Background and purpose
Argyrophilic grain disease (AGD) is a limbic‐predominant 4R‐tauopathy. AGD is thought to be an age‐related disorder and is frequently detected as a concomitant pathology with ...other neurodegenerative conditions. There is a paucity of data on the clinical phenotype of pure AGD. In elderly patients, however, AGD pathology frequently associates with cognitive decline, personality changes, urine incontinence and cachexia. In this study, clinicopathological findings were analysed in individuals younger than 75.
Methods
Patients were identified retrospectively based on neuropathological examinations during 2006–2017 and selected when AGD was the primary and dominant pathological finding. Clinical data were obtained retrospectively through medical records.
Results
In all, 55 patients (2% of all examinations performed during that period) with AGD were identified. In seven cases (13%) AGD was the primary neuropathological diagnosis without significant concomitant pathologies. Two patients were female, median age at the time of death was 64 years (range 51–74) and the median duration of disease was 3 months (range 0.5–36). The most frequent symptoms were progressive cognitive decline, urinary incontinence, seizures and psychiatric symptoms. Brain magnetic resonance imaging revealed mild temporal atrophy.
Conclusions
Argyrophilic grain disease is a rarely recognized limbic tauopathy in younger individuals. Widening the clinicopathological spectrum of tauopathies may allow identification of further patients who could benefit from tau‐based therapeutic strategies.
The anti-tumoral effects of cannabinoids have been described in different tumor systems, including pancreatic adenocarcinoma, but their mechanism of action remains unclear. We used cannabinoids ...specific for the CB1 (ACPA) and CB2 (GW) receptors and metabolomic analyses to unravel the potential pathways mediating cannabinoid-dependent inhibition of pancreatic cancer cell growth. Panc1 cells treated with cannabinoids show elevated AMPK activation induced by a ROS-dependent increase of AMP/ATP ratio. ROS promote nuclear translocation of GAPDH, which is further amplified by AMPK, thereby attenuating glycolysis. Furthermore, ROS determine the accumulation of NADH, suggestive of a blockage in the respiratory chain, which in turn inhibits the Krebs cycle. Concomitantly, inhibition of Akt/c-Myc pathway leads to decreased activity of both the pyruvate kinase isoform M2 (PKM2), further downregulating glycolysis, and glutamine uptake. Altogether, these alterations of pancreatic cancer cell metabolism mediated by cannabinoids result in a strong induction of autophagy and in the inhibition of cell growth.
Gemcitabine (GEM, 2',2'-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of < 20%. The purpose of our work was to improve GEM activity by addition ...of cannabinoids. Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments. The antiproliferative synergism is prevented by the radical scavenger N-acetyl-L-cysteine and by the specific NF-κB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-κB by GEM is required for this effect. In addition, we report that neither apoptotic nor cytostatic mechanisms are responsible for the synergistic cell growth inhibition, which is strictly associated with the enhancement of endoplasmic reticulum stress and autophagic cell death. Noteworthy, the antiproliferative synergism is stronger in GEM-resistant pancreatic cancer cell lines compared with GEM-sensitive pancreatic cancer cell lines. The combined treatment strongly inhibits growth of human pancreatic tumor cells xenografted in nude mice without apparent toxic effects. These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells.
This study analyzed the spatial distribution of Yellow Sigatoka Leaf Spot relative to soil fertility and plant nutritional status using geostatistics. The experimental area comprised 1.2 ha, where 27 ...points were georeferenced and spaced on a regular grid 18 × 18 m. The severity of Yellow Sigatoka, soil fertility and plant nutritional status were evaluated at each point. The spherical model was adjusted for all variables using restricted maximum likelihood. Kriging maps showed the highest infection rate of Sigatoka occurred in high areas of the field which had the highest concentration of sand, while the lowest disease was found in lower areas with lower silt, organic matter, total exchangeable bases, effective cation exchange capacity, base saturation, Ca and Mg in soil, and foliar sulfur (S). These results may help farmers manage Yellow Sigatoka disease more effectively, with balanced fertilization and reduced fungicide application. This practice minimizes the environmental impact and cost of production while contributing to production sustainability.
•Soil Security and Food and Nutrition Security are interconnected.•Soil degradation drives food insecurity and sustainable management is needed.•Connectivity aids awareness of impacts and encourages ...sustainable management.•Link between Security dimensions facilitate holistic land management.•Soil Security dimensions may enable refinement of Food Security indicators.
There is a nexus of seven inter-linked global existential challenges; Soil Security and Food Security are two of these. The established concept of Food Security is well defined and researched, whereas the emerging concept of Soil Security is building its currency globally. Addressing Soil Security provides the means to improve food, fibre and water quality in a sustainable manner, through enhanced soil care and development of best land-management practices. Soil is a fragile resource which is degraded in many parts of the world. The rapidly growing global population has placed further pressure on the soil resource to accommodate increased demand for food, fibre and soil-derived materials. Such pressures are accelerating degradation and so novel approaches are needed. Literature search within this review demonstrated Soil Security and Food Security to be a convergence of disciplines. To truly identify solutions to challenges faced in either realm, an interdisciplinary approach seeking to understand deeper interactions between the two concepts is needed. Driven by this need, our review sought to investigate such interactions between the challenges faced in Soil Security and Food Security. Following assessment of these interactions, four potential solutions were discussed and included sustainable intensification and management, digital agriculture, circularisation and reducing the food demand trajectory through enhanced soil care. Soil Security and Food Security are interconnected concepts which will help facilitate implementation of the above solutions, and so approaches are needed which take this connection into account.
