Analysis of radar images of the active volcanic zone at Krafla, Iceland: The effects of look azimuth biasing

The geomorphic expression of Mid-Ocean-Ridge (MOR) volcanism in a subaerial setting occurs uniquely on Earth in Iceland, and the most recent MOR eruptive activity has been concentrated in the Northeastern Volcanic Zone in an area known as Krafla. Within the Krafla region are many of the key morphologic elements of MOR-related basaltic volcanism, as well as volcanic explosion craters, subglacial lava shields, tectonic fissure swarms known as gjar, and basaltic-andesite flows with well developed ogives (pressure-ridges). The objective was to quantify the degree to which the basic volcanic and structural features can be mapped from directional SAR imagery as a function of the look azimuth. To accomplish this, the current expression of volcanic and tectonic constructs was independently mapped within the Krafla region on the E, W, and N-looking SAR images, as well as from SPOT Panchromatic imagery acquired in 1987. The initial observations of the E, W, and N images indicates that fresh a'a lava surfaces are extremely radar bright (rough at 3 cm to meter scales) independent of look direction; this suggests that these flows do not have strong flow direction related structures at meter and cm scales, which is consistent with typical Icelandic a'a lava surfaces in general. The basic impression from a preliminary analysis of the effects of look azimuth biasing on interpretation of the geology of an active MOR volcanic zone is that up to 30 percent of the diagnostic features can be missed at any given look direction, but that having two orthogonal look direction images is probably sufficient to prevent gross misinterpretation

Volcano morphometry and volume scaling on Venus

A broad variety of volcanic edifices have been observed on Venus. They ranged in size from the limits of resolution of the Magellan SAR (i.e., hundreds of meters) to landforms over 500 km in basal diameter. One of the key questions pertaining to volcanism on Venus concerns the volume eruption rate or VER, which is linked to crustal productivity over time. While less than 3 percent of the surface area of Venus is manifested as discrete edifices larger than 50 km in diameter, a substantial component of the total crustal volume of the planet over the past 0.5 Ga is related to isolated volcanoes, which are certainly more easily studied than the relatively diffusely defined plains volcanic flow units. Thus, we have focused our efforts on constraining the volume productivity of major volcanic edifices larger than 100 km in basal diameter. Our approach takes advantage of the topographic data returned by Magellan, as well as our database of morphometric statistics for the 20 best known lava shields of Iceland, plus Mauna Loa of Hawaii. As part of this investigation, we have quantified the detailed morphometry of nearly 50 intermediate to large scale edifices, with particular attention to their shape systematics. We found that a set of venusian edifices which include Maat, Sapas, Tepev, Sif, Gula, a feature at 46 deg S, 215 deg E, as well as the shield-like structure at 10 deg N, 275 deg E are broadly representative of the approx. 400 volcanic landforms larger than 50 km. The cross-sectional shapes of these 7 representative edifices range from flattened cones (i.e., Sif) similar to classic terrestrial lava shields such as Mauna Loa and Skjaldbreidur, to rather dome-like structures which include Maat and Sapas. The majority of these larger volcanoes surveyed as part of our study displayed cross-sectional topographies with paraboloidal shaped, in sharp contrast with the cone-like appearance of most simple terrestrial lava shields. In order to more fully explore the differences between large venusian edifices and volcanoes on the Earth and Mars, we developed a volume scaling algorithm which relies on conservation of volcano morphometry as basal diameter is varied

In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

© 2008 Garvin and Dabrosin; licensee BioMed Central Ltd

The Use of Preoperative Epoetin-α in Revision Hip Arthroplasty

PURPOSE: To evaluate the efficacy of preoperative epoetin-α on the revision hip arthroplasty patient. We hypothesized that epoetin-α will reduce blood transfusion. A pertinent review of the literature is provided. METHODS: Forty-six patients were retrospectively reviewed. Sixteen patients received epoetin-α. Patients were case matched by age, preoperative hemoglobin, surgery, gender, and BMI. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage was not used. RESULTS: Blood transfusion and length of stay were decreased in the epoetin-α group. Hemoglobin in the intervention group increased from 12.0 to 14.5, preoperatively. Patients who received epoetin-α were 0.78 (RR=0.225) times as likely to receive a transfusion. Number Needed to Treat (NNT) to avoid one allogeneic transfusion was 1.84. Age, Gender, BMI, ASA, total and hidden blood loss, preoperative Iron supplements, preop Hct, preop PLT, PT, PTT, and INR were similar. One (6.0%) patient developed an uncomplicated deep venous thrombosis in the intervention group. CONCLUSIONS: The mildly anemic revision hip arthroplasty patient is at increased risk for transfusion. Epoetin-α increased preoperative hemoglobin counts and reduced transfusions in this study; it also decreased patient length of hospital stay likely allowing for an earlier readiness to resume normal activities and/or meet short-term milestones. A randomized study to evaluate the direct and indirect costs of such a treatment methodology in the mildly anemic revision patient may be warranted

Effects of oestradiol and tamoxifen on VEGF, soluble VEGFR-1, and VEGFR-2 in breast cancer and endothelial cells

