Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting ...using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.
The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.
The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.
•HB-EGF antisense oligonucleotide suppressed hepatic VLDL production leading to a remarkable downregulation of circulatory lipid levels.•HB-EGF antisense also induced an effective suppression of atherosclerosis development.•Newly we observed that the HB-EGF antisense significantly improved systemic insulin sensitivity.
Environmental and economic considerations require the effective use of water and nutrients to elevate grain production in bread wheat (Triticum aestivum L.) with concomitant reduction in nitrate ...leaching to minimize contamination of underground water. We determined the effect of the root system on leaching fraction, leachate N concentration, and N, P and K uptake using bread wheat ‘Pavon 76' and its three near‐isogenic translocation lines: Pavon 1RS.1AL, Pavon 1RS.1BL and Pavon 1RS.1DL. These genotypes were grown in sand‐tube experiments under optimum and low level of nutrients for 2 years. Root, stem and leaves, and grain N, P, and K content, and agronomic characters were measured. Leaching fraction and leachate nitrate concentration were measured at early tillering, booting and early grain filling. Significant main effects for year, nutrient level and genotype were found for the characters. Genotype × N interaction was significant only for root P content. Genotype × year interaction was significant only for plant N content, root P content and plant P content. Genotype × year × N interaction was significant only for root N uptake efficiency. Thus, genotypic means averaged across years and nutrient levels are reported. Low levels of nutrients (1330, 235 and 793 mg vs. 1915, 375 and 1268 mg N, P and K, respectively) reduced mean root biomass, plant biomass and grain yield by 27 %, 25 %, and 19 %, respectively. The translocation lines produced 31-46 % more root biomass, 11-14 % heavier grains and 6-8 % greater grain yield than Pavon 76. Leaching fraction was higher under low level of nutrient at booting and grain filling. Leaching fraction at tillering, booting, and grain filling was 67%, 42% and 25%, respectively. Leaching fraction at early tillering was lower for Pavon 1RS.1AL (39 %) and Pavon 1RS.1DL (40.5 %) than for Pavon 76 (45.3 %). Leachate nitrate concentration was lower for two translocation lines at all three stages of plant growth compared to Pavon 76. The correlation coefficient between plant N content and root biomass, between plant N content and plant biomass, and between grain yield and root biomass was positive and significant. Significant positive correlation was found between root biomass and P and K uptake. Multiple small applications of N fertilizer during early plant growth with adequate irrigation water are recommended. Wheat genotypes with superior root characteristics for efficient nutrient uptake, especially during tillering and booting, should be developed in breeding programmes to increase grain yield and to minimize the nitrate leaching.
Interpretation of U-series disequilibria in midocean ridge basalts is highly dependent on the bulk partition coefficients for U and Th and therefore the mineralogy of the mantle source. ...Distinguishing between the effect of melting processes and variable source compositions on measured disequilibria (
238U-
230Th-
226Ra and
235U-
231Pa) requires measurement of the radiogenic isotopes Hf, Nd, Sr, and Pb. Here, we report measurements of
238U-
230Th-
226Ra and
235U-
231Pa disequilibria; Hf, Nd, Sr, and Pb isotopic; and major and trace element compositions for a suite of 20 young midocean ridge basalts from the East Pacific Rise axis between 9°28′ and 9°52′N. All of the samples were collected within the axial summit trough using the submersible Alvin. The geological setting and observational data collected during sampling operations indicate that all the rocks are likely to have been erupted from 1991 to 1992 or within a few decades of that time. In these samples,
230Th excesses and
226Ra excesses are variable and inversely correlated. Because the eruption ages of the samples are much less than the half-life of
226Ra, this inverse correlation between
230Th and
226Ra excesses can be considered a primary feature of these lavas. For the lava suite analyzed in this study,
226Ra and
230Th excesses also vary with lava composition:
226Ra excesses are negatively correlated with Na
8 and La/Yb and positively correlated with Mg#. Conversely,
230Th excesses are positively correlated with Na
8 and La/Yb and negatively correlated with Mg#. Th/U,
230Th/
232Th, and
230Th excesses are also variable and correlated to one another.
