Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.     

Citrate,Beneficial or Deleterious in the CNS?

Cerebellar granule neurons were incubated with or without glucose (3 mM) in the presence or absence of citrate (20 mM) using normoxic and/or hypoxic incubation conditions. During 4 h of hypoglycemia and also during hypoxia plus hypoglycemia, citrate increased lactate dehydrogenase (LDH) leakage from the cells and decreased mitochondrial activity, the latter was also the case in the presence of glucose. After 24 h of hypoglycemia, however, citrate decreased LDH leakage slightly, possibly due to its metabolism in the tricarboxylic acid cycle under these conditions. It should be noted that during mild hypoxia plus hypoglycemia a reduced LDH leakage was observed when compared to hypoglycemia alone. The 4 h low oxygen period did protect the neurons also during the 20 h re-oxygenation period. The present study might indicate that incubation of brain cell cultures in an atmosphere of air (30% oxygen) and 5% CO₂, which is used in most laboratories, can be toxic and that oxygen concentration should be lowered considerably to mimic conditions in the brain.     

Uncoupling proteins: A role in protection against reactive oxygen species—or not?

A physiological function of the original uncoupling protein, UCP1, is well established: UCP1 is the molecular background for nonshivering thermogenesis. The functions of the “novel” UCPs, UCP2 and UCP3, are still not established. Recent discussions imply that all UCPs may play a role in protection against reactive oxygen species (ROS). Here we examine critically the evidence that UCP1, UCP2 and UCP3 are stimulated by ROS (superoxide) or ROS products (4-hydroxy-2-nonenal), and that the UCPs actually diminish oxidative damage. We conclude that, concerning UCP1, it is unlikely that it has such a role; concerning UCP2/UCP3, most evidence for physiologically significant roles in this respect is still circumstantial.     

Primary or secondary? Versatile nitrilases in plant metabolism

The potential of plant nitrilases to convert indole-3-acetonitrile into the plant growth hormone indole-3-acetic acid has earned them the interim title of "key enzyme in auxin biosynthesis". Although not widely recognized, this view has changed considerably in the last few years. Recent work on plant nitrilases has shown them to be involved in the process of cyanide detoxification, in the catabolism of cyanogenic glycosides and presumably in the catabolism of glucosinolates. All plants possess at least one nitrilase that is homologous to the nitrilase 4 isoform of Arabidopsis thaliana. The general function of these nitrilases lies in the process of cyanide detoxification, in which they convert the intermediate detoxification product beta-cyanoalanine into asparagine, aspartic acid and ammonia. Cyanide is a metabolic by-product in biosynthesis of the plant hormone ethylene, but it may also be released from cyanogenic glycosides, which are present in a large number of plants. In Sorghum bicolor, an additional nitrilase isoform has been identified, which can directly use a catabolic intermediate of the cyanogenic glycoside dhurrin, thus enabling the plant to metabolize its cyanogenic glycoside without releasing cyanide. In the Brassicaceae, a family of nitrilases has evolved, the members of which are able to hydrolyze catabolic products of glucosinolates, the predominant secondary metabolites of these plants. Thus, the general theme of nitrilase function in plants is detoxification and nitrogen recycling, since the valuable nitrogen of the nitrile group is recovered in the useful metabolites asparagine or ammonia. Taken together, a picture emerges in which plant nitrilases have versatile functions in plant metabolism, whereas their importance for auxin biosynthesis seems to be minor.     

Digest: Pursue or ambush? Phenotypic disparity in the carnivore forelimb*

The way an animal moves reveals key aspects of its ecology. Carnivore forelimbs are adapted to their predation style, and the structure of the elbow joint can indicate hunting strategy. In this issue, Figueirido (2018) investigates phenotypic disparity, or morphological variation, in domestic dog breeds, the canid family, and the carnivore order using the elbow joint as an indicator of movement and predatory behavior.     

Endotoxin recognition: in fish or not in fish?

