From amino acid mixtures to peptides in liquid sulphur dioxide on early Earth.

The formation of peptide bonds is one of the most important biochemical reaction steps. Without the development of structurally and catalytically active polymers, there would be no life on our planet. However, the formation of large, complex oligomer systems is prevented by the high thermodynamic barrier of peptide condensation in aqueous solution.

Non-apoptotic TRAIL function modulates NK cell activity during viral infection.

The role of death receptor signaling for pathogen control and infection-associated pathogenesis is multifaceted and controversial. Here, we show that during viral infection, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) modulates NK cell activity independently of its pro-apoptotic function. In mice infected with lymphocytic choriomeningitis virus (LCMV), Trail deficiency led to improved specific CD8 T-cell responses, resulting in faster pathogen clearance and reduced liver pathology.

Strength, elasticity and the limits of energy dissipation in two related sea urchin spines with biomimetic potential.

The calcitic spines of the sea urchins Heterocentrotus mamillatus and H. trigonarius are promising role models for lightweight applications, bone tissue scaffolds and energy dissipating processes due to their highly porous and organized structure. Therefore, mechanical properties including Young's Modulus, strength, failure behaviour and energy dissipation efficiency have been investigated in depth with uniaxial compression experiments, 3-point bending tests and resonance frequency damping analysis.

Strength-size relationships in two porous biological materials.

Unlabelled: According to the Weibull theory for brittle materials, the mean experimental strength decreases with test specimen size. For the brittle parts of an organism this would mean that becoming larger in size results automatically in reducing strength. This unfavorable relationship was investigated for two porous, biological materials that are promising concept generators for crack deflective and energy dissipative applications in compressive overloading: the quasi-brittle coconut endocarp and the brittle spines of the sea urchin Heterocentrotus mamillatus.

Associations of nocturnal sleep with experimental pain and pain catastrophizing in healthy volunteers.

Strong alterations of night sleep (e.g., sleep deprivation, insomnia) have appeared to affect pain in inducing hyperalgesic changes.

No Impaired Glucose Tolerance in Primary Insomnia Patients with Normal Results of Polysomnography.

Background: According to recent studies, sleep restriction and disruption both have a prominent negative influence on glucose metabolism. This could also be shown in sleep disorders, such as sleep apnea and the restless legs syndrome. However, similar studies regarding insomnia have not been that consistent, yet.

Why the structure but not the activity of the immunoproteasome subunit low molecular mass polypeptide 2 rescues antigen presentation.

The proteasome is responsible for the generation of most epitopes presented on MHC class I molecules. Treatment of cells with IFN-γ leads to the replacement of the constitutive catalytic subunits β1, β2, and β5 by the inducible subunits low molecular mass polypeptide (LMP) 2 (β1i), multicatalytic endopeptidase complex-like-1 (β2i), and LMP7 (β5i), respectively. The incorporation of these subunits is required for the production of numerous MHC class I-restricted T cell epitopes.

The proapoptotic Bcl-2 family member Bim plays a central role during the development of virus-induced hepatitis.

The proapoptotic Bcl-2 homolog Bim was shown to control the apoptosis of both T cells and hepatocytes. This dual role of Bim might be particularly relevant for the development of viral hepatitis, in which both the sensitivity of hepatocytes to apoptosis stimuli and the persistence of cytotoxic T cells are essential factors for the outcome of the disease. The relevance of Bim in regulating survival of cytotoxic T cells or induction of hepatocyte death has only been investigated in separate systems, and their relative contributions to the pathogenesis of T cell-mediated hepatitis remain unclear.

Impaired glucose tolerance in sleep disorders.

Background: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders.

The proteasome inhibitor bortezomib enhances the susceptibility to viral infection.

The proteasome, a multicatalytic protease, is responsible for the generation of most MHC class I ligands. Bortezomib, a proteasome inhibitor, is clinically approved for treatment of multiple myeloma and mantle cell myeloma. In the present study, we investigated the effect of bortezomib on viral infection.

Immune cell-mediated liver injury.

Liver diseases represent an important cause of morbidity and mortality in the world. Death of hepatocytes and other hepatic cell types is a characteristic feature of several forms of liver injury such as cholestasis, viral hepatitis, drug- or toxin-induced injury, and alcohol-induced liver damage. Moreover, irrespectively of the reason, liver injury seems to be facilitated by similar immune effector mechanisms common to these various liver diseases.

A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis.

The immunoproteasome, a distinct class of proteasome found predominantly in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on class I major histocompatibility complexes (MHC-I). However, a specific role for the immunoproteasome in regulating other facets of immune responses has not been established. We describe here the characterization of PR-957, a selective inhibitor of low-molecular mass polypeptide-7 (LMP7, encoded by Psmb8), the chymotrypsin-like subunit of the immunoproteasome.

