► A global spatial assessment of crop heat-stress for wheat, maize, rice and soybean. ► Hot-spots of heat-stress were found mostly in continental lands at high latitude. ► Risk of crop damage mostly ...increased for future climate change scenario. ► Adaptation of agricultural technologies is necessary to reduce risk of heat-stress.
The productivity of important agricultural crops is drastically reduced when they experience short episodes of high temperatures during the reproductive period. Crop heat stress was acknowledged in the IPCC 4th Assessment Report as an important threat to global food supply. We produce a first spatial assessment of heat stress risk at a global level for four key crops, wheat, maize, rice and soybean, using the FAO/IIASA Global Agro-Ecological Zones Model (GAEZ). A high risk of yield damage was found for continental lands at high latitudes, particularly in the Northern Hemisphere between 40 and 60°N. Central and Eastern Asia, Central North America and the Northern part of the Indian subcontinent have large suitable cropping areas under heat stress risk. Globally, this ranged from less than 5Mha of suitable lands for maize for the baseline climate (1971–2000) to more than 120Mha for wetland rice for a future climate change condition (2071–2100) assuming the A1B emission scenario. For most crops and regions, the intensity, frequency and relative damage due to heat stress increased from the baseline to the A1B scenario. However for wheat and rice crops, GAEZ selection of different crop types and sowing dates in response to A1B seasonal climate caused a reduction in heat stress impacts in some regions, which suggests that adaptive measures considering these management options may partially mitigate heat stress at local level. Our results indicate that temperate and sub-tropical agricultural areas might bear substantial crop yield losses due to extreme temperature episodes and they highlight the need to develop adaptation strategies and agricultural policies able to mitigate heat stress impacts on global food supply.
Programmed Death-1 (PD-1) is a coinhibitory receptor expressed on activated T cells that suppresses T-cell signaling and effector functions. It has been previously shown that binding to its ligand ...PD-L1 induces a spatial reorganization of PD-1 receptors into microclusters on the cell membrane. However, the roles of the spatial organization of PD-L1 on PD-1 clustering and T-cell signaling have not been elucidated. Here, we used DNA origami flat sheets to display PD-L1 ligands at defined nanoscale distances and investigated their ability to inhibit T-cell activation in vitro. We found that DNA origami flat sheets modified with CD3 and CD28 activating antibodies (FS-α-CD3-CD28) induced robust T-cell activation. Co-treatment with flat sheets presenting PD-L1 ligands separated by ∼200 nm (FS-PD-L1-200), but not 13 nm (FS-PD-L1-13) or 40 nm (FS-PD-L1-40), caused an inhibition of T-cell signaling, which increased with increasing molar ratio of FS-PD-L1-200 to FS-α-CD3-CD28. Furthermore, FS-PD-L1-200 induced the formation of smaller PD-1 nanoclusters and caused a larger reduction in IL-2 expression compared to FS-PD-L1-13. Together, these findings suggest that the spatial organization of PD-L1 determines its ability to regulate T-cell signaling and may guide the development of future nanomedicine-based immunomodulatory therapies.
•Little is known about the between-individual variability of nutritional traits.•Meaningful between-individual variability of reticulorumen passage rate was found.•Most variability of solute passage ...rate is inherent to the individual.•Variability of passage rate of particles is partially inherent to the individual.•Our findings on individual variability help precision feeding implementation.
