Melanoma genome sequencing reveals frequent PREX2 mutations

Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.     

Folic acid levels in blood and seminal plasma of normo- and oligospermic patients prior and following folic acid treatment

Folic acid was estimated in blood and seminal plasma of normo- and oligospermic men. Following folic acid administration (10 mg TID for 30 days), the levels in blood and semen increased. However, sperm counts, motility and DNA content of spermatozoa were not affected.     

Folic acid levels in blood and seminal plasma of normo- and oligospermic patients prior and following folic acid treatment

Summary Folic acid was estimated in blood and seminal plasma of normo- and oligospermic men. Following folic acid administration (10 mg TID for 30 days), the levels in blood and semen increased. However, sperm counts, motility and DNA content of spermatozoa were not affected.     

β-Endorphin in normozoospermic and pathologic human semen

Summary -Endorphin was estimated in normozoospermic, oligozoospermic and azoospermic human semen. The mean amount in normozoospermic specimens was 278.6±43.6 (SE) pg/ml while in the others only 191.1±25 pg/ml. Both values are significantly higher than those present in the blood.     

Empathic neural responses are modulated by the perceived fairness of others

The neural processes underlying empathy are a subject of intense interest within the social neurosciences. However, very little is known about how brain empathic responses are modulated by the affective link between individuals. We show here that empathic responses are modulated by learned preferences, a result consistent with economic models of social preferences. We engaged male and female volunteers in an economic game, in which two confederates played fairly or unfairly, and then measured brain activity with functional magnetic resonance imaging while these same volunteers observed the confederates receiving pain. Both sexes exhibited empathy-related activation in pain-related brain areas (fronto-insular and anterior cingulate cortices) towards fair players. However, these empathy-related responses were significantly reduced in males when observing an unfair person receiving pain. This effect was accompanied by increased activation in reward-related areas, correlated with an expressed desire for revenge. We conclude that in men (at least) empathic responses are shaped by valuation of other people's social behaviour, such that they empathize with fair opponents while favouring the physical punishment of unfair opponents, a finding that echoes recent evidence for altruistic punishment.