The Munich vulnerability study on affective disorders: microstructure of sleep in high-risk subjects.

Vulnerability markers for affective disorders have focused on stress hormone regulation and sleep. Among rapid eye movement (REM) sleep, increased REM pressure and elevated REM density are promising candidates for vulnerability markers. Regarding nonREM sleep, a deficit in amount of and latency until slow wave sleep during the first half of the night is a characteristic for depression.

Dex/CRH-test response and sleep in depressed patients and healthy controls with and without vulnerability for affective disorders.

Sleep electroencephalographic (EEG) abnormalities and increased hypothalamo-pituitary-adrenal (HPA) axis activity are the most prominent neurobiological findings in depression and were suggested as potential biomarker for depression. In particular, increased rapid eye movement sleep (REM) density, deficit in slow wave sleep and excessive stress hormone response are associated with an unfavorable long-term outcome of depression. Recent studies indicate that the sleep and endocrine parameters are related to each other.

Acute cortisol administration increases sleep depth and growth hormone release in patients with major depression.

Acute administration of cortisol increases non-rapid-eye movement (non-REM) sleep, suppresses rapid-eye movement (REM) sleep and stimulates growth hormone (GH) release in healthy subjects. This study investigates whether cortisol has similar endocrine and electrophysiological effects in patients with depression who typically show a pathological overactivity of the hypothalamus-pituitary-adrenal (HPA) system. Fifteen depressed inpatients underwent the combined dexamethasone/corticotropin-releasing hormone test followed by three consecutive sleep EEG recordings in which the patients received placebo (saline) and hourly injections of cortisol (1mg/KG BW).

Rapid eye movement (REM) sleep: an endophenotype for depression.

Disturbed sleep is one of the hallmark signs of depression. After successful treatment, many of these signs disappear; however, changes in rapid eye movement (REM) sleep may persist and even predict recurrence of depression. High-risk studies have established these alterations to be not only biological scars but true endophenotypes for depression.

Immune-endocrine host response to endotoxin in major depression.

Objective: An impaired hypothalamic-pituitary-adrenocortical (HPA) function is a well-established finding in major depression (MD), but it is still unclear how this dysfunction affects immune responses in this disorder.

Method: To further examine the relationship between immune and endocrine responses in MD, 0.4ng/kg body weight endotoxin [LPS] or 100mug hCRH were sequentially applied to 12 patients with MD and to 12 age- and gender-matched healthy controls after pre-treatment with 1.

The Munich vulnerability study on affective disorders: premorbid polysomnographic profile of affected high-risk probands.

Background: The most characteristic alterations in the sleep electroencephalogram (EEG) during major depression are a shortened latency to rapid eye movement (REM) sleep and an elevated REM density. Because these changes persist in remission, they might represent vulnerability markers. To identify vulnerability markers, we investigated premorbid sleep EEG parameters in healthy high-risk probands (HRPs) with a positive family history of affective disorders.

Sleep in eating disorders.

Sleep research on eating disorders has addressed two major questions: (1) the effects of chronic starvation in anorexia nervosa and of rapidly fluctuating eating patterns in bulimia nervosa on the sleep regulating processes and (2) the search for a significant neurobiological relationship between eating disorders and major depression. At present, the latter question appears to be resolved, since most of the available evidences clearly underline the notion that eating disorders (such as anorexia and bulimia nervosa) and affective disorders are two distinct entities. Regarding the effects of starvation on sleep regulation, recent research in healthy humans and in animals demonstrates that such a condition results in a fragmentation of sleep and a reduction of slow wave sleep.

The Munich Vulnerability Study on Affective Disorders: risk factors for unipolarity versus bipolarity.

Background: An individual with a high genetic load for psychiatric disorders is subject to a considerable risk factor for an affective illness. Family studies usually try to distinguish between bipolar and unipolar disorders since it was suggested that they might show different modes of inheritance. The aim of this study was to differentiate between healthy members of unipolar and bipolar families without a previous history of any psychiatric disorder according to the neurobiological and psychometric findings.

The Munich Vulnerability Study on Affective Disorders: stability of polysomnographic findings over time.

Background: Some of the sleep abnormalities found in depression also persist in remission, suggesting that these parameters could represent trait or vulnerability markers. In a previous study, we found that about one third of a group of high-risk probands (HRPs) showed sleep patterns that were comparable to those of depressed patients. In the present study, we re-investigated a subsample of these HRPs to evaluate the stability of these findings over time.