Triassic rocks of the Western Canada Sedimentary Basin (WCSB) have previously been interpreted as being deposited on the passive margin of North America. Recent detrital zircon provenance studies on ...equivalent Triassic rocks in the Yukon have suggested that these rocks were in part derived from the pericratonic Yukon-Tanana terrane and were deposited in a foreland basin related to the Late Permian Klondike orogeny. Detrital zircons within a number of samples collected from Triassic sediments of the WCSB throughout northeastern British Columbia and western Alberta suggest that the bulk of the sediment was derived from recycled sediments of the miogeocline along western North America, with a smaller but significant proportion coming from the Innuitian orogenic wedge in the Arctic and from local plutonic and volcanic rocks. There is also evidence of sediment being derived from the Yukon-Tanana terrane, supporting the model of terrane accretion occurring prior to the Triassic. The age distribution of detrital zircons from the WCSB in British Columbia is similar to those of the Selwyn and Earn sub-basins in the Yukon and is in agreement with previous observations that sediment deposited along the margin of North America during the Triassic was derived from similar source areas. Together these findings support the model of deposition within a foreland basin, similar to the one inferred in the Yukon. Only a small proportion of zircon derived from the Yukon-Tanana terrane is present within Triassic strata in northeastern British Columbia, which may be due to post-Triassic erosion of the rocks containing these zircons.
Angiogenic sprouting, the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from within the cellular microenvironment, such as biochemical gradients and perfusion. ...However, many of these cues are missing in current in vitro models of angiogenic sprouting. We here describe an in vitro platform that integrates both perfusion and the generation of stable biomolecular gradients and demonstrate its potential to study more physiologically relevant angiogenic sprouting and microvascular stabilization. The platform consists of an array of 40 individually addressable microfluidic units that enable the culture of perfused microvessels against a three-dimensional collagen-1 matrix. Upon the introduction of a gradient of pro-angiogenic factors, the endothelial cells differentiated into tip cells that invaded the matrix. Continuous exposure resulted in continuous migration and the formation of lumen by stalk cells. A combination of vascular endothelial growth factor-165 (VEGF-165), phorbol 12-myristate 13-acetate (PMA), and sphingosine-1-phosphate (S1P) was the most optimal cocktail to trigger robust, directional angiogenesis with S1P being crucial for guidance and repetitive sprout formation. Prolonged exposure forces the angiogenic sprouts to anastomose through the collagen to the other channel. This resulted in remodeling of the angiogenic sprouts within the collagen: angiogenic sprouts that anastomosed with the other perfusion channel remained stable, while those who did not retracted and degraded. Furthermore, perfusion with 150 kDa FITC-Dextran revealed that while the angiogenic sprouts were initially leaky, once they fully crossed the collagen lane they became leak tight. This demonstrates that once anastomosis occurred, the sprouts matured and suggests that perfusion can act as an important survival and stabilization factor for the angiogenic microvessels. The robustness of this platform in combination with the possibility to include a more physiological relevant three-dimensional microenvironment makes our platform uniquely suited to study angiogenesis in vitro.
Organic-rich, fine-grained sedimentary rocks, such as black shales, are important geochemical archives providing information on the evolution of seawater composition and biological activity over the ...past 3billionyears. While biological productivity and sedimentation rates greatly affect the organic matter content in these rocks, mechanisms linking these two processes remain poorly resolved. Here, we examine the interactions of clay minerals with the marine planktonic cyanobacterium Synechococcus sp. PCC 7002. We suggest that clays settling through the water column could influence carbon and trace metal burial in three ways: (1) the interaction of reactive clay surfaces with the bacterial cells increases organic matter deposition via mass increase in a seawater growth medium by several orders of magnitude; (2) reactive bacterial cells become completely encased within a clay shroud, enhancing the preservation potential of this organic matter; and (3) the trace metal content of the biomass buried along with metals sorbed to the clay particles contributes to the trace metal concentrations of the black shale precursor sediments. Significantly, our findings imply that the chemical composition of ancient, organic-rich, fine-grained deposits are not only archives of ancient seawater composition and redox state, but they also provide a record of the degree of biological activity in the water column through geological time.
•A new mechanism of shale deposition involving microbes is proposed.•This mechanism involves flocculation of microbes in the presence of clay.•Encasement of cells within clay sheaths increases organic matter preservation.•Encasement of cells by clay preserves trace metal signatures of bacterial cells.
Current in vitro models to test the barrier function of vasculature are based on flat, two-dimensional monolayers. These monolayers do not have the tubular morphology of vasculature found in vivo and ...lack important environmental cues from the cellular microenvironment, such as interaction with an extracellular matrix (ECM) and exposure to flow. To increase the physiological relevance of in vitro models of the vasculature, it is crucial to implement these cues and better mimic the native three-dimensional vascular architecture. We established a robust, high-throughput method to culture endothelial cells as 96 three-dimensional and perfusable microvessels and developed a quantitative, real-time permeability assay to assess their barrier function. Culture conditions were optimized for microvessel formation in 7 days and were viable for over 60 days. The microvessels exhibited a permeability to 20 kDa dextran but not to 150 kDa dextran, which mimics the functionality of vasculature in vivo. Also, a dose-dependent effect of VEGF, TNFα and several cytokines confirmed a physiologically relevant response. The throughput and robustness of this method and assay will allow end-users in vascular biology to make the transition from two-dimensional to three-dimensional culture methods to study vasculature.