231Pa excesses are large but relatively constant and independent of Mg#, La/Yb, Th/U, and Na
8. The isotope ratios
143Nd/
144Nd,
176Hf/
177Hf,
87Sr/
86Sr, and
208Pb/
206Pb are constant within analytical uncertainty, indicating that they were derived from a common source. The source is homogeneous with respect to parent/daughter ratios Lu/Hf, Sm/Nd, Rb/Sr, and Th/U; therefore, the measured variations of Th/U,
230Th, and
226Ra excesses and major and trace element compositions in these samples are best explained by polybaric melting of a homogeneous source, not by mixing of compositionally distinct sources.
Victoria Island, in Arctic Canada, is one of the largest islands in the world, but its geology has remained largely unmapped and unstudied owing to its remoteness. Base-metal and hydrocarbon showings ...have been reported from the island, but the origin and prospectivity of these showings remain enigmatic. Regionally extensive, void-filling Phanerozoic diagenetic phases (dolomite, calcite, quartz) are conspicuous in two of the most widespread carbonate units, the Neoproterozoic Wynniatt Formation and the Cambro–Ordovician Victoria Island formation, recording repeated post-depositional movement of fluid through the rocks. These phases were studied to (a) determine whether they could have been associated with movement of metalliferous or petroliferous fluids, (b) establish a diagenetic base-line for a very large and economically unexplored area, and (c) determine whether the fluid-flow events could have been related to known episodes of deformation and mineralisation elsewhere in the Canadian Arctic archipelago. Using an innovative protocol combining in situ SIMS analysis of O and S isotopes with LA-ICP-MS trace-element analysis, the geochemical conditions attending the diagenetic evolution of host dolostone and cement phases were determined. The Wynniatt Formation dolostone contains four Phanerozoic cements: saddle dolomite, brown dolomite, replacive calcite and late calcite. Average δ18O (SMOW) values of Wynniatt Formation saddle and brown dolomite, replacive calcite, and late calcite cements are 24.7‰, 7.7‰, and 6.9‰, respectively. The PAAS-normalised rare earth element patterns of the dolostone, dolomite, and replacive calcite are smooth and flat with slightly positive Ce and Y anomalies and MREE-enrichment; late calcite cement, in contrast, has negative Ce and positive Y anomalies. Recrystallisation of the host dolostone by a reduced, saddle-dolomite-precipitating fluid in a fluid-dominated system altered the isotopic and REE pattern of the dolostone to saddle-dolomite values. This fluid had interacted with shale at depth and then mixed with a relatively high-salinity fluid. Brown dolomite precipitated from this fluid after a decrease in salinity, and oxygenated meteoric water later infiltrated the system and precipitated the calcite cements.
The Victoria Island formation dolostone contains two cements: quartz and dolomite. Host dolostone, quartz, and dolomite have average δ18O (SMOW) values of 31.7‰, 18.7‰, and 18.6‰, respectively, whereas δ34S (V-CDT) for framboidal pyrite in the quartz cement averages −7.5‰. The host dolostone has flat PAAS-normalised REE patterns with a positive Eu anomaly, no Ce anomaly, and a zig-zag HREE pattern, whereas the dolomite cements have two REE patterns: one similar to the dolostone (flat) and the other with LREE-enrichment, and negative La and Eu anomalies. These data suggest that a reduced, hydrothermal fluid altered and partially silicified the host dolostone. Quartz precipitated from a seawater-sourced fluid that had incorporated metals at depth and mixed with bacterially reduced sulphur at the site of precipitation. The dolomite cement records the change from a rock-dominant system to a fluid-dominant system. This fluid was sourced from seawater and interacted with REE-phosphate minerals.
