Adenosine A1 receptors (A1ARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of A1ARs on ischemic damage and its subsequent neuroinflammatory ...response has been scarcely explored so far. Methods: In this study, the expression of A1ARs after transient middle cerebral artery occlusion (MCAO) was evaluated by positron emission tomography (PET) with 18FCPFPX and immunohistochemistry (IHC). In addition, the role of A1ARs on stroke inflammation using pharmacological modulation was assessed with magnetic resonance imaging (MRI), PET imaging with 18FDPA-714 (TSPO) and 18FFLT (cellular proliferation), as well as IHC and neurofunctional studies. Results: In the ischemic territory, 18FCPFPX signal and IHC showed the overexpression of A1ARs in microglia and infiltrated leukocytes after cerebral ischemia. Ischemic rats treated with the A1AR agonist ENBA showed a significant decrease in both 18FDPA-714 and 18FFLT signal intensities at day 7 after cerebral ischemia, a feature that was confirmed by IHC results. Besides, the activation of A1ARs promoted the reduction of the brain lesion, as measured with T2W-MRI, and the improvement of neurological outcome including motor, sensory and reflex responses. These results show for the first time the in vivo PET imaging of A1ARs expression after cerebral ischemia in rats and the application of 18FFLT to evaluate glial proliferation in response to treatment. Conclusion: Notably, these data provide evidence for A1ARs playing a key role in the control of both the activation of resident glia and the de novo proliferation of microglia and macrophages after experimental stroke in rats.
The strength and direction of phenological responses to changes in climate have been shown to vary significantly both among species and among populations of a species, with the overall patterns not ...fully resolved. Here, we studied the temporal and spatial variability associated with the response of several insect species to recent global warming. We use hierarchical models within a model comparison framework to analyze phenological data gathered over 40 years by the Japan Meteorological Agency on the emergence dates of 14 insect species at sites across Japan. Contrary to what has been predicted with global warming, temporal trends of annual emergence showed a later emergence day for some species and sites over time, even though temperatures are warming. However, when emergence data were analyzed as a function of temperature and precipitation, the overall response pointed out an earlier emergence day with warmer conditions. The apparent contradiction between the response to temperature and trends over time indicates that other factors, such as declining populations, may be affecting the date phenological events are being recorded. Overall, the responses by insects were weaker than those found for plants in previous work over the same time period in these ecosystems, suggesting the potential for ecological mismatches with deleterious effects for both suites of species. And although temperature may be the major driver of species phenology, we should be cautious when analyzing phenological datasets as many other factors may also be contributing to the variability in phenology.
The cytokinin class of plant hormones plays key roles in regulating diverse developmental and physiological processes 1. Arabidopsis perceives cytokinins with three related and partially redundant ...receptor histidine kinases (HKs): CRE1 (the same protein as WOL and AHK4), AHK2, and AHK3 (CRE-family receptors) 2–5. It is suggested that binding of cytokinins induces autophosphorylation of these HKs and subsequent transfer of the phosphoryl group to a histidine phosphotransfer protein (HPt) and then to a response regulator (RR), ultimately regulating downstream signaling events 6, 7. Here we demonstrate that, in vitro and in a yeast system, CRE1 is not only a kinase that phosphorylates HPts in the presence of cytokinin but is also a phosphatase that dephosphorylates HPts in the absence of cytokinin. To explore the roles of these activities in planta, we replaced CRE1 with mutant versions of the gene or with AHK2. Replacing CRE1 with CRE1(T278I), which lacks cytokinin binding activity 8 and is locked in the phosphatase form, decreased cytokinin sensitivity. Conversely, replacing CRE1 with AHK2, which favors kinase activity, increased cytokinin sensitivity. These results indicate that in the presence of cytokinins, cytokinin receptors feed phosphate to phosphorelay-integrating HPt proteins. In the absence of cytokinins, CRE1 removes phosphate from HPt proteins, decreasing the system phosphoload.
In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced ...atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: −49% in LDE-PTX and −59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in −57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.
There are many studies suggesting an age-associated decline in the actin cytoskeleton, and this has been adopted as common knowledge in the field of aging biology. However, a direct identification of ...this phenomenon in aging multicellular organisms has not been performed. Here, we express LifeAct::mRuby in a tissue-specific manner to interrogate cytoskeletal organization as a function of age. We show for the first time in Caenorhabditis elegans that the organization and morphology of the actin cytoskeleton deteriorate at advanced age in the muscles, intestine, and hypodermis. Moreover, hsf-1 is essential for regulating cytoskeletal integrity during aging, so that knockdown of hsf-1 results in premature aging of actin and its overexpression protects actin cytoskeletal integrity in the muscles, the intestine, and the hypodermis. Finally, hsf-1 overexpression in neurons alone is sufficient to protect cytoskeletal integrity in nonneuronal cells.
