MS INTA 416 is a hard red winter wheat selected for high yield potential and good bread-making quality, combined with moderate resistance to Fusarium-head-blight and high resistance to leaf-rust, due ...mainly to presence of resistance genes Fhb1 and Lr47. MS INTA 416 is adapted to main production areas of Central-Argentina.
Brain iron accumulation constitutes a pathognomonic indicator in several neurodegenerative disorders. Metal accumulation associated with dopaminergic neuronal death has been documented in Parkinson's ...disease. Through the use of in vivo and in vitro models, we demonstrated that lipid dysregulation manifests as a neuronal and glial response during iron overload.
In this study, we show that cholesterol content and triacylglycerol (TAG) hydrolysis were strongly elevated in mice midbrain. Lipid cacostasis was concomitant with the loss of dopaminergic neurons, astrogliosis and elevated expression of α-synuclein. Exacerbated lipid peroxidation and markers of ferroptosis were evident in the midbrain from mice challenged with iron overload. An imbalance in the activity of lipolytic and acylation enzymes was identified, favoring neutral lipid hydrolysis, and consequently reducing TAG and cholesteryl ester levels. Notably, these observed alterations were accompanied by motor impairment in iron-treated mice.
In addition, neuronal and glial cultures along with their secretomes were used to gain further insight into the mechanism underlying TAG hydrolysis and cholesterol accumulation as cellular responses to iron accumulation. We demonstrated that TAG hydrolysis in neurons is triggered by astrocyte secretomes. Moreover, we found that the ferroptosis inhibitor, ferrostatin-1, effectively prevents cholesterol accumulation both in neurons and astrocytes. Taken together, these results indicate that lipid disturbances occur in iron-overloaded mice as a consequence of iron-induced oxidative stress and depend on neuron-glia crosstalk. Our findings suggest that developing therapies aimed at restoring lipid homeostasis may lead to specific treatment for neurodegeneration associated with ferroptosis and brain iron accumulation.
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•Iron accumulation (IA) in mice midbrain triggers astrogliosis and movement disorders.•Midbrain IA leads to ferroptosis and dopaminergic cell death.•Acylation/lipolytic imbalance results in neutral lipid cacostasis during IA.•TAG hydrolysis induced by IA depends on neuro-glia crosstalk.•Cholesterol accumulation is retreated by inhibiting ferroptosis.
Background
Adipose tissue (AT) dysfunction in obesity is commonly linked to insulin resistance and promotes the development of metabolic disease. Bariatric surgery (BS) represents an effective ...strategy to reduce weight and to improve metabolic health in morbidly obese subjects. However, the mechanisms and pathways that are modified in AT in response to BS are not fully understood, and few information is still available as to whether these may vary depending on the metabolic status of obese subjects.
Methods
Abdominal subcutaneous adipose tissue (SAT) samples were obtained from morbidly obese women (
n
= 18) before and 13.3 ± 0.37 months after BS. Obese women were stratified into two groups: normoglycemic (NG; Glu < 100 mg/dl, HbA1c <5.7 %) or insulin resistant (IR; Glu 100–126 mg/dl, HbA1c 5.7–6.4 %) (
n
= 9/group). A multi-comparative proteomic analysis was employed to identify differentially regulated SAT proteins by BS and/or the degree of insulin sensitivity. Serum levels of metabolic, inflammatory, and anti-oxidant markers were also analyzed.
Results
Before surgery, NG and IR subjects exhibited differences in AT proteins related to inflammation, metabolic processes, the cytoskeleton, and mitochondria. BS caused comparable weight reductions and improved glucose homeostasis in both groups. However, BS caused dissimilar changes in metabolic enzymes, inflammatory markers, cytoskeletal components, mitochondrial proteins, and angiogenesis regulators in NG and IR women.
Conclusions
BS evokes significant molecular rearrangements indicative of improved AT function in morbidly obese women at either low or high metabolic risk, though selective adaptive changes in key cellular processes occur depending on the initial individual’s metabolic status.
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•Crystallization of methane hydrate confined in a silica pore is described using MD.•Hydrate crystallizes occupying all the accessible volume, but presents many defects.•As in the ...case of ice, an interfacial liquid layer is observed between the hydrate and the confining silica walls.
The growth of a methane hydrate seed within a silica slit pore of fixed width has been studied using All-Atom Molecular Dynamics (AA-MD). An AA force field has been used to describe the molecules of the solid silica substrate, with α-quartz crystalline structure. The crystallisation of hydrates in confined geometries is not well understood yet, and the objective of this work is to study the hydrate growth inside a silica pore using molecular simulation. Both NVT and NpT ensembles were used in the AA-MD simulations to analyse the hydrate growth from an initial seed. Results showed that the boundary conditions imposed by the nanometric slit pore yielded a hydrate with structural defects, filling the accessible space between the silica walls. The water molecules which were not incorporated to the initial seed hydrate formed a high density water layer trapped between the silica walls and the crystallised hydrate. These results provide an interesting insight into the hydrate crystallisation process in confined geometries, resembling those found in natural hydrate deposits.
