Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides are a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interact with metal ions to potentiate their antimicrobial effectiveness, as such they have been termed metalloAMPs. In this work, we review the scientific literature of metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion, zinc (II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate their activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics.

Viroids represent the simplest, but are also among the most interesting life-like forms. They represent a great problem in agriculture. Moreover, pathogens similar to viroids, such as the hepatitis Delta virus represent a risk for human health. Viroids encode no proteins, but are still able to hijack their host cells’ metabolism to perform multiplication. This paper attempts to reply three questions about viroids. First, how can viroids hijack their host cells’ metabolism, even though they encode no proteins to achieve this? Second, what advantages do viroids have from their simplicity? Third, what can viroids, as the simplest life-like forms, tell us about life as a natural phenomenon? These questions are discussed from the perspective of biothermodynamics. In order to do this, elemental composition, biosynthesis reactions and standard thermodynamic properties of viroids have been determined and analyzed.

Hosting FIFA World Cup obviously produce immense socio-economic impacts to a nation. Proximal non-host city perception to mega event was frequently explored, while distal non-host city perception has less investigated. This study assessed the socio-economic impacts of FIFA World Cup Qatar 2022 in Chon Buri Sports City residents. Participants were 422 Chon Buri Sports City residents from eleven districts. Perception on socio-economic impacts of hosting FWC Qatar 2022 was measured from the translated Scale of Perceived Social Impacts. Extracted seven dimensions by confirmatory factor analysis is consistent with empirical data. Positive impact dimensions are Community Development, Community Pride, Economic Benefits. Negative impact dimensions are Traffic Problems, Security Risks, Economic Costs, and Environmental Concerns. Chon Buri Sports City residents perceived fewer negative impacts than other non-host city residents. Positive impacts of hosting FWC Qatar 2022 has more influenced on Chon Buri Sports City residents’ perception than negative impacts. These findings advantage for sport stakeholders to deeper understand the impacts of mega event hosting.

Metchnikovellids (Microsporidia: Metchnikovellida) are poorly studied hyperparasitic micro-sporidia that live in gregarines inhabiting the intestines of marine invertebrates, mostly poly-chaetes. Our recent studies showed that the diversity of the metchnikovellids might be signifi-cantly higher than previously thought, even within a single host. Four species of metchnikovellids were found in the gregarines inhabiting the gut of the polychaete Pygospio elegans from littoral populations of the White and Barents Seas: the eugregarine Polyrhabdina pygospionis is the host for Metchnikovella incurvata and M. spiralis, while the archigregarine Selenidium pygospionis is the host for M. dogieli and M. dobrovolskiji. The most common species in the White Sea is M. in-curvata, while M. dobrovolskiji prevails in the Barents Sea. The gregarines within a single worm could be infected with different metchnikovellid species. However, co-infection of one and the same gregarine with several species of metchnikovellids has never been observed. The difference in prevalence and intensity of metchnikovellid invasion apparently depends on the features of the life cycle and on the development strategies of individual species.

Phylogenetic trees of coronaviruses are difficult to interpret because they undergo frequent ge-nomic recombination. Here, we propose a new method, named coloured genomic bootstrap (CGB) barcodes, to highlight the polyphyletic origins of human sarbecoviruses and understand their host and geographic ori-gins. The results indicate that SARS-CoV and SARS-CoV-2 contain genomic regions of mixed an-cestry originating from horseshoe bat (Rhinolophus) viruses. First, different regions of SARS-CoV share exclusive ancestry with five Rhinolophus viruses from Southwest China (RfYNLF/31C: 17.9%; RpF46: 3.3%; RspSC2018: 2.0%; Rpe3: 1.3%; RaLYRa11: 1.0%) and 97% of its genome can be related to bat viruses from Yunnan (China), supporting its emergence in Rhinolophus species of this province. Second, different regions of SARS-Cov-2 share exclusive ancestry with eight Rhi-nolophus viruses from Yunnan (RpYN06: 5.8%; RaTG13: 4.8%; RmYN02: 3.8%), Laos (RpBA-NAL103: 3.3%; RmarBANAL236: 1.7%; RmBANAL52: 1.0%; RmBANAL247: 0.7%), and Cam-bodia (RshSTT200: 2.3%), and 98% of its genome can be related to bat viruses from northern Laos and Yunnan, supporting its emergence in Rhinolophus species of this region. Although CGB barcodes are very useful to retrace the origins of human sarbecoviruses, further investigations are needed to better apprehend the diversity of coronaviruses in bats from Cambo-dia, Laos, Myanmar, Thailand and Vietnam.

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mecha-nisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duo-denum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatographic mass-spectrometry, re-spectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were sig-nificantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration in-dicated that populations of three bacterial families –Autopobiaceae (Up), Desulfovibrionaceae (Up) and Akkermanasiaceae (Down) – were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.

Biothermodynamics of viruses is among the youngest, but rapidly developing scientific disciplines. During the COVID-19 pandemic, it has closely followed the results published by molecular biologists. Empirical formulas were published for 50 viruses and thermodynamic properties for multiple viruses and virus variants, including all variants of concern of SARS-CoV-2, SARS-CoV, MERS-COV, Ebola virus, Vaccinia and Monkeypox virus. A review of development of biothermodynamics of viruses during the last several decades and intense development during the last 3 years has been described in this paper.

The global threat of COVID-19 has led to the increasing use of metabolomics to study SARS-CoV-2 infection in humans and animals. Despite this, understanding SARS-CoV-2's metabolome during infection remains difficult and incomplete. Here, metabolic responses were characterized from sampled nasal washes collected from an asymptomatic ferret model (n = 20) at different time points before and after the SARS-CoV-2 challenge using an LC-MS-based metabolomics approach. Multivariate analysis of the nasal wash metabolome data resulted in several statistically significant features being observed. Despite no effects of gender or interaction between gender and time on the time course of SARS-CoV-2 infection, 16 metabolites were significantly different at every time point post-infection. Among these altered metabolites, the relative abundance of taurine was elevated post infection which could be an indication of hepatotoxicity, while the accumulation of sialic acids could indicate SARS-CoV-2 invasion. The pathway analysis identified several pathways influenced by SARS-CoV-2 infection. Of these, sugar, glycan, and amino acid metabolisms were the key altered pathways in the upper respiratory channel during infection. These findings provide some new insights into the progression of SARS-CoV-2 infection in ferrets at the metabolic level which could be useful for the development of early clinical diagnosis tools and new or repurposed drug therapies.

The emergence of drug-resistant parasitic nematodes of both humans and livestock calls for development of alternative and cost-effective control strategies. For the economically important ruminant strongylid Haemonchus contortus, Barbervax® remains the only registered vaccine available. Here we compared the microbiome, genome-wide diversity and transcriptome of H. contortus adult male populations that survived vaccination with an experimental vaccine after inoculation in sheep. Our genome-wide SNP analysis revealed 16 putative candidate vaccine evasion genes. However, we did not identify any evidence for changes in microbial community profiling based of 16S rRNA gene sequencing results of vaccine surviving parasite populations. A total of 58 genes were identified as significantly differentially expressed with six being long non-coding (lnc) RNAs and no putative candidate SNP associated genes. The genes highly upregulated in surviving parasites from vaccinated animals were associated with GO terms belonging to predominantly molecular function and a few biological processes that may have facilitated evasion or potentially lessened the effect of the vaccine. These included five targets: astacin (ASTL), carbonate dehydratase (CA2), phospholipase A2 (PLA2), glutamine synthetase (GLUL) and fatty acid-binding protein (FABP3). We searched all five DEG targets against the proteomes of selected Nematoda (Clades III, V, IV, C, I) and Platyhelminthes (Clades Monogenea, Trematoda, Cestoda, Rhabditophora) to determine homologs within the H. contortus NZ_HCO_NP v1.0 genome and identified single-copy orthologous groups (OGs) in selected proteomes. All but one (FABP3) demonstrated high levels of duplication and wide-spread occurrence in closely related Caenorhabditis elegans and Pristionchus pacificus, with complete absence of all five gene targets among other Clade III (Toxocara canis) and V (Ascaris suum, Ascaris lumbricoides and Parascaris univalens) nematodes, further supporting their vital biological functions in nematodes. Phylogenetic analyses inferred the presence of only ASTL and CA2 in almost all Nematoda, platyhelminthes and metazoans examined, with loss of GLULs observed among all outgroup vertebrate species and the presence of FABP3 in only three other species (Schmidtea mediterranea, Fasciola gigantica and F. hepatica). Our tertiary structure predictions and modelling analyses were used to perform in silico searches of all published and commercially available inhibitor molecules or substrate analogues with potential broad-spectrum efficacy against nematodes of human and veterinary importance.

In this opinion article, we have analyzed the relevancy of a hypothesis which is based on the idea that in Arabidopsis thaliana jasmonic acid (JA)-mediated defense system against necrotrophic fungi is weakened when NO3- supply is high. Such hypothesis is based on the fact that when NO3- supply is high, it induces an increase in the amount of bioactive ABA which induces the sequestration of the phosphatase ABI2 (PP2C) into the PYR/PYL/RCAR receptor. Consequently, the Ca sensors CBL1/9 - CIPK23 are not dephosphorylated by ABI2, thus remaining able to phosphorylate targets such as AtNPF6.3 and AtKAT1, a NO3- and K+ transporters respectively. Therefore, the impact of phosphorylation on the regulation of these two transporters, could 1) reduce NO3- influx as in its phosphorylated state AtNPF6.3 shifts to low capacity state and 2) increase K+ influx, as in its phosphorylated state KAT1 becomes more active. It is also well known that in the roots K+ loading in the xylem and its transport to the shoot is activated in the presence of NO3-. As such, the enrichment of plant tissues in K+ can impair jasmonic acid (JA) regulatory pathway and the induction of the corresponding biomarkers. The latter are known to be up-regulated under K+ deficiency and inhibited when K+ is resupplied. We therefore suggest that increased K+ uptake and tissue content induced by high NO3- supply modifies JA regulatory pathway, resulting in weakened JA-mediated plant’s defense system against necrotrophic fungi.