The loss of tree mass over time from damage can lead to underestimates in above-ground net primary productivity (ANPP) if not accounted for properly. Bias in the allometric relationship between trunk ...base diameter (
D
b, at 1.3
m height or above the buttresses) and mass can also lead to systematic errors in ANPP estimates. We developed an unbiased model of the relationship between
D
b and tree mass using data from 315 trees (≥5
cm
D
b) harvested in the central Amazon. This model was compared with other theoretical (
n=1) and empirical models (
n=4). The theoretical model, and one empirical model, made predictions that differed substantially form our central Amazon model. The other three empirical models made predictions that were consistent with our model despite being developed in different tropical forests. Models differed mostly in predicting large tree mass. Using permanent forest inventory plot data, our
D
b versus tree mass model, and a bole volume model, we estimated that tree damage amounts to 0.9
Mg
ha
−1 per year (dry mass) of litter production. This damage should be included as a mass loss term when calculating ANPP. Incorporating fine litter data from published studies, we estimated that average ANPP for central Amazon plateau forests is at least 12.9
Mg
ha
−1 per year (or 6.5
Mg
C
ha
−1 per year). Additional sources of error as described in the text can raise this estimate by as much as 4
Mg
ha
−1 per year. We hypothesize that tree damage in old-growth forests accounts for a significant portion of age related decline in productivity.
Tropical forests face increasing climate risk
, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem ...embolism resistance thresholds (for example, Formula: see text
) and hydraulic safety margins (for example, HSM
) are important predictors of drought-induced mortality risk
, little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters Formula: see text
and HSM
vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both Formula: see text
and HSM
influence the biogeographical distribution of Amazon tree species. However, HSM
was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM
are gaining more biomass than are low HSM
forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM
in the Amazon
, with strong implications for the Amazon carbon sink.
Aim
Intraspecific trait variation (ITV) within natural plant communities can be large, influencing local ecological processes and dynamics. Here, we shed light on how ITV in vegetative and floral ...traits responds to large‐scale abiotic and biotic gradients (i.e., climate and species richness). Specifically, we tested whether associations of ITV with temperature, precipitation and species richness were consistent with any of four hypotheses relating to stress tolerance and competition. Furthermore, we estimated the degree of correlation between ITV in vegetative and floral traits and how they vary along the gradients.
Location
Global.
Time period
1975–2016.
Major taxa studied
Herbaceous and woody plants.
Methods
We compiled a dataset of 18,401 measurements of the absolute extent of ITV (measured as the coefficient of variation) in nine vegetative and seven floral traits from 2,822 herbaceous and woody species at 2,372 locations.
Results
Large‐scale associations between ITV and climate were trait specific and more prominent for vegetative traits, especially leaf morphology, than for floral traits. The ITV showed pronounced associations with climate, with lower ITV values in colder areas and higher values in drier areas. The associations of ITV with species richness were inconsistent across traits. Species‐specific associations across gradients were often idiosyncratic, and covariation in ITV was weaker between vegetative and floral traits than within the two trait groups.
Main conclusions
Our results show that, depending on the traits considered, ITV either increased or decreased with climate stress and species richness, suggesting that both factors can constrain or enhance ITV, which might foster plant‐population persistence in stressful conditions. Given the species‐specific responses and covariation in ITV, associations can be hard to predict for traits and species not yet studied. We conclude that consideration of ITV can improve our understanding of how plants cope with stressful conditions and environmental change across spatial and biological scales.
Actin cables of budding yeast are bundles of F-actin that extend from the bud tip or neck to the mother cell tip, serve as tracks for bidirectional cargo transport, and undergo continuous movement ...from buds toward mother cells 1. This movement, retrograde actin cable flow (RACF), is similar to retrograde actin flow in lamellipodia, growth cones, immunological synapses, dendritic spines, and filopodia 2–5. In all cases, actin flow is driven by the push of actin polymerization and assembly at the cell cortex, and myosin-driven pulling forces deeper within the cell 6–10. Therefore, for movement and inheritance from mothers to buds, mitochondria must “swim upstream” against the opposing force of RACF 11. We find that increasing RACF rates results in increased fitness of mitochondria inherited by buds and that the increase in mitochondrial fitness leads to extended replicative lifespan and increased cellular healthspan. The sirtuin SIR2 is required for normal RACF and mitochondrial fitness, and increasing RACF rates in sir2Δ cells increases mitochondrial fitness and cellular healthspan but does not affect replicative lifespan. These studies support the model that RACF serves as a filter for segregation of fit from less-fit mitochondria during inheritance, which controls cellular lifespan and healthspan. They also support a role for Sir2p in these processes.
Display omitted
•RACF prevents inheritance of more-oxidized, less-motile mitochondria in dividing yeast•Increasing RACF rates promotes mitochondrial and cellular fitness and extends lifespan•Sir2p is required for normal RACF and mitochondrial fitness•Increasing RACF in sir2Δ cells promotes mitochondrial fitness and cellular healthspan
PDF
