Maternally-transmitted associations between endosymbiotic bacteria and insects are ubiquitous. While many of these associations are obligate and mutually beneficial, many are facultative, and the ...mechanism(s) by which these microbes persist in their host lineages remain elusive. Inherited microbes with imperfect transmission are expected to be lost from their host lineages if no other mechanisms increase their persistence (i.e., host reproductive manipulation and/or fitness benefits to host). Indeed numerous facultative heritable endosymbionts are reproductive manipulators. Nevertheless, many do not manipulate reproduction, so they are expected to confer fitness benefits to their hosts, as has been shown in several studies that report defense against natural enemies, tolerance to environmental stress, and increased fecundity.
We examined whether larval to adult survival of Drosophila hydei against attack by a common parasitoid wasp (Leptopilina heterotoma), differed between uninfected flies and flies that were artificially infected with Spiroplasma, a heritable endosymbiont of Drosophila hydei that does not appear to manipulate host reproduction. Survival was significantly greater for Spiroplasma-infected flies, and the effect of Spiroplasma infection was most evident during the host's pupal stage. We examined whether or not increased survival of Spiroplasma-infected flies was due to reduced oviposition by the wasp (i.e., pre-oviposition mechanism). The number of wasp eggs per fly larva did not differ significantly between Spiroplasma-free and Spiroplasma-infected fly larvae, suggesting that differential fly survival is due to a post-oviposition mechanism.
Our results suggest that Spiroplasma confers protection to D. hydei against wasp parasitism. This is to our knowledge the first report of a potential defensive mutualism in the genus Spiroplasma. Whether it explains the persistence and high abundance of this strain in natural populations of D. hydei, as well as the widespread distribution of heritable Spiroplasma in Drosophila and other arthropods, remains to be investigated.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Activation of the classical complement pathway occurs to varying degrees within strains of the
complex, which contain a group of pathogenic spirochetes that cause tick-borne Lyme borreliosis, ...including the agent of Lyme disease in the United States,
. Despite this information, details related to the control of
by the classical pathway are not clear. To address this question, we infected C1qα
mice, which cannot assemble the C1 complex and thus fail to activate the classical pathway, with
strain B31. Using bioluminescent
imaging, we found that C1qα
mice harbored more
following 10 days of infection relative to their isogenic C57BL/6 parent. Quantitative PCR (qPCR) demonstrated that C1qα
mice harbored significantly more
than parent mice did within lymph nodes, skin, heart, and joints. The increased
load in C1qα
mice was observed at 21 and 28 days of infection, consistent with the classical pathway promoting complement-dependent, antibody-mediated killing following the development of a
-specific humoral immune response. In addition, circulating borrelial-specific IgM was higher in C1qα
mice relative to their parent mouse strain and did not decrease at 21 and 28 days post-infection, indicating that IgG class switching was delayed in C1qα
mice. At day 28, both
-specific IgG1 and IgG3 levels were higher in infected C1qα
mice, but that these antibodies were not sufficient to control borrelial infection in the absence of the classical pathway. Furthermore, the lack of C1q also altered the balance of the Th1/Th2 response, as both circulating Th1 (MIP-1α, IL-2, IL-12, and TNFα), Th2 (IL-4, IL-10, and MCP-1), and Th17 (IL-17) cytokines were elevated in infected C1qα
mice. These data imply that C1q and the classical pathway play important roles in controlling borrelial infection
antibody and complement-dependent killing, as well as altering both antibody maturation processes and the T cell response following exposure to infectious
.
The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal ...functions in activating innate and adaptive antiviral responses; however, the mechanisms by which DC function is subverted to establish ZIKV infection are unclear. Here we develop a genomics profiling method that enables discrete analysis of ZIKV-infected versus neighboring, uninfected primary human DCs to increase the sensitivity and specificity with which ZIKV-modulated pathways can be identified. The results show that ZIKV infection specifically increases the expression of genes enriched for lipid metabolism-related functions. ZIKV infection also increases the recruitment of sterol regulatory element-binding protein (SREBP) transcription factors to lipid gene promoters, while pharmacologic inhibition or genetic silencing of SREBP2 suppresses ZIKV infection of DCs. Our data thus identify SREBP2-activated transcription as a mechanism for promoting ZIKV infection amenable to therapeutic targeting.
