Adaptive and harmful autobiographical remembering after the loss of a loved one.

Remembering one's personal past serves psychosocial functions. Adaptive use of autobiographical memory is related to well-being but little research has focused on grief. We address this in two studies theoretically grounded in the model of reminiscence and health.

The influence of sham feedback on physiological processing during fear-driven stimulation.

Biofeedback constitutes a well-established, non-invasive method to voluntary interfere in emotional processing by means of cognitive strategies. However, treatment durations exhibit strong inter-individual variations and first successes can often be achieved only after a large number of sessions. Sham feedback constitutes a rather untapped approach by providing feedback that does not correspond to the participant's actual state.

Navigated transcranial magnetic stimulation improves the treatment outcome in patients with brain tumors in motor eloquent locations.

Background: Neurological and oncological outcomes of motor eloquent brain-tumor patients depend upon the ability to localize functional areas and the respective proposed therapy. We set out to determine whether the use of navigated transcranial magnetic stimulation (nTMS) had an impact on treatment and outcome in patients with brain tumors in motor eloquent locations.

Methods: We enrolled 250 consecutive patients and compared their functional and oncological outcomes to a matched pre-nTMS control group (n = 115).

Language mapping in healthy volunteers and brain tumor patients with a novel navigated TMS system: evidence of tumor-induced plasticity.

Objective: This article explores the feasibility of a novel repetitive navigated transcranial magnetic stimulation (rnTMS) system and compares language mapping results obtained by rnTMS in healthy volunteers and brain tumor patients.

Methods: Fifteen right-handed healthy volunteers and 50 right-handed consecutive patients with left-sided gliomas were examined with a picture-naming task combined with time-locked rnTMS (5-10 Hz and 80-120% resting motor threshold) applied over both hemispheres. Induced errors were classified into four psycholinguistic types and assigned to their respective cortical areas according to the coil position during stimulation.

Assessing the functional status of the motor system in brain tumor patients using transcranial magnetic stimulation.

Background: Transcranial magnetic stimulation (TMS) is being used in the pre-operative diagnostics of patients with tumors in or near the motor cortex. Although the main purpose of TMS in such patients is to map the functional areas of the motor cortex in spatial relation to the tumor, TMS also provides some numerical neurophysiological measurements of the functional status of the patient's motor system. The aim of this paper is to provide reference values for these neurophysiological measurements from a large and varied clinical sample.

A new approach for corticospinal tract reconstruction based on navigated transcranial stimulation and standardized fractional anisotropy values.

Purpose: To establish a novel approach for fiber tracking based on navigated transcranial magnetic stimulation (nTMS) mapping of the primary motor cortex and to propose a new algorithm for determination of an individualized fractional anisotropy value for reliable and objective fiber tracking.

Methods: 50 patients (22 females, 28 males, median age 58 years (20-80)) with brain tumors compromising the primary motor cortex and the corticospinal tract underwent preoperative MR imaging and nTMS mapping. Stimulation spots evoking muscle potentials (MEP) closest to the tumor were imported into the fiber tracking software and set as seed points for tractography.

Effects of new insulin analogues HMR1964 (insulin glulisine) and HMR1423 on insulin receptors.

Aims/hypothesis: New insulin analogues have been created by amino-acid exchange to provide an improved pharmacokinetic profile. However, safety issues have been raised regarding their use, as amino-acid exchange of insulin may induce altered metabolic and mitogenic effects. For example, the insulin analogue Asp(B10) causes breast cancer in rodents.

The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta.

To study whether protein kinase C (PKC) isoforms can interact with protein-tyrosine-phosphatases (PTPs) which are connected to the insulin signaling pathway, we co-overexpressed PKC isoforms together with insulin receptor, docking proteins, and the PTPs SHP1 and SHP2 in human embryonic kidney (HEK) 293 cells. After phorbol ester induced activation of PKC isoforms alpha, beta 1, beta 2, and eta, we could show a defined gel mobility shift of SHP2, indicating phosphorylation on serine/threonine residues. This phosphorylation was not dependent on insulin receptor or insulin receptor substrate-1 (IRS-1) overexpression and did not occur for the closely related phosphatase SHP1.

PKC zeta enhances insulin-like growth factor 1-dependent mitogenic activity in the rat clonal beta cell line RIN 1046-38.

Protein kinase C seems to be linked to the regulation of insulin secretion as well as mitogenic signaling in pancreatic beta cells. To study the impact of different PKC isoforms on insulin secretion and mitogenic activity we stably overexpressed the PKC isoforms alpha, beta2, epsilon, and zeta in the rat clonal beta cell line RIN 1046-38. Under basal conditions PKC alpha, beta2, epsilon, and zeta were identified mainly in the cytosol.

