The ever-growing world population, increasingly frequent extreme weather events and conditions, emergence of novel devastating crop pathogens and the social strive for quality food products represent a huge challenge for current and future agricultural production systems. To address these challenges and find realistic solutions, it is becoming more important by the day to understand the complex interactions between plants and the environment, mainly the associated organisms, but in particular pathogens. In the past several years, research in the fields of plant pathology and plant-microbe interactions has enabled tremendous progress in understanding how certain receptor-based plant innate immune systems function to successfully prevent infections and diseases. In this review, we highlight and discuss some of these new ground-breaking discoveries and point out strategies of how pathogens counteract the function of important core convergence hubs of the plant immune system. For practical reasons, we specifically place emphasis on potential applications that can be detracted by such discoveries and what challenges the future of agriculture has to face, but also how these challenges could be tackled.

Bacterial infections of the gut are one of the major causes of morbidity and mortality worldwide. The interplay between the pathogen and the host is finely balanced, with the bacteria evolving to proliferate and establish infection. In contrast, the host mounts a response to first restrict and then eliminate the infection. The intestine is a rapidly proliferating tissue, and metabolism is tuned to cater to the demands of proliferation and differentiation along the crypt-villus axis (CVA) in the gut. As bacterial pathogens encounter the intestinal epithelium, they elicit changes in the host cell, and core metabolic pathways such as the tricarboxylic acid (TCA) cycle, lipid metabolism and glycolysis are affected. This review highlights the mechanisms utilized by diverse gut bacterial pathogens to subvert host metabolism and describes host responses to the infection.

RNA polymerase II moves along genes to decode genetic information stored in the mammalian genome into messenger RNA and different forms of non-coding RNA. However, the transcription process is frequently challenged by DNA lesions caused by exogenous and endogenous insults, among which helix-distorting DNA lesions and double-stranded DNA breaks are particularly harmful for cell survival. In response to such DNA damage, RNA polymerase II transcription is regulated both locally and globally by multi-layer mechanisms, whereas transcription-blocking lesions are repaired before transcription can recover. Failure in DNA damage repair will cause genome instability and cell death. Although recent studies have expanded our understanding of RNA polymerase II regulation confronting DNA lesions, it is still not always clear what the direct contribution of RNA polymerase II is in the DNA damage repair processes. In this review, we focus on how RNA polymerase II and transcription are both repressed by transcription stalling lesions such as DNA-adducts and double strand breaks, as well as how they are actively regulated to support the cellular response to DNA damage and favour the repair of lesions.

In accordance with the endosymbiotic theory, mitochondrial components bear characteristic prokaryotic signatures, which act as immunomodulatory molecules when released into the extramitochondrial compartment. These endogenous immune triggers, called mitochondrial damage-associated molecular patterns (mtDAMPs), have been implicated in the pathogenesis of various diseases, yet their role remains largely unexplored. In this review, we summarise the available literature on mtDAMPs in diseases, with a special focus on respiratory diseases. We highlight the need to bolster mtDAMP research using a multipronged approach, to study their effect on specific cell types, receptors and machinery in pathologies. We emphasise the lacunae in the current understanding of mtDAMPs, particularly in their cellular release and the chemical modifications they undergo. Finally, we conclude by proposing additional effects of mtDAMPs in diseases, specifically their role in modulating the immune system.

Obesity and ageing predispose to numerous, yet overlapping chronic diseases. For example, metabolic abnormalities, including insulin resistance (IR) and type 2 diabetes (T2D) are important causes of morbidity and mortality. Low-grade chronic inflammation of tissues, such as the liver, visceral adipose tissue and neurological tissues, is considered a significant contributor to these chronic diseases. Thus, it is becoming increasingly important to understand what drives this inflammation in affected tissues. Recent evidence, especially in the context of obesity, suggests that the intestine plays an important role as the gatekeeper of inflammatory stimuli that ultimately fuels low-grade chronic tissue inflammation. In addition to metabolic diseases, abnormalities in the intestinal mucosal barrier have been linked to a range of other chronic inflammatory conditions, such as neurodegeneration and ageing. The flow of inflammatory stimuli from the gut is in part controlled by local immunological inputs impacting the intestinal barrier. Here, we will review the impact of obesity and ageing on the intestinal immune system and its downstream consequences on gut barrier function, which is strongly implicated in the pathogenesis of obesity and age-related diseases. In particular, we will discuss the effects of age-related intestinal dysfunction on neurodegenerative diseases.

