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91.
In harem‐polygynous societies, body condition is often correlated with dominance rank. However, the consequences of dominance are less clear. High‐ranking males do not inevitably have the highest reproductive success, especially in systems where females mate with multiple males. In such societies, we expect male reproductive success to be more highly skewed than female reproductive success, but reproductive skew in females can still arise from rankings established within matrilineal societies. Dominance can also impact life‐history decisions by influencing dispersal patterns in yearlings. To better understand the function of dominance in harem‐polygynous societies, we studied the causes and consequences of dominance in yellow‐bellied marmots (Marmota flaviventris), a social rodent with skewed male reproductive success and female reproductive suppression. Specifically, we examined body condition as a predictor and the probability of breeding, number of offspring, and dispersal as outcomes of dominance. Additionally, we looked at variation in dominance between males and females and adults and yearlings, because marmots can engage in distinct interactions depending on the type of individuals involved. We found that marmots in better body condition have higher dominance rank than those in poorer condition. In addition, adults are dominant over yearlings. Within yearlings, dominance does not influence dispersal, but those in better body condition are less likely to disperse. Within all adults, individuals in better condition produce more offspring per year. Within adult males, more dominant males have greater reproductive success. Despite previous evidence of reproductive suppression in females, we found no effects of dominance rank on female reproductive success in the current study. The function of dominance in female marmots remains enigmatic.  相似文献   
92.
In ecology, a hypothesis is usually not discarded if a few studies reject it, as long as there are other studies supporting it. How to assess the usefulness of ecological hypotheses is therefore not straightforward. Using the enemy release hypothesis as an example, we show how creating a hierarchy of hypotheses (HoH) can help reviewing and evaluating evidence for and against an ecological hypothesis. In a HoH, a broad, overarching hypothesis branches into more specific and better testable sub‐hypotheses. The enemy release hypothesis is a major hypothesis in invasion ecology and posits that the absence of enemies in the exotic range of an alien species is a cause of its invasion success. Based on a systematic review of empirical tests of this hypothesis, we divided it into sub‐hypotheses, differentiating among 1) indicators for enemy release, 2) types of comparisons, and 3) types of enemies. We identified 176 empirical tests and weighted each test according to the number of alien species studied and the research method (experimental vs observational, field vs enclosure vs laboratory). For the broadly formulated enemy release hypothesis, we found nearly as much supporting (36%) as questioning evidence (43%). At the sub‐hypotheses level, however, we found that some sub‐hypotheses are strongly supported by empirical evidence, whereas others receive hardly any support. These differences are further emphasized for some types of habitat and focal taxonomic groups. Our findings suggest that several specific formulations (i.e. sub‐hypotheses) of the broad enemy release hypothesis are useful, whereas other formulations should be viewed more critically. In general, the approach outlined here can help evaluate major ecological hypotheses and their specific sub‐hypotheses. Our study also highlights the need for a scientific debate on how much supporting evidence is sufficient to consider an ecological hypothesis to be useful.  相似文献   
93.

Objective

The objective of this study was to develop and characterize alginate microspheres suitable for embolization with on-demand triggered doxorubicin (DOX) release and whereby the microspheres as well as the drug releasing process can be visualized in vivo using MRI.

Methods and Findings

For this purpose, barium crosslinked alginate microspheres were loaded with temperature sensitive liposomes (TSL/TSL-Ba-ms), which release their payload upon mild hyperthermia. These TSL contained DOX and [Gd(HPDO3A)(H2O)], a T1 MRI contrast agent, for real time visualization of the release. Empty alginate microspheres crosslinked with holmium ions (T2* MRI contrast agent, Ho-ms) were mixed with TSL-Ba-ms to allow microsphere visualization. TSL-Ba-ms and Ho-ms were prepared with a homemade spray device and sized by sieving. Encapsulation of TSL in barium crosslinked microspheres changed the triggered release properties only slightly: 95% of the loaded DOX was released from free TSL vs. 86% release for TSL-Ba-ms within 30 seconds in 50% FBS at 42°C. TSL-Ba-ms (76 ± 41 μm) and Ho-ms (64 ± 29 μm) had a comparable size, which most likely will result in a similar in vivo tissue distribution after an i.v. co-injection and therefore Ho-ms can be used as tracer for the TSL-Ba-ms. MR imaging of a TSL-Ba-ms and Ho-ms mixture (ratio 95:5) before and after hyperthermia allowed in vitro and in vivo visualization of microsphere deposition (T2*-weighted images) as well as temperature-triggered release (T1-weighted images). The [Gd(HPDO3A)(H2O)] release and clusters of microspheres containing holmium ions were visualized in a VX2 tumor model in a rabbit using MRI.

