600 research outputs found

    Functional connectivity during a social emotion task in adolescents and in adults

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    In this fMRI study we investigated functional connectivity between components of the mentalising system during a social emotion task, using psychophysiological interaction (PPI) analysis. Ten adults (22–32 years) and 18 adolescents (11–18 years) were scanned while thinking about scenarios in which a social or a basic emotion would be experienced. Unlike basic emotions (such as disgust and fear), social emotions (such as embarrassment and guilt) require the representation of another's mental states. In both adults and adolescents, an anterior rostral region of medial prefrontal cortex (arMPFC) involved in mentalising showed greater connectivity with the posterior superior temporal sulcus (pSTS) bordering on the temporo-parietal junction (TPJ) and with anterior temporal cortex (ATC) during social than during basic emotion. This result provides novel evidence that components of the mentalising system interact functionally during a social emotion task. Furthermore, functional connectivity differed between adolescence and adulthood. The adolescent group showed stronger connectivity between arMPFC and pSTS/TPJ during social relative to basic emotion than did the adult group, suggestive of developmental changes in functional integration within the mentalising system

    Lynch Syndrome - Cancer Pathways, Heterogeneity and Immune Escape

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    Recent work has provided evidence for genetic and molecular heterogeneity in colorectal cancers (CRCs) arising in patients with Lynch syndrome (LS), dividing these into two groups: G1 and G2. In terms of mutation and gene expression profile, G1 CRCs bear resemblance to sporadic CRCs with microsatellite instability (MSI), whereas G2 CRCs are more similar to microsatellite stable CRCs. Here we review the current state of knowledge on pathways of precursor progression to CRC in LS and how these might tie in with the new findings. Immunotherapies are an active field of research for MSI cancers and their potential use for cancer therapy for both sporadic and LS MSI cancers is discussed

    Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review

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    High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase CRC risk. We attempted to validate the association between variants in these genes and development of CRC in a systematic review of 11 publications, using sequence data from 863 familial CRC cases and 1604 individuals without CRC (controls). All cases were diagnosed at an age of 55 years or younger and did not carry mutations in an established CRC predisposition gene. We found sufficient evidence for NTHL1 to be considered a CRC predisposition gene-members of 3 unrelated Dutch families were homozygous for inactivating p.Gln90Ter mutations; a Canadian woman with polyposis, CRC, and multiple tumors was reported to be heterozygous for the inactivating NTHL1 p.Gln90Ter/c.709+1G>A mutations; and a man with polyposis was reported to carry p.Gln90Ter/p.Gln287Ter; whereas no inactivating homozygous or compound heterozygous mutations were detected in controls. Variants that disrupted RPS20 were detected in a Finnish family with early-onset CRC (p.Val50SerfsTer23), a 39-year old individual with metachronous CRC (p.Leu61GlufsTer11 mutation), and a 41-year-old individual with CRC (missense p.Val54Leu), but not in controls. We therefore found published evidence to support the association between variants in NTHL1 and RPS20 with CRC, but not of other recently reported CRC susceptibility variants. We urge the research community to adopt rigorous statistical and biological approaches coupled with independent replication before making claims of pathogenicity
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