Morphological modularity in the vertebral column of Felidae (Mammalia, Carnivora)

BACKGROUND: Previous studies have demonstrated that the clear morphological differences among vertebrae across the presacral column are accompanied by heterogeneous functional signals in vertebral shape. Further, several lines of evidence suggest that the mammalian axial skeleton is a highly modular structure. These include its composition of serial units, a trade-off between high shape variance and strong conservation of vertebral count, and direct association of regions with anterior expression sites of Hox genes. Here we investigate the modular organisation of the presacral vertebral column of modern cats (Felidae, Carnivora, Mammalia) with pairwise comparisons of vertebral shape covariation (i.e. integration) and evaluate our results against hypotheses of developmental and functional modularity. We used three-dimensional geometric morphometrics to quantify vertebral shape and then assessed integration between pairs of vertebrae with phylogenetic two-block partial least square analysis (PLS). RESULTS: Six modules were identified in the pairwise analyses (vertebrae included are designated as ‘C’ for cervical, ‘T’ for thoracic, and ‘L’ for lumbar): an anterior module (C1 to T1); a transitional module situated between the last cervicals and first thoracics (C6 to T2); an anterior to middle thoracic set (T4 to T8); an anticlinal module (T10 and T11); a posterior set composed of the last two thoracics and lumbars (T12 to L7); and a module showing covariation between the cervicals and the posterior set (T12 to L7). These modules reflect shared developmental pathways, ossification timing, and observed ecological shape diversification in living species of felids. CONCLUSIONS: We show here that patterns of shape integration reflect modular organisation of the vertebral column of felids. Whereas this pattern corresponds with hypotheses of developmental and functional regionalisation in the axial skeleton, it does not simply reflect major vertebral regions. This modularity may also have permitted vertebral partitions, specifically in the posterior vertebral column, to be more responsive to selection and achieve higher morphological disparity than other vertebral regions

Shape Covariation (or the Lack Thereof) Between Vertebrae and Other Skeletal Traits in Felids: The Whole is Not Always Greater than the Sum of Parts

Within carnivorans, cats show comparatively little disparity in overall morphology, with species differing mainly in body size. However, detailed shape analyses of individual osteological structures, such as limbs or skulls, have shown that felids display significant morphological differences that correlate with their observed ecological and behavioural ranges. Recently, these shape analyses have been extended to the felid axial skeleton. Results demonstrate a functionally-partitioned vertebral column, with regions varying greatly in level of correlation between shape and ecology. Moreover, a clear distinction is evident between a phylogenetically-constrained neck region and a selection-responsive posterior spine. Here, we test whether this regionalisation of function reflected in vertebral column shape is also translated into varying levels of phenotypic integration between this structure and most other skeletal elements. We accomplish this comparison by performing pairwise tests of integration between vertebral and other osteological units, quantified with 3D geometric morphometric data and analysed both with and without phylogenetic correction. To our knowledge, this is the first study to test for integration across a comprehensive sample of whole-skeleton elements. Our results show that, prior to corrections, strong covariation is present between vertebrae across the vertebral column and all other elements, with the exception of the femur. However, most of these significant correlations disappear after correcting for phylogeny, which is a significant influence on cranial and limb morphology of felids and other carnivorans. Our results thus suggest that the vertebral column of cats displays relative independence from other skeletal elements and may represent several distinct evolutionary morphological modules

Drivers and constraints of shape evolution in the vertebral column of felids (Felidae, Carnivora)

