Apparent Host Research Articles

The Relativistic Jet Orientation and Host Galaxy of the Peculiar Blazar PKS 1413+135

Abstract PKS 1413+135 is one of the most peculiar blazars known. Its strange properties led to the hypothesis almost four decades ago that it is gravitationally lensed by a mass concentration associated with an intervening galaxy. It exhibits symmetric achromatic variability, a rare form of variability that has been attributed to gravitational milli-lensing. It has been classified as a BL Lac object, and is one of the rare objects in this class with a visible counterjet. BL Lac objects have jet axes aligned close to the line of sight. It has also been classified as a compact symmetric object—objects that have jet axes not aligned close to the line of sight. Intensive efforts to understand this blazar have hitherto failed to resolve even the questions of the orientation of the relativistic jet and the host galaxy. Answering these two questions is important because they challenge our understanding of jets in active galactic nuclei and the classification schemes we use to describe them. We show that the jet axis is aligned close to the line of sight and PKS 1413+135 is almost certainly not located in the apparent host galaxy, but is a background object in the redshift range 0.247 < z < 0.5. The intervening spiral galaxy at z = 0.247 provides a natural host for the putative lens responsible for symmetric achromatic variability and is shown to be a Seyfert 2 galaxy. We also show that, as for the radio emission, a “multizone” model is needed to account for the high-energy emission.

Diversification and selection pattern of CYP6B genes in Japanese Papilio butterflies and their association with host plant spectra.

Herbivorous insects are thought to have evolved counteradaptations to conquer chemical defenses in their host plants in a stepwise co-evolutionary process. Papilio butterflies use CYP6B gene family members to metabolize furanocoumarins in their Rutaceae or Apiaceae host plants. CYP6Bs have functionally diverged among Papilio species to be able to metabolite diverse types of furanocoumarins in their host plants. In this study, we examined the diversification and selection patterns of CYP6B among nine Papilio species in Japan (eight Rutaceae specialists and one Apiaceae specialist) and their association with host plant spectra and furanocoumarin profiles. We compared host plant spectrum of eight Rutaceae feeding Papilio species and also performed a furanocoumarin profiling of their host plants. In addition, we reconstructed CYP6B gene phylogeny and performed selection analysis based on the transcriptome data of those nine Papilio species. Among Rutaceae-feeding Papilio species, host plant spectrum differences were correlated with their furanocoumarin profiles. However, all tested Papilio species had similar duplicated sets of CYP6B, with no apparent lineage-specific or host plant-specific pattern of CYP6B diversification. Selection analysis showed a signature of positive selection on a CYP6B branch. The positively selected sites located at predicted substrate recognition sites and we also found that these CYP6B genes were observed only in Rutaceae-feeding species. These findings indicate that most CYP6B diversification occurred in ancestral species of these Papilio species, possibly in association with specific host plant chemical defenses and subsequent gene loss due to host specialization. These processes would have shaped the complex diversification patterns of the CYP6B gene family in Papilio butterflies. Our results also show potentially important CYP6B clades among Papilio species which likely to have diverged functions and associated with host plant phytochemicals in ancestral Papilio species.

Vapochromism of Organic Crystals Based on Macrocyclic Compounds and Inclusion Complexes

Vapochromic materials, which change color and luminescence when exposed to specific vapors and gases, have attracted considerable attention in recent years owing to their potential applications in a wide range of fields such as chemical sensors and environmental monitors. Although the mechanism of vapochromism is still unclear, several studies have elucidated it from the viewpoint of crystal engineering. In this mini-review, we investigate recent advances in the vapochromism of organic crystals. Among them, macrocyclic molecules and inclusion complexes, which have apparent host–guest interactions with analyte molecules (specific vapors and gases), are described. When the host compound is properly designed, its cavity size and symmetry change in response to guest molecules, influencing the optical properties by changing the molecular inclusion and recognition abilities. This information highlights the importance of structure–property relationships resulting from the molecular recognition at the solid–vapor interface.

