Right anterior cerebellum BOLD responses reflect age related changes in Simon task sequential effects.

Participants are slower to report a feature, such as color, when the target appears on the side opposite the instructed response, than when the target appears on the same side. This finding suggests that target location, even when task-irrelevant, interferes with response selection. This effect is magnified in older adults. Lengthening the inter-trial interval, however, suffices to normalize the congruency effect in older adults, by re-establishing young-like sequential effects (Aisenberg et al., 2014). We examined the neurological correlates of age related changes by comparing BOLD signals in young and old participants performing a visual version of the Simon task. Participants reported the color of a peripheral target, by a left or right-hand keypress. Generally, BOLD responses were greater following incongruent than congruent targets. Also, they were delayed and of smaller amplitude in old than young participants. BOLD responses in visual and motor regions were also affected by the congruency of the previous target, suggesting that sequential effects may reflect remapping of stimulus location onto the hand used to make a response. Crucially, young participants showed larger BOLD responses in right anterior cerebellum to incongruent targets, when the previous target was congruent, but smaller BOLD responses to incongruent targets when the previous target was incongruent. Old participants, however, showed larger BOLD responses to congruent than incongruent targets, irrespective of the previous target congruency. We conclude that aging may interfere with the trial by trial updating of the mapping between the task-irrelevant target location and response, which takes place during the inter-trial interval in the cerebellum and underlays sequential effects in a Simon task.

Long trial durations normalise the interference effect and sequential updating during healthy aging.

We examined the effect of a task-irrelevant dimension on response times in young adults and seniors. We used the Simon task with congruent trials where the target and manual response were on the same side, incongruent trials where the target and response were on opposite sides, and neutral trials where the target appeared along the vertical meridian. We observed two age-related effects. First, there was a larger congruency effect in senior participants that was driven by greater interference; namely, their responses were slower on incongruent relative to neutral trials. Second, there was a Gratton effect; namely, a diminished Simon effect was found in young adults but not in seniors when the preceding trial was incongruent. However, these effects of aging were normalised when the inter-trial interval was increased; the Simon effect and interference were reduced and a Gratton effect appeared for seniors. We conclude that aging may impair the ability to quickly adapt to changing environmental circumstances when they require reformulating current behavioral strategies.

Development of an enzyme-linked immunosorbent assay and a beta-1 adrenergic receptor-based assay for monitoring the drug atenolol.

Two approaches for monitoring atenolol (ATL) were applied: an immunochemical assay and a competitive-binding assay, based on the interaction between ATL and its target receptor, ß1 adrenergic receptor (ß1AR). Polyclonal antibodies (Abs) for ATL were generated, and a highly specific microplate immunochemical assay, that is, an enzyme-linked immunosorbent assay (ELISA), for its detection was developed. The ATL ELISA exhibited I50 and limit of detection (I20) values of 0.15 ± 0.048 and 0.032 ± 0.016 ng/ml, respectively, and the Abs did not cross-react with any of the tested beta-blocker drugs. Furthermore, a human ß1AR (h-ß1AR) was stably expressed in Spodoptera frugiperda cells (Sf9). The receptor was employed to develop a competitive-binding assay that monitored binding of ATL in the presence of isoproteranol by quantification of secondary messenger, cyclic adenosine monophosphate (cAMP), levels in the transfected cells. The assay showed that the recombinant h-ß1AR was functional, could bind the agonistic ligand isoproterenol as well as the antagonist ATL, as indicated by a dose-dependent elevation of cAMP in the presence of isoproteranol, and decrease after ATL addition. The highly efficient and sensitive ELISA and the receptor assay represent two methods suitable for efficient and cost-effective large-scale, high-throughput monitoring of ATL in environmental, agricultural, and biological samples.

Polymorphonuclear leukocyte phagocytic function increases in plasminogen knockout mice.