Morphological studies of the skull and limbs of tetrapods are common in the literature. Nonetheless, the vertebral column has been comparatively neglected, and research shows a bias towards developmental and genetic approaches. Still, these studies have highlighted the unusual uniformity in vertebral count across mammals, unlike the great variation in vertebral numbers observed in other tetrapod clades. This meristic constraint has been suggested to drive higher regionalisation in the mammalian axial skeleton, with adaptation to discrete niches happening primarily through modification of vertebral form rather than changes in numbers. Living species of the mammalian family Felidae are an ideal group for vertebral studies as all taxa present the same count of 27 presacral vertebrae but vary in ecological specialisations and body mass. In this thesis, I explore the morphological evolution of the presacral vertebral column by, first, investigating ecological and phylogenetic influences on presacral vertebral shape, and then, examining patterns of vertebral trait covariation with an evolutionary developmental perspective. My results show clear regionalisation of vertebral column shape and function. Specifically, a highly integrated region between the diaphragmatic vertebra and the last lumbar (i.e., T10 – L7) shows the highest levels of ecological 6 specialization, and potentially higher evolvability, contrasting with a phylogenetically conserved neck region. I found strong support for a widespread two-module model of intravertebral shape based on developmental origins of vertebral components, and this analysis also provided an empirical example of phenotypic integration promoting higher morphological disparity. Exceptions to this model are at boundaries of large vertebral modules and suggest functional overprinting of developmental patterns. Further, I demonstrated the presence of modularity at the organismal level, with decoupling of the vertebral column as a whole from other skeletal structures. Combined, the work presented in this thesis demonstrates that axial evolution across Felidae reflects both developmental constraints and functional specialisation by concentrating shape change within distinct evolutionary modules. This thesis provides a foundation for further study of vertebral columns combining both functional and developmental perspectives

Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method

Background: Mismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method. Method: Fifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) patients (31 males, 25 females, mean age 24.6) and 64 matched controls (37 males, 27 females, mean age 24.8) were assessed for duration-, frequency- and combined-type MMN and P3a as well as 4 clinical, 3 cognitive and 3 psychopathological measures. To evaluate and correlate MMN at source-level, independent component analysis (ICA) was applied to the continuous EEG data to derive equivalent current dipoles which were clustered into 19 clusters based on cortical location. Results: No scalp channel group MMN or P3a amplitude differences were found. Of the localized clusters, several were in or near brain areas previously suggested to be involved in the MMN response, including frontal and anterior cingulate cortices and superior temporal and inferior frontal gyri. For duration deviants, MMN was attenuated at the right superior temporal gyrus in patients compared to healthy controls (p = 0.01), as was P3a at the superior frontal cortex (p = 0.01). No individual patient correlations with clinical, cognitive, or psychopathological measures survived correction for multiple comparisons. Conclusion: Attenuated source-localized MMN and P3a peak contributions can be identified in FEANS patients using a method based on independent component analysis (ICA). This indicates that deficits in pre-attentive auditory information processing are present at this early stage of schizophrenia and are not the result of disease chronicity or medication. This is to our knowledge the first study on FEANS patients using this more detailed method. Keywords: Mismatch negativity, Schizophrenia, First episode, EEG, IC

A fly in a tube: Macroevolutionary expectations for integrated phenotypes

Phenotypic integration and modularity are ubiquitous features of complex organisms, describing the magnitude and pattern of relationships among biological traits. A key prediction is that these relationships, reflecting genetic, developmental, and functional interactions, shape evolutionary processes by governing evolvability and constraint. Over the last 60 years, a rich literature of research has quantified patterns of integration and modularity across a variety of clades and systems. Only recently has it become possible to contextualize these findings in a phylogenetic framework to understand how trait integration interacts with evolutionary tempo and mode. Here, we review the state of macroevolutionary studies of integration and modularity, synthesizing empirical and theoretical work into a conceptual framework for predicting the effects of integration on evolutionary rate and disparity: a fly in a tube. While magnitude of integration is expected to influence the potential for phenotypic variation to be produced and maintained, thus defining the shape and size of a tube in morphospace, evolutionary rate, or the speed at which a fly moves around the tube, is not necessarily controlled by trait interactions. Finally, we demonstrate this reduced disparity relative to the Brownian expectation for a given rate of evolution with an empirical example: the avian cranium