Saprolegnia parasitica zoospore activity and host survival indicates isolate variation in host preference

The ubiquitous freshwater pathogen Saprolegnia parasitica has long been considered a true generalist, capable of infecting a wide range of fish species. It remains unclear, however, whether different isolates of this pathogen, obtained from distinct geographic locations and host species, display differences in host preference. To assess this, the current study examined the induced zoospore encystment responses of four S. parasitica isolates towards the skin of four fish species. While three of the isolates displayed ‘specialist’ responses, one appeared to be more of a ‘generalist’. In vivo challenge infections involving salmon and sea trout with the ‘generalist’ (salmon isolate EA001) and a ‘specialist’ (sea trout isolate EA016) pathogen, however, did not support the in vitro findings, with no apparent host preference reflected in infection outcomes. Survival of sea trout and salmon though was significantly different following a challenge infection with the sea trout (EA016) isolate. These results indicate that while S. parasitica isolates can be considered true generalists, they may target hosts to which they have been more frequently exposed (potential local adaptation). Understanding host preference of this pathogen could aid our understanding of infection epidemics and help with the development of fish management procedures.

Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo.

These studies compared the efficacies of our clinical agent galeterone (Gal) and the FDA-approved prostate cancer drug, enzalutamide (ENZ) with two lead next generation galeterone analogs (NGGAs), VNPP414 and VNPP433-3β, using prostate cancer (PC) in vitro and in vivo models. Antitumor activities of orally administered agents were also assessed in CWR22Rv1 tumor-bearing mice. We demonstrated that Gal and NGGAs degraded AR/AR-V7 and Mnk1/2; blocked cell cycle progression and proliferation of human PC cells; induced apoptosis; inhibited cell migration, invasion, and putative stem cell markers; and reversed the expression of epithelial-to-mesenchymal transition (EMT). In addition, Gal/NGGAs (alone or in combination) also inhibited the growth of ENZ-, docetaxel-, and mitoxantrone-resistant human PC cell lines. The NGGAs exhibited improved pharmacokinetic profiles over Gal in mice. Importantly, in vivo testing showed that VNPP433-3β (at 7.53-fold lower equimolar dose than Gal) markedly suppressed (84% vs. Gal, 47%; p < 0.01) the growth of castration-resistant PC (CRPC) CWR22Rv1 xenograft tumors, with no apparent host toxicity. ENZ was ineffective in this CRPC xenograft model. In summary, our findings show that targeting AR/AR-V7 and Mnk1/2 for degradation represents an effective therapeutic strategy for PC/CRPC treatment and supports further development of VNPP433-3β towards clinical investigation.

Molecular data infers the involvement of a marine aurantiactinomyxon in the life cycle of the myxosporean parasite Paramyxidium giardi (Cnidaria, Myxozoa).

An aurantiactinomyxon type is described from the marine naidid Tubificoides pseudogaster (Dahl, 1960), collected from the lower estuary of a Northern Portuguese River. This type constitutes the first of its collective group to be reported from Portugal, and only the fourth described from a marine oligochaete worldwide. Extensive morphological comparisons of new aurantiactinomyxon isolates to all known types without available molecular data are proposed to be unnecessary, given the artificiality of the usage of morphological criteria for actinosporean differentiation and the apparent strict host specificity of the group. Recognition of naidid oligochaetes as the hosts of choice for marine types of aurantiactinomyxon and other collective groups, suggests that the family Naididae played a preponderant role in the myxosporean colonization of estuarine communities. Molecular analyses of the type in study further infer its involvement in the life cycle of Paramyxidium giardi (Cépède, 1906) Freeman and Kristmundsson, 2018, a species that infects the kidney of European eel Anguilla anguilla (Linnaeus, 1758) and that has been reported globally, including from Portuguese waters. The low intraspecific difference registered in relation to Icelandic isolates of P. giardi (0.6%) is hypothesized to result from the emergence of genotypically different subspecies due to geographic isolation.

