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We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5–5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have investigated the stability of a mutant c-MYC i-motif in solutions containing a molecular crowding agent. The crowded nuclear environment was modeled by the addition of up to 40% w/w polyethylene glycols having molecular weights up to 12,000 g/mol. CD and DSC were used to establish the presence and stability of c-MYC i-motifs in buffer solutions over the pH range 4 to 7. We have shown that the c-MYC i-motif can exist as a stable structure at pH values as high as 6.7 in crowded solutions. Generic dielectric constant effects, e.g., a shift in the pKa of cytosine by more than 2 units (e.g., 4.8 to 7.0), or the formation of non-specific PEG/DNA complexes appear to contribute insignificantly to i-motif stabilization. Molecular crowding, largely an excluded volume effect of added PEG, having a molecular weight in excess of 1,000 g/mol, appears to be responsible for stabilizing the more compact i-motif over the random coil at higher pH values.

Continuous cropping changes soil physiochemical parameters, enzymes and microorganism communities, causing “replant problem” in strawberry cultivation. We hypothesized that soil nematode community would reflect the changes in soil conditions caused by long-term continuous cropping, in ways that are consistent and predictable. To test this hypothesis, we studied the soil nematode communities and several soil parameters, including the concentration of soil phenolic acids, organic matter and nitrogen levels, in strawberry greenhouse under continuous-cropping for five different durations. Soil pH significantly decreased, and four phenolic acids, i.e., p-hydroxybenzoic acid, ferulic acid, cinnamic acid and p-coumaric acid, accumulated with time under continuous cropping. The four phenolic acids were highly toxic to Acrobeloides spp., the eudominant genus in non-continuous cropping, causing it to reduce to a resident genus after seven-years of continuous cropping. Decreased nematode diversity indicated loss of ecosystem stability and sustainability because of continuous-cropping practice. Moreover, the dominant decomposition pathway was altered from bacterial to fungal under continuous cropping. Our results suggest that along with the continuous-cropping time in strawberry habitat, the soil food web is disturbed, and the available plant nutrition as well as the general health of the soil deteriorates; these changes can be indicated by soil nematode community.

The interactions of three related cationic porphyrins, TMPyP4, TMPyP3 and TMPyP2, with a WT 39-mer Bcl-2 promoter sequence G-quadruplex were studied using Circular Dichroism, ESI mass spectrometry, Isothermal Titration Calorimetry, and Fluorescence spectroscopy. The planar cationic porphyrin TMPyP4 (5, 10, 15, 20-meso-tetra (N-methyl-4-pyridyl) porphine) is shown to bind to a WT Bcl-2 G-quadruplex via two different binding modes, an end binding mode and a weaker mode attributed to intercalation. The related non-planar ligands, TMPyP3 and TMPyP2, are shown to bind to the Bcl-2 G-quadruplex by a single mode. ESI mass spectrometry experiments confirmed that the saturation stoichiometry is 4:1 for the TMPyP4 complex and 2:1 for the TMPyP2 and TMPyP3 complexes. ITC experiments determined that the equilibrium constant for formation of the (TMPyP4)1/DNA complex (K1 = 3.7 × 10(6)) is approximately two orders of magnitude greater than the equilibrium constant for the formation of the (TMPyP2)1/DNA complex, (K1 = 7.0 × 10(4)). Porphyrin fluorescence is consistent with intercalation in the case of the (TMPyP4)3/DNA and (TMPyP4)4/DNA complexes. The non-planar shape of the TMPyP2 and TMPyP3 molecules results in both a reduced affinity for the end binding interaction and the elimination of the intercalation binding mode.

Disrupting behaviors linked to movement of primary mosquito vectors, such as diel locomotor activity and visual sensitivity, is a novel and plausible malaria control intervention. Diel locomotor activity is an output of arthropod circadian activity and is influenced by factors such as light, temperature, and infection status. The biogenic amines histamine and serotonin (5-HT) are ingested with blood and differ between healthy hosts and those with severe malaria. They regulate malaria parasite infection in Anopheles stephensi , but the degree to which aging, temperature, and infection interact with ingested biogenic amines to influence mosquito behavior was unknown prior to these studies. We provisioned A. stephensi with histamine and 5-HT at healthy- and malaria-associated levels to examine diel locomotor activity of uninfected A. stephensi across lifespan, at temperatures that A. stephensi could encounter within its range, and on Plasmodium yoelii -infected mosquitoes during sporogony. We further evaluated treatment effects on retinal sensitivity of uninfected mosquitoes during light and dark periods typically associated with low and high activity for this crepuscular species. Treatment with malaria-associated levels of histamine and 5-HT significantly increased the locomotor activity of A. stephensi across lifespan and enhanced retinal sensitivity to a broad spectrum of wavelengths at the onset of light. This treatment in combination with higher temperatures also increased activity levels and broadened the peak hours of activity of A. stephensi . Notably, these effects were infection dependent. Together, our data suggest that histaminergic and serotonergic signaling within the gut-brain axis of A. stephensi could be targeted to alter mosquito activity and visual sensitivity as the basis for novel transmission-blocking strategies for malaria control.

Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60-99%. Of those mosquitoes that were infected, we observed a 75-99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18-20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity.

