The neutralizing effect of heparin on blood-derived antimicrobial compounds: impact on antibacterial activity and inflammatory response.

Acting through a combination of direct and indirect pathogen clearance mechanisms, blood-derived antimicrobial compounds (AMCs) play a pivotal role in innate immunity, safeguarding the host against invading microorganisms. Besides their antimicrobial activity, some AMCs can neutralize endotoxins, preventing their interaction with immune cells and avoiding an excessive inflammatory response. In this study, we aimed to investigate the influence of unfractionated heparin, a polyanionic drug clinically used as anticoagulant, on the endotoxin-neutralizing and antibacterial activity of blood-derived AMCs. Serum samples from healthy donors were pre-incubated with increasing concentrations of heparin for different time periods and tested against pathogenic bacteria (Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus) and endotoxins from E. coli, K. pneumoniae, and P. aeruginosa. Heparin dose-dependently decreased the activity of blood-derived AMCs. Consequently, pre-incubation with heparin led to increased activity of LPS and higher values of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Accordingly, higher concentrations of A. baumannii, E. coli, K. pneumoniae, and P. aeruginosa were observed as well. These findings underscore the neutralizing effect of unfractionated heparin on blood-derived AMCs in vitro and may lead to alternative affinity techniques for isolating and characterizing novel AMCs with the potential for clinical translation.

Distinct members of the Caenorhabditis elegans CeMbio reference microbiota exert cryptic virulence that is masked by host defense.

Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each distinct community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health and vice versa. Recently, a reference 12-member microbiota for the model organism Caenorhabditis elegans, known as CeMbio, was defined. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct CeMbio members differed in their ability to activate the PMK-1/p38 pathway, the ability to do so did not correlate with bacterial-induced lifespan reduction in wild-type or immunodeficient animals. In contrast, most species activated HLH-30/TFEB and showed virulence toward hlh-30-deficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host's lifespan if host defense is compromised and that HLH-30/TFEB is a fundamental and key host protective factor.

Changes in Induced-Antipredation Defense Traits and Transcriptome Regulations of Daphnia magna in Response to 5-HT1A Receptor Antagonist.

The serotonin signaling system plays a crucial role in regulating the ontogeny of crustaceans. Here, we describe the effects of different concentrations of the 5-hydroxytryptamine 1A receptor antagonist (WAY-100635) on the induced antipredation (Rhodeus ocellatus as the predator), morphological, behavioral, and life-history defenses of Daphnia magna and use transcriptomics to analyze the underlying molecular mechanisms. Our results indicate that exposure to WAY-100635 leads to changes in the expression of different defensive traits in D. magna when faced with fish predation risks. Specifically, as the length of exposure to WAY-100635 increases, high concentrations of WAY-100635 inhibit defensive responses associated with morphological and reproductive activities but promote the immediate negative phototactic behavioral defense of D. magna. This change is related to the underlying mechanism through which WAY-100635 interferes with gene expression of G-protein-coupled GABA receptors by affecting GABBR1 but promotes serotonin receptor signaling and ecdysteroid signaling pathways. In addition, we also find for the first time that fish kairomone can significantly activate the HIF-1α signaling pathway, which may lead to an increase in the rate of immediate movement. These results can help assess the potential impacts of serotonin-disrupting psychotropic drugs on zooplankton in aquatic ecosystems.

The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection.

During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.

Intensive short-term dynamic psychotherapy for irritable bowel syndrome: a randomized controlled trial examining improvements in emotion regulation, defense mechanisms, quality of life, and IBS symptoms.

Studies have provided evidence for the effectiveness of intensive short-term dynamic psychotherapy (ISTDP) in treating medically unexplained symptoms (MUS). This study aimed to examine the effectiveness of ISTDP on individuals living with irritable bowel syndrome (IBS) in terms of, emotion regulation (ER) abilities, defense mechanisms, quality of life (QOL), and IBS symptoms. A total of 30 patients diagnosed with IBS were recruited and randomly assigned to either the intervention (n = 15) or control (n = 15) group. Pre- and post-treatment assessments were conducted, along with a follow-up assessment after ten weeks. Repeated measures analyses of variance were employed to analyze the data. The findings revealed that ISTDP led to significant improvements in ER, defense mechanisms, and QOL, as well as a reduction in the severity and frequency of IBS symptoms. These results provide further support for the efficacy of ISTDP as a treatment modality for individuals with IBS.

Criminal Defense Attorneys and Client Suicide: Survey and Recommendations From Washington State.