Discovery of permuted and recently split transfer RNAs in Archaea

Background: As in eukaryotes, precursor transfer RNAs in Archaea often contain introns that are removed in tRNA maturation. Two unrelated archaeal species display unique pre-tRNA processing complexity in the form of split tRNA genes, in which two to three segments of tRNAs are transcribed from different loci, then trans-spliced to form a mature tRNA. Another rare type of pre-tRNA, found only in eukaryotic algae, is permuted, where the 3 ’ half is encoded upstream of the 5 ’ half, and must be processed to be functional. Results: Using an improved version of the gene-finding program tRNAscan-SE, comparative analyses and experimental verifications, we have now identified four novel trans-spliced tRNA genes, each in a different species of the Desulfurococcales branch of the Archaea: tRNA Asp(GUC) in Aeropyrum pernix and Thermosphaera aggregans, and tRNA Lys(CUU) in Staphylothermus hellenicus and Staphylothermus marinus. Each of these includes features surprisingly similar to previously studied split tRNAs, yet comparative genomic context analysis and phylogenetic distribution suggest several independent, relatively recent splitting events. Additionally, we identified the first examples of permuted tRNA genes in Archaea: tRNA iMet(CAU) and tRNA Tyr(GUA) in Thermofilum pendens, which appear to be permuted in the same arrangement seen previously in red alga. Conclusions: Our findings illustrate that split tRNAs are sporadically spread across a major branch of the Archaea

Collateral effect of COVID-19 on orthopedic and trauma surgery

Objectives: The purpose of this study was to assess the impact of the COVID-19 pandemic on orthopedic and trauma surgery in private practices and hospitals in Germany. Design: In this cross-sectional study, an online-based anonymous survey was conducted from April 2th to April 16th 2020. Setting: The survey was conducted among 15.0000 of 18.000 orthopedic and trauma surgeons in Germany, both in private practices and hospitals. Participants: All members of the German Society of Orthopedic and Trauma Surgery (DGOU) and the Professional Association for Orthopedic and Trauma Surgery (BVOU). were invited by e-mail to participate in the survey. Main outcome measures: Out of 50 questions 42 were designed to enquire a certain dimension of the pandemic impact and contribute to one of six indices, namely “Preparedness”, “Resources”, “Reduction”, “Informedness”, “Concern”, and “Depletion”. Data was analyzed in multiple stepwise regression, aiming to identify those factors that independently influenced the indices. Results: 858 orthopedic and trauma surgeons participated in the survey throughout Germany. In the multiple regression analysis, being employed at a hospital was identified as an independent positive predictor in the indices for “Preparedness”, “Resources”, and “Informedness” and an independent negative predictor regarding “Depletion”. Self-employment was found to be an independent positive predictor of the financial index “Depletion”. Female surgeons were identified as an independent variable for a higher level of “Concern”. Conclusions: The study confirms a distinct impact of the COVID-19 pandemic on orthopedic and trauma surgery in Germany. The containment measures are largely considered appropriate despite severe financial constraints. A substantial lack of personal protective equipment (PPE) is reported. The multiple regression analysis shows that self-employed surgeons are more affected by this shortage as well as by the financial consequences than surgeons working in hospitals. What are the new findings: The COVID-19 pandemic has a profound impact on orthopedic and trauma surgery as an unrelated specialty. Self-employed surgeons are affected especially by a shortage of PPE and financial consequences. How might it impact on clinical practice in the near future: Political and financial support can now be applied more focused to subgroups in the field of orthopedics and trauma surgery with an increased demand for support. A special emphasis should be set on the support of self-employed surgeons which are a more affected by the shortage of PPE and financial consequences than surgeons working in hospital

Genomic Heterogeneity in a Natural Archaeal Population Suggests a Model of tRNA Gene Disruption

