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Abstract MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins in the RNA-induced silencing complex (RISC) to modulate protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)-dependent synaptic plasticity by repressing the translation of proteins involved in dendritic spine morphogenesis. Rapid NMDAR-dependent silencing of Limk1 is essential for spine shrinkage and requires Ago2 phosphorylation at S387. Not all gene silencing events are modulated by S387 phosphorylation, and the mechanisms that govern the selection of specific mRNAs for silencing downstream of S387 phosphorylation are unknown. Here, we show that NMDAR-dependent S387 phosphorylation causes a rapid and transient increase in the association of Ago2 with Limk1, but not Apt1 mRNA. The specific increase in Limk1 mRNA binding to Ago2 requires recruitment of the helicase DDX6 to RISC. Furthermore, we show that DDX6 is required for NMDAR-dependent silencing of Limk1 via miR-134, but not Apt1 via miR-138, and is essential for NMDAR-dependent spine shrinkage. This work defines a novel mechanism for the rapid transduction of NMDAR stimulation into miRNA-mediated translational repression of specific genes to control dendritic spine morphology.

When comparison among groups is of major importance, it is necessary to ensure that the measuring tool exhibits measurement invariance. This means that it measures the same construct in the same way for all groups. In the opposite case, the test results in measurement error and bias toward a particular group of respondents. In this study, a new approach to examine measurement invariance was applied, which was appropriately designed when a large number of group comparisons are involved: the alignment approach. We used this approach to examine whether the factor structure of a cognitive ability test exhibited measurement invariance across the 26 universities of the Kingdom of Saudi Arabia. The results indicated that the P-GAT subscales were invariant across the 26 universities. Moreover, the aligned factor mean values were estimated, and factor mean comparisons of every group’s mean with all the other group means were conducted. The findings from this study showed that the alignment procedure is a valuable method to assess measurement invariance and latent mean differences when a large number of groups are involved. This technique provides an unbiased statistical estimation of group means, with significance tests between group pairs that adjust for sampling errors and missing data.

New strategies that augment T cell responses are required to broaden the therapeutic arsenal against cancer. CD96, TIGIT, and CD226 are receptors that bind to a communal ligand, CD155, and transduce either inhibitory or activating signals. The function of TIGIT and CD226 is established, whereas the role of CD96 remains ambiguous. Using a panel of engineered antibodies, we discovered that the T cell stimulatory activity of anti-CD96 antibodies requires antibody cross-linking and is potentiated by Fcγ receptors. Thus, soluble “Fc silent” anti-CD96 antibodies failed to stimulate human T cells, whereas the same antibodies were stimulatory after coating onto plastic surfaces. Remarkably, the activity of soluble anti-CD96 antibodies was reinstated by engineering the Fc domain to a human IgG1 isotype, and it was dependent on antibody trans-cross-linking by FcγRI. In contrast, neither human IgG2 nor variants with increased Fcγ receptor IIB binding possessed stimulatory activity. Anti-CD96 antibodies acted directly on T cells and augmented gene expression networks associated with T cell activation, leading to proliferation, cytokine secretion, and resistance to Treg suppression. Furthermore, CD96 expression correlated with survival in HPV+ head and neck squamous cell carcinoma, and its cross-linking activated tumor-infiltrating T cells, thus highlighting the potential of anti-CD96 antibodies in cancer immunotherapy.

Mariam Fathima,1 Zeeta Bawa,1 Bernadette Mitchell,1 Juliet Foster,1 Carol Armour,1 Bandana Saini1,2 1Woolcock Institute of Medical Research, University of Sydney, Glebe, New South Wales, Australia; 2School of Pharmacy, University of Sydney, Camperdown, New South Wales, AustraliaCorrespondence: Bandana Saini Rm No. N348, Building No A15The University of Sydney, Camperdown, New South Wales, 2006, AustraliaTel +61 2 93516789Fax +61 2 93514791Email bandana.saini@sydney.edu.auPurpose: To evaluate the effectiveness of a pilot community pharmacy care model for patients with chronic obstructive pulmonary disease (COPD) to improve: 1) inhaler technique; 2) medication adherence; and 3) uptake of non-pharmacological treatment and prevention activities.Patients and Methods: Forty “host” pharmacies in Sydney were invited to recruit eligible patients and to provide a counselling room/area in their pharmacy for service provision. Eligible patients were referred to two “consultant” pharmacists, specifically trained to deliver a specialized pharmacy COPD service which involved 3 in-pharmacy visits and 2 follow-up phone calls over a 6-month period. The service consisted of 1) inhaler technique assessment; 2) medication adherence assessment; and 3) referrals to the patient’s general practitioner (GP) to facilitate the uptake of non-pharmacological resources as well as to review COPD medications/devices, as required. Pre-post analyses were conducted using paired Student’s t-test and Wilcoxon Signed Rank Test for independent variables and chi-squared tests for proportional data.Results: Nine “host” pharmacies recruited 40 patients, of whom 37 completed the baseline Visit and 27 completed all Visits. A total of 270 interventions were provided by the “consultant” pharmacists with most provided at Visit 1 (176). The most common interventions were addressing patient gaps in COPD knowledge and inhaler technique. A total of 119 referrals were made to GPs for various reasons, the most common being for a COPD action plan, pulmonary rehabilitation, or pneumonia vaccination. There were significant improvements pre-post intervention in inhaler use competence, COPD knowledge, immunization rate for pneumonia, exacerbation rate and COPD plan ownership.Conclusion: In this pilot study, the specialized pharmacy-based COPD care model delivered by “consultant” pharmacists in community pharmacies provided significant health benefits for patients. Further research is needed to assess the model’s effectiveness in a larger population as well as when measured against standard care.Keywords: inhaler technique, medication review, consultant pharmacist, COPD