The results suggest that precipitation of the diagenetic cements took place before peak burial associated with the Ellesmerian Orogeny (late Devonian–early Carboniferous). The most probable cause of fluid migration, therefore, is the Ellesmerian Orogeny for the majority of the diagenetic phases. High-latitude meteoric fluid then infiltrated the system at some time after the Ellesmerian Orogeny. Similar ages, temperatures, compositions, and precipitation mechanisms as those associated with the Cornwallis zinc district (Polaris mine), highlight a possible relation to known base-metal mineralising fluids.
The results of this study provide much needed baseline knowledge of the post-depositional history of Victoria Island. It also illustrates that a “less-is-more” approach, using detailed micro-analytical methods on carefully selected and well-constrained samples, allows one to decipher a complex diagenetic history involving the mixing of fluids from different reservoirs and frequent changes in redox state, both of which may be overlooked using conventional macro-scale approaches.
•A novel approach to the study of diagenesis•Multiple in-situ microanalytical methods were used to constrain fluid characteristics.•Water–rock ratios changed from low to high during diagenesis at both sites.•This approach provides a level of detail that has not been attained in typical studies.
The Indus River system is the only major drainage system in the western Himalaya, and erodes not only the High Himalaya, but also topographically high regions within and north of the Indus Suture ...Zone, most notably the Karakoram. Ion microprobe analysis of Pb isotopes in detrital K-feldspar grains taken from the tributaries of the Indus, together with bulk Nd isotope analysis of those same sediments, is here used to identify distinct sediment source regions. These span the very radiogenic Nanga Parbat and associated Lesser Himalaya, the relatively radiogenic-intermediate High Himalaya, the unradiogenic Ladakh and Kohistan Batholiths and intermediate values in the Hindu Kush, Karakoram and Lhasa Block. The range of compositions reflects differing degrees of recycling of older continental crust during petrogenesis. K-feldspars from the Ladakh and Kohistan Batholiths are less radiogenic than the laterally equivalent Gangdese granite of Tibet, interpreted to reflect the preferential recycling of accreted oceanic arc units within the western Transhimalaya prior to India–Asia collision. Similarly the Zanskar High Himalaya are less radiogenic than their equivalents in Nepal. Isotope values from Pleistocene Indus Fan sediment are compatible with a dominant source in the Karakoram, with additional important contributions from the arc batholiths and High Himalaya, reflecting both the area and modern rates of tectonic uplift within the drainage basin. In contrast, radiogenic grains are common in the lower reaches of the modern Indus River, possibly as a result of the damming of the main river channel where it reaches the foreland.
Three methods of estimating H2O contents of geological glasses are compared: 1) ion microprobe analysis (secondary ion MS), 2) Fourier-transform infrared spectroscopy (FTIR) and 3) EPMA using the Na ...decay-curve method.
We report measurements of U‐series disequilibria, Sr, Nd, Hf, and Pb isotopic compositions and major and trace element abundances in a suite of well‐located, off‐axis MORBs that span the East Pacific ...Rise (EPR) ridge crest from 9°48′–52′N and across it for ∼4 km on either side. The geological context of the samples are well constrained as they were collected by submersible in an area that has been extensively imaged by remote sensing techniques. Sr, Nd, Hf and 208Pb/206Pb isotopic compositions of the off‐axis N‐MORB are identical to the axial lavas from this same region, suggesting that their sources are similar and that melting processes are the dominant influence in establishing the U‐Th‐Ra disequilibria and trace element fractionations. A majority of off‐axis samples have U‐Th and Th‐Ra disequilibria that are larger, and model ages that are younger, than would be predicted from their off‐axis distance and the time‐integrated spreading rate. There are, however, a few off‐axis samples with U‐Th ages that are consistent with their spreading rate ages. It is likely that these samples erupted within or close to the axial summit trough (AST) and aged at a rate proportional to the spreading rate. The anomalously young ages determined for most of the off‐axis lavas suggest that volcanic construction along this region is occurring over a zone that is wider (at least 4 km) than the AST (10s to 100s of meters). The combined observational, chemical and isotopic data support a model for the 9°0′N area that includes a significant component of crustal accumulation resulting from lavas that breach the AST and flow down the flanks of the EPR ridge crest. However, these data also require a minor component of off‐axis eruptions that occur on distinct pillow mounds and ridges. This suggests that MOR construction involves several volcanic and tectonic processes acting in concert to form a complex patchwork of lava ages and compositions along, and across, this fast spreading ridge crest.
