A look into the invisible: ultraviolet-B sensitivity in an insect (Caliothrips phaseoli) revealed through a behavioural action spectrum

Caliothrips phaseoli, a phytophagous insect, detects and responds to solar ultraviolet-B radiation (UV-B; λ ≤ 315 nm) under field conditions. A highly specific mechanism must be present in the thrips visual system in order to detect this narrow band of solar radiation, which is at least 30 times less abundant than the UV-A (315–400 nm), to which many insects are sensitive. We constructed an action spectrum of thrips responses to light by studying their behavioural reactions to monochromatic irradiation under confinement conditions. Thrips were maximally sensitive to wavelengths between 290 and 330 nm; human-visible wavelengths (λ ≥ 400 nm) failed to elicit any response. All but six ommatidia of the thrips compound eye were highly fluorescent when exposed to UV-A of wavelengths longer than 330 nm. We hypothesized that the fluorescent compound acts as an internal filter, preventing radiation with λ > 330 nm from reaching the photoreceptor cells. Calculations based on the putative filter transmittance and a visual pigment template of λ_max = 360 nm produced a sensitivity spectrum that was strikingly similar to the action spectrum of UV-induced behavioural response. These results suggest that specific UV-B vision in thrips is achieved by a standard UV-A photoreceptor and a sharp cut-off internal filter that blocks longer UV wavelengths in the majority of the ommatidia.     

Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses

The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs, APOBECs, SAMHD1, tetherin, viperin, and HERC5/6. Additionally, antiviral processes such as MHC‐I antigen presentation and stress granule signaling are enhanced in IRGM‐deficient cells, indicating a robust cell‐intrinsic antiviral immune state. Consistently, IRGM‐depleted cells are resistant to the infection with seven viruses from five different families, including Togaviridae, Herpesviridae, Flaviviverdae, Rhabdoviridae, and Coronaviridae. Moreover, we show that Irgm1 knockout mice are highly resistant to chikungunya virus (CHIKV) infection. Altogether, our work highlights IRGM as a broad therapeutic target to promote defense against a large number of human viruses, including SARS‐CoV‐2, CHIKV, and Zika virus.     

House flies delay fungal infection by fevering: at a cost

1. Many ectothermic species have evolved the ability to invoke a ‘behavioural fever’ when infected with a pathogen. The relative costs and benefits of this response, however, have rarely been quantified. 2. The aim of this study was investigate the nature and consequences of behavioural fever in the house fly, Musca domestica L., in response to infection with a possible biocontrol agent, the fungal entomopathogen, Beauveria bassiana (Balsamo) Vuillemin. 3. It was found that infected flies preferred higher temperatures and allocated more effort to thermoregulation than uninfected flies. Flies could not overcome infection but the altered thermal behaviour allowed infected flies to extend their survival and to lay more eggs relative to infected flies maintained under constant conditions. However, flies allowed to fever had lower egg viability suggesting a possible cost. 4. Under the present experimental conditions, the putative costs and benefits fever balanced one another resulting in no net change in fitness. Fever did not, therefore, limit the control potential of the fungus. We discuss whether the costs and benefits of behavioural fever might differ in other ecological contexts.     

Seasonal time bombs: dominant temperate viruses affect Southern Ocean microbial dynamics

Rapid warming in the highly productive western Antarctic Peninsula (WAP) region of the Southern Ocean has affected multiple trophic levels, yet viral influences on microbial processes and ecosystem function remain understudied in the Southern Ocean. Here we use cultivation-independent quantitative ecological and metagenomic assays, combined with new comparative bioinformatic techniques, to investigate double-stranded DNA viruses during the WAP spring–summer transition. This study demonstrates that (i) temperate viruses dominate this region, switching from lysogeny to lytic replication as bacterial production increases, and (ii) Southern Ocean viral assemblages are genetically distinct from lower-latitude assemblages, primarily driven by this temperate viral dominance. This new information suggests fundamentally different virus–host interactions in polar environments, where intense seasonal changes in bacterial production select for temperate viruses because of increased fitness imparted by the ability to switch replication strategies in response to resource availability. Further, temperate viral dominance may provide mechanisms (for example, bacterial mortality resulting from prophage induction) that help explain observed temporal delays between, and lower ratios of, bacterial and primary production in polar versus lower-latitude marine ecosystems. Together these results suggest that temperate virus–host interactions are critical to predicting changes in microbial dynamics brought on by warming in polar marine systems.     