Conclusions

In conclusion, these TSL-Ba-ms and Ho-ms are promising systems for real-time, MR-guided embolization and triggered release of drugs in vivo.  相似文献   
94.

Introduction

The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial.

Methods

Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+-transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice.

Results

Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca2+-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2-/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P<0.05). In UCP2-/- cardiomyocytes (Ca2+)m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0.05) while (Ca2+)c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-.

Conclusion

Our results indicate regulatory effects of UCP2 on mCa2+-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling.  相似文献   
95.
In tumor cells, stepwise oncogenic deregulation of signaling cascades induces alterations of cellular morphology and promotes the acquisition of malignant traits. Here, we identified a set of 21 genes, including FGF9, as determinants of tumor cell morphology by an RNA interference phenotypic screen in SW480 colon cancer cells. Using a panel of small molecular inhibitors, we subsequently established phenotypic effects, downstream signaling cascades, and associated gene expression signatures of FGF receptor signals. We found that inhibition of FGF signals induces epithelial cell adhesion and loss of motility in colon cancer cells. These effects are mediated via the mitogen-activated protein kinase (MAPK) and Rho GTPase cascades. In agreement with these findings, inhibition of the MEK1/2 or JNK cascades, but not of the PI3K-AKT signaling axis also induced epithelial cell morphology. Finally, we found that expression of FGF9 was strong in a subset of advanced colon cancers, and overexpression negatively correlated with patients' survival. Our functional and expression analyses suggest that FGF receptor signals can contribute to colon cancer progression.  相似文献   
96.
TP53 (tumour protein 53) is one of the most frequently mutated genes in human cancer and its role during cellular transformation has been studied extensively. However, the homeostatic functions of p53 are less well understood. Here, we explore the molecular dependency network of TP53 through an RNAi-mediated synthetic interaction screen employing two HCT116 isogenic cell lines and a genome-scale endoribonuclease-prepared short interfering RNA library. We identify a variety of TP53 synthetic interactions unmasking the complex connections of p53 to cellular physiology and growth control. Molecular dissection of the TP53 synthetic interaction with UNRIP indicates an enhanced dependency of TP53-negative cells on small nucleolar ribonucleoprotein (snoRNP) assembly. This dependency is mediated by the snoRNP chaperone gene NOLC1 (also known as NOPP140), which we identify as a physiological p53 target gene. This unanticipated function of TP53 in snoRNP assembly highlights the potential of RNAi-mediated synthetic interaction screens to dissect molecular pathways of tumour suppressor genes.  相似文献   
97.

Purpose

The goal of this study is to develop an estimate of water use and consumption in automotive manufacturing to enhance the data quality of vehicle life cycle assessments that include life cycle water impacts. A benchmark is developed to compare water resources across manufacturing and nonproduction-related manufacturing processes, including an indication whether indirect water consumption due to electricity generation is significant.

Methods

Data from 12 original equipment manufacturers’ (OEM’s) sustainability reports are examined for the years 2006 to 2010. Distinctions are made between “water use” and “water consumption.” These factors are divided by total reported production to develop use and consumption values in cubic meter/vehicle for comparison. Additionally, total energy consumption is converted to indirect water consumption based on the water consumed in the generation of electricity for the electricity grid mix.

