Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many ...symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.
Macro- and microalgae-based foods are becoming popular due to their high nutritious value. The algal biomass is enriched with polysaccharides, protein, polyunsaturated fatty acids, carotenoids, ...vitamins and minerals. However, the most promising fraction is polysaccharides (PS) or their derivatives (as dietary fibers) which are not entirely fermented by colonic bacteria hence act as potential prebiotic. Primarily, algae become famous as prominent protein sources. Recently, these are widely adopted as functional food (e.g., desserts, dairy products, oil-derivatives, pastas etc.) or animal feed (for poultry, cattle, fish etc.). Besides prebiotic and balanced amino acids source, algae derived compounds implied as therapeutics due to comprising bioactive properties to elicit immunomodulatory, antioxidative, anticancerous, anticoagulant, hepato-protective, and antihypertensive responses. Despite the above potentials, broader research determinations are inevitable to explore these algal compounds until microalgae become a business reality for broader and specific applications in all health domains. However, scale up of algal bioprocess remains a major challenge until commercial affordability is accomplished which can be possible by discovering their hidden potentials and increasing their value and application prospects. This review provides an overview of the significance of algae consumption for several health benefits in humans and animals mainly as prebiotics, however their functional food and animal feed potential are briefly covered. Moreover, their potential to develop an algal-based food industry to meet the people's requirements not only as a sustainable food solution with several health benefits but also as therapeutics is inevitable.
The hexanucleotide repeat expansion (HRE) GGGGCC (G4C2) in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies support an HRE RNA ...gain-of-function mechanism of neurotoxicity, and we previously identified protein interactors for the G4C2 RNA including RanGAP1. A candidate-based genetic screen in Drosophila expressing 30 G4C2 repeats identified RanGAP (Drosophila orthologue of human RanGAP1), a key regulator of nucleocytoplasmic transport, as a potent suppressor of neurodegeneration. Enhancing nuclear import or suppressing nuclear export of proteins also suppresses neurodegeneration. RanGAP physically interacts with HRE RNA and is mislocalized in HRE-expressing flies, neurons from C9orf72 ALS patient-derived induced pluripotent stem cells (iPSC-derived neurons), and in C9orf72 ALS patient brain tissue. Nuclear import is impaired as a result of HRE expression in the fly model and in C9orf72 iPSC-derived neurons, and these deficits are rescued by small molecules and antisense oligonucleotides targeting the HRE G-quadruplexes. Nucleocytoplasmic transport defects may be a fundamental pathway for ALS and FTD that is amenable to pharmacotherapeutic intervention.
We used discarded oyster shells to prepare vaterite calcium carbonate microparticles and explored the removal effects and the underlying mechanism toward several heavy metal ions. The removal ...efficiency for each ion type was: Pb2+ (99.9%), Cr3+ (99.5%), Fe3+ (99.3%), and Cu2+ (57.1%). With the exception of Cu2+, vaterite calcium carbonate particles exhibited excellent removal performance on all tested heavy metal ions, with exceptional results for Pb2+. The factor affecting the removal efficiency of heavy metal ions is shown to involve an ion exchange reaction between calcium and the heavy metal ions resulting in recrystallization. Vaterite calcium carbonate particles prepared by this method have the advantage of low price, easy synthesis, and reduction of environmental waste. Thus, this procedure for synthesizing vaterite CaCO3 provides an environmentally responsible method for preparing materials that can be economically incorporated into common consumer products such as household drinking water filtration systems.
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•Oyster shells-prepared CaCO3 has better removal efficiencies than commercial CaCO3.•Heavy metals removal could also be indirectly monitored via pH changes.•The CaCO3 remove heavy metal ions rapidly and be used in water treatments.
Hebbian plasticity is a key mechanism for higher brain functions, such as learning and memory. This form of synaptic plasticity primarily involves the regulation of synaptic ...α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) abundance and properties,whereby AMPARs are inserted into synapses during long-term potentiation (LTP) or removed during long-term depression (LTD). The molecular mechanisms underlying AMPAR trafficking remain elusive, however. Here we show that glutamate receptor interacting protein 1 (GRIP1), an AMPAR-binding protein shown to regulate the trafficking and synaptic targeting of AMPARs, is required for LTP and learning and memory. GRIP1 is recruited into synapses during LTP, and deletion of Grip1 in neurons blocks synaptic AMPAR accumulation induced by glycine-mediated depolarization. In addition, Grip1 knockout mice exhibit impaired hippocampal LTP, as well as deficits in learning and memory. Mechanistically, we find that phosphorylation of serine-880 of the GluA2 AMPAR subunit (GluA2-S880) is decreased while phosphorylation of tyrosine-876 on GluA2 (GluA2-Y876) is elevated during chemically induced LTP. This enhances the strength of the GRIP1–AMPAR association and, subsequently, the insertion of AMPARs into the postsynaptic membrane. Together, these results demonstrate an essential role of GRIP1 in regulating AMPAR trafficking during synaptic plasticity and learning and memory.