The interaction between pathogens and their multicellular hosts is initiated by activation of pathogen recognition receptors (PRRs). These receptors, that include most notably members of the toll-like receptor (TLR) family, recognize specific pathogen-associated molecular patterns (PAMPs). TLR4 is a central part of the receptor complex that is involved in the activation of the immune system by lipopolysaccharide (LPS) through the specific recognition of its endotoxic moiety (Lipid A). This is a critical event that is essential for the immune response to Gram-negative bacteria as well as the etiology of endotoxic shock. Interestingly, compared to mammals, fish are resistant to endotoxic shock. This in vivo resistance concurs with in vitro studies demonstrating significantly lowered sensitivity of fish leukocytes to LPS activation. Further, our in vitro analyses demonstrate that in trout mononuclear phagocytes, LPS fails to induce antiviral genes, an event that occurs downstream of TLR4 and is required for the development of endotoxic shock. Finally, an in silico approach that includes mining of different piscine genomic and EST databases, reveals the presence in fish of all of the major TLR signaling elements except for the molecules specifically involved in TLR4-mediated endotoxin recognition and signaling in mammals. Collectively, our analysis questions the existence of TLR4-mediated cellular responses to LPS in fish. We further speculate that other receptors, in particular beta-2 integrins, may play a primary role in the activation of piscine leukocytes by LPS.     

The roles of ABA in plant–pathogen interactions

Defence against abiotic and biotic stresses is crucial for the fitness and survival of plants under adverse or suboptimal growth conditions. The phytohormone abscisic acid (ABA) is not only important for mediating abiotic stress responses, but also plays a multifaceted and pivotal role in plant immunity. This review presents examples demonstrating the importance of crosstalk between ABA and the key biotic stress phytohormone salicylic acid in determining the outcome of plant–pathogen interactions. We then provide an overview of how ABA influences plant defence responses against various phytopathogens with particular emphasis on the Arabidopsis–Pseudomonas syringae model pathosystem. Lastly, we discuss future directions for studies of ABA in plant immunity with emphasis on, its role in the crosstalk between biotic and abiotic stress responses, the importance of distinguishing direct and indirect effects of ABA, as well as the prospect of utilizing the recently elucidated core ABA signaling network to gain further insights into the roles of ABA in plant immunity.     

Jasmonate in plant defence: sentinel or double agent?

Plants and their biotic enemies, such as microbial pathogens and herbivorous insects, are engaged in a desperate battle which would determine their survival–death fate. Plants have evolved efficient and sophisticated systems to defend against such attackers. In recent years, significant progress has been made towards a comprehensive understanding of inducible defence system mediated by jasmonate (JA), a vital plant hormone essential for plant defence responses and developmental processes. This review presents an overview of JA action in plant defences and discusses how microbial pathogens evade plant defence system through hijacking the JA pathway.     

Signaling in the plant cytosol: cysteine or sulfide?

Cysteine (Cys) is the first organic compound containing reduced sulfur that is synthesized in the last stage of plant photosynthetic assimilation of sulfate. It is a very important metabolite not only because it is crucial for the structure, function and regulation of proteins but also because it is the precursor molecule of an enormous number of sulfur-containing metabolites essential for plant health and development. The biosynthesis of Cys is accomplished by the sequential reaction of serine acetyltransferase (SAT) and O-acetylserine(thiol)synthase (OASTL). In Arabidopsis thaliana, the analysis of specific mutants of members of the SAT and OASTL families has demonstrated that the cytosol is the compartment where the bulk of Cys synthesis takes place and that the cytosolic OASTL enzyme OAS-A1 is the responsible enzyme. Another member of the OASTL family is DES1, a novel l-cysteine desulfhydrase that catalyzes the desulfuration of Cys to produce sulfide, thus acting in a manner opposite to that of OAS-A1. Detailed studies of the oas-a1 and des1 null mutants have revealed the involvement of the DES1 and OAS-A1 proteins in coordinate regulation of Cys homeostasis and the generation of sulfide in the cytosol for signaling purposes. Thus, the levels of Cys in the cytosol strongly affect plant responses to both abiotic and biotic stress conditions, while sulfide specifically generated from the degradation of Cys negatively regulates autophagy induced in different situations. In conclusion, modulation of the levels of Cys and sulfide is likely critical for plant performance.     

TPX or not TPX?

An Aurora A regulatory module has been identified in two different proteins: TPX2 in Xenopus laevis and TPXL-1 in C. elegans. The diverse roles of these two proteins in spindle assembly leave us to beckon the true C. elegans TPX2 ortholog to center stage.     

