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971.
Phosphorus and nitrogen are essential nutrient elements that are needed by plants in large amounts. The arbuscular mycorrhizal symbiosis between plants and soil fungi improves phosphorus and nitrogen acquisition under limiting conditions. On the other hand, these nutrients influence root colonization by mycorrhizal fungi and symbiotic functioning. This represents a feedback mechanism that allows plants to control the fungal symbiont depending on nutrient requirements and supply. Elevated phosphorus supply has previously been shown to exert strong inhibition of arbuscular mycorrhizal development. Here, we address to what extent inhibition by phosphorus is influenced by other nutritional pathways in the interaction between Petunia hybrida and R. irregularis. We show that phosphorus and nitrogen are the major nutritional determinants of the interaction. Interestingly, the symbiosis-promoting effect of nitrogen starvation dominantly overruled the suppressive effect of high phosphorus nutrition onto arbuscular mycorrhiza, suggesting that plants promote the symbiosis as long as they are limited by one of the two major nutrients. Our results also show that in a given pair of symbiotic partners (Petunia hybrida and R. irregularis), the entire range from mutually symbiotic to parasitic can be observed depending on the nutritional conditions. Taken together, these results reveal complex nutritional feedback mechanisms in the control of root colonization by arbuscular mycorrhizal fungi.  相似文献   
972.

Background

CC chemokine receptor 4 (CCR4) represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs) and on tumor cells in several cancer types and its role in metastasis.

Methodology

Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies.

Significance

For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR) antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing). The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer.  相似文献   
973.
Outlier detection and environmental association analysis are common methods to search for loci or genomic regions exhibiting signals of adaptation to environmental factors. However, a validation of outlier loci and corresponding allele distribution models through functional molecular biology or transplant/common garden experiments is rarely carried out. Here, we employ another method for validation, namely testing outlier loci in specifically designed, independent data sets. Previously, an outlier locus associated with three different habitat types had been detected in Arabis alpina. For the independent validation data set, we sampled 30 populations occurring in these three habitat types across five biogeographic regions of the Swiss Alps. The allele distribution model found in the original study could not be validated in the independent test data set: The outlier locus was no longer indicative of habitat‐mediated selection. We propose several potential causes of this failure of validation, of which unaccounted genetic structure and technical issues in the original data set used to detect the outlier locus were most probable. Thus, our study shows that validating outlier loci and allele distribution models in independent data sets is a helpful tool in ecological genomics which, in the case of positive validation, adds confidence to outlier loci and their association with environmental factors or, in the case of failure of validation, helps to explain inconsistencies.  相似文献   
974.

Purpose

India’s biofuel programme relies on ethanol production from sugarcane molasses. However, there is limited insight on environmental impacts across the Indian ethanol production chain. This study closes this gap by assessing the environmental impacts of ethanol production from sugarcane molasses in Uttar Pradesh, India. A comparative analysis with south-central Brazilian sugarcane ethanol is also presented to compare the performance of sugarcane molasses-based ethanol with sugarcane juice-based ethanol.

Methods

The production process is assessed by a cradle-to-gate life cycle assessment. The multifunctionality problem is solved by applying two variants of system expansion and economic allocation. Environmental impacts are assessed with Impact 2002+ and results are presented at the midpoint level for greenhouse gas emissions, non-renewable energy use, freshwater eutrophication and water use. Furthermore, results include impacts on human health and ecosystem quality at the damage level. Sensitivity analysis is also performed on key contributing parameters such as pesticides, stillage treatment and irrigation water use.

Results and discussion

It is found that, compared to Brazilian ethanol, Indian ethanol causes lower or comparable greenhouse gas emissions (0.09–0.64 kgCO2eq/kgethanolIN, 0.46–0.63 kgCO2eq/kgethanolBR), non-renewable energy use (?0.3–6.3 MJ/kgethanolIN, 1–4 MJ/kgethanolBR), human health impacts (3.6?·?10?6 DALY/kgethanolIN, 4?·?10?6 DALY/kgethanolBR) and ecosystem impairment (2.5 PDF?·?m2?·?year/kgethanolIN, 3.3 PDF?·?m2?·?year/kgethanolBR). One reason is that Indian ethanol is exclusively produced from molasses, a co-product of sugar production, resulting in allocation of the environmental burden. Additionally, Indian sugar mills and distilleries produce surplus electricity for which they receive credits for displacing grid electricity of relatively high CO2 emission intensity. When economic allocation is applied, the greenhouse gas emissions for Indian and Brazilian ethanol are comparable. Non-renewable energy use is higher for Indian ethanol, primarily due to energy requirements for irrigation. For water use and related impacts, Indian ethanol scores worse due groundwater irrigation, despite the dampening effect of allocation. The variation on greenhouse gas emissions and non-renewable energy use of Indian mills is much larger for high and low performance than the respective systems in Brazil.

