Cenozoic evolution of the eastern Black Sea: a test of depth-dependent stretching models

Subsidence analysis of the eastern Black Sea basin suggests that the stratigraphy of this deep, extensional basin can be explained by a predominantly pure-shear stretching history. A strain-rate inversion method that assumes pure-shear extension obtains good fits between observed and predicted stratigraphy. A relatively pure-shear strain distribution is also obtained when a strain-rate inversion algorithm is applied that allows extension to vary with depth without assuming its existence or form. The timing of opening of the eastern Black Sea, which occupied a back-arc position during the closure of the Tethys Ocean, has also been a subject of intense debate; competing theories called for basin opening during the Jurassic, Cretaceous or Paleocene/Eocene. Our work suggests that extension likely continued into the early Cenozoic, in agreement with stratigraphic relationships onshore and with estimates for the timing of arc magmatism. Further basin deepening also appears to have occurred in the last 20 myr. This anomalous subsidence event is focused in the northern part of the basin and reaches its peak at 15–10 Ma. We suggest that this comparatively localized shortening is associated with the northward movement of the Arabian plate. We also explore the effects of paleowater depth and elastic thickness on the results. These parameters are controversial, particularly for deep-water basins and margins, but their estimation is a necessary step in any analysis of the tectonic subsidence record stored in stratigraphy. <br/

Non-linear enhancement of laser generated ultrasonic Rayleigh waves by cracks

Laser generated ultrasound has been widely used for detecting cracks, surface and sub-surface defects in many different materials. It provides a non-contact wideband excitation source which can be focused into different geometries. Previous workers have reported enhancement of the laser generated Rayleigh wave when a crack is illuminated by pulsed laser beam irradiation. We demonstrate that the enhancement observed is due to a combination of source truncation, the free boundary condition at the edge of the crack and interference effects. Generating a Rayleigh wave over a crack can lead to enhancement of the amplitude of the Rayleigh wave signal, a shift in the dominant frequency of the wideband Rayleigh wave and strong enhancement of the high frequency components of the Rayleigh wave

Fancc regulates the spindle assembly checkpoint to prevent tumorigenesis in vivo

Indiana University-Purdue University Indianapolis (IUPUI)The Fanconi anemia (FA) pathway consists of 21 genes that maintain genomic stability and prevent cancer. Biallelic mutations within this network cause Fanconi anemia, an inherited bone marrow failure and cancer predisposition syndrome. Heterozygous inborn mutations in FA genes increase risk of breast/ovarian cancers, and somatic mutations occur in malignancies in non-Fanconi patients. Understanding the tumor suppressive functions of FA signaling is important for the study of Fanconi anemia, inherited cancers, and sporadic cancers. The FA network functions as a genome guardian throughout the cell cycle. In addition to the well-established roles of FA proteins in interphase DNA replication/repair, the FA pathway controls mitosis by regulating the spindle assembly checkpoint (SAC) to ensure proper chromosome segregation. The SAC consists of several tumor suppressors, including Mad2, and SAC impairment predisposes to aneuploidy and cancer. However, the in vivo contribution of SAC dysfunction to malignant transformation of FA-deficient cells remains unknown. Furthermore, the mechanisms by which FA proteins regulate the SAC are unclear. To test whether SAC dysfunction drives genomic instability and tumorigenesis in FA, we generated a novel FA-SAC model by intercrossing Fancc-/- and Mad2+/- mice. The intercrossed mice displayed heightened aneuploidy secondary to exacerbated SAC dysfunction. Importantly, these mice were prone to developing hematologic malignancies, particularly leukemia, faithfully recapitulating the clinical phenotype of Fanconi anemia. Upon establishing SAC dysfunction as a driver of tumorigenesis in FA, we next explored the mechanism by which FANCC regulates the SAC. We demonstrated that the mitotic kinase CDK1 phosphorylates FANCC to regulate subcellular localization and SAC function of FANCC during mitosis. Our study highlights the essential role of compromised chromosome segregation in the development of leukemia due to impaired FA signaling. This work furthers our knowledge of FANCC signaling at the SAC, and has implications for future use of mitotic-centered therapies for FA-associated tumors.2 year

Rural regeneration through direct marketing of Audubon County meats

Audubon County Family Farms direct-marketed their farm products through the downtown farmers market in Des Moines. In addition to selling their products, the farmers encouraged dialogue with urban consumers through personal interaction and educational activities

Whole-exome sequencing enables correct diagnosis and surgical management of rare inherited childhood anemia

Correct diagnosis of inherited bone marrow failure syndromes is a challenge because of the significant overlap in clinical presentation of these disorders. Establishing right genetic diagnosis is crucial for patients' optimal clinical management and family counseling. A nondysmorphic infant reported here developed severe transfusion-dependent anemia and met clinical criteria for diagnosis of Diamond-Blackfan anemia (DBA). However, whole-exome sequencing demonstrated that the child was a compound heterozygote for a paternally inherited pathogenic truncating variant (SPTA1 c.4975 C>T) and a novel maternally inherited missense variant of uncertain significance (SPTA1 c.5029 G>A) within the spectrin gene, consistent with hereditary hemolytic anemia due to disruption of red blood cell (RBC) cytoskeleton. Ektacytometry demonstrated abnormal membrane flexibility of the child's RBCs. Scanning electron microscopy revealed morphological aberrations of the patient's RBCs. Both parents were found to have mild hereditary elliptocytosis. Importantly, patients with severe RBC membrane defects may be successfully managed with splenectomy to minimize peripheral destruction of misshapen RBCs, whereas patients with DBA require lifelong transfusions, steroid therapy, or hematopoietic stem cell transplantation. As suggested by the WES findings, splenectomy rendered our patient transfusion-independent, improving the family's quality of life and preventing transfusion-related iron overload. This case illustrates the utility of whole-exome sequencing in clinical care of children with genetic disorders of unclear presentation