Biological control of Gonipterus: Uncovering the associations between eucalypts, weevils and parasitoids in their native range

The study was initiated by the relative failure of the parasitoid Anaphes nitens in controlling the eucalypt weevil Gonipterus platensis on the Iberian Peninsula. Our aim was to gain insight into the community of Gonipterus egg parasitoids occurring in Tasmania. During surveys in 2016 and 2017, adult weevils and egg pods were collected from Eucalyptus trees in Tasmania. The weevils were identified using male genital structure and DNA extracted from hatched larvae. Parasitoids that emerged from the egg pods were identified, and trophic associations of egg parasitoids, weevils and host plants were analyzed. Five species of the Gonipterus scutellatus complex, to which G. platensis belongs, were found, including Gonipterus sp. 2, which is reported for the first time from Tasmania. Molecular analysis corroborated previous phylogenetic studies of this group of species. A sixth species, G. notographus, was also collected. Most species were found to overlap in distribution in Tasmania and, despite being oligophagous, to display selectivity among Eucalyptus species used as hosts: G. platensis and G. pulverulentus were mainly found on E. ovata, Gonipterus sp. 1 on E. nitens and E. globulus and G. notographus on ‘peppermint’ species (E. amygdalina and E. pulchella). Five egg parasitoid species were found associated with these Gonipterus species: Anaphes inexpectatus, A. nitens, A. tasmaniae, Cirrospilus sp. and Euderus sp., with no apparent host specialization. Anaphes nitens, Cirrospilus sp. and Euderus sp. were more frequently found on E. ovata, possibly associated with G. platensis and G. pulverulentus, which were dominant on this host species. Conversely, A. inexpectatus was dominantly found on peppermints (43%), suggesting a main association with G. notographus. Anaphes nitens was found at 23 locations out of 117 and in 2017 was the most abundant parasitoid obtained, with an average 20% parasitism rate, indicating that this species is undergoing a geographical and population expansion since its first report from Tasmania in 2012. These findings contribute to the understanding of the parasitoid-Gonipterus-Eucalyptus trophic relationship and stand to improve future classical biological control programs against G. platensis and other invasive Gonipterus species.

The Novel Mnk1/2 Degrader and Apoptosis Inducer VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis

Currently, there are no effective therapies for patients with triple-negative breast cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC. Herein, we undertook a comprehensive study to evaluate the activity of a first-in-class Mnk1/2 protein degraders, racemic VNLG-152R and its two enantiomers (VNLG-152E1 and VNLG-152E2) in in vitro and in vivo models of TNBC. These studies enabled us to identify racemic VNLG-152R as the most efficacious Mnk1/2 degrader, superior to its pure enantiomers. By targeting Mnk1/2 protein degradation (activity), VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulated downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited remarkable antitumor (91 to 100% growth inhibition) and antimetastatic (~80% inhibition) activities against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel therapeutic strategy that can be developed as monotherapy for the effective treatment of patients with primary/metastatic TNBC.

Sepsis: evolving concepts and challenges.

Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in the pathogenesis of the syndrome has supported the modern concept of sepsis. Nevertheless, a definition of sepsis and the criteria for its recognition is a continuous process, which reflects the growing knowledge of its mechanisms and the success and failure of diagnostic and therapeutic interventions. Here we review the evolving concepts of sepsis, from the “systemic inflammatory response syndrome triggered by infection” (Sepsis-1) to “a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection” (Sepsis-3). We focused in the pathophysiology behind the concept and the criteria for recognition and diagnosis of sepsis. A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful, and we discuss that, at least in part, the apparent dysregulated host response may be an effort to adapt to a hostile environment. The new criteria for recognition and diagnosis of sepsis were derived from robust databases, restricted, however, to developed countries. Since then, the criteria have been supported in different clinical settings and in different economic and epidemiological contexts, but still raise discussion regarding their use for the identification versus the prognostication of the septic patient. Clinicians should not be restricted to definition criteria when evaluating patients with infection and should wisely use the broad array of information obtained by rigorous clinical observation.