IntroductionComplicated monochorionic twin pregnancies are often associated with high perinatal morbidity and mortality, some of which are severe enough to require a gestational reduction surgery to ...improve fetal survival and reduce disabilities. While radiofrequency ablation is currently the most commonly used procedure with higher fetal survival and fewer maternal and fetal complications compared with other surgical methods, the therapeutic effect of microwave ablation (MWA) is reported to be better, presumably due to the higher thermal effect and fewer restrictions. Currently there is limited evidence to prove the feasibility of MWA for selective reduction. The aim of this pilot study is to explore the feasibility, efficacy and safety of MWA reduction for severe complicated monochorionic pregnancies and may provide evidence for using the MWA in intrauterine surgeries extensively.Methods and analysisThis is a study protocol for a parallel-design pilot randomised controlled trial. 60 eligible patients with severe complicated monochorionic pregnancies will be randomised in a ratio of 1:1 to MWA group and radiofrequency group. Patients will be followed up until 6 months of age of the retained fetal. The primary analysis will compare the rates of neonatal survival at 28 days to evaluate the effect of MWA. The study will also evaluate the safety profile of MWA including the occurrence of postoperative adverse events and maternal and fetal complications. Additional secondary outcomes to be explored include the condition of neonatal asphyxia and the growth of surviving fetus at 6 months. Outcomes will be analysed by both a frequentist and the Bayesian statistical approach.Ethics and disseminationThis study was approved by the ethical review committee of the Peking University Third Hospital (Beijing, China). The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences.Trial registration numberNCT04014452; Pre-results.
In a previous study, we showed that
Spiroplasma
, a maternally transmitted endosymbiotic bacterium of
Drosophila hydei
, enhances larval to adult survival of its host when exposed to oviposition ...attack by the parasitoid wasp
Leptopilina heterotoma
. The mechanism by which
Spiroplasma
enhances host survival has not been elucidated. To better understand this mechanism, we compared the growth of wasp larvae in
Spiroplasma
-infected and uninfected hosts. Our results indicate that wasp embryos in
Spiroplasma
-infected hosts hatch and grow normally for ~2 days, after which their growth is severely impaired, compared to wasps developing in uninfected hosts. Thus, despite their reduced ability to complete development in
Spiroplasma
-infected hosts, developing wasps may exert fitness costs on their hosts that are manifested after host emergence. The severity of these costs will influence the degree to which this protective mechanism contributes to the long-term persistence of
Spiroplasma
in
D. hydei
. We therefore examined survival to 10-day-old adult stage and fecundity of
Spiroplasma
-infected flies surviving a wasp treatment. Our results suggest detrimental effects of wasp attack on longevity of
Spiroplasma
-infected adult flies. However, compared to
Spiroplasma
-free flies exposed to wasps,
Spiroplasma
-infected flies exposed to wasps have ~5 times greater survival from larva to 10 day-adult. The relative fecundity of wasp-attacked
Spiroplasma
-infected females was ~71% that of un-attacked
Spiroplasma
-free females. Our combined survival and female fecundity results suggest that under high wasp parasitism, the reproductive fitness of
Spiroplasma
-infected flies may be ~3.5 times greater than that of uninfected females, so it is potentially relevant to the persistence of
Spiroplasma
in natural populations of
D. hydei
. Interestingly,
Spiroplasma
-infected males surviving a wasp attack were effectively sterile during the 3-day period examined. This observation is consistent with the expectation that, as a maternally transmitted symbiont, there is little selective pressure on
Spiroplasma
to enhance the reproductive fitness of its male hosts.
•The COVID-19 pandemic increases the prevalence of depression, anxiety, distress, and insomnia.•Health care workers and COVID-19 patients are high-risk groups of mental health.•Urgent interventions ...are needed for preventing mental health problems.
The global COVID-19 pandemic has generated major mental and psychological health problems worldwide. We conducted a meta-analysis to assess the prevalence of depression, anxiety, distress, and insomnia during the COVID-19 pandemic.
We searched online biomedical databases (PubMed, Embase, Web of Science, Ovid, CNKI, and Wanfang Data) and preprint databases (SSRN, bioRxiv, and MedRxiv) for observational studies from January 1, 2020 to March 16, 2020 investigating the prevalence of mental health problems during the COVID-19 pandemic.
We retrieved 821 citations from the biomedical databases and 53 citations from the preprint databases: 66 studies with 221,970 participants were included in our meta-analysis. The overall pooled prevalence of depression, anxiety, distress, and insomnia was 31.4%, 31.9%, 41.1% and 37.9%, respectively. Noninfectious chronic disease patients, quarantined persons, and COVID-19 patients had a higher risk of depression (Q=26.73, p<0.01) and anxiety (Q=21.86, p<0.01) than other populations. The general population and non-medical staff had a lower risk of distress than other populations (Q=461.21, p< 0.01). Physicians, nurses, and non-medical staff showed a higher prevalence of insomnia (Q=196.64, p<0.01) than other populations.
All included studies were from the early phase of the global pandemic. Additional meta-analyses are needed to obtain more data in all phases of the pandemic.
The COVID-19 pandemic increases the mental health problems of the global population, particularly health care workers, noninfectious chronic disease patients, COVID-19 patients, and quarantined persons. Interventions for mental health are urgently needed for preventing mental health problems.
