A Residue Quartet in the Extracellular Domain of the Prolactin Receptor Selectively Controls Mitogen-activated Protein Kinase Signaling

Cytokine receptors elicit several signaling pathways, but it is poorly understood how they select and discriminate between them. We have scrutinized the prolactin receptor as an archetype model of homodimeric cytokine receptors to address the role of the extracellular membrane proximal domain in signal transfer and pathway selection. Structure-guided manipulation of residues involved in the receptor dimerization interface identified one residue (position 170) that in cell-based assays profoundly altered pathway selectivity and species-specific bio-characteristics. Subsequent in vitro spectroscopic and nuclear magnetic resonance analyses revealed that this residue was part of a residue quartet responsible for specific local structural changes underlying these effects. This included alteration of a novel aromatic T-stack within the membrane proximal domain, which promoted selective signaling affecting primarily the MAPK (ERK1/2) pathway. Importantly, activation of the MAPK pathway correlated with in vitro stabilities of ternary ligand·receptor complexes, suggesting a threshold mean lifetime of the complex necessary to achieve maximal activation. No such dependence was observed for STAT5 signaling. Thus, this study establishes a residue quartet in the extracellular membrane proximal domain of homodimeric cytokine receptors as a key regulator of intracellular signaling discrimination.     

Applications of biofilms in bioremediation and biotransformation of persistent organic pollutants, pharmaceuticals/personal care products, and heavy metals

In this review, the strategies being employed to exploit the inherent durability of biofilms and the diverse nutrient cycling of the microbiome for bioremediation are explored. Focus will be given to halogenated compounds, hydrocarbons, pharmaceuticals, and personal care products as well as some heavy metals and toxic minerals, as these groups represent the majority of priority pollutants. For decades, industrial processes have been creating waste all around the world, resulting in contaminated sediments and subsequent, far-reaching dispersal into aquatic environments. As persistent pollutants have accumulated and are still being created and disposed, the incentive to find suitable and more efficient solutions to effectively detoxify the environment is even greater. Indigenous bacterial communities are capable of metabolizing persistent organic pollutants and oxidizing heavy metal contaminants. However, their low abundance and activity in the environment, difficulties accessing the contaminant or nutrient limitations in the environment all prevent the processes from occurring as quickly as desired and thus reaching the proposed clean-up goals. Biofilm communities provide among other things a beneficial structure, possibility for nutrient, and genetic exchange to participating microorganisms as well as protection from the surrounding environment concerning for instance predation and chemical and shear stresses. Biofilms can also be utilized in other ways as biomarkers for monitoring of stream water quality from for instance mine drainage. The durability and structure of biofilms together with the diverse array of structural and metabolic characteristics make these communities attractive actors in biofilm-mediated remediation solutions and ecosystem monitoring.     

New horizons for lipoprotein receptors: communication by β-propellers

The lipoprotein receptor (LR) family constitutes a large group of structurally closely related receptors with broad ligand-binding specificity. Traditionally, ligand binding to LRs has been anticipated to involve merely the complement type repeat (CR)-domains omnipresent in the family. Recently, this dogma has transformed with the observation that β-propellers of some LRs actively engage in complex formation too. Based on an in-depth decomposition of current structures and sequences, we suggest that exploitation of the β-propellers as binding targets depends on receptor subgroups. In particular, we highlight the shutter mechanism of β-propellers as a general recognition motif for NxI-containing ligands, and we present indications that the generalized β-propeller-induced ligand release mechanism is not applicable for the larger LRs. For the giant LR members, we present evidence that their β-propellers may also actively engage in ligand binding. We therefore advocate for an increased focus on solving the structure-function relationship of this group of important biological receptors.     

Behavioral Responses of Nursing Home Residents to Visits From a Person with a Dog,a Robot Seal or aToy Cat

Previous studies suggest that contact with dogs can positively affect the wellbeing of elderly people in nursing homes, but there is a lack of research investigating the causal pathways of these effects. One such path- way may relate to the behavioral responses of the elderly when interacting with a dog. The present study compared the immediate behavioral responses of nursing home residents to bi-weekly visits from a person accompanied by either a dog, a robot seal (PARO®), or a soft toy cat, using a randomized controlled design. A total of 100 nursing home residents com- pleted the study. Each participant received a total of 12 visits, during which their behaviors, including interactions between the visitor and the accom- panying animal (real or artificial), were recorded. Also, data on cognitive im- pairment, presence of depressive symptoms, age, time lived in the nursing home, dementia diagnoses, and gender were collected. We found that the immediate responses to, and interaction with, the visiting animal depended on the type of animal that was brought along. The dog and the interactive robot seal triggered the most interaction, in the form of physical contact (F(2,103) = 7.50, p < 0.001), eye contact (F(4,151) = 6.26, p < 0.001), and verbal communication (F(4,195) = 2.87, p < 0.05). As well, the cognitive impairment level of the residents affected with whom they interacted. The higher the cognitive impairment level, the more interaction was directed toward the animal and less toward humans, regardless of visit type (F(2,101) = 4.10, p < 0.05). The dogs and the robot seal stimulated the residents to more in- teraction, compared with the toy cat, but the robot seal failed to maintain the attention at the same level over time. The cognitive functioning of the residents correlated with the level of interaction, and this needs to be studied further.