Identifying factors that influence an individual’s ability to utilize nutrients is a strategy for enhancing livestock sustainability. Digesta passage rate (kp) is one of the most important determinants that influence nutrient utilization. However, there is limited knowledge regarding the individual’s variability on kp. The objective of this study was to investigate between-individual variability of reticulorumen (RR) kp of solutes and particles in goats, and its relationship to total NDF digestibility (NDFd). A dataset consisting of 103 individual records from two studies of castrated male (n = 36), female (n = 34), and intact male (n = 33) growing Saanen goats fed ad libitum and slaughtered at around 16.62 ± 0.96 (n = 21), 23.09 ± 1.33 (n = 19), 30.67 ± 2.25 kg (n = 29), 38.02 ± 1.61 (n = 16), and 44.12 ± 1.95 (n = 18) kg BW was used. The RR kp of solutes and particles were measured using Cr-EDTA and indigestible NDF (iNDF), respectively. Using mixed-effect models, considering sex and BW as fixed effects and study as random effect, we aimed to identify meaningful between-individual variance of RR kp of solutes and particles. Given the characteristic of our dataset (i.e., one observation per individual), our approach focused on exploring the variance between individuals described by the residuals of our fitted models. The RR kp of solutes and particles showed significant (P < 0.05) between-individual variation (CV ≈ 27%). Only 10% of RR kp of solutes variance was explained by DM intake (DMI) (g/d and g/d and g/kg BW) and NDF intake (NDFI); g/d), while 51.8% of the variance in RR kp of particles was explained by DMI and NDFI (g/d and g/kg BW), RR wet pool size, and iNDF:NDF intake ratio. The between-individual variation of RR kp of particles explained 19.5% of the between-individual variation in NDFd (P < 0.001). However, the nutritional and individual traits cited above (i.e., DMI, NDFI, RR wet pool size, and iNDF:NDF intake ratio) explained only 51.8% of the between-individual variation of RR kp of particles, while the remaining 48.2% was attributed to the individual’s inherent characteristics, which in turn explained only 1.24% of the between-individual variation of NDFd (P = 0.146). The RR kp of particles and solutes showed meaningful between-individuals variance, which was partially related to both individual inherent characteristics and nutritional and animal traits. However, the NDFd was found to be unrelated to the inherent characteristics of RR kp of particles.
Abstract The recent progress in stem cell techniques has broadened the horizon for in vitro disease modeling. For desired in vivo like phenotypes, not only correct cell type specification will be ...critical, the microenvironmental context will be essential to achieve relevant responses. We demonstrate how a three dimensional (3D) culture of stem cell derived neurons can induce in vivo like responses related to Alzheimer's disease, not recapitulated with conventional 2D cultures. To acquire a neural population of cells we differentiated neurons from neuroepithelial stem cells, derived from induced pluripotent stem cells. p21-activated kinase mediated sensing of Aβ oligomers was only possible in the 3D environment. Further, the 3D phenotype showed clear effects on F-actin associated proteins, connected to the disease processes. We propose that the 3D in vitro model has higher resemblance to the AD pathology than conventional 2D cultures and could be used in further studies of the disease.
The spatial organization of membrane-bound ligands is thought to regulate receptor-mediated signaling. However, direct regulation of receptor function by nanoscale distribution of ligands has not yet ...been demonstrated, to our knowledge. We developed rationally designed DNA origami nanostructures modified with ligands at well-defined positions. Using these 'nanocalipers' to present ephrin ligands, we showed that the nanoscale spacing of ephrin-A5 directs the levels of EphA2 receptor activation in human breast cancer cells. Furthermore, we found that the nanoscale distribution of ephrin-A5 regulates the invasive properties of breast cancer cells. Our ligand nanocaliper approach has the potential to provide insight into the roles of ligand nanoscale spatial distribution in membrane receptor-mediated signaling.
