Turning up the heat on COVID-19: heat as a therapeutic intervention

By comparing natural immunity to Aspergillus fumigatus (AF) in vivo with the action of human or mouse phagocytes against AF in vitro, we delineated two sequential lines of defense against AF. The first line of defense was formed by macrophages and directed against spores. Macrophages prevented germination and killed spores in vitro and rapidly eradicated conidia in vivo, even in neutropenic and athymic mice. The second was the neutrophilic granulocyte (PMN), which protected against the hyphal form of AF. Human and mouse PMN killed mycelia in vitro. Normal, but not neutropenic mice, stopped hyphal growth, and eradicated mycelia. Either line of defense acting alone protected mice from high challenge doses. Natural immunity collapsed only when both the reticuloendothelial system and PMN were impaired. These findings are in keeping with the clinical observation that high doses of cortisone and neutropenia are the main risk factors for invasive aspergillosis. Cortisone inhibited the conidiacidal activity of mouse macrophages in vivo and of human or mouse mononuclear phagocytes in vitro. Cortisone damaged this first line of defense directly and not through the influence of T lymphocytes or other systems modifying macrophage function as shown in athymic mice and in vitro. In addition, daily high doses of cortisone in mice reduced the mobilization of PMN so that the second line of defense was also impaired. Thus, cortisone can break down natural resistance on its own. Myelosuppression rendered mice susceptible only when the first line of defense was overpowered by high challenge doses, by activated spores that cannot be killed by macrophages, or by cortisone suppression of the conidiacidal activity of macrophages. The host, thus, can call upon two independent phagocytic cell lines that form graded defense systems against aspergillus. These lines of defense function in the absence of a specific immune response, which seems superfluous in the control and elimination of this fungus.

Plants absorb light energy for photosynthesis via photosystem complexes in their chloroplasts. However, excess light can damage the photosystems and decrease photosynthetic output, thereby inhibiting plant growth and development. Plants have developed a series of light acclimation strategies that allow them to withstand high light. In the first line of defense against excess light, leaves and chloroplasts move away from the light and the plant accumulates compounds that filter and reflect the light. In the second line of defense, known as photoprotection, plants dissipate excess light energy through non-photochemical quenching, cyclic electron transport, photorespiration, and scavenging of excess reactive oxygen species. In the third line of defense, which occurs after photodamage, plants initiate a cycle of photosystem (mainly photosystem II) repair. In addition to being the site of photosynthesis, chloroplasts sense stress, especially light stress, and transduce the stress signal to the nucleus, where it modulates the expression of genes involved in the stress response. In this review, we discuss current progress in our understanding of the strategies and mechanisms employed by plants to withstand high light at the whole-plant, cellular, physiological, and molecular levels across the three lines of defense.

Wildfires pose a significant challenge to the natural and the built environments, as well as the safety and economic wellbeing of the communities residing in wildfire-prone areas. The electric power grid is specifically among the built environments most affected by, and contributing to, wildfires. In this paper, we propose a three lines of defense (3LD) framework for wildfire risk management in electric power infrastructure and review the literature from this lens. An overview of the physics and phenomenology of the wildfires as it relates to power grids is presented, and the logic for the proposed 3LD framework is discussed. The reviewed literature based on the 3LD theme includes the most relevant and emerging research work on wildfire prevention as the first line of defense, wildfire mitigation and proactive response as the second line of defense, and wildfire recovery preparedness as the third line of defense. This study reveals that while the state of the art, to a large extent, stands comprehensive in various aspects of power system resilience and wildfire risk management, there is a gap in the literature in addressing this emerging risk in a holistic, interdisciplinary approach.

The Secure Storage service for the gLite middleware provides users with a set of tools to store in a secure way and in an encrypted format confidential data (e.g. medical or financial data) on the grid storage elements. The data stored though provided tools will be accessible and readable by authorized users only. Moreover, it solves the insider abuse problem preventing also the administrators of the storage elements to access the confidential data in a clear format. The service has been designed and developed for the grid middleware of the EGEE Project, gLite, in the context of the TriGrid VL Project

Bacterial Retrons Function In Anti-Phage Defense

Network's speed continues to increase at a high rate resulting in massive network traffic. This results in a need to have a high-speed network intrusion detection system (NIDS) to detect malicious traffic. Snort is a software-based NIDS that can run as a single threaded application. However, it may not be able to detect intrusions in real-time especially in networks with high traffic. This paper proposes a two layer framework where Snort will run as a second line of defense and will be executed only when deep payload analysis is needed. To accelerate the efficiency of Snort, the proposed system will dynamically offload the most frequent rules or signatures to a NetFPGA based hardware. The NetFPGA will work as a first line of defense that accelerates the detection by filtering all the traffic looking for intrusions. This will be done by analyzing the captured packet header to match the offloaded rules or signatures.

