Prospective Memory: The Relation of Executive Function to Aging

The executive functions of the frontal lobe seem to play an integral role in the mediation of prospective memory, as suggested by the results of recent studies (Shallice & Burgess, 1991; Cockburn, 1995; Shapiro, Shapiro, Alper, & Russell, in press). In the present study two groups were examined in terms of their performance on four different prospective memory tasks. The two groups included younger adults (ages 18-21) and older adults (ages 62-80). Both groups were asked to perform each of four prospective memory tasks (an event-based, disembedded task; an event-based, embedded task; a time-based, disembedded task; and a timebased, embedded task) webbed within a general knowledge quiz. The participants also were tested using the Stroop Test and the Wisconsin Card Sort Task, which have been acknowledged as predictors of frontal lobe dysfunction. The Kaufmann Brief Intelligence Test, the Williams Inhibition Test, and an Immediate Recall Test were also administered. The results indicate that both groups performed significantly poorer on the TD task in comparison to the ED task. This finding suggests that a. deficit in internal cuing and attentional resources may be responsible for a PM performance deficit

Therapeutic efficacy of anti-MMP9 antibody in combination with nab-paclitaxel-based chemotherapy in pre-clinical models of pancreatic cancer

Matrix metalloproteinase 9 (MMP9) is involved in the proteolysis of extracellular proteins and plays a critical role in pancreatic ductal adenocarcinoma (PDAC) progression, invasion and metastasis. The therapeutic potential of an anti-MMP9 antibody (αMMP9) was evaluated in combination with nab-paclitaxel (NPT)-based standard cytotoxic therapy in pre-clinical models of PDAC. Tumour progression and survival studies were performed in NOD/SCID mice. The mechanistic evaluation involved RNA-Seq, Luminex, IHC and Immunoblot analyses of tumour samples. Median animal survival compared to controls was significantly increased after 2-week therapy with NPT (59%), Gem (29%) and NPT+Gem (76%). Addition of αMMP9 antibody exhibited further extension in survival: NPT+αMMP9 (76%), Gem+αMMP9 (47%) and NPT+Gem+αMMP9 (94%). Six-week maintenance therapy revealed that median animal survival was significantly increased after NPT+Gem (186%) and further improved by the addition of αMMP9 antibody (218%). Qualitative assessment of mice exhibited that αMMP9 therapy led to a reduction in jaundice, bloody ascites and metastatic burden. Anti-MMP9 antibody increased the levels of tumour-associated IL-28 (1.5-fold) and decreased stromal markers (collagen I, αSMA) and the EMT marker vimentin. Subcutaneous tumours revealed low but detectable levels of MMP9 in all therapy groups but no difference in MMP9 expression. Anti-MMP9 antibody monotherapy resulted in more gene expression changes in the mouse stroma compared to the human tumour compartment. These findings suggest that anti-MMP9 antibody can exert specific stroma-directed effects that could be exploited in combination with currently used cytotoxics to improve clinical PDAC therapy

Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility

Objective: Anxiety is associated with increased physiological reactivity and also increased “interoceptive” sensitivity to such changes in internal bodily arousal. Joint hypermobility, an expression of a common variation in the connective tissue protein collagen, is increasingly recognized as a risk factor to anxiety and related disorders. This study explored the link between anxiety, interoceptive sensitivity and hypermobility in a sub-clinical population using neuroimaging and psychophysiological evaluation. Methods: Thirty-six healthy volunteers undertook interoceptive sensitivity tests, a clinical examination for hypermobility and completed validated questionnaire measures of state anxiety and body awareness tendency. Nineteen participants also performed an emotional processing paradigm during functional neuroimaging. Results: We confirmed a significant relationship between state anxiety score and joint hypermobility. Interoceptive sensitivity mediated the relationship between state anxiety and hypermobility. Hypermobile, compared to non-hypermobile, participants displayed heightened neural reactivity to sad and angry scenes within brain regions implicated in anxious feeling states, notably insular cortex. Conclusions: Our findings highlight the dependence of anxiety state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common variant of collagen

