Unconventional structure and mechanisms for membrane interaction and translocation of the NF-κB-targeting toxin AIP56

Bacterial AB toxins are secreted key virulence factors that are internalized by target cells through receptor-mediated endocytosis, translocating their enzymatic domain to the cytosol from endosomes (short-trip) or the endoplasmic reticulum (long-trip). To accomplish this, bacterial AB toxins evolved a multidomain structure organized into either a single polypeptide chain or non-covalently associated polypeptide chains. The prototypical short-trip single-chain toxin is characterized by a receptor-binding domain that confers cellular specificity and a translocation domain responsible for pore formation whereby the catalytic domain translocates to the cytosol in an endosomal acidification-dependent way. In this work, the determination of the three-dimensional structure of AIP56 shows that, instead of a two-domain organization suggested by previous studies, AIP56 has three-domains: a non-LEE encoded effector C (NleC)-like catalytic domain associated with a small middle domain that contains the linker-peptide, followed by the receptor-binding domain. In contrast to prototypical single-chain AB toxins, AIP56 does not comprise a typical structurally complex translocation domain; instead, the elements involved in translocation are scattered across its domains. Thus, the catalytic domain contains a helical hairpin that serves as a molecular switch for triggering the conformational changes necessary for membrane insertion only upon endosomal acidification, whereas the middle and receptor-binding domains are required for pore formation. © 2023, The Author(s).This work was supported by National funds through FCT under the project UIDB/04293/2020 and by FEDER funds through Programa Operacional Factores de Competitividade – COMPETE and by national funds through FCT – Fundação para a Ciência e a Tecnologia under the project PTDC/BIA-MIC/29910/2017 to N.M.S.S. A.d.V. was funded by Portuguese national funds through the FCT and, when eligible, by COMPETE 2020 FEDER funds, under the Scientific Employment Stimulus–Individual Call 2021.02251.CEECIND/CP1663/CT0016. We acknowledge access to the HTX crystallization facility (Proposal ID: BIOSTRUCTX_8167) and SOLEIL, ESRF and ALBA synchrotrons for provision of measurement time and thank their staff for help with data collection. The authors acknowledge the support of i3S Scientific Platforms (https://www.i3s.up.pt/scientific-platforms.php) Advanced Light Microscopy, member of the national infrastructure PPBI-Portuguese Platform of BioImaging (supported by POCI-01-0145-FEDER-022122), Animal Facility, Biochemical and Biophysical Technologies and X-ray Crystallography. A special thanks to Dr. Marc Graille and Dr. João Morais Cabral for constructive discussions in structural biology and Dr. Dimitri Panagiotis Papatheodorou for providing plasmid p327

The biological origin of linguistic diversity

In contrast with animal communication systems, diversity is characteristic of almost every aspect of human language. Languages variously employ tones, clicks, or manual signs to signal differences in meaning; some languages lack the noun-verb distinction (e.g., Straits Salish), whereas others have a proliferation of fine-grained syntactic categories (e.g., Tzeltal); and some languages do without morphology (e.g., Mandarin), while others pack a whole sentence into a single word (e.g., Cayuga). A challenge for evolutionary biology is to reconcile the diversity of languages with the high degree of biological uniformity of their speakers. Here, we model processes of language change and geographical dispersion and find a consistent pressure for flexible learning, irrespective of the language being spoken. This pressure arises because flexible learners can best cope with the observed high rates of linguistic change associated with divergent cultural evolution following human migration. Thus, rather than genetic adaptations for specific aspects of language, such as recursion, the coevolution of genes and fast-changing linguistic structure provides the biological basis for linguistic diversity. Only biological adaptations for flexible learning combined with cultural evolution can explain how each child has the potential to learn any human language

Comprehensive Analysis Reveals Dynamic and Evolutionary Plasticity of Rab GTPases and Membrane Traffic in Tetrahymena thermophila

Cellular sophistication is not exclusive to multicellular organisms, and unicellular eukaryotes can resemble differentiated animal cells in their complex network of membrane-bound structures. These comparisons can be illuminated by genome-wide surveys of key gene families. We report a systematic analysis of Rabs in a complex unicellular Ciliate, including gene prediction and phylogenetic clustering, expression profiling based on public data, and Green Fluorescent Protein (GFP) tagging. Rabs are monomeric GTPases that regulate membrane traffic. Because Rabs act as compartment-specific determinants, the number of Rabs in an organism reflects intracellular complexity. The Tetrahymena Rab family is similar in size to that in humans and includes both expansions in conserved Rab clades as well as many divergent Rabs. Importantly, more than 90% of Rabs are expressed concurrently in growing cells, while only a small subset appears specialized for other conditions. By localizing most Rabs in living cells, we could assign the majority to specific compartments. These results validated most phylogenetic assignments, but also indicated that some sequence-conserved Rabs were co-opted for novel functions. Our survey uncovered a rare example of a nuclear Rab and substantiated the existence of a previously unrecognized core Rab clade in eukaryotes. Strikingly, several functionally conserved pathways or structures were found to be associated entirely with divergent Rabs. These pathways may have permitted rapid evolution of the associated Rabs or may have arisen independently in diverse lineages and then converged. Thus, characterizing entire gene families can provide insight into the evolutionary flexibility of fundamental cellular pathways