The facultative intracellular pathogen Aeromonas salmonicida survives and replicates in macrophages, a virulence trait presumed to be associated with its ability to resist reactive radicals. The mechanisms used by A. salmonicida to resist reactive radicals in vitro were shown to have both structural and physiological determinants. The sensitivity of A. salmonicida to exogenous H2O2, superoxide, and nitrogen radicals, as well as endogenous oxygen radicals, differed depending on growth conditions, cell surface structure, and preexposure to sublethal doses of radicals. Whereas sensitivities to exogenous oxygen radicals did not correlate with basal levels of catalase or Fe-superoxide dismutase, under similar culture conditions S-layer positive cells were more resistant to oxygen radicals than S-layer mutants. S-layer mutants recovered resistance when physically reconstituted with S-layer sheets. Hemin-coated S-layers, while protective against nitrogen radicals, sensitized A. salmonicida to H2O2. Sublethal concentrations of H2O2or superoxide induced a highly protective response characterized by de novo synthesis of both catalase and Mn-superoxide dismutase. It is proposed that for A. salmonicida the constitutive S-layer provides a first line of defense and the inducible catalase and Mn-superoxide dismutase provide a powerful second line of defense against macrophage-mediated killing via reactive oxygen species.Key words: Aeromonas salmonicida, oxygen radicals, nitrogen radicals, oxidative stress, S-layers.

Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer

Today, the proportion of elderly and senile people is steadily growing throughout the world. The most important factors in the first line of immune defense of the mucous membranes of the upper respiratory tract are β-defensins, which are a group of secretory proteins with antimicrobial activity. The aim of this study was to study the expression of genes for antimicrobial peptides β-defensins and the composition of the microbiome of the mucous membranes of the upper respiratory tract in elderly people and long-livers with various aging phenotypes.The main study group included 67 centenarians and 49 elderly people, who were further divided into two subgroups depending on the course of aging (pathological and successful aging). Nucleic acids were isolated from nasopharyngeal scrapings and the expression levels of the DEFB1 and DEFB4 genes were determined using real-time polymerase chain reaction. The composition of the microbiota in nasopharyngeal swabs was determined by MALDI-TOF mass spectrometry.In analyzing the expression of the DEFB1 gene in elderly people and centenarians with successful and pathological aging phenotypes, no difference was revealed between the groups. Expression of the DEFB4 gene was increased in centenarians with pathological aging compared to centenarians with successful aging and in the elderly group. Excessive production of antimicrobial peptides is dual in nature; on the one hand, they provide the first line of defense against microorganisms, and on the other, they are cytotoxic to their own cells. An increase in the expression of the DEFB4 gene during aging may be due to an increase in the number of pathogen-associated molecular patterns, which can be one’s own microbiota and/or components of microbial metabolism. Analysis of the microbiota composition showed an increase in biodiversity in individuals with a successful aging phenotype compared to a pathological phenotype. Particular attention is paid to Staphylococcus spp., the species composition of which depends on the aging phenotype. In the pathological aging group, the frequency of St. aureus colonization is significantly higher than in the successful aging group.Thus, overexpression of the DEFB4 gene and changes in the composition of the microbiota of the mucous membranes of the upper respiratory tract may be one of the mechanisms explaining the increased susceptibility to infections in various aging phenotypes.

There are many factors in mucosal secretions that contribute to innate immunity and the 'first line of defence' at mucosal surfaces. Few studies, however, have investigated the effects of exercise on many of these 'defence' factors. The aim of the present study was to determine the acute effects of prolonged exercise on salivary levels of selected antimicrobial peptides (AMP) that have not yet been studied in response to exercise (HNP1-3 and LL-37) in addition to immunoglobulin A (IgA). A secondary objective was to assess the effects of exercise on saliva antibacterial capacity. Twelve active men exercised on a cycle ergometer for 2.5 h at approximately 60% of maximal oxygen uptake. Unstimulated whole saliva samples were obtained before and after exercise. There was a significant decrease (P < 0.05) in salivary IgA:osmolality ratio, following exercise, but IgA concentration and secretion rate were unaltered. Salivary HNP1-3 and LL-37 concentrations (P < 0.01 and P < 0.05, respectively), concentration:osmolality ratios (P < 0.01) and secretion rates (P < 0.01) all increased following exercise. Salivary antibacterial capacity (against E. coli) did not change. The increased concentration of AMPs in saliva may confer some benefit to the 'first line of defence' and could result from synergistic compensation within the mucosal immune system and/or airway inflammation and epithelial damage. Further study is required to determine the significance of such changes on the overall 'defence' capacity of saliva and how this influences the overall risk for infection.