The connection between suicide and incarceration is well documented, in particular after recent arrest. Criminal defense attorneys may be one of the few people in meaningful contact with this population, and lawyers have a unique window into their clients' well-being. In this Viewpoint, we explore the experiences of attorneys who work with clients with suicidal thoughts and behaviors. We developed and administered a survey to criminal defense attorneys in the State of Washington, ascertaining their experiences with client suicide. A total of 44 responses were collected, with over 95% of respondents having been concerned about a client's risk for suicide. We conclude that client suicide widely impacts criminal defense attorneys, and lawyers' role with justice-involved clients uniquely positions them to be a potential asset in suicide prevention efforts.

Endogenous IAA affected fluoranthene accumulation by regulating H+-ATPase and SOD activity in ryegrass.

This study explores the role of endogenous indole-3-acetic acid (IAA) in modulating plant responses to pollution stress and its effect on pollutant accumulation, with a focus on fluoranthene (Flu) in ryegrass. To elucidate the mechanism, we employed an IAA promoter (α-aminobutyric acid [α-AB]) and an IAA inhibitor (naphthylphthalamic acid [NPA]) to regulate IAA levels and analyze Flu uptake characteristics. The experimental setup included a Flu treatment group (ryegrass with Flu addition) and a control group (ryegrass without Flu). Our findings demonstrate that Flu treatment enhanced IAA content and plant growth in ryegrass compared to the control. The Flu+AB treatment further enhanced these effects, while the Flu+NPA treatment exhibited a contrasting trend. Moreover, Flu+AB treatment led to increased Flu accumulation, in contrast to the inhibitory effect observed with Flu+NPA treatment. Flu treatment also enhanced the activities of key antioxidant enzymes (SOD, POD, CAT) and increased soluble sugar and protein levels, indicative of enzymatic and nonenzymatic defense responses, respectively. The Flu+AB treatment amplified these responses, whereas the Flu+NPA treatment attenuated them. Significantly, Flu treatment raised H+-ATPase activity compared to the control, an effect further elevated by Flu+AB treatment and diminished by Flu+NPA treatment. A random forest analysis suggested that Flu accumulation dependency varied under different treatments: it relied more on H+-ATPase activity under Flu+AB treatment and more on SOD activity under Flu+NPA treatment. Additionally, Flu+AB treatment boosted the transpiration rate in ryegrass, thereby increasing the Flu translocation factor, a trend reversed by Flu+NPA treatment. This research highlights crucial factors influencing Flu accumulation in ryegrass, offering potential new avenues for controlling the gathering of contaminants within plant systems.

Silencing an ATP-Dependent Caseinolytic Protease Proteolytic Subunit Gene Enhances the Resistance of Rice to Nilaparvata lugens.

The ATP-dependent caseinolytic protease (Clp) system has been reported to play an important role in plant growth, development, and defense against pathogens. However, whether the Clp system is involved in plant defense against herbivores remains largely unclear. We explore the role of the Clp system in rice defenses against brown planthopper (BPH) Nilaparvata lugens by combining chemical analysis, transcriptome, and molecular analyses, as well as insect bioassays. We found the expression of a rice Clp proteolytic subunit gene, OsClpP6, was suppressed by infestation of BPH gravid females and mechanical wounding. Silencing OsClpP6 enhanced the level of BPH-induced jasmonic acid (JA), JA-isoleucine (JA-Ile), and ABA, which in turn promoted the production of BPH-elicited rice volatiles and increased the resistance of rice to BPH. Field trials showed that silencing OsClpP6 decreased the population densities of BPH and WBPH. We also observed that silencing OsClpP6 decreased chlorophyll content in rice leaves at early developmental stages and impaired rice root growth and seed setting rate. These findings demonstrate that an OsClpP6-mediated Clp system in rice was involved in plant growth-defense trade-offs by affecting the biosynthesis of defense-related signaling molecules in chloroplasts. Moreover, rice plants, after recognizing BPH infestation, can enhance rice resistance to BPH by decreasing the Clp system activity. The work might provide a new way to breed rice varieties that are resistant to herbivores.

Molecular characterization and evaluation of novel management options for Burkholderia glumae BG1, the causative agent of panicle blight of rice (Oryza sativa L.).