Simultaneous pancreas–kidney transplantation (SPK) is an advanced treatment option for type 1 diabetes mellitus (DM) patients with microvascular disease including nephropathy. Sidestreamdarkfield ...(SDF) imaging has emerged as a noninvasive tool to visualize the human microcirculation. This study assessed the effect of SPK in diabetic nephropathy (DN) patients on microvascular alterations using SDF and correlated this with markers for endothelial dysfunction. Microvascular morphology was visualized using SDF of the oral mucosa in DN (n = 26) and SPK patients (n = 38), healthy controls (n = 20), DM1 patients (n = 15, DM ≥ 40 mL/min) and DN patients with a kidney transplant (KTx, n = 15). Furthermore, 21 DN patients were studied longitudinally up to 12 months after SPK. Circulating levels of angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2) and soluble thrombomodulin (sTM) were measured using ELISA. Capillary tortuosity in the DN (1.83 ± 0.42) and DM ≥ 40 mL/min (1.55 ± 0.1) group was increased and showed reversal after SPK (1.31 ± 0.3, p < 0.001), but not after KTx (1.64 ± 0.1). sTM levels were increased in DN patients and reduced in SPK and KTx recipients (p < 0.05), while the Ang‐2/Ang‐1 ratio was normalized after SPK and not after KTx alone (from 0.16 ± 0.04 to 0.08 ± 0.02, p < 0.05). Interestingly, in the longitudinal study, reversal of capillary tortuosity and decrease in Ang‐2/Ang‐1 ratio and sTM was observed within 12 months after SPK. SPK is effective in reversing the systemic microvascular structural abnormalities in DN patients in the first year after transplantation.
Labial microvasular tortuosity, a surgate measure of generalized microvascular disease, is reversed after simultaneous pancreas—kidney transplantation.
Nuclear genome size, as measured by flow cytometry with propidium iodide, was used to investigate the relationships within the genus Tulipa L. (Liliaceae). More than 400 accessions representing 123 ...taxa from mainly wild-collected plants were investigated. Most species of Tulipa have the same basic chromosome number, 2n = 2x = 24. However, the somatic DNA 2C value (2C) is shown to range from 32 to 69 pg for the diploids. The largest genome contains roughly 3.4 x 10¹⁰ more base pairs than the smallest and has chromosomes that are more than twice as large. These large differences in the amount of nuclear DNA predict that the hybrids, if any arise, are usually sterile. Depending on the size of the total genome, 1 pg amounts to several thousand genes. Moreover, genome sizes are evaluated here in combination with available morphological, geographical, and molecular data. Therefore, the taxonomy proposed here is not a single-character taxonomy based on genome size alone. The genus Tulipa, as here determined, has 87 species, 29 more than accepted by van Raamsdonk et al. Acta Hort (ISHS) 430:821-828, 1997, but including 25 species that were not available to them. Of these 87 species, 28 were not seen by Hall (The genus Tulipa, The Royal Horticultural Society, London, 1940) in a living state and placed by him in an addendum. Species of the subgenus Clusianae (Baker) Zonn. differ strongly in nuclear DNA content (DNA 2C value), 32 versus 40-68 pg for all other tulips, and are placed here in a separate subgenus. Also Orithyia, the only group with a style and with only 38-39 pg is placed in a separate subgenus. Therefore, all tulips are attributed to four subgenera, Clusianae (Baker) Zonn., Tulipa, Eriostemones Raamsd., and Orithyia (D. Don) Baker and divided further into 12 sections. Seven of the eight series of section Eichleres (A.D. Hall) Raamsd. are now placed in four sections: (1) section Lanatae (Raamsd.) Zonn., mainly confined to species from the Pamir-Alay and including series Lanatae Raamsd., (2) section Multiflorae (Raamsd.) Zonn. (including series Glabrae Raamsd.), (3) section Vinistriatae (Raamsd.) Zonn. (including series Undulatae Raamsd.), and (4) section Spiranthera Vved. ex Zonn. and Veldk. Triploids, tetraploids, and pentaploids were found in several species. DNA content confirmed the close relationships of the species within the different sections. The rather similar looking and therefore often confused T. armena Boiss. (51.8 pg), T. systola Stapf (56.3 pg), and T. julia K., Koch (61.6 pg) could be clearly distinguished. The same is true for T. biebersteiniana Schult. f. (56.9 pg), T. sylvestris ssp. australis (Link) Pamp. (62.0 pg), and T. primulina Baker (64.6 pg). T. doerfleri Gand. and T. whittalli (Dykes) Hall could be placed as polyploid forms of T. orphanidea Boiss. ex Heldr. On the basis of DNA content, a systematic association between T. julia K. Koch and the triploid T. aleppensis Boiss. and between T. systola Stapf and the triploid T. praecox Tenore was suggested. The new species T. lemmersii Zonn., Peterse, and de Groot is described, and four possible new species are indicated. Genome size as measured by using flow cytometry may conveniently be used to produce systematic data. It is applicable even in the case of dormant bulbs or sterile plants for monitoring the trade in bulbous species.
