Were Aqueous Ripples on Mars Formed by Flowing Brines?

The discovery in 2004 by Mars exploration rover Opportunity of sedimentary rocks with centimeter-scale trough cross-bedding is one of the compelling lines of evidence for flowing water on the Martian surface. The rocks contain a significant evaporite component mixed with weathered mafic silicates, suggesting that the aqueous fluid in contact with the sediments must have been of very high ionic strength because dissolution features are not observed. Recent thermodynamic modeling indicates that these brines could have had higher densities (by up to a factor of 1.3) and significantly higher viscosities (by up to a factor of 40) than pure water. Because fluid density and viscosity can significantly affect sediment transport mechanics, herein we analyze whether ripples could have been stable bed forms under flowing Martian brines. To this end, we compiled bed form stability diagrams with an emphasis on those studies that have considered high-viscosity fluids. For the case of viscous Martian brines, we find that ripples are stable under modest Shields numbers and low particle Reynolds numbers. These conditions translate into sediment sizes ranging from sand to gravel, and they are substantially coarser than sediment sizes for equivalent ripple-forming flows in freshwater. It is likely that ripples might also form in silt sizes under viscous brines, but these conditions (i.e., particle Reynolds numbers <0.1) have not yet been explored in flume experiments, motivating future work. Using flow-resistance equations and assuming steady uniform flow, we calculate that Marian brines must have had flow depths ranging from 0.01 to 1 m and flow velocities of 0.01 to 1 m/s, and been driven by gravity on slopes of 10^(-4) to 10^(-2) in order to generate the bed stresses necessary to produce ripples. These conditions seem reasonable given the interdune environment that has been proposed for the Burns formation. In addition to the potential for ripples in much coarser sediments, ripples formed by viscous brines also might be larger in height and wavelength than their freshwater counterparts by as much as a factor of 12. Thus, large (>.10 cm heights) and fine-grained (<1 mm particle diameter) cross strata would be compelling physical evidence for flowing brines in the Martian past, provided that independent evidence could be provided for a subaqueous (i.e., not eolian) origin of the cross-stratification. Smaller centimeter-scale ripples can also be formed by brines due to flow-depth limitations or lower-viscosity fluids, and therefore the physical sedimentological evidence in support of brines versus freshwater flows may be ambiguous in these cases

Comparative Oncogenomics Implicates the Neurofibromin 1 Gene (NF1) as a Breast Cancer Driver

Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity. Relevant mouse models are powerful for untangling this problem because such heterogeneity can be controlled. Inbred Chaos3 mice exhibit high levels of genomic instability leading to mammary tumors that have tumor gene expression profiles closely resembling mature human mammary luminal cell signatures. We genomically characterized mammary adenocarcinomas from these mice to identify cancer-causing genomic events that overlap common alterations in human breast cancer. Chaos3 tumors underwent recurrent copy number alterations (CNAs), particularly deletion of the RAS inhibitor Neurofibromin 1 (Nf1) in nearly all cases. These overlap with human CNAs including NF1, which is deleted or mutated in 27.7% of all breast carcinomas. Chaos3 mammary tumor cells exhibit RAS hyperactivation and increased sensitivity to RAS pathway inhibitors. These results indicate that spontaneous NF1 loss can drive breast cancer. This should be informative for treatment of the significant fraction of patients whose tumors bear NF1 mutations

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no effect. This decrease in Ovcar3 cell proliferation was due to a higher fraction of cells in the G(0)/G(1) stage of the cell cycle. CGZ and TGZ treatment increased apoptosis after 4 hours of treatment but not after 8 or 12 hours. Treatment with TGZ or CGZ increased PPARγ mRNA expression in Ovcar3 cells; however, protein levels were unchanged. Surprisingly, luciferase promoter assays revealed that none of the TZDs increased PPARγ activity. Overexpression of wild type PPARγ increased reporter activity. This was further augmented by TGZ, Rosi, and Pio indicating that these cells have the endogenous capacity to mediate PPARγ transactivation. To determine whether PPARγ mediates the TZD-induced decrease in proliferation, cells were treated with CGZ or TGZ in the absence or presence of a dominant negative (DN) or wild type overexpression PPARγ construct. Neither vector changed the TZD-mediated cell proliferation suggesting this effect of TZDs on ovarian cancer cells may be PPARγ independent.CGZ and TGZ cause a decrease in ovarian cancer cell proliferation that is PPARγ independent. This concept is supported by the finding that a DN or overexpression of the wild type PPARγ did not affect the changes in cell proliferation and cell cycle