Insulin inhibits leptin receptor signalling in HEK293 cells at the level of janus kinase-2: a potential mechanism for hyperinsulinaemia-associated leptin resistance.

Aims/hypothesis: Leptin resistance in obese humans seems to be predominantly caused by signalling abnormalities at the post receptor level. Leptin resistance in obese individuals is frequently associated with insulin resistance and pronounced hyperinsulinaemia indicating a negative crosstalk of the insulin and leptin signalling chain.

Methods: This hypothesis was tested using a cell model of peripheral leptin signalling, i.

Inhibition of Ret oncogene activity by the protein tyrosine phosphatase SHP1.

Germline mutations in the Ret protooncogene give rise to the inherited endocrine cancer syndromes MEN types 2A and 2B and familiar medullary thyroid carcinoma. Although it is well accepted that the constitutive active tyrosine kinase of Ret oncogenes ultimately leads to malignant transformation, it is not clear whether a decrease in the autophosphorylation of oncogenic Ret forms can affect the mitogenic and transforming activities of Ret. Potential modulators of the tyrosine kinase activity of Ret could be tyrosine phosphatases that are expressed in human thyroid tissue.

Ret oncogene signal transduction via a IRS-2/PI 3-kinase/PKB and a SHC/Grb-2 dependent pathway: possible implication for transforming activity in NIH3T3 cells.

Multiple endocrine neoplasia 2A (MEN 2A) is an inherited disease caused by mutations of the Ret proto-oncogene. Although many different Ret mutations have been described, little is known about the signaling pathways triggered by the Ret oncogene. In this study, we have determined the signaling properties of a Ret-9bp duplication encoding amino acids 634-636, which was recently identified in a patient with all clinical features of the MEN 2A syndrome.

Serine residues 1177/78/82 of the insulin receptor are required for substrate phosphorylation but not autophosphorylation.

Serine residues of the human insulin receptor (HIR) may be phosphorylated and negatively regulate the insulin signal. We studied the impact of 16 serine residues in HIR by mutation to alanine and co-overexpression in human embryonic kidney (HEK) 293 cells together with the docking proteins insulin receptor substrate (IRS)-1, IRS-2, or (SHC) Src homologous and collagen-like. As a control, IRS-1 was also cotransfected with an HIR with a juxtamembrane deletion (HIR delta JM) and therefore not containing the domain required for interaction with IRS-1.

Serine residues 994 and 1023/25 are important for insulin receptor kinase inhibition by protein kinase C isoforms beta2 and theta.

Aims/hypothesis: Inhibition of the signalling function of the human insulin receptor (HIR) is one of the principle mechanisms which induce cellular insulin resistance. It is speculated that serine residues in the insulin receptor beta-subunit are involved in receptor inhibition either as inhibitory phosphorylation sites or as part of receptor domains which bind inhibitory proteins or tyrosine phosphatases. As reported earlier we prepared 16 serine to alanine point mutations of the HIR and found that serine to alanine mutants HIR-994 and HIR-1023/25 showed increased tyrosine autophosphorylation when expressed in human embryonic kidney (HEK) 293 cells.

The inhibitory effect of 2-deoxyglucose on insulin receptor autophosphorylation does not depend on known serine phosphorylation sites or other conserved serine residues of the receptor beta-subunit.

Hyperglycemia induces insulin resistance in diabetic patients. It is known that supraphysiological levels of D-glucose or 2-deoxyglucose inhibit the insulin receptor and it is speculated that this effect is mediated by serine phosphorylation of the insulin receptor beta-subunit and other proteins of the insulin signaling chain. To test this hypothesis we prepared point mutations of the human insulin receptor where serine was exchanged to alanine at 16 different positions, either at known phosphorylation sites or at positions which are conserved in different tyrosine kinase receptors.

A 973 valine to methionine mutation of the human insulin receptor: interaction with insulin-receptor substrate-1 and Shc in HEK 293 cells.

A population-based study in the Netherlands has recently demonstrated that a mutation of the human insulin receptor (HIR-973 valine to methionine) is associated with hyperglycaemia and an increased prevalence of non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to assess whether this mutation leads to a functional alteration of the insulin receptor. We prepared the HIR-973 mutant by in vitro mutagenesis.

Impact of mutations at different serine residues on the tyrosine kinase activity of the insulin receptor.

Insulin binding to its receptor activates a cascade of signaling events which are initiated by tyrosine autophosphorylation of the receptor and activation of the tyrosine kinase activity towards the insulin receptor substrates. In addition to phosphorylation at tyrosine residues a serine phosphorylation of the insulin receptor is observed. Neither the functional significance of serine phosphorylation of the receptor nor the location of relevant regulatory sites has been determined exactly so far.