1,164 research outputs found

    Aggregation Limits Surface Expression of Homomeric GluA3 Receptors

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    AMPA receptors are glutamate-gated cation channels assembled from GluA1-4 subunits and have properties that are strongly dependent on the subunit composition. The subunits have different propensities to form homomeric or various heteromeric receptors expressed on cell surface, but the underlying mechanisms are still poorly understood. Here, we examined the biochemical basis for the poor ability of GluA3 subunits to form homomeric receptors, linked previously to two amino acid residues, Y454 and R461, in its ligand-binding domain (LBD). Surface expression of GluA3 was improved by co-assembly with GluA2 but not with stargazin, a trafficking chaperone and modulator of AMPA receptors. The secretion efficiency of GluA2 and GluA3 LBDs paralleled the transport difference between the respective full-length receptors and was similarly dependent on Y454/R461, but not on LBD stability. In comparison to GluA2, GluA3 homomeric receptors showed a strong and Y454/R461-dependent tendency to aggregate both in the macroscopic scale measured as lower solubility in nonionic detergent and in the microscopic scale evident as the preponderance of hydrodynamically large structures in density gradient centrifugation and native gel electrophoresis. We conclude that the impaired surface expression of homomeric GluA3 receptors is caused by nonproductive assembly and aggregation to which LBD residues Y454 and R461 strongly contribute. This aggregation inhibits the entry of newly synthesized GluA3 receptors to the secretory pathway

    Leaf-applied sodium chloride promotes cadmium accumulation in durum wheat grain

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    Cadmium (Cd) accumulation in durum wheat grain is a growing concern. Among the factors affecting Cd accumulation in plants, soil chloride (Cl) concentration plays a critical role. The effect of leaf NaCl application on grain Cd was studied in greenhouse-grown durum wheat (Triticum turgidum L. durum, cv. Balcali-2000) by immersing (10 s) intact flag leaves into Cd and/or NaCl-containing solutions for 14 times during heading and dough stages. Immersing flag leaves in solutions containing increasing amount of Cd resulted in substantial increases in grain Cd concentration. Adding NaCl alone or in combination with the Cd-containing immersion solution promoted accumulation of Cd in the grains, by up to 41%. In contrast, Zn concentrations of grains were not affected or even decreased by the NaCl treatments. This is likely due to the effect of Cl complexing Cd and reducing positive charge on the metal ion, an effect that is much smaller for Zn. Charge reduction or removal (CdCl2 0 species) would increase the diffusivity/lipophilicity of Cd and enhance its capability to penetrate the leaf epidermis and across membranes. Of even more significance to human health was the ability of Cl alone to penetrate leaf tissue and mobilize and enhance shoot Cd transfer to grains, yet reducing or not affecting Zn transfer

    Child Abuse Management Units: How can Mental Health Services be Further Improved?

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    Background: Child abuse is a broad term that includes physical, sexual, and emotional (e.g., psychological, verbal) abuse. There are huge variations with regard to the level of severity and the consequences of abuse. Because child abuse is such a sensitive topic, it is a challenging task to conduct studies concerning this subject.Objective: The aim of the study was to identify areas that could be improved to offer better health care services to patients. Therefore, routine assessments, the characteristics of the cases, and the types of follow up were emphasized.Method: The Norwegian Ministry of Health and Care Services provided an exception from the principle of informed consent so that this study could be conducted. We had access to the medical records of all children between the ages of 0 and 14 years old who were referred to the regional child abuse management unit in 2006 and 2007. A descriptive, cross-sectional study was performed.Results: One hundred and six children were referred to the child abuse management unit. For the majority of these patients (80.2%), sexual abuse was the only concern. The children presented diverse psychological and somatic symptoms and problems. Psychosocial functioning was in general not properly described in the records. Four out of five of the children were referred to services for follow up after the first examination in the child abuse management unit. Only 36% of the children were referred to child protective services.Conclusion: This study revealed that psychosocial functioning is seldom documented and that psychological symptoms could be described more reliably and in more detail. A systematic approach may be helpful for health care providers, and we suggest the implementation of valid evidence-based instruments, such as the Child Behavior Checklist and the Children’s Global Assessment Scale

    Synaptic AMPA receptor composition in development, plasticity and disease

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    Criteria for failure and worsening after surgery for lumbar spinal stenosis. A prospective national spine registry observational study

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    Background context: Criteria for success after surgical treatment of lumbar spinal stenosis (LSS) have been defined previously; however, there are no clear criteria for failure and worsening after surgery as assessed by patient-reported outcome measures (PROMs). Purpose: We aimed to quantify changes in standard PROMs that most accurately identified failure and worsening after surgery for LSS. Study design /setting: Retrospective analysis of prospective national spine registry data with 12-months follow-up. Patient sample: We analyzed 10,822 patients aged 50 years and older operated in Norway during a decade, and 8,258 (76%) responded 12 months after surgery. Outcome measures (proms): We calculated final scores, absolute changes, and percentage changes for Oswestry Disability Index (ODI), Numeric Rating Scale (NRS) for back and leg pain (0-10), and EuroQol-5D (EQ-5D). These 12 PROM derivates were compared to the Global Perceived Effect (GPE), a 7-point Likert scale. Methods: We used ODI, NRS back and leg pain, and EQ-5D 12 months after surgery to identify patients with failure (no effect) and worsening (clinical deterioration). The corresponding GPE at 12-months was graded as failure (GPE=4-7) and worsening (GPE=6-7) and used as an external criterion. To quantify the most accurate cut-off values corresponding to failure and worsening, we calculated areas under the curves (AUCs) of receiver operating characteristics (ROC) curves for the respective PROM derivates. Results: Mean (95% CI) age was 68.3 (68.1 - 68.5) years, and 52% were females. There were 1,683 (20%) failures, and 476 (6%) patients were worse after surgery. The mean (95% CI) pre- and postoperative ODIs were 39.8 (39.5 - 40.2) and 23.7 (23.3 - 24.1), respectively. At 12 months, the mean difference (95% CI) in ODI was 16.1 (15.7 - 16.4), and the mean (95% CI) percentage improvement 38.8% (37.8 - 38.8). The PROM derivates identified failure and worsening accurately (AUC>0.80), except for the absolute change in EQ-5D. The ODI derivates were most accurate to identify both failure and worsening. We found that less than 20% improvement in ODI most accurately identified failure (AUC=0.89 [95% CI: 0.88 to 0.90]), and an ODI final score of 39 points or more most accurately identified worsening (AUC =0.91 [95% CI: 0.90 - 0.92]). Conclusions: In this national register study, ODI derivates were most accurate to identify both failure and worsening after surgery for degenerative lumbar spinal stenosis. We recommend use of ODI percentage change and ODI final score for further studies of failure and worsening in elective spine surgery. Keywords: Cut-off; Failure; PROM; Spinal Stenosis; Spine registry; Worsening. Copyright © 2021. Published by Elsevier Inc. © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)publishedVersionThis is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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