OBJECTIVES: Acute hypoxemic respiratory failure in immunocompromised patients remains the leading cause of admission to the ICU, with high case fatality. The response to the initial oxygenation strategy may be predictive of outcome. This study aims to assess the response to the evolutionary profiles of oxygenation strategy and the association with survival. DESIGN: Post hoc analysis of EFRAIM study with a nonparametric longitudinal clustering technique (longitudinal K-mean). SETTING AND PATIENTS: Multinational, observational prospective cohort study performed in critically ill immunocompromised patients admitted for an acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1547 patients who did not require invasive mechanical ventilation (iMV) at ICU admission were included. Change in ventilatory support was assessed and three clusters of change in oxygenation modality over time were identified. Cluster A: 12.3% iMV requirement and high survival rate, n = 717 patients (46.3%); cluster B: 32.9% need for iMV, 97% ICU mortality, n = 499 patients (32.3%); and cluster C: 37.5% need for iMV, 0.3% ICU mortality, n = 331 patients (21.4%). These clusters demonstrated a high discrimination. After adjustment for confounders, clusters B and C were independently associated with need for iMV (odds ratio [OR], 9.87; 95% CI, 7.26-13.50 and OR, 19.8; 95% CI, 13.7-29.1). CONCLUSIONS: This study identified three distinct highly performing clusters of response to initial oxygenation strategy, which reliably predicted the need for iMV requirement and hospital mortality.
- MeSH
- Hypoxia * therapy mortality MeSH
- Immunocompromised Host * MeSH
- Intensive Care Units statistics & numerical data MeSH
- Critical Illness mortality therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Hospital Mortality MeSH
- Oxygen Inhalation Therapy * methods MeSH
- Prospective Studies MeSH
- Respiratory Insufficiency * therapy mortality MeSH
- Aged MeSH
- Cluster Analysis MeSH
- Respiration, Artificial * methods statistics & numerical data MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
We report avian cervical vertebrae from the Quercy fissure fillings in France, which are densely covered with villi-like tubercles. Two of these vertebrae stem from a late Eocene site, another lacks exact stratigraphic data. Similar cervical vertebrae occur in avian species from Eocene fossils sites in Germany and the United Kingdom, but the new fossils are the only three-dimensionally preserved vertebrae with pronounced surface sculpturing. So far, the evolutionary significance of this highly bizarre morphology, which is unknown from extant birds, remained elusive, and even a pathological origin was considered. We note the occurrence of similar structures on the skull of the extant African rodent Lophiomys and detail that the tubercles represent true osteological features and characterize a distinctive clade of Eocene birds (Perplexicervicidae). Micro-computed tomography (μCT) shows the tubercles to be associated with osteosclerosis of the cervical vertebrae, which have a very thick cortex and much fewer trabecles and pneumatic spaces than the cervicals of most extant birds aside from some specialized divers. This unusual morphology is likely to have served for strengthening the vertebral spine in the neck region, and we hypothesize that it represents an anti-predator adaptation against the craniocervical killing bite ("neck bite") that evolved in some groups of mammalian predators. Tuberculate vertebrae are only known from the Eocene of Central Europe, which featured a low predation pressure on birds during that geological epoch, as is evidenced by high numbers of flightless avian species. Strengthening of the cranialmost neck vertebrae would have mitigated attacks by smaller predators with weak bite forces, and we interpret these vertebral specializations as the first evidence of "internal bony armor" in birds.
The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core. This research highlights the significance of rPeptides in stability and coacervation of two distinct protoribosomal evolutionary stages. The 617nt 'big' protoribosome model, which associates with rPeptides specifically, exhibits a structurally defined and rigid nature, further stabilized by the peptides. In contrast, the 136nt 'small' model, previously linked to peptidyltransferase activity, displays greater structural flexibility. While this construct interacts with rPeptides with lower specificity, they induce coacervation of the 'small' protoribosome across a wide concentration range, which is concomitantly dependent on the RNA sequence and structure. Moreover, these conditions protect RNA from degradation. This phenomenon suggests a significant evolutionary advantage in the RNA-protein interaction at the early stages of ribosome evolution. The distinct properties of the two protoribosomal stages suggest that rPeptides initially provided compartmentalization and prevented RNA degradation, preceding the emergence of specific RNA-protein interactions crucial for the ribosomal structural integrity.