To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure.
The NEAD Study is an ongoing prospective observational multicenter study, ...which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5).
Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills.
Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed.
Wolves (Canis lupus) in North America are considered obligate predators of ungulates with other food resources playing little role in wolf population dynamics or wolf–prey relations. However, ...spawning Pacific salmon (Oncorhyncus spp.) are common throughout wolf range in northwestern North America and may provide a marine subsidy affecting inland wolf–ungulate food webs far from the coast. We conducted stable-isotope analyses for nitrogen and carbon to evaluate the contribution of salmon to diets of wolves in Denali National Park and Preserve, 1200 river-km from tidewater in interior Alaska, USA. We analyzed bone collagen from 73 wolves equipped with radio collars during 1986–2002 and evaluated estimates of salmon in their diets relative to the availability of salmon and ungulates within their home ranges. We compared wolf densities and ungulate: wolf ratios among regions with differing salmon and ungulate availability to assess subsidizing effects of salmon on these wolf–ungulate systems. Wolves in the northwestern flats of the study area had access to spawning salmon but low ungulate availability and consumed more salmon (17% ± 7% mean ± SD) than in upland regions, where ungulates were sixfold more abundant and wolves did or did not have salmon spawning areas within their home ranges (8% ± 6% and 3% ± 3%, respectively). Wolves were only 17% less abundant on the northwestern flats compared to the remainder of the study area, even though ungulate densities were 78% lower. We estimated that biomass from fall runs of chum (O. keta) and coho (O. kisutch) salmon on the northwestern flats was comparable to the ungulate biomass there, and the contribution of salmon to wolf diets was similar to estimates reported for coastal wolves in southeast Alaska. Given the ubiquitous consumption of salmon by wolves on the northwestern flats and the abundance of salmon there, we conclude that wolf numbers in this region were enhanced by the allochthonous subsidy provided by salmon and discuss implications for wolf–ungulate relations.
Background:
Of 7461 actively practicing United States American Board of Plastic Surgery certified plastic surgeons, only 17% are women. In relation to this small number, gender inequities within the ...field have been the source of national discussions. Our study assessed the status of the gender-based wage-gap in plastic surgery and sought to identify possible causes.
Methods:
An anonymous 43-question survey was distributed to 2981 members of the American Society of Plastic Surgeons in 2021. Male and female responses were compared; an analysis also considering board-certification year was performed. Chi-square and Fisher exact tests were used for bivariate analysis. Continuous variables were compared with two-sample
t
tests and Wilcoxon rank sum tests.
Results:
Ten percent of contacted American Society of Plastic Surgeons members responded to our survey. Of the 288 respondents, 111 (38.5%) were women, and 177 (61.5%) were men. Men were more likely to have salaries over $400K USD per year (
P <
0.0001). Earlier certification year was associated with pay greater than $400K per year (
P =
0.0235) but was insignificant once stratified by gender (women:
P =
0.2392, men:
P =
0.7268). Earlier certification year was associated with production-based and self-determined wages (
P =
0.0097), whereas later board-certification year was associated with nonnegotiable salaries (
P <
0.0001).
Conclusions:
Women are significantly less likely to make salaries comparable to those of male plastic surgeons, related to shorter careers on average. An increase in female representation and career duration within the field is needed to improve the current wage-gap.
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