The detection of mycotoxins in feeds and their ingredients in aquaculture gained prominence due to losses caused in production and animal health, mainly the occurrence of aflatoxin (AFB
1
). The aim ...of this study was to evaluate the effects of AFB
1
on the performance of tambaqui fingerlings (
Colossoma macropomum
). Four hundred tambaqui were used. Four different treatments were evaluated: treatment T1, considered as the control treatment (CT) with 3.84 μg kg
−1
; treatment T2, treatment T3 and treatment T4 with 500, 1000 and 2000 μg kg
−1
of AFB
1
, respectively. The AFB
1
of the samples (muscle, liver and kidney) was detected by high-pressure liquid chromatography. Four fingerlings from each treatment for histological analysis were examined. Moreover, the performance parameters (weight gain, feed conversion and feed intake) were studied. The levels of toxins used in T2, T3 and T4 represent a reduction in the growth of 14%, 35% and 45%, respectively. The T3 and T4 showed the lowest weight gain (78%) and the worst feed conversion. Aflatoxin B
1
in muscle (3.28 μg kg
−1
) and kidneys (8.8 μg kg
−1
) in the T3, as well as liver (4.4 μg kg
−1
) and kidney (4.08 μg kg
−1
) in T4, was detected. Histopathological changes in liver and kidney tissues of fingerlings were more pronounced in T3 and T4. Fingerlings that consume feed contaminated with AFB
1
in concentrations higher than 500 μg kg
−1
present decreases in growth, reduction in weight gain and feed intake with increased feed conversion. The consumption of feed contaminated with 1000 and 2000 μg kg
−1
of AFB
1
caused severe deterioration in the hepatic and renal tissues.
Maturation of functional liquid‐like biomolecular condensates into solid‐like aggregates has been linked to the onset of several neurodegenerative disorders. Low‐complexity aromatic‐rich kinked ...segments (LARKS) contained in numerous RNA‐binding proteins can promote aggregation by forming inter‐protein β‐sheet fibrils that accumulate over time and ultimately drive the liquid‐to‐solid transition of the condensates. Here, atomistic molecular dynamics simulations are combined with sequence‐dependent coarse‐grained models of various resolutions to investigate the role of LARKS abundance and position within the amino acid sequence in the maturation of condensates. Remarkably, proteins with tail‐located LARKS display much higher viscosity over time than those in which the LARKS are placed toward the center. Yet, at very long timescales, proteins with a single LARKS—independently of its location—can still relax and form high viscous liquid condensates. However, phase‐separated condensates of proteins containing two or more LARKS become kinetically trapped due to the formation of percolated β‐sheet networks that display gel‐like behavior. Furthermore, as a work case example, they demonstrate how shifting the location of the LARKS‐containing low‐complexity domain of FUS protein toward its center effectively precludes the accumulation of β‐sheet fibrils in FUS‐RNA condensates, maintaining functional liquid‐like behavior without ageing.
Biomolecular condensates importantly contribute to the spatiotemporal organization of the cell. However, condensates can age over time transitioning into gel‐like pathological aggregates. Here, by combining atomistic and coarse‐grained simulations, the authors investigate how the concentration and location of low‐complexity aromatic‐rich kinked segments—susceptible of developing inter‐protein β‐sheet transitions—control the ageing rate of protein condensates. Strikingly, the authors find how just the reposition of these segments across the protein sequence can severely regulate condensate ageing.
Sublethal renal ischemia induces tubular epithelium damage and kidney dysfunction. Using NRK-52E rat proximal tubular epithelial cells, we have established an
in vitro model, which includes oxygen ...and nutrients deprivation, to study the proximal epithelial cell response to ischemia. By means of this system, we demonstrate that confluent NRK-52E cells lose monolayer integrity and detach from collagen IV due to: (i) actin cytoskeleton reorganization; (ii) Rac1 and RhoA activity alterations; (iii) Adherens junctions (AJ) and Tight junctions (TJ) disruption, involving redistribution but not degradation of E-cadherin, β-catenin and ZO-1; (iv) focal adhesion complexes (FAC) disassembly, entangled by mislocalization of paxillin and FAK dephosphorylation. Reactive oxygen species (ROS) are generated during the deprivation phase and rapidly balanced at recovery involving MnSOD induction, among others. The use of antioxidants (NAC) prevented FAC disassembly by blocking paxillin redistribution and FAK dephosphorylation, without abrogating AJ or TJ disruption. In spite of this, NAC did not show any protective effect on cell detachment. H
2O
2, as a pro-oxidant treatment, supported the contribution of ROS in tubular epithelial cell–matrix but not cell–cell adhesion alterations. In conclusion, ROS-mediated FAC disassembly was not sufficient for the proximal epithelial cell shedding in response to sublethal ischemia, which also requires intercellular adhesion disruption.
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