Most pathogens are capable of infecting multiple host species and such cross-species transmission (CST) can have dramatic consequences, as highlighted by recent disease emergence events affecting human, animal and plant health. Understanding the ecological and evolutionary factors that constrain or facilitate the ability of disease agents to infect and establish in a novel host is therefore a timely and important research area. Previous work across different pathogens, including rabies virus (RABV), found that increased evolutionary distance between hosts reduces the frequency of cross-species transmission and of permanent host shifts. However, whether this effect of host relatedness still holds for transmission among recently diverged hosts, and the importance of this effect relative to other predictors, is not well understood. We addressed this question by quantifying the CST frequency of RABV between North American bat species within the genus Myotis, using a multi-decade data set containing 128 nucleoprotein (N) sequences from ten host species. For comparison, we also conducted an equivalent analysis of a RABV dataset from North American bat species comprising nine genera. We found that at the within genus scale, host relatedness failed to explain the frequency of CST events. However, CST frequency increased with overlap in species’ host range. Moreover, we found evidence of CST occurring among a higher proportion of species, and CST more frequently resulting in sustained transmission in the novel host in the Myotis dataset compared to the multi-genus dataset. Our results suggest that among recently diverged species, the ability to infect a novel host is no longer restricted by physiological barriers but instead is limited by physical contact. Our results improve predictions of where future CST events for RABV might occur and clarify the relationship between host divergence and pathogen emergence.

Viruses feature an evolutionary shaped minimal genome that is obligately dependent on the cellular transcription and translation machinery for propagation. To suppress host cell immune responses and ensure efficient replication, viruses employ numerous tactics to favor viral gene expression and protein synthesis. This necessitates a carefully balanced network of virus- and host-encoded components, of which the RNA-based regulatory mechanisms have emerged as particularly interesting albeit insufficiently studied, especially in unicellular organisms. Here, recent advances that further our understanding of RNA-based translation regulation, mainly through post-transcriptional chemical modification of ribonucleosides, codon usage, and (virus-encoded) transfer RNAs, will be discussed in the context of viral infection.

Enteroviruses are members of Pichornaviridae family consisting of human enterovirus group A, B, C, and D as well as nonhuman enteroviruses. Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis Hand, foot, and mouth disease (HFMD) in children worldwide especially in the Asia‐Pacific region. EV71 and coxsackievirus A16 are two viruses responsible for HFMD which are members of group A enterovirus. The identified EV71 receptors provide useful information for understanding viral replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the EV71 genome that determine virulence remain unclear. Although an EV71 vaccine has been currently approved, there is no effective therapy for treating EV71 infected patients. Therefore, understanding the host-pathogen interaction could provide the knowledge in viral pathogenesis and further benefit in the anti-viral therapy development. The aim of this study was to investigate the latest findings about the interaction of viral ligands to the host receptor as well as the activation of immune related signalling pathways for the activation of innate immunity and involvement of different cytokines and chemokines in the host pathogen interaction of EV71 along with interaction of viral proteins, mainly 2A and 3C protease, and Interferons production/signaling pathway and their inhibitory effects.

Background: Fusarium head blight (FHB) is a serious fungal disease of crop plants due to substantial yield reduction and production of mycotoxins in the infected grains. The breeding progress in increasing resistance with maintaining a high yield is not possible without a thorough examination of the molecular basis of plant immunity responses; Methods: LC-MS based metabolomics approaches powered by three-way ANOVA and differentially accumulated metabolites (DAMs) selection, correlation network and functional enrichment were conducted on grains of resistant and susceptible to FHB genotypes of barley and wheat as well as model grass Brachypodium distachyon (Bd) still poorly known at metabolomic level; Results: We selected common and genotype-specific DAMs in response to F. culmorum inoculation. Immunological reaction at metabolomic level was strongly diversified between resistant and susceptible genotypes. DAMs common for all tested species from porphyrins, flavonoids and phenylpropanoids metabolic pathways were highly correlated and reflects conservativeness in FHB response in Poaceae family. Resistant related DAMs belonged to different structural classes including tryptophan derived metabolites, pirimidines, amino acids proline and serine as well as phenylpropanoids and flavonoids. Physiological response to F. culmorum of Bd was close to barley and wheat genotypes however, metabolomic changes were strongly diversified. Conclusions: Combined targeted and untargeted metabolomics provides comprehensive knowledge about significant elements of plant immunity with potential of being molecular biomarkers of enhance resistance to FHB in grass family. Thorough examination of Bd21 metabolome in juxtaposition with barley and wheat diversified genotypes facilitate their setting as model grass for plant-microbe interaction.

The successive waves of the Covid-19 pandemic are driven by SARS-CoV-2 variants that reached critical detection levels in different parts of the world. But how evolved the Wuhan virus since its detection in December 2019 into the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants of concern? This is a story of mice and men, of up to 1,000,000 infected cells in one person, where each cell produces between 10⁵ and 10⁶ viral RNAs, of immune-compromised patients, the digestive tract and viral recombination.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

Leishmaniasis is a tropical disease caused by a protozoan parasite Leishmania that is transmitted via infected female sandflies. At present, leishmaniasis treatment mainly counts on chemotherapy. The currently available drugs against leishmaniasis are costly, toxic, with multiple side effects, and limitations in the administration route. The rapid emergence of drug resistance has severely reduced the potency of anti-leishmanial drugs. As a result, there is a pressing need for the development of novel anti-leishmanial drugs with high potency, low cost, acceptable toxicity, and good pharmacokinetics features. Due to the availability of preclinical data, drug repurposing is a valuable approach for speeding up the development of effective antileishmanial through pointing to new drug targets in less time having low costs and risk. Metabolic pathways of this parasite play a crucial role in the growth and proliferation of Leishmania species during the various stages of their life cycle. Based on available genomics/proteomics information, known pathways-based (sterol biosynthetic pathway, purine salvage pathway, glycolysis, GPI biosynthesis, hypusine, polyamine biosynthesis) Leishmania-specific proteins could be targeted with known drugs that were used in other diseases, resulting in finding new promising anti-leishmanial therapeutics. The present review discusses various metabolic pathways of the Leishmania parasite and some drug candidates targeting these pathways effectively that could be potent drugs against leishmaniasis in the future.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterized the diversity of these Carnivore protoparvovirus 1 variants in 18 faecal samples collected from domestic cats with FPL during an outbreak, using targeted parvoviral DNA metagenomics to a mean depth of >10,000 X coverage per site. All samples comprised FPV alone. Compared to the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were non-synonymous, including 9 in non-structural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit inter-host diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intra-host diversity at all polymorphic positions was low with sub-consensus variant frequencies (SVF) of >1% except for two positions (2108 and 3208) in two samples with SVF of 1.1 – 1.3%. Intra-host nucleotide diversity was measured across the whole genome (0.7 - 1.5%) and for each gene, and was highest in the NS2 gene of four samples (1.2 – 1.9%). Overall, intra-host viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.

The different cell subsets of the immune system express vitamin D receptor (VDR). Through VDR, vitamin D exerts different functions which influences on immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies have explored the impact of vitamin D levels on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results have been confirmed in a prospective cohorts trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies has also been explored. Considering this dual effect both on the immune system as well as on tumor cells in patients with hematologic malignancies, vitamin D might be useful in this setting both to decrease graft-versus-host disease and relapse rates.

Ash trees have considerable economic, cultural and environmental value on the island of Ireland. However, European ash (Fraxinus excelsior L.) is currently under threat from the invasive ascomycete pathogen Hymenoscyphus fraxineus. This pathogen is the causal agent of ash dieback disease, which was initially reported in Poland in 1992. Hymenoscyphus fraxineus has since spread across Europe and the first recorded case of the disease on the island of Ireland was in 2012 at a forestry plantation in Co. Leitrim. The pathogen is now present in all 26 counties in Ireland and 6 counties in Northern Ireland, and it is considered unfeasible to eradicate. The spread of ash dieback disease is reflected in recent policy changes, which focus on management rather than eradication strategies. Since the first formal description of H. fraxineus in 2006, considerable research efforts have been made by the international scientific community to understand the biology of the pathogen and to develop management strategies against it. This review provides an update of current knowledge of H. fraxineus biology and infection. We then explore examples of mitigation techniques that have been trialled in Europe, in order to identify strategies that are feasible for disease management at a local level on the island of Ireland. Finally, we outline five key avenues of research that have the potential to provide breakthroughs in methods to protect valuable F. excelsior resources.

The aim of this work was to test polyamines as potential natural substrates of the Acinetobacter baumannii chlorhexidine efflux protein AceI using near-UV synchrotron radiation circular dichroism (SRCD) spectroscopy. The Gram-negative bacterium A. Baumannii is a leading cause of hospital-acquired infections and an important foodborne pathogen. A. Baumannii strains are becoming increasingly resistant to antimicrobial agents, including the synthetic antiseptic chlorhexidine. AceI was the founding member of the recently recognised PACE family of bacterial multidrug efflux proteins. Using the plasmid construct pTTQ18-aceI(His₆) containing the A. Baumannii aceI gene directly upstream from a His₆-tag coding sequence, expression of AceI(His₆) was amplified in E. coli BL21(DE3) cells. Near-UV (250-340 nm) SRCD measurements were performed on detergent-solubilised and purified AceI(His₆) at 20 °C. Sample and SRCD experimental conditions were identified that detected binding of the triamine spermidine to AceI(His₆). In a titration with spermidine (0-10 mM) this binding was saturable and fitting of the curve for the change in signal intensity produced an apparent binding affinity (K_D) of 3.97 +/- 0.45 mM. These SRCD results were the first experimental evidence obtained for polyamines as natural substrates of PACE proteins.