A primary goal of biomedical research is to elucidate molecular mechanisms, particularly those responsible for human traits, either normal or pathological. Yet achieving this goal is difficult if not impossible when the traits of interest lack tractable models and so cannot be dissected through time-honoured approaches like forward genetics or reconstitution. Arguably, no biological problem has hindered scientific progress more than this: the inability to dissect a trait's mechanism without a tractable likeness of the trait. At root, forward genetics and reconstitution are powerful approaches because they assay for specific molecular functions. Here, we discuss an alternative way to uncover important mechanistic interactions, namely, to assay for positive natural selection. If an interaction has been selected for, then it must perform an important function, a function that significantly promotes reproductive success. Accordingly, selection is a consequence and indicator of function, and uncovering multimolecular selection will reveal important functional interactions. We propose a selection signature for interactions and review recent selection-based approaches through which to dissect traits that are not inherently tractable. The review includes proof-of-principle studies in which important interactions were uncovered by screening for selection. In sum, screens for selection appear feasible when screens for specific functions are not. Selection screens thus constitute a novel tool through which to reveal the mechanisms that shape the fates of organisms.

Amyloid formation is a misfolding process that has been linked to age-related diseases, including Alzheimer's and Huntington's. Understanding how cellular factors affect this process in vivo is vital in realizing the dream of controlling this insidious process that robs so many people of their humanity. SERF (small EDRK-rich factor) was initially isolated as a factor that accelerated polyglutamine amyloid formation in a C. elegans model. SERF knockouts inhibit amyloid formation of a number of proteins that include huntingtin, α-synuclein and β-amyloid which are associated with Huntington's, Parkinson's and Alzheimer's disease, respectively, and purified SERF protein speeds their amyloid formation in vitro. SERF proteins are highly conserved, highly charged and conformationally dynamic proteins that form a fuzzy complex with amyloid precursors. They appear to act by specifically accelerating the primary step of amyloid nucleation. Brain-specific SERF knockout mice, though viable, appear to be more prone to deposition of amyloids, and show modified fibril morphology. Whole-body knockouts are perinatally lethal due to an apparently unrelated developmental issue. Recently, it was found that SERF binds RNA and is localized to nucleic acid-rich membraneless compartments. SERF-related sequences are commonly found fused to zinc finger sequences. These results point towards a nucleic acid-binding function. How this function relates to their ability to accelerate amyloid formation is currently obscure. In this review, we discuss the possible biological functions of SERF family proteins in the context of their structural fuzziness, modulation of amyloid pathway, nucleic acid binding and their fusion to folded proteins.

Astrocytes are increasingly gaining attention as a major player in regulating brain functions. Not only are astrocytes important for their supporting roles in maintaining optimal neuronal activity, they also dynamically interact with synapses through their highly ramified morphology to directly influence information processing by the neural circuits and the behaviours that depend on it. Here, we take a close look at astrocyte-synapse interactions involved in the coordination of synaptogenesis and astrocyte maturation in the developing brain through to the contribution of astrocytes in synaptic plasticity in the adult brain, and end with a perspective on astrocyte function in behaviours and diseases. In particular, we focus on the roles of synapse adhesion proteins. While cell adhesion proteins that form a bridge between the presynaptic and the postsynaptic compartments have been extensively studied, recent reports highlighting the striking participation of astrocytic cell adhesion proteins in synapse formation and function underscores the importance of reconsidering the conventional neurocentric view of synaptic adhesive interactions and the underlying logic.