LKB1 modulates lung cancer differentiation and metastasis

Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis.     

Fetal load and the evolution of lumbar lordosis in bipedal hominins

As predicted by Darwin, bipedal posture and locomotion are key distinguishing features of the earliest known hominins. Hominin axial skeletons show many derived adaptations for bipedalism, including an elongated lumbar region, both in the number of vertebrae and their lengths, as well as a marked posterior concavity of wedged lumbar vertebrae, known as a lordosis. The lordosis stabilizes the upper body over the lower limbs in bipeds by positioning the trunk's centre of mass (COM) above the hips. However, bipedalism poses a unique challenge to pregnant females because the changing body shape and the extra mass associated with pregnancy shift the trunk's COM anterior to the hips. Here we show that human females have evolved a derived curvature and reinforcement of the lumbar vertebrae to compensate for this bipedal obstetric load. Similarly dimorphic morphologies in fossil vertebrae of Australopithecus suggest that this adaptation to fetal load preceded the evolution of Homo.     

Montane insular butterfly biogeography: fauna of Ball Mountain, Siskiyou County, California

Ball Mountain is an isolated, mostly heavily forested peak reaching the subalpine zone (2,330 m) in eastern Siskiyou County north of Mt. Shasta, California. It supports a rich fauna of at least 68 butterfly species showing affinities to the faunas of the Trinity Alps and Eddies, the Warners, and the Cascades. Rare or endemic entities include Speyeria monnonia, Lycaena heteronea gravenotata , and melanic forms of Speyeria atlantis and Agriades ";glandon."; Several zones of intergradation or hybridization impinge on the fauna as well.