BACKGROUND: Bacterial panicle blight, incited by Burkholderia glumae, has impacted rice production globally. Despite its significance, knowledge about the disease and the virulence pattern of the causal agent is very limited. Bacterial panicle blight is a major challenge in the rice-growing belts of North-western India, resulting in yield reduction. However, the management of B. glumae has become a challenge due to the lack of proper management strategies. METHODOLOGY AND RESULTS: Twenty-one BG strains have been characterized using the 16S rRNA and the gyrB gene-based sequence approach in the present study. The gyrB gene-based phylogenetic analysis resulted in geographic region-specific clustering of the BG isolates. The virulence screening of twenty-one BG strains by inoculating the pathogenic bacterial suspension of 1 × 10-8 cfu/ml at the booting stage (55 DAT) revealed the variation in the disease severity and the grain yield of rice plants. The most virulent BG1 strain resulted in the highest disease incidence (82.11%) and lowest grain yield (11.12 g/plant), and the least virulent BG10 strain resulted in lowest disease incidence of 18.94% and highest grain yield (24.62 g/plant). In vitro evaluation of various biocontrol agents and nano copper at different concentrations by agar well diffusion method revealed that nano copper at 1000 mg/L inhibited the colony growth of B. glumae. Under net house conditions, nano copper at 1000 mg/L reduced the disease severity to 21.23% and increased the grain yield by 20.91% (31.76 g per plant) compared to the positive control (COC 0.25% + streptomycin 200 ppm). Remarkably, pre-inoculation with nano copper at 1000 mg/L followed by challenge inoculation with B. glumae enhanced the activity of enzymatic antioxidants viz., Phenyl ammonia-lyase (PAL), Polyphenol oxidase (PPO) and Peroxidase (POX) and non-enzymatic antioxidant phenol. Additionally, we observed a substantial transcript level upregulation of six defense-related genes to several folds viz., OsPR2, OsPR5, OsWRKY71, OsPAL1, OsAPX1, and OsPPO1 in comparison to the pathogen control and healthy control. CONCLUSIONS: Overall, our study provides valuable insights into the potential and practical application of nano copper for the mitigation of bacterial panicle blight, offering promising prospects for commercial utilization in disease management.

Mitochondria and Reactive Oxygen Species: The Therapeutic Balance of Powers for Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic progressive muscle-wasting disorder that leads to rapid loss of mobility and premature death. The absence of functional dystrophin in DMD patients reduces sarcolemma stiffness and increases contraction damage, triggering a cascade of events leading to muscle cell degeneration, chronic inflammation, and deposition of fibrotic and adipose tissue. Efforts in the last decade have led to the clinical approval of novel drugs for DMD that aim to restore dystrophin function. However, combination therapies able to restore dystrophin expression and target the myriad of cellular events found impaired in dystrophic muscle are desirable. Muscles are higher energy consumers susceptible to mitochondrial defects. Mitochondria generate a significant source of reactive oxygen species (ROS), and they are, in turn, sensitive to proper redox balance. In both DMD patients and animal models there is compelling evidence that mitochondrial impairments have a key role in the failure of energy homeostasis. Here, we highlighted the main aspects of mitochondrial dysfunction and oxidative stress in DMD and discussed the recent findings linked to mitochondria/ROS-targeted molecules as a therapeutic approach. In this respect, dual targeting of both mitochondria and redox homeostasis emerges as a potential clinical option in DMD.

Development of Menthyl Esters of Valine for Pest Control in Tomato and Lettuce Crops.

Menthyl ester of valine (MV) has been developed as a plant defense potentiator to induce pest resistance in crops. In this study, we attempted to establish MV hydrochloride (MV-HCl) in lettuce and tomato crops. When MV-HCl solutions were used to treat soil or leaves of potted tomato and lettuce plants, 1 µM MV-HCl solution applied to potted plant soil was most effective in increasing the transcript level of defense genes such as pathogenesis-related 1 (PR1). As a result, leaf damage caused by Spodoptera litura and oviposition by Tetranychus urticae were significantly reduced. In addition, MV-HCl-treated plants showed an increased ability to attract Phytoseiulus persimilis, a predatory mite of T. urticae, when they were attacked by T. urticae. Overall, our findings showed that MV-HCl is likely to be effective in promoting not only direct defense by activating defense genes, but also indirect defense mediated by herbivore-induced plant volatiles. Moreover, based on the results of the sustainability of PR1 expression in tomato plants treated with MV-HCl every 3 days, field trials were conducted and showed a 70% reduction in natural leaf damage. Our results suggest a practical approach to promoting organic tomato and lettuce production using this new plant defense potentiator.

Evidence for Reductions in Physical and Chemical Plant Defense Traits in Island Flora.