The rate of Type-Ia supernovae in galaxy clusters and the delay-time distribution out to redshift 1.75

The observed delay-time distribution (DTD) of Type-Ia supernovae (SNe Ia) is a valuable probe of SN Ia progenitors and physics, and of the role of SNe Ia in cosmic metal enrichment. The SN Ia rate in galaxy clusters as a function of cluster redshift is an almost-direct measure of the DTD, but current estimates have been limited out to a mean redshift z=1.1, corresponding to time delays, after cluster star-formation, of over 3.2 Gyr. We analyze data from a Hubble Space Telescope monitoring project of 12 galaxy clusters at z=1.13-1.75, where we discover 29 SNe, and present their multi-band light curves. Based on the SN photometry and the apparent host galaxies, we assess cluster membership and SN type, finding 11 cases that are likely SNe Ia in cluster galaxies and 4 more cases which are possible but not certain cluster SNe Ia. We conduct simulations to estimate the SN detection efficiency, the experiment's completeness, and the photometric errors, and perform photometry of the cluster galaxies to derive the cluster stellar masses. Separating the cluster sample into high-z and low-z bins, we obtain rest-frame SN Ia rates per unit formed stellar mass of $2.2 ^{+2.6}_{-1.3}\times 10^{-13}{\rm yr}^{-1}{\rm M}_\odot^{-1}$ at a mean redshift z=1.25, and $3.5^{+6.6}_{-2.8} \times 10^{-13}{\rm yr}^{-1}{\rm M}_\odot^{-1}$ at z=1.58. Combining our results with previous cluster SN Ia rates, we fit the DTD, now down to delays of 1.5 Gyr, with a power-law dependence, $t^\alpha$, with $\alpha=-1.30^{+0.23}_{-0.16}$. We confirm previous indications for a Hubble-time-integrated SN Ia production efficiency that is several times higher in galaxy clusters than in the field, perhaps caused by a peculiar stellar initial mass function in clusters, or by a higher incidence of binaries that will evolve into SNe Ia.

Molecular and Morphological Phylogenetic Analyses of New World Cycad Beetles: What They Reveal about Cycad Evolution in the New World

Two major lineages of beetles inhabit cycad cones in the New World: weevils (Curculionoidea) in the subtribe Allocorynina, including the genera Notorhopalotria Tang and O’Brien, Parallocorynus Voss, Protocorynus O’Brien and Tang and Rhopalotria Chevrolat, and beetles in the family Erotylidae, including the genus Pharaxonotha Reitter. Analysis of the 16S ribosomal RNA (rRNA) mitochondrial gene as well as cladistic analysis of morphological characters of the weevils indicate four major radiations, with a probable origin on the cycad genus Dioon Lindl. and comparatively recent host shifts onto Zamia L. Analysis of the 16S rRNA gene for erotylid beetles indicates that an undescribed genus restricted to New World Ceratozamia Brongn. is the most early-diverging clade, and this lineage is sister to a large radiation of the genus Pharaxonotha onto Zamia, with apparent host shifts onto Dioon and Ceratozamia. Analysis of beetles are in accord with current models of continental drift in the Caribbean basin, support some proposed species groupings of cycads, but not others, and suggest that pollinator type may impact population genetic structure in their host cycads.

A new species of Giardia K\xfcnstler, 1882 (Sarcomastigophora: Hexamitidae) in hamsters

