The Manson impact structure (MIS) is proposed to be the result of an oblique impact (20 to 30º from the horizontal) from the southeast. Such an interpretation is based on similarities between asymmetry in the MIS and patterns produced in laboratory experiments and observed on planetary surfaces. Diagnostic signatures include the following features: (1) maximum central uplift (corresponding to deepest penetration) offset uprange from the geometric center, (2) breached central peak complex parallel to the trajectory, (3) large central uplift diameter relative to diameter, (4) larger diameter and greater disruption transverse to (rather than along) the trajectory, (5) maximum structural rim uplift transverse to the trajectory with minimum uplift downrange (northwest), and (6) shallower than expected excavation. Theproposed origin for the MIS helps to account for the preservation of sheared but insequence strata from depths of only 2 km on the central peaks. It is also consistent with the nature, distribution, and sequence of ejecta deposits including high-speed downrange ejecta represented by materials in the Crow Creek Member of the Pierre Shale and the matrix-supported ejecta debris draping the clastic overturned rim sequences and central peaks.

Klebsiella pneumoniae causes urinary tract infections, respiratory tract infections, and septicemia in susceptible individuals. Strains of Klebsiella frequently produce extended-spectrum beta-lactamases, and infections with these strains can lead to relatively high mortality rates (approximately 15%). Other virulence factors include production of an antiphagocytic capsule and outer membrane lipopolysaccharide (LPS), which mediates serum resistance, as well as fimbriae on the surface of the bacteria. Type 1 fimbriae mediate adherence to many types of epithelial cells and may facilitate adherence of the bacteria to the bladder epithelium. Type 3 fimbriae can bind in vitro to the extracellular matrix of urinary and respiratory tissues, suggesting that they mediate binding to damaged epithelial surfaces. In addition, type 3 fimbriae are required for biofilm formation by Klebsiella pneumoniae on plastics and human extracellular matrix; thus, they may facilitate the formation of treatment-resistant biofilm on indwelling plastic devices, such as catheters and endotracheal tubing. The presence of these devices may cause tissue damage, allowing Klebsiella to grow as a biofilm on exposed tissue basement membrane components. Though in vivo biofilm growth may be an important step in the infection process, little is known about the genetic factors required for biofilm formation by Klebsiella pneumoniae. Thus, we performed signature-tagged mutagenesis to identify factors produced by K. pneumoniae strain 43816 that are required for biofilm formation. We identified mutations in the cps capsule gene cluster, previously unidentified transcriptional regulators, fimbrial, and sugar phosphotransferase homologues, as well as genetic loci of unknown function, that affect biofilm formation.

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The Runx1 transcription factor plays an important role in tissue homeostasis through its effects on stem ⁄ progenitor cell populations and differentiation. The effect of Runx1 on epithelial differentiation of the secretory cell lineage of the colon was recently demonstrated. This study aimed to examine the role of Runx1 in tumor development in epithelial cells of the gastrointestinal tract. Conditional knockout mice that lacked Runx1 expression in epithelial cells of the GI tract were generated. These mice were crossed onto the Apc Min background, killed and their intestinal tumor phenotypes were compared with Apc Min Runx1 wild-type control mice. Apc-wild-type Runx1-mutant mice were also examined for tumor development. Colons from Runx1 knockout and wild-type mice were used for genome-wide mRNA expression analyses followed by gene-specific quantitative RT-PCR of whole colon and colon epithelium to identify Runx1 target genes. Runx1 deficiency in intestinal epithelial cells significantly enhanced tumorigenesis in Apc Min mice. Notably, epithelial Runx1 deficiency in Apc-wildtype mice was sufficient to cause tumor development. Absence of Runx1 was associated with global changes in the expression of genes involved in inflammation and intestinal metabolism, and with gene sets indicative of a metastatic phenotype and poor prognosis. Gene-specific analysis of Runx1-deficient colon epithelium revealed increased expression of genes linked to an expansion of the stem ⁄ progenitor cell population. These results identify Runx1 as a novel tumor suppressor gene for gastrointestinal tumors and support a role for Runx1 in maintaining the balance between the intestinal stem ⁄ progenitor cell population and epithelial differentiation of the GI tract. (Cancer Sci 2012; 103: 593-599) T he human and mouse family of RUNX transcription factors are composed of three members, RUNX1, RUNX2 and RUNX3. They function as either transcriptional activators or repressors depending on the target gene, cell type and the presence of co-factors. RUNX1 has been implicated in homeostasis of the hematopoietic stem cell number, as well as in developmental lineage specification, thereby being a critical factor for hematopoiesis and hematopoietic function.(1,2) In mice, Runx1 is essential for mammalian development as germline knockouts (KO) are embryonic lethal due to a complete failure of hematopoiesis.(3) In humans, polymorphisms that reduce the binding of RUNX1 to specific target genes have been associated with susceptibility to the autoimmune diseases psoriasis, systemic lupus erythematosus (SLE) and rheumatoid arthritis.(4) Moreover, RUNX1 is frequently mutated in a common subtype of human acute myeloid leukemia (AML), where often the rate-limiting step is formation of mutant fusion genes ⁄ proteins that combine the N-terminal DNA-binding domain of RUNX1 (RHD) with the full-length activation domains of oncogenes.(5) An example is the eight twenty-one (ETO) t(8;21) translocation that is present in approximately 40% of human AML. Notably, these ...

A problem with the impact hypothesis for the Cretaceous/Tertiary (K/T) mass extinction is the apparent absence of an identifiable impact site. The Manson impact structure is a candidate site because of its size (the largest such structure recognized in the United States); in addition, the largest and most abundant shocked quartz grains at the K/T boundary are found relatively close by, and its age is indistinguishable from that of the K/T boundary.The region of northwest central Iowa that contains the Manson impact structure is covered by Quaternary glacial deposits, which are underlain by Phanerozoic sedimentary rocks (mostly flat-lying carbonates) and Proterozoic red clastic, metamorphic, volcanic, and plutonic rocks. In a circular area about 22 mi (35 km) in diameter around Manson, Iowa, this normal sequence is absent or "disturbed." Within the structure, three roughly concentric zones of rock associations have been identified: an outer zone of displaced strata, a zone of completely disrupted strata, and a central area in which basement igneous and metamorphic rocks have been uplifted at least 1,220 ft (4,000 m). Gravity, magnetic, and seismic refraction surveys readily identify the central uplift within the structure. Manson is established as an impact structure based on its circular shape, its central uplift, and the presence of shocked quartz within the granitic central uplift.Paleontological evidence, a fission track age, and preliminary 40 Ar/ 39 Ar dating all allowed a K/T boundary age for the Manson structure. Improved 40 Ar/ 39 Ar age spectra may be interpreted in terms of samples that were incompletely degassed during heating due to the Manson impact. An age of 65.7 ±1.0 Ma was obtained, a value indistinguishable from that of the K/T boundary.