This study presents a conceptual model of how aesthetic design, avatar identification, and player co-creation behavior enhance the players' perceived authenticity of massively multiplayer online role ...playing games (MMORPGs), thereby increasing both the players' willingness to play and their virtual item purchase intention. In our model, authenticity is defined as the perception of genuineness that causes players to perceive people, and objects as real, and is considered a driving force of pleasurable game experience. Structural equation modeling was used to estimate the model based on survey data from 393 MMORPG players. The findings show that aesthetic design, players' avatar identification, and player co-creation behavior all influence play intention and virtual item purchase intention. The empirical results indicate that players' perceived authenticity increases players' intentions to play and purchase virtual items. This study contributes to a more comprehensive understanding of how perceived authenticity affects players' participation and purchase intention in MMORPGs.
4-Nonylphenol (4-NP), a phenolic endocrine disruptor chemical (EDC), is known to have high toxicity to aquatic organisms and humans. The remediation of 4-NP-contaminated marine sediments was studied ...using red algae-based biochar (RAB) thermochemically synthesized from Agardhiella subulata with simple pyrolysis process under different temperatures of 300–900 °C in CO2 atmosphere. The RAB was characterized by XRD, Raman, FTIR spectroscopy, and zeta potential measurements. The calcium in RAB efficiently activated sodium percarbonate (SPC) to generate reactive radicals for the catalytic degradation of 4-NP at pH 9.0. The oxygen-containing functional groups reacted with H2O2, which increased the generation of reactive radicals under alkaline pH condition. Ca2+ ion was the active species responsible for 4-NP degradation. CaO/CaCO3 on RAB surface enhanced direct electron transfer, increased HO production, and 4-NP degradation in marine sediments. Langmuir‒Hinshelwood type kinetics well described the 4-NP degradation process. Remediation of contaminated sediments using RAB could be a sustainable approach toward closed-loop biomass cycling in the degradation of 4-NP contaminants.
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•RAB was successfully prepared from red algae biomass.•Real marine sediments were treated with SPC oxidation for 4-NP removal.•Calcium-enriched RAB efficiently activated SPC to generate reactive radicals.•pH and RAB dose controlled 4-NP degradation.•Langmuir-Hinshelwood model described well the kinetics of 4-NP degradation.
Sensory experience plays a crucial role in regulating neuronal shape and in developing synaptic contacts during brain formation. These features are required for a neuron to receive, integrate, and ...transmit signals within the neuronal network so that animals can adapt to the constant changing environment. Insulin receptor signaling, which has been extensively studied in peripheral organ systems such as liver, muscle and adipocyte, has recently been shown to play important roles in the central nervous system. Here we review the current understanding of the underlying mechanisms that regulate structural and functional aspects of circuit development, particularly with respect to the role of insulin receptor signaling in synaptic function and the development of dendritic arbor morphology. The potential link between insulin receptor signaling malfunction and neurological disorders will also be discussed.
There has been a significant increase in the microplastic (MP) polluting the ocean in recent time which is regarded as toxic for living organisms. In this study, Fluorescent red polyethylene ...microspheres (FRPE) were administered intramuscularly to Litopenaeus vannamei juveniles at the concentration of 0.1, 0.2, 0.5 and 1.0 μg (g shrimp)−1, and the survival rate was recorded. Analysis of the hepatopancreas for antioxidant enzyme activity and gene expression were done after seven days. Further tissue morphology and accumulation of FRPE was analysed. The results showed that FRPE at 0.5 and 1.0 μg (g shrimp)−1 reduce the survival rate of L. vannamei. FRPE at 0.5 and 1.0 μg (g shrimp)−1 reduced superoxide dismutase (SOD) activity; FRPE at different concentrations reduced catalase (CAT) activity; FRPE at 0.2, 0.5 and 1.0 μg (g shrimp)−1 increased the lipid peroxide thiobarbituric acid (TBARS) content. FRPE at 0.1, 0.2, and 0.5 μg (g shrimp)−1 significantly affect the performance of SOD and CAT genes; FRPE at 0.2 and 0.5 μg (g shrimp)−1 significantly improves GPx gene performance; FRPE at 1.0 μg (g shrimp)−1 significantly reduced the expression of GPx genes. Analysis of tissue morphology shows that FRPE cause muscle, midgut gland, and hepatopancreas, and gill damage at different concentrations. In the results of accumulation of microplastic, FRPE accumulated in gill tissue at 0.2 and 0.5 μg (g shrimp)−1; FRPE accumulated in gill, muscle and hepatopancreas tissue at 1.0 μg (g shrimp)−1. Based on the above results, FRPE at 0.5 and 1.0 μg (g shrimp)−1 can regulate the antioxidant enzymes of L. vannamei, increase lipid peroxide content, cause tissue damage by accumulating in the tissues. The rate of survival decreased in L. vannamei, and the impact of FRPE at 1.0 μg (g shrimp)−1 was significant.
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•FRPE when injected reduces the survival rate of Litopenaeus vannamei.•Injection of FRPE induce oxidative stress and histology damage in L. vannamei.•FRPE is accumulated in the muscle, hepatopancreas and gills of L. vannamei.
Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in ...the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions.
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