Zinc enrichment of edible food products, through the soil and/or foliar application of fertilizers, is a strategy that can increase the contents of some nutrients, namely Zn. In this context, a ...workflow for agronomic enrichment with zinc was carried out on irrigated Vitis vinifera cv. Syrah, aiming to evaluate the mobilization of photoassimilates to the winegrapes and the consequences of this for winemaking. During three productive cycles, foliar applications were performed with ZnSO4 or ZnO, at concentrations ranging between 150 and 1350 g.ha−1. The normal vegetation index as well as some photosynthetic parameters indicated that the threshold of Zn toxicity was not reached; it is even worth noting that with ZnSO4, a significant increase in several cases was observed in net photosynthesis (Pn). At harvest, Zn biofortification reached a 1.2 to 2.3-fold increase with ZnSO4 and ZnO, respectively (being significant relative to the control, in two consecutive years, with ZnO at a concentration of 1350 g.ha−1). Total soluble sugars revealed higher values with grapes submitted to ZnSO4 and ZnO foliar applications, which can be advantageous for winemaking. It was concluded that foliar spraying was efficient with ZnO and ZnSO4, showing potential benefits for wine quality without evidencing negative impacts.
Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles ...composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD. RNA and protein levels of SEPTIN5 showed a significant decrease in human temporal cortex in relation to the increasing degree of AD-related neurofibrillary pathology. Conversely, an increase in the phosphorylation of the functionally relevant SEPTIN5 phosphorylation site S327 was observed already in the early phases of AD-related neurofibrillary pathology, but not in the cerebrospinal fluid of individuals fulfilling the criteria for mild cognitive impairment due to AD. According to the mechanistic assessments, a link between SEPTIN5 S327 phosphorylation status and the effects of SEPTIN5 on amyloid precursor protein processing and markers of autophagy was discovered in mouse primary cortical neurons transduced with lentiviral constructs encoding wild type SEPTIN5 or SEPTIN5 phosphomutants (S327A and S327D). C57BL/6 J mice intrahippocampally injected with lentiviral wild type SEPTIN5 or phosphomutant constructs did not show changes in cognitive performance after five to six weeks from the start of injections. However, SEPTIN5 S327 phosphorylation status was linked to changes in short-term synaptic plasticity ex vivo at the CA3-CA1 synapse. Collectively, these data suggest that SEPTIN5 and its S327 phosphorylation status play a pivotal role in several cellular processes relevant for AD.
•S327 phosphorylation of SEPTIN5 is increased in the early stages of AD.•SEPTIN5 affects APP processing and autophagy in mouse primary neurons.•Phosphorylation of SEPTIN5 at S327 site is linked to short-term synaptic plasticity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Kyotorphin (KTP,
l
-tyrosyl-
l
-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely ...for Alzheimer’s disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH
2
, when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid β peptide (Aβ). Animals were treated for 20 days with KTP-NH
2
(32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Aβ administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH
2
treatment, Aβ-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Aβ-injected rats that had been treated with KTP-NH
2
, which scored in memory tests as control (sham i.c.v. injected) rats. No signs of gliosis could be detected at the end of the treatment in any group of animals. LTP magnitude was significantly impaired in hippocampal slices that had been incubated with Aβ oligomers (200 nM) in the absence of KTP-NH
2
. Co-incubation with KTP-NH
2
(50 nM) rescued LTP toward control values. Similarly, Aβ caused a significant decrease in spine density in cortical neuronal cultures, and this was prevented by co-incubation with KTP-NH
2
(50 nM). In conclusion, the present data demonstrate that i.p. KTP-NH
2
treatment counteracts Aβ-induced memory impairments in an AD sporadic model, possibly through the rescuing of synaptic plasticity mechanisms.
The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer ...metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol. We observed that a ferroptosis-like mechanism, induced by xCT inhibition with Erastin, at a non-lethal level, promoted features of ECs activation, such as proliferation, migration and vessel-like structures formation, concomitantly with the depletion of reduced glutathione (GSH) and increased levels of oxidative stress and lipid peroxides. Additionally, this ferroptosis-like mechanism promoted vascular endothelial cadherin (VE-cadherin) junctional gaps and potentiated cancer cell adhesion to ECs and transendothelial migration. Propranolol was able to revert Erastin-dependent activation of ECs and increased levels of hydrogen sulfide (H
2
S) underlie the mechanism of action of Propranolol. Furthermore, we tested a dual-effect therapy by promoting ECs stability with Propranolol and boosting oxidative stress to induce cancer cell death with a nanoformulation comprising selenium-containing chrysin (SeChry) encapsulated in a fourth generation polyurea dendrimer (SeChry@PURE
G4
). Our data showed that novel developments in cancer treatment may rely on multi-targeting strategies focusing on nanoformulations for a safer induction of cancer cell death, taking advantage of tumor vasculature stabilization.
