Function, regulation and pathological roles of the Gab/DOS docking proteins

Since their discovery a little more than a decade ago, the docking proteins of the Gab/DOS family have emerged as important signalling elements in metazoans. Gab/DOS proteins integrate and amplify signals from a wide variety of sources including growth factor, cytokine and antigen receptors as well as cell adhesion molecules. They also contribute to signal diversification by channelling the information from activated receptors into signalling pathways with distinct biological functions. Recent approaches in protein biochemistry and systems biology have revealed that Gab proteins are subject to complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Thus, Gab/DOS docking proteins are at the centre of entire signalling subsystems and fulfil an important if not essential role in many physiological processes. Furthermore, aberrant signalling by Gab proteins has been increasingly linked to human diseases from various forms of neoplasia to Alzheimer's disease

Proposing a specification structure for complex products in model-based systems engineering (MBSE)

This research work presents a methodological support for the specification of complex products. This is achieved by developing a specification structure in a MBSE environment. The new method draws on success factors of complex product specification, principles of MBSE and the explanatory model of PGE – Product Generation Engineering. For evaluation, the method is applied within a student development project. A high applicability and the realization of novel synergies for coping with continuously increasing product complexity is demonstrated

4,5-Bis(2,4-di-tert-butyl­phen­oxy)phthalonitrile

In the title compound, C36H44N2O2, the dihedral angles between the phthalonitrile ring and the two di-tert-butyl­benzene rings are 68.134 (8) and 70.637 (11)°. The two nitrile groups are almost coplanar with the phthalonitrile ring except for one of the N atoms which deviates from the plane by 0.125 (4) Å. One of the tert-butyl groups is disordered over two orientations, with refined occupancies of 0.814 (6) and 0.186 (6). Intra­molecular C—H⋯O inter­actions stabilize the molecular structure. The crystal packing is stabilized by inter­molecular C—H⋯N inter­actions

Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in human

Precise Neutron Magnetic Form Factors

Precise data on the neutron magnetic form factor G_{mn} have been obtained with measurements of the ratio of cross sections of D(e,e'n) and D(e,e'p) up to momentum transfers of Q^2 = 0.9 (GeV/c)^2. Data with typical uncertainties of 1.5% are presented. These data allow for the first time to extract a precise value of the magnetic radius of the neutron.Comment: 10 pages, 2 figures, submitted to Physics Letters

Episodes of Fall Asleep During Day Time in an Elder Woman with Vascular Dementia: Impact on Cerebral Ischeamic Tolerance and Utility of ECG Holter Monitoring

Here we report the case of an 86-year-old woman with advanced dementia addressed to our service for routinary ECG Holter Monitoring (EHM) for bradycardia in AV block type I. Several day-time episodes of fall-asleep while sitting had been previously reported by the nurse and generally attributed to the dementia itself, without taking into consideration the hypothesis of an AV block. The EHM reading reported several and often subsequent pauses (561), many of them critical, the longest lasting 15,9 s with no changes in clinical condition of the patient. The results of the EHM were reported to the physicians in charge for the patient and subsequently the woman was referred to the arrhythmology unit for pace-maker device implantation. Generalizing our experience, we suggest that advanced dementia, often associated with episodes of fall-asleep, could mask a conduction disturbance causing critical pauses with syncope; therefore we suggest screening those patients for possible arrhythmic disorders. Finally, we remark that in our patient the pauses weren’t associated with a worsening of the patient as seen in the follow-up, and this fact supports the hypothesis that vascular dementia could increase cerebral ischaemic tolerance

Vector and Tensor Analyzing Powers of the H(d,gamma)He-3 capture reaction

Precise measurements of the deuteron vector analyzing power Ayd and the tensor analyzing power Ayy of the H(d,gamma)He-3 capture reaction have been performed at deuteron energies of 29MeV and 45MeV. The data have been compared to theoretical state-of-the-art calculations available today. Due to the large sensitivity of polarization observables and the precision of the data light could be shed on small effects present in the dynamics of the reaction.Comment: 11 pages, 24 figures, submitted for publication to PRC, revised after referee proces

A Measurement of the Electric Form Factor of the Neutron through d⃗(e⃗,e′n)p\vec{d}(\vec{e},e'n)p at Q2=0.5Q^2 = 0.5 (GeV/c)2^2

We report the first measurement of the neutron electric form factor $G_E^n$ via $\vec{d}(\vec{e},e'n)p$ using a solid polarized target. $G_E^n$ was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia, $^{15}$ND$_3$. The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility (TJNAF) in quasi free kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find $G_E^n = 0.04632\pm0.00616 (stat.) \pm0.00341 (syst.)$ at $Q^2 = 0.495$ (GeV/c)$^2$.Comment: Latex2e 5 pages, 3 figure

An Eye-Tracking Study of Attention Biases in Children at High Familial Risk for Depression and Their Parents with Depression

Attention biases (AB) are a core component of cognitive models of depression yet it is unclear what role they play in the transgenerational transmission of depression. 44 children (9-14 years) with a high familial risk of depression (HR) were compared on multiple measures of AB with 36 children with a low familial risk of depression (LR). Their parents: 44 adults with a history of depression (HD) and 36 adults with no history of psychiatric disorder (ND) were also compared. There was no evidence of group differences in AB; neither between the HR and LR children, nor between HD and ND parents. There was no evidence of a correlation between parent and child AB. The internal consistency of the tasks varied greatly. The Dot-Probe Task showed unacceptable reliability whereas the behavioral index of the Visual-Search Task and an eye-tracking index of the Passive-Viewing Task showed better reliability. There was little correlation between the AB tasks and the tasks showed minimal convergence with symptoms of depression or anxiety. The null-findings of the current study contradict our expectations and much of the previous literature. They may be due to the poor psychometric properties associated with some of the AB indices, the unreliability of AB in general, or the relatively modest sample size. The poor reliability of the tasks in our sample suggest caution should be taken when interpreting the positive findings of previous studies which have used similar methods and populations

Biased Maintenance of Attention on Sad Faces in Clinically Depressed Youth: An Eye-Tracking Study

The role of negative attention biases (AB), central to cognitive models of adult depression, is yet unclear in youth depression. We investigated negative AB in depressed compared to healthy youth and tested whether AB are more pronounced in depressed than at-risk youth. Negative AB was assessed for sad and angry faces with an eye-tracking paradigm [Passive Viewing Task (PVT)] and a behavioural task [Visual Search Task (VST)], comparing three groups of 9–14-year-olds: youth with major depression (MD; n = 32), youth with depressed parents (high-risk; HR; n = 49) and youth with healthy parents (low-risk; LR; n = 42). The PVT revealed MD participants to maintain attention longer on sad faces compared to HR, but not LR participants. This AB correlated positively with depressive symptoms. The VST revealed no group differences. Our results provide preliminary evidence for a negative AB in maintenance of attention on disorder-specific emotional information in depressed compared to at-risk youth