Mariam Fathima,1 Bandana Saini,1,2 Juliet M Foster,1 Carol L Armour1,3 1Woolcock Institute of Medical Research, Sydney Medical School, 2Faculty of Pharmacy, The University of Sydney, 3Central Sydney Area Health Service, Sydney, NSW, Australia Background and objective: Case finding of patients at risk of COPD by community pharmacists could identify a substantial number of people with undiagnosed COPD, but little is known about the feasibility and effectiveness of pharmacy-based COPD case finding using microspirometry. The objective of this study was to assess the feasibility and effectiveness of COPD case-finding service provided by community pharmacists, utilizing a combination of risk assessment questionnaire and microspirometry. Methods: A 6-month service was conducted in 21 community pharmacies in Australia. Pharmacists trained in COPD case finding, including lung function test (LFT), invited their patients aged ≥35 years with a history of smoking and/or respiratory symptoms to participate. High-risk patients were identified via a COPD risk assessment questionnaire (Initial Screening Questionnaire [ISQ]) and underwent LFT. Pharmacists referred patients with a forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio 3 indicating high COPD risk. Of the 157 patients who were able to complete LFT, 61 (39%) had an FEV1/FEV6 ratio of 3) were at a significantly higher risk of an FEV1/FEV6 ratio of

Learning is the acquisition and storage of information as a consequence of experience. The human brain is designed in such a way that thousands bits of sensory data are processed each minute. The brain pays attention to what is relevant to daily life, always asking: "What's going on?" and "How is it important relevant to me?" The senses pass on 40,000 bits of information every second. The Neuro-science is to yet explore thoroughly about how a new memory is formed. The sensory stimuli hit the neurons in the appropriate sensory cortex. These crude sensations are then relayed through the thalamus and sent to the sensory association area of the neo-cortex where they are put together into objects we recognize. Then the information is sent to amygdala for emotional evaluation and to the frontal cortex for content evaluation. On the basis of its analysis of physical features of the stimuli, the brain begins to construct meaning. Depending on the clarity in sense and its relevance, the new information is either retained or ignored. A thorough knowledge of the different parts of the human brain involved in the process of memory helps the teacher to adopt suitable methodology in the classroom. In this fast moving world, the learners expect the teacher to give everything in a nutshell. Hence the teacher has to organize the subject content in such a way that the students could understand, restore and retrieve the information easily and quickly. In this paper, the authors went through the meaning and needs of memory, and the categories of memory. Furthermore, they studied and explained eight aspects of memory activation strategies from the view of neurological perspective are suggested for practice in the classroom such as: Mnemonic devices are strategies for enhancing memory; Engage in Adequate rehearsal; Schedule distributed practice; Minimize interference; Engage in deep processing; Emphasize Transfer; Enrich Encoding with Verbal Mnemonics; and Enrich encoding with visual imagery.

The effect of a single-layer anti-reflective coating (ARC) on ZnO-based dye-sensitized solar cells (DSSCs) is theoretically predicted and verified by experimental fabrication. By the transfer matrix method (TMM), the absorption of the DSSC with and without the single-layer ARC is calculated and the improvement in short-circuit current density (∆Jsc%) is estimated. The optimized thickness of the ARC required to obtain maximum improvement in the short-circuit current density (∆Jsc%) is determined. By employing ARC with the calculated optimized thickness, the fabrication of spin-coated ZnO-based DSSCs is carried out. The structural and optical parameters are studied using XRD analysis and UV absorption spectra. The efficiency of the DSSC with and without the ARC is measured by intensity-modulated photocurrent and photovoltage spectroscopy. The theoretically predicted efficiency of the DSSC with and without ARC agrees well with the experimental values that provide insights about improving the electrical performance of the DSSC by the ARC. [ABSTRACT FROM AUTHOR]