A more complete understanding of the mechanisms controlling AA transport in mammary glands of dairy cattle will help identify solutions to increase nitrogen feeding efficiency on farms. It was ...hypothesized that Ala, Gln, and Gly (NEAAG), which are actively transported into cells and exchanged for all branched-chain AA (BCAA), may stimulate transport of BCAA, and that Val may antagonize transport of the other BCAA due to transporter competition. Thus, we evaluated the effects of varying concentrations of NEAAG and Val on transport and metabolism of the BCAA Ala, Met, Phe, and Thr by bovine mammary epithelial cells. Primary cultures of bovine mammary epithelial cells were assigned to treatments of low (70% of mean in vivo plasma concentrations of lactating dairy cows) and high (200%) concentrations of Val and NEAAG (LVal and LNEAAG, HVal and HNEAAG, respectively) in a 2 × 2 factorial design. Cells were preloaded with treatment media containing 15N-labeled AA for 24 h. The 15N-labeled media were replaced with treatment media containing 13C-labeled AA. Media and cells were harvested from plates at 0, 0.5, 1, 5, 15, 30, 60, and 240 min after application of the 13C-labeled AA and assessed for 15N- and 13C-AA label concentrations. The data were used to derive transport, transamination, irreversible loss, and protein-synthesis fluxes. All Val fluxes, except synthesis of rapidly exchanging tissue protein, increased with the HVal treatment. Interestingly, the rapidly exchanging tissue protein, transamination, and irreversible-loss rate constants decreased with HVal, indicating that the significant flux increases were primarily driven by mass action with the cells resisting the flux increases by downregulating activity. However, the decreases could also reflect saturation of processes that would drive down the mass-action rate constants. This is supported by decreases in the same rate constants for Ile and Leu with HVal. This could be due to either competition for shared transamination and oxidation reactions or a reduction in enzymatic activity. Also, NEAAG did not affect Val fluxes, but influx and efflux rate constants increased for both Val and Leu with HNEAAG, indicating an activating substrate effect. Overall, AA transport rates generally responded concordantly with extracellular concentrations, indicating the transporters are not substrate-saturated within the in vivo range. However, BCAA transamination and oxidation enzymes may be approaching saturation within in vivo ranges. In addition, System L transport activity appeared to be stimulated by as much as 75% with high intracellular concentrations of Ala, Gln, and Gly. High concentrations of Val antagonized transport activity of Ile and Leu by 68% and 15%, respectively, indicating competitive inhibition, but this was only observable at HNEAAG concentrations. The exchange transporters of System L transport 8 of the essential AA that make up approximately 40% of milk protein, so better understanding this transporter is an important step for increased efficiency.
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Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. ...Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutaneous site in both sides of the neck in each mare. The blood flow perfusion at the transplantation site was monitored at days 2, 4, 6, and 7 post-grafting using color-Doppler ultrasonography. Ovarian grafts were recovered 7 days post-transplantation and subjected to histological analyses. The exposure of the ovarian fragments to VEGF before grafting was not beneficial to the quality of the tissue; however, the cooling process of the fragments reduced the acute hyperemia post-grafting. Cooled grafts compared with non-cooled grafts contained similar values for normal and developing preantral follicles, vessel density, and stromal cell apoptosis; lower collagen type III fibers and follicular density; and higher stromal cell density, AgNOR, and collagen type I fibers. In conclusion, VEGF exposure before autotransplantation did not improve the quality of grafted tissues. However, cooling ovarian tissue for at least 24 h before grafting can be beneficial because satisfactory rates of follicle survival and development, stromal cell survival and proliferation, as well as vessel density, were obtained.