Angiogenesis is regulated by the balance between pro- and antiangiogenic factors. Vascular endothelial growth factor (VEGF), acting via the receptors VEGFR-1 and VEGFR-2, is a key mediator of tumour angiogenesis. The soluble form of the VEGF receptor-1 (sVEGFR-1) is an important negative regulator of VEGF-mediated angiogenesis. The majority of breast cancers are oestrogen dependent, but it is not fully understood how oestrogen and the antioestrogen, tamoxifen, affect the balance of angiogenic factors. Angiogenesis is a result of the interplay between cancer and endothelial cells, and sex steroids may exert effects on both cell types. In this study we show that oestradiol decreased secreted sVEGFR-1, increased secreted VEGF, and decreased the ratio of sVEGFR-1/VEGF in MCF-7 human breast cancer cells. The addition of tamoxifen opposed these effects. Moreover, human umbilical vein endothelial cells (HUVEC) incubated with supernatants from oestradiol-treated MCF-7 cells exhibited higher VEGFR-2 levels than controls. In vivo, MCF-7 tumours from oestradiol+tamoxifen-treated nude mice exhibited decreased tumour vasculature. Our results suggest that tamoxifen and oestradiol exert dual effects on the angiogenic environment in breast cancer by regulating cancer cell-secreted angiogenic ligands such as VEGF and sVEGFR-1 and by affecting VEGFR-2 expression of endothelial cells

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Systems model of T cell receptor proximal signaling reveals emergent ultrasensitivity

Receptor phosphorylation is thought to be tightly regulated because phosphorylated receptors initiate signaling cascades leading to cellular activation. The T cell antigen receptor (TCR) on the surface of T cells is phosphorylated by the kinase Lck and dephosphorylated by the phosphatase CD45 on multiple immunoreceptor tyrosine-based activation motifs (ITAMs). Intriguingly, Lck sequentially phosphorylates ITAMs and ZAP-70, a cytosolic kinase, binds to phosphorylated ITAMs with differential affinities. The purpose of multiple ITAMs, their sequential phosphorylation, and the differential ZAP-70 affinities are unknown. Here, we use a systems model to show that this signaling architecture produces emergent ultrasensitivity resulting in switch-like responses at the scale of individual TCRs. Importantly, this switch-like response is an emergent property, so that removal of multiple ITAMs, sequential phosphorylation, or differential affinities abolishes the switch. We propose that highly regulated TCR phosphorylation is achieved by an emergent switch-like response and use the systems model to design novel chimeric antigen receptors for therapy

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

Shared Genetics of Multiple System Atrophy and Inflammatory Bowel Disease

BACKGROUND: Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by intracellular accumulations of α-synuclein and nerve cell loss in striatonigral and olivopontocerebellar structures. Epidemiological and clinical studies have reported potential involvement of autoimmune mechanisms in MSA pathogenesis. However, genetic etiology of this interaction remains unknown. We aimed to investigate genetic overlap between MSA and 7 autoimmune diseases and to identify shared genetic loci. METHODS: Genome-wide association study summary statistics of MSA and 7 autoimmune diseases were combined in cross-trait conjunctional false discovery rate analysis to explore overlapping genetic background. Expression of selected candidate genes was compared in transgenic MSA mice and wild-type mice. Genetic variability of candidate genes was further investigated using independent whole-exome genotyping data from large cohorts of MSA and autoimmune disease patients and healthy controls. RESULTS: We observed substantial polygenic overlap between MSA and inflammatory bowel disease and identified 3 shared genetic loci with leading variants upstream of the DENND1B and RSP04 genes, and in intron of the C7 gene. Further, the C7 gene showed significantly dysregulated expression in the degenerating midbrain of transgenic MSA mice compared with wild-type mice and had elevated burden of protein-coding variants in independent MSA and inflammatory bowel disease cohorts. CONCLUSION: Our study provides evidence of shared genetic etiology between MSA and inflammatory bowel disease with an important role of the C7 gene in both phenotypes, with the implication of immune and gut dysfunction in MSA pathophysiology. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society

Effect of Strain Magnitude on the Tissue Properties of Engineered Cardiovascular Constructs

Mechanical loading is a powerful regulator of tissue properties in engineered cardiovascular tissues. To ultimately regulate the biochemical processes, it is essential to quantify the effect of mechanical loading on the properties of engineered cardiovascular constructs. In this study the Flexercell FX-4000T (Flexcell Int. Corp., USA) straining system was modified to simultaneously apply various strain magnitudes to individual samples during one experiment. In addition, porous polyglycolic acid (PGA) scaffolds, coated with poly-4-hydroxybutyrate (P4HB), were partially embedded in a silicone layer to allow long-term uniaxial cyclic mechanical straining of cardiovascular engineered constructs. The constructs were subjected to two different strain magnitudes and showed differences in biochemical properties, mechanical properties and organization of the microstructure compared to the unstrained constructs. The results suggest that when the tissues are exposed to prolonged mechanical stimulation, the production of collagen with a higher fraction of crosslinks is induced. However, straining with a large strain magnitude resulted in a negative effect on the mechanical properties of the tissue. In addition, dynamic straining induced a different alignment of cells and collagen in the superficial layers compared to the deeper layers of the construct. The presented model system can be used to systematically optimize culture protocols for engineered cardiovascular tissues