The gut microbiota interacts with the host through the mucus that covers and protects the gastrointestinal epithelium. The main component of the mucus are mucins, glycoproteins decorated with hundreds of different O-glycans. Some microbiota members can utilize mucin O-glycans as carbons source. To degrade these host glycans the bacteria express multiple carbohydrate-active enzymes (CAZymes) such as glycoside hydrolases, sulfatases and esterases which are active on specific linkages. The studies of these enzymes in an in vivo context have started to reveal their importance in mucin utilization and gut colonization. It is now clear that bacteria evolved multiple specific CAZymes to overcome the diversity of linkages found in O-glycans. Additionally, changes in mucin degradation by gut microbiota have been associated with diseases like obesity, diabetes, irritable bowel disease and colorectal cancer. Thereby understanding how CAZymes from different bacteria work to degrade mucins is of critical importance to develop new treatments and diagnostics for these increasingly prevalent health problems. This mini-review covers the recent advances in biochemical characterization of mucin O-glycan-degrading CAZymes and how they are connected to human health.

The brain is a complex organ even when viewed from a cell biological perspective. Neuronal networks are embedded in a dense milieu of diverse and specialised cell types, including several types of vascular, immune, and macroglial cells. To view each cell as a small cog in a highly complex machine is itself an oversimplification. Not only are they functionally coupled to enable the brain to operate, each cell type's functions are themselves influenced by each other, in development, maturity, and also in disease. Astrocytes are a type of macroglia that occupy a significant fraction of the human forebrain. They play a critical role in sustaining functional neuronal circuits across the lifespan through myriad homeostatic functions including the maintenance of redox balance, ionic gradients, neurotransmitter clearance, and bioenergetic support. It is becoming apparent that astrocytes' capacity to carry out these and other neurosupportive roles is not fixed, but is regulated by signals coming from the neurons themselves, both in the healthy brain but also in response to neuron-derived disease pathology. Here, we review mechanisms by which neurons control the properties of astrocytes long term in order to alter their homeostatic capacity both in development and maturity. Our working hypothesis is that these signals are designed to change and maintain the homeostatic capacity of local astrocytes to suit the needs of nearby neurons. Knowledge of the external signals that can control core aspects of a healthy astrocytic phenotype are being uncovered, raising the question as to whether this knowledge can be harnessed to promote astrocyte-mediated neurosupport in brain disorders.

Glucuronoyl esterases (GEs) are microbial enzymes able to cleave covalent linkages between lignin and carbohydrates in the plant cell wall. GEs are serine hydrolases found in carbohydrate esterase family 15 (CE15), which belongs to the large α/β hydrolase superfamily. GEs have been shown to reduce plant cell wall recalcitrance by hydrolysing the ester bonds found between glucuronic acid moieties on xylan polysaccharides and lignin. In recent years, the exploration of CE15 has broadened significantly and focused more on bacterial enzymes, which are more diverse in terms of sequence and structure to their fungal counterparts. Similar to fungal GEs, the bacterial enzymes are able to improve overall biomass deconstruction but also appear to have less strict substrate preferences for the uronic acid moiety. The structures of bacterial GEs reveal that they often have large inserts close to the active site, with implications for more extensive substrate interactions than the fungal GEs which have more open active sites. In this review, we highlight the recent work on GEs which has predominantly regarded bacterial enzymes, and discuss similarities and differences between bacterial and fungal enzymes in terms of the biochemical properties, diversity in sequence and modularity, and structural variations that have been discovered thus far in CE15.

