Kinetic principles of chemical cross-link formation for protein-protein interactions.

Proteins play a central role in most biological processes within the cell, and deciphering how they interact is key to understand their function. Cross-linking coupled with mass spectrometry is an essential tool for elucidating protein-protein interactions (PPIs). Despite its importance, we still know surprisingly little about the principles that underlie the process of chemical cross-link formation itself and how it is influenced by different physicochemical factors.

[An app for informal care : User experiences and obstacles from the perspective of family caregivers].

Background: A target group for digital services are people who are involved in informal care arrangements. Family caregivers often undertake the organization and coordination of care, which is associated with a high need for information.

Objective: The study examined the extent to which family caregivers perceive the use of a mobile digital application as facilitating day to day care, in particular regarding information needs.

Mono- and Intralink Filter (Mi-Filter) To Reduce False Identifications in Cross-Linking Mass Spectrometry Data.

Cross-linking mass spectrometry (XL-MS) has become an indispensable tool for the emerging field of systems structural biology over the recent years. However, the confidence in individual protein-protein interactions (PPIs) depends on the correct assessment of individual inter-protein cross-links. In this article, we describe a mono- and intralink filter (mi-filter) that is applicable to any kind of cross-linking data and workflow.

Structural Probing of Hsp26 Activation and Client Binding by Quantitative Cross-Linking Mass Spectrometry.

Small heat-shock proteins (sHSPs) are important members of the cellular stress response in all species. Their best-described function is the binding of early unfolding states and the resulting prevention of protein aggregation. Many sHSPs exist as a polydisperse composition of oligomers, which undergoes changes in subunit composition, folding status, and relative distribution upon heat activation.

HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA-binding domain.

Aberrant liquid-to-solid phase transitions of biomolecular condensates have been linked to various neurodegenerative diseases. However, the underlying molecular interactions that drive aging remain enigmatic. Here, we develop quantitative time-resolved crosslinking mass spectrometry to monitor protein interactions and dynamics inside condensates formed by the protein fused in sarcoma (FUS).

Site-specific ubiquitylation acts as a regulator of linker histone H1.

Decoding the role of histone posttranslational modifications (PTMs) is key to understand the fundamental process of epigenetic regulation. This is well studied for PTMs of core histones but not for linker histone H1 in general and its ubiquitylation in particular due to a lack of proper tools. Here, we report on the chemical synthesis of site-specifically mono-ubiquitylated H1.

Proteome-Wide Structural Probing of Low-Abundant Protein Interactions by Cross-Linking Mass Spectrometry.

Proteome-wide cross-linking studies have spurred great interest as they facilitate structural probing of protein interactions in living cells and organisms. However, current studies have a bias for high-abundant proteins. In this study we demonstrate both experimentally and by a kinetic model that this bias is also caused by the propensity of cross-links to preferentially form on high abundant proteins and not by the inability to detect cross-links due to limitations in current technology.

Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex.

Deregulation of the ubiquitin ligase E6AP is causally linked to the development of human disease, including cervical cancer. In complex with the E6 oncoprotein of human papillomaviruses, E6AP targets the tumor suppressor p53 for degradation, thereby contributing to carcinogenesis. Moreover, E6 acts as a potent activator of E6AP by a yet unknown mechanism.

Postprandial self-monitoring of urine glucose reflects glycaemic control in people with relatively well controlled Type 2 diabetes mellitus not treated with insulin: a retrospective cohort study.

Aim: To analyse the association of self-monitoring of urine glucose with HbA1c concentration in people with Type 2 diabetes not treated with insulin.

Methods: We studied the association of postprandial self-monitored urine glucose with HbA1c concentrations in 264 people with Type 2 diabetes (mean age 62.4 years, time since diagnosis of diabetes 6.

The effects of arterial blood pressure on rebleeding when BleedArrest, Celox and TraumaDex are used in a porcine model of lethal femoral injury.

Uncontrolled bleeding remains the leading cause of preventable death in trauma. Hemostatic agents are effective in hemorrhage control but often fail following high-volume crystalloid resuscitation. Aggressive fluid resuscitation increases the blood pressure which may dislodge the newly formed clot causing rebleeding.

[Contribution of professional nursing to the life style of patients with dementia].

The care of older people with dementia increasingly requires that the family be involved in that care. The goals of the care giver are to continue daily life rhythms, offer greatest normality, and support the quality of life. This article describes the most important approaches and strategies from the perspective of daily living.

[The role of nursing care in geriatric rehabilitation].

This article intends to present goals, tasks and focus points in different kinds of institutions of geriatric rehabilitation. This is be done under the aspects of: 1. Accompanying handicappeds during their disease.

Time estimation and the experience of time in endogenous depression (Melancholia): an experimental investigation.

The importance of disturbances in time experience in endogenous depression (melancholia) has long been under discussion. In the present study alterations of time experience were examined by means of time estimation experiments. 25 endogenous depressive patients (according to ICD-9) underestimated prospectively a 30-second interval by 6 s, whereas 12 healthy controls overestimated this interval by more than 10 s.

The daily course of the symptomatology and the impaired time estimation in endogenous depression (melancholia).

The importance of 'typical' diurnal variations in mood (depression worse in the morning) as a diagnostic criterion of endogenous depression has been challenged in previous investigations. Disturbance in time experience may contribute towards an understanding of diurnal variation in depressive symptomatology. To examine this hypothesis a series of time estimation experiments was conducted in the course of the day.