Environmental enrichment promotes neural plasticity and cognitive ability in fish

Different kinds of experience during early life can play a significant role in the development of an animal''s behavioural phenotype. In natural contexts, this influences behaviours from anti-predator responses to navigation abilities. By contrast, for animals reared in captive environments, the homogeneous nature of their experience tends to reduce behavioural flexibility. Studies with cage-reared rodents indicate that captivity often compromises neural development and neural plasticity. Such neural and behavioural deficits can be problematic if captive-bred animals are being reared with the intention of releasing them as part of a conservation strategy. Over the last decade, there has been growing interest in the use of environmental enrichment to promote behavioural flexibility in animals that are bred for release. Here, we describe the positive effects of environmental enrichment on neural plasticity and cognition in juvenile Atlantic salmon (Salmo salar). Exposing fish to enriched conditions upregulated the forebrain expression of NeuroD1 mRNA and improved learning ability assessed in a spatial task. The addition of enrichment to the captive environment thus promotes neural and behavioural changes that are likely to promote behavioural flexibility and improve post-release survival.     

An additional step in the transmission of Yersinia pestis?

Plague, caused by the bacterium Yersinia pestis, is a mammalian vector-borne disease, transmitted by fleas that serve as the vector between rodent hosts. For many pathogens, including Y. pestis, there are strong evolutionary pressures that lead to a reduction in ‘useless genes'', with only those retained that reflect function in the specific environment inhabited by the pathogen. Genetic traits critical for survival and transmission between two environments, the rodent and the flea, are conserved in epizootic/epidemic plague strains. However, there are genes that remain conserved for which no function in the flea–rodent cycle has yet been observed, indicating an additional environment may exist in the transmission cycle of plague. Here, we present evidence for highly conserved genes that suggests a role in the persistence of Y. pestis after death of its host. Furthermore, maintenance of these genes points to Y. pestis traversing a post-mortem path between, and possibly within, epizootic periods and offering insight into mechanisms that may allow Y. pestis an alternative route of transmission in the natural environment.     

Phenotypic variability in unicellular organisms: from calcium signalling to social behaviour

Historically, research has focused on the mean and often neglected the variance. However, variability in nature is observable at all scales: among cells within an individual, among individuals within a population and among populations within a species. A fundamental quest in biology now is to find the mechanisms that underlie variability. Here, we investigated behavioural variability in a unique unicellular organism, Physarum polycephalum. We combined experiments and models to show that variability in cell signalling contributes to major differences in behaviour underpinning some aspects of social interactions. First, following thousands of cells under various contexts, we identified distinct behavioural phenotypes: ‘slow–regular–social’, ‘fast–regular–social’ and ‘fast–irregular–asocial’. Second, coupling chemical analysis and behavioural assays we found that calcium signalling is responsible for these behavioural phenotypes. Finally, we show that differences in signalling and behaviour led to alternative social strategies. Our results have considerable implications for our understanding of the emergence of variability in living organisms.     

Poly(ADP-ribose) polymerase-1 is a survival factor for radiation-exposed intestinal epithelial stem cells in vivo

Poly(ADP-ribose) polymerase-1 (PARP-1) is a key enzyme mediating the cellular response to DNA strand breaks. It plays a critical role in genomic stability and survival of proliferating cells in culture undergoing DNA damage. Intestinal epithelium is the most proliferative tissue in the mammalian body and its stem cells show extreme sensitivity to low-level genotoxic stress. We investigated the role of PARP-1 in the in vivo damage response of intestinal stem cells in crypts of PARP-1^–/– and control mice following whole-body γ-irradiation (1 Gy). In the PARP-1^–/– mice there was a significant delay during the first 6 h in the transient p53 accumulation in stem cells whereas an increased number of cells were positive for p21^CIP1/WAF1. Either no or only marginal differences were noted in MDM2 expression, apoptosis, induction of or recovery from mitotic blockage, or inhibition of DNA synthesis. We further observed a dose-dependent reduction in crypt survival measured at 4 days post-irradiation in control mice, and this crypt-killing effect was significantly potentiated in PARP-1^–/– mice. Our results thus establish that PARP-1 acts as a survival factor for intestinal stem cells in vivo and suggest a functional link with early p53 and p21^CIP1/WAF1 responses.     