Rice (
L.) is one of the most economically and socially important cereals in the world. Several strategies such as biofortification have been developed in a way eco-friendly and sustainable to ...enhance crop productivity. This study implemented an agronomic itinerary in Ariete and Ceres rice varieties in experimental fields using the foliar application of selenium (Se) to increase rice nutritional value. At strategic phases of the plant's development (at the end of booting, anthesis, and at the milky grain stage), they were sprayed with sodium selenate (Na
SeO
) and sodium selenite (Na
SeO
). In the first foliar application plants were sprayed with 500 g Se·ha
and in the remaining two foliar applications were sprayed with 300 g Se·ha
. The effects of Se in the level of micro and macronutrients in brown grains, the localization of Se in these grains, and the subsequent quality parameters such as colorimetric characteristics and total protein were considered. After grain harvesting, the application of selenite showed the highest enrichment in all grain with levels reaching 17.06 µg g
Se and 14.28 µg g
Se in Ariete and Ceres varieties, respectively. In the Ceres and Ariete varieties, biofortification significantly affected the K and P contents. Regarding Ca, a clear trend prevailed suggesting that Se antagonizes the uptake of it, while for the remaining elements in general (except Mn) no significant differences were noted. Protein content increased with selenite treatment in the Ariete variety but not in Ceres. Therefore, it was possible to conclude, without compromising quality, that there was an increase in the nutritional content of Se in brown rice grain.
This study aimed to assess the implications of Zn enrichment in wheat grains as a function of contrasting genotypes, edaphic conditions and foliar fertilizers.
L. varieties Roxo and Paiva were grown ...in four production fields, and sprayed with ZnSO
(0, 16.20 and 36.40 kg/ha) Zn-EDTA (0, 6.30 and 12.60 kg/ha) and Tecnifol Zinc (0, 3.90 and 7.80 kg/ha). The heterogeneous edaphic conditions of the wheat fields were chemically characterized, it being found that soil properties determine different Zn accumulation in the grains of both genotypes. Foliar spraying enhanced to different extents Zn content in the grains of both genotypes, but the average of enrichment indexes varied among the wheat fields. Zinc mostly accumulated in the embryo and vascular bundle and to a lesser extent in the endosperm. Grain yield and test weight sprayed by ZnSO
gave the highest values in both genotypes, but the opposite was found for Zn-EDTA. Considering the color parameters, lightness and red-green transitions were found to be a conjunction of genotype characteristics, fertilization types and edaphic conditions prevailing in each field. It is concluded that the index of Zn enrichment in wheat grains is a docket of edaphic conditions, genotype and type of fertilization.
Calcium is essential for plants, yet as its mobility is limited, the understanding of the rate of Ca2+ accumulation and deposition in tissues of tubers, as well as the interactions with other ...critical nutrients prompted this study. To assess the interactions and differential accumulation of micro and macronutrients in the tissues of tubers, Solanum tuberosum L. varieties Agria and Rossi were cultivated and, after the beginning of tuberization, four foliar sprayings (at 8–10 day intervals) with CaCl2 (3 and 6 kg ha−1) or Ca(NO3)2 (2 and 4 kg ha−1) solutions were performed. It was found that both fertilizers increased Ca accumulation in tubers (mostly in the parenchyma tissues located in the center of the equatorial region). The functioning of the photosynthetic apparatus was not affected until the 3rd application but was somewhat affected when approaching the end of the crop cycle (after the 4th application), although the lower dose of CaCl2 seemed to improve the photochemical use of energy, particularly when compared with the greater dose of Ca(NO3)2. Still, none of these impacts modified tuber height and diameter. Following the increased accumulation of Ca, in the tubers of both varieties, the mean contents of P, K, Na, Fe, and Zn revealed different accumulation patterns. Moreover, accumulation of K, Fe, Mn, and Zn prevailed in the epidermis, displaying a contrasting pattern relative to Ca. Therefore, Ca accumulation revealed a heterogeneous trend in the different regions analyzed, and Ca enrichment of tubers altered the accumulation of other nutrients.