- MeSH
- Nucleic Acid Conformation MeSH
- Models, Molecular MeSH
- Peptides chemistry metabolism MeSH
- Peptidyl Transferases metabolism chemistry MeSH
- Ribosomal Proteins * metabolism chemistry MeSH
- Ribosomes * metabolism MeSH
- RNA metabolism chemistry MeSH
- RNA Stability MeSH
- Publication type
- Journal Article MeSH
The major organelles of the endomembrane system were in place by the time of the last eukaryotic common ancestor (LECA) (~1.5 billion years ago). Their acquisitions were defining milestones during eukaryogenesis. Comparative cell biology and evolutionary analyses show multiple instances of homology in the protein machinery controlling distinct interorganelle trafficking routes. Resolving these homologous relationships allows us to explore processes underlying the emergence of additional, distinct cellular compartments, infer ancestral states predating LECA, and explore the process of eukaryogenesis itself. Here, we undertake a molecular evolutionary analysis (including providing a transcriptome of the jakobid flagellate Reclinomonas americana), exploring the origins of the machinery responsible for the biogenesis of lysosome-related organelles (LROs), the Biogenesis of LRO Complexes (BLOCs 1,2, and 3). This pathway has been studied only in animals and is not considered a feature of the basic eukaryotic cell plan. We show that this machinery is present across the eukaryotic tree of life and was likely in place prior to LECA, making it an underappreciated facet of eukaryotic cellular organisation. Moreover, we resolve multiple points of ancient homology between all three BLOCs and other post-endosomal retrograde trafficking machinery (BORC, CCZ1 and MON1 proteins, and an unexpected relationship with the "homotypic fusion and vacuole protein sorting" (HOPS) and "Class C core vacuole/endosomal tethering" (CORVET) complexes), offering a mechanistic and evolutionary unification of these trafficking pathways. Overall, this study provides a comprehensive account of the rise of the LROs biogenesis machinery from before the LECA to current eukaryotic diversity, integrating it into the larger mechanistic framework describing endomembrane evolution.
The etiological agent of yaws is the spirochete Treponema pallidum (TP) subsp. pertenue (TPE) and infects the children of Papua New Guinea, causing ulcerative skin lesions that impairs normal growth and development. Closely related strains of Treponema pallidum subsp. pertenue, JE11, and TE13 were detected in an ulcer biospecimen derived from a 5-year-old yaws patient. Cloning experiments validated the presence of two distinct but similar genotypes, namely TE13 and JE11, co-occurring within a single host. While coinfection with highly related TPE strains has only limited epidemiological and clinical relevance, this is the first documented coinfection with genetically distinct TP strains in a single patient. Similar coinfections in the past were explained by the existence of over a dozen recombinant loci present in the TP genomes as a result of inter-strain or inter-subspecies recombination events following an anticipated scenario of TP coinfection, i.e., uptake of foreign DNA and DNA recombination.