Conservation priorities for Prunus africana, a tree species found across Afromontane regions, which is of great commercial interest internationally and of local value for rural communities, were ...defined with the aid of spatial analyses applied to a set of georeferenced molecular marker data (chloroplast and nuclear microsatellites) from 32 populations in 9 African countries. Two approaches for the selection of priority populations for conservation were used, differing in the way they optimize representation of intra-specific diversity of P. africana across a minimum number of populations. The first method (S1) was aimed at maximizing genetic diversity of the conservation units and their distinctiveness with regard to climatic conditions, the second method (S2) at optimizing representativeness of the genetic diversity found throughout the species' range. Populations in East African countries (especially Kenya and Tanzania) were found to be of great conservation value, as suggested by previous findings. These populations are complemented by those in Madagascar and Cameroon. The combination of the two methods for prioritization led to the identification of a set of 6 priority populations. The potential distribution of P. africana was then modeled based on a dataset of 1,500 georeferenced observations. This enabled an assessment of whether the priority populations identified are exposed to threats from agricultural expansion and climate change, and whether they are located within the boundaries of protected areas. The range of the species has been affected by past climate change and the modeled distribution of P. africana indicates that the species is likely to be negatively affected in future, with an expected decrease in distribution by 2050. Based on these insights, further research at the regional and national scale is recommended, in order to strengthen P. africana conservation efforts.
Blood-brain barrier (BBB) dysfunction is a major hallmark of many neurological diseases, including multiple sclerosis (MS). Using a genomics approach, we defined a microRNA signature that is ...diminished at the BBB of MS patients. In particular, miR-125a-5p is a key regulator of brain endothelial tightness and immune cell efflux. Our findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS.
The Sulphur Mountain Formation in the Wapiti area is subdivided into the Phroso, Meosin Mountain (new), and Vega members, which collectively span much of the Lower Triassic. The Smithian conodont ...faunas are particularly well developed and form the basis of three partly new conodont zones and two new subzones: the lachrymiformis Zone, meeki Zone, and mosheri Zone, with the last subdivided into the phryna and milleri Subzones. An informal lowermost Smithian nepalensis interval is introduced, although it has yet to be found in the area. The Phroso Member is latest Griesbachian, Dienerian, and, in its uppermost part, Smithian, specifically the lachrymiformis and meeki zones: these are shown to be equivalent to the Euflemingites romunduri ammonoid Zone. The Meosin Mountain Member is assigned to the meeki Zone in its lower part and the phryna Subzone of the mosheri Zone in its upper part: at least, the upper part of the mosheri Zone is equivalent to the Anawasatchites tardus ammonoid Zone. The Mackenzie Dolomite Lentil is at least partly older than the Meosin Mountain Member, and age equivalence of subsurface turbidite units in the Montney Formation should not be assumed. The lowermost Vega Member is also assigned to the phryna Subzone, and higher parts of that member span both the milleri Subzone of the Smithian and the entire Spathian. The following new conodont taxa are described: Neogondolella? joanae, Novispathodus latiformis, Scythogondolella lachrymiformis, Sc. phryna, and Sc. rhomboidea; several other new species are kept in open nomenclature.
Hypercholesterolemia is a major risk factor for ischemic heart disease including acute myocardial infarction. However, long-term effects of hypercholesterolemia in a rodent myocardial ...ischemia-reperfusion injury model are unknown. Therefore, the effects of diet-induced hypercholesterolemia on cardiac function and remodeling were investigated up to eight weeks after myocardial ischemia-reperfusion (MI-R) injury which was induced in either normocholesterolemic (NC-MI) or hypercholesterolemic (HC-MI) APOE*3-Leiden mice.
Left ventricular (LV) dimensions were serially assessed using parasternal long-axis echocardiography followed by LV pressure-volume measurements. Subsequently, infarct size and the inflammatory response were analyzed by histology and fluorescence-activated cell sorting (FACS) analysis.
Intrinsic LV function eight weeks after MI-R was significantly impaired in HC-MI compared to NC-MI mice as assessed by end-systolic pressure, dP/dtMAX, and -dP/dtMIN. Paradoxically, infarct size was significantly decreased in HC-MI compared to NC-MI mice, accompanied by an increased wall thickness. Hypercholesterolemia caused a pre-ischemic peripheral monocytosis, in particular of Ly-6Chi monocytes whereas accumulation of macrophages in the ischemic-reperfused myocardium of HC-MI mice was decreased.
Diet-induced hypercholesterolemia caused impaired LV function eight weeks after MI-R injury despite a reduced post-ischemic infarct size. This was preceded by a pre-ischemic peripheral monocytosis, while there was a suppressed accumulation of inflammatory cells in the ischemic-reperfused myocardium after eight weeks. This experimental model using hypercholesterolemic APOE*3-Leiden mice exposed to MI-R seems suitable to study novel cardioprotective therapies in a more clinically relevant animal model.
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