Pediatric DXA: technique and interpretation

This article reviews dual X-ray absorptiometry (DXA) technique and interpretation with emphasis on the considerations unique to pediatrics. Specifically, the use of DXA in children requires the radiologist to be a “clinical pathologist” monitoring the technical aspects of the DXA acquisition, a “statistician” knowledgeable in the concepts of Z-scores and least significant changes, and a “bone specialist” providing the referring clinician a meaningful context for the numeric result generated by DXA. The patient factors that most significantly influence bone mineral density are discussed and are reviewed with respect to available normative databases. The effects the growing skeleton has on the DXA result are also presented. Most important, the need for the radiologist to be actively involved in the technical and interpretive aspects of DXA is stressed. Finally, the diagnosis of osteoporosis should not be made on DXA results alone but should take into account other patient factors

The placebo effect in the motor domain is differently modulated by the external and internal focus of attention

Among the cognitive strategies that can facilitate motor performance in sport and physical practice, a prominent role is played by the direction of the focus of attention and the placebo effect. Consistent evidence converges in indicating that these two cognitive functions can influence the motor outcome, although no study up-to-now tried to study them together in the motor domain. In this explorative study, we combine for the first time these approaches, by applying a placebo procedure to increase force and by manipulating the focus of attention with explicit verbal instructions. Sixty healthy volunteers were asked to perform abduction movements with the index finger as strongly as possible against a piston and attention could be directed either toward the movements of the finger (internal focus, IF) or toward the movements of the piston (external focus, EF). Participants were randomized in 4 groups: two groups underwent a placebo procedure (Placebo-IF and Placebo-EF), in which an inert treatment was applied on the finger with verbal information on its positive effects on force; two groups underwent a control procedure (Control-IF and Control-EF), in which the same treatment was applied with overt information about its inefficacy. The placebo groups were conditioned about the effects of the treatment with a surreptitious amplification of a visual feedback signalling the level of force. During the whole procedure, we recorded actual force, subjective variables and electromyography from the hand muscles. The Placebo-IF group had higher force levels after the procedure than before, whereas the Placebo-EF group had a decrease of force. Electromyography showed that the Placebo-IF group increased the muscle units recruitment without changing the firing rate. These findings show for the first time that the placebo effect in motor performance can be influenced by the subject\u2019s attentional focus, being enhanced with the internal focus of attention

Zebrafish Endzone Regulates Neural Crest-Derived Chromatophore Differentiation and Morphology

The development of neural crest-derived pigment cells has been studied extensively as a model for cellular differentiation, disease and environmental adaptation. Neural crest-derived chromatophores in the zebrafish (Danio rerio) consist of three types: melanophores, xanthophores and iridiphores. We have identified the zebrafish mutant endzone (enz), that was isolated in a screen for mutants with neural crest development phenotypes, based on an abnormal melanophore pattern. We have found that although wild-type numbers of chromatophore precursors are generated in the first day of development and migrate normally in enz mutants, the numbers of all three chromatophore cell types that ultimately develop are reduced. Further, differentiated melanophores and xanthophores subsequently lose dendricity, and iridiphores are reduced in size. We demonstrate that enz function is required cell autonomously by melanophores and that the enz locus is located on chromosome 7. In addition, zebrafish enz appears to selectively regulate chromatophore development within the neural crest lineage since all other major derivatives develop normally. Our results suggest that enz is required relatively late in the development of all three embryonic chromatophore types and is normally necessary for terminal differentiation and the maintenance of cell size and morphology. Thus, although developmental regulation of different chromatophore sublineages in zebrafish is in part genetically distinct, enz provides an example of a common regulator of neural crest-derived chromatophore differentiation and morphology

An illustrated anatomical ontology of the developing mouse lower urogenital tract

Malformation of the urogenital tract represents a considerable paediatric burden, with many defects affecting the lower urinary tract (LUT), genital tubercle and associated structures. Understanding the molecular basis of such defects frequently draws on murine models. However, human anatomical terms do not always superimpose on the mouse, and the lack of accurate and standardised nomenclature is hampering the utility of such animal models. We previously developed an anatomical ontology for the murine urogenital system. Here, we present a comprehensive update of this ontology pertaining to mouse LUT, genital tubercle and associated reproductive structures (E10.5 to adult). Ontology changes were based on recently published insights into the cellular and gross anatomy of these structures, and on new analyses of epithelial cell types present in the pelvic urethra and regions of the bladder. Ontology changes include new structures, tissue layers and cell types within the LUT, external genitalia and lower reproductive structures. Representative illustrations, detailed text descriptions and molecular markers that selectively label muscle, nerves/ganglia and epithelia of the lower urogenital system are also presented. The revised ontology will be an important tool for researchers studying urogenital development/malformation in mouse models and will improve our capacity to appropriately interpret these with respect to the human situation