In his Philosophical Investigations, Wittgenstein famously noted that the formation of semantic representations requires more than a simple combination of verbal and nonverbal features to generate conceptually based similarities and differences. Classical and contemporary neuroscience has tended to focus upon how different neocortical regions contribute to conceptualization through the summation of modality-specific information. The additional yet critical step of computing coherent concepts has received little attention. Some computational models of semantic memory are able to generate such concepts by the addition of modality-invariant information coded in a multidimensional semantic space. By studying patients with semantic dementia, we demonstrate that this aspect of semantic memory becomes compromised following atrophy of the anterior temporal lobes and, as a result, the patients become increasingly influenced by superficial rather than conceptual similarities.conceptual knowledge | semantic dementia | semantic memory

Crossover recombination reshuffles genes and prevents errors in segregation that lead to extra or missing chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Here, we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses. Genotyping > 4 million informative single-nucleotide polymorphisms (SNPs) from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns of 529 chromosome pairs. We uncover a novel reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germline by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings reveal that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II.

In the contemporary literature, errorless learning is thought to have benefits over more traditional trial-and-error methods. The most prominent investigations of errorless learning are those designed for rehabilitation of severe memory impairments, including numerous demonstrations of effective amelioration of word-finding difficulties (Baddeley & Wilson, 1994; Clare, Wilson, Breen, & Hodges, 1999; Clare et al., 2000; Evans et al., 2000). Despite this, there are very few reports on the application of purely errorless learning to people with aphasia (Fillingham, Hodgson, Sage, & Lambon Ralph, 2003). The aim of this study was to compare directly the efficacy of errorless and errorful learning in a case series of 11 aphasic people with pronounced word-finding difficulties. Previous studies of errorless learning and, more recently, studies of rehabilitation have suggested that cognition is an important factor for determining outcome (Helm-Estabrooks, 2002; Robertson & Murre, 1999). Therefore, a thorough language and neuropsychological assessment battery was completed with each participant. Naming therapy was carried out to contrast errorless and errorful therapy in a case series analysis. Errorless learning proved to be as effective as the more traditional, errorful approach in the majority of cases in terms of both immediate improvement and at follow up assessment. Without exception, the patients preferred the errorless learning therapy. Strikingly, it was found that language skill did not predict therapy outcome. Participants who responded better overall, had better recognition memory, executive/problem solving skills and monitoring ability. This replicates recent findings that frontal executive skills are crucial for rehabilitation (Robertson & Murre, 1999). Also, participants who did better at errorful treatment were those with the best working and recall memory, and attention. It is probable that these factors are essential cognitive components for providing effective monitoring and feedback systems to a more general learning mechanism.

The findings support the view that cognitive abilities and in particular executive function are important contributors to rehabilitation.

SummaryDefects in segregation lead to missing or lacking chromosomes (aneuploidy) in human eggs, a major cause of pregnancy failure and congenital disorders. Physical exchanges (crossovers) between homologous chromosomes are formed during foetal development and ensure that the pair remains tethered until their separation decades later in the meiotic divisions in adult oocytes. Here, we generate genome-wide maps of crossovers and chromosome segregation patterns by recovering all three products of single female meioses (embryo or oocytes and corresponding polar bodies). Genotyping > 4 million informative single-nucleotide polymorphisms (SNPs) from 23 complete meioses allowed us to map 2,032 maternal and 1,342 paternal crossovers and to infer the segregation patterns from 529 chromosome pairs.We uncover a novel reverse chromosome segregation pattern in which both homologs separate their sister chromatids at meiosis I; detect selection for higher recombination rates in the female germline by the elimination of aneuploid embryos; and report chromosomal drive against non-recombinant chromatids at meiosis II. Collectively, our findings reveal that recombination not only affects homolog segregation at meiosis I but also the fate of sister chromatids at meiosis II.3 Main text.Errors in chromosome segregation during the meiotic divisions in human female meiosis are a major cause of aneuploid conceptions, leading to implantation failure, pregnancy loss, and congenital disorders 1 . The incidence of human trisomies increases exponentially in women from ~ 35 years of age, but despite conservative estimates that 10-30% of natural conceptions are aneuploid 2 , the underlying causes and their relative contributions are still unclear. In addition to maternal age, one important factor that is hypothesized to predispose to missegregation in both sexes is altered recombination. Recombinant chromosomes in the offspring are the result of crossovers, the reciprocal exchange of DNA between homologous chromosomes (homologs). Together with sister chromatid cohesion, crossovers physically link the homolog pair together during the prophase stage of meiosis (Fig. 1a), which takes place during foetal development in females. The linkages have to be maintained for decades, because the two rounds of chromosome segregation only occur in the adult woman. By following the pattern of genetic markers such as single nucleotide polymorphisms (SNPs) on the two chromosomes inherited from the mother in trisomic conceptions, it has been inferred that some crossovers occur too close to centromeres 1,3-6 , where they may disrupt the cohesion between the two sister chromatids 7,8 . Other crossovers have been suggested to be too far from the centromeres to mediate correct attachment, or to be lacking altogether (non-exchange, E 0 ) 1,3-6 . If these inferences are correct, it follows that events that shape the recombination landscape in oocytes during foetal development of women affect their risk of having an aneuploid conception decades later in adult lif...