Reduced defense against large herbivores has been suggested to be part of the "island syndrome" in plants. However, empirical evidence for this pattern is mixed. In this paper, we present two studies that compare putative physical and chemical defense traits from plants on the California Channel Islands and nearby mainland based on sampling of both field and common garden plants. In the first study, we focus on five pairs of woody shrubs from three island and three mainland locations and find evidence for increased leaf area, decreased marginal leaf spines, and decreased concentrations of cyanogenic glycosides in island plants. We observed similar increases in leaf area and decreases in defense traits when comparing island and mainland genotypes grown together in botanic gardens, suggesting that trait differences are not solely driven by abiotic differences between island and mainland sites. In the second study, we conducted a common garden experiment with a perennial herb-Stachys bullata (Lamiaceae)-collected from two island and four mainland locations. Compared to their mainland relatives, island genotypes show highly reduced glandular trichomes and a nearly 100-fold reduction in mono- and sesquiterpene compounds from leaf surfaces. Island genotypes also had significantly higher specific leaf area, somewhat lower rates of gas exchange, and greater aboveground biomass than mainland genotypes across two years of study, potentially reflecting a broader shift in growth habit. Together, our results provide evidence for reduced expression of putative defense traits in island plants, though these results may reflect adaptation to both biotic (i.e., the historical absence of large herbivores) and climatic conditions on islands.

The other side of the coin: systemic effects of Serendipita indica root colonization on development of sedentary plant-parasitic nematodes in Arabidopsis thaliana.

MAIN CONCLUSION: Upon systemic S. indica colonization in split-root system cyst and root-knot nematodes benefit from endophyte-triggered carbon allocation and altered defense responses what significantly facilitates their development in A. thaliana. Serendipita indica is an endophytic fungus that establishes mutualistic relationships with different plants including Arabidopsis thaliana. It enhances host's growth and resistance to different abiotic and biotic stresses such as infestation by the cyst nematode Heterodera schachtii (CN). In this work, we show that S. indica also triggers similar direct reduction in development of the root-knot nematode Meloidogyne javanica (RKN) in A. thaliana. Further, to mimick the natural situation occurring frequently in soil where roots are unequally colonized by endophytes we used an in vitro split-root system with one half of A. thaliana root inoculated with S. indica and the other half infected with CN or RKN, respectively. Interestingly, in contrast to direct effects, systemic effects led to an increase in number of both nematodes. To elucidate this phenomenon, we focused on sugar metabolism and defense responses in systemic non-colonized roots of plants colonized by S. indica. We analyzed the expression of several SUSs and INVs as well as defense-related genes and measured sugar pools. The results show a significant downregulation of PDF1.2 as well as slightly increased sucrose levels in the non-colonized half of the root in three-chamber dish. Thus, we speculate that, in contrast to direct effects, both nematode species benefit from endophyte-triggered carbon allocation and altered defense responses in the systemic part of the root, which promotes their development. With this work, we highlight the complexity of this multilayered tripartite relationship and deliver new insights into sugar metabolism and plant defense responses during S. indica-nematode-plant interaction.

The role of microbial partners in heavy metal metabolism in plants: a review.

Heavy metal pollution threatens plant growth and development as well as ecological stability. Here, we synthesize current research on the interplay between plants and their microbial symbionts under heavy metal stress, highlighting the mechanisms employed by microbes to enhance plant tolerance and resilience. Several key strategies such as bioavailability alteration, chelation, detoxification, induced systemic tolerance, horizontal gene transfer, and methylation and demethylation, are examined, alongside the genetic and molecular basis governing these plant-microbe interactions. However, the complexity of plant-microbe interactions, coupled with our limited understanding of the associated mechanisms, presents challenges in their practical application. Thus, this review underscores the necessity of a more detailed understanding of how plants and microbes interact and the importance of using a combined approach from different scientific fields to maximize the benefits of these microbial processes. By advancing our knowledge of plant-microbe synergies in the metabolism of heavy metals, we can develop more effective bioremediation strategies to combat the contamination of soil by heavy metals.

Small particles, big effects: How nanoparticles can enhance plant growth in favorable and harsh conditions.