BACKGROUND: Mice lacking plasminogen (PG-/-) require alternative pathways of fibrinolysis for survival. This may depend on polymorphonuclear leukocytes (PMN) that can clear soluble and insoluble fibrin(ogen) through PG-independent processes. Our objective was to demonstrate that PMNs from PG-/- mice exhibit increased Mac-1 dependent phagocytic activity, which may explain their increased fibrin(ogen)lytic activity compared with wild type (PG+/+) mice. METHODS: Phagocytic activity of PMNs from PG-/- and PG+/+ mice was compared following exposure to Staphylococcus aureus (S. aureus) particles and the expression of Mac-1 was assessed in parallel by flow cytometric analysis. Resistance to phorbol-12-myristate-13-acetate (PMA)-induced cell death was compared between PMNs from the different genotypes. RESULTS: Stimulation of PG-/- PMNs by opsonized S. aureus diluted in PG-/- plasma significantly increased phagocytosis (15-fold) compared with stimulation of PG+/+ PMNs in PG+/+ plasma. Incubation of PG-/- PMNs with PG+/+ plasma (control) or PG-/- plasma supplemented with human PG inhibited this increased phagocytic activity. Mac-1 cell surface density increased 6.2+/-1.0-fold in PG-/- PMNs versus 2.9+/-0.6-fold in PG+/+ PMNs (P < 0.01) indicating that Mac-1 may be associated with increased phagocytic activity. Supporting this, treatment of PG-/- PMNs with an anti-Mac-1 antibody in PG-/- plasma inhibited phagocytic activity. In addition, physiologic PG blocked Mac-1 accessibility at the surface of PMNs. Addition of PMA resulted in 33% death of PMNs from PG-/- mice versus 68% in PG+/+ controls (P < 0.001). CONCLUSIONS: PMNs from PG-/- mice exhibit a Mac-1 dependent increase in phagocytic activity that is suppressed with human PG, an anti-Mac-1 antibody or the plasma from PG+/+ mice. The propensity for PMNs from PG-/- mice to be activated in response to PMA together with their relative resistance to PMA-toxicity may contribute to increased PMN half-life and enhanced fibrin(ogen) clearance in the setting of PG deficiency.

Positron emission tomography/computed tomography with 18fluoro-deoxyglucose in the detection of local recurrence and distant metastases of pediatric sarcoma.

BACKGROUND: Combined positron emission tomography with (18)fluoro-deoxyglucose and computed tomography (FDG-PET/CT) has been used in the diagnosis and staging of various malignancies, but their use in the management of pediatric sarcomas is less well defined. The potential role of FDG-PET/CT in the diagnosis of local recurrence and distant metastases of pediatric sarcomas was investigated. PROCEDURE: Nineteen children (aged 2-21) with sarcoma (9 Ewing sarcoma, 3 osteogenic sarcoma, 7 rhabdomyosarcoma) were evaluated between January 2000 and December 2005 by FDG-PET/CT for suspected local relapse or distant metastases. The results of 21 FDG-PET studies, 16 CT scans, 9 magnetic resonance imaging (MRI) studies, and 7 bone scans (BSs) were compared with surgical pathology or clinical follow-up for at least 3 months. RESULTS: FDG-PET detected local relapse in all seven patients and distant metastases in 10/13 (77%). FDG-PET/CT and CT/MRI/BS results were discordant in eight patients. FDG-PET/CT was the only modality that detected distant metastases in two patients. PET/CT was true negative and excluded disease in three patients with abnormal CT/BSs and was false negative in three patients with distant metastases. CONCLUSION: FDG-PET/CT may be useful and complementary to other imaging modalities for the detection of recurrent pediatric sarcomas, especially at the primary site. Its potential advantages and limitations compared with conventional imaging modalities need to be further investigated in larger homogenous patient groups.

Attentional asymmetry in schizophrenia: disengagement and inhibition of return deficits.

This research examined 2 components of visual orienting in medicated schizophrenia patients: the validity effect and the inhibition of return (IOR). In the 1st experiment, patients showed the expected asymmetry in orienting attention, that is, larger validity effect in the right visual field than in the left. However, this asymmetry was due to a deficit in facilitatory processes rather than a disengagement deficit. In addition, patients showed a deficit in IOR. In the 2nd experiment, a 2nd central cue for summoning attention, explicitly, back to the center was used. In this experiment, normal IOR in schizophrenia patients was found. Because it was shown that schizophrenia patients do not have a disengagement deficit, IOR possibly could not be observed because of the increased facilitation in that location. It was proposed that the abnormality in visual attention in schizophrenia is due to a deficit in inhibitory processes.

