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Understanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from divergent bat CoVs to investigate their cell entry mechanisms. Unexpectedly, the successful recovery of rVSVs bearing the spike from SHC014-CoV, a SARS-like bat CoV, was associated with the acquisition of a novel substitution in the S2 fusion peptide-proximal region (FPPR). This substitution enhanced viral entry in both VSV and coronavirus contexts by increasing the availability of the spike receptor-binding domain to recognize its cellular receptor, ACE2. A second substitution in the S1 N-terminal domain, uncovered through the rescue and serial passage of a virus bearing the FPPR substitution, further enhanced spike:ACE2 interaction and viral entry. Our findings identify genetic pathways for adaptation by bat CoVs during spillover and host-to-host transmission, fitness trade-offs inherent to these pathways, and potential Achilles heels that could be targeted with countermeasures.

DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.

The literature has yet to review the differential effects of Natural Environment Teaching (NET) and Discrete Trial Teaching (DTT) on adaptive skills. A sample of 142 children diagnosed with ASD between the ages of 16 and 35 months received either DTT, NET, or both interventions (NET+ DTT). The Bayley Scales of Infant and Toddler Development (BSID) Adaptive Subscale and the Verbal Behavior Milestones Assessment and Placement Program (VB-MAPP) Barriers Assessment were used as baseline and posttest measures. Children who received NET and NET+DTT conditions showed significant improvements compared to the DTT condition indicating that the addition of NET leads to increased adaptive skills and decreased barrier behaviors in participants. DTT may also play a necessary foundational role for children with more significant delays. These results provide support for the use of a combination of teaching strategies in community-based early intervention and refine protocols for teaching adaptive skills to toddlers with ASD.

Research analyzing the effects of bilingual language exposure on children with autism spectrum disorder (ASD) has increased in frequency. Utilizing the Bayley Scales of Infant and Toddler Development—Third Edition, the current study analyzed the effects of bilingual language exposure and age on language development, cognitive development, and social emotional development in toddlers with ASD. Older children demonstrated higher language scores than younger children. The interaction between ASD and bilingualism did not yield statistical significance for language, cognitive, or social emotional scores; however, the interaction between age and bilingualism was found to be significant. Age may have more of an influence on language development than ASD. Children with ASD can be raised in bilingual homes without affecting long-term development.

(Series Information) European Papers - A Journal on Law and Integration, 2024 9(1), 179-208 | Article | (Table of Contents) I. Introduction: structuralising crisis. – II. “Crisification”: the incremental normalisation of exceptions. – III. The 2015 ”Refugee Crisis”: the suspension of governance (as a form of governance) – III.1. Relocation (and Dublin prorogation) – III.2. The Hotspot Fiasco – IV. The New Pact Reforms: generalising derogations – IV.1. Screening process: hotspots extended – IV.2. Border Procedure: hotspots normalised – V. Conclusion: reversing the rule, decreasing legality. | (Abstract) This Article problematises the role of crisis in the governance of asylum in Europe. It unveils its nature, predominance, and implications as a structural component of EU law and policy in this domain. The main point I intend to convey is that crisis, in and by itself, constitutes a system of governance producing very problematic effects. The association between (unwanted) migration and refugee flows with crisis in the European context has allowed for the exceptionalisation of rights and legal safeguards, with the pre-emption of unauthorised arrivals becoming the main concern. The danger, instability, and abnormality connected with crisis pervades law and policy, justifying mechanisms that contravene minimal rule of law standards, including due process guarantees and effective judicial protection. The incremental normalisation of exceptions has led to a position where the suspension of (rule of law-based) governance has become a form of governance. The prorogation of “normal” (rule of law-compliant) arrangements has given way to “exceptional” means of managing asylum, starting with the 2015 “refugee crisis” and the relocation-plus-hotspots scheme, which have now been streamlined as part of the New Pact on Migration and Asylum reforms. The resulting generalisation of derogations, the proliferation of legal fictions and rights negations that the envisaged amendments involve, is progressively normalising a situation of non-access to international protection in the EU, with deleterious consequences not only for asylum seekers, but for the integrity of the EU legal order and fundamental rights at large.

Abstract DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.

Understanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from divergent bat CoVs to investigate their cell entry mechanisms. Unexpectedly, the successful recovery of rVSVs bearing the spike from SHC014-CoV, a SARS-like bat CoV, was associated with the acquisition of a novel substitution in the S2 fusion peptide-proximal region (FPPR). This substitution enhanced viral entry in both VSV and coronavirus contexts by increasing the availability of the spike receptor-binding domain to recognize its cellular receptor, ACE2. A second substitution in the S1 N-terminal domain, uncovered through the rescue and serial passage of a virus bearing the FPPR substitution, further enhanced spike:ACE2 interaction and viral entry. Our findings identify genetic pathways for adaptation by bat CoVs during spillover and host-to-host transmission, fitness trade-offs inherent to these pathways, and potential Achilles' heels that could be targeted with countermeasures.