Understanding the mechanistic basis of the disruption of tRNA genes, as manifested in the intron-containing and split tRNAs found in Archaea, will provide considerable insight into the evolution of the tRNA molecule. However, the evolutionary processes underlying these disruptions have not yet been identified. Previously, a composite genome of the deep-branching archaeon Caldiarchaeum subterraneum was reconstructed from a community genomic library prepared from a C. subterraneum–dominated microbial mat. Here, exploration of tRNA genes from the library reveals that there are at least three types of heterogeneity at the tRNAThr(GGU) gene locus in the Caldiarchaeum population. All three involve intronic gain and splitting of the tRNA gene. Of two fosmid clones found that encode tRNAThr(GGU), one (tRNAThr-I) contains a single intron, whereas another (tRNAThr-II) contains two introns. Notably, in the clone possessing tRNAThr-II, a 5′ fragment of the tRNAThr-I (tRNAThr-F) gene was observed 1.8-kb upstream of tRNAThr-II. The composite genome contains both tRNAThr-II and tRNAThr-F, although the loci are >500 kb apart. Given that the 1.8-kb sequence flanked by tRNAThr-F and tRNAThr-II is predicted to encode a DNA recombinase and occurs in six regions of the composite genome, it may be a transposable element. Furthermore, its dinucleotide composition is most similar to that of the pNOB8-type plasmid, which is known to integrate into archaeal tRNA genes. Based on these results, we propose that the gain of the tRNA intron and the scattering of the tRNA fragment occurred within a short time frame via the integration and recombination of a mobile genetic element

Crystal structure and assembly of the functional Nanoarchaeum equitans tRNA splicing endonuclease

The RNA splicing and processing endonuclease from Nanoarchaeum equitans (NEQ) belongs to the recently identified (αβ)2 family of splicing endonucleases that require two different subunits for splicing activity. N. equitans splicing endonuclease comprises the catalytic subunit (NEQ205) and the structural subunit (NEQ261). Here, we report the crystal structure of the functional NEQ enzyme at 2.1 Å containing both subunits, as well as that of the NEQ261 subunit alone at 2.2 Å. The functional enzyme resembles previously known α2 and α4 endonucleases but forms a heterotetramer: a dimer of two heterodimers of the catalytic subunit (NEQ205) and the structural subunit (NEQ261). Surprisingly, NEQ261 alone forms a homodimer, similar to the previously known homodimer of the catalytic subunit. The homodimers of isolated subunits are inhibitory to heterodimerization as illustrated by a covalently linked catalytic homodimer that had no RNA cleavage activity upon mixing with the structural subunit. Detailed structural comparison reveals a more favorable hetero- than homodimerization interface, thereby suggesting a possible regulation mechanism of enzyme assembly through available subunits. Finally, the uniquely flexible active site of the NEQ endonuclease provides a possible explanation for its broader substrate specificity

The UCSC Archaeal Genome Browser: 2012 update

The UCSC Archaeal Genome Browser (http://archaea.ucsc.edu) offers a graphical web-based resource for exploration and discovery within archaeal and other selected microbial genomes. By bringing together existing gene annotations, gene expression data, multiple-genome alignments, pre-computed sequence comparisons and other specialized analysis tracks, the genome browser is a powerful aggregator of varied genomic information. The genome browser environment maintains the current look-and-feel of the vertebrate UCSC Genome Browser, but also integrates archaeal and bacterial-specific tracks with a few graphic display enhancements. The browser currently contains 115 archaeal genomes, plus 31 genomes of viruses known to infect archaea. Some of the recently developed or enhanced tracks visualize data from published high-throughput RNA-sequencing studies, the NCBI Conserved Domain Database, sequences from pre-genome sequencing studies, predicted gene boundaries from three different protein gene prediction algorithms, tRNAscan-SE gene predictions with RNA secondary structures and CRISPR locus predictions. We have also developed a companion resource, the Archaeal COG Browser, to provide better search and display of arCOG gene function classifications, including their phylogenetic distribution among available archaeal genomes