Older adults place lower value on choice relative to young adults

Choice is highly valued in modern society, from the supermarket to the hospital; however, it remains unknown whether older and younger adults place the same value on increased choice. The current investigation tested whether 53 older ( M age = 75.44 years) versus 53 younger adults ( M age = 19.58 years) placed lower value on increased choice by examining the monetary amounts they were willing to pay for increased prescription drug coverage options — important given the recently implemented Medicare prescription drug program. Results indicate that older adults placed lower value on increasing choice sets relative to younger adults, who placed progressively higher value on increasingly larger choice sets. These results are discussed regarding their implications for theory and policy

Emotion classification in Parkinson's disease by higher-order spectra and power spectrum features using EEG signals: A comparative study

Deficits in the ability to process emotions characterize several neuropsychiatric disorders and are traits of Parkinson's disease (PD), and there is need for a method of quantifying emotion, which is currently performed by clinical diagnosis. Electroencephalogram (EEG) signals, being an activity of central nervous system (CNS), can reflect the underlying true emotional state of a person. This study applied machine-learning algorithms to categorize EEG emotional states in PD patients that would classify six basic emotions (happiness and sadness, fear, anger, surprise and disgust) in comparison with healthy controls (HC). Emotional EEG data were recorded from 20 PD patients and 20 healthy age-, education level- and sex-matched controls using multimodal (audio-visual) stimuli. The use of nonlinear features motivated by the higher-order spectra (HOS) has been reported to be a promising approach to classify the emotional states. In this work, we made the comparative study of the performance of k-nearest neighbor (kNN) and support vector machine (SVM) classifiers using the features derived from HOS and from the power spectrum. Analysis of variance (ANOVA) showed that power spectrum and HOS based features were statistically significant among the six emotional states (p < 0.0001). Classification results shows that using the selected HOS based features instead of power spectrum based features provided comparatively better accuracy for all the six classes with an overall accuracy of 70.10% ± 2.83% and 77.29% ± 1.73% for PD patients and HC in beta (13-30 Hz) band using SVM classifier. Besides, PD patients achieved less accuracy in the processing of negative emotions (sadness, fear, anger and disgust) than in processing of positive emotions (happiness, surprise) compared with HC. These results demonstrate the effectiveness of applying machine learning techniques to the classification of emotional states in PD patients in a user independent manner using EEG signals. The accuracy of the system can be improved by investigating the other HOS based features. This study might lead to a practical system for noninvasive assessment of the emotional impairments associated with neurological disorders

The deleted in brachydactyly B domain of ROR2 is required for receptor activation by recruitment of Src

The transmembrane receptor 'ROR2' resembles members of the receptor tyrosine kinase family of signalling receptors in sequence but its' signal transduction mechanisms remain enigmatic. This problem has particular importance because mutations in ROR2 are associated with two human skeletal dysmorphology syndromes, recessive Robinow Syndrome (RS) and dominant acting Brachydactyly type B (BDB). Here we show, using a constitutive dimerisation approach, that ROR2 exhibits dimerisation-induced tyrosine kinase activity and the ROR2 C-terminal domain, which is deleted in BDB, is required for recruitment and activation of the non-receptor tyrosine kinase Src. Native ROR2 phosphorylation is induced by the ligand Wnt5a and is blocked by pharmacological inhibition of Src kinase activity. Eight sites of Src-mediated ROR2 phosphorylation have been identified by mass spectrometry. Activation via tyrosine phosphorylation of ROR2 receptor leads to its internalisation into Rab5 positive endosomes. These findings show that BDB mutant receptors are defective in kinase activation as a result of failure to recruit Src

Detection of emotions in Parkinson's disease using higher order spectral features from brain's electrical activity

Non-motor symptoms in Parkinson's disease (PD) involving cognition and emotion have been progressively receiving more attention in recent times. Electroencephalogram (EEG) signals, being an activity of central nervous system, can reflect the underlying true emotional state of a person. This paper presents a computational framework for classifying PD patients compared to healthy controls (HC) using emotional information from the brain's electrical activity