The objective of this study was to evaluate the effect of jugular infusions of 2 groups of AA on essential AA (EAA) transport and metabolism by mammary glands. Four Holstein cows in second lactation ...(66 ± 10 d in milk) were used in 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Treatments were jugular infusions of saline; Met, Lys, and His (MKH); Ile and Leu (IL); or MKH plus IL (MKH+IL). Each period consisted of 8 d of no infusion followed by 8 d of jugular vein infusion of the treatment solutions. Amino acids were infused at rates of 21 g of Met, 38 g of Lys, 20 g of His, 50 g of Leu, and 22 g of Ile per day. Cows were fed a basal diet consisting of 15.2% crude protein with adequate rumen degradable protein but 15% deficient in MP based on estimates by Cornell Net Carbohydrate and Protein System (v6.5). On the last day of each period, 13C-AA derived from algae was infused into the jugular vein over 6 h, and blood and milk samples were collected before, during, and after infusion. Plasma and milk samples were analyzed for AA isotopic enrichment, and a mammary compartmental model was fitted to the data to derive bidirectional transport and metabolism rates for individual EAA. Influx of Leu increased with IL, whereas influx of other EAA was not different among treatments. Cellular efflux of Met and Lys to venous plasma represented 12 to 34% of influx, whereas cellular efflux of Phe and BCAA represented 29 to 59% of influx. Increased efflux/influx ratios of Ile and Leu with IL but not Met and Lys with MKH demonstrated that increased Ile and Leu influx was mostly returned to plasma resulting in no change in net uptake or efficiency. The isotope results showed that mammary net uptake of Lys and Ile increased during MKH infusion. Net uptake of Met increased with MKH but only in the absence of IL. Catabolism of Lys and Met only increased with MKH alone, resulting in decreased efficiency for milk protein, which demonstrated that Ile and Leu infusion can spare Lys and Met for milk protein synthesis. Total AA uptake to milk output was not different from 1, implying the catabolized Met and Lys contributed nitrogen to nonessential AA. Overall, EAA uptake and metabolism in mammary glands of dairy cows varied across individual EAA and responded differently to respective AA supplements. In addition, uptake, retention, and end use of AA by mammary tissue is variable and dependent on the mix of AA provided. This variability, depending on the mix of AA absorbed, will change the efficiency of utilization of individual AA at the mammary gland level and consequently the whole-body level. Thus, it is inaccurate to use a fixed, constant efficiency within and across AA to represent tissue activity.
Diet formulation in a pasture-based dairy system is a challenge as the quality and quantity of available pasture, which generally constitutes the base diet, is constantly changing. The objective of ...this paper is to cover a more in-depth review of the nutritional characteristics of pasture-based diets, identifying potential system, plant, and animal factors that condition pasture dietary inclusion in dairy cows. In practice, there is a wide diversity of pasture-based systems with predominant to minimal use of pasture requiring a more specific classification that potentially considers the amount and time of access to pasture, access to housing, length of grazing season, seasonality of calving, and level and method of supplementation. There are important differences in the nutritional quality between pasture species and even cultivars. However, under management practices that promote maintenance of pasture in a vegetative state as well as controlling the availability of pasture, it is possible to achieve high dry matter intakes (∼2.9%–3.4% of live weight) of pasture with moderate to high diet energy density, protein supply, and digestibility. The amount of pasture to include in the diet will depend on several factors, such as the type of production system, the cost of supplementary feeds, and the farmer's objectives, but inclusions of ∼40% to 50% of the diet seem to potentially reduce costs while apparently not limiting voluntary feed intake. Considering that there seems to be a continuum of intermediate management systems, a better understanding of the factors inherent to the feed ingredients used, as well as the use of nutrients by cows, and potential interactions between animal × system should be addressed in greater depth. This requires a meta-analysis approach, but given the diversity of the pasture-based system in practice, the existing information is highly fragmented. A clear definition of “subsystems” is necessary to direct the future research and development of mechanistic models.
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Abstract Microenvironmental mechanical properties of stem cell niches vary across tissues and developmental stages. Accumulating evidence suggests that matching substrate elasticity with in vivo ...tissue elasticity facilitates stem cell differentiation. However, it has not been established whether substrate elasticity can control the maturation stage of cells generated by stem cell differentiation. Here we show that soft substrates with elasticities commensurable to the elasticity of the brain promote the maturation of neural stem cell-derived neurons. In the absence of added growth factors, neurons differentiated on soft substrates displayed long neurites and presynaptic terminals, contrasting with the bipolar immature morphology of neurons differentiated on stiff substrates. Further, soft substrates supported an increase in astrocytic differentiation. However, stiffness cues could not override the dependency of astrocytic differentiation on Notch signaling. These results demonstrate that substrate elasticity per se can drive neuronal maturation thus defining a crucial parameter in neuronal differentiation of stem cells.
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