Salt-induced oxidative stress in rosemary plants: Damage or protection?

Mechanisms of photoprotection and antioxidant protection, including changes in chlorophylls, xanthophyll cycle components and levels of low-molecular-weight chloroplastic antioxidants (lutein, β-carotene and α-tocopherol) were studied together with levels of malondialdehyde, a product of lipid peroxidation, in the response of rosemary (Rosmarinus officinalis L.) plants to salt stress. Plants were exposed to increasing NaCl concentrations (50, 100 and 150 mM) for 6 weeks, and two concentrations of the following chloride salts: KCl, CaCl₂, MgCl₂ and FeCl₃, were used together with 100 mM NaCl to explore the extent to which these salts can alter the mechanisms of photoprotection, antioxidant protection and malondialdehyde accumulation in leaves. Increasing concentrations of NaCl decreased leaf water contents and photosynthetic pigment levels, while the contents of α-tocopherol and malondialdehyde increased, but with completely different kinetics. α-Tocopherol levels increased in a dose-dependent manner as stress progressed, while malondialdehyde levels increased at the highest dose (150 mM NaCl) but only during early phases of stress. Furthermore, although the addition of chloride salts to NaCl-treated plants apparently improved leaf physiological status, in terms of water and chlorophyll contents, plants showed an increased photoprotective demand and increased oxidative stress, particularly in FeCl₃-treated plants. It is concluded that (i) rosemary plants can withstand moderate doses of NaCl in the medium (at least 150 mM NaCl for 6 weeks), (ii) oxidative stress may be a mechanism for protecting plants from moderate doses of salt stress rather than causing damage to plants, and (iii) the addition of chloride salts to NaCl-treated plants may dramatically increase the photoprotective demand and oxidative stress of leaves, while plant growth is not negatively affected.     

Autism: not interested or not 'tuned-in'?

Recent studies of perceptual adaptation to faces have revolutionised our understanding of neural mechanisms that support face recognition. A new study has applied this approach to autistic spectrum disorders, revealing severe deficits in such adaptation.     

Uncoupling proteins: a role in protection against reactive oxygen species--or not?

A physiological function of the original uncoupling protein, UCP1, is well established: UCP1 is the molecular background for nonshivering thermogenesis. The functions of the "novel" UCPs, UCP2 and UCP3, are still not established. Recent discussions imply that all UCPs may play a role in protection against reactive oxygen species (ROS). Here we examine critically the evidence that UCP1, UCP2 and UCP3 are stimulated by ROS (superoxide) or ROS products (4-hydroxy-2-nonenal), and that the UCPs actually diminish oxidative damage. We conclude that, concerning UCP1, it is unlikely that it has such a role; concerning UCP2/UCP3, most evidence for physiologically significant roles in this respect is still circumstantial.     

Pup mortality in laboratory mice – infanticide or not?

Background

Despite being the most commonly used mammal in biomedical research, problems with perinatal mortality in mice have received little attention and the causes of pup death are still poorly known. Females are often housed alone with their litters and since the lost pups are generally eaten, it is commonly assumed that the mother has killed them. However, more detailed observations than have been reported previously in the literature are required to establish if the cause of death is infanticide. Litter loss can only be prevented efficiently after underlying causes have been carefully investigated and interpreted. The aim of this study was to investigate if females actively kill their pups by observing the behaviour of females and pups in litters that later were lost. We used video recordings of females that lost their entire litter to observe females in detail from parturition until the pups died. In total, 10 C57BL/6 females (wildtype and the knockouts Hfe^?/? and β2m^?/?) were studied, housed in Makrolon II cages with or without access to a small amount of nesting material.

Results

Three of the females had pups that were never seen moving, and another three females had one or two pups that never moved, indicating that some pups were most likely still-born. In five females with live-born pups, detailed observations from the time when a pup was last seen moving until it died were possible to carry out. We observed females eating dead offspring and interacting with both moving and dead pups. However, we never observed a pup stop moving when manipulated by the female, nor were any wounds seen in the pups. Hence, we found no evidence of infanticide when studying females that had lost their entire litter.