BackgroundGiardia spp. are flagellated protozoan parasites that infect humans and many other vertebrates worldwide. Currently seven species of Giardia are considered valid.ResultsHere, we report a new species, Giardia cricetidarum n. sp. in hamsters. Trophozoites of G. cricetidarum n. sp. are pear-shaped with four pairs of flagella and measure on average 14 μm (range 12–18 μm) in length and 10 μm (range 8–12 μm) in width. The trophozoites of the new species are generally larger and stouter than those of most of the other Giardia spp. and exhibit the lowest length/width ratio (c.1.40) of all recognized Giardia species. Cysts of G. cricetidarum n. sp. are ovoid and measure on average 11 μm (range 9–12 μm) in length and 10 μm (range 8–10 μm) in width and are indistinguishable from the cysts of other Giardia species. Molecular phylogenetic analyses based on beta-giardin, small subunit rRNA, and elongation factor-1 alpha loci all demonstrated that G. cricetidarum n. sp. is genetically distinct from all currently accepted Giardia spp. Investigation of the host range indicated that the new species was only found in hamsters (including Phodopus sungorus, P. campbelli and Mesocricetus auratus), while all the other described mammal-parasitizing species (G. muris, G. microti and G. intestinalis) each infect multiple hosts. Cross-transmission studies further demonstrated the apparent host specificity of G. cricetidarum n. sp. as it only infected hamsters. Trophozoites were found in high numbers in hamster intestines (5 × 105 – 5 × 106) and was rarely detected co-infecting with other Giardia spp. in the common hamster, suggesting it has some advantages in parasitizing hamsters.ConclusionsThis study has identified a new species of Giardia, which appears to be specific to hamsters, and together with the three other mammal-parasitizing Giardia species with different host ranges, may be able to be used as a model system for the study of evolutionary divergence of host parasitism strategies in Giardia.

Analysis of Dipylidium caninum tapeworms from dogs and cats, or their respective fleas - Part 2. Distinct canine and feline host association with two different Dipylidium caninum genotypes.

Initial investigations suggested the existence of two distinct genotypes of Dipylidium caninum from infected cat fleas (Ctenocephalides felis). One genotype was found almost always (> 95%) in fleas collected from, and proglottids shed by, domestic dogs. The other was found almost always (> 95%) in fleas collected from, and proglottids shed by, domestic cats. Molecular investigations (Part 1, in this journal) confirmed the presence of two distinct genotypes. Due to the apparent host association observed, these were referred to as the “D. caninum canine genotype” and the “D. caninum feline genotype”. The current article reports on an in vivo experimental infection study assessing the host-parasite interaction for each genotype. Mixed infections with the two genotypes in both dogs and cats were conducted. The specific genotyping of proglottids allowed us to assess the specific prepatent periods, prolificity, and longevity of each genotype in dogs versus cats. The possible hybridisation was also studied through molecular evaluation of the proglottids expelled by infected dogs and cats. Results demonstrate a clear distinct host interaction. The canine D. caninum genotype occurred at a higher frequency in dogs, with a shorter prepatent period and a longer lifespan; and the feline genotype occurred at a higher frequency in cats, with a shorter prepatent period and a longer lifespan. The absence of any hybrids in the mixed infections of both dogs and cats confirm the hypothesis of two distinct genotypes, suggesting the possibility of two distinct species within Dipylidium caninum.

Mitochondrial genome sequencing reveals potential origins of the scabies mite Sarcoptes scabiei infesting two iconic Australian marsupials

BackgroundDebilitating skin infestations caused by the mite, Sarcoptes scabiei, have a profound impact on human and animal health globally. In Australia, this impact is evident across different segments of Australian society, with a growing recognition that it can contribute to rapid declines of native Australian marsupials. Cross-host transmission has been suggested to play a significant role in the epidemiology and origin of mite infestations in different species but a chronic lack of genetic resources has made further inferences difficult. To investigate the origins and molecular epidemiology of S. scabiei in Australian wildlife, we sequenced the mitochondrial genomes of S. scabiei from diseased wombats (Vombatus ursinus) and koalas (Phascolarctos cinereus) spanning New South Wales, Victoria and Tasmania, and compared them with the recently sequenced mitochondrial genome sequences of S. scabiei from humans.ResultsWe found unique S. scabiei haplotypes among individual wombat and koala hosts with high sequence similarity (99.1% - 100%). Phylogenetic analysis of near full-length mitochondrial genomes revealed three clades of S. scabiei (one human and two marsupial), with no apparent geographic or host species pattern, suggestive of multiple introductions. The availability of additional mitochondrial gene sequences also enabled a re-evaluation of a range of putative molecular markers of S. scabiei, revealing that cox1 is the most informative gene for molecular epidemiological investigations. Utilising this gene target, we provide additional evidence to support cross-host transmission between different animal hosts.ConclusionsOur results suggest a history of parasite invasion through colonisation of Australia from hosts across the globe and the potential for cross-host transmission being a common feature of the epidemiology of this neglected pathogen. If this is the case, comparable patterns may exist elsewhere in the ‘New World’. This work provides a basis for expanded molecular studies into mange epidemiology in humans and animals in Australia and other geographic regions.