Astrocytes are key players in brain homeostasis and function. During the last years, several studies have cemented this notion by showing that these cells respond to neuronal signals and, via the release of molecules that modulate and support synaptic activity (gliotransmission) participates in the functions of the so-called tripartite synapse. Thus, besides their established control of brain metabolism, astrocytes can also actively control synaptic activity and behavior. Among the signaling pathways that shape the functions of astrocyte, the cannabinoid type-1 (CB1) receptor is emerging as a critical player in the control of both gliotransmission and the metabolic cooperation between astrocytes and neurons. In the present short review, we describe known and newly discovered properties of the astroglial CB1 receptors and their role in modulating brain function and behavior. Based on this evidence, we finally discuss how the functions and mode of actions of astrocyte CB1 receptors might represent a clear example of the inextricable relationship between energy metabolism and gliotransmission. These tight interactions will need to be taken into account for future research in astrocyte functions and call for a reinforcement of the theoretical and experimental bridges between studies on metabolic and synaptic functions of astrocytes.

Biological macromolecules, such as proteins, nucleic acids, and carbohydrates, contain heteroatom-bonded hydrogens that undergo exchange with solvent hydrogens on timescales ranging from microseconds to hours. In hydrogen-deuterium exchange mass spectrometry (HDX-MS), this exchange process is used to extract information about biomolecular structure and dynamics. This minireview focuses on millisecond timescale HDX-MS measurements, which, while less common than 'conventional' timescale (seconds to hours) HDX-MS, provide a unique window into weakly structured species, weak (or fast cycling) binding interactions, and subtle shifts in conformational dynamics. This includes intrinsically disordered proteins and regions (IDPs/IDRs) that are associated with cancer and amyloidotic neurodegenerative disease. For nucleic acids and carbohydrates, structures such as isomers, stems, and loops, can be elucidated and overall structural rigidity can be assessed. We will provide a brief overview of technical developments in rapid HDX followed by highlights of various applications, emphasising the importance of broadening the HDX timescale to improve throughput and to capture a wider range of function-relevant dynamic and structural shifts.

Protein aggregation is now recognized as a generic and significant component of the protein energy landscape. Occurring through a complex and dynamic pathway of structural interconversion, the assembly of misfolded proteins to form soluble oligomers and insoluble aggregates remains a challenging topic of study, both in vitro and in vivo. Since the etiology of numerous human diseases has been associated with protein aggregation, and it has become a field of increasing importance in the biopharmaceutical industry, the biophysical characterization of protein misfolded states and their aggregation mechanisms continues to receive increased attention. Mass spectrometry (MS) has firmly established itself as a powerful analytical tool capable of both detection and characterization of proteins at all levels of structure. Given inherent advantages of biological MS, including high sensitivity, rapid timescales of analysis, and the ability to distinguish individual components from complex mixtures with unrivalled specificity, it has found widespread use in the study of protein aggregation, importantly, where traditional structural biology approaches are often not amenable. The present review aims to provide a brief overview of selected MS-based approaches that can provide a range of biophysical descriptors associated with protein conformation and the aggregation pathway. Recent examples highlight where this technology has provided unique structural and mechanistic understanding of protein aggregation.

Astrocytes are a heterogenous population of macroglial cells spread throughout the central nervous system with diverse functions, expression signatures, and intricate morphologies. Their subcellular compartments contain a distinct range of mitochondria, with functional microdomains exhibiting widespread activities, such as controlling local metabolism and Ca2+ signaling. Ca2+ is an ion of utmost importance, both physiologically and pathologically, and participates in critical central nervous system processes, including synaptic plasticity, neuron-astrocyte integration, excitotoxicity, and mitochondrial physiology and metabolism. The mitochondrial Ca2+ handling system is formed by the mitochondrial Ca2+ uniporter complex (MCUc), which mediates Ca2+ influx, and the mitochondrial Na+/Ca2+ exchanger (NCLX), responsible for most mitochondrial Ca2+ efflux, as well as additional components, including the mitochondrial permeability transition pore (mtPTP). Over the last decades, mitochondrial Ca2+ handling has been shown to be key for brain homeostasis, acting centrally in physiopathological processes such as astrogliosis, astrocyte-neuron activity integration, energy metabolism control, and neurodegeneration. In this review, we discuss the current state of knowledge regarding the mitochondrial Ca2+ handling system molecular composition, highlighting its impact on astrocytic homeostasis.