Conclusion

These results suggest that other causes than infanticide plays a major role in mouse pup death, and stress the need for more systematic and careful investigations of the causality of litter loss.

     

Extinction debt in fragmented grasslands: paid or not?

Fragmentation of grasslands and forests is considered a major threat to biodiversity. In the case of plants, the effect of fragmentation or landscape context is still unclear and published results are divergent. One explanation for this divergence is the slow response of long‐lived plants, creating an extinction debt. However, this has not been empirically confirmed. In this study, data were compiled from broad‐scale studies of grasslands from throughout the world that relate plant diversity to fragmentation effects. Only seven studies from northern Europe, out of a total 61, gave any information on actual habitat fragmentation in time and space. In landscapes with >10% grassland remaining, present‐day species richness was related to past landscape or habitat pattern. In landscapes with <10% grassland remaining, in contrast, plant species richness was more related to contemporary landscape or habitat pattern. Studies from landscapes with >10% grassland remaining supported the concept of an extinction debt, while studies from more fragmented landscapes did not provide any evidence of an extinction debt. In order to make generalisations about historical legacies on species diversity in grasslands it is important to consider a range of highly transformed landscapes, and not only landscapes with a high amount of grassland remaining.     

Genome-wide association studies in plant pathosystems: success or failure?

Harnessing natural genetic variation is an established alternative to artificial genetic variation for investigating the molecular dialog between partners in plant pathosystems. Herein, we review the successes of genome-wide association studies (GWAS) in both plants and pathogens. While GWAS in plants confirmed that the genetic architecture of disease resistance is polygenic, dynamic during the infection kinetics, and dependent on the environment, GWAS shortened the time of identification of quantitative trait loci (QTLs) and revealed both complex epistatic networks and a genetic architecture dependent upon the geographical scale. A similar picture emerges from the few GWAS in pathogens. In addition, the ever-increasing number of functionally validated QTLs has revealed new molecular plant defense mechanisms and pathogenicity determinants. Finally, we propose recommendations to better decode the disease triangle.     

To check or not to check? The application of meiotic studies to plant breeding

Understanding the barriers that prevent pairing and recombination of the chromosomes from two parental species is important for crop improvement strategies. It had been generally thought that plants do not possess checkpoint mechanisms during meiosis. However, recent data may question this assumption and suggest that exploitation of such mechanisms could be crucial to breeding.     

Climate mediates roles of pollinator species in plant–pollinator networks

Aim

Understanding how climate conditions influence plant–pollinator interactions at the global scale is crucial to understand how pollinator communities and ecosystem function respond to environmental change. Here, we investigate whether climate drives differences in network roles of the main insect pollinator orders: Diptera, Coleoptera, Lepidoptera and Hymenoptera.

Location

Global.

Time period

1968–2020.

Major taxa studied

Diptera, Coleoptera, Lepidoptera and Hymenoptera.

Methods

We collated plant–pollinator networks from 26 countries and territories across the five main Köppen–Geiger climate zones. In total, we compiled data from 101 networks that included >1500 plant species from 167 families and >2800 pollinator species from 163 families. We assessed differences in the composition of plant–pollinator interactions among climate zones using a permutational ANOVA. We calculated standard network metrics for pollinator taxonomic groups and used Bayesian generalized mixed models to test whether climate zone influenced the proportion of pollinator network links and the level of pollinator generalism.

Results

We found that climate is a strong driver of compositional dissimilarities between plant–pollinator interactions. Relative to other taxa, bees and flies made up the greatest proportion of network links across climate zones. When network size was accounted for, bees were the most generalist pollinator group in the tropics, whereas non-bee Hymenoptera were the most generalist in arid zones, and syrphid flies were the most generalist in polar networks.

Main conclusions

We provide empirical evidence at the global scale that climate strongly influences the roles of different pollinator taxa within networks. Importantly, non-bee taxa, particularly flies, play central network roles across most climate zones, despite often being overlooked in pollination research and conservation. Our results identify the need for greater understanding of how global environmental change affects plant–pollinator interactions.     

Vacuolar membrane structures and their roles in plant–pathogen interactions

Plant Molecular Biology - Short review focussing on the role and targeting of vacuolar substructure in plant immunity and pathogenesis. Plants lack specialized immune cells, therefore each plant...