Within-population variability in a moth sex pheromone blend: genetic basis and behavioural consequences

Evolutionary diversification of sexual communication systems in moths is perplexing because signal and response are under stabilizing selection in many species, and this is expected to constrain evolutionary change. In the moth Heliothis virescens, we consistently found high phenotypic variability in the female sex pheromone blend within each of four geographically distant populations. Here, we assess the heritability, genetic basis and behavioural consequences of this variation. Artificial selection with field-collected moths dramatically increased the relative amount of the saturated compound 16:Ald and decreased its unsaturated counterpart Z11–16:Ald, the major sex pheromone component (high line). In a cross between the high- and low-selected lines, one quantitative trait locus (QTL) explained 11–21% of the phenotypic variance in the 16:Ald/Z11–16:Ald ratio. Because changes in activity of desaturase enzymes could affect this ratio, we measured their expression levels in pheromone glands and mapped desaturase genes onto our linkage map. A delta-11-desaturase had lower expression in females producing less Z11–16:Ald; however, this gene mapped to a different chromosome than the QTL. A model in which the QTL is a trans-acting repressor of delta-11 desaturase expression explains many features of the data. Selection favouring heterozygotes which produce more unsaturated components could maintain a polymorphism at this locus.     

Adaptive and nonadaptive plasticity in changing environments: Implications for sexual species with different life history strategies

Populations adapt to novel environmental conditions by genetic changes or phenotypic plasticity. Plastic responses are generally faster and can buffer fitness losses under variable conditions. Plasticity is typically modeled as random noise and linear reaction norms that assume simple one‐to‐one genotype–phenotype maps and no limits to the phenotypic response. Most studies on plasticity have focused on its effect on population viability. However, it is not clear, whether the advantage of plasticity depends solely on environmental fluctuations or also on the genetic and demographic properties (life histories) of populations. Here we present an individual‐based model and study the relative importance of adaptive and nonadaptive plasticity for populations of sexual species with different life histories experiencing directional stochastic climate change. Environmental fluctuations were simulated using differentially autocorrelated climatic stochasticity or noise color, and scenarios of directional climate change. Nonadaptive plasticity was simulated as a random environmental effect on trait development, while adaptive plasticity as a linear, saturating, or sinusoidal reaction norm. The last two imposed limits to the plastic response and emphasized flexible interactions of the genotype with the environment. Interestingly, this assumption led to (a) smaller phenotypic than genotypic variance in the population (many‐to‐one genotype–phenotype map) and the coexistence of polymorphisms, and (b) the maintenance of higher genetic variation—compared to linear reaction norms and genetic determinism—even when the population was exposed to a constant environment for several generations. Limits to plasticity led to genetic accommodation, when costs were negligible, and to the appearance of cryptic variation when limits were exceeded. We found that adaptive plasticity promoted population persistence under red environmental noise and was particularly important for life histories with low fecundity. Populations producing more offspring could cope with environmental fluctuations solely by genetic changes or random plasticity, unless environmental change was too fast.     

Evidence that avian reovirus σNS is an RNA chaperone: implications for genome segment assortment

Reoviruses are important human, animal and plant pathogens having 10–12 segments of double-stranded genomic RNA. The mechanisms controlling the assortment and packaging of genomic segments in these viruses, remain poorly understood. RNA–protein and RNA–RNA interactions between viral genomic segment precursors have been implicated in the process. While non-structural viral RNA-binding proteins, such as avian reovirus σNS, are essential for virus replication, the mechanism by which they assist packaging is unclear. Here we demonstrate that σNS assembles into stable elongated hexamers in vitro, which bind single-stranded nucleic acids with high affinity, but little sequence specificity. Using ensemble and single molecule fluorescence spectroscopy, we show that σNS also binds to a partially double-stranded RNA, resulting in gradual helix unwinding. The hexamer can bind multiple RNA molecules and exhibits strand-annealing activity, thus mediating conversion of metastable, intramolecular stem-loops into more stable heteroduplexes. We demonstrate that the ARV σNS acts as an RNA chaperone facilitating specific RNA–RNA interactions between genomic precursors during segment assortment and packaging.     