Food security has become a major concern worldwide in recent years due to ever increasing population. Providing food for the growing billions without disturbing environmental balance is incessantly required in the current scenario. In view of this, sustainable modes of agricultural practices offer better promise and hence are gaining prominence recently. Moreover, these methods have taken precedence currently over chemical-based methods of pest restriction and pathogen control. Adoption of Biological Control is one such crucial technique that is currently in the forefront. Over a period of time, various biocontrol strategies have been experimented with and some have exhibited great success and promise. This review highlights the different methods of plant-pathogen control, types of plant pathogens, their modus operandi and various biocontrol approaches employing a range of microorganisms and their byproducts. The study lays emphasis on the use of upcoming methodologies like microbiome management and engineering, phage cocktails, genetically modified biocontrol agents and microbial volatilome as available strategies to sustainable agricultural practices. More importantly, a critical analysis of the various methods enumerated in the paper indicates the need to amalgamate these techniques in order to improve the degree of biocontrol offered by them.

A single Information security is of pivotal concern for consistently streaming information over the widespread internetwork. The bottleneck flow of incoming and outgoing data traffic introduces the issue of malicious activities taken place by intruders, hackers and attackers in the form of authenticity desecration, gridlocking data traffic, vandalizing data and crashing the established network. The issue of emerging suspicious activities is managed by the domain of Intrusion Detection Systems (IDS). The IDS consistently monitors the network for identifica-tion of suspicious activities and generates alarm and indication in presence of malicious threats and worms. The performance of IDS is improved by using different signature based machine learning algorithms. In this paper, the performance of IDS model is determined using hybridization of nestrov-accelerated adaptive moment estimation –stochastic gradient descent (HNADAM-SDG) algorithm. The performance of the algorithm is compared with other classi-fication algorithms as logistic regression, ridge classifier and ensemble algorithm by adapting feature selection and optimization techniques

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs to treat EV71 infections. In this study, we conducted an antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug’s antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be relieved greatly by exposing virus-infected cells to extracellular low-pH culture media. Together, we have identified an FDA-approved antidepressant with the new indication for the broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

In recent years, the role of non-coding RNAs (ncRNAs) in regulating cell physiology has begun to be better understood. Recent discoveries in viral molecular biology have revealed that such cellular functions are disturbed during viral infections mainly due to host cell ncRNAs, cellular factors, and virus-derived ncRNAs. Apart from the interplay between those molecules, other interactions derive from the specific folding of RNA virus genomes. These fulfill canonical regulation functions such as replication, translation, and viral packaging. In some cases, folds serve as precursors of small viral RNAs whose biogenesis is not yet clearly understood. Since ncRNAs and RNA viral genomes modulate complex molecular and cellular processes in viral infections, a new taxonomy is being proposed here overarching three main categories, considering the current information about ncRNA interactions in some well-known viral infections. The first category shows examples of host ncRNAs associated with the trigger of the immune response under viral infections. The second category describes interactions between the virus and host ncRNAs. The last category shows how the shape of the RNA viral genome is essential in processing RNAs derived from viruses. Finally, we introduce evidence of how these three categories can also work as a framework in order to organize known interactions of ncRNAs and cellular factors under DENV infection. This new taxonomy of interactions provides a comprehensive framework for organizing the ncRNA regulatory roles in the context of viral interactions and an RNA world.

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuiviruses, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and researches on phenuiviruses have made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and very important virus family.

In this paper, we present a method for detecting and quantifying pathogens in water samples. The method proposes a portable dark field imaging and analysis system for quantifying E. coli concentrations in water after being labeled with magnetic particles. The system utilizes the tracking of moving micro/nano objects close to or below the optical resolution limit confined in small sample volumes (~ 10 µl). In particular, the system analyzes the effect of volumetric changes due to bacteria conjugation to magnetic microparticles (MP) on their Brownian motion while being suspended in liquid buffer solution. The method allows for a simple inexpensive implementation and the possibility to be used as point-of-need testing system. Indeed, a work-ing prototype is demonstrated with the capacity of quantifying E. coli colony forming units (CFU) at a range of 1x10³ - 6x10³ CFU/mL.

(1) Background: We reviewed the logistics of the implementation of pathogen inactivation (PI) using the INTERCEPT Blood System™ for platelets and the experience with routine use and clinical outcomes in the patient population at the Sírio-Libanês Hospital of São Paulo, Brazil. (2) Methods: Platelet concentrate (PC), including pathogen reduced (PR-PC) production, inventory management, discard rates, blood utilization, and clinical outcomes were analyzed over the 40 months before and after PI implementation. Age distribution and wastage rates were compared over the 10 months before and after approval for PR-PC to be stored for up to 7 days. (3) Results: A 100% PR-PC inventory was achieved by increasing double apheresis collections and production of double doses using pools of two single apheresis units. Discard rates decreased from 6% to 3% after PI implementation and further decreased to 1.2% after 7-day storage extension for PR-PCs. The blood utilization remained stable, with no increase in component utilization. A significant decrease in adverse transfusion events was observed after the PI implementation. (4) Conclusion: Our experience demonstrates the feasibility for Brazilian blood centers to achieve a 100% PR-PC inventory. All patients at our hospital received PR-PC and showed no increase in blood component utilization and decreased rates of adverse transfusion reactions.

The Sugarcane yellow leaf virus (SCYLV) is associated with sugarcane yellow leaf disease (SCYLD) and is considered to be the most economically deleterious emerging pathogen that represents a potential threat and danger to sugarcane cultivation in China. Over the last two decades, high genetic diversity in the SCYLV genotypes was observed worldwide, with a greater chance of YLD incidence for sugarcane injury. SCYLV infection has significantly damaged its economic traits and is responsible for substantial losses in biomass production in sugarcane cultivars. This study aims to identify and comprehensively analyze sugarcane microRNAs (miRNAs) as therapeutic targets against SCYLV using plant miRNA prediction tools. Mature sugarcane miRNAs are retrieved and are used for hybridization of the SCYLV. A total of seven common sugarcane miRNAs were selected based on consensus genomic positions. The biologically significant, top ranked ssp-miR528 was consensually predicted to have a potentially unique hybridization site at nucleotide position 4162 for targeting the ORF5 of the SCYLV genome; this was predicted by all the algorithms used in this study. Then, the miRNA–mRNA regulatory network was generated using the Circos algorithm, which was used to predict novel targets. There are no acceptable commercial SCYLV-resistant sugarcane varieties available at present. Therefore, the predicted biological data offer valuable evidence for the generation of SCYLV-resistant sugarcane plants.

The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

Background: Babesiosis and its tick carriers cause serious problems for cattle and are among the common protozoan blood parasites in Ethiopia. Methods: A cross-sectional survey was conducted from September 2019 to August 2020 to identify babesiosis in cattle and its tick vectors in extensively managed livestock in Dasenech and Salamago District South Omo Ethiopia. A total of 470 blood samples were collected for identification of hemoparasite using a thin blood smear followed by the Giemsa staining method and Packed Cell Volume (PCV) determination for detection of anemia. Results: Accordingly, the overall prevalence of bovine babesiosis in the study districts were 21.7% and Babesia bigemina (15.53%) and B. bovis (6.17%) were identified during this study. Factors such as age, sex, body condition score, season, tick burden, and level of tick Infection were considered as risk factors; yet, the season and level of tick Infection were found significantly associated (p< 0.05) with the occurrence of babesiosis. Besides, the mean PCV value of infected cattle (21.49%) was lower than non-infected animals (28.29%) which shows there was a strong correlation (p=0.0001) between anemia and Babesiosis. The prevalence of tick Infection was 86.17% (405/470) and a total of 8040 ticks adult ticks belonging to four tick genera namely Amblyomma (32.34%), Boophilus (18.51%), Hyalomma (18.94%), and Rhipicephalus (16.38%) were identified and all have a significant role (p< 0.05) on the occurrence of babesiosis in cattle. Conclusion: Bovine babesiosis is an important hemoparasitic protozoan disease of cattle in the study areas. To address and manage the problem, nearby veterinary service systems need to diagnose blood parasites and provide alternatives, especially for tick-borne diseases. Also, it is essential to customize appropriate and integrated tick control measures and tactical treatment of overt bovine babesiosis clinical cases.

The aim of the work was to update the distribution range of Aedes (Stegomyia) albopictus Skuse in the Americas, review the blood feeding patterns and compare the minimum infection rate (MIR) between studies of vertical and horizontal transmission of arboviruses. The current distribution of Ae. albopictus encompasses 21 countries in the Americas. In eleven published papers on the blood feeding pattern of Ae. albopictus, DNA from 16 species of mammals and five species of avian species was found. The most common host is humans, and dogs. We found 24 published papers on the identification of arboviruses in wild populations of Ae. albopictus with the potential to infect humans and animals. Eight arboviruses have been isolated in different studies carried out in Brazil, USA, Mexico, Colombia, and Costa Rica. Fifty-eight percent (14/24) of the publications reported vertical transmission of arbovirus. Positive pools were higher in vertical (8.45%) compared to horizontal transmission (0.97%). This was supported by the MIR, which was 3 times greater in vertical (MIR=3.21) than horizontal transmission (MIR= 1.08). In conclusion, Ae. albopictus is an invasive mosquito with wide phenotypic plasticity to adapt to broad and new areas, high vectorial competence to transmit several arboviruses mainly by transovarial transmission, it can participate in the endemic transmission, and serve as a bridge vector for emerging arboviruses between sylvan, rural, and urban areas.

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other important viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely studied for virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models to characterize the drivers of syncytium formation and its implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

Background: Every year, millions of people are hospitalized, and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection, and thus contribute to morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds of medicines commonly prescribed in Central Norway. Then we constructed a drug-target interaction network and identified potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on viability, transcription and metabolism of mock- and A/WSN/33(H1N1)-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that many drugs, such as acetylsalicylic acid, atorvastatin, candesartan, and hydroxocobalam, could target and modulate FLUAV-host cell interaction. In vitro experiments showed that these and other compounds at non-cytotoxic concentrations differently affected transcription and metabolism of mock- and FLUAV-infected cells. Conclusion: Many commonly prescribed drugs modulate FLUAV-host cell interactions in vitro and therefore could affect their interplay in vivo, thus, contributing to morbidity and mortality of patients with influenza virus infections.