The insanity defense: examination of the extent of congruence between psychiatric recommendation and adjudication.

The insanity plea is a known defense often utilized in courts of law. In such cases the accused may be referred for an outpatient psychiatric examination or for hospital observation. In this study, we examined the extent of the accord between the medical recommendations of the forensic unit of the Yehuda Abarbanel Mental Health Center and judicial decisions. It was found that in 99.4% of the cases, the court accepted the psychiatric recommendation. In only 2 cases the recommendations were not accepted. We discuss this issue and recommend improvements and strengthening of the relationship between the psychiatric and court systems.

Component processes in task switching.

Participants switched between two randomly ordered, two-choice reaction-time (RT) tasks, where an instructional cue preceded the target stimulus and indicated which task to execute. Task-switching cost dissipated passively while the participants waited for the instructional cue in order to know which task to execute (during the Response-Cue Interval). Switching cost was sharply reduced, but not abolished, when the participants actively prepared for the task switch in response to the instructional cue (during the Cue-Target Interval). The preparation for a task switch has shown not to be a by-product of general preparation by phasic alertness or predicting target onset. It is suggested that task-switching cost has at least three components reflecting (1) the passive dissipation of the previous task set, (2) the preparation of the new task set, and (3) a residual component.

Sprouty is a general inhibitor of receptor tyrosine kinase signaling.

Sprouty was originally identified as an inhibitor of Drosophila FGF receptor signaling during tracheal development. By following the capacity of ectopic Sprouty to abolish the pattern of activated MAP kinase in embryos, we show that Sprouty can inhibit other receptor tyrosine kinase (RTK) signaling pathways, namely the Heartless FGF receptor and the EGF receptor. Similarly, in wing imaginal discs, ectopic Sprouty abolishes activated MAP kinase induced by the EGF receptor pathway. Sprouty expression is induced by the EGFR pathway in some, but not all, tissues in which EGFR is activated, most notably in follicle cells of the ovary, the wing imaginal disc and the eye disc. In the ovary, induction of sprouty expression follows the pattern of EGFR activation in the follicle cells. Generation of homozygous sprouty mutant follicle-cell clones demonstrates an essential role for Sprouty in restricting EGFR activation throughout oogenesis. At the stage when dorso-ventral polarity of the follicle cells is established, Sprouty limits the ventral expansion of the activating Gurken signal. Later, when dorsal appendage fates are determined, reduction of signaling by Sprouty facilitates the induction of inter-appendage cell fates. The capacity of Sprouty to reduce or eliminate accumulation of activated MAP kinase indicates that in vivo it intersects with the pathway upstream to MAP kinase. The ability of ectopic Sprouty to rescue lethality caused by activated Raf suggests that it may impinge upon the pathway by interacting with Raf or downstream to it.

Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis.

Previous work has demonstrated a role for the Drosophila EGF receptor (Torpedo/DER) and its ligand, Gurken, in the determination of anterioposterior and dorsoventral axes of the follicle cells and oocyte. The roles of DER in establishing the polarity of the follicle cells were examined further, by following the expression of DER-target genes. One class of genes (e.g. kekon) is induced by the DER pathway at all stages. Broad expression of kekon at the stage in which the follicle cells migrate posteriorly over the oocyte, demonstrates the capacity of the pathway to pattern all follicle cells except the ventral-most rows. This may provide the spatial coordinates for the ventral-most follicle cell fates. A second group of target genes (e.g. rhomboid (rho)) is induced only at later stages of oogenesis, and may require additional inputs by signals emanating from the anterior, stretch follicle cells. The function of Rho was analyzed by ectopic expression in the stretch follicle cells, and shown to induce a non-autonomous dorsalizing activity that is independent of Gurken. Rho thus appears to be involved in processing a DER ligand in the follicle cells, to pattern the egg chamber and allow persistent activation of the DER pathway during formation of the dorsal appendages.

Economic reform and migration in Yugoslavia: an econometric model.

"The paper analyzes the impact of external migration on the Yugoslav economy during the period 1965-1972. This is done by means of a macroeconometric model embodying various dualistic characteristics of Yugoslavia. A counterfactual simulation of the model is used to judge the impact of external migration. According to the indicators utilized, the simulation suggests that migration has been beneficial to Yugoslavia."