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Octafunctionalized spherosilsesquioxanes (Q8M8 H), decorated with Si–H functions, could be used to design, by coupling via hydrosilylation with α-methoxy-ω-undecenyl poly(ethylene oxide)s (PEOs), ...organic–inorganic nanocomposite structures. 1H, 13C, and 29Si NMR; size exclusion chromatography; and Fourier transfrom infrared spectroscopy were used to follow the grafting reaction and determine the molar mass and the functionality of the different species. Hybrid star-shaped poly(ethylene oxide)s of precise molar mass and functionality could be isolated by fractional precipitation of the raw reaction product. Absolute molar masses of the purified star-shaped PEOs, calculated with the assumption of a functionality of 8, were comparable when measured by light scattering in methanol and by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Small-angle X-ray scattering was employed to determine their molecular and structural characteristics, representing the versatility and innovative aspect to this study. Both differential scanning calorimetry and optical microscopy were utilized to elaborate and analyze the thermal properties and crystallization, respectively, of the hybrid stars. Further ongoing work is being carried out currently to investigate and foresee the use of longer PEO branches onto the core.
Occurrence and intensity coffee leaf rust (
Hemileia vastatrix
) depend mainly on the irrigation system, soil fertility and plant nutrition. The aim of this study was to evaluate the spatial ...distribution of coffee leaf rust relative to soil fertility and plant nutrition in coffee plantations irrigated by drip and center pivot using geostatistics. The experiment was installed in two experimental areas, with a drip and center pivot irrigation system of 11 and 17 ha and 52 and 50 georeferenced sampling points, respectively. The incidence of the disease, soil fertility and plant nutritional status were evaluated at each point. For the drip system, there was no significant correlation between disease incidence and leaf contents of N, P, K, and Ca. Regarding fertility, there was a positive correlation only for P and the disease incidence. For the center pivot system, there was a positive correlation between coffee leaf rust and Ca, P, and K, and negative for P and K in the leaves, varying according to the assessment date. In soil, only Ca correlated negatively whereas K positively correlated with incidence. The spatial distribution of the disease and nutrients varied over the years, being observed a gradient from foci in the kriging maps elaborated after the adjustment of the exponential model.
Amphiphilic α-undecenyl-ω-hydroxy heterobifunctional PEOs of precise molar mass and adjustable hydrophobic/hydrophilic balance were successfully synthesized by anionic ring opening polymerization of ...ethylene oxide. The most original part of the work concerns a new unsaturated heterofunctional initiator in powder form. The availability of such an initiator facilitates the processing, the reaction procedure and offers new perspectives in the synthesis of libraries of end-functional PEOs. α-Undecenyl-ω-methacryloyl and α-undecenyl-ω-acetylene heterobifunctional PEO macromonomers could be obtained. They served as building blocks for the synthesis of functional PI-b-PEO diblock copolymers and functional branched architectures. Display omitted
•Design of new heterofunctional α-undecenyl-ω-hydroxypoly(ethylene oxide) (PEO) by AROP.•Initiator in powder form that facilitates the processing and the reaction procedure.•New heterobifunctional α-undecenyl-ω-methacryloyl and α-undecenyl ω-acetylene PEOs.•New functional comb or star-shaped PEOs based on α-undecenyl-ω-methacryloyl PEOs.•Design of functional poly(ethylene oxide-b-isoprene) block copolymers by “click chemistry”.
Heterofunctional α-undecenyl-ω-hydroxy poly(ethylene oxide) (PEO) macromonomers could be designed by initiation. For their synthesis via Anionic Ring-Opening Polymerization (AROP) of ethylene oxide, a potassium alcoholate, prepared in situ by reaction of 10-undecene-1-ol with a stoichiometric amount of diphenylmethyl potassium (DPMK), was used. The applicability of the same initiator but in powder form was evaluated for the polymerization of ethylene oxide. This initiator is well-suited for, e.g., automated high-throughput screening approaches by simply weighing in the amount of initiator needed. The macromonomers were characterized by SEC, 1H NMR, MALDI-TOF MS and light scattering. Independent from the applied approach, well-defined heterobifunctional PEO macromonomers could be obtained. Their solution behavior was investigated in water and methanol by Dynamic Light Scattering (DLS) and in water by critical micelle concentration (cmc) measurements. Chemical modification of the hydroxyl end-group by methyl methacrylate or by propargyl bromide could be achieved leading to heterobifunctional PEO macromonomers. These PEOs offer a great potential as building blocks in macromolecular engineering. PI-b-PEO diblocks or comb-shaped PEOs represent typical examples.
We show that treatment with non-toxic doses of zinc in association to the ionophore compound pyrrolidine dithiocarbamate (PDTC) inhibits p53
−/− pancreatic cancer cell growth much more efficiently ...than gemcitabine, the gold standard chemotherapeutic agent for pancreatic cancer. Both the metal chelator
N,
N,
N′,
N′-tetrakis(2-pyridylmethyl)ethylenediamine and the radical scavenger
N-acetyl-
l-cysteine are able to recover cell growth inhibition by Zn/PDTC, demonstrating that this effect depends on the increased levels of intracellular zinc and of reactive oxygen species (ROS). Zn/PDTC treatment induces a strong apoptotic cell death that is associated to ROS-dependent nuclear translocation of the mitochondrial factor AIF, but not to the regulation of apoptotic genes and caspase activation. Primary fibroblasts are more resistant than pancreatic cancer cells to Zn/PDTC treatment and exhibit a lower basal and Zn/PDTC-induced enhancement of intracellular zinc. We show that Zn/PDTC induces p53 proteasomal degradation and that the proteasome inhibitor MG132 further increases fibroblast growth inhibition by Zn/PDTC, suggesting that p53 degradation plays an important role in fibroblast resistance to Zn/PDTC.
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