By 2050, the global population is projected to reach 9 billion, underscoring the imperative for innovative solutions to increase grain yield and enhance food security. Nanotechnology has emerged as a powerful tool, providing unique solutions to this challenge. Nanoparticles (NPs) can improve plant growth and nutrition under normal conditions through their high surface-to-volume ratio and unique physical and chemical properties. Moreover, they can be used to monitor crop health status and augment plant resilience against abiotic stresses (such as salinity, drought, heavy metals, and extreme temperatures) that endanger global agriculture. Application of NPs can enhance stress tolerance mechanisms in plants, minimizing potential yield losses and underscoring the potential of NPs to raise crop yield and quality. This review highlights the need for a comprehensive exploration of the environmental implications and safety of nanomaterials and provides valuable guidelines for researchers, policymakers, and agricultural practitioners. With thoughtful stewardship, nanotechnology holds immense promise in shaping environmentally sustainable agriculture amid escalating environmental challenges.

Phenylalanine treatment induces tomato resistance to Tuta absoluta via increased accumulation of benzenoid/phenylpropanoid volatiles serving as defense signals.

Tuta absoluta ("leafminer"), is a major pest of tomato crops worldwide. Controlling this insect is difficult due to its efficient infestation, rapid proliferation, and resilience to changing weather conditions. Furthermore, chemical pesticides have only a short-term effect due to rapid development of T. absoluta strains. Here, we show that a variety of tomato cultivars, treated with external phenylalanine solutions exhibit high resistance to T. absoluta, under both greenhouse and open field conditions, at different locations. A large-scale metabolomic study revealed that tomato leaves absorb and metabolize externally given Phe efficiently, resulting in a change in their volatile profile, and repellence of T. absoluta moths. The change in the volatile profile is due to an increase in three phenylalanine-derived benzenoid phenylpropanoid volatiles (BPVs), benzaldehyde, phenylacetaldehyde, and 2-phenylethanol. This treatment had no effect on terpenes and green leaf volatiles, known to contribute to the fight against insects. Phe-treated plants also increased the resistance of neighboring non-treated plants. RNAseq analysis of the neighboring non-treated plants revealed an exclusive upregulation of genes, with enrichment of genes related to the plant immune response system. Exposure of tomato plants to either benzaldehyde, phenylacetaldehyde, or 2-phenylethanol, resulted in induction of genes related to the plant immune system that were also induced due to neighboring Phe-treated plants. We suggest a novel role of phenylalanine-derived BPVs as mediators of plant-insect interactions, acting as inducers of the plant defense mechanisms.

A signaling cascade mediating fruit trait development via phosphorylation-modulated nuclear accumulation of JAZ repressor.

It is generally accepted that jasmonate-ZIM domain (JAZ) repressors act to mediate jasmonate (JA) signaling via CORONATINE-INSENSITIVE1 (COI1)-mediated degradation. Here, we report a cryptic signaling cascade where a JAZ repressor, FvJAZ12, mediates multiple signaling inputs via phosphorylation-modulated subcellular translocation rather than the COI1-mediated degradation mechanism in strawberry (Fragaria vesca). FvJAZ12 acts to regulate flavor metabolism and defense response, and was found to be the target of FvMPK6, a mitogen-activated protein kinase that is capable of responding to multiple signal stimuli. FvMPK6 phosphorylates FvJAZ12 at the amino acid residues S179 and T183 adjacent to the PY residues, thereby attenuating its nuclear accumulation and relieving its repression for FvMYC2, which acts to control the expression of lipoxygenase 3 (FvLOX3), an important gene involved in JA biosynthesis and a diverse array of cellular metabolisms. Our data reveal a previously unreported mechanism for JA signaling and decipher a signaling cascade that links multiple signaling inputs with fruit trait development.

Plant growth-defense trade-offs are general across interactions with fungal, insect, and mammalian consumers.

Plants face trade-offs between allocating resources to growth, while also defending against herbivores or pathogens. Species differences along defense trade-off axes may promote coexistence and maintain diversity. However, few studies of plant communities have simultaneously compared defense trade-offs against an array of herbivores and pathogens for which defense investment may differ, and even fewer have been conducted in the complex natural communities in which these interactions unfold. We tested predictions about the role of defense trade-offs with competition and growth in diversity maintenance by tracking plant species abundance in a field experiment that removed individual consumer groups (mammals, arthropods, fungi) and added nutrients. Consistent with a growth-defense trade-off, plant species that increased in mass in response to nutrient addition also increased when consumers were removed. This growth-defense trade-off occurred for all consumer groups studied. Nutrient addition reduced plant species richness, which is consistent with trade-off theory. Removing foliar fungi increased plant diversity via increased species evenness, whereas removal of other consumer groups had little effect on diversity, counter to expectations. Thus, while growth-defense trade-offs are general across consumer groups, this trade-off observed in wild plant communities does not necessarily support plant diversity maintenance.