- MeSH
- DNA, Bacterial genetics MeSH
- Yaws * microbiology MeSH
- Phylogeny MeSH
- Genotype * MeSH
- Coinfection * microbiology MeSH
- Humans MeSH
- Child, Preschool MeSH
- Sequence Analysis, DNA MeSH
- Treponema pallidum * genetics isolation & purification classification MeSH
- Treponema MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Geographicals
- Papua New Guinea MeSH
Chromosomal rearrangements are often associated with playing a role in the speciation process. However, the underlying mechanism that favors the genetic isolation associated with chromosomal changes remains elusive. In this sense, the genus Mazama is recognized by its high level of karyotype diversity among species with similar morphology. A cryptic species complex has been identified within the genus, with the red brocket deer (Mazama americana and Mazama rufa) being the most impressive example. The chromosome variation was clustered in cytotypes with diploid numbers ranging from 42 to 53 and was correlated with geographical location. We conducted an analysis of chromosome evolution of the red brocket deer complex using comparative chromosome painting and Bacterial Artificial Chromosome (BAC) clones among different cytotypes. The aim was to deepen our understanding of the karyotypic relationships within the red brocket, thereby elucidating the significant chromosome variation among closely related species. This underscores the significance of chromosome changes as a key evolutionary process shaping their genomes. The results revealed the presence of three distinct cytogenetic lineages characterized by significant karyotypic divergence, suggesting the existence of efficient post-zygotic barriers. Tandem fusions constitute the main mechanism driving karyotype evolution, following a few centric fusions, inversion X-autosomal fusions. The BAC mapping has improved our comprehension of the karyotypic relationships within the red brocket deer complex, prompting questions regarding the role of these changes in the speciation process. We propose the red brocket as a model group to investigate how chromosomal changes contribute to isolation and explore the implications of these changes in taxonomy and conservation.
- MeSH
- Karyotype * MeSH
- Karyotyping * MeSH
- Chromosome Painting MeSH
- Evolution, Molecular * MeSH
- Chromosomes, Artificial, Bacterial genetics MeSH
- Deer * genetics classification MeSH
- Genetic Speciation * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Pathogen adaptations during host-pathogen co-evolution can cause the host balance between immunity and immunopathology to rapidly shift. However, little is known in natural disease systems about the immunological pathways optimised through the trade-off between immunity and self-damage. The evolutionary interaction between the conjunctival bacterial infection Mycoplasma gallisepticum (MG) and its avian host, the house finch (Haemorhous mexicanus), can provide insights into such adaptations in immune regulation. Here we use experimental infections to reveal immune variation in conjunctival tissue for house finches captured from four distinct populations differing in the length of their co-evolutionary histories with MG and their disease tolerance (defined as disease severity per pathogen load) in controlled infection studies. To differentiate contributions of host versus pathogen evolution, we compared house finch responses to one of two MG isolates: the original VA1994 isolate and a more evolutionarily derived one, VA2013. To identify differential gene expression involved in initiation of the immune response to MG, we performed 3'-end transcriptomic sequencing (QuantSeq) of samples from the infection site, conjunctiva, collected 3-days post-infection. In response to MG, we observed an increase in general pro-inflammatory signalling, as well as T-cell activation and IL17 pathway differentiation, associated with a decrease in the IL12/IL23 pathway signalling. The immune response was stronger in response to the evolutionarily derived MG isolate compared to the original one, consistent with known increases in MG virulence over time. The host populations differed namely in pre-activation immune gene expression, suggesting population-specific adaptations. Compared to other populations, finches from Virginia, which have the longest co-evolutionary history with MG, showed significantly higher expression of anti-inflammatory genes and Th1 mediators. This may explain the evolution of disease tolerance to MG infection in VA birds. We also show a potential modulating role of BCL10, a positive B- and T-cell regulator activating the NFKB signalling. Our results illuminate potential mechanisms of house finch adaptation to MG-induced immunopathology, contributing to understanding of the host evolutionary responses to pathogen-driven shifts in immunity-immunopathology trade-offs.
A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base. The overlying otoconia and tectorial membranes are absent in the Irx3/5 DKO inner ear, and the primary auditory neurons project fibers to both the saccule and cochlear hair cells. The central neuronal projections from the cochlear apex-base contour are not fully segregated into a dorsal and ventral innervation in the Irx3/5 DKO cochlear nucleus, obliterating the characteristic tonotopic auditory map. Additionally, Irx3/5 deletion reveals a pronounced cochlear-apex-vestibular "vestibular-cochlear" nerve (VCN) bilateral connection that is less noticeable in wild-type control mice. Moreover, the incomplete segregation of apex and base projections that expands fibers to connect with vestibular nuclei. The results suggest the mammalian cochlear apex is a derived lagena reminiscent of sarcopterygians. Thus, Irx3 and 5 are potential evolutionary branch-point genes necessary for balance-sound segregation, which fused into a saccule-cochlea organization.