Phase holographic metasurfaces encode the phase profiles of holograms in metasurfaces formed by meta-atom arrays and accurately modulate the field distribution in desired region. Iterative ...optimization methods or data-driven learning methods are used to retrieve the phase profile under the given physical setups, such as working wavelength lambda, metasurfaces' period DELTAx, and image distance Z. However, those methods usually repeat the optimization or training process to retrieve the phase profile for different physical setups. Here, we propose a generalized phase retrieval model (GPRM) based on physics- inspired network to retrieve the phase profile from the input lambda, DELTAx, Z, and desired image without retraining the neural network. The GPRM consists of deep neural network (DNN), parabolic phase, and Fresnel diffraction propagation, which is able to generate phase profile with high reconstruction quality in extraordinary broadband, such as visible, terahertz, and microwave region. By combining with corresponding meta-atom pool, the proposed method has great potential to design versatile meta-devices for image display, data encoding, and beam shaping. Furthermore, the proposed method accelerates the design of Fresnel phase hologram, which can cooperate with programmable metasurfaces to realize dynamic three-dimensional or full-color display.
Maternally transmitted endosymbiotic bacteria of the genus Spiroplasma associate with numerous insect species, including the genus Drosophila. Among the Spiroplasma strains associated with ...Drosophila, several manipulate their host’s reproduction by killing the male offspring of the infected females. Although the male-killing mechanism is not well understood, previous studies of non-native strains transferred to D. melanogaster (strain Oregon-R) indicate that the male-killing strain achieves higher densities than two non-male-killing strains. Whether this pattern of higher male-killing strain densities occurs in other host-symbiont strain combinations is not known. Herein, we used quantitative PCR to examine infection densities of one non-male-killing strain native to D. hydei (Hyd1), and two male-killing strains; one native to D. nebulosa (NSRO), and one native to D. melanogaster (MSRO; recently discovered), upon artificial transfer to D. melanogaster (strain Canton-S). Infection densities were examined at four weekly intervals in adult flies, across three consecutive generations following artificial transfer. Infection densities of the non-male-killing strain were significantly lower than those of the two male killers immediately after adult emergence. At later time points, however, the non-male-killing strain (Hyd1) is capable of proliferating to densities similar to those of the two male-killing strains (NSRO and MSRO) in D. melanogaster (Canton-S). We also examined the effect of co-infection by the heritable bacterium Wolbachia, on Spiroplasma densities and male-killing ability. Wolbachia had little to no effect of Spiroplasma densities, but the male-killing ability of MSRO was lower in the presence of Wolbachia. Generation post-infection had little effect on Spiroplasma densities, but affected the male-killing ability.
Maternally transmitted endosymbionts of insects are ubiquitous in nature and play diverse roles in the ecology and evolution of their hosts. To persist in host lineages, many symbionts manipulate ...host reproduction to their advantage (e.g. cytoplasmic incompatibility and male-killing), or confer fitness benefits to their hosts (e.g. metabolic provisioning and defense against natural enemies). Recent studies suggest that strains of the bacterial genus Spiroplasma protect their host (flies in the genus Drosophila) against parasitoid attack. The Spiroplasma-conferred protection is partial and flies surviving a wasp attack have reduced adult longevity and fecundity. Therefore, it is unclear whether protection against wasps alone can counter Spiroplasma loss by imperfect maternal transmission and any possible fitness costs to harboring Spiroplasma. To address this question, we conducted a population cage study comparing Spiroplasma frequencies over time (host generations) under conditions of high wasp pressure and no wasp pressure. A dramatic increase of Spiroplasma prevalence was observed under high wasp pressure. In contrast, Spiroplasma prevalence in the absence of wasps did not change significantly over time; a pattern consistent with random drift. Thus, the defensive mechanism may contribute to the high prevalence of Spiroplasma in host populations despite imperfect vertical transmission.
The frequency of bacteria that protect flies against parasitic wasps increases rapidly when wasps are present.
Remdesivir (RDV; GS-5734) is currently the only FDA-approved antiviral drug for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The drug is approved for use ...in adults or children 12 years or older who are hospitalized for the treatment of COVID-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. Unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease. RDV is also unstable in plasma and has a complex activation pathway which may contribute to its highly variable antiviral efficacy in SARS-CoV-2-infected cells. Potent orally bioavailable antiviral drugs for early treatment of SARS-CoV-2 infection are urgently needed, and several, including molnupiravir and PF-07321332, are currently in clinical development. We focused on making simple, orally bioavailable lipid analogs of remdesivir nucleoside (RVn; GS-441524) that are processed to RVn monophosphate, the precursor of the active RVn triphosphate, by a single-step intracellular cleavage. In addition to high oral bioavailability, stability in plasma, and simpler metabolic activation, new oral lipid prodrugs of RVn had submicromolar anti-SARS-CoV-2 activity in a variety of cell types, including Vero E6, Calu-3, Caco-2, human pluripotent stem cell (PSC)-derived lung cells, and Huh7.5 cells. In Syrian hamsters, oral treatment with 1-
-octadecyl-2-
-benzyl-glycero-3-phosphate RVn (ODBG-P-RVn) was well tolerated and achieved therapeutic levels in plasma above the 90% effective concentration (EC
) for SARS-CoV-2. The results suggest further evaluation as an early oral treatment for SARS-CoV-2 infection to minimize severe disease and reduce hospitalizations.
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