Host–Microbial Interactions in Idiopathic Pulmonary Fibrosis

Changes in the respiratory microbiome are associated with disease progression in idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome remains unknown. To explore the host-microbial interactions in IPF. Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays. By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease. Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF.

Ecological dynamics and co-occurrence among marine phytoplankton, bacteria and myoviruses shows microdiversity matters.

Numerous ecological processes, such as bacteriophage infection and phytoplankton-bacterial interactions, often occur via strain-specific mechanisms. Therefore, studying the causes of microbial dynamics should benefit from highly resolving taxonomic characterizations. We sampled daily to weekly over 5 months following a phytoplankton bloom off Southern California and examined the extent of microdiversity, that is, significant variation within 99% sequence similarity clusters, operational taxonomic units (OTUs), of bacteria, archaea, phytoplankton chloroplasts (all via 16S or intergenic spacer (ITS) sequences) and T4-like-myoviruses (via g23 major capsid protein gene sequence). The extent of microdiversity varied between genes (ITS most, g23 least) and only temporally common taxa were highly microdiverse. Overall, 60% of taxa exhibited microdiversity; 59% of these had subtypes that changed significantly as a proportion of the parent taxon, indicating ecologically distinct taxa. Pairwise correlations between prokaryotes and myoviruses or phytoplankton (for example, highly microdiverse Chrysochromulina sp.) improved when using single-base variants. Correlations between myoviruses and SAR11 increased in number (172 vs 9, Spearman>0.65) and became stronger (0.61 vs 0.58, t-test: P<0.001) when using SAR11 ITS single-base variants vs OTUs. Whole-community correlation between SAR11 and myoviruses was much improved when using ITS single-base variants vs OTUs, with Mantel rho=0.49 vs 0.27; these results are consistent with strain-specific interactions. Mantel correlations suggested >1 μm (attached/large) prokaryotes are a major myovirus source. Consideration of microdiversity improved observation of apparent host and virus networks, and provided insights into the ecological and evolutionary factors influencing the success of lineages, with important implications to ecosystem resilience and microbial function.

HOW TO FIND GRAVITATIONALLY LENSED TYPE Ia SUPERNOVAE

ABSTRACT Type Ia supernovae (SNe Ia) that are multiply imaged by gravitational lensing can extend the SN Ia Hubble diagram to very high redshifts (z ≳ 2), probe potential SN Ia evolution, and deliver high-precision constraints on H 0, w, and Ω m via time delays. However, only one, iPTF16geu, has been found to date, and many more are needed to achieve these goals. To increase the multiply imaged SN Ia discovery rate, we present a simple algorithm for identifying gravitationally lensed SN Ia candidates in cadenced, wide-field optical imaging surveys. The technique is to look for supernovae that appear to be hosted by elliptical galaxies, but that have absolute magnitudes implied by the apparent hosts’ photometric redshifts that are far brighter than the absolute magnitudes of normal SNe Ia (the brightest type of supernovae found in elliptical galaxies). Importantly, this purely photometric method does not require the ability to resolve the lensed images for discovery. Active galactic nuclei, the primary sources of contamination that affect the method, can be controlled using catalog cross-matches and color cuts. Highly magnified core-collapse SNe will also be discovered as a byproduct of the method. Using a Monte Carlo simulation, we forecast that the Large Synoptic Survey Telescope can discover up to 500 multiply imaged SNe Ia using this technique in a 10 year z-band search, more than an order of magnitude improvement over previous estimates. We also predict that the Zwicky Transient Facility should find up to 10 multiply imaged SNe Ia using this technique in a 3 year R-band search—despite the fact that this survey will not resolve a single system.