Reported for the first time in 1955 in Malaysia, Tembusu virus (TMUV) remained for a long time in the shadow of flaviviruses with human health importance such as dengue virus or Japanese encephalitis virus. However, since 2010 and the first large epidemic in duck farms in China, the threat of its emergence on a large scale in Asia or even its spillover into the human population is becoming more and more significant. This review aims to report current knowledge on TMUV from viral particle organization to the development of specific vaccine and therapeutic with a particular focus on host-virus interaction.

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: i) primary dengue infection, ii) secondary dengue infection with the same (homologous) dengue virus and iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production, and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights on the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. As many patients develop a painful chronic stage and neither antiviral drugs nor vaccines are available, the development of a potent CHIKV inhibiting drug is crucial for CHIKF treatment. A comprehensive summary of current antiviral research and development of small-molecule inhibitor against CHIKV is presented in this review. We highlight different approaches used for the identification of such compounds and further discuss the identification and application of promising viral and host targets.

Extracellular vesicles (EVs) can transfer diverse RNA cargo for intercellular signalling. EV-associated RNAs have been found in diverse fungi and were proposed to be relevant for pathogenesis in animal hosts. In plant-pathogen interactions, small RNAs are exchanged in a cross-kingdom RNAi warfare and EVs were considered to be a delivery mechanism. To extend the search for EV-associated molecules involved in plants-pathogen communication, we have characterised the repertoire of EV-associated mRNAs secreted by the maize smut pathogen, Ustilago maydis. For this initial survey, EVs were isolated from axenic filamentous cultures that mimic infectious hyphae. The EV-associated RNAs were resistant to degradation by RNases and the presence of intact mRNAs was evident. The set of mRNAs enriched inside EVs relative to the fungal cells are functionally distinct from those that are depleted from EVs, particularly overrepresented in metabolic enzyme activities. Intriguingly, mRNAs of some known effectors and other proteins linked to virulence were found in EVs. Furthermore, several mRNAs enriched in EVs are also upregulated during infection, suggesting that EV-associated mRNAs may participate in plant-pathogen interaction.

The implementation of One Health/EcoHealth/Planetary Health approaches has been identified as key (i) to address the strong interconnections between risk for pandemics, climate change and biodiversity loss, and (ii) to develop and implement solutions to these interlinked crises. As a response to the multiple calls of scientists in that direction, we have put forward seven long term research questions regarding COVID-19 and emerging infectious diseases (EIDs) that are based on an effective integration of environmental, ecological, evolutionary, and social sciences to better anticipate and mitigate EIDs. Research needs cover the social-ecology of infectious disease agents, their evolution, the determinants of susceptibility of humans and animals to infections, and the human and ecological factors accelerating infectious disease emergence. For comprehensive investigation, they include the development of nature-based solutions to interlinked global planetary crises, addressing ethical and philosophical questions regarding the relationship of humans to nature and regarding transformative changes to safeguard the environment and human health. In support of this research, we propose the implementation of innovative multidisciplinary facilities embedded in social-ecosystems locally: the “ecological health observatories” and the “living laboratories”. This work has been carried out in the frame of the EC project HERA (www.HERAresearchEU.eu) that aims to set the priorities for an environment, climate and health research agenda in the EU by adopting a systemic approach in the face of global environmental change.

Leishmania parasites are a group of kinetoplastid pathogens that cause a variety of clinical forms while maintaining cell communication by secreting extracellular vesicles. Emerging technologies have been adapted for the studies of Leishmania-host-cell interactions to enable broad scale analysis of parasite extracellular vesicles. Leishmania extracellular vesicles (LEVS) are naturally released spheroidal nanoparticles of polydispersed suspensions surrounded by a lipid layer of membrane. Although LEVs have increasingly gained in importance, much is still unexplained, including bioavailability and function in the complex molecular mechanisms of pathogenesis. Considering the importance of LEVs in the parasite-host interaction and in the parasite-parasite relationships emerged during evolution, the current review aims at giving an overview of Leishmania summarizing knowledge and formulating guidelines for LEVs research. In the end, we report, direct methods for specific isolation of LEVs from promastigotes and amastigotes culture supernatant suitable for a range of different downstream applications increasing the compatibility and reproducibility to establish optimal and comparable isolation conditions and full LEVs characterization, and crucial immunomodulatory events triggered by this important group of parasites.

In this article we have presented a new perception of herd immunity threshold (HIT) which considers that only a “band of population” are susceptible to any pathogenic infection. This is termed as the “effective herd immunity threshold” (EHIT) and the progression of the disease (caused by this pathogenic infection) is mainly determined by this EHIT value. We have argued here that this EHIT value (considering the immunity band picture in the population) will be substantially lower than the estimated canonical HIT values obtained from various existing models. We propose that the actual prediction of the disease progression should now be calculated using the EHIT values.

Temperature and pH can expedite the ability of pathogens to cause diseases in cold-water corals (CWCs). The present study employed a combination of histology and polymerase chain reaction diagnostic techniques to investigate potential pathogens present in the CWCs Lophelia pertusa and Madrepora oculata in the Porcupine Bank Canyon (PBC), NE Atlantic. No pathogen was observed in the Madrepora samples. Neither histology nor standard PCR detected Vibrio spp. in the corals, although using Illumina technology, V. shilonii was observed in some L. pertusa samples in low abundances (0.22%). A Rickettsiales-like organisms (RLOs) occurred at a prevalence of 8.0% and at a low infection intensity of 1 - 4. Lophelia showed a few RLOs infection from the PBC canyon head (2.7%) and high infections in the south branch (5.3%). Similarly, unidentified cells observed in L. pertusa from the south branch (4.0%) were more common than those found in the canyon head (1.3%) with a prevalence of 5.3%. Although the route of pathogen infection is unclear, a likely mode of entry could be associated with particulate availability and the feeding strategies of the scleractinian corals. This suggest that L. pertusa invests energy into an enhanced immune function and reduced susceptibility to global pathogens despite a changing ocean environment.

Campylobacter is one of the major foodborne pathogens of concern in its growing trend of antimicrobial resistance. C. jejuni and C. coli are the major causative agents, with C. jejuni contributing to most of the cases in approximately 90% in the world. Infection is transmitted to humans due to consumption of contaminated food and water. Campylobacteriosis caused by C. jejuni is commonly presented with severe diarrhoea, abdominal pain, fever, headache, nausea, and vomiting with some extreme cases resulting in Guillain–Barré syndrome (GBS) and acute flaccid paralysis. Symptoms are severe in cases of children below 5 years, elderly and individuals who are immunocompromised. The infection is usually sporadic, and self-limiting and thus does not require antibiotics for treatment. Still, the antimicrobial resistance in Campylobacter is a major concern because of the transmission of resistance from animal sources to humans. This review highlights the recent epidemiology, geographical impact, resistance mechanisms, spread of Campylobacter spp. and the strategies to control the transmission of Campylobacter from veterinary sources and its antimicrobial resistance.

Host ribosome-associated scaffold protein Receptor for Activated C Kinase 1 (RACK1) is utilized by a diverse group of human viruses for Internal Ribosomal Entry Sites (IRES) – mediated translation of viral mRNAs. We recently reported inhibition of herpes virus by small molecules targeting the RACK1 functional site. Here, we tested these molecules against HIV-1 and HCV, as HIV-1 contains two potential IRES sites and HCV translation occurs exclusively through IRES. Compounds significantly downregulated activities of HIV-1- and HCV-related dicistronic reporter constructs in transfected HEK293T cells. The compounds also strongly downregulated production of the HIV-1 capsid protein p24 in HIV-infected cells, as well as production of HIV-1 Gag precursor p55 and p55-derived proteins p24 and p17 in cells infected with the HIV-1 virus. Hepatitis C virus (HCV) IRES activities were also significantly inhibited by RACK1 inhibitor compounds. Since a number of human and plant pathogenic viruses are reported to use IRES, the RACK1 compounds can be established as broad host-targeted antivirals.

Cryptosporidiosis is a major human health concern globally. Despite well-established methods, misdiagnosis remains common. Our understanding of the cryptosporidiosis biochemical mechanism remains limited, compounding the difficulty of clinical diagnosis. Here, we used a systems biology approach to investigate the underlying biochemical interactions in C57BL/6J mice infected with Cryptosporidium parvum. Faecal samples were collected daily following infection. Blood, liver tissues and luminal contents were collected 10 days post infection (dpi). High-resolution liquid chromatography and low-resolution gas chromatography coupled with mass spectrometry were used to analyse the proteomes and metabolomes of these samples. Faeces and luminal contents were additionally subjected to 16S rRNA gene sequencing. Univariate and multivariate statistical analysis of the acquired data illustrated altered host and microbial energy pathways during infection. Glycolysis/citrate cycle metabolites were depleted, while short-chain fatty acids and D-amino acids accumulated. An increased abundance of bacteria associated with a stressed gut environment was seen. Host proteins involved in energy pathways and Lactobacillus glyceraldehyde-3-phosphate dehydrogenase were upregulated during cryptosporidiosis. Liver oxalate also increased during infection. Microbiome-parasite relationships were observed to be more influential than the host-parasite association in mediating major biochemical changes in the mouse gut during cryptosporidiosis. Defining this parasite-microbiome interaction is the first step towards building a comprehensive cryptosporidiosis model towards biomarker discovery, and rapid and accurate diagnostics.

This studies the plasmonic properties of the bimetallic quantum dot Ag@Au core-shell nanostructures embedded in the non-absorbent host medium. Local field enhancement factor and coefficient of absorption of Ag-core and Au-shell are primarily studied based on quasi-static approximation of classical electrodynamics for 6-10 nm composite radius. In this quantum dot geometry, two set of plasmonic resonances in visible spectral region are observed: the first resonance associated with inner interface of gold (Ag@Au) and the second resonance associated with outer interface of gold (Au@medium). The two plasmonic resonances are close each other and enhanced when the size of composite decreased for a fixed core size while shifted to in opposite direction and the amplitude of peak decreased when the core size is increased for a fixed composite size. For the optimized size of core/composite or shell thickness and other parameters to the desired values, such type of composites are recommended for various applications like; photocatalysis, biomedical, nano-optoelectronics.