We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,311 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of ≥2 doses of COVID-19 vaccine received during pregnancy was 84% (95% confidence interval [CI]: 66, 93), 62% (CI: 39, 77) and 56% (CI: 34,71) during months 0–2, 0–4 and 0- 6 of a child’s life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 21% (CI: −21,48), 14% (CI: −9,32) and 13% (CI: −3,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged. This study investigates the impact of maternal COVID-19 vaccination during pregnancy on infant infection during the first six months of life. Using data from California, USA, the authors find that protection against infection during the period of Delta dominance was high, but that it declined during the Omicron period.

Background Parasitism is a major ecological niche for a variety of nematodes. Multiple nematode lineages have specialized as pathogens, including deadly parasites of insects that are used in biological control. We have sequenced and analyzed the draft genomes and transcriptomes of the entomopathogenic nematode Steinernema carpocapsae and four congeners ( S. scapterisci , S. monticolum , S. feltiae , and S. glaseri ). Results We used these genomes to establish phylogenetic relationships, explore gene conservation across species, and identify genes uniquely expanded in insect parasites. Protein domain analysis in Steinernema revealed a striking expansion of numerous putative parasitism genes, including certain protease and protease inhibitor families, as well as fatty acid- and retinol-binding proteins. Stage-specific gene expression of some of these expanded families further supports the notion that they are involved in insect parasitism by Steinernema . We show that sets of novel conserved non-coding regulatory motifs are associated with orthologous genes in Steinernema and Caenorhabditis . Conclusions We have identified a set of expanded gene families that are likely to be involved in parasitism. We have also identified a set of non-coding motifs associated with groups of orthologous genes in Steinernema and Caenorhabditis involved in neurogenesis and embryonic development that are likely part of conserved protein–DNA relationships shared between these two genera.

Wireworms are the larval stage of click beetles (Coleoptera: Elateridae), and some of their species are serious pests of many crops. In the present study, we evaluated the efficacy of naturally occurring and commercial entomopathogenic nematode species against the sugar beet wireworm, Limonius californicus (Mannerheim), in the laboratory. First, efficacies of Steinernema feltiae (Filipjev) (Rhabditida: Steinernematidae) collected from an irrigated (S. feltiae-SSK) and a dryland (S. feltiae-SSC) field and the two commercial entomopathogenic nematode species, S. carpocapsae (Weiser) (Rhabditida: Steinernematidae) and Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae), were examined. Efficacies of the two field-collected S. feltiae isolates were also compared against a commercial S. feltiae strain. In the first bioassay, S. feltiae-SSK caused 63.3% wireworm mortality, followed by 30% caused by S. carpocapsae, 23.3% by S. feltiae-SSC, and 6.7% by H.bacteriophora. In the second assay, S. feltiae-SSK killed 56.7% of the wireworms, ≈2.1- and ≈5.7-fold higher than S. feltiae-SSC and the commercial isolate, respectively.

Ascaroside pheromones stimulate dispersal, a key nematode behavior to find a new food source. Ascarosides produced by entomopathogenic nematodes (EPNs) drive infective juvenile (IJ) emergence from consumed cadavers and dispersal in soil. Without ascarosides from host cadavers, Steinernema feltiae (EPN) reduce dispersal substantially. To determine whether other Steinernema spp. exhibit the same behavior, we compared S. feltiae and S. carpocapsae IJs without host cadaver pheromones. Unlike S. feltiae , S. carpocapsae IJs continued to disperse. However, S. carpocapsae IJs exhibited a temperature-dependent quiescent period. The IJ quiescent period increased at ≤20 °C but did not appear at ≥25 °C. Consistent with this, S. carpocapsae IJ quiescence increased from 30 min to 24 h at ≤20 °C over 60 days. The quiescent period was overcome by dispersal pheromone extracts of their own, other Steinernema spp. and Heterorhabditis spp. Furthermore, S. carpocapsae IJ ambush foraging associated behaviors (tail standing, waving, and jumping) were unaffected by the absence or presence of host cadaver pheromones. For S. feltiae , IJ dispersal declined at all temperatures tested. Understanding the interaction between foraging strategies and pheromone signals will help uncover molecular mechanisms of host seeking, pathogenicity and practical applications to improve the EPN’s efficacy as biocontrol agents.

The 2022 invasion of Ukraine by Russia had far-reaching effects on the world. It disrupted trade and caused a shift in the global power balance. Western nations responded by imposing sanctions on Russia, but the BRICS countries, such as South Africa, took a different approach. This led experts to predict the emergence of a new global order. This article examines South Africa’s role as a member of BRICS in this new order. Specifically, it seeks to answer the following questions: Can South Africa contribute to shaping the new world order? How can it use its BRICS membership to do so? What challenges and prospects does the new order present for South Africa? The article uses a qualitative approach and document analysis to study policies, press releases, and speeches. It shows that the position taken by South Africa suggests that it supports overhauling the current world order, which is primarily controlled by Western powers who create rules without regard for international law. The article exposes South Africa’s belief that the current world order fails to account for new global developments and centres of influence. It concludes that South Africa advocates for a new, fair, and just world order based on international law. To achieve this, the article suggests that South Africa should leverage its regional influence, abundant resources, and developed financial system to establish a BRICS-driven new world order while keeping its national interests clear.