NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content.

In mature neurons, postsynaptic N-methyl-D-aspartate receptors (NMDARs) are segregated into two populations, synaptic and extrasynaptic, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content. Here, we identify the phosphorylation of the PDZ-ligand of the GluN2B subunit of NMDARs (at S1480) as a critical determinant in dynamically controlling NMDAR synaptic content. We find that phosphorylation of GluN2B at S1480 maintains NMDARs at extrasynaptic membranes as part of a protein complex containing protein phosphatase 1 (PP1). Global activation of NMDARs leads to the activation of PP1, which mediates dephosphorylation of GluN2B at S1480 to promote an increase in synaptic NMDAR content. Thus, PP1-mediated dephosphorylation of the GluN2B PDZ-ligand modulates the synaptic expression of NMDARs in mature neurons in an activity-dependent manner, a process with profound consequences for synaptic and structural plasticity, metaplasticity, and synaptic neurotransmission

Nanoparticles in Cancer Diagnosis and Treatment

The use of tailored medication delivery in cancer treatment has the potential to increase efficacy while decreasing unfavourable side effects. For researchers looking to improve clinical outcomes, chemotherapy for cancer continues to be the most challenging topic. Cancer is one of the worst illnesses despite the limits of current cancer therapies. New anticancer medications are therefore required to treat cancer. Nanotechnology has revolutionized medical research with new and improved materials for biomedical applications, with a particular focus on therapy and diagnostics. In cancer research, the application of metal nanoparticles as substitute chemotherapy drugs is growing. Metals exhibit inherent or surface-induced anticancer properties, making metallic nanoparticles extremely useful. The development of metal nanoparticles is proceeding rapidly and in many directions, offering alternative therapeutic strategies and improving outcomes for many cancer treatments. This review aimed to present the most commonly used nanoparticles for cancer applications

Application of plant products in the synthesis and functionalisation of biopolymers

The burning of plastic trash contributes significantly to the problem of air pollution. Consequently, a wide variety of toxic gases get released into the atmosphere. It is of the utmost importance to develop biodegradable polymers that retain the same characteristics as those obtained from petroleum. In order to decrease the effect that these issues have on the world around us, we need to focus our attention on specific alternative sources capable of biodegrading in their natural environments. Biodegradable polymers have garnered much attention since they can break down through the processes carried out by living creatures. Biopolymers' applications are growing due to their non-toxic nature, biodegradability, biocompatibility, and environmental friendliness. In this regard, we examined numerous methods used to manufacture biopolymers and the critical components from which they get their functional properties. In recent years, economic and environmental concerns have reached a tipping point, increasing production based on sustainable biomaterials. This paper examines plant-based biopolymers as a good resource with potential applications in both biological and non-biological sectors. Scientists have devised various biopolymer synthesis and functionalization techniques to maximize its utility in various applications. In conclusion, recent developments in the functionalization of biopolymers through various plant products and their applications are discussed

Biology and ecology of the invasive lionfishes, Pterois miles and Pterois volitans

The Indo-Pacific lionfishes, Pterois miles and P. volitans, are now established along the U.S. southeast coast, Bermuda, Bahamas, and are becoming established in the Caribbean. While these lionfish are popular in the aquarium trade, their biology and ecology are poorly understood in their native range. Given the rapid establishment and potential adverse impacts of these invaders, comprehensive studies of their biology and ecology are warranted. Here we provide a synopsis of lionfish biology and ecology including invasion chronology, taxonomy, local abundance, reproduction, early life history and dispersal, venomology, feeding ecology, parasitology, potential impacts, and control and management. This information was collected through review of the primary literature and published reports and by summarizing current observations. Suggestions for future research on invasive lionfish in their invaded regions are provided

Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia:A potential novel treatment target for perinatal asphyxia

Worldwide, perinatal asphyxia is an important cause of morbidity and mortality among term-born children. Overactivation of the N-methyl-d-aspartate receptor (NMDAr) plays a central role in the pathogenesis of cerebral hypoxia–ischemia, but the role of both endogenous NMDAr co-agonists d-serine and glycine remains largely elusive. We investigated d-serine and glycine concentration changes in rat glioma cells, subjected to oxygen and glucose deprivation (OGD) and CSF from piglets exposed to hypoxia–ischemia by occlusion of both carotid arteries and hypoxia. We illustrated these findings with analyses of cerebrospinal fluid (CSF) from human newborns affected by perinatal asphyxia. Extracellular concentrations of glycine and d-serine were markedly increased in rat glioma cells exposed to OGD, presumably through increased synthesis from l-serine. Upon reperfusion glycine concentrations normalized and d-serine concentrations were significantly lowered. The in vivo studies corroborated the finding of initially elevated and then normalizing concentrations of glycine and decreased d-serine concentrations upon reperfusion These significant increases of both endogenous NMDAr co-agonists in combination with elevated glutamate concentrations, as induced by global cerebral ischemia, are bound to lead to massive NMDAr activation, excitotoxicity and neuronal damage. Influencing these NMDAr co-agonist concentrations provides an interesting treatment target for this common, devastating and currently poorly treatable condition

Effect of Genetic Variation in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin

The identification and validation of gene–gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINSC96Y) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINSC96Y background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINSC96Y-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease

A Functional Description of Adult Picky Eating Using Latent Profile Analysis

Abstract Objective Research has indicated that adult picky eating (PE) is associated with elevated psychosocial impairment and limited dietary variety and fruit and vegetable intake; however, research operationalizing PE behaviors is limited. Previous research identified a PE profile in children, marked by high food avoidance (satiety responsiveness, fussiness, and slow eating) and low food approach (food enjoyment and responsiveness) appetitive traits. The present study aimed to replicate a similar latent eating behavior profile in an adult sample. Methods A sample of 1339 US adults recruited through Amazon’s MTurk completed an online survey that included a modified self-report version of the Child Eating Behavior Questionnaire (CEBQ-A). Latent profile analysis was employed to identify eating profiles using the CEBQ-A subscales, ANCOVAs were employed to examine profile differences on various self-report measures, and eating profiles were compared across BMI classifications. Results Analyses converged on a four-profile solution, and a picky eater profile that closely resembled the past child profile emerged. Participants in the picky eater profile (18.1%) scored higher on measures of adult PE and social eating anxiety compared to all other profiles, scored higher on eating-related impairment and depression than moderate eating profiles, and were more likely to be of normal weight. Discussion A distinct adult PE profile was observed, indicating childhood PE and appetitive behaviors may carry over into adulthood. Research identifying meaningful groups of picky eaters will help to shed light on the conditions under which picky eating is a risk factor for significant psychosocial impairment or distress, or weight-related problems