Matrix-dependent Tiam1/Rac Signaling in Epithelial Cells Promotes Either Cell–Cell Adhesion or Cell Migration and Is Regulated by Phosphatidylinositol 3-Kinase

We previously demonstrated that both Tiam1, an activator of Rac, and constitutively active V12Rac promote E-cadherin–mediated cell–cell adhesion in epithelial Madin Darby canine kidney (MDCK) cells. Moreover, Tiam1 and V12Rac inhibit invasion of Ras-transformed, fibroblastoid MDCK-f3 cells by restoring E-cadherin–mediated cell–cell adhesion. Here we show that the Tiam1/Rac-induced cellular response is dependent on the cell substrate. On fibronectin and laminin 1, Tiam1/Rac signaling inhibits migration of MDCK-f3 cells by restoring E-cadherin–mediated cell– cell adhesion. On different collagens, however, expression of Tiam1 and V12Rac promotes motile behavior, under conditions that prevent formation of E-cadherin adhesions. In nonmotile cells, Tiam1 is present in adherens junctions, whereas Tiam1 localizes to lamellae of migrating cells. The level of Rac activation by Tiam1, as determined by binding to a glutathione-S-transferase– PAK protein, is similar on fibronectin or collagen I, suggesting that rather the localization of the Tiam1/Rac signaling complex determines the substrate-dependent cellular responses. Rac activation by Tiam1 requires PI3-kinase activity. Moreover, Tiam1- but not V12Rac-induced migration as well as E-cadherin–mediated cell– cell adhesion are dependent on PI3-kinase, indicating that PI3-kinase acts upstream of Tiam1 and Rac.     

1‐Undecene from Pseudomonas aeruginosa is an olfactory signal for flight‐or‐fight response in Caenorhabditis elegans

Animals possess conserved mechanisms to detect pathogens and to improve survival in their presence by altering their own behavior and physiology. Here, we utilize Caenorhabditis elegans as a model host to ask whether bacterial volatiles constitute microbe‐associated molecular patterns. Using gas chromatography–mass spectrometry, we identify six prominent volatiles released by the bacterium Pseudomonas aeruginosa. We show that a specific volatile, 1‐undecene, activates nematode odor sensory neurons inducing both flight and fight responses in worms. Using behavioral assays, we show that worms are repelled by 1‐undecene and that this aversion response is driven by the detection of this volatile through AWB odor sensory neurons. Furthermore, we find that 1‐undecene odor can induce immune effectors specific to P. aeruginosa via AWB neurons and that brief pre‐exposure of worms to the odor enhances their survival upon subsequent bacterial infection. These results show that 1‐undecene derived from P. aeruginosa serves as a pathogen‐associated molecular pattern for the induction of protective responses in C. elegans.     

SARS‐CoV‐2–host proteome interactions for antiviral drug discovery

Treatment options for COVID‐19, caused by SARS‐CoV‐2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS‐CoV‐2–host interactomes and provided great resources for understanding viral replication. However, host proteins that functionally associate with SARS‐CoV‐2 are localized in the corresponding subnetwork within the comprehensive human interactome. Therefore, constructing a downstream network including all potential viral receptors, host cell proteases, and cofactors is necessary and should be used as an additional criterion for the validation of critical host machineries used for viral processing. This study applied both affinity purification mass spectrometry (AP‐MS) and the complementary proximity‐based labeling MS method (BioID‐MS) on 29 viral ORFs and 18 host proteins with potential roles in viral replication to map the interactions relevant to viral processing. The analysis yields a list of 693 hub proteins sharing interactions with both viral baits and host baits and revealed their biological significance for SARS‐CoV‐2. Those hub proteins then served as a rational resource for drug repurposing via a virtual screening approach. The overall process resulted in the suggested repurposing of 59 compounds for 15 protein targets. Furthermore, antiviral effects of some candidate drugs were observed in vitro validation using image‐based drug screen with infectious SARS‐CoV‐2. In addition, our results suggest that the antiviral activity of methotrexate could be associated with its inhibitory effect on specific protein–protein interactions.     