Insects possess an array of defense molecules allowing them to fight infections. They can also show a form of immune memory, named priming. However, the involvement of insect immune defense mechanisms in priming is unclear, since invertebrates lack the molecular machinery present in vertebrates to build an immune memory. In the red flour beetle Tribolium castaneum, larvae can be primed via the oral route with Bacillus thurigiensis var. tenebrionids (Btt). This results in changes in the expression of a large number of genes, among which some belong to families of ancient defense genes. In the present work, we tested whether three chosen candidate genes (a Thaumatin, a C-type Lectin and an Osiris-like gene) could be involved in the survival to a Btt exposure, as well as in the priming phenotype. We assessed changes in their expression over time and according to the priming treatment, knocked them down individually by RNA interference (RNAi), and observed how it affected survival upon challenge. The quantification of gene expression patterns in our larvae with RT-qPCR showed that up- and/or down-regulation of the genes, after the priming treatment, was quite volatile and time dependent. Upon knock-down, we did not observe the expected decrease in survival to Btt or the abolishment of the priming phenotype. We conclude that knocking down genes individually is probably insufficient to affect survival and priming in our system. This gives us insight into the complexity of the molecular processes underpinning priming.

It remains poorly understood how the life history strategies and transmission ecologies of viruses of plants, arthropods, and vertebrates are interrelated. The present analysis hinges on the virus transmission success. Virus transmission reflects where in the host-body viruses are retained or replicating. Plants, arthropods, and vertebrates share a protective outer-layer, a circulatory system, and reproductive organs. The latter enables vertical virus transmission and associates with virus-host mutualism. Two broadly opposing virus life history strategies are considered. Acute viruses tend to be replicative and are swiftly transmitted to the next host. Instead, persistent viruses keep virus replicating costs and host damage to a minimum. The intertwined life histories and transmission ecologies are accordingly pieced together, based on the virus mono- or instead dual-host tropism, the location of virus retention or replication on or in the host-body, the presence of cyclical or mechanical transmission by arthropods, and of horizontal and vertical host-to-host transmission modes. It is shown that in the arthropod and in the vertebrate animal host, virus circulation in the hemocoel or blood circulation goes hand-in-hand with vertical transmission. Instead, plant phloem viruses do not transmit via seed. The latter is the rule for the plant-only viruses. The risk management implications are discussed in brief.

The carbon-carbon cross-coupling of phenyl s-tetrazine (Tz) units at their ortho-phenyl positions allows to form constrained bis(tetrazines) with original tweezer structures. In these compounds, the face-to-face positioning of the central tetrazine cores is endorsed by pi-staking of the electron-poor nitrogen-containing heteroaromatic moieties. The resulting tetra-aromatic structure can be used as a weak coordinating ligand with cationic silver. This coordination generates a set of bis(tetrazine)‐silver(I) coordination complexes tolerating a large variety of counter anions of various geometries, namely, PF6–, BF4–, SbF6–, ClO4–, NTf2–, OTf2–. These compounds were characterized in the solid-state by single crystal XRD and reflectance spectra, and in solution by 1H NMR, mass spectrometry, electroanalysis and UV-visible absorption spectroscopy. The X-ray diffraction (XRD) structure of complexes {[Ag(3)][PF6]}∞ (4) and {[Ag(3)][SbF6]∞ (6), where 3 is 3,3'-[(1,1'-biphenyl)-2,2'-diyl]-6,6'-bis[phenyl]-1,2,4,5-tetrazine, revealed the formation of 1D polymeric chains, characterized by an evolution to a large opening of the original tweezer and a coordination of silver(I) via two chelating nitrogen atom and some C=C pi-interactions. Electrochemical and UV spectroscopic properties of the original tweezer and of the corresponding silver complex are reported and compared. 1H NMR titrations with AgNTf2 allowed to determine the stoichiometry, and apparent stability of two solution species, namely [Ag(3)]+ and [Ag(3)2]2+, that formed in CDCl3/CD3OD 2:1 v/v mixtures.

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

The novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and severe impacts on both human health and the global economy. Since the onset of the pandemic, there have been many instances of human-to-animal transmission involving companion, farmed and zoo animals, and limited evidence for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. We discuss the potential for exposure, onward transmission and persistence of SARS-CoV-2 in an initial selection of wild mammals (bats, canids, felids, mustelids, great apes, rodents and cervids). Dynamic risk assessment and targeted surveillance are important tools for the early detection of infection in wildlife, and here we describe a framework for collating and synthesising emerging information to inform targeted surveillance for SARS-CoV-2 in wildlife. Surveillance efforts should be integrated with information from public and veterinary health initiatives to provide insights into the potential role of wild mammals in the epidemiology of SARS-CoV-2.

There has been observational evidence about spin axes of quasars in large quasar groups correlated over hundreds of Mpc. This is seen in the radio spectrum as well as in the optical range. There is not yet a satisfactory explanation of this "spooky" alignment. This alignment cannot be explained by mutual interaction at the time that quasars manifest themselves optically. A cosmological explanation could be possible in the formation of superconducting vortices (cosmic strings) in the early universe, just after the symmetry-breaking phase of the universe. We gathered from the NASA/IPAC and SIMBAD extragalactic databases the right ascension, declination, inclination, position angle and eccentricity of the host galaxies of 3 large quasar groups to obtain the azimuthal and polar angle of the spin vectors. The alignment of the azimuthal angle of the spin vectors of quasars in their host galaxy is confirmed in the large quasar group U1.27 and compared with two other groups in the vicinity, i.e., U1.11 and U1.28. It is well possible that the azimuthal angle alignment fits the predicted azimuthal angle dependency in the theoretical model of the formation of general relativistic superconducting vortices, where the initial axially symmetry is broken just after the symmetry breaking of the scalar-gauge field.} \keyword{quasar groups; alignment spin vectors; host galaxy; cosmic strings; symmetry breaking; scalar-gauge field.

Understanding biological mechanisms that regulate emergence of viral diseases, in particular those events engaging cross-species pathogens spillover, are becoming increasingly important in Virology. Species barrier jumping has been extensively studied in animal viruses, and the critical role of a suitable intermediate host in animal viruses-generated human pandemics is highly topical. However, studies on host jumping involving plant viruses have been focused on shifting intra-species, leaving aside the putative role of “bridge hosts” in facilitating interspecies crossing. Here, we take advantage of several VPg mutants, derived from a chimeric construct of the potyvirus Plum pox virus (PPV), analysing its differential behaviour in three herbaceous species. Our results showed that two VPg mutations in a Nicotiana clevelandii-adapted virus, emerged during adaptation to the bridge-host Arabidopsis thaliana, drastically prompted partial adaptation to Chenopodium foetidum. Although, both changes are expected to facilitate productive interactions with eIF(iso)4E, polymorphims detected in PPV VPg and the three eIF(iso)4E studied, extrapolated to a recent VPg:eIF4E structural model, suggested that two adaptation ways can be operating. Remarkably, we found that VPg mutations driving host-range expansion in two non-related species, not only are not associated with cost trade-off constraints in the original host, but also improve fitness on it.

The alien invasive insect pest Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), commonly referred to as Fall Armyworm (FAW), is a polyphagous insect feeding on more than 350 host plants in addition to maize in its native habitat. Due to the voracious nature of FAW, significant yield losses on maize production were reported across the African continent since its detection in 2016. Despite being a polyphagous insect, little is known about its alternative host plants in the new habitat including Mozambique. This study aimed to assess the host range of FAW in the central province of Manica, Mozambique. A field survey was conducted from May to August 2019 (dry season of 2018/2019 cropping season) and in December 2019 and January 2020 (rainy season of 2019/2020 cropping season) in maize fields and crops often mixed with maize or located in the vicinity of maize fields. A total of 1291 fields were surveyed. In each field, 20 plants were selected in a “W” pattern and checked for the presence of FAW egg masses and/or larvae. At the time of the sampling, no evidence was found suggesting that in Manica province FAW feeds in crops other than maize because out of 35 different crops surveyed, FAW was only recorded on maize. Results from this study suggest that the strain of FAW occurring in Manica province might be the one specialized in maize or the continuous availability of maize fields throughout the year is influencing the choices of the host plants of this invasive insect pest.

Microbiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. Similar to higher organisms, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence and pathogen extrinsic incubation period all influence pathogen transmission. Interestingly, the mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps in the biology of the mosquito – microbe symbiosis that need to be addressed in order to understand these interactions more thoroughly and exploit them efficiently. Here, we review current evidence of the impacts of the microbiome on aspects of vectorial capacity highlighting opportunities for novel vector control strategies and areas where further studies are required.

Wheat blast caused by the hemibiotroph fungal pathogen Magnaporthe oryzae Triticum (MoT) pathotype, is a destructive disease of wheat in South America and Bangladesh. Generation of reactive oxygen species (ROS) is one of the defense responses in plants during the infection process by a pathogen. However, empirical evidence on regulation of ROS in wheat and other host and non-host plants towards MoT is limited. This study aimed to determine the susceptibility of some major cereals and weeds of Bangladesh and compare the antioxidant enzyme activities in host and non-host plants in response to artificial inoculation by MoT. Seedlings of wheat, maize, barley and swamp rice grass were susceptible to MoT and produced considerable number of conidia on infected leaves (host). Rice seedlings showed a resistant response in our laboratory conditions (non-host). The activities of ROS-detoxifying enzymes; catalase (CAT), ascorbate peroxidase (APX), Glutathione peroxidase (GPX), Glutathione S-transferase (GST), Peroxidase (POX) increased in all plants after inoculation by MoT with a few exceptions. Interestingly, an early and very high accumulation of CAT was observed within 24 hours of inoculation (hai) in wheat, barley, maize and swamp rice grass while H2O2 concentration was low during that time and immediately after that (24-48 hai). In contrast, an early and high accumulation of H2O2 was observed in rice at 48 hai with little CAT activity only at a late stage. The APX, GST and POD activity was also increased due to the inoculation of MoT at the early stage of infection in rice but were very high at the disease progression stage in wheat, barley, maize and swamp rice grass. GPX activity gradually decreased with the increase of time in rice. Taken together, our results suggest that a robust and late induction of most of the antioxidant enzyme activities occurs in susceptible/host plants whereas an early induction of antioxidant enzyme activities occurs in resistant/ non-host plant but with slow kinetics.

