site at position 158) caused a switch from avian to human receptor specificity. In cultures of differentiated human airway epithelial (NHBE) cells, which provide an ex vivo model that recapitulates the receptors in the human respiratory tract, none of the HA-mutant recombinants showed reduced susceptibility to antiviral drugs (oseltamivir or zanamivir). This finding was consistent with the results of NA enzyme inhibition assay, which appears to predict influenza virus susceptibility in vivo. Therefore, acquisition of human-like receptor specificity does not affect susceptibility to NA inhibitors. Sequence analysis of the NA gene alone, rather than analysis of both the NA and HA genes, and phenotypic assays in NHBE cells are likely to adequately identify drug-resistant H5N1 variants isolated from humans during an outbreak

Democratic experimentation in early childhood education

Qualifications of the early years workforce are a salient predictors of quality and therefore of children’s outcomes. International reports advise that a majority of staff is trained at Bachelor’s levels and rank countries according to this criterion. There is fewer consensus on what this professionalism should be. In a majority of countries, large numbers of professionals are untrained, unqualified and sometimes invisible in the official reports. Many of these unqualified “assistants” take up crucial “care” tasks, while the teacher’s tasks are defined as “education”. The separation between care and education occurs in split systems as well as in systems where education and care are supposed to be integrated. In addition, the growing diversity of families challenges our preconceived ideas about “the good life” for children. These observations urge us to rethink professionalism in terms of reflexivity and the capacity of co-constructing pedagogy with parents and children. A case study in Ghent shows how low qualified professionals develop research capacities. The analysis of their experience suggests that “learning” may be less a quality of the individual than a quality of the systemic relationships that are build in the teams as well as in the interaction between teams and their social contexts

Identifying Changes in Selective Constraints: Host Shifts in Influenza

The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known

Deficit of social cognition in subjects with surgically treated frontal lobe lesions and in subjects affected by schizophrenia

The ability of humans to predict and explain other people’s behaviour by attributing independent mental states such as desires and beliefs to them, is considered to be due to our ability to construct a “Theory of Mind”. Recently, several neuroimaging studies have implicated the medial frontal lobes as playing a critical role in a dedicated “mentalizing” or “Theory of Mind” network in the human brain. In this study we compare the performance of patients with right and left medial prefrontal lobe lesions in theory of mind and in social cognition tasks, with the performance of people with schizophrenia. We report a similar social cognitive profile between patients with prefrontal lobe lesions and schizophrenic subjects in terms of understanding of false beliefs, in understanding social situations and in using tactical strategies. These findings are relevant for the functional anatomy of “Theory of Mind”