- MeSH
- Homeodomain Proteins * genetics metabolism MeSH
- Cochlea * physiology MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Saccule and Utricle * physiology MeSH
- Auditory Pathways physiology MeSH
- Transcription Factors * genetics metabolism deficiency MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Animal and human ancestors developed complex physiological and behavioral response systems to cope with two types of threats: immediate physical harm from predators or conspecifics, triggering fear, and the risk of infections from parasites and pathogens leading to the evolution of the behavioral immune system with disgust as the key emotion. Integration of the evolutionary concepts of the fear module and behavioral immune systems has been infrequent, despite the significant survival advantages of disgust in various contexts. Studies comparing attention to ancestral and modern threats accompanied by fear have yielded ambiguous results and what qualifies as salient modern disgusting stimuli remains unclear. We do not know whether disgust or the behavioral immune system, as inherent aspects of human psychology, have adapted to safeguard us from pandemic risks or poisoning by modern toxic substances. METHODS: To test these effects, we have developed a survey comprised of 60 short vignettes describing threats evoking fear and disgust belonging to one of the three main categories of threats: (1) ancestral (phylogenetic), (2) modern (ontogenetic), and (3) pandemics of airborne disease. Each vignette was evaluated on a 7-point Likert scale based on fear, disgust, and anger. In total, 660 respondents completed the survey. The data were analysed using a factor analysis and general linear model with the respondent as a random factor. RESULTS: The results show that the strongest fear is triggered by modern threats (electricity, car accidents), while the highest disgust is evoked by ancient threats (body waste products, worms, etc.). Interestingly, disgust does not respond to modern threat stimuli such as toxic substances or radioactivity as these evoke mainly fear and anger. Finally, a distinct response pattern was found for pandemic threats, in which both fear (e.g., of disease and death) and disgust (e.g., of used face masks) are employed. DISCUSSION: Our study offers valuable insights into the emotional responses to ancestral and modern threats and their adaptation to pandemic challenges. Ancestral threats are not always more powerful stimuli than adequate threats of the modern type, but they function specifically. Thus, snakes and heights as fear-inducing ancestral threats form separate factors in a multivariate analysis, whereas all ancestral disgust stimuli group together. The threat of a pandemic forms a specific category and people process it emotionally and cognitively. These insights contribute to our understanding of human psychology and behavior in an ever-changing world.
- Publication type
- Journal Article MeSH
The remarkable fish biodiversity encompasses also great sex chromosome variability. Harttia catfish belong to Neotropical models for karyotype and sex chromosome research. Some species possess one of the three male-heterogametic sex chromosome systems, XY, X1X2Y or XY1Y2, while other members of the genus have yet uncharacterized modes of sex determination. Particularly the XY1Y2 multiple sex chromosome system shows a relatively low incidence among vertebrates, and it has not been yet thoroughly investigated. Previous research suggested two independent X-autosome fusions in Harttia which led to the emergence of XY1Y2 sex chromosome system in three of its species. In this study, we investigated evolutionary trajectories of synteny blocks involved in this XY1Y2 system by probing six Harttia species with whole chromosome painting (WCP) probes derived from the X (HCA-X) and the chromosome 9 (HCA-9) of H. carvalhoi. We found that both painting probes hybridize to two distinct chromosome pairs in Amazonian species, whereas the HCA-9 probe paints three chromosome pairs in H. guianensis, endemic to Guyanese drainages. These findings demonstrate distinct evolutionary fates of mapped synteny blocks and thereby elevated karyotype dynamics in Harttia among the three evolutionary clades.
- Publication type
- Journal Article MeSH