Global biodiversity monitoring: From data sources to Essential Biodiversity Variables

Essential Biodiversity Variables (EBVs) consolidate information from varied biodiversity observation sources. Here we demonstrate the links between data sources, EBVs and indicators and discuss how different sources of biodiversity observations can be harnessed to inform EBVs. We classify sources of primary observations into four types: extensive and intensive monitoring schemes, ecological field studies and satellite remote sensing. We characterize their geographic, taxonomic and temporal coverage. Ecological field studies and intensive monitoring schemes inform a wide range of EBVs, but the former tend to deliver short-term data, while the geographic coverage of the latter is limited. In contrast, extensive monitoring schemes mostly inform the population abundance EBV, but deliver long-term data across an extensive network of sites. Satellite remote sensing is particularly suited to providing information on ecosystem function and structure EBVs. Biases behind data sources may affect the representativeness of global biodiversity datasets. To improve them, researchers must assess data sources and then develop strategies to compensate for identified gaps. We draw on the population abundance dataset informing the Living Planet Index (LPI) to illustrate the effects of data sources on EBV representativeness. We find that long-term monitoring schemes informing the LPI are still scarce outside of Europe and North America and that ecological field studies play a key role in covering that gap. Achieving representative EBV datasets will depend both on the ability to integrate available data, through data harmonization and modeling efforts, and on the establishment of new monitoring programs to address critical data gaps

A Standardised Procedure for Evaluating Creative Systems: Computational Creativity Evaluation Based on What it is to be Creative

Computational creativity is a flourishing research area, with a variety of creative systems being produced and developed. Creativity evaluation has not kept pace with system development with an evident lack of systematic evaluation of the creativity of these systems in the literature. This is partially due to difficulties in defining what it means for a computer to be creative; indeed, there is no consensus on this for human creativity, let alone its computational equivalent. This paper proposes a Standardised Procedure for Evaluating Creative Systems (SPECS). SPECS is a three-step process: stating what it means for a particular computational system to be creative, deriving and performing tests based on these statements. To assist this process, the paper offers a collection of key components of creativity, identified empirically from discussions of human and computational creativity. Using this approach, the SPECS methodology is demonstrated through a comparative case study evaluating computational creativity systems that improvise music

Eye Size at Birth in Prosimian Primates: Life History Correlates and Growth Patterns

BACKGROUND: Primates have large eyes relative to head size, which profoundly influence the ontogenetic emergence of facial form. However, growth of the primate eye is only understood in a narrow taxonomic perspective, with information biased toward anthropoids.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: We measured eye and bony orbit size in perinatal prosimian primates (17 strepsirrhine taxa and Tarsius syrichta) to infer the extent of prenatal as compared to postnatal eye growth. In addition, multiple linear regression was used to detect relationships of relative eye and orbit diameter to life history variables. ANOVA was used to determine if eye size differed according to activity pattern. In most of the species, eye diameter at birth measures more than half of that for adults. Two exceptions include Nycticebus and Tarsius, in which more than half of eye diameter growth occurs postnatally. Ratios of neonate/adult eye and orbit diameters indicate prenatal growth of the eye is actually more rapid than that of the orbit. For example, mean neonatal transverse eye diameter is 57.5% of the adult value (excluding Nycticebus and Tarsius), compared to 50.8% for orbital diameter. If Nycticebus is excluded, relative gestation age has a significant positive correlation with relative eye diameter in strepsirrhines, explaining 59% of the variance in relative transverse eye diameter. No significant differences were found among species with different activity patterns.\ud \ud CONCLUSIONS/SIGNIFICANCE: The primate developmental strategy of relatively long gestations is probably tied to an extended period of neural development, and this principle appears to apply to eye growth as well. Our findings indicate that growth rates of the eye and bony orbit are disassociated, with eyes growing faster prenatally, and the growth rate of the bony orbit exceeding that of the eyes after birth. Some well-documented patterns of orbital morphology in adult primates, such as the enlarged orbits of nocturnal species, mainly emerge during postnatal development.\ud \u