Conclusions

Important measures can be taken across the production chain to improve the environmental performance of Indian ethanol production (e.g. avoiding the use of specific pesticides, avoiding the disposal of untreated stillage, transition to water efficient crops). However, to meet the targets of the Indian ethanol blending programme, displacement effects are likely to occur in countries which export ethanol. To assess such effects, a consequential study needs to be prepared.  相似文献   
975.
Light at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle. Here we provide evidence that light at zeitgeber time (ZT) 22 affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors. We show that complete deletion of Per1 in mice led to depressive-like behavior and loss of the beneficial effects of light on this behavior. In contrast, specific deletion of Per1 in the region of the LHb did not affect mood-related behavior, but suppressed the beneficial effects of light. RNA sequence analysis in the mesolimbic dopaminergic system revealed profound changes of gene expression after a light pulse at ZT22. In the nucleus accumbens (NAc), sensory perception of smell and G-protein coupled receptor signaling were affected the most. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene expression in the brain. Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on mood-related behavior and signaling mechanisms in the mesolimbic dopaminergic system.  相似文献   
976.
1. We examined the seasonal and diel patterns of invertebrate drift in relation to seston and various habitat characteristics in two each of four different kinds of alpine streams [rhithral (snow‐fed) lake outlets, rhithral streams, kryal (glacial‐fed) lake outlets and kryal streams]. Samples were collected at four times of the day (dawn, midday, dusk and midnight) during three seasons (spring, summer and autumn). 2. Habitat characteristics differed mainly between rhithral and kryal sites, with the latter having higher discharge and turbidity, lower water temperature, and higher concentrations of ammonium, and particulate and soluble reactive phosphorus. Seasonality in habitat characteristics was most pronounced for kryal streams with autumn samples being more similar to rhithral sites. 3. The concentration of seston was lowest in the glacial‐influenced lake outlets and slightly higher in the stream sites; no seasonal or diel patterns were evident. 4. The density of drifting invertebrates averaged less than 100 m?3 and was lowest (<10 m?3) at three of the four kryal sites. Taxon richness and diversity were lowest at rhithral lake outlets. Chironomidae dominated the drift as well as benthic communities and <30% of benthic taxa identified were found in the drift. 5. Drifting invertebrates showed no consistent seasonal pattern. However, density tended to be highest in spring at rhithral sites and in autumn at kryal sites. No diel periodicity in drift density was found at any site and the lack of diel pattern may be a general feature of high altitude streams. 6. Glacially influenced habitat parameters were a major factor affecting drift in these alpine streams, whereas no clear differences were observed between streams and lake outlets. Our findings indicate that invertebrate drift in alpine streams is primarily influenced by abiotic factors, and therefore, substantially differs from patterns observed at lower altitude.  相似文献   
977.
978.
Synthesis and SAR are described for a structurally distinct class of DPP–IV inhibitors based on aminobenzo[a]quinolizines bearing (hetero-)aromatic substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative (S,S,S)-2g possesses the best fit in the S1 pocket. However, (S,S,S)-2i, bearing a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1 pocket, displays excellent in vivo activity and superior drug-like properties.  相似文献   
979.
The ability to competitively suppress native species is key to successful invasion. Since invasions involve an increase in abundance or dominance of a species in its non-native range, competitive effects might be expected to be stronger in the non-native range of an invader; however, there have been few comparisons of the competitive effects of invasive plants on species from invaded ranges versus species from native ranges. We compared the competitive and allelopathic effects of Acroptilon repens on native North American species to effects on related species from the native range of Acroptilon in Uzbekistan. We also compared the competitive interactions among these North American and Eurasian species, in the absence of Acroptilon, examining the hypothesis that particular regional species pools may show differences in competitive ability. The results showed that Acroptilon had stronger competitive effects against native North American species than against species native to Uzbekistan. There was no difference in the competitive effects among Eurasians and North Americans. The effects of leachates collected from Acroptilon roots were weak but more negative on species from North America than on species from Uzbekistan. Our results suggest that inherently stronger competitive and allelopathic effects of Acroptilon on North American plants than on plants from its native range may contribute to its invasive success.  相似文献   
980.
If insufficiently treated, Lyme borreliosis can evolve into an inflammatory disorder affecting skin, joints, and the CNS. Early innate immunity may determine host responses targeting infection. Thus, we sought to characterize the immediate cytokine storm associated with exposure of PBMC to moderate levels of live Borrelia burgdorferi. Since Th17 cytokines are connected to host defense against extracellular bacteria, we focused on interleukin (IL)-17 and IL-22. Here, we report that, despite induction of inflammatory cytokines including IL-23, IL-17 remained barely detectable in response to B. burgdorferi. In contrast, T cell-dependent expression of IL-22 became evident within 10 h of exposure to the spirochetes. This dichotomy was unrelated to interferon-γ but to a large part dependent on caspase-1 and IL-1 bioactivity derived from monocytes. In fact, IL-1β as a single stimulus induced IL-22 but not IL-17. Neutrophils display antibacterial activity against B. burgdorferi, particularly when opsonized by antibodies. Since neutrophilic inflammation, indicative of IL-17 bioactivity, is scarcely observed in Erythema migrans, a manifestation of skin inflammation after infection, protective and antibacterial properties of IL-22 may close this gap and serve essential functions in the initial phase of spirochete infection.  相似文献   
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