A long-range RNA–RNA interaction between the 5′ and 3′ ends of the HCV genome

The RNA genome of the hepatitis C virus (HCV) contains multiple conserved structural cis domains that direct protein synthesis, replication, and infectivity. The untranslatable regions (UTRs) play essential roles in the HCV cycle. Uncapped viral RNAs are translated via an internal ribosome entry site (IRES) located at the 5′ UTR, which acts as a scaffold for recruiting multiple protein factors. Replication of the viral genome is initiated at the 3′ UTR. Bioinformatics methods have identified other structural RNA elements thought to be involved in the HCV cycle. The 5BSL3.2 motif, which is embedded in a cruciform structure at the 3′ end of the NS5B coding sequence, contributes to the three-dimensional folding of the entire 3′ end of the genome. It is essential in the initiation of replication. This paper reports the identification of a novel, strand-specific, long-range RNA–RNA interaction between the 5′ and 3′ ends of the genome, which involves 5BSL3.2 and IRES motifs. Mutants harboring substitutions in the apical loop of domain IIId or in the internal loop of 5BSL3.2 disrupt the complex, indicating these regions are essential in initiating the kissing interaction. No complex was formed when the UTRs of the related foot and mouth disease virus were used in binding assays, suggesting this interaction is specific for HCV sequences. The present data firmly suggest the existence of a higher-order structure that may mediate a protein-independent circularization of the HCV genome. The 5′–3′ end bridge may have a role in viral translation modulation and in the switch from protein synthesis to RNA replication.     

Investigating life‐history traits of Steller sea lions with multistate hidden Markov mark–recapture models: Age at weaning and body size effects

The duration of offspring care is critical to female fitness and population resilience by allowing flexibility in life‐history strategies in a variable environment. Yet, for many mammals capable of extended periods of maternal care, estimates of the duration of offspring dependency are not available and the relative importance of flexibility of this trait on fitness and population viability has rarely been examined. We used data from 4,447 Steller sea lions Eumetopias jubatus from the Gulf of Alaska and multistate hidden Markov mark–recapture models to estimate age‐specific weaning probabilities. Maternal care beyond age 1 was common: Weaning was later for animals from Southeast Alaska (SEAK) and Prince William Sound (PWS, weaning probabilities: 0.536–0.648/0.784–0.873 by age 1/2) compared with animals born to the west (0.714–0.855/0.798–0.938). SEAK/PWS animals were also smaller than those born farther west, suggesting a possible link. Females weaned slightly earlier (+0.080 at age 1 and 2) compared with males in SEAK only. Poor survival for weaned versus unweaned yearlings occurred in southern SEAK (female survival probabilities: 0.609 vs. 0.792) and the central Gulf (0.667 vs. 0.901), suggesting poor conditions for juveniles in these areas. First‐year survival increased with neonatal body mass (NBM) linearly in the Gulf and nonlinearly in SEAK. The probability of weaning at age 1 increased linearly with NBM for SEAK animals only. Rookeries where juveniles weaned at earlier ages had lower adult female survival, but age at weaning was unrelated to population trends. Our results suggest the time to weaning may be optimized for different habitats based on long‐term average conditions (e.g., prey dynamics), that may also shape body size, with limited short‐term plasticity. An apparent trade‐off of adult survival in favor of juvenile survival and large offspring size in the endangered Gulf of Alaska population requires further study.     

Host gene expression profiling of dengue virus infection in cell lines and patients

Background

Despite the seriousness of dengue-related disease, with an estimated 50–100 million cases of dengue fever and 250,000–500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virus-infected cell lines and in patients developing dengue fever.

Methodology/Principal Findings

Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-κB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway. Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication. The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication.

Conclusion/Significance

Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies. We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy.     

Why are population growth rate estimates of past and present hunter–gatherers so different?

Hunter–gatherer population growth rate estimates extracted from archaeological proxies and ethnographic data show remarkable differences, as archaeological estimates are orders of magnitude smaller than ethnographic and historical estimates. This could imply that prehistoric hunter–gatherers were demographically different from recent hunter–gatherers. However, we show that the resolution of archaeological human population proxies is not sufficiently high to detect actual population dynamics and growth rates that can be observed in the historical and ethnographic data. We argue that archaeological and ethnographic population growth rates measure different things; therefore, they are not directly comparable. While ethnographic growth rate estimates of hunter–gatherer populations are directly linked to underlying demographic parameters, archaeological estimates track changes in the long-term mean population size, which reflects changes in the environmental productivity that provide the ultimate constraint for forager population growth. We further argue that because of this constraining effect, hunter–gatherer populations cannot exhibit long-term growth independently of increasing environmental productivity.This article is part of the theme issue ‘Cross-disciplinary approaches to prehistoric demography’.