Neuroinflammation is evident and one of the primary induced responses after central nervous system (CNS) injury, lumbar puncture and CNS surgery. In rare cases, complications could arise after the lumbar puncture or CNS surgery leading to inflammation, bleeding or other problems such as cerebrospinal fluid (CSF) leakage. The present dataset describes the occurrence of such a condition after the dura breakage or postoperative complication leading to the development of neuroinflammation in the adult Wistar rats. Therefore, objective of the study is to report such a rare condition and detect the most reliable glial proteins upregulated 2-3 weeks after the lumbar puncture which may help the neuroscience community to a better understanding their cause of action. In response to neuroinflammation, glial cells leak into the extracellular space, where they can be identified in the CSF or serum and may act as diagnostic biomarkers.Laminectomy was performed at the thoraco-lumbar (T12-L1) region and the dura was punctured. After that, the exposed part was covered with silica gel and adhesive followed by dental cement. The skin was closed using sterile sutures. After, the rats were given buprenorphine (0.05 mg/kg, every 8 h for 3 days) and carprofen (5 mg/kg, once a day for 5 days) as analgesic and anti-inflammatory and baytril (5 mg/kg, once a day for 10 days) as antibiotic drugs. Note, the buprenorphine and lidocaine were also given before starting the procedure. After the laminectomy, the functional outcomes of the rats were tested (starting from the day of surgery to the last day) and the rats which were locomoting normally using all the limbs were included in the study. In case of any decompression, the functional outcomes showing any kind of laming or partial paralysis of hindlimbs were excluded from the study. Unexpected neuroinflammation has occurred 2-3 weeks after performing the given procedure.Data presented in the article implicate active microglia measured by using protein biomarker such as Iba-1 [1, 3] and astrocytes measured by using Glial fibrillary acidic protein (GFAP) [2, 3] and S100 (strongly targets S100B and weakly A1) [7, 8] in the CSF collected two-three weeks after the laminectomy and dura breakage from the adult rats. Later paraformaldehyde (PFA) fixed spinal cord slices were also collected from the animals and immunolabelled with the same biomarkers. Western blots were performed with the collected CSF which showed high expression of glial markers such as GFAP, Iba-1 and S100 which has shown to target S100B with no expression of A1 (or A2, play an important role in neuroprotection) astrocytes which have recently been shown to be produced by microglia at the site of injury [9]. However, S100B [10] and GFAP [2] are known to be adequately discharged by the distinct cells in stress conditions which seems to occur in the present report. In addition, the spinal slices immunolabelled with the same biomarkers also showed increased expression of glia. Cross-talk between microglia-astrocyte in CNS stress is crucial for the neurons to survive and function after the injury. Reactive microglia (shown by high Iba-1 expression) leading to microgliosis comprise the first line of defense to phagocytose the dead cells [11]. Astrocytes act as the second line of defense leading to a process known as astrogliosis and upregulate GFAP and S100B to limit the damage [12]. Further studies are needed to explain the molecular mechanism/s of different astrocytes release such as A2 and their interaction with microglia after the lumbar puncture.

As consumer electronics play an ever increasing role in our daily lives, the content they hold becomes more valuable and vulnerable than ever. With personalised content such as photos, e-mails, apps, and contacts - along with an increasing amount of financial data with the introduction of the e-wallet and near field communication systems - losing a phone will do more than put a consumer out of pocket. A recent study highlights that 42% of mobile phone customers have experienced phone malfunction due to water or liquid damage, whether this is accidental spills, dropping in the toilet or swimming pool, or using the device in the rain and high humidity. The first line of defence for electronic products is to prevent water splashes getting inside and this is achieved by the application of an ultra-thin hydrophobic polymer layer to the outside and inside surfaces. This patented process takes place in a low pressure chamber at room temperature. The first plasma phase activates the surface of the device, before the monomer is introduces as a vapour. A unique phase of pulsed plasma then ensures the adhesion of the layer to the device and promotes the development of the polymer coating. When a device is dropped into water, pressure will force water through small gaps and apertures. A phone that initially appears to survive a dunking may undergo corrosion over time that will eventually lead to permanent damage. In this scenario the second line of defence is to have the sensitive electrical components protected with a resistive barrier coating. This barrier prevents shortcircuiting and corrosion. This barrier is applied through an advanced plasma deposition process. With the development of the coating technology and its commercialisation, plasma processing for water protection is now becoming standard feature on many electronic devices.

Citation: 'first line of defence' in the IUPAC Compendium of Chemical Terminology, 5th ed.; International Union of Pure and Applied Chemistry; 2025. Online version 5.0.0, 2025. 10.1351/goldbook.13151 • License: The IUPAC Gold Book is licensed under Creative Commons Attribution-ShareAlike CC BY-SA 4.0 International for individual terms. Requests for commercial usage of the compendium should be directed to IUPAC.

Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine [an effective irreversible inhibitor of gamma-glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly] were sensitized to the toxic effects of CdCl2. Mice pretreated with a sublethal dose of Cd2+ to induce metallothionein synthesis were not sensitized to Cd2+ by buthionine sulfoximine. Mice sensitized to Cd2+ by buthionine sulfoximine were protected against a lethal dose of Cd2+ by glutathione mono isopropyl ester (L-gamma-glutamyl-L-cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd2+ toxicity, and that this tripeptide provides a first line of defense against Cd2+ before induction of metallothionein synthesis occurs. The experimental approach used here in which cellular levels of glutathione are decreased or increased seems applicable to investigation of other types of metal toxicity and of other glutathione-dependent biological phenomena.

Most interactions between plants and fungi or Oomycetes do not result in a successful infection but are thwarted by the host (Thordal-Christensen, 2003; Lipka et al., 2008). In many cases, the obvious visible first line of defence is the papilla, a cell wall apposition (CWA) laid down by the host at the site of attempted penetration by the fungus or Oomycete on the inside of the host cell wall. CWA are observed in many plant species but are best studied in the cereal–powdery mildew interactions where the CWA comprises the inner papilla surrounded by an outer halo. Histological and chemical analyses demonstrate the complexity of the papillae, which comprise callose, protein, and various phenolic compounds and inorganic compounds, especially opal silica and, at least transiently, reactive oxygen species (see Zeyen et al., 2002, for a review). It is clear that papillae play a significant role, since penetration is often arrested by papillae, but as to which components of papillae are important for successful defence against a particular species pathogen is unclear. In other words, the demonstration of the complexity of papillae is not a demonstration of their role in disease resistance and presents the question as to why they are so complex. What is the role of the individual components of the papilla? There are two approaches which use the tools of forward and reverse genetics to determine the role of individual components of papillae which will answer this question, at least in part. The regulation of the formation of papillae has been studied genetically in both barley and Arabidopsis. Mutants have been obtained in barley exhibiting resistance, and indeed the mlo mutant confers race-non-specific resistance in both species (Consonni et al., 2006). Other Arabidopsis mutations contribute to the assembly of papillae (Collins et al., 2003, 2007). The physiological role of the Arabidopsis gene products is uncertain in some cases (Lipka et al., 2008). Thus the forward genetics approach has favoured the identification of regulatory, like mlo, and mechanistic components, like Pen1, but has not yielded mutations in the phenolic biosynthetic pathways associated with papilla formation. The nature of the first line of defence in cereals is still something of a mystery despite many years of study. We know much but there is still much to learn. Wei and colleagues have previously developed Triticum monococcum L. (Einkorn, a diploid wheat) as an excellent model system to use as an alternative to barley. In this issue, the study by Bhuiyan et al. (2009) uses a forward genetic approach to study the role of papilla components in Einkorn wheat infected with the powdery mildew fungus Blumeria graminis. The result is compelling evidence that lignification of papillae plays an important role in defence against penetration by this fungus. Lignification is, in essence, the generation of wood. The process can be considered to comprise two phases, firstly, the biosynthesis of monolignols, the building bricks, and, secondly, the assembly and polymerization of these bricks in the papilla. This paper represents an in-depth study of the first phase, which is illustrated in Fig. 1 of Bhuiyan et al. (2009). The approach taken has been to screen an expression sequence tag (EST) library prepared from the epidermis of T. monococcum infected with B. graminis f. sp. tritici (Bgt) (Liu et al., 2005; Bhuiyan et al., 2007) which is predicted to be enriched for first line defences against Blumeria graminis (Wei et al., 1998; Collinge et al., 2002). This yielded 13 cDNAs representing eight genes encoding enzymes involved in monolignol biosynthesis, according to their bioinformatical analysis. That six of these transcripts exhibit nearly synchronized accumulation patterns, as revealed by Northern blotting of entire leaves and epidermal expression, as revealed by RT PCR, is an excellent indication of their role in papilla formation. Proof of the importance of monolignol biosynthesis comes from the reverse genetics of transient gene silencing of four of the biosynthetic genes and an additive effect was obtained by combining three of the genes pair-wise. Thus, silencing gave a statistically significant increase in the efficiency of penetration. In the control, roughly 40% of penetration attempts were successful by the host powdery mildew fungus Bgt and increased 4-fold in the non-host powdery mildew fungus, Bg. f.sp. hordei, which infects barley. The double silenced constructs gave over 70% successful penetration rates. The genes included TmPAL, which encodes the first enzyme in the phenylpropanoid pathway, and can be predicted to have other roles in defence in grasses. For example, flavonoid biosynthesis has been seen to be induced in barley in response to B. graminis (Christensen et al., 1998a, b). The combination of TmPAL with genes encoding the two final biosynthetic enzymes of