THE ROLE OF THE BACTERIAL ENDOSYMBIONT, \u3ci\u3eARSENOPHONUS\u3c/i\u3e, IN THE SOYBEAN APHID, \u3ci\u3eAPHIS GLYCINES\u3c/i\u3e

Bacterial endosymbionts can have profound impacts on their host’s ecology. Notably, endosymbionts can protect their hosts against natural enemies and influence host plant interactions. The endosymbiont Candidatus Arsenophonus infects a wide taxonomic range of arthropod hosts, and is suspected of an uncharacterized mutualistic role in hemipterous insects. In the soybean aphid, Aphis glycines, an introduced pest of soybeans in the United States, Arsenophonus is the sole facultative endosymbiont. The focus of this dissertation is to characterize the role of Arsenophonus in the aphid, with an overall emphasis on its impact on aphid management strategies. I first used diagnostic PCR to determine Arsenophonus infection frequency and strain diversity for native and introduced soybean aphids. I found that Arsenophonus infection is a uniform strain that is highly prevalent in soybean aphid. I then determined if Arsenophonus was a defense symbiont by curing two genotypes of soybean aphid of their natural Arsenophonus infection, resulting in infected and uninfected isolines within the same genetic background. I subjected these isolines to assays with three parasitoid species and a common aphid fungal pathogen, Pandora neoaphidis. I did not find differences in parasitism or fungal infections within the treatments. These results indicate that, although Arsenophonus is widespread, the symbiont should not interfere with biological control efforts. I next examined the influence of Arsenophonus on the ability of soybean aphid “biotypes” to colonize resistant Rag plants. I cured three additional soybean aphid biotypes. All isolines were subjected to growth rate assays on resistant Rag versus susceptible soybean. My results indicate that Arsenophonus infected soybean aphids have an increased population growth compared to uninfected aphids regardless of soybean plant type Finally, I induced soybean plants with jasmonic acid (JA) or salicylic acid (SA) to determine the effective plant defense against soybean aphid feeding. I also used Arsenophonus infected and uninfected aphids to determine any interaction between Arsenophonus and plant defense. I found SA treatment decreased soybean aphid population growth for one experiment, but had no effect when replicated. JA treatment had no effect, and there were no interactions between Arsenophonus infection and plant treatments

The endosymbiont Arsenophonus is widespread in soybean aphid, Aphis glycines, but does not provide protection from parasitoids or a fungal pathogen

Aphids commonly harbor bacterial facultative symbionts that have a variety of effects upon their aphid hosts, including defense against hymenopteran parasitoids and fungal pathogens. The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is infected with the symbiont Arsenophonus sp., which has an unknown role in its aphid host. Our research goals were to document the infection frequency and diversity of the symbiont in field-collected soybean aphids, and to determine whether Arsenophonus is defending soybean aphid against natural enemies. We performed diagnostic PCR and sequenced four Arsenophonus genes in soybean aphids from their native and introduced range to estimate infection frequency and genetic diversity, and found that Arsenophonus infection is highly prevalent and genetically uniform. To evaluate the defensive role of Arsenophonus, we cured two aphid genotypes of their natural Arsenophonus infection through ampicillin microinjection, resulting in infected and uninfected isolines within the same genetic background. These isolines were subjected to parasitoid assays using a recently introduced biological control agent, Binodoxys communis [Braconidae], a naturally recruited parasitoid, Aphelinus certus [Aphelinidae], and a commercially available biological control agent, Aphidius colemani [Braconidae]. We also assayed the effect of the common aphid fungal pathogen, Pandora neoaphidis (Remaudiere & Hennebert) Humber (Entomophthorales: Entomophthoraceae), on the same aphid isolines. We did not find differences in successful parasitism for any of the parasitoid species, nor did we find differences in P. neoaphidis infection between our treatments. Our conclusion is that Arsenophonus does not defend its soybean aphid host against these major parasitoid and fungal natural enemies

Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: A multicentre randomized clinical pilot trial

Background: Fever improves pathogen control at a significant metabolic cost. No randomized clinical trials (RCT) have compared fever treatment thresholds in critically ill children. We performed a pilot RCT to determine whether a definitive trial of a permissive approach to fever in comparison to current restrictive practice is feasible in critically ill children with suspected infection. Methods: An open, parallel-group pilot RCT with embedded mixed methods perspectives study in four UK paediatric intensive care units (PICUs) and associated retrieval services. Participants were emergency PICU admissions aged > 28 days to < 16 years receiving respiratory support and supplemental oxygen. Subjects were randomly assigned to permissive (antipyretic interventions only at ≥ 39.5 °C) or restrictive groups (antipyretic interventions at ≥ 37.5 °C) whilst on respiratory support. Parents were invited to complete a questionnaire or take part in an interview. Focus groups were conducted with staff at each unit. Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between group separation of temperature and safety. Results: One hundred thirty-eight children met eligibility criteria of whom 100 (72%) were randomized (11.1 patients per month per site) without prior consent (RWPC). Consent to continue in the trial was obtained in 87 cases (87%). The mean maximum temperature (95% confidence interval) over the first 48 h was 38.4 °C (38.2-38.6) in the restrictive group and 38.8 °C (38.6-39.1) in the permissive group, a mean difference of 0.5 °C (0.2-0.8). Protocol deviations were observed in 6.8% (99/1438) of 6-h time periods and largely related to patient comfort in the recovery phase. Length of stay, duration of organ support and mortality were similar between groups. No pre-specified serious adverse events occurred. Staff (n = 48) and parents (n = 60) were supportive of the trial, including RWPC. Suggestions were made to only include invasively ventilated children for the duration of intubation. Conclusion: Uncertainty around the optimal fever threshold for antipyretic intervention is relevant to many emergency PICU admissions. A more permissive approach was associated with a modest increase in mean maximum temperature. A definitive trial should focus on the most seriously ill cases in whom antipyretics are rarely used for their analgesic effects alone. Trial registration: ISRCTN16022198. Registered on 14 August 2017

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Xanthates as Synthetic Equivalents of Oxyacyl Radicals: Access to Lactones under Tin-Free Conditions

In addition to their utility in Barton–McCombie deoxygenations, xanthates can engage in 5-<i>exo-trig</i> radical cyclizations to afford lactones after oxidative workup. In this paper, we describe a tin-free protocol that provides direct access to lactones via hydrolysis of labile thioketal intermediates. Analysis of several systems of varying complexity reveals that the reaction is most applicable for constrained systems in which the reacting center is prepositioned near the radical-accepting alkene

Soybean aphid, <i>Aphis glycines,</i> collection locations, year collected, collector, and <i>Arsenophonus</i> prevalence.

<p>Soybean aphid, <i>Aphis glycines,</i> collection locations, year collected, collector, and <i>Arsenophonus</i> prevalence.</p

Oxaliplatin disrupts nucleolar function through biophysical disintegration

Platinum (Pt) compounds such as oxaliplatin are among the most commonly prescribed anti-cancer drugs. Despite their considerable clinical impact, the molecular basis of platinum cytotoxicity and cancer specificity remain unclear. Here we show that oxaliplatin, a backbone for the treatment of colorectal cancer, causes liquid-liquid demixing of nucleoli at clinically relevant concentrations. Our data suggest that this biophysical defect leads to cell-cycle arrest, shutdown of Pol I-mediated transcription, and ultimately cell death. We propose that instead of targeting a single molecule, oxaliplatin preferentially partitions into nucleoli, where it modifies nucleolar RNA and proteins. This mechanism provides a general approach for drugging the increasing number of cellular processes linked to biomolecular condensates