One-third of the world’s population is suffering from “hidden hunger” due to micronutrient deficiency. Zinc is acquired through diet, leading its deficiency to the development of disorders such as ...retarded growth, anorexia, infections, and hypogeusia. Accordingly, this study aimed to develop an agronomic workflow for Zn biofortification on two red winegrapes varieties (cv. Castelão and Syrah) and determine the physicochemical implications for winemaking. Both varieties produced in Setúbal (Portugal) were submitted to four foliar applications of ZnSO4 or ZnO (900 and 1350 g ha−1, respectively), during the production cycle. At harvest, Zn biofortification reached a 4.3- and 2.3-fold increase with ZnO 1350 g ha−1 in Castelão and Syrah, respectively (although, with ZnSO4 1350 g ha−1 both varieties revealed an increase in Zn concentration). On a physiological basis, lower values of NDVI were found in the biofortified grapes, although not reflected in photosynthetic parameters with cv. Syrah shows even a potential benefit with the use of Zn fertilizers. Regarding physical and chemical parameters (density, total soluble solids, dry weight, and color), relative to the control no significant changes in both varieties were observed, being suitable for winemaking. It was concluded that ZnSO4 and ZnO foliar fertilization efficiently increased Zn concentration on both varieties without a negative impact on quality, but cv. Castelão showed a better index of Zn biofortification and pointed to a potentially higher quality for winemaking.
Grapes and wine are widely consumed in the world, yet their mineral content can be influenced by many factors such as the mineral composition of soils, viticulture practices and environmental ...conditions. In this context, considering the importance of Zn in the human physiology, the enrichment of Moscatel and Castelão grapes (white and red variety, respectively) with this nutrient prompted this study; further assessment of tissue deposition and some implications for wine production. Using two foliar fertilizers (ZnO or ZnSO4, at 150, 450 and 900 g ha−1), decreases in net photosynthesis and stomatal conductance occurred in both varieties, suggesting that the physiological threshold of Zn toxicity was reached without visible symptoms. Following foliar spraying with both fertilizers, the content of Zn in leaves of the Castelão and Moscatel varieties showed higher values in all treatments relative to the control. Moreover, in grapes this tendency occurred only in Castelão. Concerning Cu, Fe, Ca, K, S and P, some significant differences also happened in leaves and grapes among treatments. At harvest, the indexes of Zn enrichment in grapes increased between 2.14- and 8.38-fold and between 1.02- and 1.44-fold in Castelão and Moscatel varieties, respectively. Zinc in the dried skin of Castelão only increased with ZnO and ZnSO4 sprayed at 900 g ha−1 (ca. 2.71- and 1.5-fold relative to the control, respectively), but in Moscatel a clear accumulation trend could not be found. The dry weight of grapes ranged (in %) between 16 and 23 (but did not vary significantly among treatments of each variety or in each treatment between varieties), and total soluble solids (e.g., mainly soluble sugars and proteins) and color parameters showed some significant variations. Through winemaking, the contents of Zn increased in both varieties (1.34- and 3.57-fold, in Castelão and Moscatel, respectively) and in all treatments, although non-significantly in Castelão. It is concluded that, to increase the contents of Zn in grapes without reaching the threshold of toxicity, ZnO or ZnSO4 can be used for foliar spraying of Castelão and Moscatel varieties until 900 g ha−1 and that winemaking augments the level of this nutrient.
Following an agronomic approach for the Ca enrichment of Rocha pears, this study aimed to assess the interactions between mineral nutrients in fruit tissues at harvest and after storage for 5 months ...and to characterize the implications on the profile of sugars and fatty acids (FA). A total of seven foliar sprays (with concentrations of 0.1–0.6 kg·ha−1 Ca(NO3)2 and 0.8–8 kg·ha−1 CaCl2) were applied to pear trees. After harvest, the fruits were stored for 5 months, in environmentally controlled chambers, and the mineral contents in five regions (on the equatorial section) of the fruits were assessed, while the sugar and FA content were quantified. For both dates, all foliar sprayed treatments, at different extends, increased Ca content in the center and near the epidermis of Rocha pear fruits and the levels of K, Mn, Fe, Zn and Cu also varied. At harvest, the Ca treatments did not affect the levels of sucrose, glucose, fructose and sorbitol and, after storage, their concentrations remained higher in Ca-treated fruits. Additionally, the tendency of the relative proportions of FA was C18:2 > C18:1 > C16:0 > C18:3 > C18:0 > chains inferior to 16 C (<16:0), but after storage it was C18:2 > C16:0 > C18:3 > C18:0 > C18:1 > chains inferior to 16 C (<16:0). It is concluded that the heterogeneous distribution of Ca in the tissues of Rocha pear fruits results from its absorption in the peel after Ca(NO3)2 and CaCl2 sprays and from the xylemic flux in the core prior to maturity. Additionally, the hydrolysis of complex polysaccharides affects the contents of simpler sugars during maturation, ripening and senescence, while storage decreases the amount of total fatty acids (TFA), but the double bond index (DBI) indicate that cell membrane fluidity remains unaffected.
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