The host specificity of ape malaria parasites can be broken in confined environments

Recent studies have revealed a large diversity of Plasmodium spp. among African great apes. Some of these species are related to Plasmodium falciparum, the most virulent agent of human malaria (subgenus Laverania), and others to Plasmodium ovale, Plasmodium malariae and Plasmodium vivax (subgenus Plasmodium), three other human malaria agents. Laverania parasites exhibit strict host specificity in their natural environment. Plasmodium reichenowi, Plasmodium billcollinsi, Plasmodium billbrayi and Plasmodium gaboni infect only chimpanzees, while Plasmodium praefalciparum, Plasmodium blacklocki and Plasmodium adleri are restricted to gorillas and Plasmodium falciparum is pandemic in humans. This host specificity may be due to genetic and/or environmental factors. Infrastructures hosting captive primates, such as sanctuaries and health centres, usually concentrate different primate species, thus favouring pathogen exchanges. Using molecular tools, we analysed blood samples from captive non-human primates living in Gabon to evaluate the risk of Plasmodium spp. transfers between host species. We also included blood samples from workers taking care of primates to assess whether primate-human parasite transfers occurred. We detected four transfers of Plasmodium from gorillas towards chimpanzees, one from chimpanzees to gorillas, three from humans towards chimpanzees and one from humans to mandrills. No simian Plasmodium was found in the blood samples from humans working with primates. These findings demonstrate that the genetic barrier that determines the apparent host specificity of Laverania is not completely impermeable and that parasite exchanges between gorillas and chimpanzees are possible in confined environments.

Oral delivery of anti-MDM2 inhibitor SP141-loaded FcRn-targeted nanoparticles to treat breast cancer and metastasis

We have recently discovered a specific Murine Double Minute 2 (MDM2) oncogene inhibitor, called SP141, which exerts potent anticancer activity in various breast cancer models. However, its low oral bioavailability is the major hurdle for moving this drug to clinical trial. The present study was designed to discover and validate a novel nano-oral delivery system for this promising anticancer agent. Herein, we report the preparation, characterization, and evaluation of the efficacy and safety of the SP141-loaded IgG Fc-conjugated maleimidyl-poly(ethylene glycol)-co-poly(ε-caprolactone) (Mal-PEG-PCL) nanoparticles (SP141FcNP) as an orally cancer therapeutic agent. Our results indicated that SP141FcNP showed a biphasic release pattern and increased transepithelial transport in vitro and in vivo with the involvement of FcRn-mediated transcytosis. SP141FcNP also exhibited increased intestinal epithelial permeability, cellular uptake, and oral bioavailability, with extended blood circulation time, increased tumor accumulation, enhanced MDM2 inhibition, and stronger responses in anti-tumor growth and metastasis effects in vitro and in vivo, without apparent host toxicity. Collectively, this newly developed nanoparticle oral delivery system provides a basis for evaluation of SP141 as a potential clinical candidate for cancer therapy.

Taxonomic recovery of the ant cricket Myrmecophilus albicinctus from M. americanus (Orthoptera, Myrmecophilidae).

Myrmecophilus americanus and Myrmecophilus albicinctus are typical myrmecophilous insects living inside ant nests. These species are ecologically important due to the obligate association with tramp ant species, including harmful invasive ant species. However, the taxonomy of these “white-banded ant crickets” is quite confused owing to a scarcity of useful external morphological characteristics. Recently, Myrmecophilus albicinctus was synonymized with Myrmecophilus americanus regardless of the apparent host use difference. To clarify taxonomical relationship between Myrmecophilus albicinctus and Myrmecophilus albicinctus, we reexamined morphological characteristics of both species mainly in the viewpoint of anatomy. Observation of genitalia parts, together with a few external body parts, revealed that Myrmecophilus albicinctus showed different tendency from them of Myrmecophilus americanus. Therefore, we recover Myrmecophilus albicinctus as a distinct species on the basis of the morphology.