Results and discussion

Excluding outliers, average direct water use is 5.20 and 5.95 m3/vehicle for manufacturing and company-wide activities, respectively, with corresponding standard deviations of 1.42 and 1.20 m3/vehicle. Average direct water consumption was calculated to be 1.25 and 4.29 m3/vehicle for manufacturing and company-wide activities, respectively, with corresponding standard deviations of 0.52 and 1.56 m3/vehicle. Average indirect water consumption due to electricity consumption is found to be 2.21 m3/vehicle. Variability arises through different understandings on the words “consumption” and “use,” reporting continuity between years and in classification of data as it relates to manufacturing, nonmanufacturing, or company-wide activities.

Conclusions

These water values show that needs vary widely across OEMs. Additionally, the magnitude of the indirect water consumption results indicates that OEMs should focus on both indirect and direct water consumption to reduce their overall water footprint. The results also highlight the potential for significance and variability in indirect water consumption, in particular for “cradle-to-gate” type of impact assessments, dependent on electricity generation water consumption assumptions. It is hoped that with the introduction of water reporting standards like the International Organization of Standardization 14046, manufacturers will provide a more comprehensive summary of their water use and consumption in the future.  相似文献   
98.
99.

Background

Dose continues to be an area of concern in preclinical imaging studies, especially for those imaging disease progression in longitudinal studies. To our knowledge, this work is the first to characterize and assess dose from the Inveon CT imaging platform using nanoDot dosimeters. This work is also the first to characterize a new low-dose configuration available for this platform.

Methodology/Principal Findings

nanoDot dosimeters from Landauer, Inc. were surgically implanted into 15 wild type mice. Two nanoDots were placed in each animal: one just under the skin behind the spine and the other located centrally within the abdomen. A manufacturer-recommended CT protocol was created with 1 projection per degree of rotation acquired over 360 degrees. For best comparison of the low dose and standard configurations, noise characteristics of the reconstructed images were used to match the acquisition protocol parameters. Results for all dose measurements showed the average dose delivered to the abdomen to be 13.8 cGy±0.74 and 0.97 cGy±0.05 for standard and low dose configurations respectively. Skin measurements of dose averaged 15.99 cGy±0.72 and 1.18 cGy±0.06. For both groups, the standard deviation to mean was less than 5.6%. The maximum dose received for the abdomen was 15.12 cGy and 0.97 cGy while the maximum dose for the skin was 17.3 cGy and 1.32 cGy. Control dosimeters were used for each group to validate that no unwanted additional radiation was present to bias the results.

Conclusions/Significance

This study shows that the Inveon CT platform is suitable for imaging mice both for single and longitudinal studies. Use of low-dose detector hardware results in significant reductions in dose to subjects with a >12x (90%) reduction in delivered dose. Installation of this hardware on another in vivo microCT platform resulted in dose reductions of over 9x (89%).  相似文献   
100.
We studied the impact of the seed damaging gall midge larva Geomyia alpina on its perennial alpine host plant Geum reptans. We analysed the effect of seed predation on reproduction by seeds, i.e. seed number, seed mass, and seed viability and on growth and clonal propagation of non-protected plants in comparison to plants protected from predation by an insecticide. Additionally, we assessed the consequences of seed predation for population growth using matrix projection modelling. Seed predation resulted in a decrease in total seed mass per flower head by 23.8% in non-protected plants (P < 0.05). Individual seed mass decreased with increasing infestation intensity (P < 0.05). Seed number remained unaffected because the sucking feeding behaviour by gall midge larvae does not evoke seed abortion. Percent germination of seeds from non-protected plants was reduced by 97.9% compared to seeds from protected plants. According to reduced seed viability, modelling revealed a decrease in population growth rate from λ = 1.055 to λ = 1.041. Predation did neither influence total plant biomass nor biomass fractions. But stolon dry-weight of non-protected plants increased by 24.1% (P < 0.05), which may indicate a trade-off between sexual reproduction and clonal propagation. Our results demonstrate that despite substantial reduction of viable seeds, predation by gall midge larvae only slightly affected population growth of G. reptans suggesting that in this alpine species, persistence by longevity and clonal propagation can balance potential seed losses by predation, at least for local population growth.  相似文献   
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