In this paper, we have numerically investigated a metasurface based perfect absorber design established on the impedance matching phenomena. The paper comprises of two parts. In the first part, the device performance of the perfect absorber is studied which is composed of a silicon Nano-cylindrical meta-atoms periodically arranged on the thin gold layer. The device design is unique which works for both x-oriented and y-oriented polarized light, besides independent of the angle of incidence. In the second part of the paper, CO2 gas sensing application is explored by depositing a thin layer of functional host material polyhexamethylene biguanide polymer on the metasurface. The refractive index of the host material decreases due to the absorption of the CO2 gas. As a result, the resonance wavelength of the perfect absorber performs a prominent blueshift. With the help of the proposed sensor design based on metasurface, the CO2 gas concentration range of 0-524 ppm is detected. The maximum sensitivity of ~17.3 pm/ppm is acquired for the gas concentration of 434 ppm. The study presented in this work explores the opportunity of utilizing metasurface perfect absorber for gas sensing applications by employing the functional host materials.

Symbioses between animals and bacteria are ubiquitous. To better understand these relationships, it is essential to unravel how bacteria evolve to colonize hosts. Previously, we serially passaged the free-living bacterium, Shewanella oneidensis, through the digestive tracts of germ-free larval zebrafish (Danio rerio) to uncover the evolutionary changes involved in the initiation of a novel symbiosis with a vertebrate host. After 20 passages, we discovered an adaptive missense mutation in the mshL gene of the msh pilus operon, which improved host colonization, increased swimming motility, and reduced surface adhesion. In the present study, we have determined that this mutation was a loss-of-function mutation and found that it improved zebrafish colonization by augmenting S. oneidensis representation in the water column outside larvae through a reduced association with environmental surfaces. Additionally, we found that strains containing the mshL mutation were able to immigrate into host digestive tracts at higher rates per capita. However, mutant and evolved strains exhibited no evidence of a competitive advantage after colonizing hosts. Our results demonstrate that bacterial behaviors outside the host can play a dominant role in facilitating the onset of novel host associations.

Staphylococcus aureus is a Gram-positive bacterium causing a range of mild to life-threatening infections including bone infections such as osteomyelitis. S. aureus is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study four different S. aureus strains, 2SA-ST239-III, 5SA-ST5-II, 10SA-ST228-I, and 14SA-ST22-IVh were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following a successful invasion and persistence. Methicillin-sensitive S. aureus (MSSA) ATCC-12598-ST30 was used as control. Despite the demonstrated similar abilities of internalization and persistence of ATCC-12598-ST30, 2SA-ST239-III, and 14SA-ST22-IVh strains in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the decrease in cell viability was due to the different behavior of the considered strains, with the number of intracellular bacteria playing a limited role. We focused our attention on different cellular biochemical functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show that: 1) ATCC-12598-ST30 and 2SA-ST239-III were the only two clones able to persist and maintain their number into the cellular hostile environment during the entire period of infection; 2) 2SA-ST239-III was the only clone able to significantly increase the gene expression (3 and 24 h) and protein secretion (24 h) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; 3) the same clone determined a significant up-regulation of transforming growth factor-β1 (TGF-β1) and the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h post infection; 3) neither the MSSA nor the four MRSA strains induced oxidative stress phenomena in MG-63 cells, although a very different expression pattern towards nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation was observed among the different clones. Our results can open a new way of considering therapies, going in the direction of an individualized therapeutic strategy that should take into account the difference existing between MSSA and MRSA as well as the distinctive features of the different clones. Not only, therefore, a different antibiotic approach but also a starting point for considering different host factors, i.e. the modulation of specific cytokines such as IL-6, TNF-α, and TGF-β1.

The nature of the relationship between the communities of microorganisms making up the microbiota in and on a host body has been increasingly explored in recent years. Microorganisms, including bacteria, archaea, viruses, parasites, and fungi, have often long co-evolved with their hosts. In human, the structure and diversity of microbiota vary according to the host’s immunity, diet, environment, age, physiological and metabolic status, medical practices (e.g. antibiotic treatment), climate, season, and host genetics. The recent advent of next generation sequencing (NGS) technologies enhanced observational capacities and allowed for a better understanding of the relationship between distinct microorganisms within microbiota. The interaction between the host and their microbiota has become a field of research into microorganisms with therapeutic and preventive interest for public health applications. This review aims at assessing the current knowledge on interactions between prokaryotic and eukaryotic communities. After a brief description of the metagenomic methods used in the studies analysed, we summarise the findings of available publications describing the interaction between the bacterial communities and protozoa, helminths, and fungi, either in vitro, in experimental models, or in humans. Overall, we observed the existence of a beneficial effect in situations where some microorganisms can improve the health status of the host, while the presence of other microorganisms has been associated with pathologies, resulting in an adverse effect on human health.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

The biotic and abiotic stresses are the main causes of the loss of agricultural crops productivity, their normal growth and development in the environment. It has been calculated that two-thirds of the major crops are frequently lost due to adverse environmental conditions. The productivity of crops under unfavorable environmental stresses is apparently the main challenge to the breeders and farmers where polyamines (PAs) play diverse roles in environmental stimuli. PAs (putrescine, spermidine, and spermine) are low molecular weight positively charge compounds have the active potential power to negative charge molecules (DNA, RNA, and proteins) is widely distributed in all living organisms. Evidence showed that PAs contribute a lot of different physiological and biological functions, such as cell growth and development, controlling the cell cycle, involve in gene expression, cell signaling, replication, transcription, translation, and membrane stabilization. Naturally occurring polyamines activity acuminated to their involvement with different biotic and abiotic stresses and contribute to the survival of the plant in the environment. Here, we have described the potential mechanisms, synthesis, and various roles of PAs during stresses tolerant and disease resistance.

Thermal variations affect tri-trophic interactions involving plants, herbivores, and parasitoids, causing a mismatch between their phenological cycles. In the current environmental context of climate change, climatic factors can undergo profound and sudden changes, such as sudden hot or cold snaps. Here we show that episodes of short but sustained low temperatures have increased, mainly in the month of May, in the last two decades. We subjected galls induced by Asian chestnut gall wasp (ACGW) Dryocosmus kuriphilus to cold stress to assess if and how the pest and its parasitoids were affected. Over the course of two years seasonal parasitism, parasitism rates, the relative abundance of each parasitoid species, and mortality of ACGW were calculated. We found that the cold treatment affected both pest and parasitoids, resulting in a reduction in emerging ACGWs and differing ratios of species within the parasitoid community. The striking example was the change in the relative frequency of three species of Eupelmus spp. and of Mesopolobus tibialis, which doubled in thermally-stressed galls in all chestnut fields. The thermal effects on the development of the host and the direct effects of cold temperatures on the surface of galls (i.e., humidity or hardness of the galls) warrant further research in this direction.

Grapevine is one of the most relevant crops in the world being used for economically important products such as wine. Yet, relevant grapevine cultivars are heavily affected by diseases such as the downy mildew disease caused by Plasmopara viticola. Improvements on grapevine resistance are made mainly by breeding techniques where resistance traits are introgressed into cultivars with desired grape characteristics. However, there is still a lack of knowledge on how resistant or tolerant cultivars tackle the P. viticola pathogen. In this study, using a shotgun proteomics LC-MS/MS approach, we unravel the protein modulation of a highly tolerant grapevine cultivar, V. vinifera ‘Regent’, in the first hours post inoculation (hpi) with P. viticola. At 6 hpi, proteins related to defence and to response to stimuli are negatively modulated while at 12 hpi there is an accumulation of proteins belonging to both categories. The co-occurrence of effector-triggered susceptibility (ETS) and effector-triggered immunity (ETI) is detected at both time-points, showing that these defence processes present high plasticity. The results obtained in this study unravel the tolerant grapevine defence strategy towards P. viticola and may provide valuable insights on resistance associated candidates and mechanisms, which may play an important role in the definition of new strategies on breeding approaches.

Tomato (Solanum lycopersicum L.) is a valuable horticultural crop grown and consumed worldwide. Optimum production is hindered by several factors of which Verticillium dahliae, the cause of Verticillium wilt, is one of the major biological constraints in temperate production regions. V. dahliae is difficult to manage because it is a vascular pathogen, has a broad host range and worldwide distribution, and can persist in soil for years. Understanding the pathogen virulence and genetic diversity, host resistance, and plant-pathogen interactions can ultimately inform the development of integrated strategies to manage the disease. In recent years, considerable research has focused on providing new insight into these processes as well as the development and integration of environment-friendly management approaches. In this review, we discuss and summarize the recent findings on the race and population structure of V. dahliae; pathogenicity factors; host genes, proteins, and enzymes involved in defense; the emergent management strategies, and recent approaches to managing Verticillium wilt in tomatoes.

Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.