Gregarines are a large and diverse subgroup of Apicomplexa, a lineage of obligate animal symbionts including pathogens such as Plasmodium, the malaria parasite. Unlike Plasmodium, however, gregarines are poorly studied, despite the fact that as early-branching apicomplexans they are crucial to our understanding of the origin and evolution of all apicomplexans and their parasitic lifestyle. Exemplifying this, the earliest branch of gregarines, the archigregarines, are particularly poorly studied: around 80 species have been described from marine invertebrates, but almost all of them were assigned to a single genus, Selenidium. Most are known only from light micrographs and largely unresolved rDNA phylogenies, where they exhibit a great deal of sequence variation, and fall into four subclades. To resolve the relationships within archigregarines, we sequenced 12 single-cell transcriptomes from species representing all four known subclades, as well as one blastogregarine (which frequently branch with Selenidium). A 190-gene phylogenomic tree confirmed four maximally supported individual clades of archigregarines and blastogregarines. These clades are discrete and distantly related, and also correlate with host identity. We propose the establishment of three novel genera of archigregarines to reflect their phylogenetic diversity and host range, and nine novel species isolated from a range of marine invertebrates.

Marine cyanobacteria have gained momentum in recent years as a source of novel bioactive small molecules. This paper describes the structure elucidation and pharmacological evaluation of two new (veraguamide O (1) and veraguamide P (2)) and one known (veraguamide C (3)) analogs isolated from a cyanobacterial collection made in the Las Perlas Archipelago of Panama. We hypothesized that these compounds would be cytotoxic in cancer cell lines. The compounds were screened against HEK-293, estrogen receptor positive (MCF-7), and triple-negative breast cancer (MDA-MB-231) cells as well as against a broad panel of membrane-bound receptors. The planar structures were determined based on NMR and MS data along with a comparison to previously isolated veraguamide analogs. Phylogenetic analysis of the collection suggests it to be an Okeania sp., a similar species to the cyanobacterium reported to produce other veraguamides. Veraguamide O shows no cytotoxicity (greater than 100 μM) against ER-positive cells (MCF-7) with 13 μM IC50 against MDA-MB-231 TNBC cells. Interestingly, these compounds show affinity for the sigma2/TMEM-97 receptor, making them potential leads for the development of non-toxic sigma 2 targeting ligands.

Quasi-direct current (Q-DC) filamentary electrical discharges are used to control the shock train in a back-pressured Mach 2 duct flow. The coupled interaction between the plasma filaments and the shock train leading edge (STLE) is studied for a variety of boundary conditions. Electrical parameters associated with the discharge are recorded during actuation, demonstrating a close correlation between the STLE position and dynamics. High-speed self-aligned focusing schlieren (SAFS) and high frame-rate color camera imaging are the primary optical diagnostics used to study the flowfield and plasma morphology. Shock tracking and plasma characterization algorithms are employed to extract time-resolved quantitative data during shock–plasma interactions. Four distinct shock–plasma interaction types are identified and outlined, revealing a strong dependence on the spacing between the uncontrolled STLE and discharge electrodes and a moderate dependence on flow parameters.

Background and aims: The false-root knot nematode (Nacobbus spp.) comprises polyphagous species, with pepper (Capsicum annuum) being one of the most affected crops. Due to the lack of resistant pepper genotypes, we compared the responses of different commercial cultivars to identify possible plant defence mechanisms against N. celatus. M&M: Nematodes from Río Cuarto (Córdoba Province) and Lisandro Olmos (Buenos Aires Province) were inoculated on pepper cultivars: California Wonder (control), Fyuco INTA, Yatasto, and Fenomeno RZ. Plants were grown under a greenhouse and galls were analysed by histopathological techniques. Results: The roots of the commercial cultivars showed the typical morpho-anatomical alterations induced by N. celatus: gall formation, hyperplasia reactions, development of syncytia in the central cylinder and disorganisation of vascular tissues. Syncytial cells in contact with females of nematodes from Lisandro Olmos showed a defence reaction by Fyuco INTA, whereas feeding sites in Fenomeno RZ did not denote high metabolic activity in nematodes of both origins. Conclusions: The different responses observed between populations and/or hosts demonstrate the importance of considering nematodes from different geographical origins when testing plant material for tolerance and/or resistance to N. celatus. Studies of this nature are necessary since they facilitate a more in-depth understanding of the parasite-plant interaction.

In instructional settings, evolution and natural selection are challenging concepts to teach, due to the fact that these topics are difficult to observe in the laboratory or lecture hall. In the past few years, Avida-ED has emerged as an innovative tool for teaching evolutionary principles. It allows students to directly observe effects of evolution by changing different variables, such as environmental conditions and genetic sequences. In our study, we used pretest and posttest questionnaires to investigate the use of Avida-ED in undergraduate coursework. We showed that students demonstrated similar improvement in evolutionary understanding irrespective of major, undergraduate level, sex, or final end-of-course grade. These results reinforce the idea that Avida-ED can facilitate learning of evolution in all student populations.