The microbiome, by virtue of its interactions with the host, is implicated in various host functions including its influence on inflammation, nutrition, and homeostasis. Although driven by a complex combination of intrinsic and extrinsic factors, many chronic diseases such as diabetes, cancer, Inflammatory Bowel Disease among others are characterized by a disruption of microbial communities in at least one biological niche/organ system. Various molecular mechanisms between microbial and host components such as proteins, RNAs, metabolites etc have recently been elucidated, thus filling many gaps in our understanding of how the microbiome modulates host processes. Concurrently, high throughput technologies have enabled the profiling of heterogeneous datasets capturing community level changes in the microbiome as well as the host responses. However, due to pragmatic limitations with respect to parallel sampling and analytical procedures, big gaps still exist in terms of how the microbiome mechanistically influences host functions at a systems and community level. In the past decade, various computational biology and machine learning methodologies and approaches have been developed with an aim to fill these existing gaps. Due to the agnostic nature of the tools, they have been applied in various disease contexts to analyze and infer the interactions between the microbiome and host molecular components, and in the case of a few selected tools, on downstream host processes. Generally, most of the tools are enabled by frameworks to statistically or mechanistically integrate different types of -omic and meta -omic datasets followed by functional/biological interpretation. In this review, we provide an overview of the landscape of computational approaches for investigating mechanistic microbiome-host interactions and their potential benefit for basic and clinical research. These could include but are not limited to the development of activity and mechanism based biomarkers, uncovering mechanisms for therapeutic interventions and generating integrated signatures to stratify patients.

Piscirickettsia salmonis is an intracellular bacterial fish pathogen that causes piscirickettsiosis, a disease with numerous negative impacts in the Chilean salmon farming industry. Although transcriptomic studies of P. salmonis and its host have been performed, dual host-pathogen proteomic approaches during infection are still missing. Considering that gene expression not always corresponds with observed phenotype, and bacteriological culture studies inadequately reflect infection conditions, to improve the existing knowledge for the pathogenicity of P. salmonis we present here a global proteomic profiling of Salmon salar macrophage-like cell cultures infected with P. salmonis LF-89. The proteomic analyses identified several P. salmonis proteins from two temporally different stages of macrophages infection; some of them related to key functions for bacterial survival in other intracellular pathogens. Metabolic differences were observed in early-stage infection bacteria, compared to late-stage infections. Virulence factors related to membrane, LPS and surface component modifications, cell motility, toxins and secretion systems also varied between the infection stages. Pilus proteins, beta-hemolysin and the T6SS were characteristic of the early-infection stage, while fimbria, upregulation of 10 toxins or effector proteins, and the Dot/Icm T4SS were representative of the late-infection stage bacteria. Previously described virulence-related genes in P. salmonis plasmids were identified by proteomic assays during infection in SHK-1 cells, accompanied by an increase of mobile-related elements. By comparing the infected and un-infected proteome of SHK-1 cells, we observed changes in cellular and ROS homeostasis, innate immune response, microtubules and actin cytoskeleton organization and dynamics, alteration in phagosome components, iron transport and metabolism, and amino acids, nucleoside and nucleotide metabolism, together with an overall energy and ATP production alteration. Our global proteomic profiling and the current knowledge of the P. salmonis infection process allowed us to propose a model of the macrophage-P. salmonis interaction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.

Bacterial collections are invaluable tools for microbiologists. However, their practical use is compromised by imprecise taxonomical assignation of bacterial strains. This is particularly true for soft rotting plant pathogens of the Pectobacterium genus. To solve this difficulty, we analyzed the taxonomic status of 265 Pectobacterium strains deposited at CIRM-CFBP collection from 1944 to 2020. This collection gathered Pectobacterium strains isolated in 27 countries from 32 plant species representing 17 botanical families or from non-host environments. MLSA approach completed by genomic analysis of 15 strains was performed to update the taxonomic status of these 265 strains. Results showed that the CIRM-CFBP Pectobacterium collection harboured at least one strain of each species to the exception of P. polonicum. Yet, 6 strains could not be assigned to any of the described species and may represent at least two new species. Surprisingly, the P. versatile species, recently described in 2019, is the most prevalent species among CIRM-CFBP strains. Analysis of P. versatile strains revealed that this species is endemic all over the world on various host plants and environments. At the opposite, other species gathered strains isolated from only one botanical family or exclusively from fresh water environment. Our work also revealed new host plants for several Pectobacterium spp.

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

Indirect effects of global change via changing species interactions have been largely ignored in studies predicting global change impacts on ecosystems. Antagonistic biotic interactions, however, can strongly affect ecosystems and are likely to be affected by global change drivers themselves. We synthesize current knowledge on the impact of invertebrate herbivores and pathogens on plant productivity, diversity and community composition, and outline theory and expectations on how important global change drivers – nitrogen enrichment, climate change and elevated CO², and plant and insect diversity loss, may affect enemy impact on plant communities. We illustrate that our ability to predict global change impact requires a holistic perspective, taking into account direct as well as indirect effects via the biotic component of ecosystems.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

The rhizosphere fungal community can play an important role in determining plant growth and health. In this study, using high-throughput sequencing, we investigated the fungal diversity and community composition in the roots and rhizosphere soil of 21 potato (Solanum tuberosum L.) cultivars. The samples were collected at three different sampling points. Furthermore, we assessed the differences in both diversity and composition of pathogen and saprotroph communities. In soil and roots, the fungal richness and relative abundance of pathogens and saprotrophs were mainly affected by sampling time. However, root fungal communities were also significantly affected by cultivar. The most substantial effect of cultivar was on root pathogen diversity. Moreover, the occurrence of most pathogens strongly varied among cultivars. Soil fungal community composition was primarily determined by sampling time; whereas in roots, the primary determinant was cultivar. Our results demonstrate changes in fungal communities over the potato growing season, as well as highlight the importance of potato cultivar on root fungal communities, and emphasise their importance in plant breeding.

The integrated stress response (ISR) is an adaptational signaling pathway that is induced in response to different stimuli, such as accumulation of unfolded and misfolded protein, hypoxia, amino acid deprivation, viral infection and ultraviolet light. It has been known that viral infection can activate ISR, but the role of ISR during viral infection is still unclear. In some cases, ISR is a protective mechanism of host cell against infection with virus whilst ISR may be hijacked by viruses for facilitating its replication. In this review, we highlighted recent advances on induction of ISR upon viral infection and the downstream responses involved such as autophagy, apoptosis, formation of stress granules and innate immunity response. We then discussed the molecular mechanism of ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from ISR.

Convalescent blood product therapy has been introduced since early 1900s to treat emerging infectious disease based on the evidence that polyclonal neutralizing antibodies can reduce duration of viremia. Recent large outbreaks of viral diseases for whom effective antivirals or vaccines are still lacking has revamped the interest in convalescent plasma as life-saving treatments. This review summarizes historical settings of application, and surveys current technologies for collection, manufacturing, pathogen inactivation, and banking, with a focus on COVID-19.

The simple sequence repeats (SSRs) are small 1-6bp tandem repeat elements present across diverse genomes and involved in gene regulation and evolution. Presently we analyzed SSRs in genomes of 98 species of family Polyomaviridae across four genera. The genome size ranged from 3962bp (BM87) to 7369bp (BM85) but maximum genomes were in the range of 5 to 5.5 kb. The GC% had an average of 42% and ranged between 34.69 (BM95) to 52.35 (BM81). A total of 3036 SSRs and 223 cSSRs were extracted using IMEx with incident frequency from 18 to 56 and 0 to 7 respectively. The most prevalent mono-nucleotide repeat motif was “T” (48.95%) followed by “A” (33.48%). “AT/TA” was the most prevalent dinucleotide motif closely followed by “CT/TC”. The distribution was expectedly more in coding region with 77.6% SSRs of which nearly half were in Large T Antigen (LTA) gene. Notably, most viruses with humans, apes and related species as host exhibited exclusivity of mono-nucleotide repeats in AT region, a proposed predictive marker for determination of humans as host in virus in course of its evolution. Each genome has a unique SSR signature which is pivotal for viral evolution particularly in terms of host divergence.

A novel coronavirus has been reported as the causative pathogen of the Coronavirus disease 2019 (COVID-19) outbreak Wuhan city, China in December 2019. Due to the rapid spreading of COVID-19 worldwide, it has been announced as a pandemic by the World Health Organization (WHO). Hospitalized patients in Wuhan are associated with the Huanan seafood wholesale market where live animals, such as poultry, bats, snakes, frogs, rabbits, marmots, and hedgehogs are sold in that market which suggests a possible zoonotic infection. Therefore, it is essential to identify the potential animal reservoir, and the possibility of infection for other animal species. This short review aims to provide an overview on the relation between severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection and animals.

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

The recent 2019-nCoV outbreak, spreading infection around the globe is jeopardizing the public health and global economy. The virus was reported to have emerged from an animal market in Wuhan, China at the end of 2019 and presumed to have originated from bats and eventually transmitted in humans. The entry of the virus into human cells is triggered by a series of molecular events initiated with the binding of a receptor-binding domain of viral spike protein to human Ace2 cell surface receptor. Based on the comparative sequence analysis of the well-known binding hotspots of human Ace2, cross-interacting potential of 2019-nCoV was predicted, which suggests Ace2 of wild animals like tiger, bear, orangutan, etc.; aquatic mammals like whale and dolphins; and domestic animals like cat, horse, goat, sheep, dog etc. as potential target. However, the recognition of Ace2 of bats, rats and mice by the 2019-nCoV spike protein remains under question. The study indicates that 2019-nCoV might have broad host range and may thus intensify the gravity of 2019-nCoV outbreak

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

The holistic approach of One Health, which sees human, animal, plant, and environmental health as a unit, rather than discrete parts, requires not only interdisciplinary cooperation, but standardized methods for communicating and archiving data, enabling participants to easily share what they have learned and allow others to build upon their findings.Ongoing work by NCBI and the GenomeTrakr project illustrates how open data platforms can help meet the needs of federal and state regulators, public health laboratories, departments of agriculture, and universities. Here we describe how microbial pathogen surveillance can be transformed by having an open access database along with Best Practices for contributors to follow. First, we describe the open pathogen surveillance framework, hosted on the NCBI platform. We cover the current community standards for WGS quality, provide an SOP for assessing your own sequence quality and recommend QC thresholds for all submitters to follow. We then provide an overview of NCBI data submission along with step by step details. And finally, we provide curation guidance and an SOP for keeping your public data current within the database. These Best Practices can be models for other open data projects, thereby advancing the One Health goals of Findable, Accessible, Interoperable and Re-usable (FAIR) data.

Exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane is induced by infection with several members of the Alphaherpesvirinae subfamily. There is evidence that PS is used by the equine herpesvirus type 1 (EHV-1) during entry, but the exact role of PS and other phospholipids in the entry process remains unknown. Here, we investigated the interaction of differently charged phospholipids with virus particles and determined their influence on infection. Our data show that liposomes containing negatively charged PS or positively charged DOTAP [N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium)] inhibited EHV-1 infection, while neutral phosphatidylcholine (PC) had no effect. Inhibition of infection with PS was transient, decreased with time, and was dose dependent. Our findings indicate that both cationic and anionic phospholipids can interact with the virus and reduce infectivity, while acting through different mechanisms. Charged phospholipids were found to have antiviral effects and can may be used to inhibit EHV-1 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor throughout the globe. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing ’omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A. mellifera. By highlighting the most promising traits of varroa-surviving bees and our current knowledge on their genetic bases, this work will help direct future research efforts and selection programs to control this pest. Additionally, by comparing the diverse populations of honey bees that exhibit the traits, this review highlights the consequences of anthropogenic and natural selection on the interactions between hosts and parasites.

Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21^st century. Here, the host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a shared pool of variants for the X-linked locus of ACE2 receptor. Several specific and common ACE2 variants were of the utmost importance to the viral entry and infection. In the absence of gender bias for the gene expression profiles, the hemizygous rare variants of ACE2 describe the observed higher mortality rate in males. Finally, a personalized medicine strategy is conceived for isolating high-risk individuals in epidemic circumstances.

Deforestation and associated changing landscapes are major components of environmental changes, with important implications for ecosystem functioning and biodiversity conservation. Tropical forests are hot spots of biodiversity and provide multiple goods and ecosystem services which benefit people in many ways Forest also play an important role in health-related legends, myths, and fairy tales from all over the world, and are important sources of new potential emerging microbial threats to human. Although plausibly numerous abundant microbial forms with a forest origin may exist, our systematic literature review shows that forest-derived infection studies are relatively unexplored, and both taxonomically and geographically biased. Since biodiversity has been associated with emergence of novel infectious diseases at macro-scale, we describe the main biogeographical patterns in the emerging infection-biodiversity-forest loss nexus. Then, we illustrate four fine-scale case studies to decipher the underlying processes of increased infection risk in changing forest clearing landscapes. Finally, we identify scientific challenges and regional management measures required to mitigate these important new emerging threats.

The parasitic mite, Varroa destructor, has shaken the beekeeping and pollination industries since its spread from its native host, the Asian honey bee (Apis cerana), to the naïve European honey bee (A. mellifera) used commercially for pollination and honey production around the globe. Varroa is the greatest threat to honey bee health. Worrying observations include increasing acaricide resistance in the varroa population and sinking economic treatment thresholds, suggesting that the mites or their vectored viruses are becoming more virulent. Highly infested weak colonies facilitate mite dispersal and disease transmission to stronger and healthier colonies. Here, we review recent developments in the biology, pathology and management of varroa, and integrate older knowledge that is less well known.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

The novel coronavirus, COVID-19 is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Like millions of others around the world, I am wondering, is there anything that could be done, other than keeping high personal hygiene, and be vigilant of symptoms, to reduce the chances of infection, or at least to reduce the burden of the disease. So far, the National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this opinion-based article, I want to discuss, why keeping the adequate micronutrient balance might enhance the host response and be protective of viral infections. A detailed in-depth discussion of various micronutrients is not the purpose of this article, I will mostly emphasize on the role of zinc in viral infection.

The global pandemic of COVID-19 accounts for more than 14,000 deaths worldwide. However, little is known about the host genetics interaction with infection and COVID-19 progression. To better understand the role of host genetics, we review the current literature, aggregate readily available genetic resources, and provide some updated analysis relevant to COVID-19 and associated phenotypes. Using the unrelated individuals in UK Biobank (total n = 337,579 across 5 populations), we aggregate human leukocyte antigen and ABO blood type frequencies. We find significant and consistent risk reduction of blood group O reported in Zhao et al. and encourage broad sharing of ABO blood type frequencies that are readily accessible across COVID-19 with mild, moderate, and severe/critical symptoms for robust inferences at https://tinyurl.com/abo-covid19. In addition, we generate polygenic risk scores (PRSs) weights for 29 blood measurements, including clinically relevant haematological measurements for COVID-19, such as lymphocyte count and percentage. Focusing on the 8 most COVID-19 clinically relevant blood measurements, we performed PRS-PheWAS analysis across 44 disease antigen measurements (n = 6,643 unrelated individuals in White British group), infectious diseases and acute respiratory infections (n = 20,928 cases and 349,000 controls across 3 population groups) and deaths (n = 1,846 cases and 368,082 controls), recorded in hospital inpatient record and death registry data, respectively, in UK Biobank, and find host genetic PRS associations with disease risk. Taken together, we anticipate these resources (https://github.com/rivas-lab/covid19) will aid in improving our understanding of host genetic risk factors playing a role in SARS-CoV-2 infection and COVID-19 disease severity.

A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve and resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap, and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle Callosobruchus maculatus. Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil. Mapping populations derived from each lentil-adapted line revealed a polygenic basis for two host-specific performance traits (weight and development time), which had low to modest heritabilities. We found less evidence of parallelism in genotype-phenotype associations across these lines than in allele frequency changes during the experiments. Differential gene expression caused by differences in recent evolutionary history exceeded that caused by immediate rearing host. Together, the three genomic data sets suggest that genes affecting traits other than weight and development time are likely to be the main causes of parallel evolution, and that detoxification genes (especially cytochrome P450s and beta-glucosidase) could be especially important for colonization of lentil by C. maculatus.

Despite the implementation of control strategies, the invasive parasitic mite Varroa destructor remains one of the principal causes of honey bee (Apis mellifera) colony losses in numerous countries. For this reason, the parasite represents a serious threat to beekeeping and to agro-ecosystems that benefit from the pollination services provided by honey bees. Numerous selection programmes have been initiated over the last three decades with the aim of promoting the establishment of balance in the host–parasite relationship and, thus, helping European honey bees to survive in the presence of the parasite without the need for acaricide treatments. Such programmes have focused on either selective breeding for putative resistance traits or natural selection. To date, no clear overview of these attempts has been available, which has prevented building on past successes or failures and, therefore, hindered the development of a sustainable strategy for solving the V. destructor problem. In the present study, we review past and current selection strategies, report on their outcomes and discuss their limitations. Based on this state-of-the-art knowledge, we propose a strategy for increasing response to selection and colony survival against V. destructor infestations. Developing in-depth knowledge regarding the selected traits, optimising selection programmes and communicating their outcomes are all crucial to our efforts to establish a balanced relationship between the invasive parasite and its new host.

Rodents are known to be reservoir hosts for at least 60 zoonotic diseases and are known to play an important role in their transmission and spreading in different ways. We sampled different rodent communities within and around human settlements in Northern Senegal, an area subjected to major environmental transformations associated with global changes. Herein, we conducted an epidemiological study on their bacterial communities.One hundred and seventy-one (171) invasive and native rodents were captured, 50 from outdoors trapping sites and 121 rodents from indoors habitats, consisting on 5 species. DNA of thirteen pathogens have been successfully screened on the rodent’s spleens. We found: 2.3% of positive spleens to Piroplasmida and amplified one which gives a potentially new species Candidatus “Theileria senegalensis”; 9.35% of Bartonella spp. and amplified 10, giving three genotypes. 3.5% of filariasis species; 18.12% of Anaplasmataceae species and amplified only 5, giving a new potential species Candidatus “Ehrlichia senegalensis”; 2.33 % of Hepatozoon spp.; 3.5% of Kinetoplastidae spp; and 15.2% of Borrelia spp. and amplified 8 belonging all to Borrelia crocidurae.Some of the species of pathogens carried by the rodents of our studied area may be unknown because most of those we have identified are new species. In one bacterial taxon, Anaplasma, a positive correlation between host body mass and infection was found. Overall, male and invasive rodents appeared less infected than female and native ones, respectively.

Public health agencies are increasingly using pathogen whole genome sequencing (WGS) to support surveillance and epidemiologic investigations. As access to WGS has grown, greater amounts of molecular data have helped improve our ability to detect outbreaks, investigate transmission chains, and explore large-scale population dynamics, such as the spread of antibiotic resistance. However, the wide adoption of WGS also poses challenges due to the amount of data generated and the need to transform raw data prior to analysis. This complexity means that public health agencies may need more advanced computational infrastructure, a broader technical workforce, and new approaches to data management and stewardship. As both a guide for how this development could occur, and a place to initiate discussion, we describe ten proposals for developing and supporting an informatics infrastructure for public health.

Papillomaviruses infect the skin and mucosal surfaces of diverse animal hosts with consequences ranging from asymptomatic colonization to highly malignant epithelial cancers. Increasing evidence suggests a role for papillomaviruses in the most common cutaneous malignancy of domestic cats, squamous cell carcinoma (SCC). Using total DNA sequencing we identified a novel feline papillomavirus in a nasal biopsy taken from a cat presenting with both nasal cavity lymphoma and recurrent squamous cell carcinoma affecting the nasal planum. We designate this novel virus as Felis catus papillomavirus 6 (FcaPV6). The complete FcaPV6 7453 bp genome was similar to those of other feline papillomaviruses and phylogenetic analysis revealed that it was most closely related to FcaPV3, although was distinct enough to represent a new viral species within the genus Taupapillomavirus. Archived excisional biopsy of the SCC, taken 20 months prior to presentation, was intensely positive on p16 immunostaining. FcaPV6, amplified using virus-specific, but not consensus, PCR was the only papillomavirus detected in DNA extracted from the SCC. Conversely, renal lymphoma, sampled at necropsy two months after presentation, tested negative on FcaPV6-specific PCR. In sum, using metagenomics we demonstrate the presence of a novel feline papillomavirus in association with cutaneous squamous cell carcinoma.

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures- check valve (in), check valve (out), double-check valve (in and out), and on-off valve, were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.